CVJA Volume 24, Issue 4

MAY 2013 VOL 24 NO 4

AFRICA www.cvja.co.za

CardioVascular Journal of Africa (official journal for PASCAR)

• CVJA position statement • Cardiovascular diseases in Africa • Left atrial appendage closure in patients with atrial fibrillation • NSTEMI in three hospital settings in South Africa • Congestive heart failure in a Kenyan paediatric population • Benzathine penicillin for secondary prophylaxis in patients with RHD • Pre-eclampsia, brain naturetic peptide and tissue Doppler studies • Global burden of congenital heart disease

PUBLISHED ONLINE:

Cardiovascular Journal of Africa . Vol 24, No 4, May 2013

Printed by Tandym Printers

• Acute myocardial infarction after prednisolone for the treatment of anaphylaxis • Percutaneous balloon pericardiotomy for recurrent tamponade

the CLOT

Target with Confidence

protects long term against further atherothrombotic events

Compared to the originator, Clopivas has

1

• Proven bioequivalence • No signicant difference in % of inhibi�on of platelet aggrega�on • The same chemical form II • An equivalent dissolu�on prole • A similar purity/impurity prole REFERENCE: 1. Data on file.

S3 Reg. No. 41/8.2/0766 Cipla Medpro (Pty) Ltd. Reg. No. 1995/004182/07 Rosen Heights, Pasita Street, Rosen Park, Bellville, 7530. Tel (021) 943 4200, Fax (021) 914 4699 Email: medicalpa@ciplamedpro.co.za, Website: www.cipla.co.za

ISSN 1995-1892 (print) ISSN 1680-0745 (online)

AFRICA

VOL 24, NO 4. MAY 2013

CONTENTS

Cardiovascular Journal of Africa

www.cvja.co.za

From the Editor’s Desk

103

CVJA position statement P Brink

104

A snapshot of cardiovascular diseases in Africa in the new millennium AP Kengne • BM Mayosi

Editorial

Cardiovascular Topics

107 Left atrial appendage closure in patients with atrial fibrillation in whom warfarin is contra-indicated: initial South African experience M Abelson 110

Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome? A retrospective cohort study J Moses • AF Doubell • PG Herbst • KJC Klusmann • HSVH Weich

117 Pattern of congestive heart failure in a Kenyan paediatric population JA Ogeng’o • PM Gatonga • BO Olabu • DK Nyamweya • D Ong’era 121

Comparison of results of autologous versus homologous blood transfusion in open-heart surgery BS Oz • G Arslan • E Kaya • C Gunay • F Cingoz • M Arslan

124

Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital C Musoke • CK Mondo • E Okello • W Zhang • B Kakande • W Nyakoojo • J Freers

130

Cardiovascular haemodynamics in pre-eclampsia using brain naturetic peptide and tissue Doppler studies S Fayers • J Moodley • DP Naidoo

137

Bilateral thoracoscopic sympathectomy for primary hyperhydrosis: a review of 335 cases M Öncel • GS Sunam • E Erdem • Y Dereli • B Tezcan • KG Akyol

INDEXED AT SCISEARCH (SCI), PUBMED, PUBMED CENTRAL AND SABINET Editors

SUBJECT Editors

Acting Editor in Chief (South Africa) Prof PA Brink

Nuclear Medicine and Imaging DR MM SATHEKGE

Assistant Editor Prof JAMES KER (JUN) Regional Editor DR A Dzudie

Heart Failure Dr g visagie Paediatric dr s brown Renal Hypertension dr brian rayner

Regional Editor (Kenya) Dr F Bukachi

Surgical dr f aziz

Regional Editor (South Africa) PROF R DELPORT

Adult Surgery dr j rossouw Epidemiology and Preventionist dr ap kengne

Editorial Board prof PA Brink Experimental & Laboratory Cardiology

PROF A LOCHNER Biochemistry/Laboratory Science

PROF R DELPORT Chemical Pathology

PROF BM MAYOSI Chronic Rheumatic Heart Disease

PROF MR ESSOP Haemodynamics, Heart Failure DR MT MPE Cardiomyopathy & Valvular Heart Disease DR OB FAMILONI Clinical Cardiology DR V GRIGOROV Invasive Cardiology & Heart Failure

PROF DP NAIDOO Echocardiography PROF B RAYNER Hypertension/Society

International Advisory Board PROF DAVID CELEMAJER Australia (Clinical Cardiology)

PROF KEITH COPELIN FERDINAND USA (General Cardiology) DR SAMUEL KINGUE Cameroon (General Cardiology) DR GEORGE A MENSAH USA (General Cardiology) PROF WILLIAM NELSON USA (Electrocardiology)

PROF MM SATHEKGE Nuclear Medicine/Society PROF J KER (SEN) Hypertension, Cardiomyopathy, PROF YK SEEDAT Cardiovascular Physiology Diabetes & Hypertension

DR ULRICH VON OPPEL Wales (Cardiovascular Surgery)

DR J LAWRENSON Paediatric Heart Disease

PROF ERNST VON SCHWARZ USA (Interventional Cardiology)

PROF H DU T THERON Invasive Cardiology

PROF PETER SCHWARTZ Italy (Dysrhythmias)

Letter to the Editor

136 Is double-blinding possible while administering fluids in the intensive care unit?

AB Durukan • HA Gurbuz • CEM Yorgancioglu • M Tavlasoglu

Review Article

VOL 24, NO 4. MAY 2013

CONTENTS

141 The global burden of congenital heart disease JIE Hoffman 147

Drug Trends in Cardiology

Congress report: Cardiology and Diabetes at the Limits, 22–25 March 2013 AJ Dalby • JL Aalbers

PUBLISHED ONLINE (Available on www.cvja.co.za and in Pubmed) Case Reports

e1 Multi-slice computed tomography assessment of stent position in a patient with acute coronary syndrome and anomalous origin of the coronary arteries P Cirillo • G Petrillo • R Piccolo • G Messalli • F Ziviello • M Bevilacqua • M Salvatore • F Piscione • B Trimarco e4

Acute myocardial infarction after prednisolone administration for the treatment of anaphylaxis caused by a wasp sting Z Arslan • A Iyisoy • M Tavlasoglu

e7 Delayed chylopericardium as a rare complication after combined mitral valve plus coronary artery bypass surgery BS Oz • G Arslan • S Doganci • E Kaya • K Karabacak • F Cingoz • M Arslan e10 Percutaneous balloon pericardiotomy using the Inoue balloon for patients with recurrent pericardial tamponade B Kilicaslan • I Susam • H Dursun • C Ekmekci • M Aydin • O Ozdogan e13

Acute ST-elevation myocardial infarction in early puerperium due to severe left main coronary stenosis in a woman with familial hyperlipidaemia T Bezgin • A Elveran • CEM Doğan • A Karagöz • Ş Külahçioğlu • G Kahveci • AM Esen

managing editor

GLENDA HARDY Tel: 021 976 8129 Cell: 071 819 6425 e-mail: glenda@clinicscardive.com

financial & production co-ordinator ELSABÉ BURMEISTER Tel: 021 976 8129 Fax: 086 664 4202 Cell: 082 775 6808 e-mail: elsabe@clinicscardive.com

Production Editor

SHAUNA GERMISHUIZEN Tel: 021 785 7178 Fax: 086 628 1197 e-mail: shauna@clinicscardive.com

CONTENT MANAGER

Michael Meadon (Design Connection) Tel: 021 976 8129 Fax: 0866 557 149 e-mail: michael@clinicscardive.com

GAUTENG CONTRIBUTOR

PETER WAGENAAR Cell 082 413 9954 e-mail: skylark65@myconnection.co.za The Cardiovascular Journal of Africa, incorporating the Cardiovascular Journal of South Africa, is published 10 times a year, the publication date being the third week of the designated month.

Copyright: Clinics Cardive Publishing (Pty) Ltd. Layout: Martingraphix

Printer: Durbanville Commercial Printers/ Tandym Print ONLINE SERVICES: Design Connection

Full text articles available on: www.cvja. co.za or via www.sabinet.co.za; for access codes contact elsabe@clinicscardive.com

All submissions to CVJA are to be made online via www.cvja.co.za

Subscriptions for 10 issues: To subscribe to the journal or change your postal address, e-mail elsabe@clinicscardive.com

Electronic submission by means of an e-mail attachment may be considered under exceptional circumstances.

South Africa: R650 (excl VAT) Overseas: R1306 Online subscription: R200

Postal address: PO Box 1013, Durbanville, RSA, 7551 Tel: 021 976 8129 Fax: 0866 644 202 Int.: +27 21 976 8129 e-mail: info@clinicscardive.com Electronic abstracts available on Pubmed Audited circulation

The views and opinions expressed in the articles and reviews published are those of the authors and do not necessarily reflect those of the editors of the Journal or its sponsors. In all clinical instances, medical practitioners are referred to the product insert documentation as approved by the relevant control authorities.

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CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013

103

From the Editor’s Desk CVJA position statement In the wake of the death of the founder and editor-in-chief of the Cardiovascular Journal of Africa (CVJA), Prof Andries Brink, the Journal continues to operate on the excellent foundation he and managing editor Julia Aalbers established.

The CVJA had, at the end of May, an all-time record number of manuscript submissions; already 85% of the total submitted during the course of 2012. We are also delighted to have received submissions from a greater number of African countries and covering an increasing range of fields pertinent to cardiovascular medicine. As a result, we have invited additional topic editors in our established fields and will have to create new fields of interest.

Furthermore, an increasing number of French-language submissions from African countries, accompanied by an English translation of the abstract, have been very welcome. During the 11th PASCAR meeting hosted in Dakar, Senegal, and co-hosted by the Senegalese Society of Cardiology (SOSECAR), great progress was made in sourcing appropriate reviewers for these French-language submissions. This will enable the CVJA to further expose the work of our Francophone colleagues globally.

Interviews with selected candidates for the position of editorin-chief are planned and an announcement will be made soon.

In the interim, the Journal is being steered by Prof Paul Brink.

In this he has relied on advice and support from Profs Amanda Lochner and Johann Brink. Our sincere thanks are extended to them and the topic editors who have tirelessly managed our submissions.

Julia Aalbers, after some uncertainty, has decided to leave the journal to pursue other interests; an intention she had indicated late in 2012. Julia dedicated 25 years to the CVJA and was a regular sight at academic gatherings. She is well known for her optimistic can-do attitude and creativity, and has contributed to highlighting Africa on international platforms. We will certainly miss her boundless energy and skill.

From these solid foundations, the CVJA is proudly marching into the future.

Prof Paul Brink Acting Editor-in-Chief

Cardiovascular congress diary 2013 DATE JUNE 2013 23–26 June 27–29 June

PLACE

CONFERENCE

EHRA EUROPACE 2013 CSI 2013 – Catheter Interventions in Congenital and Structural Heart Disease

Athens, Greece www.esccardio.org/congresses Frankfurt, Germany www.csi-congress.org

JULY 2013 13–15 July Asian Federation of Cardiology congress (AFCC) AUGUST 2013 25–29 August 2012 ESC, European Society of Cardiology congress SEPTEMBER 2013 11–13 September 6th international symposium on hybrid approach to congenital heart disease 2012 OCTOBER 2013 10–12 October Federation of Infectious Disease Society in South Africa (FIDSSA) 13–16 October 10th international congress on coronary and artery disease from prevention to intervention (ICCAD) NOVEMBER 2013 16–20 November 86th American Heart Association scientific sessions (AHA) Critical care refresher course 2013 21–24 November 5th international conference of fixed combination in the treatment of hypertension, dyslipidaemia and diabetes mellitus

CONTACT DETAILS TO REGISTER

Singapore

www.afcc2012.com

Munich, Germany

www.escardio.org

Columbus, US

www.nationwidechildrens.org/ishac-home

Drakensberg, SA Florence, Italy

www.fidssa.co.za www.kenes.com/iccad

Dallas, Texas, USA SA Bangkok, Thailand

http://my.americanheart.org/ www.criticalcare.org.za www.fixedcombination.com/2013

To advertise your conference/meeting, email details and half page PDF advert to info@clinicscardive.com

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CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013

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Editorial A snapshot of cardiovascular diseases in Africa in the new millennium The ageing of populations observed in many settings around the world extends to sub-Saharan Africa (SSA), where life expectancy at birth has increased by about 18 years between 1950 and 2010.1 It has been estimated that ageing of African populations will accelerate further in the coming decades, such that the gap in life expectancy with the world average will drop from 20 years in 2010, to only about 10 years by 2050. Lessons learned from other parts of the world suggest that changes in the age structure of populations with increasing proportions of elderly people, which is also known as ‘demographic transition’, is usually paralleled by changes in health profiles, which have been characterised as ‘epidemiological transitions’.2 Based on the Western models of epidemiological transitions, chronic non-communicable diseases (NCDs) replace infectious diseases as the major cause of death and disability during the demographic transition. Several lines of evidence suggest that chronic NCDs are gaining ground in Africa; however, this against a background of highly prevalent infectious diseases, some of which have chronic patterns, which are still contributing a very significant proportion of deaths on the continent. These competing disease profiles have been detrimental for chronic diseases; resulting in knowledge generation and translation, policy formulation and implementation, and health service development for chronic NCDs to severely lag behind those for infectious diseases in Africa.

A major challenge in appraising the true magnitude of chronic NCDs and on-going efforts to prevent and control them in Africa has been the lack of locally relevant scientific evidence.3 There is, however, the suggestion that the situation is rapidly improving, with the growing number of high-quality scientific publications that are emerging on NCDs in Africa.4 This was already apparent in December 2005, when the leading world journal of cardiovascular diseases, Circulation, undertook to publish a dedicated series of scientific articles on cardiovascular diseases (the leading chronic NCDs) in sub-Saharan Africa.5 This series of nine scientific articles plus an editorial had the particularity of been driven essentially by African researchers who were able to rigorously build on personal experience and published data at the time, and provide a comprehensive and representative picture of cardiovascular disease in SSA. The success of the articles in the Circulation series,5 as measured by the large number of citations attached to each of them, attests to the influential role the initiative of Circulation has played within less than 10 years in shaping the landscape of cardiovascular diseases in SSA. However, this series was mostly based on evidence from the last century, while more evidence is emerging in the context of improved access to care for major infectious diseases such as HIV infection and tuberculosis, and increasing awareness on chronic NCDs in Africa.6 Regular updates are therefore needed to carry the wave initiated by

Circulation in 2005 across time.5 It is exactly what a group of dedicated scientists, including some who were already involved in the 2005 initiative, have successfully achieved.

In a series titled ‘Cardiology in Africa 2013 Update’ published online on 15 May 2013 in Heart, a leading international cardiovascular journal from the British Medical Journals’ group, a comprehensive overview is provided on recent developments on cardiovascular diseases in Africa, and strategies to improve the prevention and control discussed by leading scientists with established research experience on CVD in Africa. The series has at least two distinctive features. One is the period covered by the included studies, which does not extend beyond the last 10 years, therefore allowing the series to project an unclouded picture of CVD in Africa in the early 21st century.

The second feature of the series is the nearly equal coverage given to diseases of modern lifestyle which are often the major focus when approaching CVD from a global perspective, and the neglected CVDs, which are rather rare elsewhere, yet remain a major challenge in Africa. For instance, in one of the articles dedicated to endomyocardial fibrosis (EMF), a condition described for the first time in Uganda in 1938,7 Drs Mocumbi and Falase8 provide findings confirming that three-quarters of a century from the first description, EMF has remained a frequent but neglected CVD in Africa. As a consequence, little is known on the mechanisms and treatment of the disease, which is still associated with a poor prognosis.

Recent advances on acute heart failure and cardiomyopathies are covered in another article in the series by Sliwa and Mayosi.9 Reliable and robust evidence on acute heart failure have recently emerged from a multicentre, cross-continental study, showing that 90% of cases of heart failure in Africa can be attributed to hypertension, rheumatic heart disease and cardiomyopathy, which is at variance with findings from the West where heart failure is largely due to coronary heart disease.10 Furthermore, heart failure in Africa is a disease of young people, with a similar high early mortality rate as found elsewhere, and the uptake of evidence-based therapies for heart failure by healthcare providers in Africa is still below optimal.

The epidemiology of cardiomyopathy, a leading cause of heart failure in Africa, has been refined in recent studies in Africa. Findings from those studies are informing the design and implementation of further investigations into the pathogenesis and management of cardiomyopathies on the continent.9 Cardiovascular diseases in specific populations within Africa are covered in two articles in the series. In their article on CVD in people with HIV, Syed and Sani11 shed light on the contrast in the spectrum of CVD among people with HIV in the West and those in Africa. While improving survival among people with HIV infection on antiretroviral therapy in the West has been associated with premature occurrence of CVD of

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CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013

modern lifestyle, the spectrum of CVD among those in Africa is still dominated by cardiomyopathies, pericardial diseases and pulmonary hypertension. While improving the detection and management of the latter is critical, it is also very important for healthcare providers in Africa to remain watchful as the CVD profile in people with HIV may change with time, as many people will live longer on antiretroviral therapies.

Childhood CVDs are discussed by Drs Zühlke, Mirabel and Marijon12 in an article demonstrating that these conditions are largely dominated by rheumatic heart diseases (RHD) and congenital heart disease (CHD). They tend to occur at much higher rates in Africa than in other parts of the world, where they are associated with poor prognosis resulting from delayed diagnosis and treatment. While appropriate prevention and/or treatment measures for these conditions exist, their uptake in Africa is still inappropriate. In spite of the resource constrains, implementation projects for early diagnosis of CHD, followed by corrective surgery are underway in many parts of the continent.13 Such efforts for RHD are limited by the many uncertainties regarding optimal age for screening, the appropriate screening tool, and course of action following screening.14 Cardiovascular diseases of a modern lifestyle and major risk factors are covered in four articles in the series. In one of these four, myocardial infarction and stroke in Africa are revisited by Ntsekhe and Damasceno.15 Their report suggests that ischaemic heart disease is still a relatively modest contributor of CVD in Africa; however, the burden of risk factors for atherosclerosis is rapidly increasing across the diversity of rural and urban settings in Africa.

Stroke on the other hand is now an established major cause of premature mortality and disabilities in Africa, resulting primarily from hypertension and less from atherosclerosis. Hypertension is covered in great detail by Ogah and Rayner,16 showing that hypertension is one of the most investigated cardiovascular risk factors in Africa. Since 2007 when the last comprehensive overview of hypertension studies in Africa was published,17 at least 38 new studies have been reported, mostly from urban Africa. Increasingly high prevalences of hypertension continue to be reported against a background of low rates of detection, treatment and control.

The last articles of the series are two companion articles

by Kengne and collaborators,18,19 focusing on diabetes and obesity. They report that diabetes incidences are on the rise in Africa, essentially paralleling those for obesity, but studies to characterise them have been less than optimal. The care of diabetes largely remains suboptimal in most countries, which are ill-prepared to face the control and prevention of diabetes, as the costs of caring for the condition pose a challenge to most local economies. Moreover, translation strategies to prevent and control diabetes and obesity in Africa are still to be evaluated.18,19 Altogether, the eight articles provide a timely and comprehensive overview of the evidence currently available to carry the fight against cardiovascular diseases into the second decade of the 21st century and beyond. In the accompanying editorial, Bongani Mayosi, the series editor, shows strong support for the 10 key population-level interventions of proven cost-effectiveness that are well-suited to the low-income settings of African countries, as the appropriate recipes for preventing cardiovascular diseases from compromising the long-expected and gradually experienced economic development of the African

105

continent.20 Concerted action will be needed to integrate the ‘10 best buys’ for the prevention and treatment of heart disease, diabetes and stroke in the national plans for action on NCDs in African countries.

ANDRE PASCAL KENGNE, andre.kengne@mrc.ac.za Department of Medicine, University of Cape Town and South African Medical Research Council, Cape Town, South Africa BONGANI M MAYOSI Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

United Nations. United Nations, Department of Economic and Social Affairs, Population Division, Population Estimates and Projections section 2012.

Omran AR. The epidemiologic transition theory revisited thirty years later. World Health Stat Q 1998; 51: 99–119.

Kengne AP, Ntyintyane LM, Mayosi BM. A systematic overview of prospective cohort studies of cardiovascular disease in sub-saharan africa. Cardiovasc J Afr 2012; 23: 103–112.

Jones AC, Geneau R. Assessing research activity on priority interventions for non-communicable disease prevention in low- and middleincome countries: A bibliometric analysis. Glob Health Action 2012; 5: 1–13.

Opie LH, Mayosi BM. Cardiovascular disease in sub-Saharan africa.

Circulation 2005; 112: 3536–3540.

Echouffo-Tcheugui JB, Kengne AP. A United Nation high level meeting on chronic non-communicable diseases: Utility for Africa? Pan Afr Med J 2012; 11: 71.

William AW. Heart disease in the native population of uganda. Part 1.

Syphilitic heart disease. East Afr Med J 1938; 15: 279.

Mocumbi AO, Falase AO. Recent advances in the epidemiology, diagnosis and treatment of endomyocardial fibrosis in Africa. Heart 2013, e-pub 16 May 2013.

Sliwa K, Mayosi B. Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathies in Africa.

Heart 2013, e-pub 16 May 2013.

Damasceno A, Mayosi BM, Sani M, Ogah OS, Mondo C, Ojji D, et al. The causes, treatment, and outcome of acute heart failure in 1006 africans from 9 countries. Arch Intern Med 2012; 172: 1386–1394.

Syed FF, Sani MU. Recent advances in HIV-associated cardiovascular diseases in africa. Heart 2013 e-pub 16 May 2013.

Zuhlke L, Mirabel M, Marijon E. Congenital and rheumatic heart disease in africa: Recent advances and current priorities. Heart 2013, e-pub 16 May 2013.

Awori MN, Ogendo SW, Gitome SW, Ong’uti SK, Obonyo NG. Management pathway for congenital heart disease at Kenyatta National Hospital, Nairobi. East Afr Med J 2007; 84: 312–317.

Zuhlke L, Mayosi BM. Echocardiographic screening for subclinical rheumatic heart disease remains a research tool pending studies of impact on prognosis. Curr Cardiol Rep 2013; 15: 343.

Ntsekhe M, Damasceno A. Recent advances in the epidemiology, outcome, and prevention of myocardial infarction and stroke in subsaharan africa. Heart 2013, e-pub 16 May 2013.

Ogah OS, Rayner BL. Recent advances in hypertension in africa. Heart 2013, e-pub 24 May 2013.

Addo J, Smeeth L, Leon DA. Hypertension in sub-Saharan Africa: A systematic review. Hypertension 2007; 50: 1012–1018.

Kengne AP, Echouffo-Tcheugui J, Sobgnwi E, Mbanya JC. New insights on diabetes mellitus and obesity in africa. Part 1: Prevalence, pathogenesis and comorbidities. Heart 2013, e-pub 16 May 2013.

Kengne AP, Echouffo-Tcheugui J, Sobgnwi E, Mbanya JC. New insights on diabetes mellitus and obesity in Africa. Part 2: Prevention, screening and economic burden. Heart 2013, e-pub 16 May 2013.

Mayosi B. The 10 ‘best buys’ to combat heart disease, diabetes and stroke in Africa. Heart 2013, e-pub 16 May 2013.

AMPLATZER™ Cardiac Plug Structural Heart Therapy

An Alternative Ther apy for Reducing the Risk of Stroke in Patients with Atrial Fibrillation1 Current evidence suggests that percutaneous occlusion of the left atrial appendage (LAA) is efficacious in reducing the risk of thromboembolic complications associated with non-valvular atrial fibrillation.1 The AMPLATZER Cardiac Plug offers secure placement in a shallow landing zone and positional forgiveness with a self-orienting disc. It is designed for a complete seal of the LAA.

SJMprofessional.com

1. Percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation for the prevention of thromboembolism. National Institute for Health and Clinical Excellence. http://www.nice.org.uk/nicemedia/live/11216/49407/49407.pdf. Published June 2010.

Accessed April 2011.

Product referenced is approved for CE Mark. AMPLATZER, ST. JUDE MEDICAL and the nine-squares symbol are trademarks and service marks of St. Jude Medical, Inc. and its related companies. Š2013 St. Jude Medical. All Rights Reserved.

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CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013

Cardiovascular Topics Left atrial appendage closure in patients with atrial fibrillation in whom warfarin is contra-indicated: initial South African experience MARK ABELSON

Abstract Atrial fibrillation is a common cause of cardiac embolic events, especially stroke. Oral anticoagulation therapy is used to reduce these events. Many patients however are unable to take such therapy. Percutaneous occlusion of the left atrial appendage (the source of 90% of these emboli) is an option in these patients. Presented here are the first 12 patients to have this procedure done in South Africa.

Keywords: atrial fibrillation, warfarin, left atrial appendage plug Submitted 4/12/12, accepted 18/3/13 Cardiovasc J Afr 2013; 24: 107–109

www.cvja.co.za

DOI: 10.5830/CVJA-2013-018

Atrial fibrillation (AF) is the most common cardiac arrhythmia.1 It is a major cause of morbidity and mortality due to not only cardio-embolic events such as stroke but also anticoagulantrelated major bleeding complications.2 The prevalence of AF increases with age (affecting up to 15% of patients over 80 years) and in patients with predisposing conditions such as hypertension, diabetes, heart failure and ischaemic heart disease.1 Approximately 25% of ischaemic strokes are due to cardiac embolism because of underlying atrial fibrillation.3 Strokes in patients with atrial fibrillation are generally larger with a worse prognosis than in patients without atrial fibrillation.4 Anticoagulation with the vitamin K antagonist, warfarin, and the recently available new agents, dabigatran and rivaroxoban, are indicated to prevent cardiac thrombo-embolism from occurring in patients with atrial fibrillation and a CHADS2/CHADS-Vasc score > 1.5-8 In many patients, however, anticoagulation is contra-indicated due to high bleeding risk (HASBLED score > 3),9 life-threatening bleeds of unknown cause while on anticoagulation, or due to perceived frailty and high risk of falls, especially in very elderly patients.10,11 Furthermore, INR control of patients on warfarin is generally poor. This is particularly so in South Africa (South African patients enrolled in the Active W Trial had the worst INR control internationally, with < 50% of patients’ INR in the therapeutic range), possibly due to no-compliance or interactions with food, drugs and lifestyle.12 Vergelegen Mediclinic, Somerset West, South Africa

MARK ABELSON, MB BCH, MRCP (UK), FCP (SA), mark@helderbergheart.co.za

An alternative approach to prevention of cardiac embolism in patients with AF is therefore desirable. One that can be used in all patients and does not require anticoagulation other than low-dose aspirin. Post-mortem and trans-oesophageal echo studies have shown that approximately 90% of all cardiac thrombi originate from the left atrial appendage (LAA) in patients with AF.13 Surgical exclusion of the LAA at the time of mitral valve surgery or CABG has been shown to reduce the incidence of cardiac embolic events in patients with AF.14 It is on this basis that percutaneous exclusion of the LAA has been developed, initially using the Plato device15 (no longer in production) and followed by the Watchman (Boston Scientific)16 and the Amplatzer CardiacPlug (ACP) (St Jude) devices.17-19 This article reports the initial safety, feasibility and clinical follow up after ACP implantation for non-valvular AF in the first 12 patients to be operated on in South Africa.

Methods Twelve consecutive patients who received LAA occlusion with the ACP from November 2010 were prospectively studied.

All patients had permanent atrial fibrillation of more than six months’ duration and a CHADS-Vasc score of > 2. All had a major contra-indication to anticoagulation. All but one patient had experienced at least one major bleed, requiring blood transfusion, despite a therapeutic INR. Patient characteristics are shown in Table 1. No patients were on warfarin at the time of the TABLE 1. PATIENT CHARACTERISTICS Patient Age Gender Type of AF CHADS2-Vasc

Wafarin contra-indication

1

73

Male

Permanent 5 (age, PVD, CCF, stroke)

Gastric bleed, labile INR

2

75

Male

Permanent 5 (age, HPT, stroke)

Stroke on warfarin, labile INR

3

75

Male

Permanent 5 (age, DM, IHD, CCF) Major GI bleed

4

82

Male

Permanent 6 (age, stroke, HPT, PVD)

Recurrent major epistaxis

5

79

Male

Permanent 2 (age)

Recurrent major GI bleed

6

67

Male

Permanent 3 (age, HPT, IHD)

Major GI bleed

7

54

Male

Permanent 3 (DM, HPT, CCF)

Major GI bleed

8

61

Male

Permanent 3 (DM, HPT, IHD)

Major GI bleed

9

61

Male

Permanent 2 (HPT, CCF)

Active ulcerative colitis

10

62 Female Permanent 3 (female, stroke)

11

68

Male

Permanent 4 (age, HPT, IHD, DM) Massive retroperitoneal bleed

12

65

Male

Permanent 4 (age, HPT, stroke)

Labile INR

Spontaneous subdural haemorrhage

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CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 4, May 2013

TABLE 2. PROCEDURE CHARACTERISTICS (n = 12) Implantation success Residual leak Device size Fluoroscopy time Hospital stay duration

12 1 25.8 mm (22–30) 23.14 min (14.9–35.4) 1 day in all patients

procedure. All patients had been pre-treated on the day of the procedure with aspirin 300 mg and clopidogrel 600 mg.

Ten procedures were done at Vergelegen Medi-Clinic, Somerset West. The first seven were with proctor guidance.

One was done at Groote Schuur Hospital, Cape Town and one at Vincent Pallotti Hospital, Cape Town. All procedures were done under general anaesthetic, as transoesophageal echocardiogram (TOE) guidance is required during the procedure. Trans-septal puncture was done via the right femoral vein in the usual manner using TOE guidance. Following trans-septal puncture, 5 000 units of intravenous heparin was given and ACT was maintained > 250 s for the procedure.

An angiogram was then taken of the left atrial appendage to size the left atrial appendage orifice. A suitably sized device was then selected and placed in the appropriate position using TOE and angiographic guidance. All patients had a transthoracic echocardiogram after the procedure and the next day to exclude a pericardial effusion or device shift.

Patients were discharged home the following day on aspirin 82–150 mg daily indefinately and clopidogrel 75 mg daily for a month. All patients were seen at one month post procedure with a transthoracic echocardiogram, and six-monthly thereafter.

Results There were no procedure-related complications and 100% implantation success was achieved. In one case the initial device chosen was too small and a second larger device was chosen (Table 2, procedure characteristics). The average device size was 25.8 mm. All patients were disharged home the following day.

There were no serious safety events, particularly pericardial effussion, device embolisation or procedure-related stroke (Table 3). No patients had pericardial effusions seen on echo immediately after the procedure and on discharge the following day.

Watchman device

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TABLE 3. COMPLICATIONS – ACUTE AND ON FOLLOW UP (n = 12) Cardiac tamponade Pericardial effusion Device embolisation Procedure-related stroke Subsequent stroke/embolic event off warfarin Access site complications Death, all cause Duration of follow up (mean)

0 0 0 0 0 0 0 12.8 months (2–20)

Clopidogrel was stopped in all patients at one month, except one patient who stopped the clopidogrel after one week due to recurrent epistaxis (Patient 4). On follow up varying between three and 20 months, no cardiac embolic events had been recorded in any patients. All devices are well seated and there have been no device-related complications.

Discussion Occluding the LAA in patients with AF and thereby preventing the vast majority of intracardiac thrombus formation is a highly attractive concept, especially for those patients who are unable to take any form of oral anticoagulant therapy. The patients, however, must be made aware that exclusion of the LAA, similar to when using warfarin, does not absolutely exclude risk of future strokes.

The Protect AF study,16 using the Watchman device, randomised 542 AF patients, 2:1 between the device versus warfarin. This study showed the device was non-inferior to warfarin in terms of stroke prophylaxis with a trend towards superiority. In the successfully treated population (device deployed and warfarin stopped) the primary efficacy event rate (all stroke) in the intervention group who discontinued warfarin was 1.9 per 100 patient years compared with 4.6 per 100 patient years in the control group who received warfarin (RR = 0.40).

Primary safety events occurred at a higher rate in the intervention group than in the control group (7.4 per 100 patient years vs 4.4 per 100 patient years; RR = 1.69). The most frequent primary safety event in the intervention group was serious pericardial effusion (requiring drainage), which occurred in 4.8% of patients. No patients with pericardial effusion died.

Amplatzer cardiac plug Disc to seal LAA orifice

Potential source of leakage between device and LAA orifice

Deep LAA anatomy is required for Watchman device

ACP implantation is possible in patient with shallow LAA because of short device length

Fig. 1. Schematic diagrams illustrating the difference between ACP and Watchman devices (with permission John Wiley and Sons18).

Fig. 2. Amplatzer cardiac plug seen on CT scan occluding the left atrial appendage orifice 12 months post deployment.

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Most safety events occurred during the first three implant procedures (12.3 vs 5.9% subsequently). These safety events have been further significantly reduced in the subsequent 460 patients enrolled in the Continued Access Patient Registry to 3.7%, most likely due to increasing operator experience.20 The ACP is used extensively in Europe and Asia as an alternative to the Watchman device due to it’s perceived superiority in sealing the LAA orifice (Figs 1, 2). The Watchman device consists of a parachute-shaped nitonol frame which plugs the LAA orifice while the ACP consists of two parts; one, the lobe, fixes the device into the left atrial appendage and second, the disc, which seals off the LAA orifice. The incidence of leaks into the LAA on follow-up TEE is approximately 30% with the Watchman device and just over 1% with the ACP.19 The European Prospective Observational Study (n = 204) using the ACP in patients with AF who have contra-indications for oral anticoagulant therapy had a 96.6% implantation success rate with a total safety event rate of 2.9% (serious pericardial effussion 1.5%). There were no procedure-related strokes or TIA. After 101 patient years’ follow up, the actual stroke rate was 1.98%. The estimated annual stroke risk was 5.6%, according to the average CHADS2 score of 2.6.19 Although randomised, controlled trials comparing the ACP device versus either warfarin or no anticoagulant treatment are still currently in progress, observational studies have shown that the actual incidence of stroke is less than half of the predicted risk using the CHADS2 score when used in patients in whom warfarin is contra-indicated.17-19 In the 12 South African patients presented here, nine had had at least one major bleed requiring blood transfusion despite a sub-therapeutic/therapeutic INR level. No bleeds were related to warfarin toxicity. The average CHADS2-Vasc score was 3.75, which gives an estimated annual stroke risk of nearly 4% in patients who are unable to take warfarin. The implantation success rate was 100%. There were no safety events – in particular no stroke or TIA, no device embolisation and no pericardial effusion.

