JUNE 2012 VOL 23 NO 5
AFRICA
www.cvja.co.za CardioVascular Journal of Africa (official journal for PASCAR)
• Global target on non-communicable diseases
• Obesity and blood pressure level of adolescents in Abeokuta
• Prevalence, awareness, treatment and control of hypertension
• Cardiovascular risk in black Africans
• Robotically controlled ablation for atrial fibrillation
• Cardiovascular disease in sub-Saharan Africa
• Effusive constrictive pericarditis
• Heart failure guidelines
• The role of aspirin in cardiovascular disease
PUBLISHED ONLINE:
Cardiovascular Journal of Africa . Vol 23, No 5, June 2012 • The dangerous fifth chamber
• Rocking mitral annuloplasty ring Printed by Durbanville Commercial Printers Tel: 021 946 4074 Tel: Printed by Durbanville Commercial Printers Today’s Prevention. Tomorrow’s Protection.
Reduce your risk of stroke and heart attack with Bayer Aspirin Cardio® 100 Why take Bayer Aspirin Cardio® 100? Aspirin, an antiplatelet agent, which slows the clotting process, is widely used among patients with cardiovascular disease, which includes heart attacks, stroke and peripheral vascular disease. 1, 2, 5, 6 During a heart attack, blood clots form in an already-narrowed artery and block the fl ow of oxygen-rich blood to the heart muscle or to parts of the brain, in the case of a stroke. 7 Studies have shown that aspirin reduced the number of strokes by 20 % and heart attacks by 30 %. It has been determined that for every 67 patients treated to protect against heart attacks and stroke, one life could be saved with low-dose aspirin therapy. 6 Doctors use different guidelines to decide who should take daily aspirin. Consult your Doctor or Pharmacist.
What are the Risk Factors for Coronary Heart Disease and Stroke? 3, 4 Major Risk Factors Include: • Cigarette smoking • Hypertension (high blood pressure) Protect • High cholesterol their passion • Diabetes mellitus for living. • Advancing age • Atrial Fibrilation Other Risk Factors Include: • Obesity • Physical Inactivity • Family History of premature coronary heart disease • Blood clotting abnormalities
Information brought to you by Bayer, the innovators of Aspirin.
References: 1. Cox D, Maree O, Dooley M, Conroy R, Byrne M, Fitsgerald DJ. Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers. 2006;2153-2158. 2. Healthwise Website. WebMD Reference from Healthwise. Last Updated: December 09,2010 3. Grundy S, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka, Housten-Millar N, Kris-Etherton P, Krumholz HM, LaRosa J, Ockene IS, Pearson TA, Reed J, Washington R, Smith SC. Primary Prevention of Coronary Heart Disease: Guidance from Framingham. A statement for healthcare professionals from the AHA task force on risk reduction. 2011;1876-1887 4. Chock AWY, O’Brien KK, Stading JA, Shea JL. Stroke risks and primary stroke prevention. 2011. The Journal of Modern Pharmacy. August 20-26 5. Package Insert for Bayer Aspirin Cardio 100 6. Weisman SM, Graham DY. Evaluation of the benefi ts and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. 2002;162:2197-2202. 7. WebMD. Heart Disease Health Centre: Low-Dose Aspirin Therapy – Topic Overview
S0 Bayer® Aspirin Cardio 100. Each tablet contains 100 mg of acetylsalicylic acid (ASA). Reg. No. 31/8/0413. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority (MCC). Bayer (Pty) Ltd, Reg.No.1968/011192/07. 27 Wrench Road, Isando, 1609. Tel (011) 921-5911. L.ZA.GM.04.2012.0409 10000141HC ISSN 1995-1892 (print) ISSN 1680-0745 (online)
AFRICA
Cardiovascular Journal of Africa www.cvja.co.za
TS Editorial 241 New global target on non-communicable diseases: a call to action for the global cardiovascular disease community EN J Ralston T
N Cardiovascular Topics
O 245 Feeding the emergence of advanced heart disease in Soweto: a nutritional survey of
C black African patients with heart failure S Pretorius • K Sliwa • V Ruf • K Walker • S Stewart
252 treatment of subaortic stenosis in hearts with single-ventricle physiology B Saritas • E Ozker • C Vuran • Ç Gunaydin • C Ayabakan • R Turkoz
255 Early diastolic functional abnormalities in normotensive offspring of Nigerian hypertensives AM Adeoye • AA Adebiyi • OO Oladapo • OS Ogah • A Aje • DB Ojji • AK Adebayo • KC Ochulor • EO Enakpene • AO Falase
260 obesity and blood pressure level of adolescents in Abeokuta, Nigeria
OL 23, NO 5. JUNE 2012 OL IO Senbanjo • KA Oshikoya V
265 Prevalence, awareness, treatment and control of hypertension among adults 50 years and older in Dakar, Senegal E Macia • P Duboz • L Gueye
270 Control of cardiovascular risk in black Africans with type 2 diabetes in Senegal (Contrôle du risque cardio-vasculaire chez les diabétiques de type 2 noirs africains au Sénégal) NV Yaméogo • A Mbaye • M Ndour • LJ Kagambega • H Diomande • R Hakim • A Thiam • A Diallo • SN Diop • D Diagne • B Diack • A Kane
274 robotically controlled ablation for atrial fibrillation: the first real-world experience in Africa with the Hansen robotic system F Lorgat • E Pudney • H van Deventer • S Chitsaz
INDEXED AT SCISEARCH (SCI), PUBMED AND SABINET
Editors SUBJECT Editors Editorial Board International Advisory Editor-in-Chief (South Africa) Nuclear Medicine and Imaging prof PA Brink PROF A LOCHNER Board PROF AJ BRINK DR MM SATHEKGE Experimental & Laboratory Biochemistry/Laboratory PROF DAVID CELEMAJER Cardiology Science Australia (Clinical Cardiology) Heart Failure Assistant Editor PROF KEITH COPELIN FERDINAND Dr g visagie PROF R DELPORT PROF BM MAYOSI Prof JAMES KER (JUN) Chemical Pathology Chronic Rheumatic Heart USA (General Cardiology) Paediatric Disease DR SAMUEL KINGUE Regional Editor dr s brown PROF MR ESSOP Cameroon (General Cardiology) DR A Dzudie Haemodynamics, Heart Failure DR MT MPE Renal Hypertension & Valvular Heart Disease Cardiomyopathy DR GEORGE A MENSAH USA (General Cardiology) Regional Editor (Kenya) dr brian rayner DR OB FAMILONI PROF DP NAIDOO Dr F Bukachi Echocardiography PROF WILLIAM NELSON Surgical Clinical Cardiology USA (Electrocardiology) dr f aziz PROF B RAYNER Regional Editor (South Africa) DR V GRIGOROV DR ULRICH VON OPPEL Hypertension/Society PROF R DELPORT Adult Surgery Invasive Cardiology & Heart Wales (Cardiovascular Surgery) dr j rossouw Failure PROF MM SATHEKGE PROF PETER SCHWARTZ Nuclear Medicine/Society Italy (Dysrhythmias) Electrophysiology and Pacing PROF J KER (SEN) PROF ERNST VON SCHWARZ dr a okreglicki Hypertension, Cardiomyopathy, PROF YK SEEDAT USA (Interventional Cardiology) Cardiovascular Physiology Diabetes & Hypertension Epidemiology and Preventionist DR J LAWRENSON PROF H DU T THERON Publishing Consultant dr ap kengne Paediatric Heart Disease Invasive Cardiology Mike Gibbs Letters to the Editor 273 the grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives PMO Owira
285 Comment on: A systematic overview of prospective cohort studies of cardiovascular disease in sub-Saharan Africa Z-H Gao • R-Y Yuan
Review Article 281 the prevalence and outcome of effusive constrictive pericarditis: a systematic review of the literature
TS M Ntsekhe • CS Wiysonge • PJ Commerford • BM Mayosi
EN Conference Report 286 Novo Nordisk incretin leadership summit, Cape Town T P Wagenaar • G Hardy • J Aalbers N
O Drug Trends C 295 New ESC heart failure guidelines with South African expert comment J Aalbers
299 EINSTEIN-PE study results, with South African expert comment J Aalbers
300 the role of aspirin in cardiovascular disease prevention P Wagenaar
PUBLISHED ONLINE (Available on www.cvja.co.za and in Pubmed)
OL 23, NO 5. JUNE 2012 OL Case Reports
V e1 severe haemoptysis due to subclavian arteritis A Lioulias • P Misthos • P Drosos • N Karagiannidis • D Pavlopoulos • M Mitselou
e3 the dangerous fifth chamber: congenital left atrial appendage aneurysm KM Tigen • CEM Dogan • A Guler • S Hatipoglu • M Yanartas • C Kirma
e5 Corrected transposition of the great arteries with previously unreported cardiac anomalies A Kaya • IH Tanboga • M Kurt • T Işik • M Ozgokce • S Topçu • E Aksakal
e8 rocking mitral annuloplasty ring
P Panduranga • MK Mukhaini HEALTHCARE
e11 repair of a right coronary artery arising from the pulmonary artery A Guler • MA Sahin • C Gunay • A Jahollari • H Tatar
managing editor Production Copyright: Electronic abstracts available on Pubmed Clinics Cardive Publishing (Pty) Ltd. julia aalbers Co-ordinator Audited circulation Tel: 021 976 4378 WENDY WEGENER Layout: Fax: 086 610 3395 Full text articles available on: www.cvja. Tel: 021 976-4378 Martingraphix e-mail: [email protected] e-mail: [email protected] co.za or via www.sabinet.co.za; for access Printer: codes contact [email protected] Durbanville Commercial Printers Production Editor GAUTENG CONTRIBUTOR Subscriptions for 10 issues: SHAUNA GERMISHUIZEN PETER WAGENAAR South Africa: R650 (excl VAT) Tel: 021 785 7178 ONLINE SERVICES: Cell 082 413 9954 Design Connection Overseas: R1306 Fax: 086 628 1197 e-mail: [email protected] Online subscription: R200 e-mail: [email protected] All submissions to CVJA are to be CONTENT MANAGER made online via www.cvja.co.za The views and opinions expressed in the articles and reviews published are those Editorial Assistant & Michael Meadon (Design Connection) Electronic submission by means of an Circulation Tel: 021 975 3785 of the authors and do not necessarily e-mail attachment may be considered reflect those of the editors of the Journal ELSABÉ BURMEISTER Fax: 0866 557 149 under exceptional circumstances. Tel: 021 976 8129 e-mail: [email protected] or its sponsors. In all clinical instances, e-mail: [email protected] Postal address: PO Box 1013, medical practitioners are referred to the Durbanville, 7551 product insert documentation as approved The Cardiovascular Journal of Africa, by the relevant control authorities. development editor incorporating the Cardiovascular Tel/Fax: 021 976 8129 GLENDA HARDY Journal of South Africa, is published 10 Int.: +27 21 976 8129 Cell: 071 8196 425 times a year, the publication date being e-mail: [email protected] the third week of the designated month. e-mail: [email protected] “THE CURRENT AHA DIETARY GUIDELINES RECOMMEND COMBINED EPA & DHA IN A DOSE OF APPROXIMATELY 1000 mg/DAY IN PATIENTS WITH CHD “ Lavie et al, Omega - 3 Polyunsaturated Fatty Acids and Vol. 54,No. 7 2009, August 11, 2009 585– 594 TRIMEGA™
* HIGH STRENGTH EPA & DHA 300 MG EPA AND 200 MG DHA IN A SINGLE CAPSULE
* ENSURED PATIENT COMPLIANCEWITH CONVENIENTBD DOSING
* SABS TESTED FOR DECLARED CONTENT OF ACTIVE MOEITIES.
* FORMULATION ALLOWS QUICK AND EASY DISSOLUTION.
* NO ERUCTATION
For further information contact
pH PHARRM AF ICA (PTY) LTD Reg. No. 1993/003911/07 PRIVATE BAG X8, ROSETTENVILLE 2130
TOLL FREE 0800 601 098 Life. It’s what you put in.
Help your patients love themselves a little more.
CRESTOR® 5 mg is suitable for select patients who need less aggressive lipid lowering1 CRESTOR® is the more effective statin at lowering LDL-C and raising HDL-C2 CRESTOR® 10 mg will get most patients to LDL-C goal1,3 CRESTOR® is well-tolerated and has a favourable benefi t-risk profi le4,5
S4 CRESTOR® 5 (Tablet) Each CRESTOR® 5 tablet contains 5 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 10 (Tablet) Each CRESTOR® 10 tablet contains 10 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 20 (Tablet) Each CRESTOR® 20 tablet contains 20 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 40 (Tablet) Each CRESTOR® 40 tablet contains 40 mg of rosuvastatin as rosuvastatin calcium. PHARMACOLOGICAL CLASSIFICATION: A. 7.5 Serum-cholesterol reducers INDICATIONS: Primary hypercholesterolaemia, mixed dyslipidaemia and isolated hypertriglyceridaemia (including Fredrickson Type IIa, IIb and IV; and heterozygous familial hypercholesterolaemia) as an adjunct to diet when response to diet and exercise is inadequate. Indicated in patients with homozygous familial hypercholesterolaemia, either alone or as an adjunct to diet and other lipid lowering treatments. CRESTOR® 40 mg should only be considered in patients with severe hypercholesterolaemia and high cardiovascular risk who do not achieve their treatment goal on 20 mg of CRESTOR® or alternative therapy. Specialist supervision is recommended when the 40 mg dose is initiated. REGISTRATION NUMBERS: CRESTOR® 5: 41/7.5/0298, CRESTOR® 10: 36/7.5/0349, CRESTOR® 20: 36/7.5/0350, CRESTOR® 40: 36/7.5/0351. DETAILS OF THE REGISTERED LICENCE HOLDER: AstraZeneca Pharmaceuticals (Pty) Ltd Reg No. 1992/005854/07. No. 5 Leeuwkop Road, Sunninghill, 2157, South Africa. Tel: 011 797 6000. Fax: 011 797 6001. www.astrazeneca.co.za. For full details relating to any information mentioned above please refer to the package insert of CRESTOR® 5 mg, 10 mg, 20 mg and 40 mg. CRESTOR® is a registered trademark of AstraZeneca group of companies. Licensed from Shionogi & Co Ltd, Osaka, Japan. EPI Date: 12/03/2008. Expiry Date: May 2014.
References: 1. CRESTOR® package insert 2. Jones P, Davidson MH, Stein EA, et al. Comparison of the Effi cacy and Safety of Rosuvastatin Versus Atorvastatin, Simvastatin, and Pravastatin Across Doses (STELLAR* Trial). Am J Cardiol 2003;92:152-160. 3. Schuster H, Barter PJ, Stender S, et al. Effects of switching statins on achievement of lipid goals. Measuring Effective Reduction in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Am Heart J 2004;147:705-712. 4. Rosenson RS. Statins: can the new generation make an impresssion? Expert Opin Emerg Drugs 2004;9(2):269-279. 5. Shepherd J, Hunninghake DB, Stein EA, et al. Safety of rosuvaststin. Am J Cardiol 2004;94:882-888.
17880 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 241
Editorial
New global target on non-communicable diseases: a call to action for the global cardiovascular disease community JOHANNA RALSTON
For many years, cardiovascular disease (CVD) was regarded as a possible. In particular, Bongani Mayosi, chair of the World lifestyle disease primarily affecting ageing, affluent populations. Heart Federation Rheumatic Heart Disease Working Group This is reflected in the virtual absence of global policies and, professor and head of the Department of Medicine at concerned with CVD control in poor and rich countries alike. the University of Cape Town, participated in a civil society However, CVD and other non-communicable diseases (NCDs), interactive hearing on NCDs at the United Nations in June 2011, including cancer, chronic respiratory disease and diabetes, to inform preparations for the UN meeting in September. At that account for nearly two-thirds (63%) of global deaths, with the High-Level meeting, Dr Kingsley Akinroye, then-president of majority of deaths from NCDs (80%) occurring in low- and the African Heart Network and board member of the World Heart middle-income countries (LMICs).1 Federation, spoke from the floor of the UN General Assembly This represents a public health emergency requiring an urgent about the importance of strengthening national policies and worldwide response. Now with the World Health Organisation’s capacity to address the control of NCDs. (WHO) adoption of a global target to prevent premature NCD But we cannot rest now. The target represents a rallying cry mortality, the time has finally arrived for the global CVD for further action by the CVD community. It automatically community to join forces in reducing CVD suffering and death elevates CVD on the global health policy agenda, providing an in all countries and among all populations. ‘opportunity springboard’ from which we can accelerate action The World Heart Federation and its members and colleagues to reduce the global CVD burden. Because CVD is responsible in the CVD community have been fighting the burden of diseases for a higher proportion of NCD deaths than cancer, chronic for years, while also advocating for governments to act. In the respiratory diseases and diabetes combined (48 vs 36.5%),1 run up to the first-ever United Nations High-Level meeting on world leaders will look to us and our efforts to help reduce the NCDs, which took place on 19 September 2011, the World Heart CVD burden – and so our challenge is great. Federation worked with its 200 member organisations globally to The next 13 years are crucial, and in order to mount a lobby for CVD and the other NCDs to be recognised as a priority comprehensive response for achieving the target, the CVD on the global health and development agendas. community must forge innovative partnerships with policy World leaders finally heeded our calls to action and they makers, the private sector and healthcare professionals to create unanimously adopted a political declaration2 agreeing to address strategies that prevent CVD at local, regional and national the prevention and control of NCDs worldwide, with an emphasis levels. We need to look beyond the health sector and consider on developing countries. The declaration highlights NCDs as a the many factors that influence heart health (including healthy major challenge for development in the 21st century, emphasising eating, physical activity and tobacco consumption). We need that NCDs undermine social and economic development, and to serve as the catalyst for renewed, global efforts to encourage threaten the achievement of global development and poverty- heart-healthy behaviours. A concerted, global response is vital eradication goals. – we won’t curtail this global epidemic by continuing the same Just eight months later, governments agreed to take fragmented responses we have followed in the past. Everyone responsibility for responding to the challenge of NCDs. At the has a crucial role to play, and we must lead the charge and propel 65th World Health Assembly, all 194 member states agreed them to act. to adopt the first ever global NCD target: a 25% reduction in To achieve the target, policy makers urgently need to take premature mortality from NCDs by 2025.3 The adoption of this action to help modify behavioural risk factors. Many CVD bold global target is the result of commitment, hard work and prevention strategies exist, however governments must do more a major lobbying effort from CVD activists. Most important to ensure that these are fully implemented and well articulated to note, the overall mortality target and additional targets to in NCD plans, which the UN political declaration requires be adopted later this year place CVD prevention and control at governments to complete by the end of 2013. As an example, the heart of the NCD agenda, with risk management, low-cost one of the success stories in the fight against CVD is the treatment and care of CVD central to achieving the mortality and WHO’s Framework Convention on Tobacco Control (FCTC), a risk-factor targets. treaty addressing issues around tobacco consumption, including Many members of the African CVD community are to be restricting sales and advertising. congratulated for their efforts to make these achievements National smoke-free legislation has been passed in Ghana, 242 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Mauritius, Niger, Kenya, Zambia and South Africa.4 However, – further targets are needed to shape a more complete framework according to the latest (2010) global progress report on and better guide collaborative, global action against CVD and its implementation of the FCTC, only 50% of parties in the African risk factors. region reported implementing a comprehensive ban on tobacco We must keep the pressure on our governments to ensure advertising, promotion and sponsorship.5 Our job therefore is to the best possible outcomes for the millions of people suffering advocate for the full implementation of the FCTC, and at the from CVDs and to avoid the 17.3 million deaths that occur each same time push for more public-health campaigns to educate year. Specific targets are being considered for adoption around people on the links between tobacco consumption, CVD and reducing the consumption of tobacco, salt/sodium, trans fats, and premature death. harmful levels of alcohol; reducing physical inactivity, elevated Collaboration with the private sector is also imperative. Let us blood pressure, cholesterol and obesity; and ensuring access consider access to healthy food as an example. The factors that to affordable, quality-assured essential medicines, including influence an individual’s ability to eat healthily are many, and multidrug therapy for people who have been identified at high are often beyond the control of that individual. In Africa, where risk of CVD. many countries are increasingly experiencing a dual burden The window of opportunity to change the face of CVD of obesity and malnutrition, strategies are required not just to forever is now and throughout the year, since the final targets affect an individual’s consumption of food but to modify food will be agreed by member states in October 2012. We call on the production processes. CVD community to champion the additional targets, and push We can spearhead strategies to reformulate food products, world leaders to agree on these promptly. Together we can avert to distribute healthy food options to those communities most deaths from CVD using proven interventions, and save lives in need, to promote and foster incentives for fruit and vegetable around the world. consumption, and to educate consumers to drive healthy food choices among those who have options available to them. We may For further information about the work of the World Heart Federation, please face resistance from some corporate leaders, policy makers and visit www.worldheart.org or follow on twitter: @worldheartfed. even donors, so advocacy to stress the need for action is required alongside the development of new and creative partnerships that JOHANNA RALSTON, [email protected] meet both health and corporate objectives wherever possible. Chief Executive Officer, World Heart Federation, Geneva, We must also campaign for companion strategies for policies to Switzerland change food production in the long term. We must work with healthcare providers to implement References strategies that improve access to care and treatment. Consider 1. World Health Organization. World Health Statistics 2012. [online] blood pressure: in high-income countries, widespread screening, Geneva: World Health Organization. Available at:
EVERY DAY IN SOUTH AFRICA
44** PATIENTS WILL HAVE AN AF* RELATED STROKE1, 2, 3
22** OF THEM WILL DIE WITHIN A YEAR (50 %)4
90 % OF STROKE PATIENTS WITH KNOWN AF WERE NOT THERAPEUTICALLY ANTICOAGULATED4 THINGS ARE ABOUT TO CHANGE IN ANTICOAGULATION THERAPY
*AF – Atrial Fibrillation ** Best Estimate
REFERENCES: 1. Stats South-Africa. Stats-Online. P0302 - Mid-year population estimates. Updated 20 July 2010. Available from: http://www.statssa.gov.za/publications/P0302/P03022010.pdf 2. Connor M. Stroke Management in South Africa – Who is responsible? S Afr Psychiatry Rev 2005; 8: 125-126. 3. Marini C, De Santis F, Sacco S, et al. Contribution of atrial fi brillation to incidence and outcome of ischemic stroke: results from a population- based study. Stroke 2005; 36:1115-9. 4. Gladstone DJ, Bui E,Fang J, et al. Potentially Preventable Strokes in Applicant details: Ingelheim Pharmaceuticals (Pty) Ltd, 407 Pine Ave, Randburg. High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Tel: +27 (011) 348 2400 • Fax: +27 (011) 787 3766 • Company Reg. No. 1966/008618/07. Anticoagulated. Stroke 2009;40;235-240. BI Ref No. 254/2010 (Nov 10) AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 245
Cardiovascular Topics
Feeding the emergence of advanced heart disease in Soweto: a nutritional survey of black African patients with heart failure SANDRA PRETORIUS, KAREN SLIWA, VERENA RUF, KAREN WALKER, SIMON STEWART
Summary Heart failure (HF) has become a major public health problem in Aim: To describe dietary habits and potential nutritional that, unlike other cardiovascular diseases, the number of people 1 deficiencies in black African patients diagnosed with heart discharged from hospital with a diagnosis of HF is increasing. failure (HF). In developed countries, HF can be observed in 2 to 3% of the Methods and Results: Dietary intake in 50 consecutively population and asymptomatic ventricular dysfunction is evident 2 consenting HF patients (mean age: 47 ± 18 years, 54% in about 4% of the population. This will increase with age, female) attending a major hospital in Soweto, South Africa and in the 70- to 80-year age group, HF can be observed in 2,3 were surveyed using validated quantitative food frequency between 10 and 20% of people. The epidemic of cardiovascular questionnaires. Food intakes, translated into nutrient data disease (CVD) has probably stabilised in developed countries, were compared with recommended values. In women, food but developing countries are increasingly suffering from the choices likely to negatively impact on heart health included emerging burden of CVD.4 added sugar [consumed by 75%: median daily intake As populations in South Africa and sub-Saharan Africa (interquartile range) 16 g (10–20)], sweet drinks [54%: undergo economic development, the disease profile shifts 310 ml (85–400)] and salted snacks [61%: 15 g (2–17)]. and CVD becomes a growing cause of death and disability.5 Corresponding figures for men were added sugar [74%: 15 Previously considered a rarity in Africa and predominantly caused g (10–15)], sweet drinks [65%: 439 ml (71–670)] and salted by infectious disease or idiopathic dilated cardiomyopathy,6 the snacks [74%: 15 g (4–22)]. The womens’ intake of calcium, syndrome of heart failure (HF) has emerged as a challenging vitamin C and vitamin E was only 66, 37 and 40% of the public health problem in sub-Saharan Africa.7 age-specific requirement, respectively. For men, equivalent The Heart of Soweto (HOS) study8 has documented a much figures were 66, 87 and 67%. Mean sodium intake was 2 372 higher-than-expected burden of modifiable risk factors9 and g/day for men and 1 972 g/day for women, 470 and 294% advanced forms of heart disease10 linked to epidemiological respectively, of recommended consumption levels. transition in one of Africa’s largest urban concentrations of Conclusions: The nutritional status of black African patients black Africans. Data from the HOS study showed that during with HF could be improved by recommending healthier the period from 2006 to 2008, of the 5 328 de novo cases food choices and by reducing the intake of sweet drinks and captured with heart disease, 2 505 (47%) of these cases presented excess salt. with chronic heart failure.11,12 Ominously, in addition to the ‘traditional’ causes of HF in Africa, such as idiopathic dilated Keywords: heart failure, Africa, food preferences, malnutrition, cardiomyopathy, rheumatic fever, HIV-related cardiomyopathy, salt peripartum cardiomyopathy and hypertensive heart failure, Submitted 17/9/10, accepted 21/5/11 ‘lifestyle’ factors, including hypertension, obesity, dyslipidaemia Cardiovasc J Afr 2012; 23: 245–251 www.cvja.co.za and type 2 diabetes mellitis (particularly in women), appear to have expanded the pathways to, and burden of, HF in this DOI: 10.5830/CVJA-2011-021 community.8 Although the natural history of HF in Africa is still different Soweto Cardiovascular Research Unit, Department of from that of high-income countries, it results in the same high Cardiology, Chris Hani Baragwanath Hospital, University of level of preventable morbidity and premature mortality.13,14 the Witwatersrand, Johannesburg, South Africa In those countries already in the midst of an epidemic of Sandra Pretorius, RD (SA), [email protected] HF, multidisciplinary management programmes targeting Karen Sliwa, MD, PhD, FESC the common factors leading to clinical instability have been Verena Ruf, MD successfully developed.15-17 Certain positive measures have been Baker IDI Heart and Diabetes Institute and Monash implemented in low- and middle-income countries for disease University, Melbourne, Australia prevention, including WHO initiatives.5 However, inadequate Karen Walker, PhD, MND (APD) funding hinders efforts to establish adequate multidisciplinary Monash University, Melbourne, Australia management programmes targeting the common factors leading Simon Stewart, PhD, FCSANZ, NFESC, FAHA to heart disease in South Africa.5 Moreover, the role of dieticians 246 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
has been largely confined to patients with lipid disorders, obesity, Hani Baragwanath Hospital, Soweto, via a prospective clinical diabetes and/renal failure.18 If, however, nutritional education registry. In 2006, this included 1 960 patients presenting with and promotion of good nutrition could be better understood and a primary or secondary diagnosis of HF (an average of 162 recognised to be inclusive of behavioural change, then it will be patients per month). All were diagnosed by echocardiography viewed as a necessary component within contemporary cardiac and specialist cardiological review. This was a prospectively rehabilitation and self-management programmes.18 planned study of 50 consecutively consenting black Africans (28 One cornerstone of HF management particularly relevant females, 22 males), referred to the Heart Failure Clinic in 2006/7 to urban Africans affected by HF is dietary modification. For with a documented diagnosis of HF. example, sodium restriction (2–3 g/day) is standard therapy in the The study was approved by the Human Research Ethics management of symptomatic chronic HF, and black individuals Committee (Medical), University of the Witwatersrand, are particularly responsive to this strategy.19,20 However, lack of Johannesburg, M050550. All participants provided written adherence and poor self-care behaviours persist, with dietary informed consent. The study fully conformed to the principles indiscretions contributing to a substantial portion (up to 20%) outlined in the Declaration of Helsinki. of hospital readmissions.21 Specific dietary interventions play an important role in improving health outcomes.21,22 Three major studies addressing food choices and dietary Dietary instrument, data and nutrient analyses and patterns in adult black South Africans were identified from the recommendations literature. However, given the historical rarity of the syndrome, In addition to the detailed clinical and demographic data collected there are very little data to describe the dietary habits of as part of the Heart of Soweto Clinical Registry, an interviewer- specifically urban African patients with HF. The Dikgale study23 administered quantitative food frequency questionnaire (QFFQ) examined food choices, nutrient intake and weight status of was collected at a point in time when patients had received either black adults. The Transition, Health and Urbanisation study limited, or no instructions for a low-sodium, low-fat therapeutic (THUSA)24 examined the food choices, health status and the diet for HF.28,29 A quantitative food frequency questionnaire effect of urbanisation on a black population. The Black Risk is a validated questionnaire to determine food choices and Factor study (BRISK)25 examined the risk factors for developing consumption. The previously validated QFFQ used in this study CVD in urban black Africans. Data from these studies show that was developed by a researcher at Northwest University. This rural black adults have a very low consumption of fat and a high QFFQ has previously been used to evaluate the food choices of consumption of carbohydrates, typical of the traditional rural the African population living in the North West Province, South African diet.23,25 Africa, as part of the THUSA study.30,31 Urbanisation is associated with markedly increased intake The quantitative QFFQ has been validated via statistical of fat, sugar, meat and beverages.23-25 Although a decrease methods in an African population.30 It includes 139 types of in the consumption of maize porridge with urbanisation was food and records how often a given type of food is consumed as: found, it is still consumed in high amounts by these black time/s per day, per week, per month. It also records preparation population groups.23 As the traditional diet is abandoned in methods. Quantities of food eaten were determined in relation favour of a Western diet, food choices shift away from complex to pictures of standardised portions of the most commonly carbohydrates and higher fibre to foods high in fat, bringing an consumed foods (e.g. maize meal porridge, rice, meat, etc.). The increased risk for chronic diseases of lifestyle.26 According to researcher also used standardised cups, teaspoons etc. to estimate Stewart et al., data on the population of Soweto have shown portion sizes. The patients were also asked to name foods eaten a low prevalence for CVD and the underlying risk factors.8 that were not included in the questionnaire and to point out This situation however may be changing, as urbanisation and questions that were unclear or difficult to understand. the nutritional transition in South Africa is accompanied by an The QFFQ was administered through interview by the increase in the CVD risk factors in black Africans.27 researcher, SP, who is a registered dietician in the Heart Failure The overall study aim was therefore to provide a detailed Outpatient Clinic, Chris Hani Baragwanath Hospital, and trained description of the dietary habits and potential nutritional in administering the QFFQ. deficiencies in a subgroup of urban black African patients Food data were translated into nutrient data using the Medical diagnosed with HF, living in Soweto, South Africa, and managed Research Council (MRC) Food Finder 3, 2007, which is based via the Cardiology Unit of the Chris Hani Baragwanath Hospital. on South African food composition tables. Total dietary starch It focused on the impact of varied dietary patterns, the poor was calculated from the total amount of carbohydrates minus socio-economic status of many patients and probable lack of the sum of total dietary fibre plus added sugars. To assess the awareness of the contribution of poor nutrition to cardiovascular consumption of high-sodium foods, data were aggregated to disease. Ultimately, these data will be used to identify key provide percentages of high-sodium foods consumed both daily targets for more culturally sensitive support and to argue for a and weekly. greater role for dieticians in the management of an increasing Collated dietary patterns and nutritional intake data were number of urban black South Africans affected by HF.12 compared to the South African Food-Based Dietary Guidelines. Importantly, one guideline advises that unrefined or minimally processed starchy foods, such as maize, wheat, sorghum, oats, Methods rice in the form of porridges, breads, pastas, samp, breakfast As part of the previously described Heart of Soweto study,8 cereals and other products should be the main food around which detailed demographic and clinical data are captured from the rest of the meal is planned.32 Promotion of carbohydrate- all individuals with heart disease presenting to the Chris rich foods contributes to optimal nutrient intake, particularly AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 247
in low-income groups. Largely unrefined carbohydrate-rich entire HF cohort was typically two decades younger than that foods are excellent sources of dietary fibre and provide several seen in high-income countries. Hypertension and obesity were important vitamins and minerals.33 It is also recommended that highly prevalent in both genders. Concurrent diabetes was also in a healthy, balanced diet, protective against chronic diseases common, particularly in men. The majority of patients had left of lifestyle, at least 55% of the total energy (%E) should be ventricular systolic dysfunction (LVEF < 45%) and symptoms provided by a variety of carbohydrate-rich foods, with around of exercise intolerance and dyspnoea indicative of NYHA 30%E provided by fat and 15%E by protein. To provide at least functional class II or III. 55%E in an 8 500 kJ diet, at least 275 g carbohydrate should be The daily food consumption of the cohort as measured by the consumed daily.32 QFFQ according to gender is shown in Table 2. Significantly, more women (79%) than men (65%) reported eating brown or Demographic and clinical data wholemeal bread, 75% of women and 48% of men consumed sweets and chocolates, processed meat were eaten by 89% of At the time the QFFQ was administered, body mass was women and 78% of men, and packet soup was consumed by measured with an electronic digital scale, measuring up to 200 kg in graduations of 0.1 kg (Seca 767), and body height was TABLE 2. DAILY FOOD CONSUMPTION OF HF PATIENTS taken with a telescopic measuring rod (Seca 220) attached to ACCORDING TO the scale, to the nearest 1 mm. Data on the clinical [including THE QUANTITATIVE FOOD FREQUENCY QUESTIONNAIRE left ventricular ejection fraction, New York Heart Association Men (n = 22) Women (n = 28) (NYHA) functional class and concurrent diagnoses] and socio- Median Median demographic profile (including age, gender and educational Propor- daily intake Propor- daily intake tion (interquartile tion (interquartile status) were collected prospectively. Foods/food groups (%) range) (%) range) Maize meal (g) 91 516 (200–750) 93 424 (140–688) Statistical analyses Mabella (g)1 52 78 (25–64) 57 111 (55–136) Data were analysed using SPSS for Windows version 14.0.1 (SPSS Oats (g) 26 88 (55–107) 32 80 (50–100) Inc, Chicago, Illinois). Normally and non-normally distributed Potatoes (g) 78 76 (28–91) 86* 59 (28–89) continuous data are given as the mean (standard deviation: SD) White bread (g) 22 88 (50–60) 29 73 (38–98) and median (interquartile range: IQR), respectively. Categorical Brown/wholegrain 65 102 (43–120) 79*** 87 (60–113) data are presented as counts and percentages. Proportional bread (g) data were compared via the Chi-squared test while all nutrient Cereals: refined (g) 13 13 (13–15) 14 7 (4–10) data were compared via the Mann Whitney U-test according Cereals: 22 29 (25–30) 21 17 (9–15) wholegrain (g) to gender, and actual versus recommended dietary intake. Mageu (ml)2 30 208 (43–321) 39 64 (16–71) Significance has been accepted as p < 0.05 (two-tailed). Added sugar (g) 74 15 (10–15) 75 16 (10–20) Sweets and 48 19 (7–30) 75*** 11 (3–12) Results chocolates (g) The demographic and clinical profile of the study cohort is Cakes and biscuits (g) 48 45(15–25) 57 7(5–10)* shown in Table 1. Reflective of the overall Heart of Soweto Cold drinks 65 439 (71–670) 54* 310 (85–400) (sweetened) (ml) study cohort, there were more women (56%) than men. Women Meat, chicken, fish, 100 150 (105–190) 100 127 (83–168) were slightly, but not significantly younger than the men and the eggs (g) Milk and milk 87 262 (129–370) 93* 113 (58-145)* products (ml) TABLE 1. DEMOGRAPHIC AND CLINICAL PROFILE OF THE STUDY COHORT Legumes (g) 43 18 (10–24) 43 18 (9–28) Men Women Fruit (fresh) (g) 100 174 (150–160) 100 147 (40–160) Socio-demographic profile n = 22 (%) n = 28 (%) Vegetables (fresh) (g) 100 76 (40–103) 100 78 (50–91) Mean age (years)1 51 ± 12 47 ± 18 Margarine on 83 15 (7–20) 75 16 (10–20) No education 1 (4.5) 4 (14) bread (g) 1–5 years’ education 5 (23) 7 (25) Salt added to cooked 91 2 (2–2) 75*** 2 (2–2) food (g) 6–10 years’ education 15 (68) 16 (57) Salted snacks (g) 74 15 (4–22) 61** 15 (2–17) Post-matriculation qualifications 1 (4.5) 1 (3.6) Take-away foods (g) 48 23 (10–15) 32*** 16 (10–25) Risk profile Sauces and 57 7 (2–10) 64 4 (2–5) 2 1 Body mass index (kg/m ) 25.2 ± 4.8 26.5 ± 6.4 condiments Hypertension 14 (65) 18 (65) Stock cubes 4 1 (1–1) 18*** 1 (1–2) Diabetes 2 (10) 2 (7.6) Packet soup 43 3 (1–5) 57** 2 (1–2) Heart failure profile Processed meat 78 35 (8–54) 89** 26 (8–35) NYHA class II 11 (50) 12 (43) 1Unrefined porridge made from sorghum; NYHA class III 4 (19) 9 (32) 2Dried and broken corn kernels; 3 NYHA class IV 0 (0) 1 (3.6) A carbohydrate-rich drink made from fermented mealie (maize) meal and malt. 1 Left ventricular ejection fraction 37.3 ± 9.1% 36.4 ± 13.4% Significant difference between men and women, *p < 0.05, **p < 0.01, 1Data are given as mean ± SD or as number (%). ***p < 0.001. 248 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
