Brazilian Journal of Cardiovascular Surgery 26.4 - 2011 by Revista Brasileira de Cirurgia Cardiovascular

AR/ BRAZILIAN JOURNAL OF C AR SURGERY VASCUL ARDIO ARDIO ASCULAR/ ASCULAR ARDIOV CARDIO ARDIOV REVISTA CARDIO VASCUL A BRASILEIRA DE CIRURGIA C REVIST

26.4 OCTOBER/DECEMBER 2011

OL. 26 Nยบ4 OCTOBER/DECEMBER 2011 V VOL.

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Sociedade Brasileira de Cirurgia Cardiovascular II Simpósio de Perfusão em Cirurgia Cardiovascular II Simpósio de Fisioterapia em Cirurgia Cardiovascular II Simpósio de Enfermagem em Cirurgia Cardiovascular I Congresso Acadêmico em Cirurgia Cardiovascular

12 a 14 de Abril de 2012 Centro de Convenções de Maceió C

CMY

Acesse o site www.sbccv.org.br

Promoção/Realização Sociedade Brasileira de Cirurgia Cardiovascular

(11) 3849-0341 www.sbccv.org.br congresso@sbccv.org.br

Organização: (51) 3061-2957 www.abev.com.br recepcao@abev.com.br

Agência de Turismo Oficial: (82) 2121.7366 / 7355 / 7386 www.transamericatur.com.br sbccv@transamericatur.com.br

Cia Aérea Oficial

1893

1954

1977

Daniel H. Williams efetua a primeira cirurgia de coração aberto

C. Walton Lillehei efetua o primeiro reparo de septo ventricular com circulação extracorpórea

Primeiro implante de válvula mecânica de duplo folheto

2011

Trifecta™

Ao Longo da História Certos Momentos se Destacam A válvula cardíaca biológica Trifecta está redefinindo os padrões para a cirurgia cardíaca. Seu design único permite que os folhetos de pericárdio abram mais e de forma eficiente com o objetivo de imitar a válvula cardíaca nativa. A válvula Trifecta oferece o mais próximo de um desempenho perfeito com média de gradientes de um só dígito em todos os tamanhos - Isso é fazer história.

br.sjm.com

Trifecta, St. Jude Medical, o símbolo dos nove quadrados e MORE CONTROL, LESS RISK (mais controle, menos risco) são marcas registradas da St. Jude Medical Inc. e das suas empresas coligadas. © 2011 St. Jude Medical, Inc. Todos os direitos reservados.

Anúncio Trifecta Timeline BR.indd 1

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Existem muitas razões para ouvir de perto o coração das brasileiras. • No Brasil, uma em cada cinco mulheres adultas corre o risco de desenvolver doença cardiovascular;1 • Sintomas de doença cardíaca em mulheres podem ser diferentes dos sintomas sentidos pelos homens;2 • No Brasil, as doenças cardiovasculares matam mais mulheres que qualquer outra doença;3

Por isso, a Medtronic está promovendo no Brasil, junto às sociedades médicas, uma campanha socioeducativa para conscientizar as mulheres sobre a importância de manter os exames cardiovasculares sempre em dia.

Outubro/2011

• Apesar do risco, apenas um pequeno número de mulheres visita o cardiologista periodicamente.3

Esta iniciativa faz parte do envolvimento da Medtronic com a campanha de ação global iniciada pela ONU, que busca combater os problemas de saúde decorrentes das DCNT – Doenças Crônicas Não Transmissíveis. Para isso, o cardiologista é o melhor médico para ser procurado. Ajude a divulgar essa campanha.

Um compromisso Medtronic com o bem-estar das brasileiras.

www.portrasdobiquini.com.br Referências: 1. IBGE - 2010 Brazilian Census. 2. <http://www.mayoclinic.com/health/heartdisease/HB00040>. 3. <http://www.cardiol.br/imprensa/jornais/impresso/sampa.htm>.

Apoio:

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RBCCV tem Fator de Impacto 0,963 A Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (RBCCV/BJCVS) obteve a excelente marca de 0,963 no seu primeiro Fator de Impacto (FI) divulgado pelo ISI-Thomson Reuters, relativo ao biênio 2009-2010. Além disso, temos o maior Immediacy Index: 0,772. Somos a 13º Revista do Brasil e a única do gênero do hemisfério sul indexada.

Visite nossos sites: www.rbccv.org.br www.scielo.br/rbccv

BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY

RBCCV

EDITOR/EDITOR Prof. Dr. Domingo M. Braile - PhD

REVIST A BRASILEIRA DE REVISTA

São José do Rio Preto - SP - Brasil domingo@braile.com.br EDITORES ANTERIORES/FORMER EDITORS • Prof. Dr. Adib D. Jatene PhD - São Paulo (BRA) [1986-1996] • Prof. Dr. Fábio B. Jatene PhD - São Paulo (BRA) [1996-2002]

BRAZILIAN JOURNAL OF

ASSESSORA EDITORIAL/EDITORIAL ASSISTANT Rosangela Monteiro PhD - São Paulo (BRA) rosangela.monteiro@incor.usp.br

EDITOR EXECUTIVO EXECUTIVE EDITOR Ricardo Brandau Pós-graduado em Jornalismo Científico - S. José do Rio Preto (BRA) brandau@sbccv.org.br

EDITORES ASSOCIADOS/ASSOCIATE EDITORS • • • • • • •

Antônio Sérgio Martins Gilberto Venossi Barbosa José Dario Frota Filho José Teles de Mendonça Luciano Cabral Albuquerque Luis Alberto Oliveira Dallan Luiz Felipe Pinho Moreira

Botucatu (BRA) Porto Alegre (BRA) Porto Alegre (BRA) Aracaju (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA)

• • • • • • •

Manuel Antunes Mario Osvaldo P. Vrandecic Michel Pompeu B. Oliveira Sá Paulo Roberto Slud Brofman Ricardo C. Lima Ulisses A. Croti Walter José Gomes

Coimbra (POR) Belo Horizonte (BRA) Recife (BRA) Curitiba (BRA) Recife (BRA) S.J. Rio Preto (BRA) São Paulo (BRA)

EDITOR DE ESTATÍSTICA/STATISTICS EDITOR • Orlando Petrucci Jr.

Campinas (BRA)

CONSELHO EDITORIAL/EDITORIAL BOARD • Adib D. Jatene • Adolfo Leirner • Adolfo Saadia • Alan Menkis • Alexandre V. Brick • Antônio Carlos G. Penna Jr. • Bayard Gontijo Filho • Borut Gersak • Carlos Roberto Moraes • Christian Schreiber • Cláudio Azevedo Salles • Djair Brindeiro Filho • Eduardo Keller Saadi • Eduardo Sérgio Bastos • Enio Buffolo • Fábio B. Jatene • Fernando Antônio Lucchese • Gianni D. Angelini • Gilles D. Dreyfus • Ivo A. Nesralla • Jarbas J. Dinkhuysen • José Antônio F. Ramires • José Ernesto Succi • José Pedro da Silva • Joseph A. Dearani

São Paulo (BRA) São Paulo (BRA) Buenos Aires (ARG) Winnipeg (CAN) Brasília (BRA) Marília (BRA) Belo Horizonte (BRA) Ljubljana (SLO) Recife (BRA) Munique (GER) Belo Horizonte (BRA) Recife (BRA) Porto Alegre (BRA) Rio de Janeiro (BRA) São Paulo (BRA) São Paulo (BRA) Porto Alegre (BRA) Bristol (UK) Harefield (UK) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Rochester (USA)

VERSÃO PARA O INGLÊS/ENGLISH VERSION • Alexandre Werneck • Fernando Pires Buosi • Marcelo Almeida • Pablo Sebastian Maluf

• • • • • • • • • • • • • • • • • • • • • • • •

Joseph S. Coselli Luiz Carlos Bento de Souza Luiz Fernando Kubrusly Mauro Paes Leme de Sá Miguel Barbero Marcial Milton Ary Meier Nilzo A. Mendes Ribeiro Noedir A. G. Stolf Olivio Souza Neto Otoni Moreira Gomes Pablo M. A. Pomerantzeff Paulo Manuel Pêgo Fernandes Paulo P. Paulista Paulo Roberto B. Évora Pirooz Eghtesady Protásio Lemos da Luz Reinaldo Wilson Vieira Renato Abdala Karam Kalil Renato Samy Assad Roberto Costa Rodolfo Neirotti Rui M. S. Almeida Sérgio Almeida de Oliveira Tomas A. Salerno

Houston (USA) São Paulo (BRA) Curitiba (BRA) Rio de Janeiro (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Salvador (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Belo Horizonte (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Ribeirão Preto (BRA) Cincinatti (USA) São Paulo (BRA) Campinas (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) Cambridge (USA) Cascavel (BRA) São Paulo (BRA) Miami (USA)

ÓRGÃO OFICIAL DA SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR DESDE 1986 OFFICIAL ORGAN OF THE BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY SINCE 1986

ENDEREÇO/ADDRESS

Sociedade Brasileira de Cirurgia Cardiovascular Rua Beira Rio, 45 • 7º andar - Cj. 72 • Vila Olímpia • Fone: 11 3849-0341. Fax: 11 5096-0079. Cep: 04548-050 • São Paulo, SP, Brasil E-mail RBCCV: revista@sbccv.org.br • E-mail SBCCV: sbccv@sbccv.org.br • Site SBCCV: www.sbccv.org.br • Sites RBCCV: www.scielo.br/rbccv / www.rbccv.org.br (também para submissão de artigos)

Publicação trimestral/Quarterly publication Tiragem: 1200 exemplares (*)

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR (Sociedade Brasileira de Cirurgia Cardiovascular) São Paulo, SP - Brasil. v. 119861986, 1: 1,2 1987, 2: 1,2,3 1988, 3: 1,2,3 1989, 4: 1,2,3 1990, 5: 1,2,3 1991, 6: 1,2,3 1992, 7: 1,2,3,4 1993, 8: 1,2,3,4 1994, 9: 1,2,3,4

1995, 10: 1,2,3,4 1996, 11: 1,2,3,4 1997, 12: 1,2,3,4 1998, 13: 1,2,3,4 1999, 14: 1,2,3,4 2000, 15: 1,2,3,4 2001, 16: 1,2,3,4 2002, 17: 1,2,3,4 2003, 18: 1,2,3,4

2004, 19: 1,2,3,4 2005, 20: 1,2,3,4 2006, 21: 1 [supl] 2006, 21: 1,2,3,4 2007, 22: 1 [supl] 2007, 22: 1,2,3,4 2008, 23: 1 [supl] 2008, 23: 1,2,3,4 2009, 24: 1 [supl]

2009, 24: 1,2,3,4 2009, 24: 2 [supl] 2010, 25: 1,2,3,4 2010, 25: 1 [supl] 2011, 26: 1,2,3,4 2011, 26: 1 [supl]

ISSN 1678-9741 - Publicação online ISSN 0102-7638 - Publicação impressa RBCCV 44205

CDD 617.4105 NLM18 WG 168

(*) ASSOCIAÇÃO PAULISTA DE BIBLIOTECÁRIOS. Grupo de Bibliotecários Biomédicos. Normas para catalogação de publicações seriadas nas bibliotecas especializadas. São Paulo, Ed. Polígono, 1972

INDEXADA EM • Thomson Scientific (ISI) http://science.thomsonreuters.com • PubMed/Medline www.ncbi.nlm.nih.gov/sites/entrez

• ADSAUDE - Sistema Especializado de Informação em Administração de Saúde www.bibcir.fsp.usp.br/html/p/ pesquisa_em_bases_de_dados/ programa_rede_adsaude

• SciELO - Scientific Library Online www.scielo.br

• Index Copernicus www.indexcopernicus.com

• Scopus www.info.scopus.com

• Google scholar http://scholar.google.com.br/scholar

• LILACS - Literatura Latino-Americana e do Caribe em Ciências da Saúde. www.bireme.org • LATINDEX -Sistema Regional de Información en Línea para Revistas Cientificas de America Latina, el Caribe, España y Portugal www.latindex.uam.mx

Distribuída gratuitamente a todos os sócios da Sociedade Brasileira de Cirurgia Cardiovascular

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY DEPARTAMENTO DE CIRURGIA DA SOCIEDADE BRASILEIRA DE CARDIOLOGIA DEPARTMENT OF SURGERY OF THE BRAZILIAN SOCIETY OF CARDIOLOGY

“Valorizando o profissional em prol do paciente” DIRETORIA 2011 - 2012 Presidente: Vice-Presidente: Secretário Geral: Tesoureiro: Diretor Científico:

Walter José Gomes (SP) João Alberto Roso (RS) Marcelo Matos Cascudo (RN) Eduardo Augusto Victor Rocha (MG) Fábio Biscegli Jatene (SP)

Conselho Deliberativo:

Bruno Botelho Pinheiro (GO) Henrique Barsanulfo Furtado (TO) José Glauco Lobo Filho (CE) Rui M.S. Almeida (PR) Henrique Murad (RJ)

Editor da Revista: Editor do Site: Editores do Jornal:

Domingo Marcolino Braile (SP) Vinicius José da Silva Nina (MA) Walter José Gomes (SP) Fabricio Gaburro Teixeira (ES) Josalmir José Melo do Amaral (RN) Luciana da Fonseca (SP)

Presidentes das Regionais Afiliadas Norte-nordeste: Rio de Janeiro: São Paulo: Minas Gerais: Centro-Oeste: Rio Grande do Sul: Paraná: Santa Catarina:

Mauro Barbosa Arruda Filho (PE) Ronald Souza Peixoto Marcos Augusto de Moraes Silva AntonioAugusto Miana Luiz Antonio Brasil (GO) Marcela da Cunha Sales Rodrigo Milani Lourival Bonatelli Filho

Departamentos DCCVPED: DECAM: DECA: DECEN: DEPEX: Departamento de Cardiologia Clínica:

Marcelo B. Jatene (SP) Alfredo Inácio Fiorelli (SP) Wilson Lopes Pereira (SP) Rui M. S. Almeida (PR) Melchior Luiz Lima (ES) Miguel Angel Maluf (SP)

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

ISSN 1678-9741 - Publicação online ISSN 0102-7638 - Publicação impressa RBCCV 44205

Fator de Impacto: 0,963

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brasil) oct/dec - 2011;26(4):525-700

CONTENTS/SUMÁRIO

EDITORIALS/EDITORIAIS Many reasons to celebrate Domingo M. Braile ....................................................................................................................................................................... I Minimally invasive cardiac surgery in Brazil Luiz Felipe Pinho Moreira, Alex Luiz Celullari .......................................................................................................................... III Apology to the use of double mammary Fernando Morais ........................................................................................................................................................................ VI Dissection of the internal thoracic artery using skeletonized technique Henrique Murad ...................................................................................................................................................................... VIII Surgical treatment of atrial fibrillation: incoherence or negligence? Renato A. K. Kalil ....................................................................................................................................................................... X

ORIGINAL ARTICLES/ARTIGOS ORIGINAIS 1317

On-pump coronary artery bypass graft surgery: biochemical, hormonal and cellular features Revascularização miocárdica com circulação extracorpórea: aspectos bioquímicos, hormonais e celulares Edmo Atique Gabriel, Rafael Fagionato Locali, Priscila Katsumi Matsuoka, Thiago Cherbo, Enio Buffolo ............................ 525

1318

Computed tomography in late evaluation of surgical treatment of pulmonary veins total anomalous connection Tomografia computadorizada na avaliação tardia do tratamento cirúrgico da conexão anômala total de veias pulmonares Ulisses Alexandre Croti, Lilian Beani, Airton Camacho Moscardini, Arthur Soares Souza Júnior, Antônio Soares Souza, Sírio Hassem Sobrinho, Carlos Henrique De Marchi, Moacir Fernandes de Godoy, Domingo Marcolino Braile ........................... 532

1319

The renewed concept of the Batista operation for ischemic cardiomyopathy: maximum ventricular reduction O conceito renovado da operação de Batista na cardiomiopatia isquêmica: máxima redução ventricular Walter J Gomes, Raul E. Saavedra, Débora M. Garanhão, Alexandre R. Carvalho, Francisco A. Alves .................................. 544

1320

Predictors of transfusion of packed red blood cells in coronary artery bypass grafting surgery Preditores de transfusão de concentrado de hemácias em cirurgia de revascularização miocárdica Michel Pompeu Barros de Oliveira Sá, Evelyn Figueira Soares, Cecília Andrade Santos, Omar Jacobina Figueiredo, Renato Oliveira Albuquerque Lima, Fábio Gonçalves de Rueda, Rodrigo Renda de Escobar, Alexandre Magno Macário Nunes Soares, Ricardo de Carvalho Lima ........................................................................................................................................................................... 552

1321

Late outcomes of mitral repair in rheumatic patients Resultados tardios da plastia mitral em pacientes reumáticos Elaine Soraya Barbosa de Oliveira Severino, Orlando Petrucci, Karlos Alexandre de Souza Vilarinho, Carlos Fernando Ramos Lavagnoli, Lindemberg da Mota Silveira Filho, Pedro Paulo Martins de Oliveira, Reinaldo Wilson Vieira, Domingo Marcolino Braile ...................................................................................................................................................................... 559

1322

Surgical treatment of atrial fibrillation using bipolar radiofrequency ablation in rheumatic mitral disease Tratamento cirúrgico de fibrilação atrial utilizando ablação com radiofrequência bipolar em doença mitral reumática Leonardo Secchin Canale, Alexandre Siciliano Colafranceschi, Andrey José Oliveira Monteiro, Bruno Miranda Marques, Clara Secchin Canale, Ernesto Chavez Koehler, Fernando Eugênio dos Santos Cruz Filho .............................................................. 565

1323

Elevated plasma D-dimer and hypersensitive C-reactive protein levels may indicate aortic disorders Níveis plasmáticos elevados do dímero D e da proteína C reativa hipersensíveis podem indicar desordens aórticas Shi-Min Yuan, Yong-Hui Shi, Jun-Jun Wang, Fang-Qi Lü, Song Gao ....................................................................................... 573

1324

Assessment of noninvasive ventilation with two levels of positive airway pressure in patients after cardiac surgery Avaliação da ventilação não-invasiva com dois níveis de pressão positiva nas vias aéreas após cirurgia cardíaca Aline Marques Franco, Franciele Cristina Clapis Torres, Isabela Scali Lourenço Simon, Daniela Morales, Alfredo José Rodrigues ................................................................................................................................................................................. 582

1325

Transcutaneous electrical nerve stimulation after coronary artery bypass graft surgery Estimulação elétrica nervosa transcutânea após cirurgia de revascularização miocárdica Paula Monique Barbosa Lima, Rebeca Taciana Fernandes de Brito Farias, Aline Carla Araújo Carvalho, Patrícia Nobre Calheiros da Silva, Nailton Alves Ferraz Filho, Rosinete Fernandes de Brito .......................................................................................... 591

1326

SjO2/SvO2 correlation during pediatric cardiac surgery with cardiopulmonary bypass Correlação entre A SvO2 e SjO2 durante a cirurgia cardíaca com circulação extracorpórea em crianças Jyrson Guilherme Klamt, Pamela Regina Teixeira Nabarro, Walter Vilella de Andrade Vicente, Luis Vicente Garcia, Cesar Augusto Ferreira ...................................................................................................................................................................... 597

1327

Coronary dominance patterns in hypoplastic left heart syndrome Dominância coronariana na síndrome da hipoplasia do coração esquerdo Decio Cavalet Soares Abuchaim, Carla Tanamati, Marcelo Biscegli Jatene, Miguel Lorenzo Barbero Marcial, Vera Demarchi Aiello ........................................................................................................................................................................................ 604

1328

Retrograde autologous priming in cardiopulmonary bypass in adult patients. Effects on blood transfusion and hemodilution Perfusato autólogo retrógrado no circuito de circulação extracorpórea em pacientes adultos. Efeitos sobre a hemodiluição e transfusão de sangue Ricardo Vieira Reges, Walter Vilella de Andrade Vicente, Alfredo José Rodrigues, Solange Basseto, Lafaiete Alves Junior, Adilson Scorzoni Filho, Cesar Augusto Ferreira, Paulo Roberto Barbosa Evora ................................................................................... 609

1329

Skeletonized internal thoracic artery is associated with lower rates of mediastinitis in elderly undergoing coronary artery bypass grafting surgery Artéria torácica interna esqueletizada está associada a menores taxas de mediastinite em idosos submetidos à cirurgia de revascularização miocárdica Michel Pompeu Barros de Oliveira Sá, Cecília Andrade Santos, Omar Jacobina Figueiredo, Renato Oliveira Albuquerque Lima, Paulo Ernando Ferraz, Alexandre Magno Macário Nunes Soares, Pablo César Lustosa Barros Bezerra, Wendell Nunes Martins, Ricardo de Carvalho Lima ......................................................................................................................................................... 617

1330

Risk factors for sternal wound infections and application of the STS score in coronary artery bypass graft surgery Fatores de risco para infecção de ferida esternal e aplicação do escore da STS em pacientes submetidos à cirurgia de revascularização miocárdica Pedro Silvio Farsky, Humberto Graner, Pedro Duccini, Eliana da Cassia Zandonadi, Vivian Lerner Amato, Jaime Anger, Antonio Flavio de Almeida Sanches, Cely Saad Abboud ........................................................................................................................ 624

1331

Non Working Beating Heart - A new strategy of myocardial protection during heart transplant Non Working Beating Heart - Novo método de proteção miocárdica no transplante cardíaco Jarbas Jakson Dinkhuysen, Carlos Contreras, Reginaldo Cipullo, Marco Aurélio Finger, João Rossi, Ricardo Manrique, Helio M. Magalhães, Paulo Chaccur ........................................................................................................................................................ 630

REVIEW ARTICLES/ARTIGOS DE REVISÃO 1332

Gene therapy for ischemic heart disease: review of clinical trials Terapia gênica para cardiopatia isquêmica: revisão de ensaios clínicos Bruna Eibel, Clarissa G. Rodrigues, Imarilde I. Giusti, Ivo A. Nesralla, Paulo R. L. Prates, Roberto T. Sant’Anna, Nance B. Nardi, Renato A. K. Kalil .................................................................................................................................................................... 635

1333

Respiratory physiotherapy and its application in preoperative period of cardiac surgery Fisioterapia respiratória e sua aplicabilidade no período pré-operatório de cirurgia cardíaca Regina Coeli Vasques de Miranda, Susimary Aparecida Trevizan Padulla, Carolina Rodrigues Bortolatto ............................. 647

SHORT COMMUNICATIONS/COMUNICAÇÕES BREVES 1334

Reflections on the 24 years durability of an isolate tricuspid bovine pericardium IMC/Braile bioprosthesis Reflexões sobre a durabilidade de 24 anos de uma bioprótese IMC/Braile de pericárdio bovino em posição tricúspide isolada Solange Bassetto, Antonio Carlos Menardi, Lafaiete Alves Junior, Alfredo José Rodrigues, Paulo Roberto Barbosa Évora ....... 653

1335

Surgical treatment of lone atrial fibrillation by mid-sternotomy Maze procedure under standard cardiopulmonary bypass Tratamento cirúrgico da fibrilação atrial paroxística em esternotomia mediana usando procedimento de Maze sob circulação extracorpórea padrão Shi-Min Yuan, Leonid Sternik .................................................................................................................................................. 658

1336

Giant ventricular myxoma obstructing right ventricular outflow tract Mixoma ventricular direito gigante obstruindo via de saída do ventrículo direito Trushar P. Gajjar, Gaurang B. Shah, Neelam B. Desai ............................................................................................................. 663

1337

Myocardial revascularization after acute myocardial infarction caused by thrombosis of coronary aneurysm Revascularização miocárdica após infarto agudo do miocárdio causado por trombose de aneurisma coronariano Victor Rodrigues Ribeiro Ferreira, Valéria B. Braile Sternieri, João Carlos Ferreira Leal, Luis Ernesto Avanci, Achilles Abelaira Filho, Mariane Spotti, Arthur Soares Souza Junior, Domingo Marcolino Braile ...................................................................... 667

CASE REPORT/RELATO DE CASO 1338

Heart valve papillary fibroelastoma associated with cardioembolic cerebral events Fibroelastoma papilífero de valva cardíaca associado a eventos cerebrais cardioembólicos Luciano Cabral Albuquerque, Vanessa Devens Trindade .......................................................................................................... 670

HOMAGE/HOMENAGEM 1339

Dr. Cid Nogueira: a medical pioneer of cardiac surgery in Brazil Paulo Rodrigues da Silva ........................................................................................................................................................... 673

1340

Cid Nogueira Paulo R. Prates ......................................................................................................................................................................... 675

SCIENCE RELEASE/DIVULGAÇÃO CIENTÍFICA 1341

National impact Fábio de Castro /FAPESP Agency ............................................................................................................................................ 676

ACKNOWLEDGMENT/AGRADECIMENTO 1342

Reviewers 2011 ..................................................................................................................................................................................678

LETTERS/CARTAS 1343

Letter to the Editor Cartas ao Editor ....................................................................................................................................................................... 680

Abstracts of the 12th Congress of SCICVESP .......................................................................................................................... 687

Impresso no Brasil Printed in Brazil

Grafic Designer: Heber Janes Ferreira

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

Editorial

Many reasons to celebrate Domingo M. Braile* DOI: 10.5935/1678-9741.20110036

n the first editorial of this year [1], I pointed out that the Brazilian Journal of Cardiovascular Surgery (BJCVS) wanted to celebrate its 25th anniversary in great style. 2011 comes to an end and I can say with great satisfaction that the expectations were fully accomplished. Since the release of all online edits until the adoption of the DOI, passing through the release of our first Impact Factor (IF), which reached the significant level of 0.963, BJCVS developed a series of actions to maintain the publication in line with best international journals and monitoring and even anticipating new trends in scientific publications. For that, it had the crucial support of the board of BSCVS (Brazilian Society of Cardiovascular Surgery). Now we have more challenges ahead. In Qualis, our journal in Medicine 1, 2 and 3 will be in stratum B2. And our intention is that our next IF is more than 1. To achieve this desire, we are developing a series of actions, such as the adoption of the DOI, which is a “seal” warranty that adds credibility to the journal, and a more rigorous review of manuscripts that are sent, so that may have greater “visibility” and, therefore, be cited. This is necessary not only because of our primary concern to disseminate scientific knowledge, but also due to the rapidly increasing demands for organs such as CAPES, which has established strict criteria to define the Qualis of the Brazilian scientific journals. But even so, I am confident that BJCVS can meet these requirements. Recently, CAPES opened a credit line that will benefit some journals and one of the criteria that will be taken into account are indicators. The number of citations of the IF has remained at a high level. In addition to the IF, one must use the “Cites per doc 2 years”, from SCIMAGO. In this indicator, BJCVS also has good numbers: 0.86 (Figures 1 and 2). The numbers enclosed in 2011 will only be available in 2012. I believe that the chance of BJCVS been awarded with fund is great. These features, together with the CNPq, whose edict we signed up, as usual, will be of fundamental importance for us to continue our ascent. We are assessing proposals to make content available online in the BJCVS flip paper, online system that lets the user to view the journal in print version and flip through pages. Also new is the availability of our journal in new media, such as tablet and I-pad. We

provide links on the site (www.rbccv.org.br) for testing. These new technologies are already being adopted by some journals and the trend is that in short time, it may reach a large number of publications. Between the 8th and 11th November, I participated in the XIII National Meeting of Scientific Editors of ABEC (Brazilian Association of Science Editors) in Gramado, RS. The central theme was “Ethics and Integrity in Scientific Publications’. The discussions were very rich on this issue, because the lack of ethics in science is a stain that must be resisted at all costs. The editors of scientific journals should

Fig. 1 - SCIMAGO graph showing the growth of articles citations of BJCVS

Fig. 2 – JCR graph with the evolution of articles citations of BJCVS. Data of 2011 are partial

always be vigilant and ensure that their publications are not victims of bad people who are a minority in science, but who, unfortunately, exist. In the last issue of 2011, as well as articles of great interest to cardiovascular surgeons and allied professionals, I would like to highlight two texts honoring the brilliant Dr. Cid Nogueira, who died on October 1. Doctors Paulo Rodrigues da Silva, from Rio de Janeiro, and Paulo Prates, from Porto Alegre, wrote inspired lines reminiscing a little about the history of this pioneer of Brazilian heart surgery. I invite everyone to read and learn a little about the history of Dr. Cid from the page 673. We have in this edition, more XXX articles available for testing by the system of Continuing Medical Education (CME): “On-pump coronary artery bypass graft surgery: biochemical, hormonal and cellular features” on page 525; “Computed tomography in late evaluation of surgical treatment of pulmonary veins total anomalous connection” on page 532; “Predictors of transfusion of packed red blood cells in coronary artery bypass grafting surgery” on page 552; “Assessment of noninvasive ventilation with two levels of positive airway pressure in patients after cardiac surgery” on page 582; “Non Working Beating Heart: a new strategy of myocardial protection during heart transplant” on page 630. CME is an excellent learning tool for assessing knowledge and recycling, in addition to having a point in the revalidation of the Specialist title. I remind colleagues that the BJCVS will prepare a supplement with all the summaries of Posters and Abstracts of the 39th Brazilian Congress of Cardiovascular Surgery, to be held 12-14 April, in the pleasant Maceió, AL. Beyond the Abstracts of the Congress, summaries of Symposia of Nursing and Physiotherapy will also be published in the Supplement. These studies belong to the annals of Congress published in a indexed journal. Information about the event can be found at www.sbccv.org.br/39congresso/ home.asp In this last edition of 2011, once again, we disclose the names of all those who reviewed the studies submitted during the year. It is a simple way to thank the anonymous and voluntary work, but critical to the journal. The list with the number of manuscripts reviewed by each partner, is on page 678. A good news for cardiovascular surgeons and patients with coronary heart disease in this end is the “2011 ACCF/

AHA Guideline for Coronary Artery Bypass Graft Surgery”, in a joint initiative of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery and Society of Cardiovascular Anesthesiologists Society of Thoracic Surgeons. (http://www.sciencedirect.com/ science?_ob=MiamiImageURL&_cid= 271027&_user=10&_pii=S0735109711029494&_check= y&_origin=&_coverDate=07-Nov2011&view=c&wchp=dGLbVlk-zSkWb&md5= 31f1dc578b3670d11ab24c77c6287b4a/1-s2.0S0735109711029494-main.pdf). It’s exhausting work, VERY supportive to Surgery. If Myocardial Revascularization surgery was already the most studied operation in the history of medicine, this work closes with a flourish this intervention. It is required reading and a source of constant consultation for all of us! The dissemination of knowledge resulting from the careful work of a true “heart team” is fundamental for incremental benefit of all patients. Returning to the beginning, I want to thank all those who allowed that BJCVS could celebrate its silver jubilee with such news. Board and Members of BSCVS, Editorial Board of RBCCV, Advertisers and colleagues from various specialties who provide us with their excellent articles. Every one of them my thanks and an invitation to continue contributing to the BJCVS. My warmest regards. To all a Merry Christmas and a 2012 prodigal in achievements!

*Editor in Chief BJCVS

REFERENCE 1. Braile DM. RBCCV: 25 anos de trajetória brilhante. Rev Bras Cir Cardiovasc. 2011;26(1):I-II.

Editorial

Minimally invasive cardiac surgery in Brazil Luiz Felipe Pinho Moreira1, Alex Luiz Celullari2

DOI: 10.5935/1678-9741.20110037

In the article â&#x20AC;&#x153;Cardiac surgery: the future is minimal!â&#x20AC;? Published in 2000, Michael Mack, in his ambiguous phrase, could predicted that the future of the cardiovascular surgeon would be guided in the search for a less aggressive approach to the patient, with smaller incisions, and if possible, without cardiopulmonary bypass (CPB), since the surgery had been losing ground to percutaneous procedures [1]. In the literature, we can find as a synonym for minimally invasive cardiac surgery the cardiac surgery performed without CPB, nevertheless, the term minimally invasive conceptually refers to surgery performed through small incisions, without direct access to the heart or other organ to be operated. In the 90s, with the creation of new surgical materials focused on endoscopic procedures, there was diffusion of minimally invasive surgery, especially in the field of thoracic surgery. The first published reports of minimally invasive coronary artery bypass grafting (CABG) were described by Robinson et al. [2], in which 16 patients underwent surgery with the aid of peripheral cannulation via the femoral vessels and left minithoracotomy, and, both of them presented good results. In 1996, Cosgrove & Sabik [3] reported minimally invasive aortic valve surgery. In the same year, Navia & Cosgrove [4] described a technique for minimally invasive mitral valve surgery. The cardiac surgery, contrary to what is believed by many people, is increasing its incidence in National Hospital Centers [5], especially in the area of congenital heart disease, followed by valve surgery and coronary artery bypass grafting [6]. This growing demand includes minimally invasive and percutaneous procedures, justifying the increase of articles published in this area. It is still impossible to perform endoscopic procedures in pediatric patient with the materials in use nowadays. Diagnostic

1. Associate Professor of Cardiovascular Surgery, University of Sao Paulo Medical School, Director of Surgical Research Unit at the Clinical Hospital Heart Institute (Incor), Sao Paulo, Brazil. 2. Medical Doctor at the Minimally Invasive & Robotic Cardiac Center at Albert Einstein Hospital, Sao Paulo, Brazil.

procedures, such as pericardioscopy, have been routinely used in some adult groups for cases of pericardial effusion of unknown origin, allowing the performance of biopsies in suspected areas and approach areas not reached by pericardial window [7]. The concern about the safety of direct aortic cannulation during surgery with smaller incisions was approached by Guedes et al. [8], which demonstrated the method safety. Poffo et al. [9] recently published their experience in this area, demonstrating a range of possible operations to be performed through a minimally invasive manner with peripheral cannulation, without complications due to cannulation and with good postoperative results. The same group demonstrated the possibility of performing the correction of associated heart diseases [10], as well as more complex techniques are also employed in minimally invasive manner [11]. At the same time, Guizilini et al. [12] demonstrated the benefits of ministernotomy for the preservation of lung function in the postoperative period of CABG. Recent therapeutic alternatives, such as the left sympathetic block, have brought new perspectives for the treatment of dilated cardiomyopathy, which is being performed by videothoracoscopy with only two minimal incisions in the chest [13]. New imaging and instrumental methods bring back procedures that had fallen into disuse, such as percutaneous mitral valvuloplasty, which currently presents better and more lasting results [14]. Finally, the treatment of atrial fibrillation also proved to be feasible through a minimally invasive approach, as demonstrated by Colafranceschi et al. [15]. Several Brazilian authors have distinguished themselves for the innovation and development of new techniques with the rapid advancement of technology and the constant search for better results in the care of cardiology patients. The introduction of techniques for percutaneos and transpical aortic valve implantation as an alternative for patients with contraindications or high risk for conventional surgical treatment [16], has been widespread in Europe and the United States. Perin et al. [17] recently reported their initial experience with a unique type of prosthesis, transfemoral percutaneously implanted, while Gaia et al. III

[18] reported their experience with the implantation of a national prosthesis in transapical way, without CPB. In the area of robotics, the dissection of the right internal thoracic artery with the aid of da Vinci robotic system was described in Brazil, performed by median sternotomy [19]. Some authors have been presenting their experience with totally closed-chest robotic heart surgery in national congresses, however, the data is not published yet. Taking into consideration this panorama of technological evolution, with longer surgeries, CPB is still a concern, because is one of the most responsible for cardiovascular surgery complications, especially those of neurological nature [20] and avoid or minimize it is also a major challenge for modern heart surgery. With increasing worldwide demand for the hybrid rooms that currently exists in the literature, we believe that the “gold standard” of cardiac surgery will be the minimally invasive surgery (video or robotic-assited), preferably without the aid of CPB and hybrid surgery (minimally invasive surgery associated with percutaneous procedures). Totally closedchest myocardial revascularization robotic surgeries are a reality in some centers in the U.S. and Europe, and the anastomoses are performed with the use of mechanical devices without the use of CPB [21], with a continuous suture with or without the use of CPB [22,23], where the grafts are tested by means of flow meters with probes inserted into the chest. The hybrids myocardial revascularization surgeries also promise better results with fewer invasions, as well as the permeability of grafts visualized by intraoperative angiography, adding greater safety to these procedures [24].

4. Navia JL, Cosgrove DM 3rd. Minimally invasive mitral valve operations. Ann Thorac Surg. 1996;62(5):1542-4. 5. Lisboa LAF, Moreira LFP, Mejia OV, Dallan LAO, Pomerantzeff PMA, Costa R, et al. Evolução da cirurgia cardiovascular no Instituto do Coração: análise de 71.305 operações. Arq Bras Cardiol. 2010;94(2):174-81. 6. Piegas LS, Bittar OJNV, Haddad N. Cirurgia de revascularização miocárdica: resultados do Sistema Único de Saúde. Arq Bras Cardiol. 2009;93(5):555-60. 7. Abrão FC, Bibas BJ, Pêgo-Fernandes PM, Jatene FB. Utilidade da pericardioscopia no diagnóstico de derrame pericárdico. Arq Bras Cardiol. 2010;94(5):e128-30. 8. Guedes MAV, Pomerantzeff PMA, Brandão CMA, Vieira MLC, Grinberg M, Stolf NAG. Cirurgia valvar mitral via toracotomia ântero-lateral direita: a canulação aórtica é segura? Rev Bras Cir Cardiovasc. 2010;25(3):322-5. 9. Poffo R, Pope RB, Selbach RA, Mokross CA, Fukuti F, Silva Júnior I, et al. Cirurgia cardíaca videoassistida: resultados de um projeto pioneiro no Brasil. Rev Bras Cir Cardiovasc. 2009;24(3):318-26. 10. Poffo R, Pope RB, Toschi AP. Correção cirúrgica da comunicação interatrial e revascularização do miocárdio minimamente invasiva videoassistida. Rev Bras Cir Cardiovasc. 2009;24(4):586-9. 11. Poffo R, Pope RB, Toschi AP, Mokross CA. Plastia valvar mitral minimamente invasiva videoassistida: abordagem periareolar. Rev Bras Cir Cardiovasc 2009;24(3):425-7. 12. Guizilini S, Bolzan DW, Faresin SM, Alves FA, Gomes WJ. Miniesternotomia na cirurgia de revascularização miocárdica preserva função pulmonar pós-operatória. Arq Bras Cardiol. 2010;95(5):587-93. 13. Pêgo-Fernandes PM, Moreira LFP, Souza GEC, Bacal F, Bocchi EA, Stolf NAG, et al. Bloqueio simpático esquerdo por videotoracoscopia no tratamento da cardiomiopatia dilatada. Arq Bras Cardiol. 2010;95(6):685-90.

REFERENCES 1. Mack MJ. Cardiac surgery: the future is minimal! J Card Surg. 2000;15(1):6-8. 2. Robinson MC, Gross DR, Zeman W, Stedje-Larsen E. Minimally invasive coronary artery bypass grafting: a new method using an anterior mediastinotomy. J Card Surg. 1995;10(5):529-36. 3. Cosgrove DM 3rd, Sabik JF. Minimally invasive approach for aortic valve operations. Ann Thorac Surg. 1996;62(2):596-7.

14. Cardoso LF, Ayres CV, Bento AM, Tarasoutchi F, Vieira ML, Grinberg M. Resultados imediatos e tardios da valvoplastia mitral percutânea em pacientes com estenose mitral. Arq Bras Cardiol. 2010;94(3):406-13. 15. Colafranceschi AS, Monteiro AJO, Botelho ESL, Canale LS, Rabischoffsky A, Costa IP, et al. Cirurgia vídeo-assistida para a ablação da fibrilação atrial isolada por radiofrequência bipolar. Arq Bras Cardiol. 2009;93(4):334-42. 16. Valle FH, Costa AR, Pereira EMC, Santos EZ, Pivatto Júnior F, Bender LP, et al. Morbimortalidade em pacientes acima de 75 anos submetidos à cirurgia por estenose valvar aórtica. Arq Bras Cardiol. 2010;94(6):720-5.

17. Perin MA, Brito Jr FS, Almeida BO, Pereira MAM, Abizaid A, Tarasoutchi F, et al. Substituição valvar aórtica percutânea para o tratamento da estenose aórtica: experiência inicial no Brasil. Arq Bras Cardiol. 2009;93(3):299-306.

21. Balkhy HH, Wann LS, Krienbring D, Arnsdorf SE. Integrating coronary anastomotic connectors and robotics toward a totally endoscopic beating heart approach: review of 120 cases. Ann Thorac Surg. 2011;92(3):821-7.

18. Gaia DF, Palma JH, Souza JAM, Guilhen JCS, Telis A, Fischer CH, et al. Implante transapical de endoprótese valvada balãoexpansível em posição aórtica sem circulação extracorpórea. Rev Bras Cir Cardiovasc. 2009;24(2):233-8.

22. Bonatti J, Rehman A, Schwartz K, Deshpande S, Kon Z, Lehr E, et al. Robotic totally endoscopic triple coronary artery bypass grafting on the arrested heart: report of the first successful clinical case. Heart Surg Forum. 2010;13(6):E394-6.

19. Jatene FB, Pêgo-Fernandes PM, Anbar R, Gaiotto FA, Barduco MS, Kalil Filho R. Dissecção robótica da artéria torácica interna direita por esternotomia mediana. Arq Bras Cardiol. 2010;94(6):139-42.

23. Folliguet TA, Dibie A, Philippe F, Larrazet F, Slama MS, Laborde F. Robotically-assisted coronary artery bypass grafting. Cardiol Res Pract. 2010;2010:175450.

20. Barbosa NF, Cardinelli DM, Ercole FF. Determinantes de complicações neurológicas no uso da circulação extracorpórea (CEC). Arq Bras Cardiol. 2010;95(6):151-7.

24. Bonaros N, Schachner T, Wiedemann D, Weidinger F, Lehr E, Zimrin D, et al. Closed chest hybrid coronary revascularization for multivessel disease: current concepts and techniques from a twocenter experience. Eur J Cardiothorac Surg. 2011;40(4):783-7.

Editorial

Apology to the use of double mammary Fernando Moraes1

DOI: 10.5935/1678-9741.20110038

Never apologize, do the best (American proverb)

Few surgical procedures have changed so dramatically the natural history of disease in the last 40 years, as coronary artery bypass grafting in relation to coronary artery disease. The relief of angina pectoris and increased life expectancy observed in the majority of the thousands of patients operated worldwide is an indisputable fact. It should be noted that these benefits were most notable in certain subgroups of patients, especially those with multivessel disease and left coronary artery trunk lesion. One of the milestones in the evolution of coronary artery bypass surgery was the demonstration by the Cleveland Clinic group, the superiority in terms of patency of the left internal thoracic artery (LITA) over the saphenous vein [1]. Later, this group observed that the use of the LITA favorably influence long-term survival of patients [2]. Confirmation of these findings by other groups made almost mandatory the use of the LITA to revascularize the left anterior descending artery, especially in high risk patients such as diabetics and those with low ejection fraction [3]. Thus, the research phase began in order to determine whether there would be additional benefits with the use of two internal thoracic arteries (ITAs). First, it was shown similar patency rates in the medium and long term, the ITAs [4]. Subsequently, numerous reports have shown increased survival and reduced need for late reintervention with the use of two ATI even in patients with poor ventricular function and serious comorbidities [5,6]. On the other hand, certain arguments are demystified such as the use of two ATI would promote more bleeding and a higher rate of sternal infection [7]. Recent studies found that diabetic patients may present high sternum infectious complication rates if they make

1. Member of Brazilian Society of Cardiovascular Surgery

use of the dissected ITA pedicle [8,9]. However, Santos Filho et al. [10] showed that in this group of patients, sternal perfusion is lower than in non-diabetics, justifying a higher rate of infectious complications. Alternatively, when the ITA is dissected in a skeletonized fashion, sternal perfusion, with the use of scintigraphy, does not suffer a significant reduction, which seems to be the reason to reduce rates of infectious complications of the sternum and mediastinal disorders in diabetic patients in which two ATI were used[8,9]. Despite all the facts listed above, the use of two ATI is only performed in about 5% of services, according to analysis of the database of the Society of Thoracic Surgeons (STS) [11]. Why? It is hard to find the answer. But whatever the reasons, it is time for all cardiovascular surgeons to consider, make self-criticism and change their practice, increasingly aiming to offer a highly efficient operation. This is vital, especially for the competition of interventional cardiology, which would hardly reach the level of excellence of surgery if it is held with the utmost quality, which includes the use of two ATI.

REFERENCES 1. Lytle BW, Loop FD, Cosgrove DM, Ratliff NB, Easley K, Taylor PC. Long-term (5 to 12 years) serial studies of internal mammary artery and saphenous vein coronary bypass grafts. J Thorac Cardiovasc Surg. 1985;89(2):248-58. 2. Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, et al. Influence of the internal-mamary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986;314(1):1-6. 3. Cameron A, Davis KB, Green G, Schaff HV. Coronary bypass surgery with internal-thoracic-artery grafts: effects on survival over a 15-year period. N Engl J Med. 1996;334(4):216-9.

4. Calafiore AM, Di Mauro M, D’Alessandro S, Teodori G, Vittola G, Contini M, et al. Revascularization of the lateral wall: long-term angiographic and clinical results of radial artery versus right internal thoracic artery grafting. J Thorac Cardiovasc Surg. 2002;123(2):225-31.

8. Milani R, Brofman PR, Guimarães M, Barboza L, Tchaick RM, Meister Filho H, et al. Dupla artéria torácica esqueletizada versus convencional na revascularização do miocárdio sem CEC em diabéticos. Rev Bras Cir Cardiovasc. 2008;23(3):351-7.

5. Lytle BW, Blackstone EH, Sabik JF, Houghtaling P, Loop FD, Cosgrove DM. The effect of bilateral internal thoracic artery grafting on survival during 20 postoperative years. Ann Thorac Surg. 2004;78(6):2005-12.

9. Sá MPBO, Soares EF, Santos CA, Figueiredo OJ, Lima ROA, Escobar RR, et al. Artéria torácica interna esquerda esqueletizada é associada a menores taxas de mediastinite em diabéticos. Rev Bras Cir Cardiovasc. 2011;26(2):183-9.

6. Stevens LM, Carrier M, Perrault LP, Hébert Y, Cartier R, Bouchard D, et al. Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome of multivessel coronary artery bypass grafting. Eur J Cardiothorac Surg. 2005;27(2):281-8.

10. Santos Filho EC, Moraes Neto FR, Silva RAM, Moraes CRR. Diabéticos devem a artéria torácica interna esqueletizada? Avaliação da perfusão esternal por cintilografia. Rev Bras Cir Cardiovasc. 2009;24(2):157-64.

7. De Paulis R, de Notaris S, Scaffa R, Nardella S, Zeitani J, Del Giudice C, et al. The effect of bilateral internal thoracic artery harvesting on superficial and deep sternal infection: the role of skeletonization. J Thorac Cardiovasc Surg. 2005;129(3):536-43.

11. Tabata M, Crab JD, Khelpev Z, Edwards FH, O’Brien SM, Cohn LH, et al. Prevalence and variability of internal mammary artery graft use in contemporary multivessel coronary artery bypass graft surgery: analysis of the Society of Thoracic Surgeons National Cardiac Database. Circulation. 2009;120(11):935-40.

VII

Editorial

Dissection of the internal thoracic artery using skeletonized technique Henrique Murad1 DOI: 10.5935/1678-9741.20110039

The article by Sá et al. “Skeletonized internal thoracic artery is associated with lower rates of mediastinitis in elderly undergoing coronary artery bypass grafting surgery” [1], published in this issue of the Brazilian Journal of Cardiovascular Surgery (p. 617) demonstrated that in patients older than 70 years, with the removal of the internal thoracic artery (ITA) using the skeletonized technique, there was a lower incidence of mediastinitis than when it was used the pedicled technique to dissect the ITA. The incidence of mediastinitis was 1.2% in the skeletonized group and 12.5% in the pedicled group. In principle, only one ITA was used and probably the left. There are no special reference to the use of double ITA or concern in noting which of the two ITAs were used. The withdrawal of the pedicled ITA was predictive of mediastinitis in multivariate analysis. The two groups were comparable, and the few differences between the groups (obesity and multiple transfusions) were more unfavorable to the skeletonized group, which still showed a lower incidence of mediastinitis. Skeletonized is a word that does not exist in our dictionaries of Portuguese language, being one of several approaches that we translate from English in our medical vernaculum. In Dicionário Novo Aurélio [2], the closest we get the English “skeletonized” was skeletal, regarding ou imitanting the skeleton. The groups skeletonized and pedicled still deserve another repair. Both groups are pedicled, only one has a thick pediculum and another pediculum skeletonized. I understand that this division of pedicled and skeletonized is somehow enshrined, but it’s always good to question the accuracy of our terms. ITA is recognized as the best graft for use in the coronary tree, and in particular for the left anterior descending artery, due to its large long-term patency, even in patients older than 75 years [3]. Obesity, diabetes, chronic obstructive

1. Titular Member of the Brazilian Society of Cardiovascular Surgery, Chief of Cardiovascular Surgery, Hospital São Vicente de Paulo, professor of cardiothoracic surgery at the Federal University of Rio de Janeiro.

VIII

pulmonary disease and advanced age are predisposing factors to mediastinitis and sternal complications, and an obstacle to the use of ITA. The withdrawal of ITA using skeletonized technique allows better preservation of sternal vascularity when compared to the technique which uses a thick pediculum, veins, muscle and fascia [4]. This has improved sternal vascularity as a consequence a lower incidence of sternal complications and precordial dysesthesia [5]. The first concern was to research whether with the withdrawal using the skeletal technique would be greater possibility of injury from ITA and lower long-term patency. There is already enough information in the medical literature to conclude that the withdrawal of ITA using the skeletonized technique is not accompanied by a greater injury of ITA and lower graft patency [6]. SEE ALSO ORIGINAL ARTICLE ON PAGES 617-623 The use of dual ITA has expanded, especially in young patients, in whom it has demonstrated improved event-free survival in 20 years of postoperative [7]. Using the withdrawal of ITA by skeletonized technique and maintenance of larger sternal revascularization, it is possible to use one or both ITAs, even in groups at higher risk for sternal complications, such as obese patients with type I diabetes, or age above 70 years old. In the “in touch’ technique of removal of the saphenous vein developed by Dashwood et al. [8], maintaining a thick pedicle of the saphenous vein, mimicking the classic way of dissecting the ITA, was accompanied by greater saphenous vein patency, perhaps because of greater local release of nitric oxide. The advantage of thick pedicle is not shown in the ITA, in which there is migration in order to perform the dissection using the skeletonized technique. The study by Sá et al. [1] brings another important evidence for the use of dissection of the ITA using the skeletonized technique in patients older than 70 years. The ITA dissection using the skeletonized technique causes lesser devascularization of the sternum, and is accompanied by a lower incidence of sternal complications

in high risk groups, even with use of both ITAs. Khuri [9], in an editorial published in Circulation, noted there are no non-randomized studies sufficient to allow or not to recommend the routine use of ITA removed using skeletonized technique, except the diabetic patients undergoing coronary artery bypass grafting with use of bilateral ITA.

REFERENCES 1. Sá MPBO, Santos CA, Figueiredo OJ, Lima ROA, Ferraz PE, Soares AMMNS, et al. Skeletonized internal thoracic artery is associated with lower rates of mediastinitis in elderly undergoing coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc. 2011;26(4):617-23. 2. Anjos M, Ferreira MB. Novo Aurélio. Rio de Janeiro:Nova Fronteira;1999.

bypass grafting: room for process improvement? J Thorac Cardiovasc Surg. 2002;123(5):869-80. 5. Boodhwani M, Lam BK, Nathan HJ, Mesana TG, Ruel M, Zeng W, et al. Skeletonized internal thoracic artery harvest reduces pain and dysesthesia and improves sternal perfusion after coronary artery bypass surgery: a randomized, doubleblind, within-patient comparison. Circulation. 2006;114(8):766-73. 6. Pevni D, Uretzky G, Mohr A, Braunstein R, Kramer A, Paz Y, et al. Routine use of bilateral skeletonized internal thoracic artery grafting: long-term results. Circulation. 2008;118(7):705-12. 7. Lytle BW, Blackstone EH, Loop FD, Houghtaling PL, Arnold JH, Akhrass R, et al. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg. 1999; 117(5):855-72.

3. Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, et al. Influence of the internal-mammaryartery graft on 10-year survival and other cardiac events. N Engl J Med. 1986;314(1):1-6.

8. Dashwood MR, Savage K, Tsui JC, Dooley A, Shaw SG, Fernández Alfonso MS, et al. Retaining perivascular tissue of human saphenous vein grafts protects against surgical and distension-induced damage and preserves endothelial nitric oxide synthase and nitric oxide synthase activity. J Thorac Cardiovasc Surg. 2009;138(2):334-40.

4. Ferguson TB Jr, Coombs LP, Peterson ED. Internal thoracic artery grafting in the elderly patient undergoing coronary artery

9. Khuri SF. To skeletonize the internal thoracic artery or not? Is that the question? Circulation. 2006;114(8):754-6.

Editorial

Surgical treatment of atrial fibrillation: incoherence or negligence? Renato A. K. Kalil1 DOI: 10.5935/1678-9741.20110040 Code of Medical Ethics, Chapter V - Relationship with Patients and Family The physician shall not: Article 32. Stop using all available means of diagnosis and treatment scientifically recognized and accessible in favor of the patient.

The literature is full of arguments and data emphasizing the relationship between atrial fibrillation (AF) and increased risk of stroke and mortality. This occurs even in primary AF, i.e., in the absence of structural heart defects and it is aggravated by risk factors, as listed in the known CHADS score. By means of the factors, the risk can be stratified, allowing the identification of cases of increased risk for stroke and death. It is known that anticoagulation is necessary and effective in reducing thromboembolism, but is not sufficient to completely prevent systemic embolization, which occurs at least 1.5% of patients a year, when carefully treated and followed [1]. Percutaneous ablation by catheter using radiofrequency energy or other, obtains success rates of up to 70% in cases of paroxysmal and persistent AF, reaching higher rates if you make two or more attempts. However, percutaneous ablation is admittedly ineffective in permanent AF, in chronic cases of long duration and dilated atria, and contraindicated in the presence of thrombi. On the other hand, the Maze procedure, known as Cox (“maze procedure”) and its amendments, as the surgical isolation of pulmonary veins by cutting and stitching has been applied with high success rates (greater than 90%) in reversion of sinus rhythm or atrial, on cases of long-term permanent refractory AF in atria usually larger than 5 cm in diameter, with or without structural heart disease [2,3]. The procedure involves extensive thoracotomy and

1. Cardiovascular Surgeon of the Institute of Cardiology RGS / FUC Associate Professor of Surgery UFCSPA. Professor of Post-Graduate Program of IC / FUC. Researcher Sponsored by CNPq. Research Director of the Brazilian Society of Cardiology

extracorporeal circulation, but the hospital risk is located around 1% for mortality. In this issue, Canale et al. [4], in the article “Surgical treatment of atrial fibrillation using bipolar radiofrequency ablation in rheumatic mitral valve disease” (p. 565) show the experience with bipolar radiofrequency ablation during mitral valve surgery. This very form of ablation is used in video-assisted surgery, which is gaining exposure in the literature. SEE ALSO ORIGINAL ARTICLE ON PAGES 565-572 These new procedures, less invasive and without cardiopulmonary bypass, use epicardial ablation, but success rates remain lower than those of surgery for cutting and suturing. As techniques improve, they may prove more effective, perhaps in the near future. An alternative that has been mentioned would be the combination of epicardial ablation by video-assisted thoracotomy with percutaneous endocardial ablation, such as hybrid procedures, simultaneously or in sequence. Thus, one could obtain complete isolation of pulmonary veins, similar to that provided by cutting and suturing, bringing the success rate of less invasive methods to conventional surgery. However, it should again be remembered that even though the thoracotomy procedure being a larger procedure, its risks in elective patients without major comorbidities are about 1% to 8% for mortality and morbidity. Therefore, based on objective evidence, it can be argued that conventional surgery to treat long-term permanent refractory AF has excellent risk / benefit ratio, because the morbidity and mortality cited would be offset in a short time by longer survival and lower risk of stroke in patients maintained in sinus rhythm postoperatively. Due to this fact, the question that remains could be summarized as: How come the surgical correction of AF in patients with primary AF is not indicated, especially in those at higher risk for stroke and death by the mere presence of AF? Consensus of the specialty societies of 2007 [5] already provided the surgical indication for primary refractory AF,

recognizing the effectiveness of Cox and its modifications. In Brazil, however, this option has been “forgotten.” The Brazilian Congresses of cardiac arrhythmias in recent years have omitted discussion of AF surgery or, on the rare occasions that they include this theme in the program, electrophysiologists are chosen to present it. As if such congresses were about electrophysiology rather than arrhythmias. The Brazilian Guidelines on Atrial Fibrillation [6] included only surgical option timidly between their recommendations because the author of this editorial brought the issue at the last meeting of the Brazilian Society of Cardiac Arrhythmias that defined the final format of the guideline. Meanwhile, about 2 million people (estimated 10% of the Brazilian population older than 60 years) [7] are exposed to the occurrence of stroke and death due solely to the presence of AF. It is well known that 45% of strokes are due to non-valvular AF. Good medical practice recommends always having the benefit of the patient as the spotlight, leaving aside the personal, corporate, economical or any other interest that may conflict with such a noble purpose of Medicine. In recent times, we are witnessing the attempt of the reserve rules of market override the interest of the patient. We must resist this deformation of the medical practice. In terms of objectivity and consistency, we could make an analogy between the surgical indication for AF and other illnesses, such as atrial septal defect (ASD) and mitral regurgitation, as examples. In both, the acceptance of surgery for the patient still asymptomatic and peaceful is a consensus. However, in none of them there are risks of death or stroke as there is in permanent AF. The natural progression of these lesions does not foresee the disastrous consequences of a stroke or death in the short to medium term. Why do we resist the AF for surgery or even it is omitted the discussion of such in the events of arrhythmias in Brazil? Apart from good care practice that should always be observed, considering the current knowledge and relating their own Code of Medical Ethics for this situation, we may

mention that the physician is ethically prohibited from omitting and stop using surgical therapy in favor of patients with permanent and refractory atrial fibrillation.

REFERENCES 1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. 2. Prasad SM, Maniar HS, Camillo CJ, Schuessler RB, Boineau JP, Sundt TM 3rd, et al. The Cox maze III procedure for atrial fibrillation: long-term efficacy in patients undergoing lone versus concomitant procedures. J Thorac Cardiovasc Surg. 2003;126(6):1822-8. 3. Albrecht A, Kalil RA, Schuch L, Abrahão R, Sant’Anna JR, de Lima G, et al. Randomized study of surgical isolation of the pulmonary veins for correction of permanent atrial fibrillation associated with mitral valve disease. J Thorac Cardiovasc Surg. 2009;138(2):454-9. 4. Canale LS, Colafranceschi AS, Monteiro AJO, Marques BM, Canale CS, Koehler EC, et al. Tratamento cirúrgico de fibrilação atrial utilizando ablação com radiofrequência bipolar em doença mitral reumática. Rev Bras Cir Cardiovasc. 2011;26(4):565-72. 5. Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, et al. HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and followup. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2007;4(6):816-61. 6. Zimerman LI, Fenelon G, Martinelli Filho M, Grupi C, Atié J, Lorga Filho A, et al. Sociedade Brasileira de Cardiologia. Diretrizes brasileiras de fibrilação atrial. Arq Bras Cardiol. 2009;92(6 supl. 1):1-39. 7. IBGE Censo 2010. http://www.censo2010.ibge.gov.br/sinopse/ webservice/

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):525-31

On-pump coronary artery bypass graft surgery: biochemical, hormonal and cellular features Revascularização miocárdica com circulação extracorpórea; aspectos bioquímicos, hormonais e celulares

Edmo Atique Gabriel1, Rafael Fagionato Locali2, Priscila Katsumi Matsuoka3, Thiago Cherbo4, Enio Buffolo5

DOI: 10.5935/1678-9741.20110041

RBCCV 44205-1317

Abstract Objective: The authors sought to assess biochemical, hormonal and cellular repercussions from use of cardiopulmonary bypass (CPB) in coronary artery bypass graft (CABG) surgery. Methods: Eighteen patients underwent on-pump CABG surgery. Mean time of CPB was 80.3 minutes. Hormonal, biochemical and cellular measurements were taken in some time points - preoperatively, immediately after coming off CPB, 24 and 48 hours postoperatively. Friedman and Wilcoxon tests were applied based on significance level of 5%. Results: There was activation and significant elevation of total leukocytes and neutrophils count over CPB, remaining this way up to 48 hours postoperatively. Total platelets count, in turn, was marked by relevant reduction immediately after coming off CPB as well as in two postoperative time points. Serum levels of total proteins and albumin, immediately after coming off CPB and also in two postoperative time points, were significantly decreased comparing with preoperative status. There was remarkable reduction of total T3, free T3 and total T4 particularly up to first 24 hours postoperatively. Conclusion: In on-pump CABG surgery, inflammatory

effects encompass activation of total leukocytes, neutrophils and platelets, reduction of serum level of total proteins and albumin and decreased thyroid hormones levels, especially within first postoperative 24 hours.

1. PhD/Full Professor; Cardiovascular Surgeon, São Paulo, SP, Brazil. 2. Resident in General Surgery at Faculty of Medicine of University of São Paulo (FMUSP), São Paulo, SP, Brasil. 3. Resident in Gynecology and Obstetrics at FMUSP, São Paulo, SP, Brazil. 4. Medicine Student at Federal University of São Paulo (UNIFESP) São Paulo, SP, Brazil. 5. Full Professor, Titular Professor of Cardiovascular Surgery at UNIFESP, São Paulo, SP, Brazil.

This study was carried out at Federal University of São Paulo, Discipline of Cardiovascular Surgery, São Paulo, SP, Brazil.

Descriptors: Extracorporeal circulation. Myocardial revascularization. Coronary disease.

Resumo Objetivo: Avaliar repercussões bioquímicas, hormonais e celulares decorrentes do emprego de circulação extracorpórea (CEC) em cirurgia de revascularização miocárdica. Métodos: Dezoito pacientes foram submetidos à cirurgia de revascularização miocárdica com emprego de CEC. A duração média da CEC foi de 80,3 minutos. Dosagens hormonais, bioquímicas e celulares foram realizadas nos seguintes tempos: pré-operatório, logo após a saída de CEC, 24 horas e 48 horas de pós-operatório. Os testes de Friedman e Wilcoxon foram aplicados, considerando-se o nível de significância 5%. Resultados: Houve ativação e elevação significante do número de leucócitos totais e neutrófilos durante o período

Correspondence address: Edmo Atique Gabriel. Rua Melo Alves, 685/171 – Jardim América – São Paulo, SP, Brazil – Zip Code: 01417-010. E-mail: edag@uol.com.br Article received on May 31st, 2011 Article accepted on August 29th, 2011

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de CEC, de tal forma que esta condição foi detectada logo após a saída de CEC, mantendo-se assim até 48 horas de pós-operatório. O número total de plaquetas, por sua vez, caracterizou-se por decréscimo relevante logo após a saída de CEC, como também nos dois momentos pós-operatórios de observação. A concentração sérica de proteínas totais e albumina, logo após a saída de CEC e nos dois momentos pós-operatórios de observação, foi significativamente menor em relação aos níveis encontrados no período pré-operatório. Houve decréscimo acentuado dos níveis séricos de T3 total e T3 livre, sobretudo até as primeiras 24 horas de pós-

operatório. De forma análoga, notou-se padrão semelhante quanto aos níveis séricos de T4 total. Conclusão: Em cirurgias de revascularização miocárdica, os efeitos inflamatórios da CEC compreendem ativação de leucócitos, neutrófilos e plaquetas, redução na concentração sérica de proteínas totais e albumina e decréscimo dos níveis séricos de hormônios tireoidianos, sobretudo, nas primeiras 24 horas de pós-operatório.

INTRODUCTION The pathogenesis of the inflammatory response triggered by CPB is multifactorial. Thus, there is synergism between various pro-inflammatory mechanisms, culminating in violation of homeostasis. Harmony usually between biochemical, hormonal and cellular processes, can be corrupted by pathological events related to the CPB, such as endothelial injury, ischemia-reperfusion, and especially pronounced release of cytokines, adhesion molecules and tissue necrosis factor [1]. Several studies have demonstrated that endothelial dysfunction during CPB is derived mainly from the interaction between neutrophils and inflammatory molecules by activated endothelium. As a direct result of this interaction, there is deficient regulation of the process of transendothelial migration of neutrophils. Thus, during CPB, there are increased numbers of neutrophils, as well as activation of them, which, in an uncontrolled manner, migrate from the circulation to the tissues, promoting various regional and systemic events. Similarly, stimuli derived from cell adhesion molecules promote the migration and displacement of platelets from the circulation into the various tissues [2,3]. In recent decades, some authors have assessed the biochemical and hormonal effects related to CPB. With regard to biochemical events, considerable emphasis has been given to the serum concentration of total proteins, particularly albumin, as these are essential in maintaining the balance and colloid osmotic regulation of vascular permeability in prime areas such as blood brain barrier. With respect to hormone, thyroid hormones and its variability over the CPB have been the target of the latest research preciput [4,5]. The aim of this study is to assess the impact of the use 526

Descritores: Circulação extracorpórea. Revascularização miocárdica. Doença das coronárias.

of CPB in CABG, from the standpoint of the biochemical, hormonal and cellular impact. METHODS After approval by the Ethics Committee of Federal University of São Paulo, according to the Declaration of Helsinki, 18 patients, 13 (72%) male and five (28%) females, underwent myocardial revascularization using CPB (pump driving roller type) on an elective basis. These patients underwent surgery by the same surgical team using aortic and right atrial cannulation, mild hypothermia and blood cardioplegia. The average age of patients was 57.8 years and average duration of CPB, 80.3 minutes. The selection of patients for CABG with CPB was based on the number of grafts and need for revascularization of the left ventricle lateral wall. Exclusion criteria were: presence of endocrine abnormalities, clinical and/or laboratory signs of infection, systemic inflammatory diseases, clinical and/or laboratory signs of malnutrition, acute coronary insufficiency and chronic renal failure (serum creatinine > 2mg/dL). Biochemical (protein, albumin), hormonal (total T3 triiodothyronine, free T3, total T4 - thyroxine, free T4, TSH - thyroid stimulating hormone) and cellular dosage (total leukocytes, neutrophils and platelets) were performed by means of sampling of peripheral venous blood, at the following times: preoperative (24 hours before the procedure), after removal of CPB, 24 and 48 hours postoperatively. From the statistical point of view, we applied the Friedman test to check possible differences between the four moments of observation, and Wilcoxon Signed rank test to identify the moments that differ from each other,

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Rev Bras Cir Cardiovasc 2011;26(4):525-31

when taken as pairs. It was adopted the significance level of 5% for implementation of these tests. SPSS (Statistical Package for Social Sciences), in its version 13.0 was used to obtain the results.

correlations between different times, taken as pairs, and were relevant to the respective variables. Based on this final step of statistical analysis, we can effectively understand the behavior and the evolutionary course of biochemical, hormonal and cellular variables, from preoperative up to 48 hours postoperatively. Figures 1-3 illustrate these correlations between different times, in pairs, but also the significance levels found. There was significant rise of total leukocyte and neutrophil counts in the postoperative, unlike the total count of platelets, which showed considerable decrease in those moments of observation. The serum concentration of total protein and albumin was characterized by decreasing levels in the postoperative, with the stabilization of the total protein levels occurring as early as possible in relation to levels of albumin. We noticed significant decrease in levels of thyroid hormones, particularly in the first 24 hours postoperatively.

RESULTS The information contained in Tables 1-5 result from the application of the Friedman test, and the data are expressed as mean value, standard deviation, minimum and maximum values, median, quartiles and significance level. Itâ&#x20AC;&#x2122;s important to note that these tables provide substrates for the simultaneous comparison of the four moments of observation considered in this research. In cases where the Friedman test showed significant differences between the four times studied, we applied the test of Wilcoxon Signed rank test, which aims to define

Table 1. Comparison between the moments of simultaneous observation for total leukocytes, neutrophils and platelets. Block of variables n Standard Minimum Maximum Quartile 25 Median Quartile 75 Average Total Total Total Total Total Total Total Total Total Total Total Total

leukocytes pre leukocyte intra leukocytes 24h leukocytes 48h Neutrophils pre Neutrophils intra Neutrophils 24h Neutrophils 48h Platelet pre Platelet intra Platelet 24 Platelet 48h

18 18 18 18 18 18 18 18 18 18 18 18

7.369.44 11.507.22 13.738.33 12.966.67 7.927.22 9.342.78 11.646.67 10.607.11 244.444.44 166.277.78 160.994.44 160.994.44

Deviation 2.629.74 2.090.00 5.950.92 2.930.00 3.763.50 7.990.00 3.933.52 8.060.00 13.646.36 690.00 5.258.52 1.140.00 3.926.20 6.310.00 4.655.99 858.00 76.814.69 130.000.00 62.520.40 85.000.00 59.754.86 73.000.00 63.178.99 83.000.00

12.450.00 21.100.00 23.980.00 23.320.00 62.000.00 19.620.00 23.260.00 20.990.00 385.000.00 311.000.00 305.000.00 306.000.00

5.980.00 6.940.00 10.655.00 10.290.00 3.920.00 5.240.00 8.920.00 8.145.00 177.750.00 117.000.00 122.250.00 129.250.00

7.180.00 9.255.00 13.680.00 12.410.00 4.670.00 8.225.00 11.480.00 9.515.00 247.000.00 160.000.00 142.500.00 147.500.00

Table 2. Comparison between the moments of simultaneous observation for total protein and albumin. Block of variables n Standard Minimum Maximum Quartile 25 Median Average Total Total Total Total Total Total Total Total

protein pre protein intra protein 24 protein 48h albumins pre albumins intra albumins 24h albumins 48h

18 18 18 18 18 18 18 18

6.78 4.70 4.85 5.11 4.05 2.72 2.86 2.94

Deviation 0.88 0.90 0.58 0.68 0.56 0.53 0.39 0.37

5.00 2.80 3.20 3.20 2.80 1.70 2.00 1.80

7.90 6.20 5.70 6.40 4.90 3.60 3.50 3.50

6.03 4.30 4.58 4.88 3.73 2.33 2.68 2.80

7.00 4.85 5.00 5.10 4.10 2.75 2.90 3.00

Table 3. Comparison between the moments of simultaneous observation for total T3 and free T3. n Standard Minimum Maximum Quartile 25 Median Average

Block of variables T3 pre T3 intra T3 24 T3 48h Free T3 pre Free T3 intra Free T3 24 Free T3 48h

18 18 18 18 18 18 18 18

134.46 103.81 84.77 138.60 2.54 2.14 1.72 1.73

Deviation 32.31 37.18 19.57 191.35 0.67 0.82 0.65 0.76

61.70 51.90 56.70 53.80 1.40 0.50 0.60 0.50

190.30 187.30 124.30 899.00 4.30 4.10 2.80 3.10

113.33 79.68 73.05 78.00 2.30 1.60 1.30 1.10

130.85 101.10 79.95 89.60 2.60 2.35 1.75 1.90

9.190.00 18.002.50 15.275.00 13.825.00 6.520.00 13.897.50 12.807.50 12.522.50 307.750.00 201.500.00 209.750.00 223.500.00

Quartile 75 7.50 5.33 5.13 5.40 4.40 3.20 3.03 3.13

Quartile 75 161.18 122.10 91.78 127.25 2.90 2.60 2.15 2.15

Calculated significance (P)

< 0.001

Calculated significance (P)

< 0.001

Calculated significance (P)

< 0.001

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Table 4. Comparison between the moments of simultaneous observation for total T4, free T4 and TSH. Block of variables

Average

T4 pre T4 intra T4 24 T4 48h Free T4 pre Free T4 intra Free T4 24h Free T4 48h TSH pre TSH intra TSH 24 HRT 48h

18 18 18 18 18 18 18 18 18 18 18 18

9.96 8.27 7.80 8.35 1.36 1.44 1.14 1.24 3.04 2.85 1.69 2.30

Standard Deviation 3.23 2.20 2.11 2.11 0.29 0.37 0.23 0.23 2.00 2.06 1.90 1.87

Minimum

Maximum

Quartile-25

Median

Quartile-75

6.00 4.70 4.90 5.00 0.90 1.00 0.80 1.00 0.20 0.30 0.30 0.10

20.50 13.00 12.10 13.90 1.80 2.30 1.70 1.70 7.90 6.90 8.60 8.90

8.08 6.58 6.00 7.08 1.10 1.18 0.98 1.08 1.40 1.25 0.68 1.45

9.45 8.30 7.55 8.25 1.30 1.40 1.10 1.20 2.75 2.50 1.25 2.00

10.90 10.00 9.40 9.70 1.70 1.53 1.25 1.40 4.55 3.83 1.95 2.75

Calculated significance (P) < 0.001

< 0.002

< 0.157

Table 5. Comparison between the moments of simultaneous observation for serum creatinine. Block of variables

Average

Creatinine Creatinine Creatinine Creatinine

18 18 18 18

1.31 1.18 1.21 1.26

pre intra 24 48h

Standard Deviation 0.55 0.44 0.35 0.44

Minimum

Maximum

Quartile-25

Median

Quartile-75

0.70 0.59 0.63 0.70

2.93 2.54 1.91 2.42

0.95 0.86 1.04 0.91

1.22 1.18 1.20 1.11

1.48 1.38 1.43 1.49

Fig. 1 - Comparison between two moments for total leukocytes, neutrophils and platelets

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Calculated significance (P) < 0.281

Fig. 2 - Comparison between two moments for total protein and albumin

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Fig. 3 - Comparison between two moments for total T3, free T3, total T4, free T4 and TSH

DISCUSSION Despite some technical advantages of the use of CPB in CABG surgery, its inflammatory effects should be systematically taken into account to obtain a satisfactory postoperative result. The inherent systemic inflammatory response to CPB is responsible for a variety of organic changes, among them the inadequacy of serum total protein and albumin, serum imbalance of thyroid hormones and qualitative and quantitative changes regarding total leukocytes, neutrophils and platelets [6,7]. The interaction between neutrophils and the endothelium depends on the action of some integrins and cell adhesion molecules such as ICAM-1 [8]. Chen et al. [2] in 2004, demonstrated, through clinical study involving patients undergoing cardiac surgery with CPB, that the release of inflammatory substances during CPB corrupts the transendothelial migration of leukocytes and platelets, with subsequent disordered displacement of these cells to the tissues. The results of our study revealed that there was significant activation and increase in the number of total leukocytes and neutrophils during CPB, so that this condition was detected soon after the CPB, remaining so until 48 hours postoperatively. The comparative analysis between the total number of leukocytes and neutrophils, in

the preoperative was significantly lower than the respective values found after weaning from CPB, but also with 24 and 48 hours postoperatively. The total number of platelets, in turn, was characterized by significant decrease after the CPB, but also in the two periods of postoperative observation, when compared with the total platelet documented in the preoperative phase. It should be noted, therefore, that the transendothelial migration of platelets from the circulation to the tissues occurred as early as possible in relation to total leukocytes and neutrophils. Data recently obtained from an experimental study developed by Okamura et al. [9] showed that ischemiareperfusion and the resulting inflammatory effects of CPB are determinant in the impairment of vascular permeability and viability of organic barriers such as the blood brain barrier. The immediate consequence of this dysfunction is significant change in serum total protein and albumin in relation to their concentration in other body fluids. It was noted in our study, that the serum concentration of total protein after the CPB, and at both time postoperative observation points was significantly lower compared to levels found in the preoperative period. However, the serum concentration of total protein with documented at 48 hours after surgery is considerably higher than the corresponding value identified soon after the CPB and 24 hours postoperatively. This latter finding allows us to infer that the process of recovery and stabilization of serum total 529

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protein after CABG with CPB, tends to start from the second day after surgery. With respect to albumin, its serum concentration after the CPB, and at both time points of postoperative observation was significantly lower compared to levels found in the preoperative period. However, serum albumin documented 48 hours after surgery was not relevant to the immediate post-CPB and 24 hours postoperative, denoting that the process of recovery of serum albumin concentration was not established until the second postoperative day. Changes in renal function after CABG with CPB are emphasized in some studies. Endothelial injury that is stablished within the renal arteries and glomeruli is the main issue of this complication [10,11]. Our results showed stability of serum creatinine over the four periods of observation, noting not even significant differences between the studied moments, when taken as pairs. This finding tends to be greatly influenced by the duration of CPB and this may have been the factor that, in our study, did not promote significant changes in renal function. The main studies correlating inflammatory effects of CPB with thyroid hormone levels revealed that the fractions of total and free T3 (triiodothyronine) tend to decrease in the post-CPB, whereas the concentrations of TSH (thyroid stimulating hormone), T4 (total thyroxine) and free T4 levels tend to remain stable. It has been assigned to this standard of hormonal variation, the concept of euthyroid syndrome. The most important pathophysiological mechanism in the occurrence of this profile is the thyroid hormone molecule reduced conversion of T4 to T3 the active component [1214]. Taylor et al. [15] have argued, since the late 70s of last century, that some aspects inherent to CPB may contribute to the changes of the thyroid hormone profile, such as hemodilution, hypothermia, and nonpulsatile flow. Among these, the most noted in the literature as effectively determining has been the nonpulsatile flow. Ohri et al. [16] have shown that changes in thyroid hormone levels are likely to detect the immediate postoperative period, since at this stage, there is an active state of catabolism associated with high rates of oxygen consumption [17-20]. Some authors have postulated that the decrease in thyroid hormones in the post-CPB favors the occurrence of global myocardial dysfunction and arrhythmias, especially atrial fibrillation [21-25]. In our study, there was marked decrease in serum total T3 and free T3, especially through the first 24 hours postoperatively. Similarly, we observed a similar pattern as the serum total T4. However, regarding the free fraction of T4, the results did not show the same pattern, since there was stability of their serum levels immediately after cessation of CPB and only significant decrease in the first 24 hours postoperatively. Given the results, this study provided information that

attest to the impact of the use of CPB in CABG surgery, with respect to some biochemical, hormonal and cellular parameters. The results allow us to suggest that in coronary artery bypass grafts, the inflammatory effects of CPB include activation of leukocytes, neutrophils and platelets, reduction in serum total protein and albumin and decreased serum levels of thyroid hormones, especially in first 24 hours postoperatively.

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18. Sabatino L, Cerillo AG, Ripoli A, Pilo A, Glauber M, Iervasi G. Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study. J Endocrinol. 2002;175(3):577-86.

9. Okamura T, Ishibashi N, Zurakowski D, Jonas RA. Cardiopulmonary bypass increases permeability of the bloodcerebrospinal fluid barrier. Ann Thorac Surg. 2010;89(1):187-94. 10. Litmathe J, Kurt M, Feindt P, Gams E, Boeken U. The impact of pre- and postoperative renal dysfunction on outcome of patients undergoing coronary artery bypass grafting (CABG). Thorac Cardiovasc Surg. 2009;57(8):460-3. 11. Antunes PE, Prieto D, Ferrão de Oliveira J, Antunes MJ. Renal dysfunction after myocardial revascularization. Eur J Cardiothorac Surg. 2004;25(4):597-604. 12. Chu SH, Huang TS, Hsu RB, Wang SS, Wang CJ. Thyroid hormone changes after cardiovascular surgery and clinical implications. Ann Thorac Surg. 1991;52(4):791-6. 13. Holland FW 2nd, Brown PS Jr, Weintraub BD, Clark RE. Cardiopulmonary bypass and thyroid function: a "euthyroid sick syndrome". Ann Thorac Surg. 1991;52(1):46-50. 14. Velissaris T, Tang AT, Wood PJ, Hett DA, Ohri SK. Thyroid function during coronary surgery with and without cardiopulmonary bypass. Eur J Cardiothorac Surg. 2009;36(1):148-54. 15. Taylor KM, Bain WH, Maxted KJ, Hutton MM, McNab WY, Caves PK. Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. I. Pulsatile system employed and its hematologic effects. J Thorac Cardiovasc Surg. 1978;75(4):569-73. 16. Ohri SK, Becket J, Brannan J, Keogh BE, Taylor KM. Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH. Ann Thorac Surg. 1994;57(5):1193-9.