All patients are currently on low-dose aspirin alone and there have been no strokes or other cardio-embolic events to date.

There have been no deaths of any cause. No patients have had any further major bleeds after stopping warfarin therapy.

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

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18.

Conclusion In patients with AF and a CHADS2-Vasc score > 2 who are unable to take oral anticoagulant therapy, percutaneous occlusion of the LAA is a reasonable option to consider. As more data regarding this procedure become available over time and the results confirm the current positive results, this procedure could potentially become a first-line consideration in patients with AF facing a lifetime of anticoagulation.

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19.

20.

Falk RH. Atrial fibrillation. New Eng J Med 2001: 344; 1067–1078.

Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham study. Stroke 1991: 22; 983–988.

Roger VL, Go AS, Lloyd-Jones DM. Heart disease and stroke statistics – 2011 update: a report from the American Heart Association.

Circulation 2011: 123; e18–e209.

Lin HJ, Wolf PA, Kelly-Hayes M. Stroke severity in atrial fibrillation.

The Framingham study. Stroke 1996: 27; 1760–1764.

Singer DE, Chang Y, Fang MC. The net clinical benefit of warfarin anti-coagulation in atrial fibrillation. Ann Int Med 2009: 151; 297–305.

Connolly SJ, Eikelboom J, Joyner C. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009: 361; 1139–1151.

Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med 2011; 365: 883–891.

European Heart Rhythm Association; European Association for CardioThoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010; 31(19): 2369–2429.

Lip GYH, Frison L, Halperin JL, et al. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2011; 57: 173–180.

Bungard TJ, Ghali WA, Teo KK. Why do patients with atrial fibrillation not receive warfarin? Arch Intern Med 2000: 160; 41–46.

Hylek EM, Evans-Molina C, Shea C. Major hemorrhage and tolerability of warfarin the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007: 115; 2689–2696.

Editors comments. Cardiovasc J Afr 2011: 22; 220.

Aberg H. Atrial fibrillation. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand 1969: 185; 373–379.

Blackshear JL, Odel JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996: 61; 755–759.

Block PC, Burstein S, Casale PN. Percutaneous left atrial appendage occlusion for patients in atrial fibrillation suboptimal for warfarin therapy: Five year results of the PLAATO study. J Am Coll Cardiol Cardiovasc Interven 2009: 2; 594–600.

Holmes DR, Reddy VY, Turi ZG. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: A randomised non-inferior trial. Lancet 209: 374; 534–542.

Park J, Bethencourt A, Sievert H. Left atrial appendage closure with the Amplatzer cardiac plug in atrial fibrillation: Initial European experience. Cathet Cardiovasc Interven 2011: 77; 700–706.

Yong G, Gattorna T, Paul V. Left atrial appendage closure with Amplatzer cardiac plug for stroke prevention in atrial fibrillation: Initial Asia-Pacific experience. Cathet Cardiovasc Intervent 2012: 79; 794–800.

Walsh K. Left atrial appendage closure with the Amplatzer cardiac plug: results of the European prospective observational study. Presented Euro-PCR 2012.

Reddy VY, Holmes DR, Doshi SK. Safety of percutaneous left atrial appendage closure: Results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation 2011: 123; 417–424.

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Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome?

A retrospective cohort study JANE MOSES, ANTON F DOUBELL, PHILIP G HERBST, KARL JC KLUSMANN, HELLMUTH SVH WEICH

Abstract Background: Guidelines advise early angiography in non-ST elevation myocardial infarction (NSTEMI) to ensure an optimal outcome. Resource limitations in secondary hospitals in the Western Cape dictate a local guideline to treat NSTEMIs medically with out-patient assessment for angiography, unless mandatory indications for early angiography occur.

Methods: A retrospective cohort study assessed NSTEMIs at Tygerberg Hospital (TBH), Karl Bremer Hospital (KBH) and Worcester Hospital (WH) over one year. Two cohorts were analysed, secondary hospitals (KBH and WH; SH) and secondary service within a tertiary hospital (TBH). Where differences were found, sub-analysis compared WH and KBH. Results: TBH and SH were similar at baseline and in clinical presentation. Cases at TBH were more likely to receive in-patient angiography (94 vs 51%, p < 0.0001), and had a lower in-patient mortality rate (6 vs 23%, p = 0.0326). There was no difference between KBH and WH in sub-analysis.

Conclusion: This study confirmed that the management and mortality of NSTEMIs in the public health sector in the Western Cape, South Africa is not influenced by geography, but rather by the level of service available in the hospital of first presentation.

Keywords: acute coronary syndrome, NSTEMI, myocardial infarction Submitted 19/9/12, accepted 18/3/13 Cardiovasc J Afr 2013; 24: 110–116

www.cvja.co.za

DOI: 10.5830/CVJA-2013-017

The European Society of Cardiology (ESC) guidelines state that patients presenting with an acute coronary syndrome (ACS) with raised cardiac markers and without ST-segment elevation (non-ST elevation myocardial infarction – NSTEMI), should receive early coronary angiography and revascularisation,1 as Division of Cardiology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, South Africa JANE MOSES, MB ChB, FCP (SA), MMed (Int Med), drjanemoses@ gmail.com ANTON F DOUBELL, MB ChB, MMed (Int Med), FCP (SA), BSc Hons, PhD (Med Biochem) PHILIP G HERBST, MB ChB, MRCP (UK), FCP (SA), Cert Cardiol (SA) HELLMUTH SVH WEICH, MB ChB, MRCP (UK), MMed (Int Med), Cert Cardiol (SA)

Department of Medicine, Stellenbosch University and Worcester Hospital, South Africa

KARL JC KLUSMANN, MB ChB, MSc (Sports Med), MMed (Int Med)

trials have shown clear mortality benefit for such an early invasive approach.2-6 The South African Heart Association is an affiliated member of the European Society of Cardiology (ESC) and therefore subscribes to its guidelines, but strict adherence is not always possible due to limited facilities and personnel.

The South African public health service is divided into three levels of care; primary care (managed by family physicians), secondary care (with certain specialists such as specialist physicians but without sub-specialist care), and tertiary care (provided by academic referral hospitals and with access to sub-specialist services such as cardiologists). These tertiary centres are usually located in large cities, resulting in inequality in the distribution of sub-specialist care. This may be detrimental to many patients presenting to secondary hospitals but the extent of this is unknown. Furthermore, the studies on which these guidelines are based were performed in the first world and may not be applicable to our patients or practice, even to those presenting primarily to sub-specialist centres.7-10 Current best-practice guidelines as practiced in secondary hospitals in the Western Cape suggest patients with NSTEMIs be admitted for medical management, including bed rest, antiplatelet treatment with aspirin, β-blockade, anti-coagulation with heparin (unfractionated or low molecular weight; LMWH) and nitrates (sub-lingual or intravenous). All patients are given a statin for secondary prevention and should their blood pressure allow, all are prescribed an angiotensin converting enzyme inhibitor (ACE inhibitor) or an angiotensin receptor blocker (ARB). This treatment is continued for 48 hours provided the patient remains pain free. Cardiac enzymes are taken at least once, six to 12 hours after the index pain.

Should the patient be haemodynamically unstable or experience on-going ischaemia (on-going/recurrent chest pain or dynamic ischaemic ECG changes), referral to a tertiary centre for angiography is indicated. Patients with a TIMI score11 of 5 or more are also referred.

Should the patient remain asymptomatic on medical management, heparin anticoagulation is discontinued after 48 hours and the patient is mobilised. If the patient develops recurrence of ischaemic chest pain on mobilisation, referral to a tertiary centre for angiography follows. Should the patient mobilise without complication, a sub-maximal exercise stress test (EST) is performed pre-discharge where possible to exclude poor prognostic features, which also dictate referral. Patients who do not demonstrate any of these features are referred to the tertiary centre as out-patients.

The current best-practice guidelines therefore aim to identify a small group of very high-risk patients who are referred for early angiography, whereas medical management is considered sufficient for those who stabilise on heparin anticoagulation

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and mobilise without complication. This is regardless of the troponin level, which is for prognostic purposes only; exposing a significant proportion of patients who would be classified as high risk according to the ESC guidelines to potentially sub-optimal care according to these guidelines.1 Despite these clear local best-practice guidelines, very little is known regarding the demographics, actual management and referral patterns of patients suffering an NSTEMI in South Africa and how this influences the outcome of those patients.

This study aimed to determine whether the management of an NSTEMI differs depending on the hospital to which the patient presents (patients presenting to secondary hospitals being less likely to receive early invasive management), and if so, whether this is a consequence of geographical remoteness or level of care, and how this influences outcome.

Methods After obtaining ethical approval, including a waiver of informed consent from the University of Stellenbosch’s Health Research Ethics Committee (reference no: N11/09/288), a retrospective cohort study was conducted looking at adults presenting with NSTEMIs to TBH, KBH and WH. This was done over a one-year period from September 2010 to August 2011. Patients presenting during the first six months of the study time were analysed in terms of clinical risk profile and in-patient management, and then subsequent management up to six months post admission.

These hospitals were chosen for their unique similarities and differences. TBH is situated in Parow, Cape Town and is one of two academic referral centres in the city. It has 1 310 beds and provides a tertiary service to about 2.64 million people.12 In addition it provides a secondary service to the immediate surrounding areas, this latter group being the subject of this study. The Division of Cardiology within the Department of Medicine at TBH manages all ischaemic chest pain and has 28 beds with three full-time cardiologists.

KBH and WH are both secondary hospitals, similar except for their physical proximity to their tertiary referral centre, namely TBH. KBH and WH have 282 and 269 beds, respectively, with 84 and 55 of those beds being assigned to the Departments of Medicine. Both hospitals have two full-time specialist physicians. Like TBH, KBH is also situated in Parow, 4.6 km from TBH, while WH is situated in the Boland/Overberg region of the Western Cape, approximately 94 km (over an hour) away from TBH. Patients 18 years and older presenting to the Departments of Medicine at KBH and WH, and to the secondary service provided by the Division of Cardiology, Department of Medicine at TBH with an NSTEMI from September 2010 until February 2011 were included in this retrospective study. NSTEMI was defined as angina-type chest pain in an unstable pattern, requiring hospitalisation and associated with elevated troponin levels (troponin I ≥ 1.0 µg/l; troponin T ≥ 0.1 ng/ml) and no signs of ST-segment elevation.1 Patients with the following were excluded: renal failure (creatinine > 200 µmol/l), patients who developed an NSTEMI during hospitalisation for a condition other than ACS, including surgery within two weeks, cerebrovascular accident (CVA), anaemia (haemoglobin < 9 g/l), septicaemia (fever and evidence of systemic infection), warfarin therapy, known high bleeding

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risk, life expectancy less than six months, patients referred from other secondary hospitals for tertiary care. Previously documented left bundle branch block (LBBB) without new changes were allowed.

Cases were identified from the records of the National Health Laboratory Service at KBH, WH and TBH. All recorded positive cardiac troponin levels from September 2010 to February 2011 were collected. After obtaining permission from the chief medical superintendent, the original medical records of all these cases were requested and screened and those identified as having suffered an NSTEMI without exclusion criteria were included in the study.

Data were collected anonymously from the medical records of those cases identified for inclusion. Two data sets were collected, data during the index admission and data from followup visits over the following six months. Those cases for which no information was available at six months were included in the initial data set and documented as lost to follow up for the second data set (Fig. 1).

Statistical analysis The statistical analysis was done in conjunction with the University of Stellenbosch’s Centre for Statistical Consultation.

Data from the two secondary-level hospitals (WH and KBH) were combined into a single data set, referred to as the secondary hospitals (SH). This data set was then analysed and compared with the TBH data. Descriptive statistics and chi-squared comparisons were done for categorical data. A p-value < 0.05 in a two-tailed test of proportions was considered significant.

Unless stated otherwise, continuous data is displayed as mean ± standard deviation (SD). Analysis of variance was done on this data and a p-value < 0.05 was considered significant.

Where statistically significant differences in management or outcome were found between the SH cohort and the TBH cohort, a sub-analysis was done comparing WH and KBH to ascertain whether these differences were due to differences in management between these hospitals.

Results The baseline characteristics of the two groups were similar except for more documented dyslipidaemia and prior aspirin use in the TBH group (Table 1).

The groups were similar in terms of their clinical presentation (Table 2). In 58% of patients it was their first presentation with chest pain. There was a large variation in time to presentation from the onset of pain (mean: 24.21 ± 33.75 hours, median: 7 hours). On presentation, patients had a heart rate of 85.73 ± 24.85 beats per minute. Cardiac failure was documented in 39%, with a relatively equal distribution between Killip II, III and IV failure.13 Very few patients (5.26%) had a normal ECG, with the most frequent abnormality being ST-segment depression, seen in 46%.

Patients presenting to TBH had a significantly higher TIMI score than those presenting to the SH (p = 0.0046). This could not be accounted for by differences between WH and KBH, where the TIMI score was 3.412 ± 1.064 and 3.615 ± 1.134, respectively (p = 0.5587).11 This difference in risk stratification was not reflected in the Grace risk score.14 Most cases were treated with aspirin (87%) and LMWH

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WH = 51 cases with positive troponin 34 cases excluded: • 18 STEMI • 12 renal failure • 3 anaemia • 1 no folder available

KBH = 82 cases with positive troponin

TBH = 202 cases with positive troponin

56 cases excluded: • 27 STEMI • 13 renal failure • 3 anaemia • 3 sepsis • 5 CVA • 1 warfarin Rx • 1 life expectancy < 6 months • 3 no folder available

WH = 17 NSTEMI cases included

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169 cases excluded: • 63 referred from secondary hospitals • 79 STEMI • 4 renal failure • 6 anaemia • 2 sepsis • 2 warfarin Rx • 13 no folder available

KBH = 26 NSTEMI cases included

Secondary hospitals = 43 NSTEMI cases included at admission • 10 died during index admission • 3 lost to follow up Secondary hospitals = 30 NSTEMI cases included at 6 months

TBH = 33 NSTEMI cases included at admission • 2 died during index admission • 3 lost to follow up TBH = 28 NSTEMI cases included at 6 months

WH: Worcester Hospital, KBH: Karl Bremer Hospital, TBH: Tygerberg Hospital, NSTEMI: non-ST-elevation myocardial infarction, STEMI: ST-segment elevation myocardial infarction, CVA: cerebrovascular accident.

Fig. 1. Data capturing.

(91%) (Table 3). Those presenting to TBH were more likely to receive early β-blockade than were those presenting to the SH (67 vs 35%, respectively, p = 0.0055). This could not be accounted for by a difference between WH and KBH where 41 and 31% of patients received β-blockers, respectively (p = 0.4839).

While the clinical presentation and initial medical management was largely similar for the two cohorts, there were significantly more angiograms performed in the TBH group (94%) compared to the SH group (51%) (p < 0.0001) (Table 4). Again this was not due to differences in the frequency of invasive management between WH (48%) and KBH (54%) in sub-analysis (p = 0.6633). There was also no difference in the frequency of referral to TBH from WH or KBH (71 and 73%, respectively; p = 0.8588), and the acceptance rate of referrals was equally high from both hospitals (92% for WH and 94% for KBH, p = 0.7347). Cases from WH did however have a significantly longer time to angiography than those from KBH (3 ± 1.60 vs 1.5 ± 1.22 days respectively, p = 0.0225).

At angiography, stenosis was seen in the left anterior descending artery (LAD) in 72% of cases, in the right coronary artery (RCA) in 72% and in the left circumflex (LCx) in 59%. In 80% of cases there was multi-vessel disease (40% double-vessel and 40% triple-vessel disease); 6% had small-vessel disease.

If percutaneous intervention (PCI) was performed, the culprit lesion was the RCA in 21%, the LCx in 21% and the LAD in 17% of cases.

When angiography was performed, both cohorts were equally likely to receive coronary revascularisation via PCI (45% for the SH and 68% for TBH, p = 0.1018). The SH group had more

TABLE 1. BASELINE CHARACTERISTICS Secondary hospitals TBH n = 43 (%) n = 33 (%) p-value Age (years) (± SD) 60.5 (± 12.6) 61.0 (± 14.88) 0.8774 Male 24 (56) 19 (58) 0.8779 Female 19 (44) 14 (42) 0.8779 Hypertension 33 (77) 23 (70) 0.4903 Diabetes mellitus 12 (28) 14 (42) 0.1868 Dyslipidaemia 16 (37) 20 (61) 0.0421* Obesity 3 (7) 1 (3) 0.4319 Smoking 24 (56) 18 (52) 0.7993 Current 17 (40) 11 (33) 0.2641 Past 7 (16) 7 (21) 0.3873 COPD 3 (7) 2 (6) 0.8727 Ischaemic heart disease 16 (37) 17 (52) 0.2123 Stable angina pectoris 5 (12) 4 (12) 0.2123 Unstable angina pectoris 1 (2) 3 (9) 0.1905 Previous MI 10 (23) 9 (27) 0.6885 Previous angiography 9 (21) 10 (30) 0.3496 Previous stent 3 (7) 8 (18) 0.1340 Previous CABG 4 (9) 7 (21) 0.1436 Family history of IHD 4 (9) 5 (15) 0.4363 Prior asprin use within 7 days 20 (47) 23 (70) 0.0415* Known stenosis > 50% 7 (16) 11 (33) COPD: chronic obstructive pulmonary disease, MI: myocardial infarction, CABG: coronary artery bypass graft. *p-values calculated comparing TBH and secondary hospital groups, p < 0.05 was statistically significant.

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TABLE 2. CLINICAL PRESENTATION Secondary hospitals n = 43 (%)

TBH n = 33 (%)

TABLE 3. INITIAL MEDICAL MANAGEMENT

p-value

Chest pain First episode

TBH n = 33 (%)

p-value

35 (81)

31 (94)

0.9558

150 mg

30 (70)

28 (85)

0.1253

Aspirin

19 (58)

0.9606

300 mg

5 (12)

3 (9)

0.7209

Time to present (hours) (± SD) 19.65 (± 29.54)

30.15 (± 38.21)

0.1963

β-blocker

15 (35)

22 (67)

0.0055*

Duration of pain (mins) (± SD) 30.15 (± 38.21)

Nitrates

Recurrence Pulse rate (beats per minute) (± SD)

25 (58)

Secondary hospitals n = 43 (%)

47.58 (± 35.51)

0.1488

25 (60)

17 (56)

0.6559

23 (55)

14 (42)

0.2880

sub-lingual

16 (40)

9 (30)

0.4046

84.16 (± 28.20)

87.84 (± 19.89)

0.4072

intravenous

9 (21)

8 (24)

0.7313 0.0829

Systolic blood pressure (mmHg) 130.67 (± 35.84) 144.84 (± 33.30) 0.0822 (± SD) Diastolic blood pressure (mmHg) (± SD)

75.90 (± 19.81)

80.21 (± 17.91)

0.9568

ECG findings Normal

2 (5)

2 (6)

0.7859

Previous MI

9 (21)

9 (27)

0.5203

ST depression

19 (44)

16 (48)

0.7094

Heparin LMWH

37 (86)

32 (97)

UFH

0 (0)

0

(0)

Morphine

7 (16)

4 (12)

0.6071

Dobutamine

6 (14)

1 (3)

0.0829

LMWH: low-molecular weight heparin, UFH: unfractionated heparin. *p-values calculated comparing TBH and secondary hospital groups, p < 0.05 was statistically significant.

T-wave changes Flattening

6 (14%

1 (3)

0.0829

Inversion

10 (23)

11 (33)

0.3315

Dynamic changes

10 (23)

12 (36)

0.2129

Wellens’ syndrome

2 (5)

4 (12)

0.2322

Left ventricular hypertrophy

5 (12)

5 (15)

0.6536

Left bundle branch block (old)

4 (9)

4 (12)

0.6925

Right bundle branch block

6 (14)

4 (12)

0.8142

Atrial fibrillation

3 (7)

2 (6)

0.8727

Atrial flutter

0 (0)

1 (3)

0.2505

1 (2)

0 (0)

0.3779

4.1–6.9

27 (63)

15 (45)

0.1319

7.0–10.0

8 (19)

6 (18)

10.1–19.9

7 (16)

≥ 20.0

0 (0)

Temperature (°C) Cardiac failure

p-value

22 (51)

31 (94)

< 0.0001*

2.14 (± 1.52) 1.70 (± 1.65)

0.8615

Coronary revascularisation 21 (68)

0.1018

Via PCI (expressed as a % of entire group)

10 (23)

21 (64)

0.0004*

Via PCI or CABG (% of angiography cases)

18 (82)

29 (94)

0.1842

Via PCI or CABG (expressed as a % of entire group)

18 (42)

29 (88)

<0.0001*

0.9624

10 (30)

0.1459

No. of stents

2 (6)

0.1018

Referred for CABG

35.85 (± 0.61)

36.10 (± 0.59)

0.0768

PCI: percutaneous coronary intervention, CABG: coronary artery bypass graft. *p-values calculated comparing TBH and secondary hospital groups, p < 0.05 was statistically significant.

18 (42)

12 (36)

0.4740

8 (19)

5 (15)

0.6919

Killip III

3 (7)

5 (15)

0.2497

Killip IV

7 (16)

2 (6)

0.1718

TIMI score (± SD)

Time (days from admission) (±SD)

TBH n = 33 (%)

10 (45)

Killip II

Serum creatinine (μmol/l) (± SD)

Angiography performed as in-patient

Secondary hospitals n = 43 (%)

Via PCI (expressed as a % of angiography cases)

Finger-prick blood glucose (mmol/l) < 4 .0

TABLE 4. INVASIVE MANAGEMENT ON INDEX ADMISSION

100.09 (± 35.46) 101.21 (± 33.75) 0.1938 3.46 (± 1.42)

4.33 (± 1.08)

0.0046*

in hospital

8.79 (± 14.60)%

5.49 (± 0.09)%

0.2321

at 6 months

15.57 (± 22.49)% 11.03 (± 12.68)% 0.2695

GRACE score (± SD) Probability of death

Probability of death or MI in hospital

18.81 (± 12.82)% 16.72 (± 8.94)% 0.4279

at 6 months

31.67 (± 19.59)% 28.39 (± 13.36)% 0.4119

*p-values calculated comparing TBH and secondary hospital groups, p < 0.05 was statistically significant.

stenosis of the left main stem (LMS) (p = 0.0477) and there was a trend for cases from the SH to be more frequently referred for coronary artery bypass grafting (CABG) (36 vs 26% in the TBH cohort, p = 0.0795), the majority as in-patients.

Patients presenting to TBH directly had a better in-hospital survival rate than those presenting to the SH (94 vs 77%, p = 0.0326) (Table 5). At six months there was a tendency to

1.3 (± 0.48) 1.3 (± 0.91) 8 (36)

8 (25)

0.8952 0.0795

better survival in the TBH group (90 vs 73%, p = 0.0614).

Most patients were discharged on aspirin, β-blockers, ACE inhibitors and statins and remained pain free; 23% of cases were re-admitted to hospital during follow up, most commonly with unstable angina pectoris (UAP) (54%, data not shown); 16% of cases underwent subsequent angiography.

As the numbers of patients re-admitted to hospital (nine for the SH group and four for TBH) and those undergoing angiography after discharge were small (six for the SH and three for the TBH cohort), it was not possible to perform a meaningful statistical analysis looking for differences between these groups; 66% of these cases received coronary revascularisation, either via PCI or subsequent CABG. Cases presenting to TBH underwent subsequent angiography after 1.33 ± 0.57 months, and those from the SH after 4.5 ± 2.07 months.

Discussion The management of patients suffering an NSTEMI presenting to the public health sector is affected by the level of service to which the patient presents. This is not a result of geographical remoteness

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TABLE 5. OUTCOMES AT DISCHARGE AND AT 6 MONTHS Secondary hospitals n = 43 (%)

TBH n = 33 (%)

p-value At Discharge Mortality 10 (23) 2 (6) 0.0326* Discharge medications (% of survivors) Asprin 31 (94) 30 (97) 0.5918 β-blocker 29 (88) 30 (97) 0.1851 ACE inhibitor 25 (76) 26 (84) 0.4201 ARB 1 (3) 2 (6) 0.5175 Statin 30 (91) 29 (94) 0.6942 Spironolactone 3 (9) 2 (6) 0.6942 Clopidogrel 8 (24) 9 (29) 0.6646 Days in hospital (± SD) (% of 6.14 (± 4.33) 5.82 (± 5.26) 0.2100 survivors) At 6 months Survived (expressed as % of 29 (73) 27 (90) 0.0614 entire group) Survived (expressed as % of 29 (97) 27 (96) 0.9247 survivors at discharge) Chest pain (% of survivors at 6 months) None 17 (59) 16 (59) 0.6206 Occasional 9 (31) 10 (37) 0.8540 CCS 2 2 (7) 1 (4) 0.5960 CCS 3 1 (3) 0.(0) 0.3302 Readmission to hospital (% of 9 (31) 4 (15) 0.1461 survivors at 6 months) Subsequent angiography (% of 6 (21) 3 (11) 0.3248 survivors at 6 months) Time from admission (months) 3.86 (± 2.07) 1.33 (± 0.58) 0.0121* Coronary revascularisation 19 (44) 28 (85) 0.0001* within 6 months (n = 43 and 33) CCS: Canadian Cardiovascular Society angina classification *p-values calculated comparing TBH and secondary hospital groups, p < 0.05 was statistically significant.

from the tertiary centre or other differences in management between the secondary hospitals. Patients presenting to the secondary-level service provided by the Division of Cardiology at TBH were more likely to receive invasive in-patient management with coronary angiography than were those presenting to the SH (94 vs 51%, p < 0.0001). This difference was due to the fact that the secondary service at TBH is provided by the sub-specialist Division of Cardiology with immediate access to angiography.

The difference in physical proximity to TBH between WH (94 km away) and KBH (4.6 km away) did not influence the accessibility of in-patient angiography, with cases being equally likely to be referred to and accepted by the Division of Cardiology at TBH from WH and KBH. The difference in the TIMI risk score for the two groups was a potential confounder in the analysis of why the TBH cohort received more angiography than the SH cohort, however both groups fell in the intermediate risk group, so the significance of this difference is unclear.11 The TIMI score was calculated by the investigators from the case records, as it was not uniformly documented. The difference in TIMI score between the TBH cohort and the SH cohort can be accounted for by the difference in frequency of documented dyslipidaemia and prior aspirin

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use in the two groups. This difference may be true, or it may be only an apparent difference due to the retrospective nature of the study.

As the baseline data were captured from patient records, only those cardiovascular risk factors documented could be captured. If there was no record of medications taken prior to admission, prior aspirin use could not be assumed. The fact that the difference between the two cohorts in the TIMI risk score11 was not reflected by the Grace risk score suggests that this might be a factor of documentation rather than one of clinical risk.14-16 This study also showed a difference in in-patient mortality between the two cohorts, with a higher mortality in the SH cohort. This was despite the fact that the TBH cohort had a greater risk for mortality within the first 14 days, as assessed by the TIMI risk score.11 As the only difference in management between the two groups was the initial use of β-blockers (although β-blocker use at discharge was similar in both groups), and in-patient invasive management, one must consider that one of these is responsible for the difference in mortality.

While β-blockers are well known to have benefit acutely in patients with ST-elevation myocardial infarctions (STEMIs),17,18 this is not known for NSTEMIs. On the other hand, it is well documented that early invasive management in patients suffering NSTEMIs improves survival.2-6 It is therefore reasonable to assume that the difference in access to in-patient coronary angiography between the TBH and SH groups was at least in part responsible for the difference in mortality between the two cohorts.

Comparing the study patients to the literature, both the TBH and SH cohorts had a higher mortality rate than expected, both in-hospital (6 and 23%, respectively) and at six months (10 and 27%, respectively). The literature predicts a mortality of 1.4–4.4% in hospital and 1.9–5.9% at six months to one year.9,10,1922 Whether this was due to differences in in-patient angiography rates among our cases (51% for the SH group and 94% for TBH) compared to the literature remains unclear, as in-patient angiography was performed in 10–98% of patients in these trials.10,19-22 The predicted mortality rates for the two cohorts as calculated by the Grace risk score14 (in-patient mortality: 8.79 ± 14.60% and 5.49 ± 0.09%; mortality at six months: 15.57 ± 22.49% and 11.03 ± 12.68% for the SH group and TBH groups, respectively) was also higher than the mortalities expected from the literature, as quoted above.9,10,19-22 The patients in this study were a high-risk group as they all suffered an NSTEMI, whereas the trials quoted above looked at all non-ST elevation ACS (NSTE-ACS), and therefore included patients with UAP. This study also demonstrated a high rate of cardiac failure.

As the presence of cardiac failure was elicited from descriptions in the records, this may have been a true reflection of the study population or it may have been due to documentation. This may explain the high mortality rate in this study, both in reality and as predicted by the Grace risk score.14 When examining the two groups separately, the patients in the TBH cohort came closer to the mortality rate predicted by the Grace risk score,14 both in-hospital and at six months (6 vs 5% in-hospital and 10 vs 11% at six months, respectively) than did those in the SH cohort (23 vs 9% in-hospital and 28 vs 12% at six months, respectively), which would imply that the difference in management (either the increased frequency of angiography

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with in-hospital coronary revascularisation, or the earlier use of β-blockers, or both) was the cause of the difference in mortality, as previously discussed. Referring to earlier literature,10,19,22,23 the rates of angiography in the TBH (94%) and SH cohorts (51%) were similar to and less than the rates of angiography in the early invasive arms of these trials (96–98%),10,19,22,23 respectively.

However, the conservative arms of these trials had lower rates of coronary angiography (11–51%) with a lower mortality rate.10,19,22,23 This implies additional factors contributing to the poorer survival in the South African state hospital setting.

The conservative arms in these earlier international trials10,19,23 included other anti-platelet agents in addition to aspirin (ADP receptor antagonists or glycoprotein IIb IIIa inhibitors), as recommended by the ESC.1 At the time of writing both of these agents were only available to patients undergoing angiography in the state hospital setting in the Western Cape. They are not available for medical management of an NSTE-ACS, even for those at high risk with NSTEMIs. Whether this was the cause of the higher-than-expected mortality rate in this study is not addressed, and further research into this question needs to be performed.

Examining specifically those cases in the SH cohort who died during the index admission, a 23.6 ± 21.98% probability of in-hospital mortality was predicted by the Grace score.14 This suggests that the recorded mortality rate was high in comparison with previous studies. Only half of these 10 cases were referred to TBH, and four of the five referred patients were accepted. It appears from this that lack of referral (50%) of those patients who subsequently died may in part be responsible for a poor outcome. This discrepancy in referral rate and acceptance rate is reflected in the cohort as a whole as well (72% referral rate and 94% acceptance rate). The lack of referral for tertiary care was likely to have been a contributing factor to the relative lack of in-patient angiography and coronary revascularisation in the SH group, and hence the higher in-patient mortality rate.

This study did not investigate the reasons for referral or lack thereof, as this information was difficult to obtain retrospectively.

Further research into this should be done in order to fully address the high mortality rate in the SH cohort.

When looking at coronary revascularisation rates in the two groups, it would appear that the rates of PCI were low in both groups (45% for SH and 68% for TBH). This can be explained by the fact that a high percentage of patients (40%) had triple-vessel disease, and when coronary revascularisation is considered in total [via PCI or coronary artery bypass grafting (CABG)], the rates of revascularisation increased to 82 and 94% for the SH and TBH groups, respectively, suggesting that lack of coronary revascularisation was not a contributing factor in the high mortality.

Limitations This study had several significant limitations. The retrospective nature of the study design left the investigators dependent on clinical records for all data capturing. Record keeping is often less than optimal and significant information such as patients’ use of medications prior to admission was often not available in the records. This could render the baseline characteristics and clinical risk stratification of the patients unreliable, limiting the comparison between the two groups.

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The sample size also limited the study findings. A number of factors contributed to a small sample size. The study intentionally targeted a high-risk group of patients with NSTEMIs. Due to the significant budget constraints experienced in the South African state healthcare system, many cases had only a single cardiac troponin value taken. Although it is part of the current best-practice guidelines that should only one troponin value be requested, it is taken six to 12 hours after the index event. There was no record in the clinical notes documenting that this was practiced. It was not possible to ascertain when the troponin samples were taken, and therefore cases may have been missed.

There were also a number of cases that were excluded due to the inability to obtain the patient’s folder (four for the SH cohort and 13 for the TBH cohort). No information was available for these cases and while it is not known whether these patients suffered an NSTEMI, it does raise concerns regarding the validity of the data. As the investigators were particularly interested in access to in-patient coronary angiography, there were strict exclusion criteria which also contributed to the small number of cases.

The small sample in the WH and KBH groups limited the data analysis in that the two groups had to be combined into a single cohort for analysis. Although sub-analysis was done comparing the WH and KBH groups when statistically significant differences were found and this did not reveal any differences between these two groups, the lack of differences may have been a factor of the sample size. The combination of WH and KBH into a single cohort may also have masked differences between these groups had they been independently compared to the TBH cohort.

Conclusion Despite these limitations, the study did reveal some significant differences in the in-patient management of patients presenting to secondary services at a tertiary centre (TBH) compared to patients presenting to secondary-level centres (KBH and WH). These included less initial β-blocker use, less in-patient invasive management and a higher in-patient mortality rate in the SH group. The lack of difference between the KBH and WH groups in this regard suggests that geographical proximity to (or remoteness from) the tertiary centre (TBH) was not a significant factor determining access to coronary angiography. Clearly factors other than geography and distance, specific to the level of service, were influencing both access to in-patient coronary angiography and in-patient mortality rates.

While it is well established that early angiography has a clear mortality benefit in patients suffering a NSTEMI,2-6 and current research is investigating the optimal timing for angiography; access to in-patient angiography remains problematic in the state hospital setting in the Western Cape, South Africa. The relative lack of access to coronary angiography for patients presenting to secondary-level hospitals, regardless of their geographical proximity to the tertiary centre TBH, results in an adverse mortality outcome for these patients. Coronary angiography remains a scarce resource, with three cardiologists in the Division of Cardiology, Department of Medicine at TBH providing a tertiary service to a population of 2.64 million.12 This inequality in access to in-patient invasive management needs to be addressed as a priority.

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2. Mehta SR, Cannon CP, Fox KA, Wallentin L, et al. Routine vs. selective invasive strategies in patients with acute coronary syndromes:a collaborative meta-analysis of randomized trials. J Am Med Assoc 2005; 293: 2908–2917.doi: 10.1001/jama.293.23.2908.