TABLE 3. ENERGY AND DAILY NUTRIENT INTAKE TABLE 4. MICRONUTRIENT INTAKE OF HF PATIENTS IN OF HF PATIENTS BASED ON A QUANTITATIVE RELATION TO RECOMMENDED DIETARY INTAKES FOOD FREQUENCY QUESTIONNAIRE Daily Difference Daily Difference Daily intake [median (interquartile range)] Micronutrient intake from DRI intake from DRI deficiency men (%) women (%) Nutrient Men (n = 22) Women (n = 28) Vitamin D (mcg) 4.5 –0.5 (90) 4.7 –0.3 (6) Energy (kJ) 9 145 (6 857–12 879) 7 472 (5 568–9 478) Vitamin C (mg) 78 –12 (87) 47 –28 (37) Protein (g) 74.0 (101–62) 58.8 (51–66)* % plant-derived 42.8 43.5 Magnesium (mg) 361 –59 (86) 292 –29 (9) % total energy 13.8 13.4 Vitamin E (mcg) 10 –5 (67) 9 –6 (40) Total carbohydrate (g) 272 (223–404) 245 (170–336) Calcium (mg) 655 –345 (66) 411 –789 (66) % total energy 47.6 52.5 Folate (mcg) 227 –173 (57) 187 –213 (53) Starch (g) 17.8 (13–27) 11.0 (8–17) Iron (mg) 9 –9 (50) Dietary fibre (g) 20.6 (14–25) 16.2 (13–23) Riboflavin (mg) 1.0 –0.1 (9) Added sugars (g) 40.2 (23–76) 33.1 (19–69) Vitamin B6 (mg) 1.2 –0.1 (8) Total fat (g) 65.7 (5–91) 47.4 (39–81) Pantothenate (mg) 4.6 –0.4 (8) % total energy 26.6 23.5 Niacin (mg) 13.4 –0.6 (4) Saturated fat (g) 19.9 (16–29) 15.1 (12–20)* % total energy 8.1 7.5 Potassium (mg) 1938 –0.62 (4) Monounsaturated fat (g) 22.9 (17–31) 17.0 (14–26) Adequate intake % total energy 9.3 8.4 Sodium (mg) 2.372 +1 872 (470) 1 972 +1 472 (294) Polyunsaturated fat (g) 15.7 (11–22) 12.7 (9–25) Potassium (mg) 2512 +0.512 (150) % total energy 6.3 6.3 Vitamin B12 (mcg) 6.3 +3.9 (260) 6.1 +3.7 (254) Total trans fat (g) 0.94 (0.62–1.8) 0.46 (0.28–0.67)** Pantothenate (mg) 6.5 +1.5 (130) Cholesterol (mg) 308 (177–403) 214 (160–307) Biotin (mcg) 39 +9.0 (130) 34 +4 (13) Significant difference between men and women, *p < 0.05, **p = 0.001. Iron (mg) 11 +3 (125) Riboflavin (mg) 1.5 +0.2 (115) 57% of women and 43% of men. Women, but few men also Niacin (mg) 18 +2.0 (113) reported eating stock cubes, 18% and 4% respectively, possibly Vitamin B6 (mg) 1.4 +0.1 (108) since the women were more aware that they were added during Thiamine (mg) 1.3 +0.1 (108) 1.1 0 (0) food preparation. Conversely, more men than women reported Vitamin A (RE) (mcg) 949 +49 (105) 970 +270 (39) the consumption of takeaway foods, 48 and 32%, respectively. Salted snacks were eaten by 74% of men and 61% of women, Fig. 1 indicates that often over half of this patient group had while more men than women reported adding salt to cooked inadequate micronutrient consumption, while all the women and food, 91% and 75% respectively. Despite differences in the the majority of men consumed excessive amounts of sodium. proportions of men and women selecting certain foods, the Sodium intake was 470% above recommended intake levels in median daily intake of foods eaten was broadly similar for men men and 294% above recommended intake levels in women. and women. Specific differences included a higher median As seen in Fig. 2, most sodium came from bread and processed intake for men of milk and milk products, and for cakes and foods. In the body, the ratio of sodium (in extracellular fluid) to biscuits (both p < 0.05). potassium (in intracellular fluid) is about 2:3. As seen in Table 4, Median daily nutrient intake in this HF population group the intake of potassium in relation to sodium was too low, due to is shown in Table 3. Although men consumed a significantly the increased consumption of processed food and the inadequate greater quantity of protein (p < 0.05), protein as a percentage intake of fruits, vegetables and unrefined cereals. of energy was similar (around 13%E) for both men and The likely cost of consuming a healthy diet in Soweto was women. Both men and women consumed high amounts of calculated based on food prices relative to minimum income carbohydrate (47–52%E). Although added sugar intake was support available in May 2008. Current food intake required low (< 10%E), fibre intake was moderately low, suggesting an expenditure of approximately 40% of the current disability that many carbohydrate foods eaten came from refined sources, grant, which in 2008 was R940 per month. A recommended food rather than from wholegrain cereals, as recommended. Both intake, where maize meal porridge is supplemented with mabella women and men consumed < 30%E from fat. Consumption (coarse), legumes, carrots, spinach, apples, oranges and full- of saturated fat and trans fat was significantly lower in women cream milk would require an expenditure of only 30% of this than men (p < 0.05, p = 0.001, respectively). Four men (18%) benefit and therefore represents an attractive option both from a consumed alcohol, with one reporting consumption equivalent to financial and health status perspective. 27 g per day. Only one woman (3.5%) drank alcohol. Table 4 indicates mean daily micronutrient intake for men and women. In men, the mean intake of calcium and magnesium Discussion and of vitamins C, D, E and folate was inadequate. Mean intakes The most significant finding is the inadequate nutrient intake of these nutrients were also inadequate in women although mean and excessive salt consumption in this high-risk HF patient intakes of vitamin D and magnesium were only marginally low. cohort. Processed and convenience foods contributed to the The mean intake of iron in women was only 50% of the level high intake of salt as well as saturated and trans fatty acids. recommended, while mean intakes of riboflavin, vitamin B6, Low consumption of fruit and vegetables contributed to the pantothenate and niacin were also moderately low. low micronutrient and dietary fibre intake. Overall, the pattern AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 249
125% 108% 113% 470% 294% 100 90% 87% 80 67% 66% 66% 60 57% 53% 50% 40% Percent 40 37%
20 8% 6% 4% 0 Vit D Vit C Vit E Ca Folate Iron Vit B6 Niacin Sodium
Men Women
Fig. 1. Proportion of men and women consuming more than the recommended daily intake of sodium or with less than the daily recommended intake of selected micronutrients. Significant difference between men and women, *p < 0.01, **p < 0.001. of dietary consumption observed is likely to have been a major disadvantaged urban populations.38 The SADG for example contributor to the pattern of sub-optimal health outcomes (i.e. recommend servings of ‘meat, fish, chicken or eggs’ should be premature mortality and recurrent morbid events) found in these eaten daily as nutrient-rich sources of high-quality protein. As patients from Soweto with HF.8 selection of fatty meats and full-fat dairy foods can increase High salt intake, particularly in men, was a major problem cardiovascular disease risk, Scholtz and colleagues39 suggest a in this black urban patient group. This, related to a high safe daily intake would comprise: 400–500 ml milk, two to three consumption of bread, processed and take-away foods and the servings of fish and four eggs, and no more than 560 g of meat use of high-salt stock cubes and sauces, consistent with North per week. American findings where salt in bread and pre-prepared and In this group of CHF patients, median intake is less than cereal foods contributed to around one-quarter of total salt half this amount, presumably as these foods are not affordable. intake.33 Possible barriers to adherence to a healthy, low-salt Nevertheless, the proportion of dietary protein was within diet in this black population were: lack of knowledge regarding accepted levels (13%E), although the majority came from plant high-salt foods and healthy affordable alternatives, perceptions rather than animal sources, with implications for micronutrient that meals prepared without added salt were tasteless and boring, intake. Calcium intake, particularly in women was inadequate. and lack of support for dietary change from family members.34 Some more affordable sources of plant protein, notably legumes, Although a salt restriction (2–3 g/day) is standard therapy rich in many nutrients, were not selected in quantity, suggesting for HF,35 black Sowetans with HF commonly consumed 5–7 g lack of familiarity with preparing meals using these foods. per day.36 This indicates the need for higher levels of dietetic The total fat intake seen in this HF cohort was within education to achieve sodium-restricted diets. At Chris Hani recommended levels (< 30%E) but saturated fat intake was Baragwanath Hospital, 10 registered dieticians currently provide excessive, particularly in men, and was related to choice of a nutritional service to 2 500 patients; clearly an inadequate ratio poor-quality fatty meat, high-fat dairy foods, cakes and biscuits, of 1:250, instead of the more acceptable ratio of 1:50.37 and take-away foods. This is consistent with the trend for higher In contrast to the rural areas of South Africa where more total fat and saturated fat consumption seen with urbanisation ‘traditional’ food patterns still apply, in the urban areas throughout South Africa.40 This patient group continued to eat undergoing very rapid epidemiological transition, poor quality more traditional carbohydrate foods such as maize porridge, oats ‘Westernised’ diets are common.26,38 The South African Dietary and mabella, but also consumed highly refined carbohydrate Guideline (SADG) addresses these nutritional issues, although foods such as cakes, biscuits, cold drinks, sweets, chocolates compliance with recommendations is not readily achieved by and added sugar, liable to increase triglycerides and to promote
100 Men
80 Women
60
Percent 40
20
0 Salt added Processed Margarine Sauces & Take-away Packet Bread Salted Stock Breakfast to cooked meat condiments foods soup snacks cubes cereal food Fig. 2. Percentage of men and women consuming the 10 foods contributing most to mean sodium intake in HF patients. 250 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
insulin resistance and obesity.33 References Fruit and vegetables provide alternative sources of 1. Mahan LK, Escott-Stump S. Krause’s Food, Nutrition & Diet Therapy. carbohydrates and contain many cardioprotective nutrients,41 11th edn. Elsevier, USA, 2004. including potassium (lowers blood pressure), folate (reduces 2. European Society of Cardiology. ESC Pocket Guidelines 2008. plasma homocysteine), vitamin C and many polyphenolic Guidelines for the diagnosis and treatment of acute and chronic heart compounds (with antioxidant activities), and soluble fibre failure, 2009, URL: http://www.escardio.org/guidelines. (lowers cholesterol). Green leafy vegetables are also high in 3. Squire I. Aetiology and epidemiology of chronic heart failure. In: Chronic Heart Failure. New York: Oxford University Press Inc, 2008. magnesium (associated with a lower CVD risk). The SADG 4. Mayosi BM, Flisher AJ, Lalloo UG, Sitas F, Tollman SM, Bradshaw therefore recommend an intake of five to eight portions (400– D. The burden of non-communicable diseases in South Africa. Lancet 600 g) of fruit and vegetables daily.41 Black urban Sowetans 2009; 374(9693): 934–947. with HF however, consumed only around one piece of fruit 5. Stewart S, Sliwa K. Preventing CVD in resource-poor areas: perspec- and one vegetable serving per day. Poor affordability and tives from the real-world. Nature Rev/Cardiol 2009; 6: 489–492. availability probably accounted for this low intake.41,42 The 1999 6. Mayosi BM. Contemporary trends in the epidemiology and manage- South African National Food Consumption Survey indicated ment of cardiomyopathy and pericarditis in sub-Saharan Africa. Heart 2007; 93: 1176–1183. that where household income was less than R12 000 per annum, 7. Damasceno A, Cotter G, Sliwa K, Mayosi BM. Heart failure in few foods were found in the house (maize, salt, white sugar, tea, sub-Saharan Africa: time for action. J Am Coll Cardiol 2007; 17: fat/oils, white rice and white bread were most common) and 1688–1693. micronutrient intakes were frequently low.42 8. Stewart S, Wilkinson D, Becker A, Askew D, Ntyintyane L, McMurray This study has several limitations. Firstly, it was a preliminary J, et al. Mapping the emergence of heart disease in a black, urban investigation, performed in a fairly homogeneous group of HF population in Africa: The Heart of Soweto Study. Int J Cardiol 2006; 108: 101–108. patients. The study was unable to explore the effects of gender 9. Tibazarwa K, Ntyintyane L, Sliwa K, Gerntholtz T, Carrington M, roles (women in Soweto still buy and prepare most of the food), Wilkinson D et al. A time bomb of cardiovascular risk factors in South effects of differences in average household income, and seasonal Africa: Results from the Heart of Soweto Study ‘Heart Awareness variance or the availability of food. These factors limit the Days’. Int J Cardiol 2009; 132: 233–239. extrapolation of these data to other patient populations. It would 10. Sliwa K, Wilkinson D, Hansen C, Ntyintyane L, Tibazarwa K, Beker be of interest in further studies to explore the effects of the media A, et al. Spectrum of heart disease and risk factors in a black urban on exposure to Western processed foods, as well as barriers to population in South Africa (the Heart of Soweto Study): a cohort study. Lancet 2008; 371: 915–922. knowledge on the selection and preparation of healthier foods. 11. Sliwa K, Wilkinson D, Hansen C, Ntyinyane, Tibazarwa K, Becker A, However, data presented here were meticulously collected using Stewart S. Spectrum of heart disease and risk factors in a black urban validated tools. population in South Africa (the Heart of Soweto Study): a cohort study. Lancet 2008; 371: 915–922. 12. Stewart S, Wilkinson D, Hansen C, Vaghela V, Mvungi R, McMurray Conclusion J, Sliwa K. Predominance of Heart Failure in the Heart of Soweto This study found that urbanised black Sowetans with HF Study Cohort. Emerging Challenges for Urban African Communities. have high salt intakes and a nutrient-poor diet, placing them Circulation 2008; 118: 2360–2367. at high risk for deteriorating cardiac function and a premature 13. Fonarow GC. Epidemiology and risk stratification in acute heart fail- death. Many poor households remain food insecure, which ure. Am Heart J 2008; 155: 200–207. limits their ability to improve their food choices and their 14. Bleumink GS, Knetsch AM, Sturkenboom MC, Straus SM, Hofman A, Deckers JW, et al. Quantifying the heart failure epidemic: preva- overall management, with potentially life-saving consequences. lence, incidence rate, lifetime risk and prognosis of heart failure. The Nutritional education should therefore focus on foods that are Rotterdam Study. Eur Heart J 2004; 25: 1614–1619. varied, available, affordable, culturally acceptable and popular, 15. Eastwood CA, Travis L, Morgenstern TT, Danaho EK. Weight and as well as consistent with the low-salt, low-fat, high-fibre symptom diary for self-monitoring in heart failure clinic patients. J guidelines.43 Home cooking should also be encouraged. By not Cardiovasc Nurs 2007; 22: 382–389. adding salt to cooking and not eating processed foods high in 16. Grancelli H, Varini S, Ferrante D, Schwartzman R, Zambrano C, Soifer S, et al. Randomized trial of telephone intervention in chronic heart salt, salt intake can be reduced,35,36 while dietary compliance failure (DIAL): study design and preliminary observations. J Card Fail can be improved by encouraging use of herbs and spices and by 2003; 9: 172–179. providing recipes for appealing low-salt foods. Patient education 17. McAlister FA, Stewart S, Ferrua S, McMurray JJ. Multidisciplinary on reading food labels and recognising high-salt foods should strategies for the management of heart failure patients at high risk for also be expanded. admission: a systematic review of randomized trials. J Am Coll Cardiol Recommendations for future research include, therefore, 2004; 44: 810–819. sustainable, practical self-management programmes for 18. Timlin MT, Shores KV, Reicks M. Behavior change outcomes in an outpatient cardiac rehabilitation programme. J Am Dietetic Assoc 2002; black patients with HF living in developing urban areas, 102(5): 664–671. where their socio-economic circumstances often remain poor. 19. Swift PA, Markandu ND, Sagnella GA, He FJ, MacGregor GA. Modest When combined with other aspects of culturally specific salt reduction reduces blood pressure and urine protein excretion in multidisciplinary care, the positive impact of such programmes black hypertensives. A randomized control trial. Hypertension 2005; is likely to be profound. 46: 308–312. 20. Tsuyuki RT, McKelvie RS, Arnold JM, Avezum A Jr, Barretto AC, The Heart of Soweto registry is supported by unconditional research grants Carvalho AC, et al. Acute precipitants of congestive heart failure exac- from Adcock-Ingram, the Medtronic Foundation and Servier. SP is support- erbations. Arch Intern Med 2001; 161: 2337–2342. ed by the University of the Witwatersrand and is the recipient of an NIH/Wits 21. Gonseth J, Guallar-Castillón P, Banegas JR,Rodríquez-Artalejo F. Non-Communicable Diseases Leadership Training award. The effectiveness of disease management programmes in reducing AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 251
hospital re-admission in older patients with heart failure: a systematic 31. Katzenellenbogen JM, Joubert G, Abdool Karim SS. Epidemiology, review and meta-analysis of published reports. Eur Heart J 2004; 25: A Manual for South Africa, 6th edn. Cape Town: Oxford University 1570–1595. Press, 2004. 22. Arcand JA, Brazel S, Joliffe C, Choleva M, Berkoff F, Allard P, et 32. Vorster HH, Nell TA. Make starchy foods the basis of most meals. S. al. Education by a dietitian in patients with heart failure results in Afr J Clin Nutr 2001; 14(Suppl): S17–S24. improved adherence with a sodium-restricted diet: a randomized trial. 33. Slavin JL, Jacobs D, Marquart L, Wiemer K. The role of whole grains Am Heart J 2005; 150: 716. in disease prevention. J Am Diet Assoc 2001; 101: 780–785. 23. Steyn NP. Nutrition and chronic diseases of lifestyle in South Africa. 34. Colonna P, Sorino M, D’Agostino C, Bovenzi F, De Luca L, Arrigo In: Chronic Diseases of Lifestyle in South Africa: 1995–2005. Cape F, et al. Nonpharmacological care of heart failure: counseling, dietary Town: South African Medical Research Council, 2006: 33–47. restriction, rehabilitation, treatment of sleep apnea, and ultrafiltration. 24. Vorster HH, Kruger A, Venter CS, Margetts BM, MacIntyre UE. Am J Cardiol 2003; 91(Suppl): 41F–50F. Cardiovascular disease risk factors and socio-economic position of 35. Selektor Y, Weber KT. The salt-avid state of congestive heart failure Africans in transition: the THUSA study. Cardiovasc J Afr 2007; 18(5): revisited. Am J Med Sci 2008; 335: 209–218. 282–289. 36. Charlton KE, Jooste PL. Eat salt sparingly – sprinkle, don’t shake! S Afr 25. Nel JH, Steyn NP. Report on South African food consumption studies J Clin Nutr 2001: 14(Suppl): S55–S64. undertaken amongst different population groups (1983–2000): Average 37. Compher C, Colaizzo T. Staffing patterns in hospital clinical dietetics intakes of foods most commonly consumed. Pretoria: Department of and nutrition support: a survey conducted by the Dietitians in Nutrition Health, 2002. Support dietetic practice group. J Am Diet Assoc 1992; 92(7): 807–812. 26. Bourne LT, Steyn K. Rural/urban nutrition-related differentials among 38. Vorster HH, Love P, Browne C. Development of food-based dietary adult population groups in South Africa, with special emphasis on the guidelines for South Africa – the process. S Afr J Clin Nutr 2001; black population. S Afr J Clin Nutr 2000; 13(1): S23–S28. 14(Suppl): S3–S6. 27. Vorster HH, Kruger. Poverty, malnutrition, underdevelopment and 39. Scholtz SC, Vorster HH jr, Matshego L, Vorster HH. Foods from cardiovascular disease: a South African perspective. Cardiovasc J Afr animals can be eaten every day – not a conundrum! S Afr J Clin Nutr 2007; 18(5): 321–324. 2001; 14(Suppl): S39–S47. 28. Cleland J, Dargie H, Drexler H, Follath F, Komajda K, Smiseth OA, et 40. Wolmarans P, Oosthuizen W. Eat fats sparingly – implications for al. Guidelines for the diagnosis and treatment of chronic heart failure: health and disease. S Afr J Clin Nutr 2001; 14(Suppl): S48–S55. executive summary (update 2005): the Task Force for the Diagnosis 41. Love P, Sayed N. Eat plenty of vegetables and fruits everyday. S Afr J and Treatment of Chronic Heart Failure of the European Society of Clin Nutr 2001; 14(Suppl): S24–S32. Cardiology. Eur Heart J 2005; 26: 1115–1140. 42. Maunder EMW, Matji J, Hlatshwayo-Molea T. Enjoy a variety of 29. MacIntyre UE, Venter CS, Vorster HH. A culture-sensitive quantita- foods – difficult but necessary in developing countries. S Afr J Clin tive food frequency questionnaire used in an African population: 1. Nutr 2001; 14(Suppl): S7–S11. Development and reproducibility. Pub Hlth Nutr 2001; 4: 53–62. 43. Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. 30. MacIntyre UE, Venter CS , Vorster HH. A culture-sensitive quantita- American Heart Association Nutrition Committee. Diet and Lifestyle tive food frequency questionnaire used in an African population: 2. Recommendations, revision 2006: A Scientific Statement from the Relative validation by 7-day weighted records and biomarkers. Publ American Heart Association Nutrition Committee. Circulation 2006; Hlth Nutr 2001; 4: 63–71. 114: 82–96.
Cardiovascular congress diary Date Conference Venue Contact details to register JUNE 2012 8–9 June CCC 2012 – Cardiovascular Complications Conference Frankfurt, Germany www.complications2012.org 22–24 June PAIN SA Congress CSIR International Convention www.painsa.co.za Centre, Pretoria 27 June ICI 2012 – Imaging in Cardiovascular Interventions Frankfurt, Germany www.ici-congress.org 28–30 June CSI 2012 – Catheter Interventions in Congenital & Structural Heart Disease Frankfurt, Germany www.csi-congress.org JULY 2012 9–12 July 18th World Congress of the International Society for the Study of Geneva, Switzerland www.isshp2012.com Hypertension in Pregnancy 13–15 July ASEAN Federation of Cardiology Congress (AFCC) Singapore www.afcc2012.com 19–22 Jul y 13th Annual SA Heart Congress Sun City, South Africa www.saheart.org AUGUST 2012 25–29 August 2012 ESC, European Society of Cardiology Congress Munich, Germany www.escardio.org SEPTEMBER 2012 29 September Trend 2012 Asia–Pacific Hong Kong www.csi-trend.org OCTOBER 2012 5 October New Horizons in Echocardiography Sandton, South Africa [email protected] 10–13 October 8th World Stroke Congress Brasilia, Brazil www.2.kenes.com/stroke/pages/home.aspx 20 October The Many Faces of AF symposium Cape Town, South Africa [email protected] 20–22 October Acute Cardiac Care Istanbul, Turkey www.escardio.org 24 October The Many Faces of AF symposium Durban, South Africa [email protected] 27 October The Many Faces of AF symposium Johannesburg, South Africa [email protected] NOVEMBER 2012 3–7 November American Heart Association Scientific Sessions Los Angeles, US www.americanheart.org 16–17 November LAA 2012 Frankfurt, Germany www.csi-laa.org DECEMBER 2012 5–8 December The 16th Annual EUROECHO and other imaging modalities Athens, Greece www.euroecho.org To advertise your conference/meeting, e-mail details and half page pdf advert to [email protected] 252 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Treatment of subaortic stenosis in hearts with single- ventricle physiology BULENT SARITAS, EMRE OZKER, CAN VURAN, ÇAĞRI GUNAYDIN, CANAN AYABAKAN, RIZA TURKOZ
Abstract ventricle, the interventricular connection that is present at birth 1 Background: We evaluated the patients who had had a may narrow in time. There is increased pulmonary blood flow in Damus-Kaye-Stansel (DKS) operation for single-ventricular DILV and TA patients with accompanying aortic arch pathology. physiology with the aorta originating from a hypoplastic In order to prevent pulmonary vascular disease, pulmonary ventricle and the pulmonary artery from the systemic artery banding is often preferred as a palliative procedure. ventricle. However, ventricular hypertrophy caused by the pulmonary 2-4 Methods: Seven patients who were operated on between May band may lead to narrowing of the interventricular connection. 2007 and November 2010 were evaluated retrospectively. A restrictive ventricular septal defect (VSD) restricts flow from The patients had been diagnosed with a transposed double- the systemic ventricle to the aorta, hence leading to progression inlet left ventricle and triscuspid atresia, and had been of subaortic stenosis. waiting for a Fontan operation. Systemic outflow stenosis Enlarging the interventricular connection either by resection was defined echocardiographically as those with a gradient or by performing a Damus-Kaye-Stansel operation are the two 5 greater than 20 mmHg, and angiographically those with most applied techniques. We present cases of DILV or TA greater than 5 mmHg in the subaortic region. patients who were found to have subaortic stenosis in their Results: The mean age and weight of the patients was 15 ± clinical follow up and underwent DKS operations. 9.7 months and 8 ± 3.3 kg, respectively. The mean gradient between the systemic ventricle and the aorta was 35 ± 25 Methods mmHg. This gradient decreased to 14.3 ± 4 mmHg postoper- Seven patients underwent DKS operations between May 2007 atively. The early hospital mortality was 14% (one patient). and November 2010. These patients had DILV and TA without The mean extubation time and mean time in the intensive any chance of bi-ventricular repair and had developed subaortic care unit (ICU) were 13 ± 7.3 hours and 2.2 ± 0.5 days, stenosis while they were waiting for Fontan operations. For the respectively. The mean follow-up time was 11 ± 2 months. No purpose of this study, we defined systemic outflow obstruction mortality and semi-lunar valve insufficiency were observed as a resting peak instantaneous gradient greater than 20 mmHg after discharge. on echocardiography or a resting peak-to-peak gradient greater Conclusions: One of the major problems that occur while than 5 mmHg with cardiac catheterisation. Systemic outflow waiting for a Fontan operation is systemic ventricular hyper- obstruction was considered clinically significant if the patient trophy and deterioration in the compliance of the ventricle had findings of left ventricular hypertrophy. due to systemic ventricular outflow stenosis. When the disad- Three patients had concomitant bi-directional cava-pulmonary vantages of outflow resection are encountered, a DKS proves connection (BCPC) operations and one patient had a central to be a good alternative. shunt operation at the time of the DKS operation. All patients Keywords: pulmonary artery band, univentricular heart, Fontan were evaluated in terms of postoperative surgical morbidity and procedure, subaortic stenosis mortality, the degree of subaortic stenosis, ventricle function and rate of re-operation, and semi-lunar valve insufficiency. Submitted 11/4/110, accepted 31/5/11 Cardiovasc J Afr 2012; 23: 252–254 www.cvja.co.za Surgical procedures DOI: 10.5830/CVJA-2011-023 Pulmonary artery banding: three patients with excessive pulmonary blood flow related to a hypoplastic aorta and the In patients with a double-inlet left ventricle (DILV) or tricuspid pulmonary artery originating from a non-hypoplastic ventricle atresia (TA) where the aorta originates from the hypoplastic underwent a pulmonary artery banding operation through an antero-lateral thoracotomy. One patient also had a Blalock-Hanlon atrial septectomy in addition to pulmonary artery banding, through a median sternotomy. The pulmonary band is tightened until the Department of Cardiovascular Surgery, Baskent University pressure distal to the band decreases to half of the systemic pressure. Hospital, Istanbul, Turkey Among these four patients on whom palliative pulmonary BULENT SARITAS, MD, [email protected] band operations were performed, one patient died in the early EMRE OZKER, MD CAN VURAN, MD postoperative period. The other three patients were followed up. ÇAĞRI GUNAYDIN, MD The mean age and weight of these four patients was 22 ± 12 days RIZA TURKOZ, MD and 3.1 ± 1.9 kg, respectively. Department of Paediatric Cardiology, Baskent University Bi-directional cava-pulmonary connection: three patients with Hospital, Istanbul, Turkey balanced pulmonary blood flow underwent BCPC operation. CANAN AYABAKAN, MD The operations were performed under cardiopulmonary bypass. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 253
The main pulmonary arteries were tied up in all patients. The When the pulmonary arteries which had been tied up in mean age and weight of the patients was 6 ± 2.1 months and 8 ± order to create pulmonary atresia in the initial BCPC operation 3.4 kg, respectively. were transected during the DKS operation, no malformation Damus-Kaye-Stansel procedure: the decision to do a DKS was observed in the pulmonary valve. However, there was a operation was taken for seven patients who had subaortic stenosis thrombus on the pulmonary valve in two patients. When the in the follow-up period. An 11-day-old patient with pulmonary thrombi were removed, the valve structures were found to be stenosis and restrictive interventricular connection underwent a normal. All six patients were discharged home on the sixth DKS and central shunt operation. The procedure was performed postoperative day in a good condition. under cardiopulmonary bypass and cardiac arrest by the same The mean duration of follow up was 11 ± 1.2 months. surgical team. Cardiopulmonary bypass was achieved with There was no mortality in the interim. In routine follow-up aortic and bi-caval cannulation. In patients in whom BCPC echocardiographical measurements, the mean gradient in the operations were planned, the innominate veins were cannulated. systemic ventricular outflow tract was 14.3 ± 4 mmHg. No semi- In these patients BCPC operations were performed without the lunar valve insufficiency was observed in the follow up. None use of aortic cross clamping. Cardiac arrest was maintained with of the patients was re-hospitalised and none of those awaiting a antegrade intermittent normothermic blood cardioplegia using Fontan operation needed re-operation. the miniplegia technique. After removing the pulmonary band, which was placed in the initial operation, the pulmonary artery and the aorta were Discussion transected. The distal pulmonary artery orifice was closed either Double-inlet left ventricle and tricuspid atresia with transposed with a patch or primarily, according to the orifice diameter. Then great arteries (TA-TGA) are two forms of a single left ventricle the adjacent walls of the pulmonary artery and aorta were joined. at risk of developing systemic outflow obstruction and poor The two facing sinuses of both great vessels were sewn together. outcomes.2 In these patients, the only way that blood can be In order to prevent a mismatch between the diameter of the new delivered to the aorta is through the VSD. Even when the VSD artery and the distal aorta, the anterior side of the distal aorta was is non-restrictive at birth, it may narrow over time and hence incised 3 to 4 mm. The new artery was sewn to the distal aorta. subaortic obstruction becomes apparent.1 On the other hand, in patients with distal aortic arch anomalies, pulmonary vascular 2,3 Results disease may develop due to the excessive pulmonary flow. In these patients, in order to reduce pulmonary blood The demographic data are shown in Table 1. The early hospital flow, palliative treatment strategies have been established and mortality was 14% (one patient). After the DKS operation, the pulmonary artery banding is the most common method used. pulmonary blood flow was maintained with a BCPC operation However, since banding induces ventricular hypertrophy, the in six patients, and with a central shunt in one patient. The VSD becomes restrictive and subaortic stenosis develops.4 The 11-day-old patient with transposed TA who underwent DKS and restrictive VSD limits the flow of blood from the systemic central shunt procedures was taken to ICU with a left ventricular ventricle to the aorta and reduces cardiac output. In addition, assist device. The patient could not be weaned from high doses ventricular hypertrophy leads to the decrease in the compliance of inotropic support and died on the fifth postoperative day due of the systemic ventricle. In patients awaiting a Fontan operation, to septicaemia and low cardiac output. The rest of the patients the ventricle with impaired compliance is unable to maintain the had an uneventful postoperative course. The mean extubation Fontan circulation.5 time and stay in ICU were 13 ± 7.3 hours and 2.2 ± 0.5 days, Franklin and colleagues reported 11% survival rate at 10 respectively. years in patients with excessive pulmonary blood flow and The mean duration between the first palliative operation and systemic outflow obstruction. They also reported 79% survival the DKS operation was 6 ± 1.8 months. There was no statistical rate at 10 years in patients with pulmonary stenosis without difference between patients who had pulmonary banding and subaortic stenosis.6 Therefore, subaortic stenosis should be patients who had BCPC operations, in terms of timing of the corrected surgically as early as possible. In order to achieve this DKS procedure. goal, the most commonly used methods are BVF resection and a DKS operation. Direct BVF resection was found to have a high incidence 7 TABLE 1. PRE-OPERATIVE AND PERI-OPERATIVE of atrio-ventricular block and high mortality rates. Lan and FINDINGS OF THE PATIENTS colleagues reported 15 complete heart blocks in 44 subaortic Age (month) 15 ± 9.7 resection patients and found that pacemaker requirement and Weight (kg) 8 ± 3.3 the presence of tachyarrhythmia were important risk factors for mortality.2 IVC area index (cm2/m2) 1.88 ± 1.18 Postoperative semi-lunar valve insufficiency is the most Systemic ventricular pressure (mmHg) 132 ± 43 important disadvantage of the DKS operation. Matitiau and Aortic pressure (mmHg) 91 ± 14 colleagues reported a 10% rate of postoperative semi-lunar valve Gradient (mmHg) 35 ± 25 insufficiency. In our echocardiographical evaluations, we did CPB time (min) 113 ± 28 not detect any semi-lunar valve insufficiency and measured mild ACC (min) 39 ± 14 gradients between the systemic ventricle and aorta. However our IVC: interventricular connection, CPB: cardio-pulmonary bypass, mean duration of follow up was not long enough. ACC: aortic cross clamp. There has been no consensus on the optimal timing of 254 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
surgery to relieve the systemic outflow obstruction in transposed References DILV and TA patients who have developed subaortic stenosis 1. Fiore AC, Rodefeld M, ViJay P, et al. Subaortic obstruction in univen- after pulmonary banding. However, Fiore and colleagues tricular heart: results using the double barrel Damus-Kaye Stansel recommended performing the operation between the third and operation. Eur J Cardiothorac Surg 2009; 35(1): 141–148. sixth month in order to prevent ventricular hypertrophy and 2. Lan YT, Chang RK, Laks H. Outcome of patients with double-inlet left related development of compensatory diastolic dysfunction.1 ventricle or tricuspit atresia with transposed great arteries. J Am Coll In our study group, this interval was approximately six months. Cardiol 2004; 43(1): 113–119. 3. Ilbawi MN, Deleon SY, Wilson WR, et al. Advantages of early relief This period is appropriate to perform DKS and concomitant of subaortic stenosis in single ventricle equivalents. Ann Thorac Surg BCPC operations, and there is then no need for a second 1991; 52: 842–849. operation to perform a BCPC. Furthermore, in cases where 4. Freedom RM, Benson LN, Smallhorn JF, Williams WG, Trusler GA, pulmonary blood flow is supplied by systemic-to-pulmonary Rowe RD. Subaortic stenosis, the univentricular heart and banding of artery shunt, low diastolic blood pressure and overload may the pulmonary artery: an analysis of the courses of 43 patients with worsen ventricular function. univentricular heart palliated by pulmonary artery banding. Circulation 1986; 73: 758–764. 5. Pass RH, Solowiejczyk DE, Quaegebeur JM, et al. Bulboventricular foramen resection: hemodynamic and electrophysiologic results. Ann Conclusion Thorac Surg 2001; 71: 1251–1254. In univentricular hearts with narrow interventricular connection, 6. Franclin RC, Spiegelhalter DJ, Anderson RH, et al. Double-inlet ventri- subaortic stenosis increases over time. Relieving the stenosis in cle presenting in infancy. I. Survival without definitive repair. J Thorac Cardiovasc Surg 1991; 101: 767–776. the interventricular connection before the dominant ventricle’s 7. Matitiau A, Geva T, Colan SD, et al. Bulboventricular foramen size in function deteriorates is important to do ahead of the Fontan infants with double inlet left ventricle or tricuspit atresia with trans- operation. This stenosis can be corrected safely with a DKS posed great arteries: influence on initial palliative operation and rate of operation. growth. J Am Coll Cardiol 1992; 19(1): 142–148.
