Brazilian Journal of Cardiovascular Surgery 28.3 - 2013 by Revista Brasileira de Cirurgia Cardiovascular

28.3 JULY/SEPTEMBER 2013

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR | BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

VOL. 28 Nยบ 3 JULY/SEPTEMBER 2013

HEART TEAM

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4º Simpósio de Enfermagem em Cirurgia Cardiovascular 4º Simpósio de Fisioterapia em Cirurgia Cardiovascular 4º Simpósio de Perfusão em Cirurgia Cardiovascular 3º Congresso Acadêmico em Cirurgia Cardiovascular

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RBCCV REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

EDITOR/EDITOR Prof. Dr. Domingo M. Braile - PhD São José do Rio Preto - SP - Brasil domingo@braile.com.br

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

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]

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

ASSESSORA EDITORIAL/EDITORIAL ASSISTANT Rosangela Monteiro Camila Safadi PhD - São Paulo (BRA) S. José do Rio Preto (BRA) rosangela.monteiro@incor.usp.br camila@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 • Carolina Zuppardi • Fernando Pires Buosi • Marcelo Almeida

• 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 Edição Impressa - Tiragem: 250 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] 2012, 27: 1,2,3,4 2012, 27: 1 [supl] 2013, 28: 1,2,3 2013, 28: 1 [supl]

ISSN 1678-9741 - Publicação on-line 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 • SciELO - Scientific Library Online www.scielo.br • Scopus www.info.scopus.com • 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

• ADSAUDE - Sistema Especializado de Informação em Administração de Saúde www.bibcir.fsp.usp.br/html/p/pesquisa_em_ bases_de_dados/programa_rede_adsaude • Index Copernicus www.indexcopernicus.com • Google scholar http://scholar.google.com.br/scholar • EBSCO www2.ebsco.com/pt-br

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 - 2013 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:

Maurílio Onofre Deininger (PB) Marcelo Sávio da Silva Martins Carlos Manuel de Almeida Brandão AntonioAugusto Miana Luiz Carlos Schimin (DF) Marcela da Cunha Sales Rodrigo Mussi Milani Lourival Bonatelli Filho

Departamentos DCCVPED: DECAM: DECA: DECEN: DEPEX: DECARDIO:

Marcelo B. Jatene (SP) Alfredo Inácio Fiorelli (SP) Luiz Paulo Rangel Gomes da Silva (PA) 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 - Online version ISSN 0102-7638 - Printed version RBCCV 44205

Impact Factor: 0.809

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brazil) jul/sep- 2013;28(3) 315-432

CONTENTS/SUMÁRIO

EDITORIALS/EDITORIAIS Enhancing the quality of scientific research Valorizando a qualidade da pesquisa científica Domingo M. Braile.................................................................................................................................................................................. I Deleterious effects of reprocessing guide wires: an alert Efeitos deletérios do reprocessamento de fios-guia: um alerta Moacir Fernandes de Godoy................................................................................................................................................................. IV Screening of fetal congenital heart disease: the challenge continues Rastreamento das doenças cardíacas congênitas fetais: o desafio continua Luciane Alves da Rocha, Edward Araujo Júnior, Luciano Marcondes Machado Nardozza, Antonio Fernandes Moron......................V SPECIAL ARTICLE/ARTIGO ESPECIAL 1475 New information technology in cardiac surgery. Development of an applicative about ascending aortic aneurysm ("Aortic Surgery") Nova tecnologia de informação em cirurgia cardíaca. Desenvolvimento de um aplicativo sobre aneurisma de aorta ascendente ("Aortic Surgery") Roberto Gomes de Carvalho................................................................................................................................................................315 ORIGINAL ARTICLES/ARTIGOS ORIGINAIS 1476 The descending branch of the lateral femoral circumflex artery is a good option in CABG with arterial grafts Ramo descendente da artéria circunflexa lateral femoral é boa opção para revascularização do miocárdio com enxertos arteriais Fábio Antonio Gaiotto, Caio B. Vianna, Fabio F. Busnardo, José R. Parga, Luis Alberto de Oliveira Dallan, Luis A. M. Cesar, Noedir A. G. Stolf, Fabio B. Jatene..................................................................................................................................................................317 1477 Minimally invasive redo mitral valve surgery without aortic crossclamp Reoperação da valva mitral minimamente invasiva sem pinçamento da aorta Rodrigo Milani, Paulo Roberto Slud Brofman, Sergio Oliveira, Luiz Patrial Neto, Matheus Rosa, Victor Hugo Lima, Luis Fernando Binder, Aline Sanches..........................................................................................................................................................................325 1478 Effects of reprocessing on chemical and morphological properties of guide wires used in angioplasty Efeitos do reprocessamento nas propriedades químicas e morfológicas de fios-guia usados em angioplastia Rogério Valentim Gelamo, Eva Cláudia Venâncio de Sene, Luciana Paiva, Cristina da Cunha Hueb Barata de Oliveira, André Luiz Maltos, Wido H. Schreiner, Mário Bica de Moraes, Alfredo R. Vaz, Stanislav A. Moshkalev, Daniel Ferreira da Cunha.................331 1479 Randomized and comparative study between two intra-hospital exercise programs for heart transplant patients Estudo randomizado e comparativo entre dois programas de exercícios intra-hospitalares para pacientes de transplante de coração Tatiana Satie Kawauchi, Patricia Oliva de Almeida, Karen Rodrigues Lucy, Edimar Alcides Bocchi, Maria Ines Zanetti Feltrim, Emilia Nozawa............................................................................................................................................................................. 338

1480 Impact of aspirin use in the incidence of thromboembolic events after bioprosthesis replacement in patients with rheumatic disease Impacto da aspirina na incidência de eventos tromboembólicos após implante de bioprótese valvar cardíaca na doença reumática crônica André Rodrigues Durães, Milena Andrade Oliveira Durães, Luis Claudio Correia, André Mauricio Souza Fernandes, Roque Aras Junior.................................................................................................................................................................................... 347 1481 Risk factors for prolonged hospital stay after isolated coronary artery bypass grafting Fatores de risco para tempo de internação prolongada após revascularização isolada do miocárdio Elayne Kelen de Oliveira, Aída Luiza Ribeiro Turquetto, Pedro Luiz Tauil, Fernando Luiz Junqueira Jr., Luiz Guilherme Grossi Porto.................................................................................................................................................................... 353 1482 Factors associated to hypoxemia in patients undergoing coronary artery bypass grafting Fatores associados à ocorrência de hipoxemia em pacientes submetidos à revascularização miocárdica Natália Pereira dos Santos, Rodrigo Martins Mitsunaga, Daniel Lago Borges, Marina de Albuquerque Gonçalves Costa, Thiago Eduardo Pereira Baldez, Ilka Mendes Lima, Karol Cristina Fonseca Moura, Josimary Lima da Silva Lula....................................................364 1483 Adult congenital heart disease: experience with the surgical approach Cardiopatia congênita no adulto: experiência com a abordagem cirúrgica Fernando Tadeu Vasconcelos Amaral, Alfredo José Rodrigues, Paulo Henrique Manso, André Schmidt, Maria Fernanda Kolachinski, Clovis Carbone, Ricardo Nilson Sgarbieri, Walter Vilela de Andrade Vicente....................................................................................371 1484 Effects of different PEEP levels on respiratory mechanics and oxygenation after coronary artery bypass grafting Efeitos de diferentes níveis de PEEP na mecânica respiratória e oxigenação após revascularização do miocárdio Daniel Lago Borges, Vinícius José da Silva Nina, Marina de Albuquerque Gonçalves Costa, Thiago Eduardo Pereira Baldez, Natália Pereira dos Santos, Ilka Mendes Lima, Eduardo Durans Figuerêdo, Josimary Lima da Silva Lula...................................................380 1485 Assessment of sternal closure using titanium plate Avaliação do fechamento esternal com placa de titânio Renato Tambellini Arnoni, Daniel Chagas Dantas, Antoninho Arnoni, Caetano Nigro Neto, Camilo Abdulmassih Neto.................386 1486 Unstable angina does not increase mortality in coronary artery bypass graft surgery Angina instável não aumenta mortalidade em cirurgia de revascularização miocárdica Carolina Pelzer Sussenbach, João Carlos Guaragna, Rômulo Soares Castagnino, Jaqueline Piccoli, Luciano Cabral Albuquerque, Marco Antônio Goldani, João Batista Petracco, Luiz Carlos Bodanese..............................................................................................391 SHORT COMMUNICATIONS/COMUNICAÇÕES BREVES 1487 Ventricular assist device implantation with CentriMag VAS® for biventricular mechanical support Assistência ventricular com implante do dispositivo CentriMag VAS® para suporte mecânico biventricular João Roberto Breda, Diego Felipe Gaia, Murilo Macedo, Pedro Motta, Márcio Martins, Daniel Alves, Andre Luppi, José Honório Palma................................................................................................................................................................ 401 1488 Presentation of a needle for direct or percutaneous myocardium stem cells injection Apresentação de uma agulha para injeção direta ou percutânea de células tronco no miocárdio Nathan Valle Soubihe Junior, Andre Schmidt, Agnes Afrodite Sumarelli Albuquerque, Paulo Roberto Barbosa Evora....................405 CASE REPORT/RELATO DE CASO 1489 Giant thymic cyst with atypical location: case report Cisto tímico gigante com localização atípica: relato de caso Mário Augusto Cray da Costa, Mário Rodrigues Montemor Netto, Joelmir Colman, Gabriela Cordeiro da Costa............................408 LETTERS TO THE EDITOR/CARTAS AO EDITOR 1490 Letters to the Editor Cartas ao Editor...................................................................................................................................................................................412

SCIENTIFIC DISSEMINATION/DIVULGAÇÃO CIENTÍFICA 1491 Changing scientific communication Transformando a comunicação científica Karina Toledo/Agência Fapesp............................................................................................................................................................420 1492 Retraction/Retratação .......................................................................................................................................................................422 1493 Erratum/Errata .................................................................................................................................................................................423 Reviewers BJCVS 28.3/Revisores RBCCV 28.3 .............................................................................................................................424

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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

Enhancing the quality of scientific research Valorizando a qualidade da pesquisa científica

Domingo M. Braile1 DOI: 10.5935/1678-9741.20130046

he creation of a number of bibliometric indices to assess the scientific production, extremely important fact in an attempt to measure and value the hard work of scientists, separating the chaff from the wheat, has been undermined in recent times. The search for studies published in journals with higher impact, especially according to the criteria of the Impact Factor (IF) adopted and published by the ISI Journal Citation Report (JCR), the index most used as a parameter, eventually caused an imbalance, often distorting the basic purpose of making public the results of research and its benefits. In Brazil, Qualis, whose criteria for classification of scientific journals, along with the assessment of postgraduation programs, leads the researchers to publish their studies in journals with high IFs. Most of them from abroad, since the CAPES requires that the researchers have at least one publication in journals at the highest level (A1) whose impact is close to 4.00. Only way to maintain or improve their personal position and the institution to which they are bound. The Brazilian journal with the highest rate is now the Brazilian Journal of Psychiatry with IF of 1.856, far from the levels required by CAPES.

guidelines to publishers, we must emphasize the significantly reduction in emphasis on the impact factor of journals (not just from the ISI, but also the SCImago, Eigenfactor, H index, etc.) as a promotional tool; encouragement in responsible practices of authorship and provision of information about the specific contributions of each author, and encouragement of the primary literature citation (original articles) instead of review articles in order to give credit to the group that first reported a finding. The Brazilian Journal of Cardiovascular Surgery (BJCVS) supports the content of DORA as well as other initiatives to promote the dissemination of good quality scientific research. More than the number of citation the value of an article is in its content. It should be written clearly and has their results reproducible. I reaffirm the importance of bibliometric indices and the Editorial Board of BJCVS is making every effort to reveter the fall of our IF, which not just occured with BJCVS, but almost all Brazilian journals. The few who improved such index did so in small scale. Our struggle is that these indicators are not the only ways to assess a journal. We can not compare, for example, a cardiovascular surgery journal with general, as the Lancet, IF of 39,060, Science, IF of 31,027, British Medical Journal, IF of 17,215, because they embrace publications and citations of all specialties. For a comparison I mention the Annals of Thoracic Surgery's IF of 3454 and the European Journal of CardioThoracic Surgery of 2674. None have achieved the level of excellence required by CAPES.

DORA In an attempt to improve the way in which the production of scientific research is assessed by funding agencies and academic institutions, editors and publishers of scientific journals gathered during the Annual Meeting of the American Society for Cell Biology, held in December 2012 in San Francisco, USA, prepared a document, the San Francisco Declaration on Research Assessment, known by the acronym DORA [1]. The document emphasizes that the Impact Factor was created as a tool to help librarians to identify journals that could be acquired and not to measure the quality of scientific research in an article. From this, a review is performed on the limitations to its use, for example, the possibility of being misused, and the lack of transparency in relation to the data used to calculate the IF. The following document has some recommendations that should be followed by agencies, institutions, publishers, companies that provide metrics and researchers. Among the

Authorship Since the last edition, the information on the participation of each of the authors in articles is obligatory, and that has to be inserted in the submission process [2]. In addition to DORA, this practice is also encouraged by the International Committee of Medical Journal Editors (ICMJE), which even entered one more item in the criteria for authorship: “Agree to be responsible for all aspects of the study in ensuring that the issues on the accuracy or integrity of any part of the study were properly investigated and resolved.” This issue is so important that was the subject of an editorial published in the prestigious journal Lancet, of August 31, 2013 [3].

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Fig. 1 - Chart showing the evolution of BJCVS, Acta CirĂşrgica Brasileira, Arquivos Brasileiros de Cardiologia and Brazilian Journal of Medical and Biological Research in Scimago

Authors of studies submitted to BJCVS prior to that determination will be required to provide this information when the item is approved.

Also when accessing our site, the English version will be opened. To switch to the Portuguese, a simply click on the icon with the stylized Brazilian flag in the top of the page will be enough. Thus, we can further increase the number of hits. In July this year, only in the journal's website there were over 123 thousand hits, a daily average of more than 3,960 hits (Fig. 1). On the SciELO's website (www.scielo.br/rbccv), there were more than 38 thousand hits to articles, a daily average of 1,250 hits, totaling over 5,200 articles read per day!

APPs We are finalizing the development of Applications (APP), which can be downloaded for free on iPhones, iPads (using iOS system) and smartphones and tablets (which use Android system) and will provide access to the complete contents of BJCVS. Thus, we will provide more options for accessing our journal and, consequently, increasing its visibility.

Clinical trial For this, we will maintain the strict criteria in the assessment of studies and also keeping the BJCVS as a discussion forum. On page 412, a letter from Dr. JosĂŠ Maria Pereira de Godoy, questions the criteria that define the phases of a clinical trial. As the subject is controversial, I sent a copy to some experts, who kindly agreed to discuss the matter. The debate does not end on this issue and all those who wish to contribute can submit their

English Starting with this edition, the titles of all articles will be written first in English and then in Portuguese, in that order. The intention is to encourage and facilitate the access of those who access the electronic version on the websites www. bjcvs.org and www.rbccv.org.br in more than 100 countries that read us every day.

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Fig. 2 - Graph with hits to BJCVS during the month of July 2013. The average is almost 4,000l hits

text to Letter to the Editor to be published in the next issues. I take this opportunity to ask all those who are registered, either as an author or reviewer, for them to check their data and, if necessary, to update them, so that they can receive the information during the submission and review of the study, avoiding delays that may affect the processing of manuscripts.

members and residents to perform testing, a feature that is found in few high-level journas, being ours the pioneer in Brazil. My warmest regards and have an excellent reading!

CME Items available for testing by the Continuing Medical Education (CME) are: "Minimally invasive redo mitral valve surgery without aortic crossclamp" (pág. 325), "Effects of reprocessing on chemical and morphological properties of guide wires used in angioplasty" (pág. 331), "Risk factors for prolonged hospital stays after isolated coronary artery bypass grafting" (pág. 353), "Unstable angina does not increase mortality in coronary artery bypass graft surgery” (pág. 391). Unfortunately, the education system has not been used in the way it deserves. I ask all colleagues to encourage team

1 – Editor-in-Chief – BJCVS

REFERENCES

1. The San Francisco Declaration on Research Assessment (DORA) [Accessed: August 29, 2013]. Available at: http://am.ascb.org/dora/ 2. Braile DM. Autoria no artigo científico: definindo o papel de cada um. Rev Bras Cir Cardiovasc. 2013;28(2):I-II. 3. Authorship and accountability. Lancet. 2013;382(9894):744.

Watch the video with a summary of this Editorial in English: http://www.rbccv.org.br/video/2139/Enhancing_the_quality_of_scientific_research

III

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Editorial

Deleterious effects of reprocessing guide wires: an alert Efeitos deletérios do reprocessamento de fios-guia: um alerta

Moacir Fernandes de Godoy1, PhD

DOI: 10.5935/1678-9741.20130047

Gelamo et al., on page 331 of this issue, present the elegant work entitled “Effects of reprocessing on chemical and morphological properties of guide wires used in angioplasty” [1], in which they describe significant morphological changes after washing the guide wires once or twice using ultrasonic vibration and enzymatic detergent, and no significant changes when sterilized with ethylene oxide. This paper becomes even more relevant at a time when health authorities have been severely restricting the reuse of medical and hospital equipment, since it differentiates reprocessing techniques which can cause visible alterations after their first application. The study is limited to structural changes and it gives no details on possible clinical repercussions. This aspect would be of great practical interest as coronary angioplasty is one of the most commonly performed invasive procedures in the world and the discussion about the cost-effectiveness of reusing equipment is still undefined.

procedures, seven different types of devices were used, guide wires being one of them, totaling 76 new and 410 reprocessed. There were no differences in adverse events as a result of using either new or reprocessed equipment. These are new times, with equipment made up of new components and different processing techniques, and there lies the need for attention. The alert is welcome and the authors must be commended for focusing on a topic of great socioeconomic interest, which should be a cause for concern to both hemodynamics and healthcare management professionals, in general.

REFERENCES

1. Gelamo RV, Sene ECV, Paiva L, Oliveira CCHB, Maltos AL, Schreiner WH, et al. Effects of reprocessing on chemical and morphological properties of guide wires used in angioplasty. Rev Bras Cir Cardiovasc. 2013;28(3):331-7.

SEE ORIGINAL ARTICLE ON PAGES 331-337

2. Batista MA, Santos MA, Pivatelli FC, Lima ARS, Godoy MF. Eventos adversos e motivos de descarte relacionados ao reuso de produtos médicos hospitalares em angioplastia coronária. Rev Bras Cir Cardiovasc. 2006;21(3):328-33.

In 2006, this journal published an article by Batista et al. [2], in which the authors presented the follow-up of 60 patients that had undergone coronary angioplasty. During the

1. Hemodinamist of the Hemodynamics and Interventionist Cardiology Services at Hospital de Base da Fundação Regional de Medicina – FUNFARME (São José do Rio Preto- SP- Brazil)

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Editorial

Screening of fetal congenital heart disease: the challenge continues Rastreamento das doenças cardíacas congênitas fetais: o desafio continua

Luciane Alves da Rocha1, MD; Edward Araujo Júnior1, MD, PhD; Luciano Marcondes Machado Nardozza1, MD, PhD; Antonio Fernandes Moron1, MD, PhD DOI: 10.5935/1678-9741.20130048

Congenital heart disease (CHD) is the most common congenital malformation [1] in fetuses. It affects eight per 1,000 live births and is more common antenatally [2-5]. In beginning, cardiac evaluation was confined to pregnancies at increased risk of CHD, such as those with a family history of CHD or where extracardiac malformations had been detected. However, up to 86% of CHD occurs in pregnancies where there are no known high risk features [6], emphasizing the need for an effective fetal cardiac screening program for all pregnancies [7,8]. For this reason, in the mid 80’s started the idea of teaching the obstetrician to assess the heart in a simplified form during routine obstetric scanning [9,10]. Four chamber view scanning became an integral part of the fetal anatomical survey in many countries by the end of the 1980s [9,10]. However, prenatal screening based on visualization of the four-chamber view has much lower sensitivity [6,11]. This is partly because the four-chamber view may appear normal in cases of many anomalies, such as transposition of the great vessels, tetralogy of Fallot, double outlet right ventricle, truncus arteriosus, pulmonary or aortic stenosis/atresia and coarctation of the aorta. Anomalies of the great vessels are associated with an abnormal four-chamber view in 30% of cases [12]. When four-chamber and great vessels view are examined, the sensitivity of ultrasound screening for congenital heart defects increases from approximately 30% to 69–83% [6,11,13]. Therefore, we support the idea of evaluation both the four-chamber view and the outflow tracts (Figure 1). Then, we could improve the rate of prenatal detection of congenital heart disease.

In 2006, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published a guideline in which they described the “basic” and “extended basic” cardiac ultrasound examinations [14]. The intention was to standardize the assessment and to maximize the detection of heart anomalies during the second-trimester scan (Figure 1). However, we agree that a comprehensive fetal echocardiography should be performed when heart anomalies are suspected. One of the problems to follow this guideline is the difficulty of obtaining images of the outflow tracts. This happens because unlike the four-chamber view, the aorta and pulmonary artery do not lie in a single axis. In

Fig. 1 - Images for evaluating the fetal cardiac screening by twodimensional ultrasound. A: four-chamber view of the fetal heart. B: left ventricular outflow tract (LVOT). C: right ventricular outflow tract (RVOT). D: three-vessel view of the fetal heart. LV: left ventricle. RV: right ventricle. LA: left atrium. RA: right atrium. P: pulmonary artery. Ao: aorta. SVC: superior vena cava

1 Federal University of São Paulo (UNIFESP), Department of Obstetrics, São Paulo, SP, Brazil. E-mail: araujojred@terra.com.br

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compliance to DeVore study [15], we state that it is necessary experienced hands to view the outflow tract. Accordingly, it is important additional training. The development of new technologies is gaining strength as they; theoretically, facilitate the evaluation of the fetal heart exam including the outflow tracts. Four-dimensional ultrasonography (4DUS) with spatio-temporal image correlation (STIC) technology allows the acquisition of a volume dataset from the fetal heart, and displays a cineloop of a complete single cardiac cycle in motion. Moreover, STIC offers the advantage of offline assessment of cardiac structures, connections, and functions [16-18] (Figure 2).

However, we believe that the new methods will be very useful for tracking in the future. Technology tends to advance and sensitivity of this new method will continue improving. Thereby, the 3D/4D technology allows for a more comprehensive and practical assessment of CHD in the fetus. Antenatal screening can offer a number of benefits. The identification of CHD can facilitate early therapy and to prevent a cardiac decompensation. Other benefits include opportunities to counsel parents, to screen for co-existing abnormalities, to plan peripartum management and intrauterine intervention in some cases. In severe cases, some patients choose for termination of pregnancy. Ultimately, the increased detection rates of congenital heart disease reduce perinatal morbidity and mortality. We believe that adequate training associated with a proper use of new technologies may improve the rate of diagnose CHD.

REFERENCES

1. Lee K, Khoshnood B, Chen L, Wall SN, Cromie WJ, Mittendorf RL. Infant mortality from congenital malformations in the United States, 1970-1997. Obstet Gynecol. 2001;98(4):620-7. 2. Hoffman JI, Christianson R. Congenital heart disease in a cohort of 19,502 births with long-term follow-up. Am J Cardiol. 1978;42(4):641-7. Fig. 2 - Images for evaluating the fetal cardiac screening by fourdimensional ultrasonography with spatiotemporal image correlation (STIC) by multiplanar mode. A: four-chamber view of the fetal heart. B: three-vessel view of the fetal heart. C: left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT)

3. Mitchell SC, Korones SB, Berendes HW. Congenital heart disease in 56,109 births. Incidence and natural history. Circulation. 1971;43(3):323-32. 4. Hoffman JI. Incidence of congenital heart disease: II. Prenatal incidence. Pediatr Cardiol. 1995;16(4):155-65.

The STIC technology has several tools to analyze all cardiac structures: dynamic multiplanar mode, render mode, omni view, M mode, volume analysis, tomographic ultrasound imaging (TUI). These are new technologies that are still in development and in study. Despite the great efforts made so far, the STIC is still considered an additional method in echocardiography and, rarely, they are available in daily practice. There are many inherent difficulties in obtaining adequate cardiac images in a STIC [16], for example: the fetal position may vary during the exam; fetal movement during the acquisition of the volume; higher maternal body mass indices or oligohydramnios may make images more difficult and acquiring the images of the heart can be time consuming.

5. Gerlis LM. Cardiac malformations in spontaneous abortions. Int J Cardiol. 1985;7(1):29-46. 6. Achiron R, Glaser J, Gelernter I, Hegesh J, Yagel S. Extended fetal echocardiographic examination for detecting cardiac malformations in low risk pregnancies. BMJ. 1992;304(6828):671-4. 7. Robinson JN, Simpson LL, Abuhamad AZ. Screening for fetal heart disease with ultrasound. Clin Obstet Gynecol. 2003;46(4):890-6. 8. S m y t h e J F, C o p e l J A , K l e i n m a n C S . O u t c o m e o f prenatally detected cardiac malformations. Am J Cardiol. 1992;69(17):1471-4.

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9. Allan L. Antenatal diagnosis of heart disease. Heart. 2000;83(3):367.

Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan. Ultrasound Obstet Gynecol. 2006;27(1):107-13.

10. Allan L. Prenatal diagnosis of structural cardiac defects. Am J Med Genet Part C Semin Med Genet. 2007;145C(1):73-6.

15. DeVore GR. The aortic and pulmonary outflow tract screening examination in the human fetus. J Ultrasound Med. 1992;11(7):345-8.

11. Xu Y, Hu YL, Ru T, Gu Y, Yang Y, Dai CY. Importance of “Guidelines for performing fetal cardiac scan” in prenatal screening for fetal congenital heart disease. Zhonghua Fu Chan Ke Za Zhi. 2009;44(2):103-7.

16. DeVore GR, Falkensammer P, Sklansky MS, Platt LD. Spatio-temporal image correlation (STIC): new technology for evaluation of the fetal heart. Ultrasound Obstet Gynecol. 2003;22(4):380-7.

12. Paladini D, Rustico M, Todros T, Palmieri S, Gaglioti P, Benettoni A, et al. Conotruncal anomalies in prenatal life. Ultrasound Obstet Gynecol. 1996;8(4):241-6.

17. Viñals F, Poblete P, Giuliano A. Spatio-temporal image correlation (STIC): a new tool for the prenatal screening of congenital heart defects. Ultrasound Obstet Gynecol. 2003;22(4):388-94.

13. Carvalho JS, Mavrides E, Shinebourne EA, Campbell S, Thilaganathan B. Improving the effectiveness of routine prenatal screening for major congenital heart defects. Heart. 2002;88(4):387-91.

18. Gonçalves LF, Lee W, Chaiworapongsa T, Espinoza J, Schoen ML, Falkensammer P, et al. Four-dimensional ultrasonography of the fetal heart with spatiotemporal image correlation. Am J Obstet Gynecol. 2003;189(6):1792-802.

14. International Society of Ultrasound in Obstetrics & Gynecology.

VII

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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

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Carvalho RG - SPECIAL New information technology in cardiac surgery. Development ARTICLE of an applicative about ascending aortic aneurysm (“Aortic Surgery”)

New information technology in cardiac surgery. Development of an applicative about ascending aortic aneurysm (“Aortic Surgery”) Nova tecnologia de informação em cirurgia cardíaca. Desenvolvimento de um aplicativo sobre aneurisma de aorta ascendente (“Aortic Surgery”)

Roberto Gomes de Carvalho1 DOI: 10.5935/1678-9741.20130049

RBCCV 44205-1475

Abstract An app in the area of Aortic Diseases (ascending aortic aneurysm) was developed. This article offers a brief introduction about the information received and transmitted in the app and the process through which it was developed as well as its contents.

Resumo Desenvolvimento de um aplicativo na área de Doenças da Aorta (aneurisma da aorta ascendente). É descrita uma breve introdução sobre as informações recebidas e transmitidas, como foi desenvolvido o aplicativo e seu conteúdo.

Descriptors: Aneurysm. Heart/surgery.

Descritores: Aneurisma aórtico, cirurgia. Cirurgia.

There are two kinds of medical information: the received and the transmitted information. A source of data (received information) is necessary to transmit any information. A long time ago, this source was provided to people by the papyrus. The evolution of “technology” gave place to the book. At the time, it was a radical change and readers had great difficulty adapting to this new situation (www.youtube.com Papiro e os Monges). In the medical field, the most important and widely accepted information came from the Index Medicus. The first volume was published in 1879. For a long time, received information was provided by the printed Index Medicus. But due to the convenient and speedy way news is spread

on the internet, the online version of the Index surpassed the printed one. The last printed volume of the Index Medicus was published in December 2004 (volume 45). The online version of the printed Index Medicus is called PubMed. Exame magazine (03/25/2013) reported that, in 2012, 3.1 million tablets were sold in Brazil. This indicates a growth of 171% compared to sales in 2011. In the same period, the domestic tablets market grew 159%. As a result of these data, we decided to transmit the information to the medical field via the rapid and accessible way: the internet. The tool in this case was the app. Throughout the years, while working in the fascinating Cardiac Surgery specialty, we documented the interesting

1 - Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil, Hospital Nossa Senhora das Graças and Hospital São Vicente, Curitiba, PR, Brazil.

Work carried out at Hospital Nossa Senhora das Graças, Hospital São Vicente, and Hospital de Clinicas da Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.

Correspondence address: Roberto Gomes de Carvalho Rua Richard Strauss, 62 - Vista Alegre – Curitiba, PR, Brazil Zip code: 80820-110 E-mail: rcarvalho62@uol.com.br

Article received on September 9th, 2013 Article approved on September 15th, 2013

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cases with photos. Diseases of the aorta have always been attractive to surgeons because of their surgical challenges. The present app describes the cases of Ascending Aorta operated on by ourselves. We chose the cases by etiology and created a proper classification. Then, we contacted an information technology enterprise (www.snowmanlabs.com). It is a group with many professionals: a designer, someone to develop the app only for smartphones; another for tablets, and yet another for adjusting photos and text. The director was responsible for contacting Apple and Google. It took approximately 12 months of hard work from the beginning to the acceptance by Apple. The time spent in reviewing the app for Apple took four months and the work had to be done according to the enterprise´s strict rules. The app was accepted on August 27th, 2013. The name of the app is Aortic Surgery and it is available for iOS (iPhone, iPad, iTouch) and Android (smartphones and tablets) systems. The content has an introduction and eight great sessions following the etiologic causes of the aneurysms. In the introduction, we described the general aspects of the aneurysm (incidence, natural history, and operative techniques). It is a bilingual (English and Portuguese) app, It is possible to add favorites and alter the brightness of the display. Furthermore, it offers slide presentations, a manual on how to use it, and bibliographic references. The references are linked to PubMed.

3. Aortic dissection: acute and chronic. The acute aortic dissection being with a cardiac tamponade. 4. Involvement of the proximal hemi-arch and aortic arch (quadrifurcated graft and stepwise anastomosis) 5. After late cardiac surgery: (1) aortic valve replacement (biological and mechanical prostheses); (2) acute type A dissection; (3) Bentall procedure; (4) correction of congenital cardiopathy (type II aortopulmonary window operated on 32 years ago); and (5) myocardial revascularization (functioning left internal thoracic artery to the left anterior descending artery) 6. Reimplantation technique (moderate aortic valve insufficiency) 7. Association with coarctation of the aorta (in adults) with extra-anatomic bypass (one case with type A dissection and severe aortic valvopathy and another with a bicuspid aortic valve stenosis in an old lady) 8. Sternal erosion (luetic) A research was performed and there was no similar app in the national or international market. The content is exclusive (cases operated on by ourselves). It has approximately 145 illustrations. Each case is briefly described with pertinent bibliography and has a link to PubMed. In other words, it is like an “online” atlas of surgical treatment of ascending aortic aneurysm. Certainly, it is an important tool for students, residents, cardiologists, interventionists, surgeons, and other health professionals.

The sessions were as follows: 1. Restricted to the ascending aorta. It has three subsessions: aortoplasty, aortic loculation, and ascending aorta. 2. Bicuspid aortic valve and Marfan Syndrome (in association with a severe pectus excavatum)

Author’s roles & responsibilities RGC

App idealization. Text writing

Download the APP Aortic Surgery

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Gaiotto FA, etORIGINAL al. - The descending branch of the lateral femoral circumflex ARTICLE artery is a good option in CABG with arterial grafts

The descending branch of the lateral femoral circumflex artery is a good option in CABG with arterial grafts Ramo descendente da artéria circunflexa lateral femoral é boa opção para revascularização do miocárdio com enxertos arteriais

Fábio Antonio Gaiotto1, MD, PhD; Caio B. Vianna1, MD, PhD; Fabio F. Busnardo2, MD, PhD; José R. Parga1, MD, PhD; Luis Alberto de Oliveira Dallan1, MD, PhD; Luis A. M. Cesar1, MD, PhD; Noedir A. G. Stolf1, MD, PhD; Fabio B. Jatene1, MD, PhD

DOI: 10.5935/1678-9741.20130050

RBCCV 44205-1476

Abstract Introduction: The descending branch of the lateral femoral circumflex artery is an option for coronary artery bypass grafting. Objective: To evaluate the early patency and adaptation of lumen diameter using multidetector computed angiotomography. Methods: Thirty-two patients were selected to undergo coronary artery bypass grafting using the descending branch of the lateral circumflex artery, the internal thoracic artery, and other grafts. Evaluations were carried out through high resolution computed tomography performed on the 7th and 90th postoperative day. Diameters of the descending branch of the lateral circumflex artery and the left internal thoracic artery were measured 3 cm before the distal anastomosis, in the middle portion, and 3 cm after the proximal anastomosis. Diameters were compared using paired t-test (P<0.05). Results: Descending branch of the lateral femoral circumflex artery wDescending branch of the lateral femoral circumflex artery was used in 26 patients, as its use was not viable in six patients (18%). It was used as composite graft in

all cases. The anterior descending branch was revascularized by the left internal thoracic artery in all cases. Patency rates of the descending branch of the lateral femoral circumflex artery were 96% and 92%, respectively. No occlusions were observed in the left internal thoracic artery (LITA) and no ischemic events were observed in the descending branch of the lateral circumflex. Descending branch of the lateral femoral circumflex artery increased the lumen diameter in the middle (P=0.001) and distal portions (P=0.006); the left internal thoracic artery (LITA) increased in the middle portion (P=0.001). Conclusion: Similar to the left internal thoracic artery, the descending branch of the lateral femoral circumflex artery showed high patency rate and positive luminal adaptation. This early evaluation confirms the descending branch of the lateral femoral circumflex artery as a potential alternative for grafting. Due to anatomical variations, preoperative femoral angiographic evaluation appears to be mandatory.

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto do Coração, São Paulo, SP, Brasil. 2 Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Disciplina de Cirurgia Plástica, São Paulo, SP, Brasil.

Correspondende address: Fábio Antonio Gaiotto Department of Surgery, Heart Institute (InCor), Av. Doutor Eneas Carvalho Aguiar 44 – Jardim Paulista – São Paulo, SP, Brazil Zip Code: 05403900 E-mail: fabio.gaiotto@incor.usp.br

Descriptors: Tomography. Myocardial revascularization. Coronary disease.

Work carried out at Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto do Coração, São Paulo, SP, Brazil.

Article received on March 11th, 2013 Article accepted on June 25th, 2013

Funding: This work was funded by FAPESP, Brazil.

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ram comparados pelo método t de Student pareado (significância P<0,05). Resultados: O ramo descendente da artéria circunflexa lateral foi adequado para a utilização em 26 pacientes. Em seis (18%) pacientes, o ramo descendente da artéria circunflexa lateral era inviável. Em todos os casos, o ramo descendente da artéria circunflexa lateral foi empregado sob a forma de enxerto composto. Todos os pacientes receberam artéria torácica interna esquerda para o ramo descendente anterior. A perviabilidade do ramo descendente da artéria circunflexa lateral foi de 96% e 92%, em 7 e 90 dias de pós-operatório, respectivamente. Não foram detectadas oclusões da artéria torácica interna esquerda. Não foram detectados sinais de espasmo do ramo descendente da artéria circunflexa lateral. O ramo descendente da artéria circunflexa lateral apresentou aumento de diâmetro nas porções média (P=0,001) e distal (P=0,006) e a artéria torácica interna esquerda, aumento na porção média (P=0,001). Conclusão: O remodelamento positivo sugere que o ramo descendente da artéria circunflexa lateral tem comportamento semelhante à artéria torácica interna esquerda e pode ser uma excelente opção para a revascularização do miocárdio com enxertos arteriais. Em virtude das variações anatômicas, estudos de pré-operatório podem auxiliar na seleção de casos.

Abbreviations, acronyms & symbols DLFCA CABG LITA SV

Descending branch of the lateral femoral circumflex artery Coronary artery bypass grafting Left internal thoracic artery Saphenous vein

Resumo Introdução: O ramo descendente da artéria circunflexa lateral é um enxerto pouco avaliado e pode ser uma opção para a revascularização do miocárdio. Objetivo: Avaliar a perviabilidade e o remodelamento arterial do ramo descendente da artéria circunflexa lateral, em três meses de seguimento, por meio de angiotomografia de artérias coronárias. Métodos: Foram analisados 32 pacientes submetidos à revascularização do miocárdio com ramo descendente da artéria circunflexa lateral, artéria torácica interna esquerda e outros enxertos. A avaliação foi realizada por meio da tomografia computadorizada de alta resolução, realizada no 7º e 90º dias de pós-operatório. O diâmetro do ramo descendente da artéria circunflexa lateral foi medido 3 cm antes da anastomose distal, na porção média e 3 cm após a anastomose proximal. As mesmas medidas foram realizadas para a artéria torácica interna esquerda. Os diâmetros fo-

Descritores: Tomografia. Revascularização miocárdica. Doença das coronárias.

INTRODUCTION

The first case in which the DLFCA was used as a graft in CABG was performed in Japan and was reported by Tatsumi et al. [13], in 1996, when the DLFCA was used as a free graft from the aorta to the right coronary artery. Two years later, Schamún et al. [14] reported promising results using the DLFCA as a coronary graft in 35 patients, with most cases employing early evaluation via angiographic studies after surgery. In these series, the left anterior descending coronary artery was revascularized by the left internal thoracic artery (LITA) in all patients, and the DLFCA was used as a composite graft with the LITA (end-to-side with a Y shape) in most cases. In a few patients, the DLFCA was used as an extension of the right internal thoracic artery (end-to-end anastomosis to revascularize the distal portion of the right coronary artery) or as a free aorta-coronary graft. In 2003, Fabbrocini et al. [15] published the most relevant study on this topic, reporting excellent clinical results and patency rates using the DLFCA as a composite graft with the LITA, in 147 patients, in the short and mid-term.

It is well known that arterial grafts provide better patency rates for coronary artery bypass grafting (CABG) than saphenous veins (SV), in both the short and long-term [1-5]. Therefore, alternative arterial grafts have been continuously researched. The most commonly used arterial grafts are the left and right internal thoracic [1,2,5-8] and radial arteries [9,10]. The inferior epigastric and gastroepiploic arteries are less frequently used [1,5,7,10]. Other arterial conduits, such as the splenic, subscapular, inferior mesenteric, ulnar, and intercostal arteries have rarely been used [5]. In plastic and reconstructive surgeries, the lateral femoral circumflex artery is often used to supply composite skin and muscle tissues, such as an anterolateral thigh flap [11,12]. The descending branch of the lateral femoral circumflex artery (DLFCA) has attractive characteristics that qualify it as an option for arterial grafting in surgical myocardial revascularization.

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We evaluated the early outcomes, technical results, patency rates and lumen diameter adaptation of the DLFCA when used as a composite graft with the LITA or SV, by multidetector computed angiotomography.

the DLFCA arises from the lateral femoral circumflex artery soon after its origin from the deep femoral artery, infrequently arising separately. The DLFCA courses downward through the intermuscular space between the rectus femoris and the vastus lateralis muscles (Figure 1B) near the femur, ending in the vastus muscle near the knee joint. Harvesting was performed carefully with minimal handling using very lowvoltage electrocautery. The dissection was started from the beginning of the DLFCA toward the end in a non-skeletonized fashion (Figure 2A). The two large veins that usually accompany the artery were left undisturbed, the femoral nerve branches were not involved, and all collateral branches were ligated for complete dissection. The distal portion of the DLFCA harvesting was cut, and a solution with papaverine was injected through it. The proximal portion was then cut, the harvesting was removed, and composite conduits of the DLFCA with the LITA or SV were prepared (Figure 2B). However, prior to construction, to prevent vasospasm, the dissected DLFCA was subjected to alternating submersions in two 0.9% saline solutions at 36Â°C: one with papaverine (1:20 dilution); another with nitroglycerin (10 mg) and diltiazem (50 mg) diluted in a physiologic solution (500 ml). Additionally, to avoid arterial vasospasm, the patients were continuously supplied with intravenous nitroglycerin throughout the operative period, and oral diltiazem was administered soon after endotracheal extubation and maintained for three months.

METHODS Patient Selection During a period of one year and eight months, a single surgical team selected 32 patients as candidates for CABG using the DLFCA as a composite graft. All patients had stable three-vessel coronary artery disease with normal or nearly normal left ventricular function. Inclusion criteria were absence of peripheral arteriopathy and critical stenosis or oclusion of coronary branches. In patients with indication for doble mammary, DLFCA was used as a complementation. All patients with suspected or established lower limb arterial disease, renal insufficiency (defined by a creatinine serum level >2 mg/dL or the patient being on dialysis), and previous cardiac operation were not included. The institutional committee on human research approved the study and all patients gave informed consent regarding the study protocol. Study Protocol After median sternotomy, the LITA and SV were simultaneously dissected, and the DLFCA was dissected soon thereafter. All coronary arteries were revascularized on cardiopulmonary bypass with normothermic perfusion and warm myocardial protection. Composite conduits of the DLFCA with the LITA were prepared (end-to-side, in a Y shape) before initiating extracorporeal circulation and were covered with gauze in physiologic saline solution and papaverine. After initiating extracorporeal circulation, the left anterior descending coronary artery was revascularized by the LITA, and the scheduled revascularizations with SV were accomplished. Other arterial grafts were used infrequently: radial artery in one and right internal thoracic artery in 4 cases. Composite grafts of the DLFCA with SV were constructed at the end of the operation while the patients were on cardiopulmonary bypass. The proximal anastomosis of the DLFCA with SV was performed near the origin of the vein in the aorta. On-pump, all composite DLFCA grafts were anastomosed onto a previously selected coronary artery with an acceptable lumen diameter and atherosclerotic obstruction of 70% or more. All anastomoses were performed using a continuous 8-0 polypropylene suture. The DLFCA was approached through an incision 15 to 20 cm in length on the anterolateral face of the thigh in its proximal and middle third along the lateral margin of the rectus femoris muscle (Figure 1A). The incision corresponded to an imaginary straight line between the anterosuperior iliac spine and the lateral border of the patella. The fascia lata of the quadriceps was incised longitudinally. Generally,

Fig. 1 â&#x20AC;&#x201C; Approach of the DLFCA. A: Arrowheads point to the line between the RFM and the VLM where the DLFCA courses downward through the intermuscular space. B: The dashed white line indicates the initial incision, which was 15 to 20 cm in length on the anterolateral aspect of the thigh in its proximal and middle third in the lateral margin of the RFM. DLFCA = descending branch of the left femoral circumflex artery; RFM = rectus femoris muscle; VLM = vastus lateralis muscle.

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aorta 10 s after infusion of contrast (SureStart, Toshiba Medical Systems, Japan). Acquisition of the contrasted set began automatically when the threshold of 180 Hounsfield units was achieved in the region of interest (descending aorta). For image reconstruction a retrospective analysis of the electrocardiographic tracing was employed, searching for the best image during the middle diastole, generally approximately 700 ms before the next R wave or 75% of the RR. From this set, the entire block was reprocessed with a thickness of 0.3 mm and analyzed in a workstation (Vitrea®, Vital Images, USA). The angiotomographies purposes were to verify patency rates, to identify technical problems (kinks and anastomotic stenoses), and to measure the lumen diameters of the DLFCA and LITA grafts at three points: 3 cm after the proximal anastomosis, in the middle of the graft, and 3 cm before the distal anastomosis. All native vessels and grafts were evaluated with transverse, coronal, sagittal, oblique and reformatted curved planes to visually identify proximal and distal anastomosis. Anastomotic stenoses were considered if the size of the proximal vessel was greater than the anastomotic site, with a 50% cutoff considered significant. Special attention was paid to bypass grafts as they were the most important data in the study. All measurements were manually traced three times at the designated portions of the vessel by a blinded reader to the design of the study (>7 year coronary experience in computed tomography). The mean value of the automatic software results were used as the reference value for comparison.

Fig. 2 – Harvesting of the DLFCA. A: Arrow points to the harvesting of the DLFCA. B: A composite graft (Y shape) constructed by the LITA and the dissected DLFCA. DLFCA = descending branch of the left femoral circumflex artery; RFM = rectus femoris muscle; VLM = vastus lateralis muscle; VIM = vastus intermedius muscle; LITA = left internal thoracic artery.

Computed Angiotomographies Computed tomography images were acquired with a multidetector system (Aquilion® 64, Toshiba Medical Systems, Japan) using previously described parameters [16] approximately 1 week after CABG, and were repeteaded 3 months later. Briefly, all patients with contraindication to contrast computed tomography were excluded and scanning was planned based on scout images to cover the entire extension of the chest from the LITA to the bottom of the heart. Unless contraindicated, patients with a heart rate above 60 bpm received intravenous metoprolol at a dose of up to 15 mg to reach between 50 and 60 bpm. Patients with a contraindication to beta-blockers were given diltiazem intravenously (0.25 mg/kg; if necessary, a second dose was given to reach the expected heart rate). Sublingual nitrates were administered just before scanning in all patients in whom it was not contraindicated (systolic blood pressure <110 mmHg, intake of phosphodiesterase inhibitors, known intolerance) in order to prevent vasospasm and increase vessel size. Scan parameters were adjusted by body mass index and a prospective acquisition electrocardiogram gating (55% to 85% of the RR), with heart rate-adjusted gantry rotation of 350-500 msec, pitch and tube currents of 240-450 mA, 120kV tube voltage, 0,5 mm slice thickness to ensure a 12-15 mSv radiation dose. The patients were then injected with 120 ml of nonionic iodinated contrast (Iopamiron® 370, Bayer Schering Pharma AG, Berlin, Germany) at a rate of 5 ml/s through the antecubital vein, followed by 30 ml of saline solution. The arrival of the contrast was monitored through the acquisition of axial images at the level of the descending

Statistical Analysis Quantitative data were expressed as mean±SD, and discontinuous values were presented as percentages. Quantitative values were compared using a two-sided paired Student’s t test or Wilcoxon signed rank test for nonGaussian distributions. All data analyses were performed using the Statistical Package for the Social Sciences (version 17.0, SPSS Inc., Chicago, IL, USA). Differences at P<0.05 were considered to be statistically significant. RESULTS After dissecting the DLFCA in the operating room, out of the 32 selected patients, the artery was considered appropriate for use in 26 (81%); 22 of whom were male (85%), aged 62±7 years (range, 44 to 73 years-old). All patients had stable triple-vessel coronary artery disease. Hypertension was present in 92% of the patients and diabetes mellitus in 26%. In six (19%) patients, four of them being male, aged 69±6 years (range, 60 to 75 years), the DLFCA was considered inappropriate for use as a graft because of the following: it was not found in one case; one had severe atherosclerosis; two were very short; and two were short and

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thin. The mean length of the grafts obtained after dissection was 9.9±4.0 cm (range, 4 to 19 cm) in the 26 patients with an appropriate DLFCA. Among the six cases with inappropriate grafts, except for the cases with a missing DLFCA and severe atherosclerosis, the mean length of the grafts obtained was 5.2±2.0 cm (range, 4 to 8 cm). Thus, the standardized surgical protocols were applied in 26 of the 32 selected patients. The mean cardiopulmonary bypass time was 85 ± 27 minutes (range, 50 to 150 minutes), and the aortic cross clamp time was 58±21 minutes (range, 34 to 110 minutes). All of the intraoperative and immediate postoperative periods were uncomplicated. On average, 3.7±0.8 (range, 3 to 5) coronary arteries were grafted for each patient. The composite DLFCA grafts were constructed with the LITA (Y shape) in 15 cases and with SV in 11 cases. The coronary arteries revascularized by the DLFCA grafts were as follows: diagonal branch of the left anterior descending artery in 13 patients, obtuse marginal branch of the circumflex artery in eight, intermediate left main coronary artery in three, right coronary artery in one, and posterolateral branch of the right coronary artery in one patient. No clinical complications related to the LITA or DLFCA grafts were observed during the hospital stay, after surgery, or during the 3-month follow-up period after discharge. No ischemic event, re-exploration for bleeding, sternal infection, or mediastinitis was observed in any patient. The first computed angiotomography was performed in-hospital in all patients, 7±1 days (range, 5 to 11 days) after the operation, and it was repeated 90±5 days (range, 83 to 103 days) after surgery. Despite previously signing

the consent form, one patient refused to undergo the tomographies after surgery. In another patient, the images of the first tomography were poor and the exam was not repeated on the 90th day after surgery. One angiotomography performed 3 months after surgery was of sufficiently good quality to measure the lumen of the DLFCA graft, but not of the LITA. As a result, the inner diameters of the DLFCA graft were measured in 24 cases, and those of the LITA graft were determined in 23 patients. The patency rates of the DLFCA grafts were 23/24 patients (96%) on the 7th day and 22/24 patients (92%) on the 90th day after surgery. The patency rates of the LITA grafts were 100% in both evaluations. Signs of vasospasm and technical complications, such as kinks in the grafts or anastomotic stenosis, were not observed in any case. The results regarding the inner diameters of the grafts are presented in Table 1. Comparison of the lumen values between the 7th and 90th day after surgery showed positive adaption both of the DLFCA and LITA grafts. The lumen of the DLFCA grafts increased significantly in the middle and distal portions, and the lumen of the LITA grafts increased significantly in the middle portion (Table 1). DISCUSSION Although the DLFCA is a recognized alternative arterial graft for CABG, especially as a composite conduct, little information is available regarding the outcomes, patency, vasospasm and the occurrence of technical complications, such as kinks or anastomotic stenosis. This study sought to evaluate these data in the short-term.