3. Lagerqvist B, Husted S, Kontny F, Naslund U, Stahle E, Swahn E, Wallentin L. A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: two-year follow-up of the FRISC-II invasive study. J Am Coll Cardiol 2002; 40: 1902–1914. doi: 10.1016/S1062-1458(03)00082-5.

4. Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol 2006; 48: 1319–1325. doi: 10.1016/j.jacc.2006.06.050.

5. Fox KA, Poole-Wilson P, Clayton TC, et al. Five-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005; 366: 914–920. doi: 10.1016/S0140-6736(05)67222-4.

6. Lagerqvist B, Husted S, Kontny F, Stahle E, Swahn E, Wallentin L. Fiveyear outcomes in the FRISC-II randomised trial of an invasive versus a noninvasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study. Lancet 2006; 368: 998–1004. doi:10.1016/S01406736(06)69416-6.

7. Damman P, Hirsch A, Windhausen F, Tijssen JGP, de Winter RJ, for the ICTUS Investigators. Five-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial: A randomized comparison of an early invasive versus selective invasive management in patients with non-ST-elevation acute coronary syndrome. J Am Coll Cardiol 2010; 55(9): 858–864.

8. Poole-Wilson PA, Pocock SJ, Fox KAA, et al. Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial. Heart 2006; 92(10): 1473–1479. doi: 10.0036/ hrt.2005.060541.

9. Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment (“cooling-off ” strategy) before intervention in patients with unstable coronary syndromes: A randomized controlled trial. J Am Med Assoc 2003; 290(12): 1593–1599. doi: 10.1001/jama.290.12.1593.

10. Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001; 344(25): 1879–1887. doi: 10.1056/ NEJM200106213442501.

11. Antman EM, Cohen M, Bernink PJLM, et al. The TIMI risk score

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Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the Global Registry of Acute Coronary Events. Arch Intern Med 2003; 163: 2345–2353. doi: 10.1001/archinte.163.19.2345.

Tatsuya N, Masami K, Kiyoshi H, et al. Comparison of Grace risk score versus TIMI risk score on angiographic findings in patients with non-st-segment elevation acute coronary syndrome. J Am Coll Cardiol 2010; 55; A115.E1071.

De Arau´jo Gonc¸alves P, Ferreira A, Aguiar C, Seabra-Gomes R. TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 2005; 26: 865–872. doi: 10.1093/eurheartj/ehi187.

López-Sendón J, Swedberg K, McMurray J, et al. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 2004; 25(15): 1341. doi: 10.1016/j.ehj.2004.06.002.

Ibanez B, Prat-Gonzalez S, Speidl WS, et al. Early metoprolol administration before coronary reperfusion results in increased myocardial salvage: analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation 2007; 115(23): 2909–2916. doi: 10.1161/ CIRCULATIONAHA.106.679639.

De Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005; 353: 1095–1104. doi: 10.1056/NEJMoa044259.

Ryan JW, Peterson ED, Chen AY, et al. Optimal timing of intervention in non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) registry Circulation 2005; 112; 3049–3057. doi: 10.1161/CIRCULATIONAHA.105.582346.

Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009; 360: 2165–2175. doi: 10.1056/NEJMoa0807986.

FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease. FRISC II prospective randomised multicentre trial. Lancet 1999; 354: 708–715. doi: 10.1016/S0140-6736(99)07349-3.

Fox, KAA, Poole-Wilson PA, Henderson RA, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet 2002; 360: 743–751. doi: 10.1016/ S0140-6736(02)09894-X.

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Pattern of congestive heart failure in a Kenyan paediatric population JULIUS A OGENG’O, PATRICK M GATONGA, BEDA O OLABU, DIANA K NYAMWEYA, DENNIS ONG’ERA

Abstract

Submitted 27/6/11, accepted 18/3/13

Background: Heart failure in children is a common cause of morbidity and mortality, with high socio-economic burden.

Its pattern varies between countries but reports from Africa are few. The data are important to inform management and prevention strategies.

Objective: To describe the pattern of congestive heart failure in a Kenyan paediatric population.

Methods: This was a retrospective study done at Kenyatta National Hospital, Nairobi Kenya. Records of patients aged 12 years and younger admitted with a diagnosis of heart failure between January 2006 and December 2010 were examined for mode of diagnosis, age, gender, cause, treatment and outcome. Data were analysed using the Statistical Programme for Social Scientists version 16.0 for windows, and presented in tables, bar and pie charts.

Results: One hundred and fifty-eight cases (91 male, 67 female) patients’ records were analysed. The mean age was 4.7 years, with a peak at 1–3 years. The male:female ratio was 1.4:1. All the cases were in New York Heart Association (NYHA) class II–IV. Evaluation of infants was based on the classification proposed by Ross et al. (1992). Diagnosis was made based on symptoms and signs combined with echocardiography (echo) and electrocardiography (ECG) (38%); echo alone (12.7%); ECG, echo and chest X-ray (CXR) (11.4%); and ECG alone (10.8%). The underlying cause was established on the basis of symptoms, signs, blood tests, CXR, echo and ECG results. Common causes were infection (22.8%), anaemia (17.1%), rheumatic heart disease (14.6%), congenital heart disease (13.3%), cardiomyopathy (7.6%), tuberculosis and human immunodeficiency virus (6.9% each); 77.9% of patients recovered, 13.9% after successful surgery, and 7.6% died.

Conclusion: Congestive heart failure is not uncommon in the Kenyan paediatric population. It occurs mainly before five years of age, and affects boys more than girls. The majority are due to infection, anaemia, and rheumatic and congenital heart diseases. This differs from those in developed countries, where congenital heart disease and cardiomyopathy predominate. The majority of children usually recover.

Prudent control of infection and correction of anaemia are recommended.

Cardiovasc J Afr 2013; 24: 117–120

Keywords: heart failure, infections, paediatric, Kenya

Department of Human Anatomy, University of Nairobi, Nairobi, Kenya JULIUS A OGENG’O, BSc, MB ChB, PhD PATRICK M GATONGA, BSc BEDA O OLABU, BSc, MB ChB, otienobeda@gmail.com DIANA K NYAMWEYA, MB ChB DENNIS ONG’ERA, BSc, MB ChB

www.cvja.co.za

DOI: 10.5830/CVJA-2013-015

Congestive heart failure in a paediatric population is a common cause of morbidity and mortality and is a serious public health concern, with tremendous socio-economic impact.1,2 Its pattern varies between and within countries.3-5 In sub-Saharan Africa, studies mainly from Nigeria reveal that it accounts for 5.8–9.0% of emergency admissions to paediatric units.2,4,5 These causes vary between developed and developing countries, age and geographical location.6,7 These data are important in diagnosis, treatment, prognosis, control and prevention. Reports from eastern Africa are, however, scarce and altogether absent for Kenya. This study therefore investigated the pattern of congestive heart failure in a black Kenyan paediatric population.

Methods This was a retrospective study at Kenyatta National Hospital (KNH), Nairobi, Kenya, which is a 1 800-bed capacity teaching and eastern African regional referral centre. It receives about 30 000 paediatric in-patients a year, mainly from black Kenyans of middle to lower socio-economic class. This hospital has four paediatric cardiologists and 40 paediatric cardiology beds.

Ethical approval for the study was granted by KNH/University of Nairobi Ethics and Research committee.

Records of patients aged 12 years and younger who were admitted to the hospital with heart failure according to New York Heart Association (NYHA) classification II–IV between January 2006 and December 2010 were retrieved from the hospital registry. In infants, diagnosis and classification was based on criteria proposed by Ross et al. (1992).8 Patients were divided into male and female gender. Each gender category was subsequently divided into infants (one year and below), and four age groups of three years each, starting at one year.

Subsequently, the records were examined for cause and sub-cause of heart failure based on clinical, echo, ECG, CXR and laboratory findings. The causes were divided into six categories, namely congenital heart disease (CHD), rheumatic heart disease (RHD), anaemia, infections, cardiomyopathy, and other. In the categories where there were more than 25 patients, they were further subdivided according to specific cause. Those cases in whom some data on the parameters above were missing were excluded from the study.

Data obtained were analysed using Statistical Programme for Social Scientists (SPSS) version 16.0 for windows, and presented in tables, bar and pie charts.

Results One hundred and sixty-five cases were retrieved. Seven were excluded from the study: four in whom age, and three in whom

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Mode(s) of diagnosis

7%

ECG and echo

6%

9% 43%

11% 11%

Echocardiography (echo) alone Chest X-ray, ECG and echo Electrocardiography (ECG) alone

Number of patients

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30 25 20 15 10 5 0

< 1 year

1–3 years

Chest X-ray alone

13%

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4–6 years

Age category

Male

7–9 years 10–12 years

Female

Chest X-ray and ECG

Fig. 2. Gender distribution by age.

Chest X-ray and echo

transfusion and haemantics to treat anaemia, and correction of malnutrition with nutritional supplements. Heart failure was treated with diuretics, β-blockers, angiotensin converting enzyme (ACE) inhibitors and digoxin in various combinations.

Successful surgical correction was done on 11 of those with CHD (7.6%) and 10 of those with RHD (6.3%). The remaining 23 cases of CHD and RHD (14.5%) were referred to other centres for surgery and were lost to follow up. Overall, 77.9% of patients recovered and only 7.6% died while in hospital.

Fig. 1. Modes of diagnosis of paediatric heart failure.

the cause of heart disease was not recorded. One hundred and fifty-eight cases (91 males, 67 females) were analysed.

Diagnosis was made on the basis of symptoms and signs. In infants, these were feeding difficulties, increased fatiguability, tachynoea, intercostal retraction, dysponoea, grunting, tachycardia, gallop rhythm, cyanosis, rales and hepatomegaly.

In older children, the symptoms and signs included exercise intolerance, somnolence, anorexia, tachypnoea, dyspnoea, orthopnoea, cough, wheezing, rales, gallop rhythm, oedema, hepatomegaly, and raised jugular venous pressure. The most common investigations used to complement clinical diagnosis were echocardiography combined with ECG (43.0%), and echo alone (12.6%). Echo, ECG and CXR were done in 11.4 %, and ECG alone in 10.8% (Fig. 1).

Routine laboratory tests done for all patients included total blood count (TBC), peripheral blood film (PBF), and urea, electrolytes and creatinine (U/E/Cs) levels. Specific tests done were brain natriuretic peptide (BNP) (12.6%), C-reactive protein (CRP) (11.4%), tumour necrotic factor (TNF) alpha (11.4%), human immunodeficiency virus (HIV) ELISA (13.8%), CD4 counts (13.8%), and blood cultures (13.3%). The Mantoux test was done in those suspected to have tuberculosis.

The mean age of these patients was 4.7 years, peaking at 1–3 years (range: 2 months – 12 years). The male:female ratio was 1.4:1, and the male predominance persisted through all age groups (Fig. 2).

The most common single cause was infections (22.8%).

Among these, the infections recorded were pneumonia (50%), upper airway (19.4%), throat (16.7%), and urinary tract (13.9%) infections. Anaemia (17.1%) was the second most common cause. The anaemia was due to malaria (48.2%), helminthiasis (22.2%), malnutrition (14.8%), and sickle cell disease (14.8%).

Other causes included rheumatic (14.6%) and congenital (13.3%) heart disease, cardiomyopathy (7.6%), tuberculosis and HIV (6.9%) (Table 1).

Eleven (7.0%) of the cases had multiple causes; six more than one, and five more than two. In six cases (3.8%), HIV was combined with tuberculosis. In five cases (3.2%), there were more than two causes: three in which bacterial infection was combined with cardiomyopathy and HIV, and two in which there was malaria, anaemia and infection.

Treatment comprised appropriate correction of cause of heart failure, such as treatment of infection with antibiotics, blood

Discussion Observations of the current study reveal that heart failure constitutes about 1:1 000 of paediatric hospital admissions. It is difficult to compare rates among hospitals due to different hospital sizes, paediatric age limit, diagnostic criteria, age distribution and profile of causes.

The modes of diagnosis combining clinical symptoms, signs and investigations are concordant with those practiced elsewhere.9,10 This implies that detection rates are comparable to those in other centres. Accordingly, any differences may result from other factors, probably related to age and cause.

The mean age at presentation was 4.7 years, comparable to the 3.7 ± 3.5 years reported from Nigeria.2 Notably, this is beyond infancy and is commensurate with observations that congenital defects constitute less than acquired causes of heart failure. In developed countries where congenital heart disease is the leading cause,1,9,11 the mean age is much lower. The mean age is also affected by one-year survival rates and is dependent

TABLE 1. DISTRIBUTION OF CAUSES AMONG CONGESTIVE HEART FAILURE PAEDIATRIC PATIENTS Cause Infections Anaemia Rheumatic heart disease Congenital heart disease Cardiomyopathy Tuberculosis HIV Adenoid hypertrophy Rickets More than one cause More than two causes Total

Male 20 17 12 10 5 5 8 2 1 6 5 91

Distribution Female Total 16 36 10 27 11 23 11 21 7 12 6 11 3 11 1 3 2 3 0 6 0 5 67 158

% 22.8 17.1 14.6 13.3 7.6 6.9 6.9 1.9 1.9 3.8 3.2 100

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on cause.11 Accordingly, age distribution is expected to vary between countries and centres.

The 1.4:1 male-to-female ratio recorded in the present study is comparable to the 1.5:1 for Nigeria,2 suggesting relative uniformity in gender-related factors affecting the distribution of congestive heart failure in a Kenyan paediatric population.

Infection was the leading cause of heart failure, followed by anaemia, and rheumatic and congenital heart diseases. This is at variance with literature reports from developed countries where most causes are congenital heart disease and cardiomyopathy.1,3 It however resembles results from Ibadan in Nigeria.12 Several other studies support variations in the leading causes of heart failure in children between developed and developing countries (Table 2). These variations may be due to differences in awareness of preventive measures and access to healthcare services.

The infections most frequently associated with cardiac failure were pneumonia, upper respiratory and throat infections.

This is concordant with reports from African countries where respiratory infection constitutes a significant cause of heart failure.12 Interestingly, the situation observed here resembles that which was obtained in the United Kingdom in the middle of the last century, when bronchitis, pneumonia and other respiratory infections were the most frequent causes of heart failure.14 A remarkable observation of the present study was that HIV in isolation or combination was associated with heart failure in 12.7% of the patients. This is commensurate with other studies, which reported that heart diseases such as pericarditis, myocarditis, cardiomyopathy and endocarditis were associated with HIV infection.15,16 The pathogenesis of heart muscle insufficiency probably involves the direct effects of the virus on the heart, an inflammatory response of the host myocardium to the virus, and the presence of auto-antibodies, as well as decreased immunity, which makes them more prone to infection.17 HIV is endemic in Kenya, and its high association with heart failure suggests that it should always be considered an important differential diagnosis, and that control of the disease is important in reducing heart failure.

Tuberculosis in HIV-negative patients was associated with heart failure in 6.9% of cases. This appears in tandem with increasing reports of tuberculous pericarditis and myocarditis with no evidence of HIV, and disseminated TB.18 Accordingly, as suggested before, myocardial involvement should be suspected as a cause of congestive cardiac failure in any patient with features of TB.19 Indeed, myocardial TB is well recognised and there are cases where cardiac TB presents with congestive cardiac failure.20 Tuberculosis is a common problem in Kenya. Its association with congestive heart failure is important for two reasons. Firstly, patients with TB should be monitored for cardiac involvement.

Secondly, in heart failure patients, TB should be considered an important differential diagnosis.

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Anaemia was the second most frequent cause of heart failure, affecting 17.1% of the children, again in sharp contrast with reports from developed countries (Table 2). This is, however, lower than the 28â&#x20AC;&#x201C;46% reported from Nigeria.5,12 The contrast between European and African countries is concordant with the suggestion that causes of congestive heart failure in a Kenyan paediatric population depend on the stage of epidemiological transaction. The anaemia, similar to literature reports,21 was multifactorial, being caused by malaria, intestinal helminths, poor nutritional status, and haemoglobinopathy. These imply that a multi-prong approach to the control of anaemia constitutes a major step in mitigating heart failure.

Rheumatic heart disease is highly prevalent in Kenya, causing 32% of adult heart failure.22,23 In the current study, it constituted 14.6% of heart failure. It was notably higher than the 1% reported in Nigeria.5,12 This implies that control of rheumatic heart disease, for example, by prudent treatment of throat infections would substantially reduce congestive heart failure in a Kenyan paediatric population due to acquired causes. Pertinent to this suggestion are reports from developed countries indicating that RHD is no longer a significant cause of CCF.1,11 Congenital heart disease is the most important cause of infant heart failure in developed countries.1,3 In the current study, it ranks fourth but constitutes 13.3%, slightly higher than the 10.5% reported in a Nigerian study.5 This is in tandem with reports that CHD are common in Kenya,24 and indicates that it already constitutes a significant cause of heart failure.

Cardiomyopathy is the major cause of heart failure among children with normal hearts in developed countries.1,9,11 In the current study, it constituted 7.6%. This, while lower than the figures reported for developed countries, is higher than implied in reports from another African country in which it is not listed among the causes of heart failure.5,12 The other causes, namely adenoids and rickets, are also concordant with literature reports.25,26 The treatment modalities provided in KNH are in tandem with conventional practice.10 Mortality rate in this series was 7.7%.

This is much lower than the 24% reported in Nigeria12 and 14% in Belgium.9 Outcomes of heart failure are difficult to compare because of different aetiological factors and accessibility to healthcare facilities. For example, in developed countries, most babies with CHD receive early surgical intervention,27 while in Kenya, a significant number may miss the opportunity to have optimal surgical care.24 Notably, however, the observation that cardiomyopathy which is known to have a relatively poor outcome,28 constitutes only a small proportion of cases, may partly explain the comparatively low mortality rate. Indeed, mortality rates have been reported to depend on the cause.9 This implies that with control of infection, the outcome of congestive cardiac failure may improve.

TABLE 2. CAUSES OF PEDIATRIC HEART FAILURE IN DIFFERENT COUNTRIES Author Adekambi et al. 20075 Massin et al. 20089 Andrews et al. 200811 Borzouee et al. 200813 Current study

Population Nigerian Belgian United Kingdom Iranian Kenyan

Top four causes (%) Anaemia (46), infection (29), anaemia + infection (11.5), CHD (10.5) CHD (51.6), cardiomyopathy (19.4), RHD (10.5), pericardits (5.6) Cardiomyopathy (55.8), myocardits (19.6), arrythmia (5.6), anthracycline toxicity (4.0) CHD (76), RHD (16.1), cardiomyopathy (4.0), other (3.8) Infection (22.8), anaemia (17.1), rheumatic heart disease (14.6), congenital heart disease (13.3)

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Conclusion Congestive heart failure is not uncommon in the Kenyan paediatric population. It occurs mainly before five years of age years and affects boys more than girls. The majority are due to infection, anaemia, and rheumatic and congenital heart diseases.

This differs from those in developed countries, where congenital heart disease and cardiomyopathy predominate. The majority of children usually recover. Prudent control of infection and correction of anaemia are recommended.

We are grateful to the KNH hospital registry for providing records, and Antonina Odock for typing the manuscript.

References 1.

Hsu DT, Pearson GD. Heart failure in children. Part 1: History. Etiology and pathophysiology. Circulation: Heart Failure 2009; 2: 63–70.

2. Oyedeji AO, Oluwayemi IO, Okeniyi JA, Fadero FF. Heart failure in Nigerian children. Cardiology 2010; 5: 18–22.

3. Venugopalan P, Agarwal AK, Akinbami FO, El Nour JB, Subramanyan R. Improved diagnosis of heart failure in children. Int J Cardiol 1998; 65(2): 125–128.

4. Lagunju IA, Omokhodion SI. Childhood heart failure in Ibadan. West Afr J Med 2003; 22(1): 42–45.

5. Adekambi AF, Ongunlesi TA, Olowu AO, Fetuga MB. Current trends in the prevalence and aetiology of childhood congestive cardiac failure in Sagamu. J Trop Pediatr 2007; 53(2): 103–106.

6. Sharma M, Nair MNG, Jatana SK, Shahi BN. Congestive heart failure in infants and children. Med J Armed Forces Ind 2003; 59: 228–233.

7. James N, Smith M. Treatment of heart failure in Children. Curr Paediatr 2005; 15: 539–548.

8. Ross RD, Bollinger RO, Pinsky WW. Grading the severity of congestive heart failure in infants. Pediatr Cardiol 1992; 13: 72–75.

9. Massin MM, Astadicko I, Dessy H. Epidemiology of heart failure in a tertiary pediatric centre. Clin Cardiol 2008; 31: 388–391.

10. Madriago E, Silberbach M. Heart failure in Infants. Paediatr Rev 2010; 31: 4–12.

11. Andrews RE, Fenton MJ, Ridout DA, Burch M. New onset heart failure due to heart muscle disease in childhood: a prospective study in the United Kingdom and Ireland. Circulation 2008; 117: 79–84.

12. Omokhodion SI, Lagunju IA. Childhood heart failure in Ibadan. West Afr J Med 2005; 24(4): 325–328.

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13. Borzouee M, Jannati M. Distribution and characteristics of the heart disease in pediatric age group in southern Iran. Iran Cardiovas Res J 2008; 2: 48–50.

14. Flint JF. The factor of infection in heart failure. Br Med J 1954; 2(4895): 1018–1022.

15. Braun K, Izak G. Acute pulmonary infection and cardiac failure in chronic emphysema. Am Heart J 1955; 49: 385–393.

16. Sudano I, Spieke L,Noll G, Corti R, Weber R, Luscher TF. Cardiovascular disease in HIV infection. Am Heart J 2006; 151: 1147–1155.

17. Gopal M, Bhaskaran A, Khalife WJ, Barbagelata A. Heart disease in patients with HIV/AIDS – An emerging clinical problem. Curr Cardiol Rev 2009; 5: 149–154.

18. Afzal A, Koehane M, Keeley E, Borzak S, Callender CW, Iannuzzi M. Myocarditis and pericarditis with tampande associa ted with disseminated tuberculosis. Can J Cardiol 2000; 16: 519–521.

19. Agarwal R, Malhota P, Awasthi A, Kakkar N, Gupta D. Tuberculous dilated cardiomyopathy an underrecognised sentity? BMC Inf Dis 2005; 5: 29–33.

20. Brar R, Prasad A, Kumar A, Bagai M, Malhotra M. Myocardial tuberculosis presenting with congestive heart failure and pulmonary venous occlusion. Eur J Radiol 2010; 74(3): e47–e50.

21. Crawley J. Reducing the burden of Anaemia in infants and young children in malaria – endemic countries of Africa: from evidence to Action.

Am J Trop Med Hyg 2004; 71(suppl): 25–34.

22. Anabwani GM, Bonhoeffer P. Prevalence of Heart disease in school children in rural Kenya using color flow echocardiography. East Afr Med J 1996; 73: 215–217.

23. Oyoo GO, Ogolla EN. Clinical and sociodemographic aspects of congestive heart failure at Kenyatta National Hospital. East Afr Med J 1999; 76: 23–27.

24. Awori MN, Ogendo SW, Gitome SW, Onguti SK, Obonyo NG. Management pathway for congenital heart disease at Kenyatta National hospital, Nairobi. East Afr Med J 2007; 84: 312–317.

25. Maiya S, Sullivan I, Allgrove J, Yates R, Malone M, Brain C. Hypocalcaemia and vitamin D deficiency: an important but preventable cause of life threatening infant heart failure. Heart 2008; 94: 581–584.

26. Brown J, Munez S, Rusell M, Spurney C. Hypocalcemic rickets and dilated cardiomyopathy: Case reports and review of literature. Pediatr Cardiol 2009; 30: 818–823.

27. Kay JD, Colan SD, Graham TP Jr. Congestive heart failure in paediatric patients. Am Heart J 2001; 142: 923–929.

28. Arola A, Jokinen E, Ruuskanen O, Saraste M, Pesonen E, Kuusela AL. Epidemiology of Idiopathic cardiomyopathies in children and adolescents. A nation wide study in Finland. Am J Epidemiol 1997; 146: 385–393.

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Comparison of results of autologous versus homologous blood transfusion in open-heart surgery BILGEHAN SAVAS OZ, GOKHAN ARSLAN, ERKAN KAYA, CELALETTIN GUNAY, FARUK CINGOZ, MEHMET ARSLAN

Abstract Background: The aim of this study was to determine a method to decrease the use of homologous blood during openheart surgery using a simple blood-conservation protocol.

We removed autologous blood from the patient before bypass and used isovolumetric substitution. We present the results of this protocol on morbidity and mortality of surgery patients from two distinct time periods.

Methods: Patients from the two surgical phases were enrolled in this retrospective study in order to compare the outcomes using autologous or homologous blood in open-heart surgery.

A total of 323 patients were included in the study. The autologous transfusion group (group 1) comprised 163 patients and the homologous transfusion group (group 2) 160 patients.

In group 1, autologous bloods were prepared via a central venous catheter that was inserted into the right internal jugular vein in all patients, using the isovolumetric replacement technique. The primary outcome was postoperative in-hospital mortality and mortality at 30 days. Secondary outcomes included the length of stay in hospital and in intensive care unit (ICU), time for extubation, re-intubations, pulmonary infections, pneumothorax, pleural effusions, atrial fibrillation, other arrhythmias, renal disease, allergic reactions, mediastinitis and sternal dehiscence, need for inotropic support, and low cardiac-output syndrome (LCOS).

Results: The mean ages of patients in groups 1 and 2 were 64.2 ± 10.3 and 61.5 ± 11.6 years, respectively. Thirty-eight of the patients in group 1 and 30 in group 2 were female.

There was no in-hospital or 30-day mortality in either group.

The mean extubation time, and ICU and hospital stays were significantly shorter in group 1. Furthermore, postoperative drainage amounts were less in group 1. There were significantly fewer patients with postoperative pulmonary complications, pneumonia, atrial fibrillation and renal disease.

The number of patients who needed postoperative inotropic support and those with low cardiac output was also significantly less in group 1.

Conclusion: Autologous blood transfusion is a safe and effective method in carefully selected patients undergoing cardiac surgery. It not only prevents transfusion-related co-morbidities and complications but also enables early extubation time and shorter ICU and hospital stay. Furthermore, it reduces the cost of surgery.

Department of Cardiovascular Surgery, Gulhane Military Academy of Medicine, Ankara, Turkey BILGEHAN SAVAS OZ, MD, bsoz@gata.edu.tr GOKHAN ARSLAN, MD ERKAN KAYA, MD CELALETTIN GUNAY, MD FARUK CINGOZ, MD MEHMET ARSLAN, MD

Keywords: autologous blood usage, open-heart surgery, postoperative morbidity Submitted 31/1/12, accepted 19/3/13 Published online 4/4/13 Cardiovasc J Afr 2013; 24: 121–123

www.cvja.co.za

DOI: 10.5830/CVJA-2013-020

Cardiac surgery is one of the major fields necessitating blood transfusion. Increasing numbers of cardiac surgery cases and the requirement of large amounts of homologous blood and blood products has long been a deterrent to this form of surgery.

This has forced surgeons to reduce their requirement for blood and blood products for cardiopulmonary bypass procedures and related surgical techniques.1,2 Negative outcomes using homologous blood transfusion, such as haemolytic, allergic and febrile reactions, infections (hepatitis, cytomegalovirus, HIV), renal problems, and transfusion-related acute lung injury have cause severe morbidity and even mortality in some cases.3,4 Several blood-conservation strategies have therefore evolved, with major advances being achieved from pre-donation of autologous blood, removal of autologous blood before bypass and use of isovolumetric substitution, re-infusion of the volume remaining in the extracorporal circuit, and autotransfusion of the shed mediastinal drainage blood.5 Other techniques, using various devices for intra-operative haemofiltration and haemoconcentration with cell separators, have been shown to decrease homologous blood usage in cardiac surgery.6 In this study we present our results on the use of homologous blood with a simple blood-conservation protocol. This involved removal of autologous blood before bypass and isovolumetric substitution. The morbidity and mortality outcomes of this protocol were compared in patients from two different surgical eras.

Methods Patients underwent isolated coronary artery bypass graft (CABG) surgery at the Department of Cardiovascular Surgery, Gulhane Military Academy of Medicine. Before 2008, CABG surgery was performed using homologous blood; thereafter we began using autologous blood.

According to the timeline, patients were retrospectively divided into two groups. A total of 323 patients were included in the study. The mean ages of the patients in groups 1 and 2 were 64.2 ± 10.3 and 61.5 ± 11.6 years, respectively. Thirtyeight of the patients in group 1 and 30 in group 2 were female.

Mean NYHA class of the patients in both groups was II. The autologous transfusion group (group 1) comprised 163 patients and the homologous transfusion group (group 2) 160 patients.

Exclusion criteria were: patients with renal disease (creatinine > 1.5 mg/dl), liver disease, coagulation disorders, anaemia

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(haematocrit < 40.5%), low ejection fraction (EF) (30%), preand postoperative infection, patients who underwent emergency operations and operations other than CABG surgery. Patients with re-operations and revisions were excluded from the study.

All patients were operated on under general anaesthesia using a midline sternotomy and cardiopulmonary bypass, with membrane oxygenators and a crystalloid priming solution. A left internal mammary artery graft was used in all patients.

In group 1, autologous bloods were prepared via a central venous catheter that was inserted into the right internal jugular vein in all patients, using the isovolumetric replacement technique. The protocol for blood conservation in elective coronary surgery was as follows: cessation of antiplatelet drugs seven days before the surgery; removal of autologous blood before bypass for re-transfusion after bypass; intra-operative re-transfusion of the oxygenator and tubing contents with the help of a leukocyte filter; and adequate rewarming of patients and control of systemic blood pressure. In group 2, homologous bloods were used.

The primary outcome was postoperative in-hospital mortality and mortality at 30 days. Secondary outcomes included the length of hospital and intensive care unit (ICU) stay, time for extubation, re-intubations, pulmonary infections, pneumothorax, pleural effusions, atrial fibrillation, other arrhythmias, renal disease, allergic reactions, mediastinitis and sternal dehiscence, need for inotropic support, and low cardiac-output syndrome (LCOS).

Pulmonary infections included pneumonia and bronchitis.

Pneumonia was defined by radiological evidence of new infiltration, consolidation or cavity, and antibiotic use in the presence of one of the three following criteria: purulent sputum, positive blood culture or positive bronchial secretion culture.

Bronchitis was defined by the presence of purulent sputum production and antibiotic use. Pleural effusion was included in the analysis only if it required drainage during hospitalisation.

Arrhythmias other than atrial fibrillation included supraventricular arrhythmias, atrio-ventricular block requiring pacemaker, ventricular tachycardia, ventricular fibrillation and asystole. LCOS was considered when postoperative inotropic support was used for more than 24 hours. Renal failure was defined as an abnormal increase in serum creatinine levels and a decrease in urinary output.

Statistical analysis Statistical analysis was performed with SPSS 15.0 for Windows.

Continuous data were presented as mean ± SD. Nominal data were presented as frequencies and percentages. Differences were analysed with the Levene’s test, Fischer’s exact test, Mann– Whitney U-test and chi-square test.

Results There was no difference between the two groups with regard to co-morbidities and other surgical risk factors. Patient characteristics are summarised in Table 1. Mean pre-operative haematocrit levels in groups 1 and 2 were 42.2 ± 3.9 and 41.7 ± 4.1%, respectively.

There was no in-hospital or 30-day mortality in either group.

There were no significant differences between the two groups related to intra-operative parameters such as cross-clamping time and cardiopulmonary bypass time. There was also no statistically significant difference in postoperative haematocrit level between the groups. However the mean extubation time, ICU and hospital stays were significantly shorter in group 1. Furthermore, postoperative drainage amounts were less in group 1 (375.8 ± 114.2 vs 543.7 ± 268.4 ml, respectively). Intra-operative and postoperative data are summarised in Table 2.

There were significant differences in postoperative morbidities. Significantly fewer patients had postoperative pulmonary complications, pneumonia, atrial fibrillation and renal disease. The number of patients who needed postoperative inotropic support and those with low cardiac output were also significantly lower in group 1. Data related to postoperative morbidities are detailed in Table 3.

Discussion Blood donation is problematic globally, largely due to donorrelated factors, which may differ from country to country. In a study by Kubio et al.,7 among donors from Ghana, positive rates for infectious disease markers were 7.5% for hepatitis B surface antigen, 6.1% for hepatitis C virus, 3.9% for human immunodeficiency virus and 4.7% for syphilis. This amounted to 22.2% of the available donors being rejected due to infectious

TABLE 1. PATIENTS’ CHARACTERISTICS Group 1 (n = 163) 64.2 ± 10.3 25.7 ± 3.3

Group 2 (n = 160) 61.5 ± 11.6 27.6 ± 3.0

Variable p-value Age (years) 0.034 0.045 BMI (kg/m2) Gender Male 125 130 0.033 Female 38 30 NYHA class 2.0 ± 0.3 2.1 ± 0.3 0.062 Hypertension 65 80 0.068 Diabetes 23 45 0.002 Hyperlipidaemia 20 9 0.037 COPD 7 8 0.764 Smoking 54 50 0.718 BMI: body mass index, NYHA: New York Heart Association, COPD: chronic obstructive pulmonary disease.

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TABLE 2. INTRA- AND POSTOPERATIVE DATA Variable

Group 1 (n = 163)

Group 2 (n = 160)

p-value

Cross-clamp time (min) 63.6 ± 21.4 64.8 ± 27.1 0.084 CPB time (min) 102.3 ± 32.0 116.3 ± 25.2 0.062 Extubation time (h) 5.6 ± 1.1 6.34 ± 1.4 < 0.01 Drainage (ml) 375.8 ± 114.2 543.7 ± 268.4 < 0.01 ICU stay (h) 23.0 ± 0.9 32.4 ± 20.2 < 0.01 Blood transfusion (intra-opera0.3 ± 0.4 1.1 ± 0.6 0.025 tive) (units) Blood transfusion (postoperative) 1.7 ± 0.7 2.1 ± 0.9 0.018 (units) Hospital stay (days) 7.0 ± 1.1 8.7 ± 3.1 < 0.01 Preoperative haematocrit (%) 42.2 ± 3.9 41.7 ± 4.1 0.628 Discharge haematocrit (%) 33.8 ± 2.9 31.8 ± 2.3 0.002 CPB: cardiopulmonary bypass.

