CVJA Volume 26 Issue 4 by Clinics Cardive Publishing

JULY/AUGUST 2015 VOL 26 NO 4

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CardioVascular Journal of Africa (official journal for PASCAR)

• Hypertension in sub-Saharan Africa • Analysis of clinical outcomes of IABP • Efficacy of milk and lemon juice during MPI • Risk factors for CKD in Uganda • Performance of re-used pacemakers and ICDs • Glycaemic, BP and cholesterol control in diabetics • First Melody ® valve implantations in Africa

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• Prevalence of infantile heart disease in Senegal

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CALL FOR WEIRD & WONDERFUL CLINICAL CASES

DEADLINES

The Congress has allocated a session to vexing or unusual clinical cases titled “Hearts In Sight : the Weird and Wonderful”. It affords an opportunity for Clinicians and Fellows in Cardiology to present interesting or unusual clinical cases, ECGs and images (Radiographs/Echo/CT/CMR/Nuclear studies) to a panel of international and local experts. This session will be combined with an abstract/original research forum.

Submission for Weird & Wonderful Clinical Cases

31 August

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4 October

Registration

12 October

Contact the SA Heart Congress Team Europa Organisation Africa Tel: 011 325 0020 Fax: 011 325 0028 Email kerrie@eoafrica.co.za

Heart

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

Vol 26, No 4, JULY/AUGUST 2015

CONTENTS

Cardiovascular Journal of Africa 151

www.cvja.co.za

From the Editor’s Desk P Commerford

Editorial 152 Hypertension in sub-Saharan Africa: a massive and increasing health disaster awaiting solution NRC Campbell • D Lemogoum

Cardiovascular Topics 155 Analysis of clinical outcomes of intra-aortic balloon pump use during coronary artery bypass surgery G Yumun • U Aydin • Y Ata • F Toktaş • AA Pala • AF Ozyazicioglu • T Turk • S Yavuz 159

Comparison of neutrophil:lymphocyte ratios following coronary artery bypass surgery with or without cardiopulmonary bypass M Aldemir • ED Bakı • F Adalı • G Çarşanba • E Tecer • HU Taş

165 Prediction of mid-term outcome after cryo-balloon ablation of atrial fibrillation using post-procedure high-sensitivity troponin level T Aksu • SE Golcuk • TE Guler • K Yalin • İ Erden 171 Efficacy of full-fat milk and diluted lemon juice in reducing infra-cardiac activity of 99mTc sestamibi during myocardial perfusion imaging K Purbhoo • M Di Tamba • W Vangu 177

Cardiovascular risk factors among patients with chronic kidney disease attending a tertiary hospital in Uganda C Babua • R Kalyesubula • E Okello • B Kakande • E Sebatta • M Mungoma • CK Mondo

181 Performance of re-used pacemakers and implantable cardioverter defibrillators compared with new devices at Groote Schuur Hospital in Cape Town, South Africa ZV Jama • A Chin • M Badri • BM Mayosi

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

Editors

SUBJECT Editors

Editorial Board

Editor in Chief (South Africa) Prof Pat Commerford

Nuclear Medicine and Imaging DR MM SATHEKGE

prof PA Brink Experimental & Laboratory Cardiology

PROF A LOCHNER Biochemistry/Laboratory Science

PROF R DELPORT Chemical Pathology

PROF BM MAYOSI Chronic Rheumatic Heart Disease

Assistant Editor Prof JAMES KER (JUN) Regional Editor DR A Dzudie Regional Editor (Kenya) Dr F Bukachi Regional Editor (South Africa) PROF R DELPORT

Heart Failure Dr g visagie Paediatric dr s brown Paediatric Surgery Dr Darshan Reddy Renal Hypertension dr brian rayner Surgical dr f aziz Adult Surgery dr j rossouw Epidemiology and Preventionist dr ap kengne Pregnancy-associated Heart Disease Prof K Sliwa-hahnle

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

International Advisory Board PROF DAVID CELEMAJER Australia (Clinical Cardiology) PROF KEITH COPELIN FERDINAND USA (General Cardiology) DR SAMUEL KINGUE Cameroon (General Cardiology)

PROF DP NAIDOO Echocardiography

DR GEORGE A MENSAH USA (General Cardiology)

PROF B RAYNER Hypertension/Society

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)

Review Articles 188

Glycaemic, blood pressure and cholesterol control in 25 629 diabetics Y Pinchevsky • N Butkow • T Chirwa • FJ Raal

Vol 26, No 4, JULY/AUGUST 2015

CONTENTS

193 Why is control of hypertension in sub-Saharan Africa poor? YK Seedat

Case Report 196

First Melody ® valve implantations in Africa DG Buys • C Greig • SC Brown

200

Cardio News

PUBLISHED ONLINE (Available on www.cvja.co.za, Pubmed and in Pubmed Central) Cardiovascular Topic

e1 The prevalence of symptomatic infantile heart disease at Louga Regional Hospital, Senegal GAB Ba Ngouala • DA Affangla • M Leye • A Kane

Case Reports e6 Unrepaired persistent truncus arteriosus in a 38-year-old woman with an uneventful pregnancy D Abid • E Daoud • SB Kahla • S Mallek • L Abid • H Fourati • Z Mnif • S Kammoun e9 Exudative pericarditis in the evolution of a diffuse large B-cell lymphoma C Bagacean • A Tempescul • J-C Ianotto • V Marion • D Pop • M Zdrenghea e12 Intermittent symptomatic functional mitral regurgitation illustrated by two cases A Aydin • T Gurol • O Soylu • B Dagdeviren e15 Unusual complication of aortic dissections: intimo–intimal intussusception U Vural • AY Balci • AA Aglar • M Kizilay • İ Yekeler • AK Tuygun e19

Bare-metal stent thrombosis two decades after stenting A Acibuca • DM Gerede • VK Vurgun

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 4, July/August 2015

151

From the Editor’s Desk In this issue of the Journal, Seedat (page 193) asks why the control of hypertension in sub-Saharan Africa is as bad as it is. Citing the importance of the disease as a cause of death and disability, he concludes that both the prevalence of hypertension and the failure to control it properly is driven by the poverty of the population of the region, the cost of pharmaceuticals, and a lack of medical resources. He finishes with a rousing call, echoing the late iconic President Mandela, to all of us to find African solutions to African problems. In an editorial comment, Campbell and Legoum (page 152) re-iterate the size of the problem of hypertension in the region, and remind us that this was not always the case. Mechanisms we do not always fully understand, but which are almost certainly driven by urbanisation and poverty, are probably driving the epidemic. Furthermore, they point out that recognition and acknowledgement of the size and importance of the problem is an important first step to finding a resolution. Crucially, they discuss that at recent meetings in Africa, local leaders and champions have emerged who can spearhead an offensive on this scourge. They also list a number of organisations committed to the project. All involved in treatment and control of hypertension in Africa need to read the contributions of Seedat and Campbell. In one of those happy moments of editorial serendipity, we are able to publish the literature review of Pinchevsky and co-authors in this same issue (page 188). These authors investigated the published results of the success of guidelinedirected control of a number of important risk factors (including blood pressure) in patients with diabetes. Only 35.2% (range 7.4–66.3%) of patients achieved a target blood pressure of 130/80 mmHg (or less), and targets for glycaemic and lipid control were not much better. It is interesting to note that even in well-resourced countries, achievement of targets in this vulnerable population were most unsatisfactory. Perhaps we need to re-think traditional methods of management and reflect on why we are so unsuccessful in our usual management strategies. It may be time for the world to look more closely at a polypill or alternative novel approach. Permanent pacemaker implantation (PPMI) is a very effective tool to treat bradyarrhythmias, particularly complete heart block. The sad fact is that many patients who should receive PPMI in many parts of Africa (and I assume other similarly poorly resourced countries) do not receive the life-saving benefit and dramatic symptomatic improvement that PPMI offers. Pacemaker implantation is simple, at least for the basic ventricular-paced, ventricular-inhibited (VVI) systems that most patients with complete heart block require. The technique can be learned in a few months, it requires basic surgical skills, which most doctors possess, and access to fluoroscopy. The challenge with pacemakers is the cost of the necessary hardware. A pacemaker generator, in its most basic form, costs US$2 500–3 000 and the leads cost US$800–1 000. The high cost of pacemakers results in limited access for deserving patients

Professor PJ Commerford

in under-resourced countries to these dramatic improvements in both quality of life and life expectancy. As outlined by Jama and colleagues (page 181), re-use of such devices is both feasible and clinically safe, provided the necessary skills for re-testing and sterilisation of the devices are available. Such programmes have been available and in place in parts of Africa for years but have not been subjected to the sort of post-implantation examination performed by Jama and co-authors, and they are to be congratulated for that. I have purposefully not addressed implantable cardioverter defibrillator (ICD) re-use, which they also discuss. I believe that we in Africa need to be able to address the relatively simple issue of pacing for complete heart block, ensure that it is relatively easily available to all who need it, and work towards simple pacemaker availability before worrying about more complex devices, which while undoubtedly effective, offer marginal benefit compared to the wonderful benefit of VVI pacing for symptomatic complete heart block. PJ Commerford Editor in Chief

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Editorial Hypertension in sub-Saharan Africa: a massive and increasing health disaster awaiting solution Norm RC Campbell, Daniel Lemogoum

Increased blood pressure is the leading risk for death globally.1 While this is also true in sub-Saharan Africa, there are many hypertension issues that are unique to the region.2 A prime and important example is that in most countries in the region, population blood pressure is increasing, while in most countries in the rest of the globe, population blood pressure is decreasing.3 Currently hypertension prevalence rates in some sub-Saharan African countries are among the highest in the world, while a few short decades ago, several countries in sub-Saharan Africa had among the lowest blood pressure levels.2 Importantly, several sub-Saharan African countries still have hypertension prevalence rates below the global average, providing an important opportunity for prevention. Recently, a needs assessment of hypertension organisations in sub-Saharan Africa also showed important and different needs from hypertension organisations in other regions of the world.4,5 Dr Seedat has comprehensively outlined relevant issues in his article ‘Why is control of hypertension in sub-Saharan Africa poor?’ (page 193) He concludes by quoting Nelson Mandela ‘We must face the matter squarely … We know that we have it in ourselves as Africans to change all this’. In my opinion, defining and acknowledging the problem is the most important step, but it is also just the first step in a long journey to improving hypertension prevention and control. That the solution to hypertension in sub-Saharan Africa is within sub-Saharan Africa is another critical observation to start that journey. What are the potential next steps?

Leadership Without strong sub-Saharan African champions who will lead and provide direction, little will change. At a recent Pan-African Departments of Medicine, Physiology and Pharmacology, and Community Health Sciences, O’Brien Institute for Public Health, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada

hypertension meeting in Douala, there were several strong hypertension champions with knowledge, vision and skill. Many other strong champions, such as Dr Seedat, reside throughout Africa. These leaders need to work together on the following actions.

Partnership There are several important and engaged organisations related to hypertension in sub-Saharan Africa [e.g. International Forum for Hypertension Control and Prevention in Africa, African Heart Network (AHN), Pan-African Society of Hypertension, World Hypertension League African regional office and Pan-Africa Society of Cardiology (PASCAR)]. Much broader partnerships are needed. There is an urgent need to partner with governments and the World Health Organisation (WHO), who have the ability to change policies for prevention and control. The recent worldleading and strong policy to regulate a reduction in salt additives to food in South Africa is a prime example.6,7 Forming partnerships with primary care, with other non-communicable disease (NCD) groups (e.g. diabetes), and with infectious disease groups and programmes will allow a sharing of limited resources and approaches to people at health risk and this is likely to be more efficient and cost effective. The WHO PENs programme provides a template that could assist in the integration of hypertension control with NCD control.8 Civil society organisations are better placed to advocate for societal changes to address fundamental issues such as poverty, corruption and other major social issues that Dr Seedat outlined. Civil society organisations will also have a strong interest in access to medications and basic health needs. Public health and epidemiological organisations are critical to assisting in advocating for improved public health policies that might prevent hypertension. Hypertension leaders need to develop the partnerships required to drive the necessary changes Dr Seedat outlined.

Norm RC Campbell, MD, ncampbel@ucalgary.ca

Strategic planning

Douala School of Medicine and Pharmaceutical Sciences, University of Douala, Cameroon, and Erasme Hospital, Free Brussels University, Belgium President of the International Forum for Hypertension Control and Prevention in Africa (IFHA), President of the Cameroon Heart Foundation, and Director of the Cameroon Heart Institute

A coalition of partner organisations needs to develop and agree to a strategic plan for hypertension prevention and control that is either independent or integrated with NCD prevention and control.9 There are several models for hypertension strategies that could be used as examples, and the Expanded Chronic Disease model can be used as a template.10-14 Recently, many African health organisations supported a fact sheet and call to action on hypertension that could form the basis

Daniel Lemogoum, MD, MPH, PhD, FESC

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 4, July/August 2015

of the start of a hypertension strategy.2 An African hypertension strategy needs broad input and support, as well as prioritisation of actions, based on the importance, feasibility and opportunities for implementing the actions in sub-Saharan Africa.

Learning from and sharing best practices and experiences Sub-Saharan Africa is a unique region therefore a sharing of resources, challenges and learnings between countries within the region may be particularly important. External experiences and practices need to be cautiously examined and applied. As Dr Seedat indicated, expensive technologies and treatment may aggravate problems by using valuable and limited resources that could be used to help many versus a few people. Nevertheless some global experiences, such as the use of task-sharing and treatment algorithms, provide a promise of enhanced outcomes at lower cost, and may be adaptable. Hypertension meetings need to be structured to share best regional experiences in prevention and control.

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to action, an infogram and a region-specific needs assessment. The International Society of Hypertension supported and co-sponsored many of these resources. The WHL is strongly encouraging national organisations to develop fact sheets and calls to action and has written a manuscript instructing how to do so.16 Furthermore, the WHL has developed a template for strategic planning.10 The WHL looks forward to working with regional sub-Saharan African organisations to prevent and control hypertension.

References 1.

Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2013; 380(9859): 2224–2260.

Campbell NR, Bovet P, Schutte AE, Lemogoum D, Nkwescheu AS. High blood pressure in sub-Saharan Africa: why prevention, detection, and control are urgent and important. J Clin Hypertens (Greenwich) 2015. 2015; DOI: 10.1111/jch.12599.

Advocacy Hypertension organisations in general are not in a position to make decisions that would influence hypertension prevention and control. Therefore advocacy plays a critical role. Usually advocacy is more effective aligned with partners who agree to common goals (e.g. the need for a reliable, affordable supply of medications). Advocacy needs to be a major part of the implementation of a hypertension strategy. The recent United Nations meeting where most countries signed on to improve control of hypertension by 25% by 2025, and to increase access to essential medication and technologies, represents an important advocacy opportunity.15

et al. National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5.4 million participants. Lancet 2011; 377(9765): 568–577. 4.

Khalsa TK, Campbell NR, Lackland DT, Lisheng L, Niebylski ML, Zhang XH. A needs assessment of national hypertension organizations for hypertension prevention and control programs. J Clin Hypertens (Greenwich) 2014; 16(12): 848–855.

Khalsa TK, Campbell NR, Redburn KA, Lemogoum D, Niebylski ML. A needs assessment of sub-Sahara African national hypertension organizations for hypertension prevention and control programs. J Clin Hypertens (Greenwich) 2015. DOI: 10.1111/jch.12632.

Sookram C, Munodawafa D, Phori PM, Varenne B, Alisalad A. WHO’s supported interventions on salt intake reduction in the sub-Saharan

Conclusion The increasing prevalence of hypertension and poor control rates in Africa represent a complex problem. A well-organised, strategic approach with a broad partnership is the best opportunity for improvement. As Dr Seedat indicates, complex societal issues and especially poverty and lack of resources make the task daunting, but emphasise the importance of partnerships, strategic approaches and advocacy. While the solution to hypertension prevention and control resides within Africa, global hypertension organisations stand supportive to provide what expertise and knowledge we have. The World Hypertension League (WHL), while resource poor, is very interested in working with sub-Saharan African health organisations. Dr Lemogoum, a board member of the WHL, has recently opened a regional office of the WHL in Cameroon. At the end of 2014, the WHL supported academic training sessions on blood pressure screening, strategic planning for reducing dietary salt, and strategic planning to control hypertension at the 7th African Scientific Meeting on Hypertension and Cardiovascular Protection, sponsored by the International Forum for Hypertension Control and Prevention in Africa in Douala, Cameroon. In 2015, with the assistance of African health organisations and experts, the WHL led the development of a fact sheet and call

Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan MJ,

Africa region. Cardiovasc Diagn Ther 2015; 5(3): 186–190. 7.

World Health Organization Regional Office for Africa. Intersectional case study: successful sodium regulation in South Africa. Report 2013: 1–12. Brazzaville, Republic of Congo, World Health Organization Regional Office for Africa.

World Health Organization. WHO package of essential noncommunicable (PEN) disease interventions for primary health care in low-resource settings. Report 2010: 1–65. 2010. Geneva, Switzerland, World Health Organization.

Campbell NR, Lackland DT, Lisheng L, Zhang XH, Nilsson PM, Redburn KA, et al. The World Hypertension League challenges hypertension and cardiovascular organizations to develop strategic plans for the prevention and control of hypertension. J Clin Hypertens (Greenwich) 2015; 17(5): 325–327.

10. Campbell NRC, Niebylski M. Prevention and control of hypertension: developing a global agenda. Curr Opin Cardiol 2014; 29(4): 324–330. 11. Committee on Public Health Priorities to Reduce and Control Hypertension in the U.S. Population, Institute of Medicine of the National Academies. A population-based policy and systems change approach to prevent and control hypertension. Report 2010: v–173. Washington, DC, USA: National Academies Press. 12. Go AS, Bauman MA, Coleman King SM, Fonarow GC, Lawrence W, Williams KA, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the

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American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension 2014; 63(4): 878–885. 13. Maryon-Davis A, Press V. Easing the pressure: tackling hypertension. A toolkit for developing a local strategy to tackle high blood pressure. Wordworks L, ed. Report 2005: 1–112. London, UK, Faculty of Public Health and the National Heart Forum.

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15. World Health Organization. Policy brief: strengthening efforts to improve access to and affordability of medicines and technologies in the prevention and control of noncommunicable diseases. Report 2014: 1–8. Geneva, Switzerland, World Health Organization. 16. Campbell NR, Lackland DT, Lisheng L, Niebylski ML, Nilsson PM, Zhang XH. Using the Global Burden of Disease Study to assist

14. Campbell N, Young ER, Drouin D, Legowski B, Adams MA, Farrell

development of nation-specific fact sheets to promote prevention and

J, et al. A framework for discussion on how to improve prevention,

control of hypertension and reduction in dietary salt: a resource from

management and control of hypertension in Canada. Can J Cardiol

the World Hypertension League. J Clin Hypertens (Greenwich) 2015;

2012; 28: 262–269.

17(3): 165–167.

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Cardiovascular Topics Analysis of clinical outcomes of intra-aortic balloon pump use during coronary artery bypass surgery Gunduz Yumun, Ufuk Aydin, Yusuf Ata, Faruk Toktaş, Arda Aybars Pala, Ahmet Fatih Ozyazicioglu, Tamer Turk, Senol Yavuz

Abstract Aim: The mortality rate of coronary artery bypass surgery increases with advanced patient age. This intra-aortic balloon pump (IABP) study was conducted to compare older patients (above 65 years of age) with younger patients (below 65 years of age) who had undergone coronary artery bypass surgery and had had an IABP inserted, with regard to hospital stay, clinical features, intensive care unit stay, postoperative complications, and mortality and morbidity rates. Methods: One hundred and ninety patients who had undergone coronary artery bypass surgery and had required IABP support were enrolled in this study. Patients younger than 65 years of age were considered younger, and the others were considered older. Ninety-two patients were in younger group and 98 patients were older group. The mortality rates, pre-operative clinical characteristics, postoperative complications, and duration of intensive care unit and hospital stay of the groups were compared. The risk factors for mortality and complications were analysed. Results: One hundred and thirty-eight of the patients were male, and the mean age was 62.7 ± 9.9 years. The mortality rate was higher in the older patient group than the younger group [34 (37.7%) and 23 (23.4 %), respectively (p = 0.043)]. The crossclamp time, mean ejection fraction, cardiopulmonary bypass time, and length of stay in the intensive care unit were similar between the two groups (p > 0.05). Cardiopulmonary bypass time was the unique independent risk factor for mortality in both groups. Conclusion: In this study, high mortality rates in the postoperative period were similar to those in prior studies regarding IABP support. The complication rates were higher in the older patient group. Prolonged cardiopulmonary bypass time and advanced age were determined to be significant risk factors for mortality.

Department of Cardiovascular Surgery, Namik Kemal University, Tekirdag, Turkey Gunduz Yumun, MD, gunduzyumun@gmail.com

Department of Cardiovascular Surgery, Bursa Yuksek Ihtisas Education and Research Hospital, Bursa, Turkey Ufuk Aydin, MD Yusuf Ata, MD Faruk Toktaş, MD Arda Aybars Pala, MD Ahmet Fatih Ozyazicioglu, MD Tamer Turk, MD Senol Yavuz, MD

Keywords: intra-aortic balloon pump, coronary artery bypass, mortality Submitted 22/11/14, accepted 22/1/15 Cardiovasc J Afr 2015; 26: 155–158

www.cvja.co.za

DOI: 10.5830/CVJA-2015-010

An intra-aortic balloon pump (IABP) increases coronary blood flow and reduces left ventricular afterload.1-3 It helps to increase the required amount of time for the heart to recover in low-cardiac output syndrome following a cardiopulmonary bypass (CPB) or ischaemic events. In earlier reports, researchers had suggested that postoperative heart failure was the single indication for IABP support.1,2 However, these indications have widened, and the use of IABP support has recently become more common. Frequently reported complications of IABP include bleeding, aorto-iliac injury and thrombocytopaenia.4,5 In-hospital mortality and the early mortality of patients requiring IABP support is high, ranging from 26 to 50%, due to the cardiac problems that initially led to the need for this support.6,7 The size of elderly population has been continuously increasing across the globe. Parallel with this increase, the number of older patients being referred for coronary artery bypass grafting (CABG) has also increased.8 Although several studies have shown a significant increase in surgical mortality rates of elderly patients,9 there have been no studies regarding clinical outcomes of IABP use in elderly patients. In this study, we aimed to compare older patients with younger patients regarding clinical features, postoperative complications, intensive care unit and hospital stays, and morbidity and mortality rates in patients who had undergone coronary artery bypass surgery and required IABP support.

Methods Patients who had undergone CABG in our clinic between 2008 and 2013 were retrospectively evaluated. Patients who had undergone combined CABG and heart valve surgery were excluded. This study was granted the full approval of the institutional Review Board. Three hundred and eighty-eight (7.4%) of 4 940 consecutive patients had required IABP support following CABG. Among these patients, IABP was used intra-operatively for 190 patients.

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One hundred and thirty-eight of the patients were male, and the mean age was 62.7 ± 9.9 years. The demographic characteristics of the patients are summarised in Table 1. All of the patients were operated on with standard cardiopulmonary bypass under general anaesthesia. Antegrade cardioplegia was used for cardiac protection. In all cases, an IABP catheter was inserted through the common femoral artery. In this study, IABP was used intra-operatively when weaning from cardiopulmonary bypass had failed. Pre-operative IABP was used in cases of low cardiac output, unstable refractory angina, or persistent arrhythmia due to myocardial ischaemia.5,10 The patients were classified according to age; whether they were younger than 65 years or older. The mortality rate, complications of IABP, intra-operative properties, pre-operative clinical characteristics of patients, and length of stay in the intensive care unit were recorded. The pre-operative parameters of the patients were age, gender, re-operation, hypertension, body mass index, diabetes mellitus, chronic renal failure, EuroSCORE value, previous cerebrovascular accident, left ventricular ejection fraction, left main coronary artery disease, chronic obstructive pulmonary disease (COPD), and the presence of a myocardial infarction more recent than one week earlier. The pre-operative clinical characteristics, postoperative complications, duration of ICU and hospital stays, and mortality rates of the groups were compared.

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Table 2. Mortality rates and clinical outcomes of the patients Younger group Older group (n = 98) (n = 92) p-value Mortality 23 (23.4) 34 (36.9) 0.043 Mortality* 8 (44.4) 7 (41.1 %) 0.964 Mortality** 15 (18.7) 27 (36%) 0.018 CPB time (min) 0.786 143 ± 59 140 ± 58 Graft number 3.1 (2–5) 3.2 (2–5) 0.789 Cross clamp time (min) 0.604 90 ± 34 88 ± 38 ICU time (days) 0.284 5.9 ± 4 6.6 ± 5 ICU: intensive care unit, CPB time: cardiopulmonary bypass time, *patients undergoing emergency operations, **patients undergoing elective operations.

p < 0.05 was considered significant. SPSS 18 was used for the statistical analysis.

Results

Demographic characteristics were compared with mean and median values. Parametric results were evaluated using a Student’s t-test and Tukey test. A chi-square method, Pearson’s test, and Fisher’s test were used to analyse the categorical parameters. Risk factors for mortality were assessed using a binary logistic regression analysis. The standard deviation value

In this study, 138 of the 190 patients were male. The mean patient age was 62.7 ± 9.9 years. Ninety-eight patients were younger than 65 years of age, and 90 patients were 65 years of age or older. The number of patients with chronic obstructive pulmonary disease and the mean EuroSCORE value of the patients were higher in the older group. By contrast, the number of patients with diabetes mellitus was higher in the younger group. In terms of other demographic characteristics, there were no statistically significant differences between the groups (Table 1). The mean cardiopulmonary bypass times, mean cross-clamp times, and number of grafts used were similar between the two groups (Table 2). Fifty-seven (30.1%) patients died in the first 30 days following the operation. Twenty-three of these patients were in the younger group. The mortality rate of the younger group was significantly

Table 1. Demographic characteristics of the patients

Table 3. Risk factors in patients who survived or died

Younger Older group group (n = 98) (n = 92) Total p-value Male/female 74/24 64/28 138/52 0.358 Mean age 54.7 ± 6.1 71.4 ± 4.5 62.7 ± 9.9 < 0.001 Mean EF 0.121 37.1 ± 8.3 39.2 ± 9.5 38.1 ± 8.9 MI, n (%) 31 (31.9) 24 (26) 55 (27.7) 0.400 COPD, n (%) 5 (5.1) 13 (14.1) 18 (9) 0.034 CRF, n (%) 3 (3) 5 (5.4) 8 (4.2) 0.487 Redo, n (%) 3 (3) 0 3 (1.5) 0.297 HT, n (%) 47 (48) 56 (60) 103 (54) 0.074 DM, n (%) 48 (49) 23 (25) 71 (37.3) 0.001 CVA, n (%) 4 (4.1) 5 (5.4) 9 (4.7) 0.745 Recent MI, n (%) 18 (18.3) 16 (17.4) 34 (17.9) 0.861 EuroSCORE 4 (0–10) 5 (2–10) 4 (0–10) < 0.001 BMI 0.112 27.2 ± 4 26.7 ± 4.4 27.2 ± 4.1 LMCA 8 (8.1) 5 (5.4) 13 (6.8) 0.457 Prophylactic levosimendan 18 (18.3) 12 (13) 30 (15.8) 0.315 Emergency 18 (18.3) 16 (17.4) 34 (17.8) 0.861 Pre-operative IABP 8 (8.1) 9 (9.7) 17 0.405 COPD: chronic obstructive pulmonary disease, CRF: chronic renal failure, HT: hypertension, DM: diabetes mellitus, CVA: cerebrovascular accident, MI: myocardial infarction, BMI: body mass index, LMCA: left main coronary artery disease, EF: ejection fraction.

Patients survived Patients died (n = 133) (n = 57) p-value Pre-operative MI, n (%) 40 (30) 15 (26.3) 0.601 BMI 0.507 27.5 ± 4.2 26.9 ± 4 EuroSCORE 4.2 (0-10) 5.1 (0-10) 0.030 DM, n (%) 47 (35.3) 24 (42.1) 0.377 CRF, n (%) 3 (2.2) 5 (8.7) 0.040 Mean EF % 0.562 38.4 ± 8 37.5 ± 9 Mean age (year) 0.051 61.8 ± 9.8 64.9 ± 10 Older patients, n (%) 58 (43.6) 34 (59.6) 0.043 Gender (female/male) 33/101 20/37 0.118 COPD, n (%) 12 (9) 6 (10.5) 0.746 Emergency operation, n (%) 19 (14.2) 15 (26.3) 0.047 LMCA, n (%) 8 (6) 5 (8.7) 0.490 CVA, n (%) 5 (3.7) 4 (7) 0.333 HT, n (%) 69 (51.8) 34 (59.6) 0.328 Re-operation, n (%) 3 (2.2) 0 0.555 Pre-operative IABP, n (%) 14 (10.5) 3 (2.2) 0.405 CPB time (min) 130 ± 48 167 ± 72 < 0.001 Cross-clamp time (min) 0.180 87 ± 35 94 ± 36 CPB time: cardiopulmonary bypass time. COPD: chronic obstructive pulmonary disease. CRF: chronic renal failure. HT: hypertension. DM: diabetes mellitus. CVA: previous cerebrovascular accident. BMI: body mass index. LMCA: left main coronary artery disease.

Statistical analysis

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Table 4. Risk factors for mortality in subgroup analysis Younger group Older group OR p-value OR p-value COPD 0.035 0.851 0.015 0.903 CRF 0.168 0.682 4.205 0.040 Re-operation 0.949 0.330 – – EF (%) 0.865 0.352 0.110 0.759 Age (year) 0.122 0.727 1.034 0.741 EuroSCORE 14.555 0.000 8.418 0.309 CPB time (min) 7.698 0.006 0.471 0.004 Cross-clamp time (min) 2.048 0.152 1.542 0.493 BMI 0.703 0.402 0.384 0.214 Emergency operation 5.401 0.020 0.400 0.536 Female gender 8.850 0.003 1.725 0.527 HT 2.007 0.157 0.095 0.189 MI 0.427 0.513 0.004 0.758 DM 7.477 0.006 0.560 0.949 ICU time 4.947 0.026 0.038 0.454 Levosimendan 0.228 0.633 0.131 0.845 CVA 1.634 0.201 0.021 0.717 LMCA 0.955 0.329 0.021 0.885 CPB time: cardiopulmonary bypass time. COPD: chronic obstructive pulmonary disease. CRF: chronic renal failure. HT: hypertension. DM: diabetes mellitus. ICU: intensive care unit. CVA: previous cerebrovascular accident. BMI: body mass index. LMCA: left main coronary artery disease.

lower compared with the older patients (p = 0.043). In the subgroup analysis, the mortality rate of emergent operations was similar in the younger and older groups (p = 0.964). However, the mortality rate was higher in the older group for elective operations (p = 0.018). Among the surviving patients, the number of older patients, rate of emergency operations, mean EuroSCORE values, and number of patients with chronic renal failure were lower than in the group of patients who died (Table 3). Binary logistic regression analysis showed that the only factor affecting mortality was prolonged cardiopulmonary bypass time. However, in the subgroup analysis of patients without emergency conditions, age was the second determinant of mortality (p = 0.018, OR = 5.5). In the subgroup analysis, cardiopulmonary bypass time and pre-operative chronic renal failure were independent risk factors for mortality in the older group. In the younger group, female gender, diabetes mellitus, high EuroSCORE, emergency operation, prolonged cardiopulmonary bypass time (p = 0.001, OR = 7.6), and prolonged stay in the intensive care unit were independent risk factors for mortality (Table 4). In our study, a few serious complications were observed due to IABP support. Iliac artery injury occurred in two patients and peripheral ischaemia was observed in three patients. The other

Table 5. IABP complications according to patient groups

Bleeding, n (%) Arterial injury, n (%) Mild thrombocytopaenia, n (%) Extremity ischaemia, n (%) Total, n (%)

Younger group 1 (1) 0 10 (10.2) 1 (1) 12 (12.2)

Older group 4 (4.3) 2 (2.1) 15 (16.3) 2 (2.1) 23 (25)

p-value 0.200 0.233 0.309 0.611 0.023

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complications were thrombocytopaenia and minor bleeding at the catheter site (Table 5). The rate of complications was similar between the groups.

Discussion Postoperative recovery in elderly patients takes a longer time than in younger patients. Postoperative atrial fibrillation requiring medical treatment, and other complications occur more frequently in the elderly; the total intubation time is also longer for this group. Therefore, delayed recovery in the elderly may simply be due to the aging process affecting all organs.9 For this reason, elderly patients may need more mechanical support in cases of low cardiac output following cardiopulmonary bypass. In the present study, while the number of COPD patients was higher in the older group, the number of diabetes mellitus patients was lower in the older group. In addition, EuroSCORE values were higher in the elderly patients. The mortality rate was higher in elderly patients; however, there were no statistically significant differences between the patients who had emergency surgery in both groups. It has been reported that IABP decreases the mortality rates of low-cardiac output and severe myocardial ischaemia patients in the pre-operative period, provides support for patients who failed to wean from cardiopulmonary bypass during the intra-operative period, and prevents low cardiac output and medically refractory arrhythmias in intensive care units in the postoperative period.11,12 In this study, IABP was used in cases of low cardiac output, persistent angina pectoris, or arrhythmia due to myocardial ischaemia in the pre-operative period. In previous studies, the use of pre-operative IABP in high-risk patients was reportedly more advantageous than peri-operative IABP support. Böning et al. compared the use of pre-operative and peri-operative IABP in high-risk patients in their study. Their results indicate that the pre-operative use of IABP was advantageous for early and long-term mortality.13 Dyub et al. showed that in a meta-analysis involving 1 034 patients, the use of pre-operative IABP in high-risk patients reduced mortality rates.14 Holman et al. reported that when shock, urgent surgery, haemodynamic instability, and MI in the last three days were excluded, the use of pre-operative IABP did not have a positive effect on morbidity and mortality rates; however, the length of the hospital stay was shorter in these patients.15 Miceli et al. proposed a scoring system that predicts the need for IABP support in high-risk coronary artery bypass patients.16 According to this study, heart failure, re-operation, emergency operation, left main coronary artery disease, patients over the age of 70 years, moderate and poor left ventricular function, and recent myocardial infarctions are independent risk factors for the need for IABP support. As a result of the study, the benefits of IABP support in patients with high-risk scores were emphasised. In our clinical practice, we did not use a risk-scoring system for prophylactic IABP support. In this study, we aimed to determine the pre-operative risk factors for mortality and other clinical outcomes. In previous studies, emergency surgery, a history of myocardial infarction, prolonged cardiopulmonary bypass, and concomitant peripheral artery occlusive disease were all found to be significant determinants of mortality in primary isolated CABG patients.17 Furthermore, risk-scoring systems were generated. We showed

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that the mortality rate of the older patient group was higher than that in the younger group. However, the logistic regression analysis indicated that the only independent risk factor for mortality was a prolonged cardiopulmonary bypass time. In addition, subgroup analysis revealed different results. For example, in the older patient group, chronic renal failure and prolonged cardiopulmonary bypass were identified as factors that affected mortality rate. In younger patients, female gender, diabetes mellitus, emergency operations, higher EuroSCORE values, prolonged cardiopulmonary bypass time, and prolonged stay in the ICU were independent risk factors for mortality. In elective operations, advanced patient age and prolonged cardiopulmonary bypass time were identified as factors that affected mortality rates. Complications with the intra-aortic balloon pump were described in previous studies: limb ischaemia, thrombocytopaenia, arterial rupture or dissection, and sepsis and local infections.4-6,10,18 Complication rates have been reported from 26 to 50% in different studies. The risk factors for IABP complications were stated as increased age, female gender, duration of IABP treatment, presence of diabetes mellitus, and having several risk factors (e.g. obesity, smoking, hypertension, cardiogenic shock, inotropic support, low cardiac output, increased systemic vascular resistance, and ankle–brachial pressure index < 0.8). In our study, the IABP complication rate was higher in older patients compared to younger patients (25 vs 12.2%). Mild thrombocytopaenia was the most frequently detected complication. When thrombocytopaenia is detected, IABP therapy is terminated immediately so that fewer bleeding complications occur.

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1971; 43–44(Suppl. I): I–77. 2.

Swank M, Singh HM, Flemma RJ, et al. Effect of intra-aortic balloon pumping on nutrient coronary flow in normal and ischemic myocardium. J Thorac Cardiovasc Surg 1978; 76: 538.

Berne RM, Levy MN. Cardiovascular Physiology, edn 6. St Louis: Mosby Year Book, ch 8, 1992.

Harvey JC, Goldstein JT, McCabe, et al. Complications of percutaneous intraaortic balloon pumping. Circulation 1981; 64(Suppl II): II–114.

Cristenson JT, Cohen M, Ferguson JJ 3rd, Freedman RJ, Miller MF, Ohman EM, et al. Trends in intraaortic balloon counterpulsation complications and outcomes in cardiac surgery. Ann Thorac Surg 2002; 74(4): 1086–1090.

MacGee E, MacCarthy P, Moazami N. Temporary mechanical circulatory support. Cardiac Surgery in the Adult. New York: MacGraw Hill, 2008: 507–533.

Pi K, Block P, Warner M, et al. Major determinants of survival and nonsurvival of intraaortic balloon pump. Am Heart J 1995; 130: 849–853.

Dalrymple-Hay MJ, Alzetani A, Aboel-Nazar S, et al. Cardiac surgery in the elderly. Eur J Cardiothorac Surg 1999; 15: 61–66.

Hirose H, Amano A, Yoshida S, Takahashi A, Nagano N, Kohmoto T. Coronary artery bypass grafting in the elderly. Chest 2000; 117(5): 1220–1221.