Table 1. Comparison of inner diameters (mm) of the LITA and DLFCA, 7 and 90 days after CABG Segment n Mean SD Graft/follow-up (days) Minimum Maximum Proximal 24 2.0 0.4 DLFCA-7th 1.3 2.9 Proximal 24 2.2 0.3 DLFCA-90th 1.3 2.9

P value 0.174

DLFCA-7th DLFCA-90th

Middle Middle

24 24

1.9 2.3

0.4 0.4

1.3 1.2

2.5 3.0

< 0.001

DLFCA-7th DLFCA-90th

Distal Distal

24 24

1.8 2.0

0.4 0.4

1.0 1.2

3.0 2.9

0.006

LITA-7th LITA-90th

Proximal Proximal

23 23

2.7 2.7

0.4 0.3

1.7 2.0

3.3 3.2

0.930

LITA-7th LITA-90th

Middle Middle

23 23

2.4 2.6

0.3 0.3

2.0 2.0

3.1 3.2

0.001

LITA-7th LITA-90th

Distal Distal

23 23

2.1 2.2

0.3 0.4

1.6 1.7

2.6 2.8

0.155

CABG = coronary artery bypass graft; DLFCA = descending lateral femoral circumflex artery; LITA = left internal thoracic artery; SD = standard deviation.

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Some authors recommend femoral arteriography before every CABG [13,17] in which the DLFCA is a planned graft because this vessel can present anatomical variations, such as short length, narrow lumen diameter or anomalous origins, that make it difficult to dissect and use [18]. Another reason to perform preoperative femoral arteriography is to verify the presence of atherosclerosis. Despite this, SchamĂşn et al. [14], in 1998, did not perform femoral angiographies before CABG in the 35 patients addressed in their report, but only carried out careful clinical preoperative evaluations to rule out lower limb arterial disease. Similarly, in the series of Fabbrocini et al. [15] (147 patients undergoing CABG using DLFCA grafts) the authors performed preoperative continuous-wave Doppler to investigate arteriosclerosis in the iliac and femoral arteries. When significant arterial disease was discovered, femoral arteriography was performed to assess the DLFCA. Our study design included only a careful clinical preoperative evaluation, and patients with suspected or proven lower limb arterial disease were excluded. However, our results showed that in six of the 32 selected patients the DLFCA was inappropriate for use as a graft since one presented severe atherosclerosis, one was not found, and four had very short length and/or narrow lumen diameter. These six cases were excluded of the study in the operating room. We deemed a 19% exclusion rate to be too high. In fact, we changed our initial opinion and concluded that some preoperative femoral arteriographic evaluation is mandatory. Preoperative continuous-wave Doppler, as performed by Fabbrocini et al. [15], can be used to investigate arteriosclerosis, but not anatomical variations of the DLFCA, which are the most common problem. Femoral angiotomography is a non-invasive type of arteriographic evaluation that can identify anatomical variations and atherosclerosis, thus avoiding dissection of the DLFCA in some patients and the aesthetic consequences of a thigh incision. No clinical complications related to the LITA or DLFCA grafts were observed during the hospital stay, after surgery, or during the 3-month follow-up period after discharge, and vasospasm was not noted. No ischemic event, reexploration for bleeding, sternal infection, or mediastinitis was observed in any patient. No significant complications in lower limbs occurred after dissection of the DLFCA in any of the patients. The surgical wound healed rapidly with no infection or compartment syndrome. Transient dysesthesia of the thigh was observed in only one patient. All patients were discharged. These results indicated very satisfactory early outcomes after surgery. The in-hospital angiotomographic evaluation of the patients (on the 7th day after surgery) did not show vasospasms, kinks or technical complications in the anastomoses, and showed very good patency rate both of the LITA and the DLFCA grafts (100% and 96%, respectively). The only patient with an early occlusion of the DLFCA graft had no

clinical complications. Furthermore, the angiotomographic evaluation performed on the 90th day of follow-up did not show any mechanical problems and revealed good patency rates (100% for the LITA graft and 92% for the DLFCA graft). Vasospasms, kinks and anastomotic stenoses were not observed on the 90th day after surgery either. Although these were early results, they were encouraging with respect to using the DLFCA as a graft in CABG. To our knowledge, this was the first study that evaluated early adaptation of lumen diameters of the DLFCA and compared it with the LITA when used as grafts in CABG. As expected, on the 90th day following surgery, the LITA showed a significant increase in the middle portion of the lumen. The DLFCA grafts also presented positive adaptation, which was statistically significant in the middle and distal portions. These were also positive, encouraging results. We should not assert that we evaluated remodeling of the grafts because this is a broader concept involving histological and structural changes. However, we assessed variation of inner diameters, which is an important part of the remodeling. Harvesting the DLFCA is usually quick and safe. Similar to all surgical techniques it depends on previous training. Dissection of the DLFCA should be performed by two surgeons because the quadriceps muscle is bulky and its exposure can be difficult. In our experience, initial dissections on cadavers require 30 to 40 minutes. During the surgery, harvesting is usually carried out quickly, in approximately 15 minutes. The fascia lata of the quadriceps should be closed after dissection to prevent herniation of the rectus femoris and vastus lateralis muscles. As observed in our results, a sensory deficit due to manipulation of the quadriceps nerve branches is very uncommon and usually transient [14,15]. To our knowledge, there are no reports of serious functional deficits of lower limbs or compartment syndrome arising from dissection of the DLFCA. The wound usually heals rapidly, and local infection is very uncommon. The aesthetic result is usually good because the lateral face of the thigh has no folds, and the healing line is thin and without retractions. Computed angiotomography in the evaluation of bypass grafts still has limitations such as high attenuation artifacts attributable to beam-hardening and partial volume-averaging effects. Surgical clips and respiratory artifacts are other sources of errors. However, the new generation of scanners is getting faster and more efficient, thereby avoiding many of these drawbacks. Reports have shown the strength of the method in the evaluation of grafts after CAGB [19-24]. Obviously, conventional angiography remains the gold standard method to assess graft patency and stenoses, but serious complications such as stroke, aortic dissection, coronary dissection, and other vascular complications can occur. Nowadays, the authors are convinced that computed angiotomography is the most appropriate method to assess graft patency after CABG in study protocol involving patients [24].

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The present study has evident limitations. The study is underpowered due to the small sample size and the short-term follow-up evaluation of graft patency. In fact, the authors did not intend to describe a new possibility of arterial graft, since the surgical technique and the patency rates have been previously evaluated [14,15]. The intention of the authors was to emphasize this viable alternative of using arterial graft in CABG and to evaluate the adaptation of lumen diameter. After the relevant publication of Fabbrocini et al. [15], in 2003, additional studies evaluating DLFCA grafts were no longer performed. In conclusion, the original design of our study did not include preoperative femoral arteriography. However, in the operating room, we observed a high rate of patients (19%) in whom the graft was considered inappropriate for use due to anatomical variations, such as short length, narrow lumen diameters, and silent atherosclerosis. These results led us to change our initial opinion, and we concluded that a preoperative femoral arteriographic or ultrassonographic evaluation was mandatory for all scheduled patients, as previously recommended by some authors [13,17]. Dissection of the DLFCA graft was usually simple, quick, free from local complications, and had good aesthetic results. We used the DLFCA in composite grafts with the LITA or SV, and we observed very promising early results with regard to outcomes, technical results, patency rates and lumen diameter adaptation of this graft. The DLFCA should be considered as representative of a good alternative arterial graft in CABG.

surgery with internal-thoracic-artery grafts: effects on survival over a 15-year period. N Engl J Med. 1996;334(4):216-9. 4. Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986;314(1):1-6. 5. He GW. Arterial grafts for coronary artery bypass grafting: biological characteristics, functional classification, and clinical choice. Ann Thorac Surg. 1999;67(1):277-84. 6. Kurlansky PA, Traad EA, Dorman MJ, Galbut DL, Zucker M, Ebra G. Thirty-year follow-up defines survival benefit for second internal mammary artery in propensity-matched groups. Ann Thorac Surg. 2010;90(1):101-8. 7. Glineur D, D’Hoore W, Price J, Dorméus S, de Kerchove L, Dion R, et al. Survival benefit of multiple arterial grafting in a 25-year single-institutional experience: the importance of the third arterial graft. Eur J Cardiothorac Surg. 2012;42(2):284-90. 8. Martins SK, Santos MA, Tirado FHP, Martins Jr FCE, Malat HF, Jatene AD, et al. Revascularização do miocárdio com emprego de ambas artérias mamárias internas em pacientes com diabetes mellitus. Rev Bras Cir Cardiovasc. 2007;22(3):291-6. 9. Acar C, Ramsheyi A, Pagny JY, Jebara V, Barrier P, Fabiani JN, et al. The radial artery for coronary artery bypass grafting: clinical and angiographic results at five years. J Thorac Cardiovasc Surg. 1998;116(6):981-9. 10. Calafiore AM, Di Giammarco G, Teodori G, D’Annunzio E, Vitolla G, Fino C, et al. Radial artery and inferior epigastric artery in composite grafts: improved midterm angiographic results. Ann Thorac Surg. 1995;60(3):517-23.

Authors' roles & responsibilities FAG CBV FFB JRP LAOD LAMC NAGS FBJ

Study design, surgical procedures and manuscript writing Patients clinical follow up Orientation in the preparation of the arterial graft Angiotomography evaluation Angiotomography evaluation Patients clinical follow up Orientation for study design and final manuscript approval Orientation for study design and final manuscript approval

11. Wei FC, Jain V, Celik N, Chen HC, Chuang DC, Lin CH. Have we found an ideal soft-tissue flap? An experience with 672 anterolateral thigh flaps. Plast Reconstr Surg. 2002;109(7):2219-26. 12. Koshima I, Yamamoto H, Hosoda M, Moriguchi T, Orita Y, Nagayama H. Free combined composite flaps using the lateral circumflex femoral system for repair of massive defects of the head and neck regions: an introduction to the chimeric flap principle. Plast Reconstr Surg. 1993;92(3):411-20.

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1. Fitzgibbon GM, Kafka HP, Leach AJ, Keon WL, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol. 1996;28(3):616-26. 2. Tatoulis J, Buxton BF, Fuller JA, Royse AG. Total arterial coronary revascularization: techniques and results in 3,220 patients. Ann Thorac Surg. 1999;68(6):2093-9.

14. Schamún CM, Durán JC, Rodríguez JM, Rodríguez M, Sanguinetti CM, Braccini G, et al. Coronary revascularization with the descending branch of the lateral femoral circumflex artery as a composite arterial graft. J Thorac Cardiovasc Surg. 1998;116(5):870-1.

3. Cameron A, Davis KB, Green G, Schaff HV. Coronary bypass

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C, Cioffi P. The descending branch of lateral femoral circumflex artery in arterial CABG: early and midterm results. Ann Thorac Surg. 2003余75(6):1836-41.

G, et al. Coronary artery bypass grafts and MDCT imaging: what to know and what to look for. Eur Radiol. 2007;17(12):3166-78. 21. Onuma Y, Tanabe K, Chihara R, Yamamoto H, Miura Y, Kigawa I, et al. Evaluation of coronary artery bypass grafts and native coronary arteries using 64-slice multidetector computed tomography. Am Heart J. 2007;154(3):519-26.

16. Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med. 2008;359(22):2324-36. 17. Faidutti B. Coronary artery bypass grafting with the descending branch of the lateral femoral circumflex artery used as an arterial couduit: is arteriographic evaluation necessary before its use? J Thorac Cardiovasc Surg. 1999余117(6):1229-30.

22. Ropers D, Pohle FK, Kuettner A, Pflederer T, Anders K, Daniel WG, et al. Diagnostic accuracy of noninvasive coronary angiography in patients after bypass surgery using 64-slice spiral computed tomography with 330-ms gantry rotation. Circulation. 2006;114(22):2334-41.

18. Fukuda H, Ashida M, Ishii R, Abe S, Ibukuro K. Anatomical variants of the lateral femoral circumflex artery: an angiographic study. Surg Radiol Anat. 2005余27(3):260-4.

23. Stein PD, Beemath A, Skaf E, Kayali F, Janjua M, Alesh I, et al. Usefulness of 4-, 8-, and 16-slice computed tomography for detection of graft occlusion or patency after coronary artery bypass grafting. Am J Cardiol. 2005;96(12):1669-73.

19. Salm LP, Bax JJ, Jukema JW, Schuijf JD, Vliegen HW, Lamb HJ, et al. Comprehensive assessment of patients after coronary artery bypass grafting by 16-detector-row computed tomography. Am Heart J. 2005;150(4):775-81.

24. Khan R, Rawal S, Eisenberg MJ. Transitioning from 16-slice to 64-slice multidetector computed tomography for the assessment of coronary artery disease: are we really making progress? Can J Cardiol. 2009;25(9):533-42.

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Milani R, et al.ORIGINAL - Minimally ARTICLE invasive redo mitral valve surgery without aortic crossclamp

Minimally invasive redo mitral valve surgery without aortic crossclamp Reoperação da valva mitral minimamente invasiva sem pinçamento da aorta

Rodrigo Milani1, MD, PhD; Paulo Roberto Slud Brofman1, MD, PhD; Sergio Oliveira1; Luiz Patrial Neto1; Matheus Rosa1; Victor Hugo Lima1; Luis Fernando Binder1; Aline Sanches1

DOI: 10.5935/1678-9741.20130051

RBCCV 44205-1477

Abstract

quires a longer duration of cardiopulmonary bypass, especially in cases where the patient already has prosthesis. The presence of a minimal aortic insufficiency also makes this procedure technically more challenging.

Introduction: Reoperations of the mitral valve have a

higher rate of complications when compared with the first surgery. With the field of video-assisted techniques for the first surgery of mitral valve became routine, reoperation cases began to arouse interest for this less invasive procedures. Objective: To assess the results and the technical difficulties in 10 patients undergoing minimally invasive redo mitral valve surgery. Method: Cardiopulmonary bypass was installed through a cannula placed in the femoral vessels and right internal jugular vein, conducted in 28 degrees of temperature in ventricular fibrillation. A right lateral thoracotomy with 5 to 6 cm in the third or fourth intercostal space was done, pericardium was displaced only at the point of atriotomy. The aorta was not clamped. Results: Ten patients with mean age of 56.9 ± 10.5 years, four were in atrial fibrilation rhythm and six in sinusal. Average time between first operation and reoperations was 11 ± 3.43 years. The mean EuroSCORE group was 8.3 ± 1.82. The mean ventricular fibrillation and cardiopulmonary bypass was respectively 70.9 ± 17.66 min and 109.4 ± 25.37 min. The average length of stay was 7.6 ± 1.5 days. There were no deaths in this series. Conclusion: Mitral valve reoperation can be performed through less invasive techniques with good immediate results, low morbidity and mortality. However, this type of surgery re-

Descriptors: Minimally invasive surgical procedures, methods. Mitral valve, surgery. Surgical procedures minimally invasive. Video-Assisted Surgery. Cardiac surgical procedures. Resumo Introdução: Reoperações da valva mitral apresentam maior índice de complicações quando comparadas com a primeira cirurgia. Com o domínio das técnicas videoassistidas para as primeiras cirurgias da valva mitral, os casos de reoperações passaram a despertar interesse para esses procedimentos menos invasivos. Objetivo: Analisar os resultados e as dificuldades técnicas da retroca valvar mitral minimamente invasiva em 10 pacientes. Métodos: A circulação extracorpórea foi instalada por meio de colocação de cânulas femorais e cânula na veia jugular interna direita, conduzida em 28 graus de temperatura em fibrilação ventricular. Realizada toracotomia lateral direita com 5 a 6 cm no terceiro ou quarto espaço intercostal. Pericárdio foi descolado apenas na região do átrio esquerdo no ponto da atriotomia. A aorta não foi pinçada.

Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil.

Pontifícia Universidade Católica do Paraná Rua Cezar Correia de Souza, 54 - Santa Felicidade, Curitiba, PR, Brazil – Zip code: 82015-220. E-mail: rodrigo.milani@sbccv.org.br

Work carried out at Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil. Correspondence address: Rodrigo Milani

Article received on January 10th, 2012 Article approved on December 28th, 2012

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70,9 ± 17,66 min e 109,4 ± 25,37 min. O tempo médio de internamento foi de 7,6 ± 1,5 dias. Não houve óbitos nessa série. Conclusão: A reoperação da valva mitral pode ser feita por meio de técnicas menos invasivas com bons resultados imediatos e baixa morbimortalidade. Entretanto, esse tipo de cirurgia requer maior tempo de circulação extracorpórea, especialmente nos casos em que o paciente já tenha uma prótese. A presença de uma mínima insuficiência aórtica também torna esse procedimento tecnicamente mais desafiador.

Abbreviations, acronyms & symbols CPB ICU CO2

Cardiopulmonary bypass Intensive care unit Carbon dioxide

Resultados: Foram avaliados 10 pacientes com idade média de 56,9±10,5 anos. Quatro encontravam-se em ritmo de fibrilação atrial e 6 em ritmo sinusal. O tempo médio entre a primeira operação e a reoperações foi de 11 ± 3,43 anos. O EuroSCORE médio do grupo foi de 8,3 ± 1,82. O tempo médio de fibrilação ventricular e de circulação extracorpórea foi respectivamente

Descritores: Cirurgia Vídeo-Assistida. Doenças das valvas cardíacas. Procedimentos cirúrgicos minimamente invasivos. Valva mitral. Cirurgia.

Objective The goal of this study is to describe the immediate results of tem patients who underwent video-assisted minimally invasive mitral valve reoperation, under hypothermic ventricular fibrillation and without aortic clamping.

INTRODUCTION The use of sternotomy for mitral valve surgeries has led to an increase in long-term survival and acceptable rates of morbidity and mortality, which is why it is the treatment of choice in cases of severe mitral valve disease. Alternatives to sternotomy have been put forward in order to reduce morbidity and mortality, provide faster recovery, and offer better aesthetic results. These alternatives include: partial sternotomy, mini right anterolateral thoracotomy performed under direct vision or video-assisted as well as robotic mitral valve surgery. These procedures can be performed either using longer common instruments coupled with small retractors or with the help of complex, expensive instruments. Myocardial protection can be achieved through the use of endovascular clamp, aortic clamping with the placement of the clamp via parallel access, or through surgeries performed without aortic clamping and with the patient under hypothermia with ventricular fibrillation. Cardiopulmonary bypass cannot be avoided in intracardiac procedures. However, total trauma caused by surgery can be minimized by a smaller incision. Using an alternative access to the sternotomy results in the preservation of chest wall integrity, which in turn leads to improved lung function, less pain, shorter hospital stay, and faster return to normal routine. In an attempt to simplify this kind of procedure, avoiding aortic clamping and the consequent ischemia, some authors have published studies [1-3] showing the possibility of performing this procedure associated with hypothermia and ventricular fibrillation, and without aortic occlusion. A hypothermic, decompressed heart, with a constant flow of oxygenated blood, is the key to myocardial protection; in other words, the heart is never ischemic and is always empty.

METHODS Tem patients who had had previous mitral valve surgery were submitted to reoperation. As previously described [3], conventional induction of anesthesia was used. Conventional orotracheal cannula was used for mechanical ventilation hence one-lung ventilation was not needed. Patients were placed in dorsal decubitus with right side elevation at 15 degrees. Cardiopulmonary bypass was established with dissection of the left femoral artery and vein, followed by the insertion of arterial cannula designed for peripheral access into the femoral artery and the positioning of long venous cannula in the right atrium close to the superior vena cava, which was inserted via the femoral vein. Another venous cannula was inserted in the right internal jugular vein via puncture. Thorocotomy was performed in the right fourth intercostal space, beginning right below the nipple and extending 4 to 6 cm laterally. The 6.5 mm 30° optics was inserted into the right pleura through the same space as the main incision, via access located 2 to 3 cm posterolateral to the main access. Cardiopulmonary bypass had begun and lungs had stopped when the intercostal space was opened and optics was inserted. Pericardium was opened at the level of the left atrium and adhesions in that area were removed. A pair of temporary pacing wires was placed in the right ventricle and connected

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to a fibrillator. Patients were cooled down to 28°C and a catheter with CO2 at 4 L/min was placed in the cavity. A small incision, less than 1 cm long, was made approximately 3 cm above the main incision in order to place the left atrial retractor. The opening of the left atrium was performed in the same way as in conventional surgeries. Prolene 4-0 sutures were applied to the edges of the left atrium to facilitate exposure. A customized retractor, which was designed specifically for this kind of surgery, was inserted into the left atrium (Figure 1). The most technically challenging part of the procedure is the removal of previously implanted prosthesis. The removal is done in a similar way to conventional surgeries; however, the distance between the valve and the edge of the incision as well as the equipment used, which is usually quite delicate for this part of the surgery, make it difficult to remove the prosthesis. The remaining steps of the surgery were performed routinely, with the passage of stitches through the valve ring done in a similar way to conventional surgeries. Both visibility of the ring and lowering of the prosthesis to its position were very good (Figure 2). A long appropriate instrument is required for placing the knots to affix the prosthesis. Once the prosthetic valve was placed (Figure 3), a left ventricle aspirator was inserted via the left atrium and through the prosthesis and atriorrhaphy was done as usual. Defibrillation was performed externally. After the cannulas were removed, heparin was completely reversed and the right pleural cavity was drained. The intercostal space used for access was closed with 2-0 ethibond suture and the skin was closed with intradermal suture. • This study was approved by the Ethics Committee, protocol 0003761/10 on October 17th, 2010.

Fig. 2 – This technique provides good visibility

Fig. 3 - Fixing the prosthetic valve

RESULTS A total of ten patients, four males and six females, were evaluated. Patient ages ranged from 46 to 76 years-old, the mean being 56.9±10.5 years. Two patients (20%) were diabetic, six (60%) had hypertension, and four (40%) had history of smoking. Four patients (40%) were in functional class II, five (50%) were in functional class III, and one (10%) was in functional class IV. Electrocardiogram at rest showed sinus rhythm in six patients (60%) and atrial fibrillation in four patients (40%). Four patients (40%) had normal ejection fraction, five patients (50%) had moderate left ventricular dysfunction, and one patient (10%) had severe ventricular dysfunction. Five patients (50%) had undergone previous mitral valve repair; the other five (50%), mitral valve

Fig. 1 - Retractor developed specifically for this type of operation introduced into the left atrium

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replacement with biological prosthesis. The diagnosis which led to a new surgical procedure was: stenosis in two patients (20%), insufficiency in three patients (30%), and double dysfunction in five patients (50%). Mean length of time between the first and second surgeries was 11±3.43 years, ranging from 7 to 17 years. EuroSCORE ranged from 7 to 12, with a mean of 8.3±1.82. Mechanical prostheses were implanted in eight patients (80%) and biological prostheses were implanted in the other two patients (20%). Size of the prosthesis ranged from 25 to 29 mm, with seven patients (70%) receiving a 27 mm prosthesis. Mean time of ventricular fibrillation was 70.9±17.66 minutes, ranging from 45 to 100 minutes. Cardiopulmonary bypass time ranged from 66 to 150 minutes, with a mean of 109.4±25.37 minutes. After surgery, patients were taken to the ICU, where mean time of mechanical ventilation was 6.4±3.2 hours, ranging from zero to 12 hours. Length of stay in the ICU ranged from 2 to 3 nights, the mean being 2.5± 0.52 nights. Six patients (60%) had low output syndrome after removal of cardiopulmonary bypass, requiring inotropic support. None of the patients in this series needed the reoperation due to bleeding nor did they have stroke, acute myocardial infarction, or acute renal failure. One patient (10%) developed pneumonia in the postoperative period. There were no deaths in this study. At hospital discharge, five patients (50%) had sinus rhythm and five patients (50%) had atrial fibrillation. Mean length of hospital stay was 7.6±1.5 days, ranging from 5 to 10 days.

Dogan et al. [11] published an article comparing conventional and minimally invasive surgeries. Forty patients were randomly assigned to two groups, Group I being comprised of patients undergoing minimally invasive surgery and Group II of patients undergoing conventional surgery. Cardiopulmonary bypass and aortic clamping times were slightly longer in Group I; however, there were no statistically significant differences. In Group I, none of the patients needed to be converted to conventional surgery and length of both mechanical ventilation and hospital stay was shorter, but again there were no statistically significant differences. There was also no difference between the two groups in terms of drainage by chest drains and pulmonary function. There were no major complications or deaths reported in this series; however, the authors stated that the biggest challenge in Group I was myocardial protection, as they faced a series of problems with endovascular aortic clamping in addition to difficulties using conventional occlusion forceps. The authors concluded that despite the lack of statistically significant data in favor of minimally invasive surgeries, they proved to be just as effective as conventional surgeries, which justifies performing the less invasive procedure. In a similar article, Holzhey et al. [16] published a study comparing conventional and minimally invasive surgeries in patients over 70 years-old. Like other studies [17-19], the authors stated that duration of cardiopulmonary bypass, aortic clamping as well as the surgery itself was longer. There were no differences in terms of major complications and mortality in 5 to 8 years of follow-up. In the immediate postoperative period, the conventional surgery group showed greater incidence of arrhythmia and pacemaker implant; once again, the difference was not statistically significant. The conclusions reached were the same as the ones from other authors: minimally invasive surgeries are at the very least equal to conventional surgeries and the biggest challenge lies in myocardial protection methods. Ventricular fibrillation associated with hypothermia has been used as myocardial protection in coronary surgeries for many years, based on the fact that a decompressed heart in ventricular fibrillation associated with hypothermia at 28°C consumes roughly the same amount of energy as a heart in cardiac arrest induced by cardioplegia [3]. On the other hand, in valve surgeries, this kind of heart protection technique has always caused certain concern related to the incidence of stroke, since the cavities are open and the aorta is not clamped. In a 2008 article, Umakanthan et al. [20] demonstrated how safe ventricular fibrillation associated with hypothermia and without aortic clamping is during minimally invasive mitral valve surgeries. The authors assessed 195 patients who had undergone minimally invasive mitral valve surgery with this kind of myocardial protection. The results

DISCUSSION Since the mid-1990s, the medical community has shown growing interest in mini-incisions for valve replacement [4-8]. The right anterolateral thoracotomy seems to be an interesting access for mitral valve surgeries as it allows for direct vision of the line where left atriotomy is usually performed, good exposure of the valve, and minimum initial discomfort for the surgeon. In addition, aesthetic result of this incision is superior to others, since, in women, the breast hides the incision [9]. In the last decade, the use of video in cardiac surgeries has become commonplace. Some studies [10-15] have demonstrated that, in video-assisted surgeries, incisions can be smaller, visualization of the surgical field is improved, and long-term results are the same as those of conventional mitral valve surgery. Furthermore, there is substantial reduction in trauma, mechanical ventilation as well as hospital stay, so the patient can return to routine activities faster than in conventional surgeries, where the patient cannot drive for 45 days as opposed to 10 to 15 days in minimally invasive surgeries.

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showed incidence of mortality in 30 days at 3%, low output syndrome at 4%, and stroke at 3%, which are equivalent to the results reported by other authors who used myocardial protection with aortic clamping [10,11,16]. The authors attributed the low incidence of stroke to: arterial pressure being kept above 30 mmHg during cardiopulmonary bypass, insertion of cannula for continuous aspiration into the left ventricle, and continuous CO2 instillation in the cavity throughout the procedure. The authors concluded this type of cardiac management is safe, easily reproduced, and it makes minimally invasive surgery simple. After this study, minimally invasive mitral valve surgery, which had been limited to patients who had had no previous surgical intervention, started to be performed in patients undergoing reoperations as well. In patients who have undergone previous surgeries, the heart tends to have a large amount of adhesions, which are difficult to remove through minimally invasive methods, making the aortic clamping almost impossible to achieve. That, as well as inconsistencies in the occlusion of the aorta via endovascular techniques severely limits the indication of less invasive procedures to patients undergoing reoperations. Aortic clamping is unnecessary when the patient is under ventricular fibrillation; therefore, it is possible to remove only the adhesions on top of the left atrium where the incision is made. In 2010, Ricci et al. [21] presented a study in which 241 patients who had undergone previous mitral valve or other cardiac surgeries were evaluated. The authors started by describing the risks of performing a resternotomy due to adhesions, which could lead to serious injuries, especially to the right ventricle and innominate vein. In the results, the authors mentioned the need to convert the surgery to sternotomy in two patients, one due to aortic dissection; the other, left ventricular perforation. Average length of stay in intensive care was 24 hours, average time of mechanical ventilation was 12 hours, and average blood drainage in 24 hours was 450 ml. Ventricular fibrillation was used in six of the patients who underwent surgery; in the remaining patients, endovascular clamping was used. Furthermore, the authors reported a stroke rate of 5.8%, none in the fibrillation group, and overall mortality of 4.9%. They concluded that the minimally invasive mitral valve reoperation is safe and its benefits are: very low incidence of surgical wound infection, short length of intensive care unit and hospital stay, good aesthetic results, and faster return to routine activities. A report was published in 2008 by Fortunato et al.[22], describing the case of a patient who underwent endoscopic mitral valve surgery reoperation. The authors performed a comissurotomy in a valve that had been repaired 12 years earlier. They reached the conclusion that the procedure was feasible and effective. In the present study, 10 patients who underwent minimally invasive mitral valve reoperation were evaluated. All patients

underwent the whole procedure without aortic clamping, under hypothermia and ventricular fibrillation, and with continuous CO2 instillation. The average EuroSCORE of the group was above 8, indicating a group of high risk patients. Yet, there were neither deaths nor strokes observed in this series. The biggest challenge faced in this study was the removal of the mitral prosthesis that had been implanted in the first surgery, which led to patients in this condition being under ventricular fibrillation for a longer period of time. Six patients developed low output syndrome after removal of cardiopulmonary bypass. Consequently, in the last cases, it took longer to start the reheating in order to avoid exposing a heart under fibrillation to higher temperatures. The effect of doing that was somewhat positive making it easier to remove the CPB. Presence of mild aortic insufficiency hinders the surgical procedure; therefore, in cases where there is slight to mild insufficiency, the procedure should not be performed. CONCLUSION Minimally invasive mitral valve reoperations under hypothermia associated with ventricular fibrillation without aortic clamping can be safely performed, with good immediate results, low incidence of complications, and no need for ample dissections of the heart. However, longer length of time on cardiopulmonary bypass is required, especially in patients who have previously implanted prosthesis. This type of procedure should not be performed in this manner if there is significant aortic insufficiency.

Authors' roles & responsibilities RM Main author PRSB Coauthor SO Coauthor LPN Coauthor MR Coauthor VHL Coauthor LFB Coauthor AS Coauthor

REFERENCES 1. Akins CW. Noncardioplegic myocardial preservation for coronary revascularization. J Thorac Cardiovasc Surg. 1984;88(2):174-81. 2. Greene PS, Cameron DE, Griffiths EM, DiNatale JM, Gardner TJ. Does hypothermic fibrillatory arrest improve myocardial protection during emergency revascularization? Ann Thorac Surg. 1989;48(1):38-42.

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3. Milani RM. Análise dos resultados imediatos da operação para revascularização do miocárdio sem pinçamento total da aorta [Dissertação de Mestrado]. Curitiba: Universidade Federal do Paraná; 2000.

valve surgery via left thoracotomy: experience with forty cases. J Thorac Cardiovas Surg. 2004;127(4):1026-31.

14. Poffo R, Bonim M, Selbach RA, Pillati M. Troca valvar mitral minimamente invasiva videoassistida. Rev Bras Cir Cardiovasc. 2007;22(4):491-4.

Cosgrove DM 3rd, Sabik JF. Minimally invasive approach for aortic valve operations. Ann Thorac Surg. 1996;62(2):596-7.

15. Fortunato Jr JA, Branco Filho AA, Branco A, Martins ALM, Pereira ML, Ferraz JGG, et al. Padronização da técnica para cirurgia cardíaca videoassistida: experiência inicial. Rev Bras Cir Cardiovasc. 2008;23(2):183-9.

5. Cosgrove DM 3rd, Sabik JF, Navia JL. Minimally invasive valve operations. Ann Thorac Surg. 1998;65(6):1535-8. 6. Koenertz W, Waldenberger F, Schmutzler M, Rilter J, Liu J. Minimal access valve surgery through superior partial sternotomy: a preliminary study. J Heart Valve Dis. 1996;5(6):638-40.

16. Holzhey DM, Shi W, Borger MA, Seeburger J, Garbade J, Pfannmüller B, et al. Minimally invasive versus sternotomy approach for mitral valve surgery in patients greater than 70 years old: a propensity-matched comparison. Ann Thorac Surg. 2011;91(2):401-5.

7. Navia JL, Cosgrove DM 3rd. Minimally invasive mitral operations. Ann Thorac Surg. 1996;62(5):1542-4. 8. Navia JL, Cosgrove DM. Minimally invasive mitral valve operations. Ann Thorac Surg. 1996;62(5):1542-4.

17. Modi P, Hassan A, Chitwood WR Jr. Minimally invasive mitral valve surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2008;34(5):943-52.

9. Mishra YK, Malhotra R, Mehta Y, Sharma KK, Kasliwal RR, Trehan N. Minimally invasive mitral valve surgery through right anterolateral minithoracotomy. Ann Thorac Surg. 1999;68(4):1520-4.

18. Chitwood WR Jr, Elbeery JR, Morgan JF. Minimally invasive mitral valve repair using transthoracic aortic occlusion. Ann Thorac Surg. 1997;63(5):1477-9.

10. Grossi EA, Galloway AC, LaPietra A, Ribakove GH, Ursomanno P, Delianides J, et al. Minimally mitral valve surgery: 6-year experience with 714 patients. Ann Thorac Surg. 2002;74(3):660-3.

19. Dagenais F. Minimally invasive mitral valve surgery: evolution, techniques and outcomes. Future Cardiol. 2008;4(6):609-16. 20. Umakanthan R, Leacche M, Petracek MR, Kumar S, Solenkova NV, Kaiser CA, et al. Safety of minimally invasive mitral valve surgery without aortic cross-clamp. Ann Thorac Surg. 2008;85(5):1544-9.

11. Dogan S, Aybek T, Risteski PS, Detho F, Rapp A, WimmerGreinecker G, et al. Minimally invasive port access versus conventional mitral valve surgery: prospective randomized study. Ann Thorac Surg. 2005;79(2):492-8.

21. Ricci D, Pellegrini C, Aiello M, Alloni A, Cattadori B, D’Armini AM, et al. Port-access surgery as elective approach for mitral valve operation in re-do procedures. Eur J Cardiothorac Surg. 2010;37(4):920-5.

12. Rodriguez E, Nifong LW, Chu MW, Wood W, Vos PW, Chitwood WR. Robotic mitral valve repair for anterior leaflet and bileafleat prolapse. Ann Thorac Surg. 2008;85(2):438-44.

22. Fortunato Júnior JA, Branco Filho AD, Branco A, Martins ALM, Pereira M. Reoperação de valva mitral totalmente endoscópica: relato de caso. Rev Bras Cir Cardiovasc. 2008;23(3):411-4.

13. Saunders PC, Grossi EA, Sharony R, Schwartz CF, Ribakove GH, Culliford AT, et al. Minimally invasive thechnology for mitral

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Gelamo RV, etORIGINAL al. - Effects ARTICLE of reprocessing on chemical and morphological properties of guide wires used in angioplasty

Effects of reprocessing on chemical and morphological properties of guide wires used in angioplasty Efeitos do reprocessamento nas propriedades químicas e morfológicas de fios-guia usados em angioplastia

Rogério Valentim Gelamo1, PhD; Eva Cláudia Venâncio de Sene1, MSc; Luciana Paiva1, MSc; Cristina da Cunha Hueb Barata de Oliveira1, MD, PhD; André Luiz Maltos1, MD; Wido H. Schreiner2, PhD; Mário Bica de Moraes3, PhD; Alfredo R. Vaz3, PhD; Stanislav A. Moshkalev3, PhD; Daniel Ferreira da Cunha1, MD, PhD DOI: 10.5935/1678-9741.20130052

RBCCV 44205-1478

Abstract Objective: To investigate the influence of the reprocessing technique of enzymatic bath with ultrasonic cleaning and ethylene oxide sterilization on the chemical properties and morphological structure of polymeric coatings of guide wire for regular guiding catheter. Methods: These techniques simulated the routine of guide wire reprocessing in many hemodynamic services in Brazil and other countries. Samples from three different manufacturers were verified by scanning electron microscopy and X-ray photoelectron spectroscopy. Results: A single or double sterilization of the catheters with ethylene oxide was not associated with morphological or chemical changes. However, scanning electron microscopy images showed that the washing method was associated with rough morphological changes, including superficial holes and bubbles, in addition to chemical changes of external atomic layers of polymeric coating surfaces, as detected by the X-ray photoelectron spectroscopy method, which is compatible with extended chemical changes on catheter surfaces. Conclusion: The reprocessing of the catheters with ethylene oxide was not associated with morphological or chemical changes, and it seemed appropriate to maintain guide wire coating integrity. However, the method combining chemical cleaning with mechanical vibration resulted in rough anatomical and

chemical surface deterioration, suggesting that this reprocessing method should be discouraged.

Universidade Federal do Triângulo Mineiro (UFTM), Uberaba, MG, Brazil. Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil. 3 Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil.

Correspondence address: Rogério Valentim Gelamo Av. Dr. Randolfo Borges Junior, 1250 – Uberaba, MG, Brazil – Zip code: 38064-200 E-mail: rogelamo@gmail.com

Descriptors: Cardiac catheterization. Health knowledge, attitudes, practice. Diagnostic techniques, cardiovascular. Equipment reuse. Angioplasty. Resumo Objetivo: Investigar a influência das técnicas de reprocessamento de banho enzimático com limpeza ultrassônica e a esterilização com óxido de etileno nas propriedades químicas e estruturas morfológicas de revestimentos poliméricos de fios-guia usados como guias em cateteres regulares. Métodos: Estas técnicas simulam a rotina de processamento de fios-guia em muitos serviços de hemodinâmica do Brasil e de outros países. Amostras de três diferentes fabricantes foram verificadas por microscopia eletrônica de varredura e espectroscopia de fotoelétrons de raios-X. Resultados: Uma única ou dupla esterilização dos cateteres com óxido de etileno não foi associada a mudanças químicas ou morfológicas. Contudo, imagens de microscopia eletrônica de varredura mostraram que o método de lavagem foi associado a intensas modificações morfológicas, incluindo bolhas e buracos superficiais, assim como mudanças nas ligações químicas das

1 2

Work carried out at Universidade Federal do Triângulo Mineiro (UFTM), Uberaba, MG, Brazil. Supported by Processo Fapemig CEX, Belo Horizonte/Brazil –protocol number APQ-03992-10

Article received on May 14th, 2013 Article accepted on July 10th, 2013

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Conclusão: O reprocessamento dos fios-guia de cateteres com óxido de etileno não está associado a mudanças químicas e morfológicas dos mesmos e pode ser considerado adequado para manter a integridade destes materiais. Entretanto, o método que combina lavagem química com vibração mecânica resulta em intensas deteriorações anatômicas e químicas, sugerindo que esse método de processamento deve ser desencorajado.

Abbreviations, acronyms & symbols PTFE SEM XPS

polytetrafluoroethylene Scanning electron microscopy X-ray photoelectron spectroscopy

camadas atômicas externas do revestimento polimérico, conforme demonstrado por resultados de espectroscopia de fotoelétrons de raios-X, compatível com extensas modificações químicas induzidas por esse processo de lavagem.

Descritores: Cateterismo cardíaco. Conhecimentos, atitudes e prática em saúde. Técnicas de diagnóstico cardiovascular. Reutilização de equipamento. Angioplastia.

INTRODUCTION

reprocessing in the chemical and morphological properties of the polymeric coatings of guide wire catheters.

The reuse of angioplasty catheters and other medical or surgical devices initially designed for single use, has been adopted in several hemodynamic services around the world, and is associated with substantial decrease in hospital costs [1]. However, this practice may be associated with malfunction of the devices related to either chemical or physical changes. To be reused, a catheter and all its complementary parts should remain free of biological hazards, including the presence of toxins, bacteria, viruses, and fungi. Moreover, its physical properties, such as flexibility and resistance to torque, should be maintained at levels that are safe for the patient [2-6]. Several physical changes have been described in the literature, including loss of the catheter deflection property after ethylene oxide and hydrogen peroxide treatment [2], or alterations in catheter morphology after the use of enzymatic detergent and hydrogen peroxide plasma [7]. For example, micro-fissures, micro-scratches, depth hollows, saliencies and micro-protrusions in polyurethane surfaces of reused catheters were reported by Lucas et al. [7]. However, these authors did not study the guide wire used in routine catheter guiding, nor submitted their devices to some of the other common methods of sterilization used in Brazil, such as ultrasound exposition followed by ethylene oxide sterilization. Therefore, as the guide wires used for routine catheter guiding are generally covered with surface polymers – macromolecules composed of repeated structural units, typically C-C or C-F covalent chemical bonds– aimed to be relatively inert and biocompatible, they should be checked after each reprocessing method used. We have not found studies describing morphological changes after the reuse of the guide wire catheter coated with polymeric material such as PTFE (polytetrafluoroethylene). Hence, in the present study, we investigated the influence of each method of

METHODS Guide wire catheters from three different manufacturers (termed samples A, B and C), composed of polymer-coated stainless steel were investigated. The guide wires were coated either with PTFE (polytetrafluoroethylene) (samples A and B) or with an unknown polymer (sample C). All guide wire samples were pristine and, to simulate the washing routine in hospitals, they were washed in enzymatic bath at least once (ultrasound 1X, termed AU1, BU1 or CU1) or twice (samples AU2, BU2 or CU2). This procedure simulates what would be done on any reuse of the material. In the same way, pristine guide wires were sterilized using ethylene oxide once (samples AS1, BS1 and CS1) or twice (samples AS2, BS2 and CS2). Cleaning with ultrasound. An ultrasonic washer was employed for the mechanical washing of the guide wire catheters, at 37 kHz frequency and ultrasonic-power of 4400 W. Initially, the guide wire was immersed in detergent enzyme and processed in ultrasound at 40oC for 15 minutes. Then, it was rinsed with three water jets using a sterile syringe, dried with sterile gauze and compressed air. Finally, it was placed in a plastic bag for transport and subsequent analysis. Sterilization with ethylene oxide The guide wire catheters were sterilized with ethylene oxide at 100% (Sterivac 5XL, 3M - sterilization equipment under low temperature). The guide wire catheters were packed in surgical papers and placed in the sterilization chamber. The sterilization cycle lasted 4 hours at a temperature of 55oC. At the end of this time, the guide wires were maintained for 18

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hours in mechanical aeration in the chamber, and as a final step, at 132oC for 4 minutes. The morphology of the guide wire surfaces was analyzed by scanning electron microscopy (SEM), using a Dual Beam FIB/SEM (Focused Ion Beam/Scanning Electron Microscopy) Model Nanolab Nova 200 (FEI Co.). All specimens (guide wire pieces of 3 cm in length) were coated with a 3-5 nm Cu film using a DC sputtering system. All images were obtained in the secondary electron mode. An electron beam of 5 kV and 0.4 nA was used. To investigate changes in the chemical composition of the coating surfaces, XPS was used. Measurements were carried out with a VG Microtech ESCA3000 spectrometer, operating at a base pressure of 3 x 10-10 mbar. The Al Kalpha non-monochromatic radiation was used for photoelectron generation. Binding energy corrections were made in the raw spectra using the Handbook reference of the saturated hydrocarbon C1s peak at 285 eV [8]. For these measurements, the samples (1.0 cm guide wires) were mounted protruding from the sample holder to avoid any sample holder signals in the spectra. RESULTS SEM Results The SEM images of surfaces of the polymeric coatings of pristine guide wires A, B, and C are shown in Figure 1. Fairly uniform surfaces are revealed by the three micrographs. The small irregularities observed in the three pictures are typical of pristine guide wires and were considered normal. The effect of ultrasonic and enzymatic detergent cleaning treatments of the three samples can be seen in the SEM images (Figure 2), which depict the surfaces of the samples after a single cleaning. Pronounced surface damage is observed in samples AU1 and CU1 while damage is less significant in sample BU1. Sample AU1 was the most affected, as seen in Figure 2. The persistence of debris larger than 200 Âľm can be observed at the surface of guide wires after the washing procedure using ultrasound. Sample BU1 shows defects in the PTFE structure, including holes and bubbles, that were not observed in the pristine material. A marked roughness in the polymer coating surface is seen in the CU1 sample, with some holes in the microstructure and micrometric flakes, smaller than those observed in sample A. At naked eye, the catheters washed only once showed slight color changes, varying from green to a yellowish-green color, a phenomenon which is markedly observed after the second washing (samples AU2 and BU2). The intense modifications are best observed through scanning electron microscopy, which allows for viewing at the micrometric level (Figure 3). Regarding the sterilization process, the images obtained (not shown) do not reveal significant changes in the PTFE coatings (catheters type A and B) as well as in the coating of guide wire type C, even after a second sterilization process.

Fig. 1 â&#x20AC;&#x201C; SEM pictures of guide wire catheter samples A, B and C. All surfaces with few small irregularities, considered normal for this material. Small artifacts from the manufacturing process are seen in Figure B.

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Fig. 2 â&#x20AC;&#x201C; SEM images of guide wires AU1 (A), BU1 (B) and CU1 (C), washing 1X using enzymatic detergent in ultrasonic bath. Debris and holes of considerable size are observed mainly in Figures A and C, while bubbles and a non-conformal surface are observed in Figure B.

Fig. 3 â&#x20AC;&#x201C; SEM images of guide wires AU2, BU2 and CU2, washing 2X using enzymatic detergent in ultrasonic bath. Persistence of debris and holes in Figures A and B and an increase in roughness is observed in Figure C.

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XPS Results Figure 4 shows high resolution photoelectron spectra in the C1s (carbon electronic level 1s) binding energy region of three samples derived from type A guide wire (pristine - A, sterilized in ethylene oxide - AS1, and washed 1X in enzymatic ultrasonic bath – AU1). Both pristine (A) and sterilized (AS1) samples show two peaks from the C1s electronic level, i.e. (i) the C-C/C-H peak, composed of carbonaceous carbon at 285 eV; and (ii) the CF2 peak, due to C bound to two F-atoms at 292 eV [9]. The higher intensity of the latter, much higher than those of the C-C/C-H peak, shows that the C atoms in the polymer coatings are predominantly in CF2 groups, confirming the presence of a typical PTFE structure. The additional peak at 278 eV for the pristine sample is due to the use of nonmonochromatic X-rays. Since the spectra do not differ from those obtained with the pristine material, the XPS results suggest that the sterilization process does not induce significant changes in the chemical structure of the polymer coating, while maintaining the chemical inertness of the material. On the other hand, the washed samples displayed intense changes in the chemical structures, as verified by the complete removal of CF bonds from the material, expected at 292 eV (Figure 4), with preservation of the C-C and C-H linkages around 285 eV. The XPS spectra of samples from guide wire type B (not shown) are similar to those of guide wire type A, indicating little or no effect of the sterilization process on the chemical structure of PTFE, but with significant changes produced by the ultrasonic bath. Again, the CF2 peak strongly

decreased while the intensity of the C-C/C-H feature was not significantly decreased. With respect to the samples from guide wire type C, the XPS spectra reveals a strong predominance of the C-C and hydrocarbon bonds, as indicated by the intense and broad peak at 285 eV (Figure 5). The similarity in the two spectra indicates that sterilization did not alter the chemical structure of the polymer. A different behavior is observed in the sample subjected to ultrasonic washing: a decrease in the C-C/C-H peak and the rise of a peak at about 293 eV, suggesting the presence of C-F bonds in CF3 groups. A possible explanation for such new groups would be some chemical reaction of the polymer with a component of the enzymatic detergent, or a removal of polymer surface layers with the exposure of CF3 from some other polymer underneath.

Fig. 5 – XPS spectra of samples from guide wire catheter type C: pristine – C1, sterilized in ethylene oxide – CS1 and ultrasonically cleaned with enzymatic detergent – CU1.

DISCUSSION A major finding in this study was that a single sterilization of the guide wire catheter with ethylene oxide was not associated with morphological or chemical changes, as indicated by SEM and XPS methodology, the same occurring after sterilizing the guide wires two times. Notwithstanding, as it can be verified by SEM images, washing the guide wires once or twice using a mix of ultrasound vibration and enzymatic detergent was associated with different degrees of structural changes. Mechanical agitation caused by ultrasound vibration results in formation of cracks in the polymer surfaces, especially on PTFE, a material known

Fig. 4 – XPS spectra of samples from guide wire catheter type A.: pristine – A1, sterilized in ethylene oxide – AS1 and ultrasonically cleaned in enzymatic detergent – AU1. Suppression of CF peak related to CF bonds is observed in sample submitted to the ultrasound washing.