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TABLE 3. POSTOPERATIVE MORBIDITY DATA OF THE GROUPS Variable Group 1 (n = 163) Group 2 (n = 160) p-value Re-intubation 0 0 1 Sternal infections 2 6 0.148 Pulmonary complications 5 24 < 0.001 Pneumonia 1 6 0.054 Atrial fibrillation 6 26 < 0.001 Renal disease 4 8 0.231 Inotropic support 2 15 0.001 LCOS 2 9 0.003 30-day mortality 0 0 1 LCOS: low cardiac output syndrome

diseases, or one in every five donors.

In another study by Madrona et al.,8 the main reasons for donor refusal were listed among 2 070 patients as deficiency anaemias (3%), major surgery (3.6%), minor surgery (1.9%), high-risk behaviour (1.0%), drug or alcohol consumption (0.3%), more than three or four donations in a year (3.5%), pregnancy or lactation (1.2%), endoscopy, tattoo and piercings (10.5%), fever, mild infections (15.4%), hypotension (1.3%), malaise, unwell (11.0%), delivery, miscarriage (2.2%), unreliable answers (0.5%), tachycardia or bradycardia (3.6%), blood pressure > 180/> 110 mmHg (6.4%), and taking medication (7.4%).

Nearly three out of every four donors in this study (72.8%) were considered unsuitable.

In cardiac surgery patients, postoperative bleeding may be considerable despite meticulous operative technique. In some regions it may be difficult to find even two units of blood for open-heart surgery. Blood-conservation strategies are therefore very important. Despite a widespread interest in reducing blood use for cardiac procedures, the practice of homologous blood transfusion is still widespread.

On average 50 to 60% of patients undergoing cardiac surgery receive blood transfusions.9 These patients are prone to transfusion-related morbidity and complications, such as allergies, renal disease, pulmonary complications and infection.3,4 Homologous blood usage also makes surgery more costly. There is growing evidence of an association between transfusion of blood products and increased morbidity and mortality, and reduced long-term survival rates.9 We therefore started blood-conservation protocols using autologous blood that was prepared before the bypass procedure and re-transfused into the patient at the end of surgery. In this study we compared results from two different surgical eras.

Although autologous blood transfusion has the potential to decrease bleeding following surgery, Helm et al.10 showed no statistical difference in the auto-transfusion group between the amount of autologous blood removed before the administration of heparin (1 532 ± 320 ml) compared with the amount of postoperative bleeding. However in our study, when we compared the amount of drainage in the two groups, there was a statistically significant difference in favour of group 1 (p < 0.01).

In their study, Paker et al.11 could not demonstrate any difference in the group with no blood or blood products used following cardiac surgery with regard to parameters of extubation time and ICU stay, compared with a group using blood/ blood products. However in our study, there were significant

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differences between the two groups in terms of extubation time, ICU and hospital stay. These parameters were less in group 1.

The number of patients needing inotropic support and patients with LCOS was also lower in group 1.

David and colleagues12 reported that in patients undergoing cardiac surgery, transfusion was found to be associated with an increased risk of atrial fibrillation, with an odds ratio of 1.18 for each unit of blood transfused. Sood et al.13 also found that atrial fibrillation was twice as common in transfused patients.

Similarly, in our study, the number of patients with postoperative atrial fibrillation was higher in group 2.

Gökşin et al.14 showed the beneficial effect of autologous blood transfusion with regard to lung damage following ischaemia–reperfusion injury. Although not directly related, in our study when compared to group 2, there were fewer pulmonary complications in group 1 following cardiac surgery.

This may have been related to the earlier extubation and less time in ICU observed in group 1 patients. Shorter ICU and hospital stay in group 1 may also have been due to the lack of early complications related to homologous blood transfusion.

Using autologous blood transfusion reduces the cost of surgery. In our hospital, one unit of fresh whole blood costs 60 Turkish Lira (TL) (nearly 25 Euro) and one unit of erythrocyte suspension costs 90 TL (nearly 38 Euro). In group 1, 328 units of blood and blood products were used, and in group 2, 517 units. Comparing costs, it was 16 480 TL (nearly 7 012 Euros) in group 1 and 41 730 TL (nearly 17 757 Euros) in group 2. The difference was more than 10 000 Euros. It is easy to see the cost effectiveness of using autologous blood transfusion.

Conclusion A simple and inexpensive blood-conservation programme, mainly combining autologous blood removal before bypass and re-transfusion of the volume remaining in the oxygenator, has enabled us to avoid homologous transfusions. Autologous blood transfusion is a safe and effective method in selected patients undergoing cardiac surgery. It not only prevents transfusionrelated co-morbidities and complications but also allows earlier extubation time, and shorter ICU and hospital stay. Furthermore, it reduces the cost of surgery.

References 1.

2.

3.

4.

5.

Moskowitz DM, Klein JJ, Shander A, Cousineau KM, Goldweit RS, Bodian C, et al. Predictors of transfusion requirements for cardiac surgical procedures at a blood conservation center. Ann Thorac Surg 2004; 77(2): 626–634.

Ovrum E, Holen EA, Abdelnoor M, Oystese R. Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations. Ann Thorac Surg 1991; 52(3): 500–505.

Douglas BC, Terri GM. Extreme normovolemic hemodilution: how low an you go and other alternative trnasfuisons? Crit Care Med 2001; 29: 908–910.

Murphy PJ, Connery C, Hicks GL, Numberg N. Homologous blood transfuison as a risk factor for postoperative infection after coronary artery bypass opeations. J Thorac Cardiovasc Surg 1992; 104: 1092–1099.

Scott WJ, Kessler R, Wernly JA. Blood conservation in cardiac surgery.

Ann Thorac Surg 1990; 50: 843–851.

continued on page 129…

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Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital CHARLES MUSOKE, CHARLES KIIZA MONDO, EMMY OKELLO, WANZHU ZHANG, BARBARA KAKANDE, WILSON NYAKOOJO, JUERGEN FREERS

Abstract Introduction: Rheumatic heart disease (RHD) frequently occurs following recurrent episodes of acute rheumatic fever (ARF). Benzathine penicillin (benzapen) is the most effective method for secondary prophylaxis against ARF whose efficacy largely depends on adherence to treatment. Various factors determine adherence to therapy but there are no data regarding current use of benzapen in patients with RHD attending Mulago Hospital. The study aims were (1) to determine the levels of adherence with benzapen prophylaxis among rheumatic heart disease patients in Mulago Hospital, and (2) establish the patient factors associated with adherence and, (3) establish the reasons for missing monthly benzathine penicillin injections.

Methods: This was a longitudinal observational study carried out in Mulago Hospital cardiac clinics over a period of 10 months; 95 consecutive patients who satisfied the inclusion criteria were recruited over a period of four months and followed up for six months. Data on demographic characteristics and disease status were collected by means of a standardised questionnaire and a card to document the injections of benzapen received.

Results: Most participants were female 75 (78.9%). The age range was five to 55 years, with a mean of 28.1 years (SD 12.2) and median of 28 years. The highest education level was primary school for most patients (44, 46.3%) with eight (8.4%) of the patients being illiterate. Most were either NYHA stage II (39, 41.1%) or III (32, 33.7%).

Benzathine penicillin adherence: 44 (54%) adhered to the monthly benzapen prophylaxis, with adherence rates ≥ 80%; 38 (46%) patients were classified as non-adherent to the monthly benzapen, with rates less than 80%. The mean adherence level was 70.12% (SD 29.25) and the median level was 83.30%, with a range of 0–100%; 27 (33%) patients had

Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda

CHARLES MUSOKE, MB ChB, MMed CHARLES KIIZA MONDO, MB ChB, MMed, PhD charlesmondo2011@gmail.com WANZHU ZHANG, MB ChB, MMed JUERGEN FREERS, MB ChB, MMed, MD

Uganda Heart Institute, Mulago National Referral Hospital, Kampala, Uganda CHARLES KIIZA MONDO, MBChB, MMed, PhD EMMY OKELLO, MB ChB, MMed BARBARA KAKANDE, MBChB, MMed WILSON NYAKOOJO, MB ChB, MMed, MD

extremely poor adherence levels of ≤ 60%. Factors associated with adherence: higher education status, residing near health facility favoured high adherence, while painful injection was a major reason among poor performers.

Conclusion: The level of non-adherence was significantly high (46%). Residence in a town/city and having at least a secondary level of education was associated with better adherence, while the painful nature of the benzapen injections and lack of transport money to travel to the health centre were the main reasons for non-adherence among RHD patients in Mulago.

Keywords: rheumatic heart disease, benzathine penicillin, secondary prophylaxis, adherence Submitted 26/4/12, accepted 17/4/13 Cardiovasc J Afr 2013; 24: 124–129

www.cvja.co.za

DOI: 10.5830/CVJA-2013-022

In developing countries, rheumatic fever (RF) is the predominant cause of acquired childhood cardiomyopathy.1,2 The prevalence of RHD is estimated to be higher in developing than in developed countries, ranging from 24/1 000 to 0.3/1 000, respectively.3-5 Rheumatic heart disease might occur following a single episode of acute rheumatic fever (ARF); however, it is most often the result of recurrent episodes.6 Those diagnosed with ARF are at higher risk of suffering further episodes of ARF than the general population, with the incidence of rheumatic fever following streptococcal infection as high as 50% in those with previous ARF,7 compared with only 1–3% in the general population.8 Long-term treatment with penicillin is recommended to prevent infection with Group A streptococcus among those with a previous diagnosis of ARF, and it has been shown to significantly reduce the morbidity and mortality associated with both recurrent ARF and RHD.9,10 The severity and prognosis of RHD depends on the extent of cardiac involvement and the frequency of recurrent events. Adherence to penicillin prophylaxis is therefore essential to prevent rapid progression of disease.

Adherence variability to three- or four-weekly injections of benzathine penicillin is well documented, both in the community setting and in hospital-based studies. Several factors could explain the non-adherence observed among these patients: intramuscular injections of benzathine penicillin are painful and may sometimes be associated with allergic reactions.6 Among asymptomatic or minimally symptomatic patients, this might prove to be a deterrent, particularly if the links to future recurrence of rheumatic fever are not repeatedly reiterated.

Furthermore, practitioners in the community might be reluctant to administer penicillin injections for fear of anaphylaxis.7

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Other factors which have been identified include: the level of education and training of health workers and/or people with ARF/RHD who may not fully understand the role of secondary prophylaxis in preventing ARF and subsequent heart damage; refusal by some people who do not want to receive treatment despite their level of understanding; difficulties accessing healthcare, that is, travelling to the health facility to receive treatment may be difficult and/or costly, especially for people living in rural and remote areas; forgetting to attend the health centre on the date when secondary prophylaxis is due; staff workloads and priorities. Healthcare staff may be unable to identify and encourage people who do not receive regular secondary prophylaxis.11,12 In Uganda, RHD is the second leading cause of acquired heart disease after hypertensive heart disease.13 Current data regarding adherence rates to secondary benzathine penicillin prophylaxis among these patients are unknown despite our knowledge that good adherence is protective for severe forms of RHD. Therefore, the study aims were (1) to determine the level of adherence to benzathine penicillin prophylaxis among rheumatic heart disease patients attending Mulago Hospital, (2) establish the patient factors associated with adherence and, (3) establish the reasons for missing monthly benzathine penicillin injections.

Methods Institutional ethics approval was obtained from the School of Medicine Research and the Ethics Committee of the College of Health Sciences, Makerere University. We obtained informed consent for all the patients and informed assent for those unable to give consent. Patients’ initials and study numbers were put on the questionnaires instead of full names to ensure confidentiality.

This was a longitudinal observational study carried out in Mulago Hospital, the national referral hospital, and Makerere University teaching hospital located in Kampala, Uganda, which receives more than 250 patients with RHD annually. The target population included all patients clinically diagnosed with rheumatic heart disease and confirmed by echocardiography, as previously described.5 New and old RHD patients aged five to 55 years who were eligible to continue prophylaxis for a period not less than one year from the time of recruitment and consented to the study were recruited. Each patient was then given a benzathine penicillin prophylaxis card recommending the appropriate monthly (four-weekly) dose of benzathine penicillin according to the Uganda clinical guidelines, which recommends 2.4 MU for adults, 0.6 MU for children ≤ 30 kg and 1.2 MU for those > 30 kg.8 Patients with known allergy to benzathine penicillin were excluded from the study.

Patients who met the inclusion criteria were consecutively recruited over a period of four months until a total of 95 patients was reached (Fig. 1). An identification number or unique patient number (UPN) was assigned to each consenting patient.

For those who refused to consent, the reason for refusal was documented in the study book.

A focused clinical assessment was done using a standardised pre-tested questionnaire in which the socio-demographic data, details of physical findings, and details of findings on the electrocardiogram and at echocardiography were recorded. In addition, data regarding the following were collected: personal

history of hypertension, diabetes, stroke and other heart diseases.

Socio-economic factors recorded were educational level, occupation, and total income (of parents in the case of children or students).

For each patient recruited, information regarding the importance of secondary prophylaxis was provided as part of the whole information package given to the RHD registry patients, including all their other treatment modalities. This was done in liaison with the primary attending clinicians. This was to help capture the dates and signatures of the health workers where the patient received the benzathine penicillin injections over the following six months. The card had the name of the patient, which would help track the patients’ UPN through the study book.

For purposes of limiting loss to follow up, data concerning the following were collected: the patients’ phone numbers if available/number of the caretaker for children; phone numbers of at least two close relatives or friends, which would be tested at the time of recording to ascertain their existence; the number for the principle investigator was written at the back of each patient’s benzathine penicillin card, and patients were urged to call and inform the principle investigator if they were planning to change their phone numbers.

After recruitment, each patient was told to continue attending his/her regular clinic, as scheduled by the primary care clinician, and he/she was to be reviewed in the general RHD registry every three months by other registry clinicians. For this particular study, the patients were reviewed again at the end of six months’ follow up.

At the six-month follow-up visit, patients were contacted by phone and were encouraged to come with their benzathine penicillin prophylaxis cards so that data regarding their rates of adherence could be extracted. Those who were unable to travel at the six-month follow for various reasons were requested to read off the number of injections received at the time of the call from the card, and this was recorded in their follow-up questionnaire.

These patients were nevertheless encouraged to take time off and Adherence to benzathine penicillin for secondary prophylaxis among patients affected with rheumatic heart disease (RHD) at Mulago Hospital 112 assessed for eligibility

95 recruited

17 ineligible • 6 probable RHD • 4 congenital heart disease • 4 mitral valve prolapse • 3 refused to consent

13 (13.7%) did not complete 6-month follow up • 10 died • 3 lost to follow up 82 (86.3%) completed 6-month follow up Of these • 71 (86.6%) had objective assessment of adherence (using the benzathine card) • 11 (13.4%) self-reported adherence (6 had lost card upon the visit and 5 followed up over the phone.)

Fig. 1. Patient flow during the study.

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come to the clinic on any other appropriate time for follow-up care.

For those patients who had lost the benzathine prophylaxis card, we relied on self-reports as to how many injections he/ she had received over the previous six months. The proportion of these patients, together with those from whom information was obtained over the phone was catered for during analysis.

At six months of follow up, a separate structured, pre-coded questionnaire was administered to those patients without 100% adherence, with the aim of capturing the factors or reasons for missing the benzathine prophylaxis injections.

Measuring benzathine penicillin injection delivery9 was calculated as a percentage of the number of injections received, divided by the number prescribed and multiplied by 100.

Receiving less than 80% of injections places an individual at a higher risk of recurrent ARF.9

Statistical analysis Data were entered in Epidata 3.1, backed and cleaned to prevent data loss and then exported to STATA version 10.0. Continuous variables were summarised in means (standard deviation) and median (interquartile range). Categorical data were summarised using frequency and percentages and results are presented in tables. To address the first objective, the adherence rates for

TABLE 1. BASELINE CHARACTERISTICS OF THE PATIENT Frequency (n = 95)

Percentage (%)

< 18 years

22

23.2

≥18 years

73

76.8

Rural

38

40.0

Town/city

57

60.0

Female

75

78.9

Male

20

21.1

College

10

10.5

Secondary

29

30.5

Vocational

4

4.2

Primary

44

46.3

None

8

8.4

Unemployed

65

68.4

Employed

30

31.6

Variable Age

Patients’ home

Gender

Level of education

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RHD patients attending Mulago Hospital were calculated as follows: The number of injections required in six months for a patient on four-weekly benzathine prophylaxis = six injections.

Adherence rates for individual patients was calculated as: no of injections received

___________________ ​ × 100% ​ no of injections expected

We then proceeded to determine the level of adherence, the mean adherence rate and median.

For the second objective, bivariate analysis was done with a confidence interval of 95%, and Pearson’s chi-square test was used to ascertain statistical significance. Variables included in the bivariate analysis included age, gender, patient’s home address, level of education, patient’s employment status, the NYHA class, tribe, and history of previous use of benzathine penicillin (all variables were put in two categories). Fisher’s exact test was used where cells had less than five readings. A p-value < 0.05 was considered significant. To ascertain for statistical significance (p < 0.05) between subjective and objective assessment for adherence, the Pearson’s chi-square test was used.

Results From June 2011 to March 2012, out of the 112 patients screened for eligibility, 95 rheumatic heart disease patients were recruited and followed up for a period of six months to assess their adherence levels and associated factors (Fig. 1). Reasons for excluding the 17 patients included: six patients with probable RHD, four patients with congenital heart disease, four with mitral valve prolapse and three declined to consent. Out of these 95 patients, 82 (86.3%) completed the six-month follow-up period; 13 (13.7%) did not complete six months of follow up because 10 had died and three were lost to follow up. Of the 82 patients who completed follow up, 71 (86.6%) were objectively assessed for adherence levels using the benzathine penicillin card provided at the beginning of the study and 11 (13.4%) were subjectively assessed using self-reporting. Of the 11 patients, six came to hospital at follow up but had lost their cards and five were followed up over the phone.

Table 1 shows the baseline characteristics of the patients. The majority was female (75, 78.9%). The patients’ ages ranged from

Employment status

NYHA class I

7

7.4

II

39

41.1

III

32

33.7

IV

17

17.9

Ganda

49

51.6

Soga

4

4.2

Toro

2

2.1

Ankole

9

9.5

Nyoro

2

2.1

Acholi

3

3.2

Others

26

27.4

Adherence rate ≥ 80% Adherence rate < 80% 54% 46%

Tribe

Fig. 2. Overall levels of adherence to monthly benzathine penicillin prophylaxis.

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50

44

Number of patients

45

TABLE 3. PATIENT FACTORS ASSOCIATED WITH ADHERENCE TO MONTHLY BENZATHINE PENICILLIN PROPHYLAXIS

40 35

Variable

30 20 15 5 0

< 80% ≥ 80% adherence adherence n = 44 (%) n = 38 (%)

OR (95% CI)

p-value

1.10 (0.34–3.58)

0.855

1.73 (0.64–4.72)

0.229

0.45 (0.12–1.63)

0.177

2.21 (0.83–5.93)

0.076

0.81 (0.29–2.26)

0.651

0.81 (0.31–2.12)

0.634

0.91 (0.35–2.38)

0.837

0.37 (0.01–4.28)

0.380

Age

25

10

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3

4

0

1–20

9

21–40

11

41–60

Adherence levels

11

61–80

< 18 years

10 (22.7)

8 (21.1)

≥ 18 years

34 (77.3)

30 (78.9)

Patients’ home

81–100

Fig. 3. Bar graph showing the number of patients across different adherence levels.

five to 55 years, with a mean age of 28.1 years (SD 12.2) and median 28 years. The majority of patients were over 18 years (73, 76.8%) and 57 (60%) patients were town/city residents compared to 38 (40%) from rural areas. The majority (44, 46.3%) had primary educational level while eight (8.4%) were illiterate. Most of the patients were either NYHA class II (39, 41.1%) or III (32, 33.7%). The majority (49, 51.6%) were in the Baganda tribe.

Fig. 2 shows the levels of adherence after six months of follow up. Of the 82 patients who completed the six-month follow up, 44 (54%) had adhered to the monthly benzathine penicillin prophylaxis, with adherence rates ≥ 80%; 38 (46%) patients were classified as non-adherent to the monthly benzathine penicillin, with rates less than 80%. The mean adherence rate was 70.12% (SD 29.25) and the median rate was 83.30% with a range of 0–100%. Fig. 3 shows the number of patients across different adherence levels; 27 (33%) of the patients had extremely poor adherence rates of ≤ 60%.

Of the 82 patients who completed the six-month follow up, 71 (86.6%) presented their cards at follow up and their adherence rates were assessed objectively by counting the number of injections received over the follow-up time, compared to the 11(13.4%) who gave a self-report of the number of injections received. Table 2 shows a lack of significant difference between adherence levels as measured among these two groups of patients.

Table 3 shows the patient factors associated with adherence to the monthly benzathine penicillin prophylaxis. Although statistically significant associations with adherence were not found, trends towards adherence were demonstrated among patients who resided in a town/city (OR 1.73; CI 0.64–4.72) and those with at least secondary levels of education (OR 2.21; CI 0.83–5.93). There was no difference in the levels of adherence between those under 18 compared with ≥18 years. The lack of previous exposure to benzathine penicillin was not associated with better adherence.

TABLE 2. COMPARISON BETWEEN OBJECTIVE AND SUBJECTIVE ASSESSMENT OF ADHERENCE Variable

< 80% adherence (n =38)

≥ 80% adherence (n =44)

OR (95% CI)

p-value

Came with card

32 (84.2)

39 (88.6)

0.684 (0.191–2.448)

0.558

Self report

6 (15.8)

5 (11.4)

Town/city

30 (68.2

21(55.3)

Rural

14 (31.8

17 (44.7)

Female

33(75.0)

33(86.8)

Male

11(25.0)

5(13.2)

Gender

Level of education1 Secondary and above

26(59.1)

15 (39.5)

Less than secondary

18 (40.9)

23 (60.5)

Employment status2 Currently employed

13(29.5)

13(34.2)

Unemployed

31(70.5)

25(65.8)

I and II

22(50.0)

21(55.3)

III and IV

22(50.0)

17(44.7)

NYHA stage

Tribe Ganda

21(47.7)

19(50.0)

Other

23(52.3)

19 (50.0)

No

41(93.2)

37(97.4)

Yes

3(6.8)

1(2.6)

Previous use of benzathine3

Employment status for the attendants was considered for children and students.

For patients < 13 years, education level of primary caretaker was considered.

3 Fisher’s exact test was used. OR = odds ratio, CI = confidence interval.

1 2

Table 4 shows the commonest reasons by the respondents for missing a benzathine penicillin dose. These reasons included those given by patients who had adherence levels above 80% but not reaching 100%. The commonest reason for missing a dose was the painful nature of the benzathine penicillin injection, reported by 27 respondents (29% of all reasons given). This was closely followed by lack of transport money to the health facility to receive the injection. The other reasons included injection abscesses, attendant too busy at home with children and unable to go for the injection, they thought it was acceptable to miss a few times, one patient had valvular surgical repair and was advised by the local health practitioner that there was no need for any more injections.

TABLE 4. REASONS FOR MISSING MONTHLY BENZATHINE PROPHYLAXIS INJECTIONS

Reasons for missing Injection painful Did not have transport money Felt healthy and well Away from home Friends advised me otherwise Felt sick and unable to take the injection Other Total

Frequency 27 25 11 7 4 3 16 93

Percentage of responses (93 responses) 29 26.9 11.8 7.5 4.3 3.2 17.2 100

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Discussion A patient with rheumatic heart disease is expected to receive at least 80% of the annual prescribed injections. Receiving less than 80% of the injections places an individual at a higher risk of recurrent ARF and its complications.9 In this study, adherence was considered as when a patient had received at least 80% of the required injections over a period of six months.

An adherence level of at least 80% was found among 44 (54%) patients, compared to 38 (46%) with adherence levels less than 80%. The mean adherence was determined at 70.12% (SD 29.25). This was similar to the adherence level determined

by Harrington in an aboriginal community in Australia, in which 59% of patients had received more than 75% of their prescribed injections during an interview.14 However, the level of adherence we determined in this study was considerably higher than that found among RHD patients in another Aboriginal community in Australia were the mean adherence level was 56% when patients were followed up for a period of 24 months.15 On the other hand, this level of adherence was considerably less than that found in several other studies such as the study done in Haryana district in India, which found that 90% of the patients had received over 80% of their benzathine injections over the previous eight years.16 The variability in levels of adherence may reflect the different systems in which these studies were done, duration of follow up, the different factors that may influence adherence, the individual study designs, and the different cut-off points for defining adherence in the different studies. This variability is still hard to explain confidently since low levels of adherence have been demonstrated in Australia were rheumatic heart disease registries exist and are fully functional. However, given all these factors, the level of adherence as was determined in this study was low, because it placed a significant proportion of patients (46%) at risk of recurrent episodes of ARF and worsening of valvular heart lesions, with resultant poor prognosis.

Analysing the association of patient factors with adherence levels provides insight into those groups at particular risk of recurrence through poor adherence. No particular patient factor was found to be significantly associated with adherence. This was not surprising as a similar study by Stewart in Australia found no significant demographic factors associated with adherence.15 However, trends towards adherence were demonstrated among patients who resided in a town/city and those with at least secondary level of education.

The fact that patients who resided in a town/city tended to have better adherence could be explained by the fact that these patients have easier access to healthcare facilities compared to those from rural areas. This finding could be supported by a study done by Kathie Walker, who found that patients who stayed far from the health facilities (> 10 km) were significantly associated with poor compliance.11 There was no difference between men and women regarding their level of adherence, although an earlier study by Dorothy12 had revealed that men are more likely to be non-adherent compared to their female counterparts.

Whether the lack of significant factors reflects a true lack of association, a limited time to follow up, or rather, the effect of a small sample size is uncertain from these results. Most of the studies done on this topic have not analysed for these patient factors, making it rather a complex area to discuss. Nevertheless,

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these trends do identify subgroups that might be at increased risk of recurrent ARF and worsening of RHD through non-adherence.

The commonest reason reported for missing monthly benzathine prophylaxis injections was the painful nature of the injection (27, 29%). This was closely followed by lack of money (26.9%) and the fact that the patients felt healthy and well (11.8%). These factors have also been described by WHO expert consultation in Geneva.6 Despite some reports which have indicated that forgetting could be an import reason for missing injections, it did not feature in this study. This could have been due to the benzathine penicillin card but it cannot be ascertained for sure, since no control group existed. However, other factors of interest included development of injection abscesses, misperceptions by the local health worker that a patient does not need prophylaxis after heart valve surgery, and missing an injection during admission. These factors will form the basis for intervention in order to improve adherence among our patients.

Limitations Providing a card, which is not routinely done in the normal setting, may have improved adherence rates as this could have acted as a reminder to go for the injection although the card was devoid of reminding dates. In our setting where records are poor, we could not find any other objective way to measure these rates.

The results obtained may not apply to the general population because of the sampling procedure used. The follow-up time of six months may have been too short to accurately assess the levels of adherence since adherence has been shown to decline with time in some studies.

Conclusions Although the mean level of adherence was fairly good, the level of non-adherence among these rheumatic heart disease patients was significant. Although no particular patient factor was found to be significantly associated with adherence, we determined that residing in a town/city and having at least a secondary school level of education was associated with a trend towards adherence. The painful nature of the benzathine penicillin injections and lack of transport money to travel to the health centre were the main reasons for non-adherence among RHD patients attending Mulago Hospital.

This study was supported by a postgraduate research grant from the Uganda National Council for Science and Technology under the Millennium Science Initiative and the Uganda Heart Institute. The expert technical assistance of Elias Sebatta is gratefully acknowledged. We thank Ms Beatrice Mwesige and Gladys Kahima of the Echocardiography laboratory and the entire staff and management of the Uganda Heart Institute for their support.

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11. Walker KG, Human DG, De Moor MM, Sprenger KJ. The problem of compliance in rheumatic fever. S Afr Med J 1987; 72(11): 781–783.

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14. Harrington Z, Thomas DP, Currie BJ, Bulkanhawuy J. Challenging perceptions of non-compliance with rheumatic fever prophylaxis in a remote Aboriginal community. Med J Aust 2006; 184(10): 514–517.

15. Stewart T, McDonald R, Currie B. Acute rheumatic fever: adherence to secondary prophylaxis and follow up of Indigenous patients in the Katherine region of the Northern Territory. Aust J Rural Health 2007; 15(4): 234–240.

16. Kumar R, Thakur JS, Aggarwal A, Ganguly NK. Compliance of secondary prophylaxis for controlling rheumatic fever and rheumatic heart disease in a rural area of northern India. Ind Heart J 1997; 49(3): 282–288.

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8. Madrona DP, Herrera MD, Jiménez DP, Giraldo SG, Campos RR. Women as whole blood donors: offers, donations and deferrals in the province of Huelva, south-western Spain. Blood Transfus 2012; 5: 1–11.

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Cardiovascular haemodynamics in pre-eclampsia using brain naturetic peptide and tissue Doppler studies S FAYERS, J MOODLEY, DP NAIDOO

Abstract Aim: To determine early haemodynamic changes in preeclampsia (PE) using tissue Doppler echocardiography and brain natriuretic peptide (BNP), and to relate these changes to obstetric outcomes.

Methods: Consenting primigravidae patients in the third trimester of pregnancy were included in the study, which was carried out in a large regional hospital in Durban, South Africa; 115 primigravidae (52 pre-eclamptics and 63 normotensive pregnant patients) attending the maternity unit including the antenatal clinics at the study site were studied.

The patients, matched for maternal and gestational age, were examined during pregnancy and within the puerperium. Transthoracic echocardiography (TTE), tissue Doppler imaging (TDI), umbilical artery Doppler and laboratory investigations were performed.

Results: BNP levels were significantly increased in the antepartum period [23.8 (2–184.1) vs 6.0 (0.5–45.2) pmol/l; p < 0.0001] and during labour [15.0 (1.8–206.4) vs 8.7 (1.9–24.8) pmol/l; p < 0.01] in the pre-eclamptic group compared to the normotensive controls. In the postpartum period, mean BNP levels were 4.2 (1.7–51.4) and 5.95 (2.2–38.7) pmol/l in the preeclamptic and normotensive groups, respectively (p > 0.05).

Tissue Doppler Em/Ea ratios were elevated in the pre-eclamptic compared to the normotensive group (11.02 ± 5.6 vs 9.16 ± 2.6; p < 0.05). Mean left atrial size was larger (38 mm) in the pre-eclamptic group than in the normotensive group (35 mm) but this difference was not significant (p > 0.05).

The umbilical artery resistance index was significantly higher in the pre-eclamptic group compared to the normotensive group (0.68 ± 0.06 vs 0.63 ± 0.05; p < 0.001). There was an increased rate of Caesarean sections performed in the pre-eclamptic group (n = 24) compared to the normotensive group (n = 18; p < 0.001). There were two stillbirths in the pre-eclamptic group and none in the normotensive group. As expected, birth weight (2.6 ± 0.8 kg vs 3.14 ± 0.42 kg; p < 0.0001) was lower in the pre-eclamptic group compared to the normotensive group.

Conclusion: In pregnancies complicated by pre-eclampsia, BNP levels were increased in comparison to normotensive pregnancies and this was accompanied by early changes in Department of Cardiology, University of KwaZulu-Natal, Durban, South Africa DP NAIDOO, FCP (SA) UKZN, magwaza4@ukzn.ac.za

Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South Africa S FAYERS, FCOG

Womens’ Health and HIV Research Group, University of KwaZulu-Natal, Durban, South Africa J MOODLEY, FRCOG, jmog@ukzn.ac.za

left ventricular diastolic function as determined by the tissue Doppler Em/Ea ratios. These changes reverted to baseline values, as indicated by return of BNP levels in the pre-eclamptic group to levels seen in the normotensive group. These changes were associated with an increased Caesarean section rate and lower birth weights in pre-eclamptic mothers.

Keywords: pre-eclampsia, brain natriuretic peptide, tissue Doppler, echocardiography Submitted 24/5/12, accepted 17/4/13 Cardiovasc J Afr 2013; 24: 130–136

www.cvja.co.za

DOI: 10.5830/CVJA-2013-023

Hypertensive disorders of pregnancy complicate approximately 10–16% of pregnancies and constitute one of the leading causes of maternal, foetal and neonatal morbidity and mortality worldwide,1,2 particularly in low- and middle-income countries.3 Most, if not all of the morbidity and mortality in hypertensive disorders of pregnancy arise from pre-eclampia (PE) and its complications.4 Pre-eclampsia arises when expression of pro-inflammatory, anti-angiogenic and angiogenic factors lead to a systemic endothelial cell dysfunction with exaggerated inflammatory and vasoconstrictor responses.5,6 Vasoactive hormones play an important role in the pathogenesis of PE, linking placental hypoperfusion with hypertension, systemic disease and proteinuria.

Until recently most of the non-invasive studies of the haemodynamic changes of PE have employed two-dimensional echocardiography to measure cardiac dimensions and systolic function. Until the advent of tissue Doppler imaging (TDI), there have been few sensitive echocardiographic measures of changes in cardiac filling pressure.

Since vasoconstriction and volume retention characterise PE, it is possible that TDI studies and biomarkers of cardiac stress may be useful in detecting early haemodynamic changes in PE. To date, several different biophysical and biochemical markers have been investigated. These include sflt-1, VEGF, soluble endoglin, P-selectin and PP-13, which reflect the pathogenesis of PE,7,8 and more recently, haemodynamic changes have been documented with brain (or B-type) natriuretic peptide (BNP).9 Measurement of both BNP and NT-proBNP have been shown to be sensitive markers for the detection of mild systolic or diastolic heart failure or asymptomatic left ventricular dysfunction,10,11 and for the diagnosis of congestive heart failure in patients with dyspnoea in an acute-care setting.12 Recent studies suggest that BNP levels are elevated in pre-eclamptics.13-16 We hypothesised that there may be alterations in the BNP levels associated with pre-eclampsia in response to changes in cardiac myocyte stretch and that this may may reflect pressure/ volume changes in the cardiac ventricles in this unique disorder of pregnancy. There are no studies that correlate BNP values with

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structural and/or functional changes in ventricular function in PE during late pregnancy and the postpartum period. Our objective was to characterise the serial changes in the BNP levels in the third trimester of pregnancy and the early postpartum period.

We performed Doppler studies of the heart and umbilical cord, measured plasma BNP levels and evaluated obstetric outcomes in PE and normotensive healthy pregnant patients.