DAKAR
Contact : BP : 6003 Dakar Tél : (221) 33 821 55 21 (221) 33 889 38 00 Poste : 3900 Fax : (221) 33 822 47 46 www.pascar.co.za Mail: [email protected] www.sosecar.org AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 255
Early diastolic functional abnormalities in normotensive offspring of Nigerian hypertensives AM ADEOYE, AA ADEBIYI, OO OLADAPO, OS OGAH, A AJE, DB OJJI, AK ADEBAYO, KC OCHULOR, EO ENAKPENE, AO FALASE
Abstract Keywords: diastolic function, offspring, hypertension, Nigerian Background: Some studies have suggested that diastolic Submitted 17/8/09, accepted 6/6/11 dysfunction precedes the clinical manifestation of hyperten- Cardiovasc J Afr 2012; 23: 255–259 www.cvja.co.za sion. Whether changes in cardiac structure and function predate the clinical manifestation of hypertension later in life DOI: 10.5830/CVJA-2011-030 is now being investigated. The aim of this study was to assess the differences in cardiac structure and function between the Worldwide, hypertension is an independent risk factor for offspring of hypertensive and normotensive parents. cardiovascular morbidity and mortality.1 Hypertension is the Methods: Eighty normotensive offspring of hypertensive most common non-communicable disease in Nigeria, a typical parents (OHyp) (41 females and 39 males) and 62 normoten- example of a developing country. Despite innovations in the sive offspring of normotensive parents (ONorm) (31 males drug-related management of hypertension, control remains poor.2 and 31 females) were recruited for echocardiography. Less than a third of individuals with a usual blood pressure Results: The mean age was 25.0 (5.31) and 24.3 (3.60) years in exceeding 140/90 mmHg are adequately treated.3 For this reason, the OHyp and ONorm participants, respectively (p = 0.369). global approaches now tend to focus on lifestyle changes and Other baseline parameters were comparable between the studies directed at the aetiopathogenesis of hypertension. The two groups. Septal wall thickness in systole was higher in the aim is to find markers for the early detection of hypertension so OHyp than the ONorm subjects [1.3 (0.35) vs 1.1 (0.25), p as to initiate preventive as well as control measures as widely as = 0.0173]. Indexed left ventricular mass [28.1 (7.33) vs 27.5 possible. (7.23), p = 0.631] and relative wall thickness [(0.3 (0.10) vs Studies on offspring of hypertensive patients have shown the 0.3 (0.90), p = 0.280] were similar in the two groups. The significant roles of heredity, salt intake, increased peripheral offspring of hypertensives had lower deceleration time [149.9 vascular resistance, insulin resistance and increased left (38.89) vs 169.0 (50.08) ms, p = 0.012], prolonged duration ventricular (LV) mass in the pathogenesis of hypertension.4-6 of pulmonary A reverse flow [113.5 (70.69) vs 81.7 (38.31) Increased LV mass and diastolic dysfunction can be either a ms, p = 0.024], increased myocardial isovolumic relaxation consequence of hypertension or precede the clinical manifestation time [173.4 (47.98) vs 156.1 (46.74) ms, p = 0.033] and a of hypertension.7-10 Diastolic dysfunction has been demonstrated lower myocardial Em [0.2 (0.05) vs 0.3 (1.38), p = 0.037] and in borderline hypertensive and normotensive offspring of myocardial Em/Am ratio [1.6 (0.01) vs 2.1 (0.01), p = 0.019] hypertensive patients in the absence of increased LV mass.10-16 than the offspring of normotensives. Since most of these studies have been carried out in Europe Conclusion: This study showed that offspring of OHyp and America, little is known about LV filling patterns in the subjects had early diastolic functional abnormalities offspring of hypertensive Nigerians, in a country with increasing when compared with offspring of ONorm participants. prevalence of hypertension, as are most other African countries. Longitudinal studies are needed to determine the implica- This study therefore aimed to determine LV diastolic filling tions of this finding in this African population. patterns in normotensive offspring of hypertensive Nigerians in comparison with normotensive control subjects without a family history of hypertension.
Department of Medicine, University College Hospital, Methods Ibadan, Nigeria The study was carried out at the cardiology unit of the AM ADEOYE, MBBS, FWACP, [email protected] Department of Medicine of the University College Hospital, AA ADEBIYI, MBBS, FWACP Ibadan, Nigeria. Eighty normotensive offspring aged 18 to 40 OO OLADAPO, MBBS, MSc, FWACP OS OGAH, MBBS, MSc, FWACP years with hypertensive parents attending the cardiac clinic of A AJE, MBBS, FMCP the Hospital were recruited over a six-month period. Subjects DB OJJI, MBBS, FWACP were offspring of consecutive hypertensive parents seen at the AK ADEBAYO, MBBS, FMCP, FWACP medical outpatient department. KC OCHULOR, MBBS, FMCP EO ENAKPENE, MBBS, MSc, FMCP, FWACP Comparable control subjects were recruited among the AO FALASE, MBBS, MD, FMCP, FWACP, FRCP children of normotensive hospital staff and relatives of patients on treatment for conditions other than hypertension or other Department of Medicine, College of Medicine, University of chronic medical conditions. Ethical approval was obtained from Ibadan, Ibadan, Nigeria AM ADEOYE, MBBS, FWACP the institutional ethics review board and informed consent was AA ADEBIYI, MBBS, FWACP obtained from each participant. OO OLADAPO, MBBS, MSc, FWACP Blood pressure was measured with a mercury AO FALASE, MBBS, MD, FMCP, FWACP, FRCP sphygmomanometer (Accosson) according to standard 256 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
guidelines.17 Systolic and diastolic blood pressure was measured The calculation of the sample size for this study was based on at Korotokoff sound phases 1 and V, respectively. Subjects with a difference of 0.2 in the mitral E/A ratio between the controls blood pressure higher than 140/90 mm/Hg and body mass and the subjects, with a 90% power to detect the difference at index (BMI) above 25 kg/m2 were excluded from the study. a significance level of 0.05 in a two-tailed test. The estimated Other exclusion criteria were existing heart disease and diabetes sample size was 63 subjects per group. [This was based on mellitus. data from a previous study where LVM (± SD) in hypertensive Echocardiographic examination was performed with the and normotensive offspring was 125 (29) and 109 (25) g, subjects in partial left lateral decubitus position using an Aloka respectively.]27 SSD1700 machine (Aloka Co. Ltd, Tokyo, Japan) with a 3.5-MHz transducer. Two-dimensional guided M-mode measurements Statistical analysis were obtained as recommended by the American Society of Echocardiography.18 Left ventricular (LV), septal, posterior wall All data generated were entered into a standard proforma. SPSS thickness and cavity dimensions were measured using leading- software, version 10.0 (SPSS Inc., Chicago, Illinois) was used edge methodology at both end-diastole and end-systole. Left for statistical analysis. Continuous variables were expressed as ventricular mass (LVM) was calculated using the formula of mean (standard deviation). Differences in continuous variables Devereux and Reichek.19 This has been shown to yield LVM between the groups were assessed with a t-test for independent closely related to autopsy measurements (r = 0.90),20 and had groups. Where data were not normal, the Mann-Whitney test good inter-observer reproducibility (p = 0.93) in one study.21 was used to compare the two groups. Data were adjusted for LVM was indexed by the allometric power of height (LVM/ covariates using analysis of covariance. A two-tailed p-value < Ht2.7).22 Left ventricular hypertrophy was considered present if 0.05 was considered significant. the left ventricular mass index (LVMI) was ≥ 46 g/m2.7. Relative wall thickness (RWT) was calculated as 2RWTd/LVIDd (left Results 7 ventricular internal diameter). Increased wall thickness was Table 1 shows the baseline characteristics of the participants 23 present when RWT > 0.45. Ejection fraction was calculated (subjects and controls). Systolic and diastolic pressure, mean 24 using the formula of Teichholz. arterial pressure, age, height and body mass index were Doppler echocardiography was used for transmitral flow comparable in the two groups. velocities, obtained with the Doppler sample volume placed The cardiac structure and systolic functional data are listed just beyond the tip of the mitral valve leaflets. The parameters in Table 2. Apart from the left atrial diameter and septal measured were early diastolic peak flow velocity (E), early wall thickness at systole that was greater in the offspring of diastolic flow time (EDFT), late diastolic peak flow velocity (A), hypertensive subjects, relative LV wall thickness, LVM, LVMI, late diastolic flow time (ADFT), the deceleration time of early aortic root diameter, left atrial diameter, LV internal diameters mitral velocity, and the ratio of E to A (E/A). and LV ejection fraction were similar in both groups. Isovolumic relaxation time (IVRT) was measured with the Table 3 shows the echocardiographic diastolic functional pulse-wave Doppler beam intersecting the LV outflow and inflow indices in both groups. The duration of the E wave and tracts. EDFT was measured from the onset of diastolic flow to pulmonary A reversal flow was significantly higher in the the intersection of a line extrapolated to the baseline, and ADFT offspring of hypertensive subjects than in the controls. The was measured from the onset of late diastolic flow to the end of deceleration time of the E wave (DT) was lower in offspring of 25 diastolic flow. hypertensive subjects. Pulmonary venous flow recordings were obtained from a Table 4 shows the measured tissue Doppler parameters. four-chamber view directed at the right upper pulmonary vein. Offspring of hypertensive subjects had a higher myocardial The sample volume was placed 1–2 cm into the pulmonary isovolumetric relaxation time as well as a lower myocardial E vein and the following measurement were recorded: peak S-wave velocity (peak systolic pulmonary venous inflow TABLE 1: BASELINE CHARACTERISTICS OF THE SUBJECTS velocity during ventricular systole), peak D-wave velocity (peak Offspring of Offspring of diastolic pulmonary venous inflow velocity during early phase hypertensive normotensive of diastole), peak AR-wave velocity (peak reversed systolic parents parents Characteristics (n = 80) (n = 62) p-value wave during atrial contraction), and duration of the reverse atrial Age (years) 25.0 (5.31) 24.3 (3.60) 0.369 contraction-induced diastolic flow.26 Myocardial Doppler velocities were measured in the apical Weight (kg) 64.2 (10.87) 63.2 (9.93) 0.565 four-chamber view with the Doppler beam well aligned to Height (cm) 1.7 (0.10) 1.7 (0.10) 0.856 2 the septum and the pulsed Doppler sample volume placed 1 Body mass index (kg/m ) 22.9 (3.07) 22.6 (2.51) 0.499 cm apically from the mitral annulus in the interventricular Body surface area (m2) 1.7 (0.18) 1.7 (0.17) 0.659 septal myocardium. The following measurements were made: Waist circumference (cm) 79.8 (9.12) 77.6 (7.21) 0.177 myocardial isovolumic contraction time, myocardial peak Hip circumference (cm) 97.2 (8.78) 94.6 (8.85) 0.121 systolic velocity (Sm), myocardial contraction time, myocardial Waist–hip ratio 0.8 (0.05) 0.8 (0.07) 0.838 isovolumetric relaxation time, myocardial early diastolic Systolic blood pressure (mmHg) 115.0 (12.88) 111.7 (10.08) 0.122 relaxation velocity (Em), and myocardial late relaxation velocity Diastolic blood pressure (mmHg) 72.8 (8.57) 70.5 (8.76) 0.131 (Am). Other measurements were the duration of the diastolic Pulse pressure (mmHg) 42.2 (11.35) 41.2 (10.19) 0.789 period and the durations of Em and Am. Measurements from Mean arterial pressure (mmHg) 86.9 (8.70) 84.3 (7.87) 0.067 three cardiac cycles were taken and averaged. Heart rate 76.6 (12.90) 76.8 (12.30) 0.909 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 257
TABLE 2. MEASURED ECHOCARDIOGRAPHIC TABLE 3. ECHOCARDIOGRAPHIC DOPPLER INDICES OF LV CHARACTERISTICS DIASTOLIC FUNCTION IN SUBJECTS AND CONTROLS Offspring of Offspring of Offspring of Offspring of hypertensive normotensive hypertensive normotensive parents parents Adjusted parents parents Adjusted Variable (cm) (n = 80) (n = 62) p-value p-value Variable (n = 80) (n = 62) p-value p-value Aortic root diameter 2.5 (0.29) 2.5 (0.27) 0.880 0.655 Transmitral E wave (m/s) 0.7 (0.17) 0.7 (0.13) 0.938 0.809 Left atrial diameter 3.1 (0.43) 3.0 (0.45) 0.197 0.042* Duration of E wave (ms) 207.3 (45.35) 228.7 (50.40) 0.009* 0.020 IVSTd 0.9 (0.19) 0.9 (0.19) 0.642 0.989 Deceleration time of E 149.9 (38.89) 169.0 (50.08) 0.012* 0.025 IVSTs 1.3 (0.35) 1.1 (0.25) 0.017* 0.038* wave (ms) PWTd 0.7 (0.18) 0.7 (0.17) 0.248 0.658 A-wave velocity (m/s) 0.4 (0.13) 0.4 (0.09) 0.123 0.100 PWTs 1.1 (0.25) 1.2 (0.24) 0.100 0.108 Isovolumetric relaxation 121.0 (30.82) 113.8 (23.14) 0.378 0.148 time (IVRT) LVIDd 4.4 (0.47) 4.3 (0.47) 0.811 0.151 E/A ratio 1.9 (0.51) 2.1 (0.61) 0.062 0.122 LVIDs 2.8 (0.46) 2.8 (0.38) 0.919 0.844 Pulmonary S wave (m/s) 0.5 (0.18) 0.4 (0.17) 0.848 0.937 Fractional shortening (%) 35.0 (7.60) 35.0 (5.90) 0.585 0.180 Pulmonary D wave (m/s) 0.3 (0.10) 0.3 (0.10) 0.740 0.655 Ejection fraction (%) 64.0 (9.80) 63.0 (7.80) 0.734 0.220 S/D ratio 1.5 (.0.44) 1.5 (0.54) 0.820 0.965 Ejection time (ms) 357.0 (46.20) 375.0 (45.80) 0.042* 0.043* Pulmonary A wave (m/s) 0.2 (0.09) 0.2 (0.06) 0.652 0.545 Absolute LVM (g) 112.6 (31.60) 110.7 (33.90) 0.736 0.212 Duration A reverse wave 113.5 (70.69) 81.7 (49.31) 0.024* 0.067 LVM/Ht (g/m2.7) 28.1 (7.33) 27.5(7.23) 0.631 0.129 (ms) RWT 0.3 (0.09) 0.3 (0.08) 0.280 0.277 *Statistically significant. Data adjusted for age, systolic blood pressure, diastol- LVM = left ventricular mass, BSA = body surface area, RWT = relative wall ic blood pressure, body surface area and body mass index. thickness, Ht = height. *Statistically significant. Data adjusted for age, systolic blood pressure, diastol- ic blood pressure, body surface area and body mass index. Discussion This study shows that normotensive offspring of hypertensive velocity and E/A ratio. The diastolic period was also longer in Nigerians had abnormal diastolic functional parameters compared the OHyp subjects compared to controls. with normotensive control subjects without a family history of Among the male gender, statistical differences were found hypertension. The changes in left ventricular filling dynamics in only some echocardiographic parameters. Hypertensive vs and an increased left ventricular mass occurred early in the normotensive offspring: left atrial diameter [3.20 (0.42) vs 2.93 development of systemic hypertension. Increased left ventricular (0.44) cm, p = 0.012]; posterior wall thickness in systole [1.13 mass and diastolic dysfunction have been demonstrated in the (0.26) vs 1.29 (0.21) cm, p = 0.008]; and deceleration time of the early stages of hypertension, in the stage of prehypertension, E wave [180.8 (60.2) vs 152.7 (44.6) ms, p = 0.034]. and in hypertensive subjects without left ventricular hypertrophy. On the other hand, among the females, statistical differences In this study, the offspring of hypertensive subjects showed were found in some of the physical and echocardiographic features of early diastolic dysfunction even in the absence parameters. Hypertensive vs normotensive offspring: height of increased left ventricular mass. This was demonstrated [1.64 (0.08) vs 1.60 (0.05) m, p = 0.032]; body surface area [1.66 by significantly higher deceleration time of E, as well as a (0.17) vs 1.59 (0.13) m2, p = 0.040]; diastolic blood pressure prolonged diastolic period, assessed by tissue Doppler. Impaired [71.1 (8.3) vs 671.(7.5) mmHg, p = 0.040]; mean arterial blood relaxation is conventionally associated with increased A velocity, pressure [84.5 (9.0) vs 80.6 (6.5) mmHg, p = 0.040]; duration and reduced E/A ratio. Our finding was similar to the work of of the medial annulus IVRT [178.0 (55.4) vs 151.2 (54.5) ms, Graettinger et al.16 who also demonstrated that the flow time and p = 0.045]. the time integral of the A wave were higher in the offspring of hypertensives, implying a shift towards late diastolic filing. Pulmonary vein flow parameters are useful non-invasive TABLE 4. TISSUE DOPPLER INDEXES AT THE MEDIAL (SEPTAL) MITRAL VALVE ANNULUS methods of assessment of LV diastolic function. The present Offspring of Offspring of study showed prolonged duration of the A reverse flow (Ar) in the hypertensive normotensive offspring of hypertensives. Prolonged Ar duration is associated Variable (medial parents parents Adjusted with impaired relaxation, as well as reduced preload.28 There annulus) (n = 80) (n = 62) p-value p-value were no demonstrable changes in the loading condition, hence Medial Sm (m/s) 0.1 (0.02) 0.1 (0.04) 0.970 0.940 the prolonged duration of Ar can only be explained by impaired Medial Em (m/s) 0.2 (0.05) 0.3 (1.38) 0.037* 0.348 relaxation. Transmitral inflow measurements may be affected by Medial Am (m/sec) 0.1 (0.03) 0.1 (0.03) 0.844 0.882 age, BMI, LV mass, and heart rate but all these variables were Medial Em/Am 1.6 (0.01) 2.1 (0.01) 0.019* 0.028 comparable in the two groups,29-31 and were corrected for. Duration of Sm (ms) 210.9 (40.58) 201.6 (42.06) 0.186 0.187 Tissue Doppler imaging is a non-invasive and easily Duration of Em (ms) 133.7 (28.87) 128.0 (26.05) 0.227 0.156 reproducible method of assessment of left ventricular function. Duration of Am (ms) 85.4 (18.40) 85.1 (27.06) 0.954 0.860 The parameters are less influenced by preload changes compared Duration of diastolic 420.6 (136.89) 401.8 (139.32) 0.424 0.390 period (ms) with transmitral and pulmonary vein flow measurements and Isovolumetric relaxation 156.1 (46.74) 173.4 (47.98) 0.033* 0.031 also believed to be more sensitive than the convectional Doppler time (IVRT) (ms) methods. Our septal myocardial tissue Doppler measurements Isovolumetric contrac- 115.9 (44.09) 113.5 (38.01) 0.731 0.740 showed reduced Em and Em/Am ratio and increased IVRT in tion time (IVCT) (ms) the offspring of hypertensives. These findings are indicative of 258 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
diastolic dysfunction and were similar to those of Aeschbacher with the institution of lifestyle modification in these subjects. et al.32 in their prospective study of the offspring of hypertensive Lifestyle modifications have been shown to reduce blood pressure subjects, particularly offspring who became hypertensive after in hypertensive patients. These interventions may prevent or five years of follow up. delay the development of hypertension in normotensive subjects In an earlier study by the same group,33 on offspring of in the long term. Longitudinal studies are needed to determine hypertensives, there was no evidence of diastolic dysfunction the prognosis of these changes in normotensive offspring of using conventional Doppler methods. At follow up, pulmonary hypertensive parents. vein flow and myocardial tissue imaging were added and despite comparable blood pressure and left ventricular masses, the We acknowledge the contribution and assistance of the ECG/ECHO unit diastolic dysfunction became more evident. Our study confirms team of Ms Ogunrinde, Adegbola, Adubi, Babatunde and Akinwale of that if sensitive methods of assessing diastolic function are University College Hospital, Ibadan. We are also grateful to Drs Ajit Mullasari and Ezhilan of Madras Medical Mission, Chennai, India, who read employed, deterioration in diastolic function can be demonstrated the manuscript and offered useful suggestions. in normotensive subjects with a parental history of hypertension. This further confirms the hypothesis that abnormalities of cardiac function may predate clinical hypertension in genetically References predisposed individuals. 1. Ezzati M, van der Hoorn S, Lawes CM, Leach R, James WP, Lopez Studies that did not demonstrate differences between diastolic AD, et al. Rethinking the ‘diseases of affluence’ paradigm: global patterns of nutritional risks in relation to economic development. PLoS function in the offspring of hypertensives and normotensives Med 2005; 2: e133. used only mitral inflow parameters, which are inadequate in 2. Whelton PK, He J, Muntner P. Prevalence, awareness, treatment and assessing diastolic function, as the parameters are easily affected control of hypertension in North America, North Africa and Asia. J by loading conditions.13,14 Our study had the advantage of Hum Hypertens 2004; 18: 545–551. assessing diastolic function in offspring of hypertensives using 3. Wolf-Maier K, Cooper RS, Kramer H, Banegas JR, Giampaoli S, conventional Doppler parameters as well as myocardial tissue Joffres MR, et al. Hypertension treatment and control in five European Doppler imaging. countries, Canada, and the United States. Hypertension 2004; 43: 10–17. Our data suggest that diastolic dysfunction was present in 4. Allemann Y, Aeschbacher B, Zwyssig P, Ferrari P, Hopf M, Shaw S, offspring of hypertensive subjects despite the fact that they had et al. Left ventricular structure and determinants in normotensive similar baseline characteristics and left ventricular dimensions offspring of essential hypertensive parents. J Hypertens 1992; 10: to the control group. Although the effect of the insignificantly 1257–1264. higher blood pressure and LVM on the findings of diastolic 5. Allemann Y, Horber FF, Colombo M, Ferrari P, Shaw S, Jaeger P, et al. function cannot be totally ruled out, our findings are similar Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents. Lancet 1993; 341: 327–331. to those of Aeschbacher et al,33 who also corrected for these 6. Allemann Y, Weidmann P. Cardiovascular, metabolic and hormonal variables in the analysis. dysregulations in normotensive offspring of essential hypertensive Gender differences noted in the analysis are not surprising. parents. J Hypertens 1995; 13: 163–173. Other workers have reported gender differences in LV parameters, 7. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation as well as parameters of LV diastolic function.33-36 In a study of of left ventricular mass and geometry to morbidity and mortality in 121 normotensive youths, Kapuku et al.36 noted that females uncomplicated essential hypertension. Ann Intern Med 1991; 114: had a higher relative wall thickness, lower E/A ratio and shorter 345–352. 8. Cuocolo A, Sax FL, Brush JE, Maron BJ, Bacharach SL, Bonow RO. IVRT than males. Left ventricular hypertrophy and impaired diastolic filling in essential Before changes in LV mass or hypertension become apparent, hypertension. Diastolic mechanisms for systolic dysfunction during various changes occur at the cellular level that cause alterations exercise. Circulation 1990; 81: 978–986. in the myocardial architecture and collagen structure. Metabolic 9. Devereux RB, de Simone G, Koren MJ, Roman MJ, Laragh JH. Left and neuro-endocrine changes also occur. Some studies have ventricular mass as a predictor of development of hypertension. Am J demonstrated acceleration of these factors in the offspring of Hypertens 1991; 4: 603S–607S. hypertensives. 10. Fouad FM, Slominski JM, Tarazi RC. Left ventricular diastolic function in hypertension: relation to left ventricular mass and systolic function. J The study had some limitations. We did not obtain information Am Coll Cardiol 1984; 3: 1500–1506. on and correct for factors such as socio-economic status, level of 11. Verdecchia P, Schillaci G, Guerrieri M, Boldrini F, Gatteschi C, physical activity, diet or biochemical parameters, and this may Benemio G, et al. Prevalence and determinants of left ventricular dias- have affected the results. tolic filling abnormalities in an unselected hypertensive population. Eur Heart J 1990; 11: 679–691. 12. Inouye I, Massie B, Loge D, Topic N, Silverstein D, Simpson P et al. Abnormal left ventricular filling: an early finding in mild to moderate Conclusion systemic hypertension. Am J Cardiol 1984; 53: 120–126. Diastolic dysfunction has been shown to affect the quality of 13. Glen SK, Elliott HL, Curzio JL, Lees KR, Reid JL. White-coat hyper- life of patients with advanced cardiac disease. Assessment of tension as a cause of cardiovascular dysfunction. Lancet 1996; 348: diastolic function is of paramount importance in the management 654–657. of this disease. Early identification of subjects with or at risk for 14. Gottdiener JS, Brown J, Zoltick J, Fletcher RD. Left ventricular hypertension and diastolic dysfunction may help to stratify risk, hypertrophy in men with normal blood pressure: relation to exagger- ated blood pressure response to exercise. Ann Intern Med 1990; 112: guide therapy and prevent target-organ damage in these patients. 161–166. The consistent independent effects of increased body weight 15. Ravogli A, Trazzi S, Villani A, Mutti E, Cuspidi C, Sampieri L, et al. and particularly male gender37,38 on the development of increased Early 24-hour blood pressure elevation in normotensive subjects with left ventricular mass reaffirms the need for early intervention parental hypertension. Hypertension 1990; 16: 491–497. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 259
16. Graettinger WF, Neutel JM, Smith DH, Weber MA. Left ventricular 27. Aeschbacher BC, de Marchi SF, Meier B. Identification of impaired diastolic filling alterations in normotensive young adults with a family ventricular relaxation by changes of pulmonary vein A-wave duration history of systemic hypertension. Am J Cardiol 1991; 68: 51–56. during Valsava. J Am Coll Cardiol 1998; 31: 423. 17. American Society of Hypertension. Recommendations for routine 28. Nishimura RA, Housmans PR, Hatle LK, Tajik AJ. Assessment of blood pressure measurement by indirect cuff sphygmomanometer. Am diastolic function of the heart: background and current applications of J Hypertens Suppl 1992: 207–209. Doppler echocardiography. Part I. Physiologic and pathophysiologic 18. Devereux RB, Lutas EM, Casale PN, Kligfield P, Eisenberg RR, features. Mayo Clin Proc 1989; 64: 71–81. Hammond IW, et al. Standardization of M-mode echocardiographic 29. De Maria AN, Wisenbaugh TW, Smith MD. Doppler echographic evalu- left ventricular anatomic measurements. J Am Coll Cardiol 1984; 4: ation of diastolic dysfunction. Circulation 1991; 84: I-288–I-295. 1222–1230. 30. Thomas JD, Weyman AE. Echocardiographic Doppler evaluation of 19. Devereux RB, Reichek N. Echocardiographic determination of left ventricular diastolic function. Physics and physiology. Circulation left ventricular mass in man. Anatomic validation of the method. 1991; 84: 977–990. Circulation 1977; 55: 613–618. 31. Aeschbacher BC, Hutter D, Fuhrer J, Weidmann P, Delacretaz E, 20. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs Allemann Y. Diastolic dysfunction precedes myocardial hypertrophy in I, et al. Echocardiographic assessment of left ventricular hypertrophy: the development of hypertension. Am J Hypertens 2001; 14: 106–113. comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458. 32. Aeschbacher BC, Allemann Y, Hopf M, Weidmann P. Normotensive 21. Palmieri V, Dahlof B, DeQuattro V, Sharpe N, Bella JN, de Simone G, et offspring of hypertensive parents: no evidence of left ventricular dias- al. Reliability of echocardiographic assessment of left ventricular struc- tolic dysfunction in a cross-sectional study. Blood Press 1998; 7: 5–9. ture and function: the PRESERVE study. Prospective randomized study 33. Bella JN, Palmieri V, Roman MJ, Paranicas MF, Welty TK, Lee ET, et evaluating regression of ventricular enlargement. J Am Coll Cardiol al. Gender differences in left ventricular systolic function in American 1999; 34: 1625–1632. Indians (from the Strong Heart Study). Am J Cardiol 2006; 98(6): 22. De Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de 834–837. Divitiis O, et al. Left ventricular mass and body size in normotensive 34. Hinderliter AL, Light KC, Willis PWT. Gender differences in left children and adults: assessment of allometric relations and impact of ventricular structure and function in young adults with normal or overweight. J Am Coll Cardiol 1992; 20: 1251–260. marginally elevated blood pressure. Am J Hypertens 1992; 5(1): 32–36. 23. Savage DD, Garrison RJ, Kannel WB, Levy D, Anderson SJ, Stokes 35. Petersen SE, Hudsmith LE, Robson MD, Doll HA, Francis JM, J, 3rd, et al. The spectrum of left ventricular hypertrophy in a general Wiesmann F, et al. Sex-specific characteristics of cardiac function, population sample: the Framingham Study. Circulation 1987; 75: geometry, and mass in young adult elite athletes. J Magn Reson 126–133. Imaging 2006; 24(2): 297–303. 24. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocar- 36. Kapuku GK, Davis HC, Shah N, McMillan AM, Harshfield GA. diographic volume determinations: echocardiographic-angiographic Gender differences in diastolic function among youth. Pediatr Cardiol correlations in the presence of absence of asynergy. Am J Cardiol 1976; 2008; 29(1): 102–107. 37: 7–11. 37. Saitoh M, Nishimura H, Tanaka T, Kondoh T. Gender-related differ- 25. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventri- ences in target organ damage in untreated patients with essential hyper- cle in health and disease: Doppler echocardiography is the clinician’s tension. Intern Med 2006; 45: 377–383. Rosetta Stone. J Am Coll Cardiol 1997; 30: 8–18. 38. Fox ER, Taylor J, Taylor H, Han H, Samdarshi T, Arnett D, et al. 26. Appleton CP, Jensen JL, Hatle LK, Oh JK. Doppler evaluation of left Left ventricular geometric patterns in the Jackson cohort of the and right ventricular diastolic function: a technical guide for obtaining Atherosclerotic Risk in Communities (ARIC) study: clinical correlates optimal flow velocity recordings. J Am Soc Echocardiogr 1997; 10: and influences on systolic and diastolic dysfunction. Am Heart J 2007; 271–292. 153: 238–244.