10. Parissis H, Soo A, Al-Alao B. Intra-aortic balloon pump (ΙΑΒΡ): from the old trends and studies to the current “extended” indications of its use. J Cardiothorac Surg 2012; 11(7): 128. 11. Ferguson JJ, Cohen M, Freedman RJ, Stone GW, Miller MF, Joseph DL, Ohman EM. The current practice of intra-aortic balloon counterpulsation: results from the Benchmark Registry. Am Coll Cardiol 2001; 38(5): 1456–1462. 12. Theologou T, Bashir M, Rengarajan A, Khan O, Spyt T, Richens D,

Limitations Our study was a single-institution, retrospective study, which had a relatively small sample size. This subject may require further multicentre, randomised trials. Unaccounted for confounders may have been inherent in such a retrospective analysis.

et al. Preoperative intra aortic balloon pumps in patients undergoing coronary arteryn bypass grafting. Cochrane Database Syst Rev 2011; 19(1): 4472. 13. Böning A, Buschbeck S, Roth P, Scheibelhut C, Bödeker R, Brück M, et al. IABP before cardiac surgery: clinical benefit compared to intraoperative implantation. Perfusion 2013; 28(2): 103–108. 14. Dyub AM, Whitlock RP, Abouzahr LL, Cinà CS. Preoperative intra-

Conclusion Intra-aortic balloon pumps are important cardiac support instruments that are easily implemented and have beneficial effects for resolving transient ischaemic situations. Whether young or old, patients who require IABP support have a high risk of mortality. Moreover, the association of elderly patients with increased incidences of co-morbid disease makes them even more susceptible to mortality. We question whether IABP may rather be used in the intra-operative period as a prophylactic device in elderly patients with multiple risk factors.

aortic balloon pump in patients undergoing coronary bypass surgery: a systematic review and meta-analysis. J Card Surg 2008; 23(1): 79–86. 15. Holman WL, Li Q, Kiefe CI, McGiffin DC, Peterson ED, Allman RM, et al. Prophylactic value of preincision intra-aortic balloon pump: analysis of a statewide experience. J Thorac Cardiovasc Surg 2000; 120(6): 1112–1119. 16. Miceli A, Duggan SM, Capoun R, Romeo F, Caputo M, Angelini GD. A clinical score to predict the need for intraaortic balloon pump in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 2010; 90(2): 522–526. 17. Huang CH, Lai ST, Weng ZC. Risk factors for mortality in primary isolated coronary artery bypass grafting surgery. J Formos Med Assoc

References 1.

2000; 100(5): 299–303. 18. Chertow GM, Lazarus JM, Christiansen CL, Cook EF, Hammermeister

Leinbach RC, Buckley MJ, Austen WG, et al. Effects of intra-aortic

KE, Grover F, et al. Preoperative renal risk stratification. Circulation

balloon pumping on coronary flow and metabolism in man. Circulation

1997; 95: 878–884.

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Comparison of neutrophil:lymphocyte ratios following coronary artery bypass surgery with or without cardiopulmonary bypass Mustafa Aldemir, Elif Doğan Bakı, Fahri Adalı, Görkem Çarşanba, Evren Tecer, Hanife Uzel Taş

Abstract Objective: Coronary artery bypass graft (CABG) surgery may induce postoperative systemic changes in leukocyte counts, including leukocytosis, neutrophilia or lymphopenia. This retrospective clinical study investigated whether offpump coronary artery bypass (OPCAB) surgery working on the beating heart without extracorporeal circulation could favourably affect leukocyte counts, including neutrophil-tolymphocyte (N:L) ratio, after CABG. Methods: In this study, 30 patients who underwent isolated CABG with cardiopulmonary bypass (CPB), and another 30 patients who underwent the same operation without CPB between May 2010 and May 2013, were screened from the computerised database of our hospital. Pre-operative, and first and fifth postoperative day differential counts of leukocytes with the N:L ratio of peripheral blood were obtained. Results: A significant increase in total leukocyte and neutrophil counts and N:L ratio, and a decrease in lymphocyte counts were observed at all time points after surgery in both groups. N:L ratio was significantly higher in the CPB group compared with the OPCAB group on the first postoperative day (20.73 ± 13.85 vs 10.19 ± 4.55, p < 0.001), but this difference disappeared on the fifth postoperative day. Conclusion: CPB results in transient but significant changes in leukocyte counts in the peripheral blood stream in terms of N:L ratio compared with the off-pump technique of CABG. Keywords: myocardial revascularisation, cardiopulmonary bypass, off-pump technique, neutrophil:lymphocyte ratio Submitted 24/3/14, accepted 27/1/15 Previously published online 23/4/15 Cardiovasc J Afr 2015; 26: 159–164

www.cvja.co.za

DOI: 10.5830/CVJA-2015-015

Department of Cardiovascular Surgery, Faculty of Medicine, Afyon Kocatepe University, Turkey Mustafa Aldemir, MD, draldemir@yahoo.com Fahri Adalı, MD Görkem Çarşanba, MD Evren Tecer, MD

Department of Anaesthesiology, Faculty of Medicine, Afyon Kocatepe University, Turkey Elif Doğan Bakı, MD

Department of Public Health, Faculty of Medicine, Afyon Kocatepe University, Turkey Hanife Uzel Taş, MD

Coronary artery bypass grafting (CABG) is the most common procedure in cardiovascular surgery. However the procedure itself is associated with significant morbidity and mortality rates. It is well known that large changes in immune reactivity occur during or after cardiac surgical operations.1 Surgical trauma has a well-known effect on increased immune mediator levels.2 Production of reactive oxygen species, decreased barrier function, induction of hypoperfusion, and tissue destruction are examples of adverse outcomes resulting from severe activation of the native immunity.3 Cardiopulmonary bypass circuit devices play a key role at that point, with contact activation of both cellular and humoral components of the blood accepted as major liability issues. T and B cells of the adaptive immune system are affected mostly in the early postoperative period with some delay in the course of surgery.4 In open-heart surgery, risk stratification has mostly been done using the European System for Cardiac Operative Risk Evaluation (EuroSCORE).5 However there are some concerns about overestimation/underestimation with the EuroSCORE, which is why more reliable predictors are needed. There are many studies in the literature about the relationship between inflammation and adverse cardiovascular outcomes.6 In this era, some biomarkers of inflammation have been investigated, such as total white blood cell count (WCC), a predictor of mortality after coronary artery bypass grafting.7 However subtypes of WCC or ratios between them have been shown to be more valuable in the prediction of outcomes.8 One of these is the neutrophil:lymphocyte ratio, a potentially useful biopredictor of inflammation in cardiovascular disease.9 It is inexpensive, readily available and easily calculable. In screening the literature, there are some studies on its prognostic value after cardiac operations,10 but there are no published studies on the relationship between cardiopulmonary bypass and the neutrophil:lymphocyte (N:L) ratio. Therefore, the current study was conducted to investigate the N:L ratio as a measure of systemic inflammation and its relationship, if any, with cardiopulmonary bypass.

Methods This retrospective clinical study was performed on 60 patients who underwent isolated CABG surgery at our institution, Department of Cardiovascular Surgery, Kocatepe University, Afyonkarahisar, Turkey, between May 2010 and May 2013. This clinical retrospective study was approved by the local ethics committee of the Faculty of Medicine, Afyon Kocatepe University. All patients had coronary artery disease with varying degrees of stenosis of the left anterior descending coronary artery. Patients with left main or left main equivalent coronary artery disease were also included in the study. The data of the 60 cases

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were collected retrospectively from a computerised clinical database. We selectively collected the data for 30 patients (group I, n = 30) who were operated on using the on-pump technique (with cardiopulmonary bypass) and another 30 patients (group II, n = 30) who were operated on using the off-pump technique (without cardiopulmonary bypass). Exclusion criteria of the study were as follows: CABG surgery associated with valvular replacement or any other procedure, circulatory support with intra-aortic balloon pump before surgery, pre-operative ejection fraction less than 30%, recent myocardial infarction (less than three months), emergency operation, re-operation, pre- or postoperative infection (obtained from progress notes in the patient files), immunological disease, tumour, acute or chronic renal failure [pre-operative renal insufficiency was defined as a serum creatinine level ≥ 1.5 mg/dl (132.6 μmol/l) prior to CABG], respiratory impairment, prior stroke, peripheral vascular disease and coagulopathy. Patients with postoperative pulmonary, infectious, neurological or gastrointestinal complications, re-exploration for bleeding, or cardiac tamponade were also excluded from the study. Relevant demographic and peri-operative clinical data were collected for the 60 patients using the above database, and findings in the two groups (on- and off-pump) were compared. The specific pre- and intra-operative data obtained for each case were patient age and gender, history of hypertension, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg, diabetes defined as fasting blood glucose levels > 140 mg/dl (7.77 mmol/l) and the use of oral anti-diabetic medication or insulin dependency, smoking, unstable angina pectoris, prior percutaneous transluminal coronary angioplasty, left ventricular ejection fraction, presence or absence of left main coronary artery disease, and number of grafts per operation. The postoperative data collected were mechanical ventilation time, need for inotropic or intra-aortic balloon pump support, peri-operative myocardial infarction (immediate postoperative period), dysrythmias, length of stay in the intensive care unit (ICU) and overall hospital stay. Pre-operative, and first and fifth postoperative day total leukocyte counts and differential counts (neutrophils and lymphocytes) were taken from patient files in our hospital archives. The calculation of N:L ratios was entrusted to one of our authors who was blinded to the neutrophil and lymphocyte samples from the two groups.

Surgical procedure All patients were given the same anaesthesia protocol. They were pre-medicated with midazolam (0.05 mg/kg IV). On the operating table, cannulae were inserted in a peripheral vein, the radial artery and the right jugular vein. Standard monitoring included pulse oximetry, leads II and V5 of the ECG for heart rate and automated ST-segment trend analysis, continuous measurements of arterial and central venous pressures, nasopharyngeal temperature, and end-tidal capnography. A balanced anaesthetic technique included fentanyl (bolus of 1–2 mg/kg followed by an intermittent bolus of 1–2 mg/ kg/h), etomidate (bolus of 0.2—0.3 mg/kg), esmeron (bolus of 1 mg/kg and an intermitant bolus of 0.3 mg/kg/h) and inhaled sevofluorane (2–3% in the pre-bypass period and 1–1.5% in the bypass period). Ventilation was modified in each patient

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to reach partial arterial oxygen pressure above 150 mmHg and partial arterial carbon dioxide pressure above 45 mmHg. A conventional median sternotomy was performed in all patients. In group I (on-pump), cardiopulmonary bypass (CPB) was established in a standardised manner with the use of a roller pump and non-pulsatile flow (2.4 l/m2/min). A heparinisation protocol of 300 U/kg was followed to maintain clotting time at longer than 400 s. Patients were cooled to 32°C when distal anastomosis was being performed, and were warmed to 36°C before weaning from CPB. After aortic cross-clamping, cold-blood cardioplegia was accomplished with anterograde delivery through the aortic root for initial diastolic arrest of the heart, and intermittently after each distal anastomosis. A final dose of ‘hot-shot’ cardioplegia was also administered antegradely just before the aorta was unclamped. Protamine was used to reverse the effects of heparinisation. In group II (off-pump), by adjusting the operating room temperature, hypothermia was avoided. Partial anticoagulation was accomplished with 1–2 mg/kg body weight of heparin until a target activated clotting time (ACT) of 250 s was achieved. Octopus 4 (Medtronic Inc, Minneapolis, MN, USA) was used as cardiac stabiliser. In order to obtain a bloodless anastomotic field after arteriotomy, we did the following: after opening the distal artery, intracoronary shunts (Clearview intracoronary shunt, Medtronic Inc, USA) were inserted into the coronary artery for each anastomosis, which were 1.5, 2.0 or 2.5 mm in size according to the coronary artery lumens, and shunts were removed after the last suture just before tying. Heparin was not neutralised by protamine sulfate at the end of the operation.

Statistical analysis The values obtained from the groups were compared to evaluate N:L ratios after coronary artery surgery with or without cardiopulmonary bypass. Statistical analysis was performed with SPSS version 15.0 (SPSS, Inc, Chicago, IL) software. Compliance of variables with a normal distribution was analysed with visual (histogram and probability plots) and analytical methods (the Kolmogorov–Smirnov test). Descriptive analyses were provided as mean and standard deviation. Relationships between cardiopulmonary bypass and N:L ratios and pre-, intra- and postoperative factors were analysed using different methods: the independent samples t-test for normally distributed continuous variables (expressed as mean ± SD), and chi-square and Fisher’s exact tests for categorical variables, as appropriate. The results were assessed within a 95% reliance and at a significance level of p < 0.05.

Results This study comprised 60 patients who underwent CABG surgery. Thirty of the patients were operated on with CPB (group I) and the other 30 without bypass (group II). The number of bypassed grafts were different between the two groups, being statistically higher in group I than in group II (3.20 ± 0.88 and 1.93 ± 0.78, respectively, p < 0.001). Hospital stay was longer in group I (8.97 ± 2.39 days) than in group II (5.90 ± 2.07 days), and this difference was also statistically significant (p < 0.001). Except

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for the difference in number of grafts and hospital stay, patient demographic and peri-operative characteristics were similar in the two groups (Table 1). For pre-operative values of the leukocyte screen, the two groups were similar in terms of leukocyte, neutrophil and lymphocyte counts and N:L ratios (Table 2). However, comparing systemic leukocyte counts affected by the surgical stress of CABG alone, with pre-operative values, a significant increase in counts of total leukocytes and neutrophils, and N:L ratio, and a decrease in lymphocyte counts was found on the first and fifth days after surgery, regardless of the technique used (with or without CPB) (Table 2). Regarding intergroup comparison of values, on the first post-operative day, there was a statistically significant difference between the two groups in terms of absolute lymphocyte counts (0.84 ± 0.92 in group I and 1.12 ± 0.73 in group II, p < 0.001). The N:L ratio was also significantly different between the two groups (20.73 ± 13.85 in group I and 10.19 ± 4.55 in group II, p < 0.001). On the fifth postoperative day, there were no statistically significant differences in absolute numbers of lymphocytes or N:L ratios between the two groups. There were however statistically significant differences between the two groups in terms of absolute numbers of total leukocytes (12.23 ± 4.75 in group I and 9.38 ± 2.23 in group II, p = 0.002) and neutrophils (9.27 ± 4.78 in group I and 5.97 ± 1.86 in group II, p < 0.001) (Table 2). Regarding the change in total leukocyte, neutrophil and lymphocyte counts, and N:L ratios on the first and fifth postoperative days, from baseline values before the operation, we observed significant intergroup differences on the first postoperative day only (Table 3). There was a significant decrease in lymphocyte counts in group I (52.70 ± 70.83) compared to group II (49.40 ±18.79) (p = 0.003), and a larger increase in N:L ratios in group I (1031.78 ± 950.53) compared to Table 1. Demographic and peri-operative clinical data of the patients

Males, n (%) Age (years) DM, n (%) Smoking, n (%) Hypertension, n (%) USAP, n (%) Previous PTCA, n (%) Pre-operative EF (%) LMCA disease, n (%) No of grafts

Group I (n = 30) 20 (66.7)

Group II (n = 30) 15 (50.0)

p-value 0.190 0.102 63.73 ± 10.49 68.10 ± 6.98 14 (46.7) 12 (40.0) 0.602 16 (53.3) 14 (46.7) 0.606 11 (36.7) 17 (56.7) 0.121 2 (6.7) 4 (13.3) 0.671 3 (10.0) 9 (30.0) 0.053 0.982 49.73 ± 10.45 49.63 ± 12.60 2 (6.7) 0 (0.0) 0.492 3.20 ± 0.88 12 (40.0) 6 (20.0) 2 (6.7) 8 (26.7)

1.93 ± 0.78 11 (36.7) 1 (3.3) 0 (0.0) 11 (36.7)

5.73 ± 2.70

5.30 ± 1.53

< 0.001 0.791 0.103 0.492 0.405 0.897

ICU stay (days)

1.87 ± 0.68

1.83 ± 1.20

0.256

Hospital stay (days)

8.97 ± 2.39

5.90 ± 2.07

< 0.001

Postoperative inotropic need, n (%) Postoperative IABCP need, n (%) Postoperative MI, n (%) Postoperative dysrhythmia, n (%) Mechanichal ventilation time (hrs)

Values are mean (± standard deviation) or median (range) as appropriate. Group I: group with cardiopumonary bypass, group II: group with offpump coronary artery bypass, DM: diabetes mellitus, USAP: unstable angina pectoris, IABCP: intra-aortic balloon counterpulsation, ICU: intensive care unit, PTCA: percutaneous transluminal coronary angioplasty, EF: ejection fraction, LMCA: left main coronary artery, MI: myocardial infarction.

Table 2. Comparison of values at all time points between the two groups

Pre-operative Total leucocytes (103/ml)

Group I (n = 30)

Group II (n = 30)

p-value

7.59 ± 1.78

7.07 ± 1.55

0.403

Neutrophils (103/ml)

4.19 ± 1.07

4.19 ± 0.97

0.604

Lymphocytes (103/ml)

2.18 ± 0.72

2.25 ± 0.95

0.609

N:L ratio

2.10 ± 0.70

2.07 ± 0.76

0.745

13.11 ± 3.94*

12.67 ± 4.60*

0.464

11.46 ± 3.54*

9.93 ± 4.14*

0.078

0.84 ± 0.92*

1.12 ± 0.73*

< 0.001**

20.73 ± 13.85*

10.19 ± 4.55*

< 0.001**

Postoperative 1st day Total leucocytes (103/ml) Neutrophils (103/ml) Lymphocytes (103/ml) N:L ratio Postoperative 5th day Total leucocytes (103/ml)

12.23 ± 4.75*

9.38 ± 2.23*

0.002**

Neutrophils (103/ml)

9.27 ± 4.78*

5.97 ± 1.86*

Lymphocytes (103/ml)

1.73 ± 0.64*

1.76 ± 0.71*

< 0.001** 0.959

N:L ratio

6.15 ± 3.86*

3.71 ± 1.31*

0.006

Values are mean (± standard deviation) or median (range) as appropriate. *p < 0.05 compared with pre-operative values within the groups. **p < 0.05 compared between groups. Group I: group with cardiopumonary bypass, Group II: group with offpump coronary artery bypass, N:L: neutrophil:lymphocyte ratio.

group II (472.15 ± 415.93) (p = 0.001). The change in other values (total leukocyte and neutrophil counts) were similar in the two groups on the first postoperative day. The change in all counts on the fifth postoperative day was not significantly different in the two groups (Table 3).

Discussion Surgical stress, regardless of the type of surgery, suppresses cellular immunity as a result of the host’s inflammatory responses. This suppression may be deleterious to the host’s defense mechanisms, along with overproduction of inflammatory mediators.11 Some morbidity parameters such as postoperative infection could be predicted from a significant increase in neutrophil and a decrease in lymphocyte counts.12 In many previous studies, morbidity and mortality of patients with cardiovascular disease have been demonstrated to be

Table 3. Change in values on the first and fifth postoperative days compared with pre-operative values in the two groups Postoperative 1st day Total leucocytes (103/ml) Neutrophils (103/ml) Lymphocytes (103/ml) N:L ratio Postoperative 5th day Total leucocytes (103/ml) Neutrophils (103/ml) Lymphocytes (103/ml) N:L ratio

Group I (n = 30)

Group II (n = 30)

p-value

(83.49 ± 74.82)↑

(77.70 ± 42.09)↑

0.802

(191.16 ± 123.34)↑ (142.43 ± 89.60)↑

0.133

(52.70 ± 70.83)↓

(49.40 ± 18.79)↓

0.003*

(1031.78 ± 950.53)↑ (472.15 ± 415.93)↑ 0.001* (70.86 ± 79.84)↑

(39.14 ± 45.56)↑

0.154

(138.00 ± 140.63)↑

(48,91 ± 55.02)↑

0.005*

(11.86 ± 46.51)↓

(10.63 ± 42.38)↓

0.442

(217.94 ± 207.83)↑ (102.74 ± 110.49)↑ 0.013*

Values are mean percent (± standard deviation) or median percent (range) as appropriate. *p < 0.05 compared between groups. Group I: group with cardiopumonary bypass, group II: group with off-pump coronary artery bypass, N:L: neutrophil:lymphocyte, ↑: increase, ↓: decrease from pre-operative values.

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associated with systemic changes in leukocyte subtypes, such as neutrophilia and lymphopaenia, and increased N:L ratios.13 In the postoperative period, increased N:L ratio not only assesses the immune condition of the patient but also provides valuable clues regarding morbidity and mortality. In addition, in clinical practice its measurement is inexpensive and simple.14 In our study patients, some morbidity markers such as postoperative inotropic need [12 (40.0%) vs 11 (36.7%) p = 0.791], postoperative IABCP need [6 (20.0%) vs 1 (3.3%) p = 0.103] and postoperative myocardial infarction (MI) [2 (6.7%) vs 0 (0.0%) p = 0.492] were found more widely in the CPB group than in the OPCAB group. This is compatable with the literature. Hospital stay was also significantly longer in the CPB group (8.97 ± 2.39 vs 5.90 ± 2.07 days, p < 0.001). Takahashi et al. demonstrated that lymphopenia represents an immunodepression status leading to the development of postoperative infection.12 It was suggested that lymphopenia may be caused by redistribution between peripheral blood and bone marrow pools in addition to tissue sequestration of activated lymphocyte subsets.15 In another study designed by Yamanaka et al., it was reported that the immune system may have been inhibited by neutrophils. Natural killer cells and lymphocytes may have been supressed, and T cells could have been activated by neutrophils in the co-culture of neutrophils and lymphocytes of normal healthy donors. The number of neutrophils added directly affected the degree of supression.13 Although conventional CABG surgery with the use of CPB is a safe and effective procedure, it is known to evoke many side effects. It is unique because synthetic non-endothelial surfaces, in which blood continuously recirculates, contribute to the inflammatory response through ‘contact activation’ of the immune system. Aortic cross-clamping causing ischaemia– reperfusion injury to vital organs such as the kidney, brain, myocardium and intestine plays a key role in the activation of a stress–response cascade.16 Multi-organ system dysfunction, such as respiratory failure, coagulopathy, renal insufficiency, neurocognitive defects and myocardial dysfunction, occur due to the hyperinflammatory cascades.17 Because of the cross relationship between multiorgan dysfunction and the hyperinflammatory state, in our study, patients with postoperative complications such as renal insufficiency, postoperative infection and respiratory problems were excluded from the study population. Aggregation of WBCs in the capillaries of the lung and degradation of complement proteins, resulting in an activated inflammatory process, cause severe pulmonary dysfunction.18 The hyperinflammatory state caused by CPB may play a key role in the genesis of catastrophic complications, leading to postperfusion syndrome, which involves decreased systemic vascular resistance, fever and accumulation of fluid in the interstitial space.19 In the literature, there are many studies related to attenuating negative outcomes of CPB by inhibiting the inflammatory response during coronary surgery. Leukocyte depletion,20 aprotinin, corticosteroids21 and heparin-coated circuits22 are noted as tools to attenuate the inflammatory reactions mediated by CPB. OPCAB techniques working on the beating heart without extracorporeal circulation may be a more radical and effective way of counteracting the effects of the inflammatory reaction

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and oxidative stress. Despite great excitement among some cardiac surgeons and patients, the real impact of OPCAB in attenuation of systemic inflammation is still uncertain.23 Many clinical comparative studies24 and meta-analyses25 have demonstrated shortened length of hospital stay, reduced neurological complications, and reduced hospital costs for patients operated on with OPCAB techniques compared to those undergoing conventional CABG with CPB.26 Decreased postoperative blood loss and need for transfusion, and shorter ventilatory support and intensive care unit time have also been reported with OPCAB operations.27 Our study had similar follow-up results, showing increased total leukocyte and neutrophil counts and N:L ratios, and decreased lymphocyte counts in both groups of patients, but this was more significant in the CPB group, indicating a more intense inflammatory reaction. In our study, hospital length of stay was longer in the CPB group than in the OPCAB group, which is compatible with the literature. The inflammatory response due to cardiac surgery is mainly related to the cellular immune system.28 During CPB, because of haemodilution, leukocyte counts decrease, but after surgery they increase dramatically.29 The contact and complement systems producing kallikrein and C5a strongly activate neutrophils during cardiopulmonary bypass.30 IL-6 and IL-8 mediating CPB may partially inhibit apoptosis of neutrophils, and thereby the period of neutrophil activity is prolonged.31 Suppression of cellular immunity by the lymphocytes and activation of the inflammatory response, characterised by neutrophilia, are substituted by the N:L ratio. The N:L ratio is increased when lymphopenia or neutrophilia develops. The favourable pattern of changes in systemic leukocyte counts could be defined as a lesser impairment of cellular immunity, determined by lymphocyte counts, and lesser activation of the inflammatory response, measured by neutrophil counts. A favourable pattern of changes in systemic leukocyte counts is indicated by a lesser value of the N:L ratio.11 CABG surgery without CPB has been presented as an alternative to minimise the deleterious effects of CPB. The superiority of OPCAB is mostly seen in the clinical era,32 but when discussing new techniques, it is also important to clarify the pathophysiology of the procedure. The risk of infection after cardiac surgery is increased with CPB because of neutrophil activation via the complement cascade,33 and also because of attenuation of lymphocyte activation.34 From the results of our study, we could conclude that a more favourable pattern of N:L ratio was ensured in the early stages of the postoperative period (on the first postoperative day of our study) but later (on the fifth postoperative day), the advantage of the OPCAB technique disappeared, determined by the difference between N:L ratios of the two groups. From the results of our study, we could infer that the change in N:L ratios on the first postoperative day, compared with pre-operative values, was more dependent on lymphocyte count changes, being more remarkable in the CPB group. On the fifth postoperative day, the change in all values were similar in both groups, compared with pre-operative values. Although OPCAB has been widely used, no studies have been performed focusing on its effect on the N:L ratio in comparison with CPB. In our study, the groups were similar in terms of pre-operative total leukocyte, neutrophil and lymphocyte

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counts, and N:L ratios. When compared with pre-operative values, the results indicated that CPB caused significantly decreased lymphocyte counts and increased N:L ratios on the first postoperative day. On the other hand, on the fifth postoperative day, total leukocyte and neutrophil counts were significantly increased in the CPB group. From these results, the influence of CPB versus OPCAB on changes in leukocyte counts after surgery was shown to be more prominent in the early stages after surgery. In the CPB group, the increase in N:L ratio was more pronounced than that in the OPCAB group only on the first day after surgery. Although we showed that pre-operative values were significantly different from those measured on the first day after surgery, the effect was transient. However, as the magnitude of the response of peripheral leukocytes has been suggested to be related to cardiac surgery, it could be postulated that this transient effect may be greater when the patient undergoes CABG with CPB. A limitation of this study was that C-reactive protein tests, being an indicator of inflammation, were not done.

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coronary artery bypass graft surgery. Turkish J Thorac Cardiovasc Surg 2013: 588–593 11. Kim WH, Jin HS, Ko JS, et al. The effect of anesthetic techniques on neutrophil-to-lymphocyte ratio after laparoscopy-assisted vaginal hysterectomy. Acta Anaesthesiol Taiwan 2011; 49: 83–87. 12. Takahashi J, Shono Y, Hirabayashi H, et al. Usefulness of white blood cell differential for early diagnosis of surgical wound infection following spinal instrumentation surgery. Spine 2006; 31: 1020–1025. 13. Yamanaka T, Matsumoto S, Teramukai S, et al. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology 2007; 73: 215–220. 14. Neal CP, Mann CD, Sutton CD, et al. Evaluation of the prognostic value of systemic inflammation and socioeconomic deprivation in patients with resectable colorectal liver metastases. Eur J Cancer 2009; 45: 56–64. 15. Kuneš P, Krejsek J. CD4 lymphopenia and postoperative immunosuppression in cardiac surgery. Cas Lek Ces 2000; 139: 361–368. 16. Baki ED, Aldemir M, Kokulu S, et al. Comparison of the effects of desflurane and propofol anesthesia on the inflammatory response and s100β protein during coronary artery bypass grafting. Inflammation

Conclusion Our data showed that OPCAB compared with CPB could favourably modify leukocyte count changes, including N:L ratio in the peripheral blood stream during the postoperative period of CABG surgery.

2013; 36: 1327–1333. 17. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003; 75: 715–720. 18. Norton JA, Bollingen RR, Lowry SF, et al. Basic Science and Clinical Evidence. Berlin: Springer Verlag 2000; 1335–1338. 19. Olthof CG, Jansen PG, de Vries JP, et al. Interstitial fluid volume during cardiac surgery measured by means of a non-invasive conductivity tech-

The authors are grateful for the cooperation of people who collected and managed the database of our institution.

nique. Acta Anaesthesiol Scand 1995; 39: 508–512. 20. Gu YJ, de Vries AJ, Boonstra PW, et al. Leukocyte depletion results in improved lung function and reduced inflammatory response after

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JankovicováK, KudlováMT, KoláckováM, et al. The effect of cardiac

Markewitz A, Lante W, Franke A, et al. Alterations of cell-mediated immunity following cardiac operations: clinical implications and open questions. Shock 2000; 16: 10–15. Siregar S, Groenwold RH, de Heer F, Bots ML, van der Graaf Y, van Herwerden LA. Performance of the original EuroSCORE. Eur J

2007; 22: 445–455. 24. Straka Z, Widimsky P, Jirasek K, et al. Off-pump versus on-pump coronary surgery: Final results from a prospective randomized study PRAGUE-4. Ann Thorac Surg 2004; 77: 789–793. 25. Wijeysundera DN, Beattie WS, Djaiani G, et al. Off-pump coronary artery surgery for reducing mortality and morbidity: Meta-analysis of randomized and observational studies. J Am Coll Cardiol 2005; 46: 872–882.

practice: A statement for healthcare professionals from the Centers for

26. Al-Ruzzeh S, Ambler G, Asimakopoulos G, et al. United Kingdom

Disease Control and Prevention and the American Heart Association.

Multi-Center Comparative Analysis of Early Clinical Outcome.

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Off-pump coronary artery bypass (OPCAB) surgery reduces riskstrati-

Bagger JP, Zindrou D, Taylor KM. Leukocyte count: a risk factor for Horne BD, Anderson JL, John JM, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005; 45: 1638–1643.

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coronary artery bypass graft mortality. Am J Med 2003; 115: 660–663. 8.

pulmonary bypass. Ann Thorac Surg 1997; 63: 105–111. 23. Raja SG, Berg GA. Impact of off-pump coronary artery bypass surgery

Cardiothorac Surg 2012; 41: 746–754. tion and cardiovascular disease: application to clinical and public health

Surg 1998; 66: 747–753. 22. Moen O, Hogasen K, Fosse E, et al. Attenuation of changes in leukocyte

(Hradec Kralove) 2008; 51: 25–29.

poreal circulation: Trial of four antiinflammatory strategies. Ann Thorac

Helmy SA, Wahby MA, El-Nawaway M. The effect of anaesthesia and

surgery on peripheral blood lymphocyte populations. Acta Medica 4.

cardiac surgery. J Thorac Cardiovasc Surg 1996; 112: 494–500. 21. Gott JP, Cooper WA, Schmidt FE Jr, et al. Modifying risk for extracor-

Gibson PH, Croal BL, Cuthbertson BH, et al. Preoperative neutrophillymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J 2007; 154: 995–1002.

10. Unal EU, Durukan AB, Özen A,Kubat E, Kocabeyoğlu SS, Yurdakök O, et al. Neutrophil/lymphocyte ratio as a mortality predictor following

fied morbidity and mortality: A United Kingdom multi-center comparative analysis of early clinical outcome. Circulation 2003; 108(Suppl 1): II1–8. 27. Bucerius J, Gummert JF, Walther T, et al. Predictors of prolonged ICU stay after on-pump versus off-pump coronary artery bypass grafting. Intensive Care Med 2004; 30: 88–95. 28. Laffey JG, Boylan JF, Cheng DC The systemic inflammatory response to cardiac surgery: Implications for the anesthesiologist. Anesthesiology 2002; 97: 215–252. 29. Rinder CS, Bonan JL, Rinder HM, et al. Cardiopulmonary bypass

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induces leukocyte-platelet adhesion. Blood 1992; 79: 1201–1205. 30. Chenoweth DE, Hugli TE Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes. Proc Natl Acad Sci USA 1978; 75: 3943–3947.

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Cardioplegic Arrest Studies (BHCAS 1 and 2): a pooled analysis of two randomized controlled trials. Lancet 2002; 359: 1194–1199. 33. Okubo N, Hatori N, Ochi M, Tanaka S. Comparison of m-RNA expression for inflammatory mediators in leukocytes between on-pump and

31. Chello M, Mastroroberto P, Quirino A, et al. Inhibition of neutrophil apoptosis after coronary bypass operation with cardiopulmonary bypass. Ann Thorac Surg 2002; 73: 123– 129.

off-pump coronary artery bypass grafting. Ann Thorac Cardiovasc Surg 2003; 9: 43–49. 34. De Angeli S, Paccagnella A, Mordacchini M, et al. The effects of

32. Angelini GD, Taylor FC, Reeves BC, et al. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against

prolonged cardiopulmonary bypass on cell-mediated immunity. Thorac Cardiovasc Surg 1994; 42: 14– 20.

16th Annual SA Heart Congress 25-28 October 2015 • Sun City North West Province • South Africa CALL FOR WEIRD & WONDERFUL CLINICAL CASES A session is allocated to vexing or unusual clinical cases titled “Hearts In Sight: the Weird and Wonderful” – an opportunity for Clinicians and Fellows in Cardiology to present interesting or unusual clinical cases, ECGs and images (Radiographs/Echo/CT/CMR/Nuclear studies). This session will be combined with an abstract/ original research forum.

Contact the SA Heart Congress Team Europa Organisation Africa Tel: 011 325 0020 Fax: 011 325 0028 Email kerrie@eoafrica.co.za

DEADLINES Submission for Weird & Wonderful Clinical Cases

31 August

Accommodation

4 October

Registration

12 October

Heart

www.saheart.org/congress2015

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165

Prediction of mid-term outcome after cryo-balloon ablation of atrial fibrillation using post-procedure high-sensitivity troponin level Tolga Aksu, Sukriye Ebru Golcuk, Tümer Erdem Guler, Kıvanç Yalin, İsmail Erden

Abstract Objective: High-sensitivity troponin I (hsTnI) assays lead to, among other things, improvement in the detection of myocardial injury and improved risk stratification of patients with atrial fibrillation (AF). The aim of this study was to investigate the association between post-procedure cardiac biomarkers and clinical outcome in patients undergoing cryo-balloon ablation (CA) for AF. Methods: A total of 57 patients (mean age 55.1 ± 12.2 years, 50.9% female) with symptomatic paroxysmal AF underwent the CA procedure. Two hundred and twenty-eight pulmonary veins (PVs) were attempted for pulmonary vein isolation (PVI) with a second-generation cryo-balloon. hsTnI, CK-MB mass and myoglobin samples were prospectively obtained before and 24 hours after ablation. Results: At a mean follow up of 214.6 ± 24.3 days, the probability of being arrhythmia free after a single procedure was 86%. Post-ablation hsTnI (p = 0.001), left atrial (LA) diameter (p = 0.002), duration of AF (p = 0.002), mean minimal temperature of the left superior pulmonary vein (p = 0.005), and age (p = 0.021) were associated with increased AF recurrence rate. On multivariate analysis, lower hsTnI level was the only independent predictor for AF recurrence (p = 0.012). Post-ablation hsTnI levels lower than 4.40 ng/ml predicted AF recurrence during follow up, with a sensitivity of 86% and a specificity of 96%. Conclusion: It is well recognised that the PV antrum contributes to initiation and/or perpetuation of AF. A lower postablation hsTnI level may predict an increased AF recurrence rate, suggesting inadequate ablation of the PV antrum. This may be used as a non-invasive marker to predict the outcome of AF. Keywords: ablation, atrial fibrillation, cryo-balloon, troponin, recurrence

Department of Cardiology, Derince Education and Research Hospital, Kocaeli, Turkey Tolga Aksu, MD, aksutolga@gmail.com Tümer Erdem Guler, MD İsmail Erden, MD

Department of Cardiology, Faculty of Medicine, Istanbul University, Istanbul, Turkey Sukriye Ebru Golcuk, MD Kıvanç Yalin, MD

Submitted 28/1/15, accepted 25/2/15 Previously published online 17/3/15 Cardiovasc J Afr 2015; 26: 165–170

www.cvja.co.za

DOI: 10.5830/CVJA-2015-027

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 1–3%.1,2 The development of AF requires both a trigger and a susceptible substrate. The most common trigger for AF is the myocardial sleeve of the left atrium (LA), which extends into the pulmonary veins (PVs).3 However, the PV antrum also contributes to initiation and/or perpetuation of AF.4,5 Therefore, ablation of these sites, particularly pulmonary vein isolation (PVI), remains the cornerstone of AF ablation procedures.6 However, in 25–50% of patients, PVI may not be sufficient due to greater extension of atrial fibrosis, or PV reconnection as a result of non-transmural lesion formation.6-8 For this reason, in addition to PVI, the creation of different ablation lines (roof, posterior line and mitral isthmus) in the left atrium (LA) has been proposed for successful radiofrequency (RF) catheter ablation.9-12 Application of RF energy leads to the release of myocardial injury markers immediately after the ablation procedure and the level of released cardiac biomarkers are linked to the extent of ablation-induced cardiac lesions.13 To determine the size of effective ablation lesions comprising different energy sources, many authors have used a variety of cardiac biomarkers.14-25 Contrasting data exist about myocardial injury biomarker trends after cryo-balloon ablation (CA) procedures.15-19 In our previously published abstract, we demonstrated that cryo-balloon ablation may be linked to significant decrease in left atrial potentials adjacent to the PVs, particularly on the posterior wall of the LA, compared to the RF-based PVI procedure in patients with long-standing persistent AF, which limited the sites of ablation.26 To date, it is unknown whether myocardial injury biomarkers could predict the extent of lesion formation at long-term follow up. We aimed to investigate the sensitivity and specificity of postprocedural cardiac biomarker levels for predicting recurrence of AF in patients undergoing CA for paroxysmal AF, and to discuss the pathophysiological basis of these relationships – inadequate left atrial ablation or unsuccessful PVI. Other potential predictors of AF recurrence were also evaluated in the same population. Isolation of all PVs was the procedural endpoint. The primary endpoints of the study were (1) comparison of peak biomarker release in patients with/or without AF recurrence before and after the procedure, and (2) comparison of procedural parameters in

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patients with/or without AF recurrence. The secondary endpoint was other potential predictors of recurrent atrial tachycardia of more than 30 seconds during mid-term follow up of six months without a blanking period.