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for its low resistance to repeated cyclic loading [10]. Since the XPS method is particularly useful for the detection of chemical changes of superficial layers of polymeric coating, including in the C-F or C-C chemical groups, it is reasonable to presume the occurrence of extended chemical changes on guide wire surfaces. To our knowledge, this is the first study that describes both morphological and chemical changes in the guide wire catheter coated with polymeric material commonly used in hemodynamic services in Brazil. Granados et al. [1], studying samples of reprocessed central venous PVC catheter sterilized with ethylene oxide verified that successive catheter recycling produced increased plasticizer loss, increased glass transition temperature, slight decrease on average molecular weight, and increased roughness and incidence of surface grooves. They concluded that the reuse could alter the original device performance, and suggested that possible adverse clinical events could include presence of toxic agents, device breakage or inflexibility, increased protein catheter retention, and increased bacterial adhesion. Avitall et al. [2] described several changes in ablation catheters submitted to more than one process of sterilization with ethylene oxide or hydrogen peroxide treatment, including: tip electrode glue separation, loss of deflection, and electrical discontinuity between the catheter handle and electrodes. Despite the limitations of their study, performed with optical microscopy magnification of 30X, they concluded their catheters could be reprocessed a maximum of five times, without any appreciable changes in the morphological and mechanical properties. Lucas et al. [7] studied morphological changes of angiographic catheters sterilized up to nine times with hydrogen peroxide plasma. They evaluated the molecular integrity of these catheters through Fourier Transform Infrared Spectroscopy, describing an increase in degradation products on the surface of catheters, including the presence of acids, esters, alcohols, and small amounts of products containing a carbonyl functional group. Using SEM, they found enhanced surface roughness after the fourth reprocessing cycle, and from then on, the well-delimited micro-pores were replaced by diffuse saliences, depressions and micro-protrusions. By carefully observing the SEM images (Figure 2), it becomes apparent that blocks of PTFE 40 to 300 micrometers in length were removed from the surface of the guide wire catheters after only one washing procedure. In addition to eventual occurrence of embolization of distal coronaries or other systemic arteries with surface detached debris, accompanied or not by tissue infarction [3], changes in wettability and in the electrical charge of catheter surface are major factors in additional platelets aggregation and thrombosis formation [11]. The chronic fate of this PTFE debris in tissues is also not known, but potential

consequences include granulomatous inflammation and/or cancer development [12]. However, the significance of these findings is not easily apparent. Investigators have not been able to document additional risks, including those of transmitting infectious diseases and of adverse reactions to disinfectants when catheters are reused after careful cleansing and resterilization by either ethylene oxide or hydrogen peroxide [13]. A randomized, controlled double blind, single center catheter clinical trial comparing the safety and efficacy of reused or pristine catheters found no differences in clinical or angiographic success and similar rates of fever, mortality, and length of hospital stay [14]. CONCLUSION The treatment of the catheters with ethylene oxide was not associated with morphological or chemical changes, and it seemed appropriate to maintain guide wire coating integrity. However, the ultrasonic cleaning was not suitable for polymer-coated guide wires, and a combination of chemical reaction with mechanical vibration may have resulted in the further deterioration observed. Therefore, the reuse of these devices is not recommended. ACKNOWLEDGMENT The Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq, the Center of Semiconductor Components / Unicamp - CCS and Fundação de Ensino e Pesquisa de Uberaba – FUNEPU.

Authors' roles & responsibilities RVG

Study design, protocol execution, data analysis and manuscript writing ECVS Material processing and manuscript writing LP Material analysis, processing samples in ultrasonic cleaning and sterilization CCHBO Study design and data analysis ALM Study design, protocol execution, data analysis and manuscript writing WHS X-ray photoelectron spectroscopy and data analysis MBM Material processing and manuscript writing ARV Material processing SAM Material processing DFC Study design, protocol execution, data analysis and manuscript writing

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REFERENCES

evaluation of cardiac angiographic catheters after simulated use and reprocessing. Appl Surface Sci. 2009;256:1419-25.

1. Granados DL, Jiménez A, Cuadrado TR. Assessment of parameters associated to the risk of PVC catheter reuse. J Biomed Mater Res. 2001;58(5):505-10.

8. Beamson G, Briggs D, High resolution XPS of organic polymers. The Scienta ESCA300 database. Chichester: John Wiley; 1992.

2. Avitall B, Khan M, Krum D, Jazayeri M, Hare J. Repeated use of ablation catheters: a prospective study. J Am Coll Cardiol. 1993;22(5):1367-72.

9. Golub MA, Lopata ES, Finney LS. X-ray photoelectron spectroscopy study of argon-plasma-treated fluoropolymers. Langmuir. 1994;10(10):3629-34.

3. Blomström-Lundqvist C. The safety of reusing ablation catheters with temperature control and the need for a validation protocol and guidelines for reprocessing. Pacing Clin Electrophysiol. 1998;21(12):2563-70.

10. Callister WD. Fundamentals of materials science and engineering: an integrate approach. 2nd ed. New York: John Wiley; 2005.

4. Food and Drug Administration, Medical Device User Fee and Modernization Act (MDUFMA). Medical devices, reprocessed single-use devices, termination of exemptions from premarket notification, requirement for submission of validation data, 2005. Available at: http://www.fda.gov/ cdrh/mdufma Accessed on: 3/4/2013

11. Bourassa MG, Cantin M, Sandborn EB, Pederson E. Scanning electron microscopy of surface irregularities and thrombogenesis of polyurethane and polyethylene coronary catheters. Circulation. 1976;53(6):992-6. 12. Ong MG, Ghali GE, Veillon D, Cotelingam J. Large cell lymphoma associated with prosthetic joint debris. J La State Med Soc. 2012;164(1):31-2.

5. Food and Drug Administration, Center for Devices and Radiological Health (CDRH). Class II special controls guidance document for certain percutaneous transluminal coronary angioplasty (PTCA) catheters, 2008. Available at: http://www.fda.gov/cdrh/ode/guidance/1608.pdf Accessed on: 3/4/2013

13. Unverdorben M, Degenhardt R, Erny D, Scholz M, Wagner E, Köhler H, et al. Clinical and angiographic procedural and mid-term outcome with new versus reused balloon catheter in percutaneous coronary interventions. Indian Hear J. 2005;57(2):114-20.

6. Ribeiro SMCP, Graziano KU, Alfa MM, Goveia VR. Reprocessamento de cateteres cardíacos: uma revisão. Rev Bras Cir Cardiovasc. 2006;21(3):334-42.

14. Zubaid M, Thomas CS, Salman H, Al-Rashdan I, Hayat N, Habashi A, et al. A Randomized study of the safety and efficacy of reused angioplasty balloon catheters. Indian Heart J. 2001;53(2):167-71.

7. Lucas TC, Oréfice RL, Pinotti M, Huebner R. Surface

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Kawauchi TS,ORIGINAL et al. - Randomized and comparative study between two intraARTICLE hospital exercise programs for heart transplant patients

Randomized and comparative study between two intra-hospital exercise programs for heart transplant patients Estudo randomizado e comparativo entre dois programas de exercícios intra-hospitalares para pacientes de transplante de coração

Tatiana Satie Kawauchi1; Patricia Oliva de Almeida1; Karen Rodrigues Lucy1; Edimar Alcides Bocchi1, MD, PhD; Maria Ines Zanetti Feltrim1, PhD; Emilia Nozawa1, PhD

DOI: 10.5935/1678-9741.20130053

RBCCV 44205-1479

Abstract Objective: To compare the effects of two physical therapy exercise in-hospital programs in pulmonary function and functional capacity of patients in the postoperative period of heart transplantation. Methods: Twenty-two heart transplanted patients were randomized to the control group (CG, n=11) and training group (TG, n=11). The control group conducted the exercise program adopted as routine in the institution and the training group has had a protocol consisting of 10 stages, with incremental exercises: breathing exercises, resistance training, stretching and walking. The programs began on the first day after extubation and stretched until hospital discharge. Assessed pulmonary function, distance walked in six minutes walk test (6MWT) and peripheral muscle strength by one repetition maximum test (1RM). Results: Similar behavior was observed between the two groups treated, with statistically significant increases between the first and second test of the following variables: FVC (59% in CG and 35.2% in TG); MIP (8.6% in CG and 53.5% in TG), MEP (28.8% in CG and 40.7% in TG) and 6MWT (44.5% in CG and 31.4% in TG). There was an increase of peripheral

strength by 1RM test, over time, to the muscle groups of the elbow flexors, shoulder flexors, hip abductors and knee flexors. Conclusion: Heart transplant patients benefit from exercise programs in hospital, regardless of the program type applied. A new training proposal did not result in superiority compared to routine programme applied. Exercise protocols provided improves in ventilatory variables and functional capacity of this population.

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto do Coração, São Paulo, SP, Brazil.

Correspondence address: Tatiana Satie Kawauchi Av. Dr. Enéas de Carvalho Aguiar, 44 – Cerqueira César – São Paulo, SP, Brazil – Zip code: 05403-000 E-mail: tatikawauchi@gmail.com

Descriptors: Heart transplantation. Rehabilitation. Physical therapy modalities. Resumo Objetivo: Comparar os efeitos de dois programas fisioterapêuticos de exercícios intra-hospitalares na função pulmonar e na capacidade funcional de pacientes no período pós-operatório de transplante cardíaco. Métodos: Vinte e dois transplantados de coração foram randomizados em Grupo Controle (GC, n=11) e Grupo de Treinamento (GT, n=11). O GC realizou o programa de exercícios adotado como rotina na instituição e o GT realizou protocolo

Work carried out at Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto do Coração, São Paulo, SP, Brazil.

Article received on February 20th, 2013 Article accepted on July 11th, 2013

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gramas tiveram início no primeiro dia após a extubação e se estenderam até a alta hospitalar. Avaliou-se função pulmonar, distância percorrida no teste de caminhada dos seis minutos (TC6M) e força muscular periférica pelo teste de uma repetição máxima (1RM). Resultados: Observou-se comportamento semelhante entre os dois grupos tratados, com aumentos estatisticamente significantes entre o primeiro e o segundo teste das variáveis: CVF (59% no GC; 35,2% no GT); PIMax (8,6% no GC; 53,5% no GT, PEMax (28,8% no GC; 40,7% no GT) e TC6M (44,5% no GC; 31,4% no GT). Houve aumento de força periférica pelo teste de 1RM para os músculos flexores de cotovelo, flexores de ombro, abdutores de quadril e flexores de joelho ao longo do tempo. Conclusão: Pacientes transplantados de coração se beneficiam da aplicação de programas de exercícios no período intra-hospitalar, independente do tipo de programa aplicado. Uma nova proposta de treinamento não resultou em superioridade em relação ao programa aplicado de rotina. Os protocolos de exercícios proporcionaram melhora das variáveis ventilatórias e da capacidade funcional dessa população.

Abbreviations, acronyms & symbols 6MWT Six Minute Walk Test BP Blood pressure CG Control group CMV Controled mandatory ventilation mode FC Functional capacity FVC Forced vital capacity HF Heart failure HR Heart rate HT Heart transplantation L Liters LL Lower limbs LVEF Left ventricular ejection fraction MEP Maximal expiratory pressure MIP Maximal inspiratory pressure PP Postoperative period PEEP Positive end-expiratory pressure RTG Resistance training group SpO2 Peripheral oxygen saturation TG Training group UL Upper limbs

Descritores: Transplante de coração. Reabilitação. Modalidades de fisioterapia.

constituído de 10 fases, com exercícios incrementais: exercícios respiratórios, resistidos, alongamentos e caminhada. Os pro-

INTRODUCTION

muscles [6]. Thus, even after HT, the peripheral changes due to advanced HF remains, resulting in a state of physical deconditioning. For this reason an exercise program should be started early, still in the hospital, with a continuing period of exercise program after discharge, so that patients can return to a lifestyle similar to that they had before the illness, allowing social interaction and satisfactory return to an active and productive life [7]. Although widely recommended in the literature, there are few studies evaluating the use of exercise protocols in the postoperative period (PP) of HT in the hospital. In our institution, patients undergoing HT perform routinely respiratory therapy and general exercises. We follow a terapeutic plan tailored to each patient. However, we don´t have these results controlled and compared to specific protocols applied to HT patients. In order to analyze the implementation of a new assistance program based on progression of exercises, we compared the effects of two programs of physical therapy exercises on pulmonary function and functional capacity in patients undergoing HT during hospitalization.

Heart failure (HF) is a clinical syndrome being the final common pathway of heart disease caused by structural or functional abnormalities, acquired or inherited, leading to worsening of filling capacity and ventricular ejection. The heart becomes unable to maintain the tissues demands resulting in symptoms such as fatigue, dyspnea and intolerance to physical exertion [1,2]. In advanced stages of HF (functional classes III and IV), heart transplantation (HT) becomes a treatment able to restore hemodynamic function, improve quality of life and survival. It is recommended for patients whose symptoms do not respond to drug therapy or other surgical procedures [3]. Since the first human HT performed in South Africa by Christiaan Barnard in 1967, HT has improved since its initial experimental stage to devote these days as a treatment of choice for patients with end-stage HF, especially after the development of immunosuppressive therapy [4]. Actually, the survival of patients submitted to HT is 80%, 70% and 60% in one, five and 10 years, respectively [3]. Most individuals waiting for a HT have prolonged hospital stay due to prolonged inotropic support or mechanical circulatory support [5]. Even after surgery, these individuals show changes in hemodynamic performance due to central alterations, such as autonomic denervation graft, endothelial dysfunction, diastolic dysfunction and accelerated coronary atherosclerosis and poor adaptation of the peripheral

METHODS This prospective, randomized and longitudinal followup study, was approved by the Hospital das Clinicas Ethics Committee from the University of São Paulo Medical School (HC-FMUSP) under the number 1080/08. The study included

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only individuals who signed an informed consent form, according to Resolution 196/96. Patients who underwent orthotopic HT at the Heart Institute, from February 2009 to November 2011, aged over 13 years participated in this study. During this period, 26 individuals who initially filled the criteria for hemodynamic stability and absence of acute or chronic lung disease, neurological and orthopedic complications hindering the realization of the proposed protocols were included. Four individuals were excluded from the program: an individual due to secondary symptomatic hypertension to cyclosporine therapy, two for neurological complications and one due to death related to acute rejection from the graft. Therefore, 22 subjects completed the study, 11 patients in the control group (CG), which performed the conventional physiotherapy program, and 11 in the training group (TG), which performed a new exercise program (Figure 1). These patients did not perform exercise programs in the preoperative period.

(MIP) and maximal expiratory pressure (MEP) was obtained by manovacuometry (Marshall Town® model). The patient was positioned sitting with a nose clip to allow only oral breathing during the test. A maximal inspiratory effort from residual volume (RV) was requested through a mouthpiece connected to a manometer. We considered the largest deflection obtained in the apparatus for the MIP value. Similarly, the expiratory effort was requested from the total lung capacity (TLC) to obtain the MEP value. The measurements were repeated for at least three times for each parameter, accepting less than 10% difference betwen the measures. The highest value was considered, since this has not been the last measure [9]. The values are expressed in cmH2O and percentage of predicted values, according to Neder [10]. The FVC was measured by ventilometry (Mark Wright Spirometer 8® model). FVC was obtained in liters (L) through a maximum inspiration followed by expiration until the maximum RV. The measurement was performed three times, accepting a difference less than 10% betwen the measures, considering the highest value obtained, since it was not the last one. All tests were performed on the first day after extubation (1st test) and on the day before hospital discharge (2nd test). The functional capacity (FC) was assessed using the Six Minute Walk Test (6MWT) performed according to the Guidelines of the American Thoracic Society [11], with the distance measured in meters and percentage of predicted values and calculated according to the equation proposed by Enright & Sherrill [12]. The first 6MWT was performed as soon as the patients had conditions for ambulation, which occurred at the end of the first week after extubation. The second test was performed on the day before discharge. The dynamics of peripheral muscle strength was assessed by the One Repetition Maximum Test (1RM), following the protocol adapted to the Guidelines of the American College of Sports Medicine [13]. Muscle groups responsible for elbow flexion, shoulder flexion, shoulder abduction, elbow extension, knee extension, hip abduction and knee flexion were tested. The first 1RM test was performed at the end of the first week after extubation and the second, on the day before discharge. Once defined the maximum load reached in the first test, we applied a load for resistance training of 50% 1RM set for each muscle group.

Fig. 1 - Flowchart of studied patients

Patients were admitted to the Surgical Intensive Care Unit in the immediate PP, in intubation and mechanical ventilation (Hamilton-Switzerland, Galileo ® model), on controled mandatory ventilation mode (CMV), with a tidal volume of 8 ml/kg, respiratory rate of 12 breaths/min; fraction of inspired oxygen of 60% and positive end-expiratory pressure (PEEP) of 5 cmH2O, as Unit routine [8]. The study began on the day after extubation, which followed institutional protocol [8]. Bedridden patients or patients using vasoactive drugs initiated protocol in phases 1 and 2 and continued to phase 3 only when they were hemodynamically stable, with or without vasoactive drugs. After the withdrawal of ventilatory support, patients were randomized to CG or TG. This randomization process was performed by sealed opaque envelopes. An independent individual generated a sequence of random numbers, putting up one by one in sealed envelopes. Patients were randomly and consecutively allocated in one of the study groups by the withdrawal of one envelope for each patient. Pulmonary function was evalueted in terms of respiratory muscle strength and forced vital capacity (FVC). Respiratory muscle strength, expressed by maximal inspiratory pressure

Exercise Programs CG performed the exercise program adopted as routine in the institution, composed by series of 10 repetitions of the following exercises: (a) diaphragmatic breathing exercises, inspiration in 3 times associated with upper limbs elevation in flexion and in abduction to 90°, (b) general exercises like bending their knees to hip height, lower limbs abduction to 45°, plantar flexion and dorsiflexion (c) orientation for ambulation without preestablished target distance. The session was conducted once a day, five times a week, under a physiotherapist supervision.

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Fig. 2 - Intra-hospital exercise program for heart transplant patients

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TG performed exercise program consisted in 10 phases of increasing complexity, including breathing exercises, active, resistance and aerobic exercises and stretching, as shown in Figure 2. The phases were established in order to promote incremental effort; progression to a new phase depended on the patient’s clinical response and ability to perform the proposed activities at each phase without compensation and independently; progression was also based on the perception effort assessed by the modified Borg scale [14] which consists in a score of 0 to 10 grades, using descriptive terms. Patients were instructed to maintain a score of 4 (somewhat severe) to 6 (severe). When the score reached 7 (very severe) the patient was oriented to regress one phase of the protocol. The progression phases were suspended or had regression when it was necessary to remain at rest, for medical request, or when the patient was unable to carry out the activities by side effects of immunosuppressive therapy. During the exercise sessions, heart rate (HR), blood pressure (BP) and peripheral oxygen saturation (SpO2) from the TG patients were monitored at the beginning, during the activity, at the end of the sessions and 5 minutes after the sessions, in order to evaluate the safety of the proposed protocol. The statistical analysis used to compare the groups consisted on Student t test for normally distributed data which are presented as mean and standard deviation, or its

corresponding Mann-Whitney, presented as median and interquartile ranges. To test the homogeneity between the proportions we used the chi-square test or Fisher’s exact test. The variables were subjected to analysis of variance for repeated measures ANOVA and when the normality assumption was rejected we used the Friedman test [15]. The level of statistical significance was 5%. RESULTS The general anthropometric characteristics and left ventricular ejection fraction (LVEF) values had no statistically significant difference between the groups, as shown in Table 1. There was a prevalence of 63.64% males in the population studied, with an equal proportion in both groups. Chagas cardiomyopathy was the etiology of HF in 28% of patients in the CG and 55% in TG; idiopathic dilated cardiomyopathy in 45% of CG and 18% in TG; ischemic cardiomyopathy in 9% in both groups and other causes 9% in both groups. Mechanical ventilation time was 11.83 hours (7.85 - 21.17) in CG and 8.33 hours (4.93 - 10.94) in TG, with no statistically significant difference between groups (P=0.094). The length of hospital stay in the postoperative period was 34 days (26 - 48) in CG and 32 days (21 - 46) in TG (P=0.768). The application period of the protocols was 26 ± 12 sessions in CG and 18 ± 6 sessions in TG, with no statistically significant difference between groups (P=0.074). When comparing the responses against exercise programs applied, we had a statistically significant increase in MIP, MEP and FVC variables in both groups, as shown in Table 2. The same was observed in the 6MWT (Table 3) and in 1RM test for the movements of elbow flexion, shoulder flexion, hip abduction and knee flexion (Table 4). Although the TG values were higher than those of the CG, they did not reach statistical significance.

Table 1. Anthropometric data and left ventricular ejection fraction Control Training P-value (n=11) (n=11) Age (years) 42.0 ± 16.46 39.0 ± 17.54 0.613 Weight (Kg) 60.0 ± 10.72 59.2 ± 9.03 0.725 Height (m) 1.68 ± 8.74 1.66 ± 6.3 0.582 BMI (Kg/m2) 21.38 ± 2.74 21.45 ± 3.26 0.956 LVEF (%) 18 (16-20) 20 (20-20) 0.278 BMI = body mass index; LVEF (%) = left ventricular ejection fraction. Kg = kilograms; m2 = square meter

Table 2. Lung function variables before and after the implementation of training programs Training P P Control Group Time 1st Test 2nd Test 1st Test 2nd Test 58 ± 30 63 ± 29* 0.619 0.007 MIP 52 ± 23 80 ± 31* 53 57* 0.616 0.009 MIP% pred 50 73* 59 ± 30 76 ± 34* 0.828 0.001 MEP 59 ± 33 83 ± 27* 50 65* 0.684 0.002 MEP% pred 54 73* 1.84 ± 0.87 2.93±1.31* 1.96±0.45 2.65 ± 1.04* 0.785 0.002 FVC (L) 45 ± 25 67 ± 26* 0.878 0.003 FVC% pred 48 ± 11 67 ± 29* MIP = maximum inspiratory pressure, MIP% pred = maximum inspiratory pressure in percentage of predicted, MEP= maximum expiratory pressure and MEP%pred = maximum expiratory pressure in percentage of predicted, FVC = forced vital capacity, FVC% pred = forced vital capacity in percentage of predicted. * P<0.05 when compared with the value obtained in 1st intra-group test

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Table 3. Functional capacity variables before and after the implementation of the training programs Training P P Control Group Time 1st Test 2nd Test 1st Test 2nd Test 272 ± 168 393 ± 155* 0.430 0.001 6MWT 322 ± 83 423 ± 70* 41 60* 0.323 0.001 6MWT%pred 50 66* 6MWT = six minute walk test, 6MWT% pred = six-minute walk test in percentage of predicted values. * P<0.05 when compared with the value obtained in the 1st test, intra-group test Table 4. Test of 1RM values before and after implementation of the training programs Control P P Training Group Time 1st Test 1st Test 2nd Test 2nd Test 3.91 0.38 0.009 Elbow flexion 3.36 4.45* 4.45* 2.18 0.22 0.024 Shoulder flexion 1.73 2.0* 2.82* 0.257 0.055 Shoulder abduction 2.09 1.45 2.0 2.36 1.91 0.353 0.132 Elbow extension 1.82 1.82 2.54 6.0 0.361 0.054 Knee extension 4.54 5.73 7.0 3.64 0.438 0.015 Hip abduction 3.18 3.91* 4.86* 3.27 0.749 0.005 Knee flexion 3.0 4.45* 4.86* 1RM= one repetition maximum test. * P<0.05 when compared with the value obtained in the 1st intra-group test

Fig. 3 - Values of maximal inspiratory pressure expressed as percentage of predicted values

Fig. 4 - Distance in the Six Minute Walk Test before and after the training programs

The mean MIP, expressed as percentage of predicted values , in CG was 53% and 57% in the first and second tests respectively and in TG was 50% and 73%, respectively. There was no statistically significant difference between groups (P=0.616), but over time, the patients showed significant gains (P=0.009) (Figure 3). 6MWT mean values were 272m in the first test and 393m in the second test for CG, and 322m and 423m, respectively, in TG. The performance of the groups was similar (P=0.430), with significant improvement in the second test (P=0.001) (Figure 4).

Peripheral muscle strength increased significantly in the second test compared to the first test for the following muscle groups: elbow flexion (P=0.009), shoulder flexion (P=0.024), hip abduction (P=0.015) and knee flexion (P=0.005), as shown in Table 4. DISCUSSION Exercise programs are important for HT patients and should be started as early as possible to restore their FC after the surgical procedure, but also to recover part of the muscle

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dysfunction due to the long period of deconditioning in the preoperative phase and to the effects of immunosuppressive therapy in skeletal muscle [16]. Our study evaluated the effects of exercise programs immediately after HT still in hospital phase. The literature is rich in studies that evaluate the effectiveness of programs in post discharge phases (II and III). However, studies addressing phase I are scarce, probably due to the diversity in patient outcomes. Protocols assistance are applied by different transplant centers, but there is little information on the impact of such assistance [17]. In our institution, the exercise program is performed tailored to each patient. To compare this program with a new proposal that includes exercise progression based on the complexity execution and resistance exercises, was the aim of this study. Two programs of therapeutic exercise have been applied to patients in the PP of heart transplantation. The CG performed exercises according to a protocol routinely practiced in the institution and TG performed a new exercise protocol based on incremental workloads. Our data show that the implementation of both protocols contributed to the improvement in lung function, in peripheral muscle strength and physical performance over time, with no differences between the protocols. Lung function may change in heart transplant in the PP, as well as in other cardio-thoracic surgery [18]. Ferreira et al. [19] observed a reduction in vital capacity 40%-50% compared to preoperative values for at least 10-14 days after cardiac surgery and abdominal surgery. It is believed that factors such as pain, abnormal respiratory mechanics due to the sternotomy and the deleterious effects of general anesthesia on pulmonary function, contributes to these findings. In HT, poor preoperative condition and the surgical procedure itself favor the reduced respiratory capacity and increased pulmonary secretions, which can be minimized through breathing exercises, bronchial hygiene and cough stimuli. Coronel et al. [20], in a retrospective cohort study evaluated 21 patients undergoing HT. The authors observed a volume and lung capacity reduction and a respiratory muscle strength decrease on the first postoperative day compared to the preoperative period and recovery of these values on the 14th postoperative day. The improvement of FVC, MIP and MEP between the first and 14th postoperative day was 70.1%, 75.1% and 62.8%, respectively. In our study, there was an improvement in ventilatory variables between the first and second tests but our medium datas are lower than those observed by Coronel et al. [20] (59% in the CG versus 35.2% in TG for FVC, 8.6% in CG versus 53.5% in TG for MIP and 28.8% in the CG versus 40.7% in TG for MEP). Our results corroborate the finding that changes in ventilatory function in patients undergoing HT are predictable, but these recover the expression of respiratory muscle strength and lung capacity within two weeks, besides improving FC, considering the association between the HT surgery and

functional rehabilitation a good therapeutic strategy for the treatment of advanced HF patients. In relation to the MIP, both groups were lower than 70% of predicted values at the beginning of the programs adopted in our study and only the TG reached average values above this threshold in the second test. According to Borges [21], respiratory muscle weakness, characterized by MIP less than 70% of predicted values, is one of the risk factors for the development of postoperative pulmonary complications in patients undergoing cardiac surgery. Thus, programs that contribute to the improvement of muscle strength are beneficial, regardless the association of specific inspiratory muscle training, thus minimizing the risk of complications. The improvement of FC in our study, 44.5% in CG and 31.4% in TG, was more expressive than in the study of Coronel et al. [20], where FC improved only 11.2% between tests. We believe that this result is due to the stimulus given to the patient to walk in the PP in our institution, either randomly (CG) or standardized by the proposed protocol (TG), where at the final phase, phase 10, the patients walked at least 900m per day and went up and down a flight of stairs. In the PP of coronary artery bypass surgery, we have demonstrated that a moderate supervised walking program during hospitalization improves walking ability at hospital discharge [22]. Thus, the inclusion of hiking seems an important feature in phase I cardiac rehabilitation programs for improvement in FC patients in the PP of cardiac surgery, as well as in HT surgery. Although the early indication of exercise in the PP of HT is a consensus, there are few publications that describe the protocols implemented in this population in the hospital phase. According to the Brazilian Cardiology Guidelines for Heart Transplantation [23], general exercises should be started in the immediate postoperative period, increased gradually until the patient develops muscle strength and adequate endurance to restore a level of fitness. The ambulation should be started as soon as possible and after discharge, the supervised program should include stretching, aerobic and endurance exercises. The intensity of aerobic activity can be prescribed between the anaerobic threshold and respiratory compensation point obtained in the cardiopulmonary exercise test, or 60%-85% of maximum HR achieved in the testing effort. Increased intensity during the program should be done gradually, taking into account the HR, BP, Borg scale and rejection episodes. Squires [24] recommend performing passive mobility exercises for upper limbs (UL) and lower limbs (LL), exercises to get up and sit in the chair and ambulation prescribed after extubation of the HT patient, which in general occurs within the first 24 hours after surgery. A walk or aerobic exercises on a stationary bicycle for 20 to 30 minutes can be tolerated using prescription based on the Borg scale between 11 and 13. Training for strength gain is indicated for the first six months after HT, when the authors recommend a maximum weight of 5 kg for bilateral UL exercises, to avoid complications with the

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surgical incision, as sternal instability. Our patients underwent resistance training with a maximum of 2 kg to 3 kg for UL and LL, considered safe within the exercise protocol proposed. The use of resistance exercises during exercise programs in the PP of HT is being increasingly used, since this method helps to minimize the deleterious effects of corticosteroids and immunosuppressants. It is common to skeletal muscle atrophy and weakness in addition to osteoporosis in recipients of organ transplantation as a side effect of this drug therapy. In this context, resistance exercise have osteogenic effect, since during its execution leads to bone deformation, generating cellular responses that determine the release of bone growth factors [16]. Braith et al. [25], in 2005, evaluated 15 HT patients who were randomized into CG, who performed a walking program (n=7), and a resistance training group (RTG), who performed walking and resistance exercise (n=8). Both programs began two months before surgery and lasted up to 6 months after HT. The exercise protocol consisted of a 5 minutes warm-up, followed by strengthening exercises for UL and LL at 50% 1RM, a series of 10 to 15 repetitions, twice a week. In biopsies of the right vastus lateralis, a significant increase in citrate synthase was observed, and 3 hydroxyacyl CoA dehydrogenase and lactate dehydrogenase activity in the RTG when compared to CG. The concentration of the type I myosin heavy chains increased 73% in the RTG, while decreased 28% in the CG. The type II myosin heavy chain increased 17% in the CG but decreased by 33% in the RTG, with P≤0.05. This was the first study to demonstrate that resistance training stimulates the change of type II muscle fiber, less oxidative, for the most fatigue-resistant, type I, in HT patients, demonstrating that resistance exercise in the post-transplant period is effective in increasing enzyme reserves and change the morphology of the muscle fiber, making the HT individual more capable to practice physical activity and to respond for the metabolic requirements necessary to perform the activities of daily living. Therefore, there is a need to develop protocols with specific exercises for the HT population, which consider both the aerobic and resistance training. Encouraging the practice of physical activity and adopting a healthy lifestyle should be initiated with educational and preventive actions still in-hospital phase [23]. Our study has the limitation, for a better power of analysis, of a small sample size. More studies are needed to evaluate exercise programs in the PP of HT, including pre-operative data and effects over time.

Authors' roles & responsibilities TSK POA KRL EAB MIZF EN

Conception and design of the study, implementation of projects and /or experiments, data analysis, writing of the manuscript Conception and design of the study, implementation of projects and/or experiments Implementation of projects and or experiments Final approval of manuscript Critical review and final approval of the manuscript Critical review and final approval of the manuscript

REFERENCES 1. Hunt SA, Haddad F. The changing face of heart transplantation. J Am Coll Cardiol. 2008;52(8):587-98. 2. Okoshi MP, Romeiro FG, Paiva SA, Okoshi K. Caquexia associada à insuficiência cardíaca. Arq Bras Cardiol. 2013;100(5):476-82. 3. Mont’Alverne DG, Galdino LM, Pinheiro MC, Levy CS, Vasconcelos GG, Souza Neto JD, et al. Clinical and functional capacity in patients with dilated cardiomyopathy after four years of transplantation. Rev Bras Cir Cardiovasc. 2012;27(4):562-9. 4. Kobashigawa JA. The future of heart transplantation. Am J Transplant. 2012;12(11):2875-91. 5. Braith RW, Edwards DG. Exercise following heart transplantation. Sports Med. 2000;30(3):171-92. 6. Lomeli HL. Rehabilitation in cardiac transplant patients. Arch Cardiol Mex. 2006;76:251-6. 7. Guimarães GV, D’Avila VM, Chizzola PR, Bacal F, Stolf N, Bocchi EA. Physical rehabilitation in heart transplant. Rev Bras Med Esport. 2004;10:408-11. 8. Lopes CR, Brandão CM, Nozawa E, Auler JO Jr. Benefits of noninvasive ventilation after extubation in the postoperative period of heart surgery. Rev Bras Cir Cardiovasc. 2008;23(3):344-50. 9. Wen AS, Woo MS, Keens TG. How many maneuvers are required to measure maximal inspiratory pressure accurately. Chest. 1997;111(3):802-7.

CONCLUSION

10. Neder JA, Andreoni S, Lerario MC, Nery LE. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res. 1999;32(6):719-27.

Results showed that HT patients had benefits with the implementation of exercise programs in-hospital period, regardless of the type of the program implemented. A new training proposal resulted in no superiority over the routine program. Exercise protocols improved ventilatory variables and the FC of this population.

11. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the sixminute walk test. Am J Respir Crit Care Med. 2002;166(1):111-7.

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12. Enright PL, Sherrill DL. Reference equations for the sixminute walk test in healthy adults. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1384-7.

20. Coronel CC, Bordignon S, Bueno AD, Lima LL, Nesralla I. Perioperative variables of ventilatory function and physical capacity in heart transplant patients. Rev Bras Cir Cardiovasc. 2010;25(2):190-6.

13. Whaley MH, Brubaker PH, Otto RM. Guidelines of the American College of Sports Medicine for stress testing and its prescription. Rio de Janeiro: Guanabara Koogan;2007.

21. Borges VM. Assessment of respiratory muscles and lung volume as a predictor of respiratory complications in the postoperative period of cardiac surgery [Dissertação de Mestrado]. Ribeirão Preto: Faculdade de Medicina de Ribeirão Preto, Universidadede São Paulo; 2008.

14. Borg GA. Perceived exertion. Exerc Sport Sci Rev. 1974;2:131-53. 15. Rosner B. Fundamentals of biostatistics. 2nd ed. Boston: PWS Publishers; 1986. 584p. 16. Braith RW, Magyari PM. RT for organ transplant recipients. In: Graves JE, Franklin BA, eds. Resistance training in health and rehabilitation. Revinter; 2006. p.255-76.

22. Hirschhorn AD, Richards D, Mungovan SF, Morris NR, Adams L. Supervised moderate intensity exercise improves distance walked at hospital discharge following coronary artery bypass graft surgery: a randomised controlled trial. Heart Lung Circ. 2008;17(2):129-38.

17. Yoshimori DY, Cirpiano Jr G, Mair V, Branco JN, Buffolo E. Assessment and medium-term follow up of heart transplant candidates undergoing low-intensity exercise. Rev Bras Cir Cardiovasc. 2010;25(3):333-40.

23. Bacal F, Souza Neto JD, Fiorelli AI, Mejia J, Marcondes-Braga FG, Mangini S, et al; Sociedade Brasileira de Cardiologia. II Brazilian Guidelines for Cardiac Transplantation. Arq Bras Cardiol. 2010;94(1 Supp):e16-76.

18. 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.

24. Squires RW. Exercise therapy for cardiac transplant recipients. Prog Cardiovasc Dis. 2011;53(6):429-36. 25. Braith RW, Magyari PM, Pierce GL, Edwards DG, Hill JA, White LJ, et al. Effect of resistance exercise on skeletal muscle myopaty in heart transplant recipients. Am J Cardiol. 2005;95(10):1192-8.

19. Ferreira FR, Moreira FB, Parreira VF. Noninvasive ventilation in the postoperative period of cardiac and abdominal surgery: a review. Rev Bras Fisioter. 2002;19(2):47-54.

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Durães AR, etORIGINAL al. - Impact ofARTICLE aspirin use in the incidence of thromboembolic events after bioprosthesis replacement in patients with rheumatic disease

Impact of aspirin use in the incidence of thromboembolic events after bioprosthesis replacement in patients with rheumatic disease Impacto da aspirina na incidência de eventos tromboembólicos após implante de bioprótese valvar cardíaca na doença reumática crônica

André Rodrigues Durães1, MD, PhD; Milena Andrade Oliveira Durães1, MD, PhD; Luis Claudio Correia2, MD, PhD; André Mauricio Souza Fernandes2, MD, MSc, Roque Aras Junior2, MD, PhD

DOI: 10.5935/1678-9741.20130054

RBCCV 44205-1480

Abstract Introduction: There is still much debate regarding the kind of antithrombotic therapy in the immediate postoperative period of bioprosthesis replacement (first three months). Thus, the authors consider relevant to determine the contemporary incidence of thromboembolic events in rheumatic patients early after implantation of aortic and mitral bioprosthesis replacement (first 90 days in the post-operative period) and perform a comparison between isolated Aspirin uses versus no-antiplatelet therapy, in this same context. Methods: Between the period of January 2010 to July 2012, all consecutive rheumatic patients, with basal sinus rhythm, who performed mitral and aortic valve replacement with bioprosthesis (pericardial bovine), were included in this prospective cohort study, 184 patients in total. The primary endpoint evaluated were the rate of embolic events. Results: In the first 30 days, there were three cerebral ischemic events among patients treated in Aspirin group (5.2%) compared with two events in patients without Aspirin therapy (1.7%), HR = 3.18; 95% CI 0.5 to 19.6; P=0.33. Between 31 and 90 days postoperatively, no patient had a primary outcome. The embolism-free survival, bleeding events and the overall survival

1 2

were not statistically significant between the aspirin and no-antiplatelet groups. Conclusion: In conclusion, in this prospective cohort of rheumatic patients, we found a low and very rare incidence rate of embolic events during the first 90 days postoperative period in mitral and isolated aortic position, respectively. The use of aspirin did not significantly reduce the rate of thromboembolism. Descriptors: Aspirin. Stroke. Bioprosthesis. Rheumatic heart disease. Resumo Introdução: Ainda existem controvérsias em relação à melhor estratégia de terapia antitrombótica nos três meses iniciais de pós-operatório de implante de bioprótese valvar cardíaca. Assim, os autores consideram relevante determinar a incidência contemporânea de episódios de isquemia cerebral nos meses iniciais (primeiros 90 dias de pós-operatório), e realizar uma comparação entre a aspirina isolada versus a não terapia antiplaquetária no mesmo contexto. Métodos: Entre o período de janeiro de 2010 a julho de 2012,

Hospital Ana Nery, Salvador, BA, Brazil. Escola Bahiana de Medicina, Salvador, BA, Brazil.

Correspondence address: André Rodrigues Durães Hospital Ana Nery Rua Saldanha Marinho, SN – Caixa d’Água – Salvador, BA, Brazil Zip code: 40320-010 E-mail: andreduraes@gmail.com

Work carried out at Universidade Federal da Bahia, Salvador, BA, Brazil. This article is part of the doctoral thesis of André Rodrigues Durães in the graduate program of Medicine and Health, Federal University of Bahia.

Article received on February 2nd, 2013 Article accepted on June 19th, 2013

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Resultados: Nos primeiros 30 dias, três (5,2%) eventos isquêmicos cerebrais foram observados em pacientes do grupo aspirina, em comparação com dois (1,7%) eventos em pacientes sem terapia aspirina, RR = 3,18, 95% IC 0,5-19,6; P=0,33. Entre 31 e 90 dias do pós-operatório, nenhum paciente apresentou episódios de embolia cerebral ou periférica. A sobrevida livre de eventos embólicos, sangramentos e a sobrevida geral não foram estatisticamente significativas entre os grupos aspirina e não-aspirina. Conclusão: Constatou-se baixa incidência de eventos embólicos durante os primeiros 90 dias de pós-operatório de troca valvar por bioprótese envolvendo a posição mitral, e uma ainda menor para mesma situação para troca aórtica isolada. O uso da aspirina não influenciou de maneira significativa na redução de episódios tromboembólicos.

Abbreviations, acronyms & symbols ASA Aspirin CI Confidence interval ECG Eletrocardiogram EuroSCORE II European System for Cardiac Operative Risk Evaluation ) HR Hazard ratio PVT Prosthetic valve thrombosis STS score Society of Thoracic Surgeons 2008 cardiac surgery risk model (the STS model) for isolated valve surgery VKA vitamin K antagonista

consecutivamente todos pacientes reumáticos com ritmo sinusal basal, que realizaram a substituição da valva mitral, e ou aórtica, por bioprótese (pericárdio bovino), foram incluídos neste estudo de coorte prospectivo, totalizando 184 pacientes. O desfecho primário avaliado foi a ocorrência de eventos embólicos.

Descritores: Aspirina. Acidente vascular cerebral. Bioprótese. Cardiopatia reumática.

INTRODUCTION

poor candidates to chronic use of vitamin K antagonist (VKA) [5,6], and were included in this prospective observational single-center cohort study. The main criteria used to classify a patient as a bad candidate to the use of VKA were the place of residence (rural or remote location of a hospital) and low socioeconomic level. The exclusion criteria were previous embolic events or atrial fibrillation, recent cerebral ischemia (6 months), coagulopathy, thrombophilia and allergies to ASA. Preoperative surgical risk was quantified with the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) [7] and the Society of Thoracic Surgeons 2008 cardiac surgery risk model (the STS model) for isolated valve surgery [8]. In this cohort, despite being an open study, the investigators did not have any influence on the postoperative administration of ASA. Of three surgical teams that performed the surgical procedures, only one recommended the routine use of ASA in this context, and the other two teams opted not to use it. The selection of the surgical team for each patient always followed a computerized electronic scheduling, and this system, through a mechanism of random distribution of patients according to the demand of the service. Clinical evaluation and follow-up after hospital discharge were performed by monthly consultations, by contacting the patients (patients who did not attend the scheduled appointments). Blood samples (blood count, renal function, electrolytes and coagulation) and ECG were carried out every 30 days. Those who presented any occurrence (for example atrial fibrillation, cerebral ischemia, bleeding events) were referred to the respective physician.

Rheumatic heart disease is a major burden in developing countries where it causes most of the cardiovascular morbidity and mortality in young people, leading to about 250,000 deaths per year [1]. Unfortunately there is not a perfect valve substitute. The bioprosthesis valve has a theoretical great advantage: chronic anticoagulation is not mandatory in the absence of other risk factors [2]. Thus, this prosthesis is recommended when good quality anticoagulation is unlikely [2], unfortunately it is still a common situation for developing countries due the high incidence of chronic rheumatic disease in areas with low socioeconomic status [3,4]. There is still much debate regarding the kind of antithrombotic therapy in the immediate postoperative bioprosthesis period [4]. Thus, the aim of this study is to determine the contemporary incidence of thromboembolic events in rheumatic patients early after isolated aortic and mitral bioprosthesis replacement (in the first 90 days of the post-operative period), and perform a comparison between isolated use of Aspirin (ASA) with no-antiplatelet therapy, in this same context. METHODS Study Protocol Between the period of January 2010 to July 2012, all consecutive rheumatic patients with basal sinus rhythm, who performed mitral and aortic valve replacement with bioprosthesis (pericardial bovine) in the cardiology service of Ana Nery Hospital in Salvador - Brazil, were classified as

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The primary endpoint was embolic events (ischemic stroke, transient cerebral ischemia or peripheral embolic event) in the first 90 days in the postoperative period. Secondary endpoints were prosthetic valve thrombosis, increase in functional NYHA class, need for a repeated operation, or death. Safety endpoint evaluated included bleeding as measured by GUSTO criteria [9]. To investigate prosthetic valve thrombosis (PVT), transthoracic echocardiography was performed 30 to 60 days after hospital discharge routinely, and transesophageal echocardiography, was performed to exclude suspected cases. All patients with confirmed PVT had urgent evaluation of cardiac surgery, and thrombolytic therapy when indicated. In this study, the term cerebral ischemia was used to situations which a sudden, focal neurological deficit of presumed vascular origin lasting 24 hours to 7 days (reversible ischemic neurological deficit) or enduring more than 7 days (cerebrovascular accident), confirmed by computed tomographic or magnetic resonance scan imaging evaluated by a skilled physician. A peripheral embolism was diagnosed when there was a sudden onset of arterial occlusion in the extremities or sudden abdominal pain requiring urgent surgical intervention.

There were 90 male and 94 female patients. The mean age of the ASA group (45 ± 16 years) was similar with that of the no-ASA group (42 ± 15; P=0.25). There were 27 cases (46%) of mitral stenosis in the ASA group versus 38 cases (30%) in no-ASA therapy (P=0.05). Surgery to isolated aortic replacement were 16 cases (27%) and 39 (31%) in ASA and no therapy (P=0.57). Distributions of aortic pathologies and mitral insufficiency were similar between the groups. There were no significant differences in gender distribution, prevalence of hypertension, diabetes and smoking (Table 1). The STS stroke risk and mean left atrium diameter was similar in both groups: 0.36% versus 0.33% (P=0.56) and 52 versus 51 mm (P=0.54). Ninety-six percent of each therapeutic group were classified as low socio-economic status (P=0.98), while 75% in both group lived in rural or remote areas (P=0.90) (Table 1). Table 1. Characteristics of patients at baseline (n = 184) ASA Nothing (n= 59) (n= 125) Male – no. (%) 24 (40) 66 (53) Age, mean, y 45 ± 16 42 ± 15 Hypertension - no. (%) 16 (27) 27 (22) Diabetes - no. (%) 2 (3.4) 3 (2.4) Smoking - no. (%)* 21 (36) 33 (27) Low socioeconomic status 57 (96) 120 (96) Living remote areas† 44 (75) 94 (75) Mitral pathology Mitral stenosis 27 (46) 38 (30) Mitral insufficiency 40 (68) 75 (60) Aortic pathology Aortic stenosis 13 (22) 24 (19) Aortic insufficiency 20 (34) 48 (38) Mitral replacement 43 (73) 86 (69) Isolated aortic replacement 16 (27) 39 (31) LVEF, mean, % 62 ± 12 60 ± 14 NYHA (III-IV) - no. (%) 56 (95) 100 (83) Euroscore II, mean,% 1.7 ± 0.5 1.9 ± 1.5 STS stroke risk, mean,% 0.36 ± 0.26 0.33 ± 0.37 Left atrium, mean, mm 52 ± 10 51 ± 13

Statistical Analysis Baseline patient characteristics were stratified by treatment strategy and summarized as percentages for categorical variables and mean±SD for continuous variables. All data were compiled and stored in a computerized database by a statistical package (SPSS Statistics 17.0.0 – IBM, Markham, Canada). Univariate analysis (Χ2 and t test) was used to compare categorical and numeric variables, respectively. Survival curves with the use of the Kaplan-Meier method were estimated to evaluate survival freedom from cerebrovascular accident, considering the time to the event consisted of the interval between 24 hours and 3 months after the surgery. Patients who did not experience a cerebrovascular accident and those who died were considered censored. To test the hypothesis of equality between survival curves, the log-rank test was used. Hazard ratio (HR) was estimated to measure the association between group treatment and event, and 95% Confidence Interval (CI), was reported. A level of significance (α=0.05) was chosen for decision-making.

P Value 0.13 0.13 0.48 0.73 0.25 0.98 0.90 0.05 0.31 0.65 0.55 0.57 0.57 0.55 0.02 0.37 0.56 0.54

Values are number (%)=unless indicated otherwise; LVEF=indicates left ventricular ejection fraction; NYHA=New York Heart Association * Previous or actual. † Rural areas and small villages.

RESULTS

Primary, secondary and safely outcomes are reported in Table 2. All embolic occurred toward the brain. In the first 30 days of the postoperative period, three cerebral ischemia were observed among patients treated in the ASA group (5%) compared with two events in patients without ASA therapy (1.6%), HR=3.18; 95% CI 0.5 to 19.6; P=0.33. This represents an incidence rate of 0.57 versus 0.19 per 1000 patients/day (p/d), in each group, respectively. Between days 31 to 90 of follow-up, no patient had cerebral ischemia,

A total of 184 consecutive rheumatic patients undergoing bioprosthesis that had been classified as bad candidates for chronic use of VKA previous to surgery, by local cardiology´s team, were included in the study. Fifty nine patients received only ASA (100 mg/daily), starting on day 2 after surgery, and 125 patients did not use ASA therapy (up to 3 monts in the postoperative period). There were no losses during follow-up, including death.

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Table 2. Outcomes according study groups ASA (n=59) Rate per 1000 No of person-day Patients 0.57 Primary endpoint: Stroke 3 (5) 0.82 Mitral replacement 3 (7) 0 Aortic replacement* 0 0.19 PVT: overall 1 (1.7) 0.27 Mitral replacement 1 (2.3) 0 Aortic replacement* 0 0 Death at follow-up‡ 0 NYHA (I) at follow-up‡ 58 (98) 0 Major bleeding§ 0

Nothing (n=125) No of Rate per 1000 Patients person-day 3 (5) 0.57 3 (7) 0.82 0 0 1 (1.7) 0.19 1 (2.3) 0.27 0 0 0 0 58 (98) 0 0

Hazard Ratio (95% CI)

P Value

3.18 (0.5-19.6) 2.27 (0.5-15.0) 0.96 (0.1-10.4) 0.96 (0.1-10.3) 0.99 (0.1-1.03) -

0.33 0.11 0.70 0.99 0.98 0.58 -

Values are number (%)=unless indicated otherwise; AF=atrial fibrillation; LVEF=indicates left ventricular ejection fraction; PVT=prosthesis valve thrombosis; NYHA=New York Heart Association * Isolated aortic replacement. † New documented Atrial Fibrillation at follow-up. ‡ Up to three months. § According GUSTO criteria.

no-antiplatelet group (0.08 per 1000 p/d); P=0.11. Prostheses valve thrombosis occurred only in mitral position. The overall rates were 0.19 (P=0.99) in both groups. Possible predictors to thromboembolic events, by including both therapeutic groups (ASA versus none), did not present statistically significant difference in univarated analysis.

regardless of ASA use. These rates, based on Kaplan-Meier estimates, were not statistically different between the two groups (Figure 1).