19. Pearce EN, Yang Q, Benjamin EJ, Aragam J, Vasan RS. Thyroid function and left ventricular structure and function in the Framingham Heart Study. Thyroid. 2010;20(4):369-73 20. Cerillo AG, Storti S, Clerico A, Iervasi G. Thyroid function and cardiac surgery: what should we measure, and when? Ann Thorac Surg. 2010;89(3):1010-1. 21. Tineli RA, Silva Jr JR, Luciano PM, Rodrigues AJ, Vicente WVA, Évora PRB, et al. Fibrilação atrial e cirurgia cardíaca: uma história sem fim e sempre controversa. Rev Bras Cir Cardiovasc. 2005;20(3):323-31. 22. Hijazi EM. É hora de adotar a cirurgia de revascularização do miocárdio com o coração batendo? Revisão de literatura. Rev Bras Cir Cardiovasc. 2010;25(3):393-402. 23. Ribeiro NAM, Stolf NAG, Silva Junior AF, Viana VJC, Carvalho EN, Athanázio R, et al. Efeito do azul de metileno na resposta inflamatória e hemodinâmica em pacientes submetidos à cirurgia de revascularização miocárdica com circulação extracorpórea. Rev Bras Cir Cardiovasc. 2004;19(1):17-23. 24. Moura HV, Pomerantzeff PMA, Gomes WJ. Síndrome da resposta inflamatória sistêmica na circulação extracorpórea: papel das interleucinas. Rev Bras Cir Cardiovasc. 2001;16(4):376-86. 25. Brasil LA, Gomes WJ, Salomão R, Fonseca JHP, Branco JNR, Buffolo E. Uso de corticóide como inibidor da resposta inflamatória sistêmica induzida pela circulação extracorpórea. Rev Bras Cir Cardiovasc 1999;14(3):254-68.

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ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):532-43

Ulisses Alexandre Croti1, Lilian Beani2, Airton Camacho Moscardini3, Arthur Soares Souza Júnior4, Antônio Soares Souza5, Sírio Hassem Sobrinho3, Carlos Henrique De Marchi3, Moacir Fernandes de Godoy6, Domingo Marcolino Braile7

DOI: 10.5935/1678-9741.20110042

RBCCV 44205-1318

Abstract Objective: To evaluate if the findings of multislice computed tomography (MSCT) are associated with clinical and laboratory tests routinely used in the late follow-up of children undergoing surgical treatment of total anomalous pulmonary venous connection (TAPVC). Methods: From January 2002 to December 2007, 12 patients operated due to CATVP were evaluated with history, physical examination, chest X-ray, electrocardiogram, echocardiography and MSCT. Specific changes observed in each one of these tests were identified and compared with MSCT qualitative findings.

Results: Eleven patients were in functional class I (NYHA), three had nonspecific murmurs, and three were below the 15th percentile of weight and height. Two had pulmonary field abnormalities and three had a slight increase of the cardiac area in the X-ray examination. In the electrocardiogram, one patient had right ventricular overload and one had junctional rhythm. All echocardiograms were within the normal range, except for one patient with stenosis between the superior vena cava and right atrium. MSCT was completely normal in four patients, three had compression of the pulmonary veins and four had significant caliber reduction, which correlated with the other findings. Thus, MSCT showed a sensitivity of

1. Full Professor. Head of the Pediatric Cardiovascular Surgery Service of São José do Rio Preto - Hospital de Base (HB) - Regional Medical School Foundation (FUNFARME)/ São José do Rio Preto Medical School (FUNFARME). 2. Pediatrics 3. Infectologist 4. Radiologist. Head of the Image Service of Santa Casa de Misericórdia de São José do Rio Preto. 5. Radiologist. President of Sociedad Latino Americana de Radiología Pediátrica and adjunct professor of São José do Rio Preto Medical School. 6. Pediactir cardiologist. 7. Full Professor. Vice-Director of Regional Medical School Foundation (FUNFARME)/ São José do Rio Preto Medical School (FUNFARME). 8. Pro-rector of Postgraduation at Regional Medical School Foundation (FUNFARME)/ São José do Rio Preto Medical School (FUNFARME). Chief Editor of Brazilian Journal of Cardiovascular Surgery.

Correspondence address: Ulisses Alexandre Croti. Av. Brigadeiro Faria Lima, 5544 – Sala 7 – São José do Rio Preto, SP, Brazil – Zip Code: 15090-000 E-mail: uacroti@uol.com.br, uacroti@cardiol.br

This study was carried out at Hospital de Base - Regional Medical School Foundation (FUNFARME)/ São José do Rio Preto Medical School (FUNFARME), SP, Brazil.

Article received on August 29th, 2011 Article accepted on November 23rd, 2011

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Potential Conflict of Interest No relevant potential conflict of interest. Sources of Funding This study had no external funding sources. The tests of computed tomography were performed for free by Ultra X Clinics Image. Study Association This article is based on the thesis presented at São José do Rio Preto Medical School (FAMERP) as part of the prerequisites for obtaining the title of Full Professor in Cardiovascular Surgery.

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87.5%, specificity of 0.75%, positive predictive value of 87.5%, negative predictive value of 75% and accuracy of 83.3% to demonstrate anatomic changes compared to changes in the physical examination or other additional tests. Conclusion: MSTC may provide valuable information and complement the diagnosis of possible anatomical and functional changes in the late follow-up of patients undergoing surgical repair of TAPVC.

Resultados: Onze pacientes estavam em classe funcional I (NYHA), três apresentavam sopros inespecíficos, três estavam abaixo do percentil 15 de desenvolvimento pônderoestatural. À radiografia de tórax, dois pacientes tinham alteração dos campos pulmonares e três, aumento discreto da área cardíaca. Ao eletrocardiograma, um paciente apresentava sobrecarga ventricular direita e um, ritmo juncional. Todos os ecocardiogramas mostraram-se dentro dos limites de normalidade, exceto em um paciente com estenose entre a veia cava superior e o átrio direito. A TCMD foi totalmente normal em quatro pacientes, em três demonstrou compressão de veias pulmonares e em quatro, redução de calibre considerada significativa, as quais se correlacionaram com os demais achados. Assim, a TCMD para demonstrar alterações anatômicas, quando comparadas a alterações do exame físico ou outros exames complementares testados, apresentou sensibilidade de 87,5%, especificidade de 75%, valor preditivo positivo 87,5%, valor preditivo negativo de 75% e acurácia de 83,3%. Conclusão: No acompanhamento tardio dos pacientes submetidos à correção cirúrgica de CATVP, a TCMD pode fornecer subsídios valiosos e complementar o diagnóstico de eventuais alterações anatômicas e funcionais.

Descriptors: Tomography. Heart defects, congenital/ surgery. Treatment outcome.

Resumo Objetivo: Verificar se os achados da tomografia computadorizada de múltiplos detectores (TCMD) apresentam associação com os parâmetros clínicos e exames complementares rotineiramente empregados na avaliação tardia das crianças submetidas ao tratamento cirúrgico da conexão anômala total de veias pulmonares (CATVP). Métodos: No período de janeiro 2002 a dezembro de 2007, 12 pacientes operados de CATVP foram avaliados tardiamente com anamnese, exame físico, radiografia de tórax, eletrocardiograma, ecocardiograma e TCMD. Alterações específicas de cada um desses exames foram identificadas e comparadas com os achados qualitativos da TCMD.

INTRODUCTION The connection of the anomalous pulmonary venous return, commonly called total anomalous connection of pulmonary veins (TAPV) is a rare congenital disease that encompasses a group of changes in which the pulmonary veins (PV) connect directly to the systemic venous circulation, and not the left atrium (LA) [1]. According to the anatomical characteristics, it can be classified into supracardiac, infracardiac or mixed, with the possible use of various surgical techniques for correction of the defect [2,3]. Regardless of the technique used, it is known that the PV can be compromised and do not present proper development, both because the tissue and the constitution of the common pulmonary vein (CPV) or suture lines used during the procedure. This situation is a late complication of most concern because it has important clinical consequences and compromises the prognosis [4,5]. Usually, these patients are followed-up with clinical assessment, chest radiography, electrocardiography (ECG)

Descritores: Tomografia. Cardiopatias congênitas/ cirurgia. Resultado de tratamento.

and Holter, and echocardiogram that demonstrates or suggests with color Doppler the presence or absence of reduced caliber of PV [4-7]. The gold standard for definitive diagnosis of this complication is still the hemodynamic study. But recently, magnetic resonance imaging and multidetector computed tomography (MDCT) have been employed with greater emphasis on congenital heart disease to replace the invasive procedure [8-10]. This fact attracted our attention to verify if the findings of MDCT are associated with clinical and laboratory tests routinely used in the assessment of children undergoing surgical treatment of TAPV, because until we know how, this is a diagnostic tool that has not been applied for late follow-up to this specific group of patients. METHODS Between January 2002 and December 2007, 1492 patients with congenital heart defects underwent surgery, 16 (1.07%) 533

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with TAPV; everyone at the Hospital de Base, São José do Rio Preto, Regional Medical School Foundation (FUNFARME)/ São José do Rio Preto Medical School (FAMERP). The study protocol was submitted to the Scientific and Ethics Committee for review of the Research Project, São José do Rio Preto Medical School, and was approved by opinion No. 013/2009. The written informed consent was signed by all responsible who participated in the study. Of the 16 patients, 3 (18.75%) died during the same hospital stay of the operation, being considered a hospital death and could not attend for assessment due to geographical difficulties.

The survival of the total group of 16 patients in 2000 days was 81%, confidence interval (CI) of 95% from 61.2% to 100%. Thus, 12 (92.31%) patients were assessed and later formed the study group. The mean follow-up of these 12 patients was 3.73 ± 1.33 years and median of 3.96 (1.34 to 5.43) years. The average age at the time of MDCT was 3.95 ± 1.32 years. The information found in medical records and intraoperative data of the group are presented in Tables 1 and 2. The late assessment was based on history, physical examination, chest radiography, ECG, echocardiography and MDCT. The anamnesis consisted of information on the functional class according to New York Heart Association (NYHA) and the use of drugs. Physical examination was focused on cardiac auscultation and anthropometric measurements of height and weight. At chest radiography, we assessed the transparency of the lung fields, the hemidiaphragm, the size of the area and other changes, if present. ECG provided rhythm and heart rate, PR, QT and QTc intervals, the axes of the P wave and QRS complex, and other changes. Echocardiography was performed using Phillips brand, model HD11 (Bothell, WA, USA) with pediatric multifrequency electronic transducer of 3 to 8 MHz, o onedimensional, two-dimensional, pulsed Doppler, continuous and color. Echocardiographic patterns were obtained. Using pulsed Doppler was possible to measure the velocities of peak venous blood flow in the right superior pulmonary vein (RSPV), called S-waves, D and A. The S wave indicated the systolic forward flow, the D wave, the diastolic antegrade flow, and A wave, retrograde flow during atrial contraction. In the other three VP, the measures were not performed due to technical difficulties inherent in the method. Also with the help of the Doppler, it was used to

Table 1. Information obtained from medical records in the group of 12 patients with total anomalous connection of pulmonary veins assessed lately Age at operation (days) 69 (31 – 122)** Gender Male 8 (66.67%)* Female 4 (33.33%)* Weight in operation (kg) 4.09±1.24*** Diagnosis Supracardiac 4 (33.33%)* Cardiac 3 (25.00%)* Infracardiac 4 (33.33%)* Mixed 1 (8.33%)* Obstructive 5 (41.67%)* Time preoperative intubation (days) 0 (0 – 0)** Postoperative intubation time (days) 4 (2 – 8)** Peritoneal dialysis in the IPO (days) 4 (33.33%)* ICU time (days) 11 (7 – 19)** Length of hospital stay (days) 24 (19 – 30)** Kg = kilogram, IPO = immediate postoperative period, ICU = intensive care unit * = data in absolute value (percentage of total), ** = data expressed as median (interquartile range) *** = data expressed in mean ± standard deviation

Table 2. Data from the intraoperative group of 12 patients with total anomalous connection of pulmonary veins assessed lately. TAPVC CPB Perfusion Myocardial TCA Temperature (ºC) (min) ischemia (min) (min) Supracardiac 22.50±3.32 92.80±15.26 49.00±27.12 19.00±12.78 Carddiac 28.33±3.51 68.67±38.07 33.80±16.01 NO Infracardiac 19.50±1.91 90.00±21.28 49.25±24.09 30.75±9.74 Mixed 26.00* 100.00* 71.00* 15.00* TAPVC = total anomalous pulmonary veins connection, CPB = cardiopulmonary bypass; C = degrees Celsius; min = minutes; TCA = total circulatory arrest, NO = not observed; * = data in absolute values, because there is only one patient. All other values are expressed as mean ± standard deviation

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calculate right ventricular systolic pressure (RVSP) by physiological tricuspid regurgitation and pulmonary artery mean pressure (MPAP). Both in the RSPV, as in other PV and around the LA, was insistently sought with the help of Doppler locations with the presence of possible reductions in size, which is considered when the flow velocity was greater than 2.0 m / s and pulsed Doppler or color Doppler when there was flow turbulence [4,5,11,12]. Chest MDCT was performed using the GE® brand (General Electric Medical Systems, Milwaukee, WI) model lighspeed, Multicut (multislice) 16-channel images were obtained at intervals between the cuts of 0.625 mm. With the child in fasting, peripheral vein was punctured with a Jelco 22 or 24 on upper limb and midazolam administered at a dose of 0.1 mg/kg propofol and 0.5% from 2 to 4 mg/kg. Mean arterial pressure and non-invasive pulse oximetry were continuously monitored and the child kept under spontaneous ventilation with oxygen mask to 100% with 2 to 4 l/min. The standardization of the examination was possible because they are all performed by one radiologist and one radiographer, accompanied by an anesthesiologist, pediatrician, cardiovascular surgeons and nurses. The contrast used was 350 Optiray® (injectable loversol 74%) containing 350 mg/mL organically bound iodine, or a non-ionic contrast toxicity and low osmolarity (Mallinickrodt Inc. - Raleigh, NC - USA). The dose was based on the child, according to the manufacturer’s instructions and administered in the smallest amount possible to obtain adequate images. Images were obtained from axial helical mode, which allowed large amounts of data to be reformatted images in sagittal, coronal and oblique plans. With this volume of images acquired by axial cuts, it was possible to obtain reformatting and volumetric three-dimensional reconstructions called MIP (maximum intensity projection) and colorful 3D reconstructions called volume Rendering. The diameter of the mouth of each pulmonary vein was measured essentially based on axial, sagittal, coronal and oblique cuts, in the short and long axes, in order to obtain the area and check for possible reductions in size when compared to qualitative description. With the diameter of each pulmonary vein, the area was calculated and indexed by the respective patient’s body surface, aiming to standardize the measurements and can compare them. We considered the possibility of size reduction when the value was at least one standard deviation of the mean area of the pulmonary vein studied. The measurements were reconfirmed in three-dimensional reconstructions and associated with descriptive findings, but with illustrative purpose and not scientific. The LA was measured in length (craniocaudal), width (lateral-lateral) and depth (anteroposterior), and the volume

can be calculated by multiplying the measurements and, in the same way as for PV was indexed to body surface of each patient. We considered the possibility that the LA be undeveloped when the value was at least one standard deviation lower than the average volumes. These data were compared with the descriptive findings. The lungs were assessed for the presence of parenchymal lesions, vascular markings and signs to indicate abnormalities. With the images obtained and measurements of PV and LA, a single observer, radiologist, experienced in congenital heart disease, assessed the morphological patterns descriptively (qualitatively) and all data were correlated with the findings of the anamnesis, physical examination, chest radiography , ECG and echocardiography. In statistical analysis, the continuous quantitative variables with Gaussian distribution were analyzed and represented as mean ± standard deviation. Continuous quantitative variables without Gaussian distribution were represented as median (25-75 percentile). All variables were represented as absolute number (percentage of total). Survival was expressed by Kaplan-Meyer and significance using the log rank test with Prism 4.0 for Windows®. The alpha error allowed for statistical significance was 5%. We calculated sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MDCT in clinical evaluations and tests ordered in routine follow-up evaluation. It was considered the gold standard when at least one of these had been changing. RESULTS The series of 12 patients are presented descriptively, with the aim of allowing better analysis of the data found. Patients MHDF, EEM, GVR and LLF were suffering from supracardiac type MDCT, LJD, MICP and EBA, cardiac type; JDSA, HVDS, KCRM and JRM, infracardiac type, and VSF, mixed type. All patients were in functional class I (NYHA), except one (LJD) with cardiac type MDCT, which presented reduced caliber of VP, was reoperated and is under use of acetylsalicylic acid. Another patient (JDSA) with MDCT of infracardiac type presented with seizures postoperatively and, although with no more symptoms after discharge, still makes use of carbamazepine. Cardiac auscultation was within normal limits, except in three patients with nonspecific murmurs (MICP, HVDS and KCRM). Of the eight male patients, five (62.50%) were below the 50th percentile of body mass index (BMI), and three 535

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(37.50%) below the 15th percentile. All patients were female with a BMI above the 85th percentile. At chest radiography, most children had normal pleuropulmonary fields with transparency, free diaphragmatic domes and heart size within normal limits. Two patients (GVR and HVDS) had a slight increase in heart size by visual impression, thea little discordant from CI,

and in three children it was noted prominence of the right cavities (GVR, HVDS and JRM). In one patient (EEM) was observed subsegmental opacity in the right lung base, adjacent to the diaphragm, which may represent subsegmental atelectasis. Another patient (LJD) presented hypertransparency of the left lung, by reduction of vascular markings.

Table 3. The local multi-detector computed tomography found anatomical changes. Patient RSPV RIPV LSPV LIPV CPV / left Pulmonary atrium parenchyma MHDF EEM GVR X X LLF X X LJD* X X X MICP EBA JDSA HVDS X X KCRM X JRM X X VSF X X RSPV = right superior pulmonary vein; RIPV = right inferior pulmonary vein, LSPV = left superior pulmonary vein; LIPV = left inferior pulmonary vein, - = within the normal range; X = changed * = patient required reoperation for size reduction of the veins lung and currently with reduced caliber in the superior vena cava

Table 4. Values obtained by multi-detector computed tomography of the pulmonary vein areas (mm2)/body surface area of each patient (m2). Patient RSPV RIPV LSPV LIPV (mm2/m2) (mm2/m2) (mm2/m2) (mm2/m2) MHDF 132.13 133.46 74.21 87.05 EEM 94.05 63.87 138.32 77.74 GVR 124.14 166.42 68.92 40.65 LLF 20.05 166.20 84.76 40.30 LJD 119.47 41.97 26.32 15.50 MICP 186.63 88.42 99.29 80.52 EBA 134.76 207.25 57.80 88.41 JDSA 75.70 41.04 67.65 57.45 HVDS 98.13 45.89 50.77 21.60 KCRM 39.75 104.03 39.33 119.25 JRM 136.96 107.95 40.36 35.32 VSF 134.18 82.47 92.81 51.18 M - DP 56.87 56.46 39.10 28.40 M - SD = mean minus one standard deviation, RSPV = right superior pulmonary vein; RIPV = right inferior pulmonary vein, LSPV = left superior pulmonary vein; LIPV = left inferior pulmonary vein; mm2 = square millimeter; m2 = square meter

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Table 5. Values obtained by multi-detector CT of left atrial volume (cm3) for each patientâ&#x20AC;&#x2122;s body surface area (m2). Patient Volume (cm3 / m2) MHDF 10.48 EEM 6.40 GVR 4.01 LLF 4.00 LJD 5.68 MICP 5.71 EBA 6.43 JDSA 5.26 HVDS 6.32 KCRM 7.03 JRM 5.88 VSF 5.01 M - DP 4.33 M - SD = mean minus one standard deviation; cm3 = cubic centimetre; m2 = square meter

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Most electrocardiograms were within normal limits, with discrete electric conduction disturbances, such as change in ventricular anteroseptal, conduction disturbance in the right branch and right ventricular hypertrophy, apparently without clinical significance. The echocardiogram showed that the measurement of blood flow velocity in the RSPV was less than 2 m/s in all patients, the largest waves found were D 1 m/s and 1.3 m/s in patients LLF and MICP . There was also no reduction in other PV caliber, as well as the anastomosis between the SVC and LA. RVSP was considered normal in all patients, the highest found in the patient LJD (37 mmHg). The MPAP can not be measured in two patients, LJD and GVR. In all other patients, the MPAP was also normal. In one patient (LJD), it was observed narrowing at the SVC mouth with the RA, with venous flow velocity of 1.89 m/s, considered by echocardiography as mild reduction of caliber. Were also observed in this patient significant dilation of the azygos vein and blood flow in the opposite direction than normal. MDCT analysis of each patient provided so many descriptive details of the anatomical changes in PV, SVC, left atrium and pulmonary parenchyma, among others. Table 3 provides an overview of the sites diagnosed as out of normal standards. The mean measurements of PV indexed by body surface area and their respective standard deviations were: 113.36 ± 56.49 mm2/m2 RSPV, 98.72 ± 42.26 VPID mm2/m2, LSPV 70.05 ± 30.94 mm2/m2, 59.58 ± 31.18 mm2/m2 LIPV. When we considered at least one standard deviation below the mean, the values that suggested a significant decrease in size and therefore could represent the anatomical impairment VP were, respectively, mm2/m2 56.87, 56.46 mm2/m2, mm2/m2 mm2/m2 39.10 and 28.40, as shown in Table 4. Thus, valuing purely measures, we should consider the significant reduction of caliber patients LLF in RSPV with mm2/m2 20.05; LJD, in RIPV, LSPV and LIPV with mm2/m2 41.97, 26.32 mm2/m2, 15.50 mm2/m2; JDSA in RIPV with mm2/ m2 41.04; HVDS, in RIPV and LIPV, with 45.89 and 21.60 mm2/m2 mm2/m2, and KCRM in RSPV, mm2/m2 with 39.75. The descriptive analysis of the findings by a radiologist experienced in congenital heart disease showed a pulmonary vein compression or size reduction in patients LLF, LJD, HVDS, KCRM, JRM and VSF. So, it was the same in four of six patients referred by the measures. Also, with respect to the affected PV there was a discrepancy in patients LJD, JDSA, HVDS and KCRM, suggesting that the measures do not help in correct diagnosis of the presence or absence of injury in PV. The average LA volume indexed by body surface area and its standard deviation was 6.02 ± 1.70 cm 3 /m 2 . Considering at least one standard deviation, LA was

considered underdeveloped when the value was less than 4.33 cm3/m2. This occurred in two patients, GVR and LLF (Table 5). The descriptive analysis of the LA by the radiologist, with the help of MDCT, suggested appropriate development in all patients, indicating that these measures were not useful. Four patients had abnormalities suggestive of lesions in the lung parenchyma, all with involvement of the left lung: GVR with hypoattenuation in the posterior basal segments of the upper and lower lobe and the entire upper lobe secondary to atelectasis; LJD with reduced vascular markings; HVDS with opacity in band in the posterior basal segment of lower lobe and middle lobe, suggesting subsegmental atelectasis, and JRM with opacity in band in the lower lobe, also suggesting subsegmental atelectasis (Table 6). Some examples of these findings are presented below to illustrate the ability of MDCT morphological definition. In MHDF patient, it was found near the big stump together with innominate vein (IV), a remnant of the vertical vein (VV). The four PV were well developed and with no reduction in caliber. There were no signs of increased PT or lesions in the lung parenchyma. These findings were in accordance with the clinical evaluation and other examinations. In the patient EEM, the MDCT showed no changes, in agreement with the clinical evaluation and laboratory tests, except with the ray, which revealed an image suggestive of atelectasis, but the CT departed this possibility. Thus, for this patient, MDCT was superior and more enlightening. In the patient GVR, it was noted that the descending aorta seemed to compress the SVC near the mouth of PV to left (Figures 1A to 1C). The left lung opacities had elongated upper and lower lobe, and hypoattenuation in other segments, suggestive of increased air space secondary to atelectasis. The right lung was normal. In clinical evaluation, the patient’s height and weight development below the 15th percentile, the chest radiograph suggested cardiac area at the upper limit of normal and showed no lung lesions. The other tests were normal, suggesting that MDCT for this patient was also higher. In the patient LLF, the right SVC presented with intramediastinal long extent. There was reduction of the caliber of the distal RSPV, which was small and reduced in size (Figure 2). The lung parenchyma was normal. In clinical evaluation, the patient was below the 15th percentile of BMI for age. The chest radiograph and ECG changes did not indicate, however, in the echocardiogram, the D wave measured at the RSPV was one of the largest found in all patients (1 m/s), therefore there is concordance between the clinical, echocardiographic and MDCT findings, although by echocardiographic definition the gauge reduction was seen when the velocity of venous flow was greater than 2 m/s. 537

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In the patient LJD, who required reoperation for a reduction in caliber of PV, we observed a significant reduction of the caliber of the left SVC and LSPV and LIPV. The right PV, which were amplified with right atrial tissue were normal. The SVC also presented significant reduction in size near its mouth in RA, with the azygos vein opacification by contrast media. There was significant reduction of the vascular markings of the left lung, despite the normal appearance of the tracheobronchial tracheobronchial tree. This was the only patient in functional class II (NYHA), with height and weight development below the 15th percentile in the use of aspirin due to reduced caliber of the SVC at the junction with RA.

Radiography was changed to the left and in ECG there was right ventricular hypertrophy, consistent with the highest RVSP found in the echocardiogram, with D-wave of 0.95 m/s. All these findings were in agreement with those found in MDCT. In the patient MICP, it was noted that the PV drained directly into the right atrium and the left VP converged on a path of CPV, which showed no reduction in caliber. There was increase in the diameter of the PT, which correlated clinically with systolic murmur at left sternal border, smooth, without irradiation, but no changes were noted on chest radiography, ECG or an increase in RVSP or PMAP. The D

Table 6. Association between multidetector CT and other forms of late assessment for patients undergoing repair of total anomalous connection of pulmonary veins. Patient Clinical assessment Chest X-ray Electrocardiogram Echocardiography Tomography MHDF EEM

Atelectasis

GVR

Below the 15th percentile

Cardiac area at the upper limit. Prominence of the right cavities

Compression of CPV Pulmonary lesions

LLF

Below the 15th percentile

High flow velocity in the RSPV

Elongated CPV. Reduction of RSPV caliber

LJD

Below the 15th percentile. Functional Class II.

Hypertransparency at left

RVO

Increased RVSP

Reduction of LSPV and CPV caliber. Pulmonary lesions.

MICP

Systolic murmur. LSB

High flow velocity in the RSPV

Increased TP in relation to the aorta

EBA

JDSA

HVDS

Systolic murmur LSB

Cardiac area at the upper limit. Prominence of the right cavities

Compression and reduction of LIPV caliber. Increased TP Pulmonary lesions

KCRM

Systolic murmur LSB

Junctional Rhythm

Compression and reduction of LIPV caliber

JRM

Prominence of the right cavities

Reduction of the LIPV caliber. Pulmonary lesions

VSF

Reduction of the LSPV and LIPV calibers. Increased TP

- = Within normal limits; CPV = common pulmonary vein, LA = left atrium, RSPV = right superior pulmonary vein, SVC = superior vena cava; RVO = right ventricular overload; RVSP = right ventricular systolic pressure, PV = pulmonary vein; LUPV = left upper pulmonary vein; LIPV = left inferior pulmonary vein; PT = pulmonary trunk, LVH = left ventricular hypertrophy; LSB = left sternal border

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Fig. 1 - Patient GVR. A: Oblique cut with rear view of the LA in MIP. The VP present unique trunks. The descent aorta seems to compress the SVC to the left, B: Oblique reformatting in MIP with CPV on the right shows a normal appearance, C: Oblique reformatting in MIP of the left SVC with detail of the aparent compression by aorta. D: right side of the patient; [E: left side of the patient, LA (AE): left atrium; MIP: maximum intensity projection; PV (VP): pulmonary veins, Ao: aorta, VPC: common pulmonary vein, RSPV (VPSD): right superior pulmonary vein; RIPV (VPID): right inferior pulmonary vein; LSPV (VPSE): left superior pulmonary vein; LIPV (VPIE): left inferior pulmonary vein]

Fig. 2 - Patient LLF. Images of three-dimensional reconstruction. A: Rear view with volume rendering reconstruction, demonstrating reduced in size and dimensions of the RSPV. [D: right side of the patient; E: left side of the patient, LA: left atrium, RSPV (VPSD): right superior pulmonary vein; RIPV (VPID): right inferior pulmonary vein; LSPV(VPSE): left superior pulmonary vein; LIPV (VPIE): left inferior pulmonary vein, CPV (VPC): common pulmonary vein]

Fig. 3 - Patient EBA. Three-dimensional reconstruction with volume rendering under posterior view, showing LA and PV and appearance of totally normal anatomy. [D: right side of the patient; E: left side of the patient; 3D: three-dimensional LA (AE): left atrium; PV: pulmonary vein; RSPV (VPSD): right superior pulmonary vein; RIPV (VPID): right inferior pulmonary vein, LSPV (VPSE): left superior pulmonary vein; LIPV (VPIE): left inferior pulmonary vein]

wave was the largest found in all patients, measured at 1.3 m/s and did not correlate with the MDCT images, which clearly demonstrate the excellent mouth of RSPV in LA. The patient EBA was an example of patient anatomy with normal development of PV. Clinical evaluation as well as all laboratory tests, indicated no change and was consistent in all MDCT findings (Figure 3).

In the patient JDSA the right PV had long extent, but such veins were symmetrical and without reductions in caliber. The pulmonary trunk and pulmonary arteries had normal development and had no signs of pulmonary parenchymal lesions. These data were in agreement with clinical cardiology, chest radiography and ECG, which were normal. In echocardiography, it was found RVSP of 36 mmHg, but with lower MPAP of 7 mmHg. 539

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The patient HVDS presented the PV less elongated, and the LIPV notably smaller caliber than the RIPV. Apparently, the descending aorta determined the compression of LIPV. The upper PV had normal caliber. The PT and the pulmonary arteries were enlarged caliber in relation to the aorta and opacity was in band in the left basal segment of lower and middle lobe, suggesting subsegmental atelectasis (Figures 4A to 4F). Thus, MDCT findings reflected the clinical assessment with a systolic murmur in left sternal and chest radiography with increased heart size. However, ECG and echocardiogram showed no changes and were not in agreement with all other findings. MDCT also showed lung lesions that were absent in the plain chest radiograph. In KCRM patient, the LIPV was elongated, with reduced size in relation to the contralateral vein, apparently suffering from compression by the descending aorta. There was no reduction in upper PV caliber. This visual interpretation

was different from measurements obtained in PV. In clinical evaluation, there was systolic murmur in left sternal vibration, chest radiography was normal, ECG drew attention by junctional rhythm, the echocardiogram with RVSP of 32 mmHg and wave D of 0.96 m/s showed no change. In patient JRM, MDCT found reduction in the caliber of LIPV, and opacity in band in the left lower lobe, with the appearance of subsegmental atelectasis. In this patient, clinical evaluation was normal and chest X-ray showed a mild prominence of the right cavities. The ECG and echocardiogram indicated no change. Thus, reduction in the diameter of the LIPV may have some association with these findings. In the patient ESV, the LSPV was short and with small caliber, the LIPV was elongated and presented reduced in size compared to other PV. The lung parenchyma was normal.

Fig. 4 - Patient HVDS. A: Oblique reformatting in MIP demonstrating inferior VP. Note that the LIPV has a smaller diameter than the RIPV and apparently suffers from compression of the descending aorta; B: Oblique reformatting in MIP measuring the short axis of the LIPV C: Oblique reformatting of short axis measuring the RIPV. D: Oblique reformatting in MIP of long axis measuring the LIPV short-axis, E: Oblique reformatting of short axis of the LIPV; F: Axial opacities in the lung bases with a band-projection of the posterior basal segment of left lower lobe and middle lobe, suggestive of subsegmental atelectasis. [D: right side of the patient; E: left side of the patient; MIP: maximum intensity projection; VP: pulmonary veins, LIPV (VPIE): left inferior pulmonary vein; RIPV (VPID): right inferior pulmonary vein, Ao: aorta, LA (ae): left atrium; RA (AD): right atrium, LV (VE): left ventricle, RV (VD): right ventricle]

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Clinical evaluation and all other examinations were also normal, indicating that the findings of MDCT should not be interpreted alone. Based on the findings above, MDCT showed changes in eight patients, seven of these also had alterations in at least one of the other variables evaluated, ie, evaluation of a clinical or laboratory tests routinely used, and in one patient, the other counts were normal. In the other four patients, MDCT indicated no change, and in three, it was consistent with other data analyzed, and in one patient, there was a change from other examinations. Thus, we find that the MDCT with respect to clinical and other laboratory tests analyzed had a sensitivity of 87.5% (95% CI 64.6% to 100.0%), specificity of 75.0% (95% 32.6% to 100.0%), positive predictive value 87.5% (95% CI 64.6% to 100.0%), negative predictive value of 75.0% (95% CI 32, 6% to 100.0%) and accuracy 83.3% (95% CI 62.2% to 100.0%), as briefly shown in Table 6.

of VV in T or Y, expanding the anastomotic site. This attention should always be in the mind of the surgeon and in surgical patients in the series; such caution was observed, avoiding incisions in PV [17]. Some experts say there is suspicion that many patients operated for TAPVC live normally, however, presented a totally silent lesion in the PV extent [17]. This statement leads us to think that MDCT can be taken with an ability to detect such changes as early as possible, since in our study changes were observed in patients totally asymptomatic. Important to emphasize that this was not the aim of the study, but opens the way for further investigation. The patient operated of TAPVC evolves, most often, clinically asymptomatic, similar to that found in our study, in which 11 (91.66%) had to be totally asymptomatic. The murmur is usually absent or, when present, is negligible and nonspecific, except in situations that they still have pulmonary hypertension or presence of significant residual defects. The heart murmurs observed in patients in our study were considered non-significant, because all were +/ 6+ or ++/6+ in the left sternal border, smooth and without irradiation. So, it would not be valued as indicative of a change in routine clinical examination, but it was noted that the three patients with murmurs (MICP, KCRM and HVDS) showed abnormalities on MDCT. It is important to remember that there is a problem in one or more PVs, the probability of strong murmur would really be minimal, because it is local low pressure, in addition to the anatomical position being posterior, and therefore hardly audible in the normal cardiac auscultation. BMI was much lower than expected in three patients (GVR, LJD and LLF), which were in functional class I, not on medication and with normal cardiac auscultation. These patients showed abnormalities on MDCT, whether pulmonary or SVC compression of the descending aorta or decrease in caliber of left PVs, there is a strong association of height and weight development with MDCT findings. Chest radiography in the late postoperative period should be normal when the patient has not evolved with PV stenosis or stenosis of the anastomotic area, as well as the lung fields should not have changed since the patient did not stay long in need of ventilatory assistance, that has caused injuries such as atelectasis or fibrosis. In our study, all patients who had abnormal chest radiographs were confirmed by MDCT, except one patient who had an image suggestive of atelectasis (MES) and his CT was normal. Therefore, there was a strong association between radiographic images and MDCT. The ECG should show sinus rhythm in almost all patients. Significant arrhythmias may exist in asymptomatic patients undergoing surgical correction of late TAPVC as occurred with the patient KCRM whose ECG showed junctional rhythm. Many patients showed

DISCUSSION The TAPV is an uncommon disease and case series of 16 patients operated on between 1492 (1.07%) with congenital heart disease in six years, despite being small, as it was expected, in line with other large studies, such as Bohemia Survival Study, which identified 40 children with TAPV among the 815,569 children born between 1980 and 1990, and the Baltimore-Washington Infant Study, which found a prevalence of 0.087 per 1000 invasive births [11,12]. The reduction of the PV caliber, commonly called stenosis, is surely the worst complication that can occur late in a patient operated by TAPVC. It usually manifests itself quickly, leading the patient to reoperation within the first six months after the repair [13]. This need for early approach still remains the cause of high mortality in centers of excellence worldwide [4,5,13-15]. There are several mechanisms that can lead to reduction in size of one or more PV, although it is still incompletely understood [13]. Among these mechanisms are inadequate alignment of the incisions between the CPA and LA, causing shrinkage in the anastomosis, which leads to distortion of PV [16]. Also, some authors attribute the need for reoperation stenosis and intimal hyperplasia with proliferation of thickened inflammatory tissue [17]. In our study, we observed that in some patients, there was a decline of PV caliber, and the LIPV was clearly the most affected. Sometimes, the only PV was compressed by the descending aorta, perhaps because of its anatomical position during formation after the pericardial sac. Incisions very close to PV can also lead to stenosis of these veins postoperatively. To avoid this complication, good technical option is opening the CPV in the direction

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no significant changes in the conduction system, for example, anteroseptal ventricular repolarization, conduction disorders or right bundle branch block. These findings are consistent with the literature, which shows a high incidence of sinus node dysfunction and low total atrioventricular block, as well as significant atrial and ventricular arrhythmias are uncommon [18]. In all children evaluated by echocardiography, RVSP was within normal limits, and the patient LJD presented the highest value, because we knew the patient had lesions on the left PV. The PMAP was also within normal limits and did not indicate pulmonary hypertension in any child. The venous flow velocity was measured during the RSPV, and although not greater than 1.5 m/s or 2.0 m/s, as recommended by some authors who consider values above these as presence of PV stenosis; in LLF and MICP patients and the speeds were: 1.0 m/s and 1.3 m/s, consistent with changes found in the RSPV under MDCT [4,5]. The correlation of the findings discussed above was correlated with the findings of MDCT. Chowdhury et al. [19], in 2008, in extensive study on TAPVC of mixed type, presented MDCT image in late evaluation of patients operated for five years, to illustrate that the anastomosis between the left atrial appendage and VV remained patent. This is the first publication we know of using MDCT in the evaluation of a patient with late TAPVC. MDCT has been considered as an alternative complementary to echocardiography in the preoperative diagnosis of TAPVC, since these patients often find themselves in unfavorable hemodynamic conditions and hemodynamic studies to clarify the anatomy may worsen the clinical picture and provide more risk to the life of child. MDCT has the great advantage of being non-invasive and therefore life-threatening almost negligible, except for a possible anaphylactic shock of the contrast [10]. Kim et al. [9], studying 14 patients with TAPVC demonstrated that the combination of MDCT with three dimensional reconstruction helped in the diagnosis of TAPVC, being a good tool in the preoperative evaluation of neonates and infants [9]. However, it is not sufficiently adequate for visualization of intracardiac structures, due to heart rate and respiratory movements generally high. Indeed, it is virtually impossible to hold the breath in children less than eight months when they are intubated, with this important problem and impediment to implementation of MDCT in neonates. All children in the study were sedated with midazolam and propofol when needed, besides the fact that they are older, with an average age of 3.95 ± 1.32 years. In this series, we measured the diameters of PV and calculated the LA volume. This had no association with the descriptive findings, and therefore we feel it should be

employed. Already, the measures of PV had some degree of association with the descriptive findings, but it was clear that the interpretation by an experienced physician is important and can complement the other findings of other examinations. The fact that MDCT is in agreement with other findings in 10 of 12 patients, ie, from the eight MDCT altered, seven also with abnormal tests and four with normal MDCT, with three other tests also normal, makes us believe that the MDCT can be used quite safely in the late follow-up of children operated on TAPVC. We found discrete and important morphological changes, being higher for the detection of subtle changes, such as simple compression or increased PVs pr PT with respect to the aorta, and it was associated with significant findings for the tests used in everyday practice. Notably, the RSPV was the most affected by compression or the presence of reduced caliber. Therefore, this analysis suggests that it can be used for follow-up evaluation of patients undergoing total anomalous connection of pulmonary veins in order to anticipate clinical deterioration, allowing more accurate and early assessment, and can anticipate reinterventions when necessary. Study limitations were the small number of patients, which does not allow statistical comparisons. In the period studied, there was progress in the technical details of experience gained by the surgeon and team. Patients were analyzed not only with ECG and Holter, because most live in other states and could not be in town for a long time. The MDCT findings were compared to non-hemodynamic study because it would not be ethically correct to pergorm invasive test, which theoretically has some lifethreatening to the patient. There is also lack of other studies with late MDCT and MRI that have assessed a series of patients undergoing surgical correction of TAPVC.

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CONCLUSION In the late follow-up of patients undergoing surgical correction of TAPVC, the MDCT can provide valuable insights and complement the diagnosis of possible anatomical and functional, with a sensitivity of 87.5%, specificity of 75% and accuracy of 83.3%. ACKNOWLEDGEMENTS To all the families who agreed to submit their children to examinations and all members of the Department of Pediatric Cardiology and Cardiovascular Surgery of São José do Rio Preto who collaborated directly and indirectly in making this study.

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REFERENCES 1. Hirsch JC, Bove EL. Total anomalous venous connection. MMCTS. 2007;507:2253. 2. Craig JM, Darling RC, Rothney WB. Total pulmonary venous drainage into the right side of the heart; report of 17 autopsied cases not associated with other major cardiovascular anomalies. Lab Invest. 1957;6(1):44-64. 3. Paulista PP, Pedra SRFF. Anomalias de conexão do retorno pulmonar e sistêmico. In: Croti UA, Mattos SS, Pinto Jr. VC, Aiello VD, ed. Cardiologia e cirurgia cardiovascular pediátrica. 1ª ed. São Paulo:Roca;2008. p.203-16. 4. Karamlou T, Gurofsky R, Al Sukhni E, Coles JG, Williams WG, Caldarone CA, et al. Factors associated with mortality and reoperation in 377 children with total anomalous pulmonary venous connection. Circulation. 2007;115(12):1591-8. 5. Lacour-Gayet F, Zoghbi J, Serraf AE, Belli E, Piot D, Rey C, et al. Surgical management of progressive pulmonary venous obstruction after repair of total anomalous pulmonary venous connection. J Thorac Cardiovasc Surg. 1999;117(4):679-87. 6. Chowdhury UK, Airan B, Malhotra A, Bisoi AK, Saxena A, Kothari SS, et al. Mixed total anomalous pulmonary venous connection: anatomic variations, surgical approach, techniques, and results. J Thorac Cardiovasc Surg. 2008;135(1):106-16. 7. Devaney EJ, Chang AC, Ohye RG, Bove EL. Management of congenital and acquired pulmonary vein stenosis. Ann Thorac Surg. 2006;81(3):992-6. 8. Uçar T, Fitoz S, Tutar E, Atalay S, Uysalel A. Diagnostic tools in the preoperative evaluation of children with anomalous pulmonary venous connections. Int J Cardiovasc Imaging. 2008;24(2):229-35. 9. Kim TH, Kim YM, Suh CH, Cho DJ, Park IS, Kim WH, et al. Helical CT angiography and three-dimensional reconstruction of total anomalous pulmonary venous connections in neonates and infants. AJR Am J Roentgenol. 2000;175:1381-6. 10. Sridhar PG, Kalyanpur A, Suresh PV, John C, Sharma R, Maheshwari S. Total anomalous pulmonary venous connection:

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helical computed tomography as an alternative to angiography. Indian Heart J. 2003;55(6):624-7. 11. Samanek M, Voriskova M. Congenital heart disease among 815,569 children born between 1980 and 1990 and their 15year survival: a prospective Bohemia survival study. Pediatr Cardiol. 1999;20(6):411-7. 12. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, et al. Congenital heart disease: prevalence at livebirth. The Baltimore-Washington infant study. Am J Epidemiol. 1985;121(1):31-6. 13. Ricci M, Elliott M, Cohen GA, Catalan G, Stark J, Leval MR, et al. Management of pulmonary venous obstruction after correction of TAPVC: risk factors for adverse outcome. Eur J Cardiothorac Surg. 2003;24(1):28-36. 14. Van Son JA, Danielson GK, Puga FJ, Edwards WD, Driscoll DJ. Repair of congenital and acquired pulmonary vein stenosis. Ann Thorac Surg. 1995;60(1):144-50. 15. Caldarone CA, Najm HK, Kadletz M, Smallhorn JF, Freedom RM, Williams WG, et al. Relentless pulmonary vein stenosis after repair of total anomalous pulmonary venous drainage. Ann Thorac Surg. 1998;66(5):1514-20. 16. Ando M, Takahashi Y, Kikuchi T. Total anomalous pulmonary venous connection with dysmorphic pulmonary vein: a risk for postoperative pulmonary venous obstruction. Interact Cardiovasc Thorac Surg. 2004;3(4):557-61. 17. Lacour-Gayet F, Zoghbi J, Serraf AE, Belli E, Piot D, Rey C, et al. Surgical management of progressive pulmonary venous obstruction after repair of total anomalous pulmonary venous connection. J Thorac Cardiovasc Surg. 1999;117(4):679-87. 18. Tanel RE, Kirshbom PM, Paridon SM, Hartman DM, Burnham NB, McBride MG, et al. Long-term noninvasive arrhythmia assessment after total anomalous pulmonary venous connection repair. Am Heart J. 2007;153(2):267-74. 19. Chowdhury UK, Airan B, Malhotra A, Bisoi AK, Saxena A, Kothari SS, et al. Mixed total anomalous pulmonary venous connection: anatomic variations, surgical approach, techniques, and results. J Thorac Cardiovasc Surg. 2008;135:106-16.

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ORIGINAL ARTICLE

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Walter J Gomes1, Raul E. Saavedra2, Débora M. Garanhão3, Alexandre R. Carvalho4, Francisco A. Alves5

DOI: 10.5935/1678-9741.20110043

RBCCV 44205-1319

Abstract Objectives: The reconstruction of the left ventricle (LV) is effective in the treatment of ischemic cardiomyopathy with large akinetic or dyskinetic areas. However, late survival outcomes are related to the remnant left ventricular cavity size, thus eliminating intracavitary patch placement provides additional LV reduction. The aim of this study was to analyze the results with left ventricular reconstruction surgery using the concept of maximum ventricular reduction, with systematic patch abolition. Methods: Seventy-six consecutive patients with ischemic heart disease (age 30-78 years, mean 57.6 ± 10.1), evolving in functional class III and IV underwent surgical ventricular reconstruction with no use of intracavitary patches or Teflon strips for closing the left ventriculotomy. Results: The left ventricular end-systolic diameter decreased from 52.3 ± 5.4 in the preoperative period to 45.2 ± 6.9 mm in the postoperative period. LV ejection fraction increased from 34.2% ± 10.4% to 45.5% ± 9.4%. Associated CABG was performed in 75/76 patients with a mean of 2.4 grafts per patient. The 30-day mortality was 3/76 (3.9%). At

an average follow up of 39 months, the majority of the patients (91.4%) remain in functional class I and II. Conclusion: The concept of maximizing LV reduction with systematic patchless reconstruction is feasible, safe and effective, the early and late outcomes comparing favorably to previous series reported in the medical literature. Additionally, the concept meets the contemporary pathophysiologic basis of heart failure.

1. 2. 3. 4. 5.

Correspondence address Walter J. Gomes, Rua Borges Lagoa, 1080 cj 608 São Paulo SP 04038-002 - Brazil. E-mail: wjgomes.dcir@epm.br

Full Professor; President of Brazilian Society of Cardiovascular Surgery Physician; Cardiovascular surgeon. Physician; Cardiovascular surgeon. Physician; Cardiovascular surgeon. Physician; Cardiologist.

This study was performed at the Pirajussara General Hospital, OSSSPDM, Taboão da Serra, São Paulo, Brazil and Luzia de Pinho Melo Clinics Hospital, OSS-SPDM, Mogi das Cruzes, São Paulo, Brazil.

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Descriptors: Heart Failure. Myocardial Ischemia. Heart Aneurysm. Coronary Artery Bypass; Coronary Disease.

Resumo Objetivo: A cirurgia de reconstrução do ventrículo esquerdo (VE) é efetiva no tratamento da cardiomiopatia isquêmica com grandes áreas acinéticas ou discinéticas. Entretanto, resultados de sobrevida tardia estão relacionados ao tamanho da cavidade ventricular esquerda remanescente, portanto eliminar retalhos intracavitários pode proporcionar redução adicional do VE. O objetivo deste trabalho foi

Article received on July 25th, 2011 Article accepted on November 28th, 2011

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analisar os resultados com a cirurgia de reconstrução ventricular esquerda utilizando o conceito da máxima redução ventricular, com sistemática eliminação de retalhos. Métodos: Setenta e seis pacientes consecutivos com cardiomiopatia isquêmica (idade 30-78 anos, média 57,6 ± 10,1), evoluindo em classe funcional III e IV foram submetidos à cirurgia de reconstrução ventricular direta sem utilização de retalhos intracavitários ou materiais protéticos. Resultados: O diâmetro sistólico final do VE diminuiu de 52,3 ± 5,4 no pré-operatório para 45,2 ± 6,9 mm no pósoperatório. A fração de ejeção aumentou de 34,2% ± 10,4% para 45,5% ± 9,4%. Revascularização miocárdica associada foi realizada em 75/76 pacientes, com média de 2,4 enxertos/

paciente. Mortalidade em 30 dias foi 3/76 (3,9%). No acompanhamento médio de 39 meses, a maioria dos pacientes (91,4%) permanece em CF I ou II. Conclusão: O conceito de maximizar a redução do VE com a reconstrução sistemática sem uso de retalhos mostrouse viável, segura e eficaz, com os resultados precoces e tardios comparando favoravelmente às séries relatadas na literatura médica. Além disso, o conceito harmoniza-se à base fisiopatológica contemporânea da insuficiência cardíaca.

INTRODUCTION Surgical ventricular reconstruction (SVR) for treatment of ischemic cardiomyopathy has been demonstrated to significantly improve left ventricular function and quality of life, with symptom relief and functional class improvement in patients with heart failure. The grounds for SVR were developed in the mid-1980s [1,2] and later modified by the RESTORE group [3], the aim of the procedure being to reduce size and reshape the left ventricular cavity with placement of a intraventricular patch. However, significant new evidences have been added over the last decades on the knowledge of pathophysiology and progression of heart failure; and its operative treatment. Recent evidence demonstrated that survival of patients evolving with heart failure and also after SVR is inversely correlated to the size of the residual left ventricular (LV) cavity, i.e., the final systolic and diastolic volumes [3]. Heart failure and myocardial ischemia have currently been recognized as disorders whose genesis and progression are related to inflammatory mechanisms and neurohormonal activation [4]. Also, the implant of prosthetic materials is documented to elicit and sustain a myocardial chronic inflammatory reaction, with ongoing release of inflammatory mediators. Therefore, eliminating the patch placement during LV reconstruction could contribute to further LV cavity reduction, virtual elimination of superimposed akinetic areas and potentially blunt myocardial chronic inflammatory reaction. The aim of this study is to report the application and outcomes of these concepts in a large series of patients subjected to a more physiological approach in LV reconstruction; with systematic intracavitary patch elimination and avoidance of prosthetic material for LV closure.

Descritores: Isquemia Miocárdica. Insuficiência Cardíaca. Aneurisma Cardíaco. Revascularização Miocárdica. Doença das Coronárias

METHODS Patients Between September 2002 and February 2008, 76 consecutive patients with ischemic cardiomyopathy and LV aneurysm (73 anterior wall and 3 inferior wall) underwent surgical LV reconstruction using the patchless technique described herein, at the Pirajussara General Hospital and Luzia de Pinho Melo Clinics Hospital. Both institutions are university-affiliated community hospitals serving lowerincome population regions in the outskirts of Sao Paulo metropolitan area. All patients were referred for operation due to uncontrollable heart failure symptoms and/or refractory angina pectoris, despite optimized evidencebased medication. Preoperative assessment included coronary cineangiography with left ventriculogram and transthoracic echocardiography. The patients age ranged from 30 to 78 years-old, with a mean of 57.6 ± 10.1 years. All operations were performed by a single surgeon and multiple assistants. The patients were followed until May 2008 and clinical follow-up was obtained via chart review, telephone interview and/or referring physician contact. The study protocol was approved by the institutional Ethics Committee. Technique Standard cardiac anesthesia was employed and SwanGanz catheter was not routinely inserted. Cardiopulmonary bypass (CPB) was established with a single two-stage cannula in the right atrium and ascending aorta cannulation, a vent was inserted through the right superior pulmonary vein and advanced across the left atrium and mitral valve into the left ventricle. The procedure was carried-out with the empty beating 545

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heart technique without aortic cross-clamping, the coronary arteries perfused by orthograde flow from the aorta sustained by normothermic cardiopulmonary bypass. Perfusion pressure was kept above 80 mmHg throughout and patient continuously rewarmed to 36.5oC. In cases of anterior wall aneurysm, the left ventricle anterior wall was carefully and sparingly incised at the aneurysmal area, parallel and at least 1.5 cm away from the interventricular septum and the left anterior descending (LAD) coronary artery, aiming to preserve both LAD and large diagonal arteries for subsequent grafting. Upon opening, LV cavity was carefully inspected and any existing thrombus entirely removed. A double layer of 3-0 polypropylene purse-string sutures were placed around the aneurysm neck (the so-called Fontan stitch), i.e., at the level of transitional area between fibrotic tissue and healthy muscle, delimitated both in the septum and in the anterolateral wall, close to the anterolateral papillary muscle base. Next, the suture is tied down redefining the size of the remaining ventricular cavity and the edges of newly created orifice are brought together

with a 3-0 polypropylene running suture. The edges of the remaining ventricular free wall were then closed using running and overlapping suture, with no use of Teflon felt strips or foreign material whatsoever (Figure 1). Great care is taken to avoid damage to diagonal branch and LAD, which are routinely revascularized using sequential LITA grafting whenever feasible (Figure 2). The distal coronary anastomoses are performed under pumpassisted circulation and with the aid of Octopus tissue stabilizer (Medtronic). The top-end anastomoses were completed using side-bite clamping. Similar technique was employed in case of inferior wall aneurysms, as can be seen is Figure 3. Moderate to severe mitral valve regurgitation was considered an indication for mitral repair, performed in three patients by employing flexible rings. In the latest one-third of this series, in eight patients a technical modification was implemented, with placement of the Fontan stich nearly one centimeter downwards the transitional zone, thereby overreducing the LV cavity.

Fig. 1 - Stepwise sequence of the operative technique as described in text; aneurysm of the left ventricular anterior wall

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Fig. 2 - A. The left ventricle anterior wall sparingly incised at the aneurysmal area, parallel and at least 1.5 cm away from the interventricular septum and the left descending anterior coronary artery. B. Sequential LITA grafting to the left anterior descending coronary artery (black arrow) and a large diagonal branch (white arrow)

Fig. 3 - Stepwise sequence of the operative technique; aneurysm of the left ventricular inferior wall

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Fig. 4 - Schematic drawing of the concept of the procedure. A. The enlarged LV with the aneurysmal area. B. Dor procedure with the intraventricular patch (arrow). C. The remnant LV after the patchless technique. RV-right ventricle. LV-left ventricle

RESULTS Mean CPB time was 87.8 minutes, ranging from 35 to 150 minutes. Concomitant coronary artery bypass grafting was performed in 98.7% of the patients (75/76), with a mean of 2.4 grafts per patient. The left internal thoracic artery was grafted to the left anterior descending artery in 75/76 patients (98.7%). One patient with single-vessel disease was found to have the LAD totally fibrotic all way down, precluding further revascularization. No patient required mechanical circulatory support with intra-aortic balloon pump (IABP) for CPB discontinuation or needed reoperation for bleeding. The median postoperative hospital stay was 6 days. In roughly one quarter of patients (20 patients, 26.3%), CPB was discontinued with use of sodium nitroprusside only. The remainder required variable dose combinations of IV dobutamine, noradrenaline, nitroprusside, nitroglycerine, and metoprolol. Overall 30-day mortality was 3.9% (3/76). Over the longterm follow-up, the left ventricular ejection fraction increased from 34.2% ± 10.4% preoperatively to 45.5% ± 9.4% postoperatively. The left ventricular end-systolic diameter decreased from 52.3 ± 5.4 in the preoperative period to 45.2 ± 6.9 mm in the postoperative period and the end-diastolic diameter from 65.0 ± 4.1 to 58.7 ± 5.8 mm. In the mean followup of 39 months, 5 patients died (survival at 39 months = 93.1%). Causes of late death included neoplasia (2 patients), chronic obstructive pulmonary disease complication (1), arrhythmia (1) and unknown (1). The majority of the patients in this series (91.4%) remain in functional class I or II after the operation. Postoperatively, all patients are on continued evidence-based medication for heart failure control using a combination of angiotensin-converting enzyme inhibitors, 548

cardioselective beta-blockers, spironolactone, digoxin, and furosemide, which are provided free-of-charge or at subsidized cost by the local public health system. DISCUSSION The present operative concept (Figure 4) and technique incorporate and merge much of recently acquired evidence on heart failure, its pathophysiology, mechanics and biochemical aspects. Our preliminary study reporting the satisfactory outcomes have encouraged us to proceed further in implementing the concept [5]. The size of the LV cavity has been unequivocally demonstrated correlate with survival in patients with heart failure [3,6]. The larger the size of the LV cavity, the lower the expected survival, thus LV dilation is an independent contributor to poor outcome in patients with advanced heart failure [7]. The ongoing progression of ventricular dilation leads to increased wall tension, according to the LaPlace’s law and the attenuation or reversion of this process is linearly associated with improved systolic performance and reduced risk of further cardiovascular events [8,9]. In the SAVER study, the postoperative LV size was also a significant and decisive risk factor for late survival. Patients with postoperativeend-systolic volume index (ESVI) up to 80 ml/m2 had higher survival at 3 years compared with those with ESVI > 80 ml/m2. strengthening that elimination of LV akinetic areas, as well as diskinetic areas could potentially lead to better restoration of LV function [8]. For accomplishment of this goal, virtual exclusion of noncontractile and non-viable myocardial areas (scar) seems imperative for left ventricular function improvement. The STICH trial, set to study the impact of revascularization plus SVR versus revascularization only

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in the treatment of severe ischemic cardiomyopathy, concluded that adding SVR to CABG was not associated with a greater improvement in symptoms, exercise tolerance or reduced immediate mortality. This disappointing finding has largely been ascribed to an inadequate SVR procedure with insufficient LV volume reduction, with an average endESVI reduction of 19% only, compared to a figure of 40% reported by the SAVER study [10]. Although studies demonstrate that current employed techniques of ventricular reconstruction (included Dor procedure and the variant SVR â&#x20AC;&#x201C; Surgical Ventricular Restoration) improve global LV systolic function, the mechanism and effect on regional LV systolic function remains poorly understood [11]. While patch (geometric) left ventricular reconstruction suggest provide favorable results, meta-analysis comparing early outcomes following geometric versus linear reconstruction found no difference between the two surgical approaches when performed in the same time span, with similar in-hospital mortality and other end-points (postoperative inotrope requirement, low output syndrome, and need of intra-aortic balloon pump) [12]. Additionally, the 10-year survival rate showed no significant difference between the linear resection and patch ventriculoplasty groups [11,13]. On the other hand, numerous evidences demonstrated that inflammation plays an important role in the development and progression of heart failure. Heart failure is now recognized as a syndrome characterized by prolonged immune and inflammatory activation, with high circulating levels of pro-inflammatory cytokines and an increased expression of several other inflammatory mediators. These inflammatory mediators are not only markers of immune activation, but also induce myocardial dysfunction by different mechanisms, including the regulation of apoptosis, the beta-adrenergic responsiveness, and adverse remodeling [14]. Studies to date have suggested that elevated circulating levels of pro-inflammatory cytokines are associated with increased mortality [15]. Likewise, coronary artery disease and LV ischemic dysfunction is also characterized by immune inflammatory activation and inflammatory mediators have a major role in the development and progression of arteriosclerosis 16]. Following LV aneurysm formation and consequent expansion of LV chamber, neurohormonal system activation (brain natriuretric peptide â&#x20AC;&#x201C; BNP, norepinephrine, renin and angiotensin II) take place and its concentrations are associated to worse prognosis and also predict long-term survival. The SVR, resulting in reduction of chamber dimensions and decrease in the ventricular filling pressures and wall tension, is accompanied by improvement of the neurohormonal response [17]. Prosthetic material customarily employed in LV reconstruction (Dacron patch, Teflon felt and bovine

pericardium) are recognized to elicit a foreign body reaction with a consequent myocardial chronic inflammatory response. Previous studies showed that Teflon and bovine pericardium are associated with predominantly mononuclear inflammatory infiltrate (monocytes and macrophages) in the adjacent tissue and induction of a graft-versus-host immunological response. These formations constitute an active source of cytokines (interleukins and tumor necrosis factor), which trigger and sustain inflammatory processes induced by foreign substances in the organism over the long-term [5-18]. A further consequence of the chronic myocardial inflammatory reaction induced by foreign materials is an exuberant scar formation around the prosthetic material and infiltrating the surrounding cardiac muscle. Extensive myocardial scar tissue and severely depressed left ventricular ejection fraction (LVEF) are independent predictors of death or recurrent ventricular arrhythmias in patients with coronary artery disease [19]. Sudden death is the most common single mode of death during long-term follow-up after left ventricular reconstruction, this high incidence of late sudden death is significantly associated to ventricular tachyarrhythmias [20]. Additionally, proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1, and interleukin-6 are synthesized not only by cells of the immune system but also by cardiac myocytes in response to ischemia or mechanical stretch, promoting decreased cardiac contractility, interstitial fibrosis and collagen deposition in noninfarct zones and deleterious effects in the heart over time. Excessive scar formation critically diminishes myocardial compliance, which contributes to diastolic and eventually systolic dysfunction, disrupts myocyte-tomyocyte electrical connectivity, and further exacerbates the cycle of ischemic stress-inflammation-stress. Sustained expression of proinflammatory cytokines can extend to involve remote, noninfarcted regions and contribute to remodeling of the entire myocardium. [15,16,21]. The technique herein reported abolishes the use of intracavitary patch, excluding and virtually eliminating LV septal and free wall akinetic/dyskinetic areas, maximizing left ventricular cavity reduction and leaving only contractile myocardial segments. This concept complies directly with Laplaces law, where the maximized reduction of the left ventricular cavity diminishes the left ventricular wall tension, reducing oxygen consumption. Patch placement has also been demonstrated reduce overall LV compliance, as a consequence of use of a non-compliant material rather than excluding non-viable but still more compliant myocardium [21]. The beating heart technique employed in this series might have played a decisive role for the attained outcome and every step of the procedure (LV reconstruction, CABG 549

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and mitral repair) could be accomplished without aortic cross-clamping and cardioplegic arrest. Beating heart surgery has been demonstrated afford enhanced left ventricular function and to reduce troponin and CK-MB (markers of myocardial tissue damage) release compared to on-pump technique with aortic cross-clamping by eliminating intraoperative global myocardial ischemia, with preservation of native coronary blood flow, reduction of myocardial injury and inflammatory response, and thus contributing to myocardial protection [22,23]. In patients with depressed LV function, preservation of every cardiomyocyte counts and aortic cross-clamping induction of troponin and CK-MB release is a translation of further cell loss. Strong previous off-pump coronary bypass surgery experience in our center certainly contributed for mastering the beating heart technique [24]. Remarkably, even operating on patients with advanced left ventricular dysfunction, mechanical circulatory support with IABP has not been utilized in any case. Additionally, in this technique the distance between mitral papillary muscles and between papillary muscles and leaflet free edge is shortened, affording reduction of the tethering mechanism with better cusp coaptation and mitral regurgitation improvement. Associated coronary revascularization is essential in SVR, contributing to further clinical improvement. Grafting of the left anterior descending artery, even when totally occluded, is particularly important to provide blood flow for viable areas of the interventricular septum, serving as a source of collateral circulation for other myocardial segments and for control of ventricular arrhythmias originating from the transitional region. As in this technique a vessel-sparing ventricular incision is performed, complete revascularization of the coronary arteries in the anterolateral wall is easily accomplished. Unlike Batista operation [25], which proposed LV reduction by mandatory excision of the inter-papillary lateral wall, this procedure excludes only scarred non-contractile segments, but following the same commandments. The introduction of new cardiac imaging methods such as MRI and enhanced software might greatly contribute to this field, targeting more accurate delimitation of LV noncontractile and non-viable areas, providing more information leading to a greater precision in the cavity reconstruction and with potential to improve performance. A limitation of the study resides in its historical prospective design and performed in multiple centers with limited imaging resources; this negatively affected our ability to obtain complete preoperative and postoperative cardiac volumetric measurements for all patients. Additionally, our study was not protocol driven, and patient care was determined by clinical judgment. Further prospectives trials with appropriate design should be able

to define the role of the concept in the management of ischemic cardiomyophaty. Finally, SVR is performed aiming to improve quality of life and possibly to extend survival. In this way, this technique has been proved to be not harmful and capable to afford to patients early and late outcomes comparing favorably to previous reported series.

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CONCLUSION Based on these results, the concept of maximizing LV reduction with systematic patchless reconstruction is feasible, safe and effective. Additionally, the concept meets contemporary pathophysiologic basis of heart failure.

REFERENCES 1. Dor V, Saab M, Coste P, Kornaszewska M, Montiglio F. Left ventricular aneurysm: a new surgical approach. Thorac Cardiovasc Surg. 1989;37(1):11-9. 2. Jatene AD. Left ventricular aneurysmectomy: resection or reconstruction. J Thorac Cardiovasc Surg. 1985;89(3):321-31. 3. Athanasuleas CL, Stanley AW, Buckberg GD, Dor V, Di Donato M, Siler W, et al. Surgical anterior ventricular endocardial restoration (SAVER) for dilated ischemic cardiomyopathy. Semin Thorac Cardiovasc Surg. 2001;13(4):448-58. 4. Anker SD, von Haehling S. Inflammatory mediators in chronic heart failure: an overview. Heart. 2004;90(4):464-70. 5. Gomes WJ, Jaramillo JI, Asanuma F, Alves FA. Physiologic left ventricular reconstruction: the concept of maximum ventricular reduction and minimum inflammatory reaction. Rev Bras Cir Cardiovasc. 2004;19(4):353-7. 6. Burns RJ, Gibbons RJ, Yi Q, Roberts RS, Miller TD, Schaer GL, et al. The relationships of left ventricular ejection fraction, end-systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by thrombolysis. J Am Coll Cardiol. 2002;39(1):30-6. 7. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Levy D. Left ventricular dilatation and the risk of congestive heart failure in people without myocardial infarction. N Engl J Med. 1997;336(19):1350-5. 8. Athanasuleas CL, Buckberg GD, Stanley AW, Siler W, Dor V, Di Donato M, et al. Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation. J Am Coll Cardiol. 2004;44(7):1439-45.

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9. Walker JC, Guccione JM, Jiang Y, Zhang P, Wallace AW, Hsu EW, et al. Helical myofiber orientation after myocardial infarction and left ventricular surgical restoration in sheep. J Thorac Cardiovasc Surg. 2005;129(2):382-90.

ventricular reconstruction surgery in ischemic cardiomyopathy. J Thorac Cardiovasc Surg. 2004;128(1):38-43.

10. Jones RH, Velazquez EJ, Michler RE, Sopko G, Oh JK, OConnor CM, et al. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J Med. 2009;360(17):1705-17. 11. Antunes PE, Silva R, FerrĂŁo de Oliveira J, Antunes MJ. Left ventricular aneurysms: early and long-term results of two types of repair. Eur J Cardiothorac Surg. 2005;27(2):210-5. 12. Parolari A, Naliato M, Loardi C, Denti P, Trezzi M, Zanobini M, et al. Surgery of left ventricular aneurysm: a meta-analysis of early outcomes following different reconstruction techniques. Ann Thorac Surg. 2007;83(6):2009-16. 13. Lange R, Guenther T, Augustin N, Noebauer C, Wottke M, Busch R, et al. Absent long-term benefit of patch versus linear reconstruction in left ventricular aneurysm surgery. Ann Thorac Surg. 2005;80(2):537-41 14. Devaux B, Scholz D, Hirche A, Klovekorn WP, Schaper J. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. Eur Heart J. 1997;18(3):470-9. 15. Sun M, Chen M, Dawood F, Zurawska U, Li JY, Parker T, et al. Tumor necrosis factor-mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation. 2007;115(11):1398-407. 16. Aukrust P, Ueland T, Lien E, Bendtzen K, Muller F, Andreassen AK, et al. Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1999;83(3):376-82. 17. Schenk S, McCarthy PM, Starling RC, Hoercher KJ, Hail MD, Ootaki Y, et al. Neurohormonal response to left

18. Hernandez-Pando R, Bornstein QL, Aguilar Leon D, Orozco EH, Madrigal VK, Martinez Cordero E. Inflammatory cytokine production by immunological and foreign body multinucleated giant cells. Immunology. 2000;100(3):352-8. 19. van der Burg AE, Bax JJ, Boersma E, Pauwels EK, van der Wall EE, Schalij MJ. Impact of viability, ischemia, scar tissue, and revascularization on outcome after aborted sudden death. Circulation. 2003;108(16):1954-9. 20. Matthias Bechtel JF, TĂślg R, Graf B, Richardt G, Noetzold A, Kraatz EG, et al. High incidence of sudden death late after anterior LV-aneurysm repair. Eur J Cardiothorac Surg. 2004;25(5):807-11. 21. Ueno T, Sakata R, Iguro Y, Yamamoto H, Ueno M, Ueno T, et al. Mid-term changes of left ventricular geometry and function after Dor, SAVE, and Overlapping procedures. Eur J Cardiothorac Surg. 2007;32(1):52-7. 22. Izumi Y, Magishi K, Ishikawa N, Kimura F. On-pump beatingheart coronary artery bypass grafting for acute myocardial infarction. Ann Thorac Surg. 2006;81(2):573-6. 23. Rastan AJ, Bittner HB, Gummert JF, Walther T, Schewick CV, Girdauskas E, et al., On-pump beating heart versus off-pump coronary artery bypass surgery - evidence of pump-induced myocardial injury. Eur J Cardiothorac Surg. 2005;27(6):1057-64. 24. Gomes WJ, Tavares GB, Jaramillo JI, Alves FA, Torrijos JMG, Catani R, et al. Off-pump grafting of the circumflex artery with pedicled retro-aortic right internal thoracic artery graft. Rev Bras Cir Cardiovasc. 2005;20(1):33-8. 25. Batista RJ, Santos JL, Takeshita N, Bocchino L, Lima PN, Cunha MA. Partial left ventriculectomy to improve left ventricular function in end-stage heart disease. J Card Surg. 1996;11(2):96-7.

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ORIGINAL ARTICLE

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Predictors of transfusion of packed red blood cells in coronary artery bypass grafting surgery Preditores de transfusão de concentrado de hemácias em cirurgia de revascularização miocárdica

Michel Pompeu Barros de Oliveira Sá1, Evelyn Figueira Soares2, Cecília Andrade Santos2, Omar Jacobina Figueiredo2, Renato Oliveira Albuquerque Lima2, Fábio Gonçalves de Rueda2, Rodrigo Renda de Escobar2, Alexandre Magno Macário Nunes Soares2, Ricardo de Carvalho Lima3

DOI: 10.5935/1678-9741.20110044

RBCCV 44205-1320

Abstract Objectives: Finding predictors of blood transfusion may facilitate the most efficient approach for the use of blood bank services in coronary artery bypass grafting procedures. The aim of this retrospective study is to identify preoperative and intraoperative patient characteristics predicting the need for blood transfusion during or after CABG in our local cardiac surgical service. Methods: 435 patients undergoing isolated first-time CABG were reviewed for their preoperative and intraoperative variables and analyzed postoperative data. Patients were 255 males and 180 females, with mean age 62.01 ± 10.13 years. Regression logistic analysis was used for identifying the strongest perioperative predictors of blood transfusion. Results: Blood transfusion was used in 263 patients (60.5%). The mean number of transfused blood products units per patient was 2.27 ± 3.07 (0-23) units. The total number of transfused units of blood products was 983. Univariate analysis identified age >65 years, weight <70 Kg, body mass index <25 Kg/m2, hemoglobin ≤ 13mg/dL, hematocrit ≤ 40% and ejection fraction <50%, use of cardiopulmonary bypass (CPB), not using an internal thoracic artery as a bypass, and multiple bypasses as significant predictors. The strongest predictors using multivariate analysis were hematocrit ≤ 40% (OR 2.58; CI 1.62-4.15; P<0.001), CPB use (OR 2.00; CI 1.27-3.17; P=0.003) and multiple bypasses (OR 2.31; CI 1.31-4.08; P=0.036).

Conclusions: The identification of these risk factors leads to better identification of patients with a grater probability of using blood, allocation blood bank resources and costeffectiveness use of blood products.

1. MD, MSc 2. MD 3. MD, MSc, PhD, ChM

Correspondence address: Michel Pompeu Barros de Oliveira Sá. Av. Engenheiro Domingos Ferreira, 4172/405 - Boa Viagem - Recife, Pernambuco, Brazil – ZIP Code: 51021-040. E-mail: michel_pompeu@yahoo.com.br

Work performed at Division of Cardiovascular Surgery of Pronto Socorro Cardiológico de Pernambuco – PROCAPE. University of Pernambuco – UPE.

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Descriptors: Blood Transfusion. Coronary Artery Bypass. Blood Cells.

Resumo Objetivos: Encontrar preditores de hemotransfusão pode facilitar a abordagem mais eficiente para utilização de serviços de banco de sangue em CRM. O objetivo deste estudo é identificar as características dos pacientes pré- e intraoperatórios que predizem necessidade de hemotransfusão durante ou após a revascularização miocárdica. Métodos: 435 pacientes submetidos à CRM isolada pela primeira vez, foram revisados para suas variáveis pré e intraoperatórias e analisados os dados pós-operatórios. Foram 255 homens e 180 mulheres, com idade média 62,01 ± 10,13 anos. Análise de regressão logística foi utilizada para identificar os preditores perioperatórios de hemotransfusão. Resultados: A hemotransfusão foi executada em 263 pacientes (60,5%). O número médio de unidades de hemoderivados por paciente foi de 2,27 ± 3,07 (0-23) unidades. O número total de unidades de hemoderivados foi de 983. A análise univariada identificou idade> 65 anos, peso <70 kg,

Article received on May 30th, 2011 Article accepted on September 16th, 2011

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IMC <25 kg/m2, hemoglobina ≤ 13 mg/dl, hematócrito ≤ 40% e fração de ejeção <50%, uso de circulação extracorpórea (CEC), não usar a artéria torácica interna como bypass, e múltiplos bypasses como preditores significativos. Os preditores mais fortes por meio de análise multivariada foram hematócrito ≤ 40% (OR 2,58; IC 1,624,15; P<0,001), o uso da CEC (OR 2,00; IC 1,27-3,17; P=0,003) e múltiplos bypasses (OR 2,31; IC 1,31-4,08; P=0,036).

Conclusões: A identificação desses fatores de risco leva a uma melhor identificação de pacientes com uma probabilidade maior de usar sangue, melhor alocação dos recursos do banco de sangue e o uso custo-efetivo dos hemoderivados.

INTRODUCTION Blood transfusion has been an important part of coronary artery bypass graft surgery (CABG) since its beginning [1]. Transfusion rates in cardiac surgery remain high despite major advances in perioperative blood conservation and institutions continue to vary significantly in their transfusion practices for CABG surgery [2-7]. Despite current reductions in transfusion requirements for patients undergoing CABG, many patients continue to require transfusion because of the increased number of acutely ill patients undergoing CABG [3], surgical complications for patients with repeat cardiac surgery procedures [4] and excessive bleeding among patients with coronary artery disease on anticoagulant therapy [2]. In addition, bypass systems and hypothermia further compromise hemostasis [1]. The overall goal for finding the predictors of blood transfusion in postoperative period is to facilitate the most efficient approach for the use of blood bank services in CABG procedures. The aim of this retrospective study is to identify preoperative (demographic and clinical) and intraoperative patient characteristics predicting the need for blood transfusion in coronary artery bypass grafting in our local cardiac surgical service.

Descritores: Transfusão de Sangue. Ponte de Artéria Coronária. Células Sanguíneas.

The independent variables were: age (years), age > 65 anos (yes or no) gender (male or female), systemic arterial hypertension (yes or no), diabetes mellitus (yes or no), smoking (yes or no), chronic obstructive pulmonary disease (yes or no), peripheral vascular disease (yes or no), weight (kilograms – Kg), weight ≤ 70kg, body mass index (BMI – kilograms per square meter – Kg/m2), BMI ≤ 25Kg/m2 (yes or no), obesity (BMI > 30Kg/m2, yes or no), hemoglobin (Hb) ≤ 13mg/dL (yes or no), hematocrit (Hct) ≤ 40% (yes or no), preoperative renal failure (defined as creatinine > 2.3mg/ dL or dialysis, yes or no), unstable angina (yes or no), class of New York Heart Association (NYHA I, II, III, IV), ejection fraction (EF - percentage measured by echocardiography), ejection fraction less than 50% (yes or no), stratification risk by EuroSCORE (standard and logistic), number of distal anastomoses (categorical and numerical), use of internal thoracic artery (ITA), type of surgery (on-pump or offpump), for the on-pump group we assessed cardiopulmary bypass time (CPB – minutes) and aortic cross clamp time (minutes). The dependent variable was blood transfusion during or after surgical procedure. Blood transfusion was reported both categorically (yes or no) and quantitatively (number of units transfused), defined as the use of red cell transfusion during operation and/or until discharge from the intensive care unit; preoperative blood usage was not evaluated.

METHODS Source Population After approval by the ethics committee of institution [8,9], we reviewed the records of patients undergoing CABG surgery at the Division of Cardiovascular Surgery of Pronto Socorro Cardiológico de Pernambuco (PROCAPE) from May 2007 to April 2010. We excluded patients whose records did not contain the necessary data concerning the variables to be studied, those who had a previous cardiac surgery and also those who underwent cardiac surgery concomitant CABG, leaving only isolated primary CABG surgery for the study. Study Design It was a retrospective cohort of exposed and nonexposed to certain factors (independent variables) with outcome (dependent variable).

Statistical Methods Data were analyzed using percentage and descriptive statistics measures: mean, median and standard deviation. The following testes were used: t-Student with equal or unequal variances (for parametric variables) and chi-square test or Fisher´s exact (as appropriate, for non-parametric variables). In the study of bivariate association between categorical variables, the values of the Odds Ratio (OR) and a confidence interval (CI) for this parameter with a reliability of 95.0% were obtained. Multivariate analysis was adjusted to a logistic regression model to explain the proportion of patients who received blood products that were significantly associated to the level of 20.0% (P <0.20). The model was constructed by a backward elimination procedure [10], remaining significant variables in the model of up to 10.0% (P<0.10). We selected only categorical variables to compose the 553

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regression model. By this procedure, we set the initial model involving all selected variables. At each step, one nonsignificant variable is removed and a new model is adjusted to a point that all other variables in the model have significant contribution to a particular level of significance chosen previously to explain the probability that a patient has used blood products. The process uses the same criterion to determine the significance (same P-value) and, each step, the variable with the smallest contribution to the model (or variable with the largest p-value) is removed and a new model is set with the remaining variables in the model. This procedure is repeated until no variable can be removed.