Methods The study population consisted of 57 consecutive patients who underwent PVI with the cryo-balloon technique for 12-lead verified, symptomatic and drug-refractory paroxysmal AF. Patients whose episodes of AF had self-terminated within seven days were defined as paroxysmal AF. The indication for ablation was based on the guidelines.6 Detailed inclusion and exclusion criteria for patients are outlined in Table 1. Symptomatic severity of the patients was recorded according to the European Heart Rhythm Association (EHRA) score. CHA2DS2-VASc scores were calculated for each patient based on the relevant guidelines.27 Written informed consent was obtained from all patients before the procedure. The local ethics committee approved the study. Pre-procedural evaluation: standard transthoracic echocardiography (TTE) was performed in all patients to evaluate left atrium diameters and to rule out structural abnormality. In all patients, left atrial thrombus was ruled out by transoesophageal echocardiography (TEE) prior to the procedure. All patients were anticoagulated with warfarin to maintain an international normalised ratio (INR) of 2–3 for at least four weeks prior to the procedure. Warfarin was interrupted before the procedure. The procedures were done if the INR value was < 1.5. Antiarrhythmic drugs were discontinued five half-lives before the procedure. Blood sampling and biomarker measurements: blood samples were obtained during venous puncture before the procedure and a further one and 24 hours after ablation. The blood level of hsTnI was measured in frozen EDTA plasma samples using the current version of the AccuTnI assay (Beckman Coulter Inc, Fullerton, Table 1. Study inclusion and exclusion criteria Inclusion criteria • Patients age ≥ 18 years • Paroxysmal AF (AF that terminates spontaneously or with intervention within 7 days of onset) • Symptomatic and drug refractory (at least one anti-arrhythmic) AF • At least three episodes of AF must have been documented by ECG or Holter before the procedure • Patients must be on continuous anticoagulation with warfarin (INR 2–3) for > 4 weeks prior to the ablation • Patients must be able and willing to provide written informed consent to the procedure Exclusion criteria • Previous abdominal surgical procedures • History of either acute or chronic neuropathies • Usage of drugs that affect gastrointestinal motility • Persistent or permanent AF • Inadequate anticoagulation as defined in the inclusion criteria • Left atrial thrombus on transoesophageal echo prior to the procedure • Contra-indications to any anticoagulant • Previous AF ablation procedure • Left atrial size > 55 mm • Left ventricular ejection fraction < 30% • Congestive heart failure with New York Heart Association class IV

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CA, USA). Serum CK activity was determined using an analyser Integra (Roche). The reference ranges in our laboratory for the cardiac markers were as follows: CK-MB mass, 0.5–5 ng/ml; myoglobin, 0–113 ng/ml; and hsTnI, 0.0–0.06 ng/ml. Cardiac hsTnI cut-off values for the diagnosis of myocardial infarction (0.06 ng/ml) were accepted as pathologically increased. Ablation procedure: the procedure was performed under local anesthesia. Trans-septal punctures were performed under fluoroscopic guidance only. After trans-septal puncture, intravenous heparin was used to maintain an activated clotting time of 300 to 400 seconds. A single or double trans-septal puncture was performed using a conventional circumferential mapping catheter (InquiryTM, OptimaTM, St Jude Medical, Sylmar, CA, USA) or the customised mapping catheter (AchieveTM, Medtronic, Minneapolis, MN, USA). Positioning of the 28-mm cryo-balloon catheter (Arctic Front AdvanceTM, Medtronic, Minneapolis, MN, USA) was achieved using a guidewire and a 12-Fr steerable sheath (Flexcath Medtronic Minneapolis, MN, USA). While delivering cryo-energy to the right PVs, a 6-F decapolar coronary sinus (CS) catheter or a quadripolar diagnostic catheter was positioned in the superior vena cava for phrenic nerve stimulation. Before each freeze, the grade of occlusion (semi-quantitative scale from 1 = poor occlusion to 4 = perfect occlusion) was quantified with an injection of contrast medium.28 After confirmation of PV occlusion by contrast injection, the 240-second freezing cycle was initiated. After two freezing cycles, PVI was assessed using a circumferential mapping catheter. If PVI was not achieved within five attempts, the customised mapping catheter was exchanged for a stiffer wire (Amplatz Ultra Stiff, COOK Medical Inc). Isolation of PVs was defined as the presence of both entrance and exit block. In all patients, rapid atrial pacing from the distal tip of the CS catheter was used to induce AF after the procedure. If AF could not be induced or sustained for longer than one minute by rapid atrial pacing, an infusion of isoproterenol (10 mcg/ min) was used to sustain AF. Complex fractionated electrogram (CFE) mapping was performed to detect any focal source except for PVs, if the AF persisted for more than one minute. CFE mapping using an automated algorithm (Ensite NavX, St Jude Medical) was performed in the LA, CS and right atrium. The technique for CFE mapping using automated mapping software has been described and validated previously.29 Patients in whom CFE was detected outside the LA were excluded from the study. For RF ablation of CFE, an open irrigated-tip catheter with a 3.5-mm tip electrode (ThermoCool, Biosense Webster) was used in conjunction with a three-dimensional electro-anatomical mapping system (NavX Fusion, St Jude Medical). The energy of the RF was delivered with power of up to 35 W and a maximum temperature of 43°C. The endpoint for CFE ablation was (1) elimination of all CFE sites in the LA or termination of AF, and (2) non-inducibility of AF post ablation with the same protocol. Post-procedural evaluation: TTE was performed immediately after the procedure to exclude the presence of pericardial effusion. All patients were followed up for at least 12 hours in the intensive care unit. Patients were then discharged provided that their clinical status was stable. Oral anticoagulation was initiated on the evening of ablation unless pericardial effusion was detected, and continued for at least three months after the procedure. The patients presenting with arrhythmia-related symptoms in the first

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three months were treated with anti-arrhythmics (amiodarone in three cases and propofenone in one case). Regular follow up consisted of out-patient clinic visits one, three and six months after the procedure. It included a detailed history for arrhythmia-related symptoms (palpitations, chest discomfort, fatigue and dizziness), a physical examination, 12-lead ECG and 24-hour Holter monitoring. The need for further oral anticoagulation was evaluated in the third month based on the CHA2DS2-VASc score. Outcome was measured as per the guidelines in the recent consensus document.6 Any episode of AF, atrial flutter, or atrial tachycardia lasting for at least 30 seconds was defined as recurrence.6 A blanking period was not considered for the study. Any recurrence in the first three months was classified as early recurrence, whereas recurrence after this period was considered late recurrence. Only patients with at least six-month follow ups were included in the study. Patients with late AF recurrence underwent redo-procedures to evaluate the cause of recurrence, following similar preparatory steps to those during the index procedure. A diagnostic catheter was used to evaluate the status of isolation or reconnection in each vein. None of the patients had clinical signs of coronary ischaemic episodes either prior to or at the end of the procedure. There were no changes in the ST-segment when comparing ECG tracings before, during and after the procedure.

Statistical analysis SPSS 17.0 software (IBM Corp, Armonk, NY, USA) was used for statistical analysis. All quantitative variables with a normal distribution were reported as mean ± standard deviation, and compared using the Student’s t-test. For values with non-normal Table 2. Baseline characteristics and demographic features of the study population (n = 57)

Failed anti-arrhythmics (n) Amiodarone Propofenone βb or CKB Age, years (mean ± SD) Gender, female, n (%) BMI, kg/m2

Total (n = 57)

Recurrence (–) (n = 50)

Recurrence (+) (n = 7)

p-value

13 27 17

11 23 15

2 4 2

0.630 0.594 0.409

55.1 ± 12.13 29 (50)

54 ± 1 26 (52)

65 ± 15 3 (42)

24.8 ± 3.7 10 (17) 25 (43) 9 (15) 28 (49)

24.8 ± 3.6 9 (18) 21 (42) 8 (16) 25 (50)

24.7 ± 3.7 1 (14) 4 (57) 1 (14) 3 (42)

3.9 ± 2.6

3.5 ± 2.5

6.7 ± 4.5

0.021 0.658 0.126

Diabetes mellitus, n (%) Hypertension, n (%) CAD, n (%) Smoking, n (%) Duration of AF history, years LA diameter, mm

0.195 0.451 0.457 0.702 0.002

41.32 ± 4.51 40.72 ± 4.16 46.23 ± 4.36

0.002

LVEF, %

59.23 ± 5.12 59.48 ± 4.78 56.42 ± 5.56

0.146

CHA2DS2-VASc score, mean ± SD

1.3 ± 1.17

1.3 ± 1.11

1.7 ± 1.60

0.414

EHRA score, mean ± SD Follow-up time, days, mean ± SD

2.45 ± 0.56

2.44 ± 0.54

2.57 ± 0.78

0.573

214 ± 24

212 ± 23

213 ± 25

0.117

AF, atrial fibrillation; βb, beta-blocker; BMI, body mass index; CKB, Ca channel blocker; CAD, coronary artery disease; EHRA, European Heart Rhythm Association; LA, left atrium; LVEF, left ventricular ejection fraction; SD, standard deviation, p < 0.05.

distribution, comparison was performed with the Mann– Whitney U-test. For the descriptive variables comparison, the Pearson χ2 or Fisher’s exact tests were used, when appropriate. The independent association of clinical variables with recurrence was assessed using multivariable linear regression. A Kaplan–Meier analysis was used to analyse the recurrent atrial tachycardia‐free survival after cryo-ablation. A p-value < 0.05 was considered statistically significant. Receiver-operator characteristic (ROC) analysis was performed on significant predictors to calculate the accuracy and other diagnostic parameters, and to determine a cut-off point at the maximum sum of sensitivity and specificity.

Results Baseline characteristics and demographic features of the patients are presented in Table 2. After a mean follow-up period of 214 ± 24 days (range 180–274), early recurrence was observed in five (8.77%) patients and late recurrence in two (3.50%) (Fig. 1). Patients with AF recurrence (group 1) were significantly older (65 ± 15 vs 54 ± 1 years, p = 0.002), had larger left atrial diameters (46.2 ± 4.3 vs 40.7 ± 4.1 mm, p = 0.002) and longer duration of AF (6.7 ± 4.5 vs 3.5 ± 1.9 years, p = 0.002) than patients with no recurrence (group 2). The other baseline demographics were comparable between the groups. All patients were in sinus rhythm at the beginning of the procedure. The procedural endpoint of PVI was reached in all patients. A left-sided common ostium was seen in two patients. Four patients were in AF at the end of cryo-ablation; the regions of CFE were located within the PV antrum or posterior LA wall in these four patients, and additionally on the LA roof in three patients, and high on the LA septum in one patient. Sinus rhythm was achieved in all four patients after CFE ablation. At the end of CFE ablation, repeat induction was attempted in all four patients but neither AF nor atrial tachyarrhythmia was induced after CFE ablation in any of them. Mean procedure time and mean duration of energy delivery were comparable in the groups, but mean minimal temperature

1.0 Freddom from AF recurrence

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0.8

>8 censored

1–8 1–8 censored

0.6 0.4 0.2 0.0 0

100 150 200 Follow up (months)

250

300

Fig. 1. A Kaplan–Meier analysis was used to analyse the recurrent atrial tachycardia‐free survival after cryoablation in the troponin group.

168

Table 3. Procedure-related data (n = 57) Recurrence (–) (n = 50)

Recurrence (+) (n = 7)

Source of the curve p-value

–50.63 ± 3.46

–46.71 ± 1.11

0.005

LIPV

48.12 ± 3.94

–48.46 ± 4.04

–45.71 ± 1.97

0.084

RSPV

51.45 ± 3.67

–51.80 ± 3.74

–49.45 ± 1.91

0.053

RIPV 45.45 ± 3.59 Occlusion grade LSPV 3.82 ± 0.38

–45.74 ± 3.59

–43.42 ± 3.10

0.111

3.88 ± 0.32

3.42 ± 0.53

0.764

LIPV

3.77 ± 0.42

3.84 ± 0.37

3.28 ± 0.48

0.605

RSPV

3.98 ± 0.13

3.98 ± 0.14

3.99 ± 0.03

0.408

3.80 ± 0.39 Freezing duration (min) LSPV 8.42 ± 1.40

3.82 ± 0.38

3.71 ± 0.48

0.143

8.40 ± 1.45

8.57 ± 0.97

0.766

LIPV

8.75 ± 1.76

8.80 ± 1.84

8.42 ± 1.13

0.602

RSPV

8.24 ± 0.82

8.28 ± 0.88

8.80 ± 0.96

0.408

10.15 ± 3.31 Number of applications LSPV 2.15 ± 0.49 LIPV 2.28 ± 0.61

9.92 ± 3.20

11.85 ± 3.80

0.141

2.14 ± 0.49

2.28 ± 0.48

0.462

2.30 ± 0.64

2.14 ± 0.37

0.537

RIPV

was higher in group 1 than in group 2 (–46.21 ± 1.55 vs –49.14 ± 3.04°C, p = 0.016). This difference was caused by higher mean minimal temperature in the left superior pulmonary vein (Table 3). Mean pre-procedural ACT levels and mean ACT level during the procedure were comparable between the groups. Complications related to CA procedures included a major haematoma in the groin in one patient, transient phrenic nerve paralysis in four patients, a gastroparesis in seven patients and a transient ischaemic attack, which had resolved the following day, in another patient. There was no correlation between post-procedural hsTn values and the number of trans-septal punctures or inserted femoral sheaths. In both groups, no patients showed pathological values for hsTnI, CK-MB mass, or myoglobin levels at baseline. Postprocedure blood tests were performed at about 26 ± 2.4 hours after the end of the procedure and pathological values for hsTnI were recorded in 100% of patients, with a median value of 11.75 ± 5.25 ng/ml. CK-MB mass was above the cut-off threshold in 54 of 57 patients (94.73%) patients, and myoglobin was above the cut-off threshold in 17 of 57 (29.82%) patients (Fig. 2). Mean hsTnI levels were significantly lower in group 1 (Table 4, Fig. 3). Blood levels of CK-MB and myoglobin were slightly higher in group 1 but these differences did not reach statistical significance (Table 4).

CKMB24

0.6 0.4 0.2 0.0 0.0

0.2

0.4 0.6 1 – Specificity

0.8

1.0

Fig. 2. Receiver-operator characteristic (ROC) curve analysis of hsTnI, CK-MB and myoglobin levels.

Pre-procedure (n = 57) Recurrence Recurrence (–) (+) Troponin Creatine kinase

Post-procedure (n = 57) Recurrence Recurrence (–) (+)

0.01 ± 0.01 0.008 ± 0.007 12.57 ± 5.06 2.02 ± 0.97

After multivariate analysis including duration of AF, postprocedure hsTnI level and left atrial diameter as covariates, only post-procedure hsTnI level remained a significant predictor for ablation recurrence. There was no correlation between post-CA biomarker levels and mean minimal temperature in the PVs. Both patients with late recurrence underwent redo electrophysiological studies (EPS) to determine the possible cause of recurrence. One of these patients underwent CFE ablation due to persistence of AF after CA. The induction of AF was achieved by rapid atrial pacing, as mentioned above. Conventional EPS showed no reconnection of the PVs. Termination of AF was achieved during CFE ablation at the anterior wall of the LA in one patient and on the LA roof in the other.

Discussion The main findings of this study were that cryo-ablation for paroxysmal AF resulted in an increase in hsTnI levels. In 40.00

30.00

20.00

10.00

Table 4. Cardiac biomarker data (n = 57)

*p < 0.001.

Mg24

2.08 ± 0.28

RIPV

Myoglobin

0.8

hsTn [ng/ml]

0.396 2.09 ± 0.30 2.13 ± 0.55 0.274 2.80 ± 1.23 2.74 ± 1.22 3.28 ± 1.25 LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein. p < 0.05.

T24

1.0

Sensitivity

Total (n = 57) Minimal temperature (°C) LSPV 50.14 ± 3.51

RSPV

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5.90 ± 1.42*

2.43 ± 1.25

30.36 ± 21.37 36.88 ± 21.12

22.27 ± 8.91 15.52 ± 3.29

72.99 ± 20.88 82.14 ± 30.31

0.00 Recurrence (–)

Recurrence (+)

Fig. 3. Comparison of hsTnI levels among patients with and without recurrence of AF.

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addition, hsTnI level was the only independent predictor of AF recurrence in multivariate analysis. The STOP-AF trial is the only randomised study that compared treatment efficacy of cryo-balloon ablation versus antiarrhythmic drugs for paroxysmal AF. After 12 months, nearly 70% of the patients treated with the cryo-balloon remained free from AF, compared to only 7.3% on drug therapy.25 The success rate of treatment was higher with CA than with standard RF ablation.30 Aytemir et al.31 studied the predictors of AF recurrence in patients who underwent cryo-balloon ablation for paroxysmal AF. In this study, freedom from AF after a single ablation procedure was 68.53 and 90.83% in patients undergoing PVI with first- and second-generation cryo-balloon catheters, respectively. Left atrial diameter, early AF recurrence and second-generation cryo-balloon catheter use were independent predictors for late AF recurrence. In our study, we used second-generation cryo-balloon catheters in all cases and 88% of patients were free of AF recurrence. In patients with AF recurrence, the LA diameter was larger and the duration of AF was longer. After multivariate analysis, these two parameters were not found to be independent predictors of recurrence. The role of troponin release after CA of PVs for paroxysmal AF in predicting ablation outcome is not clear. Cardiac biomarkers have been used to estimate myocardial lesion size after ablation procedures with different energy sources. Del Rey et al.32 demonstrated that RF ablation increased troponin levels in almost all patients, whereas other cardiac biomarkers remained within health-related reference limits. It has also been shown that increase in biomarker levels and the amount of myocardial damage after RF catheter ablation depend on the number of RF pulses and the site of ablation.22 Increase in myocardial injury biomarker levels after CA was first described by Oswald et al.15 In patients with atrial flutter, CA showed significantly higher troponin levels following ablation compared to RF ablation, with declining levels the following day. They observed equal findings for CK and CK-MB levels, both significantly higher in the CA group. Comparison of troponin increases after ablation procedures for AF with RF or cryo-energy is controversial. KĂźhne et al.16 compared troponin release in patients undergoing CA and RF ablation. In their study, post-procedural troponin levels were higher in the RF ablation group. The study by Siklody et al.20 revealed no significant differences in myocardial injury markers between patients treated with CA or RF ablation. In the same field, Schmidt et al.20 compared RF ablation and CA for their impact on markers for myocardial injury. They demonstrated that CA causes significantly higher troponin release compared to RF ablation. In our study, CA resulted in a larger troponin increase compared to previous studies using RF ablation.12,23,24 To the best of our knowledge, our study is the first that shows the prognostic role of hsTnI levels in patients undergoing CA for paroxysmal AF. Our study revealed that lower post-procedural hsTnI level is an independent predictor of AF recurrence. Although we also analysed other myocardial injury markers, we found only hsTnI level to be a predictor of AF recurrence. This may be related to the better sensitivity of hsTnI to show myocardial damage than any other markers of injury.

169

Bordignon et al.33 compared myocardial biomarker release using first- and second-generation cryo-balloons. They revealed that cumulative freezing time was related to biomarker release. In our study, there was no correlation between biomarker release and procedural data. Single-procedure success rates of PVI by RF ablation in patients with paroxysmal AF remain unsatisfactory. Although PVI is the main target in paroxysmal AF, substrate abnormality in the PV antrum may play a critical role in the AF mechanism. Additional ablation of the PV antrum after PVI may increase the efficacy of the procedure.26 Higher troponin release with CA may be linked to larger ablation damage in the LA compared to the RF-based PVI procedure. This finding may explain the potential advantage of CA beyond PV isolation. Preliminary results of our unpublished data on patients with long-standing persistent AF showed that CA of the PVs resulted in a significant decrease in the CFE area.26 This contributary role may be predominantly on the posterior wall of the LA due to its vicinity.

Limitations Our study has several limitations. A major limitation is the relatively small sample size. Another limitation is the poor relationship between biomarker measurement and lesion region, and we did not find a casual relationship. The mode of follow up, which was performed only by 24-hour Holter monitoring or occasional event-driven ECG is a further limitation, and clinical judgment may be questionable. The increase in hsTn levels after ablation was not region specific and it may not indicate ablation of the critical site maintaining the arrhythmia. Although two patients underwent redo EPS to define the exact electrophysiological cause of recurrence, EPS evaluation was unfortunately not performed on all patients with recurrence. Therefore we could not conclude whether all recurrence was associated with inadequate substrate ablation in patients with lower post-CA hsTn levels. Although patients in whom AF persisted at the end of CA underwent CFE mapping, the localisation of CFE may not predict the exact focus of triggers in patients with paroxysmal AF. Given the difficulty in precisely locating and ablating these triggers, an alternative approach that simply seeks to electrically isolate the PV from the LA seems logical. Evaluation of histopathological data would be the gold standard to assess the extent and localisation of ablation lesions. However, the requirement for animal or in vitro studies constitutes the pivotal problem in this evaluation. Cardiac magnetic resonance imaging after using a cryo-balloon in patients with/or without recurrence may contribute to providing distinct information with regard to cryo-thermal cardiac lesions and associations between biomarker release, and should be a field for future research.

Conclusion Despite these limitations, the results of this study indicate that lower post-procedural hsTn level was associated with higher recurrence rates and may be linked to inadequate atrial ablation by cryo-balloon catheter.

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Efficacy of full-fat milk and diluted lemon juice in reducing infra-cardiac activity of 99mTc sestamibi during myocardial perfusion imaging Khushica Purbhoo, Mboyo Di Tamba Willy Vangu

Abstract Background: When using 99mTc sestamibi for myocardial perfusion imaging, increased splanchnic activity creates a problem in the visual and quantitative interpretation of the inferior and infero-septal walls of the left ventricle. We sought to determine whether the administration of diluted lemon juice or full-fat milk would be effective in reducing interfering infra-cardiac activity and therefore result in an improvement in image quality. We compared the administration of full-fat milk and diluted lemon juice to a control group that had no intervention. Methods: The study was carried out prospectively. All patients referred to our institution for myocardial perfusion imaging from November 2009 to May 2012 were invited to be enrolled in the study. A total of 630 patients were randomised into three groups. Group 0 (G0), 246 patients, were given diluted lemon juice, group 1 (G1), 313 patients, were given full-fat milk, and group 2 (G2), 71 patients, had no intervention (control group). A routine two-day protocol was used and the patients were given the same intervention on both days. Raw data of both the stress and rest images were visually assessed for the presence of infra-cardiac activity, and quantitative grading of the relative intensity of myocardial activity to infra-cardiac activity was determined. The physicians were blinded to the intervention received and the data were reviewed simultaneously. Results: The overall incidence of interfering infra-cardiac activity at stress was 84.1, 84.5 and 96.6% in G0, G1 and G2, respectively (p = 0.005). At rest it was 91.7, 90.1 and 100% in G0, G1 and G2, respectively (p = 0.0063). The visual and quantitative results favoured both milk and lemon juice in reducing the amount of interfering infra-cardiac activity versus no intervention. Conclusion: The administration of milk or lemon juice resulted in a significant decrease in the intensity of infra-cardiac activity compared to the control group. This reduction in intensity was even more significant in the milk group for patients assessed during rest myocardial perfusion imaging.

Keywords: myocardial perfusion imaging, full-fat milk, lemon juice, infra-cardiac activity, sestamibi, 99mTc

Department of Nuclear Medicine and Molecular Imaging, Chris Hani Baragwanath Academic Hospital and Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa Khushica Purbhoo, MB ChB, FCNP (SA), MMed (Nucl Med), khushica.purbhoo@wits.ac.za Mboyo Di Tamba Willy Vangu, MD, MMed (Nucl Med), MSc, PhD

Submitted 26/3/13, accepted 25/3/15 Cardiovasc J Afr 2015; 26: 171â&#x20AC;&#x201C;176

www.cvja.co.za

DOI: 10.5830/CVJA-2015-033

Coronary artery disease is one of the leading causes of death throughout the world. In most African countries, cardiovascular disease (CVD) is now the second commonest cause of death after infectious disease, accounting for 10% of total deaths, and it is estimated that this burden will double from 1990 to 2020.1,2 It also presents an enormous burden due to morbidity and health care expenses. Myocardial perfusion imaging (MPI) is a valuable tool in the management of patients with CVD and is currently used in Africa.3 The use of single-photon emission computed tomography (SPECT) myocardial perfusion imaging, with technetium 99m-labelled radiopharmaceuticals [99mTc sestamibi (methoxy isobutyl isonitrile) and 99mTc tetrofosmin] in conjunction with either exercise or pharmacological stress is an established tool for both the diagnosis and prognostication of patients with ischaemic heart disease.4 The basis of the non-invasive approach is that physiological changes in regional myocardial blood flow or systolic contraction of the myocardium caused by stress may be more predictive of outcome than a knowledge of coronary anatomy alone. Patients with normal perfusion on 99mTc SPECT MPI had an excellent prognosis, whereas patients with abnormal scans had an increased rate of cardiac death and non-fatal infarction during follow up.5 For perfusion imaging with SPECT, thallium 201 (201Tl) and 99mTc-labelled radiopharmaceuticals are commonly used. The major metabolic pathway for clearance of sestamibi is the hepatobiliary system, therefore infra-cardiac activity from the liver and bowel may impact on the interpretation of the inferior wall after reconstruction. The presence of infracardiac activity leads to artifacts, reducing the desired targetto-background ratio, which creates difficulty in both visual and quantitative interpretation of myocardial perfusion.5 Activity may also be present in the stomach due to reflux of tracer into the gastric lumen from the duodenum, or because of uptake of free pertechnetate by the gastric mucosa. Infra-cardiac activity is less common with exercise and is more common with pharmacological stress and/or in rest studies.6 Several different protocols, including a fatty meal, drinking milk, milk and water, lemon juice, milkshake, carbonated drinks, iodinated oral contrast, intravenous injection of cholecystokinin, and the administration of metoclopramide or erythromycin have been described as a means to reduce the artifacts arising from abdominal activity.7-16 Depending on the protocol used, the mechanisms for these interventions include one or more of

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the following: expansion of the stomach by the volume effect, displacing it caudally, thereby increasing the distance between the heart and the bowel; increased gastric emptying; stimulation of liver clearance and peristaltic movement; and acceleration of bile secretion and gallbladder emptying. The aim of this study was to evaluate the efficacy of lemon juice or milk administration compared to a control group, to decrease infra-cardiac activity and to assess any resultant effect on image interpretation of myocardial perfusion.

Methods This was a prospective study. All patients 18 years and older who were referred for MPI were invited to be enrolled in the study. Ethics approval was obtained from the University of the Witwatersrand’s Human Research Ethics Committee and written consent was obtained from all study participants. The study commenced in November 2009 and ran until May 2012. We recruited 904 patients but data from 274 patients were excluded for various reasons [non-return for second day’s study, milk or lemon juice not followed in a patient for both the stress and rest study, and patients who fitted the exclusion criteria (Table 1)]. A total of 630 patients [304 female (48%) and 326 male (52%)] aged 19–84 years were eventually enrolled for data analysis. Patients were randomised into three groups. Group 0 (G0) drank diluted lemon juice, group 1 (G1) drank full-fat milk, and group 2 (G2) had no intervention (control group). Full-fat milk consisted of 250 ml milk. Diluted lemon juice consisted of 50 ml lemon juice and 200 ml water, with a total volume of 250 ml. Following the injection of 740 MBq 99mTc sestamibi during stress, patients in G0 received diluted lemon juice and patients in G1 received full-fat milk 20 minutes after the tracer injection, whereas patients in G2 received no intervention. After the rest injection of 740 MBq of 99mTc sestamibi, patients in G0 received diluted lemon juice and patients in G1 received milk, immediately after the tracer injection, whereas patients in G2 received no intervention.

Stress test protocol A routine two-day protocol was used. Patients were stressed on day one and a rest study was done on day two. Patients were fasted for at least four hours prior to stress testing (usually overnight) Table 1. Inclusion and exclusion criteria Inclusion criteria • Patients older than 18 years of age • Patients referred for 99m Tc sestamibi myocardial perfusion imaging

Exclusion criteria • Lactose intolerance • Patients who failed exercise stress testing and had a contra-indication to pharmacological stress testing, i.e. using vasodilators and dobutamine • Unable to drink 250 ml of fluids secondary to medically essential fluid restriction • Pregnant patients • Previous cholecystectomy, liver or biliary system disease • Peptic ulcer disease within the last six months • History of diabetes mellitus • Previous myocardial infarction within the last two months, unstable angina, severe primary valvular disease, left ventricular aneurysm, primary cardiomegaly, left ventricle hypertrophy or severe conduction disturbances

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and were required to abstain from caffeine-containing beverages and methylxanthine-containing medications for at least 24 hours. Caffeine and methylxanthines block the adenosine receptors on arterial smooth muscle cells, thereby limiting the effectiveness of vasodilator agents. Our department’s protocol is that we withhold caffeine in all patients, even if exercise stress is planned, in case there is a necessity to switch to pharmacological stress. Beta-blockers and calcium channel antagonists were withheld, where appropriate. The patients were haemodynamically and clinically stable for 48 hours prior to the test. The stress modality (treadmill, dipyridamole or dobutamine) was chosen and implemented in accordance with the recent EANM guideline.17 Routine imaging for stress is carried out 30–45 minutes post tracer injection, however in our study some patients were imaged later due to the longer acquisition times with the addition of prone imaging, which is also a routine protocol in our department. All patients were imaged supine with their arms raised. Gated prone images were acquired after the gated supine stress images. The routine rest images were acquired 45–80 minutes post injection.

Imaging protocol SPECT imaging was performed using a double-head, rotating, large field-of-view gamma camera (GE Medical Systems Infinia hybrid system), equipped with a low-energy, highresolution collimator. SPECT images were acquired on a 64 × 64 matrix. Sixty images (25 seconds for rest, 20 seconds for stress) were obtained over a semi-circular 180° arc. Filtered backprojection was performed with a low-resolution Butterworth filter and no attenuation or scatter correction was applied. Transaxial tomograms were reconstructed and the images were re-orientated into three sets of orthogonal slices, including short axis, horizontal long axis and vertical long axis for each study.

Data analysis Two experienced nuclear medicine physicians (total experience 30 years) evaluated the raw data of the anterior (Ant) and left lateral (LLAT) views of both the stress and rest studies for the presence or absence of interfering infra-cardiac activity. Slice numbers 15 and 45 of the planar display from the SPECT acquisition were used in all patients to increase reproducibility. Slice 15 was chosen because of the best visualisation of the inferior wall of the left ventricle in the anterior projection, and likewise, slice 45 displayed the best projection for the inferior wall of the left ventricle in the lateral view. Observers evaluated the images simultaneously and were blinded to the clinical information as well as the protocol details. If there was a disagreement with the values obtained, a consensus was reached. The observers used visual and semi-quantitative assessment of the raw data of both stress and rest images, as previously used by Hofman et al.8 Visually, any presence of infra-cardiac activity was graded as ‘yes’ and the absence of infra-cardiac activity was graded as ‘no’. If the infra-cardiac activity was equal to lung background, it was described as absent. If infra-cardiac activity was present, it was graded as follows: 0: absence of infra-cardiac activity; 1: infra-cardiac activity less than myocardial activity; 2: infra-cardiac activity equal to myocardial activity; 3: infracardiac activity greater than myocardial activity (Fig. 1).

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Grade 0: Absence of infra-cardiac activity Fig. 2. Anterior image. ROI in the inferior wall of the left ventricle copied to the infra-cardiac ROI (Slice 15)

For the semi-quantitative assessment, the total counts for the region of interest (ROI) were obtained on an anterior static image (slice 15). This ROI was manually drawn (six pixels wide). The same ROI was copied and pasted to the infra-cardiac area below the inferior wall of the left ventricle. On the same raw data, the images were rotated to a lateral view (slice 45), and the ROI was copied and pasted to the inferior wall and the corresponding infra-cardiac area (Figs 2, 3). Regions of interest were copied between stress and rest studies of individual patients to increase reproducibility. Grade 1: Infra-cardiac < myocardial activity

Statistical analysis Data were analysed using a Statistica 10 package (statsoft Inc, Tilsa, Oklahoma, USA).18 Descriptive results were presented as medians and range (normal or not normally distributed) for continuous variables. Categorical variables were summarised as frequencies and percentages. To assess the differences between continuous variables (age, counts in the left ventricle and infracardiac region at rest and stress) (not normally distributed), a

Grade 2: Infra-cardiac = myocardial activity

Grade 3: Infra-cardiac > myocardial activity Fig. 1. Example of the grading of the relative intensity of infra-cardiac activity compared to myocardial activity

Fig. 3. Lateral image. ROI in the inferior wall of the left ventricle copied to the infra-cardiac ROI (Slice 45)

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Kruskal–Wallis test was used between the three groups, followed by the Bonferroni correction for two-by-two comparisons. Post hoc comparison of the mean ranks of all groups was performed. To compare frequencies of different categorical variables among the three groups, the chi-squared test or Fisher’s exact test were used when appropriate. Statistical significance was set at p < 0.05, and after Bonferroni correction at p < 0.016 for two-by-two comparisons.

Results Six hundred and thirty patients were randomised to receive either milk or lemon juice, or no intervention and their characteristics are shown in Table 2. Three hundred and thirteen patients received milk, 246 patients received lemon juice and there was no intervention in 71 patients. There were 304 females (48%) and 326 males (52%). The method of stress was exercise in 51% and pharmacological stress in 49% of patients. There was a statistically significant difference in the gender (p = 0.003) and ethnicity (p = 0.0002) indexes among the different study groups. In all three groups, infra-cardiac activity was present in the majority of patients, both on the stress and rest studies (Table 3). At stress, infra-cardiac activity was seen in 84.1, 84.5 and 97% of patients in G0, G1 and G2, respectively. At rest, infra-cardiac activity was seen in 91.7, 90.1 and 100% of patients in G0, G1 and G2, respectively. The visual assessment for the presence or absence of infra-cardiac activity showed a statistically significant difference among the three groups, both in post stress (p = 0.005) and at rest (p = 0.0063) (Table 3). With regard to the quantitative grading, the majority of the patients had myocardial activity greater than infra-cardiac activity (at stress 74, 71 and 67% of patients for G0, G1 and G2, respectively) (Table 4). This finding was more evident in the groups with intervention, especially for the studies done at rest, and was more overt in G0 compared to G2 (p = 0.013). For the rest group, the majority of patients in G0 and G1 had less or equal interfering infra-cardiac activity. At rest, 81, 83 and 73% of patients for G0, G1 and G2, respectively, had myocardial activity greater than or equal to bowel activity. It was interesting Table 2. Patient characteristics Characteristics Number

Total

Total p-value*

630

Mean age ± SD (year)

Lemon juice group (G0)

Milk group (G1)

246 (39)

313 (50)

58.21 ± 11.42 62.03 ± 11.43

Gender, frequency (%) 326 (52)

Female

304 (48)

Stress, frequency (%)

71 (11) 61.37 ± 9.02

Lemon Total juice group Total p-value (G0) 0.005

Milk group (G1)

Control group (G2)

MPI Stress, frequency (%): presence of infra-cardiac activity Yes 528 201 (84.1) 257 (84.5) 70 (97) No 86 38 (15.9) 47 (15.5) 1 (3) Rest, frequency 0.0063 (%): presence of infra-cardiac activity Yes 564 219 (91.7) 274 (90.1) 71 (100) No 50 20 ( 8.3) 30 (9.9) 0 Presence of infra-cardiac activity was graded as ‘yes’ and absence as ‘no’ *Total p-value represents the p-value for the three study groups.

to note that just over one-quarter of patients in G2 (27%) had infra-cardiac activity greater than myocardial activity, compared to G0 (19%) and G1 (18%) (Figs 4, 5). The difference in visual grading was also statistically highly significant for the three groups in post stress (p = 0.0002), and a similar difference was noted at rest (p = 0.004) (Table 4). The analysis of the quantitative assessment of the total counts for all subjects and their comparisons within and between groups are shown in Table 5. The median was obtained in each group for the variable, and their minimum and maximum values are included.

Discussion The use of 99mTc sestamibi for MPI often results in increased splanchnic activity, which creates a major problem in the visual and quantitative interpretation of the inferior and inferoseptal walls of the left ventricle. Infra-cardiac activity arises predominantly from the liver, hepatobiliary system, bowel and/or gastro-duodenal reflux and can result in either an apparent increase or decrease in radiotracer uptake in the myocardium, especially in the inferior and infero-septal walls after reconstruction.7

Table 4. Visual grading of the intensity of infra-cardiac activity versus myocardial activity Grading

109 (44)

171 (55)

46 (65)

137 (56)

142 (45)

25 (35)

0.83

Exercise

319 (51)

127 (52)

144 (46)

48 (68)

Pharmacological

311 (49)

119 (48)

169 (54)

23 (32)

Ethnicity, frequency (%)

Table 3. Evaluation of infra-cardiac activity by visual assessment

Control group (G2)

0.003

Male

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0.0002

Black

193 (30)

71 (29)

81 (26)

41 (58)

Caucasian

238 (37)

95 (39)

131 (42)

12 (17)

Indian

140 (22)

59 (24)

68 (22)

13 (18)

Coloured

59 (11)

21 (8)

33 (10)

5 (7)

*Total p-value represents the p-value for the three study groups.