DISCUSSION Rheumatic heart disease causes at least 200.000250.000 premature deaths every year, and is the major cause of cardiovascular death in children and young adults in developing countries [3]. Prosthetic heart valves improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thrombotic complications in valve recipients poses challenges to clinicians and patients [1]. In this prospective cohort study of rheumatic patients, for the first time, a direct comparison between ASA versus noantiplatelet therapy was performed, early after bioprosthesis replacement, not showing a significant difference in the incidence rate of embolic events during the first 30 days of the postoperative, with no events between 31 to 90 days of this same period. The person-time measurement used in this study was obtained through calculation (and not a direct measure), using the rate incidence. Since the outcome is not a continuous variable, we should be aware of its limitations. The best evidence to date about antithrombotic management after aortic replacement was formed with the publication of a large-scale retrospective cohort study by Brennan et al. [10] with 25,656 patients and showed a low incidence of embolic events in the first 3 months of the

Fig. 1 - Stroke free survival

Patients with isolated aortic replacement in ASA group did not develop embolic event, while occurred one case in no-ASA Group, which represents an incidence rate of 0.08 per 1000 p/d for this latter. Patients who underwent mitral replacement, were observed three events of cerebral ischemia (0.82 per 1000 p/d) in ASA group, and only one in

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postoperative period (0.9%), a high variation of therapeutic strategy between various institutions, and no significant difference between patients treated with only warfarin versus patients treated only with ASA with respect to death, embolism and bleeding. Guerli et al. [11] performed the first prospective study in this same scenario, and it indicated no statistically significant difference in the overall postoperative incidence of cerebral ischemia in both groups studied (warfarin versus ASA). Moinuddeen et al. [12] and Babin-Ebell et al. [13] showed similar results when assessing patients retrospectively. Brueck et al. [14] comparing ASA with no therapy in 288 consecutive patients with sinus rhythm did not find differences in the outcomes of functional status, embolic events and survival with 3 months of aortic bioprosthesis replacement. In mitral position, Colli et al. [15] conducted a retrospective small analysis with 99 patients comparing VKA, ASA and nothing, finding no difference between the three strategies evaluated. The actual summary recommendation for antithrombotic therapy in the first 3 months after bioprosthesis surgery by the AHA/ACC is the use of ASA (class I/C) alone or combined with warfarin (class IIa/C), according to the presence or not of risk factors (atrial fibrillation, previous thromboembolism, left ventricular dysfunction, and hypercoagulable condition) [16]. The ESC and ACCP innovate when recommends the use of ASA (over warfarin) in the first 3 months for patients with bioprosthesis in aortic position, keeping the use of warfarin therapy to mitral position (class IIa/C and Grade IIc, respectively) [2,17]. This relatively low level of evidence present in all guidelines cited involving this issue is explained by the lack of large randomized clinical trials. Although there is a general recommendation (in guidelines) for the utilization of anticoagulation therapy with warfarin in the first 3 months of the postoperative period, especially in the mitral position, there are significant variations of applications between cardiovascular centers around the world (Europe, Middle East, Canada and Asia), including some locations who do not use antithrombotic therapy in this situation [18]. In our study, the number of cerebral events in the ASA group was almost double that in patient with no antiplatelet therapy in the first 30 days, without statically significance. This absolute difference can be explained by the small sample, absence of a true randomization or by the more prevalence of mitral stenosis in the ASA group that could lead to more episodes of atrial fibrillation and subsequent more embolic events. Finally, the fact that the patients had been operated by three different surgical teams may also have affected the rate of embolic events in the short and medium term. Healey et al. [19] showed that subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated

with a significantly increased risk of ischemic stroke or systemic embolism, and Olesen et al. [20] in a large cohort study, in patients with non-valvular atrial fibrillation, showed that ASA treatment has no effect on the risk of stroke/thromboembolism. CONCLUSION In conclusion, in this prospective cohort of rheumatic patients, we found a low and very rare incidence rate of embolic events during the first 90 days of the postoperative period, in mitral and isolated aortic replacement, respectively. The use of aspirin did not significantly influence the rate of thromboembolism.

Authors' roles & responsibilities ARD MAOD LCC AMSF RAJ

Study design, protocol execution, data analysis and manuscript writing Data collection and study design Statistical analysis and manuscript review Data collection Study design, data analysis and manuscript review

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8. O’Brien SM, Shahian DM, Filardo G, Ferraris VA, Haan CK, Rich JB, et al; Society of Thoracic Surgeons Quality Measurement Task Force. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2: isolated valve surgery. Ann Thorac Surg. 2009;88(1 Suppl):S23-42. 9. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med. 1993;329(10):673-82. 10. Brennan JM, Edwards FH, Zhao Y, O’Brien S, Booth ME, Dokholyan RS, et al; DEcIDE AVR Research Team. Early anticoagulation of bioprosthetic aortic valves in older patients: results from the Society of Thoracic Surgeons Adult Cardiac Surgery National Database. J Am Coll Cardiol. 2012; 60(11):971-7.

17. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH; American College of Chest Physicians. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e576S-600S.

11. Gherli T, Colli A, Fragnito C, Nicolini F, Borrello B, Saccani S, et al. Comparing warfarin with aspirin after biological aortic valve replacement: a prospective study. Circulation. 2004;110(5):496-500.

18. Colli A, Verhoye JP, Heijmen R, Strauch JT, Hyde JA, Pagano D, et al; ACTION Registry Investigators. Antithrombotic therapy after bioprosthetic aortic valve replacement: ACTION Registry survey results. Eur J Cardiothorac Surg. 2008;33(4):531-6.

12. Moinuddeen K, Quin J, Shaw R, Dewar M, Tellides G, Kopf G, et al. Anticoagulation is unnecessary after biological aortic valve replacement. Circulation. 1998;98(19 Suppl):II95-8.

19. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, et al; ASSERT Investigators. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120-9.

13. Babin-Ebell J, Schmidt W, Eigel P, Elert O. Aortic bioprosthesis without early anticoagulation--risk of thromboembolism. Thorac Cardiovasc Surg. 1995;43(4):212-4.

20. Olesen JB, Lip GY, Lindhardsen J, Lane DA, Ahlehoff O, Hansen ML, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ’real world’ nationwide cohort study. Thromb Haemost. 2011;106(4):739-49.

14. Brueck M, Kramer W, Vogt P, Steinert N, Roth P, Görlach G, et al. Antiplatelet therapy early after bioprosthetic aortic valve replacement is unnecessary in patients without thromboembolic

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Oliveira EK, ORIGINAL et al. - Risk factors for prolonged hospital stay after isolated ARTICLE coronary artery bypass grafting

Risk factors for prolonged hospital stay after isolated coronary artery bypass grafting Fatores de risco para tempo de internação prolongada após revascularização isolada do miocárdio

Elayne Kelen de Oliveira1; Aída Luiza Ribeiro Turquetto2; Pedro Luiz Tauil3, PhD; Luiz Fernando Junqueira Jr.4, PhD; Luiz Guilherme Grossi Porto1,4,5, PhD

DOI: 10.5935/1678-9741.20130055

RBCCV 44205-1481

Abstract Introduction: Characteristics of the patient and the coronary artery bypass grafting may predispose individuals to prolonged hospitalization, increasing costs and morbidity and mortality. Objective: The objective of this study was to evaluate individual and perioperative risk factors of prolonged hospitalization in intensive care units and wards. Methods: We conducted a case-control study of 104 patients undergoing isolated coronary artery bypass grafting with cardiopulmonary bypass. Patients hospitalized >3 days in the intensive care unit or >7 days in the ward were considered for the study. The association between variables was estimated by the chi-square test, odds ratio and logistic regression; P ≤0.05 was considered statistically significant. Results: Hospital stay >3 days in the intensive care unit occurred for 22.1% of patients and >7 days in the ward for 27.9%. Among preoperative factors, diabetes (OR=3.17) and smoking (OR=4.07) were predictors of prolonged intensive care unit stay. Combining the pre-, intra-and postoperative variables, only mechanical ventilation for more than 24 hours (OR=6.10) was predictive of intensive care unit outcome. For the ward outcome, the preoperative predictor was left ventricular ejection fraction

<50% (OR=3.04). Combining pre- and intraoperative factors, diabetes (OR=2.81), and including postoperative factors, presence of infection (OR=4.54) were predictors of prolonged hospitalization in the ward. Conclusion: Diabetes and smoking were predictors of intensive care unit outcome, and ejection fraction <50% of ward outcome. For the set of perioperative factors, prolonged hospitalization after isolated coronary artery bypass grafting was associated with mechanical ventilation >24 hours for the intensive care unit and presence of infection for the ward. Descriptors: Risk factors. Myocardial revascularization. Hospitalization.

Brasilia University Center (UniCEUB – DF), Brasilia, DF, Brazil. Instituto de Cardiologia do Distrito Federal - IC-DF (Federal District Institute of Cardiology), Brasilia, DF, Brazil. 3 University of Brasilia, Faculty of Medicine, Tropical Medicine Center, Brasilia, DF, Brazil. 4 University of Brasilia, Faculty of Medicine, Cardiovascular Laboratory, Brasilia, DF, Brazil. 5 University of Brasilia, Faculty of Physical Education, Brasilia, DF, Brazil.

Correspondence address: Luiz Guilherme Grossi Porto Laboratório Cardiovascular da Faculdade de Medicina da Universidade de Brasília Campus Universitário Darcy Ribeiro Asa Norte – Brasília, DF, Brazil – Zip code: 70910-900 E-mail: luizporto@unb.br

Work conducted at the Instituto de Cardiologia do Distrito Federal - IC-DF (Federal District Institute of Cardiology), Brasilia, DF, Brazil.

Article received on September 25th, 2012 Article accepted on November 18th, 2012

Resumo Introdução: Características do paciente e da cirurgia de revascularização do miocárdio podem predispor à internação prolongada, aumentando custos e a morbimortalidade. Objetivo: Avaliar fatores de risco individuais e transoperatórios para internação prolongada na unidade de terapia intensiva e na enfermaria.

1 2

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Oliveira EK, et al. - Risk factors for prolonged hospital stay after isolated coronary artery bypass grafting

Resultados: A permanência >3 dias na terapia intensiva ocorreu em 22,1% dos pacientes e >7 dias na enfermaria em 27,9%. Entre os fatores pré-operatórios, o diabetes (OR=3,17) e o tabagismo (OR=4,07) foram os preditores para permanência prolongada na terapia intensiva. Combinando-se as variáveis pré-, intra- e pós-operatórias, somente a ventilação mecânica por mais que 24 horas (OR=6,10) foi preditora para o desfecho na terapia intensiva. Para o desfecho na enfermaria, o preditor pré-operatório foi a fração de ejeção ventricular esquerda <50% (OR=3,04). Combinando os fatores pré- e intraoperatórios, o diabetes (OR=2,81) e, somando-se os pós-operatórios, a presença de infecção (OR=4,54), foram os preditores para internação prolongada na enfermaria. Conclusão: Diabetes e tabagismo foram os preditores para o desfecho na terapia intensiva, e a fração de ejeção <50% para a enfermaria. Para o conjunto dos fatores transoperatórios, internação prolongada após revascularização do miocárdio isolada associou-se à ventilação mecânica >24 horas para terapia intensiva e à presença de infecção para a enfermaria.

Abbreviations, acronyms & symbols BMI CABG CCIH CPB ICU LVEF MV OI PNMV RF SAH SC SUS

Body mass index Coronary artery bypass grafting Commission for hospital infection control Cardiopulmonary bypass Intensive Care Unit Left ventricular ejection fraction Mechanical ventilation Oxygenation index Pneumonia associated with mechanical ventilation Renal failure Systemic arterial hypertension Surgical center Unified Health System

Métodos: Realizou-se estudo de caso-controle com 104 pacientes submetidos à revascularização do miocárdio isolada sob circulação extracorpórea. Consideraram-se casos os pacientes com internação >3 para terapia intensiva ou >7 dias para enfermaria. A associação entre variáveis foi estimada pelo teste do qui-quadrado e pela razão de chances (odds ratio-OR) empregando-se a regressão logística, ao nível de P≤0,05.

Descritores: Fatores de risco. Revascularização miocárdica. Hospitalização.

INTRODUCTION

productivity [4,8], affecting family budgets, quality of life and increasing costs [1]. Bashour et al. [7] showed that, after cardiac surgery, many patients with prolonged hospital stay died soon after discharge and that the functional status of those who survived for a longer period was worse when compared with those who recovered faster. In this context, the objective of this study was to identify pre-, intra- and postoperative risk factors for long hospitalizations in the ICU or the ward, of patients undergoing isolated CABG surgery with cardiopulmonary bypass (CPB) in a specialized service of the Federal District - Brazil. METHODS

Despite advances in preventative and curative approaches to cardiovascular disease, data from the American Heart Association [1] indicate that the incidence and prevalence of these diseases remain high, although with reduced mortality. In the surgical treatment of coronary artery disease, coronary artery bypass grafting (CABG) is one of the most common therapeutic choices [1,2]. The benefits of CABG are identified as contributing factors for reduced fatal outcomes in many cases of associated cardiovascular diseases [1,2]. However, this surgery, besides being expensive, can result in reduced functional capacity due to morbidities acquired postoperatively or risks associated with the procedure [3,4]. In the Brazilian Unified Health System (SUS), over R$ 400 million have been spent to perform 32,809 isolated CABG surgeries between January-2011 and March 2012, with an average hospital stay of 12.8 days [5]. This spending comes from the costs of the operation and hospitalization in the ward and/or in the Intensive Care Unit (ICU) [6]. According to Haddad et al. [3], 66.2% of the expenses are associated with the surgery, 17.5% with the postoperative period in the ICU and 12% with the postoperative period in the ward. It is estimated that the longer the postoperative hospital stay is, the higher the costs are. Bashour et al. [7] observed that 5.4% of the 142 patients who stayed more than 10 days in the ICU were responsible for 48% of the total expenses of 2,618 patients. Postoperative hospital stay may also contribute to increased severity, reduced functional capacity and loss of professional

We conducted a case-control study of adults of both sexes, with coronary artery disease, admitted in 2007 at the Instituto de Cardiologia do Distrito Federal hospital (IC-DF) who had undergone coronary artery bypass grafting via median sternotomy with CPB. This study was approved by the Hospital Research Ethics Committee (IC-DF n° 038/2009). Of the 153 patients who underwent the procedure in the period, we excluded 34 due to associated surgical procedures, 10 who did not undergo CPB, 2 that re-operated and three that died. The anthropometric and clinical data were retrospectively collected from medical records and electronic records of the hospital. The information was categorized and organized according to the pre-, intra-and postoperative periods. The final sample consisted of 104 patients who underwent isolated CABG with median age (extremes) of 60 (37-82)

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years, 50 (48.1%) over 60 years and 72 (69.2%) male. Body mass index (BMI) before surgery was 27 (17.8 to 41) kg/m2. In this group, in a combined or isolated manner and prior to surgery, 24 (23.1%) patients had left ventricular ejection fraction (LVEF) <50%, 5 (4.8%) presented renal failure (RF), 87 (83.7%) had systemic arterial hypertension (SAH), 42 (40.4%) had diabetes mellitus type II, 12 (11.5%) were smokers and 43 (41.3%) were former smokers. Study design The length of stay in the ICU after surgery was considered to be the number of days spent at the hospital immediately after surgery, and hospitalization in the ward as the days following transfer from the ICU until discharge. Periods of time shorter than 24 hours in the ICU or in the ward were considered as one day. For the patient who was eventually readmitted to the ICU, the total number of days (first admission and readmission) was considered. We considered a prolonged stay in the ICU to be >3 days, in accordance with the study by Janssen et al. [6], and >7 days for the ward, according to Atoui et al. [8], which corresponded to the values of the 70th percentile of the sample in both cases. The cases were considered were those in which the patient spent more than 3 days in the ICU and more than 7 days in the ward, and controls those with ≤ 3 and ≤ 7 days of hospitalization, respectively.

Statistical Analysis Taking into consideration the non-normal distribution of most variables (Shapiro-Wilk test), we used non-parametric statistics. In order to analyze the association between categorical variables we used the chi-square or Fisher’s exact test when indicated. We proceeded to the bivariate analysis to verify the strength of association between the variables tested groups of smaller and longer hospitalization. We also calculated the odds ratio (odds ratio, OR) and the 95% confidence intervals. To compare the values of continuous variables we used the Mann-Whitney test, and these variables expressed as median and extremes. Sequentially, we proceeded to the multivariate analysis of the variables that had a significance level P≤0.20 in the previous analysis, using logistic regression to calculate the adjusted OR. To avoid duplication, when a continuous variable showed good conditions of to join the multivariate model and its corresponding categorical variable too, only the last one entered the model. The multivariate logistic regressions of the stepwise [6,11] backward likelihood ratio method [10] were performed with the length of stay in ICU and in the ward as a binomial outcome variable (≤ 3 versus >3 days and ≤ 7 versus >7 days, respectively). Variables were included in the equation in three blocks: the preoperative ones in the first block, these variables plus intraoperative ones in the second, and postoperative variables over the previous two were the third block. The probability (P value) HosmerLemshow was calculated to estimate how much the logistic regression model is adapted to the data [10]. The differences were considered statistically significant when the two-tailed probability of their occurrence due to chance (type I error) were less than or equal to 5% (P≤0.05). Data were analyzed using SPSS v.13.0 for Windows (SPSS Inc., Chicago, IL). RESULTS

Predictors of risk The preoperative variables evaluated as possible predictors of risk for the outcomes studied were: sex [8], age [8,9], BMI [10], LVEF [8,10], hypertension [9], diabetes [6,7,9], RF [8,11,12], smoking [7,8] and former smoking (>2 months without tobacco). The continuous preoperative variables, besides being evaluated as such, were categorized to form subgroups based on cuttoff points: older and younger than age 60 [9,12], LVEF higher and lower than 50% [9,12], creatinine levels higher and lower than 1.5 mg/dl for renal failure (RF) [13] and BMI between 18.5 and 24.9 (normal) and <18.5 or> 24.9 kg/m2 (outside the normal range). The intraoperative variables considered were number of grafts, duration of CPB [10], aortic clamping time [8,10] and oxygenation index (OI) in the surgical center (SC). In the postoperative phase, we analyzed acute RI [12], mechanical ventilation (MV) [9,14], IO at ICU admission (IO-ICU) occurrence of pneumonia associated with MV (PNMV) [12] and the presence of other infections [14]. Intra- and postoperative categories to form subgroups were CPB time longer and shorter than 120 minutes [15], SC-IO and IO-ICU higher and lower than 300 [15]. The occurrence of infection and PNMV was characterized based on the records of the Commission for Hospital Infection Control (CCIH) of the institution, categorized as presence or absence of PNMV, upper, lower, and deep surgical site infection, infection in the bloodstream, urinary tract infection, pneumonia, endocarditis, mediastinitis, and empyema.

The median total length of postoperative hospital stay was 8 (5-53) days: 3 (2-36) days in the ICU and 5 (1-36) days in the ward. Of the 104 patients, 23 (22.1%) remained for more than three days in the ICU, and 29 (27.9%) for more than seven days in the ward. ICU satay during the postoperative period Table 1 presents the frequencies and bivariate analysis of risk factors associated with prolonged ICU stay (> 3 days). Table 2 shows the comparisons between medians (extreme) of the continuous predictor variables of those who remained for less and for more than 3 days in the ICU. In the case of variable time of VM, its categorical discrimination in greater and less than 24 hours was significantly associated with length of ICU stay (Table 1), so that this discrimination was only considered for logistic regression analysis.

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Table 1. Absolute frequencies (relative) and bivariate analysis of risk factors associated with ICU for more and less than 3 days (n = 104). Variables Preoperative

Intraoperative

Postoperative

Gender Woman Man Age (years) > 60 < 60 BMI (kg/m2) <18.5 ou ≥ 24.9 18.5-24.9 Renal failure Yes No EF (%) < 50 ≥ 50 Diabetes Yes No Hypertension Yes No Smoke Yes No Former smoker Yes No On-pump time (min) ≥ 120’ < 120’ Number of bypasses ≥4 <4 OI-SC ≤ 300 >300 OI-UTI ≤ 300 > 300 MV (h) > 24 ≤ 24 Infection Yes No PNMV Yes No Renal failure Yes No

ICU > 3 days n = 23

ICU ≤ 3 days n = 81

OR (CI 95%)

10 (31%) 13 (18%)

22 (69%) 59 (82%)

0.135*

2.06 (0.79-5.38)

13 (26%) 10 (19%)

37 (74%) 44 (81%)

0.358*

1.55 (0.61-3.93)

19 (24%) 4 (17%)

61 (76%) 20 (83%)

0.463*

1.56 (0.47-5.12)

2 (40%) 21 (21%)

3 (60%) 78 (79%)

0.305†

2.48 (0.39-15.80)

8 (33%) 14 (18%)

16 (67%) 65 (82%)

0.102*

2.32 (0.83-6.48)

14 (33%) 9 (15%)

28 (67%) 53 (85%)

0.023*

2.94 (1.13-7.65)

22 (25%) 1 (6%)

65 (75%) 16 (94%)

0.111†

5.42 (0.68-43.23)

5 (42%) 18 (20%)

7 (58%) 73 (80%)

0.134†

2.90 (0.82-10.19)

9 (21%) 14 (23%)

34 (79%) 47 (77%)

0.807*

0.89 (0.35-2.29)

10 (23%) 13 (22%)

34 (77%) 47 (78%)

0.898*

1.89 (0.70-4.10)

8 (21%) 15 (23%)

30 (79%) 51 (77%)

0.843*

0.91 (0.34-2.39)

20 (23%) 2 (13%)

68 (77%) 13 (87%)

0.516†

1.90 (0.40-9.20)

19 (22%) 4 (21%)

66 (78%) 15 (79%)

1.000†

1.08 (0.32-3.64)

8 (57%) 15 (17%)

6 (43%) 74 (83%)

0.002†

6.58 (1.99-21.73)

6 (33%) 17 (20%)

12 (67%) 69 (80%)

0.221†

2.03 (0.67-6.19)

3 (75%) 20 (20%)

1 (25%) 80 (80%)

0.033†

12.00 (1.18-121.57)

3 (50%) 20 (20%)

3 (50%) 78 (80%)

0.120†

3.90 (0.73-20.80)

OR – Odds ratio; CI – Confidence Intervals; ICU – Intensive Care Unit; BMI – Body Mass Index; EF – Ejection Fraction; OI-SC – oxygenation index leaving surgical center; OI-UCI – oxygenation index ; MV - Mechanical ventilation; PNMV – pneumonia associated with MV; (*) Chisquare; (†) Fisher’s exact test. Note: the situations in groups "cases" with 22 and "controls" with 80 individuals indicate lack of data on one of the individuals

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Table 2. Comparative analysis of the median values (extremes) of continuous predictor variables presented by patients according to duration of prolonged ICU stay (n = 104). ICU length of stay (days) P >3 Variables ≤3 0.53 BMI (kg/m2) 26.0 (17.8 - 35.0) 27.8 (18.0 - 41.0) 0.35 56.5 (26.0 - 76.0) EF (%) 64.0 (31.0 - 79.0) 0.81 110.0 (55.0 - 200.0) On-pump (min) 110.0 (45.0 - 200.0) 0.57 100.0 (40 - 150) Time of anoxia (min) 90.0 (0.0 - 170.0) 0.66 200.5 (98.0 - 342.0) OI-SC 195.0 (86.8 - 574.0) 0.45 OI-UCI 229.0 (101.0 - 500.0) 196.0 (66.0 - 360.0) 0.001 18.0 (4.0 - 598.0) MV (hours) 10.0 (3.0 - 47.0) ICU – Intensive Care Unit; BMI – Body Mass Index; EF – Ejection Fraction; OI-SC – oxygenation index leaving surgical center; OI-UCI – oxygenation index ; MV - Mechanical ventilation. Statistics analyses: Mann-Whitney Test

Table 3. Multivariate logistic regression of factors associated with P ≤ 0.20 for prolonged length of stay in the ICU (n = 104). Variables Preoperative Female gender EF < 50% Diabetes Hypertension Smoke Postoperative MV > 24 h PNMV Renal Failure

1st Block OR (95% CI)

0.027

3.17 (1.34-8.85)

0.042

4.07 (1.06-15.69)

2nd Block OR (95% CI)

3rd Block OR (95% CI)

0.104

5.93 (0.69-50.81)

0.006

6.10 (1.70-21.86)

1st Block - Analysis of the preoperative variables; 2nd Block – Analysis of the pre and intraoperative variables; 3rd Block – Analysis of the pre-. intra- and postoperative variables; OR – Odds ratio; CI – Confidence Intervals; ICU – Intensive Care Unit; EF – Ejection Fraction; MV - Mechanical ventilation; PNMV – pneumonia associated with MV

Table 3 shows the results of multivariate analysis in the ICU. There were no intraoperative variables that met the criteria to join blocks 2 and 3 of multivariate analysis. The predictors found in the bivariate analysis were diabetes, MV >24h and PNMV (Table 1). In multivariate analysis, diabetes and smoking were predictors of preoperative period for prolonged ICU. Considering all operative periods altogether, MV >24 hours was an observed predictor. The HosmerLemeshow test was performed for block one (x2=0.013, P=0.910) and block 3 (x2=0.012, P=0.912), showing itself to be a suitable model for analysis. Admission to the postoperative ward Table 4 presents the frequencies and bivariate analysis of risk factors associated with hospitalization in the ward (>7 days).

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Table 5 shows the comparison between median (extremes) of continuous predictor variables presented by patients who stayed less and for more than 7 days in the postoperative ward. As continuous variables MV time and LVEF also had their corresponding categorical significant differences (Table 5), only the latter was considered in the logistic regression analysis. Predictor variables present in the final model in each block in the ward are presented in Table 6. In the case of this outcome, LVEF <50% was the risk factor of the preoperative period. Combining with the intraoperative period, diabetes was the only predictor. Considering the three operative periods, only the presence of infection was a risk factor for prolonged hospitalization in the ward. The Hosmer and Lemeshow presented for block 1, x2=0.000 and P=0.883, for block 2, x2=0.583 and P=0.965, and for block 3, x2=0.955 and P=0.917, demonstrating the adequacy of the model used.

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Table 4. Absolute frequencies (relative) and bivariate analysis of risk factors associated with staying in the ward for more and less than 7 days (n = 104). Variables Ward > 7 days Ward ≤ 7 days OR P n = 29 n = 75 (95% CI) Preoperative Gender Woman 11 (34%) 21 (66%) 1.57 (0.64-3.88) 0.325* Man 18 (25%) 54 (75%) Age (years) > 60 17 (34%) 33 (66%) 1.80 (0.76-4.30) 0.181* < 60 12 (22%) 42 (88%) BMI (kg/m2) <18.5 ou ≥ 24.9 5 (21%) 19 (79%) 1.63 (0.54-4.87) 0.380* 18.5-24.9 24 (30%) 56 (70%) Renal failure Yes 3 (60%) 2 (40%) 4.21 (0.67-26.63) 0.131† No 26 (26%) 73 (74%) EF (%) < 50 11 (46%) 13 (54%) 3.09 (1.17-8.11) 0.020* ≥ 50 17 (22%) 62 (88%) Diabetes Yes 16 (38%) 26 (62%) 2.32 (0.97-5.55) 0.056* No 13 (21%) 49 (79%) Hypertension Yes 25 (29%) 62 (71%) 1.31 (0.39-4.41) 0.774† No 4 (24%) 13 (76%) Smoke Yes 3 (25%) 9 (75%) 0.83 (0.21-3.32) 1.000 † No 26 (29%) 65 (71%) Former smoker Yes 10 (23%) 33 (77%) 0.67 (0.28-1.63) 0.377* No 19 (31%) 42 (69%) Intraoperative On-pump time (min) ≥ 120’ 16 (36%) 28 (64%) 2.07 (0.87-4.92) 0.099* < 120’ 13 (22%) 47 (78%) Number of bypasses ≥4 13 (34%) 25 (66%) 1.63 (0.68-3.90) 0.275* <4 16 (24%) 50 (76%) OI-SC ≤ 300 24 (27%) 64 (73%) 0.94 (0.27-3.27) 1.000† >300 4 (29%) 10 (71%) Postoperative OI-UTI ≤ 300 24 (28%) 61 (72%) 1.10 (0.36-3.39) 0.866* > 300 5 (26%) 14 (74%) MV (h) > 24 8 (57%) 6 (43%) 4.32 (1.35-13.86) 0.021† ≤ 24 21 (24%) 68 (76%) Infection Yes 11 (61%) 7 (39%) 5.94 (2.01-17.49) 0.001* No 18 (19%) 68 (81%) PNMV Yes 3 (75%) 1 (15%) 8.54 (0.85-85.75) 0.065† No 26 (26%) 74 (74%) Renal failure Yes 4 (67%) 2 (33%) 5.84 (1.01-33.85) 0.050† No 25 (26%) 73 (74%) OR – Odds ratio; CI – Confidence Intervals; ICU – Intensive Care Unit; BMI – Body Mass Index; EF – Ejection Fraction; OI-SC – oxygenation index leaving surgical center; OI-UCI – oxygenation index ; MV - Mechanical ventilation; PNMV – pneumonia associated with MV; (*) Chisquare; (†) Fisher’s exact test. Note: the situations in groups "cases" with 22 and "controls" with 80 individuals indicate lack of data in one of the individuals

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Table 5. Comparative analysis of the median values (extremes) of continuous predictor variables presented by the patients according to the time spent on the ward (n = 104). Length of stay on the ward (days) P* Variables ≤7 >7 0.33 Age (years) 62.0 (47.0 - 82.0) 59.0 (37.0 - 79.0) 0.14 BMI (kg/m2) 26.0 (17.8 - 33.0) 27.8 (18.0 - 41.0) 0.05 EF (%) 64.0 (31.0 - 79.0) 56.5 (28.0 - 76.0) 0.21 On-pump (min) 105.0 (45.0 - 200.0) 120.0 (55.0 - 200.0) 0.17 Period of anoxia (min) 90.0 (0.0 - 152.0) 100.0 (40.0 - 170.0) 0.22 OI-SC 205.0 (86.8 - 406.0) 180.5 (101.0 - 574.0) 0.11 OI-ICU 231.0 (86.8 - 442.0) 185.0 (101.0 - 500.0) 0.004 MV (hours) 10.0 (3.0 - 47.0) 17.0 (4.0 - 598.0) BMI – Body Mass Index; EF – Ejection Fraction; OI-SC – oxygenation index leaving surgical center; OI-UCI – oxygenation index; MV - Mechanical ventilation. Statistical analysis: Mann-Whitney Test

Table 6. Multivariate logistic regression of factors associated with P ≤ 0.20 for prolonged length of stay in the ward (n = 104). Variables Preoperative Age > 60 years Renal faliure EF < 50 % Diabetes Intraoperative On-pump > 120 min Postoperative MV > 24 h Infection PNMV Renal faliure

1st Block OR (95% CI)

0.022

3.09 (1.18-8.11)

2nd Block OR (95% CI)

0.080 0.040 0.062

2.46 (0.90-6.73) 2.81 (1.05-7.53) 2.59 (0.95-7.01)

3rd Block OR (95% CI)

0.101

2.24 (0.86-5.84)

0.010

4.54 (1.45-14.24)

0.055

6.39(0.96-42.39)

1st Block – Analysis of the preoperative variables; 2nd Block – Analysis of the pre and intraoperative variables; 3rd Block – Analysis of the pre-. intra- and postoperative variables; OR – Odds ratio; CI – Confidence Intervals; ICU – Intensive Care Unit; EF – Ejection Fraction; MV - Mechanical ventilation; PNMV – pneumonia associated with MV

DISCUSSION The focus of this study was to characterize the clinical and surgical risk factors associated with prolonged hospital stay after surgery for isolated CABG with cardiopulmonary bypass in a specialized tertiary institution, reference in the region of the study. Preliminarily, the findings should be interpreted considering that different experimental designs have been employed in the literature, as well as the lack of uniformity of key issues such as the characteristics of the samples and the cutoffs used to categorize the variables. Moreover, there are few studies in Brazil on risk factors for prolonged ICU outcomes and ward after CABG. Another important issue is that some studies include, in the same sample, patients undergoing other cardiac surgery associated with CABG [7,8,15]. The heterogeneity of the samples in the use of CPB [6,9] and diversity as the cutoff for prolonged hospitalization, rangesfrom 2 to 10 days in the

ICU [7,9] and 7-14 days of the total time in the postoperative period [13,16]. In this context our findings acquire special importance, since the sample was homogeneous as to the type of surgery, ie, exclusively CABG, as well as the fact that all have undergone CPB, aspects of probable impact on recovery time after surgery. About cutoff for prolonged hospitalization, established by the 70th percentile of the sample, similar to other studies [8,14,16], we should consider that some authors justify a clinical arbitrary choice [10,17]. Bucerius et al. [11] justified that these times of hospitalization included almost all patients with postoperative complications able to prolong the intensive treatment. Christakis et al. [14] that defined time >3 days in the ICU showed that even two days could possibly be considered as prolonged time. Among the preoperative variables, diabetes was presented as predictor of prolonged ICU, increasing by 3.2 times the odds of this outcome. Diabetes also shown to be a predictor

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for prolonged time in the ward, when combined with other preoperative and intraoperative factors as CPB >120 minutes, increasing by 2.81 times the chance of prolonged stay. These observations support the fact that diabetes per se, is a risk factor for coronary heart disease [1,18] and its more severe degree [19]. Furthermore, diabetes is associated with a greater number of surgical complications such as perioperative myocardial infarction [20], prolonged MV [20], infection [18] and cerebrovascular accidents [18], which prolongs the ICU. Also, the use of CPB worsens glycemic control, may increase the frequency of these complications [20]. Thus, the combination of diabetes with some of these variables can justify its expression as a risk factor. Our observations related to diabetes were similar to other studies that have shown a higher proportion of diabetics in the group with prolonged hospitalization [9,16,18,21], and that this disorder, itself, is a risk factor for prolonged hospitalization [11,13]. However, other studies found no association between diabetes and risk for prolonged hospitalization [6,7,16]. LVEF <50% constituted a pre-operative risk factor for prolonged stay in the ward, increasing by 3.04 times the odds for this outcome. Regarding the ICU, it is possible that the LVEF was not a risk factor in view of the cutoff point adopted and possible interaction with other variables, such as the MV [11]. The association between lower LVEF and longer hospitalization was also observed by Hein et al. [10]. Other authors [9,16] observed this association when the LVEF was <50% or even lower, between 30 and 40% [8,11]. In the group, smoking increased by 4.07 times the chance of prolonged hospitalization in the ICU. Christakis et al. [14] also observed that smoking was a predictor for pre-operative hospital stay >3 days in the ICU, with OR=2.0. Others did not observe this association to stay >10 days in the ICU and >7 days total [13]. In the study of Al-Sarraf et al. [22] smoking was associated with higher incidence of pulmonary infections, atelectasis, and MV >48 hours and stay >3 days in the ICU, as this study. These data suggest that smoking has not manifested as a risk factor when all factors for prolonged ICU stay are jointly considered due to its effect on the time of the MV, which was a predictor for this outcome. As for MV, its use for more than 24 hours was found to be a risk factor for prolonged ICU stay, as observed in other studies [9,13,21]. However, the MV is correlated with other factors associated with prolonged hospital. As pointed out by Doering et al. [23], some preoperative factors may influence postoperative factors also correlated with prolonged length of stay in the ICU. Thus, correlation between prolonged MV and higher age [12], females [12], diabetes [24], hypertension [24], LVEF <30% [24], chronic RF [24] and BMI <20 [25] have been observed. The prolonged MV also correlates with surgical factors such as aortic clamping [24], cardiopulmonary bypass time >120 minutes [25] and other postoperative factors such as RF [25]. Yende & Wunderink [26] reported that one

of the most common causes of VM >24 hours after CABG was hypoxemia, where oxygenation index <300 proved to be a risk factor for stay >5 days in the ICU, with an odds ratio of 9,1 [15]. The severe hypoxemia may still have their risk doubled when CPB is used, and the risk tripled when CPB >120 minutes [27]. Unlike the observations that associate CPB with systemic and respiratory complications, we did not observe this association, as other studies [15,17]. Other authors indicated that CPB [11] and aortic clamping [10] were risk factors that increased by 1.59 times the length of stay in the ICU when the CPB was greater than 120 minutes [11]. These findings, however, were not evident in our study, possibly because the sample was comprised only of patients undergoing CPB or possible interactions between different factors. With respect to infection nonspecifically, there was 4.7fold increase in the risk of prolonged stay in the ward when all factors were examined for this outcome. Some studies have evaluated for specific infections, such as infection presence of scar tissue, which Weintraub et al. [16] reported a relative risk of 7.9 in the univariate analysis, to be held 10 days of hospitalization. Lazar et al. [13] observed that infection scar was more prevalent in the group with length of stay >7 days total, as well as a risk factor for the outcome. It was also observed that renal impairment was a risk factor for prolonged hospitalization in the ward when installed in the postoperative period, as was to be expected. Wong et al. [12] also observed a postoperative IR an odds ratio of risk equal to 17.45 in univariate analysis and equal to 18.9 in the multivariate one. Other authors also indicated the RF as a risk factor for prolonged ICU [28], and others only when it was an existing condition in the preoperative period [8,11,12]. Differences in values of RF risk indicators between different studies may be associated with the diagnosis itself. Among these studies, Lazar et al. [13] had used the same criterion we used in this study (creatinine >1.5 mg/dl). Another finding of note was that older individuals were more likely not to prolonged stay in the ICU or in the ward, compared to younger ones. In most other studies, age was associated with longer hospital stays, with odds ratios ranging between 1.02 and 2.59. Some authors, considering the cutoff at the age of 60 years, as in our study, observed a correlation of this age with time greater than 48 hours in the ICU [6,8,10]. Other authors observed the same correlation when they adopted 70 years [10] or 80 years as the cutoff [11]. Bashour et al. [7] observed that for every 10 year increase in age, the length of stay increased by 1.9 times. The association of older age with prolonged hospitalization may be due to the fact that this age group have a higher rate of preoperative co-morbidities as hypertension, diabetes and chronic obstructive pulmonary disease, and the severity of the disease [10,29]. Such as age, other factors were not associated with length of stay or when association was observed in the bivariate

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analysis, this was not maintained in multivariate analysis. This may have occurred due to the nature of the non-associative factor, the possible interaction between the variables, the chosen cutoff or the number of individuals evaluated. One such factor was hypertension, for which Bashour et al. [7] also found no association with hospitalization time, unlike other studies [9,16]. Another factor was the female gender that, unlike our observations, was identified as a risk factor with an odds ratio equal to 1.93 [12] and relative risk of 2.6 [11]. Regarding the number of grafts, unlike our study, others have observed a correlation of this factor with prolonged ICU, using a cutoff above or equal to 2 [11] or above 3 grafts [14]. The PNMV was found to be a factor associated with longer ICU stay, only in the bivariate analysis (OR=12.0), which was also observed by Wong et al. [12] for time > 48 hours in the ICU, with an odds ratio equal to 75.6. Regarding BMI, other authors [10] did not identify the influence of this factor in the length of stay in ICU. However, in the study by Van Venrooij et al. [30] BMI ≤ 21 kg/m2 was identified as a risk factor for hospitalization > 48 hours in the ICU and BMI ≤ 23.5 kg/m2 for time >7 days after CABG indicating that parallel to the known association between overweight and morbidity and mortality, decreased weight and/or weight reduction in the preoperative phase may be indicators of increased risk for prolonged hospitalization [30]. Possible limitations in our study can be identified. It was a case-control data study using previous history recorded by different observers, which may increase the heterogeneity and reduce reliability. However, this possibility was mitigated since all observations derived from examinations, diagnoses and clinical information recorded in records of an institution of education and research, in which the data are confronted by several members of the clinical staff. With respect to the control group, the possible restrictions by differences in relation to the group of cases were obviated considering that the risk factors were analyzed for outcomes according to length of stay. This criterion also avoided the probability of erroneous inclusion of patients in the groups. Another relative limitation was the sample size that was small in comparison with similar studies and relatively lower than desired for the number of predictors that entered the final model of logistic regression [31]. This limitation, however, does not invalidate the results, which showed, undoubtedly, from the standpoint of statistical significance, that some factors were predictors of outcomes, which does not mean that other predictors could not be identified with increasing size sample. Furthermore, the use of Hosmer and Lemeshow indicated the adequacy of the model used to analyze the data. Some aspects of the study obviate or mitigate the limitations of sample size: 1) the relationship between these individuals and independent predictor variables indicates that all were present in each individual in varying proportions, which mitigates the

effects of sample size smaller than the usually recommended, although not override it. 2) our study was limited to patients undergoing isolated CABG with cardiopulmonary bypass in a given period of time (one year) in a single referral center, privileging the homogeneity of the sample against a larger number of individuals. 3) Another aspect of reliability of the results of the logistic model is obtained with the potential reproducibility of data subjects for further studies [32]. In particular, our model presents reliable as it can predict prolonged periods of stay in the ICU and in the ward for further analysis than presently done, considering that the predictor variables included are those mainly involved in these outcomes. Moreover, for each predictor variable, the significance of the odds ratio was high and the confidence intervals showed up distinctly narrow.

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CONCLUSIONS The bivariate and multivariate analyzes of the relationships between risk factors in the pre-, intra- and postoperative period and prolonged ICU stay after coronary artery bypass grafting with cardiopulmonary bypass, suggest that diabetes and smoking were risk factors predictors of the pre-operative period and mechanical ventilation the only predictor for the postoperative outcome. For the prolonged length of stay in the ward the following predictors were identified: LVEF <50% in the preoperative period, diabetes, in the period immediately after surgery, and nonspecific infection postoperatively. These findings point to the necessary evaluation of strategies aimed at reducing hospitalization time and suggests special attention to certain clinical and/or surgical conditions that may, when prevented or better controlled, reduce the length of hospital stay for patients undergoing coronary artery bypass grafting. Authors' roles & responsibilities EKO ALRT PLT LFJJ LGGP

Conception of the research proposal, data collection, statistical analysis and manuscript writing Contribution in the protocol design, data collection, manuscript revision Protocol design definition, statistical analysis and final review of the manuscript Conceptual revision of the manuscript, statistical analysis advisor, clinical-cardiologic interpretations and final manuscript revision Protocol design definition, statistical analysis, writing of the final version of the manuscript, research project advisor

ACKNOWLEDGEMENTS To Prof. Pedro Rodrigues Curi Hallal, from the School of Physical Education - Federal University of Pelotas, for helping in statistical analysis, and the Physiotherapist Louise Paim by her extensive contribution in data collection.

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Santos NP, etORIGINAL al. - Factors associated ARTICLEto hypoxemia in patients undergoing coronary artery bypass grafting

Factors associated to hypoxemia in patients undergoing coronary artery bypass grafting Fatores associados à ocorrência de hipoxemia em pacientes submetidos à revascularização miocárdica

Natália Pereira dos Santos1, PT; Rodrigo Martins Mitsunaga1; Daniel Lago Borges1, PT, MsC; Marina de Albuquerque Gonçalves Costa1, PT; Thiago Eduardo Pereira Baldez1, PT; Ilka Mendes Lima1, PT; Karol Cristina Fonseca Moura1, PT; Josimary Lima da Silva Lula2

DOI: 10.5935/1678-9741.20130056

RBCCV 44205-1482

Abstract Introduction: Hypoxemia is a frequent pulmonary complication in the postoperative coronary artery bypass graft. Detection of factors associated with their occurrence may indicate patients at risk for this complication, which allows tracing specific therapeutic and consequently reduce morbidity and mortality. Objective: To identify related factors to hypoxemia occurrence in immediate coronary artery bypass graft postoperative. Methods: In this retrospective cohort study, we studied 100 patients submitted to elective om-pump artery bypass graft , between April 2010 and December 2011, at a reference university hospital for cardiac surgery in the state of Maranhão. It was considered hypoxemia gas exchange ratio less than or equal to 300 mmHg. Associated variables with perioperative hypoxemia were defined by the Student T test, G or Mann-Whitney tests, Chi-square, or Fisher’s exact test and multiple linear regression. Results: Among studied variables, high body mass index (P=0.036) and smoking (P=0.024) were significantly associated with hypoxemia in the immediate coronary artery bypass graft postoperative. Hypoxemia incidence in this period was 55% and

did not affects mechanical ventilation duration and Intensive Care Unit lengh of stay. Conclusion: In this sample, body mass index and smoking were associated to hypoxemia. These data reinforce the importance of clinical assessment to identify patients at risk for this complication, considering its high incidence in immediate postoperative period.

Universidade Federal do Maranhão, Hospital Universitário, São Luís, MA, Brazil. 2 Hospital São Domingos, São Luís, MA, Brazil.

Correspondence address: Daniel Lago Borges Rua Barão de Itapary, 227 – Centro – São Luís, MA, Brazil Zip code: 65020-070 E-mail: dlagofisio83@hotmail.com

Descriptors: Oxygen level. Postoperative period. Myocardial revascularization. Resumo Introdução: A hipoxemia é uma complicação pulmonar frequente no pós-operatório de revascularização miocárdica. A detecção de fatores associados a sua ocorrência pode indicar pacientes de risco para essa complicação, o que possibilita traçar terapêuticas específicas e, consequentemente, diminuir a morbimortalidade. Objetivo: Identificar fatores relacionados à ocorrência de hipoxemia no pós-operatório imediato de revascularização miocárdica. Métodos: Nesta coorte retrospectiva, foram estudados 100

Research carried out at Hospital Universitário Presidente Dutra, São Luís, MA, Brazil.

Article received on September 12th, 2012 Article accepted on June 10th, 2013

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versitário de referência para cirurgia cardíaca no estado do Maranhão. Considerou-se hipoxemia índice de troca gasosa menor ou igual a 300 mmHg. A associação das variáveis perioperatórias com a ocorrência de hipoxemia foi definida por meio dos testes t de Student ou Mann Whitney, Qui-quadrado, teste G, ou Exato de Fisher, além de regressão linear múltipla. Resultados: Dentre as variáveis estudadas, o índice de massa corpórea elevado (P=0,036) e o tabagismo (P=0,024) apresentaram associação estatisticamente significante com a ocorrência de hipoxemia no pós-operatório imediato de revascularização miocárdica. A incidência de hipoxemia no pós-operatório imediato foi 55%. A ocorrência de hipoxemia não interferiu nos tempos de ventilação mecânica e de estadia na Unidade de Terapia Intensiva. Conclusão: Nesta amostra, houve associação entre o índice de massa corpórea e o tabagismo com a ocorrência de hipoxemia. Esses dados reforçam a importância da avaliação clínica para identificação do paciente de risco para ocorrência dessa complicação, já que esta apresenta elevada incidência no pós-operatório imediato.

Abbreviations, acronyms & symbols AMI Acute myocardial infarction ARF Acute renal failure BMI Body mass index CABG Coronary artery bypass graft CAD Coronary atherosclerotic disease COPD Chronic obstructive pulmonary disease CPB Cardiopulmonary bypass CTA Previous angioplasty DLP Dyslipidemia DM Diabetes mellitus FiO2 Inspired oxygen fraction ICU Intensive care unit IPO Immediate postoperative LITA Left internal thoracic artery LV Left ventricular PaO2 Pressure of oxygen in the arterial blood PEEP Positive end-expiratory pressure RR Respiratory rate VT Volume tidal WHO World Health Organization

pacientes que se submeteram à cirurgia eletiva de revascularização miocárdica com uso de circulação extracorpórea, no período de abril de 2010 a dezembro de 2011, no Hospital Uni-

Descritores: Nível de oxigênio. Período pós-operatório. Revascularização miocárdica.

INTRODUCTION

According to a recent study [7], predictor factors detection may indicate patients at high risk for postoperative hypoxemia that demand mechanical ventilation strategies, in order to prevent and treat pulmonary collapse during intra-operatory period, to minimize hypoxemia impact on mechanical ventilation duration, to reduce mobidity and mortality related to cardiac intervention, to reduce length of stay at Intensive Care Unit (ICU), and hospital costs. This study is designed to analyze factors related to hypoxemia in a specific population of patients undergoing CABG surgery, to determine its incidence in immediate post-operative period, and to evaluate if hypoxemia interfered on mechanical ventilation duration and lengh of stay in ICU.

Coronary artery bypass grafting (CABG) surgery, despite all the advances in clinical treatment and percutaneous interventions, is still used in coronary heart disease treatment [1]. Pulmonary complications in cardiac surgery postoperative period are very frequent and represent significant morbidity and mortality cause [2]. Hypoxemia is one of the main causes of pulmonary complications characterized by decrease of arterial oxygen partial pressure (PaO 2) [3,4]. Measuring severity of the pulmonary injury in mechanically ventilated patients is performed by PaO2 and inspired oxygen fraction (FiO2) ratio [5]. Diverse mechanisms have been accounted for its development on cardiac surgery postoperative, especially atelectasis, shunt increase, respiratory and thoracic mechanics alterations, capillary and pulmonary parenchyma changes secondary to the left ventricular (LV) dysfunction or pulmonary endothelium injury [3,6]. Elderly, obeses and patients with left ventricular dysfunction (ejection fraction of the left ventricle < 55%) and prolonged cardiopulmonary bypass (CPB) time (> 120 minutes) had higher risks to postoperative surgery hypoxemia [7]. Pulmonary chronicle diseases, diabetes and preoperative acute myocardial infarction are independent risk factors for hypoxemia after CABG [8].