Methods Primigravidae without any pre-existing history or clinical evidence of hypertension/cardiac or renal disease were included in the study after having obtained informed consent. PE was diagnosed when women in their first pregnancy had a blood pressure level of at least 140 mmHg systolic and 90 mmHg diastolic pressure on two occasions over four hours apart for the first time after the 20th week of pregnancy, associated with at least one plus of proteinuria on urinary dipstick. For each patient with PE, at least one healthy normotensive patient was enrolled in the study. At the time of enrolment the study participants were not on any medications to lower blood pressure.

A full history and clinical examination was performed.

Systolic and diastolic blood pressures were recorded by automated readings (Dinamap) after a 30-min period of rest in the sitting position. Baseline blood investigations included a full blood count, urea and creatinine, urates and BNP levels.

Obstetric ultrasound examination was performed on all patients.

Foetal wellbeing was assessed sonographically and by Doppler umbilical flow measurements in relation to appropriate growth for gestational age, amniotic flow index and placental sufficiency.

Pregnancies were followed and timing and mode of delivery were noted. Apgar scores and birth weight were recorded and any admissions to the neonatal intensive care noted. All babies were asseded at birth and seven days after delivery. A total of 63 normotensive pregnant women with similar age and ethnicity without a history of cardiovascular disease, pulmonary or systemic hypertension served as controls.

In this study, blood for BNP estimations from study participants were obtained at three pre-specified time points, i.e. at the time of recruitment (28–40 weeks), intra-partum, and the last specimen was collected between day one and seven post delivery. The samples were collected in plastic specimen tubes containing ethylenediamine tetra-acetic acid (EDTA) and transported on ice to the laboratory where they were centrifuged.

The plasma was stored at −20°C and NT-proBNP was assayed in batches by standard electrochemiluminescence immunoassay (ECLIA) using the Modular Analytics E170 (ELECYS module) and Elecsys 1010/2010 analyzer (Roche diagnostics,). According to the National Committee for Clinical Laboratory Satndards (NCCLS), the resting BNP values considered normal for this methodology lie below 100 pg/ml. The within-assay and total precision coefficients of variation for NT-proBNP mean 208 pmol/l is 0.8 and 4.5%, respectively. The reading sensitivity is < 2.0–5 000 pg/ml (0.58–1 445 pmol/l).

Echocardiography and TDI Shortly after enrolment standard two-dimensional directed M-mode Doppler echocardiography followed by TDI was performed with the patient in the left decubitus position. Doppler echocardiography was performed using a HDE 11 imaging

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system (Philips) with a phased-array transducer and an emission frequency of 3.0 MHz. The left ventricular (LV) end-systolic and end-diastolic dimensions, LV wall thickness, and left atrial (LA) dimensions were measured according to the American Society of Echocardiography guidelines using the leading edge method.17 The left atrial volume was estimated using the biplane ellipsoid formula. The LV end-systolic and end-diastolic volumes and the ejection fraction were measured from the apical four-chamber view using the modified Simpson’s method. TDI was performed with transducer frequencies of 1.8–3.6 MHz with as minimum optimal gain as possible to obtain the best signal-to-noise ratio.18

Foetal ultrasound and umbilical artery Doppler Foetal biometrical ultrasound was performed using a Toshiba (Nemio) scanner in B-mode and a low-frequency (3.75 MHz) curvilinear probe.19 Umbilical artery Doppler studies were then performed using pulsed-wave Doppler to measure flow velocity and calculate the resistance index (RI) as follows: peak systolic velocity was divided by the sum of measurements at peak systole and diastole [RI = systole/(systole + diastole)] and averaged over three cardiac cycles.

Statistical analysis SPSS version 11.5 (SPSS Inc. Chicago Ill, USA) was used for statistical analysis. The baseline characteristics were reported as mean ± standard deviation and were compared between the two groups using the Fisher exact test for categorical variables and the Student’s t-test for continuous variables. Outcome measures were BNP levels, echocardiographic and TDI findings and obstetric outcomes in both groups.

Chi-square statistics or Fisher’s exact tests were used where appropriate to examine associations between categorical exposures and outcomes. Independent two-sample t-tests were used to compare mean BNP levels between two categories.

Results are presented as mean and range in brackets. As BNP levels were not normally distributed, these are presented as median values and a Mann-Whitney U-test was used to compare the two groups. Spearman’s test was used for correlation studies.

A p-value of < 0.05 was considered as statistically significant.

Ethics approval was obtained from The University of KwaZulu-Natal Biomedical Research Ethics Committee.

Results One hundred and fifteen primiparous patients (63 normotensive and 52 pre-eclamptics) were recruited (Table 1). A total of 113 participants had complete longitudinal BNP values for all three pre-specified time periods. There was no difference in gestational age at entry and in mode of delivery in both groups.

The mean age of the pre-eclamptics was slightly higher (21.5 ± 4.7 vs 20.4 ± 3.7 years) but this difference was not significant (p < 0.06). The body mass index in the pre-eclamptic group was significantly higher compared to the normotensive pregnancies (29.4 ± 7.9 vs 27.9 ± 5.5; p < 0.05). There were 17 patients in each group who were HIV infected, five of whom in each group had CD4 cell counts < 200 cells/mm.

Most patients were managed with the following antihypertensive agents: methyldopa or nifedipine XL orally.

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TABLE 3. ECHOCARDIOGRAPHIC AND BNP FINDINGS WITHIN GROUPS

TABLE 1. DEMOGRAPHIC DATA BETWEEN GROUPS Normotensive Pre-eclamptic (n = 63) (n = 52)

Parameter

Age (years) 20.4 ± 3.7 21.5 ± 4.7 BMI (kg/m2) 27.9 ± 5.5 29.4 ± 7.9 Gestational age at entry (weeks) 34.5 ± 2.7 34.3 ± 2.7 Gestational age at delivery (weeks) 38.4 ± 1.9 37.8 ± 2.2 Urine dipstick 0 (0–1+) 2+ (1+ –3+) Oedema 0 (0–1+) 2+ (1+ –4+) HIV status positive 17 17 CD4 count < 200 (cells/mm) 5 5 SBP (mmHg) 127.03 ± 12.9 163.2 ± 17.6 DBP (mmHg) 78.32 ± 8.6 104.4 ± 11.9 Pulse (bpm) 84.7 (72–96) 86.0 (72–106)

p-value < 0.06 < 0.05 ns ns < 0.0001 < 0.0001

< 0.0001 < 0.0001 < 0.04

Values are expressed as mean ± standard deviation. Actual counts are reported for HIV status and CD4 count. SBP = systolic blood pressure; DBP = diastolic blood pressure; bpm = beats per minute.

Where very high blood pressure values were not adequately controlled, combination antihypertensive therapy using intravenous hydralazine or labetolol with the addition of magnesium sulphate was used.

Laboratory analysis (Table 2) showed lower platelet counts in the pre-eclamptic group; 10 patients in the pre-eclamptic group developed thrombocytopaenia and one in the normotensive pregnancies. As expected, serum creatinine, urea, uric acid and urine protein levels were significantly elevated in the pre-eclamptic group. There were no differences in gestational age and estimated foetal weight between groups. Polyhydraminos was present in one normotensive patient and in six pre-eclamptic patients. The umbilical artery resistance index was significantly higher in the pre-eclamptic group compared to the normotensive group (0.68 ± 0.06 vs 0.63 ± 0.05; p < 0.0001).

Echocardiographic and BNP findings are shown in Table 3. There were no differences in the left ventricular chamber dimensions and ejection fraction between the two groups. The left atrium diameter was slightly increased in the pre-eclamptic group but this difference was not significant. Estimates of the left ventricular filling pressure as measured by tissue Doppler E/Ea ratio were significantly higher in the pre-eclamptic group compared to the normotensive pregnancies (11.02 ± 5.6 vs 9.16 ± 2.6; p < 0.05).

TABLE 2. BASELINE CHARACTERISTICS

Parameter

Normal range

Normotensive (n = 41)

Pre-eclamptic (n = 36)

p-value

LV diastole (mm)

35–55

49 (37–56)

50 (39–60)

ns

LV systole (mm)

23–34

33 (23–40)

34 (24–41)

ns

Fractional shortening (%)

27–35

32 (27–42)

32 (26–38)

ns

Ejection fraction (%)

30–60

64 (54–62)

64 (56–66)

ns

LV posterior wall (mm)

6–10

7 (5–9)

7 (5–10)

ns

Septal thickness (mm)

6–10

7 (5–9)

7 (4–10)

ns

Left atrium (mm)

19–39

35 (25–41)

38 (32–55)

ns

Aortic root (mm)

20–37

23 (21–29)

24 (19–30)

ns

<8

9.2 (4.5–12.25)

11.0 (7.3–15.4)

< 0.05 < 0.0001

Tissue Doppler (Ea) BNP (median) (pg/mol) Antepartum (1)

6.0 (0.5–45.2)

23.8 (2–184.1)

Labour (2)

8.7 (1.9–24.8)

15.0 (1.8–206.4)

< 0.01

Postpartum (3)

5.95 (2.2–38.7)

4.2 (1.7–51.4)

< 0.01

Median values for all parameters with range in brackets

There were significant differences between the NT-proBNP levels in all pre-specified time points between the PE and normotensive controls except post delivery (Fig. 1). NT-proBNP levels were significantly increased in the antepartum period in the pre-eclamptic group compared to the normotensive group [(2–184.1) vs 6.0 (0.5–45.2) pmol/l; p < 0.0001]. BNP levels rose during labour (1.8–206.4 vs 1.9–24.8 pmol/l; p < 0.01) and subsided in the postpartum period (1.7–51.4 vs 2.2–38.7 pmol/l; p < 0.01). There was a weak positive correlation between baseline NT-proBNP and TD (r = 0.22; p < 0.051), and a stronger correlation between baseline NT-proBNP and the resistance index (r = 0.321; p < 0.001).

The number of maternal complications was higher in the pre-eclamptic group compared to the normotensive group (Table 4). In the normotensive group, 38 patients delivered vaginally and 18 were delivered by Caesarean section (CS), while in the pre-eclamptic group, 24 were delivered by CS and 27 delivered by the vaginal route. The CS rate was significantly higher in the pre-eclamptic group (24 vs 18; p < 0.05).

Among the normotensive group, most indications (8/14) were for foetal distress and cephalopelvic disproportion. Among the pre-eclamptic group severe pre-eclampsia/eclampsia and foetal distress accounted for most (17/19) indications for CS. After delivery, two PE patients were admitted to an intensive care unit and five required high-care nursing.

As expected, the birthweight was significantly lower in the pre-eclamptic pregnancies compared to the normotensives

Normotensive (n = 63)

Preeclamptic (n = 52)

p-value

Hemoglobin (g/dl)

10.9 ± 1.3

11.3 ± 1.4

ns

Platelets (× 10 /l)

251.8 ± 82.8 33.1 ± 3.1

215.5 ± 82.6

< 0.02

34.2 ± 3.6

< 0.07

20.000 15.000

Parameter Full blood count

9

Haematocrit (l/l)

25.000

Blood chemistry

2.5 ± 0. 7

Urea (mmol/l)

54.5 ± 8.9

3.08 ± 1.18

< 0.002

Creatinine (µmol/l)

0.27 ± 0.06

62.4 ± 12.7

< 0.0001

0.33 ± 0.07

< 0.0001

10.000 5.000

Uric acid (mmol/l) Urine dipstick

0 (0–1+)

Proteinuria Resistance index Gestational age Estimated foetal weight Adequate liquor

0.63 (0.5–0.62)

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2+ (1+ –3+)

< 0.0001

0.68 (0.62–0.84

< 0.0001

34 (28–39)

34 (26–39)

ns

2.6 (1.2–3.7)

2.5 (0.8–3.8)

ns

60

42

ns

0.000

Normotensive Pre-eclamptic

1

2

3

Fig 1. Median BNP level by pre-eclampsia and time point.

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TABLE 4. MATERNAL AND FOETAL OUTCOME Normotensive pregnancies (n = 62)

Pre-eclamptic (n = 48)

1 0 0 0

10 2 11 1

2.64 ± 0.8

3.14 ± 0.42

7 (0–0) 8 (0–0)

8 (3–0) 9 (0–)

Perinatal outcome

63

52

Live births

56

49

Still births

0

2

Early neonatal death

1

1

Parameter Thrombocytopaenia Pulmonary oedema Eclampsia HELLP syndrome Birth weight mean ± SD (kg) Apgar scores 1 min 5 min

Thrombocytopaenia = < 150 × 109/l.

(2.6 ± 0.8 vs 3.14 ± 0.42 kg; p < 0.0001). One neonate in the pre-eclamptic group was born with Down syndrome.

There were two neonatal deaths. Patient 1, a 25-year-old P0G1, who was HIV infected presented at 28 weeks of gestation in pulmonary oedema. The blood pressure value was 224/134 mmHg, pulse rate was 106 beats per minute, proteinuria 2+ and oedema 1+. Her tissue Doppler E/Ea ratio was 42, RI was 0.74, uric acid level was 0.43 mmol/l and platelet count was 122 × 109/l. Rapid-acting blood pressure-lowering drugs (adalat, hydrallazine, labetalol, aldomet and MgSO4) were administerd and she was induced at 30 weeks. She delivered a 1-kg baby with poor Apgar scores who died an hour later.

The second patient, a 24-year-old P0G1 who was HIV uninfected presented at 40 weeks of gestation with a BP of 126/82 mmHg. Her tissue Doppler E/Ea was 15.4, RI was 0.67, and ejection fraction was 68%. She delivered vaginally a 3.4-kg baby with low APGAR scores who died two days later in respiratory distress.

Discussion This was the first study to evaluate haemodynamic alterations in pre-eclampsia using simultaneous BNP and tissue Doppler markers of the left ventricular filling pressure (Fig. 2). The findings indicate that despite the contracted blood volumes in PE, the haemodynamic changes that accompany vasoconstriction in PE are associated with significant changes in LV filling, as reflected by the TDI and BNP levels. The study confirms that the intense vasoconstriction in PE is accompanied by increased left ventricular afterload, accompanied by a reduced cardiac output, hypovolaemia and increased cardiac filling pressures.

Recent studies have confirmed that BNP concentrations are elevated in PE and other hypertensive disorders of pregnancy.19-22 The increased serum BNP levels in PE are greater than that documented in normotensive pregnancies,23,24 suggesting that BNP activation in PE is a response to changes in the maternal circulation that reflect the pathophysiological changes in the utero–placental unit. It is known that median BNP levels are low (< 20 pg/ml) and remain stable throughout gestation in normotensive pregnancies.24 BNP levels rise in pregnancies complicated by mild PE and are even higher in severe pre-eclamptics, probably reflecting ventricular strain and/ or sub-clinical cardiac dysfunction secondary to the increased afterload that is characteristic of PE.13,24

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Itoh et al.13 reviewed the charts of 15 obstetric patients who presented with acute dyspnoea, and found that seven had PE, with elevated BNP levels. This correlated with acute ventricular overload and they responded well to volume management and diuresis. In two patients, markedly elevated serum BNP levels and significant left ventricular dysfunction was found, which was not apparent by standard clinical evaluation.13 In patients with severe pregnancy-induced hypertension, an eight-fold increase in BNP levels has been documented, with a positive correlation between the plasma BNP levels and the mean arterial blood pressure (r = 0.62, p < 0.001).18 Until recently, very little was known about BNP levels during pregnancy. Hameed et al.25 have shown that although pregnant BNP levels are approximately two-fold higher than their non-pregnant counterparts, they do not significantly fluctuate and probably reflect the physiological increase in cardiac output during pregnancy. Our study also confirms that BNP levels remain normal in the peripartum period in normotensive pregnant women.

Circulating plasma BNP levels are mildly elevated in healthy pregnancies compared to non-pregnant controls. A longitudinal study of 29 healthy pregnant women in each trimester and in the postpartum period has shown no significant differences in the median BNP levels in the various stages of pregnancy and postpartum [first trimester 20 (10–115) pg/ml]. Although pregnant BNP levels were twice as high as the non-pregnant BNP levels, there were no significant differences among the cases compared to non-pregnant controls. These authors concluded that pregnancy is associated with a small increase in the BNP levels compared with non-pregnant women.25 By contrast, women with PE show adaptations to the increase in systemic blood pressure with significant modification of left ventricular structure and function.26 Echocardiographic studies show statistically significant increases in LV mass, increased LV end-systolic and end-diastolic volumes, accompanied by significant reductions in LV ejection fraction and percentage of fractional shortening.27-29 We also found an increase in the size of the left atrium in the pre-eclamptic group and although not statistically significant, this probably reflects early cardiac structural changes in PE. More importantly, we showed elevated tissue Doppler E/Ea ratios in the pre-eclamptic patients compared to the normotensive group of patients (11.02 ± 5.6 vs 9.16 ± 2.6, p < 0.05). This increase was attributed to a rise in the tissue Doppler E wave and probably reflects rising cardiac filling pressures in PE. All other differences in the echocardiographic parameters were statistically insignificant, pointing to the sensitivity of tissue Doppler in detecting early changes in diastolic filling pressures.

Although tissue Doppler-derived Ea correlates with the ventricular time constant and is a relatively load-independent measure of myocardial relaxation in patients with cardiac disease, in our study it did not appear as sensitive as BNP, which is emerging as a new marker in identifying early haemodynamic changes. In patients with PE, BNP has been observed to be linearly related to the left ventricular structural and functional changes observed.16 In this study we have shown that plasma BNP levels were significantly increased in pre-eclamptic compared to normotensive patients in the antepartum period, and decreased significantly in the postpartum period. Women with PE have increased sensitivity to angiotensin II, resulting in increased

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A

B

A

B

A

B

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Fig. 2. M-mode Doppler and pulse-wave recordings in a normotensive patient (A) and in a pre-eclamptic patient (B).

peripheral vasoconstriction and volume retention.30,31 BNP is known to suppress renin release and one reason for its activation could be the derangement in the renin angiotensin system that occurs in PE.31 To what extent the pro-inflammatory cytokines and endothein-1 are known to stimulate natriuretic peptide release is not clear, nor is their relationship with cardiac filling pressures known.

While it appears that the increase in circulating plasma BNP is most likely explained by the rising cardiac filling pressure, it should be remembered that PE is documented to be a relatively

volume-contracted state with marked peripheral vasoconstriction.

In this regard, elevation in BNP levels may be due to myocardial remodelling and sub-clinical ventricular dysfunction that accompanies the severe vasoconstriction that is observed in PE. Our findings suggest that BNP reflects the myocardial load in PE. This hypothesis is confirmed by the decrease in BNP levels in the puerperium when the placenta has been removed.

As expected, significant changes were seen in the pre-eclamptic group with regard to blood pressure, pedal oedema, proteinuria, uric acid and serum creatinine levels, highlighting the need

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for intervention, as these factors are documented indicators of worsening disease progression in PE. The relationship between proteinuria and the heart need further evaluation, as well as its relationship to HIV infection. A significant number of our patients were HIV infected but there were no significant changes in the BNP or TDI levels, or even in outcome in these subjects.

In our study, seven pre-eclamptic patients required emergency care post delivery, in keeping with the association between PE and adverse pregnancy events. Of the seven pre-eclamptics who required emergency care, two required ICU admission. An increased rate of Caesarean sections, lower Apgar scores, lower birth weight and an increased admission rate to neonatal ICU has been described in PE.33 Numerous studies have documented similar pregnancy sequelae in patients with PE.32-34 Recently, foetal wellbeing by weekly assessment of umbilical artery Doppler examinations and biophysical profiles were investigated by Sezik et al. in patients with pre-eclampsia in their third trimester.33 It was found that 38% of patients had an abnormal Doppler on the last evaluation before delivery. In this group, significantly higher blood pressures and serum uric acid levels were recorded, lower platelet counts, higher incidence of IUGR, lower Apgar scores at five minutes, a higher incidence of perinatal deaths and higher operative delivery rates.33 We also found umbilical artery velocity to be more practical in evaluating the foetus in late pregnancy than uterine artery Doppler studies, which have been used to predict PE and IUGR.30-33 Technical difficulties in obtaining access to uterine Doppler flow readings precluded the use of this measurement in our study. The increase in the resistance index on umbilical Doppler velocimetry is well described,32,33 and abnormal Doppler umbilical artery waveforms are a strong predictor of perinatal mortality and are associated with a poor perinatal outome.32 Previous studies have shown that BNP levels were elevated in patients with pre-eclampsia but the numbers have been few and they have not correlated these changes with TDI.15,17,24

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Limitations of the study BNP is significantly affected by age, gender, renal function and obesity. Given its correlation with multiple cardiac variables, BNP has high sensitivity but low specificity for the detection of elevated left ventricular filling pressures. In our study this variability was avoided by selecting primiparous patients who were of similar age and constituted a fairly homogenous group of black patients, permitting comparisons to be made.

Also, as mentioned above, most of the changes in BNP that occurred were within normal ranges for our laboratory. It is likely that BNP activation would be more pronounced in severe PE. Furthermore, this study was conducted on patients in the third trimester. Recruitment earlier in pregnancy might have shown whether or not BNP could be used as a marker of PE.

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Conclusion This study showed that there were significant differences in BNP levels during PE and this probably reflects the haemodynamic changes in this condition. Serum BNP levels were significantly elevated in pregnancies complicated by PE, particularly in those with more severe disease. This increase was reflected in elevated tissue Doppler estimations of LV filling pressure (E/Ea ratio).

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Letter to the Editor Is double-blinding possible while administering fluids in the intensive care unit?

Dear Sir The publication by Alavi SM et al. highlights a subject with an ongoing debate, namely the ‘crsytalloid-colloid and colloid– colloid use following cardiac surgery’.1 They designed a randomised, double-blind clinical trial and compared the effects of three different solutions; 0.9% Ringer’s lactate, 4% gelatin and 6% hydroxyethyl starch (HES) solution. They concluded that the HES solution was better in terms of the volume-expanding effect; lower amounts were required compared to the other two solutions, and short-term renal functions were better.

We feel that there are several insufficiencies about the design and contents of the study. We believe that the process of double-blinding is quite challenging in this study, because the anesthesiologist or intensivist should be unaware of the solution administered. The process of double-blinding and how un-blinding was avoided should be detailed.

The haemodynamic status of the patients was defined using parameters such as cardiac index, which we think is very helpful, and also systolic and diastolic blood pressure levels of the patients. Unfortunately, no information regarding the use of inotropes intra-operatively and postoperatively was given.

Indications for the use of inotropes were defined, but information on which type, in what dose and on how many patients they Department of Cardiovascular Surgery, Medicana International Ankara Hospital, Ankara, Turkey AHMET BARIS DURUKAN, barisdurukan@yahoo.com HASAN ALPER GURBUZ, CEM YORGANCIOGLU

Department of Biology, Hacettepe University Faculty of Science, Ankara, Turkey AHMET BARIS DURUKAN, HASAN ALPER GURBUZ,

Diyarbakir Military Hospital, Department of Cardiovascular Surgery, Diyarbakir, Turkey MURAT TAVLASOGLU

were used was not mentioned. This particular variable has great influence on the haemodynamic status of the patient as well the urinary output.2 Renal effects were analysed using serum creatinine and BUN levels, and urinary output. Besides the use of inotropes, the type of fluid used for cardiopulmonary bypass (CPB) priming, and the use of diuretics during CPB and in the postoperative period affect renal functions following cardiac surgery.3 Moreover, recent developments clearly demonstrated that the measurement of glomerular filtration rate (GFR) is the best overall index of renal function rather than measurements of creatinine and BUN levels alone. Serum creatinine levels do not increase until the GFR is reduced below 50%. 3 Finally, the reference by Boldt et al. was retracted in 2011.4 This reference should not be cited in this randomised trial, since Joachim Boldt, who published many articles on crystalloids and colloids, particularly in favour of HES solutions, was suspended for scientific misconduct.5 We believe that discussion on the use of HES solutions following cardiac surgery will continue, since there are many subjects on which consensus has not been reached. Randomised, double-blind clinical trials are the most valuable studies in the search for these answers but a good design and well-defined outcomes are required.

References 1. Alavi SM, Ahmadi BB, Baharestani B, Babaei T. Comparison of the effects of gelatin, Ringer’s solution and a modern hydroxyl ethyl starch solution after coronary artery bypass surgery. Cardiovasc J Afr 2012; 23: 428–431.

2. Hasenfuss G, Teerlink JR. Cardiac inotropes: current agents and future directions. Eur Heart J 2011; 32: 1838–1845.

3. Abu-Omar Y, Ratnatunga C. Cardiopulmonary bypass and renal injury.

Perfusion 2006; 21: 209–213.

4. http://www.ncbi.nlm.nih.gov/pubmed/18305082, Accessed October 14, 2012.

5. http://en.wikipedia.org/wiki/Joachim_Boldt, Accessed October 14, 2012.

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Bilateral thoracoscopic sympathectomy for primary hyperhydrosis: a review of 335 cases MURAT ÖNCEL, GÜVEN SADI SUNAM, ESREF ERDEM, YÜKSEL DERELI, BEKIR TEZCAN , KAZIM GÜROL AKYOL

Abstract Objective: The goal of this retrospective study was to evaluate the outcomes of bilateral video-assisted thoracoscopic sympathectomy for primary hyperhydrosis.

Methods: Between January 2007 and December 2011, a total of 335 patients (192 male, 143 female, mean age 28.3 years) who underwent bilateral thoracoscopic sympathectomy for primary hyperhydrosis were reviewed retrospectively.

Results: Hyperhydrosis occurred in the palmar and axillary region in 175 (52.23%) patients, in only the palmar region in 52 (15.52%), in the craniofacial region in 44 (13.13%), in only the axillary region in 42 (12.53%), and in the palmar and pedal regions in 22 (6.56%) patients. Bilateral thoracoscopic sympathectomy was performed in all patients. The mean follow-up period was 24 (6–48) months. The initial cure rate was 95% and the initial satisfaction rate was 93%. There was no mortality in this study. The complication rate was 15.82% in 53 patients.

Conclusion: Video-assisted thoracoscopic sympathectomy for the treatment of primary hyperhydrosis was effective, with low rates of morbidity and mortality. Despite the appearance of postoperative complications, such as compensatory sweating, patient satisfaction with the procedure was high and their quality of life improved.

Keywords: primary hyperhydrosis, bilateral thoracoscopic sympathectomy, VATS Submitted 23/7/12, accepted 24/1/13 Cardiovasc J Afr 2013; 24: 137–140

www.cvja.co.za

DOI: 10.5830/CVJA-2013-007

Primary hyperhydrosis is a disorder characterised by excessive diffuse or localised sweating. Although its pathophysiology is unknown, it is believed to be caused by hyper-stimulation or over-activity of the sympathetic nervous system.1 It most often affects the palms of the hands, the axillae, or the face.

Although not life-threatening, hyperhydrosis causes educational

Department of Thoracic Surgery, Selcuklu Medicine Faculty, Selcuk University, Konya, Turkey MURAT ÖNCEL, MD, moncel01@hotmail.com GÜVEN SADI SUNAM, MD ESREF ERDEM, MD

Department of Cardiovascular Surgery, Numune State Hospital, Konya, Turkey YÜKSEL DERELI, MD

Department of Thoracic Surgery, Numune State Hospital, Konya, Turkey BEKIR TEZCAN, MD KAZIM GÜROL AKYOL, MD

and occupational difficulties, as well as psychological and social problems. Medical treatment is often ineffective and the response is usually transient.

Thoracoscopic sympathectomy is the current standard treatment for primary hyperhydrosis. This procedure is easy, safe, fast, effective and minimally invasive. The most common side effect of this method is compensatory sweating (CS) and it is believed to be due to a thermoregulatory mechanism.2 In this study, we present our experience with this technique.

Methods A total of 335 patients underwent one-stage bilateral thoracoscopic sympathectomy for treatment of primary palmar hyperhidrosis, by the same surgical team. All patients had failed to respond to adequate medical treatment and were referred for surgery.

Selection criteria included absence of previous thoracic surgery, severe and debilitating primary palmar hyperhydrosis, repercussions on social life, repercussions on professional activity, effect on intimate relationship, inefficacy of medical treatment, and patient motivation and determination. Each patient signed an informed consent after having been carefully educated on the possible side effects, such as transient compensatory dry-hand sweating, intercostal pain, Horner syndrome, pneumothoax and haemopneumothorax.

General anaesthesia using the single lung-isolation technique with a double-lumen endotracheal tube was used in all patients.

The patients were positioned in a semi-sitting position with their arms in abduction. Patients were placed in a semi-prone position for each side of the procedure, with the ipsilateral arm abducted and a mild anti-Trendeleburg position.

Monitoring included saturation, blood pressure and electrocardiogram. In those patients undergoing general anesthesia, one-lung ventilation was administered using a double-lumen endotracheal tube. Thoracoscopic ports were placed, respectively, in the fourth intercostal space on the mid-axillary line and the third intercostal space anterior to the mid-axillary line.

All patients underwent division of their sympathetic chain using controlled intermittent electrocautery after identifying the first rib. The T1 chain was kept for Horner syndrome surgical ablation of the sympathetic chain between T2 and T3, and electrocautery ablation of the accessory branches and Kuntz nerve, when present, was performed in all cases to prevent relapse of the health status immediately before and six months after surgery. In five patients, very thin adhesions were encountered that could easily be eliminated by electrocautery.

A postoperative chest X-ray was performed in the recovery room to verify the absence of a significant haemothorax or pneumothorax. A temporary intra-operative paediatric chest tube was inserted into the chest during closure of the incisional soft tissues but was removed before tying down the skin closure suture.

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Results Video-assisted thoracoscopic sympathectomies (670) were performed in 335 patients with severe primary hyperhydrosis (Table 1). Of the 113 patients, 57.31% (n = 192) were female, 42.69% (n = 143) were male, and the mean age was 28.32 (range 18–54) years. Palmar and axillary hyperhydrosis were the most common symptoms. Hyperhydrosis was observed in the palmar and axillary region in 175 (52. 23%) patients, only in the palmar region in 52 (15.52%), in the craniofacial region in 44 (13.13%), only in the axillary region in 42 (12.53%), and in the palmar and pedal regions in 22 (6.56%) patients.

Bilateral video-assisted thoracoscopic sympathectomy was performed in all patients. T2 resection was performed in 44 patients with craniofacial hyperhydrosis. T3 resection was performed in 94 patients with only palmar and only axillary hyperhydrosis. T3–T4 resection was performed in 175 patients with palmar and axillary hyperhydrosis. T3–T5 resection was performed in 22 patients with palmar and pedal hyperhydrosis.

The mean operating time was 51 (range 37–78) minutes.

Re-operation required for 3 (0.89%) patients due to bleeding.

Usually, patients were discharged within 24–48 hours after operation. The mean follow-up period was 24 (range 6–48) months. Most of the patients presented with an improvement in primary hyperhydrosis. The initial cure rate was 95% and the initial satisfaction rate was 93%. There was no mortality in this study. No recurrence was reported at the follow-up period. The complication rate was 15.82% in 53 patients. Compensatory sweating was the most frequent complication in 34 (10.14%) patients.

Discussion Primary hyperhydrosis is a disorder characterised by excessive sweating. Somewhat more frequent in women, there is an obvious family predisposition and its incidence is higher in certain populations (Asians and Sephardic Jews), representing 1% of the population.3 The condition is bilateral, symmetrical and is sometimes related to or exacerbated by emotional or seasonal situations. Although there are generalised forms, focal TABLE 1. PATIENTS CHARACTERISTICS Mean age Gender

28.32 (range 18–54) years Male Female Localisation of Palmar and axillary (T3–T4 resected) hyperhydrosis Isolated palmar (T3 resected) Craniofacial (T2 resected) Isolated axillary (T3 resected) Palmar and pedal (T3–T5 resected) Complications Compensatory sweating Hyperesthesia at the incision area Pneumothorax Bleeding Horner’s syndrome Emphysema Chylothorax Re-operation 0.89% (n = 3) Recurrence 0 Mortality 0

42.69% (n = 143) 57.31% (n = 192) 52.23% (n = 175) 15.52% (n = 52) 13.13% (n = 44) 12.53% (n = 42) 6.56% (n = 22) 10.14% (n = 34) 2.08% (n = 7) 1.49% (n = 5) 0.89% (n = 3) 0.59% (n = 2) 0.29% (n = 1) 0.29% (n = 1)

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hyperhydrosis is the most frequent presentation. Palmar and axillary hyperhydrosis are the most common, followed by plantar hyperhydrosis.

Although its pathophysiology is unclear, it is believed to be caused by hyper-stimulation or over-activity of the sympathetic nervous system that passes through the upper thoracic ganglia.1 The diagnosis of primary focal hyperhydrosis is based on symptoms, and supported by a specific clinical history. Help is needed to distinguish focal from generalised hyperhydrosis. The Multi-Specialty Working Group on Hyperhydrosis in the United States has proposed some criteria for the diagnosis of focal hyperhydrosis (Table 2).4 Although not life-threatening, hyperhydrosis causes educational and occupational difficulties, as well as psychological and social problems. Medical treatment is often unsuccessful and the response is usually transient. Therapeutic options for its management include topical anti-perspirants, anti-cholinergic drugs, iontophoresis and recently, botulinum toxin injections.5,6 Interruption of the sympathetic innervation of the ecrine sweat glands via the upper thoracic ganglia during surgery is the best procedure for hyperhydrosis. Surgery of the thoracic sympathetic nervous system has been performed since the beginning of the 20th century.7 Thoracoscopic sympathectomy was first described in 1942 by Hughes, and remained rare until the introduction of video-endoscopic techniques in the 1980s.8 Since then it has become the preferred method of treatment of primary hyperhydrosis of the palms, axillae, and more recently for facial blushing. Its popularity has grown so much that the technique is now used around the world.

Bilateral endoscopic sympathectomy can be performed by different surgical and anaesthesiological techniques. Giving the patient the chance to achieve both functional and aesthetic results with minimal risk and discomfort, together with an excellent postoperative quality of life is the gold standard.9 Different techniques are used for intra-operative ventilation of these patients. Orotracheal intubation with a double-lumen endotracheal tube is most commonly used but there are reports of the use of ventilation with a laryngeal mask, as well as surgery under sedation with spontaneous ventilation, with satisfactory results.10 In recent years, numerous articles advocating diverse surgical techniques (ablation, resection, interruption by clips, etc) for accessing the thoracic sympathetic chain have been published.