Total MPI 0 1 2 3 p-value Stress, frequency (%) 0.0002 Lemon juice (G0) 38 (16) 138 (58) 46 (19) 17 (7) Milk (G1) 47 (16) 166 (55) 49 (16) 42 (14) Control (G2) 1 (1) 47 (66) 19 (28) 4 (6) Rest, frequency (%) 0.004 Lemon juice (G0) 20 (8) 100 (42) 73 (31) 46 (19) Milk (G1) 29 (10) 137 (45) 84 (28) 54 (18) Control (G2) 0 24 (34) 28 (39) 19 (27) *Total p-value represents the p-value for the three study groups. 0: absent infra-cardiac activity 1: bowel activity < myocardial activity 2: bowel activity = myocardial activity 3: bowel activity > myocardial activity

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100%

50%

Control group (G2)

Milk group (G1)

absent infra-cardiac activity myocardial > bowel activity

Lemon juice group (G0)

Control group (G2)

Milk group (G1)

175

Lemon juice group (G0)

myocardial = bowel activity

absent infra-cardiac activity

myocardial = bowel activity

myocardial < bowel activity

myocardial > bowel activity

myocardial < bowel activity

Fig. 4. V isual grading of myocardial activity for the three groups at stress.

Fig. 5. Visual grading of myocardial activity for the three groups at rest.

Previous studies have been carried out, using both sestamibi and tetrofosmin MPI, with various agents used to reduce infracardiac activity, including the oral administration of various fluids or solid meals, and the use of pharmacological agents.8-16 The proposed mechanism of action is to fill the stomach, increasing the distance between the left ventricle and interfering infra-cardiac activity, or to increase liver clearance of radiotracer via gallbladder contraction. In our study, the rationale for using lemon juice was that physiologically, acid-rich food or drink has the potential to facilitate hepatobiliary clearance of the bile by increasing the secretion of secretin, as was demonstrated by Peace et al.12 Milk was administered in the other group, as it was demonstrated by Hofman et al. that milk resulted in a significant decrease in the intensity of infra-cardiac activity.8 The mechanism of action is thought to be that administration of a fatty meal delays gastric emptying, resulting in increased volume in the stomach, and also that milk stimulates gallbladder contraction, resulting in movement of tracer from the liver to the duodenum.8 The reason for using milk and lemon juice in our study was the ease of availability, as well as the simplicity with regard to performing the study. Our study, to our knowledge with the largest number of patients, compared whether the administration of full-fat milk or diluted lemon juice would improve the activity in the infra-cardiac region, and these interventions were compared to a group with no intervention. Our findings are overall in accordance with earlier studies in showing a decrease in infracardiac activity.7,8,11-13,15-17 The administration of milk or lemon juice showed a decrease in the presence of infra-cardiac activity, both for studies done at stress and at rest. Also it was noted that

the image quality in the groups that had received an intervention (milk or lemon juice) was better in a greater percentage of patients, with images showing absent or infra-cardiac activity less than bowel activity (50% in G0, 55% in G1 vs 34% in G2). It is known that infra-cardiac activity is more common in rest myocardial perfusion images,5 as was shown in our study, therefore our current protocol for rest MPI includes administration of 250 ml full-fat milk immediately after injection of the radiotracer. It is noted that when comparing patient satisfaction with regard to the interventions given, there was a general preference to the taste of milk compared to lemon juice. Michael et al.8 compared milk versus water in reducing infracardiac activity in 99mTc sestamibi MPI. He randomised 198 patients into two groups. One group had 150 ml chilled water and the other group had 150 ml milk five minutes after completion of the stress, and again five minutes before image acquisition. Patients also received 150 ml chilled water or milk five minutes after the rest injection, and again five minutes prior to image acquisition (total 600 ml of fluids for stress and rest images). There was a significant decrease in the intensity of infra-cardiac activity with milk compared to water. However the reduction in the intensity of infra-cardiac activity in the milk or water group did not translate into a statistically significant benefit in the image quality (p = 0.563 at stress and p = 0.502 at rest).

Study limitations By excluding almost a third of the recruited patients (274) from the original number (904), the powers in each group were not the same. There are numerous studies that have looked at interventions carried out together with the time of imaging

Table 5. Total counts in the myocardium and infra-cardiac area in the anterior and lateral views Region [median of total counts of ROI (range)] Lemon juice group (G0) Stress, inferior myocardium anterior 634.5 (185–2648)* Stress, infra-cardiac anterior 391 (79–1728) Stress, inferior myocardium lateral 584 (103–2100)* Stress, infra-cardiac lateral 419 (63–2119) Rest, inferior myocardium anterior 633.5 (186–8181)* Rest, infra-cardiac anterior 464 (83–2101) Rest, inferior myocardium lateral 617.5 (109–2986)* Rest, infra-cardiac lateral 488.5 (978–2672)* *p < 0.05 between the lemon juice group (G0) and the milk group (G1). # p < 0.05 between the milk group (G1) and the control group (G2).

Milk group (G1) 733 (160–3260)# 429 (101–2551)# 673 (175–3913)# 452 (90–2347) 694 (36–2308) 512 (89–2329) 691 (32–2628) 552 (15–3037)

Control group (G2) 553 (144–1566) 364 (73–1308) 534 (172–1693) 393 (88–1805) 586 (159–7171) 443 (145–1288) 612 (212–1897) 547 (126–1646)

Overall p-value < 0.0001 0.0106 0.019 0.1129 0.0089 0.088 0.007 0.020

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to reduce interfering infra-cardiac activity. We did not look at the effect of time in addition to the interventions carried out. Also, even though the acquisition of prone images was part of our protocol, we did not analyse the raw data, therefore in the absence of prone analyses, the overall effect on a stress study with regard to the interventions carried out is not known.

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Medicine, 4th edn. Connecticut: Lippincott, Williams & Wilkins, 2002: 273–319. 5.

Pennell DJ, Rahman SL. Cardiac stress. In: Ell PJ, Gambhir SS, eds. Nuclear Medicine in Clinical Diagnosis and Treatment, 3rd edn. London and Stanford: Churchill Livingstone, 2004: 1093–1104.

Better N, Hicks RJ. Infarct-avid imaging and myocardial perfusion scintigraphy techniques using single-photon radiotracers. In: Ell PJ, Gambhir SS, eds. Nuclear Medicine in Clinical Diagnosis and Treatment,

Conclusion

3rd edn. London and Stanford: Churchill Livingstone, 2004: 1047–1070.

When using 99mTc sestamibi, the infra-cardiac activity causes significant artifacts after reconstruction and may lead to errors in visual and quantitative assessment of myocardial perfusion, especially in the inferior and infero-septal walls. Our study demonstrated that the administration of milk or lemon juice resulted in a significant decrease in the intensity of infra-cardiac activity compared to a control group. There was a trend towards greater improvement in the group that received milk for the resting part of the study compared to the group that received lemon juice. However, we are not sure of the impact of the amount of either milk or lemon juice, as well as the timing of their administration on the study outcomes. Therefore, further studies are needed to determine the ideal amount and timing of administration of these interventions. Also, further studies should be done with regard to prone acquisition with these interventions.

We thank the staff at the Nuclear Medicine Department at Chris Hani

13. Vorster M, Satekge MM, Rheeder P. Erythromycin as an alternative to

Baragwanath Academic and Charlotte Maxeke Johannesburg Academic

reduce interfering extra-cardiac activity in myocardial perfusion imag-

Burrell S, MacDonald A. Artifacts and pitfalls in myocardial perfusion imaging. J Nucl Med Technol 2006; 34: 193–211.

Hofman M, Mckay J, Nandurkar D. Efficacy of milk versus water to reduce interfering infra-cardiac activity in Tc-99m sestamibi myocardial perfusion scintigraphy. Nucl Med Commun 2006; 27(11): 837–842.

Van Dongen AJ, van Rijk PP. Minimizing liver, bowel and gastric activity in myocardial perfusion SPECT. J Nucl Med 2000; 41(8): 1315–1317.

10. Lowenstein BA, Pezzuti R, Cohen MC. The use of prone imaging on acute resting gated myocardial perfusion imaging with Tc-99m Sestamibi. J Nucl Cardiol 2003; 10(2): 211–212. 11. Peace R, Lloyd J. The effect of imaging time, radiopharmaceutical, full fat milk and water on interfering extra-cardiac activity in myocardial perfusion single photon emission tomography. Nucl Med Commun 2005; 26(1): 17–24. 12. Cherng S-C, Chen YH, Lee MS, Yang SP, Huang WS, Cheng CY. Acceleration of hepatobiliary excretion by lemon juice on Tc-99m Tetrofosmin Cardiac SPECT. Nucl Med Commun 2006; 27(11): 859–864.

Hospitals for the practical implementation of this study. Special thanks

ing. Cardiovasc J Afr 2010; 21(3): 142–147.

go to Professor Elena Libhaber for her assistance with the statistics. The

14. Malhotra G, Upadhye TS, Nabar A, Asopa RV, Nayak UN, Rajan

work was supported in part by a grant received from the University of the

MGR. Can carbonated lime drink prior to myocardial perfusion imag-

Witwatersrand, South Africa.

ing with Tc-99m MIBI reduce the extra-cardiac activity that degrades the image quality and leads to fallacy in interpretation? Clin Nucl Med

References 1.

Mbewu A. The burden of cardiovascular disease in sub-Saharan Africa. SA Heart J 2009; 6(1): 4–10.

Med Commun 2004; 25(4): 355–360. 16. Adil B, Akin YZ, Firat G, Binnur K, Metin E. The volume effect of

al. Performance of rest myocardial perfusion imaging in the manage-

the stomach on intestinal activity on same-day exercise-rest Tc-99m

(PREMIER trial). J Nucl Cardiol 2012; 19(6): 1146–1153. De Greef J, Govender R, Vermaak W, Perumal N, Libhaber E, Vangu M-Di-T. Does dipyridamole-induced ischaemia affect NT-pro BNP secretion? Cardiovasc J Afr 2007; 18(6): 371–374. 4.

techniques to reduce bowel activity in cardiac SPECT imaging. Nucl

Better N, Karthikeyan G, Vitola J, Fatima A, Peix A, Novak MD, et ment of acute chest pain in the emergency room in developing nations

2012; 35: 160–164. 15. Iqbal SM, Khalil ME, Lone BA, Gorski R, Blum S, Heller EN. Simple

Wackers FJT. Myocardial perfusion imaging. In: Sandler MP, Coleman RE, Patton JA, Wackers FJT, Gottschalk A, eds. Diagnostic Nuclear

Tetrofosmin myocardial imaging. Clin Nucl Med 2001; 26: 622–625. 17. Hesse B, Tagil K, Cuocolo A, Anagnostopoulos C, Bardies M, Bax J, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in Nuclear Cardiology. Eur J Nucl Med 2005; 32(7): 855–897. 18. Statsoft Inc. STATISCA: data analysis software system, version 8.0. Tilsa, OK, USA: statsoft Inc; http://www.statsoft.com;2008.

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Cardiovascular risk factors among patients with chronic kidney disease attending a tertiary hospital in Uganda Christopher Babua, Robert Kalyesubula, Emmy Okello, Barbara Kakande, Elias Sebatta, Michael Mungoma, Charles Kiiza Mondo

Abstract Introduction: Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which is the primary cause of morbidity and mortality in patients with CKD. Local data about cardiovascular risk factors among CKD patients is generally scanty. Objective: To determine the prevalence of the common cardiovascular risk factors among patients with CKD attending the nephrology out-patient clinic in Mulago national referral hospital in Uganda. Methods: This was a cross-sectional study in which 217 patients with a mean age of 43 years were recruited over a period of nine months. Data on demographic characteristics, risk factors for cardiovascular disease, complete blood count, renal function tests/electrolytes, and lipid profiles were collected using a standardised questionnaire. Results: One hundred and eleven (51.2%) of the participants were male. Hypertension was reported in 90% of participants while cigarette smoking was present in 11.5%. Twenty-two participants (10.2%) were obese and 16.1% were diabetic. A total of 71.9% had a haemoglobin concentration < 11 g/dl, with the prevalence of anaemia increasing with advancing renal failure (p < 0.001); 44.7% were hypocalcaemic and 39.2% had hyperphosphataemia. The prevalence of abnormal calcium and phosphate levels was found to increase with declining renal function (p = 0.004 for calcium and p < 0.001 for phosphate). Conclusion: This study demonstrated that both traditional and non-traditional cardiovascular risk factors occurred frequently in patients with CKD attending the nephrology out-patient clinic at Mulago Hospital. Keywords: CVD risk factors, chronic kidney disease Submitted 27/10/13, accepted 12/4/15 Cardiovasc J Afr 2015; 26: 177–180

www.cvja.co.za

DOI: 10.5830/CVJA-2015-045

Department of Medicine, Gulu University, Gulu, Uganda Christopher Babua, MB ChB, MMed

Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda Robert Kalyesubula, MB ChB, MMed Emmy Okello, MB ChB, MMed Barbara Kakande, MB ChB, MMed Elias Sebatta, MB ChB, MMed Michael Mungoma, MBChB, MMed Charles Kiiza Mondo, MB ChB, MMed, PhD, charlesmondo2011@gmail.com

Cardiovascular disease is the primary cause of morbidity and premature mortality in chronic kidney disease patients.1,2 The high risk of cardiovascular morbidity and mortality in end-stage renal disease (ESRD) is a well-established fact.3 However a high rate of both fatal and non-fatal cardiovascular events has been observed in patients with earlier stages of chronic kidney disease (CKD).4 Most of the current guidelines now regard CKD as a cardiovascular risk equivalent.5 Traditional cardiovascular risk factors, those risk factors that predict ischaemic heart disease outcomes in the general population, have been reported to occur commonly in patients with CKD.5-7 These include hypertension, cigarette smoking, diabetes, dyslipidaemia and older age. The number of cardiovascular risk factors appears to correlate with the severity of kidney dysfunction.7 Non-traditional cardiovascular risk factors are CKD related and increase in frequency as renal function declines. They are thought to contribute to the cardiovascular risk excess in CKD patients compared with the general population.3 These factors include anaemia, abnormal calcium/phosphorus metabolism, malnutrition, hypo-albuminaemia, hyperhomocysteinemia, inflammation, oxidant stress, insulin resistance, altered renin– angiotensin axis and endothelial dysfunction.8 Despite the fact that cardiovascular diseases are a major cause of morbidity and mortality in patients with CKD, data on cardiovascular risk factors among CKD patients are generally lacking from low-resource countries such as Uganda. We conducted a study to determine the prevalence of the known cardiovascular risk factors among patients with CKD attending Mulago Hospital, a tertiary healthcare facility and university teaching hospital.

Methods We conducted a cross-sectional study between June 2012 and February 2013 at Mulago Hospital in Kampala, Uganda. The hospital also doubles as the teaching hospital for Makerere University’s College of Health Sciences and serves the 33 million people of Uganda as well as referrals from the neighbouring Eastern Democratic Republic of Congo and the Republic of Southern Sudan. We consecutively recruited a total of 217 adults with CKD, aged 18 years and older. CKD was defined as kidney damage for three or more months, as confirmed by kidney biopsy or proteinuria, with or without a decrease in glomerular filtration rate (GFR); or GFR < 60 ml/min/1.73 m2 for three or more months, with or without kidney damage.1 Patients who had had any form of renal replacement therapy (haemodialysis, peritoneal dialysis or renal transplant) were excluded from the study. Ethical approval was obtained from the School of Medicine Research and Ethics Committee of the College of Health Sciences, Makerere University.

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A standardised, pre-tested questionnaire was used to collect data on sociodemographic characteristics, medical history, laboratory test parameters, electrocardiography (ECG) and echocardiography variables, and physical signs, with an emphasis on cardiovascular risk factors. Six traditional cardiovascular risk factors, including male gender, older age, cigarette smoking, obesity, diabetes mellitus, hypertension (defined according to JNC 7),9 and dyslipidaemia [elevated non-high-density lipoprotein cholesterol > 130 mg/dl (3.37 mmol/l)], and two non-traditional risk factors, anaemia and abnormal calcium/ phosphate metabolism were the focus of this study. Laboratory tests focused on levels of creatinine, urea, albumin, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, phosphorus, calcium, haemoglobin and proteinuria. Haemoglobin concentration was determined using Celltac E, an automated CBC machine. Clinical chemistry tests were performed using Cobas 6000, an automated analyser from Roche pharmaceuticals. Resting ECGs were carried out using the Schillar ECG Recorder, (Basal, Switzerland). Echocardiograms were done using the Vivid 7 Dimension, GE Medical Systems (Horten, Norway) according to American Society of Echocardiography guidelines. GFR was estimated for all study participants using the Cockcroft–Gault equation. Non-HDL cholesterol and body mass index were calculated using standard methods.

Statistical analyses Data were double entered into epidata version 3.1 and exported to STATA version 10 (after validation) for analysis. Results were expressed as percentages and means with standard deviations, and presented in tables and graphs. Chi-squared tests were used to determine associations (declining renal function versus riskfactor profiles). Results were statistically significant when the p-value was < 0.05.

258 patients screened in the renal clinic (June 2012 – Feb 2013)

41 were excluded: 8 did not meet inclusion criteria • 3 declined to consent • 2 had deranged renal function for less than 3 months. • 2 were less than 18 years of age • 1 was a dialysis patient 33 did not return for further tests.

Results A total of 258 patients were screened over a period of nine months. Forty-one were excluded from the study for various reasons (Fig. 1). One hundred and eleven (51.2%) of the participants were male. The mean age of study participants was 42.8 years (95% CI = 40.6–44.9). About half of the patients had ESRD (111, 51.2%) (Fig. 2). A total of 184 patients (84.8%) had proteinuria. One hundred and sixty-two subjects (74.65%) had had a non-reactive HIV antibody test within the three months prior to recruitment, 32 patients (14.75%) were HIV positive, and the remaining 23 (10.60%) had had no evidence for taking the HIV test in the previous three months. The patient characteristics are summarised in Table 1. Twenty-five patients (11.5%) were either current smokers or had a history of tobacco smoking. There was a higher prevalence of cigarette smoking among males (18.9 vs 3.8) and this was statistically significant (p < 0.001). The prevalence of hypertension was 90%, with 88% of patients on treatment but only 24% had their blood pressure under control (Table 2). Diabetes prevalence was 16.1% and 22 patients (10.1%) were obese (BMI ≥ 30 kg/m²). Despite the fact that 89 patients (41%) had elevated non-HDL cholesterol of ≥ 130 mg/dl (3.37 mmol/l), only nine patients (4.2%) were on statin lipid-lowering therapy. One hundred and fifty-six patients (71.9%) had haemoglobin concentrations < 11 g/dl. Only three patients (1.4%) were on weekly anaemia treatment with erythropoietin and iron sucrose, as recommended by the United States NKF-KDOQI. A large proportion, 156 patients (71.9%) were on oral iron and folate therapy. Ninety-seven patients (44.70%) were found to have hypocalcaemia (calcium < 2.2 mmol/l) and 85 (39.17%) had serum phosphate concentrations above the reference range (0.9– 1.5 mmol/l). The cardiovascular risk factors are summarised in Table 2. All study participants underwent resting ECG and two-dimensional echocardiography. Echocardiographically determined left ventricular hypertrophy (interventricular septum and/or left ventricular posterior wall thickness > 11 mm in diameter) was present in 54% of the participants, followed by left ventricular systolic failure (ejection fraction < 45%) in 19.4%. Ischaemic heart disease and malignant cardiac arrhythmias were less common (Fig. 3).

120 100

217 patients were eligible and included in the final analysis

No of cases

178

80 60 40 20

Participants were evaluated for cardiovascular risk factors through medical history/physical examination and laboratory tests Fig. 1. P atient flow chart.

3 Stage of CKD

Fig. 2. Graph showing distribution of patients by stage of chronic kidney disease (CKD).

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Frequency (n = 217)

Percentage (%)

124

57.14

106

48.85

9 12 44 41 111

4.15 5.53 20.28 18.89 51.15

< 45 years Gender Female Stage of CKD 1 (GFR ≥ 90 ml/min/m²) 2 (GFR 60–89 ml/min/m²) 3 (GFR 30–59 ml/min/m²) 4 (GFR 15–29 ml/min/m²)

5 (GFR < 15 ml/min/m²) Proteinuria present 184 84.79 HIV antibody test status Non-reactive 162 74.65 Reactive 32 14.75 Not available 23 10.60 GFR: glomerular filtration rate, HIV: human immunodeficiency virus.

The major findings of this study were that (1) there was a high prevalence of both traditional and non-traditional risk factors for cardiovascular disease in our patients with CKD, (2) the majority of patients in this study were in advanced renal failure (stage 3–5), including more than half in ESRD (111, 51.2%); this represents two possibilities, including late presentation as well as limited access to renal replacement therapy, and (3) the severity and/or frequency of these factors increases with advancing stage of CKD (declining renal function) (Table 3). The prevalence of hypertension in this study was similar to the high prevalence of hypertension in other studies on patients with CKD. These include a study of 100 patients with CKD at the University of Nigeria teaching hospital, in which the prevalence of hypertension was found to be 85.2% at the first nephrology consultation.10 A similarly high prevalence of hypertension, at 72.6%, was found in Albanian patients with CKD.11 These findings show that there is a high burden of hypertension in CKD patients, regardless of the different patient populations Table 2. Traditional and non-traditional cardiovascular risk factors among CKD patients attending Mulago renal clinic

< 18.5 18.5–24.9 25–29.9 ≥ 30 Non-HDL cholesterol (mg/dl) (3.37 mmol/l) ≥ 130 Haemoglobin concentration (g/dl) < 11 11–12 > 12 Serum calcium < 2.2 mmol/l Serum phosphate > 1.5 mmol/l HDL: high-density lipoprotein.

Frequency (n = 217) 25 196 191 46 35

60 50 40 30 20 10 0

LVSF

Arr IHD Target-organ damage

LVH

Fig. 3. Target-organ damage. LVSF, left ventricular systolic failure; Arr, arrhythmias; IHD, ischaemic heart disease; LVH, left ventricular hypertrophy.

Discussion

Variable Cigarette smoking Hypertension Hypertension on treatment Hypertension under control on treatment Diabetes mellitus Body mass index (kg/m²)

Percentage of total cases

Table 1. Demographic and clinical characteristics of study participants Characteristic Age

179

Percentage (%) 11.5 90.0 88.0 24.0 16.2

9.2

113 62 22 89

52.1 28.6 10.1 41.0

156

71.9

30 31 97

13.8 14.3 44.7

39.2

studied. These figures are however four times those of the general population, where hypertension prevalence was at 20%.12,13 The available studies from sub-Saharan Africa however cannot determine with certainty whether hypertension is a cause or effect of CKD due to various limitations, such as study design, lack of histological data for participants, as well as late presentation of patients. In our study, the majority were in stage 4 and 5. This finding however underscores the importance of appropriate management of high blood pressure in patients with CKD. The prevalence of diabetes in this study was similar to the 14.8% prevalence found among CKD patients in a Nigerian study.10 The similar prevalence is probably due to similarity of study settings as well as similarities in characteristics of study participants (e.g. age, race). However the prevalence of diabetes in this study was about four times the national prevalence of 4% in 2006,14 and 2.9% in 2011.13 This higher prevalence of diabetes among patients with CKD compared with the general population may reflect the significance of diabetes as an aetiological factor for CKD in Uganda. The prevalence of smoking in this CKD population was similar to that of the general population, according to World Bank figures.15 Although data from Western countries suggest that traditional cardiovascular risk factors, including cigarette smoking, are highly prevalent in CKD populations,5-7 data for CKD patients in similar settings are scarce. As the incidence of a myocardial infarction is increased six-fold in women and threeTable 3. Variation of cardiovascular risk factors across the different CKD stages CKD stage 1 2 3 4 5 Variable (n = 9) (n = 12) (n = 44) (n = 41) (n = 111) p-value Hypertension, n (%) 4 (44.4) 8 (66.7) 41 (93.2) 39 (95.1) 99 (89.2) < 0.001 Obesity, n (%) 0 (0.00) 2 (16.7) 3 (6.8) 6 (14.6) 11 (9.9) 0.797 Non-HDL-C 6 (66.7) 5 (41.7) 21 (47.7) 19 (46.3) 38 (34.2) 0.412 > 130 mg/dl (3.37 mmol/l), n (%) Diabetes, n (%) 1 (11.11) 1 (8.33) 8 (18.18) 8 (19.81) 17 (15.32) 0.871 Haemoglobin 2 (22.2) 4 (33.3) 27 (61.4) 29 (70.7) 94 (84.7) < 0.001 < 11 g/dl, n (%) Calcium 0 (0.00) 4 (33.3) 11 (25) 17 (41.5) 65 (58.6) 0.004 < 2.2 mmol/l, n (%) Phosphate 1 (11.1) 1 (11.1) 8 (18.2) 11 (26.8) 64 (57.7) < 0.001 > 1.5 mmol/l, n (%) CKD: chronic kidney disease, HDL-C: high-density lipoprotein cholesterol.

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fold in men who smoke at least 20 cigarettes per day compared to subjects who never smoked,16 smoking cessation in patients with CKD should be part of the standard management. The burden of anaemia demonstrated in this study was similar to the high burden found in CKD populations elsewhere, including one done by Gjata et al. in Albania that showed a 100% frequency,11 and another from Nigeria where a high proportion of CKD patients with left ventricular hypertrophy (LVH) were found to be anaemic.10 The high prevalence of anaemia in all these settings is probably due to the similarity of pathogenesis, lack of erythropoietin, the most important factor in anaemia of CKD. Erythropoietin production/secretion declines with advancing renal failure in all cases of CKD, regardless of cause, hence the similarity in prevalence across the different settings. Anaemia in CKD has been associated with poorer cardiovascular outcomes, including heart failure, LVH and increased rates of morbidity and mortality.17-19 We observed the prevalence of HIV/AIDS of 14.75% to be twice that in the general population (7.2%),20 and HIV is a risk factor for CKD. This makes our study population different from those in Western countries with less incidence of HIV, suggesting that HIV/AIDS could be an emerging ‘non-traditional’ risk factor for CVD. There were limitations to our study. Our inability to do renal biopsy meant that analysis for CKD was done as a block as opposed to clusters according to aetiology. The Cockroft– Gault formula was used for estimation of GFR instead of the more accurate MDRD or CKD-EPI methods. This is because most of the drug dosing is still based on the Cockcroft–Gault formula, and most doctors in resource-limited settings do not have access to the internet-based calculation of MDRD and CKD-EPI, which would have made applicability of our study findings less desirable. Some biomarkers of poor cardiovascular outcomes, regarded as non-traditional cardiovascular risk factors (inflammation, oxidative stress, sympathetic activation, hyperhomocysteinaemia, and endogenous digitalis-like factors) were not measured due to resource limitations. The criteria for evaluating ischaemic heart disease were weak.

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References 1.

National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39: S1.

Menon V, Gul A, Sarnak MJ, et al. Cardiovascular risk factors in chronic kidney disease. Kidney Int 2005; 68: 1413–1418.

Foley R, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol 1998; 9: S16–S23.

Manjunath G, Tighiouart H, Coresh J, et al. Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003; 63: 1121.

Sarnak M, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention. Circulation 2003; 108: 2154–2169.

Muntner P, He J, Astor BC, et al. Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease: results from the atherosclerosis risk in communities study. J Am Soc Nephrol 2005; 16: 529.

Foley R, Wang C, Collins AJ. Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES III study. Mayo Clin Proc 2005; 80: 1270.

Amaresan MS. Cardiovascular disease in chronic kidney disease. Indian J Nephrol 2005; 15: 1–7.

Chobanian AV1, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. J Am Med Assoc 2003; 289(19): 2560–2572. Epub 2003 May 14.

10. Ulasi II AE, Ijoma CK, et al. Left ventricular hypertrophy in African Black patients with chronic renal failure at first evaluation. Ethn Dis 2006; 16: 859–864. 11. Gjata M, Egita N, Ledio C, Zheni G, Mihal T, et al. Left ventricular hypertrophy in chronic kidney disease. Is pulse pressure an independent risk factor? Med Arh 65(1): 30–31. 12. Mondo CK, Otim MA, Akol G, Musoke R, Orem J. The prevalence and distribution of non-communicable diseases and their risk factors in Kasese district, Uganda. Cardiovasc J Afr 2013; 24: 52–57. 13. Wamala J, Karyabakabo Z, Ndungutse D, Guwatudde D. Prevalence

Conclusion This study demonstrated the common occurrence of cardiovascular risk factors among CKD patients attending a Ugandan national referral hospital. It also showed that the prevalence of some of the risk factors (hypertension, anaemia, hypocalcaemia and hyperphosphataemia) increased with advancing stage of CKD. Furthermore it indicated late presentation of patients in advanced renal failure.

factors associated with hypertension in Rukungiri District, Uganda: A community-based study. Afr Health Sci 2009; 9(3): 153–160. 14. Wasswa H. Uganda struggles to cope with rise in diabetes incidence. Br Med J 2006; 333(7570): 672. 15. WHO warning about the dangers of tobacco. WHO report on the global tobacco epidemic 2011. 16. Njolstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year followup of the Finnmark Study. Circulation 996; 93: 450. 17. McClellan W, Flanders WD, Langston RD, et al. Anemia and renal

Research reported in this publication was supported primarily by the Fogarty

insufficiency are independent risk factors for death among patients with

International Center, the National Heart, Lung and Blood Institute, and the

congestive heart failure admitted to community hospitals: a population-

Common Fund of the National Institutes of Health under award number

based study. J Am Soc Nephrol 2002; 13: 1928.

R24 TW008861, with additional support from the ENRECA project of Gulu

18. Astor BC, Arnett DK, Brown A, Coresh J. Association of kidney func-

University with funding from DANIDA. The content is solely the responsibil-

tion and hemoglobin with left ventricular morphology among African

ity of the authors and does not necessarily represent the official views of the

Americans: the Atherosclerosis Risk in Communities (ARIC) study. Am

National Institutes of Health. The authors are grateful to the following persons for their invaluable support: Prof Nelson Sewankambo, Prof Moses R Kamya, Mr Okwakol George, and the staff of the Mulago central laboratory and the ECG and Echo laboratories at the Uganda Heart Institute.

J Kidney Dis 2004; 43: 836. 19. Parfrey P, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999; 10: 1606. 20. UNAIDS 2012. Global Report 2012: AIDSinfo. http://www.unaids.org/ en/dataanalysis/datatools/aidsinfo/

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Performance of re-used pacemakers and implantable cardioverter defibrillators compared with new devices at Groote Schuur Hospital in Cape Town, South Africa Zimasa V Jama, Ashley Chin, Motasim Badri, Bongani M Mayosi

Abstract Objectives: Little is known about the performance of re-used pacemakers and implantable cardioverter defibrillators (ICDs) in Africa. We sought to compare the risk of infection and the rate of malfunction of re-used pacemakers and ICDs with new devices implanted at Groote Schuur Hospital in Cape Town, South Africa. Methods: This was a retrospective case comparison study of the performance of re-used pacemakers and ICDs in comparison with new devices implanted at Groote Schuur Hospital over a 10-year period. The outcomes were incidence of device infection, device malfunction, early battery depletion, and device removal due to infection, malfunction, or early battery depletion. Results: Data for 126 devices implanted in 126 patients between 2003 and 2013 were analysed, of which 102 (81%) were pacemakers (51 re-used and 51 new) and 24 (19%) were ICDs (12 re-used and 12 new). There was no device infection, malfunction, early battery depletion or device removal in either the re-used or new pacemaker groups over the median follow up of 15.1 months [interquartile range (IQR), 1.3–36.24 months] for the re-used pacemakers, and 55.8 months (IQR, 20.3–77.8 months) for the new pacemakers. In the ICD group, no device infection occurred over a median follow up of 35.9 months (IQR, 17.0–70.9 months) for the re-used ICDs and 45.7 months (IQR, 37.6–53.7 months) for the new ICDs. One device delivered inappropriate shocks, which resolved without intervention and with no harm to the patient. This re-used ICD subsequently needed generator replacement 14 months later. In both the pacemaker and ICD groups, there were no procedure-non-related infections documented for the respective follow-up periods. Conclusion: No significant differences were found in performance between re-used and new pacemakers and ICDs with regard to infection rates, device malfunction, battery life and device removal for complications. Pacemaker and ICD re-use is feasible and safe and is a viable option for patients with bradyarrhythmias and tachyarrthythmias. Keywords: re-used devices, pacemakers, ICDs, performance, safety The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital, Cape Town, South Africa Zimasa V Jama, MB ChB, zvjama@gmail.com Ashley Chin, FCP (SA), MPhil Bongani M Mayosi, FCP (SA), DPhil

College of Medicine, King Saudi Bin, Abdulaziz University for Medical Sciences, Riyadh, Kingdom of Saudi Arabia Motasim Badri, PhD

Submitted 17/2/15, accepted 12/4/15 Cardiovasc J Afr 2015; 26: 181–187

www.cvja.co.za

DOI: 10.5830/CVJA-2015-048

Pacemaker implantation is an effective tool to treat bradyarrhythmias, and implantable cardioverter defibrillators (ICD) reduce mortality in patients at high risk of sudden death.1 The challenge with pacemakers and ICDs is the high cost of these devices. The pacemaker generator, in its most basic form, costs US$2 500–3 000 and leads cost US$800–1 000.2 An ICD generator costs US$20 000–40 000 and leads cost over US$10 000.2 The high cost of pacemakers and ICDs has resulted in limited access of deserving patients in poor countries to these life-saving interventions.3-5 Mond et al.6 demonstrated an increase in pacemaker and ICD implantation rates in all countries that participated in the World Survey of Cardiac Pacing in 2009. Despite this increase in implantation rates, there was a huge difference in the number of implants between the developed and underprivileged countries, with more implants in the developed world.6 This disparity was explained mainly by the high cost of these devices.6 Re-use of cardiac pacemakers has been practiced since the early 1970s.7 The major concern with this practice is the risk of device infection and malfunction.8-11 Device infection is the most feared complication of cardiac device re-use and is thought to be associated with case fatality rates between 2.6 and 18%.12-14 However, some studies from America, Europe and Asia that examined the performance of re-used pacemakers and ICDs have shown no significant difference in infection or mortality rates between patients who received re-used and new devices.14-22 The aim of this study was to investigate the performance of re-used pacemakers and ICDs at Groote Schuur Hospital, Cape Town, South Africa.

Methods This was a retrospective case comparison study of performance of re-used versus new pacemakers and ICDs at Groote Schuur Hospital, Cape Town, South Africa. We included consecutive devices that were implanted between 1 January 2003 and 1 January 2013. As shown in Fig. 1, there were 1 721 devices implanted during that time, of which 1 587 (92.2%) were pacemakers and 134 (7.8%) were ICDs. Of the 1 587 pacemakers, 1 257 (79.2%) were new implants and 330 (20.8%) were generator replacements. Of the 134 ICDs, 114 (85.1%) were new implants and 20 (14.9%) were generator replacements. There were 54 (3.4%) re-used pacemakers and 12 (9%) re-used ICDs implanted during this period, with a total number of 66

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(3.8%) re-used devices implanted, as shown in Fig. 1. Patients with re-used devices (cases) were then matched by age, gender and date of implantation on a 1:1 basis to patients with new devices (controls). In the pacemaker group, cases and controls were matched to the same month of implantation, and for the ICD group, to the same year of implantation. Devices for re-use were obtained from cadaveric donors. They were inspected for external damage and tested for remaining battery life. Devices with less than two years of battery life remaining and/ or with external evidence of damage were not re-used. Only devices with two or more years of battery life remaining with no evidence of external damage were eligible for re-use. The eligible devices were sterilised by immersion in biozyme for 24 hours, followed by peroxide for a further 24 hours and then orthozyme for another 24 hours. After the three days of chemical treatment, the devices were dried out using pressurised air and subsequently subjected to gas sterilisation. In the gas sterilisation unit, they were put in a machine with ethylene oxide for 4.5 hours and irradiated for two cycles of 30 minutes, three days apart. After device sterilisation, all devices were checked by a cardiac technologist in the department for any visual defects and for

Devices implanted 2003–2013 (n = 1721)

Pacemakers, n (%) – 1 587 (92.2)

ICDs, n (%) – 134 (7.8)

First implants, n (%) – 1257 (79.2) Generator change n (%) – 330 (20.8)

First implants, n (%) – 114 (85.1) Generator change n (%) – 20 (14.9)

Re-used pacemakers, n (%) – 54 (3.4)

Re-used ICDs, n (%) – 12 (9)

Re-used devices, n (%) – 66 (3.8) Excluded, n (%) – 3 (4.5) Missing data

Analysed (n = 126)

Pacemakers, n (%) – 102 (81) Re-used, n (%) – 51 (50) New, n (%) – 51 (50)

ICDs, n (%) – 24 (19) Re-used, n (%) – 12 (50) New, n (%) – 12 (50)

ICDs = implantable cardioverter defibrillators n = number (%) = percentage

Fig 1. Outline to assess eligibility for enrolment.

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device longevity, and were tested to determine whether they were functioning appropriately for re-use. Device manufacturer’s personnel were not involved in this process. A cardiac technologist or cardiology register in training was present at every implant procedure. Standard measurements were obtained during the implant after lead positioning (capture thresholds, battery life, sensitivities and lead impedances) and again prior to discharge. Re-used pacemakers were implanted mainly in elderly patients with multiple co-morbidities such as advanced cancer (on treatment or in remission), cerebrovascular accident (CVA), advanced chronic obstructive pulmonary disease (COPD), dementia and/or a poor baseline level of functioning (mostly bed bound) who were expected to have a significantly reduced life expectancy. Re-used ICDs were implanted in patients who met the secondary prevention criteria for sudden death, and co-morbidity was not a factor in determining who received a re-used ICD. The inherent difference between patients who received re-used pacemakers compared to those who had new pacemakers led us not to compare the outcome of patients in the two groups. The units of analysis were the devices themselves. Every patient provided a written informed consent for implantation of the device. The devices were implanted by a cardiac electrophysiologist, cardiologist or a cardiology senior registrar. Prior to implantation, patients received 1 g of intravenous infusion of cefazolin as prophylaxis. Patients were discharged from hospital the following day provided there were no complications and were followed up in the pacemaker clinic at three months and yearly thereafter. Patients with ICDs were followed up more frequently at three- to four-monthly intervals.