Diabetes congress diary Date Conference Venue Contact details to register JUNE 2012 8–12 June 72nd American Diabetes Association Scientific Sessions Pennsylvania, USA http://professional.diabetes.org 22–24 June PAIN SA Congress CSIR International Convention www.painsa.co.za Centre, Pretoria JULY 2012 9–12 July The 3rd International Congress on Abnormal Obesity (ICAO) Quebec City, Canada Icao2012.myhealthwaist.org 24–26 July CDE Centres for Diabetes and Endocrinology Johannesburg, South Africa 25–28 July 1st African Diabetes Congress Arusha, Tanzania www.africadiabetescongress.org OCTOBER 2012 1–5 October 48th EASD Annual Meeting Berlin, Germany www.easd.org 10–13 October ISPAD 2012 – 38th Annual Meeting of the International Society for Istanbul, Turkey Pediatric and Adolescent Diabetes 20–22 October 8th Asian Pacific Society of Atherosclerosis and Vascular Disease Phuket, Thailand www.apsavd2012.com DECEMBER 2012 4–6 December 1st American Diabetes Association Middle East Congress: Diabetes Dubai, UAE Prevention and Treatment To advertise your conference/meeting, e-mail details and half-page pdf advert to [email protected] 260 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Obesity and blood pressure levels of adolescents in Abeokuta, Nigeria IO SENBANJO, KA OSHIKOYA
Abstract energy-dense foods, combined with increasingly sedentary Background: We determined the prevalence of general and lifestyles such as prolonged time spent watching television, central obesity and their relationship with blood pressure playing video games or using computers. This is found levels among adolescents in Abeokuta, Nigeria. particularly in families from a higher socio-economic status in 6,7 Methods: We selected 423 adolescents from seven schools developing countries. In India, the prevalence of obesity among in Abeokuta, Nigeria, using a multistage random-sampling adolescent schoolchildren from affluent families was found to be 8 technique. Body mass index (BMI), waist circumference 7.4%. In Nigeria, among the privileged Nigerian schoolchildren 9 (WC) and blood pressures were measured. the prevalence of obesity was 18%. Results: Twenty-one (5%) children had general obesity and Several epidemiological studies support the relationship 109 (24.5%) had central obesity. Of those with general obesi- between accumulation of body fat and the occurrence of ty, 20 (95.1%) children were centrally obese. With simple non-communicable diseases such as hypertension and diabetes 10,11 linear regression analysis, BMI and WC explained 10.7 and mellitus. More importantly, the accumulation of fat in the 8.4%, respectively of the variance in systolic blood pressure central region of the body is a good, proven clinical correlate of 12 (SBP), and 3.6 and 2.7%, respectively of the variance in increased risk of these chronic diseases. diastolic blood pressure (DBP). Following logistic regression Traditionally in clinical practice, general obesity is measured analysis, BMI was the major factor determining SBP levels using body mass index (BMI). For the estimation of central (OR 0.8, 95% CI: 0.65–0.99, p < 0.05). obesity, there are several anthropometric parameters proposed for Conclusion: BMI remains an important anthropometric its reasonable estimation and they include sub-scapular skin-fold screening tool for high blood pressure in Nigerian adoles- thickness, waist circumference (WC), waist-to-hip circumference cents. ratio, and waist-to-height ratio. Waist circumference measures both the subcutaneous and visceral fat and has been shown to Keyword: overweight, obesity, central obesity, blood pressure, have the most consistent and generally the strongest correlation adolescents, Nigeria with adverse lipid concentrations and increased blood pressure 13 Submitted 30/1/11, accepted 11/7/11 levels among children and adolescents. In developing countries, both children and adult populations Cardiovasc J Afr 2012; 23: 260–264 www.cvja.co.za are characterised by lean body mass, and a high prevalence of DOI: 10.5830/CVJA-2011-037 underweight, wasting and stunting. According to Bogin, there is preferential accumulation of fat in the central portion of the Obesity is a disease in which excess body fat has accumulated body relative to peripheral fat storage in nutritionally stressed to such an extent that the person’s health may be adversely populations, with its attendant consequences of hypertension, affected.1 The International Obesity Task Force (IOTF) has coronary heart disease and diabetes mellitus.14 reported that one in 10 children are overweight, with at least Information on the pattern of obesity and its influence on 155 million schoolchildren worldwide being affected.2 About 30 blood pressure levels among children in Nigeria is limited. to 45 million of the overweight children are classified as obese Therefore the aim of this study was to determine the prevalence and account for 2–3% of the world’s children aged five to 17 of general and central obesity and their relationship with blood years old.2 pressure levels among adolescents in Abeokuta, south-west In the United Kingdom,3 Canada4 and the USA,5 obesity has Nigeria. risen to epidemic levels among children, with the prevalence having more than doubled in the last two to three decades. Under-nutrition is the major nutritional problem in developing Methods countries. Unfortunately, overweight and obesity are now This was part of a larger study on anthropometric measures becoming significantly prevalent in developing countries as a and body composition of children and adolescents in Abeokuta, result of an environment characterised by easily available, cheap, Nigeria.15 It was carried out in randomly selected primary and secondary (both public and private) schools in Abeokuta. It was a questionnaire-based, cross-sectional study. Department of Paediatrics and Child Health, Lagos State Abeokuta is located on longitude 7° 10″ N and latitude 3° University College of Medicine, Ikeja, Lagos, Nigeria 26″ E and is the capital of Ogun State in south-western Nigeria. IO SENBANJO, MB ChB, FWACP, [email protected] It is about 100 km north of Lagos, with an estimated population Pharmacology Department, Lagos State University College of four million people. Abeokuta is predominantly a Yoruba of Medicine, Ikeja, Lagos, Nigeria, and Academic Division city but urbanisation and industrialisation have brought in many of Child Health, Medical School, University of Nottingham, other ethnic groups. Derbyshire Children’s Hospital, Derby, UK Ethical clearance was obtained from the Federal Medical KA OSHIKOYA, MBBS, MSc Centre Research/Ethics Committee. Approval of the study came AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 261
from the Ogun State Ministry of Education. as having central obesity if the WC was ≥ the 75th percentile The teachers, pupils and parents were well informed on the for age- and gender-specific data, as proposed by Fernandez et scope and extent of the survey. Consent was obtained from al.19 Systolic (SBP) and diastolic blood pressures (DBP) were the parents and pupils. At the time of the survey, there was a defined as high when they were ≥ the 90th percentile, according total of 322 schools in Abeokuta (the ratio of public to private to the Task Force on High Blood Pressure in Children and primary schools was 1:1, while the ratio of public to private Adolescents.20 secondary schools was 3:1). Using the multistage random- sampling technique, seven schools comprising two private and Statistical analysis one public primary school, and one private and three public secondary schools were selected by balloting. The basis for Data analysis was by descriptive and inferential statistics, this selection was because the number of students in the public using the SPSS for Windows software version 13. The means primary schools was higher than that in private primary schools, and standard deviations (SD) of the weight, height, BMI, whereas in the secondary schools the numbers were about equal. WC, and SBP and DBP were calculated according to gender. From each of the selected schools, all grades were studied Gender differences in anthropometric and blood pressure (primary, grades 1–6; junior and senior secondary, grades 7–12). values were compared using the independent-samples t-test, On the day of the study, one section of each grade was while proportions and ratios were compared using the Pearson 2 selected by balloting. Ballot papers were served to all the Chi-squared (χ ) test. Simple and multiple logistic regression children in the selected section. These ballot papers were blank analyses were carried out on BMI and WC using blood pressure except those that were marked with numbers 1 to 15. After all the as the dependent variable. A probability (p) value of less than students had picked a paper, they were asked to open them and 0.05 was accepted as statistically significant. those with numbers 1 to 15 were selected. Ninety pupils were selected from each of the seven schools. In all, 630 pupils were Results selected but only 570 (90.5%) pupils completed the study. The A total of 423 subjects with ages ranging from 10 to 19 years other 60 pupils were excluded based on refusal to participate and had complete data sets, which were analysed. The mean age evidence of chronic diseases. was 13.2 ± 2.41 years and 233 (55.1%) were males. The social Blood pressure was not measured in 147 children aged five distribution shows that 166 (29.1%), 304 (53.3%) and 100 to nine years due to non-availability of an appropriate cuff. (17.5%) children belonged to the upper, middle and lower socio- Each student was interviewed to obtain information on the economic classes, respectively. Table 1 shows the means (± SD) demographic and socio-economic characteristics of the child’s of the various anthropometric measures according to gender. All family. The families were assigned a socio-economic class using the anthropometric measures increased with age in both genders. 16 the modified method recommended by Oyedeji. The mean weight, BMI and WC were significantly higher in the Trained student nurses took all anthropometric measurements. females (p < 0.05, p < 0.001, p < 0.001, respectively). Each measurement was taken by the same examiner to minimise The BMI of the study population ranged from 11.59 to measurement error. The children were weighed using an 34.14 kg/m2 with a mean value of 17.1 kg/m2. Twenty-one electronic scale calibrated in 100-g units (SECA/UNICEF, (5%) children were obese, 16 (76.2%) of them females, which Australia). All children were weighed wearing only underwear was statistically significant (p = 0.012). WC ranged from 50.5 and to the nearest 0.1 kg. to 97 cm and 109 (25.8%) children had a WC above the 75th The height was measured using a specifically made wooden percentile for the population age and gender. There was a stadiometer with a steel tape measure. This was done with the significantly higher prevalence of central obesity among females child standing erect without shoes and with the eyes looking than males (38.4 vs 15.5%, p = 0.000). Twenty (95.2%) of the horizontally and the feet together on a horizontal base. These measurements were done to the nearest 0.1 cm. BMI was calculated by dividing the weight (kg) by the square of the height (m). TABLE 1. ANTHROPOMETRIC AND BLOOD PRESSURE VALUES OF THE STUDY Waist circumference was measured midway between the iliac SUBJECTS ACCORDING TO GENDER crest and the lowermost margin of the ribs with bare belly and at Total Male Female 17 the end of normal expiration, according to the WHO guidelines. Variable (n = 423) (n = 233) (n = 190) p-value Standardisation checks on the weighing scale, height boards and Age (years) 13. 7 (2.4) 13.7 (2.4) 13.8 (2.4) 0.688 tape measure were done periodically during the study period. Weight (kg) 39.3 (11.2) 38.0 (11.5) 40.7 (10.7) 0.013 For blood pressure measurements, the subjects were seated Height (cm) 149.7 (13.6) 150.2 (14.8) 149.1(12.1) 0.418 and rested for five minutes. An appropriately sized cuff, covering BMI (kg/m2) 17.1 (2.7) 16.4 (2.1) 18.0 (3.1) 0.000 at least two-thirds of the upper right arm with the lower border not less than 2.5 cm from the cubital fossa, was applied after WC (cm) 63.8 (8.5) 61.5 (5.9) 66.7 (10.1) 0.000 restrictive clothing had been removed. Thereafter blood pressure SBP (mmHg) 106.9 (11.5) 105.9 (10.9) 108.2 (12.2) 0.05 was measured twice using an automatic blood pressure monitor DBP (mmHg) 60.6 (10.4) 59.0 (10.1) 62.7 (10.4) 0.000 (HEM-712C; Omron, China) and the mean was recorded. BMI > 2 SD 21 (5.0) 6 (2.6) 15 (7.9) 0.012 BMI is widely used as an index of general obesity although WC > 75th 109 (25.8) 36 (15.5) 73 (38.4) 0.000 the cut-off points vary between the 85th and 97th percentiles.18 percentile In this study, obesity was defined as BMI at or above the 95th High SBP 11 (2.6) 4 (1.7) 7 (3.7) 0.206 percentile of age- and gender-specific data. A child was regarded High DBP 14 (3.3) 7 (3.0) 7 (3.7) 0.697 262 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
TABLE 2. RELATIONSHIP BETWEEN BODY TABLE 3. RELATIONSHIP BETWEEN WAIST MASS INDEX AND BLOOD PRESSURE CIRCUMFERENCE AND BLOOD PRESSURE Systolic blood pressure, Diastolic blood pressure, Systolic blood pressure, Diastolic blood pressure, n (%) n (%) n (%) n (%) BMI percentile Normal High Normal High WC percentile Normal High Normal High Males Males ≤ 90th 225 (99.1) 2 (0.9) 220 (96.9) 7 (3.1) ≤ 75th 197 (100) 0 (0.0) 193 (98) 4 (2.0) > 90th 4 (66.7) 2 (33.3)* 6 (100) 0 (0.0) > 75th 32 (88.9) 4 (11.1)* 33 (91.7) 3 (8.3)* Females Females ≤ 90th 168 (96) 7 (4.0) 169 (96.6) 6 (3.4) ≤ 75th 113 (96.6) 4 (3.4) 113 (96.6) 4 (3.4) > 90th 15 (100) 0 (0.0) 183 (96.3) 7 (3.7) > 75th 70 (95.9) 3 (4.1) 70 (95.9) 3 (4.1) Total Total ≤ 90th 393 (97.8) 9 (2.2) 389 (96.8) 13 (3.2) ≤ 75th 310 (98.7) 4 (1.3) 306 (97.5) 8 (2.5) > 90th 19 (90.5) 2 (9.5)* 20 (95.2) 1 (4.8) > 75th 102 (93.6) 7 (6.4)* 103 (94.5) 6 (5.5) *p < 0.05 *p < 0.05 children who had a BMI above the 90th percentile had a WC few cases of overweight and obese children seen in this study above the 75th percentile (χ2 = 55.8, p < 0.001). were from families of a high socio-economic class, in contrast Both SDP and DBP increased significantly with age (r = with what is seen in developed countries. 0.341, p = 0.000; r = 0.193, p = 0.000, respectively). The mean In our earlier study on the same population,25 there was a DBP was significantly higher in females (62.7 vs 59.0 mmHg, high prevalence of under-nutrition, which was associated with p < 0.001). Eleven children (2.6%) had high SBP and another a high prevalence of moderate to vigorous physical activity 14 (3.3%) had high DBP. There was no significant gender among these adolescents. This suggests that there is a negative difference in the prevalence of high SBP and high DBP (p = balance between energy intake and the energy expended in 0.206, p = 0.697, respectively). doing exercise. However, even though the mean BMI in this The weight, height, BMI and WC had a positive and study was as low as 17.1 kg/m2, as much as 25.8% of the statistically significant correlation coefficient with SBP and DBP children had centrally accumulated fat. This is similar to the (r = 0.126–0.421, p < 0.05). The correlation coefficient of BMI findings in the Karimojong children of Uganda26 and middle- with SBP was higher than that of WC with SBP (0.327 vs 0.29). aged Indians,27 and is a characteristic feature of populations with Similarly, the correlation coefficient of BMI with DBP was chronic malnutrition. This phenomenon, coupled with adaptation higher than that of WC with DBP (0.189 vs 0.129). to western lifestyles, could explain the rise in prevalence of Table 2 show the relationship between general obesity and non-communicable diseases such as hypertension and diabetes blood pressure. There was a significantly higher prevalence of mellitus in these populations. high SBP among male children with general obesity (χ2 = 36.5, p The prevalence of elevated blood pressure in this study is < 0.001). Among the children with central obesity, a significantly similar to the 3.7% obtained earlier by Bugaje et al.28 in Zaria, higher prevalence of high SBP (χ2 = 22.3, p < 0.001) and high Nigeria and the 4% obtained by Balogun et al.29 in Ile-Ife, DBP (χ2 = 4.1, p < 0.042) was seen in only the males (Table 3). Nigeria. It is lower than the prevalence of 6.69% in India,30 In a simple linear regression analysis, BMI and WC explained 9.5% in Ilorin,31 Nigeria, and 12–23% among adolescents in 10.7 and 8.4%, respectively of the variance in SBP, and 3.6 Quebec, Canada.32 The upsurge in the prevalence of overweight and 2.7%, respectively of the variance in DBP. Each increment and obesity, which varies between populations depending on in BMI increased SBP and DBP by 0.327 and 0.189 mmHg, their lifestyle, socio-economic status and other environmental respectively, while each increment in WC increased SBP interactions, has been implicated in the differences in prevalence and DBP by 0.29 and 0.164 mmHg, respectively. When the of high blood pressure at a national and international level. effects of BMI and WC on blood pressure were studied in a In this study, general obesity was a good predictor of high multiple logistic regression equation model (Table 4), BMI SBP in males, and WC was a good predictor of high SBP and was significantly associated with high SBP (OR 0.8, 95% CI: DBP in males. Surprisingly, despite a higher prevalence of 0.65–0.99, p < 0.05). TABLE 4. MULTIPLE REGRESSIONS OF BODY MASS INDEX AND WAIST CIRCUMFERENCE AS RISK Discussion FACTORS FOR HIGH BLOOD PRESSURE* Similar to previous studies from Nigeria,21-23 the prevalence Beta coefficient Standard error p-value of overweight and obesity from this study (using BMI as the Systolic blood pressure 3 indicator) was low when compared with children in the UK, BMI –0.223 0.109 0.042 4 5 Canada and the USA. It was also lower than the prevalence WC 0.029 0.047 0.530 recorded in many North African, Middle Eastern and Latin Diastolic blood pressure American countries24 and in South Africa,6 where the prevalence BMI –0.177 0.118 0.136 of overweight and obesity has been rapidly increasing. This finding supports the fact that overweight and obesity is still an WC 0.013 0.053 0.316 emerging nutritional problem affecting children in Nigeria. The *Adjusted for age and gender. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 263
general and central fatness in females, such strong relationships (accessed June 2009). were not seen. This was different from the findings in other 3. Lobstein T, James WP, Cole TJ. Increasing levels of excess weight studies where strong relationships existed between BMI, WC among chidren in England. Int J Obes Relat Metab Disord 2003; 27: 13,30,32 1136–1138. and BP, irrespective of gender. 4. Canning PM, Courage ML, Frizzell LM. Prevalence of overweight and 33 In keeping with the work of Dobbelsteyn et al. and Yan et obesity in a provincial population of Canadian preschool children. J Am al.34 on Chinese children, BMI was a better indicator of blood Med Coll 2004; 171: 240–242. pressure levels when compared with WC. Similarly, among 5. Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends Nigerian adults who were urban civil servants, central obesity as in overweight among US children and adolescents, 1999-2000. J Am assessed by waist:hip ratio made little contribution to elevated Med Assoc 2002; 288: 1728–1732. 6. Armstrong MEG, Lambert MI, Sharwood KA, Lambert EV. Obesity blood pressure levels.35 However, in Valencia, Spain,36 the waist- and overweight in South African primary school children-the health of to-hip ratio of children significantly contributed to SBP levels, the nation study. S Afr Med J 2006; 96: 486–444. while the relationship between waist-to-hip ratio and DBP was 7. Popkin BM, Richards MK, Montiero CA. Stunting is associated with of borderline significance when compared with weight, height overweight in children of four nations that are undergoing the nutrition and ponderal index. The BMI is a measure of total adiposity. It transition. J Nutr 1996; 126: 3009–3016. has the limitation of not been able to distinguish between muscle 8. Kapil U, Singh P, Pathak P, Dwiedi N, Bhasin S. Prevalence of obesity mass and fat mass and therefore it is difficult to determine which among affluent adolescent school children in Delhi. Indian Pediatr 2001; : 49–52. is the most significant contributor to blood pressure variability. 39 9. Owa JA, Adejuyigbe O. Fat mass, fat mass percentage, body mass 37 According to Stallones et al., weight was more important index, and mid upper arm circumference in a healthy population of than fatness in predicting systolic blood pressure. However, Nigerian children. J Trop Pediat. 1997; 43: 13–19. the mechanism of the relationship between weight and blood 10. Braunschweig CL, Gomez S, Liang H, Tomey K, Doerfler B, Wang Y, pressure is not fully known. In a lean black population, there was Beebe C, Lipton R. Obesity and risk factors for the metabolic syndrome a threshold above which weight was related to blood pressure.38 among low-income urban, African American schoolchildren: the rule This was also observed in a study on urban schoolchildren in rather than the exception? Am J Clin Nutr 2005; 81: 970–975. 11. Perichart-Perera O, Balas-Nakash M, Schiffman-Selechnik E, Barbato- India where the prevalence of high SBP suddenly increased Dosal A, Vadillo-Ortega F. Obesity increases metabolic syndrome risk 2 2 beyond a BMI value of 20 kg/m in boys and 21.5 kg/m in factors in school-aged children from an urban school in Mexico city. J girls.39 This aspect of the assessment was not carried out in our Am Diet Assoc 2007; 107: 81–91. own study. 12. Daniels SR, Morrison JA, Sprecher DL, Khoury P, Kimball TR. The limitations of this study include use of the BMI-for-age Association of body fat distribution and cardiovascular risk factors in percentile of the study population to define overweight and children and adolescents. Circulation 1999; 99: 541–545. obesity rather than the internationally recommended standards. 13. Maffeis C, Pietrobelli A, Grezzani A, Provera S, Tato L. Waist circum- ference and cardiovascular risk factors in prepubertal children. Obes These international standards are designed for developed Res 2001; 9: 179–187. countries where under-nutrition is not a problem. There is a 14. Bogin B. Patterns of Human Growth. 2nd edn. Cambridge: Cambridge need to develop a national BMI classification for paediatric University Press, 1999: 260–261. populations in Nigeria and other African countries. 15. Senbanjo IO, Njokanma OF, Oshikoya KA. Waist circumference Values of Nigerian children and adolescents Ann Nutr Metab 2009; 54: 145–150. Conclusion 16. Oyedeji GA. Socioeconomic and cultural background of hospitalized Overweight and obesity is an emerging health problem among children in Ilesa. Nig J Paediatr 1985; 12: 111–117. adolescents in Abeokuta, Nigeria. However, periodic studies 17. World Health Organization expert committee: Physical status, the use and interpretation of anthropometry. WHO technical report series No coupled with preventive strategies may be necessary to prevent 894. Geneva: WHO, 1995: 424–438. childhood overweight and obesity in Abeokuta from rising 18. Guillaume M. Defining obesity in childhood: Current practice. Am J at the alarming rate that is presently experienced globally. Clin Nutr 1999; 70(Suppl): 126s–130s Although WC was a more direct measurement of body fat, 19. Fernandez JR, Redden DT, Pietrobelli A, Allisson DB. Waist circum- in this study, BMI was a better predictor of blood pressure ference percentiles in nationally representative samples of African levels. Future studies are necessary to validate each of these American, European-American, and Mexican-American children and anthropometric measures against adverse serum lipid profiles adolescents. J Pediatr 2004; 145: 439–444. 20. National High Blood Pressure Education Program Working Group on and other cardiovascular and metabolic risk factors. High Blood Pressure in Children and Adolescents: fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004; 114 (suppl 4th Report): 555–576. We thank the Ogun State Ministry of Education for giving us approval to 21. Ansa VO, Odigwe CO, Anah MU. Profile of body mass index and enter their schools, and the schools, school principals, teachers and students obesity in Nigerian children and adolescents. Niger J Med 2001; 10(2): who participated in this study. We are grateful to the student nurses who 78–80. helped with data collection. The Federal Medical Centre, Abeokuta, Nigeria, 22. Ben-Bassey UP, Oduwole AO, Ogundipe OO. Prevalence of over- funded this work. weight and obesity in Eti-Osa LGA, Lagos, Nigeria. Obes Rev 2007; 8: 475–479. 23. Akesode FA, Ajibode HA. Prevalence of obesity among Nigerian References school children. Soc Sci Med 1983; 17: 107–111. 1. World Health Organization. Obesity: Preventing and managing the 24. De Onis M, Blossner M. Prevalence and trends of underweight among global epidemic. World Health Organ Tech Resp Ser 2000; No. 894. preschool children in developing countries. Am J Clin Nutr 2000; 72: 2. International Association for the Study of Obesity. IOTF demands 1032–1039. action on childhood obesity crisis. Available on: http://www.iaso.org/ 25. Senbanjo IO, Oshikoya KA. Physical activity and body mass index of popout.asp?linkto=http%3A//www.iotf.org/media/IOTFmay12.htm school children and adolescents in Abeokuta, Southwest Nigeria. World 264 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
J Pediatr 2010; 6: 217–222. tive evaluation of waist circumference, waist-to-hip ratio and body 26. Gray S, Akol HA, Sundal M. Mixed-longitudinal growth of Karimojong mass index as indicators of cardiovascular risk factors: the Canadian girls and boys in Moroto District, Uganda. Am J Hum Biol 2009; 21: Heart Health Surveys. Int J Obes Relat Metab Disord 2001; 25: 652– 65–76. 661. 27. Ghosh A. Factor analysis of metabolic syndrome among the middle 34. Yan W, Wang X, Yao H, Dai J, Zheng Y, Yang X, Yibulayin X, Cui aged Bengalese Hindu men of Calcutta, India. Diabetes Metab Res Rev J. Waist-to-height ratio and BMI predict different cardiovascular risk 2005; 21: 58–64. factors in Chinese children. Diabetes Care 2006; 29: 2761. 28. Bugaje MA, Yakubu AM, Ogala WN. Prevalence of adolescent hyper- 35. Adams-Campbell LL, Wing R, Ukoli FA, Janney CA, Nwankwo MU. tension in Zaria. Nig J Paediatr 2005; 32: 77–82. Obesity, body fat distribution, and blood pressure in Nigerian and 29. Balogun JA, Obajuluwa VA, Abereoje OK, Olaogun MO, Oyeyemi African-American men and women. J Natl Med Assoc 1994; 86: 60–64. AY, Balogun MO, Adeodu OO. Anthropometric determinants of rest- 36. Lurbe E, Alvarez V, Youlian L, et al. The Impact of Obesity and ing blood pressure and heart rate of Nigerian school children. Ann Trop Body Fat Distribution on Ambulatory Blood Pressure in Children and Paediatr 1990; 10: 425–431. Adolescents. Am J Hypertens 1998; 11: 418–424. 30. Mohan B, Kumar N, Aslam N, et al. Prevalence of Sustained 37. Stallones L, Mueller WH, Christensen BL. Blood pressure, fatness, Hypertension and Obesity in Urban and Rural School Going Children and fat patterning among USA adolescents from two ethnic groups. in Ludhiana. Ind Heart J 2004; 56: 310–314. Hypertension 1982; 4: 483–486. 31. Obika LF, Adedoyin MA, Olowoyeye JO. Pattern of paediatric blood 38. Bunker CH, Ukoli FA, Matthews KA, Kriska AM, Huston SL, Kuller pressure in rural, semi-urban and urban communities in Ilorin, Nigeria. LH. Weight threshold and blood pressure in a lean black population. Afr J Med Med Sci 1995; 24: 371–377. Hypertension 1995; 26: 616–623. 32. Paradis G, Lambert M, O’ Loughlin J, et al. Blood pressure and adipos- 39. Rao S, Kanade A, Kelkar R. Blood pressure among overweight adoles- ity in children and adolescents. Circulation 2004; 110: 1832–1838. cents from urban school children in Pune, India. Eur J Clin Nutr 2007; 33. Dobbelsteyn CJ, Joffres MR, MacLean DR, Flowerdew G. A compara- 61: 633–641. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 265
Prevalence, awareness, treatment and control of hypertension among adults 50 years and older in Dakar, Senegal E Macia, P DUBOZ, L GUEYE
Abstract Whether carried out in Western countries or in sub-Saharan Background: Older adults are disproportionately affected by Africa, all studies show that the prevalence of arterial hypertension hypertension, which is an established risk factor for cardio- rises drastically with age and that the elderly are the population 7,16 vascular disease. Despite these facts, no study on the preva- segment the most at risk. In Dakar, again according to the lence, awareness, treatment and control on arterial hyper- previously cited study, nearly 70% of adults 50 years and older 15 tension in Senegal has been conducted, specifically among are believed to suffer from hypertension. Despite this evidence, elderly people. and to our knowledge, no study pertaining to the awareness, Methods: Five hundred people aged 50 years and older, treatment and control of arterial hypertension in sub-Saharan living in the city of Dakar were interviewed. This sample was Africa has been specifically conducted among the elderly. Most constructed using the combined quota method in order to research conducted in this geographic area considers older strive for representativeness of the target population. people as a non-specific and homogenous population category Results: Prevalence of hypertension was 65.4% in our (the ‘50 years and older’ for example). Yet, studies carried out sample. Half of those suffering from high blood pressure in both developed and developing countries demonstrate clear were aware of their problem and among the latter, 70% said evolution in the prevalence, awareness, treatment and control of 17-19 they were on treatment. However, of these, only 17% had hypertension during the aging process. controlled arterial blood pressure. The only factor associated The aims of this study were therefore to (1) assess the with awareness, treatment and control of hypertension was prevalence, awareness, treatment and control of hypertension the frequency of doctor visits. in the population aged 50 years and older living in the city of Conclusion: Improving follow-up health checks of older Dakar; (2) identify factors associated with hypertension, and also adults are necessary to limit the consequences of hyperten- its awareness, treatment and control. sion in Dakar. Keywords: hypertension, risk factors, older adults, Senegal Methods This study was conducted from January to June 2009 on a sample Submitted 11/5/11, accepted 19/7/11 of 500 individuals. The sample was constructed using the quota Cardiovasc J Afr 2012; 23: 265–269 www.cvja.co.za method (cross-section by age, gender and town of residence) in DOI: 10.5830/CVJA-2011-039 order to strive for representativeness of the population 50 years and older living in the city of Dakar. Data from the Agence Cardiovascular disease is an emerging problem in sub-Saharan Nationale de la Statistique et de la Démographie dating from Africa.1 In Senegal, mortality associated with such diseases the last census (2002) were used to this end. The quota variables is already over half that related to non-contagious diseases.2 used were gender (male/female), age (50–59, 60–69, 70 years Moreover, hypertension is a prime risk factor for cardiovascular and older) and town of residence. disease due to both its widespread prevalence and low control The towns were grouped into the four districts making up rate among populations,3 making hypertension a major public the city of Dakar: Plateau-Gorée (five towns), Grand Dakar (six health problem per se in sub-Saharan Africa. towns), Parcelles Assainies (four towns) and Almadies (four Urbanisation and the adoption of a Western lifestyle contribute towns). This method requires building up a sample that follows greatly to the rising incidence of hypertension in sub-Saharan the proportions observed in the general population: for example, Africa.4 Recent studies conducted in the region have shown that according to the last census, men aged 50–59 years living in the hypertension was already as frequent in these cities as it is in town of Medina (district of Plateau-Gorée) represented 2.4% of developed countries.5-14 In Dakar, its prevalence among adults 20 the population of 50 years and older living in the city of Dakar. years and older was 27.5% in 2009.15 These findings are particularly The sample was constructed so as to reflect this proportion and alarming due to the present low rates of detection, treatment included 12 men 50–59 years old living in this town. and control of hypertension observed in sub-Saharan Africa.5 For each town, four investigators (PhD students in the departments of Medicine and Pharmacy) started out from different points each day to measure and interview individuals in Wolof or French in every third home. Investigators had a UMI 3189 Environnement, santé, sociétés, Université Cheikh set number of individuals to interview (women and men 50–59 Anta Diop/CNRS/Université de Bamako/CNRST, Burkina- years, 60–69 years, and 70 years and over in each town) to meet Faso, Senegal the quotas. Only one person was selected as a respondent in each E Macia, PhD, [email protected] P DUBOZ, PhD home. L GUEYE, PhD The objective of this bio-anthropological survey was to carry 266 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
out a holistic study on aging in the city of Dakar. To do so, face- to-face guided interviews based on a questionnaire were used Hypertensive to collect the data required for the study. These interviews were 65.4% (95% CI: 61.5–69.3) followed by a physical examination that involved taking blood ≈ 52 700 Dakarites aged 50 years and older* pressure and anthropometric measurements.