METHODS It is a retrospective descriptive cohort study conducted in a reference university hospital for cardiac surgery in São Luis, MA, Brazil, after Research Ethics Committee approval (Protocol N° 0051/2012), as required by Resolution N° 196/96 of the National Health Council. Patients who underwent CABG between April 2010 and December 2011 and were admitted to the Cardio ICU in the referred hospital were included in research. Adult patients (> 18 years old) from both genders were included in the study, with no prior cardiac surgery,

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submitted to elective on-pump CABG not associated to other procedures and ventilated in assisted/controlled volume mode, with PEEP (positive end-expiratory pressure) 8 cmH20 and FiO2 40%. Missing data related to PaO2/FiO2 ratio, perioperative death and returning to operation room were exclusion criteria to this study. Data were collected from Physical Therapy Evaluation form – divided in pre, intra and postoperative periods, filled with information from medical records – and registered in a specifically form designed for this study. During study period, two hundred and fifty-five patients were admitted to Cardiovascular ICU after CABG (Figure 1). Among them, 100 patients fulfilled all criteria and general characteristics are described in Table 1.

Fig 1 - Patients admitted to the Cardiovascular Intensive Care Unit after coronary artery bypass graft

Preoperative data Preoperative variables were: age, considering as advanced age ≥ 60 years old; gender; nutritional status, determined by Body Mass Index (BMI) calculated by weight/height2 ratio, considered as eutrophic = 20 to 24.9 kg/m2, overweight = 25 to 29.9 kg/m2 and obese ≥ 30 kg/m2, established by the World Health Organization (WHO) [9]. Other studied variables were risk factors to coronary diseases registered in anesthesiologist assessment available in medical records: diabetes mellitus (DM), hypertension, dyslipidemia (DLP), smoking (also were considered former smokers) and associative diseases: chronic obstructive pulmonary disease (COPD), acute renal failure (ARF), acute myocardial infarction (AMI) and prior angioplasty. It was not possible to correlate left ventricular ejection fraction (left ventricular dysfunction evaluation) due lack of data, cause it is not a routine service to have an echocardiogram in all preoperative patients.

Table 1. Univariate analysis of preoperative variables. (n = 100). Variables Age (years) BMI (kg/m2) Gender (%) Female Male Hypertension Absent Present DM Absent Present Dyslipidemia Absent Present AMI Absent Present ARF Absent Present Smoking Absent Present COPD Absent Present Angioplasty Absent Present

Intraoperative data For CABG patients underwent general anesthesia, tracheal intubation, controlled mechanical ventilation, surgical access via median sternotomy and CPB, performed with graphs of the left internal thoracic artery (LITA) and/or saphenous vein and the placement of mediastinal and pleural drains. Intraoperative analyzed variables were numbers of graphs, LITA use, number of drains, surgery time, considering a prolonged intervention ≥ 210 minutes; pump time, considering prolonged when above 120 minutes; aortic clamping time, considering prolonged when above 90 minutes; and mechanical circulatory assistance use (intra-aortic balloon pump). Postoperative data After surgery, patients were admitted to the Cardiovascular ICU still under anesthesia. They were intubated and mechanically ventilated (Evita 2 Dura® - Dräger Medical, Lübeck, Germany) in assisted/controlled volume mode,

Hypoxemia No (n = 45) Yes (n = 55) 62,6 ± 7,3 61,1 ± 11,5 24,9 ± 3,4 27,2 ± 3,8 26,7 73,3

21,8 78,2

26,7 73,3

18,2 81,8

55,6 44,4

56,4 43.6

77,8 22,2

83,6 16,4

82,2 17,8

87,3 12,7

93,3 6,7

89,1 10,9

73,3 26,7

49,1 50,9

97,8 2,2

94,5 5,5

97,8 2,2

96,4 3,6

P 0,453a 0,002a 0,742b 0,437b 0,903b 0,626b 0,673b 0,354c 0,024b 0,388c 0,575c

Student’s T Test bChi-square; cFisher Exact test ; BMI – Body Mass Index; DM – Diabetes Mellitus; ARF – Acute Renal Failure; AMI – Acute Myocardial Infarct; COPD – Chronicle Obstructive Pulmonary Disease a

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according to Unit protocol [volume tidal (VT) 8 to 10 ml/kg; respiratory rate (RR) 12 to 16 bpm; inspitatory flow from 8 to 10 times minute volume (VT x RR); inspiratory time 1.0 second; FiO2: 40%; PEEP: 8 cmH2O]. Twenty minutes after admission, arterial blood was collected for a blood gas analysis (ABL 800 FLEX ® Radiometer, Bronshoj, Denmark), in which PaO2 was analyzed and, consequently, gas exchange ratio (PaO2/FiO2). Other postoperative variables studied were mechanical ventilation duration and lengh of stay in the ICU. According to 3rd Brazilian Consensus Conference on Mechanical Ventilation Consensus [5], normal PaO2/FiO2 ratio is above 300 mmHg; as gas exchange deterioration value equal or lower than 300 mmHg; and extreme severity of respiratory condition below 200 mmHg. Current Berlin definition [10] classifies hypoxemia according to its level: Mild Hypoxemia (PaO2/FiO2 ≤ 300 and > 200 mmHg), Moderate Hypoxemia (PaO2/FiO2 ≤ 200 and >100 mmHg) and Severe Hypoxemia (PaO2/FiO2 ≤100 mmHg). To determine the presence of gas exchange deterioration in researched subjects, it was considered hypoxemia a PaO2/FiO2 ratio ≤ 300, being classified according to Berlin definition [10].

20% obese. This variable presented association to hypoxemia in this population (P=0.002). Smoking was observed in 40% of patients. Among the patients who presented hypoxemia, 50.9% were smokers or former smokers. Mild level of COPD was prevalent in 4%. Hypertension prevailed in 78% of population and diabetes mellitus in 44%. Among comorbities, smoking presents statistically association (P=0.024) for hypoxemia occurence. Others variables were not statistically associated with development of hypoxemia in immediate postoperative period. The univariate analysis of hypoxemia occurrence and preoperative variable of the study group are presented in Table 1. Assessed intraoperative characteristics are shown in Table 2. Among studied patients, seven percent used only one graph, 40% two graphs and 53% three or more. Mean graphs number was 2.5±0.7, and LITA was used as graph in 91 patients. Remaining patients have received only venous graph. Average number of drains was 1.8±0.5. Twenty three percent used just one drain, seventy percent used two drains and 7% three drains. Mechanical circulatory assistance with intra-aortic balloon pump was used in only 3% of the subjects. None of these variables presented statistically association with hypoxemia in immediate postoperative period. Mean surgery time was 3 hours and 45 minutes which was considered prolonged. Average pump time was 82.9±29 minutes. In 92% of the patients, pump time was shorter than 120 minutes. Mean aortic clamp time was 59.1±22.7, and 93% less than 90 minutes. These variables did not have any association with hypoxemia during CABG immediate postoperative. For multiple regression, BMI and surgery time were considered. F value (regression) was significant (P=0.02), accepting the hypothesis that at least one of analyzed variables influenced hypoxemia occurence. Among partial regression coefficients, only BMI was statistically significant (t=-2.66, P=0.009). The median of time for interruption of ventilation device for the studied group lasted around 9 hours and 54 minutes and the ICU admission, two days. The presence of hypoxemia did not interfere with time of mechanical ventilation and ICU admission, as observed in Table 3.

Statistical analysis Quantitative variables are described as mean and standard deviation or median (minimum, maximum), according to data distribution. Qualitative variables are presented by frequency and percentage. To normality test of the quantitative variables, D’Agostino-Pearson’s test was used. To test the relation between normally distributed quantitative variables and severe hypoxia occurence, nonpaired Student’s t test was used. For quantitative variables of non-normal distribution, Mann-Whitney’s test was used. Association between categorical and outcome variables was done using Chi-square test or Fisher Exact test. Quantitative variables whose statistic univariate tests presented P<0.25 were selected to enter the multivaried analysis by a multiple linear regression. A 95%-confidence interval was set. To process and data analysis was used the software Bioestat version 5.3 (Instituto Mamirauá, Belém, Pará, Brazil).

Table 2. Univariate Analysis of the intra-operative variables (n = 100). Variables

RESULTS

Number of grafts LITA grafts (%) Yes No Number of drains Surgery time (min) Pump time (min) Aortic clamp time (min)

The incidence of hypoxemia, i.e., in the presence of PaO2/ FiO2 ≤300, in this study, was 55%. About gender, most patients were male (76%). Mean age was 61.8±9.8 years (33-84 years) and 57% of them were elderly (≥ 60 years). There was no association between hypoxemia and these variables. Mean BMI was 26.1±3.8 kg/m2. Sixty percent of the sample were dystrophic. Among patients with hypoxemia in immediate postoperative period, 50.9% were overweight and

Hypoxemia NO (n = 45) YES (n = 55) 2.5 ± 0.8 2.6 ± 0,7 6.7 93.3 1.8 ± 0.5 217.1 ± 48.1 81.4 ± 29.8 56.7 ± 23.2

10.9 89.1 1.8 ± 0.5 231.6 ± 46.7 84.1 ± 28.5 61 ± 22.2

P 0.537a 0.354b 0.934a 0.129a 0.649a 0.348a

Student’s T Test; b Fisher Exact Test; LITA – Left Internal Thoracic Artery a

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Table 3. Correlation between mechanical ventilation and permanence in the ICU, and hypoxemia time (N=100). Variables Hypoxemia NO (n = 45) YES (n = 55) P Mechanical ventilation duration (min) Median (Minimum; 596 (88; 3872) 565 (120; 5425) 0,961a Maximum)

Proposed mechanism to explain this result is obese patients’ abdominal wall, in general, being thicker due to adipose panicle, contributing to increasing abdominal pressure over diaphragm and collapsed parenchyma volume in caudal and dependent lung areas [7]. Another associated factor with hypoxemia occurrence in this study was smoking. Ambrozin et al. [14] analyzed some pulmonary function aspects after CABG related to preoperative risks and verified that half of the cases presented decreased gas exchange ratio, influenced by comorbidies such as pre-existing lung disease, respiratory symptoms and smoking. Smokers present higher respiratory complications risk during postoperative period, due not enough respiratory system integrity to maintain alveolar ventilation [15]. This data reinforces preoperative assessment importance to identify those patients [14]. According to Morsch et al. [16], damages in pulmonary function and respiratory muscle strength after CABG are associated to transoperative factors, such as sternotomy, CPB, and general anesthesia. CPB has been considered important cause of hypoxemia in immediate postoperative CABG [3,7]. Szeles et al. [7] showed that CPB was an associated factor to severe hypoxemia in univariate analysis. Hypoxemia ocurred in 37.9% of patients with pump time higher than 120 minutes; in 29.3% with pump time less than 120 minutes; and 20% in off-pump CABG. In our research we did not observe an association between hypoxemia and CPB. This result may be related to lower pump time (less than 120 minutes) in 92% of patients, with mean time 82.9 minutes. According to Nozawa et al. [17], is highly probable that inflammatory aggression due longer pump time causes higher interstitial alveolar injury and edema. However when Cox et al. [18] investigated effects of on and off-pump CABG on pulmonary function by an alveolar-arterial oxygen gradient in patients with adequate ventricular function and no pre-existing pulmonary disease, it was observed a similar level of pulmonary dysfunction in both groups. It suggests that pulmonary gas exchange deterioration associated with cardiac surgery is due to other factors, not only CPB. We highlight that in these patients, mean pump time was low (74.36 minutes), closer to our study time. Szeles et al. [7] also demonstrated high incidence of hypoxemia (54.2%), even considering gas exchange lower than 200 mmHg. Among these, 27.3% presented PaO2/FiO2 ratio lower to 150, demonstrating higher hypoxemia severity in this group of patients when compared to our research, in which no one presented this ratio lower than 150 mmHg. Some strategies to prevent hypoxemia have been used after cardio surgery, as alveolar recruitment with PEEP, showing gas exchange ratio improvement [19]. Almost half of patients needed some therapy to reverse hypoxemia such as alveolar recruitment, PEEP level elevation or oxygen therapy [20].

ICU lengh of stay (days) Median (Minimum; Maximum)

2 (2; 7)

0,503a

Mann Whitney; ICU - Intensive Care Unit

Mean PaO2 quantified after ICU admission was 117.7±35.3 mmHg; in no hypoxemia patients was 150.6±22.2 mmHg; and in patients with hypoxemia was 72.1±3.9 mmHg. Average PaO2/FiO2 ratio was 294.2±88.2, ranging 165.3 to 510 mmHg. When hypoxemia severity [10] was evaluated, 45% of 100 patients in the study had PaO2/FiO2 ratio classified as normal (> 300 mmHg). PaO2/FiO2 ratio greater than 200 mmHg and lower or equal to 300 mmHg (mild hypoxemia) was observed in 37% and 18% of them had moderate hypoxemia (100 mmHg<PaO2/FiO2<200 mmHg). None of the patients presented severe hypoxemia (PaO2/FiO2<100 mmHg). DISCUSSION Hypoxemia in CABG immediate postoperative is strictly related to risk factors associated to prior comorbidies and surgical procedure [11]. Among these comorbidities, advanced age, overweight, left ventricular dysfunction were associated to hypoxemia according to Szeles et al. [7], which analyzed risk factors to hypoxemia in CABG immediate postoperative in 481 patients with no relevant respiratory medical history. In other studies [3,7,12], age was also mentioned as a risk factor related to hypoxemia after CABG. For Szeles et al. [7], age was an independent risk factor for hypoxemia and each year after age 34 increased their risk in 0.32% [7]. In our study we did not observe a significant association between advanced age and hypoxemia. However, considering physiological aspects, pulmonary function deteriorates with aging and the primary modification that happens in healthy person lungs due to aging is a gradual elastic retraction loss, reducing expiratory flow and increasing ventilation-perfusion inefficiency [13]. Divergent outcome from previous studies may be related to cut-off point of advanced age in this research, equal or above 60 years. About weight, significant association was verified between high BMI and hypoxemia. This result is corroborated other studies in which obesity is described as a risk factor for hypoxemia [3,7].

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Laizo et al. [21] analyzed complications that increased ICU lengh of stay and found as cause those related to pulmonary function (COPD and smoking, pulmonary congestion, prolonged mechanical ventilation), besides infections, kidney failure, stroke and hemodynamic instability (as arterial hypotension, arrhythmia and AMI). Weiss et al. [3] pointed hypoxemia as responsible for increase mechanical ventilation duration, ICU lengh of stay and hospital cost in CABG postoperative patients. This association was not observed in our research. Perhaps this result is explained by transitory hypoxemia in the first few hours after ICU admission presented by a lot of patients, with no implication in those times, besides PEEP level applied in admission. Limitations of this study are related to its design, since retrospective studies may present selection and measurement biases. Regarding data collection from medical chart, with no direct patient’s evolution follow-up may also be characterized as a limitation factor. In some included patients, variables related to lifestyle such as smoking habit and intensity, preexisting diseases, and left ventricular function were only cited in a qualitative manner. While inevitable data fail, available variables were categorized in the best way possible.

REFERENCES 1. Piegas LS, Bittar OJNV, Haddad N. Cirurgia de revascularização miocárdica. Resultados do Sistema Único de Saúde. Arq Bras Cardiol. 2009;93(5):555-60. 2. Borghi-Silva A, Mendes RG, Costa FS, Di Lorenzo VA, Oliveira CR, Luzzi S. The influences of positive end expiratory pressure (PEEP) associated with physiotherapy intervention in phase I cardiac rehabilitation. Clinics (Sao Paulo). 2005;60(6):465-72. 3. Weiss YG, Merin G, Koganov E, Ribo A, Oppenheim-Eden A, Medalion B, et al. Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors and clinical significance. J Cardioth Vasc Anesth. 2000;14(5):506-13. 4. Scanlan CL, Wilkins RL, Stoller JK. Fundamentos da terapia respiratória de Egan. 7a ed. Barueri:Manole;2000. 5. Carvalho RRC, Toufen Júnior C, Franca AS. III Consenso de Ventilação Mecânica. Ventilação Mecânica: princípios, análise gráfica e modalidades ventilatórias. J Bras Pneumol. 2007;33(Suppl 2):S54-70. 6. Garutti I, Martinez G, Cruz P, Piñeiro P, Olmedilla L, la Gala F. The impact of lung recruitment on hemodynamics during onelung ventilation. J Cardiothorac Vasc Anesth. 2009;23(4):506-8.

CONCLUSION

7. Szeles TF, Yoshinaga EM, Alencar W, Brudniewski M, Ferreira FS, Auler JO, et al. Hypoxemia after myocardial revascularization: analysis of risk factors. Rev Bras Anestesiol. 2008;58(2):124-36.

In this sample, body mass index and smoking were associated to hypoxemia. These comorbities are easy to be observed during preoperative assessment. For these high risk patients, implementation of mechanical ventilation strategies such as higher PEEP and alveolar recruitment, aiming to prevent and treat pulmonary collapse should contribute to minimize hypoxemia incidence and morbid-mortality related to cardiac surgery. Therefore, there are many aspects to study, yet,searching for effective interventions able to improve the clinical outcomes for this group of patients.

8. Ji Q, Mei Y, Wang X, Feng J, Cai J, Sun Y, et al. Study on the risk factors of postoperative hypoxemia in patients undergoing coronary artery bypass grafting. Circ J. 2008;72(12):1975-80. 9. Organização Mundial da Saúde (OMS). Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity. Geneva: WHO;1998. 10. The ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526-33.

Author’s roles & responsibilities NPS RMM DLB MAGC TEPB IML KCFM JLSL

11. Guizilini S, Gomes WJ, Faresin SM, Bolzan DW, Alves FA, Catani R, et al. Avaliação da função pulmonar em pacientes submetidos à cirurgia de revascularização do miocárdio com e sem circulação extracorpórea. Rev Bras Cir Cardiovasc. 2005;20(3):310-6.

Study design, data collection and manuscript writing Study design and manuscript writing Study design and manuscript writing Data collection Data collection Data collection Data collection Statistical analysis and text revision

12. Canver CC, Chanda J. Intraoperative and postoperative risk factors for respiratory failure after coronary bypass. Ann Thorac Surg. 2003;75(3):853-7. 13. Beliveau MM, Multach M. Perioperative care for the elderly patient. Med Clin North Am. 2003;87(1):273-89. 14. Ambrozin ARP, Caetano AJM. Aspectos da função pulmonar após revascularização do miocárdio relacionados com risco pré-operatório. Rev Bras Cir Cardiovasc. 2005;20(4):408-15.

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15. Ferreira Júnior FH, Boas AGV, Gonnelli CA, Puig LB, Stolf N. Assistência ventilatória mecânica em pós-operatório de cirurgia cardíaca. An Paul Med Cir. 2003;130(1):22-30.

Effect of cardiopulmonary bypass on pulmonary gas exchange: a prospective randomized study. Ann Thorac Surg. 2000;69(1):140-5. 19. Auler JO Jr, Carmona MJ, Barbas CV, Saldiva PH, Malbouisson LM. The effects of positive end-expiratory pressure on respiratory system mechanics and hemodynamic in postoperative cardiac surgery patients. Braz J Med Biol Res. 2000;33(1):31-42.

16. Morsch KT, Leguisamo CP, Camargo MD, Coronel CC, Mattos W, Ortiz LDN, et al. Perfil ventilatório dos pacientes submetidos a cirurgia de revascularização do miocárdio. Rev Bras Cir Cardiovasc. 2009;24(2):180-7.

20. Vieira JE, Silva BAR, Garcia Júnior D. Padrões de ventilação em anestesia: estudo retrospectivo. Rev Bras Anestesiol. 2002;52(6):756-63.

17. Nozawa E, Kobayashi E, Matsumoto ME, Feltrim MI, Carmona MJ, Auler JJ. Assessment of factors that influence weaning from long-term mechanical ventilation after cardiac surgery. Arq Bras Cardiol. 2003;80(3):301-10.

21. Laizo A, Delgado FEF, Rocha GM. Complicações que aumentam o tempo de permanência na unidade de terapia intensiva na cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2010;25(2):166-71.

18. Cox CM, Ascione R, Cohen AM, Davies IM, Ryder IG, Angelini GD.

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Amaral FTV,ORIGINAL et al. - AdultARTICLE congenital heart disease: experience with the surgical approach

Adult congenital heart disease: experience with the surgical approach Cardiopatia congênita no adulto: experiência com a abordagem cirúrgica

Fernando Tadeu Vasconcelos Amaral1, MD, PhD; Alfredo José Rodrigues1, MD, PhD; Paulo Henrique Manso1, Md, PhD; André Schmidt1, MD, PhD; Maria Fernanda Kolachinski1, MD; Clovis Carbone1, MD, PhD; Ricardo Nilson Sgarbieri1, MD, PhD; Walter Vilela de Andrade Vicente1, MD, PhD

DOI: 10.5935/1678-9741.20130057

RBCCV 44205-1483

Abstract Objective: To report the institution experience with the surgical treatment of adults with congenital heart disease due to the increasing number of these patients and the need for a better discussion of the subject. Methods: Retrospective analysis describing demographic data, risk factors and results. Results: 191 patients between 16 and 74 years old were operated on. Primary correction was done in 171 cases, 93 (55%) for atrial septal defect repair. Among 20 (12%) reoperations, pulmonary valve replacement was done in six cases. The mean intensive care and hospital stay were 2.7 and 8.5 days respectively, significantly greater for the reoperated cases (P=0.001). The mean bypass and clamping times were 68.6 and 44.7 minutes respectively, greater for the reoperated cases (P<0.0001 and P=0.0003 respectively). Hospital mortality was 4.2% and male sex, functional class III-IV and older age at operation were predictive risk factors. Significant complications were more frequent in the reoperated cases (P<0.003), mainly atrial flutter and fibrillation. Among 183 patients discharged, 149 (82%) are being followed and atrial flutter and fibrillation are common. The mean functional class value improved significantly after operation (1.66 to 1.11; P<0.0001). The estimated survival was 96.2% in six years.

Conclusion: Heart surgery in adults with congenital heart disease can be accomplished with low mortality and functional class improvement. Immediate and late complications are frequent. Multicenter studies are important to better characterize this patient population in the country.

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Hospital das Clínicas, Ribeirão Preto, SP, Brazil. Work carried out at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP/USP), Ribeirão Preto, SP, Brazil.

Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP/USP) Av. Bandeirantes, 3900 – Ribeirão Preto, SP, Brazil Zip code: 14049-900 E-mail: ftamaral@cardiol.br

Descriptors: Heart defects, congenital. Adult. Cardiac surgical procedures. Resumo Objetivo: Relatar a experiência da instituição com o tratamento cirúrgico de adultos com cardiopatia congênita devido ao crescente aumento no número desses pacientes e consequentes necessidades de maior discussão do tema. Métodos: Análise retrospectiva dos pacientes operados, com análise de dados demográficos, fatores de risco e resultados. Resultados: Cento e noventa e um pacientes, com idade entre 16 e 74 anos, foram operados. Cirurgia primária foi realizada em 171 pacientes, 93 (55%) com comunicação interatrial. Dentre 20 (12%) reoperações, substituição de valva pulmonar ocorreu em seis casos. Os tempos médios de unidade de terapia intensiva e hospitalar foram 2,7 e 8,5 dias, respectivamente, maiores nas reoperações (P=0,001). Os tempos médios de cir-

Correspondence adress: Fernando Tadeu Vasconcelos Amaral

Article received on September 1st, 2012 Article accepted on March 7th, 2013

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(P<0,003), principalmente fibrilação e flutter atrial. Entre 183 pacientes com alta hospitalar, 149 (82%) foram seguidos e a fibrilação e flutter atrial foram bastante prevalentes. O valor médio da classe funcional mudou significativamente após a cirurgia (1,66 para 1,11; P<0,0001). A estimativa de sobrevida geral foi de 96,2% em seis anos. Conclusão: Cirurgia em adultos com cardiopatia congênita pode ser realizada com baixa mortalidade e melhora funcional na maioria dos pacientes. Complicações imediatas e tardias são frequentes. Estudos multicêntricos são importantes para melhor caracterização dessa população de indivíduos no país.

Abbreviations, acronyms & symbols ASD Atrial septal defect CLAMP Clamping CPB Cardiopulmonary bypass ECHO Echocardiogram NYHA New York Heart Association

culação extracorpórea e pinçamento aórtico foram 68,6 e 44,7 minutos, respectivamente, maiores nas reoperações (P<0,0001 e P=0,0003, respectivamente). Mortalidade hospitalar foi 4,2%, sem relação com reoperação. Sexo masculino, classe funcional III-IV e idade avançada foram fatores preditivos de risco. Complicações importantes foram mais frequentes nas reoperações

Descritores: Cardiopatias congênitas. Adulto. Procedimentos cirúrgicos cardíacos.

INTRODUCTION

city area (n=40, 20%) or in the region (n=133, 70%) while 17 (10%) were referred from other states. An Excel data base was created containing general information of the patients, possible preoperative risk factors such as diabetes, cyanosis, smoking, systemic hypertension, obesity and chronic lung disease, detailed information regarding the surgical procedure, hospital complications and follow up information. The preoperative data collected, using the information available in the patients notes were: diagnosis [echocardiogram (ECHO) and/or catheter], clinical function according to the New York Heart Association (NYHA) and left ventricular function assessed by ECHO or angiography and classified based on the ejection fraction value as good (>50%), reasonable (between 50% and 30%) and bad (<30%). Pulmonary hypertension was defined when the systolic pulmonary artery pressure was greater than 60 mmHg during ECHO or cardiac catheterization. The surgical informations noted were the type of procedure, the cardiopulmonary bypass (CPB) and clamping (CLAMP) time and also the intensive care and hospital length of stay. The hospital complications were classified as major (high risk) or minor (low risk). After hospital discharge, the informations noted were the length of follow up, functional class at the last outpatient visit and also the complications and comorbidities detected. The comorbidities diagnosed during the long term follow up were classified as major or minor according to the degree of clinical impairment at the assessment. The functional class was numerically transformed from I to IV to 1 to 4 [8]. Statistical analysis was performed using the GraphPad Instat (GraphPad Software, Inc) software. The non-parametric Mann Whitney test was used for comparison of the mean values. The Fisher exact test was used for univariate analysis when the following parameters were assessed: gender, age at operation, functional class, left ventricular function, pulmonary hypertension, arrhythmias, bypass and clamping time, systemic hypertension, cyanosis, plasmatic creatinin and smoking habit. Significant differences were considered when the P value was <0.05. A tendency to statistical significance was considered

The progressive improvement in the available therapeutic options for treating congenital heart diseases has allowed the great majority of these patients to be treated during pediatric age. The success of these interventions, most of them palliative, and the routine follow up assessment have been responsible for a new population of adolescents and adults [1] with residual cardiovascular lesions [2]. This group of patients, added to those with late diagnosed congenital heart disease or with late symptoms presentation might need an invasive treatment in a period when age related problems also require attention. The surgical treatment of congenital heart disease in the adult patient has peculiar characteristics. The great variety in diagnosis as well as the complications and residual lesions frequently found makes this therapeutic approach particularly challenging requiring adequate human and structural facilities in order that good results are achieved. The aim of this study was to review the experience with the surgical treatment offered to adults with congenital heart disease in a tertiary center situated in the São Paulo state where the pediatric invasive treatment for this type of disease has mainly developed during the last twenty years. Reports of global experiences with this type of patients in the country were not available until recently when a relevant experience was published [3]. However, results with specific groups of patients may be found [4-7]. METHODS A retrospective analysis of all patients 16 years and older submitted to a surgical procedure for treatment of a congenital heart defect at the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP/USP) was performed. The cases available for the study underwent surgery between 1st January 1970 to 1st April 2010. The great majority of the patients lived in the

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when the P value was situated between 0.05 and 0.10. The survival probability was assessed using the Kaplan-Meier method. Individual informed consent was not requested and the study was approved by the Ethical Committee of the institution.

Table 1. Preoperative data in 191 patients operated on for treatment of congenital heart disease number (%) Female sex Sinus rhythm Left ventricular function Good Reasonable Bad Pulmonary hypertension Cyanosis Systemic hypertension Smoking Diabetes Obesity CLD NYHA I II III IV

RESULTS One hundred and ninety one patients underwent surgery and the annual distribution of the procedures can be seen in Figure 1. One hundred and seventy-two (90%) patients were treated in the last eleven years. The mean age at operation was 34±14 years (16 to 74 years). One hundred and seventeen (61%) were female and seventy-four (39%) were male. The preoperative information can be seen in Table 1. In one hundred and seventy one (89%) patients a primary correction was done while twenty (11%) were re-operated. The diagnoses and number of procedures can be seen in Figures 2 and 3. The mean intensive care stay was 2.76±3.3 days (range 1 to 37 days). CPB was used in 171 (89%) patients and the mean time duration was 68.65±46 minutes (range 18 to 220 minutes). Procedures without CPB (11%) included relief of aortic coarctation (n=14), ductus ligation (n=5) and pulmonary valvotomy (n=1). Aortic clamping was employed in 166 patients and the mean time duration was 44.71±34 minutes (range 7 to 167 minutes).

117 (61%) 166 (97%) n=170 184 (96%) 7(4%) 0 12 (6%) 9 (5%) 63 (33%) 44 (25%) n=175 6 (3%) 16 (8%) 6 (3%) 80 (41%) 91 (48%) 19 (10.5%) 1 (0.5%)

CLD: chronic lung disease; NYHA: functional class according to the New York Heart Association

Immediate results Eight (4.2%) patients died during the 30 days after the procedure, all of them during the same admission. Mortality occurred in three patients with an atrial septal defect (ASD), two of them older than 60 years and one submitted to a simultaneous coronary bypass graft; in two patients submitted to a correction of an atrioventricular septal defect, one of them a complete form in a 63-year-old patient; one case of Fallot’s tetralogy repair; one patient submitted to a mechanical aortic valve replacement plus coronary artery bypass graft and one

Fig. 2 - Diagnosis and number of patients who underwent a primary correction ASD: atrial septal defect; CoAo: coarctation of the aorta; VSD: ventricular septal defect; SV ASD: sinus venosus atrial septal defect; Fallot: Fallot’s tetralogy; AVSD: atrioventricular septal defect; PDA: persistent ductus arteriosus; AOS: aortic stenosis; PS: pulmonary stenosis; Ebstein: Ebstein’s anomaly of the tricuspid valve; ALCAPA: anomalous origin of the left coronary artery from the pulmonary artery; Fontan: Fontan’s operation; Rastelli: Rastelli’s operation; CORONA: anomalous origin of the coronary artery from the wrong sinus of Valsalva

Fig. 1 - Anual number of operations in 191 adult patients operated on for congenital heart disease

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arrhythmias (n=14), mainly atrial flutter or fibrillation (n=9). Among these nine patients with atrial arrhythmias, six of them had been submitted to a secundum ASD closure (Table 2). In 20 reoperated patients, eight (40%) had 10 major and 3 minor complications. Among the 10 major complications, the most frequent was the acute renal failure (n=3) (Table 2). The major and minor complications were more frequent in the reoperated patients (n=8, 40%) than in the patients submitted to a primary repair (n=33, 19%) with a tendency for statistical significance (P<0.08). The major complications were more frequent in the reoperated cases (n=10, 50%) than in the patients submitted to a primary repair (n=30, 18%) (P<0.003). There was no mortality among the patients submitted to a re-operation albeit the duration of the CPB (P<0.0001) and CLAMP (P=0.0003) were significant longer and having a longer hospital length of staying (P=0.001) than the patients submitted to a primary repair. Regression results analysis for 30 day-mortality disclosed that male gender (P=0.006), older age at operation (P=0.004) and preoperative functional class III-IV (P=0.004) were considered risk factors for surgical mortality.

Fig. 3 - Diagnosis and number of patients who underwent a reoperation ARR: aortic root replacement; VSD: ventricular septal defect; ReCoAo: recoarctation of the aorta; MIT. P: mitral prosthesis; ROSS: Ross operation; TRIC. P: tricuspid prosthesis; ASD + MITRAL: closure of an atrial septal defect plus mitral prosthesis

case of Fontan operation. The causes of death were sepsis due to respiratory infection (n=3), low cardiac output (n=2), cardiac tamponade, sudden death and pulmonary edema, one case each. In 171 patients who had undergone a primary correction, 33 (19%) had 30 major and 12 minor complications. Among the 30 major complications, the more frequent were the

Table 2. Immediate postoperative complications in 191 adult patients operated on for treatment of congenital heart disease PRIMARY CORRECTION (n = 171) MAJOR Arrhythmias Atrial flutter Atrial fibrilation Complete AV block Junctional rhythm Ventricular taquicardia Reoperation for bleeding Pleural efusion Pericardium efusion Pneumotorax Hemotorax Chock Stroke Respiratory insuficiency Arterial right leg thrombosis

14 5 4 2 2 1 3 3 3 2 1 1 1 1 1

MINOR Systemic hypertension crisis Subcutaneous enphysema Recurrent laryngeal lesion Broncoaspiration Pneumonia Hipoglicemia Pericarditis Liver disease Subglotic stenosis Malnutrition

3 1 1 1 1 1 1 1 1 1

REOPERATIONS (n = 20) MAJOR Acute renal failure Sternotomy review Paraplegia Pleural efusion Pulmonary emboli Stroke Respiratory insuficiency Complete AV block

3 1 1 1 1 1 1 1

MINOR Infection Diabetes

2 1

AV: atrioventricular

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Late results Among the 183 patients discharged from hospital, two died suddenly (one with an ASD and the other a Rastelli operation in a case of congenitally corrected transposition) and another of non cardiac cause. Information regarding late follow up were available in 149 (82%) patients who had a mean follow up period of 5.4Âą6.1 years (range 4.4 to 6.4 years). One hundred and eleven (74%) of these patients were seen in the last three years. In 129 patients who underwent a primary correction, 18 (14%) had 11 major and 10 minor complications/morbidities detected during late follow up. Among the 11 major complications/morbidities, the arrhythmias (n=7) were the most frequent, and among them, atrial flutter or fibrillation (n=6). Among the six cases with atrial flutter or fibrillation, five had been submitted to a secundum ASD closure (Table 3). In the 20 patients who underwent a reoperation, 4 (20%) had two major and two minor complications/morbidities detected during late follow up (Table 3). There was no significant difference regarding the occurrence of complications between the patients submitted to a primary correction and those who were re-operated (P=0.515). After operation, a significant number of patients changed their functional class from II to I (41% to 90%) (P<0.0001). At the last outpatient visit, 134 (90%) were in NYHA class I, while 13 (9%) were in class II and 2 (1%) in class III (Figure 4). The numeric transformation of the functional class disclosed a significant difference (P<0.0001) between the mean values before (1.66) and after (1.11) the operation. The actuarial survival curve showed that 96.2% of the patients were alive within six years of follow up (Figure 5).

DISCUSSION Mainly in view of the surgical techniques improvement during the last 60 years [9], particularly verified in the neonatal treatment, a growing number of patients with congenital heart disease are reaching adulthood [10]. The great majority of these patients, however, can not be considered cured. Sequela and residual lesions are frequent [2] demanding special attention during a period of life when problems related to the individual activities and to the natural aging process might interfere with the lesion physiopathology [11,12]. An interesting and still not well discussed subject, especially in Brazil, is the surgical approach in adults with congenital heart disease, frequently necessary in those patients with late diagnosis and those in need of a reoperation. The data here presented are concerned

Fig. 4 - Functional class according to the NYHA in 149 patients followed in the long term

Table 3. Late postoperative complications and comorbidities diagnosed in 149 adult patients operated on for treatment of congenital heart disease and followed in the long term PRIMARY CORRECTION (n = 129) MAJOR Arrhythmias Atrial flutter Atrial fibrilation Supraventricular taquicardia Pericardial efusion Aortic recoarctation Cardiac failure Right ventricular disfunction

7 4 2 1 1 1 1 1

MINOR Systemic hypertension Chronic lung disease Keloide

8 1 1

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REOPERATIONS (n = 20) MAJOR Arrhythmias Atrial flutter Aortic regurgitation

1 1 1

MINOR Systemic hypertension

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reoperations [13] and also of very complex cases [19] based on the NYHA functional class. Albeit our patients with III and IV functional class corresponded to only 11% before operation, two of our early deaths occurred in patients with not complex forms of congenital heart disease, ASD and partial atrioventricular septal defect. Despite the relative benignity of the intervention in these types of defects, the possibility of complications has already been reported [20]. Another fact which certainly influences results is the number of operated patients. Our experience is relatively small when compared with other publications where the numbers varied from 438 to 2012 [3,13-15,19]. In the univariate analysis we found that male gender, older age at operation (47Âą17 years) and functional class III-IV were considered risk factors for death. Albeit the significant statistically difference found, we believe this information should be assessed with caution in view of the small number of deaths. Particularly regarding the age at operation, we found it difficult to establish a number above what the surgical risk should be considered high. Also, known risk factors as pulmonary hypertension [13] and increased CPB time [21,22] had only a tendency for statistical significance in our data. Postoperative complications occur frequently and can be multiple [13-15]. The prevalence in our material of 21% patients with major complications is similar to the experience reported by Vida et al. [14] where this number was 22%. However, it differs considerably from the results of an Italian multicentre study: 29% of 856 patients who had undergone surgery [15] and two factors could possibly explain this difference. Unlike this last investigation, we did not consider as complication the prolonged ventilatory time in the intensive care unit. Also, in a multicentre study, it is possible that the increased number of complications is contaminated by events originated from groups with small experience which participated in the study. It is interesting to note that the occurrence of complications was greater in the patients who underwent a reoperation (40%) than in those submitted to a primary correction (20%). However, the statistical analysis showed that this difference had only a tendency to significance (P<0.08). When we assess only the major complications, it is clear that they tend to occur more frequently in the reoperated patients (P<0.003). It should be remembered that the number of reoperated patients was small (n=20) with no early mortality despite the fact that they have required a prolonged time of CPB, CLAMP and intensive care stay. It is well known the fact that reoperations are more demanding and have a significant morbidity, albeit low mortality can be accomplished when the procedure is done in centers dedicated to adult congenital heart disease treatment [22]. As already reported [13-15], the arrhythmias are the most frequent complications and, among them, atrial flutter or fibrillation, which also occurred in our patients and were

Fig. 5 - Actuarial survival curve in 149 patients followed in the long term

to a tertiary institution dedicated to congenital heart disease treatment for the last 40 years. However, it should be noted that the complex forms of defects started being treated in the last 20 years, which gives a peculiar characteristic to our experience, with an important prevalence of mild and moderately complex lesions differing, in some respect, of the experience of pioneer institutions in the country [3]. Initially, attention should be drawn to the fact that 90% of the patients were treated during the last 11 years. Another interesting aspect is the high proportion of female patients (61%), certainly related to the great number of ASD, a common feature reported in other experiences [13-15]. It should also be emphasized that only 40 (20%) patients lived in the city area (population 600.000 inhabitants). This information is important when the number of patients in continuing follow up in a specific institution is discussed. Extrapolating recently published data [16], the estimated number of adults with congenital heart disease in the RibeirĂŁo Preto city is 1920 patients. In our recently published outpatient data [17] only 23% of 413 patients lived in the city, showing that the great majority of them were not followed in a specialized unity, a finding already reported [18]. Immediate results The 30-day mortality was 4.2% and numerically comparable with recent publications available where this number varies from 1.5% to 6.3% [13-15,19]. However, a detailed analysis of these experiences shows that comparison with our data is not adequate due to their high number of

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commonly associated to a secundum ASD closure. This type of complication deserves special attention, mainly due to the fact that it is the most common cause of hospital admission in adults with congenital heart disease [23].

(79%). The numeric transformation of the functional class has not been frequently used [8]. However, we believe it can be useful when a group of patients is assessed, since it reflects the occasional difficulty in classifying a specific patient in one or another functional class. The mean value difference was significant, which also allowed us to conclude that our patients were not so physiologically impaired. We believe this parameter should be continually evaluated in this group of patients, however, recent investigations have suggested that a more objective assessment be used for cardiovascular function analysis, like the ergoespirometry. The results of this test may disclose patients under higher cardiovascular risk for complications and death, indicating which of them should be more carefully followed up [25]. The survival probability according to the Kaplan-Meier method was 96.2% at six years, very similar to the numbers of Padalino et al. [15] (96% at five years) and Vida et al. [14] (97% at five years). Due to the great diagnostic variability usually found in groups of adult patients with congenital heart disease, an actuarial analysis based on groups of defects is difficult in our cases, which would be feasible with more patients. Despite the parameters above discussed have been widely employed for late results evaluation of patients followed in the long term, we share the opinion that the individual quality of life is an important aspect which should be considered in the outpatient assessment because it can give a more complete idea of the individual status [12,26]. Based on these pieces of information, we believe that the surgical treatment of adults with congenital heart disease can be accomplished with low mortality, depending on the severity of the disease. The immediate complications are frequent, particularly the arrhythmias. The long term follow up of these patients is crucial in order to know the results of the procedures. During this period, the residual lesions are frequent, specially the arrhythmias. Also, the occurrence of other morbidities is important and should be adequately addressed. Proper advice to the patient at discharge is mandatory, also to the physician in charge of the follow up [27]. Due to the excellent improvement in the invasive treatment of children with congenital heart disease a growing number of patients with complex lesions will reach adulthood. Consequently, the profile of these adult patients will change with more reoperations and percutaneous treatment being needed [28]. Considering the special characteristics of the material here presented, it should not be considered as the usual spectrum of patients to be found in centers with large experience in congenital heart disease treatment. Due to this regional characteristic, certainly present in other centers in the country, to the great diagnostic variability usually found and to the different surgical strategies employed in the treatment of these patients, we believe that multicenter studies are of extreme importance. This model of investigation [29], of crescent interest in the international literature will allow us

Late results Among 183 patients discharged, three of them died during follow up, one of a non cardiac cause and two probably due to a cardiovascular complication since the nature of the death was sudden. This low late mortality rate makes a risk factor analysis impossible. However, it is well known that arrhythmias, cyanosis, smoking and depressed left ventricular function are considered risk factors for late death in this group of patients [13]. The analysis of the late results, usually hard to be accomplished in our country, was possible in 149 (82%) patients and, despite better than the index reported by a multicenter European study (68%) [14], it is inferior to those registered in a multicenter Italian study (87%) [15] and in a Dutch study (89%) [13]. The mean follow up period of our patients was 5.2 Âą 6.1 years (median: four years, CI 95%: 4.41 â&#x20AC;&#x201C; 6.38 years) which characterize our follow up information as a medium term one. During the last three years 111 (74%) of these patients have routinely been seen at the outpatient clinic. This 26% of patients lost to follow up is worrisome, and, as already emphasized [14] a policy of active search of patients should be undertaken by any tertiary unit in order that the intervention results are known. Despite the incidence of complications and comorbities found during late follow up were more prevalent in the reoperated patients (20%) than in those submitted to a primary repair (14%) the difference had no statistical significance. It should be noted the important occurrence of arrhythmias in these patients (8/22) with significant prevalence of atrial flutter or fibrillation (six cases), frequently associated to a secundum ASD closure. Albeit the criteria for functional class classification recommended by the New York Heart Association is widely applied, recent studies have demonstrated that this method underestimates the real individual capacity [24]. However, it is generally used as a parameter of cardiovascular function and being particularly useful when a group of patients is assessed before and after an intervention. In the data here presented an analysis of the total number of patients was done aiming to have an idea of the general degree of improvement after operation. Obviously a detailed analysis by groups of patients is desirable, however difficult in our cases due to the small proportion of patients in some groups. Taking into account this information, a significant migration from class II before operation to class I after the procedure (41% to 90%) was noted, which is comparable to the experiences of Putman et al. [13] (80%), Vida et al. [14] (90%) and Padalino et al. [15]

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to know the profile of our patients, to verify the results of the procedures adopted and to discuss the efficacy of different therapies. Adults with congenital heart disease constitute a very special group of individuals, many of them survivors of several operations. The tendency is that the number of these patients will increase dramatically [30] and the institutions dedicated to this type of assistance should be ready to work efficiently. Due to the absolute absence of reports regarding this subject among us, comparison of our results becomes difficult. Despite the comparison of our data with those disclosed by a recent report [3] coming from a pioneer center in the country is possible in some aspects, they both differ fundamentally in terms of patient population, institutional characteristics, detailment of postoperative complications and information regarding follow-up. These differences, as we can see it, add to the informations we consider important regarding the management to these patients.

3. Caneo LF, Jatene MB, Riso AA, Tanamati C, Penha J, Moreira LF, et al. Avaliação do tratamento cirúrgico da cardiopatia congênita em pacientes com idade superior a 16 anos. Arq Bras Cardiol. 2012;98(5):390-7. 4. Mesquita SF, Snitcowsky R, Lopes AA. Estrutura e função ventricular direita como possíveis determinantes do resultado cirúrgico após 30 anos de correção de tetralogia de Fallot. Arq Bras Cardiol. 2003;81(5):453-7. 5. Jatene MB, Abuchaim DCS, Oliveira Jr JL, Riso A, Tanamati C, Miura N, et al. Resultados do tratamento cirúrgico da coarctação da aorta em adultos. Rev Bras Cir Cardiovasc. 2009;24(3):346-53. 6. Arruda Filho MB, Maia Jr H, Rayol S, Santos FA, Arruda APM, Gusmão CAB, et al. Anomalia de Ebstein em paciente adulto: valvuloplastia modificada para correção de insuficiência tricúspide. Rev Bras Cir Cardiovasc. 2002;17(2):132-6.

Study limitations The data here presented reveals the institution experience. The number of old patients with lost informations is probably very small and we believe it would hardly change the results. The great diagnostic diversity makes it difficult to assess the results by groups of patients. Some important parameters related to the immediate results like the intensive care length of mechanical ventilation were not studied but we believe that the information available reflect the usual outcome of these patients. The long term results analysis was improved through an active search of patients lost to follow up and should be considered when the results with other studies are compared.

7. Lisboa LAF, Abreu Filho CAC, Dallan LAO, Rochitte CE, Souza JM, Oliveira SA. Tratamento cirúrgico da coarctação do arco aórtico em adulto: avaliação clínica e angiográfica tardia da técnica extra-anatômica. Rev Bras Cir Cardiovasc. 2001;16(3):187-94. 8. Scherptong RW, Hazekamp MG, Mulder BJ, Wijers O, Swenne CA, van der Wall EE, et al. Follow-up after pulmonary valve replacement in adults with tetralogy of Fallot. J Am Col Cardiol. 2010;56(18):1486-92. 9. Garson A Jr, Allen HD, Gersony WM, Gillette PC, Hohn AR, Pinsky WW, et al. The cost of congenital heart disease in children and adults. A model for multicenter assessment of price and practice variation. Arch Pediatr Adolesc Med. 1994;148(10):1039-45.

Authors' roles & responsibilities FTVA AJR PHM AS MFK CC RNS WVAV

Research design, medical records review, data analysis and writing Satistical analysis and final writing Medical records review and writing Research design and final writing Medical records review and data organization Data organization, medical records review Medical records review and data analysis Research design, data analysis and final writing

10. Warnes CA. The adult with congenital heart disease: born to be bad? J Am Coll Cardiol. 2005;46(1):1-8. 11. Moons P, Van Deyk K, Dedroog D, Troost E, Budst W. Prevalence of cardiovascular risk factors in adults with congenital heart disease. Eur J Cardiovasc Prev Rehabil. 2006;13(4):612-6. 12. Moons P, Van Deyk K, De Bleser L, Marquet K, Raes E, De Geest S, et al. Quality of life and health status in adults with congenital heart disease: a direct comparison with healthy counterparts. Eur J Cardiovasc Prev Rehabil. 2006;13(3):407-13.

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13. Putman LM, van Gameren M, Meijboom FJ, de Jong PL, Roos-Hesselink JW, Witsenburg M, et al. Seventeen years of adult congenital heart surgery: a single center experience. Eur J Cardiothorc Surg. 2009;36(1):96-104.

1. Warnes CA, Liberthson R, Danielson GK, Dore A, Harris L, Hoffman JI, et al. Task force 1: the changing profile of congenital heart disease in the adult life. J Am Coll Cardiol. 2001;37(5):1170-5.

14. Vida VL, Berggren H, Brawn WJ, Daenen W, Di Carlo D, Di Donato R, et al. Risk of surgery for congenital heart disease in the adult: a multicenter European study. Ann Thorac Surg. 2007;83(1):161-8.

2. Perloff JK, Warnes CA. Challenges posed by adults with repaired congenital heart disease. Circulation. 2001;103(21):2637-43.

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15. Padalino MA, Speggiorin S, Rizzoli G, Crupi G, Vida VL, Bernabei M, et al. Midterm results of surgical intervention for congenital heart disease in adults: an Italian multicenter study. J Thorac Cardiovasc Surg. 2007;134(1):106-13.

heart disease undergoing cardiac reoperations. Ann Thorac Surg. 2009;88(4):1284-9. 23. Somerville J. Management of adults with congenital heart disease: an increasing problem. Annu Rev Med. 1997;48:283-93.

16. Marelli AJ, Therrien J, Mackie AS, Ionescu-Ittu R, Pilote L. Planning the specialized care of adult congenital heart disease patients: from numbers to guidelines; an epidemiologic approach. Am Heart J. 2009;157(1):1-8.

24. Diller GP, Dimopoulos K, Okonko D, Li W, Babu-Narayan SV, Broberg CS, et al. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation. 2005;112(6):828-35.

17. Amaral F, Manso PH, Granzotti JA, Vicente WVA, Schmidt A. Cardiopatia congênita no adulto. Perfil clínico ambulatorial no Hospital das Clínicas de Ribeirão Preto. Arq Bras Cardiol. 2010;94(6):707-13.