Outcomes The outcomes of interest were procedure-related infection, device malfunction, early battery depletion, and device explantation for infection, malfunction and/or battery depletion. The definitions of the outcomes are as follows. • Procedure-related infection: infections were classified into four types:23 (1) right-sided endocarditis with lead involvement; (2) sepsis with evidence of involvement of the lead and implantation pocket; (3) involvement of the pacemaker implantation pocket; and (4) involvement of the lead or generator. Infections were considered early if the onset of illness was within the first month of implantation, and late if the onset of illness was after the first month to a year after implantation.23 Infections that occurred after a year of implantation were considered not to be related to the procedure.23 • Device malfunction was defined as failure of the device to accomplish the desired role, e.g. in the case of an ICD, not able to sense ventricular tachycardia/fibrillation and deliver appropriate treatment. In the case of a pacemaker, device malfunction was defined as inability to sense or pace when required. • Early battery depletion was defined as battery depletion within six years of implantation for new devices. For re-used devices, early battery depletion was defined as battery depletion within one to two years of implantation for those with two to four years of battery life remaining, and within two

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years of implantation for those with four years or more of battery life remaining at the time of implantation, provided this depletion was not explained by high pacing outputs or abnormal electrode impedance. • Device explantation for infection, malfunction and/or battery depletion involved removal of the pacemaker or ICD due to infection, malfunction or early battery depletion.

Data extraction The cardiac clinic electrophysiology database was used to identify the cases with re-used devices and the controls with new devices. Data were extracted from clinical notes in the cardiac clinic and additional information from pacemaker cards in the cardiac catheterisation laboratory and clinical records. Patient status was taken from clinical notes, the hospital electronic record (Clinicom) and the records of the Department of Home Affairs.

Statistical analysis Categorical data were summarised as proportions and continuous data as means and standard deviations or medians and interquartile range. Categorical data were compared using the chi-squared test, and continuous data using the Student’s t-test or Mann–Whitney test. All tests were two-sided and a p-value of < 0.05 was considered significant. IBM SPSS (version 19, IBM Corp, NY, USA) was used to perform the analysis.

Results Three patients with re-used pacemakers were excluded from the analysis because of missing records. Data for 126 devices inserted in 126 patients between 2003 and 2013 were analysed, of which 102 (81%) were pacemakers (51 re-used and 51 new) and 24 (19%) were ICDs (12 re-used and 12 new). For the pacemaker group, the median follow up for patients with re-used devices (cases) was 15.1 months [interquartile range (IQR), 1.3–36.24 months] and for those with new devices (controls) it was 55.8 months (IQR, 20.3–77.8 months). In the ICD group, the median follow up for patients with re-used devices (cases) was 35.9 months (IQR, 17.0–70.9 months) and for those with new devices (controls) it was 45.7 months (IQR, 37.6–53.7 months). Baseline characteristics of patients who received pacemakers are shown in Table 1 and pacemaker parameters are shown in Table 2. As expected, the re-used pacemaker cases had more significant co-morbidities compared to the pacemaker controls. They were more likely to have advanced cancer, CVA, advanced COPD and dementia, with a poor baseline level of functioning, mainly bed bound (due to CVA, dementia, atherosclerotic and diabetic vasculopathies with lower limb amputations and arthritis). There were no differences between the two groups with regard to pacemaker parameters, as shown in Table 2. Baseline characteristics of patients who received ICDs are shown in Table 3 and there were no significant differences between the two groups. ICD parameters are shown in Table 4 and there were no significant differences between the two groups. The pacemaker group was analysed separately from the ICD group. In the pacemaker group there were no device infections, pacemaker malfunction, early battery depletion or explantation

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of pacemaker due to infection, malfunction and early battery depletion identified after a median follow up of 15.1 months (IQR, 1.3–36.24 months) for the cases and 55.8 months (IQR, 20.3–77.8 months) for the controls. For the pacemaker cases, 10 (19.6%) patients were followed up for five years or more, 18 (35.3%) for one to five years, and 23 (45.1%) for less than a year. For the pacemaker controls, 23 (45.1%) patients were followed up for five years or more, 21 Table 1. Characteristics of patients who received pacemakers Patients Patients with re-used with new pacemakers pacemakers (cases) (controls) p-value 51 51 74.33 ± 17.26 72.86 ± 16.13 0.658

Characteristics Sample size, n Age, years Gender, n (%) Male 24 (47.1) 24 (47.1) 1.00 Female 27 (52.9) 27 (52.9) Co-morbidities, n (%) Hypertension 26 (51) 35 (68.6) 0.069 Diabetes mellitus 7 (13.7) 13 (25.5) 0.135 Renal impairment 17 (33.3) 19 (37.3) 0.679 Cancer 7 (13.7) 3 (5.9) 0.49 Myocardial infarction 6 (11.8) 11 (21.6) 0.29 Cardiomyopathy 4 (7.8) 6 (11.8) 0.74 CVA 12 (23.5) 3 (5.9) 0.02 COPD 5 (9.8) 1 (2) 0.21 Dementia 10 (19.6) 1 (2) 0.008 Baseline function, n (%) NYHA functional class 1 3 (5.9) 7 (13.7) 0.32 NYHA functional class 2 15 (29.5) 27 (52.9) 0.026 NYHA functional class 3 14 (27.5) 14 (27.5) 1.00 Wheelchair bound 4 (7.8) 3 (5.9) 1.00 Bed bound 15 (29.4) 0 (0) < 0.0001 Indications Sick sinus syndrome, n (%) Yes 9 (17.6) 4 (7.8) 0.138 No 42 (82.4) 47 (92.2) AV block, n (%) Yes 38 (74.5) 43 (84.3) 0.22 No 13 (25.5) 8 (15.7) Other, n (%) Yes 4 (7.8) 4 (7.8) No 47 (92.2) 47 (92.2) 1.00 First implantation, n (%) 43 (84.3) 45 (88.2) 0.565 Battery change, n (%) 8 (15.7) 6 (11.8) 0.565 Primary implanter Cardiologist 25 25 1.00 Cardiology registrar 26 26 1.00 Temporal lead, n (%) 17 (33.3) 21 (41.2) 0.413 Follow up at 3 months, n (%) Yes 26 (51) 43 (84.3) < 0.0001 No 25 (49) 8 (15.7) Follow up at 1 year, n (%) Yes 19 (37.3) 38 (74.5) < 0.0001 No 32 (62.7) 13 (25.5) CVA = cerebrovascular accident; COPD = chronic obstructive pulmonary disease; NYHA = New York Heart Association; AV block = atrioventricular block; n = number; (%) = percentage; Other = atrial fibrillation and heart failure.

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Table 2. Pacemaker parameters Patients with Patients with re-used pace- new pacemakParameters makers (cases) ers (controls) p-value DDD, n (%) 11 (21.6) 7 (13.7) 0.30 VVI, n (%) 39 (76.5) 42 (82.4) 0.463 Other, n (%) 1 (2) 2(3.95) Minimum pacing rate, bpm 0.09 63.4 ± 6.0 61.6 ± 5.1 Ventricular pacing, n (%) 50 (98) 49 (96.1) 0.558 Battery voltage, V 2.78 (2.77–2.79) Battery current, A 13.86 ± 4.9 Battery impedance, KΩ 0.482 ± 0.3 Estimated battery life (years) 6.085 ± 1.7 Capture Amplitude, V Atrial 0.323 0.48 ± 0.15 0.57 ± 0.23 Ventricular 0.747 0.49 ± 0.34 0.48 ± 0.18 Pulse width, ms Atrial 0.5 (0.5–0.5) 0.5 (0.475–0.5) 0.485 Ventricular 0.5 (0.5–0.5) 0.5 (0.5–0.5) 0.355 Sensitivity, mV Atrial 4.3 (3.750–5.5) 3.8 (2.875–6.2) 0.255 Ventricular 0.406 14.09 ± 6.50 15.27 ± 7.14 Electrode impedance, Ω Atrial 0.289 692 ± 178 804 ± 275 Ventricular 0.289 748 ± 267 808 ± 285 Other = AAI, V = volts; mV = millivolts; ms = millisecond; Ω = ohms; KΩ = kilo-ohms; A = amperes; bpm = beats per minute; DDD = dualchamber pacemaker; VVI = single-chamber pacemaker.

(41.2%) for one to five years, and seven (13.7%) for less than a year. In the ICD group, there was one device in the re-used device group that delivered inappropriate shocks (inappropriate delivery of shocks for supraventricular tachycardia), during the early stages of implantation but this resolved without any intervention. This device subsequently needed generator replacement after 14 months from implantation. There were no device infections identified after a median follow up of 35.9 months (IQR, 17.0–70.9 months) for the cases and 45.7 months (IQR, 37.6–53.7 months) for the controls. There were no procedure-non-related infections documented for the follow-up period. For the ICD cases, five (41.7%) patients were followed up for five years or more, and seven (58.3%) for one to five years. For the ICD controls, seven (58.3%) were followed up for five years or more, and five (41.7%) for one to five years. In both groups (pacemaker and ICD) there were no devices explanted for infection or malfunctioning during the follow-up period. In the re-used pacemaker group, 26 (51%) patients attended follow up at three months, whereas 25 (49%) did not attend. Of those who did not attend, 11 (44%) had died, nine (36%) were alive, and five (20%) were lost to follow up (Fig. 2). Of those who died, eight (72.7%) were documented to have died from natural causes, one (9.1%) from cancer and two (18.2%) from non-pacemaker-related sepsis, of whom one died within 24 hours of implantation and the other after two months of implantation. The patient who died within 24 hours of device implantation was admitted with a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis prior to pacemaker implantation. In the new pacemaker group, 43 (84.3%) patients attended

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Table 3. Characteristics of patients who received implantable cardioverter defibrillators Patients with Patients with re-used ICDs new ICDs (cases) (controls) n-value 12 12 49.83 ± 17.34 50.58 ± 17.27 0.916

Characteristics Sample size, n Age Gender, n (%) Male 10 (83.3) 10 (83.3) Female 2 (16.7) 2 (16.7) Co-morbidities, n (%) Hypertension 4 (33.3) 4 (33) 1.00 Diabetes mellitus 1 (8.3) 2 (16.7) 0.537 Renal impairment 8 (66.7) 6 (50) 0.408 Cancer 0 (0) 0 (0) Myocardial infarction 7 (58.3) 4 (33.3) 0.49 Cardiomyopathy 3 (25) 2 (1.7) 1.00 CVA 1 (8.3) 1 (8.3) 1.00 COPD 2 (1.7) 0 (0) 0.48 Dementia 0 (0) 0 (0) Baseline function, n (%) NYHA functional class 1 1 (8.3) 5 (41.7) 0.20 NYHA functional class 2 7 (58.3) 7 (58.3) 1.00 NYHA functional class 3 4 (33.3) 0 (0) 0.11 Wheelchair bound 0 (0) 0 (0) Bed bound 0 (0) 0 (0) Ventricular tachycardia, n (%) 9 (75) 10 (83.3) 0.615 Other, n (%) 3 (25) 2 (16.7) 0.615 First implantation, n (%) 12(100) 11(91.7) 0.307 Battery change, n (%) 0(0) 1 (8.3) 0.307 Primary implanter, n (%) Cardiologist 11 (91.7) 12 (100) 1.00 Cardiology registrar 1 (8.3) 0 (0) Follow up at 3 months, n (%) Yes 12 (100) 12 (100) 1.00 No 0 (0) 0 (0) Follow up at 1 year, n (%) Yes 12 (100) 11 (91.7) 0.307 No 0 (0) 1 (8.3) CVA = cerebrovascular accident; COPD = chronic obstructive pulmonary disease; NYHA = New York Heart Association; AV block = atrioventricular block; n = number; (%) = percentage; Other = ventricular fibrillation and arrhythmogenic right ventricular cardiomyopathy.

follow up at three months, whereas eight (15.7%) did not attend follow up. Of those who did not attend, one (12.5%) had died and seven (87.5) were alive (Fig. 2). The patient who died was an 87-year-old man who passed away at home two days after pacemaker implantation from natural causes. In the re-used pacemaker group, at one-year follow up, 19 (37.3%) patients attended follow up, whereas 32 (62.7%) did not attend follow up. Of those who did not attend follow up, 15 (46.9%) had died, nine (28.1%) were alive, and eight (25%) were lost to follow up (Fig. 2). All deaths were due to natural causes except the two who were septic, mentioned above. For the new pacemaker group, 38 (74.5%) patients attended follow up while 13 (25.5%) patients did not attend follow up at one year. Of those who did not attend follow up, three (23.1%) had died, seven (53.8%) were alive and three (23.1%) were lost to follow up (Fig. 2). All deaths were due to natural causes.

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Table 4. Implantable cardioverter defibrillator parameters Patients with re-used ICDs (cases) 12 38.1 ± 4.7 12

Patients with new ICDs (controls) p-value 12 1.00 0.052 44.4 ± 9.4 12 1.00

Parameters VVI, n (%) Minimum pacing rate, bpm Ventricular pacing, % Capture Amplitude, V Ventricular 0.618 ± 0,28 0.708 ± 0.32 0.481 Sensitivity, mV Ventricular 12.925 ± 6.93 16.118 ± 6.17 0.258 Output Amplitude, V Ventricular 3.5 (3.3–3.875) 3.5 (3–3.5) 0.875 Electrode impedance, Ω Ventricular 784.75 ± 304 648.83 ± 147 0.177 V = volts; mV = millivolts; ms = milliseconds; Ω = ohms; KΩ = kilo-ohms; A = amperes; bpm = beats per minute; VVI = single-chamber device.

In the ICD group, there was 100% attendance for both cases and controls at three months’ follow up. At the one-year follow

up, there was 100% attendance for the cases compared to 91.7% for the controls, with one (8.3%) patient absent. However, this patient had been discharged from Groote Schuur Hospital at three months of follow up, to be followed in Port Elizabeth, and was still alive at the time of publication (Fig 2).

Discussion This study shows that the re-use of pacemakers and ICDs was feasible and safe in our group of patients at Groote Schuur Hospital in Cape Town, South Africa. There was no difference in the incidence of device infection, malfunction, battery failure or explantation due to complications between re-used and new devices. Indeed, device implantation was associated with no complications in this series. To the best of our knowledge this is the second study ever published of the outcomes of re-used ICDs.24 In our study, there were no identified device infections and/or devices explanted for malfunction. There were no patients who were lost to follow up in this group Linde et al.,22 in a retrospective case–control study, found no significant difference in device infection, although paradoxically,

Analysed (n = 126)

Pacemakers, n (%) – 102 (81) • Re-used, n (%) – 51 (50) • New, n (%) – 51 (50)

ICDs, n (%) – 24 (19) • Re-used, n (%) – 12 (50) • New, n (%) – 12 (50)

Did not follow up at 3 months, n (%): • Cases: 25 (49) –– Died – 11 (44) –– Alive – 9 (36) –– Unknown status – 5 (20) • Controls: 8 (15.7) –– Died – 1 (12.5) –– Alive – 7 (87.5) Seen at 3 months’ follow up, n (%): • Cases: 26 (51) • Controls: 43 (84.3) Did not follow up at 1 year, n (%): • Cases: 32 (62.7) –– Died – 15 (46.9) –– Alive – 9 (28.1) –– Unknown status – 8 (25) • Controls: 13 (25.5) –– Died – 3 (23.1) –– Alive – 7 (53.8) –– Unknown status – 3 (23.1) Seen at 1-year follow up, n (%): • Cases: 19 (37.3) • Controls: 38 (74.5) ICDs = implantable cardioverter defibrillators n = number (%) = percentage

Fig 2. Follow-up outline.

185

Seen at 3 months’ follow up, n (%) • Cases: 12 (100) • Controls: 12 (100)

Did not follow up at 1 year, n (%): • Controls: 1 (8.3) –– Alive – 1 (8.3)

Seen at 1-year follow up, n (%): • Cases: 12 (100) • Controls: 11 (91.7)

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more infections were found in the new pacemaker group (7%) than in the re-used pacemaker group (2%). Kantharia et al.25 found no significant complications in an Indian study cohort of 53 patients who received cadaveric donated resterilised pacemakers over a mean follow up of 661 days. Panja et al.26 found no difference in infection rates between the new pacemaker group and cadaver-donated re-used pacemakers. However, higher rates of infection were found on infected re-sterilised devices that were implanted in the same patient, which were taken out and implanted on the opposite side. They attributed this higher infection rate to haematogenous or lymphatic spread from the previously infected pocket.26 Rosengarten et al.27 also found no significant difference in major pacemaker-related complications and reported that re-use of devices is cost effective. Pavri et al.,24 in a retrospective, single-centre cohort study of re-sterilised ICDs found no device-related infections, and 60.4% re-used ICDs delivered life-saving shocks. Baman et al.,28 in a meta-analysis of 18 studies, found no significant difference in infection rates between the new device group and the re-used device group, but much higher device malfunction was associated with re-used devices compared to new devices. This malfunction was attributed to abnormality in the set screws.28 In a recent study, Nava et al.23 found no significant difference in infection rates between re-used and new devices, although more infections were found in the new device group. They also found more device malfunction in the re-use device group, which was similar to the above studies, and the fault was also attributed to faulty pacemaker screws.23 Device infection is thought to be associated with mortality rates between 2.6 and 18%.12-14 However studies that examined this issue showed no significant difference in infection or mortality rates between re-used and new device implantation.14-22 In our study we did not compare mortality rates between the two groups because of the selection bias of those who received a re-used pacemaker. From the findings of this study and also acknowledging its limitations, pacemaker and ICD re-use is feasible and safe. It is a reasonable option for those who cannot afford new devices, provided that proper selection and sterilisation measures of re-used devices are followed. In the developing world, where there are major resource constraints, this option should be explored for the benefit of those suffering from symptomatic bradyarrhythmias and life-threatening tachyarrhythmias. We acknowledge several limitations of our study. First, this was a retrospective study with a small sample size of cases with re-used pacemakers and ICDs. Second, the follow-up period of patients with re-used devices was relatively short, with a median period of 15 months, with a significant number of patients who died within three months of device insertion. Finally, the patients who were selected for re-used pacemakers had significant co-morbidities, which were associated with a shortened life-span. These factors may limit the generalisability of the study, and call for appropriate prospective studies to answer this question.

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pacemakers and ICDs are a realistic option for patients with co-morbidities who live in developing countries where there is limited access to pacemakers and ICDs.

References 1.

Tracy CM, Ebstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines and Heart Rhythm Society. Circulation 2012; 126: 1784–1800.

Baman TS, Kirkpatrick JN, Eagle KA, et al. Re-use of pacemakers and defibrillators in developing countries: logistical, legal, and ethical barriers and solutions. Heart Rhythm 2010; 7: 1623–1627.

Baman TS, Kirkpatrick JN, Lange DC, et al. Pacemaker reuse: an initiative to alleviate the burden of symptomatic bradyarrhythmia in impoverished nations around the world. Circulation 2010; 122: 1649–1656.

Mayosi BM, Millar RNS. The 1995 survey of cardiac pacing in South Africa. S Afr Med J 1998; 88(Suppl 4): C207–C213.

Mayosi B M, Scott Millar RN. Permanent cardiac pacing in Africa. East Afr Med J 2000; 77: 339.

Mond HG, Proclemer A. The 11th World Survey of Cardiac Pacing and Implantable Cardioverter–Defibrillators: calendar year 2009 – A World Society of Arrhythmia’s project. PACE 2011; 34: 1013–1027.

Hussain M, Balsara KP, Nagral S. Reuse of single-use devices: looking back, looking forward. Natl Med J India 2012; 25:151–155.

Myers GH. Is reuse financially worthwhile? Pacing Clin Electrophysiol 1986; 9(pt 2): 1288–1294.

Rydén L. Re-use of devices in cardiology: proceedings from a policy conference at the European Heart House, 5–6 February, 1998. Eur Heart J 1998; 19: 1628–1631.

10.

Hailey D, Jacobs PD, Ries NM, Polisena J. Reuse of single use medical devices in Canada: clinical and economic outcomes, legal and ethical issues, and current hospital practice. Int J Technol Assess Health Care 2008; 24: 430–436.

11. Alfa MJ, Castillo J. Impact of FDA policy change on the reuse of single-use medical devices in Michigan hospitals. Am J Infect Control 2004; 32: 337–341. 12. Catanchin A, Murdock CJ, Athan E. Pacemaker infections: a 10-year experience. Heart Lung Circ 2007; 16: 434–439. 13. Villamil Cajoto I, Rodriguez Framil M, van den Eynde Collado A, Jose Villacian Vicedo M, Canedo Romero C. Permanent transvenous pacemaker infections: an analysis of 59 cases. Eur J Intern Med 2007; 18: 484–488. 14. Baman TS, Gupta SK, Valle JA, Yamada E. Risk factors for mortality in patients with cardiac device-related infection. Circ Arrhythm Electrophysiol 2009; 2: 129–134. 15. Grendahi H. Pacemaker re-use. Tidsskr Nor Leegeforen 1994; 114: 3420–3423. 16. Pescariu S, Stiubel M, Cozma D, Ioanovici T, Branea H, Luca CT, et al. La re´utilisation des pacemakers, une alternative pour les personnes aˆge´es de´munies: etude re´trospective. Stimucouer 2003; 31: 186–189. 17. Mugica J, Duconge R, Henry L. Survival and mortality in 3,701 pacemaker patients: arguments in favor of pacemaker reuse. Pacing Clin

Conclusion Pacemaker and ICD re-use is feasible and safe in the short term (i.e. over months) provided that the devices for re-use are selected carefully and proper sterilisation methods are followed. Re-used

Electrophysiol 1986; 9(pt 2): 1282–1287. 18. Sethi KK, Bhargava M, Pandit N, Mohan JC, Arora R, Khanna SK, Khalilullah M. Experience with recycled cardiac pacemakers. Indian Heart J 1992; 44: 91–93. 19. Gakenheimer L, Lange DC, Romero J, et al. Societal views of pace-

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187

maker reutilization for those with untreated symptomatic bradycardia

Mascarenhas DA. Reuse of explanted, resterilized implantable cardi-

in underserved nations. J Interv Card Electrophysiol 2011; 30: 261–266.

overter-defibrillators: a cohort study. Ann Intern Med 2012; 157(8):

20. Hughey AB, Baman TS, Kirkpatrick JN, Crayford TC, et al. Heart Rhythm Society Members’ views on pacemaker and implantable cardioverter-defibrillator reuse. PACE 2014; 37: 1–9.

542–548. 25. Kantharia BK, Patel SS, Kulkarni G, Shah AN, Lokhandwala Y, Mascarenhas E, Mascarenhas DA. Reuse of explanted permanent pace-

21. Gakenheimer L, Crayford TC, Romero J, Baman TS, et al. Cardiac implantable electronic device reutilization: Battery life of explanted devices at a tertiary care center. PACE 2014; 37: 569–575.

makers donated by funeral homes. Am J Cardiol 2012; 109: 238–240. 26. Panja M, Sarkar CN, Kumar S, Kar AK, Mitra S, Sinha DP, et al. Reuse of pacemaker. Indian Heart J 1996; 48: 677–680.

22. Linde CL, Bocray A, Jonsson H, Rosenqvist M, Rådegran K, Rydén L.

27. Rosengarten M, Chiu R, Hoffman R. A prospective trial of new versus

Re-used pacemakers: as safe as new? A retrospective case-control study.

refurbished cardiac pacemakers: a Canadian experience. Can J Cardiol 1989; 5: 155–160.

Eur Heart J 1998; 19: 154–157. 23. Nava S, Morales JL, Jose L, et al. Reuse of pacemakers: comparison of short and long-term performance. Circulation 2013; 127: 1177–1183 24. Pavri BB, Lokhandwala Y, Kulkarni GV, Shah M, Kantharia BK,

28. Baman TS, Meier P, Romero J, Gakenheimer L, Kirkpatrick JN, Sovitch P, et al. Safety of pacemaker reuse: a meta-analysis with implications for underserved nations. Circ Arrhythm Electrophysiol 2011; 4: 318–323.

OBESITY

LIPIDAEMIA DYS

IN RESISTANCE INSUL

HYPERTENSION

ETES & DIAB

ATH EROSCLEROSIS

CUL

AR DISEASE

HYPER INSULINAEMIA THROMBOSIS

HYP

ERGLYCAEMIA

This peer-reviewed journal is available as full text at all tertiary institutions in South Africa, presenting a great opportunity to submit your good-quality original articles for speedy publication. Recent user research has shown that some 10 000 annual topic searches were done on the SA Journal of Diabetes & Vascular Disease database, which contains seven years of published material.

Call for Articles

The SA Journal of Diabetes & Vascular Disease aims to provide a forum for specialists involved in the care of people with diabetes, to exchange information, promote better management and stimulate research in Africa. This quarterly journal publishes original research and scholarly reviews about prevention and management of diabetes, relating to both general and specific issues. The SA Journal of Diabetes & Vascular Disease invites you to submit your articles online only. Read the Instructions to Authors at www.diabetesjournal.co.za for more information on the journal’s policies and the submission process.

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Review Articles Glycaemic, blood pressure and cholesterol control in 25 629 diabetics Y Pinchevsky, N Butkow, T Chirwa, FJ Raal

Abstract Objective: To examine and compare the extent to which people with type 2 diabetes (T2DM) are achieving haemoglobin A1c (HbA1c), blood pressure (BP) and LDL cholesterol (LDL-C) treatment targets. Methods: A review of databases (MEDLINE Ovid, Pubmed and Sabinet) was performed and limited to the following terms: type 2 diabetes mellitus AND guideline AND goal achievement for the years 2009 to 2014 (five years). Results: A total of 14 studies (25 629 patients) were selected across 19 different countries. An HbA1c level of 7.0% (or less) was achieved by 44.5% of subjects (range 19.2–70.5%), while 35.2% (range 7.4–66.3%) achieved BP of 130/80 mmHg (or less), and 51.4% (range 20.0–82.9%) had an LDL-C level of either 2.5 or 2.6 mmol/l (100 mg/dl or less). Conclusion: Despite guideline recommendations that lowering of HbA1c, BP and lipids to target levels in T2DM will lead to a reduction in morbidity and mortality rates, we found that control of these risk factors remains suboptimal, even across different settings. Keywords: type 2 diabetes mellitus, guidelines, goal achievement Submitted 17/10/14, accepted 17/5/15 Cardiovasc J Afr 2015; 26: 188–192

www.cvja.co.za

DOI: 10.5830/CVJA-2015-050

Diabetes mellitus (DM) is a chronic, progressive condition leading to significant morbidity and premature death, and is an economic burden to any healthcare system. According to the

Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Y Pinchevsky, BPharm, MSc (Pharm), jpinchevsky@gmail.com N Butkow, BSc (Hons), PhD

Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa T Chirwa, BSc, MSc, PGDip, PhD

Carbohydrate and Lipid Metabolism Research Unit, Division of Endocrinology and Metabolism, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa FJ Raal, FRCP, FRCPC, FCP (SA), Cert Endo, MMed, PhD

International Diabetes Federation (IDF), there were 366 million people living with diabetes in 2011.1 By 2035, it is predicted that more than half a billion people will have the disease. Trends in urbanisation and the adoption of unhealthy Western lifestyles have begun to affect low- and middle-income countries (LMICs). A prime example of this is South Africa, which previously had the dubious pleasure of infectious diseases being the primary source of mortality. Today, expansion of non-communicable diseases (NCD) is beginning to manifest and deplete the already strained health resources available.2 Rather than being limited to glycaemia alone, the management of type 2 diabetes mellitus (T2DM) includes multiple priorities, including identification and treatment of other modifiable risk factors. It is widely accepted that T2DM is associated with cardiovascular disease (CVD) and increased mortality rates.3 In addition to lifestyle changes, the importance of reduction in levels of low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) has become an essential primary goal for the prevention of CVD in T2DM.4,5 Furthermore, improved outcomes of diabetes-related chronic microvascular complications (retinopathy, neuropathy and nephropathy) are achieved through substantial reductions in incidence of both hyperglycaemia and hypertension. It is on the basis of this research that the Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) recommends that most adults with diabetes should aim for an HbA1c level of 7.0%, BP of 140/80 mmHg and LDL-C level of 2.5 mmol/l or less.6 There are many gaps in the management of T2DM that are proving difficult to close. Studies have revealed how clinical practice differs from clinical trials in that T2DM patients often cannot reach guideline-recommended targets. One of the ways to improve clinical outcomes is by comparing the performance of one clinical setting against another. In this study, our aim was to compare the achievement of the critical quality indicators: glycaemic, BP and lipid control in T2DM patients from different countries worldwide, in an attempt to benchmark which approach has been most successful.

Methods This study was a literature review using Ovid MEDLINE, Pubmed and Sabinet databases. Studies included were those conducted in the past five years (2009–2014) and limited to the following key terms: type 2 diabetes mellitus AND guideline AND goal achievement (HbA1c, glycated haemoglobin, blood pressure, systolic, diastolic, lipids, cholesterol, LDL cholesterol). We also reviewed a selected number of reference lists of other

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reviews and hand-searched several medical journals. Studies that reported achievement of guideline-recommended targets of major risk factors for T2DM were included. The primary objective of this review was to provide an overview of achievement of major risk-factor targets (HbA1c, BP and LDL-C) in the treatment of a sample of T2DM patients from different parts of the world. Specifically, the objectives would be addressed through comparison of the achievement of HbA1c, BP and LDL-C targets, according to local or international guidelines, across different study samples. The following data were extracted from the studies: author details, year of publication, study location, cohort size and achievement of major risk factors (combined systolic and diastolic BP, and HbA1c and LDL-C levels). As different samples of study countries followed different guideline targets, flexibilities around these differences was needed. Studies selected for this article may have differed in the following parameters: recruitment and randomisation methods, total number of study participants recruited, study sites (e.g. single or multicentre), gender ratios, ethnicity ratios, timelines of results presented (e.g. single or longitudinal data) and periods of enrollment. To compare results, we standardised (or converted or conformed) certain measurement units in order to maintain consistency (e.g. LDL-C in mmol/l instead of mg/dl). The control or baseline results of studies were reported instead of interventional group data. Only the latest data were selected from studies with multiple time periods. Studies excluded from the review had one or more of the following characteristics: non-English language, studies conducted before 2009, participating patients younger than 18 years of age, participants reported to have had any diabetes other than T2DM (e.g. gestational, type 1 or steroid induced), studies that reported insufficient data or less than two of the three major risk factors being compared, and studies that consisted of large HMO claims databases. The latter was chosen as an exclusion criterion as larger-sized cohort studies would have biased the results of this review. Data presented in this article were collected from the results of other studies and are limited to the authors’ definitions of control. This review did not allow for the access of patient-level data of different studies included in the review to be accessed. It was assumed that all data extracted for this study were collected from the medical records of patients who willingly participated in the studies included in this review. The relevant data were captured into a secure database using Microsoft Excel 2010. Ethical approval was obtained from the University of the Witwatersrand Human Research Ethics Committee (Medical).

Results The authors of this study set out to determine how diabetes care compared across different settings, given the healthcare challenges faced especially by under-resourced areas. Of the 511 (154 from Ovid MEDLINE + 32 Pubmed + 325 Sabinet) titles initially identified between 2009 and 2014, 14 studies fulfilled the inclusion criteria. These 14 studies originated from 19 different countries (some studies included more than a single country) and we enrolled a total of 25 629 patients. There were 17 high-income, one upper-middle- (South Africa) and one low-income (Uganda) country included in the

review (grouped according to the United Nations’ economies by per-capita country classification).7 Cohort sizes ranged from 50 to 4 926 patients. Twelve studies contained results for all major risk factors (HbA1c, BP and LDL-C), while the rest included at least two-thirds of the measured risk factors. There were eight studies (57.1%) that defined treatment targets as per the American Diabetes Association.8 The characteristics of each study are outlined in Table 1. In 12 studies (25 354 patients) that used an HbA1c level of 7.0% or less to define control, 44.5% (range 19.2–70.5%) of patients achieved target.9-20 In two studies (275 patients) where HbA1c level was defined as < 6.5 and < 8.0%, respectively, 56.6 and 60.0% of patients reached their targets, respectively.21,22 In eight studies (18 089 patients), which had the definition of target BP of 130/80 mmHg or less (systolic and diastolic combined), 35.2% (range 7.4–66.3%) of patients achieved target.9-11,16-19,21 In four studies (7 240 patients) where systolic BP targets of 130 mmHg or less (alone) defined control, 32.7% (range 21.3–50.0%) of the subjects achieved target.12,13,15,20 In two studies (300 patients) with a BP target of either < 140/90 or < 140/80 mmHg, 24.0 and 56.0% of patients achieved goal, respectively.14,22 Table 1. Study characteristics First author (reference)

Year of publication Location

Achievement of target Cohort size HbA1c BP (< 130/ LDL-C (n) (< 7%) 80 mmHg) (< 2.6mmol/l)

Al-Taweel9

2013

Kuwait

652

19.2

46.0

–

Braga10

2012

Canada

3002

52.6

53.6

64.2||

Casagrande11

2013

USA

4926

52.5

51.1

56.2

Goderis12

2009

Belgium

2495

54.0

50.0‡

Hermans13

2013

Belgium, Greece, Luxembourg, Portugal, Spain, UK

3996

49.2

27.3‡

40.8

Kibirige14

2014

Uganda

250

20.8

56.0§

20.0

Klisiewicz15

2009

South Africa

150

30.7

21.3‡

50.7||

Lee16

2009

Korea

926

49.2

66.3

51.0

Morren21

2010

Trinidad

225

56.6†

53.6

49.3**

Pinchevsky17

2013

South Africa

666

26.2

45.8

53.8||

Sease18

2013

USA

35.8

62.1

82.9

Stone19

2013

Belgium

1044

59.7

27.6

49.7

Stone19

2013

France

1056

65.3

14.9

52.4

Stone19

2013

Germany

959

48.6

7.4

30.7

Stone19

2013

Ireland

950

53.4

24.9

76.9

Stone19

2013

Italy

984

35.7

20.8

40.4

Stone19

2013

Netherlands

1021

70.5

20.3

58.9

Stone19

2013

Sweden

Stone19

2013

UmarKamara22

2011

USA

Webb20

2014

South Africa

550

56.5

27.1

47.3

1033

39.1

25.0

74.5

60.0*

24.0¶

–

599

27.0

32.0#

33.0||

Exceptions to the above targets are indicated by the following: † HbA1c < 6.5%;*HbA1c < 8.0%; ‡ systolic blood pressure only < 130 mmHg; § systolic/diastolic blood pressure < 140/80 mmHg; ¶systolic/diastolic blood pressure < 140/90 mmHg; || low-density lipoprotein cholesterol < 2.5 mmol/l; ** total cholesterol < 5.18 mmol/l.

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In the 11 studies (24 702 patients) that used LDL-C levels of either 2.5 or 2.6 mmol/l (100 mg/dl or less) to define control, 51.4% (range 20.0–82.9%) of patients achieved goal.10-20 One study (225 patients) with a total cholesterol target of < 200 mg/ dl (5 mmol/l) had 49.3% of patients at goal.21 Two studies (702 patients) did not measure lipid levels.9,22 In general, more patients reached target for LDL-C than for HbA1c levels, with the poorest achievement of targets being BP. The widest variability of target achievement was LDL-C (variation of 62.9%), followed by BP and then HbA1c (least variability). The highest and lowest achieved targets were those by an American (LDL-C, 82.9%) and a German study (BP, 7.4%), respectively.18,19

Discussion The quality of diabetes care cannot simply be measured across proportions of patients achieving guideline targets. However, a broad overview of the quality of care can be gauged when comparing target adherence across different countries, especially with adequately sized samples of patients. Hence the reason for this review, where countries from various economies were compared, according to achievement of modifiable risk factors against the guidelines. Based on the results of other studies, this review set out to establish the achievement of major risk-factor targets (HbA1c, BP and LDL-C levels) in the treatment of DM patients in different parts of the world. Given the increasing prevalence of T2DM, effective management of critical diabetes risk factors can significantly contribute towards improved outcomes. Attaining targets requires improved methods to increase adherence to lifestyle (exercise/diet) and pharmacological interventions. From this review, it was evident that certain studies appeared to be more successful at managing patients’ risk factors than others. Practitioners achieving better guideline adherence should be encouraged to share their management strategies for implementation with other healthcare facilities. Hermans et al. found that by benchmarking the level of care of ‘three paramount cardiovascular risk factors’ in a primary care setting has in itself led to a clinically significant improvement in T2DM care over time.13 There is also evidence to suggest that performance with regard to management of a disease, when compared between a physician and his/her colleagues, has brought about an intellectual, emotional and competitive incentive for change.23 The most critical ways of reducing T2DM complications is by collectively managing HbA1c, BP and LDL-C levels. More patients achieved LDL-C than HbA1c targets in the studies reviewed, potentially owing to the progressive nature of the disease, where β-cell function gradually declines over time. BP control was the least-achieved risk factor across all the studies, and according to McLean et al., may have occurred due to the ‘inadvertent under emphasis’ of treating T2DM-associated risk factors (such as hypertension, when there is strong emphasis on glucose control).24 Perhaps it was due to inadequate dosages, poor adherence to medication, poor access to follow-up care or a combination of these. A well-designed, randomised, controlled trial may help address these questions. Once considered rare in sub-Saharan Africa, the prevalence of T2DM is rapidly increasing. As many as four out of every five diabetics reside in LMICs, many of whom remain undiagnosed.1

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T2DM is a complex, resource-intensive disease requiring multifactorial yet individually tailoured, lifelong treatment. Most of the studies found and included in this review were from higher-income countries. However patterns of poor control rates were common across all settings. For instance, less than 40% of patients from the USA, Europe (specifically Italy) and the UK studies (all high-income countries) achieved HbA1c levels (< 7%) comparable with those of lower- to upper-middleincome countries (Uganda and South Africa, respectively).14,17-20 Similarly, the combined results of six European countries, and other individual studies, had less than half of patients at LDL-C target, as seen in two separate non-high-income countries.13,14,20 Yet on the other hand, and possibly as expected from moredeveloped nations, two to three times more patients from separate European (specifically the Netherlands) and a USA study achieved HbA1c (< 7%) and LDL-C (< 2.6mmol/l) targets in comparison with a lower-income country, respectively.14,19,22 The differences across the sites in their abilities to achieve guideline targets may be attributed to socio-economic reasons. In resource-rich settings, where patients supposedly receive the extra time required for diabetes care through more regular physician interactions or appointments, appropriate reminder systems and adherence monitoring, this may improve the standards of diabetes care received. Lower-income countries face the realities of inadequate healthcare infrastructure, regular medication stock outs, few educational programmes and minimal healthcare facilities/professionals.25 This literature review covered the influences of multiple background factors occurring across healthcare systems in different countries, hence the differences in targets achieved across the environments studied. As described above, Africa faces many healthcare challenges, both within and between countries. Despite resource constraints, by targeting the modifiable risk factors associated with DM, there is still the potential for improvement, and better patient outcomes. This review serves to highlight the proportion of patients achieving guideline targets across different settings. The aim of this review was to serve as a benchmark for those countries selected, in order to measure their performance against each other in terms of achieving guideline targets. By recognising those healthcare settings with increased patient numbers achieving guideline targets, this could allow for future studies to identify the mechanisms and processes used to achieve their targets. Areas of interest for the improvement of diabetes care could include: organisational characteristics such as improved implementation of adherence to clinical guidelines (evidence-based), identification of individuals to act as guideline champions to deliver more performance measures, and feedback to healthcare providers on progress made. Perhaps, once identified, the settings achieving less-favourable control of modifiable risk factors may begin to explore approaches used in the more successful settings. In addition, given the chronic progressive nature of DM, it is hoped that attention will be prioritised not just on treatment but also on prevention strategies in those settings wishing to improve their level of diabetes care offered. It has been predicted that the ageing populations of LMICs will face a significant increase in mortality rate due to NCDs over the next 25 years.26 Although not included in this review, a previous South African study revealed that only 30.4% of the 899 patients achieved HbA1c levels < 7%, which is similar to the three

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studies included in this review from the same locale.27 The three South African studies included in this review had noticeably fewer patients at HbA1c goal in comparison with other countries. One of the reasons for this may have been that all the South African studies included in this review were from the public sector, which has often been described as ‘overburdened’, and due to resource constraints, cannot always offer appropriate levels of healthcare or access to the most modern diabetes treatments currently available in South Africa’s private sector or in those high-income countries included in this study. Furthermore, many of the patients serviced in South Africa’s public sector settings originate from a lower socioeconomic background, which may indicate lower educational levels or limited access to healthier lifestyle choices. Perhaps HbA1c level is still the most challenging of risk factors to control, especially in less-developed economies.