Study definitions and measurements Blood pressure was measured twice for each participant in Not aware Aware the course of a single visit. The first measurement was taken 50.5% 49.5% (95% CI: 44.1–54.9) mid-way through the interview, just after the questions related ≈ 26 100 Dakarites aged 50 years and older* to individual health. The second measurement was taken at the end of the questionnaire, after about 15–20 minutes’ rest. These measurements were taken by medical and pharmacy students in ® Dakar, using an Omron M3 Intellisense device validated by the Not treated Treated 20 International Protocol. The mean of the two measurements was 29.4% 70.6% (95% CI: 63.8–77.4) used for the analyses. among the aware In accordance with the Seventh Report of the Joint National 37.0% (95% CI: 31.8–42.2) Committee of Prevention, Detection, Evaluation, and Treatment among the hypertensive of High Blood Pressure, individuals with systolic blood pressure ≈ 19 500 Dakarites aged 50 years and older* ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/ or who reported the current use of antihypertensive medication were considered to be suffering from high blood pressure.21 Weight was measured using a digital scale (accuracy of 100 Not controlled Controlled g) with subjects dressed in minimum clothing and barefoot. To 82.6% 17.4% (95% CI: 10.4–24.4) measure height, the subject was asked to stand ‘at attention’, among the treated arms at the sides, heels together and without shoes. Following 6.7% (95% CI: 4.0–9.4) World Health Organisation recommendations, body mass index among the hypertensive (BMI) was calculated by dividing weight (kg) by the square of ≈ 3 500 Dakarites aged 50 years and older* the height (m2). Overweight was defined as 25 ≤ BMI < 30 kg/ m2; obesity corresponded to a BMI of ≥ 30 kg/m2.22 *The numbers of older Dakarites aware of their hypertension, treated Given the large proportion of people who had not visited a and controlled were obtained by multiplying the prevalence figure by the doctor in the year preceding the interview (48%), the frequency of population aged 50 years and older, according to the last census (2002). doctor visits was split into two groups, as in the study conducted Fig. 1. Prevalence, awareness, treatment and control of by the hypertension study group in India and Bangladesh.17 hypertension in the population of Dakar aged 50 years Therefore, people who had not visited a doctor in the year and older. preceding the interview were distinguished from those who had schooling, more than eight years of schooling. Marital status was seen a doctor at least once during the year. coded as follows: married = 0, other = 1. Among the socio-demographic data collected during the interviews, four variables were taken into account for this study: age, gender, educational level and marital status. Three Statistical analysis age groups were defined: 50–59, 60–69 and 70 years and over. To answer our research questions, we used Chi-square tests and Gender was coded as follows: 1 for women, 0 for men. Three logistic regressions. The software used for the statistical analysis levels of education were defined: none, one to eight years of was PASW Statistics 18.
TABLE 1. CHARACTERISTICS OF THE SAMPLE (n = 500) Variable Category Total, n (%) Men, n (%) Women, n (%) Analysis Age (years) 50–59 268 (53.6) 144 (54.7) 124 (52.3) Chi2 (2 df) = 0.41; 60–69 136 (27.2) 71 (27) 65 (27.4) NS ≥ 70 96 (19.2) 48 (18.3) 48 (20.3) Educational level None 228 (45.6) 97 (36.9) 131 (55.3) c2 (2 df) = 29.46; 1–8 years 186 (37.2) 100 (38.0) 86 (36.3) p < 0.001 ≥ 9 years 86 (17.2) 66 (25.1) 20 (8.4) Marital status Married 372 (74.4) 234 (89) 138 (58.2) c2 (1 df) = 61.87; Not married 128 (25.6) 29 (11) 99 (41.8) p < 0.001 Doctor visits in previous year 0 240 (48) 141 (53.6) 99 (41.8) c2 (1 df) = 7.00; ≥ 1 260 (52) 122 (46.4) 138 (58.2) p < 0.01 BMI (kg/m2) < 25 231 (46.2) 149 (56.7) 82 (34.6) c2 (1 df) = 24.40; ≥ 25 269 (53.8) 114 (43.3) 155 (65.4) p < 0.001 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 267
TABLE 2. FACTORS ASSOCIATED WITH HYPERTENSION, AWARENESS, TREATMENT AND CONTROL Treatment among Treatment Control among Control Prevalence Awareness hypertensives among aware hypertensives among treated (n = 500) (n = 327) (n = 327) (n = 171) (n = 327) (n =121) Variable Category % Analysis % Analysis % Analysis % Analysis % Analysis % Analysis Total 65.4 49.5 37 70.6 6.7 17.4 Gender Men 63.9 c2 (1 df) = 0.57; 36.3 c2 = 24.20; 27.4 c2 = 13.72; 71.4 c2 = 0.34; 3.6 c2 = 5.49; 13 c2 = 0.96; Women 67.1 NS 63.5 p < 0.001 47.2 p < 0.001 70.1 NS 10.1 p < 0.05 20 NS Age (years) 50–59 58.2 c2 (2 df) = 13.60; 42.3 c2 (2 df) = 8.65; 30.8 c2 = 6.42; 66.7 c2 = 0.94; 6.4 c2 = 0.05; 18.8 c2 = 0.33; 60–69 72.1 p < 0.001 51 p < 0.05 38.8 p < 0.05 74 NS 7.1 NS 18.4 NS ≥ 70 76 63 47.9 72.9 7.8 14.3 Educational None 68.9 c2 (2 df) = 3.91; 52.2 c2 = 6.59; 34.4 c2 = 2.23; 62.8 c2 = 6.27; 8.3 c2 = 1.32; 24.1 c2 = 3.07; level 1–8 years 65.1 NS 52.9 p < 0.05 42.1 NS 75.8 p < 0.05 5.8 NS 11.8 NS ≥ 9 years 57 32.7 32.7 88.9 4.1 12.5 Marital status Married 66.1 c2 (1 df) = 0.34; 43.9 c2 =12.63; 32.9 c2 = 7.08; 71.4 c2 = 0.11; 6.1 c2 = 0.63; 18.5 c2 = 0.23; Not married 63.3 NS 66.7 p < 0.001 49.3 p < 0.01 69 NS 8.6 NS 15 NS Doctor visits in 0 62.9 c2 (1 df) = 1.26; 35.1 c2 = 23.41; 19.2 c2 = 38.12; 53.7 c2 = 10.87; 2 c2 = 10.05; 19.6 c2 = 1.31; previous year ≥ 1 67.7 NS 61.9 p < 0.001 52.3 p < 0.001 78.4 p < 0.001 10.8 p < 0.01 10.3 NS BMI (kg/m2) < 25 59.3 c2 (1 df) = 7.03; 46 c2 = 1.19; 34.3 c2 = 0.74; 69.7 c2 = 0.04; 8 c2 = 0.64; 23.4 c2 = 1.96; ≥ 25 70.6 p < 0.01 52.1 NS 38.9 NS 71.2 NS 5.8 NS 13.5 NS
Results the other hand, gender and marital status were not significantly The socio-demographic characteristics of our population sample associated with hypertension (Table 2). The bivariate results and the descriptive results regarding frequency of doctor visits were confirmed using logistic regression analysis (Table 3). and BMI are presented in Table 1. Men were better educated Aside from BMI, using bivariate analyses, all factors studied and less often overweight or obese than women. On the other were associated with awareness of hypertension. Women, the hand, more women had visited a doctor in the year preceding older and unmarried individuals were more often informed of the interview. this problem than men, younger people and married individuals. In our sample, the prevalence of hypertension was 65.4% Likewise, many more individuals who had seen a doctor at least [95% confidence interval (CI): 61.5–69.3). Nearly half of the once in the year preceding the interview were aware of their individuals suffering from hypertension were aware of their hypertensive condition than those who had not seen a doctor health problem, and 70% of the informed people reported being during this period. Lastly, and more surprisingly, people who treated for hypertension. Therefore, 37% (95% CI: 31.8–42.2) of had had at least nine years of schooling were less often aware of the people suffering from hypertension were treated. However, their hypertensive status than the less educated (Table 2). Most among people reporting they were treated for hypertension, only of these results were controlled using logistic regression analysis 17.4% had controlled hypertension; i.e. 6.7% (95% CI: 4.0–9.4) and only marital status was not significantly associated with of the hypertensives (Fig. 1). awareness of hypertension (Table 3). Bivariate analyses showed that hypertension increased steadily Multivariate analysis showed that among hypertensives, with age in our sample, from 58% among those 50–59 years old to women, older adults, and those who had seen a doctor during the 76% among those 70 years and older. These analyses also showed preceding year more often reported taking treatment than men, that overweight or obese individuals were more often affected younger people, and those who had not seen a doctor during the by hypertension than others (70.6 vs 59.3%, respectively). On previous year, respectively (Table 3).
TABLE 3. ADJUSTED ODDS RATIOS FOR HYPERTENSION, AWARENESS, TREATMENT AND CONTROL Treatment among Treatment Control among Control among Hypertension Awareness hypertensives among aware hypertensives treated (n = 500) (n = 327) (n = 327) (n = 171) (n = 327) (n = 121) Variables Categories OR IC (95%) OR IC (95%) OR IC (95%) OR IC (95%) OR IC (95%) OR IC (95%) Gender (Men) Women 1.01 0.66–1.56 2.4** 1.41–4.07 2.3** 1.31–4.06 1.45 0.59–3.56 2.79 0.92–8.47 1.56 0.41–5.9 Age (50–59 years) 60–69 1.94** 1.22–3.07 1.44 0.82–2.54 1.62 0.89–2.94 2.16 0.89–5.26 1.03 0.35–3.05 0.73 0.21–2.6 ≥ 70 2.54** 1.45–4.44 2.15* 1.11–4.17 2.24* 1.14–4.4 2.23 0.85–5.86 0.96 0.27–3.42 0.66 0.16–2.71 Educational level None 1.28 0.73–2.23 1.72 0.8–3.69 0.73 0.33–1.61 0.2 0.04–1.07 1.66 0.32–8.56 2.14 0.34–13.54 (≥ 9 years) 1–8 years 1.23 0.71–2.14 2.15* 1.01–4.6 1.36 0.63–2.94 0.49 0.09–2.56 1.31 0.24–7.06 0.98 0.15–6.29 Marital status Not 0.81 0.51–1.28 1.48 0.8–2.75 1.13 0.61–2.1 0.54 0.22–1.32 0.94 0.32–2.77 0.9 0.25–3.27 (Married) married BMI ≥ 25 kg/m2 1.86** 1.24–2.79 1.23 0.73–2.06 1.13 0.66–1.91 0.94 0.44–2.03 0.7 0.27–1.81 0.62 0.22–1.8 (< 25 kg/m2) Doctor visit in 0 0.37*** 0.23–0.6 0.24*** 0.14–0.41 0.32** 0.15–0.69 0.17** 0.05–0.6 0.32 0.07–1.43 previous year (≥ 1) *p < 0.05; **p < 0.01; ***p < 0.001. 268 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
The results for the sub-sample of individuals who were the opposite.30 More research is required to understand this aware of their hypertension problem were quite different. In this specificity, but it could be that education does not have the same logistic regression analysis, only the frequency of doctor visits implications for health management in Dakar as in developed was significantly associated with treatment of hypertension countries. Nevertheless, it is not surprising to note that the factor (Table 3). most strongly associated with awareness of hypertension was the Among the hypertensives, on multivariate analysis, only frequency of doctor visits. the frequency of doctor visits was associated with control More than 70% of individuals aware of their hypertension of hypertension (Table 3). Therefore, people having seen a reported taking treatment, which seems well above the rule of doctor during the preceding year more often had controlled halves. This theoretically encouraging statistic should, however, hypertension than those who had not seen a doctor the previous be discussed in light of the results associated with control of year. However, among treated individuals, no variable was hypertension. Fewer than 17% of the people who reported associated with control of hypertension (Table 3). being treated actually had controlled hypertension, i.e. 6.7% of hypertensives. A study conducted in Ghana could help explain why the Discussion hypertension control rate was so low among the elderly in The prevalence of hypertension in our population sample Dakar. According to this study, 93% of the people treated for corresponded with that observed among older people in hypertension did not comply with their medical prescriptions, other sub-Saharan African cities5-14 or in other developing usually due to the high cost of medication.31 The same observation countries such as India and Bangladesh.17 In Dakar, seems to hold true in Dakar where the price of medication is two out of three people 50 years and older suffered from disproportionate to average expenditure per person per day, i.e. arterial hypertension, a disease that has now become a 1 224 FCFA (≈ 2.7 dollars).32 major public health concern in the Senegalese capital. However, another explanation could be advanced. According In keeping with what has been observed among other to Salem, treatment of chronic disease is generally misunderstood. populations, aging and problems of overweight and obesity In Dakar, when a disease is identified, it is believed it should be were associated with hypertension.23,24 However, this was not the ejected as a foreign body.33 The notion of chronic illness goes case with educational level. This observation seems to indicate against this conception, which could explain the low level of that the Dakar population is currently in an advanced stage of compliance with treatment. epidemiological transition. This process is characterised by a Since pharmacological treatment of hypertension is the transfer of risk factors for chronic illnesses from the better- consequence of its detection by healthcare personnel, factors educated individuals in the early stages of the process to the less associated with treatment among hypertensives were the same educated at the end of the transition.25 as those associated with awareness of this health problem, i.e. The rate of awareness of hypertension among the hypertensives, frequency of doctor visits, gender and age. Among these factors, approximately 50%, corresponds with that observed among only the frequency of doctor visits was significantly associated the elderly living in other developing countries.17 This rate is, with the control of hypertension. Therefore it was the only factor however, much lower than that noted in the West, where over investigated that was associated with awareness, treatment and two-thirds of older hypertensives are aware of the problem.18,19 control of hypertension in this study. This result highlights the If the ‘rule of halves’26 remains valid here, it nevertheless absolute necessity of improving the follow-up health checks of conceals great disparities, especially between men and women. older adults to minimise the consequences of hypertension in Dakar. As with most developing populations, women were more often informed on their problem of hypertension than men.27 However, Strengths and limitations of the study the reasons for this association remain poorly understood.17 In This research was, to our knowledge, the first study conducted fact, it may appear surprising in Senegal, where male domination specifically on hypertension among the elderly in sub-Saharan over women is taken for granted.28 Africa. In years to come, the elderly in developing countries will The Demographics and Health Survey conducted in 2005 represent the majority of older people on the planet.34 Therefore it indicated for instance that scarcely 12% of married women is necessary to understand the prevalence of hypertension among made their own decisions about their personal healthcare these populations, as well as the rates of awareness, treatment spending, whereas for 67% of them, only their spouse made such and control of the disease, in order to combat this burden more decisions.29 However, in Senegal, it is primarily women who take effectively and in a more appropriate manner. care of the health of members of the household, accompanying This study has several limitations. As in many studies, their daughters, daughters-in-law and grandchildren to healthcare arterial blood pressure was measured twice during a single visit, institutions. This might explain both their more frequent visits to which may have led to overestimation of the prevalence of these institutions and their greater monitoring of hypertension. hypertension. Furthermore, the treatment rate of hypertension Unlike the results noted for elderly German and American was assessed solely by individual self-reporting. Verification of populations,18,19 awareness of hypertension rises with age among the actual presence of medication in the home might have limited the elderly in Dakar. Therefore the probability of having been the bias associated with these declarations. identified as hypertensive rises with age. More surprisingly, we have seen that people with a higher educational level were often less informed on their hypertension than those with Conclusion an average educational level. This result runs contrary to all The results of this study have several public health implications. research conducted on the subject, which generally demonstrates Firstly, two-thirds of the Dakar elderly suffer from hypertension, AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 269
and this disease therefore constitutes a major public health 14. Vorster HH. The emergence of cardiovascular disease during urbanisa- concern in the Senegalese capital. Detection could be considerably tion of Africans. Publ Hlth Nutr 2002; 5: 239–243. improved given that only 50% of those suffering from high 15. Duboz P, Macia E, Dia M, Gueye L. Prevalence and risk factors of hypertension in Dakar’s department. Dakar Médical (in press). blood pressure were aware of this problem. Nearly three-quarters 16. Ong KL, Cheung BM, Man YB, Lau CP, Lam KS. Prevalence, aware- of the people informed on their condition reported being treated, ness, treatment, and control of hypertension among United-States adults which is an encouraging statistic in a developing country. 1999-2004. Hypertension 2007; 49: 69–75. However, compliance with these treatments appears particularly 17. Hypertension study group. Prevalence, awareness, treatment and problematic, given that fewer than 20% of individuals treated control of hypertension among the elderly in Bangladesh and India: a had controlled hypertension. It is likely that the high cost of multicentre study. Bull Wld Hlth Organ 2001; 79: 490–500. pharmacological treatment when compared to income was 18. McDonald M, Hertz RP, Unger AN, Lustik MB. Prevalence, aware- ness, and management of hypertension, dyslipidemia, diabetes among responsible for the low rate of compliance with these treatments. United States adults aged 65 and older. J Gerontol A Bio Sci Med Sci One of the factors studied was associated with awareness, 2009; 64: 256–263. treatment and control of hypertension: the frequency of doctor 19. Van Rossum CTM, van de Mheen H, Witteman JCM, Hofman A, visits. This result highlights the absolute necessity to improve Mackenbach JP, Grobbee DE. Prevalence, treatment, and control of follow-up health checks of older adults to minimise the hypertension by sociodemographic factors among the Dutch elderly. consequences of hypertension in Dakar. Hypertension 2000; 35: 814–821. 20. Asmar R, Khabouth J, Topouchian J, El Feghali R, Mattar J. Validation This research was supported by grants from the National Institute for Heath of three automatic devices for self-measurement of blood pressure Prevention and Education (INPES) and the Department of Research (ACI according to the International Protocol: the Omron M3 Intellisense ‘Constructions, normes et écarts’ No. 045398). The manuscript was trans- (HEM-7051-E), the Omron M2 Compact (HEM 7102-E), and the lated from French by Cynthia Schoch. Omron R3-I Plus (HEM 6022-E). Blood Press Monit 2010; 15: 49–54. 21. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee of Prevention, Detection, Evaluation, and References Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252. 1. Sani MU. Cardiovascular diseases in sub-Saharan Africa: an emerging 22. World Health Organisation. Obesity: Preventing and Managing the problem. Ethn Dis 2007; 17: 574–575. Global Epidemic. Report of the WHO Consultation. WHO Technical 2. World Health Organisation. Death and DALY estimates for 2004 by Report Series 894. WHO: Geneva, 2000. cause for WHO Member States. http://www.who.int/entity/healthinfo/ 23. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The statistics/bodgbddeathdalyestimates.xls. Accessed 2006. disease burden associated with overweight and obesity. J Am Med Assoc 3. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He 1999; 282: 1593–1594. J. Global burden of hypertension: analysis of worldwide data. Lancet 24. Mufunda J, Mebrathu G, Usman A, et al. The prevalence of hyperten- 2005; 365: 217–223. sion and its relationship with obesity: results from a national blood pres- 4. Opie LH, Seedat YK. Hypertension in sub-Saharan African popula- sure survey in Erytrea. J Hum Hypertens 2006; 20: 59–65. tions. Circulation 2005; 112: 3554–3561. 25. Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in 5. Addo J, Smeeth L, Leon DA. Hypertension in sub-Saharan Africa: a developing countries. Circulation 1998; 97: 596–601. systematic review. Hypertension 2007; 50:1012–1018. 26. Marques-Vidal P, Tuomilehto J. Hypertension, awareness and control 6. Agyemang C. Rural and urban differences in blood pressure and hyper- in the community: is the “rule of halves” still valid? J Hum Hypertens tension in Ghana, West Africa. Publ Hlth 2006; 120: 525–533. 1997; 11: 213–220. 7. Amoah AG. Hypertension in Ghana: a cross-sectional community 27. Fuentes R, Ilmaniemi N, Laurikainen E, Tuomilehto J, Nissinen A. prevalence in greater Accra. Ethn Dis 2003; 13: 310–315. Hypertension in developing economies: a review of population-based 8. Bovet P, Ross AG, Gervasoni JP, et al. Distribution of blood pressure, studies carried out from 1980 to 1998. J Hypertens 2000; 18: 521–529. body mass index and smoking in the urban population of Dar es Salaam, 28. Macia E, Duboz P, Gueye L. Les dimensions de la qualité de vie subjec- Tanzania, and associations with socioeconomic status. Int J Epidemiol tive à Dakar. Sciences Sociales et Santé 2010; 28: 75–84. 2002; 31: 240–247. 29. Ndiaye S, Ayad M. Enquête Démographique et de Santé au Sénégal 9. Damasceno A, Azevedo A, Silva-Matos C, Prista A, Diogo D, (EDS-IV) 2005. Demographic and Health Surveys: Dakar, 2005. Lunet N. Hypertension prevalence, awareness, treatment, and control 30. Regidor E, Guttiérez-Fisac JL, Banegas JR, Dominguez V, Rodriguez- in Mozambic: urban/rural gap during epidemiological transition. Artalejo F. Association of adult socioeconomic position with hyperten- Hypertension 2009; 54: 77–83. sion in older people. J Epidemiol Commun Hlth 2006; 60: 74–80. 10. Edwards R, Unwin N, Mugusi F, et al. Hypertension prevalence and 31. Ohene Buabeng K, Matowe L, Plange-Rhule J. Unaffordable drug care in an urban and rural area of Tanzania. J Hypertens 2000; 18: price: the major cause of non-compliance with hypertension medication 145–152. in Ghana. J Pharm Pharm Sci 2004; 7: 350–352. 11. Kadiri S, Walker O, Salako BL, Akinkugbe O. Blood pressure, hyper- 32. Agence Nationale de la Statistique et de la Démographie (ANSD). tension and correlates in urbanised workers in Ibandan, Nigeria: a Enquête de suivi de la pauvreté au Sénégal – EPPS 2005-2006. revisit. J Hum Hypertens 1999; 13: 23–27. http://www.ansd.sn/publications/rapports_enquetes_etudes/enquetes/ 12. Mbanya JC, Minkoulou EM, Salah JN, Balkau B. The prevalence of Rapport_ESPS.pdf. Accessed 2007. hypertension in urban and rural Cameroon. Int J Epidemiol 1998; 27: 33. Salem G. La Santé dans la Vville. Géographie d’un Petit Espace Dense: 181–185. Pikine (Sénégal). Paris: Karthala; 1998. 13. Steyn K, Gaziano TA, Bradshaw D, Laubscher R, Fourie J. South 34. United Nations. Rapport de la deuxième assemblée mondiale sur le African Demographic and Health Coordinating Team. Hypertension in vieillissement. Madrid, 8-12 avril 2002. http://daccess-dds-ny.un.org/ South African adults: results from the Demographic and Health Survey doc/UNDOC/GEN/N02/397/52/PDF/N0239752.pdf?OpenElement. 1998. J Hypertens 2001; 19: 1717–1725. Accessed 2002. 270 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Control of cardiovascular risk in black Africans with type 2 diabetes in Senegal (Contrôle du risque cardio-vasculaire chez les diabétiques de type 2 noirs africains au Sénégal) NV YAMÉOGO, A MBAYE , M NDOUR, LJ KAGAMBEGA, H DIOMANDE, R HAKIM, A THIAM, A DIALLO, SN DIOP, D DIAGNE, B DIACK, A KANE
Abstract Keywords: diabetes, cardiovascular risk factors, control, Introduction: Morbidity and mortality from diabetes are diabète, facteurs de risque cardio-vasculaire, contrôle compounded by associated cardiovascular risk factors. For Submitted 16/6/10, accepted 4/8/11 this reason, taking care of these risk factors is a public health Cardiovasc J Afr 2012; 23: 270–272 www.cvja.co.za goal. In this study we evaluated the level of control of cardio- DOI: 10.5830/CVJA-2011-040 vascular risk factors in black Africans with type 2 diabetes in Senegal. Methods: Between March 2007 and July 2008, we recruited Résumé type 2 diabetes patients from outpatient care in a special- Introduction: La morbidité et la mortalité du diabète sont ised hospital in Senegal. Data were collected on a survey aggravées par l’association de facteurs de risque cardio- form designed for this purpose. An electrocardiogram and vasculaire dont la prise en charge est un objectif de santé laboratory examinations were also performed. The level of publique. Nous évaluons dans cette étude le niveau de control of diabetes and associated cardiovascular risk factors contrôle des facteurs de risque cardio-vasculaire dans une were assessed, as recommended by the American Diabetes population de diabétiques de type 2 noirs africains au Association (ADA). Sénégal. Results: A total of 318 type 2 diabetes subjects (237 women) Méthodologie: Nous avons recruté, entre mars 2007 et juil- were recruited. The average age was 58.2 ± 9.2 years let 2008, des diabétiques de type 2 suivis en ambulatoire en (40–85). The mean duration of diabetes was 6.9 ± 5.9 years. milieu hospitalier spécialisé au Sénégal. Les données ont été The average glycaemic level was 1.4 ± 0.5 g/l and glycated recueillies sur une fiche d’enquête conçue à cet effet. Un élec- haemoglobin was 7.6 ± 3.2%. The average length of patient trocardiogramme et des examens biologiques ont été aussi follow up was 6.7 ± 6.1 years with a single annual consulta- réalisés. Le niveau de contrôle du diabète et des facteurs de tion; 63.2% of the patients were on an insulin + biguanide risque cardio-vasculaire associés a été évalué selon les recom- mandations de l’American Diabetes Association (ADA). combination, with good diabetes control (HbA1c < 7%) in 25% of cases. Antihypertensive drugs were prescribed in Résultats: Un total de 318 diabétiques de type 2 (237 femmes) 28.1% of hypertensive patients. More than half (51.9%) of ont été colligés. L’âge moyen était de 58.2 ± 9.2 ans (40–85). these hypertensive patients were treated with angiotensin La durée moyenne d’évolution du diabète était de 6.9 ± converting enzyme inhibitors. Their blood pressure was well 5.9 ans avec un taux moyen de glycémie de 1.4 ± 0.5 g/l et controlled (< 130/85 mmHg) in 5.4% of the hypertensive d’hémoglobine glyquée de 7.6 ± 3.2%. La durée moyenne du patients (10/185). The low-density lipoprotein (LDL) choles- suivi des patients était de 6.7 ± 6.1 ans avec une seule consul- terol goal was achieved in 18.5% of cases (5/27). tation annuelle; 63.2% des patients étaient sous l’association Conclusion: This study shows that the prevalence of cardio- biguanide + insuline avec un bon contrôle du diabète (HbA1c vascular risk factors is higher among black Africans suffer- < 7%) dans 25% des cas. Les antihypertenseurs étaient ing from type 2 diabetes. The control of these factors was not prescrits chez 28.1% des hypertendus dont plus de la moitié optimal in our study. (51.9%) sous inhibiteurs de l’enzyme de conversion de l’angiotensine avec un bon contrôle de la tension artérielle (< 130/85 mmHg) dans 5.4% des cas (10/185). L’objectif de LDL-cholestérol était atteint dans 18.5% des cas (5/27). Conclusion: Cette étude montre que la prévalence des Service de cardiologie de l’Hôpital Général de Grand Yoff, facteurs de risque cardio-vasculaire est élevé chez les diabé- Dakar, Senegal tiques de type 2 noirs africains. Le contrôle de ces facteurs NV YAMÉOGO, MD, [email protected] n’était pas optimal dans notre étude. A MBAYE, MD M NDOUR, MD LJ KAGAMBEGA, MD Le diabète sucré est une maladie grave dont la prévalence est en H DIOMANDE, MD constante progression. Il constitue un important facteur de risque R HAKIM, MD cardio-vasculaire, avec une morbi-mortalité aggravée par les A THIAM, MD facteurs de risque communément associés telles que l’obésité, A DIALLO, MD la dyslipidémie et l’hypertension artérielle.1 Il mérite d’être SN DIOP, MD 2 D DIAGNE, MD évalué dans ce sens surtout après une longue durée d’évolution. B DIACK, MD Il requiert un suivi continu et rigoureux des patients afin A KANE, MD d’éviter la survenue les complications.3 La prise en charge des AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 271