Through this model, OR values are estimated, according to the independent variables placed on the model. The level of significance in the decision of the statistical tests was 5.0%. The program used for data entry and retrieval of statistical calculations was SPSS (Statistical Package for Social Sciences) version 15.0. RESULTS Baseline Patients’ Characteristics (Table 1) During the studied period were identified 542 patients underwent CABG surgery. We excluded 42 patients

Table 1. Baseline Patients’ Characteristics Stratified by Blood Transfusion Blood Transfusion Yes (n=263) No (n=172) Pre-operative Characteristics Age (mean) 62.37 ± 9.68 61.47 ± 10.78 Age > 65 years 123 (46.8) 53 (30.8) Male 153 102 Weight (mean) 68.70 ±12.11 70.49 ± 12.22 Weight < 70 Kg 119 (45.2) 57 (33.1) BMI (Kg/m2) 26.40 ± 3.74 26.64 ± 3.90 BMI < 25Kg/m2 128 (48.7) 64 (37.2) Obesity (IMC >30Kg/m2) 26 (9.9) 42 (24.4) Hb < 13mg/dL 115 (43.7) 46 (26.7) Ht < 40% 156 (59.3) 59 (34.3) Hypertension 235 (89.3) 155 (90.1) Diabetes 106 (40.3) 72 (41.8) Smoking 106 (40.3) 65 (37.8) COPD 26 (9.9) 12 (7.0) Peripheral vascular disease 22 (8.4) 10 (5.8) Unstable angina 54 (20.5) 42 (24.4) NYHA class I 167 (63.5) 122 (70.9) II 40 (15.2) 13 (7.5) III 33 (12.5) 17 (9.9) IV 23 (8.8) 20 (11.7) Renal Failure 18 (6.8) 11 (6.4) Ejection Fraction (mean) 54.79 ± 12.00 56.42 ± 11.49 Ejection Fraction < 50% 81 (30.8) 42 (24.4) EuroSCORE (standard) 4.61 ± 2.46 4.06 ± 2.57 EuroSCORE (logistic) 4.55 ± 4.48 4.16 ± 4.98 Intra-operative characteristics On-pump 160 (60.8) 71 (41.3) CPB time (minutes) 102.46 ± 30.53 100.71± 27.82 Ao X time (minutes) 71.21 ± 23.88 69.16 ± 23.48 ITA 202 (76.8) 147 (85.5) Number of grafts (mean) 2.31 ± 0.79 2.12 ± 0.89 Number of grafts 1 33 (12.6) 48 (27.9) 2 115 (43.7) 60 (34.9) 3 or more 115 (43.7) 64 (37.2)

P Value 0.364 <0.001 0.815 0.133 0.011 0.516 0.018 0.811 <0.001 <0.001 0.798 0.747 0.600 0.293 0.319 0.339 0.061

0.854 0.161 0.036 0.027 0.041 <0.001 0.680 0.545 0.026 0.020 0.001

NOTE. Results in numbers (percentage) or mean ± standard deviation. BMI: body mass index; Hb: Hemoglobin; Ht: Hematocrit; COPD: chronic obstructive pulmonary disease; NYHA: New York Heart Association; ITA: at least one internal thoracic artery; CPB time: cardiopulmonary bypass time; Ao X time: aortic cross clamp time

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whose records did not contain the necessary data concerning the variables to be studied, 52 patients who had a previous cardiac surgery and also 13 patients who underwent cardiac surgery concomitant CABG, leaving 435 patients who underwent isolated primary CABG surgery for the study. In 172 (39.5%) patients, no blood transfusion was needed, and in 263 (60.5%) patients, at least 1 blood product unit was transfused. Of these, 125 (47.5%) patients received 1 to 2 units of blood products, 69 (26.3%) patients received 3 to 4 units of blood products, 33 (12.6%) patients received 5 to 7 units of blood products, and 33 (12.6%) patients received 7 or more of blood products. The mean number of transfused blood products units per patient was 2.27 ± 3.07 (0-23) units. The total number of transfused units of blood products was 983. Patients receiving blood products had higher EuroSCORE (both standard and logistic). Operative characteristics also were different between the two groups;

patients receiving blood products underwent on-pump more often, less use of ITA, higher mean number of grafts, and higher number of multiple grafts.

Table 2. Transfusion risk according to univariate analysis of perioperative variables associated with blood transfusion. Blood Transfusion Odds Ratio Confidence Interval Pre-operative Characteristics Age > 65 years 1.97 1.29-3.02 Weight < 70 Kg 1.67 1.10-2.54 BMI < 25Kg/m2 1.60 1.06-242 Ejection Fraction < 50% 1.58 1.01-2.50 Hb < 13mg/dL 2.13 1.38-3.30 Hct < 40% 2.79 1.84-4.25 Intra-operative characteristics On-pump 2.21 1.49-3.27 ITA 0.56 0.33-0.97 Number of grafts 1 1.00 2 2.61 1.47-4.64 3 or more 2.79 1.57-4.98 BMI: body mass index; Hb: Hemoglobin; Hct: Hematocrit

Univariate Analysis (Table 2) Univariate analysis revealed the following preoperative risk factors for receiving blood products: age > 65 years, weight < 70 Kg, BMI ≤ 25 Kg/m2, Hb ≤ 13mg/dL, Hct ≤ 40%, and ejection fraction < 50%. Operative risk factors revealed were the use of CPB, not using an ITA as a bypass, and multiple grafts. Multivariate Logistic Regression Analysis (Table 3) All preoperative risk factors identified with univariate analyses were entered into a multivariate logistic regression model. Only Hct ≤ 40% was identified as an independent preoperative risk factor for receiving blood units. When operative risk factors were also entered in the multivariate model, the following independent risk factors were identified: on-pump CABG and multiple grafts. DISCUSSION The use of allogeneic blood transfusion after coronary artery surgery is still high despite published transfusion guidelines and costly blood conservation strategies [11,12]. Readily available patient variables can predict patients at risk for transfusion [13]. Preoperative predictor variables may facilitate blood component management and improve the efficiency of ordering blood before operations for patients undergoing CABG surgeries in order to assist blood banks in improving responsiveness to clinical needs [1,14]. This study identifies the independent risk factors for the prediction of blood transfusion during or after CABG surgery in 435 patients. In this patient population, there was an overall transfusion rate of 39.6%. In the literature, percentages of 25% to 95% of patients receiving blood products after CABG surgery have been described. Stover et al. [6] suggested that this variability could not be explained by a difference in

Table 3. Transfusion risk according to multivariate regression logistic analysis of perioperative variables associated with blood transfusion. Blood Transfusion Odds Ratio Confidence Interval P-value Characteristics Hct < 40% 2.58 1.62-4.15 <0.001 On-pump 2.00 1.27-3.17 0.003 Number of grafts 0.036 1 1.00 2 1.86 1.01-3.47 3 or more 2.31 1.31-4.08 Hct: Hematocrit

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patient preoperative characteristics or the length of CPB or solely by the calculated perioperative blood loss. This difference appeared to be institution dependent; in some institutions, the use of blood products appeared excessive relative to the perioperative blood loss [6]. In disagreement with other studies, the present authors found no difference of blood transfusion rates between genders. Some studies point female sex as a predictive factor for blood transfusion [12-17]. The reason why female patients receive more blood transfusion has been extensively studied by Shevde et al. [17]. Their conclusion was that it remains unclear why female patients receive more blood transfusion but that it may interact with other factors determining the probability of transfusion like age, weight, and duration of surgery. In a systematic review involving 21 studies [18], blood transfusions were more frequently administered to adults who were older in age. In our study, we compared this variable numerically and categorically. We did not observed difference in numerical comparison between the two groups, but when we categorized in two other groups (>65 years or ≤ 65 years), blood transfusion was more often present in the >65 years group). Elmistekawy et al [19], in a prospective observational study including 105 patients undergoing isolated primary CABG, observed difference in both numerical and categorical comparison (using the same categorization we did). But as we, in multivariate analysis model, this variable was not an independent predictor for blood transfusion. In the present study, weight ≤ 70 Kg was a predictor (not independent) of blood transfusion. It was not observed any relationship with obesity (BMI ≥ 30 Kg/m2) or BMI ≤ 25 Kg/m2. Elmistekawy et al. [19] observed the same, justifying the choice for body weight (and not BMI) for analysis in most models owing to the fact that univariate analysis and multivariate analysis proved that weight was a stronger predictor for blood transfusion than BMI in their cohort. Scott et al. [15] studied impact of decreased body weight (≤ 83 Kg) were significant predictors of transfusion. Depressed left ventricular function (EF <50%) was a risk factor (not independent) for blood transfusion during or after CABG in the present studied population. Arora et al. [12], studying 3046 consecutive isolated CABG patients over 3 years to identify independent predictors of allogeneic blood product transfusion, showed that ejection fraction 0.40 or less was a strong predictor, including this variable in a validation of a prediction model tested in 2117 consecutive CABG patients. Al-Shammari et al. [20] reviewed the medical records of 159 consecutive primary CABG patients retrospectively to determine the perioperative factors associated with intraoperative blood transfusion. One of the significant factors associated with blood transfusion on their research

was three or more coronary bypass grafts constructed. In our study, we observed that the mean of distal anastomoses was higher in the blood transfusion group. We also identified that the more the patient needs more anastomoses, the more is the risk of blood transfusion after surgery, showing that the number of distal anastomoses is an independent predictor of the need of blood transfusion after CABG. Although we have seen that several variables showed some association with the need for blood transfusion during or after CABG in the univariate analysis, two of these proved to be the strongest and independent predictors of postoperative transfusion in our institution: on-pump surgery and Hct ≤ 40%. Cardiopulmonary bypass activates the complement and fibrinolytic cascade, contributing to postoperative bleeding [21]. In a previous study in our institution [22] involving 941 women, with the aim of comparing outcomes between on-pump and off-pump CABG, there were minor rates of hemorrhagic shock and also the reduction of need for blood transfusions in the off-pump CABG group in comparison with on-pump CABG group. Nuttall et al. [23] showed that off-pump CABG surgery reduces perioperative bleeding and is associated with an overall reduction in allogeneic transfusion requirement. The present results show that onpump surgery has a detrimental effect in postoperative blood transfusion (OR 2.00; P=0.003 in multivariate analysis). Although we have not found a statistically significant difference in time of exposure to CPB between the groups, this is something that probably has some influence on the need of blood products. Souza & Moitinho [24], in a study involving 101 patients undergoing cardiovascular surgery, showed that patients with CPB time over 120 minutes show a trend of greater need of hemotransfusion if compared to those with lower CBP time. They also verifyed that, regarding patients’ age, there was no important association between hemotransfusion need and surgery in an elderly patient. However, the association of surgery in elderly patients and CBP time superior to 120 minutes resulted in a larger postoperative use of blood products. Perhaps one way to minimize the impact of CPB in necessity of blood components transfusions is the application of techniques of hemoconcentration. Souza & Braile [25] developed a study to evaluate a technique of hemoconcentration during heart surgery with CPB with and without a hemoconcentrator and the necessity of blood components transfusion in patients. They verifyed that this technique of hemoconcentration used during on-pump heart surgery was efficacious in the removal of fluids and allowed a greater utilization of the blood remaining in the oxygenator and a lesser necessity of blood component transfusion. They also argued that, apart from reducing the demand from the blood banks and diminishing the costs,

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a reduction of blood transfusions could result in a reduction of postoperative complications and, in particular, of longterm mortality rates in patients submitted to on-pump heart surgery. Another techniques promise to become more used in the future to avoid blood loss and need of transfusion, [26-28], reducing the presence of a factor associated with increased morbidity and mortality in several studies [29-34]. Preoperative anemia is an independent risk factor for morbidity and mortality after cardiac operations, and specifically for coronary operations [35,36]. The consequence of low values of Hct before or during the operation is, of course, a higher risk of receiving allogeneic blood products during or after the operation. In fact, the preoperative Hct is the major determinant of transfusions in cardiac surgery [37,38]. In our study, Hct ≤ 40% was the strongest independent predictor for blood transfusion (OR 2.58; P<0.001 in multivariate analysis). We point to the following limitations of this study: it was an observational investigation in which unknown variables could have influenced final results; the retrospective design of this study is vulnerable to a lot of bias; some data were lacking (e.g. intra-operative and/or postoperative blood loss), making the results less accurate; the sample size is relatively small, which explains some variables found to be important predictors in larger studies (e.g. age, gender) were found not to be related to transfusion in this study; our institution does not have clinical protocols or clinical thresholds for transfusion during or after CABG, so there was no uniformity in the criteria for transfusion in all patients; this is a sample of the institution, so that patients were not operated by the same surgeon, but, by various existing teams in the hospital; we did not analyze the pre-operative use of anti-platelet drugs, which possibly should have some influence on the appearance of bleeding and therefore transfusions.

2. Surgenor DM, Wallace EL, Churchill WH, Hao SH, Chapman RH, Collins JJ Jr. Red cell transfusions in coronary artery bypass surgery (DRGs 106 and 107). Transfusion. 1992;32(5):458-64.

CONCLUSION In this study, both pre-operative and intra-operative risk factors influencing postoperative blood transfusion were identified. Only the Hct ≤ 40%, use of CPB and the number of distal anastomoses were independent risk factors for blood transfusion involving the surgery.

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3. Goodnough LT, Johnston MF, Toy PT. The variability of transfusion practice in coronary artery bypass surgery. Transfusion Medicine Academic Award Group. JAMA. 1991;265(1):86-90. 4. Hasley PB, Lave JR, Hanusa BH, Arena VC, Ramsey G, Kapoor WN, et al. Variation in the use of red blood cell transfusions. A study of four common medical and surgical conditions. Med Care. 1995;33(11):1145-60. 5. Kytola L, Nuutinen L, Myllyla G. Transfusion policies in coronary artery bypass: a nationwide survey in Finland. Acta Anaesthesiol Scand. 1998;42(2):178-83. 6. Stover EP, Siegel LC, Parks R, Levin J, Body SC, Maddi R, et al. Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology. 1998;88(2):327-33. 7. Shander A, Moskowitz D, Rijhwani TS. The safety and efficacy of “bloodless” cardiac surgery. Semin Cardiothorac Vasc Anesth. 2005;9(1):53-63. 8. Sá MPBO, Lima RC. Research Ethics Committee. Mandatory necessity. Requirement needed. Rev Bras Cir Cardiovasc. 2010;25(3):III-IV. 9. Lima SG, Lima TAG, Macedo LA, Sá MPBO, Vidal ML, Gomes RAF, et al. Ethics in research with human beings: from knowledge to practice. Arq Bras Cardiol. 2010;95(3):289-94. 10. Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research: principles and quantitative methods. New York: Nostrand Reinhold; 2001. 11. Lo Cicero J 3rd, Massad M, Gandy K, Sanders JH Jr, Hartz RS, Frederiksen JW, et al. Aggressive blood conservation in coronary artery surgery: impact on patient care. J Cardiovasc Surg (Torino). 1990;31(5):559-63. 12. Arora RC, Légaré JF, Buth KJ, Sullivan JA, Hirsch GM. Identifying patients at risk of intraoperative and postoperative transfusion in isolated CABG: toward selective conservation strategies. Ann Thorac Surg. 2004;78(5):1547-54. 13. Magovern JA, Sakert T, Benckart DH, Burkholder JA, Liebler GA, Magovern GJ Sr, et al. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg. 1996;61(1):27-32. 14. Cosgrove DM, Loop FD, Lytle BW, Gill CC, Golding LR, Taylor PC, et al. Determinants of blood utilization during myocardial revascularization. Ann Thorac Surg. 1985;40(4):380-4.

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15. Scott BH, Seifert FC, Glass PS, Grimson R. Blood use in patients undergoing coronary artery bypass surgery: impact of cardiopulmonary bypass pump, hematocrit, gender, age, and body weight. Anesth Analg. 2003;97(4):958-63.

modified ultrafiltration on pulmonary function and transfusion requirements in patients underwent coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2010; 25(1):59-65.

16. Karkouti K, Cohen MM, McCluskey SA, Sher GD. A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass graft surgery. Transfusion. 2001;41(10):1193-203.

28. Benfatti RA, Carli AF, Silva GVR, Dias AEMÁS, Goldiano JA, Pontes JCDV. Epsilon-aminocaproic acid influence in postoperative bleeding and hemotransfusion in mitral valve surgery. Rev Bras Cir Cardiovasc. 2010;25(4)510-5.

17. Shevde K, Pagala M, Kashikar A, Tyagaraj C, Shahbaz N, Iqbal M, et al. Gender is an essential determinant of blood transfusion in patients undergoing coronary artery bypass graft procedure. J Clin Anesth. 2000;12(2):109-16.

29. Dorneles CC, Bodanese LC, Guaragna JCVC, Macagnan FE, Coelho JC, Borges AP, et al. The impact of blood transfusion on morbidity and mortality after cardiac surgery. Rev Bras Cir Cardiovasc 2011;26(2):222-9.

18. Shehata N, Naglie G, Alghamdi AA, Callum J, Mazer CD, Hebert P, et al. Risk factors for red cell transfusion in adults undergoing coronary artery bypass surgery: a systematic review. Vox Sang. 2007;93(1):1-11.

30. Magedanz EH, Bodanese LC, Guaragna JCVC, Albuquerque LC, Martins V, Minossi SD, et al. Risk score elaboration for mediastinitis after coronary artery bypass grafting. Rev Bras Cir Cardiovasc. 2010;25(2):154-9.

19. Elmistekawy EM, Errett L, Fawzy HF. Predictors of packed red cell transfusion after isolated primary coronary artery bypass grafting – The experience of a single cardiac center: A prospective observational study. J Cardiothor Surg. 2009;4:20.

31. Sá MPBO, Soares EF, Santos CA, Figueiredo OJ, Lima ROA, Escobar RR, et al. Risk factors for mediastinitis after coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc 2011;26(1):27-35.

20. Al-Shammari F, Al-Duaij A, Al-Fadhli J, Al-Sahwaf E, Tarazi R. Blood component transfusion in primary coronary artery bypass surgery in Kuwait. Med Princ Pract. 2005;14(2):83-6.

32. Anderson AJPG, Barros Neto FXR, Costa MA, Dantas LD, Hueb AC, Prata MF. Predictors of mortality in patients over 70 years-old undergoing CABG or valve surgery with cardiopulmonary bypass. Rev Bras Cir Cardiovasc. 2011;26(1):69-75.

21. Hijazi EM. Is it time to adopt beating-heart coronary artery bypass grafting? A review of literature. Rev Bras Cir Cardiovasc 2010;25(3):393-402. 22. Sá MPBO, Lima LP, Rueda FG, Escobar RR, Cavalcanti PEF, Thé ECS, et al. Comparative study between on-pump and offpump coronary artery bypass graft in women. Rev Bras Cir Cardiovasc.2010;25(2):238-44. 23. Nuttall GA, Erchul DT, Haight TJ, Ringhofer SN, Miller TL, Oliver WC Jr, et al. A comparison of bleeding and transfusion in patients who undergo coronary artery bypass grafting via sternotomy with and without cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2003;17(4):447-51. 24. Souza HJB, Moitinho RF. Strategies to reduce the use of blood components in cardiovascular surgery. Rev Bras Cir Cardiovasc. 2008;23(1):53-9. 25. Souza DD, Braile DM. Assessment of a new technique of hemoconcentration and the necessities of blood derivates for transfusion in patients submitted to heart surgery using cardiopulmonay bypass. Rev Bras Cir Cardiovasc. 2004;19(3):287-94. 26. Chalegre ST, Salerno PR, Salerno LMVO, Melo ARS, Pinheiro AC, Frazão CS, et al. Vacuum-assited venous drainage in cardiopulmonary bypass and need of blood transfusion: experience of service. Rev Bras Cir Cardiovasc. 2011; 26(1):122-7. 27. Torina AG, Petrucci O, Oliveira PPM, Severino ESBO, Vilarinho KAS, Lavagnoli CFR, et al. The effects of

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33. Sá MPBO, Soares EF, Santos CA, Figueiredo OJ, Lima ROA, Escobar RR, et al. Validation of MadeganzSCORE as a predictor of mediastinitis after coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(3):386-92. 34. Sá MPBO, Soares EF, Santos CA, Figueiredo OJ, Lima ROA, Escobar RR, et al. Skeletonized left internal thoracic artery is associated with lower rates of mediastinitis in diabetic patients. Rev Bras Cir Cardiovasc. 2011;26(2):183-9. 35. Bell ML, Grunwald GK, Baltz JH, McDonald GO, Bell MR, Grover FL, et al. Does preoperative hemoglobin independently predict short-term outcomes after coronary artery bypass graft surgery? Ann Thorac Surg. 2008;86(5):1415-23. 36. Karkouti K, Wijeysundera DN, Beattie WS; Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation. 2008;117(4):478-84. 37. Alghamdi AA, Davis A, Brister S, Corey P, Logan A. Development and validation of Transfusion Risk Understanding Scoring Tool (TRUST) to stratify cardiac surgery patients according to their blood transfusion needs. Transfusion. 2006;46(7):1120-9 38. Ranucci M, Castelvecchio S, Frigiola A, Scolletta S, Giomarelli P, Biagioli B. Predicting transfusions in cardiac surgery: the easier, the better: the Transfusion Risk and Clinical Knowledge score. Vox Sang. 2009;96(4):324-32.

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ORIGINAL ARTICLE

Late outcomes of mitral repair in rheumatic patients Resultados tardios da plastia mitral em pacientes reumáticos

Elaine Soraya Barbosa de Oliveira Severino1, Orlando Petrucci2, Karlos Alexandre de Souza Vilarinho3, Carlos Fernando Ramos Lavagnoli4, Lindemberg da Mota Silveira Filho3, Pedro Paulo Martins de Oliveira5, Reinaldo Wilson Vieira6, Domingo Marcolino Braile7

DOI: 10.5935/1678-9741.20110045

RBCCV 44205-1321

Abstract Introduction: The long-term results after surgical repair of rheumatic mitral valve remain controversial in literature. Our aim was to determine the predictive factors which impact the long-term results after isolated rheumatic mitral valve repair and to evaluate the effect of those factors on reoperation and late mortality. Methods: One hundred and four patients with rheumatic valve disease who had undergone mitral valve repair with or without tricuspid valve annuloplasty were included. All patients with associated procedures were excluded. The predictive variables for reoperation were assessed with Cox regression and Kaplan Meier survival curves. Results: The mean follow-up time was 63 ± 39 months (CI 95% 36 to 74 months). The functional class III and IV was observed in 65.4% of all patients. The posterior ring annuloplasty was performed in 33 cases, comissutoromy in

21 cases, and comissurotomy with posterior ring annuloplasty in 50 patients. There was no operative mortality. The late mortality was 2.8% (three patients). The late reoperation was associated with residual mitral valve regurgitation after surgery (P<0.001), pulmonary hypertension at the preoperative time (P<0.001), age (P<0.04) and functional class at the post-operative time (P<0.001). We observed freedom from reoperation rates at 5 and 10 years of 91.2 ± 3.4% and 71.1 ± 9.2%, respectively. Conclusion: Repair of mitral valve in rheumatic valve disease is feasible with good long-term outcomes. Preoperative pulmonary hypertension, residual mitral valve regurgitation after surgery, age and functional class are predictors of late reoperation.

1. Master’s Degree in Surgery. Assistant Physician of the Discipline of Cardiac Surgery at State University of Campinas (Unicamp), Campinas, SP, Brazil. 2. Postdoctoral Student; Assistant Physician at FCM/Unicamp, Campinas, SP, Brazil. 3. Master’s Degree in Surgery. Assistant Physician of the Discipline of Cardiac Surgery at State University of Campinas (Unicamp), Campinas, SP, Brazil. 4. Assistant Physician of the Discipline of Cardiac Surgery at State University of Campinas (Unicamp), Campinas, SP, Brazil. 5. Full Professor in Surgery; Assistant Professor at FCM/Unicamp, Campinas, SP, Brazil. 6. Full Professor in Surgery; Coordinator in Cardiac Surgery Discipline at Unicamp, Campinas, SP, Brazil. 7. Full Professor in Surgery; Editor-in-Chief of the Brazilian Journal

of Cardiovascular Surgery/Pro-rector in Postgraduation at Faculty of Medicine in São José do Rio Preto (Famerp). Full Professor at Unicamp, Campinas, SP, Brazil.

Descriptors: Mitral valve. Mitral valve prolapse. Mitral valve insufficiency. Mitral valve stenosis.

This study was carried out at State University of Campinas (Unicamp), Campinas, SP, Brazil. Correspondence address: Orlando Petrucci. Rua João Baptista Geraldi, 135 – Campinas, SP, Brazil – Zip Code: 13085-020 E-mail: petrucci@cardiol.br Article received on April 4th, 2011 Article accepted on October 9th, 2011

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Resumo Introdução: Os resultados tardios da plastia mitral em pacientes reumáticos são controversos na literatura. Objetivo: Estudo observacional e prospectivo que avalia os resultados tardios e identifica os fatores associados à reoperação e à mortalidade em pacientes reumáticos submetidos à plastia da valva mitral. Métodos: Incluídos somente os pacientes com valvopatia mitral reumática submetidos a plastia, com insuficiência tricúspide associada ou não. Excluídos os pacientes com outros procedimentos associados. Um total de 104 pacientes foi estudado. Sobrevida e reoperação foram avaliadas pela analise de Kaplan-Meier e regressão logística de Cox. Resultados: O tempo de seguimento foi de 63 ± 39 meses (IC 95% 36 a 74 meses). A classe funcional III e IV estava presente em 65,4% dos pacientes no pré-operatório. Foram

realizadas 33 plastias do anel posterior, 21 comissurotomias, 50 comissurotomias e plastias do anel posterior. Não houve mortalidade operatória e a tardia foi de três (2,8%) pacientes. A reoperação tardia esteve associada à insuficiência mitral residual no pós-operatório (P<0,001), presença de hipertensão pulmonar no pré-operatório (P< 0,01), idade (P<0,04) e classe funcional no pós-operatório (P<0,001). No seguimento, a probabilidade de estar livre de reoperação com 5 e 10 anos foi de 91,2 ± 3,4% e 71,1 ± 9,2%, respectivamente. Conclusão: Os resultados tardios do reparo da valva mitral em pacientes reumáticos têm fatores associados à reoperação. O reparo da valva mitral reumática é seguro e com ótima sobrevida a longo prazo.

INTRODUCTION The mitral valve repair is the procedure of choice in the cause degenerative mitral valve disease, it has lower rate of reoperation, thromboembolism and valve infection, when compared to mitral valve replacement [1]. Rheumatic heart disease is the leading cause of mitral valve disease in the developing world, including Brazil. The mitral valve repair in rheumatic disease is technically more difficult, and the outcomes may be interfered with by new exacerbations. The quality and long-term results in rheumatic mitral valve disease are controversial [1,2]. The aim of this study was to assess factors associated with reoperation and mortality in patients undergoing only conservative procedures in rheumatic mitral valve cause. We aim also to assess the effectiveness of this procedure in this population. METHODS After approval by the Research Ethics Committee and registration at National Commission on Ethics in Research (CONEP), we performed a cohort study in patients undergone surgery between January 1994 and December 2005, when there were 700 heart valve surgeries. The study included patients with rheumatic mitral valve disease submitted to the first procedure in mitral valve repair. Patients with or without tricuspid regurgitation were also included in the study. Exclusion criteria were: procedures associated with mitral valve repair, such as aortic valve replacement or coronary artery 560

Descritores: Valva mitral. Prolapso da valva mitral. Insuficiência da valva mitral. Estenose da valva mitral.

bypass grafting. Patients with prior surgery of mitral valve repair were also excluded. The surgeries were performed by median sternotomy with bicaval cannulation and normothermic cardiopulmonary bypass. Low voolume warm blood cardioplegia was used. The mitral valve was accessed through the left atriotomy through the interatrial sulcus. As intraoperative assessment, we applied the techniques of mitral valve repair, including mitral valve repair with flexible ring (Braile Biomedica®, São José do Rio Preto, Brazil), commissurotomy combined with mitral valve repair or commissurotomy. During this period, patients underwent surgery by five different surgeons at a single institution. The intraoperative echocardiogram was not performed in all cases. The demographics of patients, pre- and postoperative echocardiographic assessments, functional class, according to the New York Heart Association (NYHA), and mortality were obtained retrospectively. Follow-up was considered as the last visit at the institution. Statistical Analysis Continuous variables were expressed as mean with standard deviation. The discrete variables were described by percentage. We used the Kolmogorov-Smirnov test for the detection of a normal sample, and then used the Student’s t test or Wilcoxon test for paired samples when appropriate. Survival and reoperation were assessed by Kaplan-Meier and proportional hazards regression using the Cox stepwise method. We used the software Medcalc 4.0 (Brussels, Belgium). The P value of <0.05 was considered significant.

Severino ESBO, et al. - Late outcomes of mitral repair in rheumatic patients

RESULTS We obtained data from 104 patients. The mean followup was 63 ± 39 months (95% CI 36 to 74 months), ranging from 3 to 130 months. There was predominance of females (78.8%), mean age 32.73 ± 14.74 years. Pure mitral insufficiency was present in 35.7% of patients, pure stenosis in 27.8% and mixed lesions in 36.5%. Functional class III and IV (NYHA) were observed in 65.4% of patients preoperatively. Pre- and postoperative cchocardiographic data are shown in Table 1. We observed that there was reduction of left atrial size and ejection fraction and functional class improvement, all these parameters was statistically significant. 33 plasties were performed using ring, 21 commissurotomies and 50 commissurotomy and mitral ring.

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There was no operative mortality. The tricuspid valvuloplasty was performed concomitantly in 12 patients, all with the use of flexible ring (Braile Biomedica ®), according to the technique previously described [4]. There were no deaths until hospital discharge. In the follow-up, patients free from reoperation with five and 10 years were 91.2 ± 3.4% and 71.1 ± 9.2%, respectively (Figure 1). One patient died 90 months after surgery with pulmonary embolism caused by chronic myeloid leukemia. Another patient underwent mitral valve replacement at 77 months, and 11 months after surgery showed thrombosis of the mitral prosthesis. The third patient died of unknown causes. The survival rate with five and 10 years at follow-up was 99.0 ± 0.1% and 92.1 ± 0.04%, respectively (Figure 2).

Table 1. Pre-and postoperative echocardiographic data.

Left atrium (mm) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) LV ejection fraction (%) Functional class

Preoperative 52.50 ± 9.73 50.91 ± 10.12 32.00 ± 7.59 70.59 ± 9.95 3.0 ± 0.9

Postoperative* 48.75 ± 8.81 48.91± 7.66 31.00 ± 7.76 65.30 ± 9.91 1.0 ± 0.8

P Value < 0.001 0.035 0.215 < 0.001 < 0.001

*Average time of postoperative echocardiogram: 54,32 ± 12,45 months

Fig. 1 – Actuarial curve with patients freedom from reoperation. Values with 95% of confidence interval. Patients at risk demonstrated in different periods of follow-up.

Fig. 2 - Actuarial survival curve with confidence interval of 95%. Patients at risk demonstrated in different periods of observation.

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Table 2. Pre-and postoperative factors associated with the risk of reoperation during follow-up.

Variable Postoperative functional class Preoperative Pulmonary Hypertension Age Postoperative mitral regurgitation

OR 6.68 2.03 1.1 4.6

During follow-up, 12 patients underwent reoperation, with a mean interval to reoperation of 61 months, ranging between 27 and 116 months. Reoperated patients had mitral regurgitation (n = 5), mitral stenosis (n = 2), mitral lesion (n = 3), mitral stenosis and aortic regurgitation concomitantly (n = 2). In regression analysis with the Cox proportional hazards using the stepwise method, were found as independent predictors of reoperation the variables listed in Table 2, with respective odds ratio (OR). In this analysis, we used the clinical and echocardiographic variables. DISCUSSION The mitral valve repair is the procedure of choice in patients with mitral regurgitation caused by degenerative disease, where the techniques employed have lower rates of morbidity and mortality and good long-term survival, with most of the patients free of reoperation and/or thromboembolic complications [5]. However, the application of these techniques in rheumatic valve disease, even when feasible by valve morphology, is still controversial in the literature, with controversial results [3,4,6,7]. One of the limiting factors for the repair in rheumatic disease is the evolutionary character of valve degeneration. Duran et al. [5], dividing patients undergoing mitral valve repair by age, observed a greater chance of valve repair in patients younger than 20 years, compared with patients between 21-40 and above 40 years. However, those under the age of 20 years had a higher risk of reoperation when compared to patients with more than 20 years of age. This result was also described in Brazilian study, performed by Pomerantzeff et al. [8], where the cutoff age was 16 years. Another related factor was the moment of surgical indication. The earlier the surgery, the lower the commitment of the valve or subvalvular apparatus, less distortion of ventricular geometry and, consequently, the greater the chances of successful functional repair, and preservation of ventricular function. We obtained an independent predictor of patient age at surgery, ie, the older the patient, increases his chance of reoperation, which makes sense because these patients have their subvalvar already well 562

95% Confidence interval (OR) 2.3 to 19.37 1.15 to 3.54 1.00 to 1.11 2.19 to 9.62

P Value <0.001 0.014 0.042 <0.001

lesioned, the functional outcome of plasty can be compromised. Another decisive factor in the choice between repair or valve replacement are the results of the use of prostheses. Yau et al. [10], in a comparative study of repair, metal prostheses and bioprostheses, identified the repair as independent risk factor for longer survival for cardiac death, despite the lower survival free of reoperation for valve repair compared to the use of metallic prostheses. Reoperation was not a risk factor for mortality. In this study, the mortality rate was zero. One of the factors contributing to this mortality was the fact we have not included plasties combined with other procedures such as aortic valve replacement or coronary artery bypass grafting. We think that these procedures could be an associated factor that hinders any analysis on the evolution of these patients. The aim of this study was to study only the effect of conservative procedures in rheumatic mitral valve. The results of postoperative echocardiography can demonstrate good results with the repair in the short term, as already shown in other national studies [4]. The presence of mild regurgitation in the postoperative period does not seem to worsen the clinical outcome of these patients [9]. The moderate and severe mitral regurgitation, when detected at follow-up proved to be an independent risk factor for reoperation with an odds ratio of 4.6, ie, following mitral regurgitation increases the risk of reoperation in almost 5 times. This is corroborated by previous study of literature, with patients similar to this study [3,7,8,12,15]. The technique used in our series was described by Braile et al. [2] utilizing a malleable bovine pericardium prosthesis, which is strong and early endothelized without thromboembolic events. When comparing pre- and postoperative echocardiographic data, considering the systolic and diastolic diameters and left ventricular ejection fraction, we observed that there was a worsening of the ejection fraction. We believe it is an adaptation of the left ventricle after the repair, as the valve became competent. In this sample, 80% of patients had pure mitral insufficiency or other associated injuries, with the long-

Severino ESBO, et al. - Late outcomes of mitral repair in rheumatic patients

Rev Bras Cir Cardiovasc 2011;26(4):559-64

term ventricular remodeling. The ejection fraction alone can not lead us to infer a worsening of the patient. This is not confirmed when we assessed the patients’ functional class during follow-up, with overall improvement. The assessment of ejection fraction preoperatively may have been overestimated by the presence of mitral regurgitation, which could explain the worsening of the ejection fraction postoperatively. There was significant improvement during follow-up, with concordance with other studies in the literature [3-5]. Most studies reported significant improvement in functional class after valve procedure, either valve repair or prosthesis replacement [3,4,10]. The presence of heart failure postoperatively was another independent risk factor, which makes perfect sense. Independent factor not previously identified in the literature was the presence of pulmonary hypertension measured by echocardiography preoperatively and is considered moderate when the mean pulmonary artery pressure was measured as greater than 45 mmHg. This factor led to almost twice the risk of reoperation in these patients, this data can serve as a starting point for closer follow-up in such patients. In relation to valve morphology, few studies were able to identify a type of injury as a predictor, but it seems that the double lesion present behavior worse for late failure of valve repair [13-15]. We could not identify any variable in the anatomy of the valve that was a predictor of reoperation. Chauvaud et al. [16] in a large series studying 951 patients with mitral regurgitation of rheumatic etiology and follow-up of approximately 25 years, demonstrated probability of being free from reoperation of 55% after ten years of follow-up. In our series, at the end of 10 years of follow-up, the probability of patients being free from reoperation was 70%, but we should note that only 5 patients were at risk during this period of observation. Another important observation is that in the series of Chauvaud et al. patients with pure mitral insufficiency were included, unlike our series, and included patients with mitral stenosis, mitral regurgitation and mitral lesion. Late mortality in this series was 3.8%, consistent with the literature [4,10]. However, the deaths were not related to heart disease in itself but a result of associated neoplastic illness, one due to a thromboembolic complication after prosthetic valve reoperation, and the last patient, without apparent cause. The limitations of our study are related to its retrospective nature. Medical treatment was not standardized, it was noted the presence of atrial fibrillation in the pre- and postoperative period. In conclusion, the results of mitral valve repair in rheumatic patients, when feasible from a technical standpoint and valve morphology, have satisfactory results

in the long term, and always appear as an alternative in surgical treatment of this disease. The presence of pulmonary hypertension preoperatively should draw attention to a closer follow-up of these patients due to the long-term risk of reoperation. Older patients with rheumatic valvular heart disease have increased chance of being reoperated when the valve is very committed. Patients who in the postoperative follow-up present worsening of mitral or functional class must also be followed more often because they have increased risk for reoperation.

REFERENCES 1. Sarris GE, Cahill PD, Hansen DE, Derby GC, Miller DC. Restoration of left ventricular systolic performance after reattachment of the mitral chordae tendineae. The importance of valvular-ventricular interaction. J Thorac Cardiovasc Surg. 1988;95(6):969-79. 2. Braile DM, Ardito RV, Pinto GH, Santos JLV, Zaiantchick M, Souza DRS, et al. Plástica mitral. Rev Bras Cir Cardiovasc. 1990;5(2):86-98. 3. David TE, Armstrong S, Sun Z, Daniel L. Late results of mitral valve repais for mitral regurgitation due to degenerative disease. Ann Thorac Surg. 1993;56(1):7-12. 4. Petrucci Junior O, Oliveira PPM, Silveira LM, Passos FM, Vieira RW, Braile DM. Resultados a médio prazo de anuloplastia com órtese maleável de pericárdio bovino na insuficiência mitral reumática. Rev Bras Cir Cardiovasc. 1999;14(2):105-8. 5. Duran CM, Gometza B, Saad E. Valve repair in rheumatic mitral disease: an unsolved problem. J Card Surg. 1994;9(2 Suppl):282-5. 6. Pomerantzeff PMA, Brandão CMA, Cauduro P, Puig LB, Grinberg M, Tarasoutchi F, et al. Biopróteses de pericárdio bovino Fisics-Incor: 15 anos. Rev Bras Cir Cardiovasc. 1997;12(4):359-66. 7. Gillinov AM, Cosgrove DM, Blackstone EH, Diaz R, Arnold JH, Lytle BW, et al. Durability of mitral valve repair for degenerative disease. J Thorac Cardiovasc Surg. 1998;116(5):734-43.

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8. Pomerantzeff PMA, Brandão CMA, Faber CM, Grinberg M, Cardoso LF, Tarasoutchi F, et al. Plástica da valva mitral em portadores de febre reumática. Rev Bras Cir Cardiovasc. 1998;13(3):211-5.

13. Fernandez J, Joyce DH, Hirschfeld K, Chen C, Laub GW, Adkins MS, et al. Factors affecting mitral valve reoperation in 317 survivors after mitral valve reconstruction. Ann Thorac Surg. 1992;54(3):440-7.

9. Fix J, Isada L, Cosgrove D, Miller DP, Savage R, Blum J, et al. Do patients with less than ‘echo-perfect’ results from mitral valve repair by intraoperative echocardiography have a different outcome? Circulation. 1993;88(5 Part 2):II39-48.

14. Pomerantzeff PM, Brandão CM, Leite Filho OA, Guedes MA, Silva MF, Grinberg M, et al. Mitral valve repair in rheumatic patients with mitral insuficiency: twenty years of techniques and results. Rev Bras Cir Cardiovasc. 2009;24(4):485-9.

10. Yau TM, El-Ghoneimi YA, Armstrong S, Ivanov J, David TE. Mitral valve repair and replacement for rheumatic disease. J Thorac Cardiovasc Surg. 2000;119(1):53-60. 11. Provenzano Junior SC, Sá MPL, Bastos ES, Azevedo JAP, Murad H, Gomes EC, et al. Plastia valvar mitral na doença cardíaca reumática e degeneração mixomatosa: estudo comparativo. Rev Bras Cir Cardiovasc. 2002;17(1):24-34. 12. Shuhaiber J, Anderson RJ. Meta-analysis of clinical outcomes following surgical mitral valve repair or replacement. Eur J Cardiothorac Surg. 2007;31(2):267-75.

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15. Kalil RAK, Cunha B, Albrecht AS, Moreno P, Abrahão R, Prates PR, et al. Comparative results of maze procedure for chronic atrial fibrillation in rheumatic and degenerative mitral valve disease. Rev Bras Cir Cardiovasc. 1999;14(3):191-9. 16. Chauvaud S, Fuzellier JF, Berrebi A, Deloche A, Fabiani JN, Carpentier A. Long-term (29 years) results of reconstructive surgery in rheumatic mitral valve insufficiency. Circulation. 2001;104(12 Suppl 1):I-12-5.

ORIGINAL ARTICLE

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Leonardo Secchin Canale1, Alexandre Siciliano Colafranceschi2, Andrey José Oliveira Monteiro3, Bruno Miranda Marques4, Clara Secchin Canale5, Ernesto Chavez Koehler4, Fernando Eugênio dos Santos Cruz Filho5

DOI: 10.5935/1678-9741.20110046 Abstract Objective: To analyze the effectiveness of surgical treatment of atrial fibrillation (AF) using bipolar radiofrequency ablation during mitral valve procedures of rheumatic etiology in heart surgery. Methods: We retrospectively reviewed medical registries of 53 patients submitted to atrial ablation with bipolar radiofrequency energy during mitral valve surgery. Thirty four (64%) patients were women and the age varied from 27 to 72 years old (average: 49.3 ± 10.7 years). Aortic and/or tricuspid procedures were also present in 36 (68%) patients. Average time of reported atrial fibrillation was 41 months (from 3 to 192 months). Type of AF was classified as: paroxysmal in 8 patients, persistent in 3, permanent in 42. Left atrium had an average size of 52.9 ± 8.5 mm. The surgeries in these series were: 47 mitral valve replacements and 6 mitral valve repairs. Eletrocardiografic follow up was 83% complete in 14 months. Data from 24h Holter were explored. Results: Seven (13%) perioperative deaths were observed and survival after 14 months was 87%. Observed heart rhythm

1. Resident in Cardiac Surgery at National Institute of Cardiology, Rio de Janeiro, RJ, Brazil. 2. PhD; Head of the Surgical Procedures Division at National Institute of Cardiology, Rio de Janeiro, RJ, Brazil. 3. Head of the Pediatric Cardiac Surgery at National Institute of Cardiology, Rio de Janeiro, RJ, Brazil. 4. Cardiac Surgeon at National Institute of Cardiology, Rio de Janeiro, RJ, Brazil. 5. Medicine Student at Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. 6. Head of the Arrhythmology at National Institute of Cardiology, Rio de Janeiro, RJ, Brazil.

RBCCV 44205-1322 after 1 year of surgery was sinus rhythm in 25 (66%) patients, AF in 7 (18%), flutter in 7 (13%), junctional in 1 (3%). Conclusion: Bipolar radiofrequency ablation in patients submitted to mitral valve surgery of rheumatic etiology is effective in converting to sinus rhythm in 68% of patients after 14 months. Descriptors: Cardiovascular surgical procedures. Mitral valve. Rheumatic heart disease. Atrial fibrillation. Ablation techniques.

Resumo Objetivo: Avaliar a eficácia do tratamento cirúrgico da fibrilação atrial (FA) utilizando ablação com radiofrequência bipolar durante cirurgia cardíaca de procedimentos mitrais de etiologia reumática. Métodos: Foram avaliados, retrospectivamente, os prontuários e exames de 53 pacientes submetidos à cirurgia valvar mitral, com ou sem cirurgia tricúspide ou aórtica associada, em que foi realizada ablação de FA utilizando

This study was carried out at National Institute of Cardiology, Rio de Janeiro, RJ, Brazil. Correspondence address: Leonardo Secchin Canale Rua das Laranjeiras, 374 – Laranjeiras – Rio de Janeiro, RJ, Brazil – Zip Code: 22240-006 E-mail: leonardo.canale@gmail.com

Article received on August 7th, 2011 Article accepted on September 27th, 2011

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radiofrequência bipolar. Trinta e quatro (64%) pacientes eram mulheres e a idade variou de 27 a 72 anos (média: 49,3 anos ± 10,7 anos). O tempo médio de FA relatado foi de 41 meses (variou de 3 a 192 meses). O tipo de FA apresentado foi: paroxística em oito pacientes, persistente em três, permanente em 42. O átrio esquerdo apresentava tamanho médio de 52,9 ± 8,5 mm. As cirurgias realizadas foram: 47 trocas de valva mitral e seis plastias mitrais. O seguimento eletrocardiográfico foi completo em 83% dos pacientes, ao final de 14 meses. Informações adicionais oriundas de Holter 24h foram exploradas. Resultados: Ocorreram sete (13%) óbitos per-operatórios

e a sobrevida após 14 meses foi de 87%. Os ritmos cardíacos encontrados após um ano de cirurgia foram: sinusal em 25 (66%) pacientes, FA em sete (18%), Flutter em cinco (13%), Juncional em um (3%). Conclusão: O uso de radiofrequência bipolar para tratamento de FA em pacientes submetidos à cirurgia valvar mitral de origem reumática é efetivo no controle da arritmia em 68% dos pacientes, após 14 meses.

INTRODUCTION Atrial fibrillation (AF) may lead to significant morbidity and is associated with increased mortality [1]. While nonvalvular AF is associated with increased risk of stroke two to seven times, AF associated with valvular disease increases this risk by 17 times [2]. Up to 10% of patients undergoing cardiac surgery and 45% of those undergoing surgical procedures for rheumatic mitral valve disease are associated with AF [3]. Surgical treatment of atrial fibrillation concomitant to the primary cardiac procedure is now widely accepted as safe and effective [4]. Despite the excellent results achieved when treating patients with degenerative mitral valve and other surgeries, AF associated with rheumatic mitral valve disease is less studied. The aim of this study is to report the mid-term clinical results and heart rate of patients undergoing bipolar radiofrequency ablation (RFB) concomitant with mitral valve surgery of rheumatic origin at National Institute of Cardiology, Rio de Janeiro. METHODS Between January 2008 and December 2009, 79 patients underwent AF ablation using RFB (AtriCure®) concomitant to major surgical procedure. Of this group, 53 patients underwent mitral valve surgery, associated ou not to tricuspid and aortic surgery due to rheumatic disease, and are the object of this study. Variables of interest were retrospectively collected according to guidelines on research in surgical treatment of AF [5]. We assessed the following variables: age, type of AF, AF time reported prior to surgery, prior ablative procedures, presence of pacemaker, cardiac diagnosis motivating the indication for surgery, left atrial size, left ventricular ejection fraction, a surgical procedure performed and set of injuries performed to treat AF. 566

Descritores: Procedimentos cirúrgicos cardiovasculares. Valva mitral. Cardiopatia reumática. Fibrilação atrial. Técnicas de ablação.

Patients were followed postoperatively with clinic visits scheduled for 1, 3, 6 and 12 months postoperatively, and were assessed by a non-blind specialist to the treatment of AF, on the use of medications, cardiac rhythm, thromboembolic events, any percutaneous ablations in the postoperative period and reoperation. 24 three-channel Holter was requested from 6 months and assessed by a non-blind specialist to the treatment of AF. The therapeutic failure criterion used is of any tachyarrhythmia with a total duration greater than 24 in the 30s. In turn, the 24 hour Holter tests were assessed not only on the diagnosis of therapeutic failure, but also on other variables of interest: duration of the test, heart rate, minimum, average and maximum periods of heart rate> 120 bpm and frequency heart rate <50 bpm, supraventricular ectopy (SVE), ventricular ectopy (VE), pauses (> 2s), depression or ST segment elevation, autonomic modulation, reported symptoms during the test (and its association with arrhythmia). Three classes of supraventricular ectopy (SVE) were studied: isolated ESV, non-sustained atrial tachycardia (<30s SVE) and sustained atrial tachycardia (>30s of symptomatic atrial tachycardia or SVE). The criteria should include identification of the three SVE: prematurity, a postcontraction and morphology. Assuming that only the excess of supraventricular arrhythmias could have clinical importance, classified as supraventricular electrical instability in the presence of high incidence> 30 SVE/h and/or> following 30 SVEs. Patients with <10 SVE/h were classified as low incidence of electrical instability and those with> 10 SVE/h <30 SVE/h as the average incidence of electrical instability. The ventricular ectopy were classified as isolated or complex (polymorphic, in bigeminy, paired). The presence of> 30 VE/h were classified as ventricular electrical instability of high incidence. The presence of> 10

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VE/h <30 VE/h as ventricular electrical instability and when the average incidence was <10 VE/h classified as ventricular electrical instability of low incidence. Were considered clinically significant when pauses lasting> 2s. The ST segment in the three channels was investigated for possible elevations or depressions. The reported symptoms and their association with arrhythmias have been described. Assessment of autonomic modulation was performed with analysis of the frequency and time domains of RR variability and classified as preserved or reduced autonomic modulation. In all visits were performed conventional electrocardiograms. The Ethics and Research of the National Heart Institute approved this study in 02/02/10 under number 0257. The surgeries were performed through conventional median sternotomy, with cardiopulmonary bypass and mild hypothermia. For myocardial protection cold blood cardioplegia was infused in antegrade or retrograde via intermittently. Access to the mitral valve was performed through the left atrium in most cases. The ablation lines were defined as: 1) Isolation of the pulmonary veins: the pulmonary vein isolation was achieved wrapping the right and left pulmonary veins in pairs, in an epicardial manner (passing one of the electrodes of the ablation device later and the other prior to the pulmonary veins), during cardiac decompression with cardiopulmonary bypass and therefore the patient heparinized, with the convexity of the device facing the left atrium to save the ostia of the pulmonary veins, and before the primary cardiac procedure, applying at least three periods of energy until the buzzer of the occurrence of transmural lesion at the same point. 2) left atrial connecting lines: lines of connection between the pair of right and left pulmonary veins were performed after opening the left atrium by placing one electrode on the outside of the LA posterior wall (epicardium) and the other inside (endocardium), such that the ablation lines performed previously for the isolation of the pulmonary veins were connected upper and/or inferiorly. This procedure was performed during the primary cardiac procedure. 3) Line of connection to the mitral annulus: the connecting line to the mitral annulus was not performed with the bipolar radiofrequency clamp for anatomical impossibility. This, when performed, was done using the technique of cut and suture, connecting the mitral valve annulus to the line of isolation of right inferior pulmonary vein. 4) Cavotricuspid line: cavotricuspid line was performed using the RFB clamp encompassing the right atrial free wall after its opening, in such a way to communicate the atriotomy line to the tricuspid ring, after the coronary sinus ostium venosus.

5) Cava-cava line: with the patient under cardiopulmonary bypass and aorta clamped, through small hole in the right atrial free wall, one ablation clamp leg was introduced toward the superior vena cava and then the inferior vena cava, so that the atrial tissue stays enclosed by two clamp legs during delivery of bipolar energy. When the right atrium was opened for access to the tricuspid valve, the same lesions were performed from the atrial incision. Characteristics of patients Of the 53 patients, 34 (64%) were women and ages ranged from 27 to 72 years (mean: 49.3 years Âą 10.7 years). The mean duration reported of AF was 41 months (range 3192 months). The type of AF was presented: eight patients in paroxysmal AF, persistent in three and permanent in 42. The left atrium had an average size of 52.9 Âą 8.5 mm, ranging from 48 to 79 mm and the mean ejection fraction (LVEF) was 59% Âą 13%. One patient had prior pacemaker and none had been submitted prior to the ablation of any arrhythmia. Four patients had a history of previous cerebrovascular accident (CVA). The events related to AF were observed in four patients. One patient showed complete resolution of neurological symptoms at the time of surgery and three remained with mild language and motor sequelae. The types of injuries that led to mitral surgery were mitral stenosis in 32 patients, mitral regurgitation in 15 and mitral lesion in six. One patient had active infective endocarditis of the mitral valve causing regurgitation. In total, 10 surgeons were responsible for the surgery. RESULTS There were seven (13%) intraoperative deaths and survival after 14 months was 87%. The causes of perioperative deaths were five deaths from cardiogenic shock (two cases of atrioventricular disjunction) and two deaths from septic shock. The two cases of atrioventricular disjunction were diagnosed still during surgery and in both it was tempted surgical suture of the atrioventricular junction with bovine pericardium, but without success. This surgical accident was not associated with surgical ablation, since the lines of injury in both cases were performed away from the mitral annulus. The surgeries performed were: 47 mitral valve replacement (27 biological and 14 metal) and six mitral valve repair. In 30 patients, it was associated tricuspid valvuloplasty in eight aortic valve replacement (seven metal and one organic), and three of them, closure of patent foramen ovale (Figure 1). Of the 46 surviving patients, eight (17.3%) did not perform 24 hour Holter or ECG after 6 months after surgery, period which the presence of supraventricular tachycardia 567

Canale LS, et al. - Surgical treatment of atrial fibrillation using bipolar radiofrequency ablation in rheumatic mitral disease

is considered therapeutic failure. The reason for this failure was: one moved from state and the another could not be contacted by telephone and six gave up the exam or attend the consultation. Of the 38 patients with ECG findings after 6 months of surgery, all had conventional electrocardiogram and 34 underwent 24 hour Holter (performed at a mean of 430 ± 123 days after surgery, ranging from 176 to 763 days). 24 hour Holter and conventional ECG revealed the following rhythms: sinus in 25 (66%) patients, AF in seven (18%), Flutter in five (13%) and junctional in one (3%). Therefore, 26 of 38 (68%) patients were free of tachyarrhythmias after 14 months postoperatively. 24h Holter information can be seen in Table 1. We studied potential risk factors for therapeutic failure: AF duration prior to surgery, left atrial size, age, type of AF and achievement or not of lesions in the posterior wall of left atrium. The only risk factor who showed clinically and statistically significant was the greatest time of AF preoperatively, as shown in Table 2. Patients with AF for more than 60 months had an OR of 11.3 for therapeutic failure. The set of ablation lines performed can be assessed in Figure 2. The need to implant a permanent pacemaker postoperatively was zero. Regarding the use of antiarrhythmic medication, among 37 patients with ECG findings after 6 months of surgery, 11 were not using any drugs, 8 were in use of amiodarone only, 10 in use of atenolol only, four in use of amiodarone and atenolol and seven are missing information. Regarding the use of anticoagulants and/or antiplatelet, two were not using any of these, 30 were taking warfarin, one using ASA and five no information. Of the 26 patients in sinus rhythm, seven used no antiarrhythmic and five did not use coumarin. One patient had neurological events in the

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Table 1. Variables assessed by 24-hour Holter Variable Duration of exam (hours)

1369 ± 46

Minimum HR (bpm)

56 ± 13

Mean HR (bpm)

78 ± 15

Maximum HR (bpm)

123 ± 27

No. patients with HR > 120 bpm

16 (47%)

No. patients with HR < 60 bpm

8 (24%)

No. patients with non-sustained atrial tachycardia

14 (41%)

No. patients with a sustained atrial tachycardia Supraventricular electrical instability in high incidence Supraventricular electrical instability in the average incidence

4 (16.5%)1

Supraventricular electrical instability in low incidence

15 (62.5%)1

No. patients with pauses > 2 s

4 (12%)

No. patients with depression or ST segment elevation

Sinus 31 ± 35 57 ± 9 48 15% 58% 15% 33%

Report of symptoms during examination

9 (26%)

Symptoms related to arrhythmia

2 (22%)

No symptoms related to arrhythmia

7 (78%)

HR: heart rate, bpm: beats per minute, N: Number, s: second, 1: The percentage is calculated with denominator of 24 patients because we excluded those with sustained supraventricular tachycardia, in whom there is no possibility of supraventricular ectopy. 2: The percentage is calculated with denominator of 24 patients because we excluded those with sustained supraventricular tachycardia, in whom there is no way to assess autonomic modulation

postoperative period, with complete resolution of symptoms after 7 days. Percutaneous ablation of residual or recurrent arrhythmias was performed in only one patient for treatment of right atrial flutter successfully, 9 months after surgery.

Arrhythmia 82 ± 70 59 ± 7 51 0% 58% 66% 30%

P 0.0191 0.561 0.401 0.282 13 0.027 0.82

OR (CI 95%)

0.54 (NA) 1 (0.26 to 4.10) 11,3 (1.4 to 92) 0,85 (0.22 to 3.37)

AF: atrial fibrillation, LA: left atrium, 1: Two tailored t-test 2: Fisher Exact Probability Test 3: Pearson Chi-square

568

0 11 (46%)2

Reduced autonomic modulation

Table 2. Analyzed risk factors for therapeutic failure of ablation Variable AF duration (months) LA size (mm) Age (years) Intermittent AF Lesion in the posterior wall of LA AF > 60 months Concomitant tricuspid repair

1 (3%) 5 (21%)1

Canale LS, et al. - Surgical treatment of atrial fibrillation using bipolar radiofrequency ablation in rheumatic mitral disease

Fig. 1 - Types of surgery performed. MVR = mitral valve replacement, AVR = aortic valve replacement, tricuspid repair = TR.

DISCUSSION The bipolar radiofrequency is one of many alternative forms of energy used to attempt to reproduce the lesions made by cutting and suture during the Maze III procedure for the surgical treatment of atrial fibrillation. In our country, its feasibility, safety and efficacy have been demonstrated recently by Canale et al. [6] in a heterogeneous group of patients undergoing cardiac surgery, in general, with maintenance of sinus rhythm after 1 year of 76%. Other forms of energy were studied by the authors in our country, such as unipolar radiofrequency by Breda et al. [7] and Abreu Filho et al. [8], showing mixed results and the use of ultrasound by Brick et al. [9]. However, as far as best of our knowledge, this is the first national experience of exclusive study of patients with rheumatic mitral valve disease using a bipolar radiofrequency. Most studies of surgical treatment of atrial fibrillation comprises patients with degenerative mitral regurgitation. It is known that this group of patients is different from those with rheumatic mitral valve disease. Rheumatic disease affects not only the heart valves, but also causes chronic inflammation in the atria, leading to fibrosis and muscle fibers [10]. Electrical remodeling of the left atrium has been described in these patients, leading to higher propensity to develop atrial fibrillation [11]. The most common complication of mitral stenosis is rheumatic AF and its prevalence increases as the severity of valve obstruction and the patientâ&#x20AC;&#x2122;s age. Therefore, the presence of AF in patients undergoing mitral valve surgery for rheumatic origin is extremely common, but specific treatment in this subgroup is less studied. The comparison between AF patients with degenerative and rheumatic disease, keeping all other risk factors for controlled therapeutic failure (size of LA, AF duration, age),

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Fig. 2 - Types of injuries performed. LA = left atrium.

is very difficult by the large number of patients required for this. Therefore, in the scientific literature, are predominant the reports on safety and efficacy in the treatment of concomitant AF in patients undergoing mitral valve surgery for rheumatic etiology. Guang et al. [12] compared 96 patients with rheumatic mitral valve disease who also underwent AF ablation, with only 87 patients undergoing mitral valve surgery. The maintenance of sinus rhythm after 3 years was significantly higher in the group undergoing ablation (77%) compared to those without ablation (25%). Cui et al. [13] reported 74.5% of sinus rhythm after 12 months of surgery in a group of 91 patients comprising mostly rheumatic, with persistent/permanent AF, using RFB. In this study, three different sets of lesions were used (Cox-Maze III, Cox Mini-Maze and modified left Maze), with no difference between them as to the outcome of sinus rhythm. Abreu Filho et al. [14] performed interesting randomized study in patients with isolated rheumatic mitral valve disease and permanent atrial fibrillation using unipolar ablation device (SICTRA). Seventy patients were assigned randomly to be submitted only to mitral valve surgery or mitral valve surgery concomitant with unipolar ablation of modified Maze III type. The study revealed not only the efficacy of ablation in this group of patients with rheumatic disease only (79.4% of sinus rhythm after 1 year follow-up) but also to demonstrate the low efficacy of treating only the mitral valve with respect to heart rate: 26 9% of sinus rhythm only. In this study, there were no accidents related to ablation. In our series, the therapeutic failure of 31% is comparable to reports in the literature. However, we believe there is possibility for improvement in the future regarding the execution of the most complete lines of ablation, especially those of the posterior wall of the LA. Only 29/53 (54%) patients received posterior communication line of LF, while 569

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45/53 (85%) had persistent or permanent AF, a group that theoretically should receive this injury. Some studies involving patients with different etiologies for mitral valve disease who underwent AF ablation concomitantly recognize rheumatic ethiology as a risk factor for failure of ablation therapy in univariate analysis. Fayad et al. [15], assessing 70 patients who underwent left atrial ablation only, exclusively in individuals with mitral valve disease, identified rheumatic ethiology as a risk factor for AF return. After 2 years of follow-up, 62.5% of patients were in sinus rhythm. On the other hand, Chen et al. [16] when assessing 99 patients with persistent AF undergoing mitral valve surgery for various reasons associating them to the RFB ablation, found the rheumatic etiology as a risk factor for postoperative AF. In this study, only LA size and AF duration were determinants of the rhythm in the 2-years follow-up. Some randomized studies of AF ablation using various alternative energy sources show that the benefits are found in the dimensions of symptoms and decreased use of medications. von Oppell et al. [17] randomized 50 patients for mitral valve surgery with or without concomitant AF ablation. Those who remained in sinus rhythm had better scores on quality of life questionnaires and were more in free use of anticoagulants and antiarrhythmics. However, mortality and thromboembolic events during follow-up were low and similar in both groups. Doukas et al. [18] in a randomized study of 97 patients found low efficacy of ablation (45% in one year), but it was possible to determine the benefits of maintaining sinus rhythm, especially the main and most functional capacity in walk test and smaller serum B-type natriuretic peptide. It was not possible to find differences in mortality or embolic complications during one year of follow-up. Among the classics and more recognized risk factors for treatment failure in AF ablation (age, left atrial size and AF duration), we found as significant only the time of AF before surgery. However, this proved to be highly predictive of failure of ablation. Patients with AF history of more than 5 years are 11.3 times more likely to continue at a AF/flutter rhythm than patients with less than 5 years. In our sample, it becomes a good predictor of treatment failure and serve as a marker to exclude patients for ablation by the high failure rate. Similarly, Chen et al. [16] found an OR of 9.45 for therapeutic failure in patients with AF duration prior to surgery more than 66 months. The mortality rate in our sample (13%) reflects the severity of the disease and the late moment in which these patients are referred for surgery. The presence of AF in itself demonstrates mitral valve disease evolved. Another characteristic of our sample is the high frequency of multivalvular patients. Only 17/53 (32%) were patients with isolated mitral valve disease. Twenty-eight (53%) patients

underwent, in addition to mitral valve surgery, concomitant tricuspid valve repair. Six (11%) patients needed mitralaortic and two (4%) trivalvular surgery (double mitral-aortic and tricuspid valve replacement). The 24-hour Holter is an important tool to assess recurrence of AF/flutter after any ablative procedure [19]. However, in addition to generating information about heart rate and thus detect failures of ablation, it may also investigate the association between symptoms and heart rate, presence of supraventricular and ventricular ectopy, preservation of autonomic modulation and help heart rate control. In reviewing all the 24 hour Holter tests performed in this sample, some data gain importance. The presence of excessive supraventricular ectopia (> 30SVE/h) in patients in sinus rhythm was common (5/24, 21%) as well as the incidence of non-sustained atrial tachycardia (41%). The importance of the excessive presence of supraventricular ectopia as a risk factor for atrial fibrillation, stroke and death was well established in a large healthy population sample studied by 48-hour Holter [20]. In this study, the high incidence of supraventricular activity (we use the same definition) was found in 14.6% of subjects and was associated in the monitoring of more than six years, with a greater chance of the composite outcome of death/stroke (HR: 1.64) and hospital admission for HF (HR: 2.78). Engstrรถm et al. [21] also outlined strong correlation between men with excessive supraventricular activity (> 218 SVE/ 24h) and increased risk of stroke (RR: 1.9). Our sample has a higher prevalence of individuals with high incidence of supraventricular activity (21%), but the importance of this condition in the context of late postoperative ablation has not yet been investigated. In our environment, Cunha et al. [22] quantified the incidence of supraventricular ectopia in the late postoperative period of Cox-Maze III associated to valvular surgery, finding an average of 2.3% of heart rate as derived from atrial ectopy and 35% presenting non-sustained atrial tachycardia. The importance of 24 hour Holter in our context can be also included in the adjustment of medications that control the heart rate. Twelve percent of patients had prolonged pauses (> 2s) and 24% had some time with HR <60 bpm, all associated with high doses of amiodarone and/or beta blockers. The reduced autonomic modulation was found in 46% of those in which it could be assessed (it is not possible to assess in patients with sustained tachyarrhythmia). This finding may be explained by a process of sympathetic and parasympathetic denervation resulting from multiple mechanical injuries made in the atria. Nine (26%) patients reported symptoms during the test, but in only two of them (22%) the symptom was associated with rhythm disorder, showing how weak is the correlation between symptoms and arrhythmias in this context. Cunha

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et al. [22] reported a similar experiment, revealing that 41% of patients in their sample reported symptoms during the examination, but only 43% of them exhibited electrical substrate at the time of the symptom.

3. Geidel S, Ostermeyer J, Lass M, Boczor S, Kuck KH. Surgical treatment of permanent atrial fibrillation during cardiac surgery using monopolar and bipolar radiofrequency ablation. Indian Pacing Electrophysiol J. 2003;3(3):93-100.

Limitations of the study This study has several limitations. It is retrospective and open. The number of patients studied is small, which can compromise the analysis of risk factors for therapeutic failure. Some traditional risk factors such as size of LA and type of AF, were not significant in this series. In addition, our loss of monitoring is high (17%). All surgeons involved in the surgeries were in the process of learning curve with this method. CONCLUSIONS The use of bipolar radiofrequency for the treatment of atrial fibrillation in patients undergoing surgery for rheumatic mitral valve is effective in controlling the arrhythmia in 68% of patients after 14 months. The duration of preoperative AF was an important predictor of treatment failure. The 24 hour Holter, in addition to detect arrhythmias, adds relevant information such as supraventricular ectopic excessive activity, assessment of autonomic modulation and correlation between symptoms and electrocardiographic events.

4. Albrecht A, Kalil RA, Schuch L, Abrahão R, Sant’Anna JR, Lima G, et al. Randomized study of surgical isolation of the pulmonary veins for correction of permanent atrial fibrillation associated with mitral valve disease. J Thorac Cardiovasc Surg. 2009;138(2):454-9. 5. Shemin RJ, Cox JL, Gillinov AM, Blackstone EH, Bridges CR; Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. Guidelines for reporting data and outcomes for the surgical treatment of atrial fibrillation. Ann Thorac Surg. 2007;83(3):1225-30. 6. Canale LS, Colafranceschi AS, Monteiro AJ, Coimbra M, Weksler C, Koehler E, et al. Uso da radiofrequência bipolar para o tratamento da fibrilação atrial durante cirurgia cardíaca. Arq Bras Cardiol. 2011;96(6):457-64. 7. Breda JR, Breda ASCR, Meneguini A, Freitas ACO, Pires AC. Ablação operatória da fibrilação atrial por radiofrequência. Rev Bras Cir Cardiovasc. 2008;23(1):118-22. 8. Abreu Filho CAC, Dallan LAO, Lisboa LAF, Spina GS, Scanavacca M, Grinberg M, et al. Resultados da ablação cirúrgica por radiofrequência da fibrilação atrial crônica. Rev Bras Cir Cardiovasc. 2004;19(3):301-8. 9. Brick AV, Seixas TN, Portilho CF, Peres AK, Vieira Jr JJ, Melo Neto R, et al. Tratamento intra-operatório da fibrilação atrial crônica com ultra-som. Rev Bras Cir Cardiovasc. 2001;16(4):337-49. 10. Otto CM, Bonow RO. Valvular heart disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald’s heart disease: a textbook of cardiovascular medicine. Philadelphia:Elsevier;2008. p.1649. 11. John B, Stiles MK, Kuklik P, Chandy ST, Young GD, Mackenzie L, et al. Electrical remodelling of the left and right atria due to rheumatic mitral stenosis. Eur Heart J. 2008;29(18):2234-43.

REFERENCES

12. Guang Y, Zhen-jie C, Yong LW, Tong L, Ying L. Evaluation of clinical treatment of atrial fibrillation associated with rheumatic mitral valve disease by radiofrequency ablation. Eur J Cardiothorac Surg. 2002;21(2):249-54.

1. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-52.

13. Cui YQ, Meng X, Li Y, Wang JG, Zeng W, Gao F, et al. Intraoperative treatment for atrial fibrillation using bi-polar radiofrequency ablation system: a clinical report of 91 cases. Zhonghua Wai Ke Za Zhi. 2009;47(7):533-6.

2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-8.

14. Abreu Filho CA, Lisboa LA, Dallan LA, Spina GS, Grinberg M, Scanavacca M, et al. Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in patients with

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permanent atrial fibrillation and rheumatic mitral valve disease. Circulation. 2005;112(9 Suppl):I20-5.

of Thoracic Surgeons. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and followup. A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace. 2007;9(6):335-79.

15. Fayad G, Le Tourneau T, Modine T, Azzaoui R, Ennezat PV, Decoene C, et al. Endocardial radiofrequency ablation during mitral valve surgery: effect on cardiac rhythm, atrial size, and function. Ann Thorac Surg. 2005;79(5):1505-11. 16. Chen MC, Chang JP, Chang HW, Chen CJ, Yang CH, Chen YH, et al. Clinical determinants of sinus conversion by radiofrequency maze procedure for persistent atrial fibrillation in patients undergoing concomitant mitral valvular surgery. Am J Cardiol. 2005;96(11):1553-7. 17. von Oppell UO, Masani N, O’Callaghan P, Wheeler R, Dimitrakakis G, Schiffelers S. Mitral valve surgery plus concomitant atrial fibrillation ablation is superior to mitral valve surgery alone with an intensive rhythm control strategy. Eur J Cardiothorac Surg. 2009;35(4):641-50.

20. Binici Z, Intzilakis T, Nielsen OW, Køber L, Sajadieh A. Excessive supraventricular ectopic activity and increased of atrial fibrillation and stroke. Circulation. 2010;121(17):1904-11.

18. Doukas G, Samani NJ, Alexiou C, Oc M, Chin DT, Stafford PG, et al. Left atrial radiofrequency ablation during mitral valve surgery for continuous atrial fibrillation: a randomized controlled trial. JAMA. 2005;294(18):2323-9.

21. Engström G, Hedblad B, Juul-Möller S, Tydén P, Janzon L. Cardiac arrhythmias and stroke: increased risk in men with high frequency of atrial ectopic beats. Stroke. 2000;31(12):2925-9.

19. Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, et al. Heart Rhythm Society; European Heart Rhythm Association; European Cardiac Arrhythmia Society; American College of Cardiology; American Heart Association; Society

22. Cunha B, Kalil RA, Albrecht AS, Lima GG, Kruse JC. Evaluation of the heart rate and arrhythmias following the maze procedure for chronic atrial fibrillation. Arq Bras Cardiol. 1999;72(5):607-14.

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ORIGINAL ARTICLE

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Elevated plasma D-dimer and hypersensitive Creactive protein levels may indicate aortic disorders Níveis plasmáticos elevados do dímero D e da proteína C reativa hipersensíveis podem indicar desordens aórticas

Shi-Min Yuan1, Yong-Hui Shi2, Jun-Jun Wang3, Fang-Qi Lü4, Song Gao5 DOI: 10.5935/1678-9741.20110047

RBCCV 44205-1323

Abstract Objective: D-dimer and C-reactive protein are of diagnostic and predictive values in patients have thrombotic tendency, such as vascular thrombosis, coronary artery disease and aortic dissection. However, the comparative study in these biomarkers between the patients with acute aortic dissection and coronary artery disease has not been sufficiently elucidated. Methods: Consecutive surgical patients for acute type A aortic dissection (20 patients), aortic aneurysm (nine patients) or coronary artery disease (20 patients) were selected into this study. Plasma from preoperative blood samples and supernatant of aortic homogenate of the surgical specimens were detected for D-dimer and hypersensitive C-reactive protein (hs-CRP). Results: Plasma D-dimer and hs-CRP values in type A aortic dissection or aortic aneurysm were much higher than in coronary artery disease patients or the healthy control (for D-dimer, aortic dissection: coronary artery disease, 0.4344 ± 0.2958 µg/ml vs. 0.0512 ± 0.0845 µg/ml, P < 0.0001; aortic dissection: healthy control, 0.4344 ± 0.2958 µg/ml vs. 0.1250 ± 0.1295 µg/ml, P = 0.0005; aortic aneurysm: coronary artery disease, 0.4200 ± 0.4039 µg/ml vs. 0.0512 ± 0.0845 µg/ml, P = 0.0013; and aortic aneurysm: healthy control, 0.4200 ± 0.4039 µg/ml vs. 0.1250 ± 0.1295 µg/ml, P = 0.0068; and for hs-CRP, aortic dissection: coronary artery disease, 4.400± 3.004 mg/L vs. 1.232±0.601 mg/L, P < 0.0001; aortic dissection:healthy control, 4.400 ± 3.004 mg/L vs. 0.790 ± 0.423 mg/L, P < 0.0001; aortic aneurysm: coronary artery disease, 2.314 ± 1.399 mg/L

vs. 1.232 ± 0.601 mg/L, P = 0.0084; aortic aneurysm: healthy control, 2.314 ± 1.399 mg/L vs. 0.790 ± 0.423 mg/L, P = 0.0002; and coronary artery disease: healthy control, 1.232 ± 0.601 mg/L vs. 0.790 ± 0.423 mg/L, P = 0.0113). Besides, there were close correlations between plasma D-dimer and hs-CRP in overall (Y = 4.8798X + 0.8138, r2 = 0.4497, r = 0.671, P < 0.001), aortic dissection (Y = 2.6298X + 1.2098, r2 = 0.5762, r = 0.759, P < 0.001), and aortic aneurysm (Y = 7.1341X + 1.3006, r2 = 0.4935, r = 0.7025, P = 0.048) groups rather than in the coronary artery disease or healthy control subjects. In addition, there were no significant differences between D-dimer and hs-CRP values of the aortic supernatant among groups except for undetectable D-dimer in the aortic supernatant of the coronary artery disease group. Conclusions: The patients with acute aortic dissection and aortic aneurysm may reflect the extensive inflammatory reaction and severe coagulopathies in the patients with acute type A aortic dissection, and thoracic aortic aneurysm in comparison to the coronary patients and healthy control individuals. The detections after onset in the patients with acute chest pain may help making a differential diagnosis between the aortopathies and ischemic heart disease. The scanty significance of the tissue biomarkers may preclude their diagnostic value in clinical practice.

1. MD, PhD; Professor of Surgery & Head, Department of Cardiothoracic Surgery, Affiliated Hospital of Taishan Medical College, Taian, Shandong Province, People’s Republic of China. 2. MD; Department of Clinical Laboratory, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, People’s Republic of China. 3. MD; Department of Clinical Laboratory, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, People’s Republic of China. 4. MD; Professor of Surgery & Director, Departments of Surgery. Affiliated Hospital of Taishan Medical College, Taian, Shandong Province, People’s Republic of China. 5. MD; Professor of Surgery & Deputy Chairman, Affiliated Hospital of Taishan Medical College, Taian, Shandong Province, People’s Republic of China.

Work performed at Department of Cardiothoracic Surgery, Affiliated Hospital of Taishan Medical College, Taian, Shandong Province, and Departments of Cardiothoracic Surgery & Clinical Laboratory, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, People’s Republic of China.

Descriptors: Aorta, thoracic. Clinical laboratory techniques. Coronary artery disease. C-reactive protein. Fibrin fibrinogen degradation products.

Corresponding author Shi-Min Yuan, MD, PhD; Department of Cardiothoracic Surgery, Affiliated Hospital of Taishan Medical College, Taian 271000, Shandong Province, People’s Republic of China. E-mail: s.m.yuan@v.gg Article received on April 2nd, 2011 Article accepted on October 9th, 2011

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Resumo Objetivo: D-dímero e proteína C reativa são de valores de diagnóstico e preditivo em pacientes com tendência trombótica, como a trombose vascular, doença arterial coronária e dissecção aórtica. No entanto, o estudo comparativo desses biomarcadores entre os pacientes com dissecção aguda da aorta e doença arterial coronariana não foi suficientemente esclarecido. Métodos: Pacientes cirúrgicos consecutivos foram selecionados para este estudo por tipo de dissecção aguda aórtica (20 pacientes), aneurisma da aorta (9 pacientes) ou doença arterial coronária (20 pacientes). O plasma a partir de amostras de sangue no pré-operatório e sobrenadante de homogenato de aorta dos espécimes cirúrgicos foi detectado para o D-dímero e proteína C reativa hipersensível. Resultados: Os valores do plasma de D-dímero e proteínaC reativa em dissecção aórtica tipo A ou aneurisma da aorta foram muito superiores em pacientes com doença arterial coronariana ou de controles saudáveis (pelo D-dímero, dissecção aórtica: doença arterial coronariana, 0,4344 ± 0,2958 µg/ml vs 0,0512 ± 0,0845 µg/ml, P <0,0001; dissecção aórtica: controle saudável, 0,4344 ± 0,2958 µg/ml vs 0,1250 ± 0,1295 µg/ml, P = 0,0005; aneurisma da aorta: doença arterial coronariana, 0,4200 ± 0,4039 µg/ml vs 0,0512 ± 0,0845 µg/ml, P = 0,0013; e aneurisma de aorta: controle saudável, 0,4200 ± 0,4039 µg/ml vs. 0,1250 ± 0,1295 µg/ml, P = 0,0068 e para a hsCRP, dissecção aórtica: doença arterial coronariana, 4,400 ± 3,004 mg/L vs. 1,232 ± 0,601 mg/L, P <0,0001; dissecção aórtica: grupo controle saudável, 4,400 ± 3,004 mg/L vs 0,790 ± 0,423 mg/L, P <0,0001; aneurisma da aorta: doença arterial

coronariana, 2,314 ± 1,399 mg/L vs. 1,232 ± 0,601 mg/L, P = 0,0084; aneurisma da aorta: grupo controle saudável, 2,314 ± 1,399 mg/L vs. 0,790 ± 0,423 mg/L, P = 0,0002; e doença arterial coronariana: grupo controle saudável, 1,232 ± 0,601 mg/L versus 0,790 ± 0,423 mg/L, P = 0,0113). Além disso, houve correlações próximas de plasma de D-dímero e proteína C reativa em em todos os pacientes com dissecção aórtica (Y = 4.8798X + 0,8138, r2 = 0,450, r= 0,671, P < 0,001), (Y = 2.6298X + 1,2098, r2 = 0,5762, r = 0,759, P < 0,001), e aneurisma de aorta (Y = 7.1341X + 1,3006, r2 = 0,4935, r = 0,7025, P = 0,048) ao contrário dos grupos de doença arterial coronariana ou grupo controle de pacientes saudáveis. Além disso, não houve diferenças significativas dos valores de D-dímero e proteína C reativa de sobrenadante de aorta entre os grupos, exceto para o D-dímero indetectável no sobrenadante de aorta do grupo com doença coronária. Conclusões: Os pacientes com dissecção aguda da aorta e aneurisma da aorta podem refletir a reação inflamatória extensa e coagulopatias graves nos pacientes com o dissecção aguda aórtica tipo A e aneurisma da aorta torácica em comparação com os doentes coronários e indivíduos-controle saudáveis. As detecções após o acomentimento nos pacientes com dor torácica aguda podem ajudar a fazer um diagnóstico diferencial entre a aortopatias e doença isquêmica cardíaca. A escassa significância dos biomarcadores de tecido pode impedir o seu valor diagnóstico na prática clínica.