Hashmonai et al. compared surgical techniques for the treatment of hyperhydrosis (resection or electrocoagulation) based on a review of the studies published between 1974 and 1999.11 Although resection seems to provide better results, the authors

TABLE 2. CRITERIA FOR PRIMARY FOCAL HYPERHYDROSIS DIAGNOSIS A Focal, visible, excessive sweating for a period of at least six months with no known secondary cause B At least one of the following characteristics: • bilateral and symmetrical • frequency of at least one episode per week • interferes with daily activities • presentation before the age of 25 • family history • cessation of excessive sweating during sleep.

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noted that the majority of surgeons tend to use electrocoagulation, perhaps because of its simplicity and shorter surgical time.

Thoracoscopic resection of the upper thoracic sympathetic chain has been defended by numerous authors over the last decade as the treatment of choice for hyperhydrosis.12,13 As previously reported by Garcia and Espania in all cases via video-assisted thorascopic surgery: one or more ganglia between T2 and T5 are usually resected depending on the area affected by hyperhydrosis.14 They recommend intervention on the T2 ganglia for craniofacial hyperhydrosis or rubor, on the T3 ganglia for palmar hyperhidrosis, and on the T3 and T4 ganglia for combined palmar and axillary hyperhydrosis.

Using the Lin-Teleranta classification as a basis, the results of various authors can be analysed, finding enough differences between them to not be able to categorically indicate the precise levels for action, but at the same time finding enough evidence to recommend specific cut levels: • Patients with facial flushing and/or sweating, cut level T2 and/or T3.

• Patients with palmar hyperhydrosis, cut level T3 and/or T4.

• Patients with axillary hyperhydrosis, cut level T4 or T4–T5.15-17 In our study, T2 resection was performed in 44 patients with craniofacial hyperhydrosis, T3 resection was performed in 94 patients with only palmar and only axillary hyperhydrosis, T3–T4 resection was performed in 175 patients with palmar and axillary hyperhydrosis, and T3–T5 resection was performed in 22 patients with palmar and pedal hyperhydrosis.

Studies of patient series in which primary hyperhydrosis has been treated surgically reveal a high degree of patient satisfaction. The best results are reported by Lardinois and Ris, with improvement in quality of life in 94.6% of the patients, and Cohen et al., with a satisfaction rate of 98.2%.18,19 The most frequent postoperative complication is the appearance of pneumothorax, which is usually small and requires pleural drainage in 30% of cases. In a few patients, pleural effusion, haemothorax or chylothorax can occur.20 In general, pain is moderate and is resolved with conventional analgesics over a maximum period of two to four weeks. Horner syndrome appears permanently in less than 0.5% of cases.

Other less frequent complications are subcutaneous emphysema, infection of the surgical wound, the presence of segmental atelectasis and transitory lesions of the brachial plexus.21 In our study, most of the patients presented with an improvement in primary hyperhydrosis. The initial cure rate was 95% and the initial satisfaction rate was 93%. There was no mortality and no recurrence was reported at the follow-up period. The complication rate was 15.82% in 53 patients. CS was the most frequent complication in 34 (10.14%) cases.

CS remains the most common and most disabling complication of video-assisted thoracoscopic sympathectomy and it is believed to be due to a thermoregulatory mechanism.2 CS is defined as intense sweating in other anatomical areas after sympathectomy. The most frequent sites are the thorax, back, abdomen and inguinal region.22 This situation can change over time and is usually difficult to evaluate. The reported frequencies vary considerably, with conflicting views as to its severity and predisposition. Factors such as geographic location, working environment, climatic conditions (temperature and humidity), together with heterogeneity of the population can also affect the incidence of CS.

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According to the series reviewed by Dumont, the mild form oscillates between 15 and 90% and the severe form between 1 and 30%.21 According to some authors, the higher up the sympathectomy is done (T2) and the more extensive the resection (T2–T5), the greater the probability of there being serious CS.20,21 We had 34 cases with compensatory sweating.

In our experience, if you protect the T2 ganglion, you have less reflex compensatory sweating.

Conclusion Bilateral video-assisted thoracic sympathectomy is currently a standard surgical technique to treat primary hyperhydrosis because it is a safe, easy, fast, effective and minimally invasive method. Despite the appearance of postoperative changes such as CS, patient satisfaction with the procedure is high and their quality of life improves.

References 1.

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Drott C, Gothberg G, Claes G. Endoscopic transthoracic sympathectomy: an efficient and safe method for the treatment of hyperhidrosis. J Am Acad Dermatol 1995; 33: 78–81.

Chou SH, Kao EL, Lin CC, Chang YT, Huang MF. The importance of classification in sympathetic surgery and a proposed mechanism for compensatory hyperhidrosis: experience with 464 cases. Surg Endosc 2006; 20(11): 1749–1753.

Ro KM, Cantor RM, Lange KL, Ahn SS. Palmar hyperhidrosis: evidence of genetic transmission. J Vasc Surg 2002; 35: 382–386.

Hornberger J, Grimes K, Naumann M, Glaser DA, Lowe NJ, Naver H, et al. Multi-Specialty Working Group on the Recognition. Diagnosis and Treatment of primary focal hyperhidrosis. J Am Acad Dermatol 2004; 51: 274–286.

Stolman LP. Treatment of hyperhidrosis. Dermatol Clin 1998; 16: 863–867.

Shelly WB, Talanin NY, Shelly ED. Botulinum toxin therapy for palmar hyperhidrosis. J Am Acad Dermatol 1998; 38: 227–229.

Hashmonai M, Kopelman D. History of sympathetic surgery. Clin Auton Res 2003; 1: 16–19.

Hughes J. Endothoracic sympathectomy. Proc R Soc Med 1942; 35: 585–586.

Sihoe AD, Ho KM, Sze TS, Lee TW, Yim AP. Selective lobar collapse for video-assisted thoracic surgery. Ann Thorac Surg 2004; 77: 278–283.

Hsieh YJ, Chen CM, Lin HY, Young TF. Experience of anesthesia during transthoracic endoscopic sympathectomy for palmar hyperhidrosis: comparison between double-lumen endobronchial tube ventilation and laryngeal mask ventilation. Acta Anaesthesiol Sin 1994; 32: 13–20.

Hashmonai M, Assalia A, Kopelman D. Thoracoscopic sympathectomy for palmar hyperhidrosis. Ablate or resect? Surg Endosc 2001; 15: 435–441.

Kim BY, Oh BS, Park YK, Jang WC, Suh HJ, Im YH. Microinvasive video-assisted thoracoscopic sympathicotomy for primary palmar hyperhidrosis. Am J Surg 2001; 181: 540–542.

Krasna MJ, Demmy TL, McKenna RJ, Mack MJ. Thoracoscopic sympathectomy: the U.S. experience. Eur J Surg 1998; 580(Suppl): 19–21.

Garcia F, Espania A. Usefulness of bilateral sympathectomy using video-assisted thorascopic surgery in the treatment of essential hyperhidrosis. ActasDermosifiliogr 2008; 99: 523–711.

Moya J, Ramos R, Morera R, Villalonga R, Perna V, Macia I, et al.

Resultados de la simpaticólisis y la simpatectomía torácica superiorbilateral endoscópica en eltratamiento de la hiperhidrosis primaria.

Estudio de 1.016 procedimientos. Arch Bronconeumol 2006; 42: 230–234.

Lin CC, Telaranta T. Lin-Telaranta classification: the importance of different procedures for different indications in sympathetic surgery.

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Ann Chir Gynaecol 2001; 90: 161–166.

17. Liu Y, Yang J, Liu J, Yang F, Jiang G, Li J, et al. Surgical treatment of primary palmar hyperhidrosis: a prospective randomized study comparing T3 and T4 sympathicotomy. Eur J Cardiothorac Surg 2009; 35: 398–402.

18. Lardinois D, Ris HB. Minimally invasive video-endoscopic sympathectomy by use of a transaxillary single port approach. Eur J Cardiothorac Surg 2002; 21: 67–70.

19. Cohen Z, Levi I, Pinsk I, Mares AJ. Thoracoscopic upper thoracic sympathectomy for primary palmar hyperhidrosis–the combined paediatric, adolescents and adult experience. Eur J Surg 1998; 580(Suppl):

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5–8.

20. Rodríguez PM, Freixinet JL, Hussein M, Valencia JM, Gil RM, Herrero J, et al. Side effects, complications and outcome of thoracoscopic sympathectomy for palmar and axillary hyperhidrosis in 406 patients.

Eur J Cardiothorac Surg 2008; 34: 514–519.

21. Dumont P. Side effects and complications of surgery for hyperhidrosis.

Thoracic Surg 2008; 18: 193–207.

22. Araújo CAA, Azevedo ÍM, Ferreira MAF, Ferreira HPC, Dantas JLCM, Medeiros AC. Compensatory sweating after thoracoscopic sympathectomy: characteristics, prevalence and influence on patient satisfaction.

J Bras Pneumol 2009; 35: 213–220.

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Review Article The global burden of congenital heart disease JULIEN IE HOFFMAN

Abstract Although the incidence of congenital heart disease (CHD) is similar worldwide, the burden of supporting these patients falls more heavily on countries with high fertility rates. In a country with a fertility rate of about eight per woman, the population has to support four times as many children with CHD as in a country with a fertility rate of two. Countries with the highest fertility rates tend to have the lowest incomes per capita, thus accentuating the disparity. Countries with high fertility rates have more children with congenital heart disease per wage earner. Improving local health services and controlling infectious diseases (diarrhoeal illness, rheumatic fever, measles, rotoviral infection) are important but are mere ‘band-aids’ compared to improving education, empowering women and reducing birth rates.

Keywords: fertility rate, per capita income, population age structure, cost disparities Submitted 11/3/13, accepted 17/4/13 Cardiovasc J Afr 2013; 24: 141–145

www.cvja.co.za

DOI: 10.5830/CVJA-2013-028

Patients Congenital heart disease, a major cause of serious morbidity and mortality, is common. It is usually defined as clinically significant structural heart disease present at birth;1 anomalies such as minor changes in the vena caval drainage that have no clinical importance are not included. Some caveats apply.

For example, subaortic stenosis almost always develops well after birth but is included because it resembles other congenital forms of left ventricular outflow tract obstruction. Furthermore, some structural abnormalities that are genetically determined but usually present after infancy are not usually included in the totals; examples include the valve lesions of Marfan’s syndrome or obstruction due to hypertrophic cardiomyopathy. These genetic forms of heart disease are uncommon (Table 1) and including or excluding them from the totals makes little difference to the total incidence of congenital heart disease.

The incidence of congenital heart disease at birth (sometimes referred to as birth prevalence) depends on how a population is studied.2,3 Before the introduction of echocardiography, incidence figures ranged from five to eight per 1 000 live births but better Department of Paediatrics, Cardiovascular Research Institute, University of California, San Francisco, California, USA JULIEN IE HOFFMAN, BSc Hons (Wits), MD (Wits), FRCP (London), julien.hoffman@ucsf.edu

TABLE 1. BIRTH INCIDENCE OF DIFFERENT FORMS OF CONGENITAL HEART DISEASE Disease Structural CHD Bicuspid aortic valve Genetic disorders Dilated cardiomyopathy Hypertrophic cardiomyopathy Neuromuscular dystrophies Connective tissue disorders: large countries, Marfan, mucopolysaccharidoses, etc

Incidence/million live births 10 000–12 000 10 000–12 000 776 6 50 300 420

diagnosis has detected many more with milder forms, so that current estimates range from eight to 12 per 1 000 live births.

Much depends on how early and how intensively the diagnosis is made.

Performing echocardiograms on all neonates has shown that about 5% have small muscular ventricular septal defects, most of which close spontaneously before a year of age. Even more have small atrial septal defects that also close spontaneously. Many neonates have delayed closure of a patent ductus arteriosus. It therefore makes more sense to consider only lesions that need treatment in infancy or are present at a year of age. I think that the best current figure to use is 10–12 per 1 000 live births. Even though this includes some with small and mild defects, these patients still have significant cardiac murmurs, often come to medical attention, and cause much distress to families.

In addition to these, another 10–12 children per 1 000 live births have bicuspid aortic valves that are not stenotic. These seldom cause problems in childhood but account for a large

Fig. 1. Annual births in selected countries. Data from United Nations Children’s Fund accessed at http://data. un.org/Data.aspx?d=SOWC&f=inID%3A75. Map from Wikipedia accessed at ttp://en.wikipedia.org/wiki/World_ population. The panel at the side indicates the population ranges of the different countries, with China and India each having over one billion inhabitants.

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Fig. 2. Total annual births of children with congenital heart disease by continent, based on Table 1 and data on total births. The panel at the side indicates the population ranges of the different countries.

number of adult patients who require treatment for late-onset aortic stenosis or regurgitation. Any consideration of the burden of congenital heart disease must take these into account. Table 1 shows some of these figures.

As far as we can tell, the incidence of congenital heart disease is similar in all countries. There are some minor differences in types of congenital heart disease by country. For example, China and Japan have a higher incidence of subpulmonic ventricular septal defects, whereas coarctation of the aorta and aortic stenosis may be slightly less common in Asian countries. These variations do not appear to cause major differences in total incidence of congenital heart disease. Therefore, because we have good data on the annual number of births in different countries (Fig. 1), we can estimate how many children are born with congenital heart disease in different countries and continents (Fig. 2) The important datum is not how many children with congenital heart disease are born per country but how many of these children are born per million population, because this ratio tells us more about the burden of congenital heart disease. We can derive this information by knowing the fertility rate (the number of children born per woman) in different countries (Fig. 3). These data were taken from Wikipedia, based on data from the United Nations and the CIA World Factbook, accessed at http://en.wikipedia. org/wiki/List_of_sovereign_states_and_dependent_territories_ by_fertility_rate.

Because countries with higher fertility rates have more births per unit of population, they have a disproportionate number of children born with congenital heart disease (Fig. 4) and this imposes an added burden. This disproportionate burden on countries with high fertility rates is made even worse by the age structure of the population. As shown in Fig. 5, countries with

Fig. 3. Fertility rates by country. Published with permission from the World Health Organisation.

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Fig. 4. Number of children born with congenital heart disease per million population.

high fertility rates have a higher proportion of younger people.

Because the burden of supporting children with congenital heart disease falls on those who are wage earners, it is reasonable to examine numbers of children with congenital heart disease per million wage earners. Therefore the 463 children with congenital heart disease per million population in Niger, where only 54% of the people are over 15 years of age, would be 463/0.54 = 857 per million wage earners. In Singapore, where 82% of the population is over 15 years of age, the ratio of children with congenital heart disease per million population is about 120.

Not only does this disproportion in population ages increase the burden on countries with a high fertility rate, almost all of which are in sub-Saharan Africa, but the higher proportion of women of child-bearing age exacerbates their problems by leading to more future births of children with congenital heart disease.

In addition to having a higher proportion of children with congenital heart disease per wage earner, countries with high fertility rates tend to be those with lower per capita income.

Therefore if we contrast two extremes of Niger and Singapore, we get the inequality shown in Table 2. This disparity is reduced somewhat by lower local costs in poorer countries.

Costs such as labour to run hospitals, items constructed locally, food for patients, and fees paid to surgeons and anaesthetists, for example, are almost certainly much less in Niger than in Singapore. Other costs for imported goods, such as machines

Fig. 5. Age distribution in Singapore with a low fertility rate, and Niger with a high fertility rate. Based on data from the Department of Statistics, Singapore, and US Census Bureau International data base.

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TABLE 2. ESTIMATES OF POTENTIAL MONEY TO SPEND ON CHILDREN WITH CHD IN SINGAPORE AND NIGER. THE GDP VALUES ARE CORRECTED FOR LOCAL COST OF LIVING Country Singapore Niger

CHD/million CHD/million population wage earners ~100 ~120 ~500 ~850

GDP per capita $63 000 $1 000

GDP/CHD $525 $0.85

used for cardiopulmonary bypass, antibiotics and catheters used for interventional treatment are still very expensive and almost out of reach of the poorer countries.

Table 3 gives some representative costs in Africa, India and the United States. The International Children’s Heart Foundation sends teams to underdeveloped countries, and cites $2 500 for the cost of open-heart surgery; this is almost certainly subsidised.

There are additional costs to congenital heart disease beyond surgical treatment: medical treatment, cost of transport to hospital, which is often difficult in rural Africa and Asia, and loss of parental working time when they have to take the children to a medical centre.6 These costs are disproportionately severe in countries with low incomes per capita.

In addition, both treated and untreated children with congenital heart disease are at risk of infective endocarditis. This risk may differ from country to country but we do not have good data.

One current estimate by Knirsch and Nadal7 assessed the risk of congenital heart disease as 1.5 to six episodes per year per 100 000 adults, and 0.34–0.64 episodes per year per 100 000 children.

Infective endocarditis produces considerable morbidity, involves lengthy and costly treatment, and severely affects longevity. A follow-up study of patients with infective endocarditis and a variety of underlying heart diseases showed that fewer than 50% survived more than 20 years after the infection.8 Finally, children with congenital heart disease have more than heart disease to contend with. There can be associated defects in several other organ systems, and neurodevelopmental problems are particularly burdensome. Marino et al.9 reported in an American Heart Association scientific statement that moderate to severe neurodevelopmental disabilities occurred in over 50% of children with severe congenital heart disease or congenital heart disease palliated as neonates, and in 25% of those with less severe anomalies.

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TABLE 4. RATIO OF CARDIAC SURGEONS TO POPULATION ON DIFFERENT CONTINENTS Continent North America Europe South America Asia Africa

Ratio cardiac surgeons:population 1:3.5 million 1:3.5 million 1:6.5 million 1:25 million 1:38 million

Prospects and potential solutions The issues are so complex that it is difficult to know where to begin. Poverty, the greatest barrier to successful treatment of congenital heart disease, has multiple causes that are complex and difficult to remove. Natural resources may be inadequate or, where resources (oil, diamonds, ores) exist, corrupt and inefficient governance may prevent fair distribution. This is often compounded by limited education of the population, including its leaders, by unfair trade practices of the developed nations, and at times by well-meaning but ill-advised help from outside agencies.13-15 In addition, in sub-Saharan Africa, there is a huge deficit of all types of skilled medical personnel.16 Treatment of congenital heart disease by surgery or interventional cardiac catheterisation will always be relatively expensive, and expense will always be a major barrier to achieving good cardiac care of these children. This problem is not unique to congenital heart disease, and treatment of some non-cardiac diseases such as cancer, AIDS, drug-resistant tuberculosis and some chronic diseases may be as expensive.

Unfortunately, attempts to alleviate poverty have had limited success. Nevertheless there are several strategies that can help to improve cardiac care. Because the specific problems may differ between countries, the mix of strategies may also need to be different.

Easing the burden of congenital heart disease can be divided into specific cardiac approaches that can be used on a near and mid-term time scale, and a more general socio-economic approach that will take much longer to implement. There are several models for the cardio-specific goals for treating congenital heart disease in underdeveloped countries, and they are discussed in detail by Hewitson and Zilia.6

Resources The resources to treat congenital heart disease are both inadequate and seriously maldistributed.10-12 The 2007–2009 World Society for Paediatric Heart Surgery Manpower Survey11 noted that about 75% of the world’s population have no access to cardiac surgery, and that the distribution of cardiac surgeons was very unbalanced (Table 4). This is in keeping with the variation in distribution of cardiovascular centres (Fig. 6).

TABLE 3. REPRESENTATIVE COSTS. DATA TAKEN FROM KUMAR AND BALAKRISHNAN4 AND PASQUALI ET AL.5 Service Africa India USA Open-heart surgery US$10 000 $5 000 $12 000–50 000 128-slice CT angiogram $350 $4 000 Colour Doppler echocardiography $100 $30 $200

Fig. 6. Distribution of cardiovascular centres in selected countries and continents. The area of the bubble is proportional to the population.

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Fig. 7. Causes of global mortality in children under five years old.

Fig. 9. Fertility rate versus income per capita for several countries on different continents. The continents are colour coded, and the area of the circles is proportional to each countryâ&#x20AC;&#x2122;s population. Note that countries in Africa with high fertility rates are at the lowest end of the income scale.

The least appealing is to have the child and parents go where experts can treat the child optimally. This option is available to only a few privileged and wealthy families and does nothing to help the majority of people in the country. A second slightly more productive model is to have teams of doctors, nurses and technicians go to a country for a few weeks, and treat a set of patients who have been selected beforehand. This certainly benefits more children, but their follow up may be inadequate, the majority of children with congenital heart disease remain untreated, and this model does little to improve medical services in the country.

A better model would be to have these teams come to a country and help train local doctors, nurses and technicians, so that when the visitors leave, a functioning medical service is in place locally. This course, however, involves substantial investment by the host country that may be unwilling or unable to maintain this degree of sophisticated medical care. Developing locally low-cost substitutes for expensive imported products may reduce some of this disadvantage.

For long-term socio-economic goals, larger issues than treatment of congenital heart disease come into play. It is far from clear that children with congenital heart disease should get preferential use of scarce resources. In underdeveloped countries, congenital heart disease plays a minor role in child

morbidity and mortality (Fig. 7).

As shown in Fig. 7, congenital anomalies of all types account for only 5% of deaths, compared with 8% for malaria, 4% for measles, 17% for diarrhoeal diseases, and 29% for pneumonia and other infections, all of which are easier and cheaper to prevent or treat than are congenital heart diseases, and would be a better way to invest scarce resources. Fig. 8 shows, for example, the enormous death rate from rotovirus disease, for which an excellent and low-cost vaccine is now available but not yet extensively used.

Finally, in this list of preventable diseases, we should mention rheumatic heart disease. Although its prevalence is not well defined, it probably affects as many patients as do all forms of congenital heart disease, including bicuspid aortic valves.

Inasmuch as rheumatic heart disease usually follows repeated episodes of acute rheumatic fever, and that treatment of acute streptococcal pharyngitis with penicillin is cheap and effective, this would be an excellent field into which to put scarce resources.6 Treating congenital heart disease, however, is always going to be expensive, and it may be worth giving more thought to its prevention. An approach that has been shown to be effective in a variety of countries is to educate women and improve efforts for family planning. The relationships between excessive fertility

Fig. 8. Distribution of rotovirus mortality across the world. Reproduced with permission from the World Health Organisation.

Fig. 10. Fertility rate versus deaths under five years of age per 1 000 live births. The area of the circle is proportional to the population. There is a direct relationship between fertility rate and child mortality, with African countries being worst off.

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and income (Fig. 9) and child mortality (Fig. 10) suggest that reduction in fertility would be more effective than any other intervention we could make at present.

For example, if it were possible to reduce fertility in Niger from eight to four children per woman, the incidence of congenital heart disease would be reduced by one-half, and if each woman had only two children, the incidence would be reduced by 75%. This is a dramatically greater reduction than possible with any form of treatment; it comes at little cost to the medical services and has the added benefit that it may be associated with an increased per capita income.16 In Mali, a country with a very high fertility rate (before the coup), with the cooperation of imams who understood the problems, the fertility rate dropped from 7.29 in 2009 to 6.35 in 2012. Once such a change starts, the gains accumulate so that there is more money available to treat congenital heart disease in the remaining children.

Reductions in fertility rate with improvement in the national economy have been demonstrated in China, Vietnam and many other countries, even though multiple factors were probably involved. Hans Rosling, an epidemiologist who has worked in this field for many years, made a superb YouTube presentation that demonstrates these changes.17 It is well worth looking at it.

Improvement in treating congenital heart disease is a longrange enterprise. In keeping with the notion that preventing disease is often cheaper than treating it, reducing the fertility rate is perhaps the most important approach and one that has many benefits beyond reducing the incidence of the disease.

Second, investing resources in preventing or treating diseases such as malnutrition, malaria, diarrhoea, measles, pneumonia and rheumatic fever would greatly reduce the child mortality rate, and would then free up money for other purposes, such as establishing regional centres for treating congenital heart disease.

One way of achieving these goals with the least expenditure might be for governments in Africa and Asia to invest in local clinical centres where people have access to health education, diagnosis and treatment for common illnesses. Experience in countries such as China and the former southern Rhodesia, now Zimbabwe, have shown that it is possible to train nurses or nurses’ aides for relatively short periods and have them work in local centres where they can diagnose and treat the simple common illnesses. If this were done after consulting the local population and their leaders, whether these be chieftains, sangomas, ngangas, shamans or imams, this would secure their cooperation and reduce resistance from the population to a government structure imposed on them.

lowering the fertility rate. Money for treating chronic diseases, such as congenital heart disease is always in short supply but can be freed up if more easily preventable acute diseases, such as malnutrition, measles, rotavirus infections or rheumatic fever are made the targets for concerted action. Finally, establishing local health centres with the support of the local population may make it easier to give advice about health and nutrition, administer vaccines and treat streptococcal infections early.

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Conclusion The burden of congenital heart disease falls most heavily on countries with the lowest incomes and the highest fertility rates. Strategies for improvement include preventing excessive numbers of births of children with congenital heart disease by

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Mitchell SC, Korones SB, Berendes HW. Congenital heart disease in 56,109 births. Incidence and natural history. Circulation 1971; 43: 323–332.

Hoffman JIE, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39: 1890–1900.

Wren C. The epidemiology of cardiovascular malformations. In: Moller JH, Hoffman JIE, Benson DW, van Hare GF, Wren C, eds. Pediatric Cardiovascular Medicine. Oxford, England: Wiley-Blackwell; 2012: 268–275.

Kumar RR, Balakrishnan KT. Low cost Cardiac Therapies for Developing Countries – A Health Economic analysis. Africa Medical Opinion; Available from: http://africamedicalopinion.com/Cardiac_ Therapies_for_Developing_Countries.aspx.

Pasquali SK, Sun JL, d’Almada P, et al. Center variation in hospital costs for patients undergoing congenital heart surgery. Circulation Cardiovasc Qual Outcomes 2011; 4: 306–312.

Hewitson J, Zilia P. Children’s heart disease in sub-Saharan Africa: Challenging the burden of disease. S Afr Heart J 2010; 7: 18–29.

Knirsch W, Nadal D. Infective endocarditis in congenital heart disease.

Eur J Pediatr 2011; 170: 1111–2788.

Delahaye F, Ecochard R, de Gevigney G, et al. The long term prognosis of infective endocarditis. Eur Heart J 1995; 16(Suppl B): 48–53.

Marino BS, Lipkin PH, Newburger JW, et al. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 2012; 126: 1143–1172.

Unger F. Worldwide survey on cardiac interventions 1995. Cor Europaeum 1999; 7: 128–146.

Bernier PL, Stefanescu A, Samoukovic G, et al. The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. Sem thorac cardiovasc surg. Pediatr Card Surg A 2010; 13: 26–34.

Kinsley RH, Edwin F, R CP, et al. Paediatric cardiac surgery for a continent – The experience of the Walter Sisulu Paediatric Cardiac Centre for Africa. S Afr Heart J 2011;b 8: 122–129.

Neirotti R. Paediatric cardiac surgery in less privileged parts of the world. Cardiol Young 2004; 14: 341–346.

Neirotti R. Access to cardiac surgery in the developing world: social, political and economic considerations. Federacion Argentina de Cardiolgia, 5th International Congress of Cardiology on the internet; 2007; Available from: http://www.fac.org.ar/qcvc/llave/c010i/neirottir. php.

Zheleva B. Linked by a common purpose: global efforts for improving pediatric heart health: a report by Children’s Heart Limk. Cong Cardiol Today 2007; 5: 1–8.

Kasper J, Bajunirwe F. Brain drain in sub-Saharan africa: Contributing factors, potential remedies and the role of academic medical centres.

Arch Dis Child 2013; 97: 973–979.

Rosling H. Stats that reshape your world-view. 2007; Available from: http://www.youtube.com/watch?v=hVimVzgtD6w.

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Coralan® specifically reduces heart rate without affecting cardiac contraction1, conduction 2 or blood pressure 3

For full prescribing information, refer to package insert approved by medicines regulatory authority.

S3 CORALAN ® 5 mg Tablets. Ivabradine 5 mg. Reg. No. A39/7.1.4/0410 S3 CORALAN ® 7,5 mg Tablets. Ivabradine 7,5 mg. Reg. No. A39/7.1.4/4011 NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE: SERVIER LABORATORIES SOUTH AFRICA (Pty) Ltd. Reg. No. 72/14307/07. Building Number 4, Country Club Estate, 21 Woodlands Drive, Woodmead, 2191. P.O. Box 930, Rivonia, 2128, Republic of South Africa. TEL: +27 (0) 861 700 900. FAX: +27(0)11 525 3401.

REFERENCES: 1. Vilaine JP et al. J Cardiovasc Pharmacol 2003;42:688-696. 2. Camm A et al. Drugs R&D 2003;4:83-89.

3. Borer J et al. Circulation 2003;107:817-823.

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Drug Trends in Cardiology Congress report: Cardiology and Diabetes at the Limits, 22–25 March 2013 The 15th At the Limits conference was held in Cape Town under the auspices of the Hatter Institute and organised and chaired by Prof Derek Yellon of University College London and Prof Lionel Opie of the University of Cape Town. The meeting was sponsored by AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Discovery Health, Medtronic, Novo Nordisk, Roche, Servier, Takeda and the Coca-Cola Company.

Early programming of diabetes and cardiovascular disease: an update Alan Lucas, Institute of Child Health, University College London Lucas discussed programming during foetal development and the effect of diet in the postnatal period, specifically comparing breast milk and formula feeding. Although better foetal growth is associated with better cognitive function, accelerating the growth of small infants in the postnatal period to ‘catch up’ is associated with increases in blood pressure, obesity and risk of cardiovascular disease. It may therefore be necessary to avoid encouraging weight gain by overfeeding smaller babies.

Expressed breast milk does not represent the composition of suckled breast milk which changes during a feed and, in the longer term, with the length of time that breast feeding continues. Recognition of this has led to the reformulation of infant feeds.

The Lancet lecture: The renin–angiotensin–aldosterone system: have we reached the limits?

Marc Pfeffer, Brigham and Women’s Hospital, Boston, USA Marc Pfeffer told how he had gone to extraordinary academic lengths over many years to undertake and publish over 100 studies dealing with the renin–angiotensin– aldosterone system (RAAS) system to show that in the end the more extensively studied drugs were the cheaper ACE inhibitors. The more modern ARBs now also have strong supporting data.

Overall, both ACE inhibitors and ARBs give a 20% reduction in mortality in vascular disease. The ARBs have specific data for ACE-intolerant patients and for post-infarct

heart failure. Combining ACE inhibitors and ARBs has not, on the whole, given improvements except in one heart failure study by Pfeffer.

He also pointed out that spironolactone and eplerenone were very similar, and that studies (including one by his group) were under way to evaluate whether spironolactone provides the same benefits in heart failure as the now well-established but much more costly eplerenone. To obtain funding for this study, Pfeffer had to gain US government support via NIH. The direct renin inhibitors failed to give any further benefit. ‘So we are at the limit of blocking the RAAS system; we have tried to inhibit more, with no benefit’, Dr Pfeffer concluded.

This is a personal South African view of the meeting. The full talks and slides are accessible on the Lancet website, so interested CVJA readers can select any talks they would like to see and hear.

Transcatheter aortic valve implantation (TAVI) surgery: where are the limits?

Axel Linke, University of Leipzig, Germany In inoperable patients, TAVI, using Medtronic core valve self-expanding prostheses, offers resolution of severe aortic stenosis but with complications of stroke (2.9%), major vascular complications (10%) and major bleeding events (10%). TAVI has proved better than balloon valvuloplasty and superior to drug therapy in inoperable patients.

The future includes valves that are repositionable, retrievable and steerable.

Attempts are also being made to reduce strokes by using filters to capture calcific debris and to design valves that reduce aortic regurgitation.

What is the future of cardiac intervention: have we reached the limits?

Stephan Windeker, Bern University Hospital, Switzerland In the COURAGE trial, PCI, which resulted in a reduction in ischaemia, was associated with an improvement in longer-term outcome. FAME II showed marked benefit of PCI guided by FFR compared to medical therapy, the endpoint being driven by urgent

revascularisation. The ISCHEMIA trial is in progress and may clarify the best approach to treatment.

The comparison of PCI with CABG in SYNTAX showed that risk stratification yielded different results in the different categories. Newer DES may influence future outcomes. Though PCI and CABG seem to offer similar benefits in left main coronary artery (LMCA) stenosis, difficulties remain in choosing the best treatment for patients with multi-vessel disease. The EXCEL trial is evaluating LMCA PCI vs CABG. Effective STEMI treatment requires improvements in the management net-work.

Bio-absorbable stents may result in positive remodelling of the coronary vessel.

The duration of dual antiplatelet therapy (DAPT) remains an open question. One trial is in progress which will compare standard DAPT to ticagrelor, given with only one month of aspirin.

Heart failure: where are the new targets?

Martin Cowie, the Royal Brompton Hospital, London There has been a progressive improvement in heart failure survival over the past two decades, with a currently low rate of mortality in societies able to provide modern treatment. Treatment can be improved by attending to the delivery of care. Triple therapy with ACE inhibitors, beta-blocker and MRA are standard in HeF-REF. Ivabradine has an important role in reducing hospitalisation and improving quality of life.

New agents being investigated are serelaxin, which improves symptoms in acute heart failure with 48 hours of treatment but has no effect on re-admission rates.

Mortality at six months may be reduced.

Ultrafiltration is not beneficial, with more adverse effects (Bart, N Engl J Med 2012).

Other areas of research are the effects of mechanical circulatory support, autonomic modulation with vagal stimulation or renal denervation, the influence of sleep-disordered breathing and cardiac myosin activators, ryanodine receptor stabilisers and SERCA2a gene transfection of the myocardium (CUPID 2a). Nonetheless the major problem remains the lack of implementation of known therapies.

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Exercise and fitness in diabetes and heart disease: when do we reach the limits?

Carl Lavie, John Ochsner Heart and Vascular Institute, New Orleans Cardiorespiratory fitness is graded: low fitness is defined as the lowest quintile of individuals assessed according to their time on the treadmill, adjusted for gender and age. Small improvements in fitness result in a significant reduction in incidence of diabetes and mortality. Physical inactivity and low fitness increases total mortality 1.7- to two-fold in males. Fitness overrides fatness as a cause of cardiovascular disease.

There are multiple mechanisms mediating the effect of fitness. An important factor is improvement in mood and anxiety. The exercise dose is important, more not necessarily being better. Resistance training is important in addition to aerobic exercise; 40 minutes per day of vigorous exercise probably provides the maximal benefit.