facteurs de risque cardio-vasculaire chez le diabétique de type % (extrêmes: 4.5–10.9%) (tableau 1). 2 constitue ainsi un objectif prioritaire.4-6 Les objectifs de cette Les facteurs de risque cardio-vasculaire de nos patients sont prise en charge sont de réduire l’incidence des complications indiqués dans le tableau I. Ils étaient dominés par la sédentarité dégénératives et le risque de survenue d’événements cardio- (82.4%), l’hypertension artérielle (58.2%), la dyslipidémie vasculaires, d’augmenter l’espérance de vie et d’améliorer la (43.1%) et la microalbuminurie (36.8%). qualité de vie de ces patients. Plus de la moitié des patients (63.2%) était sous l’association Notre étude avait pour but d’évaluer la prise en charge des biguanide + insuline + mesures hygiéno-diététiques. Les facteurs de risque cardio-vasculaire et leur niveau de contrôle différents traitements antidiabétiques utilisés figurent dans le chez les diabétiques de type 2 au Sénégal. tableau 2. Les antihypertenseurs étaient prescrits chez 28.1% des hypertendus. Les inhibiteurs de l’enzyme de conversion de Patients et méthode l’angiotensine étaient les médicaments les plus utilisés (51.9%). Nous avons mené une étude transversale, descriptive, Les médicaments utilisés pour le traitement de l’hypertension multicentrique de Mars 2007 à Juillet 2008 dans trois des artérielle figurent dans le tableau 3. principaux centres hospitaliers de Dakar (Centre Hospitalier L’aspirine était prescrite dans 6,9 % des cas. Quant aux National Abass Ndao, Hôpital Général de Grand Yoff, CHU statines, ils étaient prescrits chez 8.5% des patients. Aristide Le Dantec). Elle a porté sur les diabétiques de type 2 Le diabète était contrôlé dans 14.8% des cas. Dans 75.2% des deux sexes âgés d’au moins 40 ans. des cas, l’hémoglobine glyquée était supérieure à 7%; elle était Tous les patients ont bénéficié d’un interrogatoire, comprise entre 7 et 8% chez 38.4% des patients et supérieure à d’un examen physique, d’un ECG et d’un bilan biologique 8 chez 36.8% des diabétiques. comprenant la glycémie, l’hémoglobine glycosylée, la Parmi les patients hypertendus, 28.1% avaient un traitement créatininémie, la microabuminurie, une protéinurie des 24 antihypertenseur. La tension artérielle était supérieure à 130/85 heures et un lipidogramme (cholestérol total, HDL-cholestérol, mmHg chez tous les hypertendus non traités et chez 80.8% des LDL-cholestérol, triglycérides). hypertendus traités (soit 42 patients). L’hypertension artérielle Les facteurs de risque cardio-vasculaire modifiables était ainsi contrôlée dans 5.4% des cas. Lorsque le seuil de recherchés étaient l’hypertension artérielle (HTA), la sédentarité, 140/90 mmHg était considéré, elle était contrôlée dans 11.9% le tabagisme actif ou sevré depuis moins de 3 ans, l’obésité, la des cas. dyslipidémie et la microalbuminurie. Les atteintes des organes La dyslipidémie à LDL était observée dans 39.3 % des cas cibles recherchées étaient les atteintes cardio-vasculaire, rénale soit 125 patients. Parmi ces patients, 27 étaient sous statines. et cérébrale. Nous avons analysé le traitement en cours et Une LDLémie normale était retrouvée chez 18.5 % d’entre eux. considéré les objectifs thérapeutiques de l’American Diabetes Dans la population globale, la LDLémie était inférieure à 1 g/l Association (ADA).7-9 Ces objectifs comprenaient une pression dans 62.3% des cas et inférieure à 1.3 g/l dans 67.9% des cas. artérielle < 130/85 mmHg, un taux de LDL-cholestérol < 1 mg/ L’indice de masse corporelle était normal (< 25 kg/m2) dans dl et une hémoglobine glyquée < 7%. 57.7% des cas. La surcharge pondérale était retrouvée dans Les données ont été recueillies à l’aide d’une fiche d’enquête, 32.2% des cas et l’obésité dans 10.1% des cas. saisie sur micro-ordinateur et analysées à l’aide du logiciel SPSS La pratique d’une activité physique régulière n’était version 17 for Windows. retrouvvée que chez 17.6% des diabétiques. Le tabagisme était observé dans 6.0% des cas dont 2.5% avaient arrêté la consommation mais depuis moins de 3 ans. Résultats L’échantillon était composé de 318 diabétiques de type 2 dont 237 femmes (74.5%) et 81 hommes (25.5%). L’âge moyen des patients était de 58.2 ± 9.2 ans (extrêmes : 40–85 ans). La durée TABLEAU 2. UTILISATION DES TRAITEMENTS moyenne d’évolution du diabète était de 6.9 ± 5.9 ans (extrêmes: ANTIDIABETIQUES 0.1–31 ans). La durée moyenne du suivi des patients était de 6.7 Traitement Effectif (n) Pourcentage (%) ± 6.1 ans (extrêmes : 0.1–28.5 ans) avec une seule consultation Régime seul 91 28.6 annuelle. La glycémie moyenne était de 1.4 ± 0.5 g/l (extrêmes : Biguanide + insuline 201 63.2 0.7–4.9 g/l), celle de l’hémoglobine glycosylée était de 7.6 ± 3.2 Biguanide 21 6.6 Sulfamides 5 1.6 Total 318 100 TABLEAU 1. CARACTÉRISTIQUES GÉNÉRALES DES DIABÉTIQUES DE TYPE 2 (n = 318) Population TABLEAU 3. UTILISATION DES MEDICAMENTS Facteurs de risque globale Femmes Hommes ANTIHYPERTENSEURS Sédentarité (%) 82.4 87.19 77.27 Effectifs Fréquence Hypertension artérielle (%) 58.2 58.2 58.0 Médicaments antihypertenseurs (n) (%) Tabac (%) 6.0 3.8 17.3 Inhibiteurs de l’enzyme de conversion 27 51.9 Dyslipidémie (%) 43.1 36.3 62.9 Antagonistes des récepteurs de l’angiotensine II 8 15.4 Microalbuminurie (%) 36.8 30 25.9 Bêta bloquants 8 15.4 Obésité (%) 10.1 12.6 7.8 Diurétiques 12 23.1 Consommation d’alcool (%) 3.8 0.8 12.3 Inhibiteurs calciques 5 9.6 272 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Discussion diabétiques noirs africains. Les recommandations internationales Moins de 15 % de nos patients étaient bien contrôlés sur la base méritent d’être suivies pour une meilleure prise en charge de nos de l’hémoglobine glyquée. Moins du tiers des patients étaient patients. contrôlés dans l’étude de Mcfarlane.10 Dans l’étude française ESPOIR, la proportion des patients contrôlés était de 27%.11 Ces Références résultats illustrent toute la difficulté de contrôle du diabète. 1. Detournay B, Vauzelle-Kervroedan F, Charles MA. Epidémiologie, Très peu de patients étaient sous traitement antihypertenseur prise en charge et coût du diabète de type 2 en France en 1998. Diabetes dans notre étude; seulement 28.1% d’entre eux. La valeur cible Metab 1999; 25: 356–365. n’était obtenue que chez 5.4% des patients hypertendus. Dans 2. Sidibé EH. Le diabète ancien en Afrique et idées récentes sur les l’étude ESPOIR,11 moins du tiers des patients étaient contrôlés produits finaux de la glycation avancée. À propos de 39 cas dakarois. Santé 2007; 17(1): 23–27. sur le plan de la tension artérielle bien que la valeur cible fut 3. American Diabetes Association. Standards of medical care in diabetes 140/90 mmHg. La difficulté de contrôle de la pression artérielle – 2010. Dabetes Care 2010; 33(S1): S11–S61. serait liée aux comorbidités qui rendent difficile la prise en 4. Agence nationale d’accréditation et d’évaluation en santé (ANAES). charge, mais aussi à l’inadéquation du traitement (peu sont Stratégie de la prise en charge du patient diabétique de type 2 à traités).10 Ces observations confirment la nécessité d’utiliser l’exclusion de la prise en charge des complications. Diabetes Metab souvent une polymédication antihypertensive pour atteindre 2000; 26: 232–243. la cible thérapeutique. Dans notre étude, seuls 13 patients 5. Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS). Recommandations de Bonne Pratique Clinique: étaient sous bithérapie antihypertensive et 6 sous trithérapie Traitement médicamenteux du diabète de type 2 (actualisation). www. antihypertensive. afssaps.fr.Novembre 2006; 45 p. L’hypercholestérolémie à LDL était de 39.3% dans notre 6. Agence Française de Sécurité Sanitaire des Produits de Santé étude. La proportion des patients qui avaient une LDLémie (AFSSAPS). Recommandations de Bonne Pratique Clinique: la prise inférieure à 1 g/l était de 62.3%. Dans l’étude de Mcfarlane,10 en charge thérapeutique du patient dyslipidémique. www.afssaps.fr 35.5% des patients avaient un LDL cholestérol < 1 g/l. Dans Mars 2005; 11 p. l’étude ESPOIR, 66% des patients avaient une LDLémie < 1.3 7. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al, National High Blood Pressure Education Program Coordinating g/l. Ce taux a été retrouvé dans 67.9% des cas dans notre étude. Committee. Seventh Report of the Joint National Committee (JNC7) La prescription des statines n’était pas courante dans notre étude, on Prevention, Detection, Evaluation, and Treatment of High Blood et concernait seulement 8.5% des patients. Pressure. Hypertension 2003; 42: 1206–1252. L’utilisation des antiagrégants plaquettaires était très faible 8. Sowers JR, Reed J. 1999 Clinical advisory treatment of hypertension dans notre étude (6.9%). Or selon les recommandations12 and diabetes. J Clin Hypertens 2000; 2: 132–133. la prescription d’antiagrégant plaquettaire est justifiée chez 9. American Diabetes Association: Standards of medical care for patients with diabetes mellitus (Position Statement). Diabetes Care 2001; les diabétiques qui ont en plus un des éléments suivants : 24(Suppl 1): S33–S43. cardiopathie ischémique, artériopathie des membres inférieurs, 10. Mcfarlane SI, Jacober SJ, Winter N, Keur J, Castro JP, et al. Control of hypertension artérielle ou hypercholestérolémie. Cette situation cardiovascular risk factors in patients with diabetes and hypertension était présente chez 52.51% de nos patients. at urban academic medical centers. Diabetes Care 2002; 25: 718–723. 11. Charpentier G, Genès N, Vaur L, Amar J, Clerson P, Cambou JP, Guéret P. On behalf of the ESPOIR Diabetes Study Investigators. Conclusion Control of diabetes and cardiovascular risk factors in patients with Ce travail montre une prévalence élevée des facteurs de risque type 2 diabetes: a nationwide French survey. Diabetes Metab 2003; 29: cardio-vasculaire modifiables chez les diabétiques de type 2 152–158. 12. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, noirs africains. Le contrôle du diabète et des facteurs de risque et al. Effects of intensive blood-pressure lowering and lowdose aspirin associés n’était cependant pas optimal dans notre étude. Cette in patients with hypertension: principal results of the Hypertension étude montre par ailleurs que la prise en charge des facteurs Optimal Treatment (HOT) randomized trial: HOT Study Group. Lancet de risque cardio-vasculaire est souvent inadéquate chez les 1998; 351: 1755–1762. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 273
Letter to the Editor
Dear Sir PMO Owira, BSc, Med Hons (UCT), MSc (Medicine) (UCT), The letter by Mullier1 in response to our article titled ‘The grape- PhD (Pharmacology) (UKZN), [email protected] fruit: an old wine in a new glass? Metabolic and cardiovascular perspectives’2 refers. The author states that amiodarone is not References only a prodrug but also has inherent pharmacodynamic effects, 1. Mullier FO. The grapefruit: an old wine in a new glass. Cardiovasc J just like its metabolite N-desethyamiodarone (N-DEA), which Afr 2011; 22(1): 37. he correctly suggests could have even greater pharmacological 2. Owira PMO, Ojewole JAO. The grapefruit: an old wine in a new glass. effects than the parent compound. However, we need to Cardiovasc J Afr 2010; 21: 280–285. 3. Wellens HJ, Brugada P, Abdollah H, Dassen WR. A comparison of the emphasise that even though N-DEA has similar class III anti- electrophysiologic effects of intravenous and oral amiodarone in the arrythmic effects, it has faster sodium channel blockade and same patient. Circulation 1984; 69: 120–124. lower class IV effects than amiodarone.3-8 4. Morady F, DiCarlo LA Jr, Krol RB, et al. Acute and chronic effects The inhibition of pre-hepatic/hepatic CYP3A4 metabolism of of amiodarone on ventricular refractoriness intraventricular conduc- amiodarone alters both plasma and cardiac substrate:metabolite tion and ventricular tachycardia induction. J Am Coll Cardiol 1986; ratios. It therefore reduces alterations of PR and QT intervals,9 7: 148–157. C 5. Shenasa M, Denker S, Mahmud R, et al. Effect of amiodarone on and hence diminishes the anti-arrythmic effects of amiodarone. conduction and refractoriness of the His-Purkinje system in the human Both amiodarone and N-DEA have long half-lives (50 and 60 heart. J Am Coll Cardiol 1984; 4: 105–110. days, respectively),10-12 and at normal therapeutic doses, the 6. Torres V, Tepper D, Flowers D, et al. QT prolongation and the relative contribution of either to the anti-arrythmic and overall antiarrhythmic efficacy of amiodarone. J Am Coll Cardiol 1986; 7: cardiac electrophysiological effects is not presently known, 142–147. despite the aforementioned interaction with grapefruit juice. 7. Connolly SJ, Latini R, Kates RE. Pharmacodynamics of intravenous This, however, does not disqualify amiodarone as a prodrug. amiodarone in the dog. J Cardiovasc Pharmacol 1984; 6: 531–535. 8. Ikeda T, Nadamanee K, Kannan R, Singh BN. Electrophysiologic The interaction of grapefruit juice with amiodarone is more effects of amiodarone: experimental and clinical observation relative to complicated than previously thought. Naringenin, the naringin serum and tissue drug concentrations. Am Heart J 1984; 108: 890–898. (the predominant flavonoid in grapefruit juice) aglycone, has 9. Libersa CC, Brique SA, Mote KB, et al. Dramatic inhibition of amiodar- recently been reported to prolong QTC by inhibiting the rapid one metabolism induced by grapefruit juice. Br J Clin Pharmacol 2000; + 49: 373–378. component of delayed rectifier K current (Ikr), leading to significant QT prolongation in healthy subjects and in patients 10. Harris L, Mckenna W, Rowland DE, et al. Plasma amiodarone and desethylamiodarone levels in chronic oral therapy. Circulation 1981; with dilated or hypertensive cardiomyopathy,13 as well as in 64 (Suppl IV): 263. 14 experimental conditions. It is therefore envisaged that the 11. Holt DW, Tucker GT, Jackson PR, Storey GCA. Amiodarone pharma- pro-arrythmic actions of naringin or grapefruit juice, just like all cokinetics. Am Heart J 1983; 106: 840–847. class III anti-arrythmic agents, may put patients with myocardial 12. Marchiset D, Bruno R, Djiane P, et al. Amiodarone and deseth- structural disorders at risk of provoking torsades des pointes. ylamiodarone elimination kinetics following withdrawal of long-term Even though cases of QT prolongation and torsades de amiodarone maintenance therapy. Biopharm Drug Dispos 1985; 6: pointes with amiodarone are rare, a case has been reported of 209–515. 13. Piccirillo G, Magri D, Matera S, et al. Effects of pink grapefruit juice a female patient who presented with marked QT prolongation on QT variability in patients with dilated or hypertensive cardiomyo- associated with ventricular arrhythmias including torsades de pathy and in healthy subjects. Translational Res 2008; 151: 267–272. pointes, requiring electrical cardioversion after amiodarone 14. Lin C, Ke X, Ranade V, Somberg J. The additive effects of active administration, after she had been drinking large quantities component of grapefruit juice (naringenin) and antiarrythmic drugs on of among others grapefruit juice.15 Perhaps we should have HERG inhibition. Cardiology 2008; 110(3): 145–152. included these references in our previous article to emphasise the 15. Agosti S, Casalino L, Bertero G. A dangerous fruit juice. Am J fact that the interaction between grapefruit juice and amiodarone Emergency Med 2012; 30: 248.e5–248.e8. is more elaborate than previously thought. We thank the author for pointing out the typing errors in our references. 274 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Robotically controlled ablation for atrial fibrillation: the first real-world experience in Africa with the Hansen robotic system FAIZEL LORGAT, EVAN PUDNEY, HELENA VAN DEVENTER, SAM CHITSAZ
Abstract Atrial fibrillation (AF) is the most common sustained cardiac 1 Background: We report the first single-centre experience rhythm disturbance in the general population. As life expectancy in Africa with the Sensei X robotic navigation system in an and average age increase, it is estimated that the number of patients 2 unselected subset of patients with atrial fibrillation (AF). affected by AF will increase 2.5-fold over the next five decades. Methods: Data were recorded prospectively of all consecutive Uncontrolled AF may result in devastating complications such as patients who underwent robotically assisted catheter abla- haemodynamic impairment and increased risk of stroke, which tion therapy using the Sensei X robotic navigation system in turn have a dramatic impact on quality of life, morbidity at the Christiaan Barnard Memorial Hospital, Cape Town, and mortality. Hence, it is imperative to advance treatment South Africa, from July 2009 to July 2010. Outcomes were options available for patients suffering from this condition. defined at one and nine months. Over the past decade, catheter ablation has been proven to Results: A total of 95 patients were included: 63% had be effective in treating various types of arrhythmias. According only AF and 37% had AF plus atrial flutter. AF was of the to the latest guidelines, catheter ablation is indicated in cases persistent type in 81% of patients. The mean procedure, of symptomatic arrhythmias refractory to conventional anti- 3-6 fluoroscopy and ablation times were 220.6 ± 89.6 min, 31.0 ± arrhythmia therapies. Specifically, limited success of anti- 20.4 min, and 61.3 ± 28.1 min, respectively. Both fluoroscopy arrhythmia drugs in the treatment of AF has made this condition and procedure times were significantly longer for the first the dominant indication for catheter ablation in high-volume 1 19 patients compared with the remaining 76 patients (43.5 ± electrophysiology centres. 22.7 vs 27.8 ± 18.5 min and 274.7 ± 90.2 vs 207.1 ± 84.7 min, So far, two catheter-based approaches have emerged as respectively, p = 0.002). The procedural endpoint of the study accepted strategies for AF treatment: (1) ostial segmental was successfully achieved in all patients. After one attempt, disconnection of all pulmonary veins from the adjacent atrial 6 27% were discharged from hospital off anti-arrhythmic tissue, and (2) circumferential pulmonary vein ablation (CPVA). drugs (AADs). At a median of nine months’ follow up, 74% The circumferential approach was found to be significantly more were AF-free off AADs, and 11% were AF-free on AADs, effective than segmental ablation for paroxysmal AF. However, yielding a total freedom from AF of 84% without any redo these two seemingly different strategies are converging towards a procedures. Freedom from relapse after 1.12 procedures unified strategy (i.e. circumferential approach) and are reporting 7 was 88%. similar success rates. Regardless of strategy, however, the safety Conclusion: The Sensei X™ robotic navigation system offers and efficacy of these strategies and others under investigation a safe and effective approach for the treatment of AF. There are highly operator dependent and require reproducible catheter was a learning curve with regard to fluoroscopy and proce- movements and optimal catheter stability and contact during dure time, after which point reduction in radiation exposure mapping and ablation energy delivery. and operator strain, as well as improvement in procedure In recent years, remote catheter navigation systems throughputs were even more pronounced. have been introduced to improve precision during catheter manipulation, reduce physical demands on the operator, Keywords: atrial fibrillation, catheter ablation, atrial flutter, minimise fluoroscopy time, and increase patients’ safety robotic navigation, computer-assisted ablation by avoiding serious complications.8 The Sensei X robotic navigation system (Hansen Medical, Mountain View, CA) Submitted 28/11/11, accepted 24/2/12 and the Niobe magnetic navigation system (Stereotaxis, St Cardiovasc J Afr 2012; 23: 274–280 www.cvja.co.za Louis, MO) are two commercially available remote catheter navigation systems currently available on the market. DOI: 10.5830/CVJA-2012-015 Performance of the Sensei X system has been evaluated in American and European studies.9-12 Researchers investigated technical characteristics and outcomes of robotic AF ablation and found that the complications and recurrence rates with the 13 Department of Cardiology, Christiaan Barnard Memorial robotic system were comparable to those of manual ablation, Hospital, Cape Town, South Africa while the amount of radiation exposure was significantly lower FAIZEL LORGAT, MB ChB, PhD, [email protected] with the robotic navigation.14 The learning curve in early cases EVAN PUDNEY resulted in longer procedure times at each centre, mostly due to HELENA VAN DEVENTER lack of experience with the set-up, which gradually improved.15 Cardiac Biomechanics Laboratory, University of California In this article, we report the first real-world experience San Francisco, San Francisco, California, USA in Africa with the Sensei X robotic navigation system in an SAM CHITSAZ, MD unselected subset of patients with predominantly persistent AF. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 275
Methods of postoperative nausea. The use of corticosteroids may also This was a prospective, single-centre, single-operator study be effective for preventing post-ablation recurrence of atrial 16 performed at the Christiaan Barnard Memorial Hospital, Cape tachycardia. Town, South Africa. The data of all consecutive symptomatic A temperature probe was routinely placed into the oesophagus patients with AF who underwent robotically assisted catheter for continuous intra-oesophageal monitoring during radio- ablation therapy using the Sensei X robotic navigation system frequency (RF) ablation. A multipolar catheter was placed into (Hansen Medical, Mountain View, CA) from July 2009 (the time the coronary sinus via a 7F sheath in the right femoral vein. ® of acquisition of the robotic system) to July 2010 were recorded An ablation catheter, either a 3.5-mm ThermoCool catheter in an electronic database. (Biosense-Webster, Diamond Bar, CA, USA) or a Cool Path™ The exclusion criteria were: (1) patients with cardiac Duo RF ablation catheter (St Jude Medical, St Paul, MN, USA) dysrhythmia without documented AF, e.g. only atrial flutter was placed into the Artisan sheath (Hansen Medical, Mountain (AFlut) or regular supraventricular tachycardia (SVT), (2) View, CA). The steerable sheath system (SSS) was inserted via a congestive heart failure with New York Heart Association 14F sheath in the right femoral vein and advanced manually into class IV or ejection fraction of < 30%, (3) recent acute the right atrium under fluoroscopic visualisation. coronary syndrome within two weeks, (4) impaired mental Approximately 0.5 cm of the ablation catheter was exposed. status that may affect timely taking of anti-arrhythmia drugs, (5) After placement of the SSS in the inferior right atrium was severe cerebrovascular disease, and (6) patient’s decline to sign confirmed, the position of the SSS was registered into the robotic informed consent. Ninety-five patients were finally included. catheter remote-control system. This registration involved the Institutional research board approval was waived for this study. use of LAO 30 and RAO 30 fluoroscopic views of the heart AF types were defined based on the latest European Society (anterior–posterior and lateral) to allow localisation of the SSS of Cardiology (ESC) guidelines5 as follows: paroxysmal AF is in the 3D space. a self-terminating episode that lasts up to seven days; persistent In all patients, one trans-septal puncture was performed AF either lasts between seven days and one year, or requires under fluoroscopic guidance. In exceptional patients trans- termination by cardioversion with drugs or direct current; long- oesophageal echocardiographic guidance was used to facilitate standing persistent AF lasts a year or more. trans-septal puncture. The trans-septal puncture was performed Screening (fluoroscopy) time involved the total minutes the manually. Through this trans-septal puncture, a long sheath was X-ray was applied by the operator to visualise the position of advanced into the left atrium, and a circular mapping catheter devices or set up the system in the patient, using single-plane was introduced into the left atrium. The ablation catheter was pulsed fluoroscopy with a rate of seven frames per second, robotically guided into the left atrium through the same trans- i.e. the time needed to place the diagnostic catheter in the septal puncture site (adjacent to the shaft of the circular mapping coronary sinus, to perform a trans-septal puncture, to assist catheter). This catheter was used for ablation. with the initial creation of a three-dimensional (3D) map, and Systemic anticoagulation was initiated after the first trans- occasionally thereafter to verify accuracy of 3D mapping. septal puncture with the use of intravenous unfractionated heparin Ablation (radiofrequency) time was defined as the total minutes with a target activated clotting time (ACT) of approximately 250 the operator used electrical current to ablate the rebel atrial s. A 15–25 variable loop Biosense LASSO circular mapping foci. The procedure time was defined as the time between first catheter (Biosense-Webster, Diamond Bar, CA, USA) was venipuncture in the operating room and full recovery of the used for mapping the pulmonary vein (PV) antrum. With this patient from anaesthesia. configuration, the final set up before initiation of ablation included the following: a robotically controlled steerable sheath All high-risk patients (CHADS2 score ≥ 2 or patients with impaired left ventricular function) and all patients with long- housing the ablation catheter (this is performed by a physician at standing persistent AF were anticoagulated on warfarin for the console) and a manually controlled circular mapping catheter four weeks until five to seven days prior to the procedure. handled and moved by the same physician at the procedure Subcutaneous enoxaparin (1 mg/kg daily) was administered tableside. When intra-oesophageal temperature rises were noted, power three to four days pre-procedure. Low-risk patients (CHADS2 score < 2) who had persistent AF by definition but who were in output was reduced to 20 W. At the end of the procedure, sinus rhythm prior to the procedure because of drugs or recent systemic anticoagulation was discontinued and occasionally direct-current cardioversion were not always anticoagulated on partially reversed with intravenous protamine before removal of warfarin. All patients were instructed not to ingest any solid the vascular sheaths. foods within six hours prior to their procedure. Three-dimensional mapping was performed to facilitate Ablation robotically assisted catheter ablation. In all patients, 3D reconstruction of the corresponding atrial chamber anatomy was Ablation along the pulmonary vein antrum, which encompasses performed with either the EnSite NavX system (76 patients) or the posterior wall, septal aspect of the right-sided pulmonary CARTO electro-anatomic mapping system (19 patients). veins, and the ridge between the left atrial appendage and left pulmonary veins, was performed with the Artisan robotic system until disappearance of local PV potential, with the endpoint of Procedure electrical isolation of all PV antra. Radiofrequency power was All procedures were performed under general anaesthesia using set at 30 W with a maximum temperature limit of 45°C with propofol and remifentanil. All patients received a bolus of irrigation using a heparinised saline infusion (2 000 IU/l) at a dexamethasone as part of the anesthesia to reduce the incidence rate of 17 ml/min via the Cool Flow pump (Biosense-Webster, 276 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Diamond Bar, California, USA). continuous parameters, the independent samples Student’s After PV isolation was conducted, the circular ablation t-test was performed, while the Mann-Whitney test was used catheter was withdrawn. If AF persisted after PV isolation, to compare non-normally distributed variables. Categorical flecainide was administered intravenously up to a maximum of parameters were compared using the Fisher’s exact or χ2 test. 150 mg unless contraindicated, in which case amiodarone up Statistical Package for the Social Sciences (SPSS) v 15.0 was to a maximum dosage of 300 mg was infused. If this restored used for plotting the graphs and statistical analyses and tests. sinus rhythm then no further left atrial ablation was performed. Differences were considered significant at p < 0.05. If AF persisted, then mapping for complex fractionated atrial electrograms was performed. If complex fractionation was noted along the coronary sinus musculature, then ablation Results was performed along the endocardial aspect of the coronary A total of 100 procedures were performed in the defined period. sinus. If AF organised into a regular tachycardia at any stage Five robotic ablations were redo procedures on patients who had during mapping and ablation, then a detailed activation map previously undergone robotic ablation in our centre. Ninety-five was constructed and the appropriate ablation was performed to patients met all the selection criteria and were enrolled in the terminate the flutter or focal atrial tachycardia. If AF persisted final analysis. Demographics and baseline clinical characteristics despite all of these efforts, a direct-current cardioversion was are summarised in Table 1. Fourteen patients (15%) were performed. receiving more than one AAD pre-procedure. For eight patients Ablation along the posterior cavo-tricuspid isthmus was (8%), manual ablation was tried previously at least once (i.e. the performed in 30 patients with the robotic system in conjunction robotic procedure was a redo ablation). with the 3.5-mm Navistar® ThermoCool® catheters or Cool Path Sixty patients (63%) had only AF, and 35 patients (37%) Duo. Bidirectional block was confirmed with differential pacing had documented atrial flutter (AFlut) along with their AF. In techniques (proximal coronary sinus/postero-lateral right atrial the majority of patients (81%), AF was of the persistent type. In pacing). All patients received enoxaparin (Clexane) 40 mg bd a patients who had AF + AFlut, AFlut was mainly typical (78%). few hours post procedure until discharge the next day (two doses Different types of AF and AFlut in the study population are on average). summarised in Table 2. The procedural endpoint was achieved in all 95 patients enrolled in the study. All ablation procedures were performed Follow up using the Sensei X robotic navigation system. Seven patients The procedural endpoint of the study was whether isolation (7%) needed medical cardioversion during the ablation of all PV or SVC potential foci was successfully achieved, or procedure, three (3%) needed electrical cardioversion, and nine conversion to manual catheter ablation was needed. Our primary patients (9%) needed both. endpoints were recurrence of symptomatic AF lasting more than one minute at nine months post procedure, major cardiac complications that needed intervention/surgery, and all-cause mortality. A two-month blanking period was defined in which TABLE 1. BASELINE CHARACTERISTICS OF ALL ENROLLED PATIENTS (n 95) episodes of AF occurring within that time period were not = considered recurrence. Male, n (%) 71 (75) Follow up was scheduled at one and six months. A resting Age (years) 59.4 ± 9.9 ECG was performed in each follow-up visit. Outside of the AF duration (years) 5.3 ± 6.1 scheduled follow ups, additional assessment or investigation Ischaemic heart disease, n (%) 23 (24) was considered if symptoms warranted it. Patients previously Diabetes mellitus, n (%) 9 (9) on warfarin resumed oral anticoagulation therapy with warfarin Systemic hypertension, n (%) 49 (52) the day after the procedure, and oral anticoagulation therapy was Hypercholesterolaemia, n (%) 38 (40) continued for at least one month for patients with paroxysmal AF. Structural heart disease, n (%) 11 (12) Patients with persistent and long-standing persistent AF Pre-procedure anti-arrhythmic drugs, n (%) received a recommendation to take warfarin for at least three Sotalol 19 (20) months, after which warfarin was discontinued if sinus rhythm Amiodarone 27 (28) was maintained and the CHADS score was less than 2. 2 Flecainide 10 (11) Warfarin-naïve patients were commenced on aspirin 81 mg and Plavix 75 mg for one month only. Dronedarone 1 (1) All of these patients were advised to take aspirin indefinitely. Propafenone 1 (1) Antiarrhythmic drugs were continued for a one- to three-month Sotalol + Flecainide 1 (1) period. All patients received esomeprazole (Nexium) 40 mg Beta-blockers 34 (36) daily for one month. Pre-procedure digitalis, n (%) 4 (4) Pre-procedure warfarin, n (%) 36 (38) Statistical analysis Ejection fraction (%) 61.3 ± 8.2 Left atrial size (cm) 4.3 0.6 Categorical and continuous variables are presented as frequency ± (percentage) and mean ± one standard deviation, respectively. Procedure time (min) 220.6 ± 89.6 Distribution of the continuous variables was assessed using the Screening time (fluoroscopy time, min) 31.0 ± 20.4 Kolmogorov-Smirnov test. To compare normally distributed Ablation time (min) 61.3 ± 28.1 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 277
TABLE 2. TYPES OF DYSRHYTHMIA IN THE STUDY The mean procedure, fluoroscopy and ablation times were POPULATION 220.6 ± 89.6 min, 31.0 ± 20.4 min, and 61.3 ± 28.1 min, Dysrhythmia n (%) respectively. Both fluoroscopy (screening) and procedure times were significantly longer for the first 19 patients compared Atrial fibrillation 95 (100) with the remaining 76 patients (43.5 ± 22.7 vs 27.8 ± 18.5 min, paroxysmal 13 (14) p = 0.002 and 274.7 ± 90.2 vs 207.1 ± 84.7 mins, p = 0.002, persistent 77 (81) respectively), whereas ablation time did not change significantly long-standing persistent 5 (5) as the number of performed procedures increased (ANOVA p = Atrial flutter 35 (37) 0.455) (Fig. 1). typical 29 (31) Fluoroscopy time showed a significant decrescendo trend for atypical 2 (2) the first half of the patients, with an R2 of 0.25 and p = 0.006 (Fig. left atrial 3 (3) 2). There was no significant correlation for the second half of the peri-mitral 1 (1) procedures (p = 0.619).