INTRODUCTION D-dimers are fibrin degradation products which are released during local or systemic activation of coagulation. D-dimer testing is widely used in the diagnosis of deep vein thrombosis, pulmonary embolism [1], or disseminated intravascular coagulopathy [2]. Patients with thrombotic tendency such as paroxysmal atrial fibrillation often had increased plasma fibrinogen and D-dimer levels, while the cardioversion of atrial fibrillation to sinus rhythm in such patients may decrease the levels of these markers in the plasma [3]. Yasaka et al. [4] found, in patients with mitral stenosis, significantly higher D-dimer plasma levels with detectable left atrial thrombi. Patients receiving warfarin therapy may have their plasma D-dimer levels reduced [5]. D-dimers in patients with an impaired left ventricular function were higher than those with a normal left ventricular function [6]. Intraoperative elevated D-dimer during cardiopulmonary bypass was considered the result of activation of temperature-dependent enzymes during the rewarming phase, whereas the elevation of D-dimer 24 hours postoperatively in the cardiac surgical patients without the 574

Descritores: Aorta torácica. Técnicas de laboratório clínico. Doença das coronárias. Proteína C-reativa. Produtos de degradação da fibrina e do fibrinogênio.

use of cardiopulmonary bypass was considered a protective mechanism of the body to clear the hemostatic plugs to restore vascular patency [7]. D-dimer is a strong predictor of recurrent coronary events. D-dimer elevation along with dysfunctional apolipoprotein concentrations may predict coronary events [8]. Moreover, D-dimer showed earlier positive test (within 2 hours from the onset) than troponin T in the detection of acute coronary syndrome [9]. D-dimer of the patients with large vessel disease was significantly higher than that of the patients with acute coronary syndrome (6.99 µg/ml vs. 0.89 µg/ml, P<0.05). Nevertheless, increased D-dimer levels are encountered in many non-thrombotic conditions. Recently, normal D-dimers were also taken as exclusion criteria of acute aortic dissection in patients with chest pain [10]. D-dimers may increase progressively during cardiac surgery with cardiopulmonary bypass [11]. D-dimer can be detectable prior to the release of troponin or creatine kinase MB into bloodstream [10]. Nevertheless, this diagnostic criteria was doubted by several authors as it may misjudge some patients with suspected acute aortic dissection, and hence a combined diagnostic strategy

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inclusive of alternative coagulation tests and imaging techniques may be mandatory in particular in reaching a definite diagnosis of aortic dissection. C-reactive protein (CRP) may be significantly elevated in the plasma of the patients with aortic dissection and atherosclerosis, which may be associated with the arterial damage and immune reaction [12]. Aortic dissection and atherosclerosis are low-grade inflammatory reactions for which CRP testing might be less sensitive. Instead, hypersensitive C-reactive protein (hs-CRP) measurements would provide with high sensitive results. Elevated hsCRP may predict recurrent coronary events, like heart attack, restenosis of coronary arteries after angioplasty, stroke, and peripheral vascular disease, etc. [13]. A comparative study between aortic and ischemic heart diseases was rarely described with regard to the diagnostic values of plasma D-dimer and hs-CRP. This study was designed to test plasma D-dimer and hs-CRP of the patients with acute type A aortic dissection, in comparison to those with thoracic aortic aneurysm or with the coronary artery disease, and healthy control. In addition, we examined the D-dimer and hs-CRP levels of the aortic supernatant of the surgical specimens of the patients with acute type A aortic dissection, thoracic aortic aneurysm and coronary artery disease.

with a Hitachi Model 7600 Series Automatic Analyzer (Hitachi High-Technologies Corporation, Hitachi, Japan). The kits used in the experiments were D-dimer PLUS (Simens Healthcare Diagnostics Products GmbH) and Reagent kit for hs-CRP test (latex agglutination assay). Their reference values were 0.1417 (90%CL 0.0638-0.2464) µg/ml for D-dimer, and < 6 mg/L for hs-CRP, respectively. All data were expressed in mean ± standard deviation, and intergroup comparisons were made by t-test. P < 0.05 was considered of statistical significance. This study was approved by the institutional ethical committee, and was conducted following the guidelines of the Declaration of Helsinki. Informed consent was obtained from each patient.

METHODS From 2008 to present, consecutive surgical patients for type A aortic dissection (20 patients), aortic aneurysm (nine patients) or coronary artery disease (20 patients) were selected into this study. Patients with aortic dissection or aortic aneurysm due to Marfan’s syndrome during the study period were excluded from this study. Blood samples (4 ml) were obtained from the surgical patients from the indwelling catheter of the radial artery in the operating theater after systemic heparinization and before cardiopulmonary bypass, while control fast morning blood samples were drawn from young healthy volunteers. Plasma was collected by centrifugation 3000 × g for 5 min, and stored at -80ºC until detection. The surgical specimens of large aortic tissues were obtained immediately after they were severed in the operations of the replacement of the aorta in the patients with aortic dissection or aortic aneurysm. The aortic tissues 0.2-0.4 cm in size taken from the punch holes of the proximal anastomosis on the anterior wall of the ascending aorta in patients receiving coronary artery bypass were collected. The aortic tissue was stored at -80ºC, which would be thawed and made into supernatant until detection. Blood and the aortic tissue specimens were tested for D-dimer with an Sysmex® CA-7000 system coagulation analyzer (Sysmex, Kobe, Japan), and detection of hs-CRP

RESULTS Plasma D-dimers of the aortic dissection and aortic aneurysm groups were significantly higher than the reference value. There appeared no statistical significance in plasma D-dimer levels between the aortic dissection and aortic aneurysm groups (0.4344 ± 0.2958 µg/ml vs. 0.4200 ± 0.4039 µg/ml, P = 0.9352), or between the coronary artery disease and healthy control groups (0.0512 ± 0.0845 µg/ml vs. 0.1250 ± 0.1295 µg/ml, P = 0.0519). However, plasma D-dimer levels of the aortic dissection or aortic aneurysm were significantly higher than those of the coronary artery disease or healthy control groups (aortic dissection:coronary artery disease, 0.4344 ± 0.2958 µg/ml vs. 0.0512 ± 0.0845 µg/ml, P< 0.0001; aortic dissection:healthy control, 0.4344 ± 0.2958 µg/ml vs. 0.1250 ± 0.1295 µg/ml, P = 0.0005; aortic aneurysm:coronary artery disease, 0.4200 ± 0.4039 µg/ml vs. 0.0512 ± 0.0845 µg/ ml, P = 0.0013; and aortic aneurysm:healthy control, 0.4200 ± 0.4039 µg/ml vs. 0.1250 ± 0.1295 µg/ml, P = 0.0068) (Figure 1).

Fig. 1. Plasma D-dimer levels. AA - aortic aneurysm; AD - aortic dissection; CAD - coronary artery disease; Control - healthy control

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There was no statistical significance in plasma hs-CRP values between the aortic dissection and aortic aneurysm groups (4.400 ± 3.004 mg/L vs. 2.314 ± 1.399 mg/L, P = 0.1131). However, plasma hs-CRP values of the aortic dissection or aortic aneurysm were significantly higher than those of the coronary artery disease or healthy control groups (aortic dissection: coronary artery disease, 4.400 ± 3.004 mg/L vs. 1.232 ± 0.601 mg/L, P < 0.0001; aortic dissection: healthy control, 4.400 ± 3.004 mg/L vs. 0.790 ± 0.423 mg/L, P < 0.0001; aortic aneurysm: coronary artery disease, 2.314 ± 1.399 mg/L vs. 1.232 ± 0.601 mg/L, P = 0.0084; and aortic aneurysm: healthy control, 2.314 ± 1.399 mg/L vs. 0.790 ± 0.423 mg/L, P = 0.0002), and between the coronary artery disease and healthy control groups (1.232 ± 0.601 mg/L vs. 0.790 ± 0.423 mg/L, P = 0.0113) (Figure 2).

No significant difference was found in the D-dimer values of the supernatant of the aortic tissues between the aortic dissection and aortic aneurysm groups (37.411 ± 69.865 mg/mg vs. 37.022 ± 37.697 mg/mg, P = 0.9907). However, D-dimer was undetectable in the supernatant of the aortic tissues of all cases of the coronary artery disease group (Figure 3). No significant difference was found in the hs-CRP levels of the supernatant of the aortic tissues among the three investigated groups (aortic dissection: aortic aneurysm, 169.205 ± 134.240 mg/mg vs. 172.873 ± 74.549 mg/mg, P = 0.9464; aortic dissection: coronary artery disease, 169.205 ± 134.240 mg/mg vs. 148.413 ± 89.130 mg/mg, P = 0.709; 172.873 ± 74.549 mg/mg vs. 148.413 ± 89.130 mg/mg, P = 0.5321) (Figure 4).

Fig. 2. Plasma hypersensitive C-reactive protein levels. AA - aortic aneurysm; AD - aortic dissection; CAD - coronary artery disease

Fig. 3. D-dimers of the supernatant of the aortic tissues. AA aortic aneurysm; AD - aortic dissection; CAD - coronary artery disease

Fig. 4. Hypersensitive C-reactive protein levels of the supernatant of the aortic tissues. AA - aortic aneurysm; AD - aortic dissection; CAD - coronary artery disease; Control - healthy control

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Fig. 5. Linear correlation between plasma D-dimer and plasma hypersensitive C-reactive protein levels of all four investigated groups

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There was a significant correlation between plasma Ddimer and plasma hs-CRP when the results of all four groups were included (Y = 4.8798X + 0.8138, r2 = 0.4497, r = 0.671, P < 0.001) (Figure 5). A significant correlation between plasma D-dimer and plasma hs-CRP was also noted in the aortic aneurysm (Y = 2.6298X + 1.2098, r2 = 0.5762, r = 0.759, P < 0.001) (Figure 6), the aortic dissection (Y = 7.1341X + 1.3006, r2 = 0.4935, r = 0.7025, P = 0.048) (Figure 7). However, there appeared no close correlation between plasma D-dimer and plasma hs-CRP in the coronary artery disease (Y = 0.655X + 1.225, r2 = 0.008, r = 0.088, P = 0.738) and in the healthy control (Y = -0.013X + 0.135, r2 = 0.002, r = - 0.041, P = 0.863) groups.

When plasma D-dimer or plasma hs-CRP was taken as an independent variable, no inclusive dependent variables of the aortic dissection group (diseased course, time interval from the onset, preoperative fibrinogen levels, and D-dimer or hs-CRP levels in the supernatant of the aortic tissues) displayed a siginificant correlation with it.

Fig. 6. Linear correlation between plasma D-dimer and plasma hypersensitive C-reactive protein levels of the aortic aneurysm group

Fig. 7. Linear correlation between plasma D-dimer and plasma hypersensitive C-reactive protein levels of the aortic dissection group

DISCUSSION D-dimer D-dimer is a primary product of the cross-linked fibrin relating to fibrinolytic activation involving in atherosclerotic progression and endogenous fibrinolysis [14]. D-dimer antigen remains undetectable until it is released from crosslinked fibrin by the action of plasmin [15]. D-dimer is usually detectable 1 hour after the formation of the thrombus with a half-life time of 4-6 hours [16]. The D-dimer values could be detectable and remain high in the plasma 1.2 Âą 2.5 days after onset of acute aortic dissection, and the mean value could be 8.610 (2.982-20.000) Âľg/ml, significantly higher than the control [17]. D-dimer measurement is a rapid, easy-to-use, costeffective method [18]. Test strip (Roche Diagnostics) for rapid bedside D-dimer assay is highly sensitive for early exclusion of acute aortic dissection in patients with chest pain [19]. A value of 0.5 Âľg/ml was defined as the threshold for a positive D-dimer [20]. Circulating D-dimers and CRP values appear to have prognostic value in the diagnosis of the underlying disorders with sufficient sensitivity and specificity [21]. D-dimer and ischemic heart disease Lowe et al. [22] reported the positive correlation between CRP and D-dimer, and suggested combination of CRP and D-dimer may potentially predict ischemic heart disease. Bayes-Genis et al. [10] have recently demonstrated that plasma D-dimer values are significantly higher in patients with acute ischemic events than in non-ischemic patients. However, ischemic diseases may cause limited specificity of D-dimer testing as cerebrovascular disease, peripheral vascular disease, prior coronary revascularization, and renal or hepatic insufficiency may cause thrombosis with elevated D-dimer. Multivariate analysis showed that D-dimer levels were a significant independent variable for myocardial infarction, and elevated D-dimers were more likely to be associated with death compared with subjects with the lowest D-dimer values [23]. A five-fold increase in D-dimers was found in patients with unstable angina pectoris [24], and in those with an acute myocardial infarction [25]. Ddimer may reflect the severity of arteriosclerosis [26], indicating an increased formation and splitting of fibrin [6] in coronary patients. During thrombolytic therapy the fibrinogen levels drop to 12%-20% of their original values 577

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and plasma D-dimer concentrations rise to 70-130-fold of the original values [6]. Plasmin has a broad range of actions: degrading fibrin, fibrinogen, factors V and VIII, proteins involved in platelet adhesion (glycoprotein I and vWF), and aggregation (glycoprotein IIb/IIIa), retaining platelet aggregates (thrombospondin, fibronectin, and histidine-rich glycoprotein), and enhancing the attachment of platelets and fibrin to the endothelial surface. α2-antiplasmin, also termed as plasmin inhibitor, is a serine protease inhibitor (serpin) responsible for inactivating plasmin, an important enzyme that participates in fibrinolysis and degradation of various other proteins. This protein is encoded by the SERPINF2 gene [27]. If there happens an enhanced plasmin or attenuated α2-antiplasmin in the atherosclerotic process, there might be scanty D-dimer production, which may lead to undetectable D-dimer in the plasma or aortic tissues of the coronary patients.

length can be closely related to the formation of D-dimer [31]. Mean plasma D-dimer levels may increase or decrease with the progressive enlarging or regressive dwindling aortic dissection [32]. The cutoff level of 0.5 µg/ml within 24 hours after onset was used for excluding pulmonary embolism, now also used for acute aortic dissection [33]. A plasma D-dimer value > 0.25 µg/ml increased the cardiovascular mortality risk almost 4-fold [34]. Elevated D-dimer levels > 0.58 µg/mL was predictive of death or myocardial infarction [10]. Furthermore, a positive relationship between D-dimer and in-hospital mortality rate among patients with acute aortic dissection was observed [35]. In acute type A aortic dissection, Weber et al. [36] proposed that plasma D-dimer may predict mortality. Immer [37] objected this viewpoint, and explained that prediction of mortality in acute aortic dissection based on D-dimer concentrations, may be extremely dangerous, as this may exclude some patients that may survive. D-dimer, but not CRP, troponin, lactate dehydrogenase, or leukocyte count, was predictive of a diagnosis of acute aortic dissection, with a sensitivity and specificity of 99% and 34%, respectively. D-dimer concentration positively correlated with the anatomical extension of the dissection to the different segments of the aorta [17]. D-dimer test could be negative in acute aortic syndrome due to acute aortic dissection, especially in patients without a patent false lumen presenting with an aortic intramural hematoma [38]. D-dimers may become significantly lower in aortic intraluminal hematoma (median 1.230 µg/ml, range 0.685-2.645 µg/ml) than in conventional dissection (median 9.290, range 3.890-20.000). This may be associated with the lack of a thrombotic patent false lumen in the patients with intraluminal hematoma [39].

D-dimer and aortic diseases Serum D-dimers may be remarkably elevated in the patients with acute aortic dissection [28]. The patients with acute aortic dissection had significantly elevated D-dimer values compared to both the chronic aneurysm patients as well as the normal subjects; patients with chronic aortic aneurysms also had significantly higher D-dimer compared to the control [29]. Eggebrecht et al. [21] reported that Ddimers were highly increased in patients with acute aortic dissection similar to those of the patients with pulmonary embolism, but significantly higher than those of the patients with chronic aortic dissection, acute myocardial infarction, or chest pain. These results were in agreement with ours. The research on the elevations of circulating D-dimers have revealed substantial correlation with the time interval from the onset to the testing, and the type and dissection extent of aortic dissection: type A 8.8 ± 14.5 µmg/ml, type B 10.1 ± 14.8 µg/ml, involvement of thoracic, abdominal aorta, and iliac arteries 18.9 ± 19.9 µg/ml, thoracic and abdominal aorta without iliac arteries 11.1 ± 17.8 µg/ml, and intramural hematoma 2.7 ± 1.9 µg/ml, respectively. Sbarouni et al. [29] reported 18 patients with acute aortic dissection having a mean D-dimer of 0.700 µg/ml, significantly higher than the patients with chronic aneurysms and the normal controls. The correlation between D-dimer value and the time interval from onset to detection was emphasized by many authors. However, Paparella et al. [11] described no correlation between these two parameters, suggesting that elevation of D-dimer may not depend on time. In addition, the Ddimer value was significantly lower in patients with a thrombosed false lumen than with a patent false lumen and in patients with De Bakey type II than with De Bakey type I, indicating that the D-dimer value depends on the length of the dissection [30]. The size of false lumen and dissection 578

CRP CRP can also be produced locally in atherosclerotic lesions [40]. The major part of CRP is synthesized by hepatocytes, driven by interleukin-6 with synergistic enhancement of interleukin-1 or tumor necrosis factor [41,42]. CRP directly influences several phases of atherosclerosis via complement activation, apoptosis, vascular cell activation, monocyte recruitment, lipid accumulation, and thrombosis [43]. Therefore, exaggerated CRP itself might exert harmful effects that promote the atherosclerosis of the dissected aortic wall. CRP continued to increase at 48 hours after arrival to intensive care unit after surgery [44]. Strong correlations were observed in D-dimer values with circulating CRP values [45]. Contrary to what was reported in the literature, we did not find any correlation between plasma D-dimer and hs-CRP values. Instead, we noted close correlation between plasma D-dimer and hs-CRP values in overall, acute aortic dissection or aortic aneurysm groups.

Yuan SM, et al. - Elevated plasma D-dimer and hypersensitive Creactive protein levels may indicate aortic disorders

On multivariate analyses, D-dimer retained a significant association with coronary risk, whereas CRP did not [46]. CRP has been preliminarily shown a less predictive value as an inflammatory risk score for aortic aneurysm endovascular treatment [47]. Maximal CRP was only predicting the impaired oxygenation, but not Stanford type, thrombosed false lumen, pleural effusion, atelectasis, and intravenous vasodilator use. At admission, CRP was normal and increased significantly since day 2 in the impaired oxygenation group [48]. Increased admission CRP correlated with high mortality irrespective of management policy [49]. However, Sakakura et al. [50] proposed that it may take 3-6 days to reach a peak CRP, initial CRP levels might not reflect the whole severity of aortic dissection, and therefore the peak CRP level was a better marker than the initial CRP level in the risk evaluation of type B aortic dissection. hs-CRP is a useful risk predictor for recurrent coronary events, stroke or peripheral arterial disease [51]. Xu et al. [52] reported that serum hs-CRP was much higher in acute aortic dissection than in chronic aortic dissection and normal control, and serum hs-CRP had significant correlation with hypertension and serum fibrinogen levels. In this study, we found that plasma D-dimers of the patients with acute type A aortic dissection and aortic aneurysm were significantly higher than the reference value. Plasma D-dimer and hs-CRP values in type A aortic dissection or aortic aneurysm were much higher than in coronary artery disease patients or the healthy control. Besides, there were close correlations plasma D-dimer and hs-CRP in overall, aortic dissection, and aortic aneurysm groups. These results suggested that plasma D-dimer and hs-CRP reflect the severity of the inflammatory reactions in the aortopathies including aortic dissection, aortic aneurysm and atherosclerosis, and could be important diagnostic biomarkers for aortic dissection and aortic aneurysm. In addition, the results of D-dimer and hs-CRP of the supernatant aortic tissues were scanty of intergroup significance, and showed undetectability of D-dimer in the aortic tissue of the coronary patients. In conclusion, the patients with acute aortic dissection and aortic aneurysm may have remarkable elevations of plasma D-dimer and hs-CRP than the patients with coronary artery disease. The results may reflect the extensive inflammatory reaction and severe coagulopathies in the patients with acute type A aortic dissection, and thoracic aortic aneurysm patients in comparison to the coronary and healthy control subjects. The detections after onset in the patients with acute chest pain may help making a differential diagnosis between the aortopathies and ischemic heart disease. The undetectable D-dimer in aortic tissues of coronary patients may preclude its diagnostic value and require further investigations.

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ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):582-90

Aline Marques Franco1, Franciele Cristina Clapis Torres1, Isabela Scali Lourenço Simon1, Daniela Morales2, Alfredo José Rodrigues3

DOI: 10.5935/1678-9741.20110048

RBCCV 44205-1324

Abstract Introduction: The application of two levels of ventilation by positive pressure (BiPAP®) associated with conventional respiratory therapy (CRT) in postoperative periord of cardiac surgery may contribute to reduction of pulmonary complications. Objectives: To evaluate the safety and compliance of preventive application of BiPAP ® CRT associated with immediate postoperative myocardial revascularization. Methods: 26 patients undergoing coronary artery bypass grafting were randomly allocated in one of the groups. Patients of the Control Group (CG) were treated only with conventional respiratory therapy, compared to BiPAP group (BG) (in addition to conventional respiratory therapy the patients were subjected to 30 minutes of ventilation by two levels twice a day). The conventional respiratory therapy was held in both groups, twice a day. All patients were evaluated for vital capacity, airway permeability, maximal respiratory pressures, oxygen saturation, heart rate, respiratory frequency, Volume Minute, tidal volume, systolic

and diastolic blood pressure. Evaluations were performed during hospitalization preoperatively, immediately after extubation, 24h and 48h after extubation. Results: In CG 61.5% of patients had some degree of atelectasias, in comparison to 54% of BG (P=0.691). The vital capacity was higher in the GB postoperatively (P<0.015). All the other ventilometric, gasometric, hemodynamic and manometric parameters were similar between groups. Conclusion: Coronary artery bypass grafting leads to deterioration of respiratory function postoperatively, and the application of positive pressure ventilation (BiPAP®) may be beneficial to restore lung function more quickly, especially vital capacity, safely, and well accepted by patients due to greater comfort with the sensation of pain during the execution of respiratory therapy.

1. Master, Physiotherapist of the Emergency Unit of Hospital das Clínicas, School of Medicine of Ribeirão Preto - USP, Ribeirão Preto, Brazil. 2. Physiotherapist of the Emergency Unit of Hospital das Clínicas, School of Medicine of Ribeirão Preto - USP, Master, Department of Neuroscience and Behavioral Sciences, Ribeirão Preto, Brazil. 3. Professor, Division of Thoracic and Cardiovascular Surgery, School of Medicine of Ribeirão Preto - USP, Ribeirão Preto, Brazil.

Correspondence Address: Aline Marques Franco. Rua Dr. Bernardino de Campos, 851 – São Carlos, SP, Brazil Zip Code: 13574-030 E-mail: amfranco@hcrp.usp.br Supported by: FAEPA CAPES

Study conducted at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCFMRP-USP), Ribeirão Preto, Brazil.

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Descriptors: Cardiovascular surgical procedures. Physical therapy modalities. Postoperative care. Pulmonary ventilation.

Article received on April 9th, 2011 Article accepted on September 5th, 2011

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Resumo Introdução: A aplicação de ventilação por dois níveis de pressão positiva (BiPAP ® ) associada à fisioterapia respiratória convencional (FRC) no pós-operatório (PO) imediato de cirurgia cardíaca pode contribuir para a diminuição das complicações pulmonares. Objetivo: Avaliar a segurança e a adesão da aplicação preventiva do BiPAP® associado a FRC no PO imediato de revascularização do miocárdio. Métodos: Vinte e seis pacientes submetidos a revascularização do miocárdio foram aleatoriamente alocados. O Grupo Controle (GC) foi tratado com FRC, o Grupo BiPAP (GB) foi submetido a 30 minutos de BiPAP®, duas vezes ao dia, associado à FRC. A FRC foi realizada em ambos os grupos, duas vezes ao dia. Todos os pacientes foram avaliados quanto: capacidade vital, permeabilidade das vias aéreas, pressões respiratórias máximas, saturação de oxigênio, frequência cardíaca, frequência respiratória, volume minuto, volume corrente, pressões arteriais sistólica e diastólica. As avaliações foram realizadas durante a

internação no pré-operatório, imediatamente após a extubação, e na 24a e 48a horas após extubação. Resultados: No GC, 61,5% dos pacientes tiveram algum grau de atelectasias, no GB, 54% (P=0,691). A capacidade vital foi estatisticamente maior no GB no PO (P<0,015). Todos os outros parâmetros de ventilometria, gasometria, manovacuometria e hemodinâmicos foram semelhantes entre os grupos. Conclusão: A cirurgia de revascularização do miocárdio leva à degradação da função respiratória no PO, e a aplicação da ventilação com pressão positiva (BiPAP®) pode ser benéfica para reestabelecer a função pulmonar mais rapidamente, principalmente a capacidade vital, de forma segura, sendo bem aceita pelos paciente, devido ao maior conforto em relação à sensação de dor durante a execução da fisioterapia respiratória.

INTRODUCTION The frequency of surgical procedures has increased steadily in recent decades [1]. Despite the modernization of the procedures used in cardiac surgery, pulmonary function is still affected and postoperative pulmonary complications are still a significant cause of mortality and morbidity in the postoperative period [1-6]. Patients undergoing cardiac surgery, most of the time, influenced by pre-, peri- and post-operative (PO) factors, are predisposed to pulmonary complications that become more evident in the postoperative period. In the preoperative period, the factors that contribute to changes in pulmonary function are mainly pulmonary disease, smoking, obesity and lung congestion from heart failure [7]. During the postoperative period, patients may experience changes in lung volume and capacity, due to several factors, including a restrictive phenomenon of change in thoracic dynamics caused by chest pain generated by drains and surgical incisions of the type median sternotomy, thereby undermining the ventilatory dynamics. Another factor interfering with lung function includes positioning for surgery and cardiopulmonary

Descritores: Procedimentos cirúrgicos cardiovasculares. Modalidades de fisioterapia. Cuidados pós-operatórios. Ventilação pulmonar.

bypass (CPB) itself, leading to a significant inflammatory reaction. Also anesthesia, as well as its time of use, lead to a change in the breathing pattern, which becomes superficial, which added to the diaphragmatic dysfunction culminate in alveolar hypoventilation, reduction in airway responsiveness and hypoxemia [8]. The abnormalities in pulmonary mechanics after cardiac surgery are characterized by a restrictive pattern with decreased vital capacity (VC) and functional residual capacity (FRC) [9.10]. The VC is usually reduced to about 40% to 50% of preoperative values during a period of at least 10 to 14 days [11-14]. The FRC is reduced to about 70% of preoperative levels returning to normal within 7 to 10 days [15]. This pattern of restrictive lung disease and hypoxemia prevalent in cardiac surgery PO cannot be prevented, but can be modified. Therefore, the basis of therapeutic modalities used is the maintenance or restoration of Functional Residual Capacity (FRC) [7]. The mechanical and physiological changes add up, compromising lung function and decreasing respiratory muscle strength (RMS) in order to delay the recovery of the patient in the postoperative cardiac surgery, for the 583

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proper maintenance of RMS is essential for ventilation and facilitation of airway clearance [15]. Atelectasis and pneumonia, caused by changes in respiratory mechanics, are the main pulmonary complications resulting from heart surgery, and these can cause increased breathing effort and decreased lung capacity, thus, increasing predisposition to lung infections [10]. The incidence of atelectasis in patients undergoing cardiac surgery with CPB is high, ranging from 60% to 90% [16]. Pneumonia can be attributed to the decrease in expiratory flow and ciliary rate and the inhibition or ineffective cough [10]. Physical therapy in the postoperative period after the arrival of the patient in the intensive care unit contributes much to the appropriate ventilation and successful extubation [17]. Respiratory therapy is often used in the prevention and treatment of postoperative complications such as retention of secretions, atelectasis and pneumonia [18]. In recent years, scientific studies have investigated therapeutic strategies that could prevent or minimize pulmonary complications after cardiac surgery [19,20]. For treatment and prevention of respiratory complications that usually occur in the postoperative period of cardiac surgery many different therapies have been applied such as: Conventional Respiratory Physiotherapy (CRF), Incentive Spirometry, Positive Pressure in a noninvasive mask with Positive end-expiratory pressure (PEEP), continuous positive airway pressure (CPAP) and ventilation with two levels of Positive Airway Pressure (BiPAP 速), leading to significant decrease in the incidence of these complications compared to patients who did not undergo any physical therapy approach [21 -23]. The non-invasive ventilation (NIV) reduces the work of breathing and increased respiratory system compliance by reversing lung microatelectasis [24], and it is independent of patient effort to generate deep breaths, and thus an advantage over other methods, especially in the immediate postoperative period in which the patient is uncooperative or unable to perform maximal inspiration, promoting an increase of both volume and lung capacity [25]. It is also found that the use of NIV for at least two days after surgery, leads to beneficial effects on pulmonary function and oxygenation indices [7]. There are also the hemodynamic benefits such as reduced preload by reducing venous return, decreased afterload of the left ventricle by reducing its transmural pressure and increased cardiac output, which leads to improved performance of the heart as a pump [26]. Several authors have shown that the use of NIV may be useful in improving lung function and gas exchange in the postoperative period of CABG surgery, however the clinical

significance of these findings need confirmation [27,28]. Given the number of complications that occur in the postoperative cardiac surgery and the beneficial effects of NIV by applying two pressure levels, found in the literature, this study is appropriate, contributing to greater number of scientific works substantiating this technique of ventilation. The objective of this study is to evaluate the safety and adherence, and effectiveness of application of noninvasive ventilation for two levels of positive pressure associated with CRF, on the early postoperative period of patients undergoing coronary artery bypass grafting.

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METHODS We evaluated 26 patients undergoing elective cardiac surgery for CABG with CPB and median incision performed at the Hospital of the School of Medicine of Ribeir達o Preto - USP. All patients signed an informed consent by providing guidance on the proposed protocol, in compliance with Resolution 196/96 of the CNS, and this study was approved by the Ethics Committee of Hospital das Cl鱈nicas de Ribeirao Preto. We excluded those who underwent emergency surgery, low level of understanding and age less than 40 years and surgeries performed without the use of CPB. The protocol was extended by two days after surgery. Patients were randomly selected and gathered into two groups, forming a BiPAP Group (BG), with 13 patients treated with CRF associated with BiPAP 速 applications (twice a day, lasting 30 minutes each application), and Control Group (CG) with 13 patients treated with CRF. Evaluations were performed preoperatively, immediately after extubation (IPE), 24 and 48 hours after extubation. Preoperatively, patients received information about surgical procedures and physical therapy to be performed in different periods of recovery (hospitalization period), all being subject to an assessment clinic, which contained personal data, demographics, medical diagnosis, personal history data related to surgery, and specific measures such as RMS, Spirometry and peak expiratory flow. RMS was obtained with a manometer Ger-Air brand, scaled in cmH2O, according to the methodology proposed by Black and Hyatt [29]. For the maneuver, the patient was instructed to perform a maximal inspiratory effort after full exhalation to measure maximal inspiratory pressure (MIP). Likewise, the patient was instructed to perform a maximal expiratory effort at the end of a maximal inspiration, to measure maximal expiratory pressure (MEP). Spirometry was used to obtain tidal volume (TV), minute volume (MV) and vital capacity (VC), through the use of a brand of portable digital spirometer Electronic spirometer. All measurements (TV, MV and VC) were evaluated with the patient breathing spontaneously, sitting position,

Franco AM, et al. - Assessment of noninvasive ventilation with two levels of positive airway pressure in patients after cardiac surgery

Rev Bras Cir Cardiovasc 2011;26(4):582-90

wearing a nose clip. To obtain the MV, the patient was asked to inhale and exhale slowly for a minute, where it was recorded the value of MV and respiratory rate (RR). The VC was obtained by dividing the MV by RR. To obtain the VC, the patient was asked to inhale deeply as much as I could and then drop all the air until the lungs completely empty. The maneuvers were performed three times. RMS was measured by the movements of the chest during the respiratory cycles performed in one minute. After performing heart surgery, patients received the treatment proposed in accordance with your group, and the CRF consisted of diaphragmatic breathing exercises associated with active movement and / or active-assisted on upper limbs, lower limb mobilization, clearance maneuvers, relief of cough and reexpansion techniques. The application of BiPAP ® was used in the spontaneous mode, cycled at two levels of positive pressure with a pressure level during inspiration (IPAP) 8 to 12 cmH2O and a pressure level during exhalation (EPAP) of 6 cmH2O. RESULTS Table 1 shows the anthropometric characteristics, demographic, clinical and surgical patients involved in this study for CG and BG. Figure 1 illustrates the behavior of the values of respirometry. Both the MV, such as TV and VC showed significant decreases when compared to those of postoperative to preoperative, all with P <0.001. However, only the VC values between groups were significant (P = 0.015). With regard to the FP, Figure 2 shows the results obtained from the pre-operative until the 48th hour after extubation, and we observed that in both groups, the significant drop when comparing the values obtained in the postoperative the pre-operative with P <0.001. However, there was no significant difference in values between the groups (P = 0.327).

Table 1. Anthropometric, clinical and surgical characteristics in mean and standard deviation of the patients studied. Variables Gender (n, %) Male Female Weight (kg) Height (m) BMI (kg/m2) Time of surgery (min) Time of Ao clamping (min) Time of CPB (min)

Control Group N = 13

BiPAP Group N = 13

7 (53.8%) 6 (46.2%) 74.14 ± 14.90 1.63 ± 0.06 27.96 ± 5.57 238.5 ± 33.69

10 (76.9%) 3 (23.1%) 68.52 ± 11.64 1.64 ± 0.13 25.56 ± 2.55 253.1 ± 54.07

0.411

50.2 ± 21.4 68.9 ± 22.7

56.6 ± 19.8 76.3 ± 27.1

0.064 0.152

Unpaired Student’s t test / Mann-Whitney

0.488 0.572 0.448 0.503

Fig. 1 - A: Distribution of the changes in Minute Volume Preoperatively, immediate postextubation, 24 and 48 hours after extubation, on average, in control groups and BiPAP (P <0.001 within groups, P = 0.250 between groups) ; B: Distribution of the changes in tidal volume in the preoperative, immediate postextubation, 24 and 48 hours after extubation on average in the groups (P <0.001 within groups, P = 0.250 between groups), C: Distribution of the changes of vital capacity preoperatively, immediately after extubation, 24 and 48 hours after extubation on average in the BiPAP and control groups (P <0.001 within groups, P = 0.15 between groups). Pre-op = preoperatively and PE = Post-extubation

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Regarding the RR in both groups, a significant increase when comparing the values obtained postoperatively with the preoperative (P <0.001), similarly in both groups. But there was no significant difference between groups (P = 0.265) (Figure 3). Figure 4 illustrates the behavior of the values of MRR (MIP and MEP), which can be seen that both the MIP and MEP present in both groups, significant drop in their values when compared with those obtained postoperatively with the preoperative period (P <0.001). But there was no significant difference between groups (P = 0.463 and P = 0.843, respectively).

Fig. 2 - Distribution of changes in expiratory flow peak preoperatively, immediately after extubation, 24 and 48 hours after extubation on average in the BiPAP and control groups. Pre-op = preoperatively and PE = Post-extubation. (P <0.001 within groups, P = 0.327 between groups)

Fig. 3 - Distribution of the changes in respiratory rate in the preoperative, immediate post-extubation, 24 and 48 hours after extubation on average in the BiPAP and control groups. Pre-op = preoperatively and PE = Post-extubation. (P <0.001 within groups, P = 0.265 between groups)

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Fig. 4 - A: Distribution of the changes in maximal inspiratory pressure preoperatively, immediately after extubation, 24 and 48 hours after extubation on average in the BiPAP and control groups. Pre-op = preoperatively and PE = Post-extubation. (P <0.001 within groups, P = 0.123 between groups), B: Distribution of changes in maximal expiratory pressure preoperatively, immediately after extubation, 24 and 48 hours after extubation on average in the BiPAP and control groups. Pre-op = preoperatively and PE = Post-extubation. (P = 0.540 within groups, P = 0.056 between groups)

Fig. 5 - Evolution of the mean scores of atelectasis on days 1, 2 and 3 post-operative and control groups in the BiPAP. PO: postoperative. (P = 0.070 within groups, P = 0.080 between groups)

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No patient had radiological findings compatible with atelectasis in the preoperative radiographs. In the control group, 61.5% of patients had some degree of postoperative atelectasis in the group BiPAP 速, the incidence was 54% (P = 0.080). When comparing the degree of atelectasis, the severity score according to the adopted, although we observed a tendency to less severe atelectasis in the BiPAP group, the differences were not statistically significant (P = 0.070) (Figure 5). The evolution of measures of heart rate, systolic and diastolic blood pressure preoperatively, immediately after extubation, 24th and 48th hours after extubation, on average, the BiPAP and control groups is shown in Figure 6. DISCUSSION

Fig. 6 - The Evolution of Heart Rate measures preoperatively, immediately after extubation, 24 and 48 hours after extubation on average in the BiPAP and control groups. Pre-op: Pre-operative PE: Post-extubation (P <0.001 within groups, P = 0.123 between groups), B: Change in systolic blood pressure measurements preoperatively, immediately after extubation, 24th and 48th hour postextubation on average in the BiPAP and control groups. Pre-op: Pre-operative PE: Post-extubation. (P = 0.540 within groups, P = 0.056 between groups), C: Changes in diastolic blood pressure measurements preoperatively, Immediate Post-extubation, 24th and 48th in average hours post extubation, BiPAP and control groups. Pre-op: Pre-operative PE: Post-extubation. (P = 0.358 within groups, P = 0.224 between groups)

The NIV administered continuously or intermittently has been used alone or in combination with physical therapy maneuvers to prevent atelectasis and hypoxemia in the postoperative period of abdominal surgeries, but with conflicting results [30,31]. The patients studied had no radiological findings compatible with atelectasis in the preoperative radiographs. In the control group, 61.5% of patients had some degree of postoperative atelectasis in the BiPAP group, the incidence was 54% (P = 0.691). When comparing the degree of atelectasis, the severity score according to the adopted, although they note a tendency to less severe atelectasis in the BiPAP group, the differences were not statistically significant (P = 0.070). Decreased effectiveness of cough, decreased mobility in bed, reduced discharges and airway narrowing and muscle fatigue associated with physiological changes in breathing pattern, diaphragmatic breathing to a more superficial and predominantly thoracic, are responsible for the decrease in the expansion of lower lung lobes [32]. Lung damage in reinsufflation may culminate in the continuation or worsening of the situation, encouraging the development of pneumonic processes [33]. It was verified in this study that the peak expiratory flow in the BiPAP group had an average value at the 48th hour of 244.62, while the control group the average was 132.31, but there was no significant difference between groups. We believe that the increase in the raid chest with the use of BiPAP速 improves the effectiveness of cough, increasing discharges and, consequently, the permeability of the airways, improving the values of flow peak. The ventilation of patients undergoing this type of surgery is impaired due to the shallow breathing and lowamplitude in an attempt to minimize the pain. It was found that statement, because the tidal volume and vital capacity in the postoperative moments immediate postoperative 587

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period, 24th and 48th hours were lower than the preoperative in both groups, with statistical significance. Moreover, the vital capacity was statistically different when comparing the two groups, where group means BiPAP preoperatively, immediately after extubation and 24 and 48 hours after extubation were 2.64, 0.99, 1, 53 and 1.94, respectively, and in the control group, the averages were 2.11, 0.90, 0.90 and 0.97, respectively. In the study by Stell et al. [34], the use of NIV in the postoperative period also contributed to the increase in vital capacity, vital capacity proved to be an important parameter to determine whether the patient has risk of reintubation. NIV reduces the work of breathing and improves respiratory system compliance by reversing microatelectasis lung [23], and is independent of patient effort to generate deep breaths, so an advantage over other methods, particularly in the immediate postoperative period in which the patient is uncooperative or unable to perform maximal inspiration due to pain, by increasing the values of lung volumes and capacities [24]. However, the acceptance of the proposed treatment of the BiPAP group was better, not because the dependence on patient effort to generate deep breaths, reduces pain during exercise, which is run more efficiently, which creates an advantage over FRC group of individuals who feel more insecure to perform deep breaths. It is also found that the use of NIV for at least two days after surgery, leads to beneficial effects on pulmonary function and oxygenation indices [7]. In the present study, we observed an increase in pulmonary function parameters measured after 48 hours after surgery. It is understood, therefore, the statement indicates that the therapeutic application of positive pressure in the first hours after surgery with the goal of restoring lung volume and capacity, and respiratory complications often encountered in postoperative cardiac surgery, and decrease in tidal volume and vital capacity in the first hour is a common finding and can cause serious systemic complications, mainly due to cellular hypoxia. As for the variable minute volume, there was no significant difference between the two groups, pre-and postoperatively, but the respiratory rate of patients undergoing conventional treatment, despite remaining within the normal range, had higher average values of elevated at 24 hours (respiratory rate of 22.77 rpm) and 48 h (respiratory rate of 22.38 rpm) compared to patients in the group undergoing treatment with BiPAP 速, mean values remained lower at 24 hours (respiratory rate of 21.00 rpm) and 48 h (respiratory rate of 18.92 rpm). By correlating the values of tidal volume, minute volume and respiratory rate, we can see the interrelationship between them and the form of compensation used by

patients in both groups, trying to keep an adequate minute volume. They had significantly lower tidal volume, therefore, adopted a compensatory mechanism, increasing the breathing rate, which was significantly higher. The peak of postoperative diaphragm dysfunction, a reduction of its strength, occurs in the period between two and eight hours after surgery, returning to preoperative values in 15 days approximately. These changes occur in response to surgery and can progress to respiratory complications when modifying the course originally planned for postoperative recovery. The complications are related to decreased contractile capacity of the diaphragm, directly represented by the reduction of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) [35,36]. Regarding the results obtained from the MIP in our study, decreased significantly in both groups postoperatively compared to preoperative values. When compared to the control group at the 48th hour, the group submitted the application of BiPAP 速 showed improvement in inspiratory muscle function (average of 51.92 for the BiPAP group and 31.54 for the control group), but there was no statistical significance. These results may have been identified as a result of removal of chest tubes, made around 36 hours after surgery, because with the reduction of pain caused by the presence of the drain, the patient has a greater ability to contraction of the respiratory muscles, but the best thoracic mobility to the BiPAP 速 due to increased inspiratory capacity allows the diaphragm better amplitude of incursion, which may condition the red fibers of high-oxidative, fatigue resistant, generate higher intrathoracic pressure, resulting in increased MIP. In relation to the MEP, it behaved similarly to the MIP, with significantly lower in both groups when compared to postoperative values with preoperative values. There was an increase in the average values in the 24 and 48 hours compared to immediate post-extubation time, with no statistical significance between groups, but with higher values for the BiPAP group. Respiratory muscle strength increases directly with the clinical improvement after surgery, probably by reducing pain in consequence of the removal of drains and the improvement of elastic recoil of the chest through the healing process. After removal of drains, the patient improves the degree of mobility, achieving better posture, decreasing, and hence the degree of respiratory muscle weakness and improving its mechanism of action [37]. The length of ICU stay ranged from 2 to 3 days in both groups. In the BiPAP group only one patient remained three days, while in the control group, four patients remained three days. Already, the average length of hospital stay in the control group was 9.30 days, while in the BiPAP group the average was 7.38 days.

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It can be observed that there is a tendency to more rapid improvement of the parameters evaluated in the BiPAP group patients compared to the group of CRF (Figures 1 to 4). The application of NIV in a preventive postoperative proved to be safe, maintaining stable hemodynamic parameters (Figure 6) and without any other complication, such as vomiting and aspiration, chest discomfort, nasal congestion, pneumothorax, pneumocephalus, pain in sinuses, sinusitis, nasal dryness, subcutaneous emphysema in the lower eyelids, aerophagia and epistaxis.

5. Borges DL, Sousa LRT, Silva RT, Gomes HCR, Ferreira FMM, Lima WL, et al. Complicações pulmonares em crianças submetidas à cirurgia cardíaca em um hospital universitário. Rev Bras Cir Cardiovasc. 2010;25(2):234-7.

CONCLUSION In conclusion, we observed that patients undergoing coronary artery bypass grafting associated with CPB showed losses on lung function, and the use of BiPAP ® associated with postoperative CRF was safe and well accepted by patients and have increased vital capacity.

6. Lima PMB, Cavalcante HEF, Rocha ARM, Brito RTF. Fisioterapia no pós-operatório de cirurgia cardíaca: a percepção do paciente. Rev Bras Cir Cardiovasc. 2011;26(2):244-9. 7. Ferreira FR, Moreira FB, Parreira VF. Ventilação não-invasiva nos pós-operatórios de cirurgias abdominais e cardíacas. Rev Bras Fisioter. 2002;6(2):55-62. 8. Senra DF, Iasbech JA, Oliveira SA. Pós-operatório em cirurgia cardíaca de adultos. Rev SOCESP. 1998;8(3):446-54. 9. Craig DB. Postoperative recovery of pulmonary function. Anesth Analg. 1981;60(1):46-52. 10. Pazzianotto-Forti EM, Nalet OMCC, Giglioli MO. A eficácia da aplicação de pressão positiva contínua nas vias aéreas (CPAP), com utilização do Bird Mark 7, em pacientes em pósoperatório de cirurgia de revascularização do miocárdio. Rev Bras Fisioter. 2002;6(1):31-5. 11. Jorris JL, Sottiaux TM, Chiche JD, Desaive CJ, Lamy ML. Effect of bi-level positive airway pressure (BiPAP) nasal ventilation on the postoperative pulmonary restrictive syndrome in obese patientes undergoing gastroplasty. Chest. 1997;111(3):665-70. 12. Knobel E. Condutas no paciente grave. 2ª ed. São Paulo:Atheneu;1998. p.322-51. 13. Lindberg P, Gunnarsson L, Tokics L, Secher E, Lundquist H, Brismar B, et al. Atelectasis and lung function in the postoperative period. Acta Anaesthesiol Scand. 1992;36(6):546-53.

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31. Varon J, Walsh GL, Fromm RE Jr. Feasibility of noninvasive mechanical ventilation in the treatment of acute respiratory failure in postoperative cancer patients. J Crit Care. 1998;13(2):55-7.

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ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):591-6

Transcutaneous electrical nerve stimulation after coronary artery bypass graft surgery Estimulação elétrica nervosa transcutânea após cirurgia de revascularização miocárdica

Paula Monique Barbosa Lima1, Rebeca Taciana Fernandes de Brito Farias1, Aline Carla Araújo Carvalho2, Patrícia Nobre Calheiros da Silva3, Nailton Alves Ferraz Filho4, Rosinete Fernandes de Brito5 DOI: 10.5935/1678-9741.20110049 Abstract Introduction: After cardiac surgery, patients have a limitation in respiratory muscle strength, which favors the appearing of pulmonary complications. Objective: To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) on the painful process and respiratory muscle strength in patients undergoing coronary artery bypass graft (CABG). Methods: The study included patients after on-pump CABG through sternotomy, general anesthesia, without being under the influence of neuromuscular blockade, with use of chest and mediastinal tubes, and extubation within 6 hours after the procedure and presenting index equal to or greater than three visual analog scale (VAS) of pain being on the first day after surgery. We recruited 20 patients divided into two groups with no predominance of sex: the control group (n = 10), who received more physiotherapy analgesic therapy, and TENS group received analgesic therapy, physiotherapy and TENS. The TENS was applied for 30 minutes, three times a day, a 3-hour period each application. Results: For the degree of pain, there was an average start and end, respectively, 7.0 / 1.0 for the TENS group and 7.0 / 8.0 for the control group. For inspiratory muscle strength, - 102.5 cmH2O / - 141.17 cm H2O to the TENS group and - 97.0 cmH2O / - 100.3 cm H2O for control. The expiratory muscle strength, 63cmH2O/125 cmH2O for the TENS group and 55.3 cmH2O/ 53, 2 cmH2O for the control group.

1. Physiotherapist, Specialist in Hospital Physical Therapy from the University Center CESMAC, Maceió, AL, Brazil. 2. Physiotherapist, Specialist in Traumatology and Orthopaedics by UGF, Professor of Physical Therapy University Center CESMAC, Maceió, AL, Brazil. 3. Physiotherapist, Professor of Physical Therapy University Center CESMAC, Maceió, AL, Brazil. 4. Physiotherapist, Specialist in Applied Exercise Physiology for Health and Performance UNCISAL - Maceió / AL; Professor of Physical Therapy Graduate Hospital of FCBS - CESMAC, Maceió, AL, Brazil. 5. Physiotherapist, Specialist in Intensive Care and Rehabilitation by REDENTOR, Maceió, AL, Brasil.

RBCCV 44205-1325 Conclusions: TENS has shown significant effectiveness in reducing pain, and the increase in respiratory muscle strength at first-day after CABG surgery. Descriptors: Pain. Muscle strength. Transcutaneous electric nerve stimulation. Cardiovascular surgical procedures.

Resumo Introdução: Após a cirurgia cardíaca, os pacientes apresentam limitação na força muscular respiratória, o que favorece a instalação de complicações pulmonares. Objetivo: Analisar a eficácia da estimulação elétrica nervosa transcutânea sobre o processo doloroso e força muscular respiratória em pacientes submetidos à cirurgia de revascularização do miocárdio (CRM). Métodos: Foram inclusos pacientes em pós-operatório de CRM por meio de esternotomia, com uso de circulação extracorpórea, anestesia geral, sem estar sob efeito de bloqueio neuromuscular, uso de drenos de tórax e mediastino, extubados até 6 horas pós-procedimento e apresentando índice igual ou superior a três na escala analógica visual da dor (EVA), estando no primeiro dia de pós-operatório (1º DPO). Foram recrutados 20 pacientes, divididos em dois grupos, sem predomínio de sexo: Grupo Controle (n=10), que recebeu terapia analgésica mais

Work performed in the Cardiac ICU of the Instituto de Doenças do Coração (IDC) of Santa Casa de Misericórdia de Maceió, Maceió, AL, Brazil.

Correspondence address: Paula Monique Barbosa Lima Rua Deputado José Lages, 200, ap 203 – Ponta Verde – Maceió, AL, Brazil – Zip Code: 57035-330 E-mail: ftpaulamonique@hotmail.com

Article received on May 18th, 2011 Article accepted on September 20th, 2011

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fisioterapia; e Grupo TENS, que recebeu terapia analgésica, fisioterapia e TENS. A TENS foi aplicada por 30 minutos, três vezes ao dia, num intervalo de 3 horas cada aplicação. Resultados: Para o grau de dor, houve uma média inicial e final, respectivamente, de 7,0 e 1,0 para o Grupo TENS e 7,0 e 8,0 para o Grupo Controle. Para a Pimáx, a média inicial e final foi de, respectivamente, -102,5 cmH2O e 141,17 cmH2O para o Grupo TENS e -97,0 cmH2O e -100,3 cmH2O para o Controle. Quanto a Pemáx, a média inicial e final foi de, respectivamente, 63 cmH2O e 125 cmH2O para o

Grupo TENS e 55,3 cmH2O e 53,2 cmH2O para o Grupo Controle. Conclusão: A TENS demonstrou eficácia significativa na redução da algia e no aumento das forças musculares respiratórias no 1º DPO de CRM.

INTRODUCTION Pulmonary complications have been described by several authors as a major cause of postoperative morbidity [1-9]. Complications such as: decrease in forced expiratory volume in the first second (FEV1), functional residual capacity (FRC), tidal volume (TV), arterial pressure oxygen (PaO2), besides the increase of atelectasis [7.10, 11]. However, few studies are found reporting the effect on respiratory muscle strength [7,12]. According to the International Association for the Study of Pain, pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential damage of tissues, or described in terms of this” [13]. Pain after surgery has completely multifactorial origin and may be caused due to surgical incision, pleural tubes, and procedures that the patient is subjected [14]. This is present even before the surgery and it is important in respiratory function in the postoperative period, which may aggravate bronchial hygiene. These findings lead us to develop different strategies in the treatment of pain and physical therapy that might interfere with pain, with consequent improvement in lung function [15]. The transcutaneous electrical nerve stimulation (TENS) is a physical therapy feature widely used for symptomatic relief of pain and it can be a useful adjunct in the management of postoperative pain [11-16]. This form of stimulation does not produce systemic effects, it is not invasive or pharmacological, it is not addictive, nor does it have side effects and absolute contraindications it is a lowcost procedure, in addition to allow the patient to participate more completely in physical therapy [11 , 17]. It has been reported in the literature that pain relief after surgery by the use of TENS is associated to the reduction of the use of opiates [10,16,18-20].

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Descritores: Dor. Força muscular. Estimulação elétrica nervosa transcutânea. Procedimentos cirúrgicos cardiovasculares.

Its physiology stimulates nerve fibers that transmit signals to the brain, interpreted by the thalamus as pain. The basis of the effect of TENS is given as the Theory of Gates, developed in 1965 by Melzack & Wall, who claimed that the overstimulation of type A fibers promotes blocking of incoming stimulus by type C fibers in the gates of the posterior horn of the spinal cord in the jelly substance and the transmission cells (T cells) [16]. The objective of this study was to analyze the effectiveness of conventional TENS on the painful process and respiratory muscle strength in patients undergoing coronary artery bypass grafting through median sternotomy. METHODS This study was performed in 5-month period from November 2008 until April 2009, at the Cardiac ICU of the Instituto de Doenças do Coração (IDC) of Santa Casa de Misericordia de Maceió. It was a field study, controlled, which included 20 patients of both genders, aged from 40 to 60 years of age, undergoing coronary artery bypass grafting through median sternotomy with cardiopulmonary bypass (CPB), general anesthesia, use of chest and mediastinal tubes, extubated within six hours after ICU admission (Fast Track) and showing a rate equal to or greater than three in the visual analog scale of pain (VAS). We used as exclusion criteria: diabetes mellitus, age under 40 and over 60 years, patients with cognitive deficit, with center and / or peripheral neurological sequelae, with painful symptoms of undiagnosed cause, with the presence of metallic implants, pacemaker patients undergoing coronary artery bypass grafting by thoracotomy, who had local infection, still under the effect of neuromuscular blocking agent, and not adapting to the use of TENS.

Lima PMB, et al. - Transcutaneous electrical nerve stimulation after coronary artery bypass graft surgery

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Patients were approached directly and individually, on the first day after surgery (1 POD) in the cardiac ICU, and after being informed about the procedures they would be exposed, we obtained the signatures of the term of informed consent (IC) according to the resolution 196/96 CONEP. The study protocol was approved by the Ethics and Research Committee of FCBS (CEP-FCBS / CESMAC), protocol 511/08 on September 1, 2008. The distribution of patients according to sex, was sequentially and alternately, where the first patient received the number one, number two the second and so on, the odd numbers being directed to the control group and even numbers to the TENS group. Patients, thus, were divided into two groups: control group (followed the usual routine of analgesics and physiotherapy at the hospital) and TENS group (followed the usual routine of analgesics and physiotherapy at the hospital, plus the conventional TENS). Both groups consisted of 10 patients, with no predominance of gender. We used an electrical stimulation unit that contains the conventional TENS brand Orion, with two channels, with silicon electrodes, rectangular shape (5 x 3.5 cm). As a means of contact it was used aqueous gel, and for attachment, masking tape. We used two channels where the electrodes were arranged in parallel and pericicatricial fashion at 4 cm from the surgical incision. The duration of application was 30 minutes, being held on the 1st POD for three times, at 14, 17 and 20 hours. The frequency that was used in TENS was 80 to 110 Hz,

with pulse widths between 50 and 80 µs. The intensity of stimulation was modified according to the patient’s report and being adjusted based on an intense feeling of numbness that would not cause discomfort, not being increased during application. For pain assessment it was used VAS, graduated from zero to ten, where zero means no pain and ten, severe pain, being applied before and after. Similarly, measurement was made of muscle strength (MIP) and expiratory muscle strength (MEP) through the manometer brand Marshall Town, before and after, being carried from the functional residual capacity (FRC) for three times, where the highest value was considered, and the patient placed in a 60° Fowler. The data were stored on a folder developed for this purpose. The sample size was calculated in 10 subjects for each group (standard deviation of 10, a difference of 12 to be detected; significance level of 5% test power of 80%) via the software online Graphpad ® using as a means of calculation the page of the Laboratory of Epidemiology and Statistics of the Institute Dante Pazzanese, which is available online (www.lee.dante.br/pesquisa/amostragem / calculo_amostra.html). To compare the ratings between the control group and TENS group it was used the nonparametric test of Mann-Whitney, adopting the significance level of 5% (0.05). To compare the ratings before and after for each group we used the nonparametric test of Wilcoxon, adopting the significance level of 5%. Subsequently, being tabulated and processed in a spreadsheet (Microsoft Excel 2000 for Windows).

Table 1. Description of the sample regarding the time of cardiac surgery, cardiopulmonary bypass time, degree of pain, MIP and MEP in patients undergoing coronary artery bypass grafting through median sternotomy. TENS (n=10) Control (N=10) Before Before After After SD Mean SD P N Mean SD Mean SD P N Mean Total 10 10 T. CPB

95´

75´

T. CC

255´

240´

Age

54.2

55.1

Pain

7.0

MIP MEP

1.78

-102.5 14.87 63.0

37.23

1.0

0.67

0.001

7.0

2.01

-141.17 13.65

0.003

-97.0

54.65

0.003

55.3

8.96

125.0

34.47

8.0

1.96

-100.30 54.52 53.20

8.96

0.2748 1 1

T. CPB- Cardiopulmonary bypass time (min), T. CC - Time of cardiac surgery (min) MIP - Maximal inspiratory pressure (cmH2O), MEP – Maximal expiratory pressure (cmH2O)

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RESULTS Twenty individuals consisted the homogeneous sample, with no predominance of gender in the ICU of Instituto de Doenças do Coração (IDC) of Santa Casa de Misericordia de Maceió. The description of sex in groups, the mean duration of surgery and CPB, degree of pain, MIP and MEP start and end are shown in Table 1. We observed the use of medication in the control group during the time of intervention, from 14h to 20h30. Of the ten patients in the control group, four were treated with sodium dipyrone and two with morphine sulfate. Only one patient of the TENS group requested analgesic and the remaining patients did not require drug therapy in the schedule above due to significant pain relief. As for heart rate (bpm), no significant changes were noted during the hours of research, both in the control group as in the TENS group. Comparisons within the TENS group showed to be significant in all parameters evaluated, with a reduction in algia, increased respiratory muscle strength and decrease in requests for analgesics. This was not seen in the control group. DISCUSSION Several authors [21-23] evaluated patients who underwent cardiac surgery for the location and intensity of pain during the hospitalization, pain influence on pulmonary function and its correlation with the characteristics of the individual and the surgical procedure and concluded that there was significant damage to lung function, without full recovery until the 5th POD. The postoperative pain control is essential for comprehensive care to surgical patients, as prolonged painful stimuli appear to predispose to more severe pain and complications in the postoperative period [24]. Since the 1970s, the effects of TENS have been studied on acute and chronic pain. Some studies were extended to also benefit the algesic processes occurring in the postoperative period [25]. According to Brodsky and Mark [26], the results after lateral thoracotomy or sternotomy are varied; with many studies supporting the effectiveness of TENS in patients undergoing such surgeries and others claiming that TENS has little or no value after these procedures. In a study of 324 patients undergoing different types of chest surgery, Benedetti et al. [27] reported that TENS has little or no benefit after procedures associated with severe pain (posterolateral thoracotomy). In pain score suggested by the authors, the patients in this study had a moderate degree of pain, however, unlike the results seen by them, the patients in this study had reduced the degree of pain 594

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regardless of TENS having been associated with drug therapy or not. Nonetheless in their study there was no assessment of pain, but the consumption of opioid analgesics. After heart surgery, patients have a limitation in respiratory muscle strength compared to before surgery, which facilitates the installation of pulmonary complications. Emmiller et al. [28], Navarathnam et al. [29], Lima et al. [30] and Klin et al. [31] evaluated the effects in their studies of TENS in cardiac postoperative and found that electrical stimulation decreases the level postoperative pain and reduces the amount of analgesics compared to placebo group or control group. A similar result was found in this study regarding pain reduction in TENS group, differing only in reducing pain in the control group, where it remained in this study. This fact has allowed the improvement of respiratory muscle strength and increased volumes and lung capacity, proving to be a valuable tool in the hands of the physiotherapist in hospital [31]. Cipriano et al. [32], after studying the transcutaneous electrical nerve stimulation in short-term pain control after cardiac surgery, concluded that there was an improvement in respiratory muscle strength and increased lung volume and capacity, as well as reducing the degree of pain demonstrating the positive effects on pulmonary function after use of TENS [32]. In this study, the use of TENS led to significant increase in both MIP (P <0.003) and in the MEP (P <0.003), whereas in the control group results were maintained. Several studies have concluded that TENS is effective in controlling postoperative pain after median sternotomy after cardiac surgery, confirming the results of this study, and it could be useful when patients had burning pain [27,28,32-34]. Although there are many controversies and rejection in relation to the use of TENS in any post-operative and the few studies specifically in cardiac surgery, we observed that there is a tendency to the effectiveness of TENS in the results found than otherwise, which was confirmed in the present study, which showed a significant reduction in the degree of pain and also significant increases in MIP and MEP values after the use of TENS. CONCLUSION According to our results, TENS was effective in controlling postoperative pain in patients in the 1st POD of coronary artery bypass grafting, avoiding excessive use of analgesics, as well as the improvement in respiratory muscle strength, especially in MEP, this muscle is so important for airway patency and prevention of pulmonary complications. Hence, we suggest the inclusion of TENS in the hospital postoperative routine as an alternative to drug therapy,

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which is effective, inexpensive, non-invasive, with no side effects, providing better welfare, without pain within an intensive care unit. It is suggested, therefore, the continuity of the study in order to reinforce the results found in this study, as well as broaden the scientific answers on the subject.

11. Dean E. Complicações, síndrome do desconforto respiratório do adulto, choque, sepse e falência de múltiplos órgãos. In: Dean E, Frownfelter D, eds. Fisioterapia cardiopulmonar. 3ª ed. Rio de Janeiro:Revinter;2004. p.485-6.

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12. Vieira GB, Bregagnol RK, Santos ACB, Paiva DN. Avaliação da eficácia da estimulação elétrica nervosa transcutânea sobre a intensidade da dor, volumes pulmonares e forca muscular respiratória no pós-operatório de cirurgia abdominal: estudo de caso. Rev Bras Fisioter. 2004;8(2):145-8. 13. Slullitel A, Souza A. Analgesia, sedação e bloqueio neuromuscular em UTI. Medicina. 1998;31:507-16. 14. Lima FVSO. Fisioterapia em cirurgia cardíaca. In: Sarmento GJV, ed. Fisioterapia respiratória no paciente crítico. São Paulo:Manole;2005. p.300-6. 15. Sasseron AB, Figueiredo LC, Trova K, Cardoso AL, Lima NMFV, Olmos SC, et al. A dor interfere na função respiratória após cirurgias cardíacas? Rev Bras Cir Cardiovasc. 2009;24(4):490-6. 16. Tonella RM, Araújo S, Silva AMO. Estimulação elétrica nervosa transcutânea no alívio da dor pós-operatória relacionada com procedimentos fisioterapêuticos em pacientes submetidos a intervenções cirúrgicas abdominais. Rev Bras Anestesiol. 2006;56(6):630-42. 17. Johnson M. Estimulação elétrica nervosa transcutânea (TENS). In: Bazin S, Kitchen S, eds. Eletroterapia: prática baseada em evidências. 11ª ed. São Paulo: Manole;2003. p.259-62. 18. Sabino GS, Souza MVS, Resende MA. Estimulação elétrica nervosa transcutânea no pós-operatório de cirurgia torácica ou abdominal. Fisioterapia em Movimento. 2006;19(1):59-71. 19. Marin LI, Castro CES. Estimulação elétrica nervosa transcutânea no controle da dor pós-laparotomia: estudo preliminar. Rev Bras Anestesiol. 1986;36(3):207-14. 20. Bjordal JM, Johnson MI, Ljunggreen AE. Transcutaneous electrical nerve stimulation (TENS) can reduce postoperative analgesic consumption. A meta-analysis with assessment of optimal treatment parameters for postoperative pain. Eur J Pain. 2003;7(2):181-8. 21. Giacomkazzi CM, Lagni VB, Monteiro MB. A dor pósoperatória como contribuinte do prejuízo na função pulmonar em pacientes submetidos à cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2006;21(4):386-92. 22. Borges JBC, Ferreira DLMP, Carvalho SMR, Martins AS, Andrade RR, Silva MAM. Avaliação da intensidade de dor e da funcionalidade no pós-operatório recente de cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2006;21(4):393-402. 23. Baumgarten MCS, Garcia GK, Frantzeski MH, Giacomazzi CM, Lagni VB, Dias AS, et al. Comportamento da dor e da

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função pulmonar em pacientes submetidos à cirurgia cardíaca via esternotomia. Rev Bras Cir Cardiovasc. 2009;24(4):497-505.

for postoperative analgesia following cardiac surgery. Anaesth Intensive Care. 1984;12(4):345-50.

24. Chaves lD, Pimenta CAM. Controle da dor pós-operatória: comparação entre métodos analgésicos. Rev Latino-am Enfermagem. 2003;11(2):215-9. 25. Gregorini C, Cipriano JG, Aquino LM, Branco JNR, Bernardelli GF. Estimulação elétrica nervosa transcutânea de curta duração no pós-operatório de cirurgia cardíaca. Arq Bras Cardiol. 2010;94(3):345-51. 26. Brodsky JB, Mark JB. Postthoracoscopy pain: is TENS the answer? Ann Thorac Surg. 1997;63(3):608-10. 27. Benedetti F, Amanzio M, Casadio C, Cavallo A, Cianci R, Giobbe R, et al. Control of postoperative pain by trancutaneous electrical nerve stimulation after thoracic operations. Ann Thorac Surg. 1997;63(3):773-6. 28. Emmiller M, Solak O, Kocogullari C, Dundar U, Ayva E, Ela Y, et al. Control of acute postoperative pain by trancutaneous electrical nerve stimulation after open cardiac operations: a randomized placebo-controlled prospective study. Heart Surg Forum. 2008;11(5):E300-3. 29. Navarathnam RG, Wang IY, Thomas D, Klineberg PL. Evaluation of the transcutaneous electrical nerve stimulator

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30. Lima PMB, Filho NAF, Brito RTF. Avaliação da estimulação elétrica nervosa transcutânea sobre a dor, força muscular respiratória e função pulmonar de pacientes submetidos a revascularização do miocárdio [monografia]. Maceió:Centro Universitário CESMAC, Pós-Graduação em Fisioterapia Hospitalar;2011. 31. Klin B, Uretzky G, Magora F. Transcutaneous electrical nerve stimulation (TENS) after open heart surgery. J Cardiovasc Surg (Torino). 1984;25(5):445-8. 32. Cipriano G Jr, Carvalho AC, Bernardelli GF, Tayar Peres PA. Short-term transcutaneous electrical nerve stimulation after cardiac surgery: effect on pain, pulmonary function and electrical muscle activity. Interact Cardiovasc Thorac Surg. 2008;7(4):539-43. 33. Bayindir O, Paker T, Akpinar B, Erenturk S, Askin D, Aytac A. Use of trancutaneous electrical nerve stimulation in the control of postoperative chest pain after cardiac surgery. J Cardiothorac Vasc Anesth. 1991;5(6):589-91. 34. Luchesa CA, Greca FH, Guarita-Souza LC, Santos JLV, Aquim EE. Papel da eletroanalgesia na função respiratória de pacientes submetidos à operação de revascularização do miocárdio. Rev Bras Cir Cardiovasc. 2009;24(3):391-6.

ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):597-603

SjO2/SvO2 correlation during pediatric cardiac surgery with cardiopulmonary bypass Correlação entre a SvO2 e SjO2 durante a cirurgia cardíaca com circulação extracorpórea em crianças

Jyrson Guilherme Klamt1, Pamela Regina Teixeira Nabarro2, Walter Villela de Andrade Vicente3, Luis Vicente Garcia4, Cesar Augusto Ferreira5

DOI: 10.5935/1678-9741.20110050

RBCCV 44205-1326

Abstract Objectives: To compare the SjO2 (cerebral oxygenation indicator) and SvO2 (cardiac output indicator) during pediatric cardiac surgery with cardiopulmonary bypass (CPB). Methods: Retrospective study. Data of SjO2 and SvO2 measured simultaneously at critical time periods during cardiac surgery with CPB were analyzed by the Spearman correlation test and Bland- Altman plot. Results: Regression analysis of the pooled data showed poor correlation between SjO2 and SvO2 (r2=0.14, P=0.03) and Bland- Altman plot had a high bias (-7.9), indicating independency of the two variables. SjO2<50% (indicative of cerebral ischemia-hypoxia) were observed in 50% of the measurements after rewarming during hypothermic CPB. Conclusions: SvO2 is not a good predictor of SjO2 during

pediatric cardiac surgery with CPB, and low SjO2 can be undetected measuring SvO2 only.

1. PhD Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Superior Title in Anesthesiology by the Brazilian Society of Anesthesiology, Assistant Professor, Doctor in the Department of Biomechanics, Medicine and Locomotive Apparatus Rehabilitation, FMRP USP, Ribeirão Preto, Brazil. 2. Master by the FMRP-USP, Graduate, Ribeirão Preto, Brazil. 3. Professor, Department of Surgery and Anatomy, FMRP-USP, Head of the Department of Cardiothoracic Surgery, Department of Surgery and Anatomy, FMRP-USP, Ribeirão Preto, Brazil. 4. Assistant Professor-Doctor, Department of Biomechanics, Medicine and Locomotive Apparatus Rehabilitation, FMRP-USP, Director of the Department of Anesthesiology, Ribeirão Preto, Brazil. 5. PhD Department of Surgery and Anatomy, FMRP-USP Physician Assistant in the Department of Cardiothoracic Surgery,

Department of Surgery and Anatomy, FMRP-USP, Ribeirão Preto, Brazil.

Descriptors: Extracorporeal circulation. Child. Oxygenation. Jugular veins.

Resumo Objetivos: Analisar a correlação entre a SvO2 (indicador do débito cardíaco) e a SjO2 (indicador da oxigenação cerebral) durante cirurgias cardíacas com circulação extracorpórea (CEC) em crianças. Métodos: Estudo retrospectivo. Dados da SjO2, SvO2 e SaO2, mensurados simultaneamente em momentos críticos da cirurgia cardíaca com CEC, em 12 crianças, foram

Work performed at University Hospital of Ribeirão Preto Faculty of Medicine of Ribeirão Preto - University of São Paulo (FMRP-USP), Ribeirão Preto, Brazil.

Correspondence Address: Jyrson Guilherme Klamt Av. Bandeirantes, 3900 – Monte Alegre – Ribeirão Preto, SP, Brazil – CEP 14048-900 E-mail: jgklamt@fmrp.usp.br Article received on May 22nd, 2011 Article accepted on October 23rd, 2011

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analisados pelo teste de correlação de Spearman e pela representação gráfica de Bland-Altman. Resultados: Foram encontrados baixa correlação entre a SjO2 e a SvO2 (r 2=0,14, P=0,03) e um viés alto (-7,8) na plotagem de Bland-Altman, indicando independência entre as duas variáveis. SjO2 < 50% (indicativo de isquemia-hipoxia cerebral) foi observada em cerca de 50% das medidas após o

reaquecimento no final da CEC hipotérmica. Conclusões: A medida de SvO2 não é preditiva da SjO2 durante a cirurgia cardíaca com CEC em crianças e baixa SjO2 pode deixar de ser detectada medindo-se apenas a SvO2.

INTRODUCTION The hemoglobin saturation of blood from the internal jugular vein (SjO2), particularly near the jugular bulb, is an objective measure of oxygen delivery to the brain, the quality of neuroprotection during cardiopulmonary bypass (CPB) in cardiac surgery and allows the immediate detection of cerebral hypoxia-ischemia [1-3]. The hemoglobin saturation of central venous blood (SvO2), near the right atrium, is commonly used as an indicator of the adequacy of cardiac output and oxygenation throughout the body [4,5], however, it does not reflect the oxygenation of specific organs, particularly the brain [6]. The desaturation (SjO2 <50%) of hemoglobin in the jugular vein, commonly observed during the rewarming period, is not reflected in SvO2, and also it would not be detected without the monitoring of specific SjO2 [1-3]. Similar prospective studies in adults and a few retrospective pediatric studies show a weak correlation between SvO2 and SjO 2 during CPB, especially after rewarming [1 to 3.7]. Intermittent collections of jugular blood samples can provide useful information for the proper management of cerebral perfusion and oxygenation, particularly when regional cerebral oxygenation (NRS-nearinfrared spectroscopy) or venous co-oximetry are not available. In the present study, we evaluated data from SjO2 and SvO2 of pediatric patients undergoing surgery for correction of congenital heart disease with CPB, which had the right internal jugular vein (central venous catheter) and left internal jugular vein (jugular cephalic catheter) cannulated. The SjO2 and SvO2 were correlated at successive times during cardiac surgery. METHODS We selected 18 children aged between 3 and 120 months, submitted to heart surgery with CPB between July and 598

Descritores: Circulação extracorpórea. Criança. Oxigenação. Veias jugulares.

December 2009, in which it was possible cannulation of right internal jugular vein with double-lumen catheter Fr5 designed for junction between the vena cava and the right atrium, left internal jugular vein in cephalic direction (jugular bulb) from the cricoid ring with venous catheter 20G and radial or femoral artery. In 12 patients, the data were able to be analyzed at all protocol times of the study. This retrospective cohort study of data from selected patients, which were monitored the SjO2, was authorized by the Ethics Committee in Research of the Hospital das Clínicas of Ribeirão Preto-USP. We excluded patients who underwent reoperation, which required the use of a pacemaker after CPB, presented preoperative hemodynamic instability and bronchospasm, and it was not possible to collect all scheduled blood samples. Anesthesia consisted of fentanyl (20 µg.kg-1, followed by 5 µg.kg-1.h-1), midazolam (0.2 mg.kg-1) in the induction and initiation of CPB, supplemented with isoflurane for control of hyperdynamic responses (increases in blood pressure and heart rate greater than 30%). Vecuronium (0.4 mg.kg-1) was used for intubation. Milrinone (50 µg . Kg-1, followed by 0.7 µg.kg-1.min.-1) and adrenalin (0.03 – 0.05 µg.kg-1.min..-1) was initiated in start of rewarming. The rate of infusion of adrenaline was set up at the end of CPB. Noradrenalin (0.03 – 0.05 µg.kg-1.min-1) was used temporarily to raise blood pressure in some patients. The fractional concentration of O2 (FiO2) was maintained between 0.6 to 1.0 and PETCO2 between 35 and 45 mmHg and PEEP at 2-5 cmH2O. During CPB, the perfusion flow was 2.5 to 3 L.min-1.mm2, hematocrit was maintained between 25 to 30% and the pH was handled by the alpha-stat strategy, the mean arterial pressure was maintained between 30 to 70 mmHg and the temperature reduced to values between 26 to 32ºC (at the criterion of the surgeon). The flow of perfusion and / or mean arterial pressure were adjusted to maintain SvO2 ≥ 70%. Samples of arterial blood (SaO2), central venous blood (SvO2) and jugular blood (SjO2) were collected immediately after cannulation (time CAN) before the start of CPB

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(moment BCPB), after reaching the minimum nasopharyngeal temperature during cooling of CPB (moment TM), after rewarming (moment RQ) and after protamine administration after leaving CPB (moment PROTA). In addition to the saturation of hemoglobin, blood glucose levels and concentrations of lactate were recorded. The correlation between SvO2 and SjO2 was analyzed by Spearman correlation test and Bland-Altman plot. Data are presented as means and standard deviations. Statistical significance was set at P <0.05. RESULTS The demographic data, congenital heart defects diagnosed by ultrasound, CPB and aortic clamping times and rate of infusion of vasoactive drugs at surgery of 12 pediatric patients are presented in Table 1. There was wide age range (3-120 months) and weights (4.1 to 33.6 kg). In all patients, it was possible the rapid cannulation in the cephalic direction of the left internal jugular vein without complications, particularly hematomas. Atrioventricular septal defect was the most prevalent defect of this series of patients assigned. The average of SjO2 tended to be lower than those of SvO2 at all times recorded, however, there was statistically significant difference only after the end of CPB (moment PROTA). The lowest values of SjO2 and SvO2 were observed after rewarming (moment RQ) (Figure 1). Values of SjO2

Fig 1 - saturation of arterial, central venous and internal jugular hemoglobin measured simultaneously during cardiac surgery with cardiopulmonary bypass (CPB) in children at the following times: CAN - right after artery cannulation, central vein, jugular vein in cephalic, BCPB - before the start of CPB; TM - upon reaching the minimum nasopharyngeal temperature (26-32 째 C) RQ - after rewarming on CPB; PROTA after administration of protamineout of the CPB. * Statistically significant difference (P> 0.05) between SvO2 and SjO2

<50%, indicative of cerebral hypoxia-ischemia were detected more frequently (50% of measurements) in moment RQ (Figure 1). On the other hand, values indicative of lush cerebral blood flow (SjO2> 75%) were detected at all times, particularly at moment PROTA, and, except at moment RQ.

Table 1. Data of pediatric patients (P) undergoing cardiac surgery for correction of congenital heart disease with CPB, which were correlated in the SjO2 SvO2 at successive times and surgery. P CongenitalCardiopathy Weight (kg) Age (months) CBP PAo ADR NOR 1 AVSD 8.7 9 90 0 0.03 0 2 PS 15 36 90 55 0.05 0 3 AVSD 3.5 6 110 85 0.04 0 4 VSD 6.6 12 72 62 0 0 5 ASD 34.8 108 50 29 0 0.03 6 AOS 33.6 120 95 74 0 0.04 7 VSD 6.9 9 65 51 0.03 0 8 AVSD, VSD 16.9 72 112 79 0 0.03 9 ASD, VSD, PDA 6.5 9 70 45 0.04 0 10 ASD, PS 12.3 24 174 127 0 0 11 ASD,VSD, PDA, AVSD 4.3 3 128 93 0.04 0 12 TA 14.7 60 81 0 0.03 0.03 SjO2 = saturation of hemoglobin in the blood of the internal jugular vein; SvO2 = saturation of hemoglobin in the central venous blood; AVSD = atrioventricular septal defect, PS = pulmonary stenosis, VSD = ventricular septal defect, ASD = atrial septal defect; AOS = aortic stenosis; PDA = patent ductus arteriosus, TA = tricuspid atresia. Time (minutes) CPB (cardiopulmonary bypass) and Cao (aortic clamping). Infusion rate (microg.kg-1.min-1) of adrenaline (ADR) and noradrenaline (NOR) at the end of surgery. Note: All patients were receiving milrinone at surgery

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The Spearman regression analysis, of all values of SvO2 and SjO2 grouped, showed low correlation between SvO2 and SjO2 (r2 = 0.14, P = 0.03). The Bland-Altman plot (mean x difference) showed a bias (-7.9) considered high, confirming the independence between the simultaneous measurements of SvO2 and SjO2, that is, or low predictive value of SvO2 to detect cerebral hypoxia-ischemia during CPB with hypothermia.