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risk factors. Our review revealed that control of major risk factors did not differ significantly between countries or healthcare settings. There is substantial room for improvement in the way T2DM patients are being managed for their condition. Further efforts through multidisciplinary action to improve guideline adherence is critical for the prevention or delay of diabetesrelated complications.

References 1.

International Diabetes Federation. IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, 2013. http://www. idf.org/diabetesatlas (accessed 16 October 2014).

Hall V, Thomsen RW, Henriksen O, et al. Diabetes in sub-Saharan Africa 1999–2011: epidemiology and public health implications. A systematic review. BMC Public Health 2011; 11: 564. [http://dx.doi.

Study limitations Studies included in this review differed with regard to guidelines or targets, however, we tried to overcome this by consistently capturing and comparing similar risk factors using standardised units. Patients selected for the studies included in the review were treated to ‘moving targets’ and therefore studies conducted in the past five years only (2009–2014) were included, as recent guidelines have more similar targets. Some eight out of the 14 studies provided information on the type of methods used for clinical and laboratory-based measurements, but with differing levels of detail. Notably, only two studies confirmed use of DCCT-standardised laboratory analysers for HbA1c analysis. By converting to similar units (e.g. LDL-C from mg/dl to mmol/l), target values in this retrospective study (Table 1) were presented in a format that would allow for comparison. Ideally, a centralised laboratory should have been used for measurements included in this study, however, we relied on previously obtained measurements from other studies. We therefore cannot guarantee the accuracy or precision of measurements in the studies selected for this review, as methodologies may have differed. Studies from resourcerich settings may have implemented newer, more sophisticated and improved methods for A1c and LDL-C measurements, influencing the results of those specific studies. This review did not stratify the selected individual studies according to patient profiles, severity of disease, clinical settings (clinic or hospital) or involvement of specialists (factors affecting how individuals are managed and able to reach guideline targets). Although smoking is considered a critical risk factor in the prevention and management of CVD, it was not included as a crucial study parameter for this review (partly due to many studies not reporting this). Although previously identified as a source of bias, we only included studies published in English, which according to an analysis, has little effect on summaries of treatment effect estimates.28 Publication bias may have occurred in our study in that a single reviewer (author) carried out the searches without the use of specific methodology (e.g. Cochrane data system).

org/10.1186/1471-2458-11-564]. 3.

Hayat SA, Patel B, Khattar RS, et al. Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clin Sci 2004; 107(6): 539–557. [http:// dx.doi.org/10.1042/CS20040057].

Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685–696. [http:// dx.doi.org/10.1016/S0140-6736(04)16895-5].

UK Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38). Br Med J 1998; 317: 703–713. [http:// dx.doi.org/10.1136/bmj.317.7160.703].

The 2012 SEMDSA guideline for the management of type 2 diabetes. J Endocrinol Metab Diabetes S Afr 2012; 17(1): S1–S95. http://www. semdsa.org.za/images/2012_SEMDSA_Guideline_July_FINAL.pdf (accessed 16 October 2014).

Development Policy and Analysis Division (DPAD) of the Department of Economic and Social Affairs of the United Nations Secretariat (UN/ DESA). World Economic Situation and Prospects 2013. http://www. un.org/en/development/desa/policy/wesp/wesp_current/2013country_ class.pdf (accessed 16 October 2014).

American Diabetes Association. Standards of medical care in diabetes 2011. Diabetes Care 2011; 34(Suppl 1): S11–S61. [http://dx.doi. org/10.2337/dc11-S011].

Al-taweel DM, Awad AI, Johnson BJ. Evaluation of adherence to international guidelines for treating patients with type 2 diabetes mellitus in Kuwait. Int J Clin Pharm 2013; 35(2): 244–250. [http://dx.doi. org/10.1007/s11096-012-9738-8].

10. Braga MF, Casanova A, Teoh H, et al. Poor achievement of guidelinesrecommended targets in type 2 diabetes: findings from a contemporary prospective cohort study. Int J Clin Pract 2012; 66(5): 457–464. [http:// dx.doi.org/10.1111/j.1742-1241.2012.02894]. 11. Stark Casagrande S, Fradkin JE, Saydah SH, et al. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988–2010. Diabetes Care 2013; 36(8): 2271–2279. [http://dx.doi. org/10.2337/dc12-2258]. 12. Goderis G, Borgermans L, Heyrman J, et al. Type 2 diabetes in primary care in Belgium: need for structured shared care. Exp Clin Endocrinol Diabetes 2009; 117(8): 367–372. [http://dx.doi.

Conclusion The results presented in this study demonstrate that T2DM patients remain inadequately controlled for their cardiovascular

org/10.1055/s-0028-1103286]. 13. Hermans MP, Elisaf M, Michel G, et al. Benchmarking is associated with improved quality of care in type 2 diabetes: the OPTIMISE randomized, controlled trial. Diabetes Care 2013; 36(11): 3388–3395. [http://

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dx.doi.org/10.2337/dc12-1853].

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2010; 18(5): 335–343.

14. Kibirige D, Atuhe D, Sebunya R, et al. Suboptimal glycaemic and

22. Umar-Kamara M, Adams Tufts K. Impact of a quality improvement

blood pressure control and screening for diabetic complications in adult

intervention on provider adherence to recommended standards of care

ambulatory diabetic patients in Uganda: a retrospective study from a

for adults with type 2 diabetes mellitus. J Am Assoc Nurse Pract 2013;

developing country. J Diabetes Metab Disord 2014; 13(1): 40. [http:// dx.doi.org/10.1186/2251-6581-13-40].

25(10): 527–534. [http://dx.doi.org/10.1111/1745-7599.12018]. 23. Nobels F, Debacker N, Brotons C, et al. OPTIMISE (OPtimal Type

15. Klisiewicz AM, Raal FJ. Sub-optimal management of type 2 diabetes

2 dIabetes Management Including benchmarking and Standard trEat-

mellitus – a local audit. J Endocrinol Metab Diabetes S Afr 2009; 1(14):

ment) International Steering Committee. Study rationale and design of

13–16. [http://dx.doi.org/10.1080/22201009.2009.10872186].

OPTIMISE, a randomised controlled trial on the effect of benchmark-

16. Lee YS. The current status of type 2 diabetes management at a university hospital. Korean Diabetes J 2009; 33: 241–250. [http://dx.doi. org/10.4093/kdj.2009.33.3.241].

ing on quality of care in type 2 diabetes mellitus. Cardiovasc Diabetol 2011; 10: 82. [http://dx.doi.org/10.1186/1475-2840-10-82]. 24. Mclean DL, Simpson SH, McAlister FA, et al. Treatment and blood

17. Pinchevsky Y, Butkow N, Raal FJ, Chirwa T. The implementation

pressure control in 47,964 people with diabetes and hypertension: a

of guidelines in a South African population with type 2 diabetes. J

systematic review of observational studies. Can J Cardiol 2006; 22(10):

Endocrinol Metab Diabetes S Afr 2013; 18(3): 154–158 [http://dx.doi. org/10.1080/22201009.2013.10872322]. 18. Sease JM, Franklin MA, Gerrald KR. Pharmacist management of patients with diabetes mellitus enrolled in a rural free clinic. Am J Health Syst Pharm 2013; 70(1): 43–47. [http://dx.doi.org/10.2146/ajhp120221]. 19. Webb EM, Rheeder P, van Zyl DG. Diabetes care and complications in primary care in the Tshwane district of South Africa. Prim Care Diabetes 2015; 9(2): 147–154. [http://dx.doi.org/10.1016/j.pcd.2014.05.002].

855–860. [http://dx.doi.org/10.1016/S0828-282X(06)70304-X]. 25. Motala AA. Diabetes trends in Africa. Diabetes Metab Res Rev 2002; 18 (Suppl 3): S14–20. [http://dx.doi.org/10.1002/dmrr.284]. 26. Mathers C, Fat DM, Boerma JT. The global burden of disease: 2004 update. Geneva: World Health Organization, 2008. http://www.who.int/ healthinfo/global_burden_disease/GBD_report_2004update_full.pdf (accessed 16 October 2014). 27. Amod A, Riback W, Schoeman HS. Diabetes guidelines and clinical

20. Stone MA, Charpentier G, Doggen K, et al. Quality of care of people

practice: Is there a gap? The South African cohort of the International

with type 2 diabetes in eight European countries: findings from the

Diabetes Management Practices Study. J Endocrinol Meetab Diabetes

Guideline Adherence to Enhance Care (GUIDANCE) study. Diabetes

S Afr 2012; 17(2): 85–90. [http://dx.doi.org/10.1080/22201009.2012.10

Care 2013; 36(9): 2628–2638. [http://dx.doi.org/10.2337/dc12-1759].

872282].

21. Morren JA, Baboolal N, Davis GK, McCrae A. Assessment of treat-

28. Jüni P, Holenstein F, Sterne J, et al. Direction and impact of language

ment goals attained by patients according to guidelines for diabetes

bias in meta-analyses of controlled trials: empirical study. Int J

management in primary care centres in North Trinidad. Qual Prim Care

Epidemiol 2002; 31(1): 115–123. [http://dx.doi.org/10.1093/ije/31.1.115].

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Why is control of hypertension in sub-Saharan Africa poor? YK Seedat

Abstract In sub-Saharan Africa (SSA) in 2010, hypertension (defined as systolic blood pressure ≥ 115 mmHg) was the leading cause of death, increasing 67% since 1990. It was also the sixth leading cause of disability, contributing more than 11 million adjusted life years. In SSA, stroke was the main outcome of uncontrolled hypertension. Poverty is the major underlying factor for hypertension and cardiovascular disease. This article analyses the causes of poor compliance in the treatment of hypertension in SSA and provides suggestions on the treatment of hypertension in a poverty-stricken continent. Keywords: hypertension, control, sub-Saharan Africa Submitted 23/3/15, accepted 31/7/15 Cardiovasc J Afr 2015; 26: 193–195

www.cvja.co.za

DOI: 10.5830/CVJA-2015-065

In sub-Saharan Africa (SSA) in 2010, hypertension (defined as systolic blood pressure ≥ 115 mmHg) was the leading cause of death, increasing 67% since 1990. Hypertension was estimated to have caused over 500 000 deaths and 10 million years of life lost in 2010.1,2 It was also the sixth leading risk for a life of disability, contributing more than 11 million disability-adjusted life years. Hypertension is the major cause of 50% of heart disease, stroke and heart failure. It is involved in 13% of deaths overall and over 40% of deaths in those with diabetes.1,2 Hypertension is a leading risk for foetal and maternal death during pregnancy, as well as for dementia and renal failure.1,2 In SSA, stroke, the major outcome of uncontrolled hypertension, has increased 46% since 1990 to become the fifth leading cause of death.1,2 In 1983, an age-adjusted prevalence study of the adult population of Durban showed that hypertension, according to the World Health Organisation (WHO) criteria, was highest in urban blacks of the Zulu tribe (25%), intermediate in whites (17%), lower in ethnic Indians, and lowest in rural blacks (9%). Our studies showed that 90% of our Zulu patients had undiagnosed hypertension, and 58% of Indian patients and 77% of white subjects had hypertension that was untreated or they had discontinued therapy.3 The first Demographic and Health Survey in South Africa in 1998 showed high levels of hypertension with inadequate treatment status.4 Low compliance is the main reason for poor control of blood pressure. Compliance has assumed great importance because it plays a major role in the successful treatment of health problems. Compliance is defined as the extent to which a person’s behaviour

Department of Internal Medicine, University of KwaZulu Natal, Durban, South Africa YK Seedat, MD (NU, Irel), FRCP (Lond), FACC, Seedaty1@ukzn.ac.za

coincides with medical or health advice. This behaviour includes taking medication, keeping health-related appointments, and making lifestyle changes (diet, alcohol consumption, smoking cessation and physical exercise). It is difficult to define compliance in terms of appointment keeping. Compliance is measured by quantitative and qualitative measurement of medications, pill counting, hospitalisation of patients, characteristics of medication, and physician–patient relationship. Physician compliance is assessed by patient perceptions, socio-demographic characteristics, behaviour modification, physician instruction, social support, and reduction in complexity of drugs. Compliance in SSA is a major problem in the treatment of hypertension. However, little is known about the pricing of drugs in SSA. What is known is that the cost is borne by the patient (out-of-pocket expenditure) and medication is not subsidised by government or social insurance. Antihypertensive drugs within the same class and between classes have large differences in price. Those drugs listed in the WHO International Drug Indicator Guide were found to be cheaper. Adding advocated drugs onto countries’ national lists could reduce the price. The Oxfam report5 (2007) titled ‘Pharma companies deny medicine to millions’ states that big pharmaceutical companies need to change the way they work, so as to reach 83% of the world’s consumers who don’t have access to medicines. The report lists the shortcomings of industry, which (1) had failed to implement a transparent, tiered pricing policy when prices are set for all essential medicines according to people’s ability to pay; (2) continues largely not to channel research and development into diseases that predominantly affect poor people in developing countries; (3) continues to be inflexible in protecting intellectual property, including challenging poor countries in court to stop using legal public health safeguards; and (4) continues to rely heavily on donations to get affordable medicines to people, even though this is unsustainable and sometimes counterproductive. Affordability of drugs is defined as the number of days’ wages required for the lowest-paid individual to purchase a one-month supply of generic aspirin (100 mg), atenolol (100 mg), angiotensin converting enzyme inhibitor, lisinopril (10 mg) and simvastatin (20 mg) daily. The affordability of treatment for the secondary prevention of coronary heart disease would be 1.6 days in Bangladesh, 5.1 days in Brazil, 18.4 days in Malawi, 6.1 days in Nepal, 5.4 days in Pakistan and 1.5 days in Sri Lanka.6 In order to improve compliance in patients, drugs need to be made more affordable. Methods to improve affordability are: increase efficiency and volume of production of drugs, clarify treatment guidelines so that manufacturers can concentrate on fewer drugs, negotiate with manufacturers, publicise the lowest price, and reduce the credible threat of government action.7 Drugs are also not always equally available in SSA. The reasons for unavailability of drugs are: bureaucratic factors delay licensure and discourage manufacturers from introducing drugs into low-income countries, manufacturers’ prices are important causes of unaffordability, import tariffs, a lack of comparative

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price data, and mark-ups by distributers, pharmacies and dispensing doctors. Poverty is the main underlying factor for hypertension and cardiovascular diseases.8 There are 57 countries in SSA. Africa has huge amounts of natural resources and is a source of natural strategic minerals. It is not overpopulated compared to the Asian continent yet economic conditions have deteriorated alarmingly in recent years. This is due to corruption and maladministration. Africa is the poorest continent and has the lowest per capita income in the world. The effect of poverty and its impact on health, particularly cardiovascular diseases, has been previously described.8 The number of poor people, defined as those making less than one dollar a day, has increased substantially in both relative and absolute terms. The absolute number of poor people has grown five times more than the figure for Latin America and twice that of South Asia. There is a critical shortage of doctors and nurse midwives to achieve 80% coverage for deliveries by skilled birth attendants, or for measles immunisation. The staff shortages in SSA derive from a combination of underproduction of qualified healthcare workers, internal maladministration of professionals, and emigration of trained workers. The shortage of health workers in SSA reached 4.3 million in 2006, including 2.4 million doctors, nurses and midwives. It is more critical in rural areas as 38% of the world’s nurses and less than 25% of doctors work in rural areas.9 Obesity is associated with increased blood pressure levels in blacks. In the South African Demographic and Health Survey of 1998, the prevalence of obesity (body mass index ≥ 30 kg/ m2 was 30% in black females and 8% in black males.4 It has been suggested that in Africa, the rural diet is relatively healthy, but with urbanisation, the diet is replaced with higher fat and lower carbohydrate intake. Poverty and cultural factors hinder the implementation of the DASH (Dietary Approach to Stop Hypertension) high-fruit, high-vegetable, low-salt diet, which was found to be very effective in African-Americans.10 For most low- and middle-income countries, the major obstacle to the control of blood pressure-related disease is the absence of appropriate primary healthcare services. Strategies for the prevention of cardiovascular disease (CVD) are to prevent the acquisition or enhancement of CVD risk factors. This is done by avoidance or decrease of the social, economic and cultural factors that contribute to the development of hypertension. In primordial prevention, the main objective is to prevent the acquisition or enhancement of CVD risk factors. This is done by avoidance or decrease of the social, economic and cultural determinants that contribute to the development of hypertension. Primordial prevention relies on health policies that create a congenial environment to promote healthy behaviour, and population-wide education programmes. These in turn depend on many factors, including the involvement of political leaders and the mass media. Primordial prevention relies on healthy behaviour and population-wide education programmes. Primary prevention is to reduce or reverse the risk factors in urban communities. This is done by reducing the risk factors for hypertension through appropriate policies, or modifying the risk factors in order to prevent or delay the development of hypertension. Since a substantial number of adults have blood pressure above the optimal level, even a small reduction in blood

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pressure can produce a significant decrease in cardiovascular risk in the population. At the individual level, primary prevention of hypertension consists of adopting healthy lifestyles at an early age. These should be non-pharmacological, populationbased and lifestyle-linked measures, such as salt restriction in food, increased exercise, control of obesity, increased potassium consumption in the form of fresh fruit and vegetables, reduced alcohol intake, and stopping cigarette smoking. There is a need to develop cost-effective methods for the diagnosis of hypertension, and low-cost, saving measures such as microscopic urine examination, and testing for urinary albumin and glucose levels, and serum creatinine, potassium and glucose levels. Coronary heart disease, while rising in incidence, is still relatively uncommon in SSA. Because serum cholesterol levels in blacks are lower than in whites and the Indian population in SSA, it may not be necessary to routinely measure lipid patterns in black hypertensive patients.10 However, we need data on the cost effectiveness of routine measuring of lipid patterns in blacks, with the current stage of knowledge of elevation of serum lipid levels in many individuals. At a tertiary level, we need to avoid high-cost, low-yield technologies such as routine echocardiography for hypertension, and computerised resonance tomography and magnetic tomography for reno-vascular hypertension.8 While it is important to use modern technology in medicine for the treatment of hypertension, particular attention should be given to cost-effectiveness and affordability, as many countries in SSA have severe resource constraints.9-11 In some countries, the health budget per capita does not exceed US$10 per year and this is completely insufficient to address the needs created by the double burden of non-communicable and infectious diseases, such as HIV/AIDS. For most low- and middle-income countries in SSA, the major obstacle is the absence of appropriate healthcare services. In many regions, primary care provides only episodic care with little record kept of previous visits. These services must be adapted not only for the management of blood pressure-related disease but also for the management of other serious diseases, including HIV infection. Many of the clinics are poorly staffed and lack adequate equipment and medication. It is the norm to have large queues of patients waiting for many hours after entry to a clinic, to be seen by nursing or medical personnel.12

Conclusion Treatment of hypertension in the poverty-stricken continent of SSA presents a challenge that needs to be addressed urgently. A similar plea has been made to the South African medical fraternity.13 The future approach to CVD prevention should be aimed at societal change throughout the life of the individual, and on large changes in multiple risk factors. There is a need to solve the problem by working with goverments, the WHO and other national and international organisations. We must remember the wise words of our beloved Nelson Mandela, ‘We must face the matter squarely, that where there is something wrong in how we govern ourselves, it must be said that the fault is not in the stars, but in ourselves. We know that we have it in ourselves as Africans to change all this. We must assert our will to do so; we must say there is no obstacle (large) enough to stop us bringing about an African renaissance’.

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References 1.

Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, et al. A comparative

tries. N Eng J Med 2007; 357: 1996–1999. 7. 8.

Campbell NR, Nieylski M, Lackland D. High blood pressure: why

10. Douglas JG, Bakris GL, Epstein M, Ferdinand KC, et al. Management

Hypertension. J Clin Hypertens 2014; 16: 551–553.

of high blood pressure in African Americans: consensus statement

Seedat YK. Race, environment and blood pressure: The South African

of the Hypertension Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med 2003; 163: 525–541.

experience. J Hypertens 1983; 1: 7–12. 4.

Steyn K, Gaziano TA, Bradshaw D, Laubscher R, et al. South African

11. Lemogoum D, Seedat YK, Mabadeje AFB, Mendis S. Recommendations

Demographic and Health Coordinating Team. Hypertension in South

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vascular risk factors in sub-Saharan Africa. J Hypertens 2003; 21:

J Hypertens 2001; 19: 739–747. 5.

Oxfam report. Big pharmaceutical companies need to change the way they work to reach 83% of the worlds’ consumers who don’t have proper access to medicine. 28-11-2007. http://www. Oxfam org/en/policy/briefing papers/bp109_for life_0711.

United Nation Population Fact. Health workers, international migration and development, August 2010. No. 2010/2.E/Rev: 1–4.

prevention and control are urgent and important. A fact sheet from the World Hypertension League and the International Society of

Seedat YK. Impact of poverty on hypertension and cardiovascular disease in sub-Saharan Africa. Cardiovasc J Afr 2007; 18: 316–320.

for the Global Burden of Disease Study. Lancet 2013; 380: 2224–2260. 2.

Seedat YK. Fixed drug combination in hypertension and hyperlidaemia in the developing world. Cardiovasc J Afr 2008; 19: 124–126.

risk assessment of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic review analysis

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MacMahon S, Alderman MH. Lindholm LH, Liu L, et al. Blood pressure-related disease is a global health priority. Lancet 2008; 371: 1480–1482.

13. Seedat YK. Control of hypertension in South Africa: Time for action. S Afr Med J 2012; 102: 25–26.

In Memoriam Cephas Musabayane, 1948–2015 It is with sadness that we report the death of Prof Cephas Musabayane, professor of physiology at the University of KwaZulu-Natal, and leader of a team of researchers who discovered a new method of administering insulin into the bloodstream via a skin patch. The discovery could eventually pave the way for diabetic patients to control their insulin levels in a pain-free manner with reduced negative side effects. Musabayane was born in Zimbabwe and when his academic potential was recognised, he was sent to England to finish his schooling. He obtained his BSc from Hertfordshire University in the UK, and then returned to the University of Zimbabwe where he obtained his MSc and PhD. He joined the University of KwaZulu-Natal as professor of human physiology in 2003, and served as head of the School of Medical Sciences for four years. Musabayane was an academic who was passionate about teaching and research. He inspired his students and motivated them to achieve success. His areas of research included diabetes, malaria and renal physiology, and he obtained national and international recognition for his work. He was a life fellow of the Physiology Society of Southern Africa and a member of the US and UK physiological societies.

In Africa, plants have always served as a dependable and ever-ready source of medicines for the treatment of a plethora of chronic and acute diseases. Traditional remedies have been used for ailments such as hypertension, diabetes mellitus, arthritis and erectile dysfunction, among others. In a search for plants with the potential for use as effective and safe ethnomedical remedies in the management of a range of human diseases, Musabayane and colleagues subjected many African medicinal plants to phytochemical and pharmacological investigation. They showed that some African medicinal plants possess hypoglycaemic, antiinflammatory, analgesic and other pharmacological properties. Musabayane published several articles in the Cardiovascular Journal of Africa on the effects of medicinal plants on glucose concentrations, renal function and blood pressure in normal and diabetic laboratory animals. His aim was to develop some of the existing African traditional remedies into scientifically acceptable natural remedies that are affordable, safe and effective. He believed that the goals of medicine, whether allopathic, traditional or complementary, are the same, namely to benefit patients therapeutically and improve their quality of life. He hoped to help develop affordable, safe and effective natural medicines for various human diseases.

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Case Report First Melody® valve implantations in Africa DG Buys, C Greig, SC Brown

Abstract Congenital heart lesions involving the right ventricular outflow tract (RVOT) are a common problem in paediatric cardiology. These patients need multiple surgical interventions in the form of valved conduits over a lifetime. Surgical re-valvulation was the standard treatment option until the introduction of percutaneous pulmonary valves over a decade ago. These valves can be used to prolong the lifespan of conduits and reduce the number of re-operations. The Melody® valve (Medtronic, Minneapolis, MN, USA) was introduced as the first dedicated percutaneous pulmonary valve. Percutaneous pulmonary valves can be implanted successfully and have the advantage of short hospitalisations. We describe the first three Melody® valve implantations in Africa. Keywords: Melody® valve, Africa, percutaneous valve, implantation

Case report Only patients meeting standard indications for surgical re-intervention were evaluated for transcatheter valve implantation. Extensive work up included: chest radiography, electrocardiography (ECG), evaluation of exercise capacity, echocardiography, and high-resolution computed tomographic angiography (CTA) (Fig. 2). The right ventricle size and function as well as the severity of pulmonary regurgitation (PR) and/or pulmonary stenosis (PS) were assessed and quantified. CTA in all three patients demonstrated favourable coronary artery anatomy and we proceeded with valve implantation in March 2012.

Case 1

Submitted 12/12/13, accepted 11/1/15 Cardiovasc J Afr 2015; 26: 196–199

transcatheter delivery system (Medtronic, Minneapolis, MN, USA). We describe the first three Melody® valve implantations in Africa. These were done at the Universitas Academic Hospital complex in Bloemfontein, South Africa.

www.cvja.co.za

DOI: 10.5830/CVJA-2015-007

Right ventricle-to-pulmonary artery (RV–PA) conduit failure is a vexing problem in post-operative congenital cardiac lesions involving the right ventricular outflow tract (RVOT). Typical lesions include tetralogy of Fallot, pulmonary atresia, truncus arteriosus, and others. These lesions often require early intervention and multiple RVOT revisions. Surgical re-interventions may result in prolonged hospital stay with increased morbidity and mortality rates.1,2 Due to the invasive nature of surgery, some patients with RVOT dysfunction are managed for years before surgical re-valvulation is considered. The first percutaneous pulmonary valve was implanted in the year 2000, and led to the development of the Melody® valve (Medtronic, Minneapolis, MN, USA).3-5 The Melody® valve consists of an 18-mm valve segment, the Contegra® modified bovine jugular vein, sutured into a platinum iridium stent of 34-mm length (Fig. 1). The valve can be crimped down to 6 mm and re-expanded from 18 to 22 mm using the Ensemble®

The patient was a 17-year-old male (weight 46.2 kg) with tetralogy of Fallot. As initial intervention, he had had surgical correction and a RVOT patch at 18 months of age. This was later followed by a RV-PA outflow tract reconstruction and insertion of a 20-mm homograft at age 11 years. He was considered for percutaneous valve implantation because of exercise intolerance, right ventricular dysfunction and severe PR. A

Department of Paediatric Cardiology, University of the Free State, and Universitas Hospital, Bloemfontein, South Africa DG Buys, MMed (Paed), Cert Paed Cardiol, buysdg@ufs.ac.za C Greig, MMed (Paed) SC Brown, MMed (Paed), FCPaed (Cardio)

Fig. 1. A: competent Melody® valve with ID tag, B: the valve crimped on to the Ensemble® delivery system pre valve implantation.

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 4, July/August 2015

The echocardiogram demonstrated a severely dilated right ventricle, free PR and a RVOT peak instantaneous gradient (PIG) of 60 mmHg. After successful pre-stenting of the RVOT, a Melody® valve was successfully implanted using a 22-mm Ensemble® system (see Methods). No residual PS or PR was demonstrated post valve implantation.

Case 2 The second case was a 16-year-old female (weight 50.0 kg) with double-outlet right ventricle (DORV) and pulmonary stenosis. She had had a DORV correction and a 20-mm aortic homograft insertion at the age of 12 years. RVOT rehabilitation was indicated due to a mixed lesion of PS and PR. Echocardiography demonstrated a calcified RVOT with a PIG of 52 mmHg and a dilated right ventricle with moderate to severe PR. Coronary artery anatomy was favourable. A 22-mm Ensemble® delivery system was used to successfully implant a Melody® valve (see Methods). The right ventricle pressure was reduced with no residual PR.

Case 3 The patient was a 31-year-old male (weight 47.5 kg) with DORV and pulmonary stenosis. He had had RVOT reconstruction with a 21-mm homograft at age 17 years. Surgery was considered risky due to a direct retrosternal location of the original homograft (Figs 2, 3). His main indication for re-valvulation was pulmonary stenosis with a RVOT PIG of 60 mmHg. A stable ‘landing site’ was constructed using two stents and pre-dilation with a high-pressure balloon (see Methods). The Melody® valve was then delivered using an 18-mm Ensemble®

Table 1. Haemodynamic information RV pressure MPA pressure (mmHg) (mmHg) PR pre post pre post pre post Case 1 35/6 32/6 20/7 20/8 severe none Case 2 74/6 42/6 52/13 32/17 severe none Case 3 56/6 34/6 24/6 24/9 moderate none RV: right ventricle; MPA: main pulmonary artery pressure; PR: pulmonary regurgitation.

delivery system. The valve was dilated using a high-pressure balloon and a good result was achieved. The patient did well with mild transient retrosternal chest pain as the only complaint.

Methods Valve implantation was performed under general anaesthesia. All patients were heparanised following our standard protocol, and prophylactic antibiotics (Cefazolin) were given. Vascular access was obtained via the femoral vessels and haemodynamic data were collected pre and post Melody® valve implantation (Table 1). Simultaneous coronary angiography and inflation of a low-pressure balloon (AmplatzerTM sizing balloon II, St Jude Medical, St Paul, MN, USA) in the RVOT was performed to exclude coronary artery occlusion (Fig. 4).There were no coronary artery occlusions or ECG changes detected during balloon inflation, and the decision was made to continue with the procedure. Preparing the landing zone for Melody® valve implantation is a crucial step in the procedure. It is important to record any stent recoil during balloon deflation. A stiff guide wire [Meier (Boston Scientific, Natick, MA, USA), LunderquistTM extra stiff (Cook Medical, Bloomington, USA)] with stable position was obtained. In our experience, pre-stenting of the RVOT is more challenging and once the landing site is prepared, the Melody® valve is implanted with minimal difficulty. A

Fig. 2. C T angiography. The homograft (large arrow) in case 3 is positioned anterior and to the right of the aorta (ao). Note the direct retrosternal position of the calcified homograft. The coronary arteries (small arrows) are at low risk for compression during valve implantation.

197

Fig. 3. Direct retrosternal position of the stenotic RVOT with inflation of a high-pressure balloon (Atlas® PTA dilatation catheter, Bard Medical). The arrows indicate stent indentation pre and post dilatation (Case 3).

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Fig. 4. S imultaneous inflation of a compliant balloon (small arrow) in the RVOT and coronary artery angiogram (large arrow) with no coronary artery obstruction.

Pre-dilation and pre-stenting was performed in all three cases. This was achieved using BIB® (NuMED, Hopkins, NY, USA) balloons and bare-metal stents (IntraStentTM LD MaxTM, ev3 Endovascular, Plymouth, USA) in cases 1 and 2. Both patients needed only one pre-stent to obtain a stable RVOT with no recoil of stent during balloon deflation and no residual stenosis. Case 3 was more complicated due to the direct retrosternal position of the RVOT. The RVOT was severely calcified and residual stenosis and recoil of a 45-mm covered CP stent (NuMED, Hopkinton, NY, USA) using a 22-mm BIB® warranted a second stent implantation to secure a stable landing zone. This was achieved using a 36-mm IntraStentTM LD MaxTM (ev3 Endovascular, Plymouth, USA) on a 22-mm BIB®. Residual indentation of the stents was abolished using a high-pressure balloon (Bard Atlas® PTA dilatation catheter, Bard Peripheral Vascular, Tempe, AZ, USA) (Fig. 3). Once RVOT rehabilitation was completed, the Melody® valves were successfully implanted. Patient 3 needed post-valve implant dilatation due to the residual stenosis and gradient. Post-stent implantation gradients were measured using a MultitrackTM angiographic catheter (NuMED, Hopkinton, NY, USA). At the time of implantation, the decision was made that the results were satisfactory and no further dilatation was indicated. Melody® valve implantation was successful in all three patients, with reduction of RVOT gradients and elimination of the PR (Fig. 5). Post valve implantation coronary angiograms were normal with no vessel obstruction. There were no ischaemic changes on ECG for 48 hours and no pericardial effusion on echocardiography. The patients were observed overnight and discharged home within 48 hours. The patients have now been followed up for two years and demonstrated RV size and function improvements with normal pulmonary valve function. Subjectively all patients reported improved exercise tolerance.

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Fig. 5. Melody® valve competency was demonstrated using a Multi-tractTM catheter.

Discussion Percutaneous pulmonary valve implantation has become an accepted alternative to surgical pulmonary re-valvulation, with low morbidity and mortality rates.4,5 More than 7 000 Melody® valves have been implanted in 156 centres worldwide, and these are the first cases in Africa (direct correspondence with Medtronic). Indications for percutaneous valve implantation are identical to surgical indications. Classic indications for Melody® valve implantation include: patients above 20 kg, conduit dysfunction with stenosis or moderate regurgitation, conduit size > 16 mm and < 22 mm, and favourable RVOT morphology.4-8 Contraindications consist of active endocarditis and a conduit size that is incompatible with the valve size.4,7 Helpful information obtained from CTA includes the anatomical aspects of the RVOT and its spatial relationship to the coronary arteries. The risk of coronary artery compression is the most frequent exclusion factor and cause of procedurerelated deaths. Major procedural complications include dislodgement of the valve, coronary artery compression, rupture of the homograft, and haemothorax due to pulmonary artery perforation. Follow-up complications include stent fracture and endocarditis.4-6,8,9 Stent fracture rates diminished after the practice of presenting became common place. Case 3 demonstrates that percutaneous valve implantation may be a useful alternative to surgery. The transient chest pain in this patient was secondary to RVOT stretching and similar to that of surgery. The benefits of percutaneous valve implantation include short hospital stay and no ICU care. The availability of these valves may reduce the duration of RV dysfunction and the total number of RV–PA conduit replacements.

Conclusion Introduction of the Melody® valve has been proven a safe and effective alternative to surgery for RVOT re-valvulation.

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The Melody® valve can be implanted with a high success rate and low morbidity and mortality rates. Our cases show that a percutaneous valve is a reasonable alternative to surgical re-valvulation in developing countries due to short hospital stay and reduced re-operation rates.

cal outcome. Circulation 2008; 117: 1964–1972. 5.

expanded multicenter US Melody valve trail. Circulation 2010; 122: 507–516.

Circulation 2005; 112: 1189–1197.

Gober V, Berdat P, Pavlovic M, et al. Adverse mid-term outcome follow-

transcatheter pulmonary valve in patients with a dysfunctional right

Ann Thorac Surg 2005; 79: 625–631.

ventricular outflow conduit: early results from the U.S. clinical trial. J Am Coll Cardiol 2009; 18: 1722–1729.

Sugita T, Ueda Y, Matsumoto M, et al. Repeated procedure after radical 8.

conduit with valve dysfunction Lancet 2000; 356: 1403–1405.

Eichen A, Ewert P, Hager A, et al. Percutaneous pulmonary valve implantation: two-center experience with more than 100 patients. Eur

Bonhoeffer P, Boudjemline Y, Saliba Z, et al. Percutaneous replacement

Heart J 2011; 32: 1260–1265.

of pulmonary valve in a right-ventricle to pulmonary-artery prosthetic 4.

Zahn EM, Hellenbrand WE, Lock JE, et al. Implantation of the melody

ing RVOT reconstruction using the Contegra valved bovine jugular vein.

surgery for tetralogy of Fallot. Ann Thorac Surg 2000; 70(5): 1507–1510. 3.

Khambadkone S, Coats L, Taylor A, et al. Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients.

References

McElhinney DB, Hellebrand WE, Zahn EM, et al. Short- and mediumterm outcomes after transcatheter pulmonary valve placement in the

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Lurz P, Coats L, Khambadkone S, et al. Percutaneous pulmonary valve

tion of pulmonary valves for treatment of right ventricular outflow tract

implantation: impact of evolving technology and learning curve on clini-

dysfunction: a single-centre experience. J Pead 2009; 19: S116–S119.