60 60
50 50
40 40
30 30
20 20 screening time (min) screening time (min) I I 10 10 95% C 0 95% C 0 1st 2nd 3rd 4th 5th First 19 patients Rest Subgroups of 19 patients First fifth vs rest of the patients
90 90
80 80
70 70
60 60
radiofrequency time (min) 50 radiofrequency time (min) 50 I I
40 40 95% C 1st 2nd 3rd 4th 5th 95% C First 19 patients Rest Subgroups of 19 patients First fifth vs rest of the patients
350 350
300 300
250 250 procedure time (min) procedure time (min) I 200 I 200 95% C 150 95% C 150 1st 2nd 3rd 4th 5th First 19 patients Rest Subgroups of 19 patients Subgroups of 19 patients
Fig. 1. Error bars representing screening time, radiofrequency time and procedure time for subgroups of 19 patients; CI, confidence interval. 278 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
100 most likely related to fluid overload and inflammatory response to ablation and was treated successfully with pericardiocentesis. 80 There were three major complications. One patient had 60 y = –0.7012x + 46.979 cardiac tamponade, treated immediately with pericardiocentesis. R 2 = 0.2488 The patient was female and rather small in size. Another patient 40 had left atrial perforation, which was repaired surgically. 20 Similarly, the patient was female and rather small in size. This creening time (min)
S case was caused by ‘catheter snap’ during ablation on the upper 0 aspect of the ridge between the appendage and left superior 0 10 20 30 40 50 pulmonary vein (LSPV). Poor tissue quality/elasticity probably Patient number contributed to this complication, as the patient had rheumatoid Fig. 2. Scatter plot showing a decrescendo trend in arthritis and was on long-term methotrexate therapy. screening time for the first half of the study group. One patient had aspiration pneumonia and blurring in the right eye due to embolus; his vision recovered after two months. Complications This complication occurred because the patient was morbidly obese (160 kg) and it was difficult to keep his ACT above Eighty-six patients (91%) completed the postoperative 250 s; he seemed resistant to unfractionated heparin. No case in-hospital period and were discharged without any remarkable of pulmonary vein stenosis, transient ischaemic attack or stroke complication. There were four minor complications. One patient was reported throughout the post-procedure follow up. had a groin haematoma and one had meralgia paresthetica, both of which resolved spontaneously and were most likely related to the large 14F sheath used for Artisan™. One patient developed Follow up for relapse congestive heart failure 24 hours post procedure, which was As of March 2011, patients were followed up for an average of related to the underlying structural heart disease and significant 13.4 ± 3.6 months. A freedom from AF of 94.7% was achieved fluid infusion (at 17 ml/min) necessary at the time for cooling after an average of 1.15 attempts per patient. One patient of the ablation catheter. Septicaemia was suspected in one case, refused to undergo more attempts after developing relapse, which was probably co-incidental and was controlled with and four patients (4.2%) finally underwent AV node ablation antibiotic therapy and supportive measures. with placement of a permanent pacemaker, one of which had There were two intermediate-level complications. One patient developed late-onset relapse 13 months after robotically assisted developed a groin arteriovenous fistula, which was related to the ablation. Five patients (5.3%) underwent a redo ablation within large 14F sheath and was repaired surgically. One patient had late- the six-month follow up, seven patients (7.4%) had a redo onset pericardial effusion (on postoperative day 10), which was procedure after six months, and one patient received two redo
95 patients 1st robotic ablation
78 free from 17 developed relapse relapse
15 relapse within 2 relapse after 69 off AAD 9 on AAD 6 months 6 months
6 on previously 1 AVN ablation 2 without redo 1 AVN ablation + 12 redo ablation ineffective AAD (already had a PPM) ablation PPM after 1st redo
9 controlled after 1 without redo 3 on new AAD 1st redo ablation
1 controlled after 2nd redo
2 AVN ablation + PPM after 1st redo
Fig. 3. Flow chart showing outcomes for the whole study group; AAD, antiarrhythmic drugs; AVN, atrioventricular node; PPM, permanent pacemaker. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 279
ablations at five and 10 months (Fig. 3). As shown by the multivariate analysis, longer-standing The nine-month follow-up period was completed for 100% types of AF and ablation (radiofrequency) time are independent of patients; no cardiac mortality was observed among the study predictors of arrhythmia relapse within the nine-month period population within the nine-month period. However, one patient post ablation therapy (Table 3). As described in the methods died of prostate cancer seven months post ablation. After one section, some of the more complex cases required ablation along attempt, 26 patients (27.4%) were discharged from hospital off the endocardial aspect of the coronary sinus or in an attempt to any sort of AADs. terminate the flutter or focal atrial tachycardia in addition to the At nine months’ follow up, 70 patients (73.7%) were free standard PV isolation. Therefore, longer ablation time in fact from arrhythmia off AADs, and 10 (10.5%) were AF-free on points to a more complex underlying arrhythmia circuitry, which AADs, yielding a total freedom from AF of 84.2% without is the most likely explanation for its correlation with higher any redo procedures (Table 3). Considering those patients who frequency of relapse. Association of long-standing AF type with relieved completely after a redo procedure within the nine higher relapse rate may also be related to the same aetiology. months post ablation, freedom from relapse rose to 88.4%. In general, because the robotic navigation system significantly Multivariate logistic regression analysis showed that longer- reduces physical operator strain, mitigates concerns over standing types of AF and ablation (radiofrequency) time are excessive radiation exposure during complex cases, and enables independent predictors of arrhythmia relapse within the nine- operators to perform complex ablation patterns regardless month period post ablation therapy (Table 4). of catheter skills, operators are more likely to take on more complex and challenging AF cases. Hence, we expect to see longer ablation times as a surrogate for more complex cases Discussion associated with higher relapse rates in future studies. This is the first report on mid-term efficacy of robotically As shown in Fig. 1, mean procedure and fluoroscopy times navigated catheter ablation in an unselected subset of patients were statistically reduced after the first fifth of the patients (n = with predominantly persistent AF. Overall success rate without 19). Furthermore, fluoroscopy time showed a linear decrescendo any redos reported in this study is comparable to the results trend for the first half of the patients (n = 48), after which point obtained in the largest randomised, controlled trial (n = 390 it reached a plateau. This observation was in line with the results total; 197 robotic arm) performed to date by Di Biase et al. (84.2 reported by Di Biase et al., who showed statistically significant 11 v 85%). In the subset of patients with persistent AF, the results reduction in fluoroscopy time after the first 50 cases.11 These of this study compare favourably to that reported by Di Biase et observations confirm that there is a learning curve in using 11 al. (82 vs 70.9%). These results bolster our confidence in the the robotic navigation system and that operators can anticipate robotic system as an efficacious treatment modality for patients further reduction in fluoroscopy time, and hence safer operation with persistent AF. once they overcome this learning curve. Reduction in procedure The overall mid-term success rate of 88.4% after the 1.12 time allows for shorter cases, less physical operator strain and procedures per patient reported in this study is comparable to the higher laboratory throughput. results reported by Hlivak et al. (n = 69, success rate 86% after Regarding major complications related to the robotic 13 1.2 procedures per patient). These studies consistently show navigation system, specifically the incidence of cardiac that robotic ablation is also a clinically viable option for redo tamponade and left atrial perforation, Hansen Medical’s new procedures in patients who do not respond to ablation on the Lynx™ catheter, which is smaller in size (requires a 12F sheath) first attempt. and more gentle (less rigid and lighter) than the Artisan™ Recently, an updated worldwide survey on the methods, catheter used in all the procedures reported herein, will probably efficacy and safety of manual catheter ablation for AF showed reduce the risk of these complications, especially in small that across all surveyed centres, median overall success rates were female patients with previous tissue quality/elasticity problems. 84.0% (79.7–88.6%; n = 9 590), 74.8% (66.1–80.0%; n = 4 712) Arteriovenous fistula, considered here as an intermediate-level and 71.0 (67.4–76.3%; n = 1 853) for paroxysmal, persistent and complication, will likely occur less frequently with the new long-standing AF, respectively. For the main subset of patients Lynx™ catheter that requires a 12F sheath as opposed to the 14F in this study (i.e. patients with persistent AF), we see that overall sheath size of Artisan™. success rate with the robotic ablation compared favourably with Additionally, the next generation of ablation catheters such that of manual ablation. Given that robotic ablation technology, as Carto SF (Biosense-Webster, Diamond Bar, CA, USA), techniques and catheters are still in their infancy, the efficacy of this treatment modality has the potential to reliably surpass its manual counterpart in the near future. TABLE 4. MULTIVARIATE LOGISTIC REGRESSION ANALYSIS OF AF RELAPSE PREDICTORS AFTER ROBOTIC ABLATION TABLE 3. FIRST-ATTEMPT SUCCESS RATES Variable Odds Ratio 95% CI IN RELATION TO THE TYPE OF AF AND Age 0.9957 0.9386–1.0562 ANTIARRHYTHMIC DRUGS (AADs) Concomitant flutter 0.8580 0.2334–3.1539 Success off Success on Overall AADs AADs success AF type 12.8330 1.4454–113.9412 Type of AF n (%) n (%) n (%) Mapping system/ablation catheter 1.8701 0.4034–8.6688 Paroxysmal 12/12 (100) 1/1 (100) 13/13 (100) Procedure time 0.9835 0.9700–0.9973 Persistent 57/58 (98) 6/19 (32) 63/77 (82) Radiofrequency time 1.0508 1.0104–1.0929 Long-standing persistent 0/0 2/5 (40) 2/5 (40) Screening time 1.0177 0.9838–1.0527 280 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
which require a lower infusion rate (8 ml/min) due to design J Cardiol 2005; 96: 59L–64L. changes, producing more efficient cooling, will reduce the 3. Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, likelihood of post-procedural pericardial effusion or congestive et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for person- heart failure. Lastly, the smaller size of the new Lynx catheter nel, policy, procedures and follow-up. A report of the Heart Rhythm will significantly reduce the risk of minor complications such as Society (HRS) task force on catheter and surgical ablation of atrial groin haematoma or meralgia paresthetica. fibrillation developed in partnership with the European Heart Rhythm It is important to note that despite our modified post-ablation Association (EHRA) and the European Cardiac Arrhythmia Society anticoagulation regimen, which differs substantially from the (ECAS); in collaboration with the American College of Cardiology international guidelines due to poor patient compliance with (ACC), American Heart Association (AHA), and the Society of anticoagulation on warfarin and INR testing, no case of transient Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart ischaemic attack or stroke was reported in the median nine- Association, the European Cardiac Arrhythmia Society, the European month post-ablation period. Physicians who care for similar Heart Rhythm Association, the Society of Thoracic Surgeons, and the types of patients in areas where compliance is an issue may find Heart Rhythm Society. Europace 2007; 9: 335–379. our modifications to the standard post-ablation anticoagulation 4. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes regimen helpful. NA, 3rd, et al. 2011 ACCF/AHA/HRS focused update on the manage- The main limitations of this study are the fact that it lacked a ment of patients with atrial fibrillation (updating the 2006 guideline). A report of the American College of Cardiology Foundation/American matched control group with manual ablation and that there were Heart Association task force on practice guidelines. J Am Coll Cardiol relatively few subjects in the paroxysmal and long-standing 2011; 57: 223–242. persistent AF groups. Furthermore, some of the therapeutic 5. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et modifications presented in this article, mainly the modified al. Guidelines for the management of atrial fibrillation: the Task force post-ablation anticoagulation regimen, were based on clinical for the management of atrial Fibrillation of the European Society of experience and characteristics of our specific patient population Cardiology (ESC). Eur Heart J 2010; 31: 2369–2429. and are not in conformity with international guidelines. Hence, 6. Willems S, Hoffmann B, Steven D, Drewitz I, Servatius H, Mullerleile K, et al. Catheter ablation for atrial fibrillation: Clinically established or we do not propose that our methods be adopted by other centres. still an experimental method? Herz 2008; 33: 402–411. As a real-world study, we were treating symptomatic patients, 7. Pappone C, Santinelli V. Towards a unified strategy for atrial fibrilla- with the main clinical endpoint being relief of symptoms. We tion ablation? Eur Heart J 2005; 26: 1687–1688; author reply: 1688. were not able to confirm the absence of asymptomatic recurrence 8. Chun KR, Schmidt B, Kokturk B, Tilz R, Furnkranz A, Konstantinidou of AF without ECG Holter monitoring. Nevertheless, we believe M, et al. Catheter ablation – new developments in robotics. Herz 2008; that the safety and mid-term efficacy results of this study may 33: 586–589. provide valuable insights for the daily practice of medicine. 9. Saliba W, Reddy VY, Wazni O, Cummings JE, Burkhardt JD, Haissaguerre M, et al. Atrial fibrillation ablation using a robotic cath- eter remote control system: initial human experience and long-term follow-up results. J Am Coll Cardiol 2008; 51: 2407–2411. Conclusion 10. Wazni OM, Barrett C, Martin DO, Shaheen M, Tarakji K, Baranowski The Sensei™ robotic navigation system offers a safe and B, et al. Experience with the Hansen robotic system for atrial fibrilla- effective approach for the treatment of AF. Its efficacy in tion ablation – lessons learned and techniques modified: Hansen in the patients with persistent AF is encouraging. Its overall success real world. J Cardiovasc Electrophysiol 2009; 20: 1193–1196. rate is comparable to manual techniques and impressive for a 11. Di Biase L, Wang Y, Horton R, Gallinghouse GJ, Mohanty P, Sanchez J, et al. Ablation of atrial fibrillation utilizing robotic catheter naviga- treatment approach that is relatively in its infancy. There is a tion in comparison to manual navigation and ablation: single-center learning curve with regard to fluoroscopy and procedure times, experience. J Cardiovasc Electrophysiol 2009; 20: 1328–1335. after which point reduction in radiation exposure and operator 12. Steven D, Servatius H, Rostock T, Hoffmann B, Drewitz I, Mullerleile strain, as well as improvement in procedure throughputs are K, et al. Reduced fluoroscopy during atrial fibrillation ablation: benefits even more pronounced. Lynx™ as well as the newer generation of robotic guided navigation. J Cardiovasc Electrophysiol 2010; 21: of ablation catheters compatible with the Sensei™ system offer 6–12. operators the possibility of even safer procedures with lower 13. Hlivak P, Mlcochova H, Peichl P, Cihak R, Wichterle D, Kautzner J. Robotic navigation in catheter ablation for paroxysmal atrial fibrilla- risks for complications. tion: Midterm efficacy and predictors of postablation arrhythmia recur- rences. J Cardiovasc Electrophysiol 2011; 22(5): 534–540. 14. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, We acknowledge the anaesthetists, Drs Dirk Lilienfeld, Adi Smit, Claire Calkins H, Camm AJ, et al. ACC/AHA/ESC guidelines for the Zondagh and Rene Verbeek, who worked on the patients. management of patients with supraventricular arrhythmias – executive summary. A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European References society of cardiology committee for practice guidelines (writing 1. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen committee to develop guidelines for the management of patients with KA, et al. ACC/AHA/ESC 2006 guidelines for the management of supraventricular arrhythmias) developed in collaboration with NASPE- patients with atrial fibrillation – executive summary: a report of the Heart Rhythm Society. J Am Coll Cardiol 2003; 42: 1493–1531. American College of Cardiology/American Heart Association Task 15. Malcolme-Lawes L, Kanagaratnam P. Robotic navigation and ablation. Force on Practice Guidelines and the European Society of Cardiology Minerva Cardioangiol 2010; 58: 691–699. Committee for Practice Guidelines (writing committee to revise the 16. Koyama T, Tada H, Sekiguchi Y, Arimoto T, Yamasaki H, Kuroki K, 2001 guidelines for the management of patients with atrial fibrillation). et al. Prevention of atrial fibrillation recurrence with corticosteroids J Am Coll Cardiol 2006; 48: 854–906. after radiofrequency catheter ablation: a randomized controlled trial. J 2. Pappone C, Santinelli V. Atrial fibrillation ablation: State of the art. Am Am Coll Cardiol 2010; 56: 1463–1472. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 281
Review Article
The prevalence and outcome of effusive constrictive pericarditis: a systematic review of the literature MPIKO NTSEKHE, CHARLES SHEY WIYSONGE, PATRICK J COMMERFORD, BONGANI M MAYOSI
Abstract referred with effusive pericarditis.3 In the same study, 46.7% There is sparse information on the epidemiology of effusive of participants with the diagnosis underwent pericardiectomy constrictive pericarditis (ECP). The objective of this article within four months, and the overall mortality rate was 60% over 3 was to review and summarise the literature on the preva- the subsequent seven-year mean follow-up period. lence and outcome of ECP, and identify gaps for further The influence of the aetiology of pericarditis on the prevalence research. The prevalence of ECP ranged from 2.4 to 14.8%, and outcome of ECP is not known. For example, tuberculous 4 with a weighted average of 4.5% [95% confidence interval pericarditis is associated with significant inflammation, 5 (CI) 2.2–7.5%]. Sixty-five per cent (95% CI: 43–82%) of chronicity, and a high rate of development of constrictive 5-7 patients required pericardiectomy regardless of the aetiol- pericarditis in about 25% of cases. It is likely therefore that the ogy. The combined death rate across the studies was 22% prevalence of ECP in patients with tuberculous pericarditis may (95% CI: 4–50%). The prevalence of ECP is low in non- be much higher than seen in acute forms of pericardial disease, tuberculous pericarditis, while pericardiectomy rates are such as idiopathic or viral pericarditis, which have formed the 8 high and mortality is variable. In this review, of 10 patients basis of the previous studies of ECP. identified with tuberculous ECP, only one presumed case With regard to the natural history, in the study of Sagrista- had a definite diagnosis of ECP. Appropriate studies are Sauleda, those with neoplastic disease had a high mortality and needed to determine the epidemiology of ECP in tuberculous low pericardiectomy rate, whereas those with idiopathic disease 3 pericarditis, which is one of the leading causes of pericardial had a low mortality rate but high pericardiectomy rate. The disease in the world. impact of the aetiology of pericarditis on these outcomes of ECP among patients whose life expectancy is not severely limited by Keywords: effusive constrictive pericarditis, prevalence, peri- malignant disease is not known. cardiectomy and death There are very few investigators who have used the ‘gold Submitted 14/6/11, accepted 22/11/11 standard’ to establish the diagnosis of ECP, which is invasive measurement of intra-pericardial and intra-cardiac pressures Cardiovasc J Afr 2012; 23: 281–285 www.cvja.co.za before and after pericardiocentesis.2 Even though non-invasive DOI: 10.5830/CVJA-2011-072 tools, such as echocardiography and magnetic resonance imaging are gaining wider acceptance as methods for establishing the Effusive constrictive pericarditis (ECP) is a clinical diagnosis,9 none has been compared to invasive haemodynamic haemodynamic syndrome in which constriction of the heart by diagnosis of ECP.9,10 the visceral pericardium occurs in the presence of a compressive It has been proposed that visceral pericardiectomy may pericardial effusion. ECP is believed to be a rare manifestation be necessary for a good clinical result in cases with ECP of pericardial disease1 that occurs as part of a continuum from because drainage of pericardial fluid alone leads to incomplete effusive to constrictive pericarditis. The outcome of ECP relief of cardiac compression.3 The timely recognition of ECP with regard to the development of constrictive pericarditis, therefore enables the clinician to choose the most appropriate 2 pericardiectomy rates and death is not well defined. In the therapy. Information about the prevalence and outcome of only prospective study of ECP, the prevalence was 6.8% of ECP is particularly important in the developing world, where patients undergoing pericardiocentesis and 1.2% of all patients tuberculosis causes hundreds of thousands of cases of pericarditis every year.5 There are at present no recommendations on the diagnosis and management of ECP in tuberculous pericarditis. Cardiac Clinic, Department of Medicine, Groote Schuur We have conducted a systematic review of the literature to Hospital and University of Cape Town, Cape Town, South Africa determine the prevalence and outcome of ECP in patients with MPIKO NTSEKHE, MD, PhD, [email protected] viral, tuberculous, uraemic, purulent and idiopathic pericarditis. PATRICK J COMMERFORD, MBChB The outcomes of interest were pericardiectomy and mortality BONGANI M MAYOSI, DPhil (Oxon) rates at 12 months. Furthermore, we determined whether the Institute of Infectious Disease and Molecular Medicine, and prevalence and the outcome of ECP were related to the aetiology School of Child and Adolescent Health, University of Cape of the effusion. We limited the review to observational studies of Town, Cape Town, South Africa pericarditis due to these non-neoplastic medical conditions that CHARLES SHEY WIYSONGE, MD commonly progress to constrictive pericarditis.1 282 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Methods be extracted from the published manuscripts, we were able to MEDLINE, EMBASE and Google Scholar were searched obtain the information on individual participants from the study for English-language publications of observational studies of authors. We conducted a meta-analysis of the individual patient ECP that were conducted from inception of the respective data using the StatsDirect software (www.statsdirect.com). For database through to December 2009. Search terms included: the meta-analysis, StatsDirect first transformed proportions into acute pericarditis, pericardial effusion, ECP, pericardial a quantity (the Freeman-Tukey variant of the arcsine square root- tamponade, cardiac tamponade, tuberculous pericarditis, uraemic transformed proportion) suitable for the usual fixed and random- 16,17 pericarditis, purulent pericarditis, idiopathic pericarditis, viral effects summaries. The pooled prevalence was calculated as pericarditis and constrictive pericarditis. Limits included: the the back-transform of the weighted mean of the transformed English language, human beings and the following MeSH terms proportions, using inverse arcsine variance weights for the 16 17 (‘Case-Control Studies’[MeSH] OR ‘Cohort Studies’[MeSH] fixed-effects model and DerSimonian-Laird weights for the OR ‘Epidemiologic Studies’[MeSH] OR ‘Cross-Sectional random-effects model. Studies’[MeSH] OR ‘Retrospective Studies’[MeSH] OR We used the Cochran Q test to assess statistical heterogeneity ‘Prospective Studies’[MeSH]). In addition to searching the between studies and, in the absence of significant heterogeneity databases, we contacted researchers in the field, and searched the (p > 0.1), combined the data using a fixed-effects method. bibliographies of published reviews and studies on pericardial Otherwise, we used the random-effects method. In addition, 2 disease for relevant studies. we used Higgins I statistic to quantify inconsistency across the The eligibility criteria for inclusion and exclusion from the studies included in the meta-analysis. The test statistic describes study, which are based on the Loney criteria for critical appraisal the percentage of the variability in effect it estimates that is due 2 of research articles on prevalence of disease, are shown in to true heterogeneity rather than chance. The closer the I value Table 1.11 To be included in the review, a study had to provide is to 100%, the more likely it is that true heterogeneity exists, sufficient information to enable determination of the proportion and therefore the less reliable the combined estimate becomes. of study participants diagnosed with ECP and at least six other MN conducted the electronic searches and selected the eligibility criteria. studies, all of which were reviewed by CW and BMM. Studies where malignancy was the predominant cause of The reporting of the systematic review is in keeping with pericarditis were excluded from this systematic review because standard recommendations for reporting systematic reviews of 18 patients with this diagnosis generally do not survive long observational studies. enough to develop constrictive pericarditis.1,12 Studies of patients with pericardial effusion that resulted from aortic dissection, Definitions myocardial infarction, and trauma to the thorax were also Effusive constrictive pericarditis was classified as definite or excluded because pericardial sequelae are uncommon among probable, based on the methods used to establish the diagnosis.2,9 long-term survivors of these conditions.1,13-15 Studies where the diagnosis was based on clinical assessment After the relevant studies were selected, individual patient alone were rejected. data were extracted and reviewed in order to exclude patients Patients were classified as having definite ECP if the with malignancy-associated ECP. Where relevant data could not diagnosis was based on intra-pericardial and intra-cardiac haemodynamics, determined before and after pericardiocentesis. TABLE 1. ELIGIBILITY CRITERIA FOR STUDIES This haemodynamic definition required that: (1) the OF THE SYSTEMATIC REVIEW pre-pericardiocentesis transmural filling pressure (i.e. the Inclusion criteria difference between the elevated intra-pericardial pressure and 1. The study design was observational (case control, cross sectional the right atrial pressure) was less than 2 mmHg; (2) the and cohort); cross sectional studies were accepted for the determi- post-pericardiocentesis intra-pericardial pressure fell to near 0 nation of prevalence. mmHg; and (3) the post-pericardiocentesis right atrial pressure 2. A definition of the syndrome of effusive constrictive pericarditis 3 was given. failed to fall by 50% or to a level below 10 mmHg. 3. The inclusion and exclusion criteria for the participants were The diagnosis of ECP was considered probable if it was clearly stated. established on the basis of echocardiography or magnetic 4. There was a clear description of the number of participants in the resonance imaging. There are no published prospectively derived study. consensus diagnostic criteria for ECP using these imaging 5. The number or proportion of participants in the study with effu- modalities,9 but widely accepted criteria include evidence of the sive constrictive pericarditis was clearly stated. following criteria in a patient with a pericardial effusion: (1) 6. The method of diagnosis of effusive constrictive pericarditis was pericardial thickening; (2) abnormal or paradoxical movement of described and determined in an unbiased manner. the interventricular septum; (3) a plethoric dilated inferior vena 7. There was an adequate description of the study setting. cava with reduced narrowing during inspiration; and (4) marked 8. There was an adequate description of the study population. respiratory variation of the mitral inflow Doppler pattern. Exclusion criteria Finally, the diagnosis of ECP was rejected if it was established 1. The number or proportion of participants with effusive constric- without ancillary imaging or haemodynamic assessment, i.e. if tive pericarditis was not available. the diagnosis was made on clinical assessment alone. 2. The aetiology of pericarditis was a malignancy, myocardial infarc- tion, aortic dissection, or trauma to the thorax. 3. The diagnosis of effusive constrictive pericarditis was based on Results clinical assessment only. A flow chart for the selection process is provided in Fig. 1. Five AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 283
studies were included in the systematic review.3,19-22 The five compare echocardiographic differences between tuberculous and studies had a total of 642 patients, 26 of whom met diagnostic idiopathic pericardial effusions.20 The prevalence of ECP in these criteria for ECP; 58% (15/26) had probable ECP and 42% two studies was 4.3 and 14.8%, respectively. (11/26) definite ECP. Of the 26 patients, 50% (13/26) had Overall there was significant variability in the prevalence idiopathic pericarditis, 38% (10/26) had tuberculous pericarditis, of ECP across the five studies (p = 0.04; I2 = 61%); therefore 8% (2/26) had post-radiation pericarditis and 4% (1/26) post- we used both the random-effect and fixed-effect meta-analysis pericardiotomy pericarditis. models to combine the prevalence. Using the fixed-effect model, the pooled prevalence of ECP in the five studies was 4.0% (95% Prevalence of effusive constrictive pericarditis CI: 2.7–5.7%). This increased marginally to 4.5% (95% CI: 2.2–7.5%) using the random-effects model (Fig. 2). The study design and strength of diagnosis of ECP varied across the five selected studies. Three of the five studies were prospective cohorts.3,19,21 One of the three prospective case Outcomes of patients with effusive constrictive series was a single-centre South African study, designed to pericarditis determine the 30-day and one-year outcomes of consecutive One-year mortality data was available for only nine participants patients with predominantly tuberculous pericarditis, who were with non-malignant disease from two studies.19,22 These mortality each given a standardised therapeutic protocol, which included rates are provided in Table 2. 19 pericardiocentesis. The proportion of those with ECP was 2.6% Two of the nine patients were dead at 12 months; one from based on clinical and echocardiographic criteria. peri-operative complications, and the other with tuberculous The second prospective case series was a single-centre ECP died while awaiting pericardiectomy. The combined death French study designed to determine the role of surgical rate across the studies was 22%, with wide 95% confidence pericardioscopy as a diagnostic tool among patients with large intervals (4–50%) due to the small numbers involved. Seven 21 pericardial effusion of uncertain aetiology. The proportion of patients did not undergo pericardiectomy. These seven included: patients diagnosed with ECP was reported as 1.4%. All patients the patient with tuberculosis who died from heart failure while underwent pericardiocentesis, and echocardiography was used to awaiting surgery, three participants, also with tuberculosis, assess pericardial physiology and content. who did not consent to the procedure, and three participants The third prospective case series was a single-centre Spanish with idiopathic disease in whom a conservative ‘wait-and-see’ study, which aimed to determine the prevalence of ECP and the approach had been adopted. The six participants, who survived incidence of pericarditis-related outcomes over a median follow- the early stages of their illness without surgery were alive and 3 up period of seven years. Consecutive participants presenting well at their last follow-up visit. with a diagnosis of pericardial tamponade over 15 years Only three of the studies provided data on the pericardiectomy underwent measurement of the pre- and post-pericardiocentesis rates.3,19,22 Overall, the combined pericardiectomy rate was intra-pericardial and right atrial pressures. The prevalence of 65% (95% CI: 43–82%) and the between-study variability in ECP was 5.8% in those patients undergoing pericardiocentesis, pericardiectomy rates was marginally significant (p = 0.10; I2 = 6.8% in those with clinical tamponade, and 0.93% in patients 56%). A breakdown of the pericardiectomy rates by aetiology 3 with any pericardial disease. revealed that 73% of participants with idiopathic ECP, 60% of The remaining two studies of patients with a probable those with tuberculous ECP, and 50% of those with ECP of other diagnosis of ECP were designed to (1) determine the long- aetiologies underwent the pericardiectomy. 22 term outcome of patients with symptomatic effusion; and (2) The persistence of heart failure was the reason for surgery in 54% of cases, making it the most common indication, followed 1 138 potentially relevant by prophylaxis against progression to fibrous constrictive publications pericarditis in 23%. Recurrence of pericardial effusion was an indication in 15%. In only 8% was the operation performed 1 089 articles eliminated after 2.5% (0.9, 6.0) review of the titles Reuter 2007 and abstract Tsong 2003 4.3% (1.2, 10.8)
49 articles evaluated Sagrista-Sauleda 2004 5.5% (2.9, 10.1)
Nugue 1995 1.4% (0.2, 5.0) Three studies excluded because No data on proportion diagnosis of ECP of patients with ECP George 2004 14.8% (4.2, 33.7) established by clinical in 41 studies assessment only Combined 4.5% (2.2, 7.5)
Five articles selected for 0 10 20 30 40 inclusion in review Prevalence (95% confidence interval) Fig. 2. Forest plot for the prevalence of ECP (random Fig. 1. Flow chart for selection process. effects). 284 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
TABLE 2. 12-MONTH MORTALITY AND PERICARDIECTOMY RATES OF PARTICIPANTS WITH NON-NEOPLASTIC EFFUSIVE CONSTRICTIVE PERICARDITIS Absolute number of study Number of patients with ECP who participants with underwent pericardiectomy within Study non-neoplastic ECP 12 months Number of patients with ECP dead at 12 months Sagrista-Sauleda 2004 11 7/11 (64%) Mortality data at 12 months not available for all patients Reuter 2007 5 2/5 (40%) 2/5 (40%) Tsang 2003 4 4/4 (100%) 0/4 (0%) Nugue 1996 2 Pericardiectomy data not available Mortality data not available George 2004 4 Pericardiectomy data not available Mortality data not available Total 26 13/20 (65%) 2/9 (22%) because of progression to non-effusive fibrous constrictive and the impact of the syndrome on mortality, a study of well- pericarditis. characterised participants with adequate follow up and clearly defined outcomes is required to inform the development of clinical guidelines on the diagnosis and management of effusive Discussion constrictive pericardial disease. This systematic review highlights that there are very few prospective studies on the prevalence and outcome of ECP. The References prevalence of this syndrome in the available studies ranged from 1. Cameron J, Oesterle SN, Baldwin JC, Hancock EW. The etiologic 1.4 to 14%. Although there was little information to ascertain spectrum of constrictive pericarditis. Am Heart J 1987; 113(2 Pt 1): the mortality rate reliably, the pericardiectomy rate was clearly 354–360. high (44–100%). 2. Hancock EW. A clearer view of effusive-constrictive pericarditis. New There was a total of 10 participants who had effusive Engl J Med 2004; 350(5): 435–437. constrictive tuberculous pericarditis in this review, one of whom 3. Sagrista-Sauleda J, Angel J, Sanchez A, Permanyer-Miralda G, Soler- had a definite diagnosis of ECP. Commerford and Strang have Soler J. Effusive-constrictive pericarditis. N Engl J Med 2004; 350(5): 469–475. suggested that ECP may be a common form of presentation of 4. Reuter H, Burgess LJ, Carstens ME, Doubell AF. Characterization of tuberculous pericarditis that frequently progresses to fibrous the immunological features of tuberculous pericardial effusions in HIV constrictive pericarditis.8 By contrast, the IMPI Africa Registry positive and HIV negative patients in contrast with non-tuberculous has suggested that using clinical criteria alone, ECP may be effusions. Tuberculosis (Edinb) 2006; 86(2): 125–133. present in only 15% of cases of tuberculous pericarditis.23 5. Mayosi BM, Burgess LJ, Doubell AF. Tuberculous pericarditis. The results of this comprehensive review show a low Circulation 2005; 112(23): 3608–3616. prevalence of ECP in patients with tuberculous pericarditis, 6. Desai HN. Tuberculous pericarditis. A review of 100 cases. S Afr Med J 1979; 55(22): 877–880. which ranged from 3 to 14%. It is noteworthy that there are no 7. Schrire V. Experience with pericarditis at Groote Schuur Hospital, studies that have systematically used an invasive haemodynamic Cape Town: an analysis of one hundred and sixty cases studied over a method to establish the diagnosis of effusive constrictive disease six-year period. S Afr Med J 1959; 33: 810–817. in patients with tuberculous pericarditis. There is therefore a 8. Commerford PJ, Strang JIG. Tuberculous pericarditis. In: Coovadia need for a definitive study of the prevalence of tuberculous ECP HM, Benatar SR, eds. A Century of Tuberculosis South African that is based on invasive haemodynamic methods. Perspectives. 1st edn. Capetown: Oxford University Press, 1991: Although the pericardiectomy rate across the studies was 123–137. 9. Zagol B, Minderman D, Munir A, D’Cruz I. Effusive constrictive peri- high, the indications for surgical intervention were not uniform carditis: 2D, 3D echocardiography and MRI imaging. Echocardiography among the 13 participants who had the operation. A significant 2007; 24(10): 1110–1114. proportion of patients who were managed conservatively had 10. Grizzard JD. Magnetic resonance imaging of pericardial disease and complete resolution of their effusive constrictive disease. This intracardiac thrombus. Heart Fail Clin 2009; 5(3): 401–419, vii. suggests that there is room for a study to test a strategy of 11. Loney PL, Chambers LW, Bennett KJ, Roberts JG, Stratford PW. watchful waiting compared to prophylactic pericardiectomy in Critical appraisal of the health research literature: prevalence or inci- dence of a health problem. Chronic Dis Can 1998; 19(4): 170–176. those without persistence of heart failure. 12. Colombo A, Olson HG, Egan J, Gardin JM. Etiology and prognostic Finally, the mortality rate for tuberculous pericarditis in the implications of a large pericardial effusion in men. Clin Cardiol 1988; HIV era is as high as 40% in patients with AIDS, at the end of six 11(6): 389–394. months of treatment with anti-tuberculosis medication.24 Despite 13. Ling LH, Oh JK, Schaff HV, Danielson GK, Mahoney DW, Seward the absence of data on mortality in patients with non-neoplastic JB, et al. Constrictive pericarditis in the modern era: evolving clinical ECP, it is possible that because of its well-documented spectrum and impact on outcome after pericardiectomy. Circulation haemodynamic sequelae,2 the pericardial syndrome is associated 1999; 100(13): 1380–1386. 14. Correale E, Maggioni AP, Romano S, Ricciardiello V, Battista R, with a higher mortality rate than those without the syndrome. Salvarola G, et al. Comparison of frequency, diagnostic and prognostic significance of pericardial involvement in acute myocardial infarction treated with and without thrombolytics. Gruppo Italiano per lo Studio Conclusion della Sopravvivenza nell’Infarto Miocardico (GISSI). Am J Cardiol In light of the lack of clarity on the prevalence of ECP 1993; 71(16): 1377–1381. among patients with proven tuberculous pericarditis, the role 15. Correale E, Maggioni AP, Romano S, Ricciardiello V, Battista R, of prophylactic pericardiectomy in cases of varying aetiology, Santoro E. Pericardial involvement in acute myocardial infarction in AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 285
the post-thrombolytic era: clinical meaning and value. Clin Cardiol Heart 2004; 90(11): 1338–1339. 1997; 20(4): 327–331. 21. Nugue O, Millaire A, Porte H, de Groote P, Guimier P, Wurtz A, et al. 16. Mantel N, Haenszel W. Statistical aspects of the analysis of data Pericardioscopy in the etiologic diagnosis of pericardial effusion in 141 from retrospective studies of disease. J Natl Cancer Inst 1959; 22(4): consecutive patients. Circulation 1996; 94(7): 1635–1641. 719–748. 22. Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Outcomes of 17. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin clinically significant idiopathic pericardial effusion requiring interven- Trials 1986; 7(3): 177–188. tion. Am J Cardiol 2003; 91(6): 704–707. 18. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie 23. Mayosi BM, Wiysonge CS, Ntsekhe M, Volmink JA, Gumedze F, D, et al. Meta-analysis of observational studies in epidemiology: A Maartens G, et al. Clinical characteristics and initial management of proposal for reporting. J Am Med Assoc 2000; 283(15): 2008–2012. patients with tuberculous pericarditis in the HIV era: the Investigation 19. Reuter H, Burgess LJ, Louw VJ, Doubell AF. The management of the Management of Pericarditis in Africa (IMPI Africa) registry. of tuberculous pericardial effusion: experience in 233 consecutive BMC Infect Dis 2006; 6: 2. patients. Cardiovasc J South Afr 2007; 18(1): 20–25. 24. Mayosi BM, Wiysonge CS, Ntsekhe M, Gumedze F, Volmink JA, 20. George S, Salama AL, Uthaman B, Cherian G. Echocardiography in Maartens G, et al. Mortality in patients treated for tuberculous pericar- differentiating tuberculous from chronic idiopathic pericardial effusion. ditis in sub-Saharan Africa. S Afr Med J 2008; 98(1): 36–40.