Fig 4 â&#x20AC;&#x201C; Concentrations: pressure, central venous and jugular (venous) of lactate. Moments equal to Figure 1. * Statistically significant difference (P> 0.05) in relation to the moment CAN

Fig 2 â&#x20AC;&#x201C; Hyperglycemia: pressure, central venous (vein) and left internal jugular vein (jugular). * Statistically significant difference (P> 0.05) in relation to the moment CAN. Moments equal to Figure 1

Fig 3 - Arterio-jugular difference [cerebral extraction of glucose (G (a-j)] and central venous-arterial difference [G (a-v)] glucose. * Statistically significant difference (P> 0.05) G (a-j) and G (a-v) each time. There are no differences between successive moments in G (a-j). Moments similar to Figure 1

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Fig 5 - Central arterio-venous difference [L (a-v)] and arteriojugular [L (a-j)] of lactate. Moments equal to Figure 1. * Statistically significant difference when compared to the moment CAN

Klamt JG, et al. - SjO2/SvO2 correlation during pediatric cardiac surgery with cardiopulmonary bypass

Rev Bras Cir Cardiovasc 2011;26(4):597-603

Blood glucose increased significantly from the moment TN in CPB and reached an average of 209 ± 34 mg.dL-1 at the moment PROTA. The central venous blood, arterial blood and jugular blood glucose were similar (Figure 2). The cerebral glucose extractions (arterio-jugular difference) were significantly higher than the systemic extraction (arterio-venous difference), and remained constant at all times recorded (Figure 3). The jugular lactate rose similarly in the three sources of blood, from the moment RQ (Figure 4). The arterio-venous differences of lactate [L (a-v)] showed clear lung extraction after removal of CPB and the arterio-jugular difference [L (a-j)] also revealed distinct cerebral extraction during rewarming (moment PROTA) (Figure 5).

it guides also the effectiveness of clinical interventions (increase of CBF, PaCO2, hypothermia and anesthesia) designed to prevent or manage conditions of risk of cerebral hypoxia-ischemia. Normal values are between 55% -75%, which are always smaller than the simultaneous SvO2. It is a global measure, and it may not reflect hypoperfusion (focal ischemia), therefore, normal or lower values do not necessarily ensure adequate oxygenation, on the other hand, low values (<50-54%) indicate focal or global ischemia severe enough to cause low SjO 2 , associated with postoperative neurological deficits [1-3,8,9]. There are few studies, mostly retrospective and with limited sample size, especially in children, correlating SjO2 and SvO2 during heart surgery with CPB [1-3,8,9-11]. Similar to adults, discrepancies between the two variables are consistently observed. In the present study, this low correlation was confirmed, although the averages differ only after the end of CPB. The rewarming period is the highest risk for cerebral hypoxia-ischemia, defined as SjO2 <50% associated with normal systemic oxygenation (SvO2> 60%), and this phenomenon seems consistent with our clinical data. Invariably, rewarming at the end of CPB has been identified as the period of greatest risk for cerebral hypoperfusion. There is an increased oxygen consumption associated with increased brain temperature, which temporarily exceeds the increased circulatory supply of oxygen during rewarming. This imbalance seems to be due to: the impaired primary autoregulation, cerebral vasoconstriction consequent to the nonpulsatile flow of CPB, microemboli, low hematocrit, hypocapnia [1-3,7-12,15]. The relative ischemia resulting from global cerebral vasoconstriction seems to be the main mechanism in pediatric patients, particularly neonates [11.13-15]. In contrast, the increase of SjO2 (> 75%) when reaching the hypothermia temperature routinely observed [12,15,16], was not confirmed in all patients. Maybe it is due to the practice of establishing a flow based on age, temperature and mean arterial pressure, and then correct it by SvO2. On the other hand, important CBF (SjO2> 75) was found in several patients after the end of CPB, which seems to be a consequence of vasoactive support initiated during reheating. Cerebral monitoring, particularly oxygenation, has became mandatory in routine cardiac surgery, whereas postoperative neurological sequelae are minimized with early detection of the occurrence of cerebral hypoxia [12]. Until the establishment of routine use of noninvasive cerebral oximetry (NIRS) measurements of SjO2 and cerebral extraction of oxygen (SaO2-SjO2) represented reliable indirect indicators of the efficiency of brain cooling and neuroprotection quality and depth of anesthesia [9.12 , 13]. Cephalic catheterization of the internal jugular vein of children, preferably near the jugular bulb, is now used only

DISCUSSION This retrospective study investigated the correlation between SvO2 and SjO2 of pediatric patients during cardiac surgery with hypothermic CPB. The linear regression analysis of all data recorded in the moments considered critical revealed a weak correlation between two variables. SjO2 <50%, understood as an indicator of cerebral hypoxiaischemia, was observed more frequently after reheating at the end of CPB, and not accompanied by similar reductions of SvO2. The primary working hypothesis was confirmed, in which the SvO2 is not predictive of SjO2, and its single measure as an indicator of oxygenation throughout the body, may leave undetected cerebral hypoxia-ischemia. Other markers of ischemia, such as jugular artery difference of lactate and glucose showed no clinically significant changes. Monitoring of cerebral oxygenation during cardiac surgery with CPB can be performed in continuous mode (co-oximetry with catheter in the jugular vein, regional oximetry, -NIRS) or intermittently by collecting frequent jugular venous blood, disposing the venous catheter tip near the jugular bulb. The intermittent monitoring has some disadvantages, such as not being constant, invasive, leading to blood loss and complications such as hematoma and infection. However, it is feasible when there is blood gas analysis readily available and it is inexpensive. The SjO2 is a reliable marker, or indicator of global cerebral oxygenation. Reflects the balance between supply, which is the product of cerebral blood flow (CBF) and oxygen content of arterial blood (CaO2, ml/100 ml) and the demand (oxygen consumption - CMRO2: “Cerebral metabolic rate for oxygen” ), and defined by the formula SjO2á CBF/ CMRO2. Serial measurements of SjO2 (every 5-10 min.) provide information, though indirect, on cerebral oxygenation, effectiveness and consistency of the complete cooling of the brain, neuroprotection quality and depth of anesthesia;

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for research, which can be performed by percutaneous puncture or surgical approach through the superior vena cava with co-oximetry catheter (continuous hemoglobin saturation ), which also allows measurement of other markers of adequate cerebral oxygenation such as lactate and glucose (glucose extraction), which can provide relevant information to the therapeutic management of ischemia or prevention of risk, particularly children during CPB with behaviors such as increased cardiac output (perfusion in CPB) and PaCO2 in order to maintain the relationship CBF/CMRO2 normal, in addition to these indicators having high prognostic value of neurological sequelae in children [10,14,15,17]. In our study, the extraction of glucose was constant during CPB, and showed no evidence, however, the expected reduction in cooling time and the production of lactate was the expected [10]. Several prospective studies of selective cerebral perfusion, with demonstrated efficacy in the prevention of neurological sequelae [18,19], and reviews about intraoperative neuroprotection, particularly during CPB do not emphasize the brain monitoring as a means of evaluating the quality of neuroprotection in real or capable time [20,21]. Certainly this is due to the unavailability in the domestic market and high cost of brain monitors, however, as frequent measurement of SjO2 may be feasible and useful. The limited sample size (cases) and retrospective observational design are the main limitations of this study. Despite the success of 18 technical cannulations of the internal jugular vein on the cephalic direction (of the jugular bulb), the procedure is time consuming and requires a specific skill, offers difficulty keeping the catheter patent for obtaining samples in the critical moments of brain ischemia / hypoxia during CPB and carries risks of complications. Only in 12 patients it was possible the fulfillment of the research protocol, however, about 100 paired data were generated for statistical analysis with significance in tests of correlation. During data analysis, study in children undergoing cardiac surgery with CPB showed a close correlation between the saturation of hemoglobin in the superior vena cava (SvcsO2) and rcSO2 (NIRS brain) [22]. Although mixing with blood from extra-cerebral structures and upper limbs, analysis of blood samples taken from the superior vena cava is a reliable representation of the metabolic state (oxygenation and the occurrence of anaerobic metabolism) of the brain and they are predictive of rcSO2 in real time . This reciprocal correlation and predictive value of static and dynamic (acute variations) between the SvcsO2 rcSO2 and were recently confirmed in another similar study [23]. The sample sizes in these two studies are similar to ours. In our current routine, supported by the arguments exposed, we used samples of the superior

vena cava in the monitoring of cerebral oxygenation, and correction (increase of perfusion and PaCO2 and/ or deeper anesthesia) of any low cerebral perfusion. It would be desirable to classify patients on the cardiac output and severity of postoperative neurological sequelae to quantify the predictive value, specificity and sensitivity of measures of SjO2 or the difference between SvO2 and SjO2 on the neurological outcome. This was not possible in our study, since all patients in our series were discharged without any apparent neurological alteration. Currently, few patients transported to the PICU with low output, and developing gross neurological injuries, which, of course, is due to the quality of cardiac protection during cardiopulmonary bypass and surgical repair, and possibly the neuroprotection. The subtle neurological sequelae are feasible to study after 1 year of age, and they require the participation of trained neurologists and psychologists (not available in our area) and a large number of patients [15].

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CONCLUSION In conclusion, this study suggests that it is possible to predict the value of SjO2 thus cerebral oxygenation, based on measurements of SvO2. The period of greatest risk of desaturation in the jugular blood during rewarming was the end of CPB and routine vasoactive support which can produce increased brain blood flow after CPB.

REFERENCES 1. Schell RM, Cole DJ. Cerebral monitoring: jugular venous oximetry. Anesth Analg. 2000;90(3):559-66. 2. Macmillan CS, Andrews PJ. Cerebral oxygen saturation monitoring: practical considerations and clinical relevance. Intensive Care Med. 2000;26(8):1028-36. 3. Shaaban Ali M, Harmer M, Latto I. Jugular bulb oximetry during cardiac surgery. Anaesthesia. 2001;56(1):24-37.

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4. Liakopoulus OJ, Ho JK, Yezbick A, Sanchez E, Naddell C, Buckberg GD, et al. An experimental and clinical evaluation of novel central venous catheter with integrated oximetry for pediatric patients undergoing cardiac surgery. Anesth Analg. 2007;105(6):1598-604.

during normothermic and hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1994;107(5):1020-8.

5. Duarte JJ, Pontes JCDV, Gomes OM, Silva GVR, Gardenal N, Silva AF, et al. Correlação entre a gasometria atrial direita e índice cardíaco no pós-operatório de cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2010; 25 (2):160-5. 6. McDaniel LB, Zwischenberger JB, Vertrees RH, Nutt L, Uchida T, Nguyen T, et al. Mixed venous saturation during cardiopulmonary bypass poorly predicts regional venous saturation. Anesth Analg. 1995;80(3):466-72. 7. Kern FH, Ungerleider RM, Schulman SR, Meliones JN, Schell RM, Baldwin B, et al. Comparing two strategies of cardiopulmonary bypass cooling and jugular venous oxygen saturation in neonates and infants. Ann Thorac Surg. 1995;60(5):1198-202. 8. Croughwell ND, Newman MF, Blumenthal JA, White WD, Lewis JB, Frasco PE, et al. Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass. Ann Thorac Surg. 1994;58(6):1702-8. 9. Kerr FH, Ungerleider RM, Schulman SR, Meliones JN, Schell RH, Baldwin B, et al. Comparing two strategies of cardiopulmonary bypass cooling jugular venous oxygen saturation in neonates and infants. Ann Thorac Surg. 1995;60(5):1198-202. 10. Greeley WJ, Kern FH, Ungerleider RM, Boyd JL 3rd, Quill T, Smith LR, et al. The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants and children. J Thorac Cardiovasc Surg. 1991;101(5):783-94. 11. Greeley WJ, Ungerleider RM, Smith LR, Reves JG. The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children. J Thorac Cardiovasc Surg. 1989;97(5):737-45. 12. Andropoulos DB, Stayer SA, Diaz LK, Ramamoorthy C. Neurological monitoring for congenital heart surgery. Anesth Analg. 2004;99(6):1365-75. 13. Cook DJ, Oliver WC Jr, Orszulak TA, Daly RC. A prospective, randomized comparison of cerebral venous oxygen saturation

14. Schell RM, Kern FH, Greeley WJ, Schulman SR, Frasco PE, Croughwell ND, et al. Cerebral blood flow and metabolism during cardiopulmonary bypass. Anesth Analg. 1993;76(4):849-65. 15. Hoffman GM, Mussatto KA, Brosig CL, Ghanayem NS, Musa N, Fedderly RT, et al. Systemic venous oxygen saturation after the Norwood procedure and childhood neurodevelopmental outcome. J Thorac Cardiovasc Surg. 2005;130(4):1094-100. 16. Tortoriello TA, Stayer SA, Mott AR, Mckenzie CD, Fraser CD, Andropoulos DB, et al. A noninvasive estimation of mixed venous oxygen saturation using near-infrared spectroscopy by cerebral oximetry in pediatric cardiac surgery patients. Pediatric Anaesth. 2005;15(6):495-503. 17. Trubiano P, Heyer EJ, Adams DC, McMahon DJ, Christiansen I, Rose EA, et al. Jugular venous bulb oxyhemoglobin saturation during cardiac surgery: accuracy and reliability using a continuous monitor. Anesth Analg. 1996;82(5):964-8. 18. Martins MSS, Sá MPL, Abad L, Bastos ES, Franklin Junior N, Baptista ALXBM, et al. Tratamento cirúrgico da aorta ascendente e arco com perfusão anterógrada e hipotermia moderada. Rev Bras Cir Cardiovasc. 2006;21(4):461-7. 19. Carreira VJ, Oliveira DM, Honório JF, Pinheiro ITF, Chissonde EM, Faria RM. Cirurgia do arco aórtico com perfusão cerebral bilateral pelo isolamento do tronco braquiocefálico e da artéria carótida esquerda. Rev Bras Cir Cardiovasc. 2008;23(1):70-7. 20. Dias RR, Silva IA, Fiorelli AI, Stolf NAG. Proteção cerebral: sítios de canulação arterial e vias de perfusão do cérebro. Rev Bras Cir Cardiovasc 2007;22(2):235-40. 21. Martin JFV, Melo ROV, Sousa LP. Disfunção cognitiva após cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2008;23(2):245-55. 22. Ranucci M, Isgrò G, De la Torre T, Romitti F, Conti D, Carlucci C. Near-infrared spectroscopy correlates with continuos superior vena cava oxygen saturation in pediatric cardiac patients. Paediatr Anesth. 2008;18(12):1163-9. 23. Ginther R, Sebastian VA, Huang R, Leonard SR, Gorney R, Guleserian KJ, et al. Cerebral near-infrared spectroscopy during cardiopulmonar bypass predicts superior vena cava oxygen saturation. J Thorac Cardiovasc Surg. 2011;142(2):359-65.

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ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):604-8

Coronary dominance patterns in hypoplastic left heart syndrome Dominância coronariana na síndrome da hipoplasia do coração esquerdo

Decio Cavalet Soares Abuchaim1, Carla Tanamati2, Marcelo Biscegli Jatene3, Miguel Lorenzo Barbero Marcial4, Vera Demarchi Aiello5

DOI: 10.5935/1678-9741.20110051

RBCCV 44205-1327

Abstract Introduction: Although hypoplastic left heart syndrome (HLHS) is extensively studied this disease still has a high mortality rate compared to other diseases treated as univentricular physiology. In this context, morphological differences between phenotypes within the spectrum of HLHS may be recognized as risk factors, and their identification can assist in choosing treatment between subgroups. Objective: To identify the most prevalent form of coronary artery dominance in HLHS in subgroups with atresia and mitral stenosis. Methods: Analysis of the coronary anatomy according to the distribution of epicardial branches and the dominance patterns classified as right, left, or balanced (co-dominant). Control group was composed of nine specimens of morphologically normal hearts; the HLHS group consisted of nine specimens with MA and 24 specimens with MS. We applied Chi-square test for statistical analysis. Results: There were significant differences between the two groups in relation to coronary artery dominance (÷2 =

9.298; P = 0.01). Left dominance was present in 75% of MS cases and the balanced (co-dominant) dominance was observed only in MS. In the control group, right dominance was observed in all cases (P <0.01). Conclusions: Left dominance is more common in HLHS than in the control group of normal hearts and in HLHS. The left coronary dominance is more frequent in the subgroup with mitral stenosis.

1. M.S.; Supervisor physician of legal risk at Hospital Santa Catarina, Blumenau, SC, Brazil. 2. Full Professor; Assistant Medical Cardiac Surgery Unit Pediatric of Heart Institute, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, SP, Brazil. 3. Full Professor; Director of Pediatric Cardiac Surgery Unit of Heart Institute, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, SP, Brazil. 4. Full Professor; Emeritu Professor at the School of Medicine University of Sao Paulo. Former director of Pediatric Cardiac Surgery Unit of Heart Institute, Hospital das Clínicas, University of São Paulo Medical School, São Paulo,SP, Brazil. 5. Full Professor; Medical chief of surgical pathology of Heart

Institute of Hospital das Clínicas, University of São Paulo Medical School, São Paulo, SP, Brazil.

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Descriptors: Heart/anatomy & histology. Coronary vessels. Hypoplastic left heart syndrome. Heart defects, congenital.

Resumo Introdução: Apesar de a síndrome do coração esquerdo hipoplásico (SCEH) ser extensamente estudada, esta doença ainda apresenta mortalidade elevada se comparada a outras doenças tratadas como fisiologia univentricular. Assim, diferenças morfológicas entre fenótipos dentro do espectro

This study was carried out at the Heart Institute (InCor), University of São Paulo Medical School, Brazil Correspondence address: Decio Cavalet Soares Abuchaim Av. Dr. Enéas de Carvalho Aguiar, 44 - São Paulo/SP - Brazil - Zip Code:05403-900. E-mail: decioabu@terra.com.br Article received on August 2nd, 2011 Article accepted on September 27th, 2011

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da SCEH podem ser fatores de risco e sua identificação pode auxiliar na escolha terapêutica entre os subgrupos anatômicos. Objetivos: Determinar a forma mais frequente de dominância coronariana em corações com SCEH nos subgrupos com atresia (AM) e estenose mitral (EM). Métodos: Análise da anatomia coronariana de acordo com a distribuição dos ramos epicárdicos e o padrão de dominância, classificadas em direita, esquerda ou balanceada. O grupo controle foi composto por nove peças de corações morfologicamente normais. O grupo SCEH constituiu-se de nove peças com AM e 24 peças com EM. Para análise estatística foi utilizado o teste do quiquadrado.

Resultados: Houve diferença significativa entre os dois grupos em relação à dominância coronariana (x2= 9,298; P=0,01). A dominância esquerda esteve presente em 75% dos casos de EM, e a balanceada só foi observada na EM. No grupo controle, observou-se dominância direita em todos os casos (P<0,01). Conclusões: A dominância esquerda é mais frequente na SCEH que no grupo controle de corações normais e, na SCEH, a dominância coronariana esquerda é mais frequente no subgrupo com EM.

INTRODUCTION The hypoplastic left heart syndrome (HLHS) is a spectrum of cardiac malformations characterized by severe underdevelopment of the left heart complex and aorta. It includes both the left ventricular cavity and mass. At one end of the spectrum is the mitral and aortic atresia with absent/not detectable left ventricular cavity. At the other end are the cases with varying degrees of hypoplasia of the mitral and aortic valves and ventricular hypoplasia [1], leading to the impossibility of maintaining cardiac output and systemic perfusion by the left heart. In anatomic series, there is a predominance of the phenotype with a patent mitral valve (67%) [2]. Although the HLHS is extensively studied, the surgical treatment performed by the Norwood-type palliative surgery [3-4] or by the so-called hybrid procedures [5-6] has satisfactory results in many centers [7-8]. Nevertheless, this disease still has a high mortality rate between the first and second stage, when compared to other diseases treated as univentricular physiology. There has also been a lot of controversy over whether the subgroup patients with mitral stenosis and aortic atresia present a higher risk of death after the first stage of palliative surgery [9-11] due to factors related to myocardial perfusion or histological changes. Although mortality from postoperative coronary heart disease is commonly caused by technical factors related to the aortic arch reconstruction [12], it can also be caused by intrinsic coronary abnormalities such as hypoplasia of the epicardial branches. In addition, the steal phenomenon of epicardial coronary flow by fistula is further considered an intrinsic coronary abnormality, particularly if it is associated with myocardial hypertrophy, as observed in the subgroup

Descritores: Coração/anatomia & histologia. Vasos coronários. Síndrome do coração esquerdo hipoplásico. Cardiopatias congênitas.

with mitral stenosis, which compromises myocardial perfusion [13]. These coronary fistulas usually arise from the left coronary artery branches [14]. In this context, morphological differences between phenotypes within the spectrum of HLHS may come to be recognized as limiting factors for a favorable postoperative course. Thus, their identification can possibly contribute to the therapeutic choice between the anatomical subgroups in near future. Objective To determine the most common form of coronary artery dominance in HLSH hearts in groups with mitral atresia and mitral stenosis. METHODS This study was approved by the Research and Ethics Committee of InCor-HCFMUSP. It received the protocol number 0786/09, and represents the partial result of the author’s doctorate dissertation. Selection of Anatomic Specimens Anatomic specimens selection was carried out at the Museum of the Laboratory of Pathology; Heart Institute (InCor), University of São Paulo Medical School (InCorHCFMUSP) according to the following criteria: Inclusion Criterion Anatomic specimens of HLHS obtained from deceased patients of both sexes under the age of 30 days. Exclusion Criteria - Anatomic specimens in which surgical procedures or 605

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the state of preservation prevented proper morphology identification. - Age over 30 days. - Other congenital anomalies with hypoplastic left ventricle but not with all criteria for HLHS.

RESULTS The numbers of hearts with HLHS in each morphological subgroup are shown in Table 1. We found significant differences between the two groups in relation to coronary dominance (χ2 = 9.298; P = 0.01). Left dominance was present in 75% of MS cases. The balanced dominance (co-dominance) was observed in MS only. The distribution of data is shown in Table 2.

Morphological Analysis Anatomic specimens were classified according to their morphological diagnosis as follows: I – group with mitral atresia (MA) associated with either atresia or stenosis of the aortic valve. II – group with mitral stenosis (MS) associated with either atresia or stenosis of the aortic valve.

Comparisons with the control group We did Chi-square tests including the controls. There was a statistically significant difference in the pattern of coronary dominance(P<0.01), once the right dominance was only be observed in the control group.

Anatomical Study The gross examination of the epicardial coronary artery anatomy was done under a magnifying glass. The distribution of the major epicardial branches and the pattern of dominance were determined. Coronary dominance was defined as the main artery (the right or the left) that supplies the posterior interventricular artery. Thus, it was classified as right, left or balanced (co-dominant) [15]. Control group consisted of nine specimens of morphologically normal hearts with from patients who died in the neonatal period due to non-cardiac causes. HLHS group consisted of nine specimens with MA and 24 specimens with MS. We used the Chi-square test for statistical analysis and P values less than 0.05 were considered statistically significant.

DISCUSSION The right coronary dominance is the most prevalent dominance pattern observed in normal humans [16,17], occurring in 72% of individuals [15]. In HLHS, the dominance has hardly been studied [18], and most studies analyzed their morphological and histological changes only [19-22]. In HLHS, the spatial distribution of the epicardial coronary vessels is similar to that of normal hearts [20]. The presence of coronary-cavitary fistulas, anomalous origin and tortuosity of the coronary arteries are related to complications and higher mortality [13]. The finding of coronary fistulas prevails in the hearts with mitral stenosis associated with aortic atresia [19]. Sauer et al. [21] showed that in hearts with mitral stenosis and aortic atresia, there is an association of 42% of coronary anomalies, such as thickening and tortuosity of the proximal left coronary artery in cases presenting associated endocardial fibroelastosis. The preoperative identification of such anomalies can avoid a direct injury or damage to the underlying areas in a surgery that involves the reconstruction of the aortic root [23]. Vida et al. [9] proposed that the patients’ subgroup with mitral stenosis and aortic atresia should undergo

Table 1. Divisions between the morphological subgroups of hearts with HLHS N Morphologic subgroup Mitral atresia and Aortic atresia 9 Mitral stenosis and Aortic atresia 13 Mitral stenosis and Aortic stenosis 11 HLHS = Hypoplastic Left Heart Syndrome

Table 2. Coronary dominance

MA Group Total

N % within subgroup n % within subgroup n % within subgroup

Right 5 55.6% 2 8.3% 7 21.2%

MA = Mitral atresia group; MS = Mitral stenosis group

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Dominance Left 4 44.4% 18 75.0% 22 66.7%

Total Balanced __ __ 4 16.7% 4 12.1%

9 100.0% 24 100.0% 33 100.0%

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preoperative cineangiocoronariography to define the magnitude of coronary-cavitary fistulas due to the greater surgical risk, suggesting heart transplantation or hybrid procedures as therapeutic options. Based on the study of their series of cases, the hospital mortality rate was significantly higher (29% vs 7.9%; P=0.002) in this subgroup compared to others. Coronary-cavitary communications were also associated with increased mortality (50% vs 6%; P=0.004). Glatz et al. [10] conducted a retrospective study of 72 patients undergoing the Norwood procedure. They observed that the interstage mortality was higher in patients with aortic atresia and mitral stenosis. Thus, they correlated it to possible coronary abnormalities, such as thickening of the tunica media and ventricular-coronary connections. The abnormalities could predispose to ischemia and ventricular dysfunction, and also to potentially lifethreatening arrhythmias. These authors consider the possibility that the Tuguo-Sano surgery, which interposes the tube between the right ventricle and the pulmonary trunk, if performed in the subgroup of patients with fistulas, could limit the flow steal during diastole to the pulmonary arteries to the detriment of the potentially vulnerable coronary arteries. Considering the Brazilian experience, da Silva et al. [24] revealed no differences between the Norwood and Sano procedures. Some authors presume that the best results with the Sano technique would be more related to the increased experience of the groups than to hemodynamic peculiarities. Sathanandam et al., [11] analyzing the 30-day survival in 100 patients undergoing Norwood-type surgery have obtained a 90%-success rate in the whole group and 89.9% in the subgroup with mitral stenosis and aortic atresia. At 60 days, they obtained 70% 70.4%, respectively without a significant difference. For these authors, the presence of coronary-cavitary fistulas had no effect on mortality. Following the neonatal period, patients with HLHS have a similar outcome to other patients with single ventricle physiology [25]. Based on our present study, the left dominance was prevalent in HLHS. Hansel et al. [18], in an angiographic study also found that the left dominance had been more frequent in HLHS than in the normal population, although in the series studied the right dominance has prevailed. In that sample, the right dominance occurred in 51.2% of the patients, left dominance on 36.9%, and the balanced (codominance) in 11.9%. They, however, did not find statistically significant differences between the morphological groups. The left and balanced (codominance) dominances were significantly more common in the absence of the left ventricular cavity, in contrast to our findings where the left dominance was significantly

higher in cases with mitral stenosis and detectable ventricular cavity. The main clinical implication of our study is that patients with HLHS should be treated individually, considering the anatomical peculiarities. It is possible that patients with fistulas and left dominance have different prognosis and progression compared to those with fistulas but right dominance. However, the limitation of our study is to have been conducted using autopsy specimens. Thus, these hearts would presumably represent cases with the most severe morphological changes. However, we support that it is possible for patients with coronary fistulas and left coronary dominance to have different prognosis and clinical evolution compared with patients with fistula and right coronary dominance. In order to support this statement, the total area of irrigated myocardium, its potential for ischemia, and secondary arrhythmias must be considered. These data will be evaluated in an ongoing histological investigation. CONCLUSION The data presented here, which result from the study of autopsy hearts, allowed us to conclude that the pattern of left dominance is more frequent in HLHS than in the control group with normal hearts, and even more prevalent in the subgroup with mitral stenosis.

REFERENCES 1. Tchervenkov CI, Jacobs ML, Tahta SA. Congenital Heart Surgery Nomenclature and Database Project: hypoplastic left heart syndrome. Ann Thorac Surg. 2000;69(4 Suppl):S170-9. 2. Aiello VD, Ho SY, Anderson RH, Thiene G. Morphologic features of the hipoplastic left heart syndrome: a reappraisal. Pediatr Pathol. 1990;10(6):931-43. 3. Stasik CN, Gelehrter S, Goldberg CS, Bove EL, Devaney EJ, Ohye RG. Current outcomes and risk factors for the Norwood procedure. J Thorac Cardiovasc Surg. 2006;131(2):412-7. 4. Fantini FA, Gontijo Filho B, Martins C, Lopes RM, Heiden E, Vrandecic E, et al. A operação de Norwood modificada para tratamento da síndrome de hipoplasia do coração esquerdo. Rev Bras Cir Cardiovasc. 2004;19(1):42-6. 5. Galantowicz M, Cheatham JP, Phillips A, Cua CL, Hoffman TM, Hill SL, et al. Hybrid approach for hypoplastic left heart syndrome: intermediate results after the learning curve. Ann Thorac Surg. 2008;85(6):2063-70.

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6. Assad RS, Zamith MM, Silva MF, Thomaz PG, Miana LA, Guerra VC, et al. Nova bandagem ajustável das artérias pulmonares na síndrome de hipoplasia de câmaras esquerdas. Rev Bras Cir Cardiovasc. 2007;22(1):41-8.

Malafaia O. Dominância coronariana em corações humanos em moldes por corrosão. Rev Bras Cir Cardiovasc. 2009;24(4):514-8.

7. Silva JP, Fonseca L, Baumgratz JF, Castro RM, Franchi SM, Lianza AC, et al. Síndrome do coração esquerdo hipoplásico: estratégia cirúrgica e comparação de resultados com técnicas de Norwood x Sano. Rev Bras Cir Cardiovasc. 2007;22(2):160-8. 8. Furlanetto G, Furlanetto BHS, Henriques SS, Kapins CEB, Lopes LM, Olmos MCC, et al. Nova técnica: operação de Norwood com perfusão regional cerebral e coronariana. Rev Bras Cir Cardiovasc. 2009;24(4):447-52. 9. Vida VL, Bacha EA, Larrazabal A, Gauvreau K, Dorfman AL, Marx G, et al. Surgical outcome for patients with the mitral stenosis-aortic atresia variant of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg. 2008;135(2):339-46. 10. Glatz JA, Fedderly RT, Ghanayem NS, Tweddell JS. Impact of mitral stenosis and aortic atresia on survival in hypoplastic left heart syndrome. Ann Thorac Surg. 2008;85(6):2057-62. 11. Sathanandam SK, Polimenakos AC, Roberson DA, elZein CF, Van Bergen A, Husayni TS, et al. Mitral stenosis and aortic atresia in hypoplastic left heart syndrome: survival analysis after stage I palliation. Ann Thorac Surg. 2010;90(5):1599-607. 12. Bartram U, Grunenfelder J, van Praagh R. Causes of death after the modified Norwood procedure: a study of 122 postmortem cases. Ann Thorac Surg. 1997;64(6):1795-802. 13. DeRose JJ Jr, Corda R, Dische MR, Eleazar J, Mosca RS. Isolated left ventricular ischemia after the Norwood procedure. Ann Thorac Surg. 2002;73(2):657-9. 14. O’Connor WN, Cash JB, Cottrill CM, Johnson GL, Noonan JA. Ventriculocoronary connections in hypoplastic left hearts: an autopsy microscopic study. Circulation. 1982;66(5):1078-86. 15. Abuchaim DCS, Spera CA, Faraco DL, Ribas Filho JM,

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16. Kato T, Yasue T, Shoji Y, Shimabukuro S, Ito Y, Goto S, et al. Angiographic difference in coronary artery of man, dog, pig and monkey. Acta Pathol Jpn. 1987;37(3):361-73. 17. Falci Jr. R, Prates NEVB. Anatomia das artérias coronárias. Rev Med. 1994;72(1/4):21-4. 18. Hansen JH, Uebing A, Scheewee J, Kramer H-H, Fischer G. The coronary arteries in patients with hypoplastic left heart syndrome: an angiographic study and its clinical implications. Cardiol Young. 2011;121(S1):134. 19. Baffa JM, Chen SL, Guttenberg ME, Norwood WI, Weinberg PM. Coronary artery abnormalities and right ventricular histology in hypoplastic left heart syndrome. J Am Coll Cardiol. 1992;20(2):350-8. 20. Freedom RM, Nykanen D. Hypoplastic left heart syndrome: pathologic considerations of aortic atresia and variations on the theme. Prog Pediatr Cardiol. 1996;5(1):3-18. 21. Sauer U, Gittenberger-de Groot AC, Geishauser M, Babic R, Buhlmeyer K. Coronary arteries in the hypoplastic left heart syndrome. Histopathologic and histometrical studies and implications for surgery. Circulation. 1989;80(3 Pt 1):I168-76. 22. Anderson RH, Spicer D. Fistulous communications with the coronary arteries in the setting of hypoplastic ventricles. Cardiol Young. 2010;20(Suppl 3):86-91. 23. Saroli T, Gelehrter S, Gomez-Fifer CA, van der Velde ME, Bove EL, Ensing GJ. Anomalies of left coronary artery origin affecting surgical repair of hypoplastic left heart syndrome and Shone complex. Echocardiography. 2008;25(7):727-31. 24. Souza AH, Fonseca L, Franchi SM, Lianza AC, Baumgratz JF, Silva JP. A síndrome do coração esquerdo hipoplásico não constitui fator de risco para operação de Fontan. Rev Bras Cir Cardiovasc. 2010;25(4):506-9.

ORIGINAL ARTICLE

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Ricardo Vieira Reges1, Walter Vilella de Andrade Vicente2, Alfredo José Rodrigues3, Solange Basseto4, Lafaiete Alves Junior4, Adilson Scorzoni Filho4, César Augusto Ferreira4, Paulo Roberto Barbosa Évora5

DOI: 10.5935/1678-9741.20110052 Abstract Introduction: Retrograde autologous priming (RAP) is a cardiopulmonary bypass (CPB) method, at low cost. Previous studies have shown that this method reduces hemodilution and blood transfusions needs through increased intraoperative hematocrit. Objective: To evaluate RAP method, in relation to standard CPB (crystalloid priming), in adult patients. Methods: Sixty-two patients were randomly allocated to two groups: 1) Group RAP (n = 27) of patients operated using the RAP and; 2) Control group of patients operated using CPB standard crystalloid method (n = 35). The RAP was performed by draining crystalloid prime from the arterial and venous lines, before CPB, into a collect recycling bag. The main parameters analyzed were: 1) CPB hemodynamic data; 2) Hematocrit and hemoglobin values; 3) The need for blood transfusions. Results: It was observed statistically significant fewer transfusions during surgery and reduced CPB hemodilution using RAP. The CPB hemodynamic values were similar,

1 - Resident (Division of Thoracic and Cardiovascular Surgery and Department of Anatomy, Ribeirão Preto Medical School, University of São Paulo) 2 - Associate Professor (Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo). 3 - Professor Doctor (Division of Thoracic and Cardiovascular Surgery and Department of Anatomy, Ribeirão Preto Medical School, University of São Paulo) 4 - Assistant Physician (Division of Thoracic and Cardiovascular Surgery and Department of Anatomy, Ribeirao Preto Medical School, University of São Paulo) 5 – Full Professor; Division of Thoracic and Cardiovascular Surgery and Department of Anatomy, Ribeirão Preto Medical School, University of São Paulo).

RBCCV 44205-1328 observing a tendency to use lower CPB flows in the RAP group patients. Conclusion: This investigation was designed to be a small-scale pilot study to evaluate the effects of RAP, which were demonstrated concerning the CPB hemodilution and blood transfusions. Descriptors: Extracorporeal circulation. Hemodilution. Cardiac surgical procedures.

Resumo Introdução: Perfusato autólogo retrógrado (PAR) é uma técnica de circulação extracorpórea (CEC) com baixos custos. Estudos anteriores demonstraram que esta técnica reduz a hemodiluição e a necessidade de transfusões de sangue por meio do aumento do hematócrito intraoperatório. Objetivo: Avaliar técnica de PAR em relação à CEC técnica padrão (perfusato cristaloide) em pacientes adultos. Métodos: Sessenta e dois pacientes foram aleatoriamente

Work performed at the Division of Thoracic and Cardiovascular Surgery and Department of Anatomy, Ribeirão Preto Medicine School, University of São Paulo, Ribeirão Preto, SP, Brazil. Support: Education Support Foundation of the Clinical Hospital of Riberão Preto Medical School at University of São Paulo, Ribeirão Preto, Brazil. Correspondence address Paulo Roberto B. Évora - 367 Rui Barbosa Street, Ap.15 – Ribeirão Preto, SP, Brazil – Zip Code: 14015-120 E-mail: prbevora@netsite.com.br Article received on July 24th, 2011 Article accepted on October 25th, 2011

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alocados em dois grupos: 1) Grupo PAR (n = 27), constituído por pacientes operados utilizando a técnica de PAR e; 2) Grupo Controle, constituído por pacientes operados utilizando técnica padrão de CEC com cristaloides (n = 35). A PAR foi realizada drenando-se o perfusato cristaloide das linhas arterial e venosa, antes da CEC, para uma bolsa coletora de recirculação. Os principais parâmetros analisados foram: 1) parâmetros hemodinâmicos da CEC; 2) valores de hematócrito e hemoglobina; e; 3) necessidade de transfusões de sangue. Resultados: Observaram-se diferenças estatisticamente significativas de transfusão no intraoperatório e diminuição da hemodiluição em CEC utilizando PAR. Os valores

hemodinâmicos durante a CEC foram semelhantes, observando-se tendência de utilização de fluxos menores na CEC dos pacientes do grupo PAR. Conclusão: O presente estudo foi projetado em pequena escala para avaliar os efeitos do PAR, o que foi demonstrado em relação aos já conhecidos efeitos na diminuição da hemodiluição em CEC e transfusão sanguínea, porém não mostrou vantagens hemodinâmicas em relação à técnica padrão com perfusato cristaloide.

INTRODUCTION To reduce the need for homologous blood, and its known risks, the use of crystalloid priming in CPB has been considered the standard practice for decades. It has advantages for blood flow and organ preservation, but results in a mixture with the patient’s blood, causing a hemodilution, and, paradoxically, may lead to the need for blood transfusions during surgery. Although this method is widely used as standard CPB, hemodilution is associated with significant mortality and other adverse conditions, especially when the hematocrit reaches values below 20% [1]. In an effort to reduce the effects caused by hemodilution or transfusion requirements in cardiac surgery, several strategies have been proposed including the donation of preoperatively or intraoperatively autologous blood, the use of cell saver to concentrate red blood cells and increased hematocrit, autotransfusion of blood postoperatively lost, and the use of pharmacologic agents to promote clotting after CPB [2,3]. Among these options, studies have shown that the routine use of hemofiltration and/or cell saver improves the quality of surgical care [4-6]. Retrograde autologous priming (RAP) is a method of CPB, at low cost, which has been described [1,7] as modification of the method proposed, in 1959, by Panico and Neptune [8]. Previous studies have shown that this method reduces hemodilution during CPB, the reduction of blood transfusions by increasing the hematocrit intraoperatively, especially in patients who have risk factors as anemia, small body surface area, and refuses to receive blood products [1]. This method uses the patient’s own blood while setting up the pump system. Jansen et al. [9] had already shown that reducing the volume it was possible to attenuate the hyperdynamic response after CPB and reported a significant reduction in the use of the blood bank. 610

Descritores: Circulação extracorpórea. Hemodiluição. Procedimentos cirúrgicos cardíacos.

This prospective, randomized study was carried out to evaluate the RAP method in relation to CPB standard method, analyzing the hemodynamic values, lactate, hemoglobin and hematocrit, and the need for blood transfusions in adult patients undergoing CABG with CPB. The study does not pretend to be original, it only intended to draw attention to a CPB method, not always remembered, which positively affects two critical parameters: the hemodilution and the transfusion of blood and blood components. It is an inexpensive and effective practice in relation to other more sophisticated methods such as “minicircuits” and “cell-savers.” METHODS Composition of the groups The study was approved by the ethical committee of the Clinical Hospital of Ribeirão Preto Medical School at University of São Paulo, Brazil. A group (RAP group; n=27) of adult patients was operated using the RAP method and another group was operated, without RAP method, using standard crystalloid prime CPB (group control, n=35). Exclusion criteria were age less than 18 years or greater than 85 years, left ventricular ejection fraction smaller than 30% and emergency surgery. In both groups membrane oxygenator was used. All patients were admitted to the intensive care unit and treated as the same standard clinical practice. The physicians responsible for postoperative care of the patients were blinded with respect to the study group. Method of the retrograde autologous priming (RAP) The original RAP method, described by Rosengart et al. [7], modified by Eising et al. [10], as follows, was adopted in this investigation (Figure 1). Before RAP starting, mean arterial pressure (MAP) was elevated to approximately 100 mmHg, using small doses of intravenously administered

Reges RV, et al. - Retrograde autologous priming in cardiopulmonary bypass in adult patients. Effects on blood transfusion and hemodilution

Fig. 1 – Schematic representation of the retrograde autologous priming circuit (Adapted from Eising et al., 2003)

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phenylephrine. A recirculation bag was connected to the venous line. The crystalloid priming fluid of the venous reservoir was drained to a minimal level into the bag. The venous side of the circuit was then drained, slowly replacing the crystalloid priming volume by filling the circuit with patient’s blood. The recirculation bag was then disconnected from the venous line and connected with the purge line of the arterial filter. The retrograde priming was then continued until the blood volume in the venous reservoir reached approximately 200 mL. This fluid mixture of the venous reservoir was slowly pumped through the membrane oxygenator and the arterial filter, displacing the priming fluid of the tubing, the oxygenator, and the arterial filter into the recirculation bag. The arterial line connecting the patient with the arterial filter was clamped at that time. Finally, the arterial line was drained into the recirculation bag by replacing the crystalloid fluid with the patient’s blood. The procedure was performed with the patient’s hemodynamics carefully controlled. The recirculation bag was then reconnected with the venous reservoir so that

Fig. 2 – Hemodynamic data of cardiopulmonary bypass. 2A - Mean arterial pressure, MAP (mmHg), P> 0.05; 2B - blood flow (ml s) P >0.05 and *P <0.05 at 30 minutes; 2C-arterial vascular resistance, P > 0.05; 2D - Lactate (mmol/l), P> 0.05). Data are presented as mean ± standard deviation, RAP group (n = 27), control group (n = 35). *Lower in the RAP

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crystalloid fluid replacement could be performed during CPB upon hemodynamic requirements. The retrograde priming procedure requires 4 to 5 minutes before the onset of CPB. The results analysis included: 1) Characteristics and surgical data of RAP and control groups; 2) CPB hemodynamic data (mean arterial pressure/MAP, blood flow rate/BF, arterial vascular resistance/AVR); 3 total crystalloid infusion and diuresis); 4) Hemoglobin (Hb), hematocrit (Hct), pH and lactate, and; 5) Bleeding and transfusion data.

Fig. 3 – Total volume of crystalloid solution used in the CPB and diuresis (P <0.05*). Data are presented as mean ± standard deviation, PAR group (n = 27), control group (n = 35). *Lower in the RAP

Statistical analysis All the data described in the results were analyzed through the Student‘s t-test, when it was normal, or MannWhitney test, when they were not normal. The chi-square test was adopted to analyze the number of transfused bags of blood and derivates. The adopted level of significance was P<0.05.

Fig. 4 – Blood transfusion and hematological data. 4A: Percentage of patients who received transfusions of blood products, P>0.05; 4B: Volume of blood transfusions and derivatives, P> 0.05; 4C: Hemoglobin (g/dl) before and after CPB, P>0.05 and P<0.05 during CPB, * 4D: Hematocrit (%) before and after CPB, P> 0.05 and P <0.05 during CPB *. Data are presented as mean ± standard deviation, PAR group (n = 27), control group (n = 35). *Higher in the RAP

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Table 1. Demographic data, surgical and postoperative. Note: Some general data are lost, mainly in the control group, which is why the (n) was individualized for each group, P> 0.05. RAP group Control group (n=27) (n=35) (n) (n) 58.3 ± 2.0 Age (years) 26 58.4 ± 2.1 25 Male gender 27 18 (66.7%) 25 22 (62.9%) 25 75.7 ± 2.2 Weight (kg) 26 74.6 ± 2.7 Ejection fraction 25 0.68 ± 0.03 28 0.70 ± 0.04 25 40.4 ± 1.0 28 39.7 ± 1.2 Hematocrit Pre-CPB (%) 12.9 ± 0.4 Hemoglobin Pre-CPB (g/dl) 24 13.2 ± 0.4 28 CPB time (min) 26 86.2 ± 7.0 25 89.9 ± 5.0 25 71.6 ± 4.7 Aorta clamping time (min) 26 68.5 ± 6.4 Distal anastomosis number 27 2.7 ± 0.3 25 2.8 ± 0.3 ICU time (dias) 27 3.1 ± 0.2 25 2.8 ± 0.2 25 402 ± 48 Postoperative bleeding (ml) 27 419 ± 71 First postoperative uremia (mg/dl) 27 46.1 ± 4.5 25 43.1 ± 4.2 25 0* 35 729 ± 75.6 Saved priming (ml) Table 2. Mean arterial pressure (mmHg) during cardiopulmonary bypass (CPB). Data are presented as mean ± standard deviation, P> 0.05. CPB time RAP group Control group (n = 27) (n = 35) 53.4 ± 2.4 Beginning 54.0 ± 2.1 10 min 71.2 ± 2.6 67.7 ± 2.3 20 min 76.0 ± 2.6 74.5 ± 2.0 30 min 77.1 ± 2.5 74.1 ± 2.1 69.3 ± 3.1 40 min 73.4 ± 2.2 66.5 ± 2.6 50 min 71.2 ± 2.1 60 min 69.7 ± 2.9 70.1 ± 2.6 Table 3. Blood flow in milliliters per second (ml/s) during cardiopulmonary bypass (CPB). Data are presented as mean ± standard deviation, P> 0.05 at 30 min P <0.05 (flow group RAP<Flow Control group) CPB time RAP group Control (n = 27) group(n=35) Beginning 3448.4 ± 143.0 4053.5 ± 117.2 10 min 2922.8 ± 135.2 3565.8 ± 127.5 20 min 2808.4 ± 145.1 3213.8 ± 126.4 30 min 2693.5 ± 138.0 2973.5 ± 117.3 40 min 2537.4 ± 116.1 2998.2 ± 115.8 50 min 2468.9 ± 149.4 3068.1 ± 135.8 60 min 2532.1 ± 154.0 3060.4 ± 131.0 Table 4. Systemic arterial resistance (dynes.s.c -5 ) during cardiopulmonary bypass (CPB). Data are presented as mean ± standard deviation, P> 0.05. CPB time RAP group Control (n=27) group(n=35) Beginning 1165.8 ± 94.8 1178.7 ± 125.4 1690.1 ± 133.3 10 min 1835.4 ± 162.7 20 min 2009.8 ± 177.1 2021.9 ± 160.9 2076.2 ± 170.8 2280.4 ± 254.4 30 min 40 min 1974.9 ± 167.8 2210.7 ± 242.9 2174.4 ± 281.5 50 min 2146.5 ± 127.6 60 min 2226.3 ± 114.3 2129.0 ± 323.9

RESULTS Characteristics and surgical data of RAP and control groups Both, RAP and control groups, presented similar clinicalsurgical characteristics, which are presented in Table 1. Mean arterial pressure (MAP) values during CPB were similar in both RAP and control groups (P>0.05) (Table 2, Figure 2A). Blood flow (BF) (ml/s) was statistically lower in the RAP group than the control group (P<0.05), except at the thirty minute when the flows were similar (P>0.05) (Table 3, Figure 2B). The CPB systemic arterial resistance (dynes.s.c -5) calculated from the relationship between MAP and BF was statistically similar (P>0.05) (Table 4, Figure 2C). The values of lactate were significantly lower during CPB in the RAP group in relation to the control group (P<0.05) (3.4 ± 0.2 vs. 4.3 ± 0.2 nmol/l), but they were similar to previous CPB (1.8 ± 0.2 vs. 1.8 ± 0.1 nmol/l) (P>0.05) and post-CPB (3.5 ± 0.3 vs. 3.6 ± 0.2 mlmol/l) (P>0.05), respectively (Figure 2). Total CPB crystalloid solution volume and diuresis The total CPB crystalloid volumes were smaller in the RAP than in the control group (1131.1 ± 82.4 vs. 2415.1 ± 77.2 ml) (P<0.05). The intraoperative diuresis (755.9 ± 113.6 vs. 1054.1 ± 93.6 ml) and postoperative 24 hours (2239.3 ± 142.9 vs. 2838.2 ± 142.0 ml), were smaller in the RAP group revealing indirectly that the method supplies an economy of priming (Figure 3). Clinical and laboratory data The results chose to reflect the patients intensive care unit evolution were, respectively, the blood levels of urea 613

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on the first postoperative day (46.1 ± 4.4 vs. 43.1 ± 4.2 mg/ dl) and the internment times (3.1 ± 0.2 vs. 2.8 ± 0.2 days), which were not statistically different in the RAP and control groups (Table 1).

lower the hematocrit to a desired level by adding aliquots of clear prime from the prime bags. Another advantage is that most prime displacement occurs in an antegrade direction from the venous line. This contributes to avoid hemodynamic instability at the onset of CPB. These advantages were fully observed on the 27 RAP patients included in the study. The hemodilution associated with the use of an asanguineous (crystalloid) CPB priming results in decreased intraoperative and postoperative hematocrit values in patients undergoing cardiac operations. The current study demonstrated that RAP can safely be used to decrease the crystalloid pump prime and the associate hemodilution. Therefore, the number of patients requiring red blood cell transfusion could be reduced by avoiding the compulsory transfusions triggered by low hematocrit values below minimum safety limit. In the present series of patients this advantage was observed during CPB, and IT was not the case considering the intra-operative period as a whole, and in the early postoperative period. Patients undergoing cardiac operations who will require transfusions can be predicted before the operation by a number of variables, including red blood cell mass [11]. This is consistent with the assumption that patients with a low red cell mass are more likely to have low hematocrit values and therefore require transfusions after CPB as a result of the proportionately greater hemodilution caused by CPB in these patients. As already described in this article, RAP is safe and extremely well tolerated with none morbidity and mortality, related to the method, among patients enrolled in the study. However, there are potential risks described in the literature, and deserve consideration. One potential risk of RAP, paradoxically, is related to its efficiency in minimizing hemodilution in patients undergoing CPB. Early investigators had demonstrated that an inverse linear relationship exists between temperature and blood viscosity, since blood viscosities can increase 10% to 30% under the hypothermic conditions associated with CPB Therefore, moderate hemodilution during CPB has been considered desirable in avoiding this increased viscosity and potential microcirculation damage, and such a degree of hemodilution has generally been provided by a total crystalloid prime [12]. A second theoretical risk of RAP is related to the potential of hemodynamic instability caused by the large volumes of crystalloid solution withdrawn during the RAP process [10]. It is somewhat unexpected in considering the relative hypovolemia induced by RAP that a significant volume or pressor requirement was not subsequently observed in patients subjected to RAP. In fact, withdrawal of RAP volumes was well tolerated, with hemodynamic parameters and pressor requirements that were equivalent to those in control patients. Although some

Blood transfusion and hematimetric data The results showed that there was a tendency, but not statistically significant (P>0.05), to a smaller percentage of RAP patients in receiving less blood transfusions (11.1% vs. 17.1%), as well as of plasma (7.4 vs. 14.3%), in the intraoperative period, respectively. Among the patients that received blood products in the intraoperative period, it was observed a tendency in the RAP group in receiving less blood (300 ± 0 vs. 500 ± 104.1 ml), as well as of plasma volume transfusion (175 ± 75.0 vs. 430 ± 88.9 ml), respectively. This tendency was not observed so much in relation to the blood transfusion in the postoperative number of patients (37.0 vs. 34.3%) as in the transfused volume (580 ± 80.0 vs. 500 ± 85.3 ml) in those patients that received blood in the RAP group compared to the control patients, respectively. Despite not observing this tendency related to the percentage of patients that received plasma in the postoperative period (40.7 vs. 45.7%), the amount of transfused plasma was smaller tendentious in the RAP group, compared to the group control, (384.6 ± 52.9 vs. 637.5 ± 103.6 ml), respectively. All these results are synthesized in Figure 4. The hemoglobin values before (13.158 ± 0.353 vs. 12.864 ± 0.384 g/dl) and post-CPB (11.225 ± 0.396 vs. 10.521 ± 0.287 g/dl), and hematocrit before (40.408 ± 1.019 vs. 39.675 ± 1.168%) and post-CPB (34.524 ± 1.140 vs. 32.500 ± 0.862%) were similar in the RAP and control groups, as well as the hematocrit in the first postoperative day (32.271 ± 0.757 vs. 33.932 ± 1.051%), respectively (P>0.05). However, during CPB the hemoglobin values (10.654 ± 0.266 vs. 8.818 ± 0.294 g/dl) and hematocrit (32.748 ± 0.778 vs. 27.382 ± 0.887%) were significantly increased (P<0.05) in the RAP group than in the control group, demonstrating the significant reduction of the CPB hemodilution with the use of RAP. About platelets transfusion, any patient one was transfused in the intra-operative, in both groups, and only 5.7% of the control patients received platelets transfusions in the postoperative. In the RAP group the patients did not received platelets in the postoperative. DISCUSSION Autotransfusion under the RAP modality has only gained popularity during the last few years. Low hematocrits during CPB are associated with increased risk of in-hospital mortality intra or postoperatively, use of intra-aortic balloon, and return to the pump after initial weaning. The method described has the potential to allow for the perfusionist to 614

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patients require reinfusion of RAP volumes, clinical experience suggested that correction of preoperative dehydration minimized the incidence of RAP reinfusion. Despite the advantages attributed to the use of RAP, few studies were carried out in the last decade. Although recent isolated studies confirm the benefits of recent RAP [13], at least two studies in meta-analysis are not favorable [14,15]. These results suggest that overall. A literature review and meta-analysis was carried out to assess the clinical effectiveness of retrograde autologous priming of the CPB circuit to reduce allogeneic packed red blood transfusions in adult cardiac surgery. A total of 21,643 patients were identified and eighteen trials were retrieved for full-text review. Six trials met eligibility criteria. Pooled estimates demonstrated that retrograde autologous priming significantly reduced the number of patients receiving intraoperative packed red cell transfusions, total hospital stay packed red cell transfusions, and the number of units transfused of total hospital stay packed red blood cells. Retrograde autologous priming, however, did not provide a clinical benefit in reducing the number of units transfused of intraoperative packed red blood cells. The combined patient population studied in the six trials was mainly primary isolated coronary artery bypass surgery. Assessing the safety of retrograde autologous priming was not possible due to limited data [15]. These observations are consistent with the results obtained in this service experience. Over the past 10 years there has been a marked decrease of the publications on PAR. It is curious to observe that over the same past 10 years, the concept of minimized CPB has been devised with the same aim of reducing the side effects and strengthening the advantages of standard CPB [16,17]. Alternatively, CPB method with decreased need for blood transfusion, merits citing the increasing the routine use of vacuum assisted venous drainage [18]. Finally, the present study was designed to be a smallscale pilot study to evaluate effects of RAP, which could be demonstrated, without any proved hemodynamic advantage. RAP should be further investigated in a larger cohort, preferably in high-risk patients with congestive heart failure, lung disease, or renal failure. RAP has, nowadays, to be compared in terms of cost-effectiveness with CPB minicircuits already available for clinical use.

2. Taylor KM. Perioperative approaches to coagulation defects. Ann Thorac Surg. 1993;56(5 Suppl):S78-82.

REFERENCES 1. Cormack JE, Forest RJ, Groom RC, Morton J. Size makes a difference: use of a low-prime cardiopulmonary bypass circuit and autologous priming in small adults. Perfusion. 2000;15(2):129-35.

3. Jatene FB, Pomerantzeff PMA, Monteiro AC, Estebes R, Silva MC, Bechara M, et al. Autotransfusão de coleta pré-operatória em cirurgia cardíaca. Rev Bras Cir Cardiovasc. 1988;3(1):29-35. 4. Babka RM, Petress J, Briggs R, Helsal R, Mack J. Conventional haemofiltration during routine coronary bypass surgery. Perfusion. 1997;12(3):187-92. 5. Sakert T, Gil W, Rosenberg I, Carpellotti D, Boss K, Williams T, et al. Cell saver efficacy for routine coronary artery bypass surgery. Perfusion. 1996;11(1):71-7. 6. Souza DD, Braile DM. Avaliação de nova técnica de hemoconcentração e da necessidade de transfusão de hemoderivados em pacientes submetidos à cirurgia cardíaca com circulação extracorpórea. Rev Bras Cir Cardiovasc. 2004;19(3):287-94. 7. Rosengart TK, DeBois W, O’Hara M, Helm R, Gomez M, Lang SJ, et al. Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements. J Thorac Cardiovasc Surg. 1998;115(2):426-38. 8. Panico FG, Neptune WB. A mechanism to eliminate the donor blood prime from the pump-oxygenator. Surg Forum. 1960;10:605-9. 9. Jansen PG, Velthuis H, Bulder ER, Paulus R, Scheltinga MR, Eijsman L, et al. Reduction in prime volume attenuates the hyperdynamic response after cardiopulmonary bypass. Ann Thorac Surg. 1995;60(3):544-9. 10. Eising GP, Pfauder M, Niemeyer M, Tassani P, Schad H, Bauernschmitt R, et al. Retrograde autologous priming: is it useful in elective on-pump coronary artery bypass surgery? Ann Thorac Surg. 2003;75(1):23-7. 11. Helm RE, Klemperer JD, Rosengart TK, Gold JP, Peterson P, DeBois W, et al. Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding. Ann Thorac Surg. 1996;62(5):1431-41. 12. Rand PW, Lacombe E, Hunt HE, Austin WH. Viscosity of normal human blood under normothermic and hypothermic conditions. J Appl Physiol. 1964;19:117-22. 13. Hou X, Yang F, Liu R, Yang J, Zhao Y, Wan C, et al. Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood transfusion in small adults: a prospective, randomized trial. Eur J Anaesthesiol. 2009;26(12):1061-6. 14. Murphy GS, Szokol JW, Nitsun M, Alspach DA, Avram MJ, Vender JS, et al. The failure of retrograde autologous priming of the cardiopulmonary bypass circuit to reduce blood use after cardiac surgical procedures. Anesth Analg. 2004;98(5):1201-7.

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15. Saczkowski R, Bernier PL, Tchervenkov CI, Arellano R. Retrograde autologous priming and allogeneic blood transfusions: a meta-analysis. Interact Cardiovasc Thorac Surg. 2009;8(3):373-6.

17. Puehler T, Haneya A, Philipp A, Zausig YA, Kobuch R, Diez C, et al. Minimized extracorporeal circulation system in coronary artery bypass surgery: a 10-year single-center experience with 2243 patients. Eur J Cardiothorac Surg. 2011;39(4):459-64.

16. Puehler T, Haneya A, Philipp A, Camboni D, Hirt S, Zink W, et al. Minimized extracorporeal circulation in coronary artery bypass surgery is equivalent to standard extracorporeal circulation in patients with reduced left ventricular function. Thorac Cardiovasc Surg. 2010;58(4):204-9.

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18. Chalegre ST, Salerno PR, Salerno LMVO, Melo ARS, Pinheiro AC, Frazão CS, et al. Drenagem venosa assistida a vácuo na circulação extracorpórea e necessidade de hemotransfusão: experiência de serviço. Rev Bras Cir Cardiovasc. 2011;26(1):122-7.

ORIGINAL ARTICLE

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Michel Pompeu Barros de Oliveira Sá1, Cecília Andrade Santos2, Omar Jacobina Figueiredo2, Renato Oliveira Albuquerque Lima2, Paulo Ernando Ferraz2, Alexandre Magno Macário Nunes Soares2, Pablo César Lustosa Barros Bezerra2, Wendell Nunes Martins2, Ricardo de Carvalho Lima3

DOI: 10.5935/1678-9741.20110053 Abstract Background and Objectives: Mediastinitis is a serious complication of median sternotomy and is associated with significant morbidity and mortality. The aim of this study is to identify which option of harvesting internal thoracic artery (ITA), pedicled or skeletonized, is associated with lower rates of mediastinitis after coronary artery bypass grafting surgery (CABG) in elderly, at the Division of Cardiovascular Surgery of PROCAPE. Methods: Retrospective study of 160 elderly who underwent consecutive CABG between May 2007 and June 2011. Eleven preoperative variables, four intraoperative variables and eight postoperative variables possibly involved in the development of postoperative mediastinitis were evaluated between two groups: CABG with skeletonized ITA (n=80) and pedicled ITA (n=80). Univariate and multivariate logistic regression analyses were applied. Results: The incidence of mediastinitis was 6.8% (n=11), with a lethality rate of 54.5% (n=6). The skeletonized ITA group were more exposed than pedicled ITA group to obesity (n=12 vs. n=4; 15% vs. 5%; P=0.035) and multiple transfusions (n=25 vs. n=11; 31.2% vs. 13.7%; P=0.008). The pedicled ITA group presented a greater risk of mediastinitis after CABG than skeletonized ITA group (n=10 vs. n=1; 12.5% vs. 1.2%; Unadjusted OR 11.3; 95% CI 1.4 - 241.5; P=0.008). In multivariate analysis, this difference

1. MD, MSc. 2. MD. 3. MD, MSc, PhD, ChM.

Work performed at the Division of Cardiovascular Surgery of Pronto Socorro Cardiológico de Pernambuco - PROCAPE. University of Pernambuco – UPE, Recife, PE, Brazil.

RBCCV 44205-1329 maintained statistically significant (Adjusted OR 5.2; 95% CI 1.5-495.8; P=0.012), being considered an independent association. Conclusions: We suggest that elderly should be considered for strategies to minimize risk of infection. In elderly that undergo unilateral ITA, the problem seems to be related to how ITA is harvested. Elderly should always be considered for the use of skeletonized ITA. Descriptors: Myocardial revascularization. Mediastinitis. The elderly.

Resumo Justificativa e Objetivos: Mediastinite é séria complicação da esternotomia mediana e está associada a significativa morbidade e mortalidade. O objetivo deste estudo é identificar qual técnica de obtenção da artéria torácica interna (ATI), dissecção pediculada ou esqueletizada, está associada a menores taxas de mediastinite após cirurgia de revascularização miocárdica (CRM) em idosos, na Divisão de Cirurgia Cardiovascular do PROCAPE. Métodos: Estudo retrospectivo de 160 idosos submetidos consecutivamente à CRM entre maio/2007 e junho/2011. Onze variáveis pré-operatórias, quatro intraoperatórias e oito pós-operatórias, possivelmente envolvidas no

Correspondence address: Michel Pompeu Barros de Oliveira Sá Av. Eng. Domingos Ferreira, 4172/405 – Recife, PE, Brazil ZIP Code: 51021-040. E-mail: michel_pompeu@yahoo.com.br Article received on July 31st, 2011 Article accepted on November 16th, 2011

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desenvolvimento de mediastinite após CRM, foram avaliadas entre dois grupos: CRM com ATI esqueletizada (n=80) e ATI pediculada (n=80). Análises univariada e multivariada por regressão logística foram aplicadas. Resultados: A incidência de mediastinite foi 6,8% (n=11), com taxa de letalidade de 54,5% (n=6). Grupo ATI esqueletizada foi mais exposto à obesidade (n=12 vs. n=4; 15% vs. 5%, P=0,035) e múltiplas transfusões (n=25 vs. n=11; 31,2% vs. 13,7%; P=0,008) do que grupo ATI pediculada. Grupo ATI pediculada apresentou maior risco de mediastinite após CRM que grupo ATI esqueletizada (n=10 vs. n=1; 12,5% vs. 1,2%; OR não-ajustado 11,3; IC 95% 1,4-

241,5; P=0,008). Na análise multivariada, esta diferença manteve-se estatisticamente significativa (OR ajustado 5,2; IC 95% 1,5-495,8; P=0,012), sendo considerada uma associação independente. Conclusões: Sugerimos que os idosos devem ser considerados para estratégias de minimização de risco de infecção. Em idosos submetidos à CRM com ATI unilateral, o problema parece estar relacionado à forma como a ATI é obtida. Idosos devem ser sempre considerados para o uso de ATI esqueletizada.

INTRODUCTION Mediastinitis is a deep wound infection after median sternotomy, with clinical evidence and / or microbiological commitment of the retrosternal space, associated with sternal osteomyelitis with or without its instability [1-4]. It is one of the most serious complications of median sternotomy and is associated with significant morbidity and mortality [5]. It is also known as a deep sternal wound infection [5]. This is an entity with low incidence, occurring in only 1% to 3% of patients after cardiac surgery [6]. However, when it occurs, is associated with high mortality rates, reaching 35% [7]. It has been shown that coronary artery bypass grafting (CABG) is associated with a higher risk of developing mediastinitis compared to other procedures in cardiovascular surgery (valve surgery, correction of congenital heart disease) [8]. In recent years, studies [9-11] have emphasized the use of bilateral internal thoracic artery (ITA or mammary) as the major cause of higher incidence of mediastinitis in coronary artery bypass grafts. However, Sá et al. [8] performed a study at the Division of Cardiovascular Surgery of Pronto Socorro Cardiológico de Pernambuco - PROCAPE, noting an interesting aspect in comparison to these studies: bilateral ITA was performed in almost no patient in this service, in which unilateral ITA was mostly used. Although we have performed almost exclusively CABG with unilateral ITA, this surgery was associated with increased risk of developing mediastinitis compared to other procedures. In a recent publication of our institution [1], we have demonstrated that in patients undergoing CABG who do not undergo bilateral ITA, the problem seems to be unrelated to the use or not of unilateral ITA, but related to how ITA is harvested (with favorable results to skeletonized ITA in comparison to pedicled ITA). 618

Descritores: Revascularização miocárdica. Mediastinite. Idoso.

Age is always a feared risk factor for mediastinitis and viewed with caution by cardiovascular surgeons [12]. Therefore, the aim of this study is to identify, in the specific subgroup of elderly patients, which option of harvesting ITA is associated with lower rates of mediastinitis after CABG with the use of unilateral ITA at our institution. METHODS Source population We studied 160 consecutive elderly patients (age ≥ 70 years) undergoing CABG with the use of left internal thoracic artery at the Division of Cardiovascular Surgery of PROCAPE from May 2007 to June 2011. Study design Retrospective cohort was performed from the database of medical and surgical records from the previously mentioned center and, initially, two groups were created: CABG with skeletonized ITA (80 patients) and with pedicled ITA (80 patients). The two groups were compared and the following variables were assessed (all categorized into yes or no): 1. Characteristics of patients a. Gender (male ou female); b. Obesity (body mass index ≥ 30 kg/m2, BMI); c. Hypertension (reported by patient and/or use of anti-hypertensive medication); d. Diabetes (reported by patient and/or use of oral hypoglycemic medication and/or insulin); e. Smoking (reported by patient; active or inactive for less than 10 years); f. Chronic obstructive pulmonary disease - COPD (dyspnea or chronic cough AND prolonged use of bronchodilators or corticosteroids AND/OR compatible radiological changes - hypertransparency by hyperinflation

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and/or rectification of ribs and/or rectification diaphragmatic); g. Renal disease (creatinine ≥ 2.3 mg/dL or preoperative dialysis); h. Previous cardiac surgery; i. Ejection fraction < 50%; j. Acute myocardial infarction (AMI) < 90 days; k. New York Heart Association functional class (III/IV).

symptoms with no other recognized cause: fever (38o C), chest pain, or sternal instability and at least one of the following: a. purulent discharge from mediastinal area; b. organisms cultured from blood or discharge from mediastinal area; c. mediastinal widening on X-ray. We also assessed the following characteristics: intensive care unit length of stay (days) and hospital length of stay (days), outcome at hospital discharge (survival or death). All information was considered about in-hospital period. No patient was discharged and returned.

2. Characteristics of procedure a. Emergency surgery (during acute myocardial infarction, ischemia not responding to therapy with intravenous nitrates, cardiogenic shock); b. Concomitant cardiac surgery; c. Number of bypass; d. Use of cardiopulmonary bypass – CPB (on-pump or off-pump). 3. Postoperative complications a. Low cardiac output (need for inotropic support with dopamine 4 ì g/kg/min or dobutamine or intraaortic baloon at least for a minimum of 12 hours); b. Reoperation (new sternotomy for bleeding, tamponade, or other reasons during the intra-hospital period); c. Respiratory complications (pulmonary infection, acute respiratory distress syndrome, atelectasis, need for intubation for more than 48 hours); d. Renal complications (creatinine ≥ 2,3 mg/dL or postoperative dialysis); e. Hyperglicemia (first blood glucose after closure of skin > 200 mg/dL); f. Multiple transfusions (more than 3 units of any blood products in postoperative period before diagnostic definition of mediastinitis); g. Infection at another site; h. Sternal dehiscence. The outcome evaluated was mediastinitis after surgical procedure. This variable was categorized into yes or no. Isolated superficial infections from sternal wound with stable and / or sterile sternal dehiscence and / or no macroscopic evidence of deep infection (purulent drainage) were not considered as having mediastinitis. Mediastinitis were considered only with those who met at least one of the criteria according to the Centers for Disease Control and Prevention (CDC) [13]: 1. Patient has organisms cultured from mediastinal tissue or fluid obtained during a surgical operation or needle aspiration; 2. Patient has evidence of mediastinitis observed during a surgical operation or histopathologic examination; 3. Patient has at least one of the following signs or

Details of surgical procedures All patients received prophylactic antibiotics. It is part of the institutional protocol use of intravenous cefazolin as it follows: 2 g as the initial dose during anesthesia induction, 1g during entering CPB, 1 g every 4 hours during surgery, 1g every 8 hours for 24 to 48-hours after surgery. All patients used bone wax for hemostasis of the sternal marrow (it is part of the protocol of our institution its use in all patients undergoing median sternotomy). Patients were selected for cardiopulmonary bypass (on-pump or off-pump CABG) and type of ITA harvesting technique (pedicled or skeletonized) according to the preference of the attending surgeon. Skeletonized ITA was obtained with artery dissection with scissors and clipping intercostal branches with metal clips without involving any margins tissue around ITA. Pedicled ITA was obtained with direct dissection of surrounding margin of tissue around the ITA with electrocautery. There was no change in the way of dissection of ITA during the procedure. When a certain technique was started, it was performed until the end. All mediastinitis cases were treated with specific antibiotics for germs identified on culture and antibiograms associated with reoperation with mediastinal toilet (many times as necessary). Data analysis The data were stored in SPSS program (Statistical Package for Social Sciences) version 15, from which calculations were performed with statistical analysis, and interpretation. The data storage was done in double-entry to validate and carry out analysis of data consistency, in order to ensure minimal error in recording information in software. Univariate analysis for categorical variables was performed with the chi-square test or Fisher’s exact test. For continuous variables we used Student’s t test. Verification of the hypothesis of equality of variances was performed using the Levene’s F test. Potential risk factors with P<0.20 in univariate analysis were included in multivariate analysis, which was performed by stepwise 619

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forward logistic regression, remaining variables with P<0.10. P values <0.05 were considered statistically significant.

Characteristic of the procedures There were no statistically significant differences between groups related to the characteristic of the procedures (Figure 3).

Ethics on research This research was submitted to the approval of the Research Ethics Committee of Complexo Hospitalar do Hospital Universitário Oswaldo Cruz / Pronto Socorro Cardiológico de Pernambuco – HUOC/PROCAPE, according to resolution 196/96 of the National Health Council [14,15]. RESULTS Characteristics of patients Patients undergoing CABG with skeletonized ITA had a mean age of 73.9 ± 3.6 years and those undergoing CABG with pedicled ITA had a mean age of 74.7 ± 4.6 years (P=0.797). The skeletonized ITA group presented more obese patients than pedicled ITA group (n=12 vs. n=4; 15% vs. 5%; P=0.035). The other variables showed no statistically significant differences between groups (Figures 1 and 2).

Fig. 3 – Description of surgical procedures characteristics in elderly undergoing CABG. ITA =- internal thoracic artery; CABG = coronary artery bypass graft

Fig. 1 – Description of preoperative clinical characteristics in elderly undergoing CABG. ITA = internal thoracic artery; CABG = coronary artery bypass graft

Fig. 4 – Description of postoperative complications in elderly undergoing CABG. ITA = internal thoracic artery; CABG = coronary artery bypass graft; LCOS = low cardiac output syndrome

Fig. 2 – Description of preoperative clinical characteristics in elderly undergoing CABG. ITA = internal thoracic artery; CABG = coronary artery bypass graft; COPD = chronic obstructive pulmonary disease; EF = ejection fraction; AMI = acute myocardial infarction; NYHA = New York Heart Association

Fig. 5 – Description of postoperative complications in elderly undergoing CABG. ITA = internal thoracic artery; CABG = coronary artery bypass graft

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Postoperative complications The skeletonized ITA group presented more patients that received multiple transfusions than pedicled ITA group (n=25 vs. n=11; 31.2% vs. 13.7%; P=0.008). The other variables showed no statistically significant differences between groups (Figures 4 and 5). Analysis of outcome We observed incidence of 6.8% (n=11) of mediastinitis after CABG in the total group (Figure 6). The isolated agents are described in Table 1. The pedicled ITA group presented a greater risk of mediastinitis after CABG than skeletonized ITA group (n=10 vs. n=1; 12.5% vs. 1.2%; Unadjusted OR 11.3; Confidence Interval 1.4 – 241.5; P=0.008). Proceeding multivariate logistic regression analysis, this difference maintained statistically significant (Adjusted OR 5.2; Confidence Interval 1.5 – 495.8; P=0.012), being considered an independent association. Evolution Elderly who developed mediastinitis stayed six more days in the intensive care unit (16.5 ± 12.3 vs. 5.1 ± 6.1, P <0.001) and presented a longer hospital stay (52.1 ± 28.7 vs. 30.9 ± 16.4; P <0.001) compared with those who did not develop mediastinitis. Lethality rate for mediastinitis were 54.5% (n=6).

Fig. 6 – Incidence of mediastinitis in elderly after CABG and comparison between groups. ITA = internal thoracic artery; CABG = coronary artery bypass graft; OR = Odds Ratio. The adjusted OR was obtained comparing pedicled ITA group with skeletonized ITA group, taking into consideration differences between groups about preoperative, intraoperative and postoperative characteristics

Table 1. Analysis of etiologic agents in cases of mediastinitis in the postoperative period by the culture of exudates. Isolated agents N % Staphylococcus aureus 5 45,4 Staphylococcus epidermidis 2 18,2 Klebsiella pneumoniae 2 18,2 Pseudomonas aeruginosa 2 18,2

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DISCUSSION In our study, the incidence of mediastinitis was 6.8% (n=11), above the rates reported in other studies, ranging from 0.2% to 5.0% [16-18]. However, we should note two points. First, a previous study at our institution [8] showed an incidence of 2.4% between 1038 cardiovascular surgeries (involving all types of surgeries - within the range defined in the literature) and CABG was associated with increased risk compared with other cardiac surgeries (CI 3.44 to 8.30, P = 0.0001). Second, age is recognized as an important risk factor for sternal wound infections after cardiac surgery [12]. Therefore, we are analyzing a “doubled” risk group, justifying excess incidence in the present study. Many factors have been associated with development of mediastinitis after cardiac surgery [19]. However, there is no consensus as to which factors are most important and how each one of them is an independent risk predictor for postoperative mediastinitis [19]. We discovered that there was higher incidence of mediastinitis in elderly who used pedicled ITA compared with skeletonized ITA (statistically significant independent association). In other words, the skeletonized ITA was an independent protective factor for postoperative mediastinitis in elderly people. Several studies have shown favorable results to the use of skeletonized ITA [20-22]. Saso et al. [20] demonstrated that skeletonization of ITA in patients undergoing CABG was associated with reduced incidence of deep sternal infection (OR 0.41, 95% CI from 0.26 to 0.64) and this effect was even more evident when the specific analysis of diabetic patients (OR 0.19, 95% CI from 0.1 to 0.34). Kai et al. [21] observed that the incidence of deep sternal infection was significantly lower in diabetics that underwent CABG with the use of skeletonized ITA compared to diabetics using pedicled ITA (0.6% vs. 13.0% P = 0.01). Milani et al. [22] studied 70 diabetic patients submitted to CABG, dividing them into two groups: in group A, thoracic arteries were dissected as a pedicle, while in group B they were skeletonized. Three (8.57%) patients from group A developed mediastinitis. The use of skeletonized ITA significantly decreased the incidence of mediastinitis (P = 0.044). They concluded that the utilization of skeletonized ITA significantly decreases the incidence of mediastinitis. These results were found, probably as a result of a better sternal perfusion after ITA skeletonization compared to the pedicled ITA [23-25]. Boodhwani et al. [23] conducted a study with 48 patients, in which each patient was submitted to CABG using bilateral ITA, and all ITAs were dissected in a skeletonized manner on the left side, while pedicled dissected on the right side. Patients were then evaluated 621

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for sternal perfusion through scintigraphy (radionuclear image). The authors found that sternal perfusion was increased in skeletonized side compared with pedicle side (increase of 17.6%, P = 0.03). Kamiya et al. [24] showed that the oxygen saturation and blood flow in the microcirculation of the sternum tissue were better when using the skeletonized ITA compared to pedicled ITA. Santos Filho et al. [25] studied 35 patients submitted to CABG, dividing them into two groups: group A (n=18) had ITA dissected using skeletonization technique and group B (n=17) as pedicle preparation. There was no difference in the two groups relating gender, age and demographic characteristics. On the seventh postoperative day the patients underwent bone scintillography. They observed that group A (skeletonized ITA) showed higher perfusion than group B (pedicled ITA) patients, however, it was not statistically significant (P = 0.127). On the other hand, comparing the diabetic population, seven in each group, there was a 47.4% higher perfusion of the sternum in group A (skeletonized ITA) comparing to group B (pedicled ITA) and this difference reached statistical significance (P = 0.004). They concluded that in diabetic subgroup, a significant preservation of the sternal perfusion was observed in patients that undergone skeletonized ITA. One aspect that reinforces the importance of skeletonized ITA is the fact that the group that underwent CABG with this type of graft in our study, although more exposed than the pedicled ITA group to two factors strongly and independently associated with mediastinitis in other studies – obesity [1] and multiple transfusions [2,26,27], still had a lower incidence of mediastinitis after CABG. Our study showed that patients who developed mediastinitis had a longer stay in ICU and had higher length of hospital stay (statistically significant) compared with those who did not developed mediastinitis, which reflects the high morbidity and high costs involved with this complication [28]. The lethality rate found (54.5%) was higher to that observed in other studies [29-31], but we must consider that we are studying an older population (only elderly patients). Other risk factors may be involved, but they are difficult to be measured. The aspect of the bone, which can sometimes show signs of osteoporosis or ischemia, the use of bone wax on sternal hemostasis [32], the surgeon’s ability, failure to follow the antisepsis procedures, errors in the sternotomy and in the sternum rewiring, and excessive use of an electric scalpel, permanence of central venous catheters [33] are factors that are not frequently mentioned but can be important in the pathophysiology of mediastinitis.

undergo unilateral ITA, the problem seems to be related to how ITA is harvested. Elderly should always be considered for the use of skeletonized ITA during CABG surgery.

CONCLUSION We suggest that elderly patients should be considered for strategies to minimize risk of infection. In elderly that 622

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11. Friedman ND, Bull AL, Russo PL, Leder K, Reid C, Billah B, et al. An alternative scoring system to predict risk for surgical site infection complicating coronary artery bypass graft surgery. Infect Control Hosp Epidemiol. 2007;28(10):1162-8.

thoracic artery vs. double conventional internal thoracic artery in diabetic patients submitted to OPCAB. Rev Bras Cir Cardiovasc. 2008;23(3):351-7.