Modern drug therapy for type 2 diabetes: a cardiological perspective Mansoor Husain, Toronto General Hospital Research Institute The DECODE study showed that IGT increases mortality risk. HbA1c level has been shown to correlate with macrovascular disease and heart failure. Reducing HbA1c level has not been shown to change this outcome.

Good glycaemic control improves quality of life and microvascular disease. A metaanalysis of sulphonylureas showed that they increase in mortality 2.5- to three-fold.

There are no convincing data on survival for any other hypoglycaemic therapy.

GLP-1 is rapidly degraded (2.5 min) therefore only a small proportion reaches the heart. GLP metabolites may be the active substances affecting cardiovascular function. Experimental evidence has shown that DPP4 inhibition and GLP1 agonism improve survival in mice after myocardial infarction (MI). GLP1 agonism but not DPP4 inhibition has reduced experimental infarct size.

The Hatter lecture: Blood pressure control in diabetes: what are the limits, what are the drugs and how are they defined?

Morris Brown, University of Cambridge, UK Brown discussed the control of hypertension in diabetics, pointing out that in all hypertensives, the risk for MI is greater than that for stroke, although the less linear relationship of blood pressure to stroke makes it easier to detect changes in the frequency of stroke

than of MI when blood pressure is reduced.

Masked hypertension occurs more frequently in diabetics and carries a risk equivalent to that of stage 1 hypertension. Treating blood pressure to target level in diabetics does not restore the cardiovascular risk to that of normotensive (untreated) diabetics.

Brown has found evidence of primary hyperaldosteronism in hypertensives. This may be identified by inappropriate suppression of the renin level. Hypokalaemia is found less frequently. About 10% of this group have adrenal micro-adenomas, which may be identified by PET scanning. Early identification and excision may cure the hypertension but is less likely to be effective in those whose elevated blood pressure is long standing.

Debate: diabetologist vs cardiologist The major aim in the therapy of type 2 diabetes (DM2) lies in limiting microvascular damage Steven Kahn (diabetologist) University of Washington, Seattle The 10-year mortality rate was 40% in UKPDS. The mortality rate in diabetes was lower in a high-income group of patients.

In the high-income group, the expenditure on diabetes far exceeded the expenditure in middle- and lower-income groups.

Around 50% of all-cause mortality in diabetes is non-cardiovascular. The combination of diabetes and chronic kidney disease (CKD) had an all-cause mortality rate of 30% compared to 7.5% in a group in whom neither condition was present. Similarly, the combination of CKD and albuminuria had a mortality of 47% compared to those with neither condition.

The 10-year results of UKPDS showed reductions in both mortality and MI. In the ACCORD study, although negative overall, better results were obtained in the subgroups with albuminuria. The most recent NHANES report on diabetics found worsening percentages of glycaemic control, blood pressure control, control of low-density lipoprotein (LDL) cholesterol and diminishing numbers on statin therapy, with a very low percentage of patients achieving control of all these parameters.

The major aim in the therapy of DM2 lies in limiting macrovascular damage Bryan Williams (cardiologist), University College London Increased pulse pressure develops with ageing and begins earlier in diabetes. The presence of an increased pulse pressure in diabetes is strongly correlated with mortality. The pathogenesis involves loss of elas-

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tin, collagen deposition and modification of the collagen by advanced glycation endproducts, which result in cross linkage of collagen, aortic stiffness, loading of the left ventricle and a reduced work capacity.

In diabetics there is a loss of the reflected wave in the aorta with transmission of pulsatile flow more distally in the peripheral circulation. This leads to increased pulsatility in the microcirculation and promotes microvascular disease. Diabetes differs from the effects seen in hypertension and ageing in that autoregulation within the microcirculation is impaired.

Beyond warfarin: are there any limits?

Stefan Hohnloser, JW Goethe University, Frankfurt The results of the RE-LY, ROCKET-AF and ARISTOTLE trials were reviewed.

Given the reduced stroke risk, diminution of intracranial bleeding and ease of use, Hohnloser preferred the use of one of the novel oral anticoagulants to warfarin, although admitting that cost constraints were problematic. His preference overrode considerations of good control of the INR on warfarin or moderate chronic kidney injury (GFR 30–60 ml/min).

Debate: Lifestyle changes vs drugs: which best limits cardiovascular disease?

Tim Noakes, University of Cape Town and Peter Libby, Brigham and Women’s Hospital, Harvard Medical School, Boston The debate between Tim Noakes and Peter Libby was an excellent closing event, both arguing well. Noakes proposed that lifestyle with increased exercise and a low-carbohydrate diet could in his view achieve excellent results on general health, including levels of blood glucose and lipids. Thus drug therapy could often be avoided. However, no controlled studies were presented.

Libby agreed that the standard recommended low-fat diet was not the best. He gave his support to the Mediterranean diet (fresh vegetables, high fruit intake, fish rather than meat, and nuts and olive oil).

In the first controlled outcome diet study ever (New Engl J Med, April 2013), the Mediterranean diet decreased cardiovascular outcomes and total mortality compared with a low fat diet. However, Libby argued, the major problem with any diet was poor long-term adherence, less than 40% at one year, so that in clinical practice drug therapy was more effective.

AJ Dalby, JL Aalbers

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Case Report Multi-slice computed tomography assessment of stent position in a patient with acute coronary syndrome and anomalous origin of the coronary arteries PLINIO CIRILLO, GIANLUCA PETRILLO, RAFFAELE PICCOLO, GIANCARLO MESSALLI, FRANCESCA ZIVIELLO, MICHELE BEVILACQUA, MARCO SALVATORE, FEDERICO PISCIONE, BRUNO TRIMARCO

Abstract We describe the case of a woman with acute coronary syndrome who was treated by percutaneous coronary intervention (PCI) and stenting of the proximal right coronary artery, which shared its short origin with the left anterior descending artery. A multi-slice computed tomography study of the patient’s coronary tree, performed after percutaneous treatment, played a fundamental role in obtaining a clearer view of the coronary anatomy, as well as of stent positioning in this particular anatomy, eliminating any doubt about the PCI result.

Keywords: acute coronary syndromes, coronary artery anomalies, percutaneous coronary intervention, multi-slice computed tomography Submitted 11/3/12, accepted 13/3/13 Cardiovasc J Afr 2013; 24: e1–e3

www.cvja.co.za

DOI: 10.5830/CVJA-2013-012

Coronary arteries with an anomalous origin from the aorta or an anomalous course may present a problem for the interventional cardiologist. Percutaneous coronary intervention (PCI) of these arteries may be very complicated. Specifically, when the origin of these aberrant coronary arteries is positioned along the ascending aorta, it is not easy to access them.1 Moreover, the presence of an anomalous course does not help the interventional cardiologist to choose the appropriate strategy to treat the atherosclerotic lesion.

Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples, Naples, Italy PLINIO CIRILLO, MD, PhD, pcirillo@unina.it GIANLUCA PETRILLO, MD RAFFAELE PICCOLO, MD FRANCESCA ZIVIELLO, MD MICHELE BEVILACQUA, BSc FEDERICO PISCIONE, MD BRUNO TRIMARCO, MD

Division of Radiology, Department of Advanced Biomedical Sciences, University of Naples, Naples, Italy GIANCARLO MESSALLI, MD MARCO SALVATORE, MD

In the present report we describe the case of a patient admitted to our hospital for an acute coronary syndrome (ACS) who was treated with primary PCI with stent implantation at the origin of the right coronary artery (RCA). Unfortunately, the RCA shared a common origin with the left anterior descendent artery (LAD). A multi-slice computed tomography (MSCT) study of the patient’s coronary tree played a fundamental role in obtaining a clearer view of the coronary anatomy and the stent position, considering this particular anatomy.

Case report A 58-year-old-woman was admitted to the emergency room with chest pain and vomiting. On admission, an electrocardiogram (ECG) showed bradycardia with slight ST elevation in the inferior leads (DIII and aVF). Serum levels of the markers of myocardial damage were increased. The patient was sent to the catheter laboratory to undergo coronary angiography.

The angiography showed that the circumflex artery (LCx) originated from the left sinus of Valsalva, and the RCA and LAD might have a common origin from the right sinus of Valsalva (Fig. 1A–C). Moreover, the proximal segment of the RCA had severe stenosis with evidence of thrombus, causing a slow run-off in the distal vessel (Fig. 1C).

Unfortunately, the coronary angiography did not allow us to firmly establish whether the LAD and RCA had a very short common origin or emerged separately. However, since the patient’s clinical conditions had worsened and ECG changes were observed, we decided to perform a PCI on the culprit lesion.

The anomalous coronary artery was cannulated with a 6-Fr JR 4.0 guiding catheter and a 0.014-inch hi-torque balance heavyweight guidewire was used (Abbott Vascular, Santa Clara, CA, USA). Two paclitaxel-eluting stents (Taxus Element 4.0 × 8 mm and Taxus Element 3.5 × 12 mm; Boston Scientific, Natick, MA, USA) were successfully implanted.

Control angiography showed a good angiographic result with perfect visualisation of the RCA and LAD (Fig. 1D). However, it was still unclear whether the RCA and LAD had a common origin or not, and whether the stents were implanted without involving the origin of the LAD. A few days later, the patient underwent MSCT. Tomography showed that the LAD and RCA had a very short common origin and that the LAD’s course was inter-arterial (Fig. 2). Moreover, MSCT indicated that the stents were adequately implanted and that they did not cause obstruction of the LAD origin.

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Fig. 1. Coronary angiograms showing the coronary anatomy. A: The left circumflex artery (LCx) originated from the left sinus of Valsalva. B: The right coronary artery (RCA) and left anterior descending artery (LAD) originated from the right sinus of Valsalva. Arrow indicates the stenosis of the proximal RCA. C: Final result after stent implantation. Note the complete visualisation of both the RCA and LAD.

Surgical correction of the anomalous coronary artery was proposed to the patient but she refused surgery. Therefore, the patient was discharged on medical therapy with the advice to avoid strenuous physical activity.

Discussion Abnormalities of the coronary arteries can be reported in approximately 0.3 to 1% of the population. Because these abnormalities are usually not associated with other congenital cardiac malformations, patients do not show any clinical manifestations and have a good prognosis.2 A systematic classification of abnormalities of the coronary tree has been obtained by imaging techniques.2-5 Specifically, coronary angiography performed in patients with atherosclerotic disease have obtained an ‘invasive’ evaluation of these coronary anomalies.3,4 Alternatively, these abnormalities have been studied by a ‘semi-invasive’ imaging technique, such as transoesophageal echocardiography.5 In the last few years, non-invasive imaging techniques such as MSCT have allowed physicians to obtain a clear reconstruction of the coronary tree.6 In patients in which coronary angiography gives a clear picture of the coronary anatomy, MSCT usually does not add any further information. On the other hand, in those cases in which coronary arteries are not clearly visualised by angiography, MSCT is a significant help. Specifically, this technique is extremely sensitive in demonstrating atherosclerosis of the coronary arteries and it is very useful in the evaluation of coronary artery stenosis in individuals without known coronary artery disease.7,8 Moreover, MSCT use in the coronary intervention laboratory has recently increased because this technique may help in

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Fig. 2. Multi-slice computed tomography imaging (MSTC) and 3D coloured volume rendering of the coronary arteries. A and B: Three dimensional reconstruction of the coronary arteries shows the RCA and LAD sharing a very short common coronary vessel before continuing separately. C and D: Contrast-enhanced 64-slice CT coronary angiography indicates that the stent in the RCA is perfectly implanted and that it does not obstruct the LAD.

evaluating the length of coronary occlusion, the calibre of the distal vessel and the presence of distal disease. This information could have a pivotal role in driving the interventional strategy before PCI.9 Advantages and disadvantages of CT over conventional angiography are still debated. As reported above, the main value of MSTC seems to rule out only ‘significant’ coronary artery disease and it is almost as good as coronary angiography for detecting true false-positives. On the other hand, it seems to be poorer in its rate of false-positives.10 Therefore, although it is a highly effective non-invasive alternative to coronary angiography for the exclusion of obstructive coronary artery stenosis, it is likely that it will still require coronary angiography for MSTC positives, partly to identify MSCT false-positives, but also because angiography provides other information that CT currently does not. Specifically, details of the insertion site and distal run-off for possible coronary artery bypass graft.10 Moreover, the diagnostic accuracy varies at the individual artery level, because results are slightly worse for the LAD and CX arteries compared with the RC and LM arteries. Another important issue to bear in mind is that patients undergoing MSCT are exposed to higher radiation doses compared with invasive coronary angiography. This has resulted in concerns being raised about repetitive use of 64-slice CT or its use in younger individuals or women of childbearing age.11 In the present report, we described a clinical case in which coronary angiography did not permit us to fully elucidate whether the RCA and LAD originated separately or not.

Unfortunately, the patient’s clinical conditions did not permit us to perform MSCT before PCI, therefore the culprit lesion of the proximal RCA was acutely treated with PCI. This choice arose

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because of the doubt whether the stent had covered the LAD’s origin, thus potentially preventing selective access in the future.

MSCT played a key role in obtaining a complete overview of the coronary anatomy because the three-dimensional visualisation of the coronary arteries permitted us to overcome the angiographic limitations described above. Indeed, this technique clearly displayed the congenital coronary artery anomaly because it showed the LAD and RCA had a very short common origin and, in addition, allowed a detailed evaluation of the course of the anomalous vessel, showing its inter-arterial course. Furthermore, MSCT gave important post-procedural information because it revealed that the origin of the LAD was not covered by the stent.

Previous studies have demonstrated that congenital anomalies of the coronary arteries may cause ischaemic manifestations.12 In the past, these patients have been extensively treated with surgery,13 with less-than-ideal long-term results.14 Therefore, the greater use of coronary stents for treating atherosclerotic coronary lesions has progressively increased the use of coronary angioplasty in this setting.15 However, several important considerations regarding the coronary anatomy and technical difficulties of the percutaneous approach should be evaluated to choose the best method of revascularisation in patients with these coronary anomalies.

Conclusion Multi-slice computed tomography may be considered a fundamental non-invasive technique to study the coronary tree, especially in those patients with a particular coronary anatomy.

Although it is unlikely that this imaging technique will replace coronary angiography in assessment for revascularisation of patients with coronary artery disease, particularly because angiography and angioplasty are often performed at the same time, MSCT may allow us to refine angiographic diagnosis by providing a detailed description of anomalous coronary arteries.

In addition, it may give pivotal information to obtain the best evaluation of procedural outcomes in the subset of patients treated with PCI.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

References 1.

Leberthson RR, Dinsmore RE, Bharati S, Rubenstein JJ, Caulfield J, Wheeler EO, et al. Aberrant coronary artery origin from the aorta:

15.

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Diagnosis and clinical significance. Circulation 1974; 50: 774–779.

Angelini P, Velasco JA, Flamm S. Coronary anomalies: incidence, pathophysiology, and clinical relevance. Circulation 2002; 105(20): 2449–2454.

Tuncer C, Batyraliev T, Yilmaz R, Gokce M, Eryonucu B, Koroglu S. Origin and distribution anomalies of the left anterior descending artery in 70,850 adult patients: multicenter data collection. Catheter Cardiovasc Interv 2006; 68(4): 574–585.

Dodge-Khatami A, Mavroudis C, Backer CI. Congenital heart surgery nomenclature and database project: Anomalies of the coronary arteries.

Ann Thorac Surg 2000; 69: 270–297.

Fernandes F, Alam M, Smith S, Khaja F. The role of transesophageal echocardiography in identifying anomalous coronary arteries.

Circulation 1993; 88: 2532–2540.

Manghat NE, Morgan-Hughes GJ, Marshall AJ, Roobottom CA. Multidetector row cometed tomography: imaging congenital coronary artery anomalies in adults. Heart 2005; 91:1515–1522.

Prat-Gonzalez S, Sanz J, Garcia MJ. Cardiac CT. Indications and limitations. J Nucl Med Technol 2008; 36: 18–24.

Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individual without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) Trial. J Am Coll Cardiol 2008; 52: 1724–1732.

Van Mieghem C, Ramcharitar S, de Feyter PJ. Adjunctive use of cardiac CT in the coronary intervention laboratory. Curr Cadiovasc Imaging Rep 2009; 2: 427–436.

Paech D, Weston R. A systematic review of the clinical effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of suspected coronary artery disease. BMC Cardiovasc Disord 2011; 11: 32–43.

Garcia MJ. Noninvasive coronary angiography: hype or new paradigm?

J Am Med Assoc 2005; 293(20): 2531–2533.

Angelini P. Coronary artery anomalies – current clinical issues: definitions, classification, incidence, clinical relevance, and treatment guidelines. Tex Heart Inst J 2002; 29: 271–278.

Fernandes ED, Kadivar H, Hallman GL, Reul GL, Ott DA, Cooley DA. Congenital malformations of the coronary arteries: the Texas Heart Institute experience. Ann Thorac Surg 1992; 54: 732–740.

Rinaldi RG, Varballido J, Giles R, Del Toro E, Porro R. Right coronary artery with anomalous origin and slit ostium. Ann Thorac Surg 1994; 58: 829–832.

Hariharan R, Kacere RD, Angelini P. Can stent-angioplasty be a valid alternative to surgery? Tex Heart Inst J 2002; 29: 308-313.

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Case Report Acute myocardial infarction after prednisolone administration for the treatment of anaphylaxis caused by a wasp sting ZEKERIYA ARSLAN, ATILA IYISOY, MURAT TAVLASOGLU

Abstract Background: Wasp stings have been demonstrated to cause a wide spectrum of allergic reactions from localised reactions to anaphylaxis. Acute coronary syndromes have been described as potential complications of anaphylactic reactions or some of the drugs used for the treatment of anaphylaxis. We know of only a few cases reported of acute myocardial infarction (MI) following corticosteroid administration or anaphylaxis in subjects with normal coronary arteries. If it exists, underlying subclinical coronary atherosclerosis may become clinically evident.

Case report: A 20 year-old male with anaphylaxis due to a wasp sting, complicated by acute ST-elevation MI after intravenous methyl prednisolone administration, is the subject of this report. He was admitted to our emergency service for dizziness, blurred vision, presyncope and mild respiratory distress 10 minutes after the wasp had stung him on the nape of the neck. Six to seven minutes after administration of prednisolone, the patient complained of typical chest pains.

A high posterolateral MI with mild mitral regurgitation were seen on examination. He was treated conservatively with aspirin and heparine. Coronary angiography and intravascular ultrasound imaging, performed 10 days later, showed no evidence of obstructive coronary artery disease.

Conclusion: Although reduced coronary perfusion, local histamine release-induced coronary vasospasm or severe hypoxia have been suggested, the pathophysiology remains unclear. Acute STEMI may be a rare but clinically important complication of a wasp sting, anaphylaxis or the corticosteroid used for its treatment, even in young adults with normal coronary arteries. Therefore, physicians should be aware of such serious complications in order to diagnose them early.

Keywords: acute myocardial infarction, wasp sting, anaphylactic reaction, prednisolone administration Submitted 2/4/12, accepted 13/3/13 Cardiovasc J Afr 2013; 24: e4–e6

www.cvja.co.za

DOI: 10.5830/CVJA-2013-013

Department of Cardiology, Gelibolu Military Hospital, Canakkale, Turkey ZEKERIYA ARSLAN, MD, zekeriya.arslan@gmail.com ATILA IYISOY, MD MURAT TAVLASOGLU, MD

Acute coronary syndromes may occur as a result of anaphylactic reaction or the drugs used for its treatment. Rare reports have revealed acute myocardial infarction (MI) following anaphylaxis in subjects with normal coronary arteries,1-6 or in subjects with underlying ischaemic heart disease.7-9 Although coronary vasospasm, plaque activation and systemic hypotension have been suggested,10 its pathophysiology remains unclear.

Corticosteroids have many side effects on the cardiovascular system and may provoke acute MI.11 We present a case of acute ST-elevation MI (STEMI) after intravenous methyl prednisolone administration for the treatment of anaphylaxis following a wasp sting in a young patient with normal coronary arteries. The medical literature that pertains to this phenomenon is discussed.

Case report A 20-year-old male was admitted to our emergency service with the symptoms of dizziness, blurred vision and mild respiratory distress 10 minutes after a wasp sting on the nape of the neck.

There was only minimal local reaction and he was not in cardiac distress. He had no allergic history or any other cardiovascular risk factors, such as hypertension, diabetes, hyperlipidaemia, overweight, or family history of heart disease, but had been smoking for seven years. His blood pressure was 140/80 mmHg, heart rate was 88 beats per minute and oxygen saturation was 93% in room air. His white blood cell count was also normal [7.3 × 103 (with 3.6% eosinophils; n < 4%)].

Considered as an allergic reaction, 40 mg methyl prednisolone and 10 mg chlorpheniramine maleate were administered intravenously in a slow infusion. However, the patient’s condition deteriorated six to seven minutes later. He had typical chest pains and an ECG showed ST elevation with a reciprocal depression (Fig. 1a). His blood pressure also decreased markedly to 80/60 mmHg, the heart rate increased up to 100 beats per minute but O2 saturation was normal.

Conservative therapy including aspirin, heparine, and volume replacement was administered but nitrates or calcium channel blockers could not be used due to hypotension at that time. The first bedside echocardiography revealed left ventricular posterior, lateral and apical wall movement abnormalities and mild mitral regurgitation (Fig. 2a). Left ventricular ejection fraction (LVEF), estimated by the modified Simpson method, was 35%.

The symptoms and clinical findings began to improve in approximately 25 minutes and the ST deviations resolved (Fig.

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A

B

Fig. 1. A. ECG shows ST elevation with a reciprocal depression. B. After 25 min the ST deviations resolved.

1b). The wall movement abnormalities were limited to the posterior wall only and mitral regurgitation disappeared in two hours, as seen on the control echo (Fig. 2b). The cardiac enzyme levels had increased about two-fold in the sixth hour from that of baseline [creatinine kinase (CK-MB): 42 U/l (22 U/l at baseline; n < 25 U/l), troponin I: 3.12 ng/ml (0.01 ng/ml at baseline; n = 0–2.00 ng/ml)].

Because no coronary intervention facility existed closer than three hours away and the patient had stabilised in a short time, transferral of him was delayed for 10 days, for recovery. Coronary angiography showed no evidence of obstructive coronary artery disease. Intravascular ultrasound imaging (IVUS) (Atlantis 40 mHz, Boston Scientific Co, USA) also clearly demonstrated no evidence of coronary artery disease. An allergic stimulation test was not performed because the patient refused approval.

Discussion An allergic reaction following a wasp sting has a wide spectrum varying from local reactions to anaphylaxis. Severe anaphylaxis may induce bronchospasm, profound vasodilation and angiooedema. Underlying subclinical coronary atherosclerosis may also become clinically evident.

Cardiac involvement is an uncommon but important clinical finding with these conditions. There have been some such cases in subjects with normal coronary arteries,1-6 and in subjects with coronary artery disease.7-9 Some originated from the anaphylaxis itself,4,8,9 or from drugs used for its treatment, including epinephrine1-3,5-7 The use of epinephrine to counteract possible systemic reaction in anaphylaxis has been revealed to cause MI.1,3 Although chlorpheniramine maleate rarely causes mild ventricular depression and transient bradytachycardia (if the administration is too fast), there is no known incidence of MI due to prednisolone or chlorepheniramine maleate administration in the literature.

The main mechanism proposed is vasospasm of the coronary arteries. Other mechanisms, such as plaque activation and systemic hypotension, may play a role in its pathogenesis.

Hypotension may lead to global ischaemia in the heart rather than local myocardial infarction, therefore diffuse ST depressions

A

B

Fig. 2. A. Echocardiography shows left ventricular posterior, lateral and apical wall movement abnormalities and mild mitral regurgitation. B. Control echo after 2h shows posterior wall movement abnormalities only.

with ST elevation in the aVR would have been evident.

An hypothesis of the central role of mast cells, inflammatory cell activation and release of potent vasoactive mediators, called cardiac anaphylaxis, is also suggested.8 Kounis syndrome or allergic MI is defined as resulting in coronary vasospasm, which is mediated by vasoactive amines released by mast cells, and patients may also have eosinophilia.12 The chemical composition of wasp venom basically consists of vasoactive amines and thrombogenic substances that are able to create vasospasm, and coronary thrombosis may play a role in the pathophysiological determination.

Clinically, anaphylaxis may induce an acute ischaemic burden due to a combination of reduced coronary perfusion pressure, tachycardia, and sometimes severe hypoxia. This combination of events may hamper adequate cardiac response to the extreme vasodilation, and even lead to reduced cardiac output and further deterioration. MI during the course of the allergic reaction in the absence of systemic hypotension has rarely been reported.13 However, our patient’s blood pressure was not low, so it was not hypotension-induced myocardial infarction in our case. In a similar case, the possibility of severe coronary spasm associated with anaphylactic reaction was considered, even though other symptoms were mild or absent.7 Local histamine release seems to induce spasm of the coronary vasculature, thus leading to myocardial ischaemia and infarction. Eosinophilic basic proteins or vasoactive cytokines may directly stimulate constriction of nearby smooth muscle.

Eosinophilic infiltration has been shown around the vasa vasorum and nerve fibres.14 Stimulation of these nerve fibres in the adventitia is another possible explanation for the vasospasm.

ST elevation was seen in the majority of cases of vasospasm associated with eosinophilia, similar to prinzmental angina.15 Vasospasm-related symptoms may continue despite high-dose vasodilators but respond well to prednisone.

Corticosteroids may be speculated to have some role on the cardiovascular response. Owecki et al.11 presented a case of a woman who received high doses of methylprednisolone (1 g iv daily) for active Graves’ ophthalmopathy. Severe hypertension developed, followed by myocardial infarction on the fifth day of treatment, but in this case, the drug dose was high and hypertension played the major role in developing the MI. On the other hand, a Löffler’s endocarditis associated with unusual ECG change mimicking posterior myocardial infarction was succesfully treated with prednisolone.16 Azar et al. reported a 48-hour course of anti-inflammatory therapy with methyl prednisolone did not change the short-term outcome of patients

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with unstable angina.17 In this study, the mean C-reactive protein levels decreased with methyl prednisolone but the primary endpoint did not improve and the coronary revascularisation rates were equal.

Takotsubo-like cardiomyopathy, which results from emotional or physical stress, is also another possible mechanism. However, ST-segment changes similar to this phenomenon, negative T and U waves and prolonged QT interval did not occur in our patient, and improvement was very fast.

It can be proposed that the MI in this case was caused by coronary spasm not anaphylactic reaction because the patient experienced the chest pain seven minutes after the prednisolone administration had ended. Additionally, an antihistaminic agent had already been given. During the allergic condition, the patient had had no cardiac discomfort for the first 10 minutes before admision.

Rarely, fast parenteral administration of corticosteroids for anaphylactic reactions may cause cardiovascular collapse, especially in patients with a history of drug allergy. Some authors postulate that acute episodes could be induced by corticosteroids, which increased the production of epinephrine and augmented the sensitivity of cardiomyocytes for catecholamines.18 However, in our case, the administration was longer than three minutes and the drug was diluted with saline.

Furthermore, the effect of prednisolone would not have been evident within seven minutes. So the reason for the coronary spasm was anaphylactic reaction, and the prednisolone could have treated the coronary spasm in the subsequent minutes.

Conclusion Acute STEMI is a rare but clinically important complication of a wasp sting, anaphylaxis or corticosteroid used for its treatment, even in young adults with normal coronary arteries. Physicians should be aware of such serious complications in order to diagnose them early and treat properly. Therefore corticosteroid use should always be carefully considered and the patient should be monitored throughout.

References 1.

2.

Gikas A, Lazaros G, Kontou-Fili K; Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report. BMC Cardiovasc Disord 2005; 5(1): 6.

Brener ZZ, Zhuravenko I, Bergman M Acute myocardial injury following penicillin-associated anaphylactic reaction in a patient with normal

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coronary arteries. Am J Med Sci 2007; 334(4): 305–307.

Shaver KJ, Adams C, Weiss SJ. Acute myocardial infarction after administration of low-dose intravenous epinephrine for anaphylaxis.

Can J Emergency Med 2006; 8(4): 289–294.

Rich MW. Myocardial injury caused by an anaphylactic reaction to ampicillin/sulbactam in a patient with normal coronary arteries. Tex Heart Inst J 1998; 25(3): 194–197.

Conraads VM, Jorens PG, Ebo DG, Claeys MJ, Bosmans JM, Vrints CJ. Coronary artery spasm complicating anaphylaxis secondary to skin disinfectant. Chest 1998; 113(5): 1417–1419.

Austin SM, Barooah B, Kim CS. Reversible acute cardiac injury during cefoxitin-induced anaphylaxis in a patient with normal coronary arteries. Am J Med 1984; 77(4): 729–732.

Lee S, Nikai T, Kanata K, Koshizaki M, Nomura T, Saito Y. [A case of severe coronary artery spasm associated with anaphylactic reaction caused by protamine administration] Masui 2005; 54(9): 1043–1046.

Del Furia F, Querceto L, Testi S, Santoro GM. Acute ST-segment elevation myocardial infarction complicating amoxycillin-induced anaphylaxis: a case report. Int J Cardiol 2007; 117(1): e37–39.

Salgado Fernández J, Penas Lado M, Vázquez González N, López Rico MR, Alemparte Pardavila E, Castro Beiras A. Acute myocardial infarction after anaphylactic reaction to amoxicillin. Rev Esp Cardiol 1999; 52(8): 622–624.

Del Furia F, Matucci A, Santoro GM. Anaphylaxis-induced acute ST-segment elevation myocardial ıschemia treated with primary percutaneous coronary ıntervention: Report of two cases. J Invasive Cardiol 2008; 20(3): E73–76.

Owecki M, Sowiński J Acute myocardial infarction during high-dose methylprednisolone therapy for Graves’ ophthalmopathy. Pharm World Sci 2006; 28(2): 73–75. Epub 2006 Jun 22.

Kounis N. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006; 110: 7–14.

Gupta MK, Gupta P, Rezai F. Histamine – can it cause an acute coronary event? Clin Cardiol 2001; 24(3): 258–259.

Kajihara H, Kato Y, Takanashi H, Nakagawa E, Tahara E, Otsuki T, et al. Periarteritis of coronary arteries with severe eosinophilic infiltration: a new pathologic entity (eosinophilic periarteritis)? Pathol Res Pract 1989; 184: 46–52.

Wong CW, Luis S, Zeng I, Stewart R. Eosinophilia and coronary artery spasm. Heart Lung Circ 2008; 17: 488–496.

Maruyoshi H, Nakatani S, Yasumura Y, Hanatani A, Yamaguchi T, Yutani C, et al. Löffler’s endocarditis associated with unusual ECG change mimicking posterior myocardial infarction. Heart Vessels 2003; 18(1): 43–46.

Azar1 RR, Rinfret S, Theroux P, Stone PH, Dakshinamurthy R. A randomized placebo-controlled trial to assess the efficacy of anti-inflammatory therapy with methylprednisolone in unstable angina (MUNA trial).

Eur Heart J 2000; 21: 2026–2032 Takagi S, Miyazaki S, Fujii T, Daikoku S, Sutani Y, Morii I, Yasuda S, Goto Y, Nonogi H. Dexamethasone-induced cardiogenic shock rescued by percutaneous cardiopulmonary support (PCPS) in a patient with pheochromocytoma. Jpn Circ J 2000; 64(10): 785–788.

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Case Report Delayed chylopericardium as a rare complication after combined mitral valve and coronary artery bypass surgery BILGEHAN SAVAS OZ, GOKHAN ARSLAN, SUAT DOGANCI, ERKAN KAYA, KUBILAY KARABACAK, FARUK CINGOZ, MEHMET ARSLAN

Abstract Chylopericardium is a rare complication of cardiac surgery that is performed from a midline sternotomy. Here we present a case of a 61-year-old male patient with late-onset postoperative chylopericardium following combined coronary artery bypass grafting and mitral valve surgery, and the applied treatment modality.

Keywords: cardiac surgery, chylopericardium, late onset Submitted 12/11/12, accepted 17/4/13 Cardiovasc J Afr 2013; 24: e7–e9

www.cvja.co.za

DOI: 10.5830/CVJA-2013-026

Chylopericardium is a rare but life-threatening complication that occurs as a result of collection of chylous liquid in the pericardial cavity. The aetiology may be both congenital and acquired. Chylous collection following cardiac surgery may cause nutritional imbalance and infection. In this case report, we present the first case of late chylopericardium after combined coronary artery bypass surgery and mitral valve replacement and we discuss the administered therapy.

Case report A 61-year-old male patient was admitted to our cardiology clinic with symptoms of dyspnoea, palpitations and fatigue over a six-month period. After his physical examination, coronary angiogram and echocardiographic evaluation, coronary artery lesions and mitral valve disease were detected. Transthoracic echocardiography revealed a serious mitral regurgitation (grade 4) with mild aortic and tricuspid regurgitation. The ejection fraction was 60%.

Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey BİLGEHAN SAVAS OZ, MD, bsoz@gata.edu.tr GOKHAN ARSLAN, MD SUAT DOGANCİ, MD ERKAN KAYA, MD KUBİLAY KARABACAK,MD FARUK CİNGOZ, MD MEHMET ARSLAN, MD

The patient was prepared for mitral valve replacement and coronary artery bypass grafting surgery. A central venous catheter through the right internal jugular vein was placed and the patient was monitored from the right radial artery after the application of standard open-heart surgical anaesthesia.

A median sternotomy was performed. The two pleural spaces remained intact. The thymus was divided medially using electrocauterisation without extracting the gland. The superior and inferior vena cavae were snared with tapes. Following the cross-clamping of the aorta, isothermic blood cardioplegia was used for myocardial protection. The mitral valve was replaced with a 25-mm St Jude bileaflet mechanical prosthesis and the posterior leaflet was preserved. After performing bypass between the left anterior descending artery and saphenous vein graft, the operation was accomplished successfully and then only one drainage tube was put into the mediastinal space. The patient could be extubated within six hours of arrival in the cardiac ICU. On his first day, 400 ml total of haemorrhagic drainage was obtained from the mediastinal drain. There was no intra-operative complication and the patient made an uneventful post-operative recovery. He was discharged on the seventh post-operative day, at which time he was doing well and the chest X-ray did not show any signs of cardiomegaly.

The patient re-presented on the 17th postoperative day with symptoms of dyspnoea and palpitations. He was in apparent distress. His heart rate was 120 beats/min, blood pressure was 90/47 mmHg, temperature was 37.0°C, and his jugular venous pressure was elevated. No pulsus paradoxus was detected. The liver was 2 cm enlarged. Bilateral (+1) pretibial oedema was present. Auscultation revealed a grade 2/6 systolic ejection murmur at the right upper sternal border, a distant S1 and S2, and no gallops or rubs.