25. Dimopoulos K, Okonko DO, Diller GP, Broberg CS, Salukhe TV, Babu-Narayan SV, et al. Abnormal ventilatory response to exercise in adults with congenital heart disease relates to cyanosis and predicts survival. Circulation. 2006;113(24): 2796-802.

18. Moons P, Meijboom FJ, Baumgartner H, Trindade PT, Huyghe E, Kaemmerer H; ESC Working Group on Grown-up Congenital Heart Disease. Structure and activities of adult congenital heart disease programs in Europe. Eur Heart J. 2010;31(11):1305-10.

26. Bol Raap G, Meijboom FJ, Kappetein AP, Galema TW, Yap SC, Bogers AJ. Long-term follow-up and quality of life after closure of ventricular septal defect in adults. Eur J Cardiothoracic Surg. 2007;32(2):215-9.

19. Srinathan SK, Bonser RS, Sethia B, Thorne SA, Brawn WJ, Barron DJ. Changing practice of surgery in adult patients with congenital heart disease. Heart. 2004;91(2):207-12.

27. Gatzoulis MA. Adult congenital heart disease: education, education, education. Nat Clin Pract Cardiovas Med. 2006;3(1):2-3.

20. Évora PRB, Ribeiro PJF, Vicente WAV, Menardi AC, Rodrigues AJ, Reis CL, et al. Eventos catastróficos associados ao tratamento da comunicação interatrial tipo ostium secundum: razões para não se subestimar esse tipo de cardiopatia congênita. Rev Bras Cir Cardiovasc. 2004;19(4):391-8.

28. Monro J. The changing state of surgery for adult congenital heart disease. Heart. 2005;91(2):139-40. 29. Khairy P, Hosn JA, Broberg C, Cook S, Earing M, Gersony D, et al; Alliance for Adult Research in Congenital Cardiology (AARCC). Multicenter research in adult congenital heart disease. Int J Cardiol. 2008;129(2):155-9.

21. Dore A, Glancy DL, Stone S, Menashe VD, Somerville J. Cardiac surgery for grown-up congenital heart patients: survey of 307 consecutive operations from 1991 to 1994. Am J Cardiol. 1997;80(7):906-13.

30. Therrien J, Siu SC, McLaughlin PR, Liu PP, Williams WG, Webb GD. Pulmonary valve replacement in adults late after repair of tetralogy of Fallot: are we operating too late? J Am Coll Cardiol. 2000;36(5):1670-5.

22. Giamberti A, Chessa M, Abella R, Butera G, Carlucci C, Nuri H, et al. Morbidity and mortality risk factors in adults with congenital

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Borges DL, etORIGINAL al. - Effects ofARTICLE different PEEP levels on respiratory mechanics and oxygenation after coronary artery bypass grafting

Effects of different PEEP levels on respiratory mechanics and oxygenation after coronary artery bypass grafting Efeitos de diferentes níveis de PEEP na mecânica respiratória e oxigenação após revascularização do miocárdio

Daniel Lago Borges1, PT, MsC; Vinícius José da Silva Nina1, MD, PhD; Marina de Albuquerque Gonçalves Costa1, PT; Thiago Eduardo Pereira Baldez1, PT; Natália Pereira dos Santos1, PT; Ilka Mendes Lima1, PT; Eduardo Durans Figuerêdo1, MD, MsC; Josimary Lima da Silva Lula2 DOI: 10.5935/1678-9741.20130058

RBCCV 44205-1484

Abstract Objective: To compare the effects of different levels of positive end-expiratory pressure on respiratory mechanics and oxygenation indexes in the immediate postoperative period of coronary artery bypass grafting. Methods: Randomized clinical trial in which 136 patients underwent coronary artery bypass grafting between January 2011 and March 2012 were divided into three groups and admitted to mechanical ventilation with different positive endexpiratory pressure levels: Group A, 5 cmH2O (n=44), Group B, 8 cmH2O (n=47) and Group C, 10 cmH2O (n=45). Data about respiratory mechanics were obtained from mechanical ventilator monitor and oxygenation indexes from arterial blood gas samples, collected twenty minutes after intensive care unit admission. Patients with chronic obstructive pulmonary disease and patients submitted to off-pump, emergency or combined operations were not included. For statistical analysis, we used Kruskal-Wallis, G and Chi-square tests, considering results significant when P<0.05. Results: Groups were homogeneous in terms of demographic, clinical and surgical variables. Patients ventilated with positive end-expiratory pressure of 10 cmH2O (Group C) had best compliance (P=0.04) and airway resistance values, this, however, without statistical significance. They also had best oxygenation indexes, with statistical difference in all analyzed variables, and lower frequency of hypoxemia (P=0.03).

Conclusion: Higher levels of positive end-expiratory pressure in immediate postoperative period of coronary artery bypass grafting improved pulmonary compliance values and increased oxygenation indexes, resulting in lower frequency of hypoxemia.

Hospital Universitário da Universidade Federal do Maranhão (HUUFMA), São Luís, MA, Brazil. 2 Hospital São Domingos, São Luís, MA, Brazil.

Correspondence address: Daniel Lago Borges Hospital Universitário da Universidade Federal do Maranhão (HUUFMA) Rua Barão de Itapary, nº 227, Centro - São Luis, MA, Brazil Zip code: 65020-070 E-mail: dlagofisio83@hotmail.com

Descriptors: Positive end-expiratory pressure. Respiratory mechanics. Oxygenation. Myocardial revascularization. Resumo Objetivo: Comparar os efeitos de diferentes níveis de pressão expiratória positiva final na mecânica respiratória e nos índices de oxigenação no pós-operatório imediato de revascularização do miocárdio. Métodos: Ensaio clínico randomizado no qual 136 pacientes submetidos à revascularização do miocárdio, entre janeiro de 2011 e março de 2012, foram distribuídos em três grupos e admitidos na ventilação mecânica com diferentes níveis de pressão expiratória positiva final: Grupo A, 5 cmH2O (n=44), Grupo B, 8 cmH2O (n=47) e Grupo C, 10 cmH2O (n=45), sendo os dados da mecânica respiratória obtidos do monitor do ventilador mecânico e os índices de oxigenação por meio de gasometria arterial coletada vinte minutos após a admissão na unidade de terapia intensiva. Não foram incluídos pacientes com doença pulmonar obstrutiva crônica, cirurgias associadas, de emergência ou sem circulação

This study was carried out at Hospital Universitário da Universidade Federal do Maranhão (HUUFMA), São Luís, MA, Brazil.

Article received on January 25th, 2013 Article accepted on April 1st, 2013

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10 cmH2O (Grupo C) apresentaram os melhores valores de complacência (P=0,04) e de resistência das vias aéreas, esta, porém sem significância estatística. Apresentaram, ainda, os melhores índices de oxigenação, com diferença estatística em todas as variáveis estudadas, além de menor frequência de hipoxemia (P=0,03). Conclusão: Níveis mais elevados de pressão expiratória positiva final no pós-operatório imediato de revascularização do miocárdio incrementaram os valores de complacência pulmonar e melhoraram os índices de oxigenação, resultando acarretando em menor frequência de hipoxemia.

Abbreviations, acronysm & symbols CABG COPD CPB ICU PEEP

Coronary artery bypass grafting Chronic obstructive pulmonary disease Cardiopulmonary bypass Intensive Care Unit Positive end-expiratory pressure

extracorpórea. Para análise estatística, empregaram-se os testes de Kruskal-Wallis, Teste G e Qui-quadrado, considerando os resultados significantes quando P<0,05. Resultados: Os grupos apresentaram-se homogêneos em relação às variáveis demográficas, clínicas e cirúrgicas. Os pacientes ventilados com pressão expiratória positiva final de

Descritores: Respiração com pressão positiva. Mecânica respiratória. Oxigenação. Revascularização miocárdica.

INTRODUCTION

January 2011 and March 2012. We excluded patients with chronic obstructive pulmonary disease (COPD) and those requiring emergency, concomitant or off-pump surgeries. We also excluded patients who died in the perioperative period before weaning from mechanical ventilation.

Despite clinical treatment and percutaneous interventions advances, coronary artery bypass grafting (CABG) is widely used in treating patients with coronary heart disease [1]. Surgical treatment goals are symptoms relief, ischemic myocardium protection, ventricular function improvement, prevent heart attack, regain of physical, mental and social conditions and prolonging life and its quality [2]. Moreover, this surgery may cause organic alterations, such as respiratory and oxygenation failure in postoperative period, especially in elderly, obese and patients with left ventricular dysfunction (left ventricular ejection fraction <55%) and prolonged cardiopulmonary bypass (CPB) time (>120 minutes) [3]. Pulmonary complications associated to cardiac surgery include respiratory mechanics and gas exchange alterations, mainly due to alveolar collapse [4]. Positive end-expiratory pressure (PEEP) may improve oxygenation and prevent atelectasis [5], while keeping airway pressure positive throughout expiration, especially at the end, promoting alveolar and small airways recruitment and stabilization, reducing pulmonary shunt and increasing functional residual capacity, thus preventing alveolar collapse [6]. In this study, we compare the effects of different PEEP levels on respiratory mechanics and oxygenation indexes after CABG to identify the most effective mechanical ventilation parameter.

Data Collection Preoperatively, patients received information and an explanation about the research. Postoperatively, data were collected from a Physical Therapy Evaluation Form and medical records. This form was designed for the study and was divided into three parts: pre-, intra- and postoperative periods. After ICU admission, mechanical ventilation was applied using mechanical ventilator Evita 2 dura (Dräger Medical, Lübeck, Germany). Patients were admitted to volume control mode, as service protocol, with following parameters: tidal volume between 6 and 8 ml/kg, respiratory rate equal to 14 bpm, inspiratory flow of 8 to 10 times the minute volume, inspiratory time equal 1 second and inspired oxygen fraction 40%. Patients were assigned to one of three groups using a simple draw and ventilated with different PEEP values postoperatively, as follows: Group A, PEEP=5 cmH 2O (n=44); Group B, PEEP=8 cmH2O (n=47); and Group C, PEEP=10 cmH2O (n=45). After draw, information about which group the patient would be allocated, was given to ICU members. Intraoperatively, all patients were ventilated with PEEP 5 cmH2O. Twenty minutes after admission, respiratory mechanics data were recorded from mechanical ventilator monitor and arterial blood sample was collected and processed by ABL 800 FLEX blood gas analyzer (Radiometer, Bronshoj, Denmark), as routine, and then identified and calculated oxygenation indexes. After blood gas analysis, mechanical ventilation parameters were adjusted according to patient’s therapeutic needs. Once satisfactory clinical conditions were achieved,

METHODS Study design Randomized clinical trial in a northeastern Brazilian federal universitary hospital. Sample Composition We studied 136 adult patients undergoing CABG between

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including hemodynamic stability; absence or minimal bleeding; Glasgow Coma Scale score >10; and minimum mechanical ventilation parameters on pressure support mode (PS=7 cmH2O, PEEP=5 cmH2O, FiO2 <40%), patients were extubated and oxygen was administered by nasal catheter, as established by routine service.

the Institution (No. 346/10), as required by Resolution 196/96 of the National Health Council and all patients signed written informed consent. Statistical Analysis Collected data were assessed using Stata/SE statistical software version 11.1 (StataCorp, College Station, TX, USA). We used Shapiro-Wilk test for normality in groups. Quantitative variables were described as mean and standard deviation and differences were confirmed using Kruskal– Wallis test. Qualitative variables were expressed as proportions and association between these variables and outcome was tested using G and Chi-square tests. Results were considered statistically significant when P<0.05.

Definitions Arterial oxygen partial pressure and inspired oxygen fraction ratio (PaO2/FiO2) was classified as [7]: • Normal: PaO2/FiO2 > 300 mmHg; • Mild hypoxemia: 200 mmHg < PaO2/FiO2 < 300 mmHg; • Moderate hypoxemia: 100 mmHg < PaO2/FiO2 < 200 mmHg; • Severe hypoxemia: PaO2/FiO2 < 100 mmHg.

RESULTS

For arterial-alveolar oxygen partial pressure ratio (PaO2/ PAO2), which estimates pulmonary shunt, the reference values was considered as 0.74 to 0.90 mmHg [8]. For Respiratory Index (RI), alveolar-arterial oxygen gradient and arterial oxygen partial pressure ratio [P(A-a) O2/PaO2], normal values are between 0.74 and 1.0 mmHg. Index greater than 2 mmHg reflects refractory hypoxemia and elevated pulmonary shunt [8].

One hundred sixty-seven patients underwent CABG during the study period, with 29 not participating because of CABG and another surgical procedure association (22 patients); COPD (6 patients); and off-pump surgery (1 patient). Two other patients were excluded because of death before weaning from mechanical ventilation. The mortality in this population was 1.2%. Final sample was composed by 136 patients, predominantly male (70.6%) with mean age 60±9.3 years and body mass index 26.6±3.8 kg/cm2. Groups did not differ significantly in demographic, clinical and surgical parameters (Tables 1 and 2).

Ethical Aspects The study was approved by Research Ethics Committee of

Table 1. Demographic and clinical data for patients undergoing CABG Variables Gender Male Female Age group < 60 years > 60 years Origin Capital Countryside BMI (kg/cm2) Normal Overweight Obese Comorbidities Hypertension Diabetes mellitus Smoking Dyslipidemia Myocardial infarction Chronic renal failure Coronary angioplasty Stroke a

Group A PEEP = 5 cmH2O (n = 44)

Group B PEEP = 8 cmH2O (n = 47)

Group C PEEP = 10 cmH2O (n = 45)

Total (%)

29 15

32 15

35 10

96 (70.6) 40 (29.4)

20 24

22 25

19 26

61 (44.9) 75 (55.1)

23 21

17 30

16 29

56 (41.2) 80 (58.8)

18 17 9

16 24 7

14 22 9

48 (35.3) 63 (46.3) 25 (18.4)

33 22 17 6 9 4 1 2

39 19 12 13 9 2 1 1

34 23 15 12 11 8 2 1

106 (77.9) 64 (47.1) 44 (32.4) 31 (22.8) 29 (21.3) 14 (10.3) 4 (2.9) 4 (2.9)

Chi-square test; bG test; BMI, body mass index

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P 0.42a 0.90a 0.19a 0.74a

0.58a 0.52a 0.40a 0.21a 0.81a 0.10b 0.80b 0.79b

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Table 2. Surgical data for patients undergoing CABG. Variables Number of bypasses Number of drainage tubes Pump time (min) Aortic clamp time (min) Surgery time (min)

Group A PEEP = 5 cmH2O (n = 44) 2.5 ± 0.6 1.8 ± 0.5 89.9 ± 34.2 63.3 ± 24.7 241.4 ± 58.1

Group B PEEP = 8 cmH2O (n = 47) 2.5 ± 0.8 1.7 ± 0.6 83.7 ± 29.2 60.6 ± 23.6 227.5 ± 47.5

Group C PEEP = 10 cmH2O (n = 45) 2.5 ± 0.7 1.9 ± 0.3 85. 9 ± 2.8 61.6 ± 21.8 234.5 ± 43.2

Mean ± SD

2.5 ± 0.7 1.8 ± 0.5 86.4 ± 30.3 61.8 ± 23.2 234.3 ± 49.9

0.99 0.15 0.87 0.97 0.42

Data displayed as mean ± standard deviation. Kruskal-Wallis test Table 3. PEEP level, respiratory mechanics and oxygenation indices association. Variável Compliance (ml/cmH2O) Airway resistance (cmH2O/l.s-1) SpO2 (%) PaO2 (mmHg) PaO2/FiO2 (mmHg) PaO2/PAO2 (mmHg) P(A-a)O2 (mmHg) P(A-a)O2/PaO2 (mmHg)

Group A PEEP = 5 (n = 44) 47.4 ± 12.5 8.1 ± 2.7 97.1 ± 2.6 108.0 ± 36 269.9 ± 89.8 0.43 ± 0.14 139.3 ± 34.3 1.53 ± 0.78

Group B PEEP = 8 (n = 47) 47.9 ± 19.3 7.6 ± 4.2 97.5 ± 1.7 111.6 ± 28.3 278.9 ± 70.6 0.45 ± 0.11 136.3 ± 28.0 1.38 ± 0.65

Group C PEEP = 10 (n = 45) 55.8 ± 19.1 7.0 ± 2.6 98.5 ± 1.2 131.3 ± 33.9 328.2 ± 84.8 0.53 ± 0.13 116.8 ± 33 1.02 ± 0.55

P 0.04 0.14 0.002 0.002 0.002 0.002 0.004 0.003

SpO2 – oxygen saturation; PaO2 – arterial oxygen partial pressure; FiO2 – inspired oxygen fraction; PAO2 – alveolar oxygen partial pressure; P(A-a)O2 – alveolar-arterial oxygen gradient; P(A-a)O2/PaO2 – respiratory index. Kruskal-Wallis test

Oxygen saturation (SpO2) mean was 97.7±2%. Arterial oxygen partial pressure (PaO2) mean, determined immediately after ICU admission, was 116.9±34.1 mmHg, ranging from 53.7 to 203 mmHg. PaO2/FiO2 ratio mean was 292.3±85.2, ranging from 134.3 to 507.5. Regarding hypoxemia severity, we found that 42.6% of patients had normal PaO2/FiO2 ratio. Mild hypoxemia was also observed in 42.6% of patients and 14.7% of patients had moderate hypoxemia. No patient had severe hypoxemia. Arterial-alveolar oxygen partial pressure ratio (PaO2/ PAO2) mean was 0.47±0.14 mmHg. Only 4.4% of the patients presented normal value. Alveolar-arterial oxygen gradient [P(A-a)O2] mean was 130.8±34.3 mmHg. Respiratory Index mean was of 1.31±0.69 mmHg and was normal in only 15.4% of patients. Highest SpO2, PaO2, PaO2/FiO2 and PaO2/PAO2 and lowest P(A-a)O2 and RI means were found in patients ventilated with PEEP 10 cmH2O (Group C), and all of these variables had statistically significant differences between groups. Group C patients had also less hypoxemia occurrence (68.2% vs. 61.7% vs. 42.4%, P=0.03) (Figure 1). Respiratory mechanics and oxygenation association between groups are shown in Table 3. In the present study hemodynamics measurements such as arterial blood pressure and heart rate were not assessed. However, no significant hemodynamic changes were observed in any patient.

Fig. 1 - Hypoxemia frequency, by group, in patients undergoing CABG and ventilated with different PEEP levels in immediate postoperative period. PaO2 - arterial oxygen partial pressure, FiO2 - inspired oxygen fraction, PEEP - Positive end-expiratory pressure. Chi-square test.

Compliance mean was 50.3±17.5 ml/cmH2O while airway resistance mean was 7.6±3.3 cmH2O/L/s. When associated different levels of PEEP to respiratory mechanics, patients ventilated with PEEP 10 cmH 2O (Group C) had higher compliance values (P=0.04) and lower airway resistance values with no statistical significance.

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DISCUSSION

Moreover, Dongelmans et al. [10] comparing application of high level of PEEP (10 cmH2O) with physiological level (5 cmH 2O) after CABG, showed that higher values of PEEP improves oxygenation and lung compliance, despite association with increased mechanical ventilation duration. Oxygenation index or PaO2/FiO2 ratio routinely quantifies alveolar collapse in mechanically ventilated patients in postoperative period [20], being the preferred method for pulmonary function assessment [21]. Weiss et al. [22] reported PaO2/FiO2 decrease during the first 12 hours after on-pump CABG, calculated after anesthesia induction and compared with values obtained one, six and 12 hours after pump in 460 patients. These authors concluded that, despite improvements in cardiopulmonary bypass techniques, hypoxemia is still common in cardiac surgery postoperative period. In our study, we observed similar data, since more than half patients had some hypoxemia degree in ICU admission, being reduced when we used higher PEEP (10 cmH2O). Alveolar-arterial gradient [P(A-a)O2] is increased in patients with impaired gas exchange in any FiO2 range, with higher values than normal individuals. As reported by Terzi and Dragosavac [23], P(A-a)O2 values in on-pump postoperative patients ranged from 119 mmHg (FiO2 40%) to 338 mmHg (FiO2 100%). Similar results were found in our study, which showed high values in all groups, being lower when applied higher PEEP.

In this study that assessed the relation between different PEEP levels and respiratory mechanics and oxygenation indexes on postoperative CABG, showed that higher levels of PEEP (10 cmH2O) may promote a respiratory mechanics values increase and provide better oxygenation indexes in immediate postoperative period. Previous studies showed that use of PEEP in high level after elective CABG improves oxygenation and lung compliance [9,10]. Decreased lung compliance after CABG is well established, probably due interstitial edema, hemorrhage and vascular congestion that increases lung stiffness [11]. In cardiac surgery immediate postoperative period, static compliance is lower than normal, probably reflecting atelectasis [9]. These changes may be related to intraoperative procedures as mechanical ventilation with low volumes and low PEEP levels and sternotomy, which alters chest wall compliance [12]. Staton et al. [13] compares pulmonary outcomes in patients undergoing on- or off-pump CABG, concluding that compliance is lower in patients undergoing on-pump surgery, instead of worse gas exchange and later extubation. In our study, all patients underwent on-pump surgery, being expected worst compliance values. High PEEP was able to improve compliance in this sample. Babik et al. [14] assesses respiratory mechanics changes during cardiac surgery, showing that airway resistance increases more than 70% in patients undergoing on-pump surgery, does not changing in off-pump. Auler Jr et al. [11] in a prospective trial that assessed effects of PEEP on respiratory mechanics and hemodynamics of CABG patients concluded that higher levels of PEEP promote reduction in airway resistance. Similar findings were found in our study, but with no statistical significance. According to Singh et al. [15], gas exchange changes are the most significant postoperative CABG complications. Thence, we chose study oxygenation indexes because they appropriately reflect changes in pulmonary function after onpump surgery [16]. Despite this and other studies show advantages of high PEEP on oxygenation and compliance, controversies about their real advantages still remain. In randomized controlled trial performed by Marvel et al. [17] with patients undergoing CABG and ventilated with PEEP levels of 0, 5 or 10 cmH2O, it was demonstrated that higher levels of PEEP not provides sustained beneficial effect on arterial oxygenation. This effect was also found by Celebi et al. [18] in another randomized controlled trial in which patients were ventilated with PEEP titrated to achieve the best PaO2. Michalopoulos et al. [19] examined the effects of different levels of PEEP (0.5 and 10 cmH2O) in arterial oxygenation in patients after cardiac surgery and showed no advantage in gas exchange applying low levels of PEEP when compared to no PEEP.

CONCLUSION Higher levels of PEEP provided beneficial effects for patients undergoing CABG by increasing oxygenation indexes, reducing hypoxemia and significantly improving lung compliance in immediate postoperative period. Authors' roles & responsabilities DLB VJSN MAGC TEPB NPS IML EDF JLSL

Study design, data collection and manuscript writing Study design and manuscript writing Data collection Data collection Data collection Data collection Statistical analysis Text revision

REFERENCES 1. Piegas LS, Bittar OJ, Haddad N. Cirurgia de revascularização miocárdica: resultados do Sistema Único de Saúde. Arq Bras Cardiol. 2009;93(5):555-60. 2. Lima RC, Kubrusly LF, Nery ACS, Pinheiro BB, Brick AV, Souza DSR, et al. Diretrizes da cirurgia de revascularização miocárdica,

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valvopatias e doenças da aorta. Arq Bras Cardiol. 2004;82(supl. 5):1-20.

13. Staton GW, Williams WH, Mahoney EM, Hu J, Chu H, Duke PG, et al. Pulmonary outcomes of off-pump vs on-pump coronary artery bypass surgery in a randomized trial. Chest. 2005;127(3):892-901.

3. Szeles TF, Yoshinaga EM, Alencar W, Brudniewski M, Ferreira FS, Auler Jr. JOC, et al. Hipoxemia após revascularização miocárdica: análise dos fatores de risco. Rev Bras Anestesiol. 2008;58(2):124-36.

14. Babik B, Asztalos T, Peták F, Deák ZI, Hantos Z. Changes in respiratory mechanics during cardiac surgery. Anesth Analg. 2003;96(5):1280-7.

4. Wynne R, Botti M. Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice. Am J Crit Care. 2004;13(5):384-93.

15. Singh NP, Vargas FS, Cukier A, Terra-Filho M, Teixeira LR, Light RW. Arterial blood gases after coronary artery bypass surgery. Chest. 1992;102(5):1337-41.

5. Auler Jr JOC, Galas FRBG, Hajjar LA, Franca S. Ventilação mecânica no intra-operatório. J Bras Pneumol. 2007;33(suppl. 2):137-41.

16. Cui H, Zhang M, Xiao F, Li Y, Wang J, Chen H. Comparison and correlative analysis of pulmonary function markers after extracorporeal circulation. Beijing Da Xue Xue Bao. 2003;35(2):195-9.

6. Alexandre BL, Araújo SG, Machado MGR. Pressões respiratórias máximas. In: Machado MGR, ed. Bases da fisioterapia respiratória: terapia intensiva e reabilitação. Rio de Janeiro: Guanabara-Koogan; 2008.

17. Marvel SL, Elliott CG, Tocino I, Greenway LW, Metcalf SM, Chapman RH. Positive end-expiratory pressure following coronary artery bypass grafting. Chest. 1986;90(4):537-41.

7. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-33.

18. Celebi S, Köner O, Menda F, Korkut K, Suzer K, Cakar N. The pulmonary and hemodynamic effects of two different recruitment maneuvers after cardiac surgery. Anesth Analg. 2007;104(2):384-90.

8. José A, Dias EC, Santos VLA, Chiavone PA. Valor preditivo dos gases arteriais e índices de oxigenação no desmame da ventilação mecânica. Rev Bras Ter Intensiva. 2001;13(2):50-7.

19. Michalopoulos A, Anthi A, Rellos K, Geroulanos S. Effects of positive end-expiratory pressure (PEEP) in cardiac surgery patients. Respir Med. 1998;92(6):858-62.

9. Valta P, Takala J, Eissa NT, Milic-Emili J. Effects of PEEP on respiratory mechanics after open heart surgery. Chest. 1992;102(1):227-33.

20. Reis-Miranda D, Struijs A, Koetsier P, van Thiel R, Schepp R, Hop W, et al. Open lung ventilation improves functional residual capacity after extubation in cardiac surgery. Crit Care Med. 2005;33(10):2253-8.

10. Dongelmans DA, Hemmes SN, Kudoga AC, Veelo DP, Binnekade JM, Schultz MJ. Positive end-expiratory pressure following coronary artery bypass grafting. Minerva Anestesiol. 2012;78(7):790-800.

21. MacNaughton PD. Assessment of lung function in the ventilated patient. Intensive Care Med. 1997;23(8):810-8. 22. Weiss YG, Merin G, Koganov E, Ribo A, Oppenheim-Eden A, Medalion B, et al. Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance. J Cardiothorac Vasc Anesth. 2000;14(5):506-13.

11. Auler JO Jr, Carmona MJ, Barbas CV, Saldiva PH, Malbouisson LM. The effects of positive end-expiratory pressure on respiratory system mechanics and hemodynamics in postoperative cardiac surgery patients. Braz J Med Biol Res. 2000;33(1):31-42.

23. Terzi RGG, Dragosavac D. Monitorização do intercâmbio gasoso pulmonar no paciente submetido à ventilação mecânica. In: Carvalho CRR, ed. Ventilação mecânica. Vol. 1. São Paulo:Atheneu;2000. p.199-204.

12. Ambrozin ARP, Cataneo AJM. Aspectos da função pulmonar após revascularização do miocárdio relacionados com risco pré-operatório. Rev Bras Cir Cardiovasc. 2005;20(4):408-15.

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Arnoni RT, etORIGINAL al. - Assessment of sternal closure using titanium plate ARTICLE

Assessment of sternal closure using titanium plate Avaliação do fechamento esternal com placa de titânio

Renato Tambellini Arnoni1, MD, PhD; Daniel Chagas Dantas1, MD; Antoninho Arnoni1, MD; Caetano Nigro Neto1, MD; Camilo Abdulmassih Neto1, MD

DOI: 10.5935/1678-9741.20130059

RBCCV 44205-1485

Abstract Introduction: The use of plates and screws for more rigid fixation of the sternum, without maintaining contact between the upper portion of the sternum and mediastinum. The present study seeks new choice of plate with a significant difference, the same does not need to be removed in order to proceed to open when necessary sternal emerging opening of the bone. Objective: The current study aims to evaluate the efficacy and safety of this procedure. Methods: To this end, we selected ten patients with coronary artery disease have shown no significant risk factors for mediastinitis. The surgery was thus performed in the usual way that all patients with coronary artery disease surgeries are done at the institution. Only at the time of sternal closure is that there was a change, with the combination of steel wires and plates. Results: All cases had sternal closure properly with good outcome in the medium term. Conclusion: The use of plates ENGIMPLAN proved safe and effective for sternal closure.

Resumo Introdução: A utilização de placas e parafuso para a mais rígida fixação do esterno, sem manter contato entre a porção superior do esterno e o mediastino. O estudo atual busca nova opção de placa, com um diferencial importante; a mesma não precisa ser retirada para que se proceda à abertura esternal em caso de necessidade emergente de abertura do osso. Objetivo: O presente estudo tem por objetivo avaliar a eficácia e a segurança de tal procedimento. Métodos: Para tal, foram selecionados dez pacientes portadores de doença arterial coronária que não apresentassem importantes fatores de risco para mediastinite. As cirurgias foram, portanto, realizadas da maneira habitual, a todas os procedimentos em portadores de coronariopatias são feitas na Instituição. Somente no momento do fechamento esternal é que houve uma modificação, com a associação de fios de aço e placas. Resultados: Todos os casos apresentaram fechamento esternal de forma adequada com boa evolução a médio prazo. Conclusão: O emprego das placas ENGIMPLAN se mostrou seguro e eficaz no fechamento esternal.

Descriptors: Coronary Artery Bypass. Titanium. Sternum. Bone Plates. Bone Screws.

Descritores: Esterno. Revascularização Miocárdica. Titânio. Parafusos Ósseos.

Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil.

Correspondence address: Renato Tambellini Arnoni Av. Dr. Dante Pazzanese, 500 – Vila Mariana, São Paulo, SP, Brazil Zip code: 04012-180 E-mail rarnoni@uol.com.br

Work carried out at Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil.

Article received on February 2nd, 2013 Article accepted on April 28th, 2013

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previously in oral maxillofacial surgery, have been already used for sternal osteosynthesis [6]. This study demonstrated a lower incidence of mediastinitis in high-risk patients when using plates for sternal closure. Several steps were followed to the present time that allowed the possibility of using implant plates in patients undergoing myocardial revascularization in the Institute Dante Pazzanese Cardiology: 1) In vitro study of screws and plates; 2) To study the placement of plates and screws in corpses. The current study aims to assess the efficacy and safety of this procedure in humans.

Abbreviations, acronyms & symbols BMI CONEP

Body mass index Comissão Nacional de Ética em Pesquisa/ National Committee for Research Ethics EuroSCORE European System for Cardiac Operative Risk Evaluation STS Society of Thoracic Surgeons

INTRODUCTION Cardiac surgery has been performed mostly through median sternotomy since 1957, when Julian re-introduced the technique previously established by Milton. in 1897 [1]. In 2001, approximately 760,000 surgeries with this type of incision were performed in the United States [2]. Despite its good exposure, it is not free of complications. Mediastinitis is a serious complication that appears with a mortality of about 15% [3]. At Institute Dante Pazzanese of Cardiology, about 1,600 cardiac surgeries are performed per year with an infection rate of 6%. Some methods to prevent mediastinitis after sternotomy included prophylactic methods like antibiotics and special techniques to skin closure, but little has been studied in the prevention of the infectious process by better bone fixation [4]. The current technique for sternal osteosynthesis is to fix the bone with steel wire that involves and approaches both sides of the bone. This procedure, usual in our country, enables the progression of the process of the upper mediastinum into the mediastinal cavity, which is ineffective for the fixation of the sternum [5]. Several new fixing methods have been studied for more rigid fixation of the sternum, among them the use of plates and screws without maintaining contact between the upper portion of the sternum and mediastinal cavity. These boards used

METHODS To develop this new device, some materials were produced to assist their implantation, such as: screwdrivers, fasteners, drill bits and stabilizers plates. Plates and screws used for sternal closure have various designs. The current study seeks new board option, with a significant difference; it does not need to be removed to proceed with the sternal opening in case of emergent need of opening the bone. The great advantage of this material is its design and the various models of plates, giving the possibility to the surgeon to choose the one that best suits the situation required. Moreover, the central pin allows opening the sternum, without removing the plate in case of surgical reoperation (Figure 1). It was initially implanted “in vitro” (corpse) by assessing resistance and strength of the plates (Figure 2). It was performed the opening and closing of the corpses sternum with test pins and proper sternal fixation. After these tests the material was made available to perform procedures in patients with coronary artery disease who required surgical treatment. The study was submitted to the Research Ethics

Fig. 1 - Models of plates with central pin - From right to left.: Star, straight, “X”, “H”

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Table 1. How to use the plates. Patient Plate 1 2 3 4 5 6 7 8 9 10

"X" shaped steel wire "H" narrow plate 4 X 4 / Straight plate 2 X 2 3 "H" narrow plate 4 X 4 / Star plate 3 X 3 2 "H" narrow plate 4 X 4 / Star plate 3 X 3 3 "H" narrow plate 4 X 4 / Star plate 3 X 3 2 "H" narrow plate 4 X 4 / Star plate 3 X 3 2 "H" narrow plate 4 X 4 / Star plate 3 X 3 2 "H" narrow plate 4 X 4 / Star plate 3 X 3 2 "H" narrow plate 4 X 4 / Star plate 3 X 3 2 "H" narrow plate 4 X 4 / Star plate 3 X 3 3 "H" narrow plate 4 X 4 / Star plate 3 X 3 2

RESULTS

Fig. 2 - "In vitro”- straight plate undergone endurance test

Revascularization of the affected vessels by coronary artery disease was performed using the left internal thoracic artery to the left anterior descending artery and saphenous vein grafts to the other vessels, the average number of bridges performed per patient was 3.2 bridges, with cases ranging three to four bridges. Sternal closure, as already reported, was performed with plates and screws (Table 1) according to the preference of the surgical team to maintain greater stability of the sternum. Patients were followed-up, without presenting any complications regarding coronary artery disease, all being asymptomatic at the standpoint. The median follow-up was 5.7 months. Regarding the closure, only one patient had wound dehiscence requiring surgical reoperation. This patient had an instable bone fixation with apparent poor coaptation of the bone plate. One of the bolts was not tight. We opted to remove the material synthesis, culture collection and closure with steel wires. Cultures were negative, patient improved after resuture and discharge was possible after a week. This patient is in the

Committee under number 3823, approved by the institutional Ethics Committee and CONEP (Comissão Nacional de Ética em Pesquisa/ National Committee for Research Ethics) on 02/03/2010. After obtaining written informed consent we selected ten patients with coronary artery disease, which had no significant risk factors for mediastinitis. It was excluded patients with some comorbidities: 1) Obesity [body mass index (BMI) greater than 30], 2) Elderly (over 75 years), 3) Chronic kidney disease, 4) Diabetes mellitus, 5) Chronic pulmonary obstructive disease, 6) Bilateral internal thoracic artery used as a graft. Underwent surgery ten patients, aged between 46 and 66 years, mean 56 years. The mean body mass index was 27.5 kg/m², ranging 25-30. The patients’ past medical history were restricted to hypertension (present in all). Regarding the context of heart disease, three patients had acute myocardial infarction during the past 30 days, and the remaining patients had stable angina. The study showed low-risk score to all patients; assessed both by EuroSCORE and the Society of Thoracic Surgeons (STS). The first between zero and three that corresponds to a likelihood of death around 1.43%, and 1.68% to the second. All surgeries were performed in patients requiring coronary artery bypass grafting with cardiopulmonary bypass with myocardial protection achieved by intermittent aortic clamping. The mean duration of cardiopulmonary bypass was 71.7 minutes (55-80), while the anoxic time ranged between 45 and 65 minutes, averaging 52.4 minutes. The surgeries were performed as the same way as it always be done to all coronary surgeries performed in the institution. Only the time of sternal closure was changed, with the combination of metal wires and plates. Plates were selected according to the preference of the surgeon; steel wires used in “X” or in simply wrap, reinforcing bone fixation. The following table shows how the plates and screws were employed (Table 1).

Fig. 3 – Fixing the sternum - Image of the plates little star and “H” narrow

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sixth month postoperatively, clinically and with chest x-ray. Two steel wires in the upper and lower ends, had to be used only to join the floorboards and facilitate the fixation of the bone plate. An important issue tested was the easy removal of the “pin” that joins the two sides of the plate for a possible need of reoperation postoperatively. This fact allows not to remove the plate already fixed to the bone, and streamlines the reoperation. It also provides that these patients can be reoperated on another center that does not have special materials for implantation and removal of plates and screws. The card can be opened and closed again using a Kelly clamp. We had one case requiring reoperation even in the initial stage of the series, probably due to deficiency in the technique of fixing the board. A difference was observed in the absence of fractures and preserving the integrity of the sternum. Another important issue that emerges is the cost of the method, not assessed in this series. Based on the good results, we planned a randomized study, between standard closing with steel wires and synthesis with plates and screws, with larger number of patients at high risk of postoperative sternal dehiscence, where in addition to compare the results of two techniques, we will look at the cost effectiveness of the method.

Fig. 4 - Postoperative radiological picture - Chest X-ray

fifth month post-resuture with favorable clinical course without further complications. The other patients had no complications regarding the synthesis material, which was effective and safe for the fixation of the sternum (Figures 3 and 4).

CONCLUSION

DISCUSSION

The use of ENGIMPLAN boards proved to be safe and effective in sternal closure. Further randomized studies should be done comparing the employment of this material and other techniques like steel wires in patients at high risk for mediastinitis to bring confirmations about the safety of this form of sternal closure.

Cardiac surgery has had a major breakthrough in recent years, but the access road trough median sternotomy and its synthesis are almost the same with standard steel wire that is adopted by most centers. This has a non-negligible rate of failure from fatigue of the wires, bone fractures, allowing sternal instability, dehiscence, infection, leading patients to hospitalization and prolonged antibiotic therapy with procedures dressings, debridement and resutures [3,7-9]. Taking as a basis for a good sternal healing and stability, material synthesis with titanium plates and screws is an alternative technique, already in wide use in orthopedic procedures and other cardiac surgery centers primarily in Europe, with proven results [6,8,10,11]. The present study, using plates and screws with domestic technology for its manufacture, aimed to prove the safety and practicality of the method, a lower risk of bleeding than with sternotomy wires and runtime similar after the initial learning curve. Being an initial treatment of new implantable devices, the study began with the evaluation “in vitro” of plates and screws. All models were tested with regard to static bending test (plates) and static test of firmness (screws). The plates are made using a titanium alloy ASTM F 136, as well as screws. All “in vitro” of this innovative material showed great resistance to bending of the plate, as well as secure fixation of the screws. We proved good results in monitoring all patients in this series from the immediate postoperative period until the

Authors’ roles & responsibilities RTA Main author DCD Coauthor AA Coauthor CNN Coauthor CAN Coauthor

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4. Krischak GD, Janousek A, Wolf S, Augat P, Kinzl L, Claes LE. Effects of one-plane and two-plane external fixation on sheep osteotomy healing and complications. Clin Biomech (Briston Avon). 2002;17(6):470-6.

8. Schimmer C, Reents W, Berneder S, Eigel P, Sezer O, Scheld H, et al. Prevention of sternal dehiscence and infection in high-risk patients: a prospective randomized multicenter trial. Ann Thorac Surg. 2008;86(6):1897-904.

5. Trumble DR, McGregor WE, Magovern JA. Validation of a bone analog model for studies of sternal closure. Ann Thorac Surg. 2002;74(3):739-44.

9. Casha AR, Gauci M, Yang L, Saleh M, Kay PH, Cooper GJ. Fatigue testing median sternotomy closure. Eur J Cardiothorac Surg. 2001;19(3):249-53.

6. Song DH, Lohman RF, Renucci JD, Jeevanandam V, Raman J. Primary sternal plating in high-risk patients prevents mediastinitis. Eur J Cardiothorac Surg. 2004;26(2):367-72.

10. Hirose H, Yamane K, Youdelman BA, Bogar L, Diehl JT. Rigid sternal fixation improves postoperative recovery. Open Cardiovasc Med J. 2011;5:148-52.

7. Jutley RS, Shepherd DE, Hukins DW, Jeffrey RR. Preliminary evaluation of the Sternum Screw: a novel method for improved sternal closure to prevent dehiscence. Cardiovasc Surg. 2003;11(1):85-9.

11. Raman J, Lehmann S, Zehr K, De Guzman BJ, Aklog L, Garrett HE, et al. Sternal closure with rigid plate fixation versus wire closure: a randomized controlled multicenter trial. Ann Thorac Surg. 2012;94(6):1854-61.

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Sussenbach CP, et al. - Unstable angina does not increase mortality in coronary ORIGINAL ARTICLE artery bypass graft surgery

Unstable angina does not increase mortality in coronary artery bypass graft surgery Angina instável não aumenta mortalidade em cirurgia de revascularização miocárdica

Carolina Pelzer Sussenbach1, MD; João Carlos Guaragna1, MD, PhD; Rômulo Soares Castagnino1, MD; Jaqueline Piccoli1, PhD; Luciano Cabral Albuquerque1, MD, PhD; Marco Antônio Goldani1, MD; João Batista Petracco1, MD; Luiz Carlos Bodanese1, MD, PhD

DOI: 10.5935/1678-9741.20130060

RBCCV 44205-1486

Abstract Introduction: Coronary artery bypass graft is often the treatment of choice for patients who suffer from unstable angina. We do not know whether this condition adds morbidity in this scenario. Objective: To compare the outcomes of patients undergoing coronary artery bypass graft with unstable angina framework with patients who underwent coronary artery bypass graft showed no unstable angina. Methods: Retrospective cohort study. Unstable angina was defined as acute coronary syndrome without ST elevation and without enzymatic alteration and/or class IV angina. Results: Between February 1996 and July 2010, to 2,818 isolated coronary artery bypass graft performed, 1,016 (36.1%) patients had unstable angina. Multivariate analysis showed that patients with preoperative unstable angina used more medications such as acetylsalicylic acid, beta-blocker, heparin (anticoagulation), nitrate and less need for diuretics than patients without unstable angina. Patients with unstable

angina used increased monitoring with Swan-Ganz and support with intra-aortic balloon than stable patients. On outcomes, required longer hospitalization (P=0.030) and had a lower death rate (P=0.018) in the post-coronary artery bypass graft alone. Conclusion: Submit patients to coronary artery bypass graft in the presence of acute coronary syndrome such as unstable angina did not increase the mortality rate.

Hospital São Lucas of the Pontifícia Universidade Católica do Rio Grande do Sul (HSL/PUCRS), Porto Alegre, RS, Brazil.

Correspondence address: Carolina Pelzer Sussenbach Serviço de Cardiologia do Hospital São Lucas da PUCRS Av. Ipiranga, 6690 sala 300 - Porto Alegre, RS, Brazil - Zip code: 90610-000 E-mail: carol_pelzer@hotmail.com

Descriptors: Angina, unstable. Myocardial revascularization. Mortality.

Resumo Introdução: A cirurgia de revascularização do miocárdio muitas vezes é o tratamento de escolha de pacientes que sofrem angina instável. Não sabemos se essa condição acresce morbimortalidade nesse cenário.

This study was carried out at Hospital São Lucas of the Pontifícia Universidade Católica do Rio Grande do Sul (HSL/PUCRS), Porto Alegre, RS, Brazil.

Article received on June 25th, 2012 Article accepted on August 26th, 2012

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Métodos: Coorte retrospectiva. A angina instável foi definida como síndrome coronariana aguda sem supradesnivelamento de ST e sem alteração enzimática e/ou angina classe IV. Resultados: No período entre fevereiro de 1996 a julho de 2010, de 2.818 a cirurgia de revascularização do miocárdio isoladas realizadas, 1.016 (36,1%) pacientes apresentaram angina instável. A análise multivariada demonstrou que os pacientes com angina instável no pré-operatório utilizaram mais medicações como ácido acetilsalicílico, betabloqueador, heparina (anticoagulação plena), nitrato e menor necessidade de diureticoterapia, do que pacientes sem angina instável. Pacientes com angina instável utilizaram maior monitorização com Swan-Ganz e suporte com balão intra-aórtico do que os pacientes estáveis. Sobre os desfechos, necessitaram de maior tempo de internação (P=0,030) e apresentaram menor taxa de óbito (P=0,018) no pós-operatório de cirurgia de revascularização do miocárdio isolada. Conclusão: Submeter pacientes a cirurgia de revascularização do miocárdio isolada na vigência de síndrome coronariana aguda como angina instável não elevou a taxa de mortalidade.

Abbreviations, acronyms & symbols ASA Acetylsalicylic acid UA Unstable Angina BB Beta-Blocker preop IAB Preoperative Intra-aortic balloon CPB Cardiopulmonary bypass FC functional class DM Diabetes mellitus CKD Chronic kidney disease LVEF Left ventricular ejection fraction SAH Hypertension CI confidence interval ACE inhibitor angiotensin converting enzyme SL LCT Severe lesion of the left coronary trunk P Statistical Significance OR Odds Ratio ACSST Acute coronary syndrome without ST elevation

Objetivo: Comparar os desfechos dos pacientes submetidos a cirurgia de revascularização do miocárdio com quadro de angina instável com os pacientes submetidos a cirurgia de revascularização do miocárdio que não apresentaram angina instável.

Descritores: Angina instável. Revascularização miocárdica. Mortalidade.

INTRODUCTION

twenty minutes (if not interrupted by the nitroglycerin), 2) is described as an intense and frank pain and recent onset (less than 1 month), 3) occurs in a crescendo pattern (e.g., more intense, prolonged or frequent than previously), in the absence signs of myocardial necrosis (elevation of cardiac enzymes). On the ohter hand, the European System Risk in Cardiac Operations (EuroSCORE) defines UA as anginal pain at rest that requires treatment with intravenous nitroglycerin to the surgical procedure. For purposes of this study UA was defined as acute coronary syndrome without ST elevation (ACSST) and without enzyme and/or class IV angina [6,7]. According to current recommendations on UA, taking into account the patient’s risk, CABG is indicated in cases of severe injury of the left main coronary artery, threevessel disease with impaired left ventricular function (left ventricular ejection fraction < 0.5 ); two-vessel lesion with involvement of the proximal left anterior descending artery or decreased left ventricular function or provoked ischemia. Life expectancy, associated diseases, symptom severity and amount of viable myocardium at risk are also important factors [5,8,9].

Unstable angina (UA) is a leading cause of hospital admission, and their occurrence is correlated with increased mortality in both the short- and the long-term [1]. Recent studies have shown that treatment with angioplasty or coronary artery bypass graft (CABG ) have less favorable outcomes in the treatment of patients with unstable angina (UA) compared with those with stable angina. Advances in the treatment of coronary artery and the techniques tend to decrease the difference [2,3]. Treatment of UA can vary from conventional strategy to an early invasive strategy and may be indicated both surgical and percutaneous revascularization [4]. Myocardial revascularization can control the persistent ischemia and progression to acute myocardial infarction, in addition to providing symptomatic relief as well as prevent ischemic complications [5]. There are different ways to define UA. According Braunwald, UA is angina pectoris (ischemic or equivalent) with at least one of three clinical characteristics: 1) occurs at rest (or with minimal effort), usually lasting longer than

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It is not well defined which the real impact of UA on the prognosis of patients undergoing CABG in this context, or whether there is an optimal time interval between the acute event and revascularization. The aim of this study is to assess the characteristics of patients presenting UA and indication of CABG and compare with patients without UA in the preoperative of CABG as well as compare the in-hospital outcomes of these patients in this context.

- Analysis of surgical risk by EuroSCORE. - The need for intra-aortic balloon preoperatively (preop IAB). - Presence of severe injury of the left main coronary artery (SL LCT) - considered as obstructive lesion greater than 50%. - Previous use of drug: acetylsalicylic acid (ASA), beta blockers (BB), antiarrhythmics (amiodarone and propafenone), digoxin, corticosteroids, calcium channel antagonists, diuretics, statins, Heparin, angiotensin-converting enzyme inhibitors (ACEI), nitrates, oral hypoglycemic agents, insulin. - Need for vasopressor and invasive monitoring with Swan-Ganz. - Time of cardiopulmonary bypass (CPB), all CABG used CPB. - Complete revascularization, considered when all vessels with a caliber greater than 1.5 mm and lesions with obstruction ≥ 50 % were revascularized. - Use of revascularization (all used internal thoracic artery graft). - AMI postoperatively. - Stroke (CVA) postoperatively. - Atrial fibrillation (AF) postoperatively. - Acute renal failure (ARF) in the postoperative period, considered with a 50% increase in serum creatinine. - Increased bleeding after surgery, it is considered excessive bleeding 200 ml/hr to 3 ml/h/kg during the first two hours postoperatively, or persisting around 100 ml/h or 1.5 ml/h/kg from the third hour. - Need for multiple blood transfusions, need for transfusion to treat increased bleeding that triggers significant anemia (hemoglobin <8.0 mg/dl) or hemodynamic changes. - Need for reintervention. - Length of hospital stay. - In-hospital mortality postoperatively.