12. Bellchambers J, Harris JM, Cullinan P, Gaya H, Pepper JR. A prospective study of wound infection in coronary artery surgery. Eur J Cardiothorac Surg. 1999;15(1):45-50. 13. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309-32. 14. Sá MP, Lima RC. Research Ethics Committee: mandatory necessity. Requirement needed. Rev Bras Cir Cardiovasc. 2010;25(3):III-IV. 15. Lima SG, Lima TA, Macedo LA, Sá MP, Vidal ML, Gomes AF, et al. Ethics in research with human beings: from knowledge to practice. Arq Bras Cardiol. 2010;95(3):289-94. 16. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg. 1997;63(2):356-61. 17. Toumpoulis IK, Anagnostopoulos CE, Balaram S, Swistel DG, Ashton RC, DeRose JJ Jr. Does bilateral internal thoracic artery grafting increase long-term survival of diabetic patients? Ann Thorac Surg 2006; 81:599-607. 18. De Paulis R, de Notaris S, Scaffa R, Nardella S, Zeitani J, Del Giudice C, et al. The effect of bilateral internal thoracic artery harvesting on superficial and deep sternal infection: the role of skeletonization. J Thorac Cardiovasc Surg. 2005;129(3):536-43. 19. Toumpoulis IK, Anagnostopoulos CE, Derose JJ Jr, Swistel DG. The impact of deep sternal wound infection on long-term survival after coronary artery bypass grafting. Chest. 2005;127(2):464-71.

23. Boodhwani M, Lam BK, Nathan HJ, Mesana TG, Ruel M, Zeng W, et al. Skeletonized internal thoracic artery harvest reduces pain and dysesthesia and improves sternal perfusion after coronary artery bypass surgery: a randomized, doubleblind, within-patient comparison. Circulation. 2006;114(8);766-73. 24. Kamiya H, Akhyari P, Martens A, Karck M, Haverich A, Lichtenberg A. Sternal microcirculation after skeletonized versus pedicled harvesting of the internal thoracic artery: a randomized study. J Thorac Cardiovasc Surg. 2008;135(1):32-7. 25. Santos Filho EC, Moraes Neto FR, Silva RA, Moraes CR. Should the diabetics have the internal thoracic artery skeletonized? Assessment of sternal perfusion by scintillography. Rev Bras Cir Cardiovasc. 2009;24(2):157-64. 26. Dorneles CC, Bodanese LC, Guaragna JC, Macagnan FE, Coelho JC, Borges AP, et al. The impact of blood transfusion on morbidity and mortality after cardiac surgery. Rev Bras Cir Cardiovasc. 2011;26(2):222-9. 27. Sá MP, Figueira ES, Santos CA, Figueiredo OJ, Lima RO, Rueda FG, et al. Validation of MagedanzSCORE as a predictor of mediastinitis after coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(3):386-92. 28. Laizo A, Delgado FEF, Rocha GM. Complications that increase the time of hospitalization at ICU of patients submitted to cardiac surgery. Rev Bras Cir Cardiovasc. 2010;25(2):166-71. 29. De Feo M, Renzulli A, Ismeno G, Gregorio R, Della Corte A, et al. Variables predicting adverse outcome in patients with deep sternal wound infection. Ann Thorac Surg. 2001;71(1):324-31. 30. Abboud CS, Wey SB, Baltar VT. Risk factors for mediastinitis after cardiac surgery. Ann Thorac Surg. 2004;77(2):676–83.

20. Saso S, James D, Vecht JA, Kidher E, Kokotsakis J, Malinovski V, et al. Effect of skeletonization of the internal thoracic artery for coronary revascularization on the incidence of sternal wound infection. Ann Thorac Surg. 2010;89(2):661-70.

31. Sá MP, Soares EF, Santos CA, Figueiredo OJ, Lima RO, Escobar RR, et al. Skeletonized left internal thoracic artery is associated with lower rates of mediastinitis in diabetic patients. Rev Bras Cir Cardiovasc. 2011;26(2):183-9.

21. Kai M, Hanyu M, Soga Y, Nomoto T, Nakano J, Matsuo T, et al. Off-pump coronary artery bypass grafting with skeletonized bilateral internal thoracic arteries in insulindependent diabetics. Ann Thorac Surg. 2007;84(1):32-6.

32. Volpe MA, Martinez JDG. Geli Putty®: a new alternative on sternal hemostasis in cardiac surgery. Rev Bras Cir Cardiovasc. 2011;26(3):485-7.

22. Milani R, Brofman PR, Guimarães M, Barboza L, Tchaick RM, Meister Filho H, et al. Double skeletonized internal

33. Ledur P, Almeida L, Pellanda LC, Schaan BD. Predictors of infection in post-coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(2):190-6.

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ORIGINAL ARTICLE

Rev Bras Cir Cardiovasc 2011;26(4):624-9

Pedro Silvio Farsky1, Humberto Graner2, Pedro Duccini2, Eliana da Cassia Zandonadi3, Vivian Lerner Amato4, Jaime Anger5, Antonio Flavio de Almeida Sanches6, Cely Saad Abboud7 DOI: 10.5935/1678-9741.20110054

RBCCV 44205-1330

Abstract Background: Sternal wound infection (SWI) after coronary artery bypass graft (CABG) surgery is a major complication. Identifying patients at risk of SWI is essential for the application of preventive measures. Objective: To identify the pre- and intra-operative risk factors, apply the STS risk score and determine the correlation between the risk score and microorganisms isolated from surgical wounds in a Brazilian hospital. Methods: This is a retrospective analysis of a database of all CABG surgeries performed in a single institution from 2006 to 2008. Chi-square analysis was used for categorical variables and Student’s t-test was used for quantitative variables. Multivariate logistic regression model was used to identify independent risk factors for SWI. P <0.05 was considered significant. Results: The infection rate was 7.2% (143/1975). The multiple regression analysis found the following risk factors: female gender (OR 2.06; 95%CI 1.40-3.03; P<0.001), BMI>40 kg/m 2 (OR 6.27, 95%CI 2.53-15.48; P<0.001), diabetes (OR 2.33; 95%CI 1.56-3.49; P<0.001), number of affected coronary arteries (OR 7.78; 95%CI 1.04-57.79; P<0.001) and use of bilateral internal thoracic artery (OR 3.85; 95%CI 2.10-7.07; P<0.001). Infected patients had a mean score of 9, whereas non-infected patients had a mean score

of 7 (P<0.001). There was no correlation between microorganisms, scores and risk factors. Conclusion: Female gender, diabetes, BMI>40 kg/m2, number of affected coronary arteries and use of bilateral internal thoracic artery were associated with a higher risk of infection. The STS risk score can be successfully used and there was no correlation between microorganisms, the score and risk factors at our institution.

1. PhD at the University of São Paulo; Effective Physician at Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil. 2. Residence in Cardiology at Dante Pazzanese Cardiology Institute, Sao Paulo, SP, Brazil. 3. Clinical Nurse Specialist in Cardiology; Nurse at Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil. 4. PhD in Science; Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil. 5. Plastic Surgeon; Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil. 6. PhD in Science; Doctor of Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil. 7. MSc; Physician-in-Chief at the medical section of the Infectious

Diseases at Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil.

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Descriptors: Infection. Risk factors. Mediastinitis. Myocardial revascularization.

Resumo Fundamento: A infecção de ferida operatória esternal após cirurgia de revascularização miocárdica (CRM) é uma grave complicação. Identificar pacientes com risco elevado é fundamental para introdução de medidas de preventivas. Objetivo: Identificar os fatores de risco pré e intraoperatórios, avaliar o escore de risco da STS e correlação entre o escore e os microorganismos isolados em ferida operatória em hospital brasileiro. Métodos: Análise retrospectiva de um banco de dados prospectivamente coletado de todas as CRM realizadas em centro único, no período de 2006 a 2008. Teste do qui-

Work performed at Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil. Correspondence address Pedro Silvio Farsky - Av. Dante Pazzanese, 500 – São Paulo, SP, Brazil - Zip Code: 04012-909 E-mail: farskyp@uol.com.br Article received on June 8th, 2011 Article accepted on August 29th, 2011

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quadrado foi utilizado para variáveis categóricas e teste tStudent, para variáveis quantitativas. Modelo multivariado por regressão logística foi utilizado para identificação de fatores de risco independente para infecção de ferida esternal. P<0,05 foi considerado significativo. Resultados: A incidência de infecção foi de 7,2% (143/ 1975). Na regressão múltipla, identificamos os seguintes fatores de risco: sexo feminino (OR 2,06; IC95%; 1,40-3,03; P<0,001), IMC>40 kg/m2 (OR 5,38; IC95%; 2,24-12,90; P<0,001), diabetes (OR 2,33; IC95% 1,56-3,49; P<0,001), número de artérias coronárias acometidas (OR 2,06; IC95%; 1,40-3,03; P<0,001) e uso bilateral de artéria torácica interna (OR 3,44; IC95% 1,89-6,26; P<0,001). Os pacientes

infectados apresentaram média de escore da STS de 9 versus 7 nos não infectados (P<0,001). Não houve correlação entre microorganismos, escore e fatores de risco. Conclusão: Sexo feminino, diabetes, IMC>40 kg/m 2, número de artérias coronárias acometidas, uso bilateral da artéria torácica interna foram associados a maior risco de infecção. O escore de risco da STS pode ser aplicado com sucesso, não havendo correlação entre microrganismos, escore e fatores de risco em nossa instituição.

INTRODUCTION Sternal wound infection (SWI) is one of the most serious complications associated with coronary artery bypass graft (CABG) surgery. It is associated with an increase in the period of hospitalization, hospital costs and need for surgical re-intervention [1-5]. It is extremely important to identify patients undergoing CABG surgery who have a high risk of developing wound infection in order to provide effective preventive measures. Several pre- and intra-operative risk factors have been associated with an increased incidence of SWI with the incidence of mediastinitis ranging from 0.4% to 5.3%, and early and in-hospital lethality varying between 10% and 47% [1,2,4-10]. Gardlund et al. [11] have shown a correlation between the presence of microorganisms and risk factors for SWI. Fowler et al. [12] published, in 2005, a wound infection risk score, using logistic regression analysis, based on data from 331,429 cases from the Society of Thoracic Surgeons National Cardiac Database (STS). A simple model with 12 variables was developed and validated for the identification of patients who are at high risk for infections after cardiac surgery. Dante Pazzanese Cardiology Institute, located in São Paulo, is a public university hospital with 350-bed capacity for cardiovascular surgeries. Approximately 2,000 heart surgeries are performed annually, and about 1,000 of these are isolated CABGs. The Institution has a hospital infection control and prevention program and performs active disease surveillance, following criteria from the Center for Disease Control and Prevention (CDC) [13]. There may be population differences, and this model has not yet been applied to our population. The objectives of the present study were: to identify the pre- and intraoperative risks associated with sternal wound infection; to apply the STS risk score to patients undergoing coronary artery bypass graft surgery in a Brazilian Tertiary Hospital

Descritores: Infecção. Fatores de risco. Mediastinite. Revascularização Miocárdica.

of Cardiology; and to analyze the correlation between etiological agents of SWI with the STS risk score and associated risk factors. METHODS Study design Data were prospectively collected from January 2006 to December 2008 from CABGs performed at this institution. The STS risk score [12] was applied to the study population. The pre- and intra-operative risk factors were evaluated, and group of patients who had sternal wound infections were compared with patients without infection based on their pre- and intra-operative characteristics. The diagnosis of sternal wound infection followed the criteria for infection set by the CDC [13]. All patients were evaluated for a period of up to 30 days after hospital discharge, and patients who had infection during this period were identified. Details of surgical procedures for treatment of SWI Acute wound infection treatment consisted of drainage of purulent collections, aggressive debridement of necrotic tissue and closure. Some patients required sternal rewiring or the use of pectoralis major muscle or omental flaps to increase the vascularization [14]. Although these treatments were effective in most of the patients, some did not respond and developed a wound dehiscence at different anatomical levels, sometimes even with a loss of the sternum and rib portions. In these secondary wounds plastic reconstruction was necessary. Dehiscent wounds without loose of tissue were closed by bilateral pectoralis major fasciocutaneous flaps. For wounds with insufficient amount of bordering tissues different flaps were used according to the type of defect: advanced or rotated pectoralis major musculocutaneous flap [15], isled rectus abdominis musculocutaneous flap and omental flap followed by skin grafting. Composed breast skin flaps may be used in females [16]. 625

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Statistical analysis The Chi-square test or Fisher’s exact test were used to confirm the association between qualitative variables and infection in univariate analysis. To identify differences between groups using quantitative variables, Student’s ttest was used for variables with normal distribution. The Mann-Whitney test was used for variables without normal distribution. A multivariate logistic regression model was used to identify independent risk factors for SWI. Pvalues<0.05 were considered statistically significant.

described in Table 1. In univariate analysis, female gender, diabetes, arterial hypertension, body mass index (BMI) greater than 40kg/ m2, number of affected coronary arteries and use of bilateral internal thoracic artery were associated with a greater risk of SWI. Multiple regression analysis identified female gender (OR 2.06; 95%CI; 1.40-3.03; P<0.001), diabetes (OR 2.33; 95%CI; 1.56-3.49; P<0.001), BMI greater than 40 kg/ m2 (OR 6.27; 95%CI 2.53-15.40; P<0.001), number of affected coronary arteries (OR 7.78; 95%CI 1.04-57.79; P<0.001) and use of bilateral internal thoracic artery (OR 3.85; 95%CI 2.10-7.07; P<0.001) as factors independently associated with SWI (Table 2). The intra-aortic balloon pump was only used in 61 (3.1%) patients, and four (2.8%) of them developed wound infection. In relation to the analysis of the wound risk score proposed by the STS, it was observed that the patients suffering from sternal infection had a higher score than non-infected patients (9 and 7, respectively; P<0.001). The isolated etiological agents of infection, with the possibility of more than a single agent affecting each patient, are described in Table 3.

Ethical aspects The study was approved by the Local Medical Ethics Committee. RESULTS During the study period, 1,975 patients underwent CABG surgery; of these, 143 (7.2%) developed wound infection, with 38 (1.9%) showing superficial wound infection, 58 (2.9%) showing deep wound infection and 47 (2.4%) showing mediastinitis. The clinical characteristics of patients with SWI are

Table 1. Clinical characteristics and risk factors evaluated. Variable Patient with SWI Age (years) 62.48 Female gender 68/143 (47.6%) Diabetes mellitus 93/143 (65%) Arterial hypertension 133/143 (93%) Current smoking 29/143 (20.3%) Dyslipidemia 91/143(63.6%) COPD 9/143 (6.3%) CRD 17/143 (11.9%) Preoperative AMI 80/143 (55.9%) Preoperative stroke 3/143 (2.1%) PAD 35/143 (24.5%) LVEF < 50% 57/143 (39.9%) BMI (kg/m2) <30 83/140 (59.2%) 30 – 40 45/140 (32.1%) >40 12/140 (8.5%) Number of diseased coronaries 1 1/85 (1.29%) 2 16/301 (5.3%) 3 73/767 (9.5%) Left main coronary 24/414 (5.8%) Emergency Surgery 7/84 (8.3%) Bilateral ITA 17/143 (11.8%) Period of anoxia (minutes) 54.9 Period of CPB (minutes) 81.22

Patient without SWI 62.48 531/1832 (29%) 728/1832 (39.7%) 1563/1832 (85.3%) 367/1832 (20%) 1148/1832(62.7%) 78/1832(4.3%) 180/1832 (9.8%) 940/1832 (5.1%) 67/1832 (3.6%) 336/1832 (18.3%) 656/1817 (36.1%)

P-value 0.815 0.001 0.001 0.011 0.858 0.817 0.253 0.428 0.286 0.331 0.070 0.369 < 0.001

1410/1821 (77.4%) 381/1821 (20.9%) 30/1821 (1.6%) 0.005 84/85 (98.8%) 285/305 (94.6%) 694/767 (90.4%) 390/414 (94.2%) 136/1886 (7.2%) 118/1832 (6.4%) 53.9 80.7

0.698 0.001 0.871 0.073

COPD – chronic obsrtructive pulmonary disease; CRD – chronic renal disease; AMI – acute myocardial infarction; PAD – peripheral arterial disease; LVEF – left ventricular ejection fraction; BMI – body mass index; ITA – internal thoracic artery; CPB – cardiopulmonary bypass

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The patients affected by Gram-negative bacteria had scores of 11, as compared with a score of 9 for patients affected by Gram-positive bacteria (P=0.063). There was no correlation between the different etiological agents and pre-operative risk factors and mortality. There was also no difference in mortality between infected and non-infected patients (8.4% vs. 6.8%, respectively; P=0.309) during hospitalization.

Diabetes was associated with a higher rate of SWI, in accordance with some studies [7,10] and in contrast with others [1,4,5,19,20]. A high BMI was identified as an important risk factor for SWI, and is supported by the majority of studies on this topic [2,4,5,10]. Milano et al. [5] discuss some factors that may explain why obesity is a risk factor, such as, for example, the dose of the prophylactic antibiotic, which is not corrected on the basis of the patient body mass index, difficulty for patientâ&#x20AC;&#x2122;s skin folds to remain sterile during the procedure, and adipose tissue itself, which may function as a substrate for infection. The number of affected coronary arteries, found in our study, was associated with higher rates of SWI, which was in agreement with the study presented by Risnes et al. [18]. The use of bilateral internal thoracic arteries was strongly related with higher rates of SWI. Walkes et al. [21] found a 4.4% incidence of mediastinitis when using bilateral internal mammary artery grafts, as compared with 2.2% when using single mammary artery grafts (P=0.06). A metaanalysis [22] places the use of bilateral internal thoracic artery grafts as an important risk factor for greater wound infection, but there is no consensus in the literature [23]. This fact may be explained by lower sternal and operative wound irrigation after bilateral use. Studies that have focused on the use of skeletonized internal thoracic arteries [22-24] have not found an increase in SWI associated with the use of bilateral internal thoracic artery grafts. In a study by Milani et al. [24], in 70 diabetes patients, the use of the skeletonized bilateral internal thoracic artery significantly reduced the incidence of mediastinitis (P=0.044). Some recently published studies have emphasized the importance of the skeletonized ITA harvesting [25-27]. This technique was rarely used in patients at our institution and therefore, it was not analyzed. Recent studies [17,28,29] have found some different risk factors for SWI, identifying age, COPD and reoperation as markers. These differences may be attributed to population differences. In our sample, age was not a statistically significant factor, and neither was COPD and reoperation. There was also no increase in mortality in our population relative to those not affected by SWI. This finding is in agreement with a recent study presented by Risnes et al. [18]. The early identification of SWI, in association with broad-spectrum antibiotic therapy and adequate surgical intervention can explain this finding. In our study population, a higher STS risk score was found in patients with SWI than in non-infected patients (9 vs. 7, P<0.001). Despite the differences between the populations from the STS database and a Brazilian public teaching hospital, the STS score was validated and showed similar results; thus, it can be applied to other populations. The correlation between microorganism presence and the depth and severity of wound infections has not been

Table 2. Multivariate logistic regression analysis. OR 95.0% CI Lower Upper Age (by year) 0.996 0.973 1.019 0.338 0.732 Male gender 0.497 0.878 3.655 Arterial hypertension 1.791 Diabetes 2.337 1.561 3.497 4.068 COPD 1.862 0.852 2.464 BMI 30-40 kg/m2 1.561 0.988 6.270 2.539 15.485 BMI >40 kg/m2 1.135 0.759 1.697 LVEF < 50% PAD 1.188 0.751 1.878 1.048 57.791 3-vessel disease 7.784 2.103 7.079 Bilateral ITA 3.858

Table 3. Microorganisms Associated with SWI. Type of microorganisms Coagulase-negative Staphylococcus Staphylococcus aureus (MSRA= nÂş17-11.9%) Klebsiella pneumoniae Enterococcus faecalis Enterobacter aerogenes Enterococcus ssp Pseudomonas aeruginosa Acinetobacter ssp Morganella morganii

NÂş 62 41 18 17 12 7 5 5 3

P-value 0.736 <0.001 0.109 <0.001 0.119 0.056 <0.001 0.537 0.462 0.045 <0.001

% 43.4 28.7 12.6 11.9 7 4.9 3.5 3.5 2.1

DISCUSSION Our institution is a public teaching hospital and has an infection control service that performs active disease surveillance, which enables the identification of wound infections after discharge. The higher rate of SWI found in the current study may be due to the post-discharge notification, which was different from what has been published in scientific journals [12,17]. According to the multivariate logistic regression analysis, female gender was associated with higher rates of SWI, which differed from results presented by Risnes et al. [18], who found males to be associated with higher rates of mediastinitis. However, in our study, there was a higher prevalence of diabetes in males.

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well studied. Gardlung et al. [11] have shown that there is a relationship between high BMI and SWI caused by coagulase-negative Staphylococcus. In our population, the correlation between microorganisms that cause SWI and the risk score proposed by Fowler was evaluated; however, there was no significant difference between Gram-negative and Gram-positive bacteria (11 vs. 9, P=0.063). These data are unique given that most studies do not evaluate the risk of infection according to the etiological agent. This may suggest that the sample did not have enough statistical power for an association with risk factors for SWI, or it may also indicate that all patients are susceptible to SWI regardless of the microorganism causing it. The patients referred for CABG with high risk scores require preventative measures that will reduce the development of SWI. Given the risk factors found in this study, intervention would not be effective at reducing the rate of wound infections because a high BMI, female gender and the number of arterial lesions are not amenable to intervention. The intervention possibilities are limited to surgical procedure, and the use of bilateral internal thoracic artery grafts in women with a high BMI and three vessel injuries are not recommended. Adequate glycemic control in diabetic patients is mandatory. New strategies have been developed to improve the sternal hemostasis, and possibly in the future will result in a lower incidence of SWI [30]. The actions to prevent hospital infection and good practices in general must be practiced in patients with higher risk factors to avoid this problem that is associated with an increase in the period of hospitalization, hospital costs and need for surgical re-intervention [31]. Study limitations A limitation of this study is that only one public hospital in São Paulo was evaluated, such that the sample may not represent the general Brazilian population. Only pre- and intra-operative risk factors were analyzed. The use of the intra-aortic balloon pump and skeletonized internal thoracic artery grafts were not analyzed both because they were not used very much in during this study. Some other known risk factors for SWI (for example, blood transfusions [32]), were not analyzed. In our sample, there were high risk patients with scores higher than 9 who did not develop an infection, and low risk patients with scores lower than 7 who developed wound infection, which is similar to what was shown by Fowler et al. [12]. Further studies are necessary to better understand this phenomenon, as high scores do not necessarily mean wound infection but it is associated with a higher risk of developing wound infection. Similarly, low scores do not guarantee that the patient is safe from developing an infection and only indicates that they are at lower risk. 628

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CONCLUSIONS Female gender, diabetes, BMI > 40 kg/m2, number of affected coronary arteries and the use of bilateral internal thoracic artery grafts were associated with a higher risk of SWI. The STS risk score can be successfully used in a study population in a Brazilian Tertiary Hospital of Cardiology for patients undergoing revascularization surgery. In this study, no correlation was found between the etiological agents isolated in SWI and risk score.

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23. Choo SJ, Lee SK, Chung SW, Kim JW, Sung SC, Kim YD, et al. Does bilateral pedicle internal thoracic artery harvest increase the risk of mediastinitis? Yonsei Med J. 2009;50(1):78-82.

13. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16(3):128-40. 14. Brito JD, Assumpção CR, Murad H, Jazbik AP, Sá MPL, Bastos ES, et al. One-stage management of infected sternotomy wounds using bilateral pectoralis major myocutaneous advancement flap. Rev Bras Cir Cardiovasc. 2009;24(1):58-63. 15. Ascherman JA, Patel SM, Malhotra SM, Smith CR. Management of sternal wounds with bilateral pectoralis major myocutaneous advancement flaps in 114 consecutively treated patients: refinements in technique and outcomes analysis. Plast Reconstr Surg. 2004;114(3):676-83. 16. Anger J, Farsky PS, Amato VL, Abboud CS, Almeida AF, Arnoni RT, et al. Use of a flap composed of skin and breast tissue for repairing a recalcitrant wound resulting from dehiscence of sternotomy in cardiac surgery. Arq Bras Cardiol. 2004;83(Spec No):43-5. 17. Ariyaratnam P, Bland M, Loubani M. Risk factors and mortality associated with deep sternal wound infections following coronary bypass surgery with or without concomitant procedures in a UK population: a basis for a new risk model? Interact Cardiovasc Thorac Surg. 2010;11(5):543-6.

24. Milani R, Brofman PR, Guimarães M, Barboza L, Tchaick RM, Meister Filho H, et al. Double skeletonized internal thoracic artery vs. double conventional internal thoracic artery in diabetic patients submitted to OPCAB. Rev Bras Cir Cardiovasc. 2008;23(3):351-7. 25. Sá MPBO, Soares EF, Santos CA, Figueiredo OJ, Lima ROA, Escobar RR, et al. Risk factors for mediastinitis after coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc. 2011;26(1):27-35. 26. Sá MPBO, Soares EF, Santos CA, Figueiredo OJ, Lima ROA, Escobar RR, et al. Skeletonized left internal thoracic artery is associated with lower rates of mediastinitis in diabetic patients. Rev Bras Cir Cardiovasc. 2011;26(2):183-9. 27. Santos Filho EC, Moraes Neto FR, Silva RAM, Moraes CRR. Should the diabetics have the internal thoracic artery skeletonized? Assessment of sternal perfusion by scintillography. Rev Bras Cir Cardiovasc. 2009;24(2):157-64. 28. Magedanz EH, Bodanese LC, Guaragna JC, Albuquerque LC, Martins V, Minossi SD, et al. Risk score elaboration for mediastinitis after coronary artery bypass grafting. Rev Bras Cir Cardiovasc. 2010;25(2):154-9. 29. Sá MPBO, Figueira ES, Santos CA, Figueiredo OJ, Lima ROA, Rueda FG, et al. Validation of MagedanzSCORE as a predictor of mediastinitis after coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(3):386-92.

18. Risnes I, Abdelnoor M, Almdahl SM, Svennevig JL. Mediastinitis after coronary artery bypass grafting risk factors and long-term survival. Ann Thorac Surg. 2010;89(5):1502-9.

30. Volpe MA, Martinez JDG. Geli Putty®: a new alternative on sternal hemostasis in cardiac surgery. Rev Bras Cir Cardiovasc. 2011;26(3):485-7.

19. Bitkover CY, Gardlund B. Mediastinitis after cardiovascular operations: a case-control study of risk factors. Ann Thorac Surg. 1998;65(1):36-40.

31. Laizo A, Delgado FEF, Rocha GM. Complications that increase the time of Hospitalization at ICU of patients submitted to cardiac surgery. Rev Bras Cir Cardiovasc. 2010;25(2):166-71.

20. Stahle E, Tammelin A, Bergstrom R, Hambreus A, Nystrom SO, Hansson HE. Sternal wound complications: incidence, microbiology and risk factors. Eur J Cardiothorac Surg. 1997;11(6):1146-53.

32. Dorneles CC, Bodanese LC, Guaragna JCVC, Macagnan FE, Coelho JC, Borges AP, et al. The impact of blood transfusion on morbidity and mortality after cardiac surgery. Rev Bras Cir Cardiovasc. 2011;26(2):222-9.

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ORIGINAL ARTICLE

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Non Working Beating Heart: a new strategy of myocardial protection during heart transplant “Non Working Beating Heart”: novo método de proteção miocárdica no transplante cardíaco

Jarbas Jakson Dinkhuysen1, Carlos Contreras2, Reginaldo Cipullo3, Marco Aurélio Finger4, João Rossi3, Ricardo Manrique5, Hélio M. Magalhães6, Paulo Chaccur2

DOI: 10.5935/1678-9741.20110055

RBCCV 44205-1331

Abstract Background and Objective: We attempt to reduce the ischemic time during implantation of the donor heart in the bicaval bipulmonary orthotopic position using normothermic beating heart and thus, facilitate the transplanted heart adaptation to the recipient. This study presents a small experience about a new strategy of myocardial protection during heart transplant. Methods: In cardiopulmonary bypass, the aorta anastomosis was done first, allowing the coronary arteries to receive blood flow and the recovering of the beats. The rest of the anastomosis is performed on a beating heart in sinus rhythm. The pulmonary anastomosis is the last to be done. This methodology was applied in 10 subjects: eight males, age 16-69 (mean 32.7 years), SPAo 90-100 mmHg (mean 96 mmHg), SPAP 25-65 mmHg (mean 46.1 mmHg), PVR 0.9 to 5.0 Wood (mean 3.17 Wood), GTP 4-13 mmHg (mean 7.9 mmHg), and eight male donors, age 15-48 years (mean 27.7 years), weight 65-114 kg (mean 83.1 kg). Causes of brain coma: encephalic trauma in five hemorrhagic stroke in four, and brain tumor in one. Results: The ischemic time ranged from 58-90 minutes (mean 67.6 minutes) and eight donors were in hospitals of Sao Paulo and two in distant cities. All grafts assumed the cardiac output requiring low-dose inotropic therapy and

maintained these conditions in the postoperative period. There were no deaths and all were discharged. The late evolution goes from 20 days to 10 months with one death occurred after 4 months due to sepsis. Conclusion: This method, besides reducing the ischemic time of the procedure, allows the donated organ to regain and maintain their beats without pre or after load during implantation entailing the physiological recovery of the graft.

1. Full Professor at the University of São Paulo Medical School (USP), Head Physician of the Medical Section of Transplantation at Dante Pazzanese Cardiology Institute (IDPC / SP), São Paulo, Brazil. 2. Doctor of Medicine, Cardiovascular Surgeon at the IDPC / SP, Sao Paulo, Brazil. 3. Doctor of Medicine, Cardiologist at the IDPC / SP, Sao Paulo, Brazil. 4. Graduate Student, Cardiologist at the IDPC / SP, Sao Paulo, Brazil. 5. Doctor of Medicine, Immunologist at the IDPC / SP, Sao Paulo, Brazil. 6. PhD in Medicine, Cardiologist at the IDPC / SP, Sao Paulo, Brazil.

Study conducted at Dante Pazzanese Cardiology Institute (IDPC / SP), São Paulo, Brazil.

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Descriptors: Ischemia. Heart transplantation. Cardiac surgical procedures.

Resumo Introdução e Objetivo: Trata-se do implante em posição ortotópica bicaval bipulmonar do coração doado batendo em normotermia. Este estudo busca diminuir o tempo isquêmico e criar condições de ir se adaptando ao organismo hospedeiro. Métodos: Já em CEC, a primeira anastomose a ser feita é a da aorta, reperfundindo as artérias coronárias e recuperando os batimentos. As restantes são realizadas com o coração batendo em ritmo sinusal, sendo a da artéria pulmonar a última. Esta metodologia foi aplicada em 10 pacientes receptores, sendo oito do sexo masculino, com

Correspondence address: Jarbas J. Dinkhuysen 500 Dr. Dante Pazzanese de Cardiologia Avenue 10th floor, Ibirapuera - São Paulo, SP, Brazil. Zip Code: 04012-909. E-mail: j.dinkhuysen@uol.com.br

Article received on Monday, May 23, 2011. Article approved on Thursday, October 13, 2011.

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idades entre 16 e 69 (média de 32,7 anos), PSAo 90-100 (média de 96 mmHg), PSAP 25-65 (média de 46,1 mmHg), RVP 0,95,0 (média de 3,17 Wood), GTP 4-13 (média de 7,9 mmHg). Entre os 10 doadores, sete eram do sexo masculino, com idade entre 15 e 48 (média 27,7 anos), peso entre 65 e 114 kg (média de 83,1 kg). As causas do coma encefálico foram: TCE (cinco), AVCH (quarto) e tumor cerebral (um). Resultados: O tempo isquêmico variou de 58 a 90 minutos (média 67,6 minutos), sendo que oito doadores estavam em hospitais da região metropolitana de São Paulo e dois em cidades distantes. Todos os enxertos, após completadas as anastomoses, retomaram o fluxo e o débito, mantendo bons parâmetros, com baixa dosagem de inotrópico e mantiveram

estas condições no pós-operatório imediato. Não ocorreram óbitos e todos os pacientes obtiveram alta hospitalar. A evolução tardia variou de 20 dias a 10 meses, tendo ocorrido um óbito ao 4º mês pós-transplante, por sepse. Conclusões: Esta metodologia, além de reduzir o tempo isquêmico, permite ao órgão doado recuperar e manter seus batimentos sem pré nem pós-carga durante o implante, o que enseja proporcionar recuperação fisiológica, ultraestrutural, imunológica, inflamatória e mecânica do enxerto, com resultados consistentes precoces e tardios.

INTRODUCTION The effective myocardial protection is a commitment that lies between two opposite strategies, reducing the metabolic needs by cardiac arrest at low temperatures, and increasing the myocardial temperature during the arrest, to increase the chances of immediate recovery of cardiac function. The crystalloid cardioplegia at 4°C obviously reduces the metabolic needs; however, it is not enough to provide adequate protection [1] and warm reperfusion that provides immediate recovery of cardiac function which reverses protection induced by cold crystalloid cardioplegia [2]. Despite advances in heart transplantation, the lack of donors is still a reality, and, whenever possible, the ideal situation is to capture the graft preferably without long ischemic times. The various protocols of donor organ preservation using hypothermic arrest induced by various crystalloid cardioplegic solutions, however, it is the suboptimal state associated with long ischemic times. The ischemic damage contributes to the risk of primary graft dysfunction and limits from 4 to 6 hours the safe period between stopping the beating heart donor and recovering the beating already implanted in the receiver. Several studies have been developed to improve results and, in 1991, Lichtenstein et al. [3] introduced the normothermia with a beating heart and other authors [4,5] followed the technique. On the other hand, blood cardioplegia has been suggested as the most appropriate method to preserve the donor heart [6] and continuous infusion with a beating heart extends the time and helps the recovery of the contractile function [7,8].

Descritores: Isquemia. Transplante de coração. Cardiac surgical procedures.

The hypothesis on this study is that, the earlier coronary reperfusion is performed at normothermia with the recovery of heart rate without the presence of pre-or post-load during the heart transplant, the better the results will be. METHODS In the Medical Section of Transplant at IDPC/SP, 288 cardiac transplants were performed in the period from November 1991 to February 2011. In 10 (3.4%) of these transplants, the new methodology was applied in the preservation of the donated organ, called “Non Working Beating Heart”, which is to reperfuse the coronary arteries of the graft, restoring and maintaining the beat at normothermia without its pre-and afterload during implantation. The process of capturing and removal of the donor organ did not change, and after visual examination and palpation of possible modificatoin (atherosclerotic plaques in coronary arteries, palpable thrill, anatomical changes, etc.) cardiectomia is performed after the application of 1000 ml of 4°C crystalloid cardioplegic solution (Celsior ®) in the aortic root, obtaining complete myocardial relaxation. The body is then placed in sterile conditions at 4 ° C for air or ground transportation. Meanwhile, the compatible receiver is placed in the operating room, monitored and then, the native heart is exposed under general anesthesia with mechanical ventilation using transsternal median thoracotomy. At the time the donor organ arrives in the operating room, extracorporal circulation is installed into the receiver (EC) by aortic and both venae cavae cannulation. After initiation 631

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of EC and stabilization through anoxic arrest, the organ is removed, remaining stumps of right and left pulmonary veins, inferior and superior vena cava, pulmonary artery and aorta [9], maintaining the esophageal temperature around 35 ° C. Immediately before anastomosis were started, a new application of 500 ml 4°C Celsior ® solution was made in the ascending aortic graft. The first suture to be made is the medial half of the left pulmonary vein, followed by aortic anastomosis and, after its completion, the aortic clamping is stopped, reperfusing the coronary arteries of the graft, which spontaneously or after electrical defibrillation, resumes the beats in sinus rhythm, narrow QRS and positive T-wave. Under these conditions, the anastomosis of the pulmonary veins, inferior and superior venae cavae, and, finally, pulmonary artery are concluded, assuming, by the application of a low dose of inotropic drugs, the debt and systemic/pulmonary flow of the receiver. With stable hemodynamic and metabolic parameters, the EC is interrupted and, after review of hemostasis and mediastinal drainage, the chest is closed in layers and the patient is referred to ICU, using breathing apparatus. In addition to routine monitoring, it is common in our service the installation of the pulmonary artery catheter for continuous control of systolic pressure (PASP), to diagnose and treat right ventricular failure possibly determined by several factors in the postoperative period. This methodology was applied to 10 receivers, 8 male, aged 16 to 69 years (mean 40 ± 18 years) weighing 53 to 81 kg (mean 62 ± 10 kg). Regarding etiology, 4 receivers had ischemic cardiomyopathy, 2 of them dilated cardiomyopathy, 2 were presented with cardiomyopathy and 2 were valvular and chagasic.

to 140 min (mean 116 ± 19 min). The length of stay in ICU in nine patients ranged from 2 to 5 days (mean 3.4 ± 1.3 days), except one case with neurological damage, which lasted 30 days. The length of stay in the ward ranged from 7 to 36 days (mean 16 ± 10 days), and in two cases (neurological and mediastinitis), were 30 to 36 days. All patients were discharged in good clinical condition. The late evolution ranged from 20 days to 10 months, with one death occurring 4 months after the transplant due to sepsis.

RESULTS The hemodynamic data in the pre-transplant evalutaion were: • ASPo 90 to 100 (mean 96.4 ± 4.4 mmHg); • PASP 25 to 65 (mean 50.5 ± 22.8 mmHg); • RVP from 0.9 to 5.0 (mean 3.0 ± 1.3 Wood U); • GTP 4.3 to 13.0 (mean 6.9 ± 2.7 mmHg). This methodology was applied to 10 receivers, 8 male, aged 16 to 48 years (mean 28 ± 10 years) weighing 53 to 114 kg (mean 85 ± 10 kg). The causes of encephalic coma were 5 cranioencephalic traumas (CET), 4 hemorrhagic cerebrovascular accidentstrokes (HCVA) and 1 case of brain tumor. There were no immediate deaths and all patients, both in the operating room and ICU, showed good hemodynamic, metabolic, and electrocardiographic conditions, therefore, the use of inotropic drugs was limited. The ischemia time ranged from 58 to 100 min (mean 68 ± 14 min) and EC was 90 632

DISCUSSION The graft preservation with the purpose of transplantation is a fundamental process due to scientific and technological advances, allowing full evaluation of the organ and its availability and various alternatives for their preservation during ischemia after removal of the donor and implantation in the receiver. It is clear that invariably tissue damage will occur to a greater or lesser degree in the process of searching, preservation and implantation of the organ [10,11], such that the pathophysiological effects of brain death, hypoxia at the time of removal and transportation, as well as lesions due to ischemia / reperfusion are deleterious factors in the process of heart transplantation. Taking into account the current preservation techniques, it is considered as a safe ischemia time a period between 4 to 6 hours [9.12] and longer periods are related to primary graft failure, especially if there is association with an inadequate preservation procedure. The organic viability maintenance during graft preservation is an important prerequisite for good results and, considering the current practice of accepting organs from older, and possibly adjacent donors, the preservation techniques have become more relevant. Many teams use the hypothermic arrest, however, this method was developed when there was ample supply of younger donors and quality of the graft, and currently, with the need to extend the selection criteria, limitations to this methodology can be questioned. Maathuis et al. [13], in an elegant article, draw attention to this scenario with suggestions for new techniques of myocardial protection. Heart surgery on a beating heart has gained ground in recent times, however, there are few studies to verify its effectiveness. Mo et al. [14] reported good results, expanding this concept little used in the past. Osaki et al. [15] draw attention to the use of continuous myocardial perfusion for resuscitation of donor hearts, initially with blood cardioplegia at 20 ° C, and after, oxygenated blood at a temperature ranging from 20 ° to 37 ° C, which somehow is applied to the method described in this study. On the other hand, keeping the heart beating

Dinkhuysen JJ, et al. - Non Working Beating Heart: a new strategy of myocardial protection during heart transplant

during the graft preservation showed better results when compared to preservation with hypothermia and cardioplegic solution at the University of Wisconsin, extending the preservation time safely and giving surgeons better means of assessing the applicability of this organ and facilitating long distance transport [8]. Within this line of reasoning and assumption of maintaining continuous perfusion of donor heart to keep their beats, a portable apparatus was developed to preserve it and to be used during transport [7], which are monitored contractility, metabolism and vasomotor functions, extending the time preservation and avoiding injury caused by time-dependent ischemia. The potential benefits are many [16,17], since the continuous supply of oxygen and energy substrates facilitate aerobic metabolism, making the application of important hypothermia not viable. Continuous washing of toxic metabolisms occurs, which increases the graft time preservation safely, facilitating logistics, that often seems to be difficult and complex [18,19]. In 1986, we had the opportunity to publish experimental methodology for thoracic organs preservation at normothermia and in physiological conditions called heartlung preparation [20], which included the removal all cardiopulmonary block from the donor, and was kept for up to 11 hours and then transplanted to another animal experimentation, presenting good results. This embodies the concept of keeping the beat at normothermia, and the organ preservation seems to be more consistent than the application of cardioplegic solutions and hypothermia. Brockmann et al. [21] claimed that the organ preservation by normothermic perfusion maintains the physiological pressure-flow parameters, providing more time and success in transplantation, with the possibility of increasing the number of organs donated for transplant. In experimental research designs, there are several publications [22-26], in which heterotopic heart implant was applied taken from experimental animals and implanted in the abdomen or neck after the suture occlusion of the functions of superior and inferior venae cavae with right atrium and right and left pulmonary veins with the left atrium, in which the aortic graft is end-to-side anastomosed or with the common carotid artery, and the pulmonary artery with the abdominal portion of the inferior vena cava or the jugular, establishing a situation where the beats of the graft are maintained due to coronary perfusion and coronary sinus return directed to the venous system (Figure 1). The beats are kept under these conditions, however, without pre or after-load, a process called â&#x20AC;&#x153;non working beating heartâ&#x20AC;?, which one of the methods of myocardial protection that is closest related to the normal physiology. The methodology presented in this work is actually a hybrid process of preservation using hypothermic cardioplegic solution during the removal of the donor

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Fig. 1 - Heterotopic implantation without pre-or afterload

organ and transport, and also coronary reperfusion at normothermia with a beating heart without pre-or afterload while the graft implant is being performed into the receiver. The aortic anastomosis is the first one to be made and then the coronary arteries are immediately reperfused at normothermia, recovering its beating early and, these conditions are maintained throughout this procedure, allowing the graft to the possibility of an earlier recovery of contractile function, toxic metabolic elimination and positive interaction with the host, without the need for maintaining the flow and cardiac output, since the EC performs this function. The results that draw attention for their performance was noted in this small sample (10 cases) by taking full cardiac function with good contractility and demonstrating very satisfactory postoperative parameters, with no evidence of death, low output or other clinical events. 633

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REFERENCES 1. Pichon H, Chocron S, Alwan K, Toubin G, Kaili D, Falcoz P, et al. Crystalloid versus cold blood cardioplegia and cardiac troponin I release. Circulation. 1997;96(1):316-20. 2. Chocron S, Alwan K, Yan Y, Toubin G, Kaili D, Anguenot T, et al. Warm reperfusion and myocardial protection. Ann Thorac Surg. 1998;66(6):2003-7. 3. Lichtenstein SV, Ashe KA, el Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg. 1991;101(2):269-74. 4. Wei H, Mingwu C, Wensheng W. Beating heart mitral valve replacement in 2 cases under mild hypotermia cardiopulmonary bypass. Guangxi Med Coll J. 1993;10:320-1. 5. Hui L, Wei H, Shifeng W. Aortic valve replacement on the beating heart with continuous retrograde coronary sinus perfusion. Guangxi Med Univ. 1996;13:4-6. 6. Ferrera R, Larase A, Marcsek P, Guidollet J, Verdys M, Dittmar A, et al. Comparison of different techniques of hypotermic pig heart preservation. Ann Thorac Surg. 1994;57(5):1233-9. 7. Hassanein WH, Zellos L, Tyrrel TA, Healey NA, Crittenden MD, Birjiniuk V, et al. Continuous perfusion of donor hearts in the beating state extends preservation time and improves recovery of function. J Thorac Cardiovasc Surg. 1998;116(5):821-30. 8. Lin H, Mo A, Zhang F, Huang A, Wen Z, Ling S, et al. Donor heart preservation in an empty beating state under mild hypothermia. Ann Thorac Surg. 2010;89(5):1518-23. 9. Dinkhuysen JJ. Transplante cardíaco ortotópico bicaval/ bipulmonar. Rev Bras Cir Cardiovasc. 2003;18(3):268-72. 10. Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988;45(4):673-6. 11. Fragomeni LS, Bonser RS, Stempfle U, Ring SW, Kaye MP, Jamieson SW. Relationship between ischemic time and postoperative performance in cardiac transplantation. Rev Bras Cir Cardiovasc. 1989;4(2):139-42. 12. Conte JV. Heart preservation. In: Franco KL, Verrier ED, eds. Advanced therapy in cardiac surgery. 2nd ed. Hamilton:BC Decher;2003. p.560-9. 13. Maathuis MH, Leuvenink HG, Ploeg RJ. Perspectives in organ preservation. Transplantation. 2007;83(10):1289-98. 14. Mo A, Lin H, Wen Z, Lu W, Long X, Zhou Y. Efficacy and

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safety of on-pump beating heart surgery. Ann Thorac Surg. 2008;86(6):1914-8. 15. Osaki S, Ishino K, Kotani Y, Honjo O, Svezawa T, Kanki K, et al. Resuscitation of non-beating donor hearts using continuous myocardical perfusion: the importance of controlled initial reperfusion. Ann Thorac Surg. 2006;81(6):2167-71. 16. Jacobs S, Rega F, Meyns B. Current preservation technology and future prospects of thoracic organs. Part 2: heart. Curr Opin Organ Transplant. 2010;15(2):156-9. 17. Cobert ML, West LM, Jessen ME. Machine perfusion for cardiac allograft preservation. Curr Opin Organ Transplant. 2008;13(5):526-30. 18. Ho EK, Vlad G, Colovai AI, Vasilescu ER, Schwartz J, Sondermeijer H, et al. Alloantibodies in heart transplantation. Hum Immunol. 2009;70(10):825-9. 19. Tenderich G, Zittermann A, Prohaska W, Koerfer R. No evidence for an improvement of long-term survival by HLA matching in heart transplant recipients. Transplant Proc. 2007;39(5):1575-9. 20. Dinkhuysen JJ, Souza LCB, Chaccur P, Neger F, Paes Neto F, Arnoni AS, et al. Preparado cardiopulmonar. Rev Bras Cir Cardiovasc. 1986;1(1):20-31. 21. Brockmann J, Reddy S, Coussios C, Pigott D, Guirriero D, Hughes D, et al. Normothermic perfusion: a new paradigm for organ preservation. Ann Surg. 2009;250(1):1-6. 22. Alonso DR, Starek PK, Minick CR. Studies on the pathogenesis of atheroarteriosclerosis induces in rabbit cardiac allografts by the synergy of graft rejection and hypercholesterolemia. Am J Pathol. 1977;87(2):415-42. 23. Foegh ML, Khirabadi BS, Nakanishi T, Vargas R, Ramwell PW. Estradiol protects against experimental cardiac transplant atherosclerosis. Transplant Proc. 1987;19(4 Suppl 5):90-5. 24. Clausell N, Molossi S, Sett S, Rabinovitch M. In vivo blockade of tumor necrosis factor-alpha in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation. Circulation. 1994;89(6):2768-79. 25. Mitchell SV, Mottram PL, Purcel LJ, Dumble LJ, Millar RJ, Clunie GJ. A rabbit model for heterotopic cardiac transplantation. Transplantation. 1990;49(4):835-7. 26. Contreras CAM. Efeito da nanoemulsão lipídica associada a paclitaxel na prevenção da doença vascular do coração transplantado. Estudo experimental em coelhos [Tese de Doutorado]. São Paulo:Faculdade de Medicina da Universidade de São Paulo;2010. 143p.

REVIEW ARTICLE

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Gene therapy for ischemic heart disease: review of clinical trials Terapia gênica para cardiopatia isquêmica: revisão de ensaios clínicos

Bruna Eibel1, Clarissa G. Rodrigues2, Imarilde I. Giusti1, Ivo A. Nesralla3, Paulo R. L. Prates3, Roberto T. Sant’Anna4, Nance B. Nardi5, Renato A. K. Kalil6 DOI: 10.5935/1678-9741.20110056

RBCCV 44205-1332

Abstract Severe ischemic heart disease with refractory angina, occurs in increasing incidence. Alternative forms of treatment, in an attempt to reduce myocardial ischemia and relief of symptoms has been studied. In this context, gene therapy is an option, for the possibility of inducing angiogenesis, establish collateral circulation and reperfuse ischemic myocardium. Several clinical trials have been conducted and, except for specific cases of adverse effects, there is indication of safety, feasibility and potential effectiveness of therapy. The clinical benefit, however, is not yet well established. In this article we review the clinical trials of gene therapy for patients with ischemic heart disease. The approach includes: (1) myocardial ischemia and angiogenesis on the pathophysiological aspects involved, (2) growth factors, dealing with specific aspects and justifying the use in cardiac patients with no option for conventional therapy, (3) controlled clinical trials, where a summary of the main studies involving gene therapy for severe ischemic heart disease is presented, (4) our experience, especially on preliminary results of the first gene therapy clinical trial in Brazil and (5) future prospects.

Resumo Cardiopatia isquêmica grave com angina refratária a formas convencionais de tratamento apresenta-se em uma crescente incidência. Para tratar angina refratária, terapias alternativas na tentativa de redução da isquemia miocárdica e alívio de sintomas têm sido estudadas. Neste contexto, a terapia gênica representa uma opção, pela possibilidade de induzir angiogênese, estabelecer circulação colateral e reperfundir miocárdio isquêmico. Diversos ensaios clínicos têm sido conduzidos e, com exceção de casos isolados e específicos de efeitos adversos, há indicação de segurança, viabilidade e potencial eficácia da terapia. O benefício clínico não está bem definido. Neste artigo, revisamos os ensaios clínicos que utilizaram terapia gênica para tratamento de pacientes cardiopatas isquêmicos. A abordagem inclui: (1) isquemia miocárdica e angiogênese, sobre os aspectos fisiopatológicos envolvidos; (2) fatores de crescimento, tratando sobre aspectos específicos e justificando a utilização em pacientes cardiopatas isquêmicos sem opções pela terapêutica convencional; (3) ensaios clínicos controlados, onde é apresentado um resumo dos principais estudos envolvendo terapia gênica para tratamento da cardiopatia isquêmica grave; (4) nossa experiência, especialmente sobre resultados preliminares do primeiro ensaio clínico de terapia gênica do Brasil e (5) perspectivas.

Keywords: Gene therapy. Myocardial ischemia. Angina pectoris.

Descritores: Terapia de genes. Isquemia miocárdica. Angina pectoris.

1. Master’s Degree of the Postgraduation Program of the Cardiology Institute of Rio Grande do Sul/University Foundation of Cardiology (IC/FUC), Porto Alegre, RS, Brazil. 2. PhD Student of the Postgraduation Program of IC/FUC, Porto Alegre, RS, Brazil. 3. Cardiac Surgeon of IC/FUC, Porto Alegre, RS, Brazil. 4. Cardiologist of IC/FUC, Porto Alegre, RS, Brazil. 5. Biologist and Collaborator Researcher of IC/FUC, Porto Alegre, RS, Brazil. 6. PhD; Institute of Cardiology of Rio Grande do Sul/University Foundation of Cardiology (IC/FUC) and Federal University of Health Sciences of Porto Alegre (UFSCPA), Porto Alegre, RS, Brazil.

This study was carried out at Cardiology Institute of Rio Grande do Sul/ University Foundation of Cardiology (IC/FUC) and Federal University of Health Sciences of Porto Alegre (UFSCPA), Porto Alegre, RS, Brazil. Correspondence address: Renato A. K. Kalil Av. Princesa Isabel, 370 – Santana – Porto Alegre, RS, Brazil – Zip Code: 90620-000 E-mail: kalil.pesquisa@cardiologia.org.br Article received on June 14th, 2011 Article accepted on September 5th, 2011

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INTRODUCTION It is estimated that cardiovascular disease (CVD) cause approximately 17 million deaths worldwide each year, with higher prevalence in developed countries [1]. CVD should be leaders in mortality in the developing world within the next decades, reaching epidemic levels [1]. Coronary artery disease (CAD) is a problem of increasing prevalence, especially in large cities and the populations of older age, its mortality is 80% of deaths from CVD [2,3]. Angina refractory to traditional forms of treatment in cardiology, including percutaneous and surgical revascularization and optimal drug therapy, represents up to 15% of all cases of angina [2]. According to statistics from the American Heart Association [3], the prevalence of refractory angina in the U.S. population is 4.6%, affecting 58% of patients with CAD and growing rapidly with increasing age. Despite advances in treatment modalities, it is estimated that the incidence of patients with refractory angina will increase in coming years [4,5], pointing to the need for new treatment options. In this context, gene therapy could be an option, due to the potential to induce myocardial angiogenesis and establish collateral circulation [5]. Gene therapy can be defined as a set of techniques that allow the insertion and expression of a therapeutic gene in target cells that have some kind of disorder of genetic origin (not necessarily hereditary), enabling the correction of inappropriate gene products that cause diseases, therefore being an alternative for the treatment of diseases based on the transfer of genetic material [6-8]. Studies have tested the effects on ischemic heart disease patients using different growth factors, several doses, vectors and routes of administration. It can be emphasized the vascular endothelial growth factor (VEGF), a regulator of endothelial cells, which has the property of mediating angiogenesis during tissue repair [4]. The availability of vectors with tropism for the myocardium, capable of a long and stable protein expression [9], and the isolation of progenitor cells with regenerative and angiogenic potential [10] offers possibilities for development of therapy based on protection and regeneration of ischemic myocardium. Although promising, the clinical effects on the myocardial vasculature provided by gene therapy remain to be clarified fully. The aim of this study is to review the clinical trials of gene therapy for the treatment of ischemic heart disease patients. GENE THERAPY APPLIED TO ISCHEMIC CARDIOMYOPATHY Myocardial Ischemia and Angiogenesis In the pathophysiology of ischemic heart disease, two 636

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processes are involved: supply and demand of myocardial oxygen. Myocardial ischemia occurs when there is imbalance between supply and demand for oxygen. Two situations alter the oxygen supply to the myocardium, ischemia and hypoxia. In some conditions, the impairment of oxygen is secondary to decreased blood flow and in other situations, the increase in oxygen demand is the main responsible for myocardial ischemia [11]. Features of molecular biology and gene therapy have been developed for application in cardiovascular therapy, in situations where there are no options, or when these conventional methods have limitations. The main area of development of gene therapy in cardiology is the induction of myocardial angiogenesis with potential benefits in endstage ischemic heart disease, after exhaustion of pharmacological, surgical and interventional resources using catheter, ie, in those refractory cases to all forms of treatment, where only the use of cardiac transplantation would be possible[4]. Angiogenesis, the formation of new vessels from existing endothelium of blood vessels, has an important role in embryonic development, tissue repair and progression of a variety of pathological processes [12,13]. Angiogenesis induced by administration of growth factors is intended to promote the formation of new blood vessels, capillaries and arterioles. The mechanism of angiogenesis can be initiated by factors of a mechanical nature, by inflammatory or hypoxic process (energy imbalance). The process of angiogenesis occurs in stages (Figure 1) comprising: vessel dilation, endothelial cell activation, platelet activation, secretion of plasminogen activators and proteolytic enzymes, mast cell degranulation, activation of macrophages, disruption of the basement membrane and increased permeability with release of fibrin and other proteins. Following, formation of pseudopodia occurs, degradation of extracellular matrix, migration of endothelial cells to the extravascular space with the same proliferation and formation of shoots of vascular tissue. Finally, they form new basement membrane and maturation of the new establishment of the vascular wall to blood flow, formation of tubes and conections, establishing new vessels [14]. The idea that angiogenic factors may promote revascularization of ischemic tissues is called therapeutic angiogenesis [15]. The concept of therapeutic angiogenesis in humans through clinical trials phase I went ahead with the idea of testing this strategy in ischemic cardiomyopathy. Therefore, therapeutic angiogenesis is a strategy designed to amplify the natural process of angiogenesis and reperfuse ischemic tissues, which may represent a new process of revascularization in these high-risk patients [16]. There is a direct influence of inflammation and hypoxia on angiogenesis. Inflammation increases the production

Eibel B, et al. - Gene therapy for ischemic heart disease: review of clinical trials

Rev Bras Cir Cardiovasc 2011;26(4):635-46

of PR-39macrophage-derived peptide, this inhibits the degradation of HIF-1 Îą (hypoxia-inducible factor 1-Îą) leading to increased expression of VEGF and its receptors [17]. Inflammation induces the production of cytokines that promote angiogenesis [18]. In contrast, PR-39 increases the production of fibroblast growth factors (FGF), which have angiogenic power. Mechanical factors may act by activating the same mechanism, resulting in angiogenesis [10]. Vascular Endothelial Growth Factor, Fibroblast Growth Factor (FGF), hepatocyte growth factor (HGF) Plasmid and Aenoviral vector. The formation of new blood vessels responds to the stimulation of angiogenic factors, which regulate endothelial migration, proliferation, survival, and proteolytic activity. Among the factors described in the literature, VEGF has emerged as a critical regulator of pro-angiogenic process [19-21]. This molecule promotes the formation of new vessels and their morphogenesis, through a complex process of angioregulatory events [22,23].

VEGF, family member of VEGF A, which consists of five isoforms resulting from alternative divisions of a single gene, ie, VEGF121, VEGF145, VEGF165, VEGF189 and VEGF206, is a growth factor specific to the endothelium [24.25 ]. It acts mainly by activating two Flt-1 tyrosine kinase receptors (fms-like tyrosine kinase-1, VEGF receptor-1) [26] and KDR (kinase-insert domain-containing receptor, VEGF receptor-2) [27] but can also activate other receptors, such as Neuropilins-1 and 2 [28]. VEGF may represent a new treatment modality for ischemic heart disease. This is due to the possibility of developing new blood vessels or promote the reformation of existing vessels [29]. The VEGF165 contains 165 amino acids and works by interacting with specific receptors on endothelial cells, initiating the cascade of events that culminates in endothelial cell migration, proliferation and aggregation of microtubules that will eventually form a network of arterial and venous systems. Gene therapy in cardiovascular diseases is not intended

Fig. 1 - Sequence of events in the angiogenesis process [30]

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to replace an abnormal gene, but suprarregular the expression of a useful protein, increasing DNA content. Its effectiveness depends on the gene vector and method of administration used [30]. VEGF functions both as an important marker of endothelial damage, as the mediator of repair. In cases of injury such as ischemia, inflammation and infarction have their expression increased. In addition, it encourages the maintenance, mobilization and recruitment of endothelial progenitor cells (EPC) from bone marrow [31]. The angiogenic potential of VEGF stimulates endothelial production of nitric oxide through activation of nitric oxide synthase (eNOS) (Figure 2). The endothelium synthesizes important substances,

playing a key role on the vascular control, both in physiological conditions and in pathological processes such as acute coronary syndromes. The monolayer of endothelial cells acts as a nonstick surface for platelets and leukocytes, producing a variety of important regulatory factors, such as NO [32]. Thus, influences not only vascular tone but also its remodeling through the production of substances promoting and inhibiting their growth [33]. Dysfunction in endothelial cells leads to a loss of antithrombotic properties of vascular wall and corresponds to the beginning of the atherosclerotic process [32]. The reconstruction occurs by endothelial migration and proliferation of circulating mature endothelial cells.

Fig. 2 - Mobilization of endothelial progenitor cells for neovascularization. Adapted from Murasawa et al. [68]

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However, these cells have low proliferative potential and their ability to repair is limited. Evidence indicates that peripheral blood contains bone marrow cell subsets, with properties similar to embryonic angioblastic. EPCs have a proliferative capacity and differentiate into mature endothelial cells, and can be induced by various cytokines or growth factors, acquiring different phenotypes [32]. The FGF family comprises at least nine polypeptides, including acidic FGF and basic FGF. Unlike VEGF, FGF acts in the mitogenesis of endothelial cells, fibroblasts and smooth muscle cells [18]. The increased availability of FGF provided the use of this gene has been most studied. Among the experimental studies, we highlight the report by Kawasuji et al. [34] in a model of acute myocardial infarction, where the response to FGF demonstrated to increase the number of capillaries in the border zone and in the epicardium of the infarcted area, the increased blood flow in these areas and the improvement in left ventricular ejection fraction 7 days after infarction. On the other hand, HGF is a potent mitogen for a wide variety of cells, and angiogenic, antiapoptotic and possess antifibrotic properties [35,36]. In a pilot study of gene therapy in patients with CAD, Yang et al. [37] reported the growing evidence of the beneficial effects of HGF in myocardial infarction, heart failure and peripheral arterial disease. The aim of this study was to assess the effects of intracoronary administration of an adenovirus vector encoding the human HGF gene (Ad-HGF) on serum levels of cytokines and mobilization of CD34 (+) and CD117 (+) cells in patients with heart disease. Given the findings, it was concluded that gene therapy with HGF may play an important role in the regulation of inflammatory cytokines and induce mobilization of EPCs in patients with CAD. Genetic vectors are all DNA molecules with potential for autonomic replication within the host cell in which DNA sequences can be inserted and expanded. The origin of the vector plasmid allows to classify in bacteriophage or viral infections [38]. They are used to transport genes into recipient cells. They have not only markers for ease of recognition as well as replicating sequences. Common vectors include plasmids carriers for transportation of naked DNA and viral vectors such as adenovirus, retrovirus and lentivirus. Advantages and disadvantages compared to the vector used include the size of the inserted gene, the site of incorporation in the nucleus, the duration of expression, the transfer efficiency and the degree of bodyâ&#x20AC;&#x2122;s immune response [39]. The plasmid vector is expressed by only a few days after viral vector administration and shows gene expression for several weeks [40]. Thus, the clinical studies that attempt to treat end-stage ischemic disease through gene therapy may be limited by duration of exposure to inadequate angiogenic agent [4]. Gene therapy suffered a major setback when the

occurrence of death in a research subject, probably due to high viral load administered, and there was cancellation of several clinical projects and return to the laboratory research. Since 2000, few projects have been developed for clinical application. Theoretically, before being introduced into the patient, the viruses used as vectors suffer from several genetic changes, so that the therapeutic gene is inserted, while several other genes that confer virulence are removed or inactivated [7,41,42]. Thus, when binding and invading the target cell, the viral vectors inject its genetic material containing the therapeutic gene in the patientâ&#x20AC;&#x2122;s DNA, allowing transcription and translation of the gene to their corresponding functional protein, or using the molecular machinery of the host cell to express their genes. However, in specific cases, the virulence became something uncontrollable, where the therapy became the cause of death of patients undergoing such intervention. On the other hand, plasmid vectors have no gene size limit to be inserted and induces minimal immune response, resulting in sustained transgenic expression. The disadvantage is the low rate of transfer of the encoding gene of the angiogenic factor [43]. The ideal vector would be one that combines low immunogenicity and a satisfactory safety profile, with high efficiency of transfection and transgene expression to specific time periods [4]. Gene transfer to the myocardium has been used as an alternative strategy to achieve a sustained local expression of angiogenic proteins [44]. There is a variety of different methods to replace or repair the genes targeted in gene therapy. A normal gene can be inserted into a nonspecific location within the genome to replace a nonfunctional gene, which is the most common approach, though, an abnormal gene could be replaced by a normal gene through homologous recombination, an abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal functions and also the regulation of a gene can be altered, such regulation corresponding to the degree to which a gene is active or inactive [6-8]. Controlled Clinical Trials of Gene Therapy Despite more than a decade of achievement of the first clinical trial of gene therapy [45], the real clinical benefits of this therapy still need to be better elucidated. Research has attempted to identify other parameters and outcomes that can provide objective evidence of bioactivity and clinical improvement [4]. Thus, among the studies, it can be observed the use of different genes, doses, types of vectors and routes of administration. In Table 1, are gathered clinical trials involving gene therapy with VEGF with interventions performed via left minithoracotomy, in Table 2, studies using the percutaneous method, and in Table 3 are gathered clinical trials of gene therapy with FGF. 639

Eibel B, et al. - Gene therapy for ischemic heart disease: review of clinical trials

Rev Bras Cir Cardiovasc 2011;26(4):635-46

Table 1. Clinical trials involving gene therapy with intramyocardial VEGF by left mini-thoracotomy. Author and Year

Vector

Patients

Outcomes

Results

Losordo et al. [45], 1998

VEGF165

5 patients; CAD, refractory angina, underperfused myocardial areas, but viable AC (3/4)

Myocardial perfusion and symptoms of disease in 60 days

Reduction in angina between 10 and 30 days after treatment, reducing the consumption of nitrate in 60 days (P <0.05), no reduction of myocardial ischemia in 60 days

Symes et al. [48], 1999

VEGF165

125 ì g/n=10, 250 ì g/ n=10;CAD, refractory angina, reversible ischemia, AC (3/4)

Safety of the therapy and myocardial perfusion in 180 days

Safety and feasibility of therapy, improvement of myocardial perfusion in 60 days, SSS = 19.4 ± 3.7 versus 15.9 ± 3.4, P = 0.025)

Vale et al. [49], 2000

VEGF165

13 patients; CAD, refractory angina, myocardial areas underperfused but viable, AC (3/4)

Myocardial perfusion and left ventricular performance

Reduction of ischemia before (15.26 ± 0.98%) versus after (9.94 ± 1.53%, P = 0.004) therapy, improvement of myocardial function

Reilly et al. [50], 2005

VEGF2

30 patients; CAD, AC (3/ 4) with no revascularization options;

Safety and adverse events at 1 year of therapy

After 1 year, 3 (11.5%) patients had AC 3 and 23 (88.5%) AC 1 or 2, there were 4 deaths (13.8%), MI 5 (17.2%) 7 CABG (24.1%), 15 hospitalizations and two new cancer diagnoses

REVASCStewart et al. [51], 2006

Adenoviral VEGF121

Active/placebo group (32/ 35), CAD not eligible for revascularization, refractory angina, AC (2/4)

Time on ergometric test and ST segment depression in 1 mm in diameter at 26 weeks

Time on ergometric test at 1 mm ST segment depression was significantly higher in VEGF121-ad (P=0,026); AC improved in the group adVEGF121(P<or =0.001)

Ruel et al. [52], 2008

Plasmid VEGF165 and supplemental oral L-arginine associated with CABG.

VEGF/L-arg (5),Placebo/Lar (6),VEGF/placebo (7),Placebo/placebo (1);CAD with commitment of the ADA

Myocardial perfusion, left ventricular contractility and AC in 3 months

Group VEGF/L-arg showed improvement in perfusion and contractility of the anterior myocardial wall (P = 0.02)

Kalil et al. [53], 2010

plasmid VEGF165

13 patients, ischemic heart disease, LV ejection fraction greater than 25%symptoms of angina and/or IC, myocardial hypoperfusion

Myocardial perfusion, ergometric test time, quality of life, CF according to NYHA in 3 months

Improvement of myocardial perfusion SSS (18.38 ± 7.51 versus 15.31 ± 7.29, P = 0.003) and SRS (11.92 ± 7.49 versus 8.53 ± 6.68, P = 0.002); trend towards improvement in ergometric test time (7.66 ± 4.47 versus 10.29 ± 4.36, P = 0.08), improved quality of life, second IC accordingNYHA class and AC.

VEGF: Vascular Endothelial Growth Factor, CAD: coronary artery disease, AC, angina class, Ad, adenoviral; P: Placebo, AMI: acute myocardial infarction, CABG, Coronary Artery Bypass Surgery, G-CSF-stimulating factor Granulocyte colony, L-arg: L-arginine; LV: left ventricle, CI: Heart Failure, NYHA: New York Heart Association; SSS: Stress score in addition scintigraphy, SRS score rest score in scintigraphy

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Table 2. Clinical trials involving gene therapy with VEGF percutaneously. Author and year Vector

Patients

Outcomes

Results

VEGFVale et al. [54], 2001

Intramyocardial of VEGF2 guided by electromechanical mapping (NOGA)

6 patients, angina refractory to therapy of CAD, reversible ischemia, AC(3/4)

Myocardial perfusion, time during ergometric testing, angina episodes in 360 days

Reduction of episodes of angina, improvement in ergometric test performance from 7 to 127 seconds (72 ± 25 s), improvement in myocardial perfusion at rest and stress

Losordo et al. [25], 2002

Intramyocardial administration via electromechanical mapping of plasmid VEGF2

Group active/placebo (12 / 7), CAD not eligible for revascularization, refractory angina, AC (3/4)

Change in AC and exercise tolerance in 12 weeks

Improvement in AC - VEGF2 group versus placebo (-1.3 versus -0.1, P = 0.04), exercise tolerance (91.8 versus 3.9 seconds)

KATHedman et al. [28], 2003

Intracoronary administration of adenoviral plasmid VEGF165 and after percutaneous coronary intervention

VEGF-ad (37), VEGF-P (28), Placebo (38); CAD, AC (2/3), percutaneous coronary intervention

% minimal luminal diameter stenosis in coronary angiography at 6 months

Clinical restenosis rate: 6%, minimum diameter and percent stenosis were not different between groups, myocardial perfusion showed a significant improvement in the VEGF-ad group

VIVA TrialHenry et al. [46], 2003

Intracoronary infusion, VEGF - high dose (59), followed by intravenous VEGF - low dose (56), infusion of VEGF placebo (63); refractory angina, underperfused myocardium, but viable

Myocardial perfusion time during exercise testing, AC and quality of life in 120 days

There was no significant improvement in myocardial perfusion, increase in performance under exercise test (high dose versus placebo: 48 versus 23 seconds, P = 0.15), reduction of angina episodes and improved quality of life

Euroinject One Kastrup et al. [55], 2005

Percutaneous intramyocardial administration via electromechanical mapping of plasmid VEGF165

Group active/placebo (40/ 40), coronary artery disease not eligible for revascularization, refractory angina, AC (3/4)

Myocardial perfusion, wall motion mapping by NOGA, left ventriculography and AC in 3 months

Myocardial perfusion was not different between the VEGF165 and placebo group (38 ± 3%, 44 ± 2%), wall motion by NOGA (P = 0.04) and left ventriculography (P = 0.03) improved compared to placebo; improvement in AC with no difference between

Ripa et al. [56], 2006

Percutaneous intramyocardial administration of VEGF165 using electromechanical mapping and subcutaneous injection of G-CSF

VEGF165 + G-CSF (16), VEGF165 (16), Placebo (16); coronary artery disease not eligible for revascularization, refractory angina, AC (3/4)

Change of perfusion defects, measured by SPECT in 3 months

There was no improvement in myocardial perfusion in both treated groups and clinical symptoms have not changed

NORTHERN TrialStewart et al. [57], 2009

Administration of Plasmid VEGF165 by endocardial catheter through the NOGA electroanatomic catheter

A multicenter study: group active/placebo (48/ 45), advanced coronary artery disease, AC (3/4)

Myocardial perfusion, time in ergometric time and AC at 6 months

There was no improvement in myocardial perfusion; significant reduction in the ischemic area in both groups, increase in exercise test time and improvement in AC

VEGF: Factor Vascular Endothelial Growth; AC: Angina Class, Ad, adenoviral; P: Placebo, AMI: acute myocardial infarction, G-CSF, colony-stimulating factor Granulocyte; LV: left ventricle, CI: Heart Failure ; NYHA: New York Heart Association; SSS: Stress score addition, SRS: Score addition of Rest

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Table 3. Clinical trials involving gene therapy with FGF. Author and Year

Vector

Patients

Outcomes

Results

FGFAGENTGrines et al. [58], 2002 AGENT-

Administration of Ad5-FGF4 by intracoronary via

Group active/placebo (60/19), coronary artery disease, AC (2/3)

Safety and time of exercise testing in 12 weeks

Single administration of Ad5-FGF4 was safe and well tolerated; Ad5-FGF4 group showed improvement in the time of exercise testing in subgroup analysis (1.6 versus 0.6 minutes, P = 0.01, n=50)

2 Grines et al. [59], 2003

Administration of Ad5-FGF4 by intracoronary via

Group active/placebo (35/17), coronary artery disease, not eligible for revascularization, refractory angina, AC (2/4)

Change of perfusion defects, measured by adenosine SPECT in 8 weeks, follow-up of 12 months

Ad5-FGF4 resulted in a significant reduction of ischemia (4.2% absolute, 21%, P <0.001), while placebo did not improve (P = 0.32)

AGENT-3 AGENT-4 Henry et al. [60], 2007

Administration of Ad5-FGF4 by intracoronary via

High dose (175), Low-dose (180), Placebo (177), coronary artery disease and refractory angina, AC (2/4); 3 AGENT: no immediate need for revascularization AGENT 4: not eligible for revascularization

Change in time of exercise testing in 12 weeks, follow-up of 12 months

Significant beneficial effect of gender, women showed improvement in exercise test time and improvement of AC

FGF: fibroblast growth factor; AC: Class of Angina

This study highlights the potential clinical applications of growth factors in humans, since experimental studies have shown favorable results and initial clinical studies in humans do not report adverse events related. Current tests report that the use of high doses of VEGF, compared with low doses and placebo, improves myocardial perfusion in patients with severe angina and provides evidence of a dose-dependent positive effect [46.47]. Confronted with evidence, VEGF has been shown to be a potential angiogenic factor, which benefits in medium and long term follow-up have been or are being assessed, including the improvement of quality of life, functional class of heart failure, angina class, functional capacity and reduction of myocardial ischemia [25,28,45,46,48-57]. FGF [58-60] and HGF [61] have also been demonstrating its potential benefits in the induction of myocardial angiogenesis, and to further develop this promising therapeutic approach we must critically assess the results and the experimental protocols, to identify factors that may have undermined the effectiveness of therapy or confounding data interpretation [4]. 642

As the route of administration, the intramyocardial route proved to be more effective and, therefore, have been the most widely used in studies involving gene therapy in cardiology [38]. Previous studies suggest that administration by intramuscular injection offers the possibility to offer more effective in focal areas of ischemic muscle [4]. There are questions concerning the safe transfer of angiogenic factors, and also in relation to time of expression [4.62], where it is known that plasmids carriers of angiogenic factors protein, because they have more short expression and do not incorporate DNA to which the cell will connect to, have a lower risk of this adverse effect. Since the viral vectors require care in biosafety, it is unnecessary measure with non-viral vectors. Studies indicate temporary events related to use of adenovirus, such as fever or elevated serum C-reactive protein, liver enzymes and antibody titration [22]. Hao et al. [63] published in 2007, an experimental study on myocardial angiogenesis VEGF165 compared with adenoviral plasmid vector. These authors demonstrated equivalent benefits in terms of ventricular

Eibel B, et al. - Gene therapy for ischemic heart disease: review of clinical trials

Rev Bras Cir Cardiovasc 2011;26(4):635-46

function (P<0.05) for plasmids and adenovirus after 4 weeks, however, in this study, the TUNEL technique that detects DNA breaks that occur during the process of apoptosis, demonstrated an increase in frequency of cardiomyocyte apoptosis in adenovirus group (P <0.02). Almost all clinical trials of gene therapy and study population are patients with end stage ischemic disease, since the possible increased risk in relation to the benefits associated with new treatments are acceptable and can be used as an adjunct to conventional therapy. However, in very advanced clinical situations, therapy may not lead to an improvement of great intensity and measurable by available methods, even when treatment shows some clinical benefit [4.64].

will require more follow-up time and number of patients undergoing therapy [4]. Thus, gene therapy has emerged as a potentially beneficial alternative to ischemic heart disease patients, when conventional therapies are exhausted. The definition of angiogenic success, for better assessment of the results needs to be rethought and defined by methods of higher sensitivity and specificity. Traditionally, therapy for the treatment of cardiovascular disease should demonstrate improvements in morbidity and mortality. However, for this patient population, the fact of improving quality of life, and decrease or elimination of episodes of angina and reduction of events of hospitalization may be considered the biggest gains on this new therapy. Knowing that the manifestations of cardiovascular disease is progressive, the main aim is to offer patients significant decrease of symptoms and delay this progression. The future directions of gene therapy indicate probable combinations of angiogenic factors or individual factors (HIF 1-α) that activate different pathways of neovascularization. Combinations of cell therapy and angiogenic factors, as well as the use of biomaterials to improve the microenvironment are other promising strategies for ischemic tissue repair [4].

Local Experience In the Cardiology Institute of RS/FUC and the Discipline of Cardiology of UFCSPA, in collaboration with the Laboratory of Immunogenetics, UFRGS, we previously developed experimental studies [65-67] and recently performed the first gene therapy clinical trial in Brazil, using VEGF165 for refractory angina [53]. In experimental studies, we used a canine model of myocardial infarction in acute and chronic phases in an attempt to assess the processes of gene therapy. Recently, we developed a controlled clinical trial, phase I/II (ClinicalTrial NCT00744315) [53] in order to clinically assess the effects of gene therapy with VEGF165 in patients with advanced coronary artery disease (CAD), not eligible for revascularization or percutaneous surgical. The thirteen patients received optimal drug therapy for at least six months and underwent administration of intramyocardial injections of 2000 µg of plasmid VEGF165. Patients were assessed by myocardial scintigraphy, exercise testing, quality of life questionnaire (Minnesota) and determination of classes of heart failure (NYHA) and angina (CCS). In partial results of 3 months of evolution, it was concluded that the therapy proved to be safe and feasible, tending to improvement in severity of angina and reducing the intensity of myocardial ischemia.

ACKNOWLEDGEMENTS The authors acknowledge the participation in group projects of Gene Therapy of the Institute of Cardiology of Rio Grande do Sul/University Foundation of Cardiology, toe following colleagues: Leonardo Karam Teixeira, Felipe Borsu de Salles, Ana Paula Furlani, Eduardo Mastalir, Paulo Lavanière Moreno, Sang Won Han, Eduardo Ludwig, Gabriel Grossman, João Ricardo Michielin Sant’Anna, Guaracy Fernandes Teixeira Filho, Melissa Medeiros Markoski, Andrés Delgado Cañedo, Melissa Camassola, Iran Castro, Maria Cláudia Irigoyen, Luiza Macedo Braga and Rogério Sarmento Leite.

CONCLUSIONS Over 1,000 patients were enrolled in controlled clinical trials of gene therapy, covering more than a decade and so far, except for specific cases, no adverse safety signal was detected, indicating that the therapy is safe, feasible and potentially effective although they have not produced conclusive evidence of its benefits definitely. Reports of retinopathy, cancer or other diseases that could be driven by vascular growth were perceived as equally distributed in treated and placebo groups in randomized clinical trials. More definite conclusions about risks and complications

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38. Bae J, Cho M. Gene therapy for heart failure. Korean Circ J. 2005;35(5):345-52. 39. Giordano FJ, Ping P, McKirnan MD, Nozaki S, DeMaria AN, Dillmann WH, et al. Intracoronary gene transfer of fibroblast growth factor–5 increases blood flow and contractile function in an ischemic region of the heart. Nat Med. 1996;2(5):534-9. 40. Wright MJ, Wightman LM, Lilley C, de Alwis M, Hart SL, Miller A, et al. In vivo myocardial gene transfer: optimization, evaluation and direct comparison of gene transfer vectors. Basic Res Cardiol. 2001;96(3):227-36. 41. Wilson DR. Viral-mediated gene transfer for cancer treatment. Curr Pharm Biotechnol. 2002;3(2):151-64. 42. Rubanyi GM. The future of human gene therapy. Molecular Aspects Med. 2001;22(3):113-42. 43. Dulak J, Zagorska A, Wegiel B, Loboda A, Jozkowicz A. New strategies for cardiovascular gene therapy: regulatable preemptive expression of pro-angiogenic and antioxidant genes. Cell Biochem Biophys. 2006;44(1):31-42. 44. Mack CA, Patel SR, Schwarz EA, Zanzonico P, Hahn RT, Ilercil A, et al. Biologic bypass with the use of adenovirusmediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg. 1998;115(1):168-76. 45. Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, et al. Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation. 1998;98(25):2800-4. 46. Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, et al; VIVA Investigators. The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation. 2003;107(10):1359-65. 47. Hendel RC, Henry TD, Rocha-Singh K, Isner JM, Kereiakes DJ, Giordano FJ, et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dose-dependent effect. Circulation. 2000;101(2):118-21. 48. Symes JF, Losordo DW, Vale PR, Lathi KG, Esakof DD, Mayskiy M, et al. Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thorac Surg. 1999;68(3):830-6. 49. Vale PR, Losordo DW, Milliken CE, Maysky M, Esakof DD, Symes JF, et al. Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic

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59. Grines CL, Watkins MW, Mahmarian JJ, Iskandrian AE, Rade JJ, Marrott P, et al; Angiogene GENe Therapy (AGENT-2) Study Group. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J Am Coll Cardiol. 2003;42(8):1339-47.