Book Launch ECG Book Advert

October 2015

SA Heart Congress

The ECG Atlas of Cardiac Rhythms

Rob Scott Millar

Orders at elsabe@clinicscardive.com

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Cardio News Cardiac surgery and intervention highlights at the SA Heart Congress 2015 Interventional procedures and cardiothoracic surgery feature prominently at the SA Heart Congress 2015, to take place from Sunday 25 to Wednesday 28 October at Sun City in the North West province.

Cardiac intervention Held under the auspices of the SA Society of Cardiovascular Intervention (SASCI), the adult interventional stream at the congress features four prominent international faculty, who include Drs Robert Byrne (Germany), Jacek Legutko (Poland), Ariel Roguin (Israel) and Ralf Birkemeyer (Germany). Although Dr Byrne is a newcomer to South Africa, he is a stalwart of the PCR community and is regularly featured on Medscape. The interventional stream commences with a half-day, post-graduate course on Sunday 25 October, hosted by Terumo, with the entire afternoon being dedicated to the topic of radial intervention. Veteran radialists will provide tips and tricks on all aspects of radial angiography/intervention that will prove to be useful for both novices and established radialists alike. At one of the opening plenary sessions at the Congress, Dr Farrel Hellig will be focusing on the results and future developments pertaining to a fellowship being offered by the South African private sector in interventional cardiology. Congress chairman, Prof Francis Smit will complement this presentation by focusing on the African cardiac interventionist of the future from a public healthcare perspective. During the Monday afternoon interventional track, Dr Robert Byrne, a newcomer to South Africa but a stalwart of the PCR community, who features regularly on

Dr Robert Byrne

Medscape cardiology, will address the difficult topic of triple anti-thrombotic therapy following stent implantation. He will also provide insights into technological developments with newer drug-eluting stents and their impact on clinical outcomes. Although the primary focus during the interventional track will be on improving patient care, a notable topic of interest will be ‘Risks to the interventional cardiologist in the cath lab’, to be addressed by Prof Ariel Roguin from Israel. A STEMI update will take place on Tuesday morning, with Prof Bernard Gersh (USA) focusing on reperfusion therapy for STEMI in 2015, Prof Fausto Pinto (Portugal) weighing up the best combination for the pharmaco-invasive strategy, Dr Carlos Agular (Portugal) discussing the management of cardiogenic shock, and Dr Byrne (Germany) debating whether there is consensus regarding the management of multi-vessel disease in STEMI.

The cardiac surgery track The cardiothoracic surgery track commences with a pre-congress, postgraduate course on Sunday afternoon, with international faculty including Drs Carlos Mestres (Spain), Volkmar Falk (Germany) and Manuel Antunes (Portugal). Initial presentations will focus on the future challenges of coronary artery surgery and whether off-pump CABG is a passing fad. The diagnostic, surgical and peri-operative challenges of constrictive pericarditis will be examined by four speakers, with Dr Carlos Mestres from Spain sharing perspectives on pericarditis from the industrialised world. Late-afternoon presentations will cover minimally invasive mitral valve surgery by Prof Volkmar Falk (Germany) and mitral

Dr Volkmar Falk

Prof Jacek Legutko

valve repair in 2015 by Dr Manuel Antunes (Portugal). During the first plenary session on Monday 26 October, Prof Charles Yankah (Germany) will discuss an approach to the development of cardiac surgery in Africa. This will be followed in the second plenary session by Dr Martin Sussman discussing the pros and cons of the development of a surgical fellowship in the South African private sector. A two-hour session on TAVI takes place on Tuesday morning, 27 October, with Prof Volkmar Falk (Germany) sharing perspectives on the development, results and future of TAVI, and Prof Pascal Dohmen (Germany) debating whether TAVR and sutureless aortic valves are complementary or competitive procedures. Dr Helmuth Weich will discuss the long-term outcomes of TAVI and TAVI in the young, with Dr Farrel Hellig concluding the session by discussing the management of para-valvular leak and valve failure. Half-day courses on Tuesday afternoon include the options of a valvular mini symposium or a special focus on perfusion. The Congress concludes on Wednesday 28 October with a half-day course focusing on heart failure in sight, with international speakers featuring Drs Volkmar Falk, Charles Yankah and Mattias Roser from Germany, Alexandre Mebazaa (France), Bernard Gersh (USA) and Manuel Antunes (Portugal). For full-programme details, and to register for the radial intervention or cardiac surgery post-graduate courses, visit http:// saheartcongress2015.co.za. For queries, contact Europa Organisation Africa on (011) 325-0020, or email enquiries@ eoafrica.co.za.

Prof Ariel Roguin

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Cardiovascular Topics The prevalence of symptomatic infantile heart disease at Louga Regional Hospital, Senegal Georges Antoine Bazolo Ba Ngouala, Désiré Alain Affangla, Mohamed Leye, Abdoul Kane

Abstract The management of congenital or acquired infantile heart diseases in sub-Saharan African countries still presents problems, particularly with diagnosis and access to surgical treatment. Our objectives were to describe the heart diseases observed in the paediatric setting of the Louga Regional Hospital (LRH) and report their short-term evolution. In the study period from 1 July 2009 to 31 December 2012, 82 children out of 18 815 presented with heart disease, which was a prevalence of 4.3/1 000. There was a female predominance, with a ratio of 1.2. The most frequent presenting conditions were dyspnoea at 47.5%, followed by

Department of Paediatrics, Centre Hospitalier Régional de Louga, Louga, Sénégal Georges Antoine Bazolo Ba Ngouala, MD, bazoloantoine@yahoo.fr

Department of Cardiology, Hôpital Saint Jean de Dieu, Thiès, Sénégal Désiré Alain Affangla, MD

Department of Medicine, Hôpital Barthimée, Thiès, Sénégal

heart murmurs at 35.3%, and congestive heart failure at 13.4%. Congenital heart diseases were the most frequent, representing 69.5% of the cases, followed by acquired heart diseases at 29.3%, and mixed-type cases at 1.2%. The most frequently encountered congenital heart diseases were ventricular septal defect (24.4%), followed by atrioventricular septal defect (12.2%), tetralogy of Fallot (9.8%) and patent ductus arteriosus (7.3%). Acquired heart disease was represented by rheumatic heart disease, found in 25.6% of the cases, and tuberculous pericarditis in 3.7%. The mortality rate was high, with 20 children dying (24.4%) during the study period. Only 13 out of 82 patients (15.9%) were operable and surgery was carried out in France, courtesy of the association Humanitarian Mécénat Chirurgie Cardiaque. Infantile heart diseases were therefore not very frequent in the paediatric unit of Louga Regional Hospital. However, congenital heart disease was more frequent than acquired heart disease, with a high mortality rate. Access to surgery remains limited. Keywords: congenital heart disease, acquired heart disease, cardiac surgery, humanitarian association, Africa

Mohamed Leye, MD

Department of Cardiology, Hôpital Général Grand Yoff, Dakar, Sénégal

Submitted 8/5/14, accepted 16/3/15 Cardiovasc J Afr 2015; 26: e1–e5

www.cvja.co.za

Abdoul Kane, MD DOI: 10.5830/CVJA-2015-031

Prevalence des cardiopathies infantiles symptomatiques au Centre Hospitalier Régional de Louga, Senegal Georges Antoine Bazolo Ba Ngouala, Désiré Alain Affangla, Mohamed Leye, Abdoul Kane Service de pédiatrie, Centre Hospitalier Régional de Louga, Louga, Sénégal

Service de médecine, Hôpital Barthimée, Thiès, Sénégal

Georges Antoine Bazolo Ba Ngouala, MD, bazoloantoine@yahoo.fr

Service de cardiologie, Hôpital Général Grand Yoff, Dakar, Sénégal

Service de cardiologie, Hôpital Saint Jean de Dieu, Thiès, Sénégal Désiré Alain Affangla, MD

Mohamed Leye, MD

Abdoul Kane, MD

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 4, July/August 2015

Resumé La prise en charge des cardiopathies infantiles congénitales ou acquises dans les pays d’Afrique au sud du Sahara posent encore d’énormes difficultés de diagnostic et d’accès au traitement notamment chirurgical. Les objectifs de ce travail rétrospectif étaient de déterminer la prévalence des cardiopathies observées en milieu pédiatrique au Centre Hospitalier Régional (CHR) de Louga, de décrire les différents types observés et de rapporter leur évolution à court terme. Durant la période d’étude, 1 Juillet 2009 au 31 Décembre 2012, 82 enfants sur 18 815 enfants présentaient une cardiopathie, soit une prévalence de 4.3/1 000. On note une prédominance du sexe féminin avec un sexe ratio de 1.2. Les circonstances de découverte les plus fréquentes sont représentées par la dyspnée 47.5% suivie du souffle cardiaque 35.3% et de l’insuffisance cardiaque congestive 13.4%. Les cardiopathies congénitales sont les plus fréquentes avec 69.5% des cas suivi des cardiopathies acquises avec 29.3% des cas et des formes mixtes avec 1.2%. Les principales cardiopathies congénitales retrouvées sont la communication inter ventriculaire (24.3%) suivie des canaux atrio-ventriculaires (12.1%), de la tétralogie de Fallot (9.7%) et de la persistance du canal artériel (7.3%). Les cardiopathies rhumatismales retrouvées dans 25.6% des cas et les péricardites tuberculeuses dans 3.7% des cas représentent les formes acquises. La mortalité est élevée avec 20 enfants décédés (24.4%) pendant la période d’étude. Seuls 13 patients sur 82 (15.9%) présentant une indication opératoire ont été opérés en France grâce à une prise en charge par l’association humanitaire Mécénat Chirurgie Cardiaque. Ainsi donc les cardiopathies infantiles sont peu fréquentes dans le service de pédiatrie du CHR de Louga. Les formes congénitales sont plus fréquentes que les formes acquises. Leur mortalité est élevée et l’accès à la chirurgie reste faible. Mots clés: cardiopathie congénitale, cardiopathies acquises, chirurgie cardiaque, association humanitaire, Afrique Submitted 8/5/14, accepted 16/3/15 Cardiovasc J Afr 2015; 26: e1–e5

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Hospitalier Régional (CHR). Ce centre est un hôpital de référence au niveau régional situé en zone semi désertique, avec des ressources humaines et matérielles très limitées polarisant une population estimée à environ 960 621 habitants en 2012.3 Il s’agit d’une étude rétrospective portant sur les enfants de 0–17 ans vus en consultation externe ou hospitalisés dans le service de pédiatrie du CHR de Louga du 1 Juillet 2009 au 31 Décembre 2012. La consultation externe est effectuée par un pédiatre ou par un infirmier. Cependant tous les cas suspects de cardiopathies vus par l’infirmier sont examinés ultérieurement par le pédiatre et bénéficiaient ainsi d’un examen clinique complet. Les patients hospitalisés sont tous vus par le pédiatre. Une cardiopathie était suspectée devant les symptômes d’appel suivants: la cyanose, la bronchite à répétition, un souffle cardiaque de caractère organique, une insuffisance cardiaque, une cardiomégalie à la radiographie du thorax. Les données des consultations externes étaient recherchées à partir des registres de consultation et celles des malades hospitalisés à partir des dossiers patients. Les doublons étant recherchés à partir de l’âge, du sexe, du lieu de résidence et du type de cardiopathie et supprimés. Une échographie cardiaque n’était prescrite qu’aux enfants présentant ces signes évocateurs d’une cardiopathie (Fig. 1). L’examen d’échographie cardiaque était effectué par un cardiologue sur un appareil HP SONOS 100 munie d’une sonde phased array de 2–4 MHz de fréquence et des modes Doppler pulsé, continue et couleur. Le diagnostic de cardiopathie n’était retenu qu’après confirmation à l’échocardiographie. Les autres paramètres suivants ont été analysés: l’âge, le sexe, la notion de consanguinité, le niveau socio-économique, les circonstances de découverte, le type de cardiopathie acquise ou congénitale, le type de traitement médical ou chirurgical et les modalités évolutives. Tous les parents d’enfants présentant une cardiopathie étaient informés du diagnostic et ceux ayant nécessités d’une prise en charge chirurgicale avaient donnés leur consentement préalable. Les données recueillies ont été traitées et analysés par le logiciel Epi Info version 3.5.4.

www.cvja.co.za

DOI: 10.5830/CVJA-2015-031

La prévalence des cardiopathies infantiles en Afrique sub-Saharienne est estimée à environ 8 pour mille naissances vivantes pour les cardiopathies congénitales et au moins 1 à 14 pour mille pour les cardiopathies rhumatismales.1 La prise en charge de ces cardiopathies infantiles dans les pays d’Afrique au sud du Sahara et au Sénégal en particulier posent encore d’énormes difficultés de diagnostic et d’accès au traitement notamment chirurgical contribuant ainsi à une augmentation de la mortalité et de la morbidité infantile.1,2 Les objectifs de ce travail étaient de déterminer la prévalence des cardiopathies observées en milieu pédiatrique au Centre Hospitalier Régional (CHR) de Louga, de décrire les différents types observés et de rapporter leur évolution à court terme.

Methodes La présente étude est réalisée à Louga situé à environ 200 km au nord de la capitale, dans le service de pédiatrie du Centre

Resultats Quatre-vingt-dix enfants sur les 18 815 vus durant la période d’étude présentaient des signes évocateurs d’une cardiopathie. Cinquante ont été recensé en consultation externe et 40 en hospitalisation. Ils ont tous bénéficié d’une prescription d’une échographie cardiaque, mais seuls 87 ont bénéficié de cette exploration, les parents de trois enfants ne se sont pas présenté. Cinq échographies étaient normales et 82 cardiopathies ont été confirmées soit une prévalence de 4.3/1 000. L’âge moyen de découverte des cardiopathies congénitales est 8 ans 6 mois (extrêmes 1 mois et 15 ans) et celui des cardiopathies rhumatismaux 9 ans 5 mois (extrêmes 4ans et 15 ans). On note une prédominance du sexe féminin avec un sexe ratio de 1.2. Le niveau socio-économique des parents est estimé moyen dans 62.2% des cas et plus de la moitié des patients (52.4%) provenaient d’un milieu urbain. Les mariages consanguins sont retrouvés chez presque tous les parents des patients (92.7%). Les circonstances de découverte les plus fréquentes sont la dyspnée (47.5%), le souffle cardiaque (35.3%), l’insuffisance cardiaque congestive (13.4%) et la cyanose (9.7%) (Fig. 2).

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ENFANTS MALADES

CONSULTATION EXTERNE

ENFANTS VUS PAR L’INFIRMIER

HOSPITALISATION

SI SUSPICION DE CARDIOPATHIE

ENFANTS VUS PAR LE PEDIATRE

SI DIAGNOSTIC DE CARDIOPATHIE NEGATIF

RETOUR A DOMICILE

SIGNES CLINIQUES ET RADIOLOGIQUES EVOCATEURS DE CARDIOPATHIE (dyspnée, souffle, insuffisance cardiaque, cyanose Bronchites à répétition, cardiomégalie)

ECHO CARDIOGRAPHIE

DIAGNOSTIC DE CARDIOPATHIE REJETE

DIAGNOSTIC DE CARDIOPATHIE CONFIRME Fig. 1. T riage d’enfants suspects de cardiopathies dans le service de pediatrie.

Les cardiopathies congénitales sont plus fréquentes (69.5%) que les cardiopathies acquises (29.3%) (Tableau 1 et 2). Les cardiopathies congénitales sont les plus fréquentes 69.5% que les cardiopathies rhumatismales 25.6%. (Tableau 1 et 2). La mortalité est élevée avec 20 enfants décédés (24.4%) pendant la période d’étude. Il s’agissait de 11 cas de valvulopathies rhumatismales sévère au stade d’insuffisance cardiaque réfractaire, huit cas de cardiopathie congénitale et un cas d’un décès post opératoire précoce d’une chirurgie correctrice de tétralogie de Fallot. Treize enfants sur 82 (15.9%) présentant une indication opératoire ont été opérés en France grâce à une prise en charge de l’association humanitaire Mécénat Chirurgie Cardiaque. Cependant sept enfants présentaient

2.4 1.2 4.9

Dyspnee

4.9

Souffle Insuffisance cardiaque

13.4 42.7

Cyanose et souffle Cyanose et dyspnee

30.5

Bronchite Cardiomegalie

Fig. 2. M odalités de découverte.

une indication opératoire dépassée du fait d’une hypertension artérielle pulmonaire sévère au stade d’Eisenmenger compliquant une cardiopathie congénitale avec shunt gauche-droite sont régulièrement suivi. Six patients (7.3%) on été transférés: cinq présentant une persistance de canal artériel (PCA) ont été transférés vers le centre de chirurgie thoracique et cardiovasculaire de Dakar pour une prise en charge chirurgicale et sont sur la liste d’attente. le dernier a été référé dans un autre hôpital proche de son lieu de résidence; 15 enfants (18.3%) sont perdus de vue.

Discussion Cette étude montre la faible prévalence des cardiopathies infantiles dans le service. Nous notons un diagnostic tardif des cardiopathies congénitales avec un âge moyen de 8 ans témoignant de la faible performance de nos structures sanitaires notamment l’extrême rareté en spécialiste dans les régions.4 Cet âge est plus élevé que Tableau 1. Répartition selon le type de cardiopathie Type Nombre Pourcentage Acquise Non-rhumatismale (péricardite tuberculeuse) 3 3.7 Rhumatismale 21 25.6 Congénitale 57 69.5 Mixte (congénitale et acquise: CIV, IA + IM) 1 1.2 Total 82 100 CIV = communication inter ventriculaire; IA = insuffisance aortique; IM = insuffisance mitrale.

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dans la série de Diop à Dakar,5 de Mpemba à Brazzaville au Congo6 et Chaabouni à Sfax en Tunisie7 qui trouvent respectivement 6.8, 6.3 et 5 ans. L’âge des cardiopathies congénitales est cependant légèrement plus bas que dans une série de cas opérés à Dakar.8 L’âge moyen de découverte des cardiopathies rhumatismales est de 9 ans 5 mois, plus bas que dans la série chirurgicale de Ciss à Dakar.9 Les cardiopathies congénitales étaient plus fréquentes que les cardiopathies rhumatismales pouvant s’expliquer par la plus grande incidence des malformations cardiaques comparée aux cardiopathies rhumatismales. Ceci a été également retrouvé par Ba en Mauritanie10 et Brousse au Sénégal;11 92.7% des enfants de l’étude sont issue de mariage consanguins. Cet aspect a été noté comme un important facteur contributif de malformation cardiaque.12 Le pronostic est défavorable dans notre contexte avec un taux de mortalité de 24.4% dépassant les 20% retrouvés à l’Hôpital Principal de Dakar en 1997 par Brousse11 et s’expliquant par le retard diagnostic et l’accès difficile à la chirurgie cardiaque. Il est à observer que si les cardiopathies se caractérisent par leur faible prévalence hospitalière elles représentent une des principales causes de morbidité et de mortalité chez l’enfant dans les pays en développement.13 Le taux de perdus de vue de 18.3% est plus élevé que celui retrouvé dans la série similaire au Sénégal de Brousse.11 Il pourrait s’expliquer par le caractère asymptomatique de certaines cardiopathies notamment congénitales et l’amélioration clinique des enfants opérés. Seul 15.9% des enfants ont pu être opéré. Ce faible taux d’accès au traitement chirurgical s’explique par plusieurs facteurs notamment l’impossibilité actuelle d’opérer des enfants de moins de 15 kg et les enfants présentant une hypertension artérielle pulmonaire avec une pression systolique supérieure à 50 mmHg.8 Dans ce contexte, les associations humanitaires comme ‘Mécénat Chirurgie cardiaque enfants du monde’, offrant une prise en charge jouent encore un rôle très important. Cependant il y a un intérêt indiscutable à développer la chirurgie cardiaque localement.5,7

Limites de l’etude Il s’agit d’une étude rétrospective qui a l’inconvénient de ne pas fournir toutes les données souhaitées notamment la Spo2 et les aspects électrocardiographiques. Le diagnostic de cardiopathie fait par un infirmier peut constituer un facteur limitant dans la mesure où une cardiopathie peu grave ou asymptomatique n’est pas détectée par ce dernier conduisant au sous diagnostic et à la sous estimation de la prévalence. Par ailleurs les nouveau-nés porteurs de cardiopathies congénitales sévères décédés peu après leur naissance ne sont pas pris en compte. Il s’agit d’une étude hospitalière dans un contexte où l’accessibilité aux soins est limitée. Le seul moyen paraclinique de confirmation de cardiopathie était un échographe peu performant. Les autres moyens à savoir le cathétérisme cardiaque et l’imagerie résonnance magnétique qui aurait pu apporter un diagnostic précis ou limiter les faux négatifs sont indisponibles sur place et hors de portée des populations. Eu égard à la nature hospitalière de l’étude et aux facteurs limitant précités, les données ne peuvent être extrapolées à la population générale mais donnent une idée de l’existence du problème qui pourrait être mieux diagnostiqué par d’autres études.

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Tableau 2. Répartition des différentes cardiopathies Diagnostics Nombre (n = 82) Pourcentages Cardiopathies congénitales CIV 20 24.4 CAV 10 12.2 Tétralogie de Fallot 8 9.8 PCA 6 7.3 CIA 3 3.7 APSO 2 2.4 HTAP primitive 2 2.4 CMD congénitale 2 2.4 VDDI 1 1.2 Oreillette unique 1 1.2 TGV avec CIV 1 1.2 Sténose pulmonaire 1 1.2 Cardiopathies acquises IM 10 12.2 IM + IA 9 11 RM 2 2.4 Péricardites tuberculeuses 3 3.7 Cardiopathies mixtes CIV + IM 1 1.2 Total 82 100 CIV = communication inter ventriculaire; CIA = communication inter auriculaire; CAV = canal atrioventriculaire; VDDI = ventricule droit à double issu; APSO = atrésie pulmonaire à septum ouvert; PCA = persistance du canal artériel; TGV = transposition des gros vaisseaux; CMD = cardiomyopathie dilatée; HTAP = hypertension artérielle primitive; IM = insuffisance mitrale; IA = insuffisance aortique; RM = rétrécissement mitral.

Conclusion Cette étude bien que comportant des limites montre que les cardiopathies infantiles sont peu fréquentes au service de pédiatrie du CHR de Louga avec une prévalence de 4.3 pour 1 000. Les formes congénitales sont plus fréquentes que les formes acquises. L’accès à la chirurgie cardiaque est faible et la mortalité est élevée. II est donc nécessaire de mettre l’accent sur le dépistage précoce de cardiopathies infantiles et d’améliorer leur accès à la chirurgie cardiaque localement.

Bibliographie 1.

Zuhlke L, Mirabel M, Marijon E. Congenital heart disease and rheumatic heart disease in Africa: recent advances and currents priorities. Heart 2013; 99: 1554–1561.

Mocumbi AO, Lameira E, Yaksh A, et al. Challenges on the management of congenital heart disease in developing countries. Int J Cardiol 2011; 148: 285–288.

Service Régional de la Statistique et de la Démographie de Louga. Situation économique et Sociale de la région de Louga 2010: 3–7.

Observatoire Africain des Ressources Humaines pour la Santé, Profil pays en ressources humaines pour la santé du Sénégal. Mars 2009: 25–26.

Diop IB, Ndiaye M, Ba SA, Sarr M, Kane A, Hane L, Sow D, Ba K, Diack B, Diouf SM, Fall M. Congenital heart disease surgery in Senegal. Indications, evaluation and perspectives. Dakar Med 1996; 41(2): 85–90.

M’Pemba Loufoua Lemay AB, Johnson EA, Nzingoula. Les cardiopathies congénitales observées dans le service de pédiatrie Grands Enfants

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du CHU de Brazzaville à propos de 73 cas: Aspects épidémiologiques. Médecine d’Afrique Noire 2005; 52: 173–177. 7.

Chaabouni M, Kamoun T, Mekki N, Mahfoudh A, Karray A, Daoud

mauritanien. Médecine d’Afrique Noire 2000; 47(11): 492–493. 11. Brousse V, Imbert P, Mbaye P, Kieffer K, Thiam M, Ka AS, Gerardin

congénitales dans le service de pédiatrie de Sfax: A propos de 123 cas.

P, Sidi D. Evaluation au Senegal du devenir des enfants transférés pour chirurgie cardiaque. Méd Trop 2003; 63: 506–512.

Fall ML, Leye PA , Ba PA, Bah MD , Ndiaye PI , Ciss AG, Sene E,

12. Yunis K, Mumtaz G, Bitar F, Chamsedine F, Kassar M, Rashkidi J,

Kane K, Kane O, Diouf E. La prise en charge péri opératoire des

et al. Consanguineous marriage and congenital heart defects: A case–

cardiopathies congénitales au Sénégal. Rev Afr Anesth Méd Urg 2012;

control study in the neonatal period. Am J Med Genet A 2006; 140:

17(3): 3–10. 9.

2009; 69: 278–280. 10. Ba ML, Kane FB. Etude préliminaire des cardiopathies chez l’enfant

M, Triki A. Aspects épidémiologiques et évolutifs des cardiopathies Tunisie Médicale 1999; 77(5): 264–271. 8.

1524–1530.

Ciss AG, Diarra O, Dieng PA, N’diaye A, Ba PS, Touré A, Diatta S,

13. Deen J, Vos T, Huttly SRA, Tulloch J. Traumatismes et maladies non

Beye SA, Kane O, Diop IB, N’diaye M. La plastie mitrale sur valve

transmissibles: des pathologies émergentes chez les enfants des pays en

rhumatismale chez l’enfant au Sénégal: 100 observations. Med Trop

développement. Bull WHO 1999; 77: 518–524.

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Case Report Unrepaired persistent truncus arteriosus in a 38-year-old woman with an uneventful pregnancy Dorra Abid, Emna Daoud, Sahar Ben Kahla, Souad Mallek, Leila Abid, Hela Fourati, Zeineb Mnif, Samir Kammoun

Abstract Persistent truncus arteriosus (PTA) is a rare conotruncal defect, defined as a single arterial vessel arising from the heart, which gives origin to the systemic, pulmonary and coronary circulations. It has an extremely poor prognosis and carries a high mortality rate during the early years of life unless surgically repaired. A few known cases have been reported of patients reaching maturity, and exceptionally, patients suffering from this disease having lived into the fourth decade. The purpose of this report was to present a new case of PTA type 1, diagnosed by echocardiography and MRI, in a 41-year-old woman, with the peculiarity of long survival into adult life. She had also experienced a full-term pregnancy and delivery of a normal infant three years prior to her diagnosis. Pulmonary vascular disease made her condition inoperable but she was doing well with medical management after a follow up of 15 months. Based on this work, we concluded that pulmonary arterial hypertension is deleterious for life in some cardiovascular diseases, but in others, allows survival, as occurred in these patients with PTA. The patient’s clinical course and anatomical findings are reported, along with factors that may have contributed to her longevity.

Persistent truncus arteriosus (PTA) is an uncommon congenital heart disease (CHD) that was first described by Wilson in 1798. In 1976, Calder et al. reported it accounted for approximately 0.7 to 1.2% of all congenital heart malformations and occurred equally in men and women.1 Truncus arteriosus (TA) is defined as a single arterial vessel, usually arising from both the left and the right ventricle, which gives rise to the systemic, pulmonary and coronary artery circulations.1 It is mostly associated with a large, non-restrictive ventricular septal defect (VSD) situated below the semilunar truncal valve. PTA is also reported to be associated with a high rate of mortality if uncorrected. Calder et al. stated that about 65% of patients treated medically did not survive beyond six months of age, and more than 90% who did not have surgical repair died before one year of age.1 Surgical intervention is required to avoid pulmonary vascular disease, which is common in the unrepaired patient. Because of this extremely poor prognosis, PTA is uncommonly encountered in adult life. Here we report on the unusual case of a woman with unrepaired TA who was evaluated by echocardiography and magnetic resonance imaging (MRI).

Case report Keywords: persistent truncus arteriosus, adult, echocardiography, pulmonary artery hypertension, magnetic resonance imaging Submitted 22/5/13, accepted 11/1/15 Cardiovasc J Afr 2015; 26: e6–e8

www.cvja.co.za

DOI: 10.5830/CVJA-2015-005

Cardiology Department, Hedi Chaker Hospital, Sfax, Tunisia Dorra Abid, MD, dorraabid@yahoo.com Sahar Ben Kahla, MD Souad Mallek, MD Leila Abid, MD Samir Kammoun, MD

Department of Radiology, Hedi Chaker Hospital, Sfax, Tunisia Emna Daoud, MD Hela Fourati, MD Zeineb Mnif, MD

A 41-year-old housewife initially presented to the Cardiology Department of Hedi Chaker Hospital in Tunisia in November 2011 with symptoms of exercise intolerance and occasional palpitations of several months’ duration. She had no family history of congenital defects. Three years earlier, when she was 38 years old, she gave birth to a normal baby after undergoing an uneventful full-term pregnancy and delivery. Cyanosis and dyspnoea on exertion had been present throughout her life, but despite this, she appeared to have had a fairly normal life, being able to tolerate daily activities well. Two weeks prior to admission, she reported having experienced an exacerbation of dyspnoea. She was a small-built woman and appeared deeply cyanosed on examination but not dyspnoeic at rest. Prominent clubbing of the fingers was noticeable. Congestion of the jugular veins was also striking. Her oxygen saturation in room air was about 80%. Physical examination revealed a mild systolic murmur over the left parasternal border and a loud second heart sound in the right second intercostal space. A 12-lead resting electrocardiogram revealed sinus rhythm, right bundle branch block and high QRS voltage suggestive of

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Fig. 1. T ransthoracic echocardiogram revealed a hypertrophied right ventricle, a single great vessel (persistent truncus arteriosus) overriding both ventricles, and a large single subtruncal ventricular septal defect. LA, left atrium; RA, right atrium; LV, left ventricle; RV, right ventricle; TV, troncal valve; PA, pulmonary artery.

biventricular hypertrophy. A chest radiograph revealed marked cardiomegaly with a prominent main pulmonary trunk and increased pulmonary vascularity. Transthoracic echocardiography indicated a levocardia heart with atrial situs solitus and concordant atrioventricular connections. Marked biventricular hypertrophy in the fourchamber view was also evident. The left ventricle demonstrated a normal ejection fraction. The most striking finding was a single large vessel arising from the base of the heart, with mild regurgitation related predominantly to the summit of the right ventricle (70%). A large, non-restrictive outlet VSD was noted A

beneath the truncal valve (Fig. 1). Neither the pulmonary artery (PA) nor the pulmonary valve could be seen. Cardiac MRI was also performed to better delineate the origin of the pulmonary arteries. It demonstrated a dilated common arterial trunk with the left and right pulmonary arteries arising from a short main pulmonary trunk at the posterior side of the common arterial trunk. The left ventricle (LV) was normal in size. The right ventricle (RV) was also normal in size with concentric hypertrophy. A large, subarterial VSD was noted beneath the truncal valve, which was trileaflet, with mild insufficiency (Fig. 2). C

Fig. 2. M RI demonstrated a dilated common arterial trunk with the left and right pulmonary arteries arising from a short main pulmonary trunk at the posterior side of the common arterial trunk. LV, left ventricle; RV, right ventricle; TV, troncal valve; LPA, left pulmonary artery.

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From on the above findings, for this patient, a diagnosis in keeping with a conotruncal anomaly could best be classified as type 1, based on Collette and Edwards’ classification.2 Furthermore, the thoracic vasculature was significantly altered, with irreversible pulmonary hypertension. Taking this into account, conservative management was recommended. The patient appeared to make good progress on medical treatment, which included bed rest and fluid restriction. She was advised against pregnancy, considering her mature age and in light of the underlying severe pulmonary hypertension. Her condition appeared to have remained stable 15 months after discharge from hospital. Chromosomal studies were not undertaken, however her child appeared in a good state of health.

Discussion PTA usually includes a large VSD with the presence of a significant left-to-right shunt, and is dependent on the resistance ratios between the systemic and pulmonary circulation. Indeed, pulmonary vascular resistance (PVR) decreases during the first weeks of life, and neonates experience congestive heart failure because of the increased pulmonary blood flow, unless the pulmonary arteries are hypoplastic or stenosed or there is persistently elevated PVR. These factors may delay the appearance of symptoms and babies appear mildly cyanosed due to the high PVR. According to Marcelletti et al.,3 these first effects are mainly beneficial and some patients unusually survived through to adulthood. Such survival is achieved only at the price of subjecting the pulmonary vasculature to the effects of severe pulmonary hypertension due to occlusive intimal fibro-elastosis.3 Echocardiography is a reliable, non-invasive, first-line imaging tool that proved to be beneficial in the diagnosis of differentiating this lesion from pulmonary atresia with VSD. The hallmark of PTA is that only a single semilunar valve is seen.4 MRI, although expensive and not easily accessible to all patients, is a complementary modality that has been shown to be accurate in the diagnosis and follow up of CHD.5 It is a useful adjunct, currently recognised by paediatric cardiologists and cardiac surgeons because it includes a wide field of view and multiplanar capabilities and reconstructions. The strength of MRI includes comprehensive access and coverage, providing imaging of all parts of the right ventricle, pulmonary arteries, pulmonary veins and aorta.6 Our case illustrates the major role of cardiac MRI, due to it

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being a fairly safe technique that allows precise definition and high resolution, and in this case, it demonstrated the complex anatomy of PTA. In this patient, the truncal valve was trileaflet and competent, which may have played an important role in her survival, since it is well established that truncal valve insufficiency is associated with higher rates of early and late mortality.7 Eisenmenger physiology is an absolute contraindication to pregnancy. Maternal mortality is reported to be as high as 36%.8 However, in this case, the patient had not received prior counselling before she fell pregnant, since her diagnosis was made three years after delivery. She was fortunate not to have had a complicated pregnancy.

Conclusion Echocardiography and MRI played an important role in detecting the PTA in this patient, which assisted in appropriate management. PTA is an uncommon cardiovascular anomaly with a poor prognosis, and without surgical repair, is regarded to be incompatible with life. This unique case study (type 1 PTA) offers an example of the natural history of an unrepaired complex congenital cardiac disease that overcame the odds of a short life expectancy.

References 1.

Calder R, van Praagh R, van Praagh S, et al. Truncus arteriosus communis. Clinical, angiocardiographic, and pathologic findings in 100 patients. Am Heart J 1976; 92(1): 23–38.

Collett RW, Edwards JE. Persistent truncus arteriosus; a classification according to anatomic types. Surg Clin North Am 1949; 29: 1245–1270.

Marcelletti C, McGoon DC, Mair DD. The natural history of truncus arteriosus. Circulation 1976; 54(1): 108–111.

Ferdman B, Singh G. Persistent truncus arteriosus. Curr Treat Options Cardiovasc Med 2003; 5(5): 429–438.

Choe YH, Kang IS, Park SW, Lee HJ. MR imaging of congenital heart diseases in adolescents and adults. Korean J Radiol 2001; 2(3): 121–131.

Kilner PJ. Imaging congenital heart disease in adults. Br J Radiol 2011; 84: S258–S268.

Rajasinghe HA, McElhinney DB, Reddy VM, Mora BN, Hanley FL. Long-term follow-up of truncus arteriosus repaired in infancy: a twentyyear experience. J Thorac Cardiovasc Surg 1997; 113: 869–878.

Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: A systematic overview from 1978 through 1996. J Am Coll Cardiol 1998; 31: 1650–1657.

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Case Report Exudative pericarditis in the evolution of a diffuse large B-cell lymphoma Cristina Bagacean, Adrian Tempescul, Jean-Christophe Ianotto, Veronique Marion, Dana Pop, Mihnea Zdrenghea

Abstract Cardiac involvement in non-Hodgkin’s lymphoma is a rare occurrence with a dismal prognosis, which may evolve with different clinical presentations, the most frequent being heart failure. Diagnosis of cardiac involvement is generally made by cardiac ultrasound. We report a case of lymphomatous pericarditis in the evolution of a non-Hodgkin’s lymphoma, diagnosed by PET-CT scan, and occurring concomitantly with complete isotopic remission of enlarged mediastinal lymph nodes following chemotherapy. Keywords: lymphomatous pericarditis, DLBCL, cardiac involvement Submitted 30/12/13, accepted 4/2/15 Cardiovasc J Afr 2015; 26: e9–e11

www.cvja.co.za

DOI: 10.5830/CVJA-2015-024

Case report We report on the case of a 51-year-old man diagnosed with a CD20-positive diffuse, large B-cell lymphoma (DLBCL), Ann Arbor stage IV (bone marrow), bulky (largest retroperitoneal adenopathy of 18 cm), with an international prognostic index of

Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Cristina Bagacean, MD Dana Pop, MD Mihnea Zdrenghea, MD, mzdrenghea@umfcluj.ro

Department of Clinical Hematology, Institute of Cancerology and Hematology, Teaching Hospital Brest, France Adrian Tempescul, MD Jean-Christophe Ianotto, MD

Laboratory of Hematology, Teaching Hospital Brest, France Veronique Marion, MD

Cardiology Department, Rehabilitation Hospital, Cluj-Napoca, Romania Dana Pop, MD

Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania Mihnea Zdrenghea, MD

4. Cytogenetic analysis showed t(14,18) and deletion of the p53 gene. The patient was HIV negative. At presentation, the patient had peritoneal effusion, whose cytological examination failed to prove the presence of lymphoma cells. Chemotherapy was started with one cycle of rituximab(R)COP (cyclophosphamide, vincrsitin and prednisolone), followed by four cycles of R-VACP (rituximab plus vincristin, doxorubicin, cyclophosphamide and prednisolone), according to GOELAMS protocol, leading to complete remission, demonstrated by 18-F-FDG-PET scan. The patient subsequently underwent autologous stem cell transplantation conditioned by BEAM 140 (BCNU, cytarabine, etoposide and melphalan); the number of re-infused CD34+ cells was 3 × 106 cells/kg. Six months post autograft, he presented with weakness and malaise. The CT scan showed enlarged, compressive mediastinal lymphadenopathy. Rescue chemotherapy was initiated with two cycles of R-ESHAP (rituximab plus etoposide, cytarabine, methylprednisolone and cisplatin), with only minimal response. Because of his young age and good performance index, continuation of the rescue treatment was decided, with two courses of IVA75 (ifosfamide, etoposide and doxorubicin), leading to partial remission. Since the total anthracycline dose received to that date (490 mg/m2, close to the conventional maximal dose of 550 mg/m2) was concerning for cardiotoxicity, treatment was continued with two cycles of liposomal doxorubicin (anthracycline preparation with far lesser cardiac toxicity) and cyclophosphamide. The patient developed dyspnoea and lower leg oedema.18 F-FDG PET scan evaluation showed complete remission of the enlarged mediastinal lymph nodes, but also a large pericardial effusion (Fig. 1). The patient was admitted to the intensive care unit. Two-dimensional echocardiography confirmed the presence of a massive, 4-cm-thick pericardial effusion. Pericardial tap drained 1 000 ml of liquid. Cytological analysis demonstrated massive infiltrate with large CD19+ and CD5– lymphoma cells. On fluorescence in situ hybridisation analysis, these cells showed identical cytogenetic abnormalities to the original diagnosis. The presence and development of lymphomatous pericardial effusion was discordant with complete remission of the mediastinal lymph nodes observed on the PET scan. A cycle of R-DA-EPOCH (dose-adjusted etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone, plus rituximab) chemotherapy was administered. This was followed by febrile neutropenia, and death due to septic shock 13 months after the initial diagnosis.