METHODS Population and sample In the period from February 1996 to July 2010 2,818 isolated CABG were performed at Hospital São Lucas. Of these, 1,016 patients ( 36.1 % ) showed UA preoperatively. UA was defined as acute coronary syndrome without ST elevation (ACSST ) and without enzyme and/ or class IV angina. Study design Observational historical cohort study. Data were prospectively collected and entered into the database of the postoperative unit of cardiac surgery at the Hospital São Lucas at PUCRS. Inclusion Criteria Patients aged over 18 years led to cardiac surgery for coronary artery bypass graft (CABG) alone. Exclusion Criteria We excluded from the analysis valvular surgery alone or combined with CABG, urgent or emergency CABG, acute myocardial infarction with very recent (≤ 30 days) ST elevation preoperatively, acute myocardial infarction without very recent surgery (≤ 30 days) ST segment elevation in the preoperative. Study variables The variables included in the analysis were: - Presence of UA in preoperative of CABG, making comparative analysis with CABG without UA preoperatively. - Age calculated based on the average age and also divided into groups for analysis: less than 60 and greater than or equal to 60 years. - Gender (male/female). - Ejection fraction (LVEF ) calculated by echocardiography, values divided for analysis in less than 40% and greater than or equal to 40%. - Chronic kidney disease (CKD) - diagnosed by serum creatinine> 1.5 mg/dl. - Diabetes Mellitus (DM). - High blood pressure (HBP). - Acute Myocardial Infarction (AMI) defined as acute coronary syndrome occurred in 30 to 90 days after surgery.

Outcome We assessed death rates, need for vasopressor support with intra-aortic balloon and length of stay in the postoperative of CABG. Procedures The anesthesia techniques of cardiopulmonary bypass (CPB) and cardioplegic solution (St. Thomas No. 2) were performed according to the standardization of the Hospital São Lucas, as previously described [10]. After surgery, all patients were transferred to the ICU postoperatively in cardiac surgery, under mechanical ventilation. Statistical Analysis The data were plotted on a spreadsheet Microsoft Access® and assessed in SPSS version 11.0. Descriptive statistics were performed, as well as the univariate tests: Chi

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- square test for ordinal variables and quantitative data was used for analysis of variance or Student’s t test (for unpaired variables) followed by post hoc test for Bonferroni data. Multivariate analysis was performed by logistic regression (backward conditional method). Statistical differences were considered when P<0.05.

highest rate of use of aspirin and heparin in patients with UA in preoperative of CABG, there was no difference between groups in relation to bleeding: 12 % in the group with UA and 10.7 % in the group without UA (OR: 1.14, 95% CI 0.89 to 1.45, P=0.29), need for reintervention: 4.1% in the group with UA and 5.3 % in the group without UA (OR: 0.77 95% CI 0.53 to 1.12, P=0.17), and need for multiple transfusions tended to be higher in patients with UA (OR: 1.22, 95% CI 1.02 to 1.45, P=0.027), not confirmed in the multivariate analysis. The CPB time was similar between the groups with values > 90 minutes in 37.9 % in the group with UA compared to 40.7% without UA (OR: 0.89, 95% CI 0.75 to 1.04; P=0.98), use of Swan-Ganz was higher in patients with UA preoperatively (Table 2). Multivariate analysis showed that patients with UA in the preoperative of CABG were mostly female, used more medications such as aspirin, beta-blockers, heparin (anticoagulation), nitrate and needed less diuretics. More patients received monitoring with SwanGanz and support with intra-aortic balloon (Table 3). The overall rate of death in the study population was 5.4%, and the patients with UA had a lower death rate, 4.1% compared to the UA without preoperative rate of 6.1%, data with statistical significance (OR: 0.64, 95% CI 0.443 to 0.925, P=0.018), with a protective effect of 36% of deaths in patients with UA in preoperative of CABG. The hospitalization was higher in patients with UA requiring 10.96 days compared to 10.27 days for patients without UA (OR: 1.009, 95% CI 1.001 to 1.018, P=0.030), this difference was due to higher waiting time for CABG for patients with UA (Table 3). Given the long period examined, from 1996 to 2010, and considering the changes in the management of acute coronary syndromes during this period, including UA, as the benefit of beta-blockers, statins, angiotensinconverting enzyme inhibitors and maintenance of acetylsalicylic acid for patients with UA undergoing CABG, we performed an analysis comparing two periods, as shown in Figures 1 and 2. Through this analysis, we conclude that patients with UA treated from 1996 to 2003 received more beta blockers, angiotensin-converting enzyme inhibitors, aspirin, Heparin and nitrate, less use of diuretics, and the death rate (3% versus 5.3%) was significantly lower in this group compared to those without UA, P=0.028. On the other hand, patients treated from 2004 to 2010 with UA received more aspirin, statins, Heparin and nitrate, and less use of diuretic, but no difference in the treatment of beta-blockers, angiotensinconverting enzyme inhibitors, showing similar mortality rate (6.4 % versus 7.7%) and higher in comparison with the previous period, perhaps for the greater complexity of patients undergoing CABG with the evolution of time (older, with more comorbidities).

Ethical Considerations The research design of the study was submitted to the Research Ethics Committee of FAMED PUCRS, with protocol number 06003478. RESULTS In the period from February 1996 to July 2010 2,818 isolated CABG were performed, all using CPB. Of these, 1,016 patients (36.1%) showed UA preoperatively. The average age of the study population with UA preoperatively was 60.42 ± 10 years, left ventricular ejection fraction with average of 54.05±15%, CPB time of 85.54±34 minutes, average use of mammary graft in 74.1% and average rate of incomplete revascularization of 6.8%. All these characteristics were similar between the groups with UA and without UA in the preoperative of CABG. Regarding the surgical risk analysis performed by logistic EuroSCORE, the average of surgical risk of patients with UA in preoperative of CABG was 5.19 compared with 3.30 for patients without UA in preoperative P=0.012. The mean hospital stay was 10.96±9.74 days, and waiting times for CABG in total was on the average 9.18 days, with longer interval for patients with UA (11.7 days) compared with no UA (7.8 days) (OR 1.30, 95% CI 1.29 to 6.41, P=0.003). Postoperative time was similar between groups, in total the average was 10.5 days, in patients with UA 10.99 days and without UA 10.27 days (OR:0.36, 95% CI 0.006 - 1.42, P=0.048). The longer length of stay in patients with UA preoperatively (10.96 days versus 10.27 days) was at the expense of longer waiting times for CABG. The preoperative and postoperative characteristics with univariate analysis are described in Tables 1 and 2, respectively. Table 3 describes the characteristics and clinical outcomes in postoperative of CABG alone in patients with UA preoperatively, with statistical significance. Univariate analysis showed that females were more prevalent among patients with UA in preoperative of CABG, in addition, these patients used more IAB preoperatively and medications such as aspirin, angiotensin-converting enzyme angiotensin nitrate, heparin and beta-blockers. But the use of diuretics were lower in this group of patients (Table 1). On the evolution postoperatively, there was no difference in outcomes such as myocardial infarction, stroke or acute renal failure and need for vasopressor among patients with UA preoperatively and those who did not. Even with the

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Table 1. Preoperative characteristics of the study population and univariate analysis. Variable Age >60 <60 Gender Male Female LVEF <40% >40% CKD Yes No DM Yes No SAH Yes No Recent AMI Yes No FC 1 and 2 3 and 4 SL of LCT LCT Yes No Preop IAB Yes No AAS Yes No Statin Yes No ACE Yes No Nitrate Yes No Diuretic Yes No Heparin Yes No BB Yes No

Total 2794 (100%)

UA 1007 (36,0%)

n UA 1787 (64,0%)

CI 95%

1482 (53%) 1312 (47%)

518 (51.4%) 489 (48.6%)

964 (53.9%) 823 (46.1%)

0.90

0.77 – 1.05

0.20

1912 (67.9%) 904 (32.1%)

643 (63.3%) 372 (36.7%)

1269(70.5%) 523 (29.5%)

1.38

1.17 – 1.62

<0.01

538 (19.1%) 2272(80.9%)

194 (19.2%) 818 (80.8%)

344 (19.1%) 1454 (80.9%)

1.00

0.82 – 1.21

0.98

253 (9.0%) 2565 (91.0%)

101 (9.9%) 915 (90.1%)

152 (8.4%) 1650 (91.6%)

1.19

0.92 – 1.56

0.18

866 (30.7%) 1952 (69.7%)

308 (30.3%) 708 (69.7%)

558 (30.1%) 1244 (69.0%)

0.97

0.82 – 1.47

0.72

2090 (74.2%) 728 (25.8%)

754 (74.2%) 262 (25.8%)

1336 (74.1%) 466 (25.9%)

1.00

0.82 – 1.19

0.96

150 (5.3%) 2668 (94.7%)

59 (5.8%) 957 (94.2%)

91 (5.0%) 1711 (95.0%)

1.16

0.83 – 1.62

0.39

321 (11.4%) 2497(88.6%)

113 (11.1%) 903(88.9%)

208(11.5%) 1594(88.5%)

0.95

0.75 – 1.22

0.73

649 (23.0%) 2169 (77.0%)

243 (23.9%) 773 (76.1%)

406 (22.5%) 1396 (77.5%)

1.08

0.90 – 1.29

0.40

213 (7.6%) 2605 (92.4%)

97 (9.5%) 919 (90.5%)

116 (6.4%) 1686 (93.6%)

1.53

1.16 – 2.03

0.003

674 (23.9%) 2144 (76.1%)

303 (29.8%) 713 (70.2%)

371 (20.6%) 1431 (79.4%)

1.63

1.37 – 1.95

<0.01

1555 (55.2%) 1263 (44.8%)

543 (53.4%) 473 (46.6%)

1012 (56.2%) 790 (43.8%)

0.89

0.77 – 1.05

0.16

1521 (54.0%) 1297 (46.0%)

523 (51.5%) 493 (48.5%)

998 (55.4%) 804 (44.6%)

0.85

0.73 – 0.99

0.046

1847 (65.5%) 971 (34.5%)

747 (73.5%) 269 (26.5%)

1100 (61.0%) 702 (39.0%)

1.77

1.49 – 2.09

<0.01

655 (23.2%) 2163 (76.8%)

180 (17.7%) 836 (82.3%)

475 (26.4%) 1327 (73.6%)

0.62

0.49 – 0.73

<0.01

932 (33.1%) 1886 (66.9%)

449 (44.2%) 567 (55.8%)

483 (26.8%) 1319 (73.2%)

2.16

1.84 – 2.54

<0.01

1972 (70.0%) 846 (30.0%)

749 (73.7%) 267 (26.3%)

1223 (67.9%) 579 (32.1%)

1.33

1.12 – 1.58

0.001

UA: unstable angina, OR: odds ratio , CI: confidence interval, P: statistical significance, LVEF: left ventricular ejection, CKD: chronic kidney disease, DM : diabetes mellitus, Hypertension: hypertension, CF: functional class, preop IABP: preoperative intra-aortic balloon, SI of LCT: severe injury of the left coronary trunk, ASA: acetylsalicylic acid, ACE: angiotensin converting enzyme angiotensin BB: beta- blocker

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Table 2. Postoperative evolution of the study population: univariate analysis. Variable AMI Yes No Stroke Yes No AF Yes No ARF Yes No Vasopressor Yes No CPB >90 min ≤90 min Bleeding Yes No Reinterven. Yes No Tranfusions Yes No Swan-Ganz Yes No Death Yes No

Total 2794 (100%)

UA 1007 (36.0%)

n UA 1787 (64.0%)

CI 95%

412 (14.6%) 2406 (85.4%)

158 (15.6%) 858 (84.4%)

254 (14.1%) 1548 (85.9%)

1.12

0.90 – 1.39

0.29

82 (2.9%) 2736 (97.1%)

29 (2.9%) 987 (97.1%)

53(2.9%) 1749 (97.1%)

0.97

0.61 – 1.53

0.89

572 (20.3%) 2246 (79.7%)

196 (19.3%) 820 (80.7%)

376 (20.9%) 1426 (79.1%)

0.90

0.75 – 1.09

0.31

203 (7.2%) 2615 (92.8%)

71 (7.0%) 945 (93.0%)

132 (7.3%) 1670 (92.7%)

0.95

0.70 – 1.28

0.74

670 (23.8%) 2148 (76.2%)

245 (24.1%) 771 (75.9%)

425 (23.6%) 1377 (76.4%)

1.03

0.86 – 1.23

0.75

1078 (39.7%) 1636 (60.3%)

373 (37.9%) 610 (62.1%)

705 (40.7%) 1026 (59.3%)

0.89

0.75 – 1.04

0.98

315 (11.2%) 2503(88.8%)

122 (12%) 894 (88%)

193 (10.7%) 1609 (89.3%)

1.13

0.89 – 1.44

0.29

137 (4.4%) 2681(95.1%)

42 (4.1%) 974 (95.9%)

95 (5.3%) 1707 (94.7%)

0.77

0.53 – 1.12

0.17

698 (24.8%) 2120 (75.2%)

276 (27.2%) 740 (72.8%)

422 (23.4%) 1380 (76.6%)

0.02

1.02 – 1.45

1.22

47 (1.7%) 2771 (98.3%)

24 (2.4%) 992 (97.6%)

23 (1.3%) 1779 (98.7%)

1.87

1.05 – 3.33

0.03

152 (5.4%) 2666 (94.6%)

42 (4.1%) 974 (95.9%)

110 (6.1%) 1692(93.9%)

0.66

0.46 – 0.95

0.026

UA: unstable angina, OR: odds ratio, CI: confidence interval, P: statistical significance, AMI: acute myocardial infarction, Stroke, AF: atrial fibrillation, ARF: acute renal failure, CPB: cardiopulmonary bypass, min.: minutes

Table 3. Multivariate analysis of preoperative factors and associated outcomes in patients with unstable angina during preoperative period of isolated CABG. VARIABLE Female AAS BB Diuretic Full Heparin Nitrate Swan-Ganz Preop IAB Length of hospital stay Death

OR 1.41 1.62 1.19 0.57 2.01 1.63 1.93 1.52 1.01 0.64

CI 95% 1.19 – 1.67 1.35 – 1.95 0.99 – 1.43 0.47 – 0.70 1.69 – 2.38 1.37 – 1.94 1.03 – 3.61 1.12 – 2.07 1.01 – 1.02 0.44 – 0.93

P <0.001 <0.001 0.055 <0.001 <0.001 <0.001 0.039 0.007 0.030 0.018

OR: odds ratio, CI: confidence interval, P: statistical significance ASA: acetylsalicylic acid, BB: beta-blocker, IABP: preop intra-aortic balloon

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additional risk to patients undergoing CABG, deserving score in their scores, but when alone does not alter the risk, so when presenting this feature as an isolated risk factor it remains as low risk. On the other hand, score developed at the Hospital SĂŁo Lucas/PUCRS found no increased risk of operative mortality and in-hospital postoperative of CABG in patients with signs of UA, not receiving score [11]. The use of Swan-Ganz catheter was significantly higher in patients with UA in preoperative of CABG. Most invasive monitoring was not associated with higher rates of cardiogenic shock, postoperative infarction or sepsis, since the use of diuretics was significantly lower in this group of patients (OR 0.57), possibly due to the use of this tool. The increased use of Swan-Ganz could be related as a marker of severity for this group of patients. Nevertheless, obtaining specific hemodynamic parameters, contributed to lower outcomes postoperatively. Monitoring of fluid replacement is a fundamental aspect to be avoided complications caused by overload or lack of volume in the intravascular space. The use of invasive hemodynamic monitoring in the postoperative period of cardiac surgery in patients with hemodynamic instability is useful in guiding the control of plasma volume, use of vasoactive drugs, requiring circulatory assistance. Another fact to be noted is that there is no reliable correlation between central venous pressure (CVP) and pulmonary capillary pressure (PCP), and the control of blood volume according to CVP is not safe [12]. However, studies show that these valuesâ&#x20AC;&#x2039;â&#x20AC;&#x2039; are somewhat inaccurate with respecti to assessment of blood volume, especially in patients on mechanical ventilation due to changes in systolic volume induced by preload also which depend on contractility and afterload, which are not assessed by these parameters. Other methods such as echocardiography and transesophageal Doppler with measurements of aortic flow and end-diastolic volume are interesting options with drawback of relying on experienced operator and can not be used continuously for a long period of time. Another sensitive indicator of response to blood volume in mechanically ventilated patients is the change in systolic blood pressure and its ddown, with good correlation with negative deflection and fluid infusion and concomitant improvement in cardiac output and increase in atrial filling pressures [13]. The need for intra-aortic balloon was also significantly higher in the group with UA, which may represent the most severity of these when compared to the group without acute event in the preoperative of CABG alone. The indication of intra-aortic balloon in our service is limited to low ejection fraction (< 30 %), cardiogenic shock, severe injury to the left main coronary (> 50 %) and intractable angina, the latter being the main reason for using this study. Even needing this support preoperatively, death rates were lower.

Fig. 1 - Rates of death, use of statins, beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), diuretic, Heparin (heparin) and nitrate in patients with unstable angina (UA) and without preoperative surgical myocardial revascularization. Analysis of the period between 1996 - 2003, total of 1799 patients

Fig. 2 - Rates of death, use of statins, beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), diuretic, Heparin (heparin) and nitrate in patients with unstable angina (UA) and without preoperative surgical myocardial revascularization. Analysis of the period 2004 - 2010, total of 1019 patients

DISCUSSION The risk scores that estimate the risk of operative mortality and morbidity of heart surgery in adults based on demographic and clinical variables, such as the European System Risk in Cardiac Operations (EuroSCORE) and the Society of Thoracic Surgeons (STS), consider the UA as

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The benefits of intra-aortic balloon were studied by Santarpino et al. [14], which assessed the use of intra-aortic balloon in the preoperative period of CABG of high risk (EuroSCORE>12) and found similar outcomes to low risk CABG (EuroSOCORE<5) without the device, with low rates of associated complications, advocating a more liberal use of intra-aortic balloon, especially in high-risk CABG. Macruz et al. [15] retrospectively assessed the early (intraoperative) and late (postoperative) use of intra-aortic balloon. 130 patients were studied at Texas Heart Institute. Data from this study suggest that the intra-aortic balloon is effective as a method of circulatory support in patients with low cardiac output after cardiopulmonary bypass, with a tendency to better results when used early; it was observed influence of age and CPB time, suggesting that more efficient methods of circulatory support should be used in elderly patients and in patients with low cardiac output syndrome after cardiac surgery with CPB times greater than 120 minutes. Females had an odds ratio of 1.4 for UA in the preoperative of CABG. It is believed that the behavior of coronary heart disease is different between genders. Campbell et al. [16] compared the histological structure of the myocardium and coronary microvasculature of men and women and found differences in the arterioles wall and the ratio of the cardiac myocyte and body surface area that can justify the presence of ischemic symptoms in more frequent in females, although not always correlating with more severe coronary artery disease than in males. Hasdai et al. [17] assessed the outcome of 10,000 patients after ACS in relation to gender and observed in this record that females had older age, no association with increased mortality, lower use of antiplatelet agents (such as glycoprotein IIbIIIa) and less use of less beta blockers, antiplatelet and statin, and more diuretics and digoxin at discharge [17]. Although studies suggest female as a risk indicator for CABG and being part of the scores [18], others did not confirm this risk in the context of ACS [19-21], as well as the present study. The length of stay was longer in patients with UA in preopearative of CABG, at the expense of longer wait times for CABG, and not due to prolonged ventilation, need for vasopressors, sepsis and delirium. There are no clear recommendations on which the ideal timeout for conducting CABG after UA. The advantages of early CABG for the treatment of UA include limiting the area of ischemia and left ventricular remodeling, however, it can lead to reperfusion injury and further damage to the myocardium, thereby increasing the systemic inflammatory response [22]. The optimal time interval between the ACS and CABG is still controversial. The PL-ACS registry included 2028 patients with acute coronary syndrome (ACS), in which 55% had UA and indication for CABG, 60% underwent surgery at different time intervals. They concluded that after 12 months of waiting for CABG the risk of death rises in twice

and CABG performed during the first month after ACS is associated with increased prevalence of mortality, considering the ideal interval to wait between 1-3 months [22]. This result is different compared to the found in this study, in which the average waiting time was 11.7 days; unrelated to increased mortality, probably due to not including patients with acute transmural myocardial infarction. Weiss et al. [23], in a study with analysis of records of more than 40,000 patients with ACS, including transmural infarction, observed that patients undergoing CABG in 2 days of hospitalization had higher mortality rates than those who were taken to surgery with waiting time of three or more days of hospitalization in non-emergency cases, suggesting that the optimal time interval between CABG after ACS should be greater than or equal to 3 days. Costa et al. [24] found similar conclusion after comparing outcomes between two groups of patients waiting for less than 30 days and more than 30 days undergoing CABG: overall mortality was 5.9 % (1 death in 15 patients in Group I and 1 death in 19 patients in group II - P=1.0); they argue that CABG can be performed safely, especially after the first 72 hours of the ischemic event. The UA in preoperative of CABG alone, different from the expected, showed a lower rate of in-hospital mortality in this study, compared with the group without UA, even with higher surgical risk by assessing the logistic EuroSCORE in this group (5.19 compared with 3.30 of the patients without preoperative UA P=0.012). Possibly by the fact that this sample of patients with signs of UA has received optimized medical treatment, compared with the group with no UA, such as greater use of acetylsalicylic acid, beta-blockers, full-dose heparin and nitrate (OR 1.62; 1.19, 2.01, 1.63 , respectively) compared with those who did not have the acute event. But the use of diuretics was significantly lower in this group of patients (OR 0.57). This fact reveals the great importance in medical management for all groups. The average mortality rate was 5.4 %. Mortality in patients with preoperative UA undergoing isolated CABG was 4.1 %, versus 6.1% in the group without acute event in this study. The death rate is similar to that presented by other authors as Kaul et al. [18] (5.9%), Hochman et al. [25] (4.3%), Howard et al. [26] (4.3%) and Jatene et al. [21] (4.1%), in the context of ACS. However, when we compared the mean death for periods, we observe that there is a significant difference when assessing the period 1996-2003 (4.3%) and 2004-2010 (7.3%) P=0.001, despite advances in treatment and management of ischemic patients undergoing CABG, with greater use of statins, beta-blockers, angiotensin-converting enzyme inhibitors and acetylsalicylic acid, which can be explained by the increased complexity of patients undergoing CABG, with more comorbidities, age and more complex pathologies. When assessing patients with UA undergoing isolated CABG in the period 1996-2003, we found that this group

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of patients showed a lower mortality rate compared to those without UA and that there was no significant difference in death rate between the patients with and without UA in the period 2004-2010. In this period, the optimal medical treatment did not appear to reduce mortality, perhaps because both groups of this period present more uniform clinical treatment and management, particularly regarding the use of beta-blockers and angiotensin converting enzyme angiotensin.

disease in patients with unstable angina compared with stable angina. Circulation. 2002;105(20):2367-72. 3. Luksienè D, Milvidaitè I, Slapikas R, Jarusevicius G, Siudikas A, Venclovienè J, et al. The impact of myocardial revascularization after acute coronary syndromes on one-year cardiovascular mortality. Medicina (Kaunas). 2011;47(6):305-12. 4. Weber MM. Surgical management of unstable angina and symptomatic coronary artery disease. J Cardiovasc Nurs. 2000;15(1):27-42.

Limitations Although the data collection was performed prospectively, the data analysis was performed retrospectively, and data were not collected for the specific purpose of this analysis. Thus, some important issues were not raised as a risk assessment according to the scores of acute coronary syndrome as TIMI score or GRACE, which would enable a more detailed assessment regarding the severity of patients preoperatively. Another limitation is the monitoring of the patient, performed until hospital discharge of which we have no data on outcomes after this time.

5. Sociedade Brasileira de Cardiologia. Guidelines for Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction of the Brazilian Society of Cardiology (II Edition, 2007). Arq Bras Cardiol. 2007;89(4):e89-131. 6. Bonow RO, Zipes DP, Libby P. Braunwald: tratado de doenças cardiovasculares. 8ª ed. Rio de Janeiro:Elsevier; 2009. p.1319. 7. Naschef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16(1):9-13. 8. Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(23):e652-735.

CONCLUSION The present study showed that patients with UA undergoing isolated CABG showed no increased mortality. Rather, possibly because they have received better medical treatment, and invasive monitoring and hemodynamic support more frequently, patients with UA had lower death rates than those considered stable.

9. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, et al. Guidelines on myocardial revascularization. Eur Heart J. 2010;31(20):2501-55.

Authors' roles & responsibilities

10. Guaragna JCVC. Cirurgia cardíaca e hipertensão arterial no pósoperatório imediato: fatores pré e transoperatórios [Dissertação]. Porto Alegre: Pontíficia Universidade Católica do Rio Grande do Sul; 1999.

CPS Main author JCG Coauthor RSC Coauthor JP Coauthor LCA Coauthor MAG Coauthor JBP Coauthor LCB Coauthor

11. Cadore MP, Guaragna JCVC, Anacker JFA, Albuquerque LC, Bodanese LC, Piccoli JCE, et al. Proposição de um escore de risco cirúrgico em pacientes submetidos à cirurgia de revascularização miocárdica. Rev Bras Cir Cardiovasc. 2010;25(4):447-56.

REFERENCES

12. Dragosavac D, Araújo S, Carieli MCM, Terzi RGG, Dragosavac S, Vieira RW. Monitorização hemodinâmica invasiva no pós-operatório de cirurgia cardíaca. Arq Bras Cardiol. 1999;73(2):129-38.

1. Movahed MR, John J, Hashemzadeh M, Hashemzadeh M. Mortality trends for non-ST-segment elevation myocardial infarction (NSTEMI) in the United States from 1988 to 2004. Clin Cardiol. 2011;34(11):689-92.

13. Carlos RV, Bittar CS, Lopes MR, Auler Júnior JOC. Variação da pressão sistólica como método diagnóstico da hipovolemia durante anestesia para cirurgia cardíaca. Rev Bras Anestesiol. 2005;55(1):3-18.

2. Feyter PJ, Serruys PW, Unger F, Beyar R, Valk V, Milo S, et al. Bypass surgery versus stenting for the treatment of multivessel

14. Santarpino G, Onorati F, Rubino AS, Abdalla K, Caroleo S, Santangelo E, et al. Preoperative intraaortic ballon

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pumping impoves outcomes for high-risk patients in routine coronary artery bypass graft surgery. Ann Thorac Surg. 2009;87(2):481-8.

days of acute myocardial infarction. Early and late results in 406 patients. J Thorac Cardiovasc Surg. 1991;102(5):745-52. 21. Jatene FB, Nicolau JC, Hueb AC, Atik FA, Barafiole LM, Murta CB, et al. Fatores prognósticos da revascularização na fase aguda do infarto agudo do miocárdio. Rev Bras Cir Cardiovasc. 2001;16(3):195-202.

15. Macruz HMS, Frazier OH, Cooley DA. Análise dos resultados do uso precoce e tardio da assistência circulatória com balão intra-aórtico (BIA) em pacientes submetidos a correção de cardiopatias com auxílio de circulação extracorpórea. Rev Bras Cir Cardiovasc. 1995;10(4):190-7.

22. Zembala M, Trzeciak P, Gasior M, Gierlotka M, Hudzik B, Taistra M, et al. Optimal timing for surgical revascularization in survivors of acute coronary syndromes elegible for elective coronary artery bypass graft surgery. Int J Cardiol. 2011;153(2):173-8.

16. Campbell DJ, Somaratne JB, Jenkins AJ, Prior DL, Yii M, Kenny JF, et al. Differences in myocardial structure and coronary microvasculature between men and women with coronary artery disease. Hypertension. 2011;57(2):168-92.

23. Weiss ES, Chang DD, Joyce DL, Nwakanma LU, Yuh DD. Optimal timing of coronary artery bypass after acute myocardial infarction: a review of California discharge data. J Thorac Cardiovas Surg. 2008;135(3):503-11.

17. Hasdai D, Porter A, Rosengren A, Behar S, Boyko V, Battler A. Effect of gender on outcomes of acute coronary syndromes. Am J Cardiol. 2003;91(12):1466-9.

24. Costa WA, Santos JMV, Sampaio DT, Lobo Jr. NC, Figueroa CCS. Cirurgia de revascularização do miocárdio no paciente infartado: quando operar? Rev Bras Cir Cardiovasc. 1999;14(1):19-26.

18. Kaul TK, Fields BL, Riggins SL, Dacumos GC, Wyatt DA, Jones CR. Coronary artery bypass grafting within 30 days of an acute myocardial infarction. Ann Thorac Surg. 1995;59(5):1169-76.

25. Hochman JS, Boland J, Sleeper LA, Porway M, Brinker J, Col J, et al. Current spectrum of cardiogenic shock and effect of early revascularization on mortality. Results of an International Registry. SHOCK Registry Investigators. Circulation. 1995;91(3):873-81.

19. Naunheim KS, Kesler KA, Kanter KR, Fiore AC, McBride LR, Pennington DG, et al. Coronary artery bypass for recent infarction. Predictors of mortality. Circulation. 1988;78(3 Pt 2):I122-8.

26. Howard M, Irarrazaval MJ, Corbalán R, Morán S, Zalaquett R, Maturana G, et al. Surgical myocardial revascularization during the 1st 15 days of evolution of acute myocardial infarction. Rev Med Chil. 1996;124(1):37-44.

20. Applebaum R, House R, Rademaker A, Garibaldi A, Davis Z, Guillory J, et al. Coronary artery bypass grafting within thirty

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Breda JR,SHORT et al. - Ventricular assist device implantation with CentriMag VAS® COMMUNICATION for biventricular mechanical support

Ventricular assist device implantation with CentriMag VAS® for biventricular mechanical support Assistência ventricular com implante do dispositivo CentriMag VAS® para suporte mecânico biventricular

João Roberto Breda1, MD, PhD; Diego Felipe Gaia1, MD, PhD; Murilo Macedo1, MD; Pedro Motta1, MD; Márcio Martins1, MD; Daniel Alves1, MD; Andre Luppi1, MD; José Honório Palma1, MD, PhD

DOI: 10.5935/1678-9741.20130061

RBCCV 44205-1487

Abstract Despite recent advances in acute heart failure treatment, actual results remain limited in refractory cardiogenic shock. Temporary ventricular assist devices have emerged as an alternative in this serious and challenging medical. The purpose of this communication is to present a case of refractory cardiogenic shock, underwent temporary left ventricular assistance device implantation, progressing to right ventricular failure and conversion to biventricular support.

Resumo Apesar dos avanços no tratamento de portadores de insuficiência cardíaca aguda, os resultados permanecem insatisfatórios nos portadores de choque cardiogênico refratário. Uma opção para o tratamento dessa desafiadora e grave situação clínica é o implante de dispositivos de assistência ventricular temporária. O objetivo desta comunicação é apresentar um caso de choque cardiogênico refratário, com indicação de assistência ventricular, que evoluiu com falência ventricular direita após o implante de assistência esquerda com necessidade de conversão para o suporte biventricular.

Descriptors: Shock, cardiogenic. Ventricular dysfunction, right. Ventricular dysfunction, left.

Descritores: Choque cardiogênico. Disfunção ventricular direita. Disfunção ventricular esquerda.

INTRODUCTION

offer an alternative for the treatment of this serious and challenging medical issue. Although there are still some doubts about the ideal type of assistance, the length of stay of the device, and the best time to start long-term treatment, this technology should be more employed and disseminated [1]. Initially, these devices were used in case of heart failure after the removal of cardiopulmonary bypass during open heart

Despite recent advances in the treatment of acute heart failure, results remain unsatisfactory for patients with refractory cardiogenic shock. These patients are often referred to specialized centers when it is too late, which leads to adverse results. Temporary ventricular assist devices

Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Correspondence Address: João Roberto Breda UNIFESP - Rua Borges Lagoa, 1080 - Vila Clementino, São Paulo, SP, Brazil. Zip code: 04038-002. E-mail: jrbreda@hotmail.com.br

Work performed at Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

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Article received on November 22nd, 2012 Article accepted on March 7th, 2013

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left ventricular function (ejection fraction of 16%), with mild to moderate right ventricular dysfunction. After discussing the refractory cardiogenic shock diagnosis with several experts, the recommended procedure was emergency temporary left ventricular assist device implantation, with the Levitronix CentriMag (VAS)® device. The procedure was performed with normothermic cardiopulmonary bypass (CPB), without aortic clamping. Suitable cannulas were inserted at the left ventricle apex and ascending aorta. After the removal of CPB, the device was set for 3200 rotations per minute (RPM) with a flow of 4.5 L/min/ m² and continuous infusion of vasoactive drugs. Postoperative hemodynamic conditions were improved, with the return of diuresis (approximately 1 ml/Kg/hour), venous oxygen saturation of 75%, and serum lactate of 22 mmol/L. Six hours after the procedure, the patient was awake and had neither neurological deficits nor bleeding from coagulopathy.

Abbreviations, acronyms & symbols CI CO CPB RV

Cardiac index Cardiac output Cardiopulmonary bypass Right ventricle

surgery; however, their use has changed and spread to other kinds of therapy, such as support therapy for patients waiting for a heart transplant or as a choice of destination therapy. The Levitronix CentriMag (Levitronix LLC, Waltham, Mass) - Ventricular Assist System (VAS)® device has been especially designed for the treatment of patients with acute cardiogenic shock of any kind, including: acute myocardial infarction, myocarditis, postcardiotomy, and complications after procedures carried out in the hemodynamic laboratory. It can be used for the support of the left or right ventricles as well as for biventricular support. In addition, since its handling and implantation are considered easy, the device can even be used in centers where prolonged ventricular assistance programs and heart transplants are not available [2]. Several authors have established an increase in mortality of patients with right ventricular dysfunction after they were treated with these devices. They concluded there is a need to identify factors predictive of right ventricular failure after left ventricular assist device implant, making it possible to decide for biventricular implantation preoperatively [3]. The purpose of this communication is to present a case of refractory cardiogenic shock, in which the patient underwent left ventricular assist device implantation, progressing to right ventricular failure, and subsequent conversion to biventricular support. CLINICAL CASE

Fig. 1 – Chest radiograph

A 36-year-old male was admitted to the Intensive Care Unit after a two-week stay at another hospital with clinical, hemodynamic, and echocardiographic picture suggestive of severe refractory cardiogenic shock (he was using more than one vasoactive drug at optimized doses). The patient had had viral myocarditis two years before and had been suffering from progressive dyspnea, which had worsened in the previous six months. A month before being admitted, there was intensive worsening with dyspnea at rest, orthopnea, paroxysmal nocturnal dyspnea, and anasarca. Upon admittance, hemodynamic monitoring was performed through the insertion of a Swan-Ganz catheter, with the following parameters: cardiac index (CI) at 1.3 L/min/m², cardiac output (CO) at 2.5 L/min, right atrium pressure at 18 mmHg, pulmonary artery pressure at 66x30 mmHg, and pulmonary capillary pressure at 23 mmHg. The chest radiograph can be seen in Figure 1. The two-dimensional transthoracic echocardiography showed severely impaired

However, after 12 postoperative hours, there was substantial reduction in urine volume, increase in the right atrium pressure, and decrease in the pulmonary artery pressure. The right ventricular failure diagnosis was corroborated by the echocardiography, which showed there was a sharp decrease in right ventricular contractility. Consequently, the patient was once again taken to the operating room for right ventricular assist implantation, with pulmonary artery and right atrium cannulation, without CPB (Figure 2). Once appropriate flows were established (kept at 10% less on the right side), the patient was taken to the postoperative unit. Even though the biventricular assist device and the optimized vasoactive drugs were working properly, evolution was unsatisfactory with the development of anuria and a hard

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to control coagulopathy (liver failure), leading to death 38 hours after the procedure. The indication of the procedure was carried out according to ethical principles. Both the patient and his relatives agreed to the procedure and signed the informed consent form provided by the hospital.

avoiding multiple organ failure by re-establishing systemic perfusion. Preoperative laboratory evaluations did not reveal any alterations in liver and kidney function parameters, nor thrombocytopenia, underscoring the need for immediate support. The choice of this device was based on its versatility, mono- or biventricular support, and the possibility of interposition of oxygenator for ventilatory support, if needed. Moreover, the device could be used for several weeks until destination therapy was chosen and cannulas that were exteriorized in the chest could be used for a long-term device. After a multidisciplinary discussion, it was decided a long-term device would be a better option than ECMO (Extracorporeal membrane oxygenation) considering that, currently, it takes a long time for a heart to be available for transplant. Despite the great technological advances of these devices, mortality in this group of patients remains high due to complications such as infection, bleeding, and embolism [3]. In 2011, a multicenter study with the CentriMag (VAS)® device described the effectiveness of the pump in emptying both ventricles and acting as a biventricular circulatory support in cases of cardiogenic shock. Overall mortality was 47% out of 38 patients and the benefits of using the device included: easy handling and implantation, low incidence of complications related to the device, and support until final course of treatment [1]. In 2012, the results of the use of Centrimag (VAS)® in 12 patients with cardiogenic shock and multiple organ dysfunction, published by John et al., showed overall survival of 75% thirty days after the implantation [4]. In the present case, the ease of both handling and implantation of the Centrimag (VAS)® device was confirmed; however, right ventricular failure was considered a major factor in the adverse development which culminated in the employment of biventricular support. Although the initial intention was the immediate implantation of the biventricular device, it was decided not to do so because of the hemodynamic conditions after left ventricular support implantation (after removal of CPB, it was noted there was improvement in right ventricular contractility, as confirmed by clinical, hemodynamic, and echocardiography parameters). It seems essential to predict right ventricular failure. Fitzpatrick et al. [5] have shown that the conversion from left to biventricular support have worse results when compared to an insertion that had been previously indicated and performed at the same time. Furthermore, the authors demonstrated that despite a higher mortality in the biventricular support group, survival rate after transplant is the same in both groups (mono- or biventricular). After reviewing the case, it became apparent the decision not to implant the biventricular support may have influenced the evolution, considering the subsequent conversion to the biventricular system. For this reason, in another related

Fig. 2 – A – Right atrium cannula; B – Ascending aorta cannula; C – Pulmonary artery cannula

DISCUSSION Temporary assist devices are used as rescue therapy in order to re-establish hemodynamic conditions and avoid multiple organ failure, until a decision is made regarding whether to have prolonged assistance or a heart transplant. It is important to note that clinical and hemodynamic criteria are used in the selection of candidates for mechanical circulatory support devices implantation. Some of the important clinical factors taken into consideration are: age (65 to 70 years-old), refractory cardiogenic shock due to the use of vasoactive drugs in high doses combined with persistent hypotension, and preoperative factors associated with poor prognosis (acute liver or renal failure, cerebrovascular disease, active infectious process, and thrombocytopenia). Hemodynamic factors are important for the likely identification of right, left, and/or biventricular failure, and are obtained by determining cardiac index, right atrium pressure, pulmonary capillary pressure, and systolic arterial pressure. In the case being presented in this communication, the fact the patient was young was taken into consideration. In addition, despite the severity of the hemodynamic conditions at the time of admittance, no clinical criteria that would prevent a circulatory support device implantation were identified. On the contrary, there was the potential benefit of

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publication, Fitzpatrick et al. [6] showed the main factors involved in right ventricular failure are: cardiac index (below 2.2 L/min/mÂ˛), right ventricular (RV) systolic work index (below 0.25 mmHg), severe preoperative RV dysfunction, higher levels of plasma creatinine (above de 1.9 mg/dL), previous cardiac surgery, and systolic arterial pressure below 96 mmHg. There have been many advances in the treatment of patients with chronic heart failure; however, in cases of severe cardiogenic shock, results are still below expectations. Many times, unfavorable results are related to unavailability of mechanical ventricular support as well as the critical conditions of patients referred to specialized centers. In the case presented in this communication, the need for biventricular support after the mono-ventricular implantation was highlighted as a complicating factor.

REFERENCES 1. John R, Long JW, Massey HT, Griffith BP, Sun BC, Tector AJ, et al. Outcomes of a multicenter trial of the Levitronix CentriMag ventricular assist system for short-term circulatory support. J Thorac Cardiovasc Surg. 2011;141(4):932-9. 2. Mueller JP, Kuenzli A, Reuthbuch O, Dasse K, Kent S, Zuend G, et al. The CentriMag: a new optimized centrifugal blood pump with levitating impeller. Heart Surg Forum. 2004;7(5):E477-80. 3. Worku B, Naka Y, Pak SW, Cheema FH, Siddiqui OT, Jain J, et al. Predictors of mortality after short-term ventricular assist device placement. Ann Thorac Surg. 2011;92(5):1608-12. 4. John R, Liao K, Lietz K, Kamdar F, Colvin-Adams M, Boyle A, et al. Experience with the Levitronix CentriMag circulatory system as a bridge to decision in patients with refractory acute cardiogenic shock and multisystem organ failure. J Thorac Cardiovasc Surg. 2007;134(2):351-8. 5. Fitzpatrick JR 3rd, Frederick JR, Hiesinger W, Hsu VM, McCormick RC, Kozin ED, et al. Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device. J Thorac Cardiovasc Surg. 2009;137(4):971-7.

Authors' roles & responsibilities JRB DFG MM PM MM DA AL JHP

Main author, writing and documentation Review of the paper Data collection Data collection Data collection Data collection Bibliographic research Review and guidance

6. Fitzpatrick JR 3rd, Frederick JR, Hsu VM, Kozin ED, O`Hara ML, Howell E, et al. Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support. J Heart Lung Transplant. 2008;27(12):1286-92.

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Soubihe Junior NV,COMMUNICATION et al. - Presentation of a needle for direct or percutaneous SHORT myocardium stem cells injection

Presentation of a needle for direct or percutaneous myocardium stem cells injection Apresentação de uma agulha para injeção direta ou percutânea de células tronco no miocárdio

Nathan Valle Soubihe Junior1, MD; Andre Schmidt1, MD, PhD; Agnes Afrodite Sumarelli Albuquerque1, BsC; Paulo Roberto Barbosa Evora1, MD, PhD;

DOI: 10.5935/1678-9741.20130062

RBCCV 44205-1488

Abstract The instrument has a locking mechanism and is composed of an external needle with blunt tip, with multiple 0.5 mm diameter holes. Internally it is fitted with a mandrill needle, which can be mobilized inside occluding or releasing the lateral holes. The procedure for producing micro lesions is done by exchanging the blunt mandrill for a brush-mandrill, provided with micro bristles that are structurally designed to fill the holes with small exteriorization of bristles. As an option to brush mandrill there is a second self-expandable feather shaped mandrill.

Resumo O instrumento tem um mecanismo de bloqueio e é composto por uma agulha externa de ponta romba com vários furos de diâmetro de 0,5 mm. Internamente é equipada com uma agulha de mandril, que pode ser mobilizada ocluindo ou liberando os orifícios laterais. O procedimento para a produção de microlesões é feito por meio da troca do mandril de ponta romba por um mandril escova provido de microcerdas metálicas estruturalmente concebidas para preencher os orifícios com a exteriorização das pequenas cerdas. Como alternativa para mandril escova há um segundo mandril autoexpansível com o formato de uma pequena pena.

Descriptors: Stem cells. Myocardial infarction. Biopsy. Myocardium.

Descritores: Células-tronco. Infarto do miocárdio. Biópsia. Miocárdio.

INTRODUCTION

percutaneous routes was demonstrated in 1956 [4]. These old experiences proved that the heart tolerated these procedures very well, the myocardium quickly contracting around the small effect so that bleeding spontaneously ceased. Studies on stem cells, based on laboratory data demonstrate functional improvement and reduction of myocardial ischemia when used in animals with acute myocardial infarction. Animal studies have shown different results, depending on the route used for the injection of the cells.

Sutton et al. [1] wrote, in 1964, a brief historical review reporting that percutaneous introduction of a needle into the cardiac ventricular cavities of human beings was performed many years ago for therapeutic reasons. Summaries of indications and technics were published by Henschen [2] and Lauter [3]. The feasibility of obtaining ventricular myocardial specimens from human beings either by open or closed

Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Correspondence address: Paulo Roberto Barbosa Evora Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo Avenida Bandeirantes, 3900 – Monte Alegre – Ribeirão Preto, SP, Brazil – Zip Code: 14048-900 E-mail: prbevora@fmrp.usp.br

Work carried out at Faculty of Medicine of Ribeirão Preto – USP (FMRP-USP), Ribeirão Preto, SP, Brazil. Work funded by CNPq, FAPESP, FAEPA and USP

Article received on April 7th, 2013 Article accepted on June 25th, 2013

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Soubihe Junior NV, et al. - Presentation of a needle for direct or percutaneous myocardium stem cells injection

There is a clear superiority of results when direct myocardial injections are compared with intracoronary injections. Alternative methods of application of cell therapy products in myocardial infarction, acute or subacute, were tested. Direct injection as adjunctive therapy to revascularization surgery is a viable proposition, but it caters to a select group of patients referred for surgical revascularization immediately after an acute ischemic event [5-8]. The aim of this presentation is to describe a method of percutaneous puncture and injection of stem cells in the myocardium. This device is an adaptation Soubihe needle that was used in the fifties and sixties for myocardial biopsies [9]. METHODS Fig. 2 – Photo presentation. A: Locking mechanism; B: External needle with blunt tip, with multiple 0.5 mm diameter holes. C: Brushmandrill; D: Self-expandable feather shaped mandrill

The instrument is equipped with a locking mechanism, which allows its perfect mobilization as one single unit for micro lesions, and it can be used only as a needle, so it becomes a biological injection instrument. The instrument for myocardium puncturing and injection of biological material is composed of an external needle, which contains at its end a blunt tip and multiple 0.5 mm diameter holes. Internally it is fitted with a blunt mandrill, which when introduced into the external needle, can be mobilized inside to fill the lateral holes occluding or releasing them. This instrument is harmless to myocardial fibers and coronaries as it had been proved when its first designed shape was used to perform heart biopsies, in the past (Figures 1 and 2).

The main objective of the puncturing procedure is to release steam cells into the myocardium. For that, micro lesions should be performed to “receive” the stem cells. The procedure for producing micro lesions is done by exchanging the blunt mandrill by a brush-mandrill, provided with micro bristles that are structurally designed to fill the holes with small exteriorization of bristles. As an option to brush mandrill there is a second self-expandable feather shaped mandrill. DISCUSSION A very important characteristic of this instrument is safety. The blunt end of the needle guaranties that during the punching process, in case of unexpected touch of a coronary artery, the vessel will not be hurt or cut, but the needle will slide sideways from it. Therefore, steam cells are injected into the heart while it is perfectly pumping, with the chest unopened. A real possibility is the direct intramyocardial injection during thoracotomy through specific or during the surgical treatment of coronary artery disease [10,11].

Fig. 1 – Schematic presentation. The instrument has a locking mechanism (1,2,3) and is composed of an external needle with blunt tip, with multiple 0.5 mm diameter holes (4,5). Internally it is fitted with a mandrill needle, which can be mobilized inside occluding or releasing the lateral holes. The procedure for producing micro lesions is done by exchanging the blunt mandrill for a brush-mandrill, provided with micro bristles that are structurally designed to fill the holes with small exteriorization of bristles (6). As an option to brush mandrill there is a second self-expandable feather shaped mandrill (7)

Authors’ roles & responsibilities NVSJ AS AASA PRBE

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ACKNOWLEDGEMENTS

5. Strauer BE, Kornowski R. Stem cell therapy in perspective. Circulation. 2003;107(7):929-34.

To FAPESP, CNPq, FAEPA and University of São Paulo for funding the research. To Dr. José Eduardo Krieger and Dr. Rafael Dariolli for their support and guidance during preliminary testing needle in INCOR-SP.

6. Perin EC, Geng YJ, Willerson JT. Adult stem cell therapy in perspective. Circulation. 2003;107(7):935-8. 7. Ladage D, Ishikawa K, Tilemann L, Müller-Ehmsen J, Kawase Y. Percutaneous methods of vector delivery in preclinical models. Gene Ther. 2012;19(6):637-41.

REFERENCES

8. Krause K, Jaquet K, Schneider C, Haupt S, Lioznov MV, Otte KM, et al. Percutaneous intramyocardial stem cell injection in patients with acute myocardial infarction: first-in-man study. Heart. 2009;95(14):1145-52.

1. Sutton GC, Driscoll JF, Gunnar RM, Tobin JR Jr. Exploratory mediastinotomy in primary myocardial disease. Progr Cardiovasc Dis. 1964;7:83-97.

9. Soubihe NV. Herzbiopsie. Thoraxchirurgie. 1961;9:31.

2. Henschen K. Die wiederbelebung des herzens dureh peri- und intrakardiale injektion dureh herzaderlass und herzinfusion. Schweiz Med Wchnschr. 1920;1:261.

10. Galantier M, Moreira GB, Bub RF, Galantier J, Buffolo E, Carvalho AC, et al. Revascularização transmiocárdica a laser. Rev Bras Cir Cardiovasc. 1996;11(2):67-74.

3. Lauter S. Kreislaufprobleme. Miinchener Med Wclmschr. 1930;77:526.

11. Dallan LA, Gowdak LH, Lisboa LA, Schettert I, Krieger JE, Cesar LA, et al. Cell therapy plus transmyocardial laser revascularization: a proposed alternative procedure for refractory angina. Rev Bras Cir Cardiovasc. 2008;23(1):46-52.

4. Kent G, Sutton DC, Sutton GC. Needle biopsy of the human ventricular myocardium. Q Bull Northwest Univ Med Sch. 1956;30(3):213-4.

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Costa MAC, et al.CASE - GiantREPORT thymic cyst with atypical location: case report

Giant thymic cyst with atypical location: case report Cisto tímico gigante com localização atípica: relato de caso

Mário Augusto Cray da Costa1, MD, PhD; Mário Rodrigues Montemor Netto1, MD, MSc; Joelmir Colman2; Gabriela Cordeiro da Costa3

DOI: 10.5935/1678-9741.20130063

RBCCV 44205-1489

Abstract A 47-year-old woman was admitted with a history of dyspnea on mild exertion as her only symptom. Clinical exam, laboratory tests, and electrocardiography were normal. Chest X-ray demonstrated right hemithorax base mass, and CT scan revealed a well-defined cystic mass measuring approximately 11.3 x 10.6 x 10.9 cm, suggesting the diagnosis of pericardial cyst. The patient underwent right thoracotomy for resection of the cyst. The patient’s progress- was uneventful. The result of histopathological examination, contrary to expectations, revealed thymic cyst.