51. Stewart DJ, Hilton JD, Arnold JM, Gregoire J, Rivard A, Archer SL, et al. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther. 2006;13(21):1503-11.

60. Henry TD, Grines CL, Watkins MW, Dib N, Barbeau G, Moreadith R, et al. Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J Am Coll Cardiol. 2007;50(11):1038-46.

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63. Hao X, Månsson-Broberg A, Grinnemo KH, Siddiqui AJ, Dellgren G, Brodin LA, et al. Myocardial angiogenesis after plasmid or adenoviral VEGF-A(165) gene transfer in rat myocardial infarction model. Cardiovasc Res. 2007;73(3):481-7. 64. Rana JS, Mannam A, Donnell-Fink L, Gervino EV, Sellke FW, Laham RJ. Longevity of the placebo effect in the therapeutic angiogenesis and laser myocardial revascularization trials in patients with coronary heart disease. Am J Cardiol. 2005;95(12):1456-9 65. Kalil RA, Teixeira LA, Mastalir ET, Moreno P, Fricke CH, Nardi NB. Experimental model of gene transfection in healthy canine myocardium: perspectives of gene therapy for ischemic heart disease. Arq Bras Cardiol. 2002;79(3):223-32. 66. Sant’Anna RT, Kalil RAK, Moreno P, Anflor LCJ, Correa DLC, Ludwig R, et al. Gene therapy with VEGF 165 for angiogenesis in experimental acute myocardial infarction. Rev Bras Cir Cardiovasc. 2003;18(2):142-7.

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67. Furlani A, Kalil RA, Castro I, Cañedo-Delgado A, Barra M, Prates PR, et al. Effects of therapeutic angiogenesis with plasmid VEGF165 on ventricular function in a canine model of chronic myocardial infarction. Rev Bras Cir Cardiovasc. 2009;24(2):143-9.

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REVIEW ARTICLE

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Respiratory physiotherapy and its application in preoperative period of cardiac surgery Fisioterapia respiratória e sua aplicabilidade no período pré-operatório de cirurgia cardíaca

Regina Coeli Vasques de Miranda1, Susimary Aparecida Trevizan Padulla1, Carolina Rodrigues Bortolatto2

DOI: 10.5935/1678-9741.20110057

RBCCV 44205-1333

Resumo Procedimentos cirúrgicos torácicos podem alterar a mecânica respiratória, repercutindo na função pulmonar. A presença de profissionais fisioterapeutas é fundamental no preparo e na reabilitação dos indivíduos que são submetidos à cirurgia cardíaca, visto que dispõem de um grande arsenal de técnicas. O objetivo foi verificar a efetividade de exercícios respiratórios, com e sem a utilização de dispositivos, e o treinamento muscular respiratório pré-cirurgia cardíaca na redução das complicações pulmonares pós-operatórias. Mesmo existindo controvérsias a respeito de qual técnica utilizar, estudos demonstram a eficácia da fisioterapia respiratória pré-cirúrgica na prevenção e na redução de complicações pulmonares pós-operatórias.

Abstract Cardiac surgical procedures change respiratory mechanics, defecting in lung dysfunction. The physical therapists play an important role in the preparation and rehabilitation of individuals who are undergoing cardiac surgery, as they have a large quantity of techniques. The objective was to evaluate the effectiveness of breathing exercises with and without the use of devices, and respiratory muscle training in preoperative period of cardiac surgery in reducing postoperative pulmonary complications. Although there are controversies as to which technique to use, studies show the effectiveness of preoperative physiotherapy in the prevention and reduction of postoperative pulmonary complications.

Descritores: Procedimentos cirúrgicos cardíacos. Modalidades de fisioterapia. Reabilitação. Complicações pósoperatórias.

Descriptors: Cardiac surgical procedures. Physical therapy modalities. Rehabilitation. Postoperative complications.

1. PhD; Assistant Professor at Faculty of Sciences and Technology at State University of São Paulo (UNESP) Júlio de Mesquita Filho – Campus Presidente Prudente, Presidente Prudente, SP, Brazil. 2. Graduation in Physiotherapy; Student Specialist in Hospital Physiotherapy at Faculty of Sciences and Technology at State University of São Paulo (UNESP) Júlio de Mesquita Filho – Campus Presidente Prudente, Presidente Prudente, SP, Brazil.

Correspondence address: Regina Coeli Vasques de Miranda. Rua Roberto Simonsen, 305 – Jardim das Rosas – Presidente Prudente, SP, Brazil Zip Code: 19060-900 E-mail: re.miranda@fct.unesp.br

This study was carried out at Faculty of Sciences and Technology at State University of São Paulo (UNESP) Júlio de Mesquita Filho – Campus Presidente Prudente, Presidente Prudente, SP, Brazil.

Article received on April 5th, 2011 Article accepted on August 29th, 2011

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Miranda RCV, et al. - Respiratory physiotherapy and its application in preoperative period of cardiac surgery

INTRODUCTION An important moment in the history of medicine of the twentieth century was the performance of the open surgical technique, allowing constant technical advances, including relevant national contributions [1]. Following the path of conquest, surgical treatment remains the best therapeutic modality related to survival of individuals with coronary heart disease, as well as in individuals with valvular dysfunction [1,2]. Despite numerous advances, the occurrence of complications after cardiac interventions is very common and is a major cause of postoperative morbidity and mortality [2,3]. Historically, respiratory physiotherapy has been used in patients undergoing cardiac surgery in order to reduce the risk of pulmonary complications, such as retention of secretions, atelectasis and pneumonia [4], both in adults and in children [5]. Participation in the preparation of physiotherapists and rehabilitation of individuals who are undergoing surgical procedures are relevant, given the great arsenal of techniques available [6]. It is described in the literature, in addition to the relative scarcity, that studies related to the approach of physiotherapy in the preoperative have different techniques [7]. Given the importance of physiotherapy in the prevention and treatment of postoperative complications, this literature review was written, in order to gather relevant information on this subject. REVIEW Leguisamo et al. [8] recommended that physiotherapy should be started preoperatively, to assess and educate patients. Studies have shown that preoperative physiotherapeutic significantly reduced the risk of developing pulmonary complications after the surgery of children under the age of six years [9]. Garbossa et al. [6] suggest that the time spent is better spent, and the professional can answer questions of the individual and guide him as to new situations that will face. The importance of proper preoperative assessment in cardiac patients is due to the fact that it is common the reduced lung volumes postoperatively. The decrease in functional residual capacity (FRC) is one of the key determinants of hypoxemia and atelectasis, which can occur in this type of surgery [10]. Surveys performed in Australia and New Zealand by Reeve et al. [11] and in Sweden by Westerdahl & Mรถller [12] found that the majority of physiotherapists provides preoperative information for patients undergoing elective cardiac surgery, such as early mobilization, sternotomy restrictions, risk of pulmonary complications techniques 648

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for getting in and out of bed/chair, breathing exercises, cough techniques and information on exercise lower limb. Thus, the guidance given to patients regarding their responsibilities in relation to treatment, helps their direct participation during the postoperative period [8,12,13]. Studies on post-surgical changes show that lung volume does not depend solely on the activity of respiratory muscles, but also the mechanical properties of the lungs. The reduction in lung compliance, increased airway resistance and the abolition of sighs are also factors observed after cardiac surgery. The lower diaphragmatic mobility implies the pain associated with reduced FRC, reducing ventilation and expandability of the lower areas of the lungs [10]. Giacomazzi et al. [14] demonstrated in their studies that the pain was the most persistent complaints, as well as significant reduction in lung function until the fifth postoperative day. Several protocols of preoperative pulmonary assessment were established over the years. Some studies confirm the relevance of the history of the patient, the presence of chronic obstructive pulmonary disease, smoking, obesity and age [2,7-10,15,16]. They used spirometry to determine the values of forced vital capacity and forced expiratory volume in one second, measurement of maximum inspiratory and expiratory pressures by manometer and cirtometry for obtaining measurements of the circumferences and thoracoabdominal motion [2,7,10,14-16]. The chest radiograph, taken to be a useful, minimally invasive, low cost, although rarely requested preoperatively, became routine in the postoperative period [17]. Due to the increasing costs of health services and more options for the treatment of heart diseases, the identification of patient risk factors for postoperative complications may influence the decision about the appropriate course of action. Similarly, funding organizations of procedures need to define the complications of risk parameters to improve resource planning and the final cost of hospitalization [18]. It is important therefore to identify the preoperative period, patients with higher risk of postoperative complications, because it is high the number of variables that can interfere with a surgical procedure [19]. Several scales and scores can be used in the evaluation processes involved in cardiorrhespiratory rehabilitation in cardiac surgery. The Torrington and Henderson Scale, useful in the preoperative clinical evaluation of surgical patients can adequately stratify the risk of low, moderate and high intensity for the occurrence of pulmonary complications and death due to pulmonary elective general surgery. This stratification ensures that specific strategies and preventive measures are dispensed to patients at higher risk [20].

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The heart rate variability has also emerged as a simple noninvasive measure in the evaluation of autonomic nervous system, a regulator of physiological processes in the human body and indicator of health commitment [21]. The Tuman score identifies the group of patients with increased risk of infectious complications, as the infection remains a major cause of morbidity and mortality in surgical patients, with a special interest in identifying risk factors for its occurrence [18] . Prolonged hospitalization of patients awaiting coronary artery bypass surgery presents potential risk of immobilization [22]. Taking into account the presentation of pulmonary dysfunction associated with cardiac surgery and its possible repercussions, respiratory physiotherapy has been requested in order to reverse or prevent the development of pulmonary complications [4.23], using variety of techniques. However, a systematic review of the literature shows that there are controversies on the subject, making it difficult to decide which resource would be more useful and less expensive in the management of these patients. The techniques used in respiratory physiotherapy vary according to countries and with the practice of each service [18]. The ventilatory exercises consists in the adjustment of inspiratory and expiratory ventilation depth to the more appropriate pattern of ventilatory muscle, both in terms of respiratory rate and tidal volume. Physiotherapy guides the patient to properly use the ventilatory muscle and understand the different types of ventilatory patterns, through practical demonstration of this process [3,24,25]. An observational study performed in Spain with 263 patients, of whom 159 received preoperative physiotherapy showed that incentive spirometry, deep breathing exercises, early ambulation and assisted cough are related to lower incidence of atelectasis (17% vs. 36 %) after CABG with CPB, the difference being considered significant and clinically relevant [26]. In 2005, Westerdahl et al. [23] concluded that preoperative physiotherapy, with deep breathing exercises when compared to the system without breathing instructions significantly decreased atelectasis and improved ventilation spirometry. Physiotherapy treatment of difficult resolution of atelectasis during pediatric cardiac surgery had better mucociliary clearance after inhalation of hypertonic saline with 6% NaCl [27]. Leguisamo et al. [8] studied the effectiveness of a physiotherapy program of breathing patterns in the preoperative coronary artery bypass grafting. They concluded that patients educated preoperatively will be better prepared to collaborate with the postoperative treatment and understanding of the aims of pre- and postoperative physiotherapy and the proposed technique can reduce the length of stay in hospital.

Comparative data between groups of children who received pre- and postoperative physiotherapy and group that performed exercises only in the postoperative period showed that pulmonary complications were significantly lower in the group that underwent physiotherapy before and after surgery [9]. Studies by Garbossa et al. [6] found that individuals instructed and advised to exercise ventilatory physiotherapy (ventilatory pattern as 1:1, 2:1 and 3:1) and hospital routines in the preoperative period showed lower levels of anxiety compared to individuals who had not received guidance . A pre- and postoperative cardiopulmonary rehabilitation program performed on patients who are awaiting surgery in hospital, showed superior results to standard treatment, reducing postoperative complications and length of hospital stay [22]. In contrast, Brasher et al. [4] concluded that the removal of breathing exercises from routine physiotherapy did not alter significantly the result of the patient. Similarly, Pasquina et al. [28] in a review concluded that there is insufficient evidence about the benefits of any type of prophylactic respiratory therapy after cardiac surgery, and that is broader than has been justified by the results of clinical research. In patients undergoing elective cardiac surgery, BorghiSilva et al. [29] demonstrated a high prevalence of spirometric changes in the preoperative and justified the importance of early physiotherapy intervention in reducing the incidence of respiratory complications after the surgery. Similarly, Westerdahl et al. [23] recognized that a mechanical device could help patients to remember to do breathing exercises, and that they found these devices useful and motivating. The literature suggests that several treatments commonly used by physiotherapists in the postoperative period, including incentive spirometry (IS) may be adequate in meeting the physiological demands of lung re-expansion [30]. The use of IS is performed through slow and deep inspiration from FRC to total lung capacity, followed by sustained inspiration. The use of the device provides a visual feedback to patients, generating better gas flow to the alveoli and increased lung expansion [31]. Thus, it is justified the preemptive use of IS in the period before the procedure, since the individuals presented breathing disorders after surgery. Some studies have shown that the spirometer volume (SV) develop lower respiratory activity when compared to the spirometer flow (SF). Other authors found that during the use of SV, there is greater mobility of the abdominal cavity, the lower recruitment of accessory muscles of respiration and increased tidal volume when compared to the use of SF [32,33]. Renault et al. [34] aimed to identify the effect of deep breathing exercises (DBE) and SF in patients undergoing 649

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coronary artery bypass grafting and found no significant differences in maximal respiratory pressures, spirometric variables and oxygen saturation in patients in the different techniques used. Tomich et al. [33] compared three breathing exercises: diaphragmatic breathing, SF (Trifle II) and SV (Voldyne). They found that the difference between breathing and diaphragmatic Voldyne was a significant increase in the inspiratory cycle compared to baseline. The Trifle II was associated with increased respiratory rate and electromyographic activity of the sternocleidomastoid muscle, and concluded that diaphragmatic breathing and Voldyne showed similar results, while Trifle II showed disadvantages compared to others. Similarly, results of the Yamaguti et al. [35] suggested that the use of SV and diaphragm exercises seem to be equally effective in the treatment of respiratory disorders, whose therapeutic aim is the development of diaphragmatic motion. This study noted that it is considered an indication of the careful and appropriate type of incentive spirometer to be used in clinical practice. Finally, they found that women presented better performance in all breathing exercises when compared to men. Agostini et al. [36] concluded that physiotherapy, with or without incentive spirometry reduces the incidence of postoperative complications and improves lung function. However, there is currently no evidence that the use of non-oriented incentive spirometry could replace or significantly increase the work of physiotherapists. It is known that a dysfunction of respiratory muscles due to surgery may lead to a reduction in vital capacity, tidal volume, total lung capacity and consequent failure of the cough. These low values can cause atelectasis, a risk factor for lung infections, and decreased functional residual capacity, which, in turn, alters the properties of exchange and increased ventilation/perfusion. Some researchers indicate - in order to prevent postoperative atelectasis - the maintenance of adequate respiratory muscle strength [37]. According Saglam et al. [38], adequate muscle strength preoperatively of thoracic surgery is responsible for increased functional capacity when compared to subjects who had muscle weakness in the period prior to surgery. The respiratory muscle weakness preoperatively increases the risk of pulmonary complications in the postoperative period and inspiratory muscle training (IMT) can help prevent complications in the postoperative period [33,34]. A study using IMT of linear load based on 30% of PImax, with a gradual increase in the preoperative period presented reduced pulmonary complications in 50% when compared to studies with patients who underwent physiotherapy without inspiratory muscle training. And

therefore, the duration of postoperative hospitalization was significantly lower [39]. The conclusion to this finding, according Feltrim et al. [40], was that IMT has avoided major pulmonary complications because improved strength and endurance of respiratory muscles, but was unable to prevent those of minor grade, whose pathophysiology may be associated with effects but respiratory muscle dysfunction. Thus, the benefit obtained by the reduction of pulmonary complications of greater impact supports the indication of IMT in the preoperative elective surgery of coronary artery bypass grafting in patients at high risk. There is the possibility of residential programs for inspiratory muscle training, according the study by Ferreira et al. [41], which proved to be safe and resulted in improvement in forced vital capacity and maximum voluntary ventilation, although its clinical benefits are not evident.

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FINAL CONSIDERATIONS The analysis of these studies revealed that the patient care in the preoperative period, information on post-surgical restrictions, technics of bed/chair transfer, and the importance of breathing and physical exercises accelerate the process of postoperative recovery. As noted, many patients have basal respiratory disorders, which, coupled with anxiety and pain due to surgery, induce changes in respiratory rhythm and pattern. In addition to post-surgical restrictions, the ineffectiveness of the cough has negative influence on the patient’s respiratory status. However, in clinical practice there are controversies about the techniques, making it difficult to decide which resource would be more useful and less expensive in the management of these patients. Several studies have demonstrated the effectiveness of breathing exercises with and without the use of devices, when compared to the groups who did not perform exercise. With regard to respiratory physiotherapy, increasingly required, it is up to the professional to verify the patient’s need and the availability of resources and devices, considering the individuality of each patient to perform breathing exercises, as noted, different techniques have similar results.

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10. Cavalheiro LV, Chievegato LD. Avaliação pré-operatória do paciente cardiopata. In: Regenga MM, ed. Fisioterapia em cardiologia da UTI à reabilitação. São Paulo:Rocca;2000.

22. Herdy AH, Marcchi PL, Vila A, Tavares C, Collaço J, Niebauer J, et al. Pre- and postoperative cardiopulmonary rehabilitation in hospitalized patients undergoing coronary artery bypass surgery: a randomized controlled trial. Am J Phys Med Rehabil. 2008;87(9):714-9.

11. Reeve J, Denehy L, Stiller K. The physiotherapy management of patients undergoing thoracic surgery: a survey of current practice in Australia and New Zealand. Physiother Res Int. 2007;12(2):59-71. 12. Westerdahl E, Möller M. Physiotherapy-supervised mobilization and exercise following cardiac surgery: a national questionnaire survey in Sweden. J Cardiothorac Surg. 2010;5:67. 13. Bethune DD, Potter HM, McKenzie D. Técnicas fisioterápicas. In: Pryor JA, Webber BA, eds. Fisioterapia para problemas respiratórios e cardíacos. 2ª ed. Rio de Janeiro:Guanabara Koogan;2002. p.97-150.

23. Westerdahl E, Lindmark B, Eriksson T, Friberg O, Hedenstierna G, Tenling A. Deep-breathing exercises reduce atelectasis and improve pulmonary function after coronary artery bypass surgery. Chest. 2005;128(5):3482-8. 24. Renault JA, Costa-Val R, Rossetti MB. Respiratory physiotherapy in the pulmonary dysfunction after cardiac surgery. Rev Bras Cir Cardiovasc. 2008;23(4):562-9. 25. Sciaky AJ. Educação do paciente. In: Frownfelter D, Dean E, eds. Fisioterapia cardiopulmonar: princípios e prática. 3ª ed. Rio de Janeiro:Revinter;2004.

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26. Yánez-Brage I, Pita-Fernández S, Juffé-Stein A, MartínezGonzález U, Pértega-Díaz S, Mauleón-García A. Respiratory physiotherapy and incidence of pulmonary complications in off-pump coronary artery bypass graft surgery: an observational follow-up study. BMC Pulm Med. 2009;9:36.

34. Renault JA, Costa-Val R, Rossetti MB, Houri Neto M. Comparação entre exercícios de respiração profunda e espirometria de incentivo no pós-operatório de cirurgia de revascularização do miocárdio. Rev Bras Cir Cardiovasc. 2009;24(2):165-72.

27. Silva NLS, Poitto RF, Barboza MAI, Croti UA, Braile DM. Inalação de solução salina hipertônica como coadjuvante da fisioterapia respiratória para reversão de atelectasia no pósoperatório de cirurgia cardíaca pediátrica. Rev Bras Cir Cardiovasc. 2006;21(4):468-71. 28. Pasquina P, Tramèr MR, Walder B. Prophylactic respiratory physiotherapy after cardiac surgery: systematic review. BMJ. 2003;327(7428):1379. 29. Borghi-Silva A, Di Lorenzo PVA, Oliveira CR, Luzzi S. Comportamento da função pulmonar e da força da musculatura respiratória em pacientes submetido à revascularização do miocárdio e a intervenção fisioterapêutica. Rev Bras Ter Intensiva. 2004;16(3):155-9. 30. Agostini P, Singh S. Incentive spirometry following thoracic surgery: what should we be doing? Physiotherapy. 2009;95(2):76-82. 31. Wilkins RL, Scanlan CL. Terapias de expansão pulmonar. In: Scanlan CL, Wilkins RL, Stoller JK, eds. Fundamentos da terapia respiratória de Egan. São Paulo:Manole;2000. p.797843. 32. Parreira VF, Tomich GM, Britto RR, Sampaio RF. Assessment of tidal volume and thoracoabdominal motion using volume and flow-oriented incentive spirometers in healthy subjects. Braz J Med Biol Res. 2005;38(7):1105-12. 33. Tomich GM, França DC, Diório AC, Britto RR, Sampaio RF, Parreira VF. Breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises. Braz J Med Biol Res. 2007;40(10):1409-17.

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35. Yamaguti WP, Sakamoto ET, Panazzolo D, Peixoto CC, Cerri GG, Albuquerque AL. Diaphragmatic mobility in healthy subjects during incentive spirometry with a flow-oriented device and with a volume-oriented device. J Bras Pneumol. 2010;36(6):738-45. 36. Agostini P, Calvert R, Subramanian H, Naidu B. Is incentive spirometry effective following thoracic surgery? Interac Cardiovasc Thorac Surg. 2008;7(2):297-300. 37. Hulzebos EH, van Meeteren NL, van den Buijs BJ, de Bie RA, Brutel de la Rivière A, Helders PJ. Feasibility of preoperative inspiratory muscle training in patients undergoing coronary artery bypass surgery with a high risk of postoperative pulmonary complications: a randomized controlled pilot study. Clin Rehabil. 2006;20(11):949-59. 38. Saglam M, Arikan H, Savce S, Inal-Ince D, Bosnak-Guclu M, Degir-Mence B, et al. Relationship between respiratory muscle strength, functional capacity and quality of life in pre-operative cardiac surgery patients. Eur Respir Rev. 2008;17:39-40. 39. Hulzebos EH, Helders PJ, Favié NJ, De Bie RA, Brutel de la Riviere A, Van Meeteren NL. Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery: a randomized clinical trial. JAMA. 2006;296(15):1851-7. 40. Feltrim MIZ, Jatene FB, Bernardo WM. Em pacientes de alto risco, submetidos à revascularização do miocárdio, a fisioterapia respiratória pré-operatória previne complicações pulmonares? Rev Assoc Med Bras. 2007;53(1):8-9. 41. Ferreira PE, Rodrigues AJ, Évora PR. Effects of an inspiratory muscle rehabilitation program in the postoperative period of cardiac surgery. Arq Bras Cardiol. 2009;92(4):75-82.

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Rev Bras Cir Cardiovasc 2011;26(4):653-7

Solange Bassetto1, Antonio Carlos Menardi2, Lafaiete Alves Junior3, Alfredo José Rodrigues4, Paulo Roberto Barbosa Évora5

DOI: 10.5935/1678-9741.20110058

RBCCV 44205-1334

Abstract We were challenged by the experience of one patient reoperation for a bioprosthetic bovine pericardium degenerative stenosis, 24 years after implantation. This bioprosthesis was implanted due to tricuspid valve bacterial staphylococcal endocarditis after septic abortion.

Resumo Vivenciamos a experiência de reoperar uma paciente por estenose degenerativa de uma prótese biológica de pericárdio bovino, após 24 anos de implante. Essa prótese degenerada havia sido implantada devido à destruição da valva tricúspide por endocardite bacteriana estafilocócica após aborto séptico.

Descriptors: Endocarditis, bacterial. Tricuspid valve. Bioprosthesis. Cardiac surgical procedures.

Descritores: Endocardite bacteriana. Valva tricúspide. Bioprótese. Procedimentos cirúrgicos cardíacos.

1. MSc, Cardiovascular Surgery; Attending Physician, Division of Thoracic and Cardiovascular Surgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 2. PhD; Attending Physician, Division of Thoracic and Cardiovascular Surgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 3. MSc, Surgery; Assistant Physician, Division of Thoracic and Cardiovacular, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 4. PhD, Surgery; Professor, Division of Thoracic and Cardiovascular Surgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 5. Full Professor; Division of Thoracic and Cardiovascular Surgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

This work was performed at Surgery and Anatomy Departament – Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Correspondence address: Paulo Évora. Av. Bandeirantes, 3900 – Monte Alegre – Ribeirão Preto/SP, Brazil – Zip Code: 14049-900.

This study had partial support of Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FAEPA/HCFMRP/ USP), Ribeirão Preto, SP, Brazil.

Article received on June 10th, 2011 Article received on September 27th, 2011

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Bassetto S, et al. - Reflections on the 24 years durability of an isolate tricuspid bovine pericardium IMC/Braile bioprosthesis

INTRODUCTION Tricuspid valve replacement has been performed with mechanical or bioprosthetic valves. However, the relative advantages of the two types are incompletely known. In most cases of tricuspid valve disease, repair with annuloplasty is considered the procedure of choice. However, when tricuspid valve repair or annuloplasty is not feasible, or not successful, tricuspid valve replacement should be considered. There are limited numbers of reports about the long-term results of tricuspid valve replacement, and controversies still exist regarding prosthesis choice. Both bioprosthetic and mechanical valves revealed similar long-term outcomes. However, 没ndings suggest that greater care is needed to prevent valve thrombosis in mechanical valves in the early postoperative period, and there is a greater chance for reoperation in bioprosthetic valves. On this conjuncture we were challenged by the experience of one patient reoperation for a bioprosthetic bovine pericardium degenerative stenosis, 24 years after implantation. This bioprosthesis was implanted due to tricuspid valve bacterial staphylococcal endocarditis after septic abortion. CLINICAL SUMMARY Female patient, 46 years-old who suffered a spontaneous abortion and underwent uterine curettage. Was discharged and developed perseverant fever treated with various antibiotics. After about one month presented severe sepsis with multisystem involvement, diagnosed as Staphylococcus viridans uterine infection. Because the severe situation underwent a total hysterectomy, bilateral salpingectomy andr right oophorectomy. At that time already presented tricuspid systolic murmur and an echocardiogram showed valve regurgitation and vegetations. As the infection persisted, even after gynecologic surgery, it was opted for surgical treatment, in April 1987, and the tricuspid valve was replaced by bovine pericardium prosthesis (IMC / Braile M-31). The patient had regular follow-up until 1995, when she left to attend the scheduled appointment. She returned after 13 years, in 2008, with heart failure and underwent echocardiography and hemodynamic studies that diagnosed severe stenosis of the tricuspid valve bioprosthesis. The patient remained under regular outpatient follow-up, echocardiography persisted with the same characteristics, showing an increase of right atrium, but with normal performance of both ventricles. It is noteworthy that the patient had bronchial asthma and sometimes symptoms were associated to pulmonary dysfunction. As dyspnea deepened, associated with signs of venous congestion and 654

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hepatomegaly, it was opted, in March 2011, for the prosthesis replacement. The surgery indication was based on clinical data suggestive of heart failure, but mainly based on echoDopplercardiography data that showed severe stenosis and degeneration of the bioprosthesis. Surgical planning included left thoracotomy in the fourth space in semi-lateral decubitus (the previous surgery was performed through median sternotomy with infected dehiscence), cardiopulmonary bypass femoro-femoral, bicaval cannulation with cuffed cannulas and normothermia with heart beating. Under these conditions the degenerated prosthesis was replaced by another bovine pericardium bioprosthesis (Braille-M29). The case illustrations are represented in a single composite figure (Figure 1). DISCUSSION The decision as to whether a patient should undergo isolated tricuspid valve replacement is one of the most difficult challenges facing clinicians in the management of valvular heart disease. The clinical outcome of isolated tricuspid valve replacement is not well defined because this procedure is usually performed concomitantly with other valve surgery. Isolated tricuspid valve replacement is characterized by a poor short and long-term outcome. The only previous report that focused on isolated tricuspid valve replacement was limited to a selected group of patients with endocarditis; including a cohort of young drug addict patients without previous cardiac surgery [2]. Isolated tricuspid procedures are exceptionally rare. Prosthetic valve replacement is also seldom required. Generally, these patients face a high risk of operative mortality and long-term outcome is poor. Tricuspid valve repair is associated with better perioperative and long-term outcome than valve replacement. However, patients undergoing replacement showed a significant higher incidence of risk factors for operative mortality. The incidence of reoperation is low with no significant difference when the tricuspid valve has been repaired or replaced [3]. Tricuspid valve reoperation is associated with a high mortality rate. McCarthy et al. [4] reported hospital mortality rate of 37%. These authors emphasizes that the discrepancy between the high recurrence rates of regurgitation and the low re-operation rates may be explained by the fact that reoperation is associated with a high mortality and thus, these patients are managed medically as long as possible before referral to surgery. Controversy exists as to the most suitable prosthesis for the tricuspid position. Some authors have reported good results with bioprostheses, while others have shown good results with mechanical valves. Little is known of timerelated outcome and comparative performance of biological

Bassetto S, et al. - Reflections on the 24 years durability of an isolate tricuspid bovine pericardium IMC/Braile bioprosthesis

Rev Bras Cir Cardiovasc 2011;26(4):653-7

Fig. 1 - 1) Transesophageal echoDopplercardiogram showing prosthesis stenosis and cardiac measurements (upper panels), 2) transprosthetic gradients kept constant in a 3-year period (middle panels) and 3) macroscopic view of one of the replaced mitral prosthesis and histology photomicrograph histological section showing a thick fibrous connective tissue with a predominance of collagen fibers (CF) (red), and parallel to a ventricular connective tissue layer rich in elastic fibers (â&#x2020;&#x2019;) (in black). Verhoeff iron hematoxylin. 400x (lower panels)

and mechanical prostheses following tricuspid valve replacement. A retrospective UK Heart Valve Registry study (Jan 1, 1986 to June 30, 1997) concluded that tricuspid valve replacement carries high 30-day mortality and a poor longer term survival. No superiority could be identified for biological or mechanical prostheses in the tricuspid position for either survival or reoperation. Early mechanical prostheses (caged all or disc and tilting disc) were replaced by biological prostheses, which in turn are being challenged by the new generation of mechanical bileaflet prostheses.

Many have advocated the use of a bioprosthesis at the tricuspid position because of lower pressures and thus lower stress in the right heart leading, potentially, to a greater durability, without the need for higher levels of anticoagulation for mechanical prosthesis In addition, it is prudent to take in consideration that the internal morphology of the right ventricle can, directly, infringes on the mechanism of mechanical valves at the tricuspid site. A less dogmatic approach to the choice of prostheses at the tricuspid site may, therefore, be emerging [5]. 655

Bassetto S, et al. - Reflections on the 24 years durability of an isolate tricuspid bovine pericardium IMC/Braile bioprosthesis

In a general overview, the vast majority of highly experienced surgical teams are inclined to use bioprostheses, since hemodynamic results are excellent, does not require anticoagulation, but this overview changes if the patient has other prosthetic devices that require treatment, or if is in atrial fibrillation. One possibility for the use of mechanical tricuspid prostheses would be the patient’s age, since bioprostheses may have a shorter duration. However, as shown in the review of the literature, even when this situation arises, the vast majority of surgical groups prefer the use of bioprostheses [6]. The American and European societies in its latest guidelines indicate biological prosthesis in the tricuspid position [7-9]. It is noteworthy that the European directive recognizes that there are controversies, but still maintains the bioprosthesis indication. Clearly this is an outstanding matter. Thus, seems reasonable the exercise of the surgeon personal preference in the choice of biological or mechanical prosthesis for the tricuspid position [5]. The Society of Thoracic Surgeons Clinical Practice, in its guidelines for endocarditis surgical management keeps the American and European recommendations but, in the presence of intravenous drug use, more tissue valves are implanted because of anticipated noncompliance with anticoagulation therapy. Thus, the rate of reoperation for this group is higher. However, the only predictor for poor long-term survival was age [10]. After several discussions, this criterion was adopted in the case herein presented, when choosing by the implant of another bovine pericardium prosthesis. Finally, it is necessary, a review of the bioprostheses durability in the tricuspid position. Outcomes exceeding 20 years are not uncommon in the literature, excluding patients with rheumatic heart disease and excluding patients stranded drug addicts, even after repeated episodes of bacterial endocarditis. A very recent publication describes a case of an unexpected Ionescu-Shiley bioprosthesis durability in the mitral and tricuspid positions, deployed to deal with endomyocardial fibrosis, suggesting that bovine pericardial valves may have excellent hemodynamic performance and durability over 20 years even in young patients [11]. In a period of more than 30 years at the Mayo Clinic, 333 surgical patients received biological prostheses and 45 received mechanical prostheses for surgical treatment of Ebstein Anomaly and, a comparative study concluded that the presence of a bioprosthesis is an independent predictor of increased survival [12]. Puig et al. reported three patients with tricuspid insufficiency who underwent valve replacement with homologous dura mater cardiac bioprostheses glycerol-preserved (Two patients were well 28 and 27 years later, and the third was lost to follow-up after 20 years) [13,14]. These reports strongly suggest the good results of isolated tricuspid valve bioprosthesis. 656

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CONCLUSION It is curious that an unusual situation in cardiology services can generate interesting discussions and, when seeking assistance in specialized medical literature, is a subject fraught with controversy. This observation led to the present “Brief Communication” based on the apparently single isolated tricuspid valve bioprosthesis. The question of the surgical team, composed by the authors, was the same never end story: what kind of prosthesis to use? As already mentioned, biological prosthesis were unanimous in relation to mechanical older prostheses (caged ball or disc and tilting disc), but have been “challenged” by the bileaflet mechanical prostheses. Other considerations include: a) the high perioperative mortality (10-37%), highlighting the bias of prolonged medical treatment, and therefore, the surgical treatment should be indicate before the onset of heart failure, b) the choice of prosthesis for isolated tricuspid valve replacement tends to be less dogmatic, pointing out that, although the issue is an open discussion, the American and European guidelines recommend the use of bioprosthesis c) The durability of both types of prostheses, as far as we can study are similar in patients without rheumatic disease (endomyocardial fibrosis, congenital heart defects, more specifically the Ebstein’s disease). Finally, it is an anecdotal observation that the rheumatic inflammatory activity may be able to interfere with the process of calcic bioprosthetic degeneration. The reported patient had her prosthesis implanted due to bacterial endocarditis after septic abortion. The durability of bioprosthetic tricuspid valve is not clear in the literature, because the studied populations involves a vast majority of drug addicts, that are operated and return to use of drugs, therefore interfering with survival outcome. The case of the reported patient suggests that endocarditis, as well as other non-rheumatic diseases, seems not to interfere or, at least, be consistent with the durability of bioprostheses over 20 years. In time, in her latest ambulatory appointment the patient was clinically well, but presenting atrial fibrillation. Anticoagulation was suggested, but she refused for experiencing serious anticoagulation complications in a friend.

REFERENCES 1. Chang BC, Lim SH, Yi G, Hong YS, Lee S, Yoo KJ, et al. Longterm clinical results of tricuspid valve replacement. Ann Thorac Surg. 2006;81(4):1317-23.

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2. Stern HJ, Sisto DA, Strom JA, Soeiro R, Jones SR, Frater RW. Immediate tricuspid valve replacement for endocarditis. Indications and results. J Thorac Cardiovasc Surg. 1986;91(2):163-7.

Task Force. 2008 Focused update incorporated into the ACC/ AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008;118(15):e523-661.

3. Guenther T, Noebauer C, Mazzitelli D, Busch R, TassaniPrell P, Lange R. Tricuspid valve surgery: a thirty-year assessment of early and late outcome. Eur J Cardiothorac Surg. 2008;34(2):402-9. 4. McCarthy PM, Bhudia SK, Rajeswaran J, Hoercher KJ, Lytle BW, Cosgrove DM, et al. Tricuspid valve repair: durability and risk factors for failure. J Thorac Cardiovasc Surg. 2004;127(3):674-85. 5. Ratnatunga CP, Edwards MB, Dore CJ, Taylor KM. Tricuspid valve replacement: UK Heart Valve Registry mid-term results comparing mechanical and biological prostheses. Ann Thorac Surg. 1998;66(6):1940-7. 6. Juárez Hernández A. Is the tricuspid valve an enigma? Surgical treatment: valvuloplasty or valve change? Which prosthesis? Arch Cardiol Mex. 2001;71(1):73-7. 7. American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons, Bonow RO, Carabello BA, Kanu C, de Leon AC Jr, Faxon DP, Freed MD, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. 2006,114(5):e84-231. 8. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, et al; 2006 Writing Committee Members; American College of Cardiology/American Heart Association

9. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, et al; Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology; ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease. The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007;28(2):230-68. 10. Byrne JG, Rezai K, Sanchez JA, Bernstein RA, Okum E, Leacche M, et al. Surgical management of endocarditis: the Society of Thoracic Surgeons clinical practice guideline. Ann Thorac Surg. 2011;91(6):2012-9. 11. Fiore A, Cooley DA, Grande AM, Viganò M, Angelini P. Unusual 25-year durability of an Ionescu-Shiley pericardial bioprosthesis. Ann Thorac Surg. 2011;91(4):e52-3. 12. Brown ML, Dearani JA, Danielson GK, Cetta F, Connolly HM, Warnes CA, et al. Comparison of the outcome of porcine bioprosthetic versus mechanical prosthetic replacement of the tricuspid valve in the Ebstein anomaly. Am J Cardiol. 2009;103(4):555-61. 13. Puig LB, Brandão CM, Pomerantzeff PM, Gaiotto FA, Oliveira SA. Tricuspid dura mater bioprostheses: more than 20-year follow-up of 3 patients. Ann Thorac Surg. 2001;72(2):615-7. 14. Puig LB, Brandão CM, Kawabe L, Verginelli G, Ramires JA, Oliveira SA. Dura mater mitral and tricuspid bioprostheses: 30 years of follow-up. Rev Hosp Clin Fac Med Sao Paulo. 2003;58(3):163-8.

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Rev Bras Cir Cardiovasc 2011;26(4):658-62

Shi-Min Yuan1, Leonid Sternik2

DOI: 10.5935/1678-9741.20110059

RBCCV 44205-1335

Abstract The aim of article is to give a brief description to the surgical strategies for patients with lone atrial fibrillation without associated cardiac operations, and present the possible indications of on-pump Maze procedures through a mid-sternotomy approach.

Resumo O objetivo do artigo é fazer uma breve descrição das estratégias cirúrgicas para pacientes com fibrilação atrial isolada sem operações cardíacas associadas, e apresentar possíveis indicações de procedimentos Maze com circulação extracorpórea por meio de esternotomia mediana.

Keywords: Arrhythmias, cardiac. Atrial fibrillation. Cardiovascular surgical procedures.

Descritores: Arritmias cardíacas. Fibrilação atrial. Procedimentos cirúrgicos cardíacos.

INTRODUCTION Lone atrial fibrillation (LAF) was defined as atrial fibrillation in patients younger than 60 (or 70) years old in the absence of an underlying structural heart disease, such as dilated cardiomyopathy, coronary heart disease, hypertension, and occult thyrotoxicosis [1-4]. LAF can be chronic paroxysmal, persistent or permanent [5]. The prevalence of atrial fibrilation is 0.4% in the general population, increasing to 9% of people over the age of 80 [6]. Palpitations, dizziness, dyspnea, angina and worsening heart failure were the clinical presentations of patients with LAF [6]. Atrial fibrillation now remains the most frequent cause of embolic event, stroke and death

[7-10]. The drugs used to lower the ventricular rate are digitalis, verapamil, propranolol and diltiazem. Electric cardioversion is used in serious cases [11]. Catheter ablation has a risk of stroke associated with thrombus produced when tissue impedance increases, heating the blood pool. Left atrial appendage exclusion is impossible with catheter-based ablation. It is often associated with postoperative atrial tachyarrhythmias that might be caused by incomplete and nontransmural ablation lines [12]. Some patients could not tolerant prolonged antiarrhythmic or anticoagulant medications, and percutaneous ablation has brought about some major complications including pulmonary vein stenosis, thromboembolism, and atrioesophageal fistula [2]. The

1. MD, PhD; Professor of Surgery and Head, Department of Cardiothoracic Surgery, Affiliated Hospital of Taishan Medical College, Taian, Shandong Province, People’s Republic of China. 2. MD, PhD; Deputy Director, Department of Cardiac and Thoracic Surgery; Director, Atrial Fibrillation Surgery Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.

Affiliated Hospital of Taishan Medical College, Taian 271000, Shandong Province, People’s Republic of China. E-mail: s.m.yuan@v.gg

Corresponding author Shi-Min Yuan - MD, PhD; Department of Cardiothoracic Surgery,

Article received on June 17th, 2011 Article received on September 12nd, 2011

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major indications for surgical treatment of LAF were intolerance for antiarrhythmic or anticoagulant medication, and medically refractory arrhythmia [2]. We hereby report our experiences with on-pump mid-sternotomy Maze procedure in three LAF patients without associated cardiac operations.

bundle branch block (Figure 1). No cardioversion was necessary, and antiarrhythmic drugs were gradually withdrawn 3 months after the operation. He was complicated with post-pericardiotomy syndrome and was treated with nonsteroidal anti-inflammatory agents.

METHODS From October 2004 to June 2008, three patients were diagnosed as LAF and were scheduled only for Maze procedure without associated cardiac operations by midsternotomy approach (Table 1). Patient 1 A 54-year-old male patient had a persistent atrial fibrillation for 4 years with hyperlipidemia and transient ischemic attack. He was diagnosed as LAF and received percutaneous pulmonary vein isolation (PVI). However, atrial fibrillation persisted after the procedure during the follow-up. He was thus referred to the Department of Cardiac & Thoracic Surgery for a surgical treatment. He was undergone an open-chest Maze procedure under standard cardiopulmonary bypass and aortic root infused cold blood cardioplegia. After induced cardiac arrest, left atrial appendage was excised. An irrigated bipolar radiofrequency ablation system (Cardioblate BP, Medtronic, Minneapolis, MN, USA) and a Medtronic CardioblateTM pen (Medtronic, Minneapolis, MN, USA) were used to make transmural lesions, including encircling radiofrequency lesion on right pulmonary vein, left atriotomy in the interatrial groove, a radiofrequency lesion and a cryolesion at the mitral annulus, left atrial appendage excision and a perpendicular radiofrequency lesion to the anteromedial tricuspid valve annulus, and another encircling the left pulmonary vein. After the operation, his heart rhythm was sinus with incomplete right

Patient 2 A 51-year-old male patient had a persistent atrial fibrillation for 4 years with hyperlipidemia and diabetes mellitus. He was diagnosed as LAF but he had intolerance prolonged oral anticoagulant therapy. He received Maze procedure via port access. However, atrial fibrillation persisted after the procedure, and he came to us for an open-chest Maze procedure under standard cardiopulmonary bypass and aortic root infused cold blood cardioplegia as described above. After the operation, his heart rhythm recovered to sinus but with fist degree atrioventricular block. No cardioversion was necessary, and antiarrhythmic drugs were gradually withdrawn 3 months after operation. He was uncomplicated. Patient 3 An obese 67-year-old female patient had a paroxysmal atrial fibrillation for 7 years presenting with syncope. She was diagnosed as LAF and received percutaneous PVI but the procedure turned to be a failure. She was referred to our department for an open-chest Maze procedure under standard cardiopulmonary bypass and aortic root infused cold blood cardioplegia as described above. After the operation, her heart rhythm was junctional (Figure 2). She was uncomplicated. She was then transferred to the cardiologist for antiarrhythmic treatment, but her rhythm was still junctional at a 2-year follow-up. This study was approved by the Ethical Committee of the Institute where the work was conducted. An informed consent was obtained from each patient.

Table 1. A comparison of the clinical features of the patients undergoing open-chest Maze procedure. Patient Sex

Age

Male

Nature of atrial fibrillation Persistent

Associated disorder

Surgical indication

Complication

Male

Female

Postoperative heart rhythm Sinus rhythm, incomplete right bundle branch block

Hyperlipidemia, cerebrovascular accident

Failed pulmonary vein isolation

Postpericardiotomy syndrome

Persistent

Hyperlipidemia, diabetes

Failed Maze procedure via port access

None

Sinus rhythm, 1st degree atrioventricular block

Paroxysmal

Syncope

Failed pulmonary vein isolation and obesity

None

Accelerated junctional rhythm

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Fig. 1 - Postoperative electrocardiogram of patient 1 showing sinus rhythm with first degree atrioventricular block 3½ years after Maze procedure

Fig. 2 - Postoperative electrocardiogram of patient 3 showing accelerated junctional rhythm 6 months after Maze procedure

DISCUSSION Maze has been popularly used as an alternative of antiarrythmic procedure [13]. Maze procedures can be classified into 2 types: surgical procedures (Cox-maze/cut-and-sew, and mini-partial maze) and energy-based procedures with radiofrequency, microwave, or cryothermy, etc. [14]. However, we prefer a classification in view of the application of cardiopulmonary bypass (Table 2). Table 2. Classification of Maze procedures. Classification Off-pump

On-pump

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Procedures • Video-assisted epicardial pulmonary vein isolation (Guidant Microwave Surgical Ablation System AFx FLEX 10) • Bilateral small (mini-)thoracotomy for bipolar epicardial pulmonary vein isolation (Medtronic AtriCure Bipolar System) • Mid-sternotomy epicardial pulmonary vein ablation • Mid-sternotomy Maze (cut-and-sew, bi-atrial) • Mid-sternotomy left or left and right atrial surgical ablation

Most of the surgical procedures were carried out under the aid of cardiopulmonary bypass, and therefore they were performed endocardially [15]. The minimally invasive procedure with bipolar radiofrequency devices was developed to achieve bilateral PVI and excision of left atrial appendage through bilateral mini-thoracotomies and thoracoscopy, namely, an epicardial approach [15,16]. This could avoid sternotomy or rib-spreading thoracotomy, and cardiopulmonary bypass [12], and has minimized morbidity of surgical treatment of atrial fibrillation [16]. PVI alone might be effective for most patients with paroxysmal atrial fibrillation and some of the patients with persistent atrial fibrillation [16]. However, the right-sided approach has the drawback of not dealing with the left atrial appendage, and the uncertainty of transmurality of the lesions with microwave energy on the beating heart [2]. No complication was noted concerning bipolar radiofrequency in six patients with off-pump video-assisted PVI, and all six patients were in sinus rhythm within 6month observation as reported by Bisleri et al. [17]. Videoassisted bilateral PVI with endoscopic stapling of the left atrial appendage has achieved an atrial fibrillation-free rate

Yuan SM & Sternik L - Surgical treatment of lone atrial fibrillation by mid-sternotomy Maze procedure under standard cardiopulmonary bypass

of 91.3% at 3-month follow-up [12]. The classic Maze procedure could obtain a sinus rhythm in more than 90% of the patients with atrial fibrillation [18]. In this report, two patients were in sinus rhythm and one was in conjunctional at a 1-45-month follow-up. Debates exist on the mechanisms of atrial fibrillation on whether macro reentry circuits in the atria or the drivers within the pulmonary veins [14]. Cox-Maze III surgery was developed on basis of the concept of macro reentry circuits in the atria [14]. Others believe that an atrial fibrillation driver predominates within the pulmonary veins thereby solely PVI was introduced for chronic atrial fibrillation, and it has proved that PVI incorporating the antrum of the pulmonary veins would increase the success rate of ablation [14]. However, this approach was technically complex and invasive [16]. Besides, the postoperative pacemaker implantation rate and postoperative atrial fibrillation rate were high [19]. Energy source approaches including radiofrequency, microwave, cryoablation were developed as alternatives to Cox-Maze III surgery. Continuous linear transmural atrial lesions made by these energy sources may produce heart block [19]. With a unipolar probe, energy disperses in multiple directions, and thus may damage the adjacent structures, such as the esophagus and coronary arteries [14]. With bipolar, the energy produces a transmural lesion, both epicardial and endocardial, within shorter ablation time [14]. Nevertheless, the Maze procedure by mid-sternotomy approach still plays an important role in patients with LAF in several occasions, especially in patients with failed percutaneous PVI. Currently, the Maze procedure for LAF is quite suitable for the patients with previous cardiac surgery and previous catheter ablation [12]. It does not lose its function as an alternative to antiarrhythmic medical treatment, long-term anticoagulation, electrical cardioversion, or catheter-based ablation [12,17]. In the near future, off-pump PVI with additional interatrial lesion and left atrial appendage exclusion or hybrid approaches incorporating both surgical and percutaneous techniques are favored for the surgical treatment of LAF [14]. Even though, the importance of open-chest Maze could not be overlooked. CONCLUSIONS Our experiences with on-pump mid-sternotomy Maze procedure was indicated for the patients with failed percutaneous PVI, failed heart port Maze procedure, and obesity patients either for left or right Maze. We suggest this procedure should be used in patients older than 70 years, a history of atrial fibrillation of over one year, a history of aortic valve replacement, and failed or repeatedly failed percutaneous PVIs.

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REFERENCES 1. Engel TR, Topalian SK. The pathology of lone atrial fibrillation. Chest. 2005;127(2):424-5. 2. Yilmaz A, Geuzebroek GS, Van Putte BP, Boersma LV, Sonker U, De Bakker JM, et al. Completely thoracoscopic pulmonary vein isolation with ganglionic plexus ablation and left atrial appendage amputation for treatment of atrial fibrillation. Eur J Cardiothorac Surg. 2010;38(3):356-60. 3. Scardi S, Mazzone C, Pandullo C, Goldstein D, Poletti A, Humar F. Lone atrial fibrillation: prognostic differences between paroxysmal and chronic forms after 10 years of follow-up. Am Heart J. 1999;137(4 Pt 1):686-91. 4. Jessurun ER, van Hemel NM, Defauw JA, Stofmeel MA, Kelder JC, de la Rivière AB, et al. Results of maze surgery for lone paroxysmal atrial fibrillation. Circulation. 2000;101(13):1559-67. 5. Jahangir A, Lee V, Friedman PA, Trusty JM, Hodge DO, Kopecky SL, et al. Long-term progression and outcomes with aging in patients with lone atrial fibrillation: a 30-year followup study. Circulation. 2007;115(24):3050-6. 6. Ninio DM. Contemporary management of atrial fibrillation. Aust Prescr. 2000;23(5):100-2. http:// www.australianprescriber.com/magazine/23/5/100/2/. 7. Grandmougin D, Tiffet O. Video-assisted thoracoscopic epicardial ablation of left pulmonary veins for lone permanent atrial fibrillation. Interact Cardiovasc Thorac Surg. 2007;6(1):136-8. 8. Breda JR, Ragognette RG, Breda ASCR, Gurian DB, Horiuti L, Machado LN, et al. Avaliação inicial da ablação operatória biatrial por radiofrequência de fibrilação atrial. Rev Bras Cir Cardiovasc. 2010;25(1):45-50. 9. Breda JR, Breda ASCR, Meneguini A, Freitas ACO, Pires AC. Ablação operatória da fibrilação atrial por radiofrequência. Rev Bras Cir Cardiovasc. 2008;23(1):118-22. 10. Breda JR, Ribeiro GCA. Tratamento operatório da fibrilação atrial: revisão integrativa da literatura. Rev Bras Cir Cardiovasc. 2011;26(3):447-54. 11. Larsen SR. Lone atrial fibrillation. http://www.afibbers.org/ atrial_fibrillation.htm. 12. Zollino M, Lecce R, Selicorni A, Murdolo M, Mancuso I, Marangi G, et al. A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in WolfHirschhorn syndrome. Eur J Hum Genet. 2004;12(10):797804. 13. Flores DM, Kalil RA, Lima GG, Abrahão R, Sant’anna JR, Prates PR, et al. Chronotropic response to exercise after

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pulmonary veins isolation or Cox-maze operation. Rev Bras Cir Cardiovasc. 2008;23(4):474-9.

systematic review. Herzschrittmacherther Elektrophysiol. 2007;18(2):68-76.

14. Harling L, Athanasiou T, Ashrafian H, Nowell J, Kourliouros A. Strategies in the surgical management of atrial fibrillation. Cardiol Res Pract. 2011;2011:439312.

17. Bisleri G, Manzato A, Argenziano M, Vigilance DW, Muneretto C. Thoracoscopic epicardial pulmonary vein ablation for lone paroxysmal atrial fibrillation. Europace. 2005;7(2):145-8.

15. Wolf RK, Schneeberger EW, Osterday R, Miller D, Merrill W, Flege JB Jr, et al. Video-assisted bilateral pulmonary vein isolation and left atrial appendage exclusion for atrial fibrillation. J Thorac Cardiovasc Surg. 2005;130(3):797802.

18. Gillinov AM, Wolf RK. Surgical ablation of atrial fibrillation. Prog Cardiovasc Dis. 2005;48(3):169-77.

16. Khargi K, Keyhan-Falsafi A, Hutten BA, Ramanna H, Lemke B, Deneke T. Surgical treatment of atrial fibrillation: a

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19. Suwalski P, Suwalski G, Wilimski R, Kochanowski J, Scis続o P, Gaca H, et al. Minimally invasive off-pump video-assisted endoscopic surgical pulmonary vein isolation using bipolar radiofrequency ablation: preliminary report. Kardiol Pol. 2007;65(4):370-4.

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Giant ventricular myxoma obstructing right ventricular outflow tract Mixoma ventricular direito gigante obstruindo via de saída do ventrículo direito

Trushar P. Gajjar1, Gaurang B. Shah1, Neelam B. Desai2

DOI: 10.5935/1678-9741.20110060

RBCCV 44205-1336

Abstract Intracardiac myxoma is predominantly located in the left atrium but their location in the right ventricle is quite unusual. We present a case in which successful excision of the tumor was done through bicameral approach.

Resumo Mixoma intracardíaco localiza-se predominantemente no átrio esquerdo, e sua localização no ventrículo direito é bastante incomum. Apresentamos um caso no qual excisão bem sucedida do tumor foi feita por meio de abordagem bicameral.

Descriptors: Myxoma. Echocardiography. Ventricular septum.

Descritores: interventricular.

INTRODUCTION Intracardiac myxoma is the most common tumor of the heart, with an estimated incidence of 0.5 cases per million people per year [1]. Approximately 75% of these tumors arise from the left atrium and 18% from the right atrium. Few others originate from atypical sites such as left or right ventricle and valves. Depending on the size and location of the tumor presenting symptoms may vary. Very few cases of isolated right ventricular myxomas have been reported in the literature. We are reporting a case of young female

1. Sri Sathya Sai Institute of Higher Medical Sciences, Consultant Cardiothoracic Surgeon. 2. Sri Sathya Sai Institute of Higher Medical Sciences, Senior Consultant, Cardiothoracic Surgery Department. This work was performed at Department of Cardiothoracic and Vascular Surgery, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthigram, District Anantapur Andhra Pradesh, India.

Mixoma.

Ecocardiografia.

Septo

with a huge right ventricular myxoma obstructing the right ventricular outflow tract. CASE REPORT A 42 year old female patient presented with difficulty in breathing on moderate exertion, syncope, palpitation and chest pain. On examination there was a grade 3/6 ejection systolic murmur. There was no evidence of the Carney’s complex or family history of the cardiac mass. Chest X-ray revealed cardiothoracic ratio of 60% with no evidence of

Correspondence address Trushar P. Gajjar C-7, Residential Block – SSSIHMS Campus – Prasanthigram-515134 – District Anantapur, Andhra Pradesh, India E-mail: trushargajjar@gmail.com Article received on August 17th, 2011 Article accepted on October 25th, 2011

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the pulmonary metastasis. Electrocardiogram showed sinus rhythm with heart rate of 70 per minute. Transthoracic and transesophageal echocardiogram showed dilated right atrium and ventricle with a 9 cm x 6 cm x 5 cm sized homogenous mass, attached on the right ventricular side of interventricular septum without calcification or hyperlucency (Figure 1A). The mass was prolapsing into the right ventricular out flow tract (RVOT) and pulmonary artery (PA) (Figure 1B) producing the RVOT gradient of 75 mmHg. The tricuspid annulus was dilated which was measuring about 42 mm with severe tricuspid regurgitation and severe right ventricular dysfunction. The contrast enhanced computed tomogram was negative for the pulmonary and hepatic metastasis. A few days after the diagnosis, patient was taken up for surgery. The approach was through a conventional median sternotomy; the pericardium was opened and stayed.

Cardiopulmonary bypass was established after the aortic and bicaval cannulation. Under moderate hypothermia the aorta was cross clamped and a cold blood antegrade root cardioplegia was given. Both vena cava were looped after cross clamping the aorta to prevent embolization of tumor. The main pulmonary artery (MPA) and the right atrium (RA) were opened. A 9 cm x 6 cm x 5 cm sized, grayish brown, well encapsulated mass without any frond like projections was attached to the mid muscular part of the interventricular septum with narrow well defined stalk. The surrounding muscles were hypertrophied with some amount of fibrosis. The mass was obstructing the right ventricle and its outflow tract and was prolapsing into the main pulmonary artery (Figure 2). The tumor was excised from the MP A and the RA along with its stalk and the surrounding portion of the interventricular septum without creating a ventricular septal defect. After completing the excision, the MPA, branch pulmonary arteries, right ventricle, right atrium and the pericardial cavity were examined for tumor debris and thorough normal saline washes were given. The tricuspid and pulmonary valves were examined and found to be normal. Weaning from the cardiopulmonary bypass was smooth. The macroscopic findings showed a 9 cm x 6 cm x 5 cm sized grayish brown well encapsulated mass. On microscopic examination it revealed, the presence of polygonal, spindle shaped and stellate cells with the perivascular cuttings in a myxomatous and hemorrhagic background suggestive of the myxoma. The patient was recovered uneventfully. The echocardiogram done during immediate postoperative period and prior to the discharge showed, no residual myxoma, trivial tricuspid regurgitation and the right ventricular systolic pressure was 25 mmHg with good biventricular function. As patient was operated recently she is awaiting for her first follow up at 3 months.

Fig. 1 – Transesophageal echocardiogram showing: A – right ventricular myxoma with its attachment to the septum; B – right ventricular myxoma prolapsing into the main pulmonary artery causing right ventricular outflow tract obstruction. LA = Left Atrium; Ao = Aorta; RA = Right Atrium; RV = Right Ventricle, MPA = Main Pulmonary Artery

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Fig. 2 – Figure showing widely opened main pulmonary artery with right ventricular myxoma prolapsing across the pulmonary valve into it (Picture is taken from the head end of the patient)

Gajjar TP, et al. - Giant ventricular myxoma obstructing right ventricular outflow tract

DISCUSSION Cardiac myxomas are usually seen in adults, accounting for 25%-40% of all cardiac tumors from birth to adolescence [2]. The majority of myxomas (75%) are located in the left atrium whereas right ventricular myxomas are only found in 2-4% of cases [2] and multiple tumors are rarely [3]. A careful review of the literature on cardiac myxomas revealed 36 patients with tumor located in the right ventricle [4,5]. Czapek, in 1891, was among the first to provide a pathological description of a right ventricular myxoma [4]. Almost seventy years elapsed before Kishimoto and Sakaibori described another such tumor, which was recognized at postmortem examination, and Michaud and associates reported successful surgical removal of a right ventricular myxoma [5,6]. Myxomas were inserted mainly on the right ventricular wall or interventricular septum; in rare instances they involved the tricuspid valve [2,7]. The tumor was described to be infiltrating the ventricular myocardium in five patients [2,7]. In five patients a right ventricular myxoma was associated with other intracardiac myxomas and in one, with extracardiac anomalies [8-10]. From November 1991 till December 2010, total 220 cases of cardiac myxoma underwent surgical removal at our institute and the current case was the first one presented as an isolated right ventricular myxoma. The right sided cardiac tumors can present with signs and symptoms of congestive cardiac failure or shortness of breath, syncope, fatigue, edema, jugular venous distension, ascites, night sweats and pericardial effusion [11,12]. The right ventricular myxoma leads to some of the complications, and these are: vena cava syndrome, pulmonary embolism, right ventricular dysfunction and restrictive cardiomyopathy [11,12]. Electrocardiogram may show partial right bundle branch block due to right ventricular hypertrophy. Plain chest Xray is not diagnostic except for the pulmonary metastasis in cases of malignancy or the metastatic tumor. However the fluoroscopic evaluation may be helpful if the calcification is present in the myxoma [12]. Echocardiography is an excellent way to make a diagnosis by noninvasive means [12,13]. Echocardiogram will show a characteristic narrow stalk, tumor mobility and distensibility. Although broad based, non-mobile myxomas can occur [12]. The myxomas may be homogenous or may have central areas of hyperlucency representing hemorrhage and necrosis [12]. Presence of calcification with echogenic foci can be detected by echocardiogram [12]. Gadoliniumenhanced cardiovascular magnetic resonance imaging is one more noninvasive imaging modalities to differentiate between two different etiologies myxoma and thrombus. This study shows delayed heterogeneous enhancement of

Rev Bras Cir Cardiovasc 2011;26(4):663-6

the myxoma, whereas it does not show delayed enhancement of thrombus, which helps in conûrming the diagnosis of myxoma [13]. Various surgical approaches have been reported from the right atrium or the right ventricle in the literatures [1012]. The right atrial approach is sufficient in most of the right ventricular myxoma of small to average size. The right ventriculotomy approach may cause postoperative right ventricular dysfunction and it is not advisable. In our case the patient presented in her early 40’s with predominant symptoms of syncope and the difficulty in breathing, which is the classical presentation of intracavitary tumor. The family history was negative for the cardiac mass and the Carney’s complex was absent on examination. The diagnosis was confirmed by transthoracic and transesophageal echocardiography. The possibility of metastatic tumor was ruled out by 1) absence of signs and symptoms of the primary tumor, 2) absence of the pulmonary and hepatic metastasis on computed tomography scan and 3) absence of the typical locations (valves and extension in inferior vena cava) and appearance of the metastatic tumor on echocardiography. To prevent the recurrence certain basic and important points to be followed during the intraoperative period and they are, 1) the cardiac manipulation should be minimized to prevent intraoperative embolization until aortic cross clamping, 2) wide resection of the myxoma should be done including adjacent cardiac tissue and septum if required, 3) if the myxoma is removed in piecemeal, all debris should be cleared with careful removal and massive irrigation and suction, 4) an attempt to be made to remove the myxoma intact as far as possible. In our case the surgical approach was bicameral through the right atrium and the pulmonary artery. The bicameral approach helps in easy delivery of the large tumor in total, like in this case. The right atrial approach helps in identifying the stalk and its attachment to the ventricular septum and it also helps to repair the tricuspid valve if required. The pulmonary artery approach helps in 1) an easy delivery of a large tumor in total without damaging the pulmonary valve, 2) examination of the pulmonary valve and 3) exploration with removal of the tumor debris from the branch pulmonary arteries. In our experience with right ventricular myxomas, complete excision of the tumor was obtained by limiting the parts removed to the endocardium and to the myocardium surrounding the insertion of the pedicle. Full-thickness excision of the right ventricular wall is not justified in our opinion, since there are no reports of recurrence of such neoplasm; however, it would be necessary in the case of obvious or even suspected local infiltration. In conclusion, the right ventricular myxoma is a rare anomaly and very few cases of this condition are reported 665

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in the literature. The presenting symptoms are syncope and right sided failure. Echocardiography is an ideal diagnostic modality. Surgical removal by the right atrial approach is sufficient in a small or an average size tumor but, the bicameral approach is advisable and preferable for a large tumor along with all the basic precautions to prevent an embolism and recurrence. Complete excision of the tumor with excision of the tissue surrounding the pedicle including endocardium and myocardium is sufficient.

6. Kishimoto M, Sakaibori S. Primary tumor of the heart: report of a case with myxofibroma of the right ventricle. Am Heart J. 1959;57(5):769-74.

REFERENCES 1. Gottsegen G, Wessely J, Arvay A, Temesvari A. Right ventricular myxoma simulating pulmonic stenosis. Circulation. 1963;27:95-7. 2. Crummy AB, Hipona FA. The radiographic aspects of right ventricular myxoma. Brit J Radiol. 1964;37:468-71.

7. Hubbard TJ, Neil RN. Myxoma of the right ventricle. Report of a case with unusual findings. Am Heart J. 1971;81(4):548-53. 8. Liebler GA, Magovern GJ, Park SB, Cushing WJ, Begg FR, Joyner CR. Familial myxomas in four siblings. J Thorac Cardiovasc Surg. 1976;71(4):605-8. 9. Balk AH, Wagenaar SS, Bruschke AV. Bilateral cardiac myxomas and peripheral myxomas in a patient with recent myocardial infarction. Am J Cardiol. 1979;44(4):767-70. 10. Inoue L, Kobayashi K, Kato Y. A cardiac myxoma: case report of a massive right ventricular myxoma associated with a left atrial myxoma. Heart. 1971;2:1157.

3. Pontes JCDV, Silva GVR, Benfatti RA, Duarte JJ. Multiple left atrial myxoma: case report. Rev Bras Cir Cardiovasc. 2011;26(3):497-9

11. Paraskevaidis IA, Triantafilou K, Karatzas D, Kremastinos DT. Right ventricular multiple myxomas obstructing right ventricular outflow tract. J Thorac Cardiovasc Surg. 2003;126(3):913-4.

4. Melendez LJ, Sears GA, Coles JC. Right ventricular tumour demonstrated by echocardiography. Can Med Assoc J. 1978;118(1):62-3.

12. van der Heusen FJ, Stratmann G, Russell IA. Right ventricular myxoma with partial right ventricular outflow tract obstruction. Anesth Analg. 2006;103(2):305-6.

5. Bortolotti U, Mazzucco A, ValfrĂŠ C, Valente M, Pennelli N, Gallucci V. Right ventricular myxoma: review of the literature and report of two patients. Ann Thorac Surg. 1982;33(3):277-84.

13. Satitthummanid S, Tumkosit M, Benjacholamas V, Chattranukulchai P, Boonyaratavej S, Puwanant S. Right ventricular myxoma. J Am Coll Cardiol. 2011;57(5):630.

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Coronary artery bypass graft surgery after acute myocardial infarction caused by thrombosis of coronary aneurysm Cirurgia de revascularização miocárdica após infarto agudo do miocárdio causado por trombose de aneurisma coronariano

Victor Rodrigues Ribeiro Ferreira1, Valéria B. Braile Sternieri2, João Carlos Ferreira Leal3, Luis Ernesto Avanci4, Achilles Abelaira Filho5, Mariane Spotti6, Arthur Soares Souza Junior7, Domingo Marcolino Braile8

DOI: 10.5935/1678-9741.20110061

RBCCV 44205-1337

Abstract The morphology of coronary aneurysm sets a predisposing factor to thrombus formation. However, the blood stasis caused by the change in flow may not be enough to cause thromboembolic events.

Resumo A morfologia do aneurisma coronariano configura um fator predisponente para formação de trombos. Porém, a estase sanguínea causada pela alteração do fluxo pode não ser o suficiente para causar fenômenos tromboembólicos.

Descriptors: Myocardial infarction. Coronary thrombosis. Coronary aneurysm.

Descritores: Infarto do miocárdio. Trombose coronária. Aneurisma coronário.

1. Cardiologist at Domingo Braile Institute; Cardiointensivist of postoperative cardiovascular surgery at Domingo Braile Institute, São José do Rio Preto, SP, Brazil. 2. Clinical Cardiologist; Director at Domingo Braile Institute; Clinical Director at Hospital Beneficência Portuguesa of São José do Rio Preto, SP, Brazil. 3. Master’s Degree in Cardiovascular Surgery at Campinas University (UNICAMP); Adjunct Professor at FAMERP, São José do Rio Preto, SP, Brazil. 4. Cardiovascular Surgeon; Coordinator of the Postoperative of Cardiovascular Surgery at Domingo Braile Institute, São José do Rio Preto, SP, Brasil. 5. Cardiovascular Surgeon, São José do Rio Preto, SP, Brazil. 6. Specialist in Cardiology and Cardioradiology, São José do Rio Preto, SP, Brazil. 7. Member of the Pediatric Radiology Service at Base Hospital – Faculty of Medicine of São José do Rio Preto and Ultra-X Diagnóstico por Imagem of São José do Rio Preto, São José do Rio Preto, SP, Brazil.

8. Emeritus Professor at FAMERP and Senior Professor at Campinas University (UNICAMP); Head Editor of Brazilian Journal of Cardiovascular Surgery; São José do Rio Preto, SP, Brazil.

This study was carried out at Domingo Braile Institute and Beneficência Portuguesa Hospital of São José do Rio Preto, São José do Rio Preto, SP, Brazil.

Correspondence address: Victor Rodrigues Ribeiro Ferreira Rua Luiz Vaz de Camões, 3111 – São José do Rio Preto, SP, Brazil – Zip Code: 15015-750 E-mail: dr.victorrodrigues@yahoo.com.br

Article received on September 12th, 2011 Article accepted on October 25th, 2011

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Ferreira VRR, et al. - Coronary artery bypass graft surgery after acute myocardial infarction caused by thrombosis of coronary aneurysm

INTRODUCTION Currently, the diagnostic resources have been extensively explored, in order to modify the natural course of disease. Even with the growing availability of coronary angiography, coronary aneurysms in young patients has been an unusual finding. Early diagnosis is essential to avoid undesirable outcomes. However, the big problem is how to proceed in asymptomatic patients. The coronary aneurysm can be defined as a focal dilatation that exceeds 50% the diameter of the adjacent normal coronary region, and may also be considered giant when the transverse dimension of the vessel exceeds 2 cm [1]. The prevalence of angiographic coronary aneurysms varies from 0.15% to 4.9% depending on the considered literature [2]. The first descriptions of coronary aneurysms began in 1761 with Morgagni, obviously based on autopsies. Most patients do not present any symptoms. Atherosclerosis is the most common cause, reaching 50% in data released in Europe and the United States [2]. However, we should always consider as relevant causes the Kawasaki Disease and other vasculitides such as polyarteritis nodosa and Takayasuâ&#x20AC;&#x2122;s arteritis, autoimmune diseases, infectious diseases (including syphilis and Lyme disease), connective tissue diseases, congenital malformations, trauma, dissections and complications of procedures such as angioplasty [3]. This last cause has increased in direct proportion to the growth of its practice. Currently, we have discussed the pathophysiology of coronary aneurysm formation after implantation of drugeluting stents that lead to high local inflammatory activity, followed by vasculitis. Products such as sirolimus suppresses smooth muscle proliferation and neointima for a long time. Since some drugs used in the coating stents may disappear in a few weeks, the persistent inflammatory process has been attributed to the polymer structure of the prosthesis, as well as poor positioning of the filaments [4,5]. Considering atherosclerosis as the main cause of the formation of aneurysms, the histological study of these vessels revealed deposition of lipids in the vessel wall associated with diffuse hyalinization, focal calcification and fibrosis, leading to rupture of the intima and media layers, and intramural hemorrhage [6 ]. The morphology of coronary aneurysm itself sets a predisposing factor to thrombus formation. However, the blood stasis caused by the change in flow may not be enough to cause thromboembolic events. Therefore, the investigation of thrombophilia is critical, especially in young patients, since this association will influence the diagnostic therapeutic management of the patient. 668

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CASE REPORT A case that illustrates what is being discussed is that of a 24-year-old female patient, white, body mass index (BMI) of 29, who sought medical care in our hospital complaining of severe chest pain of constrictive type without improving or worsening. The electrocardiogram performed on admission revealed ST segment elevation in inferolateral wall. Ischemic serum markers revealed CPK 338 U/l (NR:145), CK 39 U/l (NR:24), troponin I 3.384 ng/ml (VR:0.060). The patient underwent coronary angiography, which showed obstructive coronary artery disease by total occlusion of the right coronary artery with thrombosed vascular malformation and an image suggestive of coronary dissection, which was performed balloon percutaneous transluminal angioplasty and thrombus aspiration with partial success (Figure 1).

Fig. 1 - Coronary Computed Tomography Angiogram, showing the right coronary artery aneurysm formation obstructed in its proximal third, with no wall plaque

The echocardiogram revealed concentric left ventricular remodeling, with medium-basal asynergy inferoseptal of the right ventricular inferior wall, but with preserved contractile function. About four hours after the procedure, the patient had a new episode of chest pain associated with typical electrocardiographic changes, reinfarction was diagnosed and administration of tirofiban hydrochloride was started. The patient had remission of symptoms and laboratory improvement. Two days later, the patient developed

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paresthesia in the first and second fingers in a region adjacent to the puncture of catheterization. Artery color Doppler was performed right upper limb, which revealed obstruction of the radial artery. Later, it was decided to perform angiography of the coronary arteries by computed tomography, which revealed complete obstruction of the proximal right coronary artery, mural and unmarked sharp increase in the diameter of the portion of pre-obstructive coronary artery, reaching 10 mm in transverse diameter. The coronary artery appeared to have continuity caliber almost completely thrombosed, which later presented the course in a semicircle, having its distal end an amorphous collection of iodinated contrast, located in an antero-superior position to the right pulmonary vein, anteromedial in relation to vena cava inferior and posterior to the ascending aorta at the time of the left atrial appendage. This collection was in contiguity with the wall of the left atrium and presented an image that suggested communication with the superior vena cava through a small path, which may represent a finding of overlapping images. There was opacification of the distal and middle thirds of the right coronary artery, including the marginal artery, probably by collateral.

Two months after the event described above, the patient underwent a new cineangiocoronariography via the right limb, which revealed malformation of the right coronary artery, with severe tubular dilation and significant obstruction affecting approximately 80% of the vessel lumen. The patient developed pain and numbness in the right limb, being performed arterial color Doppler, which revealed occlusion in the distal third of brachial artery by hypoechoic and homogeneous content, suggestive of thrombus located 4 cm from the dissection scar of the catheterization. The patient then underwent brachial artery embolectomy. This was followed by investigation of thrombophilia, with no significant abnormalities in blood tests. So we opted for surgical treatment, being performed coronary artery bypass grafting with right aortocoronary venous graft, with cardiopulmonary bypass. The patient remained in intensive care unit for 48 hours and was discharged after seven days of hospitalization. The patient is asymptomatic to date and treated with dual inhibition of platelet aggregation with the use of aspirin and clopidogrel. After 18 months of surgery, the patient underwent a new coronary angiography, which revealed proximal right coronary artery aneurysm containing an image suggestive of thrombus, total occlusion of the artery and saphenous vein graft in the distal segment of the right coronary artery patency and without lesions (Figure 2).

REFERENCES 1. Nichols L, Lagana S, Parwani A. Coronary artery aneurism: a review and hypothesis regarding etiology. Arch Pathol Lab Med. 2008;132(5):823-8. 2. Syed M, Lesch M. Coronary artery aneurysm: a review. Prog Cardiovasc Dis. 1997;40(1):77-84. 3. Pahlavan PS, Niroomand F. Coronary artery aneurysm: a review. Clin Cardiol. 2006;29(10):439-43. 4. Bavry AA, Chiu JH, Jefferson BK, Karha J, Bhatt DL, Ellis SG, et al. Development of coronary aneurysm after drug-eluting stent implantation. Ann Intern Med. 2007;146(3):230-2. 5. Slota PA, Fischman DL, Savage M, Rake R, Goldberg S. Frequency and outcome of development of coronary artery aneurysm after intracoronary stent placement and angioplasty. STRESS Trial Investigators. Am J Cardiol. 1997;79(8):1104-6. Fig. 2 - Coronary Computed Tomography Angiogram, showing obstructive lesion in the right coronary artery with saphenous vein graft in the distal region of this patent artery

6. Hawkins JW, Vacek JL, Smith GS. Massive aneurysm of the left main coronary artery. Am Heart J. 1990;119(6):1406-8.

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CASE REPORT

Heart valve papillary fibroelastoma associated with cardioembolic cerebral events Fibroelastoma papilífero de valva cardíaca associado a eventos cerebrais cardioembólicos

Luciano Cabral Albuquerque1, Vanessa Devens Trindade2 DOI: 10.5935/1678-9741.20110062

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Abstract Papillary fibroelastomas of the heart valves are benign, slow-growing, rare tumors of the heart. This tumor represents a potential cause of systemic embolism, stroke, myocardial infarction and sudden death. Early diagnosis is very important, as surgical excision of these tumors can prevent cerebrovascular and cardiovascular complications. Diagnosis is usually made by transesophageal echocardiogram. We describe two cases of patients with papillary fibroelastomas causing cardioembolic cerebral events, which underwent successful surgical treatment. The authors present a brief review of the literature.

Resumo Fibroelastoma papilífero é um tumor benigno, raro e de crescimento lento, que geralmente tem origem no endocárdio das valvas cardíacas. Este tumor representa uma causa potencial de embolia sistêmica, infarto agudo do miocárdio, acidente vascular cerebral e morte súbita. O diagnóstico precoce é fundamental, já que a excisão cirúrgica pode evitar complicações cerebrovasculares e cardiovasculares. O diagnóstico geralmente é feito pelo ecocardiograma transesofágico. Neste trabalho, são descritos dois casos de pacientes com fibroelastoma papilífero de valva aórtica, causando eventos cerebrais cardioembólicos, que foram submetidos com sucesso a tratamento cirúrgico. Apresenta-se, ainda, uma sucinta revisão da literatura.

Keywords: Fibroma. Heart neoplasms. Aortic valve. Stroke.

Descritores: Fibroma. Neoplasias cardíacas. Valva aórtica. Acidente cerebral vascular.