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Fig. 1. C oronal and sagittal CT and fused PET-CT reformatted images demonstrate large pericardial effusion (arrow). No abnormal FDG uptake is noted.

Discussion Cardiac involvement in lymphomas is a rare clinical presentation with a dismal prognosis, occurring either as a primary cardiac lymphoma,1 or, more frequently, as secondary involvement in the late evolution of aggressive lymphomas.2 The clinical presentation of cardiac involvement in lymphoma is variable. Often, diagnosis is made by routine echocardiography. This is regularly performed because evaluation of cardiac function is important for assessment of the tolerability and side effects of chemotherapy, especially in anthracycline-containing regimens, which are known for their cardiotoxicity.3,4 Even if the frequency of this type of tumour appears to be increasing, real epidemiological figures are unknown, helped by the fact that involvement of the heart is often asymptomatic. Although rarely diagnosed during neoplastic clinical evolution, cardiac metastases have been found in more than 10% of post mortem examinations of patients succumbing to cancer,5 more frequently in melanoma, lung and breast cancer. In lymphoma patients, post mortem figures for cardiac involvement range from nine to 20%.5,6 The diagnostic difficulty in late evolution of non-Hodgkin lymphoma is associated with the fact that heart failure may also be due to cumulative cardiac toxicity of multiple lines of treatment and of the toxic cardiac effects of anthracyclin-based chemotherapy regimens.7,8 The role of 18F-FDG PET scans in detecting cardiac involvement of lymphoma has been described in several case reports of extralymphatic tumour involvement in lymphoma.9,10 In our patient, cardiac involvement appeared as a late evolution of an aggressive DLBCL. After four lines of chemoimmunotherapy, including autologous stem cell transplantation, the patient relapsed with mediastinal lymphadenopathy. Because of the high cumulative dose of anthracyclines, well known for their cardiotoxic effect, we chose to continue with a regimen containing less cardiotoxic pegylated anthracycline, associated with alkylating agent cyclophosphamide. After two cycles the patient developed clinical signs of right cardiac failure. Examination by PET scan found the presence of a massive pericardial effusion (Fig. 1), but discordantly, complete remission of the initial localisations of the lymphoma.

Our first hypothesis on the cause of the effusion was the cumulative toxic effect of chemotherapy, but cytology, immunophenotyping and cytogenetic analysis of the liquid obtained by puncture showed the presence of lymphoma. Lymphoproliferative disease is regarded as systemic and pericardial, i.e. extralymphatic involvement is a sign of the highest degree of dissemination in lymphoma staging, warranting systemic therapy after removal of the pericardial effusion fluid, rather than performing pericardiectomy or pericardial sclerosis.

Conclusion We suggest that, if signs or symptoms of cardiac failure develop during or after chemotherapy for lymphoma, the hypothesis of cardiac involvement of lymphoma should be considered. The diagnosis of this usually late complication requires cytological confirmation. This work was supported by grant 1494 /2014 from the University of Medicine and Pharmacy Cluj (to M Zdrenghea) and the European Social Fund, Human Resources Development Operational Programme 2007-2013, project POSDRU/159/1.5/S/138776 (to C Bagacean and M Zdrenghea). The sponsors had no involvement in the collection, analysis and interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication.

References 1.

Ceresoli GL, Ferreri AJ, Bucci E, Ripa C, Ponzoni M, Villa E. Primary cardiac lymphoma in immunocompetent patients: diagnostic and therapeutic management. Cancer 1997; 80: 1497–1506.

Mikdame M, Ennibi K, Bahrouch L, Benyass A, Dreyfus F, Toloune F. [Cardiac localization of non Hodgkin’s lymphoma: a study on four cases]. Rev Med Interne 2003; 24: 459–463.

Sarjeant JM, Butany J, Cusimano RJ. Cancer of the heart: epidemiology and management of primary tumors and metastases. Am J Cardiovasc Drugs 2003; 3: 407–421.

Meng Q, Lai H, Lima J, Tong W, Qian Y, Lai S. Echocardiographic and pathologic characteristics of primary cardiac tumors: a study of 149

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cases. Int J Cardiol 2002; 84: 69–75. 5. 6.

Goldberg AD, Blankstein R, Padera RF. Tumors metastatic to the heart. Circulation 2013; 128: 1790–1794.

Cardiac complications and manifestations of chemotherapy for cancer. Heart 2014; 100(14): 1133–1140.

Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol 2007; 60: 27–34.

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Cho JM, Sohn IS, Yang YJ. Heart in the heart: dual faced primary cardiac lymphoma on PET-CT. Int J Cardiol 2010; 142: e40–41.

10. Lee JC, Platts DG, Huang YT, Slaughter RE. Positron emission tomog-

Lotrionte M, Biondi-Zoccai G, Abbate A, et al. Review and meta-anal-

raphy combined with computed tomography as an integral component

ysis of incidence and clinical predictors of anthracycline cardiotoxicity.

in evaluation of primary cardiac lymphoma. Clin Cardiol 2010; 33:

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E106–108.

Khawaja MZ, Cafferkey C, Rajani R, Redwood S, Cunningham D.

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Case Report Intermittent symptomatic functional mitral regurgitation illustrated by two cases Alper Aydin, Tayfun Gurol, Ozer Soylu, Bahadir Dagdeviren

Abstract Functional mitral regurgitation may have different haemodynamic consequences, clinical implications and treatment options, such as surgical or percutaneous interventions or implanting a pacemaker. Here we present two cases with haemodynamically significant intermittent functional mitral regurgitation as the underlying mechanism of heart failure. The cases underline the importance of a high index of suspicion in patients with intermittent heart failure, and a careful analysis of echocardiographic images with simultaneous ECG, in order to delineate systolic and diastolic mitral regurgitation. Keywords: mitral regurgitation, electromechanical delay, Doppler echocardiography, left bundle branch block, mitral insufficiency Submitted 24/4/13, accepted 25/2/15 Cardiovasc J Afr 2015; 26: e12â&#x20AC;&#x201C;e14

www.cvja.co.za

DOI: 10.5830/CVJA-2015-026

Heart failure (HF) in patients with normal left ventricular ejection fraction accounts for half of the diagnoses of HF. Careful echocardiographic analysis with simultaneous ECG in

Department of Cardiology, Faculty of Medicine, Bahcesehir University, Istanbul, Turkey Alper Aydin, MD, dralperaydin@gmail.com Tayfun Gurol, MD Ozer Soylu, MD Bahadir Dagdeviren, MD

two patients developing acute heart failure allowed identification of an unusual cause of HF with normal left ventricular ejection fraction (LVEF), but related to sudden reversible functional mitral regurgitation in the absence of significant coronary artery stenosis.

Case 1 A 54-year-old female was admitted to hospital with acute pulmonary oedema. Her ECG showed sinus tachycardia with left bundle branch block (LBBB) morphology, with a rate of 125 beats per min (bpm). Her symptoms improved following spontaneous conversion to sinus rhythm without LBBB. Two-dimensional echocardiography revealed concentric left ventricular (LV) hypertrophy with normal systolic function (LVEF 70%), with mild rheumatic mitral regurgitation (MR), mild left atrial dilatation (4.3 cm) and elevated pulmonary artery systolic pressure (50 mmHg). The tenting area of the mitral leaflets and the tenting length was measured as 3.9 cm2 and 1.3 cm, respectively. The mitral annular dimension was 4.2 cm. The results of her laboratory examination were normal. Her medical history was unremarkable for cardiovascular disease and she was not taking any anti-arrhythmia drugs. Since her symptoms occurred again the following day, the echocardiographic examination was repeated. In the second study, the rhythm was sinus tachycardia with LBBB morphology. The QRS duration was 150 ms. Transoesophageal echocardiography (TEE) revealed marked asynchronous contraction and dilatation of the left ventricle and atrium (5.1 cm). The left atrium was seen as being larger in this second assessment (5.1 cm), with severe MR (Fig. 1). The effective regurgitant orifice area was 0.6 cm2 with a regurgitant volume of 67 ml. The tenting area of the mitral leaflets and the C

Fig. 1. T ransoesophageal echocardiography images demonstrating severe mitral regurgitation (A) during left bundle branch block. The arrow in B shows impaired coaptation of the mitral valve leaflets (LA: left atrium, LV: left ventricle). The tenting area was measured as 7.8 cm2 (C), and the pulmonary artery pressure (D) was elevated to 95 mmHg.

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Fig. 2. T ransoesophageal echocardiography images demonstrating mild mitral regurgitation (panels A and B) with a 3.9-cm2 tenting area (panel C), and decreased pulmonary artery pressure to 40 mmHg (panel D). (RA: right atrium, RV: right ventricle, Ao: aorta.)

tenting length were 7.8 cm2 and 1.8 cm, respectively. The mitral annular dimension was 4.8 cm. After spontaneous narrowing of the QRS duration to 60 ms, the third echocardiography showed mild MR with improved pulmonary pressure (Fig. 2). Ischaemic heart disease was excluded by coronary angiography. During follow up, paroxysmal LBBB recurred repeatedly, all with pulmonary oedema symptoms resolving with conversion to sinus rhythm without LBBB. Because of the severe symptoms, which were resistant to medical therapy, we decided to perform mitral valve repair surgery. Mitral valvuloplasty with a rigid annuloplasty ring (Sorin Memo 3D 28-mm semi-rigid mitral) was performed. Within two years following the procedure, the patient had no symptoms of heart failure despite having paroxysmal LBBB attacks.

Case 2 A 56-year-old female had complained of exertional dyspnoea and gradual intolerance during exercise for the previous three months. Transthoracic echocardiography (TTE), which was performed in another hospital, had revealed moderate-to-severe mitral regurgitation and therefore she was referred to have surgery for mitral valve replacement. Her medical history was unremarkable for cardiovascular disease and she was not taking any anti-arrhythmia drugs. Initially, ECG revealed sinus rhythm with a heart rate of 66 bpm. TTE showed normal chamber volumes and functions with mild MR. During the TTE assessment she developed sudden dyspnoea with 2:1 atrio-ventricular (AV) block, and colour Doppler echocardiography revealed moderate early and mid-diastolic mitral regurgitation jets (Vmax = 1.2 m/s, Vâ&#x20AC;&#x201C;A gradient of 6 mmHg) that regularly followed blocked P waves (Fig. 3). A

She was treated with a DDD pacemaker. No symptoms occurred during one year of follow up. Further TTE examinations showed no diastolic mitral regurgitation.

Discussion Competence of the mitral valve requires a temporally and spatially coordinated interaction of the mitral leaflets with the annulus, chordae tendinae and papillary muscles. Dysfunction of any of these components affects the normal systolic coaptation of the anterior and posterior leaflets and causes mitral regurgitation. Mechanistically, mitral regurgitation (MR) is classified as either primary (intrinsic valve disease) or functional.1 Functional MR occurs in patients with a structurally normal valve (generally with restricted leaflet mobility), mitral annular dilation, and left ventricular remodelling.2 Functional MR is further classified as systolic and diastolic due to timing in the cardiac cycle. Ischaemia is a well-known cause of functional MR.3 The underlying mechanism is apical tenting of structurally normal leaflets with subsequent papillary muscle displacement away from the mitral annulus plane.4 Eclipsed mitral regurgitation is an atypical form of sudden transient functional MR and is reported as sudden apical tenting of both leaflets in the absence of epicardial coronary artery stenosis and pre-existing LV systolic dysfunction or remodelling.5 Avierinos et al. reported severe mitral regurgitation with symptoms of heart failure that was induced by methylergonovine injection. Possible underlying mechanisms were epicardial focal spasm, diffuse epicardial vasoconstriction or microvascular dysfunction. Rhythm and conduction disturbances are also common causes of mitral regurgitation. Electromechanical asynchrony can alter the left ventricular contraction pattern. Left bundle branch block (as in our first case) is an example of ventricular C

Fig. 3. C olour (A) and continuous-flow Doppler (B) images demonstrating diastolic mitral regurgitation. The bold arrows represent diastolic regurgitation; open arrows represent blocked P waves.

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asynchrony related to functional mitral regurgitation.6,7 Functional mitral regurgitation in patients with left bundle block has multiple components, including asynchrony of the papillary muscles due to delay in ventricular conduction, which causes a delay in the contraction of the papillary muscles.8,9 The delayed movement of certain areas of the left ventricle (lateral wall or interventricular septum) leads to a reduction in the force of mitral valve closure due to the fall in systolic volume caused by the asynchronous mechanical contraction. Long-term right ventricular (RV) apical pacing can also cause MR. It has been shown in canine models that RV pacing can increase mitral and tricuspid valve incompetence.10 While the incidence of MR appeared to be low at baseline, this study showed that MR can increase in the course of time due to permanent RV apical pacing. This holds true, especially in patients with pre-existing MR. Left ventricular dyssynchrony can be considered as a cause of MR after long-term RV apical pacing. There are a few reported cases of acute severe MR as an immediate perioperative complication of pacemaker insertion, leading to acute haemodynamic deterioration. Rita et al. demonstrated that RVA pacing may immediately induce severe MR and acute cardiac failure, even in patients with preserved LV contraction.11 This case also shows RV outflow tract pacing improves MR compared with apical pacing, probably by improving ventricular dyssynchrony. Diastolic mitral regurgitation (DMR) is a common phenomenon seen in patients with AV blocks, hypertrophic cardiomyopathy, advanced left ventricular systolic dysfunction, aortic valve disease, and in the presence of atrial fibrillation with long cardiac cycles. The haemodynamic mechanism leading to DMR is due to a positive ventricular-to-atrial (V–A) pressure gradient occurring during diastole.12,13 Because of the AV dyssynchrony, the AV pressure gradient reverses (ventricular pressure becomes higher than atrial), resulting in DMR in the presence of an incompletely closed mitral valve.14

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References 1.

Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet 2009; 373: 1382–9134.

Agricola E, Oppizzi M, Galderisi M, et al. Role of regional mechanical dyssynchrony as a determinant of functional mitral regurgitation in patients with left ventricular systolic dysfunction. Heart 2006; 92:1390–1395.

Finelli D, Mehta J. Transient severe mitral regurgitation due to myocardial ischemia. Chest 1982; 82: 376–378.

Otsuji Y, Gilon D, Jiang L, et al. Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering. J Am Coll Cardiol 1998; 32: 398–340.

Avierinos JF, Thuny F, Tafanelli L, et al. Eclipsed mitral regurgitation: a new form of functional mitral regurgitation for an unusual cause of heart failure with normal ejection fraction. Cardiology 2008; 110(1): 29–34.

Leclercq C, Kass DA. Retiming the failing heart: principles and current clinical status of cardiac resynchronization. J Am Coll Cardiol 2002; 39: 194–201.

Ypenburg C, Lancellotti P, Tops LF, et al. Acute effects of initiation and withdrawal of cardiac resynchronization therapy on papillary muscle dyssynchrony and mitral regurgitation. J Am Coll Cardiol 2007; 50: 2071–2077.

Breithardt OA, Sinha AM, Schwammenthal E, et al. Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol 2003; 41: 765–770.

Alessandri N, Mariani S, Messina FR, et al. Diastolic mitral regurgitation: A borderline case in cardiovascular physiology. Eur Rev Med Pharmacol Sci 2003; 7: 161–170.

10. Maurer G, Torres MA, Corday E, et al. Two-dimentional echocardiographic contrast assessment of pacing-induced mitral regurgitation: relation to altered regional left ventricular function. J Am Coll Cardiol 1984; 3: 986–991. 11. Rita M, Sofia A, Luis B, et al. Acute severe mitral regurgitation as an early complication of pacemaker implantation. Europace 2010; 12: 1791–1792. 12. Raffa S, Zito C, Oliva S, et al. Diastolic mitral and tricuspid regurgita-

Conclusion These two cases illustrate different mechanisms of mitral regurgitation, which may have different haemodynamic consequences and clinical implications. The cases underline the importance of a high index of suspicion in patients with intermittent heart failure, and a careful analysis of echocardiographic images with simultaneous ECG, in order to delineate systolic and diastolic MR.

tion. Ecocardiography 2006; 23: 251–253. 13. Schnittger I, Appleton CP, Hatle LK, et al. Diastolic mitral and tricuspid regurgitation by Doppler echocardiography in patients with atrioventricular block: New insight into the mechanism of atrioventricular valve closure. J Am Coll Cardiol 1988; 11: 83–88. 14. Panidis IP, Ross J, Munley B, et al. Diastolic mitral regurgitation in patients with atrioventricular conduction abnormalities: A common finding by Doppler echocardiography. J Am Coll Cardiol 1986; 7: 768–774.

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Case Report Unusual complication of aortic dissections: intimo–intimal intussusception Unsal Vural, Ahmet Yavuz Balci, Ahmet Arif Aglar, Mehmet Kizilay, İbrahim Yekeler, Abdullah Kemal Tuygun

Abstract Angiography with a pre-diagnosis of acute coronary syndrome was performed in a 76-year-old female patient presenting to another hospital with symptoms of chest pain and syncope. Upon determination of type III aortic dissection, the patient was referred to our clinic. On CT angiography, the ascending aortic diameter was 57 mm and no dissection flap was observed. There was a filling defect suggestive of intimo–intimal intussusception at the level of the aortic arch, occlusion of the left arteria carotid communis, and a double-channel aorta extending from the left subclavian artery to the iliac artery. On transoesophageal echocardiography, the ascending aorta was seen to be larger than normal and no dissection flap was observed. There were findings suggestive of haematoma and intimo–intimal intussusception at the proximal part of the aortic arch. The dissection flap causing occlusion in the vascular structures was resected. Supracoronary graft replacement of the ascending aorta was performed. Transoesophageal echocardiography is an invasive investigative method with high sensitivity and specificity for the diagnosis of intimo–intimal intussusception.

Keywords: intimo-intimal intussusception, complication of aortic dissections, DeBakey type I and type II, surgical treatment, urgent surgical intervention Submitted 30/12/14, accepted 16/3/15 Cardiovasc J Afr 2015; 26: e15–e18

www.cvja.co.za

DOI: 10.5830/CVJA-2015-029

Intimo–intimal intussusception is a rare but fatal complication of aortic dissection. Emergency surgery is a life-saving procedure in aortic dissection. Intimo–intimal intussusception is an atypical manifestation of aortic dissection produced by circumferential

Dr Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey Unsal Vural, MD, unsalvural@gmail.com Ahmet Yavuz Balci, MD Ahmet Arif Aglar, MD Mehmet Kizilay, MD İbrahim Yekeler, PhD, MD Abdullah Kemal Tuygun, MD, PhD

dissection of the media and intimal layer of the aorta and invagination of the intimal flap in the aortic arch in DeBakey type I and type II aortic dissections. Due to the absence of the intimal flap and crescent sign in the ascending aorta, it is difficult to diagnose this condition. A definitive diagnosis is made on transoesophageal echocardiography (TEE) with the observation of a prolapse of the dissection flap into the ascending aorta. Delaying the diagnosis may result in delayed treatment and increased risk of mortality. We present our case with a literature review of diagnosis and treatment of intimo-intimal intussusception.

Case report Angiography was performed for a pre-diagnosis of acute coronary syndrome in this case presenting to a cardiology centre with symptoms of syncope and chest pain lasting for three days. She was referred to our clinic with a pre-diagnosis of type III aortic dissection since a catheter had been placed into the false lumen and it could not be advanced into the aortic arch. The 76-year-old female patient was admitted for the purpose of investigation and treatment. It was learned from her history that she had had hypertension for 10 years, and had been receiving treatment for 15 years for diabetes mellitus. On physical examination, she had poor consciousness with a poor general condition and a tendency to sleepiness. Her blood pressure and pulse rate were determined at 180/100 mmHg and 120 beats/min, respectively. Her left radial pulse was absent. While the rhythm on a 12-lead ECG tracing taken three days earlier was normal sinus rhythm, the rhythm was ‘atrial fibrillation’ on the subsequent ECG. There was no finding suggestive of coronary ischaemia. Troponin T levels were within the normal ranges (troponin T = 0.05 ng/ml). Echocardiography was reported as ‘left ventricular functions were normal, the ascending aorta and the aortic root were larger than the normal diameter of the aorta, a mild aortic valve regurgitation was present, pericardial effusion was absent, no dissection flap was determined in the ascending aorta’. On CT angiography, the ascending aortic diameter was 57 mm and no dissection flap was present. A filling defect suggestive of intimo–intimal intussusception was observed at the level of the aortic arch. The left arteria carotid communis was occluded from the left subclavian artery. A double-channel aorta extending to the iliac artery was observed in the thoracic and abdominal aorta (Fig. 1). On TEE, the ascending aorta was seen to be larger than normal and no dissection flap was observed. There was the

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CA B

Fig. 1. P ost-contrast axial computed tomography scan demonstrates intussuscepted dissection flap (A) in aortic arch with very narrow residual true lumen (C) and a larger false lumen (B).

appearance of a haematoma at the proximal part of the aortic arch and a flap entering into the aorta from the aortic arch during ventricular diastole. Mild aortic valve regurgitation due to dilation was confirmed. A filling defect had been determined at the level of the aortic arch on the angiography performed in another centre. It was learned that the angiography could not be continued since the catheter had been placed into the false lumen. Considering the poor condition of the patient and the possibility of rupture of the dissection, she was operated on emergently.

Surgical treatment A median sternotomy was performed under general anaesthesia. Arterial cannulation was performed through a 10-mm graft anastomosed to the right subclavian artery in an end-toside fashion. Venous cannulation was performed through the right atrium and cardiopulmonary bypass was established. Left ventricular decompression was achieved through the right upper pulmonary vein. Total circulatory arrest (TCA) was established by reducing the temperature to approximately 18°C. Iced saline was applied around the patient’s head for brain protection. Cerebrovascular circulation was established by administering one-fifth of the total cardiac output to the right carotid artery through the right subclavian artery during circulatory arrest. Coronary perfusion was established with antegrade blood cardioplegia. The ascending aorta was opened in an oblique fashion. It was observed that the intimal layer of the ascending aorta caused an obstruction by prolapsing into the aortic arch (Fig. 2). A definitive diagnosis was made by observation of the prolapse of the circumferential dissection flap into the aortic arch. The prolapsed intimal layer flap was resected through the aortic arch. The coronary ostia were seen to be open and retrograde flows were sufficient in the aortic arch. The distal part of the ascending aorta was constructed using a 30-mm Dacron graft (Gorotex®) with a continuous suture

Fig. 2. Photograph during surgery shows total circumferential intimal tear with intimo–intimal intussusception of the internal channel into the arch.

technique. The posterior part of the anastomosis was supported with single-pledget mattress sutures. After draining the air bubbles in the artery, the ascending aorta was cross-clamped to the new vascular graft and cardiopulmonary bypass was established. Deep hypothermia was terminated. TCA lasted 13 minutes. The function and structure of the aortic valve and coronary ostia were normal. Fibrin glue was used to adhere the dissection flap at the proximal anastomosis site of the graft in the supracoronary region. The flap was sutured over itself with a continuous suture technique. The Dacron graft (Gorotex®) was anastomosed to the supracoronary aorta with a continuous suture technique. The posterior part of the anastomosis was supported with pledget mattress sutures. The aortic cross-clamp was terminated after draining the air bubbles in the heart and the new aorta. Cardiopulmonary bypass was terminated after normothermia. After bleeding was controlled, the tissues were closed. The patient was discharged after one day of postoperative intensive care and 12 days of follow up. During hospitalisation, antihypertensive and prophylactic antibiotic therapies were administered. Lifelong antihypertensive treatment was recommended. No problem was determined at the first month’s postoperative follow up. After six months, it was observed that the false lumen was closed on CT angiography.

Discussion A dissection of the ascending aorta is only rarely circumferential. Complete circular dissection of the aorta was reported for the first time by Bostroem in 1887.1 Hufnagel named this complication intimo–intimal intussusception.2 Intussusception of the internal cylinder in the external aortic cylinder during circumferential dissection may induce obstruction of the aortic lumen or obstruction of the ostia of the supra-aortic vessels.3 Typical features of intimo–intimal intussusception are acute onset of chest or back pain. Goldberg et al. reported that when

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the cerebral vascular bed was affected, adverse neurological events were reported in 5–10% of cases.4 As in our case, when the subclavian artery was affected, asymmetric upper extremity blood pressures occurred.5 When the spinal canal and peripheral nerves are affected, symptoms such as paresis and plegia occur.6 One of the most important factors in making a diagnosis of aortic dissection is a high index of suspicion. Usually physical examination leads to a diagnosis of suspicion. Hypertension is either the main reason for dissection or it develops secondary to severe pain. Hypotension is an important finding of tamponade or coronary flow impairment. Since chest pain was followed by unconsciousness in the history of our patient with hypertension, our pre-diagnosis was aortic dissection. Absence of a left radial pulse on physical examination strengthened the diagnosis of aortic dissection. Absence of flow in the left common carotid and subclavian artery was confirmed with CT angiography. TEE revealed that the absence of flow was due to intimo–intimal intussusception. During surgery, it was observed that the cause of occlusion was a dissection flap prolapsing into the aortic arch. Suspicion of a diagnosis of intimo-intimal intussusception is life saving. On CT angiography, the intimal flap, false lumen and crescent sign in the ascending aorta observed in DeBakey type I and type II aortic dissections are absent in these patients. As in our case, a filling defect may be determined in the aortic arch by prolapsing of the intima (Fig. 1). ‘False occlusions’ may be observed in the vascular structures of the brain and extremities. Delay in treatment causes transformation of the occlusion to a ‘real occlusion’.7 There was no evidence of dissection of the ascending aorta in our case. TEE confirmed the haematoma in the distal part of the ascending aorta and motion of the intimal flap towards the ascending aorta during diastole. Lajevardi et al. and Nohara et al. reported that the proximal part of the circumferential dissection in the ascending aorta occluded the coronary ostia and caused severe aortic valve insufficiency by entering the aortic valve.3,8 Aortic valve insufficiency due to a dissection flap is present in 60–70% of type I dissections.9 This condition occurs with three mechanisms of action: (1) central regurgitation due to annular dilation, (2) distortion of aortic root geometry due to prolapse of the dissection across a leaflet, (3) annulus rupture or tearing of one of the leaflets.10 Sometimes aortic valve insufficiency can be the only finding suggestive of dissection of the ascending aorta in patients without symptoms of dissection.10 In our case, aortic valve insufficiency was considered to be due to annular dilation. Cases resulting in a fatal outcome due to occlusion in the coronary ostia during diastole, caused by the proximal part of the dissection flap, have also been reported.3 Myocardial infarction is seen at a rate of 1–2% in aortic dissections.11 The dissection flap in the coronary ostia can be seen during angiography, with a diagnosis of coronary syndrome, as in our case.11 A diagnosis of aortic dissection must be excluded in acute coronary syndrome, otherwise antiplatelet and anticoagulant therapy may have fatal outcomes. Angiography was also performed in our case, with a diagnosis of acute coronary syndrome. Not being able to advance the angiography catheter into the aortic arch and determination of the false lumen caused a misdiagnosis of type III aortic dissection. Since angiography could not be completed, the coronary ostia could not be seen.

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During surgery, we determined that the coronary ostia were occluded by the distal part of the dissection flap during diastole. In the literature, cases have frequently been reported of patients misdiagnosed with type III aortic dissection when the dissection flap was not observed in the ascending aorta.12 Where other diagnostic methods are insufficient in the diagnosis, TEE may be helpful, as the motion of the dissection flap invaginated in the aortic arch can be observed. Due to motion of the proximal part of the dissection flap toward the ventricle, it may be observed that it causes aortic valve insufficiency. TEE is considered to be the reference investigation with 98% sensitivity.8,12 TEE was also the most powerful diagnostic method in our case.

Conclusion Intimo–intimal intussusception is a rare complication of aortic dissection. However, it may be severe or fatal due to its effect on the cerebral and peripheral vascular structures in the distal part of the ascending aorta, and its effect on the coronary arteries and aortic valve in the proximal part of the ascending aorta. It should definitely be considered in elderly patients with hypertension in the presence of chest pain and unconsciousness. TEE is the chosen investigative method with high sensitivity and specificity in the diagnosis. It is important for a differential diagnosis during the pre-operative period and for determination of intra-operative treatment strategy.

References 1.

Von bostroem E. Das geheilte aneurysma dissecans. Deut Arch Klin Med 1887; 42: 1.

Hufnagel CA, Conrad PW. Intimo-intimal intussusception in dissecting aneurysms. Am J Surg 1962; 103: 727–731. PMID: 14449761.

Lajevardi SS, Sian K, Ward M, Marshman D. Circumferential intimal tear in type A aortic dissection with intimo-intimal intussusception into left ventricle and left main coronary artery occlusion J Thorac Cardiovasc Surg 2012; 144: 21–23. DOI: 10.1016/j.jtcvs.2012.05.010.

Goldberg SP, Sanders C, Nanda NC, Holman WL. Aortic dissection with intimal intussusception: diagnosis and management. J Cardiovasc Surg (Torino). 2000; 41: 613–615. PMID: 11052292.

Neri E, Capannini G, Carone E, Tucci E, Diciolla F, Sassi C. The missing flap: consideration about a case of aortic intussusception. J Thorac Cardiovasc Surg 1999; 117: 829–830. DOI: 10.1016/S00225223(99)70309-0.

Khan IA, Nair CK. Clinical, diagnosis, and management perspectives of aortic dissection. Chest 2002; 122: 311–328. DOI:10.1378/ chest.122.1.311.

Reitknecht FL, Bhayana JN, Lajos TZ Circumferential intimal tear causing obstruction of the aortic arch: an unusual complication of aortic dissection Ann Thorac Surg 1988; 46: 100–101. PMID: 3289513

Nohara H, Shida T, Mukohara N, Nakagiri K, Matsumori M, Ogawa K. Aortic regurgitation secondary to back-and-forth intimal flap movement of acute type A dissection. Ann Thorac Cardiovasc Surg 2004; 10: 54–56. PMID:15008702

Fann JI, Glower DD, Miller DC, Yun KL, Rankin JS, White WD, et al. Preservation of aortic valve in type A aortic dissection complicated by aortic regurgitation. J Thorac Cardiovasc Surg 1991; 102: 62–73. PMID: 2072730.

10. Lijoi A, Scarano F, Canale C, Parodi E, Dottori V, Passerone GC, et al.

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Circumferential dissection of the ascending aorta with intimal intussusception. Case report and review of the literature. Tex Heart Inst J 1994; 21: 166–169. PMID: 8061542.

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of acute aortic dissection. Circulation 2011; 123: 2213–2218. DOI: 10.1161/CIRCULATIONAHA.110.988568. 12. Chow JL, Mariano ER, Liang D. Transesophageal Echocardiography

11. Rogers AM, Hermann LK, Booher AM, Nienaber CA, Williams DM,

assessment of severe aortic regurgitation in type A aortic dissection

Kazerooni EA, et al. Sensitivity of the aortic dissection detection risk

caused by a prolapsed circumferential intimal flap. J Cardiothorac

score, a novel guideline-based tool for identification of acute aortic

Vasc Anesth 2007; 21: 85–87. DOI: http://dx.doi.org/10.1053/

dissection at initial presentation: results from the international registry

j.jvca.2005.09.005.

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Case Report Bare-metal stent thrombosis two decades after stenting Aynur Acibuca, Demet Menekse Gerede, Veysel Kutay Vurgun Case report

Abstract Very late bare-metal stent (BMS) thrombosis is unusual in clinical practice. To the best of our knowledge, the latest that the thrombosis of a BMS has been reported is 14 years after implantation. Here, we describe a case of BMS thrombosis that occurred two decades after stenting. A 68-year-old male patient was admitted with acute anterior myocardial infarction. This patient had a history of BMS implantation in the left anterior descending coronary artery (LAD) 20 years previously. Immediate coronary angiography demonstrated acute thrombotic occlusion of the stent in the LAD. With this case, we are recording the latest reported incidence of BMS thrombosis after implantation. Keywords: bare-metal stent, very late stent thrombosis, acute coronary syndrome, antiplatelet therapy Submitted 7/1/15, accepted 25/3/15 Cardiovasc J Afr 2015; 26: e19–e21

www.cvja.co.za

DOI: 10.5830/CVJA-2015-034

Stent thrombosis is a rare but serious complication that can lead to death or myocardial infarction (MI). Premature cessation of dual antiplatelet therapy is the most important risk factor. Stent thrombosis is classified according to the ARC (academic research consortium) criteria as definite, probable or possible.1 Stent thrombosis can occur acutely (within 24 hours), sub-acutely (within 30 days), or as late as one year (late) or more (very late) after stent placement. Both randomised trials and observational study data have demonstrated that the cumulative rate of stent thrombosis is similar for bare-metal and first-generation drug-eluting stents for up to five years.2,3 There may be a slight predominance of bare-metal stent (BMS) thrombosis between 30 days and one year, with a slight preponderance of drug-eluting stent (DES) thrombosis beyond one year.4 Here, we report a case of very late BMS thrombosis that presented as anterior myocardial infarction 20 years after stent implantation for left anterior descending coronary artery (LAD) disease. Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey Aynur Acibuca, MD, aynuracibuca85@gmail.com Demet Menekse Gerede, MD Veysel Kutay Vurgun, MD

A 68-year-old non-diabetic, normotensive, ex-smoking male patient was admitted to our coronary care unit complaining of chest pain of one hour onset, which was unresponsive to nitroglycerin. This patient’s history included a bare-metal stent implantation for a proximal LAD lesion 20 years previously. He had been discharged on acetyl salicylic acid; however, one month later, he discontinued antiplatelet medication and stopped attending his control visits. The electrocardiogram showed acute anterior myocardial infarction (Fig. 1), and an immediate coronary angiography showed total occlusion of the implanted stent in the proximal LAD (Figs 2A, B). Balloon angioplasty was therefore performed (Alvimedica balloon, 3 × 15 mm). TIMI 3 (thrombolysis in myocardial infarction) coronary flow was achieved (Fig. 2C); however, there appeared to be a need to perform percutaneous transluminal coronary angioplasty (PTCA) for the diagonal coronary artery branch (Advancer Hp balloon, 2 × 15 mm). Plaques were found on the right and circumflex coronary arteries. Following the administration of a bolus, tirofiban infusion was initiated post-procedurally and was continued for 24 hours. During the follow-up period, ST-segment resolution was achieved. Transthoracic echocardiography showed modest impairment of the left ventricular systolic function with a global ejection fraction of 52%. On the sixth day after admission, this patient was discharged on dual antiplatelet therapy.

Discussion While very late stent thrombosis may be expected with the use of DES, it is rare with the use of BMS. A large, retrospective study reported that the cumulative incidence of stent thrombosis after BMS implantation was 1.3% at five years, and 2.0% at 10 years.5 The expected risk factors related to very late stent thrombosis are delayed neo-intimal proliferation and ongoing vessel inflammation.6 This is unexpected for BMS because stent endothelialisation is considered to be complete four weeks after the intervention. There are some case reports in the literature of very late thrombosis of BMS presenting with acute coronary syndrome occurring up to 14 years after implantation.7-9 However, many of them have no established cause.8,9 We believe this case of acute MI was caused by very late stent thrombosis, for a number of reasons. First, the patient was asymptomatic until this point; he had no angina or anginaequivalent symptoms. Second, a guide wire was easily passed through the occluded stent. Finally, balloon angioplasty was enough to obtain TIMI 3 coronary flow; there was no need for stent re-implantation. The pathophysiology of very late BMS thrombosis is

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Fig. 1. U pon admission, the ECG showed ST elevation in the V2â&#x20AC;&#x201C;6 leads.

poorly defined. Independent predictors of stent thrombosis are premature discontinuation of antiplatelet therapy, renal failure, bifurcation lesions, diabetes, and lower ejection fraction.10 There are other presumed causes of BMS thrombosis, such as brachytherapy, exercise-induced procoagulant state, underdeployment of stents, malignancy, greater stent length, and small A

stent size.11 With the exception of the early discontinuation of antiplatelet therapy, our patient had none of these predisposing conditions. Interestingly, stent thrombosis did not occur immediately after the discontinuation of acetyl salicylic acid; it appeared after 20 years. C

Fig. 2. L eft coronary angiogram. A. Left caudal spider view shows acute total occlusion of the LAD stent. B. Right caudal view shows acute thrombotic occlusion of the LAD stent. C. Right cranial view shows TIMI III flow after balloon angioplasty.

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Conclusion Our report demonstrated evidence of the latest reported case of stent thrombosis with the use of BMS in the literature. Discontinuation or irregular use of antiplatelet agents can cause acute stent thrombosis, even decades after BMS implantation. This case emphasises the significance of lifelong antiplatelet therapy after stenting.

Engl J Med 2007; 356(10): 1020–1029. 5.

metal coronary stents. Circulation 2007; 116(21): 2391–2398. 6.

alization. Circulation 2007; 115(18): 2435–2441.

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