Resumo Paciente do sexo feminino, 47 anos, admitida com queixa de dispneia aos pequenos esforços como único sintoma. Exames clínico, eletrocardiográfico e de laboratório normais. Radiografia de tórax demonstrou massa em base de hemitórax direito, que a tomografia computadorizada de tórax revelou tratar-se de massa cística bem delimitada, medindo cerca de 11,3 x 10,6 x 10,9 cm, sugerindo o diagnóstico de cisto pericárdico. A paciente foi submetida a toracotomia direita para ressecção do cisto. A paciente evoluiu sem intercorrências. O resultado do exame anatomopatológico, ao contrário do esperado, diagnosticou cisto tímico.

Descriptors: Mediastinal cyst. Thymus gland. Thoracotomy.

Descritores: Cisto mediastínico. Timo. Toracotomia.

INTRODUCTION

cysts due to the associated risk of malignancy (ATC), there is no consensus in the literature about whether to operate congenital thymic cyst (CTC) [2]. The following case describes a thymic cyst initially diagnosed as a pericardial cyst based on image exams.

Thymic cysts are infrequent benign lesions, comprising 1% to 3% of the lesions located in the anterior mediastinum [1]. They are usually asymptomatic, however, chest pain and dyspnea may occur [2]. Diagnosis is typically incidental, occurring during routine examinations (radiography and tomography, with anatomopathological examination required to differentiate it from other anomalous tissue) [3]. Thymic cysts are more prevalent in young and middle-aged adults and their origin can be congenital or acquired [1]. Despite surgical indication being well-established in acquired thymic

CASE REPORT A 47 year-old female patient was admitted with a history of dyspnea on mild exertion, progressing for three years. The patient had no history of cardiac or pulmonary disease, or any other pathology.

Santa Casa de Ponta Grossa, Ponta Grossa, PR, Brazil. Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil. 3 Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil.

Correspondence address: Mário Augusto Cray da Costa Av. General Carlos Cavalcanti, 4748 – Ponta Grossa, PR, Brazil – Zip code: 84030-900 E-mail: drmarioaugusto@uol.com.br

1 2

Work carried out at Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil.

Article received on March 20th, 2012 Article accepted on August 8th, 2012

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10.9 cm at its largest points, located in the middle lobe, in the anterior mediastinum, with internal attenuation of soft tissue and surrounded by a thin wall, which was discretely enhanced after endovenous contrast, indicating compression over the heart as it was in close contact with the heart and the right anterolateral chest wall (Figure 1A). The patient underwent right thoracotomy, which revealed a giant mass adhered to the right side of the pericardium and the right lung, and enveloping the right phrenic nerve (Figure 1B). The cyst, filled with a lumpy liquid, was dissected from the lung. Next, the mass was dissected from the pericardium, where part of the cyst wall (approximately 1 cm) was left along the phrenic nerve in order to avoid injuring it. The transoperative period was uneventful.

Abbreviations, acronyms & symbols ATC CTC

Acquired thymic cyst Congenital thymic cyst

Chest radiography showed hypotransparent image, irregular in the right hemithorax, suggestive of pericardial cyst. There were no cardiac alterations in the echocardiography, but there was a well-defined hypo-echoic mass, 10 x 12 cm in size, with thin walls and soft tissue in its interior structure, closely connected to the right atrium in its inferior surface, suggestive of pericardial cyst. Computed tomography showed a welldefined mass with regular margins, measuring 11.3 x 10.6 x

Fig. 1 - A: Computed tomography indicating well-defined mass with regular margins, in close contact with the heart and the right anterolateral chest wall. B: Right thoracotomy showing giant mass adhered to the right pericardial surface and the right lung. C: Hassall’s corpuscle (multiple layers of epithelial reticular cells arranged concentrically, in the shape of an “onion”). In general, reticular cells are in the center of the Hassall’s corpuscle, lined by a layer of medullary epithelial cells. D: Hassall’s corpuscle in the lesion (smaller increase)

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Patient was discharged on the fifth postoperative day. After the procedure, there was complete remission of the symptom. The anatomopathological exam identified cystic lesion wall with fibrosis and areas of dystrophic calcification associated with residual areas of hyperplastic thymic tissue and Hassall’s corpuscles (Figures 1C and D), indicating a diagnosis of congenital thymic cyst. The present case was reported with the express permission of the patient and the hospital.

visualization of septa and linear calcification of the wall [5]. Computed tomography is considered the method of choice for diagnosing mediastinal masses, as it allows for the differentiation of different types of cysts as well as from other diseases. It is important to differentiate between acquired and congenital lesions because, in ATC, histopathological analysis is needed to eliminate the possibility of neoplastic association [1]. The criteria to confirm the thymic cyst diagnosis is the presence of Hassall’s corpuscles and remnant thymic tissue, observed during microscopic analysis [6]. In terms of size, there was only one case of a thymic cyst measuring 11.5 x 6.8 x 9.0 cm in the literature [2]. In the present report, the patient’s cyst measured 11.3 x 10.6 x 10.9 cm, the largest ever recorded in the literature, at an unusual location in the anterior mediastinum. Differential diagnoses include malignant lesions, such as thymomas, teratoma, lymphomas, hemangiomas, fibrosarcoma, neuroblastoma [4], among others, and benign lesions, such as pericardial, bronchogenic, and branchial cysts [4,6-8], as well as other lesions in that region. The ideal approach to thymic cysts has not been well established yet. Most authors recommend resection of ATC,

DISCUSSION Thymic cysts can be classified as CTC or ATC [1,3] (Table 1). In general, thymic cysts are asymptomatic and diagnosis is done incidentally through image exams of the chest area. In addition, patient’s age can range from 30 to 60 years-old [2]. When symptomatic, the most reported symptoms are chest pain, cough, hoarseness, dyspnea, and dysphagia [1,3,4]. The patient described in this report was diagnosed at 47 years-old with dyspnea as her only symptom. Radiologically, thymic cysts are shown as well-defined anterosuperior mediastinal masses, with occasional

Table 1. Morphological differences between acquired and congenital thymic cysts Characteristic

Acquired thymic cyst

Congenital thymic cyst

Origin [1,3]

Inflammatory/Infectious (HIV, LES) or neoplastic (non-Hodgkin lymphoma, thymoma, thymic carcinoma, and mediastinal seminoma) processes

Thymopharyngeal duct or branchial cleft remnants and ectopic thymic tissue

Morphology [1,3]

Multilocular, fibrovascular proliferation, necrosis, hemorrhage, and formation of cholesterol granuloma and reactive lymphoid hyperplasia with multiple germination centers

Unilocular (usually), thin and translucent walls

Fluid [1]

Can become thick and bloody, light brown in color

Clear and acellular

Histopathology [2,6]

Cystic cavities are partially lined by squamous or columnar epithelium and can have capillary excrescences; scattered nests of non-neoplastic thymic tissue inside cyst walls. The surrounding stroma contains lymphoplasmacytic inflammatory infiltrate. Due to the chronic nature of the process, the cyst can degenerate and develop either a thick and calcified capsule or fibrous tissue

There is no evidence of inflammation; Epithelial surface of the cystic cavity is lined by squamous cells and there are no hemorrhages nor granulomas

Hassall’s corpuscles [6]

Hard to find since the inflammation destroys the cyst wall, replacing it with fibrosis; thus, causing degeneration of the corpuscle

Easily found

Location [2,6]

Usually in the anterior mediastinum

Usually in the neck

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due to the risk of malignancy. The resection can be performed through videothoracoscopy, longitudinal sternotomy, or thoracotomy [2]. In case of CTC, the approach can be more conservative; however, some authors are in favor of resection, since histological differentiation between ATC and CTC is needed for a definite diagnosis. The patient described here underwent right thoracotomy, procedure recommended based on the size and compression effect of the mass in addition to histological analysis being needed. The initial pericardial cyst diagnosis, which anatomopathological studies revealed it to be congenital thymic cyst, was significant.

2. Tiveron MG, Dias RR, Benvenuti LA, Stolf NAG. Cisto tímico como diagnóstico diferencial de doença aguda da aorta torácica. Rev Bras Cir Cardiovasc. 2008;23(4):575-7. 3. Nomori H, Horio H, Suemasu K, Orikasa H, Yamazaki K, Nakano K. A case of rapidly enlarging unilocular thymic cyst. J Clin Pathol. 2002;55(8):636-7. 4. Bastos P, Magalhães A, Fernandes G, Cruz MR, Saleiro S, Gonçalves L, Piñon M. Cistos e tumores primários do mediastino. Rev Port Pneumol. 2007;13(5):659-73. 5. Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part 1. Tumors of the anterior mediastinum. Chest. 1997;112(2):511-22.

Authors' roles & responsibilities MACC MRMN JC GCC

6. Suma MN, Jeyachandran P, Jena M, Revadi PS. Cervical thymic cysts masquerading as thyroid cysts. Online J Health Allied Sci. 2011;10(1):1-3.

Preparation of work, final review Anatomopathology review, text review Writing and literature review Medical records review and literature review

REFERENCES

7. Martins IM, Fernandes JM, Gelape CL, Braulio R, Silva VC, Nunes MCP. Grande cisto pericárdico manifestando-se com compressão das câmaras cardíacas direitas. Rev Bras Cir Cardiovasc. 2011;26(3):504-7.

1. Choi YW, McAdams HP, Jeon SC, Hong EK, Kim YH, Im JG, et al. Idiopathic multilocular thymic cyst: CT features with clinical and histopathologic correlation. AJR Am J Roentgenol. 2001;177(4):881-5.

8. Nina VJS, Manzano NCE, Mendes VGG, Salgado Filho N. Cisto pericárdico gigante: relato de caso. Rev Bras Cir Cardiovasc. 2007;22(3):349-51.

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Letters to the Editor/Cartas ao Editor DOI: 10.5935/1678-9741.20130064

RBCCV 44205-1490

What is phase 0 and phase I in clinical research?

National Council for Research and Development (CNPq), São José do Rio Preto, SP, Brazil.

Dear Editor,

REFERENCE

The registration of research as an international trial has become a reality and a necessity. However, the categorization of different types of studies in International Trial Registries is badly defined for both researchers and editors. Thus, a clearer description is required. According to the definition of the World Health Organization, Phase I clinical trials “test a new biomedical intervention in a small group of people (e.g., 20-80) for the first time to evaluate safety (e.g., to determine a safe dosage range and to identify side effects)” [1]. So when I sent a case report of about 15 patients submitted to established clinical treatment using an elastic stocking for vascular insufficiency to a well-known journal, I was surprised to hear the editor say that he required the registration number before it could be published, as this was a Phase I trial. And even more so when I tried to register the study as a Phase I trial in an International Trial Registry and was told it was not a Phase I trial. Why does the WHO state specifically that 20-80 people are a small group? How are trials of 15 individuals taking new drugs considered as Phase 0 while this study was considered as Phase I? With the creation of the phase 0 classification, there seems to be no doubt when investigating drugs in small scale studies with about 15 patients. And, in general, it seems logical that we should be more careful with the prescription of new drugs than existing clinical therapies, such as elastic stockings or the evaluation of non-invasive complementary examinations. There are many other ill-defined situations such as, for example, what is the classification of a series of five case reports – a "micro-study", a phase 0, or a phase I? Some journal editors think that a series of five case studies should be classified as phase I. I think it would be very beneficial if you, as Editor, would take the initiative to assist researchers, editors, and even the Research Ethics Committees by publishing a clear definition in your journal and to start a debate about the direction of clinical trials and their registration.

1. World Health Organization. The secretariat of the registry platform. Available at: http://www.who.int/ictrp/glossary/en/ index.html#TrialPhase). Accessed on: 8/13/2013.

Comments on Letter to the Editor Dr. José Maria Pereira de Godoy raises several questions: 1. Whether his study of application of elastic stockings to treat vascular insufficiency in 15 people should be qualified as a phase 1 or phase 0 trial? 2. Ethics of Phase 0 trial. To answer these questions one has to define the intent of the trial. It is the formulated goal rather than the number of study subjects per se that determines the qualification. The stated goals of Phase 1 trials — establishing the maximal tolerated dose of the tested medication and the determination of its toxicity — require larger numbers of enrolled subjects and the emphasis of pharmacokinetics rather than the therapeutic effects and benefits (endpoints of Phase 2 and 3 trials). In contrast, the goals of Phase 0 trials avoid the determination of maximal tolerated dose and its toxicity, specifically lack the therapeutic intent, and focus mostly on establishing whether the proposed medication has the intended pharmacokinetic profile (e.g., interacts with the intended enzymes, or it is absorbed as anticipated). Therefore, Phase 0 trials involve “micro-dosing” (avoiding toxicity, and neither expected nor intended to produce therapeutic or diagnostic benefits) and require significantly lower numbers of enrolled patients. It is important to understand that Phase 0 trial does not obviate the requirements of undergoing the full 3 phases of the required regulatory process. FDA created this process to alleviate the notorious problem of a “clogged pipeline” in development of promising medications, and allows early “weeding out” of (initially promising) medications.

José Maria Pereira de Godoy1, MD, PhD 1. Faculdade de Medicina de São José do Rio Preto/ Medicine School São José do Rio Preto (FAMERP), Department Cardiology and Cardiovascular Surgery and

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Therefore, we would agree with the assessment that the scenario presented by Dr. Godoy probably does not satisfy the definitions for Phase 1 nor Phase 0 trials. From ethical, statistical, and scientific standpoints, the introduction of Phase 0 trials elicited vigorous debates. Ethically, the controversy focuses on the dynamics of a trial, which enrolls patients not expected to derive any benefit from the intervention. Statistically, the challenge lies in maintaining the scientific rigor despite low number of patients who are subjected to an intervention which is neither toxic nor therapeutic. Consequently, Phase 0 trials may be applicable to a rather limited number of biological interventions. Additionally, linking Phase 0 with Phase 1 trials may be challenging as well. Therefore, we are grateful to Dr. Godoy for raising these issues. We believe that a thorough understanding of the regulatory process is vital for a proper description of a study and its qualification as a trial or a case review [1-5].

The phase 0 studies, also known as exploratory first-inhuman, follows the guidelines of the Food and Drug Administration (FDA) established in 2006 to guide the Exploratory Investigational New Drug Studies [1]. This modality also receives designation of a microdosing study , since the amounts of agents administered are too small to present any therapeutic effect . Thus, there is no evaluation of safety or efficacy, but only the pharmacokinetics and pharmacodynamics of the test agent [2]. The main purpose of phase 0, which includes 10 to 15 healthy individuals, is to streamlines the process of molecular investigation or promising interventions, since they allow to obtain early data from human beings, besides those from animal research, which are often inconsistent and non - reproducible. The phase I studies include from 20 to 100 healthy individuals, and discusses the pharmacodynamics and pharmacokinetics of the therapeutic agent, as well as their safety and tolerability. These studies are usually funded by the pharmaceutical or equipment industry and conducted in highly controlled locations known as Pharmacology Central Units. Interventions that succeeded at this stage will then have its efficacy tested in phase II , II and IV (postmarketing) [3]. Regarding the study proposed by Dr. Godoy, we do not believe it meets the definition of a clinical study, since a therapeutic measure with a known efficacy (by elastic compression stockings) was used in the treatment of venous insufficiency. We believe that such a study would be best characterized as a series of case report (descriptive study). We still think that what is more important than the correct classification of the study within their evolutionary stages, is the facilitation of access of health professionals to the document known as Clinical Study Report ( CSR ) a wide and unrestricted report for the study , where individual date regarding safety and efficacy are presented in detail, such information that are commonly lost or just summarized in the tables present in numerous scientific publication, skewing the correct evaluation and application of evidence-based measures.

Edward Gologorsky1, MD; Tomas A. Salerno1, MD, PhD 1 University of Miami Miller School of Medicine and Jackson Memorial Hospital Miami, FL, USA.

REFERENCES 1. Fromer MJ. FDA introduces new phase 0 for clinical trials: some enthusiastic, some skeptical. Oncology Times. 2006;28(15):18-9. 2. Kummar S, Kinders R, Rubinstein L, Parchment RE, Murgo AJ, Collins J, et al. Compressing drug development timelines in oncology using phase '0' trials. Nat Rev Cancer. 2007;7(2):131-9. 3. Kinders R, Parchment RE, Ji J, Kummar S, Murgo AJ, Gutierrez M, et al. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Mol Interv. 2007;7(6):325-34. 4. Hill TP. Phase 0 trials: are they ethically challenged? Clin Cancer Res. 2007;13(3):783-4. 5. Rubinstein LV, Steinberg SM, Kummar S, Kinders R, Parchment RE, Murgo AJ, et al. The statistics of phase 0 trials. Stat Med. 2010;29(10):1072-6.

Marcelo Derbli Schafranski, Ponta Grossa, PR/ Brazil REFERENCES 1. Food and Drug Administration. Guidance for industry, investigators, and reviewers, 2006 [Acessed on: 23/7/2013]. Avaliable at: http://www.fda.gov/downloads/Drugs/GuidanceC omplianceRegulatoryInformation/Guidances/ucm078933.pdf 2. Phase 0 trials: a platform for drug development? Lancet. 2009;374(9685):176.

Dear editor, The questions presented by the researcher JosĂŠ Maria Pereira de Godoy seems quite relevant although some considerations should be observed.

3. Goldacre B. Bad pharma. London:Fourth Estate;2012.

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Dear editor,

This distortion might explain, in part, the difficulties faced by Dr. Godoy to define his clinical study.

José Maria Pereira de Godoy raises interesting questions about the definitions of phase 0 and phase I clinical trials in his letter to the editor entitled “What is phase 0 and phase I in clinical research?”, which was published in this issue of the Brazilian Journal of Cardiovascular Surgery. His main arguments can be summarized as follows:

Lilia Nigro Maia, MD, PhD REFERENCES 1. Friedman LM, Furberg CD, DeMets DL. Fundamentals of clinical trials. Springer 4th ed. New York:Springer;2010.

1. Bearing in mind that the study was conducted in order to assess the safety and effectiveness of a brand new product (elastic stockings designed to treat venous insufficiency), the author argues for considering the study as a phase I clinical trial.

2. World Health Organization. International standards for clinical trial registries. Geneva: World Health Organization; 2012 [Acessed on 20/7/2013]. Avaliable at: http://apps.who.int/iris/bi tstream/10665/76705/1/9789241504294_eng.pdf

2. The study could not be registered in an International Trial Registry as phase I because the number of patients evaluated was deemed insufficient.

3. Food and Drug Administration. Guidance for institutional review boards and clinical investigators [Acessed on 20/7/2013]. Avaliable at: http://www.fda.gov/ScienceResearch/SpecialTopics/ RunningClinicalTrials/GuidancesInformationSheetsandNotices/ ucm113709.htm

In my opinion, there are pros and cons to Dr. Godoy’s clinical trial being regarded as phase I:

4. Association of the British Pharmaceutical Industry. Guidelines for phase 1 clinical trials. 2012 edition [Acessed on 20/7/2013]. Avaliable at: http://www.abpi.org.uk/our-work/library/guidelines/ Pages/phase-1-trials-2012.aspx

Pros: 1. What determines whether a clinical trial is phase I is primarily its goal, not the number of patients evaluated [1].

5. Food and Drug Administration. Guidance for industry, investigators, and reviewers, 2006 [Acessed on 20/7/2013]. Avaliable at: http://www.fda.gov/downloads/Drugs/GuidanceC omplianceRegulatoryInformation/Guidances/ucm078933.pdf

2. The definition of phase I clinical trials from the World Health Organization [2] states that a phase I clinical trial shall evaluate “a small number of patients”, without specifying the minimum or maximum number of participants. Cons: 1. Usually, a phase I clinical trial evaluates healthy volunteers. Patients may be included in some cases: when the treatment being evaluated can make healthy individuals sick, such as cancer drugs, or when every existing traditional treatment known to man has been used without providing beneficial results to the patient [3]. The participants in Dr. Godoy’s trial do not meet any of those criteria.

Phase 0, Phase I in clinical research and the registering of publications

2. The high risk involved in the early stages of clinical research demands strict regulations and careful monitoring during every single phase of the reserch [4]. As far as I know, the monitoring was not performed.

In most countries, the structure of clinical research for the release of new drugs, biological drugs, and human health devices is, in general, similar to the provisions of the North American law. Food and Drug Administration (FDA) regulations started to evolve from the mid-1880s until 1997, when the Food and Drug Administration Modernization Act (FDAMA) was enacted. They continue to evolve, especially in order to guarantee safe access to newly developed products. Primary regulations on drugs, biological drugs, and medical devices are part of the Code of Federal Regulations (CFR) Title 21. They were designed to avoid a series of problems of the past and to protect public interest and health in terms of new health products. Specifically, Investigational

Dr. Godoy argues that a clearer definition of the different types of clinical research available should be made by the International Trial Registry. In my point of view, these definitions are designed mainly for the study of drugs, especially the newly created phase 0 [5]. The criteria used to determine the ideal number of participants have as their main goal the assessment of pharmacokinetics, pharmacodynamics and dosage of drugs; aspects involving diagnostics, medical equipment, and procedures are relegated to the background.

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New Drugs (IND) are governed by Part 312; Devices and In Vitro Diagnostics, by Parts 800 - 861. The regulatory approach for drugs and/or biological drugs is different from the one for devices. In the latter, it is understood its action or result is not achieved through chemical actions in the human body or other animals and its treatment goal is not dependent on metabolism. New drugs and/or biological drugs follow specific development and evaluation steps [1]. In the USA, as mentioned, it starts with the IND Application, which is eventually followed by the New Drug Application (NDA). Initial exploration of the product in preclinical phases, usually in animals, supports the design of exploratory phases in humans. In general, the clinical stage is divided into three phases of pre-commercialization research aimed at examining the safety and efficacy of the drug and/ or biological drug. Phase I studies are comprised of small studies (20 to 100 individuals), with dose escalation, which may include either patients with certain conditions or healthy volunteers. Their main goal is to assess the safety of a particular route of administration. In addition, drug metabolism and pharmacokinetics can also be evaluated. Phase II studies are comprised of one or more larger clinical studies, for a particular population of patients, whose main goal is to offer preliminary evidence of efficacy and dosage as well as additional data on therapeutic safety. After this phase, the regulatory authority and the sponsor should refine their strategy for subsequent studies in larger populations. Phase III studies are larger in scale, usually multicenter and international. They are aimed at evaluating the risks and benefits of a product in a particular population of patients, with a given clinical indication. Safety and efficacy data from those last studies provide the product with the possibility of approval for commercialization as well as detailed instructions on usage for the particular condition [2]. As with any scientific research, methodology for each phase should be well established and meet the minimum requirements needed to accurately reflect results. Among the aspects to be considered are desired outcomes, study population, randomization, stratification, blinding, sample size, adherence, and statistical analysis techniques. All of these requirements are planned before the study. The development of the clinical research lasts approximately two to ten years. After that, the product enters the post-commercialization studies phase (Phase IV studies), where, besides safety monitoring, new applications and recommendations are added to it. This phase continues throughout the life cycle of the drug [1,2]. Several mechanisms have been created to speed up the development and approval of drugs and biological drugs, especially those designed for patients suffering from serious, debilitating, life-threatening diseases, and without

complementary alternatives (21 CFR 312 Subpart E, 314.510 and 601.41). One of these mechanisms was created in 1998, in the Fast Track Guidance, and revised in 2004. It set out mainly to facilitate the development and review of new drugs and biological products for conditions which are health risks and show the potential to quickly reach unmet medical needs. In the 2004 Critical Path Report, the FDA suggested new strategies were needed to help identify promising molecules, in an effort to reduce the time and resources spent on developing new drugs. As a result, in 2006 the FDA launched the new FDA Guidance on Exploratory Investigational New Drug (IND) Studies, in which an exploratory phase previous to Phase I studies is described. This phase is consistent with the regulatory requirements for the protection of human beings, involves few resources, and accelerates the development of promising components by defining, previously, if the behavior in human beings is the same as what it would be in the preclinical phase [3-5]. These studies were named “Phase 0” or “microdosing trials”, and they referred specifically to exploratory studies, prior to Phase I, with controlled human exposure and without diagnostic or therapeutic value. “Phase 0” studies are characteristically limited to a few individuals, usually 15, and they last a week. Their main goal is to collect preliminary pharmacokinetic and pharmacodynamic (PK/PD) data of the component being investigated, including image data of the bond to the receptor, and they do not allow inferences to be made about either safety or efficacy since non-therapeutic dosages are used. Preliminary data derived from a “Phase 0” study assist in the decision-making process and in judging potential candidates in the development of drugs. In general, this phase is limited to specific drugs whose target as well as the effects on their biomarkers must be known (2010 Qualification Process for Drug Development Tools). This approach in addition to methods of evaluating images of organs, tissues, cells, and molecules (Optical images, Positron Emission Tomography – PET, Single Photon Emission Computed Tomography – SPECT, among others) are essential to validate this phase and to either obtain proof of concept for the development of future studies or interrupt the clinical trial process [2-5]. Clinical trials of medical devices and equipment are not divided into phases in the way drug studies are. In the USA, they are governed by the Code of Federal Regulations (CFR), Title 21, Parts 800 – 861, and, in particular, Part 860.7 (Determination of Safety and Effectiveness) which deals with important aspects in clinical studies of these devices, prior to PMA (Premarket Approval). These aspects include: valid scientific evidence, safety, effectiveness, controlled clinical research, and data analysis, in accordance with the usual methodology for any scientific research [6]. In Brazil, the Brazilian Health Surveillance Agency (ANVISA) has very clear regulations governing the

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the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal. The ICMJE secretariat office is unable to review specific studies to determine whether registration is necessary. If researchers or others have questions about the need to register a specific study, they should err on the side of registration or consult the editorial office of the journal they wish to publish the study in” [10].

development of drugs, biological drugs, and materials to be used in healthcare. As a result of its most recent development, they are similar to the provisions of the FDA [7]. In the USA, clinical studies of new drugs, biological drugs, equipment, devices, or procedures had to be registered in accordance with the 1997 Food and Drug Administration Modernization Act (Modernization Act), section 113, which had created the Clinical Trials Data Bank to regulate the registration of clinical trials of drugs which would be studied and commercialized in the country. Subsequently, this platform was transformed into ClinicalTrials.gov. As of 2004, the International Committee of Medical Journal Editors (ICMJE) and, in 2005, the World Association of Medical Editors established the registration of clinical studies as a prerequisite to publish in their journals. In 2006, the World Health Organization (WHO) started to reveal the importance of registering in their International Clinical Trials Registry Platform (WHO ICTRP). Information fed into the WHO platform comes from primary registries and worldwide collaborators, including ClinicalTrials.gov. As of 2007, BIREME recommended that journals indexed in the LILACS (Latin-American and Caribbean Center on Health Sciences Information) and SciELO (Scientific Electronic Library Online) databases should abide by the WHO and ICMJE provisions [8]. The Brazilian platform, Brazilian Clinical Trials Registry – REBEC (Registro Brasileiro de Ensaios Clínicos) [9], was launched in December, 2010 and was integrated into the WHO ICTRP in April, 2011, in accordance with all ICMJE provisions. The WHO ICTRP, ClinicalTrials.gov, ICMJE, and REBEC guidelines emphasize the importance of registering every clinical study performed on human beings who are subject to diagnostic, therapeutic, or other procedures, whether interventional, observational, experimental or not. There is still some doubt about whether to register studies which are not characterized as clinical trials, as recommended by WHO and highlighted in the ICMJE guidelines below:

Overall, the Brazilian platform REBEC has accepted the registration of clinical studies that do not formally meet the criteria for clinical trials, as established, and it is formally recognized as a Primary Registry in the WHO ICTRP and ICMJE, which minimizes the issue for Brazilian researchers. Carlos Antonio Caramori1, MD, PhD Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP, Brazil. 1

REFERENCES

1. Zoon KC, Yetter RA. The regulation of drugs and biological products by the Food and Drug Administration. In: Gallin JI, Ognibene FP, eds. Principles and practice of clinical research. 3rd ed. London: Elsevier, 2012 [Acessed on: 20/8/2013]. Avaliable at: http://www.sciencedirect.com/science/book/9780123821676 2. Lertora JJL, Vanevski KM. Clinical pharmacology and its role in pharmaceutical development. In: Gallin JI, Ognibene FP, eds. Principles and practice of clinical research. 3rd ed. London: Elsevier, 2012 [Acessed on: 20/8/2013]. Avaliable at: http://www. sciencedirect.com/science/book/9780123821676 3. Kinders R, Parchment RE, Ji J, Kummar S, Murgo AJ, Gutierrez M, et al. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Mol Interv. 2007;7(6):325-34.

“..the ICMJE adopted the WHO’s definition of clinical trial: “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.” Healthrelated interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.” “Those who are uncertain whether their trial meets

4. The Lancet (editorial). Phase 0 trials: a platform for drug development? Lancet. 2009;374(9685):176. 5. Food and Drug Administration. Guidance for industry, investigators, and reviewers, 2006 [Acessed on: 20/8/2013]. Avaliable at: http://www.fda.gov/downloads/Drugs/GuidanceC omplianceRegulatoryInformation/Guidances/ucm078933.pdf 6. Food and Drug Administration. Medical devices. Device regulation guidance. premarket approval [Acessed on: 20/8/2013]. Avaliable at: http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/HowtoMarketYourDevice/ PremarketSubmissions/PremarketApprovalPMA/ucm050419. htm

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of patients to determine the outcome of the risk/benefit in the short- and long-term of the formulations of the active ingredient, exploring the type and profile of the most common adverse reactions; d) Phase IV - are researches performed after marketing the product and/or medical specialty. These researches are performed based on the characteristics of which that drug and/or medical specialty was authorized. They are generally studies on post-marketing surveillance to establish the therapeutic value, the emergence of new adverse reactions and/ or confirming the frequency of appearance of those already known, and treatment strategies.

7. Brasil. ANVISA Agência Nacional de Vigilância Sanitária [Acessed on: 20/8/2013]. Avaliable at: http://portal.anvisa.gov. br/wps/portal/anvisa/home Acesso em: 20/8/2013. 8. Caramori CA. Construction of ethics in clinical research: clinical trials registration. J Venom Anim Toxins Incl Trop Dis. 2007;13(4):729-36. 9. Brasil. Registro Brasileiro de Ensaios Clínicos REBEC [Acessed on: 20/8/2013]. Avaliable at: http://www.ensaiosclinicos.gov.br/ 10. ICMJE – International Committee of Medical Journal Editors. FAQs: what is the ICMJE definition of a clinical trial? [Acessed on: 20/8/2013]. Avaliable at: http://www.icmje.org/faq_clinical. html

Domingo Braile Editor-in-Chief/BJCVS

Screening of fetal congenital heart disease: the challenge continues

EDITOR'S NOTE Regarding the Letter to the Editor “What is phase 0 and phase I in clinical research?”, Authored by Dr. José Maria Pereira de Godoy, is timely to take readers' knowledge, as important information, a call from the Ministry of Science, Technology and Innovation (MCTI), along with the National Council for Scientific and Technological Development (CNPq), Ministry of Health (MOH) and Department of Science, Technology and Strategic Inputs (SCTIE) about Clinical Research on which it is defined in the context of different entities the clinical trials in phases I, II, III and IV nationwide. It is considered a clinical trial any research on human beings, aiming to discover or verify the pharmacodynamic, pharmacological, clinical and/or other effects of product (s) and/or identify adverse reactions to the product (s) under investigation, with the aim of ascertaining its safety and/or efficacy (EMEA, 1997). Clinical trials are classified into four stages (I to IV), as defined by Resolution No. 251/97 of the National Health Council, namely: a) Phase I - the first study in humans, in small groups of volunteers, generally healthy, of a new active ingredient or new formulation to establish a preliminary safety and pharmacokinetic profile; b) Phase II - aims to demonstrate the activity and establish short-term safety of the active ingredient, assessing the doseresponse relationship in a limited number of sick patients; c) Phase III – performed in a large and varied groups

Rastreamento das doenças cardíacas congênitas fetais: o desafio continua Dear Editor, The initiative of inviting a group of obstetricians to write an editorial for a cardiovascular surgery journal emphasizing the need of an adequate prenatal diagnosis of congenital heart diseases should be commended. The authors provide a comprehensive summary of the recent advances and advantages of intrauterine diagnosis, encouraging obstetricians not to limit the screening to those known to be at risk of developing a cardiac malformation. They also recognize the value and the limitations of the four chambers view with which the obstetricians feel comfortable. Furthermore, the authors stress the fact that there are a number of cases, particularly the cono-troncal anomalies, where the visualization of the great arteries is difficult and the pitfalls important. They also underline the importance of expanding the training, knowledge and abilities of those performing the studies to allow a broader detection of cardiac anomalies [1]. As in other specialties, there is an increasing interest in the newly developed technologies which will certainly improve the images and facilitate a precise detection and diagnosis. However, the key for an accurate screening continues to be the operator’s knowledge of the cardiac anatomy and a proper

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understanding of the unique and complex spatial arrangement of the cardiovascular system. The concept of spatial thinking — a cognitive skill used by architects and urban planners — can help in understanding the world around us by using the properties of space in everyday life, the workplace, as well as in science, to structure problems, find answers and articulate solutions [2]. While we firmly believe that a proper utilization of the present tools should enable us to improve detections, we recognize the importance of a conscientious labor force that makes excellent use of modern technologies as they become widely available and affordable. Whether we liked it or not, technology will continue to shape our practices. Although it is not our intention to write a paper within a letter to the Editor, there are important concepts such as proximity, product space, structure of production, collaborative rationality, and team work that should be at least mentioned. Their application will improve our understanding of the complexity of the cardiovascular services and thereby enhance performance. Proximity formalizes the idea that the ability of a center to generate a product depends on its ability to produce other ones — structure of production. When a center with many complex capabilities adds a new one, this can create a range of new, possible complex procedures. Conversely, adding a single new capability in a center that has few to begin with won’t leverage an existing matrix of capabilities in the same way — it might not produce any new procedures at all [3]. As a pediatric cardiologist and a cardiovascular surgeon we strongly advocate the need of an inclusive team approach for the proper management of the neonate with congenital heart disease: a work structure in which all components of the cardiovascular services — a cluster of people focused on excellence according to their relatedness and interests — contributes to the quality of the final outcome with an integrated approach [4]. This leads to collaborative rationality, of getting better together, which is a different way of knowing and generating, of making and justifying decisions based on diversity, interdependence and dialogue [5,6]. It is a team integrated by pediatric cardiologists, neonatologists, cardiovascular surgeons, anesthesiologists, nurses and specialized critical care units in which obstetricians with imaging expertise have a place. The role of the latter should not be limited to the image detection but also to participate in the decision making process: that is, diagnosis, intrauterine treatment, time, type and place of delivery, etc. In other words, an effort centered in the fetus’ health, encouraging collaboration among professionals and sharing knowledge that contributes to reciprocal medical education in a multidisciplinary environment.

to understand, report on, and predict different aspects of performance. After making theoretical considerations, which, among practical people, has a connotation of impracticality, we feel compelled to include information about our policies as well as unpublished data on our experience. Recently, we reviewed our findings on early detection of congenital cardiac anomalies in a group of 49 neonates under 30 days of life that underwent surgery [7]. Interestingly, in this cohort of the patients, 40% had prenatal diagnosis and 90% of them had severe forms of univentricular heart — the majority with hipoplastic left heart syndrome. In all cases, the malformations were detected by an obstetrician specialized in images and confirmed by a pediatric cardiologist, both aware of the importance of visualizing the outflow tracts and the great vessels, using a conventional four chambers view. It is our policy to discuss all patients with prenatal diagnosis of heart disease by a group formed of general obstetricians, obstetricians specialized in images, pediatric cardiologists, neonatologists and cardiovascular surgeons. This team decides the management of the patient — that includes consulting the mother — with special consideration to the need of prenatal intervention, the time, type and place of delivery, and the timing for surgery. We strongly believe that a joint management benefits the patients and improves surgical results by diminishing morbidity and mortality. However, the findings disclosed in the Editorial as well as ours clearly indicate that there is room for improvement by training those involved in the screening process, realizing the need of a team approach, and the adoption of modern technologies. It is, among other things, the ability to recognize where there is room for improvement that allows an expert operator to reach great heights. “The ability to see room for improvement, however, is not of much use unless one also has a strong and continuing desire to improve” [8]. Neonates face unique incremental risk factors related to the patient’s variables and to structural hospital characteristics that should be properly individualized and addressed in a timely fashion in order to improve surgical outcomes. An accurate prenatal diagnosis can make a significant contribution to accomplishing this goal. Mariano Ithuralde1, MD; Rodolfo Neirotti2, MD, MPA, PhD 1 Clínica y Maternidad Suizo-Argentina, Buenos Aires, Argentina. 2 Michigan State University, East Lansing, MI, USA. REFERENCES 1. Rocha LA, Araujo Júnior E, Nardozza LMM, Moron AF. Screening of fetal congenital heart disease: the challenge continues. Rev Bras Cir Cardiovasc. 2013;28(3):V-VII.

How are we doing? The use of information about one’s business is vital

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2. Bar-Sinai KL. The role of architects in negotiations. Cambridge: Harvard School of Education; 2012.

6. Neirotti RA. Cardiac surgery: complex individual and organizational factors and their interactions. Concepts and practices. Rev Bras Cir Cardiovasc. 2010;25(1):VI-VII.

3. Hausmann R, Hidalgo C. In: Jonathan Shaw on Complexity and the wealth of nations. Harvard Magazine. March-April; 2010.

7. Ithuralde M, Manara C, Ithuralde A, Balestrini M, Comas F, Gallo JP, et al. Cirugia cardiaca neonatal: resultados quirúrgicos en recién nacidos menores de 30 días. Abstract submitted to the XXXIX Congreso Argentino de Cardiologia. October 18-20, 2013. Buenos Aires Argentina.

4. Ithuralde M, Neirotti R. Neonatal heart surgery: evaluation of risk factors. NeoReviews. 2011;12;e252-9. 5. Innes JE, Booher DE. Planning with complexity: an introduction to collaborative rationality for public policy. New York: Routledge; 2010.

8. Montero BG. The myth of “just do it’. The New York Times, June 9, 2013. Posted in Harvard Magazine. June 14; 2013.

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Changing scientific communication SCIENTIFIC DISSEMINATION

Changing scientific communication Transformando a comunicação científica

Karina Toledo1

DOI: 10.5935/1678-9741.20130065

RBCCV 44205-1491

Making the results of performed research accessible to the greatest number of people - in the shortest possible time - and allow the scientific community to judge the relevance of the article after its publication. This innovative idea guided the creation of the PLoS One journal, in 2006, and is transforming scholarly communication worldwide. The evaluation was made by Eric Martens, senior editor of the journal, during a conference presented at the 28th Annual Meeting of the Federation of Experimental Biology Societies (Fesbe) held in Caxambu (MG) between 21 and 24 August. According to Martens, in 2012 PLoS One published 24,000 articles, with an acceptance rate of 70%. On average, 200 submissions are received and 140 articles are posted daily. “While many journals reject up to 90% of submitted articles to raise their impact factor, the PLoS One has a unique philosophy: all research consistent from ethical and scientific principles, that contribute in some way to the knowledge of a given area must be published and have free access. We do not reject an article based on its alleged impact”, said Martens. As the PLoS One aims to disseminate research from all fields of science and medicine, there is no risk of an article, a result of interdisciplinary study be rejected as not fit into the scope of a particular area of study. Studies with negative results, i.e., those that do not prove the hypothesis initially proposed are also welcome. “There are areas with few options of open access journals, like Paleontology. PLoS One is a good option in these cases”, said Martens. The editor, however, points out that there are criteria that must be met for the study to be accepted. Besides not having been published earlier and provide new knowledge to the area, it needs to rely on experiments, statistics and analysis of high technical level. All data should be described with a degree of detail that allows its reproduction by anyone interested. The findings should be presented properly and be supported by the data obtained in the experiments and assessments. The 1

article must be written in an intelligible form, according to the standard of English language. The research should follow the international standard of ethics and integrity in research. According to Martens, the reasons for rejection of an article in PLoS One are generally related to fundamental problems of methodology and interpretation of results. “Factors such as poorly designed experiments, insufficient samples, lack of statistical power of the results and improper technique analysis", exemplified. In addition to the journal's staff, participate in the review process - which lasts on average 40 days – the so-called academic publishers, experts in various fields who act as collaborators fixed. They decide whether there is need for external reviewers. “To ensure transparency of the process, a letter of acceptance or rejection of an article is always signed by the responsible academic publisher and this information is also published. The external auditors are also encouraged to sign the evaluation” said Martens. The model of judgment based on the consistency of the research and its impact has not been shown to be successful in Martens' opinion. But, according to him, there is a number of crucial tools to the successful of such model. The journal's website offers, for example, a comment section and a series of indicators that show how many times the article was accessed and cited, with graphs showing its evolution over time. Furthermore, the scope of study among the general public is measured by the number of times it has been shared on blogs and social networks. “We believe that this model of individual metric is a good alternative to the impact factor based on the journal. This is changing the way people think and evaluate scientific research”, he said. The problem with the concept of impact factor, according to Martens, is the fact that it is based on the average number of citations that articles in a journal receive in a given period - which masks the variations that exist within each journal. “Nature, for example, has an impact factor greater than 30. But if we analyze the distribution of citations of the journal we will find that it is highly variable. There are some articles that

FAPESP Agency

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have also adopted policies to encourage the practice, such as Harvard, Columbia, Duke, Princeton, Stanford and MIT [Massachusetts Institute of Technology]”, he said. Martens, however, recognizes that currently the cost of publication for those who choose the open access model rests with the researcher. In the case of PLoS One, it necessary to spend about $1300 for each item. In the journals in which the rejection rate is higher the cost of publication is also usually higher. “We want to get to the point that the institutions that fund research to understand that make their results accessible freely is an essential part of the process and to assume that cost”, he argued.

have much impact and are cited until today, like the Human Genome Project. And there are others who have been cited only once or twice throughout its history”, he said. Successful model For a journal to be considered truly open access (open access), two criteria must be met: the content needs to be available for free on the Internet, without requiring registration or subscription, and readers must have copyright permission to republish or reuse the content as they wish. The only condition is the accreditation of the study to the authors and publishers. According to his evaluation, Martens states that this model has proven successful and is growing rapidly, driven primarily by institutions such as the European Commission, UK Research Councils, the National Institutes of Health (NIH) in the United States, and the Organization United Nations Educational, Scientific and Cultural Organization (UNESCO). “These bodies have determined that all the research funded by them should be freely accessible. Some major universities

Posted by FAPESP Agency on September 11, 2013.

URL: http://agencia.fapesp.br/17851

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Changing scientific communication RETRACTION

Cardiology in Brazilian scientific journals: an overview Cardiologia em revistas científicas brasileiras: um panorama

Kavita Kirankumar Patel1; Mauricio Rocha e Silva1, MD, PhD

DOI: 10.5935/1678-9741.20130066

RBCCV 44205-1492

Notice of retraction

articles to be included. The retraction is formally approved by the Editor of Revista Brasileira de Cirurgia Cardiovascular/ Brazilian Journal of Cardiovascular Surgery, Domingo Marcolino Braile.

The undersigned persons, being the authors of the article herein specified, of their own free will have decided to retract the said article. This article is a limited review of articles previously published in Brazilian scientific journals. It contains no reports on newly obtained scientific results and was written merely for the information of readers of Revista Brasileira de Cirurgia Cardiovascular. The reason for retraction is that an honest error was committed in the method used for collecting

Retracted article: Patel KK, Silva MR. Cardiology in Brazilian scientific journals: an overview. Rev Bras Cir Cardiovasc. 2012;27(2):302-311. doi:10.5935/16789741.20120048.

Correspondence address: Kavita Kirankumar Patel Rua Dr. Ovídio Pires de Campos, 225 – 6º andar – São Paulo, SP, Brazil CEP 05403-010 E-mail: kavita.patel@hc.fm.usp.br

1. Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brazil.

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ERRATUM/ERRATA

DOI: 10.5935/1678-9741.20130067

RBCCV 44205-1493

In the printed version of issue 28.2, the tables were not published on the editorial “Estudio Syntax: de la evidencia a la desobediência”(pág. III to V). Below, the tables:

Tabla 1. Características del grupo quirúrgico en el estudio SYNTAX Revascularización completa con injertos arteriales Al menos una mamaria interna Doble mamaria interna Mamaria + safenas Uso arteria radial Solamente injertos venosos Injertos por paciente Anastomosis distales por paciente

Tabla 4. Resultados del SYNTAX a 5 años en enfermedad de 3 vasos coronários

18,90% 97,30% 27,60% 78,10% 14,10% 2,60% 2,8 +/‑ 0,7% 3,2 +/‑ 0,9%

N.º de pacientes Muerte Muerte cardíaca IAM ACVA Muerte + muerte cardíaca + IAM Nueva revascularización coronária

15,0% operados se realizaron sin circulación extracorpórea

P Cirugía revascularización 0,37 3,50% 0,11 3,20% 0,89 3,40% 0,003 2,20% 0,96 10,30% 0,0025 3,90%

Cirugía (%) N.º de pacientes 348 Muerte 14,6 (+1,8%) Muerte cardíaca 7,2 (–1,4%) IAM 4,8 (–3,4%) ACVA 4,3 (+2,8%) Muerte + Muerte cardíaca+ IAM 20,8 (+1,8%) Nueva revascularización coronária 15,5 (–11,2%)

Tabla 3. Resultados clínicos del estudio SYNTAX a los 4 años Stent (%) 33,5 18 11,7 7,6 2,3 8,3 23

0,006 0,001 0,001 0,66 0,001 0,001

Tabla 5. Resultados del SYNTAX a 5 años en la enfermedad de tronco izquierdo

ACVA: accidente cerebrovascular agudo

Cirugía (%) Eventos mayores 2,3 Muerte/infarto/ACVA 14,6 Mortalidad todas las causas 8,8 Muerte causa cardíaca 4,3 ACVA 3,7 Infarto 3,8 Nueva revascularización 11,9

Stent (%) 546 14,6 9,2 10,6 3 22 25,4

ACVA: accidente cerebrovascular agudo; IAM: infarto agudo de miocardio. Si analizamos el SYNTAX score, no hay diferencias significativas entre ambos grupos de pacientes en el score de bajo riesgo (< 23), pero si en el riesgo intermedio (23‑32) y alto (> 32)

Tabla 2. Resultados al año de seguimiento del estudio SYNTAX Stent TAXUS Mortalidad total 4,30% Infarto agudo de miocardio 4,80% Oclusión del injerto/trombosis stent 3,30% ACVA 0,60% Muerte por ACVA o infarto 10,10% Nueva revascularización 16,10%

Cirugía (%) 549 9,2 (–5,4%) 4 (–5,2%) 3,3 (–7,3%) 3,4 (+0,6%) 14 (–8%) 12,6 (–12,8%)

P < 0,001 0,07 0,048 0,04 0,06 < 0,001 < 0,001

Stent (%) 357 12,8 8,6 8,2 1,5 19 26,7

0,53 0,46 0,1 0,03 0,57 0,001

ACVA: accidente cerebrovascular agudo; IAM: infarto agudo de miocardio. Si analizamos el SYNTAX score, no hay diferencias significativas entre ambos grupos en score bajo y medio, pero si en score alto (> 32) donde la cirugía tiene mejores resultados que el stent

ACVA: accidente cerebrovascular agudo

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Reviewers BJCVS 28.3 Below, the names of those people who reviewed the papers published in this issue of the Brazilian Journal of Cardiovascular Surgery/Revista Brasileira de Cirurgia Cardiovascular (BJCVS/RBCCV). Thanks to them.

Domingo Braile Editor-in-Chief RBCCV

Ana Maria Rocha Pinto e Silva

Isabella Martins Albuquerque

Anderson Benício João Carlos Leal Bruno Botelho Pinheiro

Josiane Marques Felcar

Bruno da Costa Rocha

Juliana Brassalobre Borges Karlos Alexandre de Sousa Vilarinho

Carlos Manuel de Almeida Brandão

Lindemberg M Silveira Filho

David Peitl

Marcelo Matos Cascudo

Eduardo Keller Saadi

Mauro Paes Leme de Sá

Ektor Correa Vrandecic

Melchior Luiz Lima

Elaine S Barbosa de Oliveira Severino

Michel Pompeu Oliveira Sá

Guilherme Agreli

Paulo Manuel Pêgo Fernandes

Guilherme de Menezes Succi Simone Cavenaghi Henrique Murad

Solange Guizilini

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RBCCV em números 27 anos de circulação ininterrupta Fator de Impacto 0,809

www.rbccv.org.br www.scielo.br/rbccv www.bjcvs.org

Consultada por leitores de mais de 110 países 788.564 acessos no site próprio (www.rbccv.org.br) em 2012 709.180 acessos no site da SciELO (www.scielo.br/rbccv) em 2012 4092 visitantes diariamente 469,65 gigabytes (GB) transferidos, média de 1,28 GB por dia 47.232.073 impressões de páginas em 2012 (requisição do navegador de um visitante para uma página web que possa ser exibida), média diária de 129.049,38. Presente em nas bases de dados EBSCO, Lilacs, Scielo, Latindex, Index Copernicus, Scopus, PubMed, Thomson Scientific (ISI), Google Scholar

Fig.1 – Número de acessos ao site da RBCCV em 2012

Fig. 2 – Transferência de bytes no site da RBCCV durante 2012

Fig. 3 – Número de impressões de páginas da RBCCV em 2012