INTRODUCTION Papillary fibroelastoma is a rare primary benign cardiac tumor that usually involves cardiac valves. It represents about 7% of all primitive cardiac tumors, third for frequency after myxoma and lipoma [1]. Their early detection is important because they are a potential cause of systemic emboli, stroke, myocardial infarction and sudden death. Although there is no consensus, prompt surgical excision of these tumors is recommended owing to the risk of preoperative thromboembolic phenomena disabling consequences [2]. We present two cases of papillary

1. PhD and ScD in Cardiovascular Surgery. 2. Medicine Student.

Work performed at São Lucas Hospital of Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

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fibroelastomas located in the non-coronary cusp of the aortic valve causing cardioembolic cerebral events. CASES REPORT Patient 1 A 77-year-old woman was admitted with history of transitory vertigo and syncope. Her past medical history was significant for hypertension and hyperlipidemia. On physical examination the patient was well nourished, alert and oriented. Her blood pressure was 130/68 mmHg, pulse was 52 bpm. Chest auscultation did note revealed

Correspondence address: Vanessa Devens Trindade Av. Ipiranga, 6690 – cjto, 615 – Azenha – Porto Alegre, RS Brazil – Zip Code: 90160-090 E-mail: vanessad.trindade@gmail.com Article received on August 31st, 2011 Article accepted on November 14th, 2011

Albuquerque LC & Trindade VD - Heart valve papillary fibroelastoma associated with cardioembolic cerebral events

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abnormalities. Neurological physical examination was normal. Electrocardiogram showed only sinus bradycardia. Computed tomography demonstrated hypodense lesions of the upper right cerebellar hemisphere and lenticular nucleus with embolic characteristics. Carotid duplex Doppler studies showed no vascular abnormalities. On transesophageal echocardiography, a mobile, rounded echodense mass with 7 mm was attached to the noncoronary cusp of the aortic valve (Figure 1). Based upon clinical symptoms and echocardiographic findings, the patient underwent surgical excision of the aortic tumor. On cardiopulmonary bypass, aortotomy revealed a friable pink granular mass, which was present at the middle portion of the non coronary cusp. The mass was carefully excised, and, due to impossibility of reconstruction, aortic valve replacement was performed with a 23 mm aortic bioprosthesis. A final pathologic report revealed the presence of a papillary fibroelastoma and the patientâ&#x20AC;&#x2122;s postoperative course was smooth and uncomplicated. She was discharged on the sixth day of post-operative.

image studies. Surgical excision showed a pinkish, friable, myxomatous circumferential lesion attached to the non coronary aortic cusp. The leaflet was sutured with 6-0 polypropylene sutures, but by excessive tension on the suture line, proceeded to aortic valve replacement with a 25 bioprosthesis. The patient experienced an uneventful postoperative course. Histological examination showed papillary formations with homogenized stroma and slightly broadened endothelial cells on the surface, confirming the diagnosis of papillary fibroelastoma (Figure 2).

Fig. 2 â&#x20AC;&#x201C; Endothelium-coated tumor rich in extracellular matrix, collagen and elastin, both muscle cells and elastic fibers (orcein 10x magnification)

DISCUSSION

Fig. 1 â&#x20AC;&#x201C; Transesophageal echocardiography showing a rounded echodense mass with 7 mm attached to the non-coronary cusp of the aortic valve

Patient 2 A 42-year-old woman was admitted with transient and reversible right hemianopsia associated with paresthesia in the left arm. The patient had no relevant cardiologic history and physical examination showed no pathological findings. Neurological clinical examination was normal. Computerized tomography showed no abnormalities. Echocardiographic examination of the carotid arteries was normal. A transoesophageal echocardiography showed a pedunculated, mobile structure on the aortic surface of the non-coronary cusp of the aortic valve (0.9 cm long), probably a fibroelastoma or vegetation for its physical aspect on

Papillary fibroelastoma is a rare and benign cardiac tumor [3]. Is the third primitive cardiac tumor after myxoma and lipoma, representing nearly 80 to 90% of tumors which take their origin from valvular endocardium. Aortic cusps are the most frequently involved, followed by mitral leaflets [1]. The incidence appears to be equal in males and females. Macroscopically, it is a small mobile mass, measuring between 2 and 28 mm, only 1% being bigger than 20 mm [1]. Microscopically, the tumor is covered by endothelium, which surrounds a core of loose connective tissue consisting of an acid mucopolysaccharide matrix, smooth cells, collagen, and elastin fibers. It may also contain cysts and areas of hemorrhage. Pathogenesis is unclear. Some authors consider it to be congenital, however, the majority seem to be acquired, most likely of neoplastic or thrombotic origin. However the most accepted hypothesis considers these lesions to originate from giant Lambl excrescences, formed by affixing layers of fibrin on the endothelium [2]. 671

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The clinical presentation varies widely from asymptomatic to severe embolic complications. Some common presentations include transient ischemic attacks, stroke, angina, myocardial infarction, death, acute coronary syndrome, and syncope. Embolic fragments may originate from the tumor itself and this occurs because of it very friable and soft texture, or from surface formation of platelet and fibrin thrombi [4]. In the past, the majority of papillary fibroelastomas were occasional findings found during necropsy. More recently, with the advent of echocardiography, an in vivo diagnosis became more frequent, since only masses measuring less than 2 mm are not clearly visible [1,2,5]. The most reliable diagnostic tool is transesophageal echocardiography, and it should be performed before surgery, in order to define location and relation with adjacent structures. The differential diagnosis of this rare and benign tumor is rather extensive and includes the presence of myxoma [6], lipoma [7,8], rhabdomyoma or amorphous tumors [9]. The presence of vegetative endocarditis and Lambl’s excrescences should also be considered during the differential diagnosis. While myxomas primarily affect the left atrium, lipoma and rhabdomyoma are characteristically intramural. Endocarditis has clinical diagnostic criteria accurate enough, absent in cases of fibroelastoma. Moreover, the appearance of fibroelastoma is quite characteristic, resembling a “sea anemone” with multiple ramifications held by a pedicle to endocardium. The best clinical treatment of asymptomatic patients remains unclear. Most authors recommend elective surgical resection in asymptomatic and symptomatic patients because of the unpredictable nature of these pedunculated tumors [1,2], especially larger ones attached to the aortic valve via a pedicle. It is our opinion that tumor resection is mandatory, even if the patient is asymptomatic, unless clinical conditions indicate high surgical risk. In both our cases, there was an occurrence of recurrent cerebral ischemia. Surgical management of papillary fibroelastoma in aortic valve may include simple resection of the mass, resection with valve repair or resection with valve replacement. Ngaage et al. [10], reporting on the treatment and outcome of patients with cardiac papillary fibroelastoma, demonstrated an 83% rate of simple shave excision without report of recurrence. However, most authors recommend the excision of valve cusp, and valve replacement if repair is not possible. Although we are not in favor or a routine valve replacement, in our cases simple suture after resection of the lesion presented tension, judged as a risk for the development of late dysfunction. Some authors have encouraged the use of the fiberscope for resecting of intracardiac masses as a promising technique [3]. 672

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CONCLUSIONS It is our understanding that surgical treatment of papillary fibroelastoma should be performed to avoid stroke, even in asymptomatic patients. It should be considered in the differential diagnosis of cerebral ischemia, especially those with embolic nature shown in CT with unknown cause.

REFERENCES 1. Borsani P, Mariscalco G, Blanzola C, Leva C, Bruno VD, Cozzi G, et al. Asymptomatic cardiac papillary fibroelastoma: diagnostic assessment and therapy. J Card Surg. 2006;21(1):77-80. 2. Saxena P, Konstantinov IE, Lee A, Newman MA. Papillary fibroelastoma of aortic valve: early diagnosis and surgical management. J Thorac Cardiovasc Surg. 2007;133(3):849-50. 3. Dallan LA, Oliveira SA, Barreto ACP, Iglézias JCR, Verginelli G, Jatene AD. Fibroma cardíaco mimetizando cardiomiopatia hipertrófica. Rev Bras Cir Cardiovasc. 1989;4(3):242-8. 4. Abdulmassih Neto C, Salerno PR, Dinkhuysen JJ, Chaccur P, Arnoni AS, Zamorano MMB, et al. Correção cirúrgica dos tumores primários do coração. Rev Bras Cir Cardiovasc. 1992;7(2):145-52. 5. Silva RP, Pinheiro A, Costa I, Costa Filho JE, Rodrigues Sobrinho CRM, Andrade PJN, et al. Tumores cardíacos: aspectos clínicos, ecocardiográficos e histopatológicos. Rev Bras Cir Cardiovasc. 2003;18(1):60-4. 6. Pontes JCDV, Silva GVR, Benfatti RA, Duarte JJ. Multiple left atrial myxoma: case report. Rev Bras Cir Cardiovasc. 2011;26(3):497-9. 7. Figueira F, Moraes Neto F, Moraes CRR. Lipoma resection of the interventricular septum. Rev Bras Cir Cardiovasc. 2010;25(4):591-3. 8. Joaquim MR, Braile DM, Arruda MVF, Soares MJF. Right atrial lipoma resection and partial reconstruction using bovine pericardium. Rev Bras Cir Cardiovasc. 2009;24(2):239-41. 9. Sousa JS, Tanamati C, Marcial MB, Stolf NAG. Calcified amorphous tumor of the heart: case report. Rev Bras Cir Cardiovasc. 2011;26(3):500-3. 10. Ngaage DL, Mullany CJ, Daly RC, Dearani JA, Edwards WD, Tazelaar HD, et al. Surgical treatment of cardiac papillary fibroelastoma: a single center experience with eighty-eight patients. Ann Thorac Surg. 2005;80(5):1712-8.

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Dr. Cid Nogueira A medical pioneer of cardiac surgery in Brazil Paulo Rodrigues da Silva1

DOI: 10.5935/1678-9741.20110063

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Dr. Cid Nogueira, a cardiovascular surgeon, was born Janeiro, open heart surgery with cardiopulmonary bypass, in the city of Araguari, Minas Gerais, on May 6, 1929, son when he had his first contact with Dr. Cid Nogueira. of Achileu Nogueira and Carmen Nogueira. The President of Brazil, newly elected at the time, Dr. He died in Brasilia on October 1, 2011, at 82 years of Juscelino Kubitschek de Oliveira, who was also a physician, age, after some health problems later in his life when, due witnessed this surgery, along with Professor Dr. Jose Hilario to a cardiomyopathy, had to have a synchronizer and an and then young Dr. Cid Nogueira (Figure 1). automatic cardiac defibrillator implanted. Thanks to the action of our President and all these He graduated as a doctor by the National School of figures, including the young Dr. Cid Nogueira; Dr. Earl B. Medicine, Federal University in Rio de Janeiro. Kay left in Brazil a heart-lung pump discs system, KayHe started his activities in cardiovascular and thoracic Cross model. surgery as Medical Officer of the Navy, stationed at Naval This machine was then used by Dr. Hugo Felipozzi in Hospital Marcilio Dias, of Rio de Janeiro. São Paulo, starting in that city its mass production for all In 1955, he was referred by his boss at the Hospital Brazilian cardiac surgeons. Marcilio Dias, Dr. Edídio Guertzenstein to start residency Dr. Cid Nogueira played an important role in world in Thoracic and Cardiovascular Surgery at St. Vincent cardiac surgery, specifically in plastic heart valve surgery Charity Hospital in Cleveland, Ohio, USA, in the Service of (aortic and mitral), as well as in prosthetic valve Dr. Earl B. Kay. replacements. Dr. Kay was already known and creator of the disc oxygenator for open heart surgery, Kay-Cross model. In the same hospital, under the leadership of Dr. Earl B. Kay, Dr. Cid Nogueira also had the guidance of other famous medical experts such as Dr. Henry A. Zimmerman, a cardiologist and of the pioneers of cardiac catheterization in the world, David Mendelsohn, Jr., intensivist and anesthesiologist, and Córcoran, who was researcher in cardiac physiology. In Cleveland, immediately, Dr. Cid Nogueira stood out, becoming the first assistant of Dr. Kay’s Service. We were witnesses of his personal and technical prestige on that service, when in 1960 we began our training as residents in the service of Dr. Kay. Fig. 1 - Record of the 1st heart bypass surgery in Rio de Janeiro. Among those present: Dr. It is interesting to note that Dr. Kay Jose Hilario, Henry A. Zimmerman, Earl B. Kay, Cid Nogueira and President of Brazil, Dr. came to Brazil in 1956 and held in Rio de Juscelino Kubitschek de Oliveira, who was also a physician 673

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Importantly to highlight his work on resection of aortic valves of patients, followed by replacement of the valves for individualized prosthetic leaflets, made with a plastic fabric of Teflon coated with polyurethane, in order to prevent leakage of blood between the meshes of plastic material. Dr. Cid Nogueira, along with another resident of Dr. Kay, Dr. Akio Suzuki, of Japanese origin, was one of those who hand-sewn these valve prostheses. In 1958, Dr. Cid Nogueira in the National Congress of Cardiology in Rio de Janeiro, at the Copacabana Palace Hotel, demonstrated how these valve prostheses were made and implanted in the aorta. I remember the reason we were there, it was a presentation very useful and informative for all of us in Brazil. Dr. Cid Nogueira, after five years of residence in Cleveland, had the honorable invitation to work in Holland, with medical and surgical groups in Amsterdam and Utrecht, when he had the opportunity to introduce the open heart surgery of the mitral and aortic valves in that country. In 1966, at the invitation of Professor of Surgery Dr. Jose Hilario, he had the opportunity to organize and manage the Service of Cardiovascular Surgery of the Department of Surgery, Federal School of Medicine in Porto Alegre (UFRGS). He spent six years working in Porto Alegre. It was him who introduced the use of mitral and aortic prostheses in that city. In 1968, at the invitation of Professor Dr. Mariano de Andrade, he started working at the Faculty of Medicine in which he had graduated, as well as in several other teaching hospitals in Rio de Janeiro. From the Public Hospitals of the State of Rio de Janeiro, he was invited to operate in Brasilia, where he was appointed as Chief of Cardiovascular Surgery of the General Staff of the Armed Forces. Dr. Cid Nogueira in his activity as a heart surgeon, trained and prepared numerous specialty surgeons in Brazil, namely, forgive us any omissions: in Porto Alegre, we highlight Dr. John Batista Pereira, Felisberto Ferreira, Nelson Pizatto Ernesto Figueiredo, Ivo Abrahão Nesralla, Polyguara Silveira da Costa, Paul Prates,

Gilberto Venossi Barbosa and Blau Fabrício de Souza; in Rio de Janeiro, Drs Antonio Augusto Miana, Alexandre Brick, Eduardo Sergio Bastos and Marco Antonio Cunha, as well as his cousin, also competent expert, Dr. Odilon Nogueira Barbosa, who is currently a cardiovascular surgeon at the National Institute of Cardiology, previously known as Hospital of Cardiology of Laranjeiras. We shall emphasize that some of his assistants, besides excellent experts, attained the presidency of the Brazilian Society of Cardiovascular Surgery (BSCVS). At the end of his life, in Brasilia, Dr. Cid Nogueira was appointed and served as a physician in the Senate. In addition to the aforementioned, Dr. Cid Nogueira made several important technical-surgical contributions, namely: a. contributions to the surgical treatment of septal and valvular complications after acute myocardial infarction; b. contributions in the resection of left ventricular chagasic aneurysms; c. “Valve prosthesis. Clinical application of Kay-Suzuki valve.” Title of his Thesis defended in his Concourse for Full Professor of Cardiovascular Surgery at Federal University of Rio de Janeiro in 1970, in which he was approved. This thesis refers to the application in 60 patients with prosthetic valve disk of pyrolytic carbon, which passed into the left ventricle without turning to a vertical position, thus occupying the smallest space in the left ventricle. Dr. Cid Nogueira was a Founder and Member of the Brazilian Society of Cardiovascular Surgery. In 1969, the XXV Brazilian Congress of Cardiology in Belo Horizonte, at the time of the First Ordinary General Assembly of the Department of Cardiovascular Surgery of the Brazilian Society of Cardiology, Dr. Cid Nogueira was elected to the board of the latter, together with the Dr. Domingos Junqueira de Moraes, Delmont Bittencourt, Luiz Carlos Bento de Souza and Ivo Nesralla. In addition, we can say that cardiovascular surgery in Brazil as a whole deeply grieves over the death of this brilliant Brazilian Cardiovascular Surgeon.

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Cid Nogueira Paulo R. Prates1

DOI: 10.5935/1678-9741.20110064

The history of Medicine, which began when a human being first felt the need to alleviate the suffering of a fellow, is very rich. Within this history, the development of cardiac surgery is certainly the most beautiful one. The pioneering spirit has always been its most striking feature, since the first suture of a heart wound by Ludwig Rehn in 1896, when the heart was still considered an untouchable organ. Less than one hundred years later, the man, after cutting and suturing the heart, replacing its valves and even the beats, removed the organ of a person and put it back in another personâ&#x20AC;&#x2122;s chest, where he continued making progress. Dr. Cid Nogueira was, undoubtedly, one of these pioneers. He arrived in Porto Alegre, Rio Grande do Sul in 1961, where mechanical ventilation was little-known, where there were very few Postoperative Recovery, and, where the surgery was still performed by a specialist in general

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practice and surgery with anesthesia in many towns of Rio Grande do Sul countryside, often being performed by a nurse technician. His goal was to develop a program of cardiac surgery with cardiopulmonary bypass use. The first surgery performed with cardiopulmonary bypass was performed by John Gibbon in 1953 in the USA. In 1961, our city and our state had in its midst a team performing what was considered an important leap in the history of medicine: the use of a machine to replace the heart, while the cavities were approached surgically. In September 1960, a heart valve was replaced for the first time by Albert Starr, in Oregon, also in the United States. In 1962, Dr. performed the same procedure in Porto Alegre. The diagnostic methods in cardiology had their great development. Surgery as a whole, achieved an unexpected progress, since the heart surgery required more than general surgery for their accomplishment. Excellent technician, trained in Cleveland, one of the cradles of modern cardiac surgery, leveraged the progress in many fields of medicine in our state. At his 82 years old, Dr. Cid deceased on 1 October, 2011, but left among us a school that followed in his footsteps. I am very proud to have been recognized by him as one of his disciples. Thank you very much, Dr. Cid Nogueira!

Figure 1 - Picture from 1962 showing Dr. Cid Nogueira (facing forward) during a cardiac surgery in Porto Alegre. Photo Credit: Bortolo Achutti

1. Cardiovascular Surgeon at Rio Grande do Sul Cardiology Institute / University Foundation of Cardiology (IC / FUC) Full Member of the Brazilian Society of Cardiovascular Surgery, Porto Alegre, RS, Brazil.

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National impact Fábio de Castro /FAPESP Agency

DOI: 10.5935/1678-9741.20110065

Compared to all the countries of Latin America and the BRIC (Brazil, Russia, India and China), Brazilian scientists are those who can impact rates higher with publications in national journals. The analysis was performed by Felix Moya, a researcher at the Department of Dynamics of Science and Innovation at Policy Institute and Public Goods in Granada (Spain) during the 2nd Seminar on Performance Evaluation of Brazilian journals on JCR, held last Friday Monday (16/9) at the headquarters of FAPESP, São Paulo. The event was supported by the Scientific Electronic Library Online (SciELO), created in 1997 through a partnership between FAPESP and the Latin American and Caribbean Information Center in Health Sciences (Bireme). The aim of the seminar was to discuss the growing visibility achieved by Brazilian science in Journal Citation Reports (JCR), the most important international index of citations. The quantity of national periodicals indexed in JCR grew by 43% from 2009 to 2010. According to Moya, besides the increased presence of Brazilian scientific publications in the international scenario, these publications clearly improved their impact abroad as well. Proof of this is that when compared to other Latin American countries or BRIC countries, Brazil has managed to attain the highest impact rates by publishing in national journals. “SciELO has a lot to do with this, undoubtedly. No other country in the world has a national project providing open access to publications like this one. It’s not everything that is needed in the area for disclosure of Brazilian science, but it is a very important step forward and has not been done in other countries,” he told FAPESP Agency. Impact in itself is not an end, however, according to Moya. “The pursuit of greater impact is a measure that can be considered a symptom of the improved quality of research. There is a clear co-relation between impact and research excellence. The importance of this, however, is not limited to the scientific field: the high impact of research has major social relevance,” he says. The analysis, however, should be performed carefully, according to Moya. In his opinion, what is not true for a researcher could be true for the country. 676

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“If someone says that every study published in a high impact journal will be a work of excellence it is a lie. But if someone says that the Brazilian researchers who tend to publish in higher impact journals will have a greater quantity of works of excellence, this is true,” he affirms. According to him, it is preferable that researchers submit to more rigorous and competitive processes for publication of their study because this guarantees the overall quality of these studies in the scientific community. But even if they are not the favorites, low impact journals serve a purpose. “Lower impact magazines will only allow authors to be published if they can publish in high impact publications. For others, one should have other journals. The works published in lower impact magazines are not necessarily of worse quality. The same researcher may publish alternatively in both types of magazines. This subject is very poorly analyzed and the conclusions are weak when looking at individual cases. It is a subject that should be analyzed as a system,” affirms. According to the Spanish researcher, the complex system of communication in science manages to disseminate knowledge in distinct levels of journals. “Neither the researchers, nor the journals are stagnant. What is lacking is greater observance of the trends that both journals and researchers should follow,” he says. If for the researchers it is recommendable to pursue publication in high impact journals, for journals developing an editorial policy that increases international collaboration is fundamental. For Moya, the editors should develop scientific marketing activities. “It would be interesting, for example, if the editors of Brazilian journals sent each one of scientists cited in its journals a communiqué about their citation. This would generate a process of dialogue, prompting the authors of the works to become familiar with journal, since they are potential collaborators. This type of scientific marketing practice improves the international visibility of works,” he notes. According to Moya, when the journal has more international collaborations, the authors increase the spectrum of the origins of their citations. “I believe that

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this is why there is a difference between the activities of an editor, who is focused on the journal’s scientific level, and the publisher, who is the professional editor focused on obtaining the highest possible visibility for the journal in the communication arena. Not all journals have publishers, but it is a central role in the process,” he says. Internationalization of science During the event, Carlos Henrique de Brito Cruz, scientific director at FAPESP, highlighted the Foundation’s interest in accompanying the performance of Brazilian journals that would garner more international interest and increase visibility. “We are interested in accompanying the performance and development of these journal collections to know which actions we can take to step up our progress in this area. On the other hand, we hope that the debate helps to diagnose the bottlenecks and problems so that we can seek solutions to them.” he noted. Brito Cruz also highlights the importance that internationalization of Brazilian science affords for consolidation of scientific publications. According to him, the progress of science occurs more intensely when there is dialogue between scientists from several parts of the world. “When we measure the impact of publications, we want to evaluate communication. Publishing a scientific article is an act of communication. It is a means of communicating discoveries to others and submitting them to criticism. I would like for science conducted in Brazil to converse more with the world. The more intelligent people from here dialogue with intelligent people from around the world, the more Brazilian science will progress,” he sums up. According to Abel Packer, operational coordinator of SciELO, there was a 17% increase in the periodicals published under the program from 2007-2010. The mean growth rate in this period was 5% per annum. On the other hand, from 2007 to 2008 the Brazilian presence has increased

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fourfold in one of the main the international databases - a Web of Science-ISI (WoS), where JCR is based. “The insertion of more Brazilian periodicals on WoS and other major databases has contributed to Brazil’s rise to13th place in the global ranking for scientific production. In this production, counting articles and revisions, the weight of Brazilian periodicals is 33% of the total,” says Packer. With 33%, Brazil has a large percentage of articles with an impact factor published in domestic periodicals in relation to other countries like South Africa (21%), India (17%), China (16%), Mexico (10%) and Spain (10%). “Brazil is not bad in terms of impact factor among domestic periodicals. Roughly 10% of the periodicals have an above average impact factor in their respective areas. Our challenge is to rise to 15% to 20% of the periodicals with an above average impact factor,” affirms Packer. Rogério Meneghini, coordinator of SciELO’s scientific program, highlighted that science is a cyclical process. According to him, scientific production in itself is not the last step in the process, which is also part of the scientific communication and informal discussion with partners. “Publishing is a complex task that is a very important part of the process of performing science,” he affirms. According to Meneghini, contrary to developed countries where the number the periodicals is directly related to commercial interests, in developing countries the number of publications is connected to the need to disseminate scientific production. “At the moment of publication, there are two possible routes, domestic or international. What we have been discussing in the last few years – and which will continue to be discussed – is how much Brazilian publication begins to overlap with international production. Or rather, to what extent what we publish here is part of the international context of scientific publications,” he said. *Text published by the FAPESP Agency (www.agencia.fapesp.br) on September 20 th, 2011. Reprinted with permission.

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Luciano Cabral Albuquerque ........................................... 3 Luiz Augusto Ferreira Lisboa ........................................... 1 Luiz César Guarita Souza .................................................. 2 Luiz Felipe Pinho Moreira ................................................ 3 Magaly Arrais dos Santos ............................................... 1 Marcela da Cunha Sales ................................................... 2 Marcos Aurélio Barboza de Oliveira ................................ 2 Marcos Rogerio Joaquim ................................................. 1 Marcos Vinícius Pinto e Silva ........................................... 3 Marcus Vinicius Ferraz de Arruda .................................... 1 Maria Cristina de Oliveira Santos Miyazaki ..................... 1 Mario Vrandecic ............................................................... 1 Mauricio de Nassau Machado ......................................... 3 Mauro Paes Leme de Sá ................................................... 1 Michel Pereira Cadore ...................................................... 2 Michel Pompeu Barros de Oliveira Sá .............................. 6 Milton Ary Meier ............................................................. 1 Moacir Fernandes de Godoy ........................................... 1

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Paulo Paredes Paulista ..................................................... 1 Paulo Roberto Barbosa Evora .......................................... 5 Paulo Roberto Brofman .................................................... 4 Paulo Roberto Lunardi Prates .......................................... 1 Paulo Roberto Prates ....................................................... 1 Reinaldo Bestetti .............................................................. 4 Reinaldo Wilson Vieira ..................................................... 2 Renato Abdala Karam Kalil .............................................. 4 Ricardo de Carvalho Lima ................................................ 1 Ricardo Ribeiro Dias ........................................................ 5 Roberto Gomes de Carvalho ............................................ 1 Simone Cavenaghi ........................................................... 1 Solange Guizilini ............................................................... 2 Stevan Krieger Martins .................................................... 1 Tomas Salerno .................................................................. 2

Neuseli Marino Lamari ..................................................... 4

Ulisses Alexandre Croti .................................................... 2

Orlando Petrucci .............................................................. 8 Otoni Moreira Gomes ....................................................... 3

Vera Demarchi Aiello ........................................................ 1 Vinicius José da Silva Nina .............................................. 2

Pablo Maria Alberto Pomerantzeff ................................... 3

Walter J Gomes ................................................................ 5

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DOI: 10.5935/1678-9741.20110066

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ACKNOWLEDGMENT We thank the reviewers listed below with the number of manuscripts assessed, by revisions performed during the year 2011. Thanks to this volunteer work, the Brazilian Journal of Cardiovascular Surgery (BJCVS) has published high quality articles, always assessed within strict criteria and the most absolute scientific accuracy, enabling our first Impact Factor was extremely positive.

Domingo Braile BJCVS Editor

REVIEWERS 2011 Alexandre C Hueb ............................................................ 3 Alfredo Inácio Fiorelli ...................................................... 2 Alfredo José Rodrigues ................................................... 6 Ana Maria Rocha Pinto e Silva ........................................ 3 Antoninho Sanfins Arnoni .............................................. 1 Bruno Botelho Pinheiro .................................................... 3 Bruno da Costa Rocha ..................................................... 2 Carla Tanamati .................................................................. 1 Carlos Manuel de Almeida Brandão ................................. 5 Carolina Baeta Neves Duarte Ferreira .............................. 1 Claudia Maria Rodrigues Alves ....................................... 1 Diego Felipe Gaia ............................................................. 1 Djair Brindeiro Filho ......................................................... 1 Dorotéia Souza ................................................................. 2 Edmo Atique Gabriel ........................................................ 5 Eduardo Augusto Victor Rocha ....................................... 1 Eduardo Keller Saadi ........................................................ 3 Ektor Correa Vrandecic ..................................................... 2 Elaine Soraya Barbosa de Oliveira Severino .................... 2 Eliana Márcia Sotello Cabrera .......................................... 2 Ellen Hettwer Magedanz .................................................. 1 Emmanuel A. Burdmann ................................................... 1 Enio Buffolo ..................................................................... 3 Fabio Antonio Gaiotto ..................................................... 2 Fábio Papa Taniguchi ....................................................... 4 Fausto Miranda Junior ..................................................... 2 Fernando Antoniali .......................................................... 2 Fernando Platania ............................................................ 3 678

Fernando Ribeiro de Moraes Neto ................................... 1 Francisco Costa ............................................................... 2 Frederico José Di Giovanni .............................................. 2 Frederico Pires de Vasconcelos Silva ............................... 1 Gilberto Goissis ................................................................ 4 Gilberto Venossi Barbosa ................................................. 5 Glaucia Basso ................................................................... 1 Guilherme de Menezes Succi ........................................... 2 Gustavo Calado de Aguiar Ribeiro ................................... 4 Gustavo Glotz de Lima ..................................................... 1 Hélcio Giffhorn ................................................................. 4 Henrique Murad ............................................................... 4 Ivan Sergio Joviano Casagrande ..................................... 1 Jarbas Jakson Dinkhuysen .............................................. 1 João Carlos Ferreira Leal .................................................. 6 João de Deus e Brito ........................................................ 2 Jorge Luis dos Santos Valiatti .......................................... 2 José Carlos Dorsa Vieira Pontes ....................................... 1 José Maria Pereira de Godoy ........................................... 1 Josiane Marques Felcar ................................................... 1 Juliana Bassalobre Carvalho Borges ................................ 2 Karlos Alexandre de Sousa Vilarinho ............................... 5 Lais Helena Carvalho Marino ........................................... 2 Leonardo Andrade Mulinari ............................................. 3 Lilian Beani ...................................................................... 1 Lindemberg da Mota Silveira Filho .................................. 3 Luciana da Fonseca ......................................................... 2

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Letters to the Editor DOI: 10.5935/1678-9741.20110067

Cardiac resynchronization therapy Dear Dr. Braile, We have recently discussed about the non-responsive patients to cardiac resynchronization therapy (CRT) and, I found the proper results in reviewing the publication of the cardiac troponin I as a marker in the evolution of resynchronization. Leal et al. [1] observed high mortality in patients undergoing CRT with serum cardiac troponin I elevated, suggesting a worse prognosis. Although this study aimed to evaluate a prognostic biomarker with high sensitivity and sensitivity to myonecrosis in patients with idiopathic dilated cardiomyopathy undergoing optimized treatment, I would like to emphasize the existence of other important aspects and criteria to determine the responsiveness to the treatment [2] and worse prognosis in CRT. Lack of functional class regression and improvement in the parameters evaluated mainly by echocardiography, and, increased physical capacity in the six-minute walk test are some of the criteria used to classify patients as non-responsive to CRT [3]. On the other hand, the enlargement of the QRS complex set one of the main evaluation parameters of patients undergoing CRT. In cases with QRS duration between 120 and 150 ms, patients stimulated by definitive pacemaker and patients with right bundle branch block make this parameter become controversial. Therefore, further evaluation of these patients by imaging becomes extremely important for the asynchrony determination, since it is one of the causes of non-responsiveness to CRT [4]. Another important aspect to evaluate is the location of stimulation. There is a tendency to individualize the choice of local implantation of electrodes in order to obtain the best result. Patients with myocardial fibrosis and aneurysmal regions corrected or not, should have their devices indicated and implanted with great care and the possibility of further evaluation by cardiac magnetic resonance imaging should be considered. Factors such as the persistence of arrhythmias, loss of control of the electrode, inappropriate inhibition of the pacing system, inadequate device programming and improper electrodes position are also determinants in the 680

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responsiveness to the treatment [5]. In addition, ventricular dyssynchrony leads to reduced expression of sarcoplasmic calcium regulatory proteins, which determines a lower availability of calcium by the sarcoplasmic reticulum [6]. Hence, the conduction in post-operative patients with cardiac resynchronization seems to be a determinant factor in the evolution of treatment, in which electrical, mechanical and molecular aspects should be taken into consideration. REFERÊNCES 1. Leal JCF, Braile V, Abelaira Filho A, Avanci LE, Godoy MF, Braile DM. Impacto da troponina I cardíaca sérica na evolução tardia de pacientes submetidos a ressincronização com estimulação biventricular: seguimento de até 59 meses. Rev Bras Cir Cardiovasc. 2005;20(3):286-90. 2. Birnie DH, Tang AS. The problem of non-response to cardiac resynchronization therapy. Curr Opin Cardiol. 2006;21(1):20-6. 3. Fornwalt BK, Sprague WW, BeDell P, Suever JD, Gerritse B, Merlino JD, et al. Agreement is poor among current criteria used to define response to cardiac resynchronization therapy. Circulation. 2010;121(18):1985-91. 4. Chung ES, Leon AR, Tavazzi L, Sun JP, Nihoyannopoulos P, Merlino J, et al. Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation. 2008;117(20):2608-16. 5. Levine PA. Cardiac resynchronization therapy: evaluation and management of non-responders. ISHNE 2009. 6. Vanderheyden M, Mullens W, Delrue L, Goethals M, de Bruyne B, Wijns W, et al. Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy responders versus nonresponders. J Am Coll Cardiol. 2008;51(2):129-36. Maria C. Valéria Braga Braile Sternieri 1 , Victor Rodrigues Ribeiro Ferreira 2, São José do Rio Preto/SP 1. Clinical Cardiologist, Chief of Domingo Braile Institute, Clinical Chief of Beneficiencia Portuguesa Hospital in Sao Jose do Rio Preto, Sao Paulo, Brazil. 2. Clinical Cardiologist at Domingo Braile Institute, Cardiac Intesivist at Domingo Braile Institute Postoperative Room, Sao Jose do Rio Preto, Sao Paulo, Brazil.

Letters to the Editor

Can we predict disease? “The shortest distance between two points is not a straight line.” Albert Einstein Dear Editor, I read with great interest the article by Sá et al. [1]: “Validation of MagedanzSCORE as a predictor of mediastinitis after coronary artery bypass graft surgery”, published in Revista Brasileira de Cirurgia Cardiovascular. 2011, 26 (3) :386-92. The subject itself is very relevant, but some considerations are relevant. I quote Escrivão Jr. [2]: “It also grows the demand for health services, both private and public, organize yourselves to respond to people’s needs and offer a humane and effective care, providing all information the user needs. “ And I also quote Dobrow et al. [3]: “... they suggest that it is necessary to distinguish between the “impact of the evidence” in the results of organizations and simple “ use of evidence” in the decision-making process.” The main topic would be: Can we predict disease? If we can, who should we share these information with? This topic and these doubts I also had when I described a case report using EuroSCORE (1999) for the assessment of operative risk and Fowler et al. score (2005) on risk analysis for mediastinitis [4]. In this case study, the use of two scales did not show power to predict preoperatively the surgical problems that followed postoperatively. If the accuracy of data collected to detect serious complications such as mediastinitis enter into our practice of routine assessment, which would be the ideal time for this introduction to the patient? During pre-operative? In post-operative? And, most importantly in this age of information, should the patient know that he has high risk for developing postoperative infection (a surgical complication?), Even with low preoperative risk? I agree with Turpin et al. [5] that performance indicators are not direct measures of quality but “...flags to alert users to possible opportunities for improvement in processes and outcomes”. Given these uncertainties, I agree with Vallet et al. [6]: Ces publications ne sont compréhensibles que par un public de professionnels avertis qui dénonce massivement les exploitations des données telles qu’elles sont faites et les carences méthodologiques de la presse grand public”. Hélcio Giffhorn, Curitiba-PR REFERENCES 1. Sá MP, Figueira ES, Santos CA, Figueiredo OJ, Lima RO, Rueda FG, et al. Validation of MagedanzSCORE as a predictor

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of mediastinitis after coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(3):386-92. 2. Escrivão Jr. A. Uso da informação na gestão de hospitais públicos. Ciênc Saúde Coletiva. 2007;12(3):655-66. 3. Dobrow MJ, Goel V, Upshur RE. Evidence-based health policy: context and utilisation. Soc Sci Med. 2004;58(1):207-17. 4. Giffhorn H. Podemos predizer doenças? Avaliando um caso de mediastinite pós-operatória em cirurgia cardíaca. Rev Med Paraná. 2009;67(1-2):17-9. 5. Turpin RS, Darcy LA, Koss R, McMahill C, Meyne K, Morton D, et al. A model to assess the usefulness of performance indicators. Int J Qual Health Care. 1996;8(4):321-9. 6. Vallet G, Perrin A, Keller C, Fieschi M. Accès du public aux informations sur les prestations et la qualité des soins dans les établissements pulics de santé. Presse Med. 2006;35(3 Pt 1):388-92.

An overview of basic research articles recently published by Clinics Introduction This is an insight on articles on basic research recently published by Clinics with direct or indirect interest to the cardiopulmonary system. We believe they may be of interest to readers of Revista Brasileira de Cirurgia Cardiovascular. Cardiovascular The most cited article of this collection describes the effects of hypertension time course in spontaneously hypertensive rats. Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of reninangiotensin system. Zamo et al. [1] investigated the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. They observed that autonomic dysfunction and modulation of Reninangiotensin system activity are contributing factors to endorgan damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established endorgan damage is reached. 681

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Memantine, a drug used in the treatment of AlzheimerÂ´s disease was tested by Meneghini et al. [2] to evaluate its effects on nuclear size reduction in cardiac cells exposed to cold stress in rats and conclude that memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress. Duarte et al. [3] induced myocardial infarction in rats in order to evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction. They found that tobacco smoke induced oxidative stress is associated with the intensification of ventricular reremodeling after myocardial infarction. The microcirculation was the object of most articles in this collection. The degree of vascular occlusion, vascular recanalization, and necrosis of the vascular wall caused by polyvinyl alcohol-covered polyvinyl acetate particles compared to trisacryl particles after renal embolization was evaluated by Barbosa et al. [4] in female albino New Zealand rabbits Their conclusion is that polyvinyl alcohol-covered polyvinyl acetate particles exhibited adequate tissue reactions, more expressive vascular occlusion and necrosis, and less recanalization than the trisacryl material. Coelho da Mota et al. [5] investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation of hamsters, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. Their results show that functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. The interaction between liver steatosis and ischemia reperfusion in rats was the object of Andraus et al. [6] who hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. They suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver. The classic rat paw edema model for the study of inflammatory agents was studied by Hajhashemi et al. [7] who further investigated the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats. They found that amitriptyline has a considerable anti-inflammatory effect on carrageenaninduced paw edema in rats and suggest that at least a part of this property could be mediated through supraspinal sites. Moreover, it seems unlikely that the investigated adrenergic and opioid receptors have a significant role in this effect of amitriptyline. Mechanical ventilation with positive end expiratory pressure (PEEP) improves oxygenation and treats acute pulmonary failure. However, increased intrathoracic pressure may cause regional blood flow alterations that 682

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may contribute to mesenteric ischemia and gastrointestinal failure. Aikawa et al. [8] investigated the effects of different PEEP levels on mesenteric leukocyte-endothelial interactions in male Wistar rats. They found that high intrathoracic pressure was harmful to mesenteric microcirculation in the experimental model of rats with normal lungs and stable systemic blood pressure, a finding that may have relevance for complications related to mechanical ventilation. The aortic wall structure was studied by Adam et al. [9] who observed the effects of consuming repeatedly heated soy oil on the aortic tissues of estrogen-deficient rats in female Sprague Dawley rats and found that fresh soy oil offered protection in the estrogen-deficient state, as these rats had similar features to those of the NC group. The damage to the tunica intima and the increase in the ratio of tunica intima/media thickness showed the deleterious effect of consuming repeatedly heated soy oil in castrated female rats. Two highly interesting and intensely cited physiological studies in consciopus rats are by Valenti et al. are included in this series. In the first [10], a subset of normotensive Sprague-Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. The study compared baroreflex sensitivity among conscious rats of this specific subtype and found there is variability regarding baroreflex sensitivity among WKY rats from the same laboratory. In the second [11], the importance of oxidative stress on the cardiovascular system was studied The effects of central catalase inhibition on cardiopulmonary reflex in conscious Wistar rats was evaluated. It is claimed that catalase injected into the fourth cerebral ventricle increases sympathetic inhibition but does not change the parasympathetic component of the cardiopulmonary reflex in conscious Wistar rats. Two interesting exercise murine models are described. Ferreira et al. [12] analyzed the effects of exhausting longduration physical exercise (swimming) sessions of different durations and intensities on the number and phagocytic capacity of macrophages and neutrophils in sedentary rats and conclude that exercise intensity, duration and frequency are important factors in determining immune response to physical effort: neutrophils and macrophages of sedentary rats respond differently to exercise-induced stress. Adaptation sessions reduce exercise-induced stress on the immune system. Malysz et al. [13] investigated the effects of treadmill training (10 weeks) on hindlimb motor function and nerve morphometric parameters in diabetic rats submitted to sciatic nerve crush. And found that the diabetic condition promoted delay in sciatic nerve regeneration. Treadmill training is able to accelerate hindlimb motor function

Letters to the Editor

recovery in diabetic injured rats and prevent or revert morphometric alterations in proximal nerve portions in nondiabetic and diabetic injured rats. Two articles cover the ever interesting subject of the interaction of shock with hypertonic saline. Rocha Filho et al. [14] evaluated the effects of terlipressin versus fluid resuscitation with normal saline, hypertonic saline or hypertonic-hyperoncotic hydroxyethyl starch, on hemodynamics, metabolism, blood loss and short-term survival in hemorrhagic shock in pigs subjected to severe liver injury. They show that hyperkalemia accompanies hemorrhagic shock and, in addition to providing an early sign of the acute ischemic insult severity, may be responsible for cardiac arrest related to hemorrhagic shock. Costantini et al. [15] designed a study to combine the hemodynamic and immune benefits of hypertonic saline with the anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline as a hemorrhagic shock resuscitation strategy to reduces lung injury in Male Sprague-Dawley rats. They conclude that the decreases lung inflammation following hemorrhagic shock compared with conventional. Two articles cover themes in microcirulation The previously described Aikawa et al. [8] study shows that high intrathoracic pressure was harmful to mesenteric microcirculation in the experimental model of rats with normal lungs and stable systemic blood pressure, a finding that may have relevance for complications related to mechanical ventilation. Pulmonary system Pulmonary lung development in the preterm rabbit was the object of a study by Mascaretti et al. [16]: elastic and collagen fiber deposition is known to increase throughout normal lung development, and this fiber network significantly changes when development of the lung is disturbed. In preterm rats and lambs, prolonged hyperoxic exposure is associated with impaired alveolization and causes significant changes in the deposition and structure of elastic fibers. The study evaluated the effects of hyperoxic exposure on elastic and collagen fiber deposition in the lung interstitial matrix and in alveolarization in preterm rabbits. And found that prolonged oxygen exposure impaired alveolization and also lowered the proportion of collagen fibers, with an evident fiber network disorganization. Nutrition and dislipidemia have become highly siginficant themes in contemporary medical investigation Four reports are included in this review. Toscano et al. [17] investigated the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. A poor nutrition supply during fetal development is known to affect physiological functions of

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the fetus. They find that the increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness. Nutrition An original article by von Wilmsdorff et al. [18] investigated the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats. And found that haloperidol and ziprasidone induced a significantly decrease in weight gain and food consumption. No differences were seen in the alcove test, but locomotor activity was significantly reduced in the haloperidol group. Except for rats in the clozapine and ziprasidone groups, after 2 weeks of drug application, no changes were found in the leptin blood concentrations among the four groups or among animals within each group. No specific differences in hypothalamic leptin receptor expression occurred among the groups. Thus, the treatment did not act directly on the leptin regulatory system. Rodrigues et al. [19] investigated the effect of carnitine supplementation on alcoholic malnourished ratsâ&#x20AC;&#x2122; hepatic nitrogen content. And found: (i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. (ii) Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (similar to 10 g/ 100 g, P>0.05) was highest in the alcoholic animals. They conclude that Carnitine supplementation did not induce better nutritional recovery. The effects of natural product on diabeteic rats were the object of two papers: Budin et al. [20] examined the effects of palm oil tocotrienol-rich fractions on streptozotocin-induced diabetic rats. And found that such fractions lower the blood glucose level and improve dyslipidemia. Levels of oxidative stress markers were also reduced by administration of tocotrienol-rich fractions. Vessel wall integrity was maintained due to the positive effects mediated by tocotrienol-rich fractions. Movahedian et al. [21] studied the effects of Peucedanum pastinacifolium, an antihyperlipidemic vegetable used in Iranian folk medicine and found that there were significant (P < 0.05) increases in total serum cholesterol, triglyceride and low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol in streptozotocininduced diabetic rats. Treatment of diabetic rats with the extract over a period of a month returned these levels close to control levels, suggesting that it has hypolipidemic effects in streptozotocin-induced diabetic rats. 683

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Neuro-psychiatric themes Learning and memory were the subject of four murine model studies. Because of the well-established severe cognitive impairment which follows thyroid hormone deficiency during the neonatal period and the role of nitric oxide in learning and memory Hosseini et al. [22] investigated the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Their results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism. The consequences of ill studied consequences of the very widespread use of mobile phones Narayanan et al. [23] exposed male Wistar rats to 50 missed calls/day for 4 weeks from a GSM (900/1800MHz) mobile phone in vibratory mode (no ring tone). Animals were subsequently tested for spatial memory performance using the Morris water maze test. They claim that mobile phone exposure affected the acquisition of learned responses in Wistar rats. Mobile phone emissions on free radical metabolism and sperm motility in rats was studied by Mailankot et al. [24] in an often cited paper: Their results show that in animals sacrificed 24 hours after the last exposure mobile phones emissions negatively affect semen quality and may impair male fertility. Still on the subject of the mobile phone, Hosseini et al. [25] evaluated the effect of L-arginine on the learning and memory of estradiol-treated ovariectomized rats. And propose that chronic treatment with estradiol enhances the spatial learning and memory of ovariectomized rats, and that long term L-arginine treatment attenuates the effects of improvement produced by estradiol in OVX rats. Kumar et al. [26] studied the protective effects of ascorbic acid in memory loss induced by chronic restraint stress in rats exposed to restraint stress alone and in animals pretreated with vehicle solution before restrained stress: both groups showed deficits in learning and impaired memory retention in the memory tests when compared to animals in other experimental groups. Animals pretreated with ascorbic acid before restraining showed significant improvement in memory retention in the same memory tests. Other neuro-psychiatric studies include a previously cited study by von Wilmsdorff et al. [18] on the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats. Haloperidol and ziprasidone induced a significantly decrease in weight gain and food consumption. With listtle or no effect on leptin blood concentrations or on hypothalamic leptin receptor expression. Suggesting the treatment did not act directly on the leptin regulatory system. A second study by von Wilmsdorff et al. [27] 684

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investigated sex-dependent differences in motor coordination and activity as well as in cognitive and social behavior in Fisher rats (postnatal days, PD 56-174) that had received intracerebroventricular injections of kainic acid. These results demonstrate important differences between males and females in terms of weight gain, response to fear, working memory and social behavior. Sex-dependent differences in the lengths of hippocampal neurons were also found. Natural products Apart from their effects on the cardiovascular system and and nutrition, natural product were studied for a number of different effects. Hajhashemi et al. [28] investigated the antianxiety and sedative effects of the essential oil of Ducrosia anethifolia. Boiss. (Apiaceae). In elevated plus maze, Ducrosia anethifolia essential oil at doses of 25-200 mg/kg increased the percentage of open arm time and entries. Unlike diazepam, ducrosia anethifolia essential oil could not suppress spontaneous motor activity and did not alter ketamine-induced sleep parameters. They claim that these results are indicative of antianxiety effect of Ducrosia anethifolia essential oil without sedative effect. Paval et al. [29] evaluated the anti-arthritic potential of the plant Justicia gendarussa using two different rat models and claim that it showed significant anti-arthritic activity that was statistically similar to that of aspirin. Wahab et al. [30] examined the ability of Eurycoma longifolia Jack to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. And claim that the natural product acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment. Mauricio Rocha e Silva - Editor, Clinics Hospital das ClĂnicas, Faculdade de Medicina Universidade de SĂŁo Paulo. E-mail: mrsilva36@ hcnet.usp.br

REFERENCES 1. Zamo FS, Lacchini S, Mostarda C, Chiavegatto S, Silva IC, Oliveira EM, et al. Hemodynamic, morphometric and autonomic patterns in hypertensive rats: renin-angiotensin system modulation. Clinics. 2010;65(1):85-92. 2. Meneghini A, Ferreira C, Abreu LC, Valenti VE, Ferreira M, F Filho C, et al. Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress. Clinics. 2009;64(9):921-6.

Letters to the Editor

3. Duarte DR, Minicucci MF, Azevedo PS, Matsubara BB, Matsubara LS, Novelli EL, et al. The role of oxidative stress and lipid peroxidation in ventricular remodeling induced by tobacco smoke exposure after myocardial infarction. Clinics. 2009;64(7):691-7. 4. Barbosa LA, Caldas JG, Conti ML, Malheiros DM, Ramos FF Jr. Effect of renal embolization with trisacryl and PAVc. Clinics. 2009;64(11):1105-12. 5. Coelho da Mota DS, Furtado E, Bottino DA, Bouskela E. Effects of buflomedil and pentoxifylline on hamster skin-flap microcirculation: prediction of flap viability using orthogonal polarization spectral imaging. Clinics. 2009;64(8):797-802. 6. Andraus W, Souza GF, Oliveira MG, Haddad LB, Coelho AM, Galvão FH, et al. S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver. Clinics. 2010;65(7):715-21. 7. Hajhashemi V, Sadeghi H, Minaiyan M, Movahedian A, Talebi A. The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats. Clinics. 2010;65(11):1183-7. 8. Aikawa P, Farsky SH, Oliveira MA, Pazetti R, Mauad T, Sannomiya P, et al. Effects of different peep levels on mesenteric leukocyte-endothelial interactions in rats during mechanical ventilation. Clinics. 2009;64(5):443-50. 9. Adam SK, Das S, Othman F, Jaarin K. Fresh soy oil protects against vascular changes in an estrogen-deficient rat model: an electron microscopy study. Clinics. 2009;64(11):1113-9. 10. Valenti VE, de Abreu LC, Imaizumi C, Petenusso M, Ferreira C. Strain differences in baroceptor reflex in adult Wistar Kyoto rats. Clinics. 2010;65(2):203-8. 11. Valenti VE, Abreu LC, Sato MA, Ferreira C. ATZ (3-amino1,2,4-triazole) injected into the fourth cerebral ventricle influences the Bezold-Jarisch reflex in conscious rats. Clinics. 2010;65(12):1339-43. 12. Ferreira CK, Prestes J, Donatto FF, Verlengia R, Navalta JW, Cavaglieri CR. Phagocytic responses of peritoneal macrophages and neutrophils are different in rats following prolonged exercise. Clinics. 2010;65(11):1167-73. 13. Malysz T, Ilha J, Nascimento PS, Angelis KD, Schaan BD, Achaval M. Beneficial effects of treadmill training in experimental diabetic nerve regeneration. Clinics. 2010;65(12):1329-37.

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pulmonary transcription factor activation in a murine model of hemorrhagic shock. Clinics. 2010;65(6):621-8. 16. Mascaretti RS, Mataloun MM, Dolhnikoff M, Rebello CM. Lung morphometry, collagen and elastin content: changes after hyperoxic exposure in preterm rabbits. Clinics. 2009;64(11):1099-104. 17. Toscano AE, Ferraz KM, Castro RM, Canon F. Passive stiffness of rat skeletal muscle undernourished during fetal development. Clinics. 2010;65(12):1363-9. 18. von Wilmsdorff M, Bouvier ML, Henning U, Schmitt A, Gaebel W. The impact of antipsychotic drugs on food intake and body weight and on leptin levels in blood and hypothalamic ob-r leptin receptor expression in Wistar rats. Clinics. 2010;65(9):885-94. 19. Rodrigues LP, Portari GV, Padovan GJ, Jordão AA, Suen V, Marchini JS. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats. Clinics. 2010;65(9):877-83. 20. Budin SB, Othman F, Louis SR, Bakar MA, Das S, Mohamed J. The effects of palm oil tocotrienol-rich fraction supplementation on biochemical parameters, oxidative stress and the vascular wall of streptozotocin-induced diabetic rats. Clinics. 2009;64(3):235-44. 21. Movahedian A, Zolfaghari B, Sajjadi SE, Moknatjou R. Antihyperlipidemic effect of peucedanum pastinacifolium extract in streptozotocin-induced diabetic rats. Clinics. 2010;65(6):629-33. 22. Hosseini M, Dastghaib SS, Rafatpanah H, Hadjzadeh MA, Nahrevanian H, Farrokhi I. Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth. Clinics. 2010;65(11):1175-81. 23. Narayanan SN, Kumar RS, Potu BK, Nayak S, Mailankot M. Spatial memory perfomance of Wistar rats exposed to mobile phone. Clinics. 2009;64(3):231-4. 24. Mailankot M, Kunnath AP, Jayalekshmi H, Koduru B, Valsalan R. Radio frequency electromagnetic radiation (RF-EMR) from GSM (0.9/1.8GHz) mobile phones induces oxidative stress and reduces sperm motility in rats. Clinics. 2009;64(6):561-5. 25. Hosseini M, Headari R, Oryan S, Hadjzadeh MA, Saffarzadeh F, Khazaei M. The effect of chronic administration of L-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze. Clinics. 2010;65(8):803-7.

14. Rocha Filho JA, Nani RS, D’Albuquerque LA, Holms CA, Rocha JP, Sá Malbouisson LM, et al. Hyperkalemia accompanies hemorrhagic shock and correlates with mortality. Clinics. 2009;64(6):591-7.

26. Kumar RS, Narayanan SN, Nayak S. Ascorbic acid protects against restraint stress-induced memory deficits in Wistar rats. Clinics. 2009;64(12):1211-7.

15. Costantini TW, Deree J, Martins JO, Putnam JG, de Campos T, Coimbra R. A novel fluid resuscitation strategy modulates

27. von Wilmsdorff M, Sprick U, Bouvier ML, Schulz D, Schmitt A, Gaebel W. Sex-dependent behavioral effects and

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morphological changes in the hippocampus after prenatal invasive interventions in rats: implications for animal models of schizophrenia. Clinics. 2010;65(2):209-19.

29. Paval J, Kaitheri SK, Potu BK, Govindan S, Kumar RS, Narayanan SN, et al. Anti-arthritic potential of the plant Justicia gendarussa Burm F. Clinics. 2009;64(4):357-62.

28. Hajhashemi V, Rabbani M, Ghanadi A, Davari E. Evaluation of antianxiety and sedative effects of essential oil of Ducrosia anethifolia in mice. Clinics. 2010;65(10):1037-42.

30. Wahab NA, Mokhtar NM, Halim WN, Das S. The effect of eurycoma longifolia Jack on spermatogenesis in estrogentreated rats. Clinics. 2010;65(1):93-8.

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Abstracts of the 12th Congress of SCICVESP (Society of Cardiovascular Surgery of São Paulo)

TL 01 ASPECTOS INFLAMATÓRIOS E DE TROMBOGENICIDADE DE CIRCUITOS DE CEC REVESTIDOS COM CO-POLÍMERO SINTÉTICO: ESTUDO EXPERIMENTAL Edmo Atique Gabriel, Fredy Max Ayala Montevilla, Valeria Vieira Chida, Fabio Nunes Dias, Cynara Viterbo Montoya, Hiroaki Otsubo, Zenício Francisco Pires, Sergio Luiz Nogaroto CETEC Hospital Israelita Albert Einstein Resumo: Comparar ativação do sistema complemento e índice de trombogenicidade e agregação plaquetária entre circuito de circulação extracorpórea (CEC) revestido com co-polímero sintético e circuito sem revestimento. Método: Vinte seis porcos foram igualmente divididos em 2 grupos – com e sem revestimento com co-polímero sintético. Foram mantidos em CEC por 90 minutos, sendo que amostras de sangue foram colhidas em três diferentes momentos (T0 -imediatamente antes de estabelecer CEC, T1-45 minutos de CEC, T2-90 minutos de CEC) para mensurar contagem total de células inflamatórias(leucócitos, neutrófilos, linfócitos e plaquetas) e concentração da fração C3 do sistema complemento.Ao final dos 90 minutos, fragmentos de diferentes compartimentos do circuito de CEC foram obtidos para avaliação do índice de trombogenicidade e agregação plaquetária. Teste t de Student; Teste t de Student para dados pareados, ajustado pela correção de Bonferroni; Teste de Friedman; Teste de Mann-Whitney foram empregados, considerando nível de significância de 5%. Resultados: Não houve diferenças entre ambos os grupos quanto à contagem de leucócitos, neutrófilos e linfócitos; porém, em T2, notou-se menor contagem de plaquetas no grupo com revestimento (P=0,020). A concentração sérica da fração C3 foi menor no grupo com revestimento, nos tempos T1(P=0,020) e T2(P=0,017). Maiores índices de trombogenicidade e agregação plaquetária foram observados no grupo sem revestimento (77% dos animais

do grupo sem revestimento), em comparação com grupo com revestimento (46% dos animais do grupo sem revestimento). Conclusão: Em cirurgias cardíacas com CEC, o emprego de circuitos revestidos com co-polímero sintético pode ser útil para reduzir ativação do sistema complemento e atenuação do processo de trombogenicidade e agregação plaquetária

TL 02 AVALIAÇÃO CLÍNICA EM ONZE PACIENTES COM PRÓTESES STENTLESS DE PRODUÇÃO NACIONAL – SEGUIMENTO DE 11 ANOS Marcos G. Tiveron, Rubens T. de Barros, Sérgio M. Pereira, Juliana B. C. Borges, Eraldo Pelloso, Antônio C. G. Penna Junior. Irmandade da Santa Casa de Misericórdia de Marília – São Paulo Introdução: As próteses stentless surgiram no final da década de 80 para substituição valvar aórtica no intuito de melhorar o desempenho hemodinâmico em relação às próteses existentes. Entretanto, houveram problemas relacionados com a dificuldade no implante destas próteses como, por exemplo, tempo cirúrgico prolongado. Objetivo: Analisar evolução clínica em longo prazo após troca da valva aórtica por próteses stentless de produção nacional. Método: A pesquisa analisou a evolução em longo prazo de 11 pacientes submetidos à substituição valvar aórtica por próteses stentless de pericárdio bovino preservadas em formaldeído entre abril de 1999 e abril de 2000. Dos 11 pacientes submetidos à operação, 7 (63,6%) são do sexo masculino. O implante foi realizado com uma sutura da prótese em 2 planos (anel valvar e parede da aorta seguindo os postes comissurais). Resultados: O seguimento dos pacientes foi alcançado em 72% dos casos. Na análise pré-operatória, 5 (45,5%) 687

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pacientes, encontravam-se em classe funcional (CF) II da New York Heart Association (NYHA), 4 (36,3%) em CF III e 2 (18,2%) em CF IV. Os tempos médios de circulação extracorpórea e de anóxia foram de 113,4 (+-12,7) minutos e de 88,7 (+-8,2) minutos respectivamente. O tempo médio de sobrevida dos pacientes submetidos à cirurgia foi de 2984 dias (99 meses) com IC95% [1718,6 – 4249,5]. Atualmente, 2 (40%) pacientes encontram-se em CF I, 2 (40%) em CF II, e 1 (20%) em CF III. A análise de sobrevivência do grupo em estudo foi realizada por meio do método de Kaplan-Meier sendo a sobrevida estimada de 82% em 14 meses e de 72% ao final do seguimento. Não houve casos de endocardite ou fenômenos tromboembólicos relacionados à prótese. A mortalidade total foi de 27% e a mortalidade de causa cardiovascular de 9%. Conclusão: Os pacientes submetidos à operação para substituição da valva aórtica com próteses stentless apresentaram boa evolução clínica em longo prazo apresentando baixas taxa de complicações clínicas e relacionadas à prótese.

ideal (37,8% sobrepeso e 25,6% obesidade). No componente físico da QV houve diferença significativa no domínio Capacidade Funcional e Dor, sendo que os escores foram mais baixos na alta e mais altos nos 60 dias de PO. No domínio Aspectos Físicos não houve diferença significativa nos momentos estudados. Com relação ao Estado Geral de Saúde os maiores escores ocorreram em 60 dias de PO. No componente mental do SF-36 foram observadas diferenças significantes nos domínios Vitalidade e Saúde Mental com aumento dos escores em 60 dias de PO. Os domínios Aspectos Sociais e Emocionais não apresentaram diferença significante. Em relação à independência funcional, na subescala motora, o momento da alta apresentou os valores menores e o momento 60 dias de PO os maiores. A subescala cognitiva/social não apresentou diferença significativa nos momentos. Conclusões: A QV dos pacientes melhorou em 60 dias de PO e a funcionalidade piorou na alta hospitalar, já aos 60 dias de PO apresentou melhora, tanto em relação à alta como a fase anterior ao procedimento.

TL 03 AVALIAÇÃO DA QUALIDADE DE VIDA E FUNCIONALIDADE EM PACIENTES COM DOENÇA ARTERIAL CORONARIANA SUBMETIDOS À REVASCULARIZAÇÃO CIRÚRGICA

TL 04 BONS RESULTADOS DA REVASCULARIZAÇÃO DO MIOCÁRDIO SEM CIRCULAÇÃO EXTRACORPÓREA. EXPERIÊNCIA DE 2013 CASOS.

Freschi L, Borges JBC, Silva MAM

José de Lima Oliveira Junior; Renato B. Dauar; Heloisa Calife; Fares G. Adbulmassih; Roberto R. dos Santos; Mario Lucio B. Filho

Disciplina de Cirurgia Cardiovascular - Depto. de Cirurgia e Ortopedia, Programa de PG Bases Gerais da Cirurgia Faculdade de Medicina de Botucatu, FMB- UNESP

Hospital Bandeirantes, Hospital São Luiz, Hospital do Coração

Introdução: A doença arterial coronariana (DAC) é multidimensional e exerce impactos físicos, emocionais e sociais, por isso são indispensáveis informações sobre a qualidade de vida (QV) e funcionalidade dos pacientes para uma análise mais precisa de suas condições. O objetivo deste estudo foi avaliar a QV e a funcionalidade em pacientes com DAC submetidos à revascularização cirúrgica do miocárdio com CEC comparando-as nos momentos pré, alta hospitalar e 60 dias de pós operatório (PO). Métodos: Foram avaliados 45 pacientes com DAC. Utilizouse ficha com perfil demográfico, questionário de QV SF-36 e escala de independência funcional MIF. O questionário de QV é composto por 36 questões que abordam o componente físico e mental subdivididos em oito domínios. A escala MIF trata-se de um conjunto de 18 tarefas, divididas em duas subescalas: motora e cognitiva/social. Resultados: Observou-se a predominância do sexo masculino (58,9%), escolaridade com o ensino fundamental incompleto (64,4%) e índice de massa corporal acima do

Introdução: A maior expectativa de vida da população aliada ao aumento da prevalência da doença aterosclerótica arterial coronária (DAC) em função da faixa etária, tem contribuído para uma mudança do perfil dos pacientes encaminhados para cirurgia. A revascularização do miocárdio (RM) sem circulação extracorpórea (CEC) está sendo mais empregada para o tratamento cirúrgico da DAC multi arterial, embora possa haver dificuldades técnicas intra-operatórias em alguns casos, principalmente no momento da realização do deslocamento anteroposterior do coração, para a realização das anastomoses distais nas artérias marginais. Casuística e Método: Análise retrospectiva e prospectiva de uma série sequencial de 2013 pacientes submetidos à RM sem CEC, entre janeiro de 2004 e dezembro de 2010. A idade variou de 36 a 85 anos (67 ± 20,33), 78,45% eram do sexo masculino. A fração de ejeção do ventrículo esquerdo pré-operatória variou de 18% a 78% (50,56% ± 25,07). Resultados: A conversão para RM com CEC ocorreu em apenas 1,25% dos casos. Infarto peri-operatório ocorreu

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em 2,34% dos pacientes, complicações neurológicas em 4,81%, insuficiência renal em 3,1%. O tempo médio de permanência na unidade de terapia intensiva foi de 2,19 ± 1,4 dias e de internação hospitalar 5,6 ± 2,53. A extensão da revascularização do miocárdio planejada no pré-operatório, foi alcançada em 95% dos pacientes. O número médio de anastomoses distais realizadas foi de 2,86 ± 1,03. A mortalidade hospitalar foi de 2,93%. Conclusão: Respeitando-se a limitação de uma série de casos, podemos observar que a RM sem CEC pode ser realizada, mesmo em pacientes com pior função ventricular e doença coronária mais extensa, com bons resultados.

TL 05 PLÁSTICAVALVAR MITRALMINIMAMENTE INVASIVA VÍDEO-ASSISTIDA Stevan K Martins, Frederico CC Mendonça, Veridiana S de Andrade, Antonio Carlos Carvalho, Daniel Christianes França, Alberto Takeshi Kiyose, Jairo Pinheiro Jr, Jeffer Luiz Morais, Adib Domingos Jatene Introdução: Importantes evoluções técnicas tem ocorrido na cardiologia da atualidade com o desenvolvimentos de procedimentos menos agressivos e melhor tolerados. Técnicas cirúrgicas minimamente invasivas foram desenvolvidas nos últimos anos, principalmente para o tratamento de portadores de insuficiência mitral tratados por meio desta técnica no período de setembro de 2010 a setembro de 2011. Métodos: No período de setembro de 2010 a setembro de 2011, 9 pacientes foram submetidos a operações de reparo da valva mitral por técnica minimamente invasiva videoassistida em nosso serviço. Cinco eram do sexo feminino, com média de 58,4 anos (variância 31 a 67 anos). Todos os pacientes foram avaliados com Ecocardiograma pré e pós operatório, coronariografia foi realizada nos pacientes considerados de risco para doença arterial coronária (DAC). Em caso de DAC concomitante, o procedimento mini invasivo era contraindicado e o paciente encaminhado para cirurgia convencional. As operações foram realizadas com abordagem por toracotomia mínima no 4º espaço intercostal à direita (incisão de aproximadamente 4cm) e três orifícios acessórios para introdução da câmera de vídeo, manipulação e aspiração continua do pericárdio. Resultados: Nove pacientes foram submetidos a plástica valvar, a técnica padrão realizada é ressecção parcial do folheto superior com reforço do anel e implante de anel flexível – anel de Duran® (Medtronic Inc). Dois pacientes necessitaram de reintervenção para substituição valvar. Um por falha da plastia (ruptura de

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cordoalha) no 5º dia de pós operatório (PO) e outro por endocardite 30 dias após a operação. Dois pacientes apresentaram fibrilação atrial no PO, ambos controlados com tratamento medicamentoso oral. Um paciente necessitou implante de desfibrilador por episódios freqüentes de taquicardia ventricular secundários a miocardiopatia chagásica. Conclusões: Consideramos justificado o esforço para aquisição e aprimoramento de novas técnicas capazes de oferecer ao mesmo tempo a segurança já alcançada pelos consistentes resultados dos procedimentos consagrados e menos trauma operatório que permita períodos de convalescença menores e mais conforto durante esta etapa. Concluimos que a abordagem mini invasiva videoassistida para procedimentos de reconstrução valvar mitral é técnica segura e hoje em nosso serviço é método de aplicação rotineira.

TL 06 CIRURGIA DE REVASCULARIZAÇÃO MIOCÁRDICA COM CIRCULAÇÃO EXTRACORPÓREA: ASPECTOS BIOQUÍMICOS, HORMONAIS E CELULARES Edmo Atique Gabriel, Rafael Fagionato Locali, Priscila Katsumi Matsuoka, Thiago Cherbo, Enio Buffolo Universidade Federal de São Paulo – Disciplina de Cirurgia Cardiovascular Objetivo: Avaliar repercussões bioquímicas, hormonais e celulares decorrentes do emprego de circulação extracorpórea (CEC) em cirurgia de revascularização miocárdica. Método: Dezoito pacientes foram submetidos à cirurgia de revascularização miocárdica com emprego de CEC. A duração média da CEC foi de 80,3 minutos. Dosagens hormonais, bioquímicas e celulares foram realizadas nos seguintes tempos – pré-operatório, logo após saída de CEC, 24 horas e 48 horas de pós-operatório. Os testes de Friedman e Wilcoxon foram aplicados, considerando nível de significância 5%. Resultados: Houve ativação e elevação significante do número de leucócitos totais e neutrófilos durante o período de CEC, de tal forma que esta condição foi detectada logo após a saída de CEC, mantendo-se assim até 48 horas de pós-operatório. O número total de plaquetas, por sua vez, caracterizou-se por decréscimo relevante logo após a saída de CEC, como também, nos dois momentos pós-operatórios de observação. A concentração sérica de proteínas totais e albumina logo após a saída de CEC e, nos dois momentos pós-operatórios de observação, foi significativamente menor em relação aos níveis encontrados no período pré689

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operatório. Houve decréscimo acentuado dos níveis séricos de T3 total e T3 livre, sobretudo até as primeiras 24 horas de pós-operatório. De forma análoga, notou-se padrão semelhante quanto aos níveis séricos de T4 total. Conclusão: Em cirurgias de revascularização miocárdica, os efeitos inflamatórios da CEC compreendem ativação de leucócitos, neutrófilos e plaquetas, redução na concentração sérica de proteínas totais e albumina e decréscimo dos níveis séricos de hormônios tireiodianos, sobretudo, nas primeiras 24 horas de pós-operatório.

endovenosa – sem maiores intercorrências. Ecocardiogramas tardios aos 3 e 6 meses mostram adequada função da valva tricúspide com regurgitação mínima e diâmetros normais das cavidades cardíacas. Conclusões: Técnicas mini invasivas podem ser capazes de oferecer ao mesmo tempo a segurança já alcançada pelos procedimentos consagrados e menos trauma operatório, o que poderá permitir períodos de convalescença menores. Sugerimos que este método pode ser aplicado em pacientes com endocardite.

TL 07 TRATAMENTO DE ENDOCARDITE DE VALVA TRICÚSPIDE COM PLÁSTICAVALVAR MINIMAMENTE INVASIVA VÍDEO-ASSISTIDA

TL 08 USO DO BALÃO INTRA-AÓRTICO EM PACIENTES COM INSTABILIDADE HEMODINÂMICA DURANTE REVASCULARIZAÇÃO DO MIOCÁRDIO SEM CIRCULAÇÃO EXTRACORPÓREA

Stevan K. Martins, Guilherme HC Furtado, Pedro A Mathiasi, Frrderico CC Mendonça, Veridiana S de Andrade, Jairo Pinheiro Jr, Jeffer Luiz Morais Introdução: Novas técnicas e procedimentos menos agressivos como cirurgias minimamente invasivas foram desenvolvidas nos últimos anos, principalmente para o tratamento de patologias valvares. Mesmo pacientes portadores de doenças de caráter infeccioso podem se beneficiar desta abordagem. Métodos: Paciente de 50 anos, sexo masculino, apresentava febre de origem desconhecida, admitido em nosso serviço para investigação, ecocardiograma mostrou massa móvel localizada na valva tricúspide (VT). Após 5 dias de antibioticoterapia não se percebia alteração expressiva da imagem, mantinha quadro sub-febril diariamente. Optamos por abordagem cirúrgica, realizada após 10 dias de tratamento para endocardite. Empregamos técnica minimamente invasiva videoassistida com abordagem por toracotomia mínima no 5º espaço intercostal à direita (incisão de aproximadamente 4 cm) e três orifícios acessórios para introdução da câmera de vídeo, manipulação e aspiração contínua do pericárdio. Instalada circulação extracorpórea (CEC) por canulação de artéria e veias femorais e veia jugular interna D. Foi realizada ressecção parcial do folheto septal, removendo a área de implantação da vegetação, reconstrução do folheto com sutura direita e reforço do anel com implante de anel flexível (Duran AnCore, Medtronic Inc). Ecocardiografia intraoperatória comprovou com resultado da operação, o tempo da CEC foi de 90 minutos, com 70 minutos de isquemia. Resultados: O paciente foi extubado no mesmo dia, teve alta da UTI no 2º dia de pós-operatório. Apresentou recuperação adequada, completou o tratamento previsto para endocardite – 6 semanas de antibioticoterapia 690

José de Lima Oliveira Junior; Renato B. Dauar; Heloisa Calife; Fares G. Abdulmassih; Richard H. Cabral; Roberto R. dos Santos. H. Bandeirantes, Hospital São Luiz, Hospital do Coração. Introdução: A revascularização do miocárdio (RM) sem circulação extracorpórea (CEC) pode ser difícil quando ocorre instabilidade hemodinâmica no intraoperatório. Neste estudo realizamos uma avaliação inicial dos resultados da operação de RM sem CEC, com uso do balão intra-aórtico (BIA), como suporte hemodinâmico para se evitar a instalação da CEC. Casuística e Método: Análise retrospectiva e prospectiva de uma série sequencial de 2013 pacientes submetidos à RM sem CEC, entre 2004 e 2010, dos quais, apenas 36 (1,78%) necessitaram do implante de um BIA. A idade variou de 45 a 85 anos (64 ± 24,31), 26 eram do sexo masculino. A fração de ejeção do ventrículo esquerdo pré-operatória variou de 20% a 35% (25,56% ± 5.97). Resultados: A mortalidade hospitalar foi de 2,77%. Apenas um paciente (2,77%) necessitou da instalação da CEC. Não houve infarto no período peri-operatório, nem nenhuma complicação associada ao balão intra-aórtico foi observada. O tempo médio de permanência na unidade de terapia intensiva foi de 3,79 ± 2,8 dias e de internação hospitalar 8,6 ± 3,93. A extensão da revascularização do miocárdio planejada no pré-operatório, foi alcançada em todos os pacientes. Quatro pacientes (11,2%) receberam um enxerto, vinte (55,55%) receberam dois, dez (27,78%) receberam três e dois (5,55%) receberam quatro enxertos. Conclusão: A utilização precoce do balão intra-aórtico, no intra-operatório, para estabilização hemodinâmica do paciente sem uso da circulação extracorpórea é uma alternativa viável com bons resultados.

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TL 09 USO DO DISPOSITIVO IMPELLA 5.0 PARA SUPORTECIRCULATÓRIO MECÂNICO EM PÓSOPERATÓRIO DE CIRURGIAVALVAR COM FALÊNCIA VENTRICULAR Stevan K. Martins, Paulo Chaccur, Jorge Farran, Leda Lotaif, Veridiana S de Andrade Introdução: O uso de assistência circulatória mecânica tem se difundido nas últimas décadas. Novos dispositivos, menores e mais eficientes, tem contribuído para este panorama e podem auxiliar no tratamento de pacientes graves. Métodos: Paciente de 48 anos, sexo feminino, submetida a troca valvar mitral, implantada prótese valvar mecânica de duplo folheto associada a plastia valvar tricúspide tipo deVega. Já havia sido submetida a comissurotomia mitral há 19 anos. Apresentou tamponamento cardíaco por coágulo no saco pericárdio, sendo feita re-exploração cirúrgica no 1º dias de pós operatório (PO). No segundo dia de PO apresentava piora clínica, com uso de drogas vasoativas e foi introduzido balão intra-aórtico (BIA) para suporte circulatório. No 3º PO havia piora hemodinâmica com emprego de altas doses de noradrenalina. O ecocardiograma evidenciava fração de ejeção do ventrículo esquerdo (FEVE) de 20%, lactato sérico em 88mg/dl. Devido ao quadro de choque cardiogênico refratário, foi indicada assistência circulatória mecânica. Foi submetida no 3º PO a implante de dispositivo Implella LP 5.0® para suporte circulatório. O cateter introduzido por dissecção da artéria femoral esquerda (através de enxerto de dacron de 8mm), posicionado com êxito no ventrículo esquerdo em posição transvalvar aórtica, guiado por radioscopia e ecocardiografia transesofageana. Foi então iniciada assistência circulatória com performance máxima do aparelho – fluxo de 5.3l/min. Em 2 horas foi possível a redução da noradrenalina para níveis usuais, o BIA foi reduzido para 1:3 e ajustado para 70% da inflagem. No 4º PO o BIA foi removido e iniciada hemodiálise com balanço negativo de 50ml/h, ecocardiograma mostrava FEVE 30%, recebia 2ml/h de noradrenalina. No 5º e 6º dias de PO se manteve estável, sem drogas vasoativas, fluxo do Impella também estável em 5 l/min. Apresentou sangramento vaginal associado a plaquetopenia, tratado com hemotransfusões. No 7º PO a FEVE era estimada em 35% sem drogas vasoativas, o fluxo do Impella foi reduzido para 4 l/min. Após 24 horas com fluxo em 4 l/min, realizamos ecocardiografia transesofageana que mostrou melhora importante da FEVE (estimada em 54%) sem drogas inotrópicas e exames laboratoriais dentro dos limites

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previstos. Iniciado desmame da assistência reduzindo o fluxo para 1,8 l/min, após 2h houve alteração do quadro reduzimos o fluxo para 0,5 l/min e procedemos a remoção do sistema com sucesso no 9º dia de PO e 6º dia de suporte circulatório mecânico. Resultados: A paciente foi extubada no 19º PO. Se mostrava adequadamente respondia a estímulos e movia ativamente os membros. Teve alta da UTI no 26º PO, no 36º PO foi capaz de inicial deambulação ativa e não apresentava sequelas. Conclusões: O dispositivo de assistência circulatória Impella 5.0® foi efetivo em manter as condições hemodinâmicas estáveis e favoráveis para a recuperação da função do VE a níveis adequados. Suporte circulatório de curta permanência pode ser aplicado com sucesso mesmo em casos de gravidade como o descrito.

TL 10 ESTUDO PROSPECTIVO E RANDOMIZADO DA REVASCULARIZAÇÃO DO MIOCÁRDIO MINIMAMENTE INVASIVA COM DISSECÇÃO DA ARTÉRIA TORÁCICA INTERNA ESQUERDA POR VIDEOTORACOSCOPIA ROBÓTICA VS. REVASCULARIZAÇÃO POR TÉCNICATRADICIONAL. Milanez, AMM; Dallan, LAO; Platania, F; Dallan, LRP; Carneiro, LJ; Stolf, NG. Instituto do Coração (InCor)- Faculdade de Medicina- Univ. de São Paulo. Objetivo: Comparar a perviedade da artéria torácica interna esquerda (ATIE) dissecada por videotoracoscopia robótica para revascularização minimamente invasivado ramo interventricular anterior (RIA), com a revascularização do miocárdio na qual a ATIE foi dissecada de formaconvencional. Casuística e Métodos: De 2007 a 2010, 36 pacientes foram randomizados para revascularização do miocárdio minimamente invasiva (RMMI) ou revascularização do miocárdio convencional (RMC). Pacientes randomizados para o grupo RMMI foram submetidos à dissecção da ATIE por videotoracoscopia auxiliada pelo braço robótico AESOP, seguida de minitoracotomia anterior esquerda (4º espaço intercostal) para anastomose com o RIA. Pacientes randomizados para o grupo RMC foram submetidos a revascularização do miocárdio convencional com esternotomia mediana completa, dissecção aberta da ATIE e anastomose ao RIA. Foi utilizada a Fluxometria por tempo de trânsito (FTT) para a avaliaçãoimediata da perviedade da ATIE. Em todos os pacientes foram realizadas 691

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tomografiasmultislicenum período de 24 meses, visando avaliar a perviedadeda ATIE a médio prazo. Resultados: O tempo médio de dissecção da ATIE no grupo RMMI foi de 50,1 ± 11,2 vs. 22,7 ± 3,3 min no grupo RMC. Não houve diferença significativa no fluxo médio da ATIE para o RIA entre os grupos estudados (46,17 ± 20,11 vs. 48,61 ± 23,42 mL/min, p=0,86) respectivamente. Não houve diferença significante na incidência de infecção de ferida profunda (0 vs. 2, P=0,48) e necessidade de reoperação por sangramento (0 vs. 1, P=1,00) nos grupos RMMI e RMC,

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Rev Bras Cir Cardiovasc 2011;26(4):687-92

respectivamente. A angiotomografia mostrou perviedade da ATIE em 100% dos pacientes do grupo RMMI vs. 94,1% no grupo RMC (p=1,00). Não houve mortalidade nos grupos estudados. Conclusão: A revascularização do miocárdio minimamente invasiva do ramo interventricular anterior com dissecção da artéria torácica interna esquerda por videotoracoscopia robótica foi factível e segura. A perviedade da artéria torácica interna esquerda imediata e a médio prazo foi similar quando comparadas ambas as técnicas.

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