Laboratory results included a white blood cell count of 9.3 × 109/l. An electrocardiogram revealed sinus tachycardia. A chest X-ray showed signs of cardiomegaly (Fig. 1). An echocardiogram showed a normally functioning prosthetic mitral valve and a large circumferential pericardial effusion (8 cm) with diastolic right ventricular collapse.

He underwent emergency pericardiocentesis using transthoracic echocardiography and 1 300 ml of milky, yellowish fluid was removed. The pericardial fluid was analysed and showed chylomicrons with elevated triglyceride levels, consistent with chylous fluid. Microbiological studies were negative. A 24-F drain was positioned in the pericardial space.

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Fig. 1. Chylopericaridum after mitral valve and coronary artery bypass surgery. PA chest radiograph showing pericardial effusion and cardiomegaly.

Oral food intake was ceased and total parenteral nutrition (TPN) was initiated for two weeks. After the second week, TPN was stopped and his diet was changed to a high-protein one containing medium-chain triglycerides for 10 days. However on the second day, the drainage tailed dramatically to 50 ml/day.

The drainage fluid was completely chylous and the patient had a milky chylous drainage for 24 days, producing 50 ml of drainage daily. The chylous leak continued to diminish in volume, with no drainage by the last five days. The patient was subsequently put on a normal diet. The drain output was observed closely for five days after re-institution of the normal diet. There was no further chylous leak.

An echocardiogram confirmed no re-accumulation in the pericardial space and the drain was therefore removed and the patient discharged uneventfully. Clinical and echocardiographic follow up at four weeks showed no recurrence of pericardial fluid.

Discussion Chylopericardium after intra-thoracic surgery is rare. Thomas and McGoon reported the first case of a chylous pericardial effusion following cardiac surgery.1 The most common causes are trauma (blunt or penetrating), thoracic or cardiac surgery (especially for congenital heart disease) and congenital lymphangiomatosis.

Thymus gland injury is reported mainly in the paediatric literature as a cause of chylous pericardial effusion, because the thymus gland involutes after adolescence. This particular complication becomes rare in the adult population, with most of the literature consisting of single case reports. These include chylopericardium after aortic valvotomy, repair of tetralogy of Fallot and coronary artery bypass graft surgery.2,3 Chylopericardium may also be the result of explorative procedures during the preparation of patients for surgery. Overretraction of the chest wall may harm the lymphatic channels where the ductus thoracicus drains. Encircling of the inferior vena cava during the cannulation procedure may cause lymphatic

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Fig. 2. PA chest radiograph of patient after treatment.

leakage due to damage of the lymph channels. Lymphatic channels around the thymus may be damaged during surgical exploration. Cauterised perithymic and intrathymic lymphatics may cause postoperative chylous leakage if the thymus lobes were not blunt dissected and ligated.4 Chylous drainage may occur in the early and late period following cardiac surgery. Early chylopericardium is characterised by a progression in serious drainage and the colour changes to white-yellow after the start of fatty oral intake. Late-onset chylopericardium comes with signs of cardiac tamponade that causes increased cardiac silhouette, prominent neck veins and palpable liver. This may change from the first postoperative day to the post-discharge period.

Diagnosis and treatment of patients who develop a chylopericardium vary. The chylous pericardial fluid is a sterile, milky, odourless fluid containing microscopic fat droplets and is alkaline with a density of 1 010–1 020 mg/dl.5 The presence of fat globules in a Sudan III stain of the drainage fluid helps to diagnose the cyhlous nature. In late-onset symptomatic cases, the condition may be diagnosed with the help of telecardiography and echocardiography.

In our case, the symptoms began 10 days after discharge, with normal oral nutrition. The patient was diagnosed with echocardiography as cardiac tamponade. Chylopericardium was diagnosed macroscopically after pericardiosynthesis and confirmed with biochemical analysis of the fluid.

Treatment may be conservative or surgical in patients with chylous drainage. In early cases, follow up of the mediastinal drainage and changing the patient’s diet to TPN that is rich in medium-chain fatty acids is generally accepted.6 In late-onset cases with signs of pericardial tamponade, pericardiosynthesis, re-insertion of a mediastinal drain or surgical ligation of the ductus thoracicus may be the treatment options.5 Also, somatostatin infusion has been shown to decrease the drainage.7 Surgical ligation is advised in cases with daily drainage amounts of more than 1 500 ml, unchanged amounts of drainage for more than 14 days or in patients with nutritional complications.8 The management strategy for non-responding patients is a dietary modification, and later a TPN regimen within the first

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three weeks. Exploratory surgery is recommended in cases with continued drainage after three weeks. Ligation of the thoracic duct is the final choice of treatment for non-responding patients to other strategies.

In our case, oral nutrition was ceased after confirmation of the chylous drainage and TPN was started. It was stopped on the 21st postoperative day and a diet high in protein and low in medium-chain fatty acids was started. On the fifth day of the new therapy, the drainage disappeared. On the 10th day, a normal oral diet was restarted and the mediastinal drain was removed due to lack of drainage. Thereafter, there was no increase in cardiac silhouette on telecardiographies (Fig. 2) and no pericardial fluid on echocardiography.

Conclusion Our case, as far as we know, is rare and the first lateonset chylopericardium case in the literature that was treated conservatively without the need for surgical ligation following combined coronary artery bypass grafting and mitral valve replacement via median sternotomy.

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References 1.

2.

3.

4.

5.

6.

7.

8.

Thomas CS Jr, McGoon DC. Isolated massive chylopericardium following cardiopulmonary bypass. J Thorac Cardiovas Surg 1971; 61(6): 945–948.

Tchervenkov C, Dobell AR. Chylopericardium following cardiac surgery. Can J Surg 1985; 28: 542–543.

Lee Y, Lee WK, Doromal N, Ganepola GA, Hutchinson J, 3rd. Cardiac tamponade resulting from massive chylopericardium after an aortacoronary bypass operation. J Thorac Cardiovasc Surg 1987; 94: 449–450.

Pollard WM. Colonel L, Schuchmann GF, et al. Isolated chylopericardium after operations. J Thorac Cardiovasc Surg 1981; 81: 943–946.

Akamatsu H, Amano J, Sakamoto T, Suzuki A. Primary chylopericardium. Ann Thorac Surg 1994; 58: 262–266.

Biewer ES, Zürn C, Arnold R, Glockler M, Schulte-Mönting J, Schlensak C, Dittrich S. Chylothorax after surgery on congenital heart disease in newborns and infants – risk factors and efficacy of MCT-diet.

J Cardiothorac Surg 2010; 5: 127.

Rimensberger PC, Müller-Schenker B, Kalangos A, Beghetti M. Treatment of a persistent postoperative chylothorax with somatostatin.

Ann Thorac Surg 1998; 66: 253–254.

Chaiyaroj S, Mullerworth MH, Tatoulis J. Surgery in the management of chylothorax after coronary by-pass with the left internal mammary artery. J Thorac Cardiovasc Surg 1993; 106: 754–756.

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Case Report Percutaneous balloon pericardiotomy using the Inoue balloon for patients with recurrent pericardial tamponade BARIS KILICASLAN, IBRAHIM SUSAM, HUSEYIN DURSUN, CENK EKMEKCI, MEHMET AYDIN, ONER OZDOGAN

Abstract Background: Recurrent pericardial effusion is often caused by pericardial metastases of extra-cardiac tumours. These effusions may be moderate to severe, leading to cardiac tamponade. The treatment is emergency pericardiocentesis but in spite of the initial success of that treatment, the effusions have high recurrence rates. Here we describe our experience of percutaneous balloon pericardiotomy (PBP) using the Inoue balloon for the management of three patients with malignant pericardial effusions secondary to lung cancer.

Methods: In our clinic, three patients with recurrent pericardial effusion secondary to lung cancer were treated with percutaneous pericardiotomy with an Inoue valvuloplasty balloon catheter through the subxiphoid approach.

Results: Successful drainage with balloon pericardiotomy was achieved in all patients without severe complications. In all cases, only one pericardial site was dilated at least three times. During the four to six months of follow up, there were no recurrences of the effusion or tamponade. All patients were still alive.

Conclusions: In our experience, PBP with the Inoue balloon appears to be a simple and safe procedure with a high success rate. PBP is an effective method for the management of patients with recurrent, large, malignant pericardial effusions.

Keywords: recurrent pericardial tamponade, Inoue balloon, percutaneous balloon pericardiotomy Submitted 9/12/12, accepted 18/3/13 Cardiovasc J Afr 2013; 24: e10–e12

www.cvja.co.za

DOI: 10.5830/CVJA-2013-019

The incidence of metastatic malignancies of the myocardium and pericardium has been reported in between 2 and 21% of all cancer patients. Pericardial effusions related to malignancies usually lead to cardiac tamponade, which requires emergency

drainage by pericardiocentesis. However they have high recurrence rates after this treatment.1 For the prevention of recurrences, several surgical and non-surgical approaches have been developed. Intrapericardial installation of chemotherapeutic drugs, radiation therapy, surgical creation of a pleuropericardial window via the lateral approach, or subxiphoid pericardiotomy, and pericardiectomy have been used.1-3 In 1991 Palacios et al. first described percutaneous balloon pericardiotomy (PBP).4 Then Chow and Chow reported on and described the Inoue balloon catheter for this procedure.5 This technique is less invasive and more comfortable than surgery.

We describe our experience of PBP using the Inoue balloon in the management of malignant pericardial effusion secondary to lung cancer.

Case report We performed PBP with the Inoue balloon in three patients with lung cancer. The clinical characteristics of the patients are summarised in Table 1. All cases had severe pericardial effusion causing clinical and echocardiographic signs of cardiac tamponade. Pericardiotomy was performed in patients with at least one recurrence after the previous drainage (Fig. 1). In the first patient, we had performed PBP with another balloon but two weeks later, he was admitted our clinic with pericardial tamponade, so we performed PBP with the Inoue balloon.

Methods In the catheterisation laboratory, after administration of local anaesthesia, the pericardium was entered with an 18-gauge pericardial needle via the standard subxiphoid approach. A 0.025-inch guide wire was advanced into the pericardial space under fluoroscopy, and the needle was removed. The tract of the needle was dilated with an 8-F dilator, and an 8-F pericardial pigtail catheter was inserted.

TABLE 1. CLINICAL CHARACTERISTICS OF PATIENTS

Tepecik Research and Training Hospital, Izmir, Turkey BARIS KILICASLAN, MD, kilicaslanbaris@yahoo.com, IBRAHİM SUSAM, MD HUSEYİN DURSUN, MD CENK EKMEKCİ, MD MEHMET AYDİN, MD ONER OZDOGAN, MD

Age (years)/ Patients gender Disease 1 50/male Lung cancer 2 65/male Lung cancer 3 63/male Lung cancer

Number of pericardiocenteses before PBP 3 2 3

Follow up Recurrences (months) No 6 No 6 No 6

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Fig. 1. The echocardiographic signs of cardiac tamponade.

Fig. 5. Echocardiography after the procedure.

Pericardial fluid was then evacuated through the pigtail catheter but approximately 100 to 200 ml of fluid was left within the pericardium to provide a measure of safety. The pigtail catheter was then removed and a 12-F dilator was advanced over the guide wire.

A self-positioning catheter, the Inoue balloon catheter set (Shineyard Medical Device Co. Ltd, Shenzhen, China) at 22 mm was exchanged over the guide wire and advanced into the pericardial space. The distal portion of the balloon was inflated first and the catheter was then pulled back gently until the distal balloon anchored itself at the parietal pericardium (Fig. 2). The balloon was then rapidly inflated to its full extent until the waist disappeared (Fig. 3). Three inflations were performed to ensure adequate tearing of the pericardium. After this procedure, 10 to 15 ml of contrast medium was rapidly injected to determine the exit of free fluid (Fig. 4).

We performed an echocardiography at the end of the procedure (Fig. 5). After draining the pericardial fluid, a drain was left in place until the next day (as long as less than 100 ml was drained over the next 24 hours).

recurrences of pericardial effusion. In all cases, the pericardial fluid was bloody and varied in volume from 750 to 1 200 ml. Almost complete evacuation of the pericardial effusion was achieved in all patients. There were no post-procedure complications in any of the patients.

During the four to six months of follow up, all patients were alive. Massive pericardial effusion and pericardial tamponade did not recur in any of the patients. In two, we found minimal pericardial effusion. The patients did not re-admit to the hospital for symptoms related to the pericardium and showed no signs of constrictive pericarditis.

Results In all patients, the procedure was successful in a single session with one pericardial puncture. A sufficient opening was obtained by inflating the balloon at least three times. There were no later

Fig. 2. The distal portion of the balloon was inflated first.

Discussion The incidence of recurrent pericardial effusion after pericardiocentesis is 15 to 40%, according to different authors.1,4,5 In patients with recurrent large pericardial effusions or failed pericardiocentesis, two surgical options have been described: creation of a pericardial window through a subxiphoid approach or via a thoracotomy, followed by pericardiectomy.

The subxiphoid pericardial window has been the surgical option of choice during the last few years due to its high rate of success (91%) and low incidence of complications.2,3 Despite this, because patients with malignancies are frequently undernourished and in poor general condition, any kind of surgical approach has an increased risk of peri-operative complications.

Fig. 3. The balloon was rapidly inflated to its full extent until the waist disappeared.

Fig. 4. Contrast medium was washed out from the pericardial space.

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Recently, PBP has been applied as a useful and less-invasive therapy for recurrent, large pericardial effusions and is an alternative option to surgical pericardiotomy.1,5 Ziskind et al. reported the effectiveness of creating a pericardial window with PBP and described a success rate of 92%.1 Then Chow and Chow described the Inoue balloon catheter for this procedure.5 Several authors have reported on the usefulness of this procedure with the Inoue balloon catheter but there have been no such case reports from Turkey.

Our cases were end-stage lung cancer patients who presented with recurrent cardiac tamponade. We performed PBP with the Inoue balloon and this technique prevented collection of fluid and recurrent pericardial tamponade. We preferred the Inoue balloon rather than the double-balloon technique, which differ from each other in several important aspects.

The Inoue technique has been reported to be easier to perform and needs shorter total procedure and fluoroscopic times.

The dilating shape achieved in the Inoue balloon is circular, and different from the elliptical dilating shape achieved in the double balloon.6,7 These findings are consisted with our previous experiences. Also the Inoue balloon with its bi-lobular structure, self-centering mechanism and high radial strength, which is required for tearing the pericardium, are advantages of the Inoue balloon over other type of balloon.

Previous reports have described that the balloon should be inflated at least twice.8-10 For this procedure, we performed three inflations to ensure an adequate tear in the pericardium.

The mechanism of pericardial window creation was studied by Falciolas et al.9 They reported the balloon inflation had resulted in a localised tearing in the parietal pericardium, creating a communication between the pericardial and pleural or rarely the abdominal cavities, in patients treated with PBP. We suggest that the indication for balloon pericardiotomy should be restricted to selected cases of pericardial effusion with recurrent cardiac tamponade despite drainage by pericardiocentesis, or for cases not allowing further drainage with a catheter at the time of recurrence. These cases demonstrate the efficacy of PBP with the Inoue balloon in patients where a pericardial window may be needed. However, the Inoue balloon

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is more expensive than other balloon systems, so we recommend using it only in selected cases.

Conclusions We found PBP with the Inoue balloon to be a safe, simple procedure with a high rate of success and low incidence of complications and recurrences. PBP with the Inoue balloon appears to be an effective method for the palliation of patients with large, malignant pericardial effusions. In spite of its relatively high cost, this technique could be used in our country for selected cases of critically ill patients, instead of the surgical subxiphoid pericardial window.

References 1.

Ziskind AA, Pearce AG, Lemmon CC, et al. Percutaneous balloon pericardiotomy for the treatment of cardiac tamponade and large pericardial effusions: Description of technique and report of the first 50 cases. J Am Coll Cardiol 1993; 21: 1–5.

2. Mill SA, Julian S Holliday RH. Subxiphoid pericardial window for pericardial effusive disease. J Cardiovasc Surg 1989; 30: 768–773.

3. Park JS, Rentschler R, Wilbur D. Surgical management of pericardial effusion in patients with malignancies: comparison of subxiphoid window versus pericardiectomy. Cancer 1991; 67: 76–80.

4. Palacios IF, Tuzcu EM, Ziskind AA, Younger J, Block PC. Percutaneous balloon pericardial window for patients with malignant pericardial effusion and tamponade. Cathet Cardiovasc Diagn 1991: 22; 244–249.

5. Chow LT, Chow WH. Mechanism of pericardial window creation by balloon pericardiotomy. Am J Cardiol 1993; 72: 1321–1322.

6. Bassand J. P, Schiele F, Bernard Y, et al. The double-balloon and Inoue techniques in percutaneous mitral valvuloplasty. Comparative results in a series of 232 cases. J Am Coll Cardiol 1991; 18: 982–989.

7. Park SJ, Kim JJ, Park SW, et al. Immediate and one year results of percutaneous mitral balloon valvuloplasty using Inoue and double balloon techniques. Am J Cardiol 1993; 71: 938–943.

8. Puri A, Agarwal N, Dwivedi K, Narain VS. Percutaneous balloon pericardiotomy for the treatment of recurrent malignant pericardial effusion. Indian Heart J 2012; 64: 88–89.

9. Falciolas CN, Beldekos DL, Foussas SG. Percutaneous balloon pericardiotomy as a therapeutic alternative for cardiac tamponade and recurrent pericardial effusion. Acta Cardiol 1995; 50: 65–70.

10. Ohke M, Bessho A, Haraoka K, i Ohgou T, et al. Percutaneous balloon pericardiotomy by the use of Inoue balloon for the management of recurrent cancer. Int Med 2000; 39(12).

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Case Report Acute ST-elevation myocardial infarction in early puerperium due to severe left main coronary stenosis in a woman with familial hyperlipidaemia TAHIR BEZGIN, ALI ELVERAN, CEM DOĞAN, ALI KARAGÖZ, ŞEYHMUS KÜLAHÇIOĞLU, GÖKHAN KAHVECI, ALI METIZN ESEN

Abstract Acute myocardial infarction (AMI) is a rare but often catastrophic event during pregnancy, delivery or puerperium, leading to a high mortality rate. It has different pathogenic mechanisms, such as atherosclerosis, vasospasm, thrombosis and coronary dissection. Although MI has been reported in pregnant women at all stages of pregnancy and postpartum, it occurs more commonly in the third trimester and most commonly involves the anterior wall. Evidence suggests that pregnancy itself is an independent risk factor for MI, conferring a three- to four-fold higher risk than that of nonpregnant women matched for age, possibly due to the unique physiological changes required to meet the demands of a growing foetus.

We report a case of a 27-year-old woman with familial hyperlipidaemia presenting with myocardial infarction six days after caesarean delivery, secondary to severe left main coronary stenosis (LMCA), who was treated with emergency coronary artery bypass grafting (CABG).

Keywords: pregnancy-related myocardial infarction, left main stenosis, peripartum myocardial infarction Submitted 19/5/12, accepted 18/3/13 Cardiovasc J Afr 2013; 24: e13–e16

www.cvja.co.za

DOI: 10.5830/CVJA-2013-016

Acute myocardial infarction (AMI) is a rare but often a catastrophic event during pregnancy, delivery or puerperium, leading to a high mortality rate.1-4 It has different mechanisms, such as atherosclerosis, vasospasm, thrombosis and coronary dissection. Maternal mortality after MI has decreased from 5.1–37%1,2 to 5.1–7.3%, owing to improvements in diagnosis and treatment.3,4 It was reported with a frequency of one in 35 700 to one in 16 129 pregnancies. However, the frequency is increasing

due to the growing number of pregnancies in women in their forties or fifties.1,3,4 Although MI has been reported in pregnant women at all stages of pregnancy and postpartum, it occurs more commonly in the third trimester and most commonly involves the anterior wall.5 Evidence suggests that pregnancy itself is an independent risk factor for MI, conferring a three- to four-fold higher risk than that of non-pregnant women matched for age, possibly due to the unique physiological changes required to meet the demands of a growing foetus.4

Case report A 27-year-old woman with familial hypercholesterolaemia presented to the emergency room with symptoms of dyspnoea and chest pain over two days. She had had a successful labour via caesarean section six days earlier. She denied smoking and using alcohol or illicit drug abuse. There was no family history of premature coronary artery disease or haematological abnormalities.

On physical examination she was pale, apprehensive and clammy. Arterial blood pressure was 90/50 mmHg. The electrocardiogram showed 4-mm ST-segment elevation in the aVR lead and ST depression in the anterior and inferior leads (Fig. 1). An echocardiogram showed severe apical hypokinesia with a drastic decrease in left ventricular systolic function (ejection fraction = 35%). There were eruptive xanthomas in various areas of her body (Fig. 2).

Cardiology Clinic, Kartal Koşuyolu Heart and Research Hospital, Cevizli-Kartal, Istanbul, Turkey TAHIR BEZGIN, MD, bezgintahir3@yahoo.com ALI ELVERAN, MD CEM DOĞAN, MD ALI KARAGÖZ, MD ŞEYHMUS KÜLAHÇIOĞLU, MD GÖKHAN KAHVECI, MD ALI METIZN ESEN, MD

Fig. 1. Electrocardiogram showing ST-segment elevation in the aVR lead and ST-segment depression in the anterior and inferior leads.

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operatively. She was started on atorvastatin, acetylsalicylate, clopidogrel and meteprolol, and discharged uneventfully on day eight.

Discussion

Fig. 2. Eruptive xanthomas on the skin of the elbow (vegatative), knee and both ring fingers.

She was transferred to the cardiac catheterisation laboratory to perform emergency coronary angiography, which revealed a severe stenosis of the LMCA, together with diffuse atherosclerotic lesions of varying degrees in the left anterior descending (LAD) coronary artery. The left circumflex coronary artery (LCX) and right coronary artery were free of clinically significant disease (Fig. 3). The patient was transferred to the operating room for emergency coronary artery bypass grafting (CABG) and the surgery was performed successfully.

The pre-operative cardiac troponin level was > 50 ng/ml and gradually decreased after CABG. Blood tests performed one week after surgery revealed the presence of severe dyslipidaemia [total cholesterol 797 mg/dl, high-density lipoprotein (HDL) cholesterol 127 mg/dl, low-density lipoprotein (LDL) cholesterol 599 mg/dl].

She recovered well and was extubated on the first day post-

Peripartum myocardial ischaemia is a different entity because the underlying cause is not usually atherosclerosis, in contrast to ischaemic disease in the older population.6 Factors such as increasing maternal age, increasing rates of maternal obesity, smoking, diabetes mellitus and hypertension are possible contributors to the rise in frequency of pregnancy-associated AMI.7 Coronary atherosclerotic lesions have been reported in only 20â&#x20AC;&#x201C;43% of pregnancy-related AMIs.2,5 Risk factors for coronary artery disease in pregnancy are similar to traditional risk factors observed in the general population. More common cardiac risk factors in young women include a family history of atherosclerotic disease, dyslipidaemia, diabetes mellitus, cigarette smoking and previous use of oral contraceptives.

Dyslipidaemia may be worsened during pregnancy because HDL cholesterol is significantly decreased during gestation.8 Spontaneous coronary dissection is a rare event, observed in only 15% of cases and often associated with haemodynamic stress during labour. Such spontaneous dissection is most often encountered in fairly young,9,10 otherwise healthy women, with approximately 30% of cases occurring in late pregnancy (near term) or within three months postpartum. Coronary dissection most commonly affects the left main coronary artery, the left anterior descending artery or both.9,11,12 This causes extensive ischaemia or thrombosis/infarction or both, which can precipitate severe haemodynamic compromise with a high risk of maternal and foetal adverse outcomes.13 Possible causes of coronary spasm include enhanced vascular reactivity to angiotensin II and norepinephrine, and endothelial

Fig. 3. The left anterior oblique cranial projection shows a severe atherosclerotic lesion in the left main coronary artery (thick arrow) and diffuse atherosclerotic disease of the left anterior descending artery (thin arrow). A normal left circumflex and right coronary artery is seen. LMCA: left main coronary artery, LAD: left anterior descending artery.

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dysfunction, renin release and angiotensin production due to decreased uterine perfusion in the supine position, ergot derivatives that are used to control postpartum or post abortion haemorrhage or to suppress lactation.

Several case reports described coronary embolism as a cause of MI during pregnancy. Sources of emboli included prosthetic valves, the left atrium in mitral stenosis or vegetations in infective endocarditis, intracavitary thrombus in peripartum cardiomyopathy or paradoxical embolism.

Coronary thrombosis without evidence of atherosclerotic disease was reported in 8% of cases and was explained by the hypercoagulable state of pregnancy.1 The main reason for the increased risk of thrombosis is hypercoagulability, which has most likely evolved to protect women against the bleeding challenges associated with miscarriage and childbirth. The hypercoagulability of pregnancy is present as early as the first trimester, as is the increased risk of thrombosis.

Acute coronary syndrome during pregnancy and puerperium will continue to pose a great challenge for the physician for many reasons. First, the challenge of initial diagnosis; owing to the relative rarity of this condition, the misinterpretation of its signs and symptoms and because of a low level of suspicion, a rapid and accurate diagnosis of this condition will continue to be a challenge for physicians.

Second, the different pathophysiology; unlike ACS in non-pregnant women and in men where acute MI is typically due to atherosclerosis, most of the coronary events complicating pregnancy are not due to coronary atheroma. Different aetiologies of ACS during pregnancy make uniform recommendations very difficult. AMI in pregnant women is diagnosed in the same way as in non-pregnant patients, including the constellation of symptoms, electrocardiographic changes, and cardiac markers.14 At the same time, however, the diagnostic approach is also influenced by foetal safety and the normal changes in pregnancy.

The management of AMI during pregnancy should follow the usual principles of care for AMI; however, selection of diagnostic and therapeutic approaches may be influenced by foetal safety.

For patients with ischaemic symptoms characteristic of acute MI of up to two hoursâ&#x20AC;&#x2122; duration and persistent ST-segment elevation, prompt and complete restoration of flow in the infarct-related artery can be achieved with a pharmacological (fibrinolysis), percutaneous coronary (PCI) or surgical intervention.

PCI has been well documented during pregnancy and is considered safe for maternal and foetal survival.1,4,15-18 In most cases PCI is preferred over thrombolysis because of the decreased risk of haemorrhage in pregnancy and because coronary dissection is a significant cause of AMI in pregnancy.

The first reports of angioplasty in a patient with postpartum MI came in the 1990s.

All patients with STEMI who seek medical care within the first 12 hours of onset of symptoms should be considered for urgent reperfusion of the infarct-related artery. Although it is not uncommon, because the symptoms and signs can be mistaken for normal manifestations of pregnancy and labour, and because there is a low index of suspicion, many pregnant women with STEMI will present beyond the ideal time frame for reperfusion.

The cardiovascular risks of angioplasty in pregnancy are similar to those in the non-pregnant patient.19 The bleeding and radiation risks can be reduced by use of a radial approach,20 appropriate abdominal shielding, and decreasing fluoroscopy

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time. The use of an intra-aortic balloon pump to improve left ventricular output and coronary perfusion is also considered safe,21 although the patient should be positioned in the left lateral recumbent position to reduce compression of the inferior vena cava.

All reported stenting during the acute phase of MI during pregnancy was performed with bare-metal stents;1,4 the safety of drug-eluting stents in pregnant women is currently still unknown.

Because drug-eluting stents require prolonged antiplatelet therapy with clopidogrel and the incidence of cesarean deliveries in patients with heart disease is relatively high, the use of a drugeluting stent during pregnancy may be problematic and should be avoided if possible.14 Hundreds of cases of cardiopulmonary bypass have been reported in the literature since it was first used during pregnancy in 1959. Over time, there have been significant improvements in maternal and foetal outcomes. At present, maternal mortality in CABG is the same as that in the general population, at 1.7 to 3%, with a foetal mortality rate of 9.5 to 19%.22-25 Surgery in the first trimester is associated with more foetal congenital malformations but does not affect foetal mortality.23,24 The timing of the CABG does affect foetal mortality, and if the foetus is over 28 weeks of gestation, consideration must be given to deliver the child immediately before or during the cardiac surgery.24 CABG surgery is considered the gold-standard treatment of unprotected left main coronary artery (ULMCA) disease.

Severe LMCA disease will reduce flow to a large portion of the myocardium, placing the patient at high risk for life-threatening events of left ventriculrar dysfunction and arrhythmias.

Thrombolytic therapy is considered to be relatively contraindicated in pregnancy,26 and because pregnant patients have been traditionally excluded from clinical trials, the available information is anecdotal.27-29 Although maternal and foetal outcomes were favourable in most cases,30 some reports have documented complications, such as maternal haemorrhage, preterm delivery, foetal loss, and spontaneous abortion.30-34 The most appropriate medication regimen for pregnant patients with ischaemic heart disease or AMI is unknown. There is a significant amount of anecdotal evidence supporting the use of salicylates, β-blockers, nitroglycerin, calcium antagonists and heparin during pregnancy but little is known about the optimal combination of these medications.19 In the present case, multiple factors (such as hypercholesterolaemia and hypercoagulability state) may have contributed to the AMI. To our knowledge, this is the first case reporting severe atherosclerotic LMCA stenosis as a cause of post-partum AMI.

Conclusion This case underlines how during pregnancy or puerperium, it is important to evaluate the cardiovascular risk profile in order not to underestimate clinical signs of myocardial ischaemia. AMI in pregnancy is uncommon but not as rare as it used to be. As pregnancy itself represents a risk factor, clinicians should be aware of classical risk factors for coronary artery disease and typical symptoms of myocardial ischaemia. Particularly older childbearing women should be closely monitored. If coronary artery disease is suspected or diagnosed, interdisciplinary teamwork between the general practitioner, cardiologist, cardiovascular surgeon, obstetrician and anaesthetist is required.

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Roth A, Elkayam U. Acute myocardial infarction associated with pregnancy. J Am Coll Cardiol 2008; 52: 171–180.

Badui E, Enciso R. Acute myocardial infarction during pregnancy and puerperium: a review. Angiology 1996; 47: 739–756.

Ladner HE, Danielson B, Gilbert WM. Acute myocardial infarction in pregnancy and the puerperium: a population-based study. Obstet Gynecol 2005; 105: 480–484.

James AH, Jamison MG, Biswas MS, et al. Acute myocardial infarction in pregnancy: a United States population-based study. Circulation 2006; 113: 1564 –1571.

Roth A, Elkayam U. Acute myocardial infarction associated with pregnancy. Ann Intern Med 1996; 125(9): 751–162.

Macarthur A, Cook L, Pollard JK, Brant R. Peripartum myocardial ischemia: a review of Canadian deliveries from 1970 to 1998. Am J Obstet Gynecol 2006; 194(4): 1027–1033.

Yu-Ling Tan J. Cardiovascular disease in pregnancy. Obstet Gynaecol Repro Med 2010; 20(4): 107–115.

Lewis CE, Funkhouser E, Raczynski JM, Sidney S, Bild DE, Howard BV. Adverse effect of pregnancy on high density lipoprotein (HDL) cholesterol in young adult women. Am J Epidemiol 1996; 144: 247–254.

Badmanaban B, McCarty D, Mole DJ, McKeown PP, Sarsam MA. Spontaneous coronary artery dissection presenting as cardiac tamponade. Ann Thorac Surg 2002; 73: 1324–1326.

Thistlethwaite PA, Trazi RY, Giordano FJ, Jamieson SW. Surgical management of spontaneous left main coronary artery dissection. Ann Thorac Surg 1998; 66: 258–260.

Aliyary S, Mariani MA, Verhorst PM, Hartmann M, Stoel MG, von Birgelen C. Staged therapeutic approach in spontaneous coronary dissection. Ann Thorac Surg 2007; 83: 1879–1881.

Kearney P, Singh H, Hutter J, Khan S, Lee G, Lucey J. Spontaneous coronary artery dissection: a report of three cases and review of the literature. Postgrad Med J 1993; 69: 940–945.

Sherif HM, Nguyen HC, Sarter BH, et al. Spontaneous coronary dissection in late pregnancy: a multidisciplinary approach to management.

Ann Thorac Surg 2008; 85: 1793–1794.

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Bredy PL, Singh P, Frishman WH. Acute inferior wall myocardial infarction and percutaneous coronary intervention of the right coronary during active labor. Cardiol Rev 2008; 16: 260–268.

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16. Reizig K, Diar N, Walcker JL. Myocardial infarction, pregnancy and anesthesia. Ann Fr Anesth Reanim 2000; 19: 544–548.

17. Sebastian C, Scherlag M, Kugelmass A, et al. Primary stent implantation for acute myocardial infarction during pregnancy: use of abciximab, ticlopidine, and aspirin. Cathet Cardiovasc Diagn 1998; 45: 275–279.

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23. Bernal JM, Miralles PJ. Cardiac surgery with cardiopulmonary bypass during pregnancy. Obstet Gynecol Surv 1986; 41: 1–6.

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the CLOT

Target with Confidence

protects long term against further atherothrombotic events

Compared to the originator, Clopivas has

1

• Proven bioequivalence • No signicant difference in % of inhibi�on of platelet aggrega�on • The same chemical form II • An equivalent dissolu�on prole • A similar purity/impurity prole REFERENCE: 1. Data on file.

S3 Reg. No. 41/8.2/0766 Cipla Medpro (Pty) Ltd. Reg. No. 1995/004182/07 Rosen Heights, Pasita Street, Rosen Park, Bellville, 7530. Tel (021) 943 4200, Fax (021) 914 4699 Email: medicalpa@ciplamedpro.co.za, Website: www.cipla.co.za

MAY 2013 VOL 24 NO 4

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CardioVascular Journal of Africa (official journal for PASCAR)

• CVJA position statement • Cardiovascular diseases in Africa • Left atrial appendage closure in patients with atrial fibrillation • NSTEMI in three hospital settings in South Africa • Congestive heart failure in a Kenyan paediatric population • Benzathine penicillin for secondary prophylaxis in patients with RHD • Pre-eclampsia, brain naturetic peptide and tissue Doppler studies • Global burden of congenital heart disease

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• Acute myocardial infarction after prednisolone for the treatment of anaphylaxis • Percutaneous balloon pericardiotomy for recurrent tamponade