Letter to the Editor
Comment on: A systematic overview of prospective cohort studies of cardiovascular disease in sub-Saharan Africa
Dear Sir References It was with interest that I read the article titled ‘A systematic 1. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor overview of prospective cohort studies of cardiovascular disease of coronary events in four racial or ethnic groups N Engl J Med 2008; in sub-Saharan Africa’ by André Pascal Kengne, et al., which 358(13): 1336–1345. 2. Mcclelland RL, Chung H, Detrano R, et al. Distribution of coronary was published recently in this journal. In this excellent article, artery calcium by race, gender, and age: results from the Multi-Ethnic the author introduced the association between cardiovascular Study of Atherosclerosis (MESA). Circulation 2006; 113(1): 30–37. diseases and related risk factors by performing a systematic 3. Braveman PA, Cubbin C, Egerter S, et al. Socioeconomic status review. However, we feel the article did not cover all aspects in health research: one size does not fit all. J Am Med Assoc 2005; of the relationship between cardiovascular disease and related 294(22): 2879–2888. risk factors. 4. Lawlor DA, Davey SG, Patel R, et al. Life-course socioeconomic posi- Firstly, habits may be very different among different ethnic tion, area deprivation, and coronary heart disease: findings from the British Women’s Heart and Health Study. Am J Public Health 2005; groups, which is obvious in China, consisting of 56 ethnicities. 95(1): 91–97. 1 This would have affected the outcome of the study, and it would 5. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs have been better if there had been further subgroup analysis.2 in the prevention of cardiovascular disease: meta-analysis of 147 Secondly, socio-economic status3,4 may be different in randomised trials in the context of expectations from prospective epide- different regions in sub-Saharan Africa. Many studies may have miological studies. Br Med J 2009; 338: 1665. come from different levels of hospitals, such as community and 6. Vorster HH, Kruger A, Venter CS, et al. Cardiovascular disease risk factors and socio-economic position of Africans in transition: the central hospitals, which also means that the available medical THUSA study. Cardiovasc J Afr 2007; 18(5): 282–289. 5,6 interventions may have been different. 7. Steyn K, Sliwa K, Hawken S, et al. Risk factors associated with Thirdly, it is evident that that the study did not include all myocardial infarction in Africa: the INTERHEART Africa study. cardiovascular risk factors.7-9 There was no classification of the Circulation 2005; 112(23): 3554–3561. selected risk factors.10 8. Kaptein KI, de Jonge P, van den Brink RH, et al. Course of depressive All of these factors may increase the differences between symptoms after myocardial infarction and cardiac prognosis: a latent the studies and affect the results to a certain extent. There is class analysis. Psychosom Med 2006; 68(5): 662–668. 9. Zatu MC, van Rooyen JM, Schutte AE. Smoking and vascular dysfunc- undoubtedly a need for well-designed, prospective, cohort tion in Africans and Caucasians from South Africa. Cardiovasc J Afr studies from sub-Saharan Africa to clarify these issues. 2011; 22(1): 18–24. 10. Erbel R, Mohlenkamp S, Moebus S, et al. Coronary risk stratification, Zhen-Hua Gao discrimination, and reclassification improvement based on quantifica- Ru-Yu Yuan, [email protected] tion of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall Department of Cardiology, Second Hospital of Tianjin Medical study. J Am Coll Cardiol 2010; 56(17): 1397–1406. University, Tianjin, People’s Republic of China 286 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Conference Report
Novo Nordisk incretin leadership summit, Cape Town
A faculty of top local and international a normal beta-cell mass is required for 2 diabetes, and the major factor driving opinion leaders were unanimous at glucose homeostasis. resistance is obesity. Obese individuals the incretin leadership summit hosted Autopsy studies have shown that need more than three times as much by Novo Nordisk in Cape Town on 5 those with type 2 diabetes experience insulin to maintain normoglycaemia as May 2012. The incretin-based therapies an increased rate of beta-cell apoptosis.1 normal-weight individuals. Those with a represent a major advance on what was ‘We have no clear answers yet as body mass index (BMI) > 30 kg/m2 have previously available for the treatment and to why this is the case, but there are a 15% greater risk of developing diabetes. management of type 2 diabetes and are many factors associated with it. In ‘But if these are the causes of diabetes, revolutionising the way the condition is chronic hyperglycaemia, the higher then all obese individuals should develop viewed. the glucose concentrations, the higher the condition; yet 85% don’t. The the rate of apoptosis, which means that differentiator is that those who don’t hyperglycaemia per se accelerates the have a healthy pancreas develop diabetes, GLP-1 and the beta-cell loss of beta-cells.’ which leads to the conclusion that Islet cell dysfunction: an under- ‘Islet amyloid deposits, which are obesity, insulin resistance and impaired lying defect in the pathophysiol- seldom seen in non-diabetics, are also insulin secretion are important co-factors ogy of type 2 diabetes a likely cause of the apoptosis; they increasing diabetes risk, but are not Juris Meier, head: Division of Diabetology are the result of IAPP, a beta-cytotoxic themselves the underlying causes.’ and GI Endocrinology, St Josef-Hospital, factor secreted with insulin. Other factors Turning to the question of whether Ruhr-Universitat, Bochum, Germany implicated include high concentrations loss of beta-cell mass or function is the of free fatty acids, endoplasmatic key issue, Prof Meier argued that both reticulum stress and autoimmune factors.’ are important, as one goes along with the He suggested that there might also be other. ‘If beta-cells are the key problem treatment-related factors involved over where insulin impairment in diabetes is and above these endogenous ones. concerned, we should be able to restore ‘The consequences of all of this include normal function by normalising beta- loss of first-phase insulin secretion, 85% cell mass and function. We’ve shown of which is lost in type 2 diabetes patients. this by transplanting a healthy pancreas Loss of insulin pulsatility leads to into a previously diabetic patient. After peripheral insulin resistance. The clinical two years, glucose values were normal, implications thereof are deficits in alpha- evidence that healthy beta-cell mass and and beta-cell function in the postprandial function can overcome insulin resistance.’ context, along with disturbances in Summarising, Prof Meier observed Over the past 10 to 15 years, there has glucagon secretion. The normal glucose- that deficits in beta-cell mass can lead been a shift away from the focus on insulin induced decline in glucagon is almost to stress and impaired function, allied to resistance as the major cause of type 2 absent in type 2 diabetes, leading to disturbances in alpha-cell function and diabetes, with increasing recognition of postprandial hyperglycaemia.’ insulin action. Beta-cell mass and function the role of beta-cell mass and function. Prof Meier cited an animal study, are closely related. ‘Restoration of beta- ‘We now look at many polymorphisms, which showed a link between the cell mass can normalise hyperglycaemia’, few of which are found in adipose tissue, reduction in insulin secretion, increased he concluded. bone or the liver. The majority of the glucagon secretion and beta-cell loss.2 genes associated with type 2 diabetes ‘Reduction in beta-cell mass in pigs was are in the pancreas, making it primarily a associated with high fasting glucagon Targeting beta cells: the rationale pancreatic disease’, said Prof Meier. levels, an almost identical picture to that for GLP-1 use in type 2 diabetes On average, patients with type 2 seen in humans.’ Wolfgang E Schmidt, chair and professor diabetes have 65% less beta-cells than There is an inverse relationship of Internal Medicine and director of non-diabetics, a finding that has been between insulin and glucagon, with the the Department of Medicine, St Josef- replicated often and in many different former driving down the latter. ‘This Hospital, Ruhr-Universitat, Bochum, populations, irrespective of whether inverse interaction is lost in type 2 Germany the individuals in question were lean or diabetes, leading to a failure to suppress obese. Prof Meier therefore feels that glucagon’, said Prof Meier. The UKPDS showed that type 2 diabetes there is an important relationship between Both insulin resistance and impaired is associated with a progressive decline beta-cells and glycaemic control and that insulin secretion increase the risk of type in beta-cells and by the time they are AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 287
analogue, liraglutide, has been shown to improve both phases of insulin secretion. Its restoration of beta-cell sensitivity is an immediate effect, and it also works in a chronic setting, improving metabolic control, with positive effects on glycaemia, weight loss, insulin secretion and insulin sensitivity. ‘Liraglutide improves two markers of beta-cell function, HOMA-B and the pro-insulin/insulin ratio’, said Prof Schmidt. ‘Animal and in vitro studies have shown that it promotes beta-cell diagnosed, most patients will already have survival, stimulating proliferation and out that endogenous GLP-1 is degraded lost 50% of their beta-cells. Prof Schmidt inhibiting apoptosis and, as a consequence, by DPP-4 and rendered inactive within underscored that stopping that decline increasing mass.’ He added the rider that two minutes. ‘This means we need to is a challenge, but that glucagon-like while the evidence for proliferation is prolong the activity of GLP-1 to achieve peptide 1 (GLP-1), an incretin whose currently indirect, it is hoped that long- metabolic effects. We can either inhibit role in diabetes is increasingly being running clinical studies will, in time, DPP-4 to lengthen GLP-1’s action, or we recognised, could help to achieve some confirm this. can use a GLP-1 analogue that acts in the currently unmet treatment goals. The Liraglutide’s induction of weight loss, same way as GLP-1, but is not degraded so-called ‘incretin effect’ is severely as seen in the LEAD studies,3-8 is a key by DPP-4.’ GLP-1 analogues are given impaired in type 2 diabetes patients, advantage of the treatment. More than subcutaneously. DPP-4 inhibitors are oral which suggests that if the ‘something 75% of patients on liraglutide lost weight, medications. missing’ is reconstituted, the condition with one-quarter losing an average of Liraglutide is a once-daily GLP-1 could be positively impacted on. 7.7 kg. ‘Data from LEAD also support analogue with a 97% amino acid ‘The progressive loss of beta-cells starts its being used as early as possible to sequence similarity to human GLP-1. early in the disease process, during the preserve beta-cell mass and function, with Its half-life has been prolonged to 13 pre-clinical phase’, he said. ‘Even those greatest effectiveness seen in those with hours. By contrast, the other GLP-1 who have only impaired fasting glucose early-stage type 2 diabetes who still had a analogue, exenatide, has only a 53% levels experience beta-cell loss, and this relatively high beta-cell mass.’ sequence homology compared to native loss is the basis for the deterioration in In conclusion, Prof Schmidt reiterated GLP-1. It too is resistant to DPP-4 and glucose control seen in so many studies. that targeting islet cell dysfunction resulted has a longer half-life, though not as Different drugs have differing effects on in preservation of beta-cell function long as liraglutide’s. It is also available beta-cell apoptosis. Incretin therapy now and mass, with restoration of insulin in an extended-release delivery system, gives us the opportunity to intervene by pulsatility, normalisation of excessive exenatide ER, which is administered once targeting an aspect of islet cell dysfunction glucagon secretion and normalisation of a week (not available in South Africa). that other drugs don’t, namely the alpha- excessive hepatic glucose output. ‘GLP- Turning to pharmacodynamics, Prof cell dysfunction/hyperactivity that causes 1 therapy is a promising option to help Omar said that the concentration of active hyperglucagonaemia.’ achieve this.’ liraglutide is significantly higher than the GLP-1 and 2 were discovered in 1983 GLP-1 concentration achievable with a and the former’s role in stimulating Incretin-based therapies in DPP-4 inhibitor. This is significant in that insulin secretion was identified in 1985. type 2 diabetes: the clinical small levels have only modest effects and ‘It’s a player in the pathophysiology evidence higher levels are necessary to increase of diabetes as well as a promising satiety and reduce weight. Are all incretin-based therapies candidate for therapy’, observed Prof The clinical advantages of liraglutide Schmidt. ‘It normalises glucose levels in created equal? have been demonstrated in head-to- poorly controlled type 2 diabetes without Mahomed AK Omar, specialist physi- head trials. The 1860 LIRA-DDP-4 inducing hyperglucagonaemia. Beta- cian/endocrinologist/diabetologist, trial compared liraglutide to the DPP-4 cells are resensitised to glucose, elevated Parklands Medical Centre, and honorary inhibitor, sitagliptin.9 There was a glucagon levels are reduced, and because professor, Department of Diabetes and significant drop in HbA1c levels in the GLP-1 is glucose dependent, its effects Endocrinology, University of KwaZulu- liraglutide group, but only a modest benefit taper off as glucose levels normalise, Natal, Durban in the sitagliptin-treated patients. Sixty per therefore also minimising the risk of cent of those on liraglutide achieved their hypoglycaemic episodes. There are two types of incretin therapy, target HbA1c level of < 7%, compared with Because higher doses of GLP-1 namely GLP-1 receptor agonists and only a quarter of those taking sitagliptin.’ improve the insulin response in type 2 dipeptidyl peptidase-4 (DPP-4) inhibitors, When it came to body weight, diabetes, elevating GLP-1 levels is the each with differing modes of action liraglutide produced a 3- to 3.6-kg loss, basis for the therapeutic concept behind and hence differing efficacy and safety where the drop with sitagliptin was only the use of GLP-1 analogues. One such profiles. Prof Omar began by pointing 1 kg. When it came to side effects, both 288 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
agents were associated with some minor DURATION-6 compared exenatide especially in urban women, are a further episodes of hypoglycaemia, while there ER to liraglutide.12 Liraglutide performed clinical challenge, as one can’t address was also some transient nausea with better, with 60% of patients reaching their glucose control without also looking at liraglutide’, Prof Omar noted. HbA1c target level of < 7%, compared obesity.’ Patient satisfaction rates were with 52%. Weight-loss results were also Where contradictions are concerned, higher with liraglutide. After a year, better with liraglutide. When it came to normalising HbA1c levels has not yielded some sitagliptin patients were switched side effects, liraglutide was associated the risk reductions expected. ‘It was to liraglutide; they experienced with higher rates of nausea and vomiting, thought that normalisation of HbA1c improvements in HbA1c level as well as while injection site reactions were more levels would lead to better cardiovascular additional weight loss. ‘It is impressive common with exenatide ER (published at outcomes, yet in the ACCORD trial, that patients rated treatment satisfaction present as an abstract only). intensive glucose lowering led to increased higher with an injectable therapy that cased ‘In conclusion, there is evidence that mortality rates, possibly as a result of mild gastrointestinal (GI) symptoms than HbA1c lowering is better with GLP-1 increased hypoglycaemia and highly an oral therapy with fewer GI symptoms.’ analogues than with DPP-4 inhibitors, and significant weight gain’, said Dr Wing. In the DURATION-2 study, which that of the former, liraglutide is superior So obesity needs to be addressed. compared exenatide once weekly to to both exenatide formulations’, said Treatment should not aggravate weight sitagliptin or pioglitazone, superior HbA1c Prof Omar. GLP-1 analogues, liraglutide gain, and weight loss would be a bonus. 10 levels were achieved with exenatide ER. in particular, also performed better in HbA1c levels need to be lowered to < 7%, Sixty per cent of patients reached target respect of weight loss. Exenatide ER, and with no hypoglycaemia. Looking at on exenatide ER compared with only 30% however, was superior overall in terms current drug options, Dr Wing underscored on sitagliptin. ‘As expected, weight loss of side effects. Patient satisfaction was that metformin is associated with cardiac was also better with exenatide’, observed higher with the injectable GLP-1 agents protection. ‘So you would need a very Prof Omar. ‘Side-effect profiles were than with the oral DPP-4 inhibitors. good reason not to start with metformin. similar, with no major hypoglycaemic ‘As far as the thiazolidinediones episodes and only a low frequency of Incretin-based therapies: focus (TZD) are concerned, rosiglitazone is bad, minor hypoglycaemia.’ on clinical effectiveness pioglitazone less so. The sulphonylureas So if the GLP-1 analogues are superior do not yield cardioprotection and most to the DPP-4 inhibitors, how do they Jeffrey Wing, chief physician, professor of do badly relative to metformin, with the compare against each other? In LEAD-6, Medicine and clinical head, Department exception of gliclazide. So there is a exenatide was compared to liraglutide, of Medicine, Charlotte Maxeke Johannes- real need for new therapies that lower 8 burg Hospital with HbA1c level as the primary endpoint. glucose levels without weight gain and Liraglutide had a significantly greater hypoglycaemia, while providing the effect in lowering HbA1c levels than bonus of cardiovascular protection.’ exenatide. Those switched from the latter Dr Wing pointed out that there were to the former at 26 weeks experienced very consistent messages coming through further improvement. Weight loss was with regard to the clinical effectiveness similar with both agents. of incretin therapies. ‘Vildagliptin Where side effects were concerned, produces very little hypoglycaemia and there was transient nausea with is associated with little or no weight liraglutide, but the rates of nausea were gain, except when combined with higher with exenatide and persisted for sulphonylureas. There are convincing longer. ‘Antibody formation was also data that exenatide lowers blood glucose, much greater with exenatide, because whether used as monotherapy or in of its only having a 53% homology combination with other agents. There is with human GLP-1, compared with There are many challenges and impressive weight loss and little or no liraglutide’s 97%’, said Prof Omar. ‘This contradictions to be overcome where hypoglycaemia, except when it is used is significant because these antibodies diabetes is concerned, and we want to together with sulphonylureas. may blunt exenatide’s effectiveness.’ have our cake and eat it, with access to ‘The LEAD studies send the same DURATION-1 compared exenatide therapeutic options that are safe, effective, message about liraglutide. It produces 11 twice daily to exenatide ER. The latter cheap and free of side effects. This was impressive reductions in HbA1c levels was associated with a significantly greater the view expressed by Dr Wing. in various combinations, with similarly drop in HbA1c levels, with many more The first challenge is the numbers. impressive weight loss and little or no exenatide ER-treated patients attaining the ‘There has been a 98% increase in the hypoglycaemia except, once again, when target of < 7%. Those switched to the ER number of diabetics in Africa,13 and South it is combined with sulphonylureas.’ formulation after 52 weeks experienced Africa has a strikingly high prevalence. Looking at the composite endpoints further improvements in HbA1c levels, According to the NHLS database, glucose of HbA1c lowering, weight loss and suggesting that exenatide ER is more control is poor in patients treated in the minimising of hypoglycaemia, Dr efficacious than exenatide twice daily. public sector, and based on the Ampath/ Wing assigned the following grades Exenatide ER also had a superior side- Lancet databases, the private sector is not to the various drugs available. Both effect profile. doing any better. Rising rates of obesity, the thiazolidinediones (TZD) and AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 289
sulphonylureas failed to impress, with control, a second oral agent may be exendin-4, has similar effects to native scores of 15 and 33%, respectively. added; with more than half of patients GLP-1. Exenatide was awarded a 72% pass, ultimately requiring insulin therapy. Concerns surrounding conventional while liraglutide achieved a 78% pass for Dr Adri Kok, specialist physician at oral diabetic therapies include risk of achieving composite endpoints. Union Hospital (Alberton), expressed her hypoglycaemia; however, the glucose- ‘To date, no other class of agent has views that an algorithmic approach to dependant action of incretin-based achieved this level and incretin therapies, the management of T2DM is ‘reactive’ therapies provides good glycaemic whether oral or injectable, perform much and may lead to unacceptable delays control with a low risk of hypoglycaemia. better than what we have. High-dose in treatment intensification, leaving The incretin agents are also associated liraglutide will be leading the way.’ He patients exposed to long periods of with weight neutrality, or even weight added that it seemed almost greedy to hyperglycaemia. Dr Kok expressed loss, whereas most conventional therapies want more, but that liraglutide 1.8 mg particular concern about those patients are associated with weight gain. Also also reduced a secondary risk factor, who are diagnosed late, as is often the promising are findings that incretin-based namely systolic blood pressure. case in South Africa. therapy may have beneficial effects on
‘The era of the incretins has arrived, In patients with an HbA1c level > 9%, beta-cell function, potentially slowing and the new guidelines will reflect this’, the recommendation is to implement the progression of diabetic disease. Dr Wing concluded. ‘Diabetes is a early use of insulin therapy combined Dr Kok commented on her practical progressive condition and the incretins with oral agents to control initial clinical experience, which included may well be able to modify the disease hyperglycaemia within two weeks. a significant number of patients who process before overt type 2 diabetes Thereafter, the insulin can be withdrawn were put on liraglutide therapy through manifests, delaying beta-cell failure and other therapies considered. Dr compassionate-use approval from the and providing long-term durability by Kok emphasised that it is of particular South African Medicines Control Council preserving beta-cell function.’ importance that pathophysiology, over (MCC) prior to recent regulatory approval
and above HbA1c levels, needs to be of liraglutide in South Africa. In her Early use of incretin-based addressed. experience, she had patients losing up to therapies in type 2 diabetes To provide better glycaemic control 38 kg of weight while achieving excellent treatment: clinical benefits and improve treatment outcomes, Dr glycaemic control. Kok recommends the implementation of Dr Kok went on to more closely Adri Kok, specialist physician, Union a more pro-active approach than those examine the indications for incretin-based Hospital, Gauteng. CEO of Faculty of suggested by historical guidelines. The therapy, specifically the GLP-1 receptor Consulting Physicians of South Africa, most recent AACE/ACE guidelines agonists. There is a body of evidence chairperson of the Medical Advisory include multiple options for first-line supporting the use of GLP-1s across the and Ethics Committee of Netcare, and monotherapy, including incretin-based continuum of disease progression, both a director of the South African Private therapy. The incretins are among the as monotherapy and in combination with Practitioners Forum many hormones responsible for glucose a number of other agents. homeostasis. Dr Kok advises an early combination Incretins, including glucagon- approach for early management of glucose like peptide-1 (GLP-1), are released levels that can then be maintained. She by intestinal enteroendocrine cells noted that as yet, it is not known for how in response to a meal. GLP-1 elicits long beta-cell failure will be delayed with glucose-dependent insulin secretion; early use of GLP-1s. suppresses glucagon secretion, appetite ‘Such information should emerge with and food intake; slows gastric emptying the GRADE study (Glycaemia Reduction and stimulates beta-cell proliferation in Approaches in Diabetes), a cohort of 7 pre-clinical models. Circulating GLP-1 500 recently diagnosed type 2 diabetes is short lived; 80% is degraded within patients. The metabolic effects of five two minutes by the enzyme dipeptidyl different agents in combination with peptidase-4 (DPP-4). metformin are being compared; as well as Type 2 diabetes (T2DM) has traditionally GLP-1 secretion is diminished the benefits of early combination therapy been managed algorithmically. Following in patients with T2DM; however its versus sequential therapy in drug-naïve a T2DM diagnosis, initial interventions insulinotropic activity is maintained, patients’, Dr Kok said. are diet and lifestyle modifications. resulting in the targeting of this hormone Usage trials of exenatide and liraglutide The natural disease progression of for diabetic therapy. Incretin agents were then presented. Monotherapy T2DM implies that glycaemic control include GLP-1 receptor agonists and trials of exenatide at doses of 5 and 10 will continue to deteriorate over time DPP-4 inhibitors. GLP-1 receptor agonists µg yielded good results. Compared to and once required, oral therapy (usually produce effects similar to native GLP-1 placebo, there was a distinct improvement metformin first) is prescribed. The dose and are resistant to degradation by DPP-4. in HbA1c levels, with the higher dose of metformin is gradually uptitrated as the DPP-4 inhibitors inactivate the enzyme shown to be more effective in reaching disease worsens, and when the maximal responsible for GLP-1 degradation. target HbA1c levels of < 7.0%. dose no longer maintains glycaemic Exenatide, a synthetic formulation on An exenatide ER trial showed the 290 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
best change in HbA1c level, with 49% member of the Indian Council of Medical American college of Endocrinology) of patients achieving HbA1c levels of < Research. He is principal investigator on algorithm underscores the need for those
6.5%, and 63% achieving HbA1c < 7.0%. a number of international phase II, III agents to be in our armamentarium – Prof In an exenatide monotherapy trial, an and IV trials. Kumar, Patna, India average weight loss of 3 kg was evident in Although impressed with the very patients. ‘However, a number of patients promising results of clinical trials, Dr lost significantly more weight, with those Kumar did emphasise that the true on the higher dose (10 µg) losing the most potential of any therapy cannot be fully weight’, Dr Kok stressed. determined until it has been extensively Also of note was evidence of beta- used in clinical practice, and that costs, cell protection, particularly as loss of particularly in developing economies beta-cell mass prior to diagnosis such as India, are a limiting factor. is estimated to be as much as 70%. Recent findings from the Association In these trials, exenatide was used as of British Clinical Diabetologists (ABCD) monotherapy or in combination with suggest that the GLP-1 receptor agonists metformin, sulfonylureas (SFUs) and exenatide and liraglutide have been thiazolidinediones (TZDs). Exenatide can widely used in clinical practice in the be safely used with insulin.14 Key challenges to be addressed as UK since 2008 and 2009, respectively.15 The LEAD-3 trial compared T2DM progresses are a decline in Improvements in glycaemic control monotherapy with liraglutide (1.2 and 1.8 beta-cell function and beta-cell mass, a and body weight in the clinical setting mg) against glimepiride (sulfonylurea) deterioration in glycaemic control and an correlate with that observed in the trial monotherapy. It was found that the 1.8-mg increase in cardiovascular disease. Data setting. liraglutide dose proved most effective in from the ACCORD, ADVANCE, UKPDS With experience from his own
HbA1c level change from baseline, with and VADT trials have indicated that practice, Dr Kumar commented that 42% achieving target of < 6.5% and 51% delayed treatment of T2DM can increase incretin therapies were superior to achieving target of < 7.0%, while 27.8% the risk of cardiovascular mortality. insulin, sulfonylureas and thiazides for of glimepiride-treated patients reached an Anti-diabetic agents themselves weight advantage and avoidance of
HbA1c level of < 7%. may contribute to the development of hypoglycaemia. With an excellent safety The use of liraglutide also showed a cardiovascular disease. As early as the and tolerability profile (nausea usually 2.8-kg weight benefit over glimepiride, 1970s, the UGDP study indicated adverse settles within a week), incretin therapy as well as significant benefits in reducing cardiovascular outcome with the use of has high acceptability in patients. hypoglycaemic events. A trial comparing early sulfonylureas (tolbutamide). Newer Furthermore, Dr Kumar finds liraglutide and metformin therapy to agents within the sulfonylurea family incretin therapy suitable for use in the therapy with both agents and added insulin may have varying and reduced degrees of patient failing metformin; and has noted detemir showed that the greater the beta- adverse cardiovascular outcome. efficacy in combination with almost cell mass (as assessed by baseline HbA1c The availability of incretin-based all other oral anti-diabetic agents (as level) at initiation of liraglutide, the better therapies addresses some of the concerns well as insulin) at different stages of the the treatment outcomes, most likely due surrounding progression and treatment of natural history of disease progression. to greater beta-cell protection. T2DM. Dr Kumar summarised clinical Cost as a limiting factor was the only In summary, Dr Kok noted that trial data on the safety and efficacy of disadvantage highlighted, with Dr Kumar liraglutide can be used as monotherapy these therapies, showing successfully postulating that he expects this to also be or in combination with metformin, a improved glycaemic control with a low a disadvantage for use in South Africa. sulphonylurea or a TZD. The concurrent risk of hypoglycaemia and the added Source use of liraglutide with insulin is still under benefit of being weight neutral (DPP-4 Ussher JR, Drucker DJ. Cardiovascular Biology investigation. inhibitors) or resulting in weight loss of the Incretin System. Endocrine Rev 2012; 33: Source (GLP-1 receptor agonists). 187–215. Dr Adri Kok, Johannesburg. Early treatment Evidence of preservation of beta-cell prevents loss of glycaemic control and beta-cell function also emerged. ‘There is limited Incretins in combination with function. information on the cardiovascular actions insulin Campbell, RK. Clarifying the role of incretin- of incretin-based therapy. Short-term The rationale for using incretin mimetics based therapies in the treatment of type 2 diabetes studies in human subjects demonstrate with insulin was discussed by Prof mellitus. Clin Therapeut 2011; 33(5); 511–527. modest, yet beneficial action on cardiac Mahomed Omar (South Africa) and Dr function in patients with ischaemic heart Ajay Kumar (India) with reference to Incretin-based therapies in disease. These agents also decrease blood relevant studies. clinical practice pressure and have been shown to reduce Dr Ajay Kumar, consultant physician and inflammation in pre-clinical studies’, Prof diabetologist. Director of the Diabetes Kumar noted. Adding incretins to insulin- Care and Research Centre in Patna, India. The early advocation of incretin-based treated patients He also holds a position at the University therapy in the AACE/ACE (American ‘At the outset, this approach should seek of Newcastle, Australia and is a committee Association of Clnical Endocrinologists/ to mitigate the problems associated with AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 291
increasing insulin dosages such as weight to self-titrate, and in this well-controlled There have been no studies as yet using gain, hypoglycaemia and complications therapy reached the recommended range incretin-based therapies in children/ of high insulin dose therapy’, Prof Omar of 35–40 U/day of insulin detemir. adolescents under the age of 18 years said. He addressed firstly, the addition Importantly, the addition of insulin and clinicians should wait for these stud- of DPP-4 inbhibitors, vildagliptin and detemir resulted in a further drop of 0.5% ies before treating this category of patient – Prof Juris Meier sitagliptin to type 2 diabetes patients who in HbA1c level and patients did not gain are poorly controlled on insulin.16,17 weight. The rate of hypoglycaemia was
‘The reductions in HbA1c levels very low at 0.23 in these insulin-treated were modest, about 0.59%, but were patients. ‘If you contrast this to the Treat- Practical advice sustained over a year, when these agents To-Target study, where a rate of three to Adding liraglutide therapy to a were added to patients on insulin, with 3.5 episodes/patient year was seen, this sulphonylurea (SU) plus metformin or without metformin. Experience strategy was very successful’, Prof Omar therapy, clinicians can halve the SU with hypoglycaemia was mixed, with noted. dose and then monitor glucose levels vildagliptin reducing hypoglycaemic ‘In conclusion, it is better to put to decrease the risk of hypoglycaemia. events and sitagliptin increasing these patients onto a GLP-1 agonist before events, perhaps due to the latter study using insulin than using the reverse Hypoglycaemic events mark design, which tried to improve overall strategy’, Dr Ajay Kumar. vulnerability glucose control. The weight reduction Prof Brian Frier, honorary professor of effect was neutral in both studies’, Prof Incretins and pancreatitis Omar pointed out. diabetes at the University of Edinburgh, Turning to the incretin mimetics, Prof Dr Adri Kok and Prof Juris Meier affiliated to the BHF Centre for Omar cited a proof-of-concept study This session scrutinised the evidence Cardiovascular Science. where the addition of exenatide to patients related to the increased prevalence of on insulin glargine resulted in a greater acute pancreatitis in type 2 diabetes patients, acknowledging that these decrease in HbA1c level (a reduction of 1.9%), a low hypoglycaemic event rate patients have a three-fold higher risk of and weight loss of 1 to 2 kg in the developing pancreatitis (4.5 cases per exenatide arm.18 1 000 patient years). ‘We know that In a further study of exenatide, which the exocrine pancreas is also affected in was given to patients with diabetes of diabetic patients, with increased fibrosis long duration (10 years) and an expected occuring in both type 1 and type 2 low level of residual beta-cell function, diabetes’, Dr Adri Kok noted. who were already on insulin, metformin Prof Meier presented the animal studies and pioglitazone, exenatide (bd) resulted on incretins and the risk of pancreatitis, in improved glucose control accompanied noting the difficulty of extrapolating by a very significant reduction in insulin these findings to humans. ‘Hypoglycaemia is a marker of a patient’s (glargine) dose.19 ‘The adverse GI events Following the published analysis vulnerability to a wide spectrum of with incretin mimetics were as expected of the Adverse Event Reports (AERS) cardiovascular, cerebrovascular and 21 but did improve over time’, Prof Omar as reported to the FDA, the EASD musculoskeletal events. It is not a transient noted. has recently published their expert event, as commonly perceived. There are comment on their website http://www. longer-term effects on cardiac function, A newer concept: patients easd.org/easd/index.php/easd-statements. platelets, the inflammatory response and Their evaluation indicates that at this overall endothelial function’. already on liraglutide who are juncture the AERS evaluation cannot be then given added insulin Expressing this view, Prof Brian Frier, considered as robust data on which to University of Edinburgh, drew on his 20 In a well-conducted study over a year, base clinical decisions. clinical insights gained from a research the addition of insulin detemir to a group Dr Kok concluded that physicians career focused on the pathophysiology of of patients on metformin and liraglutide, should not over-interpret this matter, but hypoglycaemia. While hypoglycaemia is who were not yet at target HbA level, should be cautious. In summary, Prof 1c more common in type 1 diabetes patients, was contrasted with the larger primary Ascott-Evans noted that there is no major type 2 diabetes patients on insulin group, which had reached optimal control signal of concern about either incretin experience on average one severe event on these two agents (61% of the 988 mimetics or DDP-4 inhibitors and the per month. patients), and to a control group within causation of pancreatitis. ‘In the definitive UK Hypoglycaemia the poorer-controlled arm without insulin. study,22 we were surprised to see in a The patients receiving insulin were told real-world setting that hypoglycaemia ‘There is no value in doing HOMA tests in type 2 diabetes patients treated When adding liraglutide to insulin-treated prior to using these incretin-based thera- with sulphonylureas was higher than patients, one can pragmatically reduce pies, as they have been shown to be we thought, at a rate of 7% per year. the insulin units by 20–25%, and then effective across the diabetes spectrum – Hypoglycaemic events also increased monitor – Dr Mahomed AK Omar Prof Juris Meier over time in type 2 diabetes patients on 292 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
insulin but remained less frequent than in insulin hypothesis. Diabetes 2006; 55(4): ty of exenatide once weekly versus lira- type 1 diabetes patients.’ 1051–1056. glutide in subjects with type 2 diabetes This study used patients’ self-reporting 3. Buse JB, Rosenstock J, Sesti G, et al. (DURATION-6): a randomised, open-label Liraglutide once a day versus exentatide study. Diabetologia 2011; 54(suppl 1): 538. and biochemical episodes of less than 2.2 twice a day for type 2 diabetes: a 26-week EASD 2011 congress abstract: oral pres- mmol/l on continuous glucose monitoring randomised, parallel-group, multinational, entation. to determine events over nine to 12 open-label trial (LEAD-6). Lancet 2009; 13. Hall V, Thomson RW, Henriksen O, Lohse N. months in UK secondary care diabetes 374(9683): 39–47. Diabetes in sub-Saharan Africa 1999–2011: centres. Insights from continuous glucose 4. Garber A, Henry R, Ratner R, Garcia- Epidemiology and public health implica- monitoring has shown that the majority of Hernandez PA, Rodriguez-Pattzi H, et al. tions. A systematic review. BMC Public hypoglycaemic events occur at night, and Liraglutide versus glimepiride monotherapy Health 2011; 15(11): 564. for type 2 diabetes (LEAD-3 Mono): a 14. Levin P, Wei W, Wang L, et al. Combination in the younger patient, do not appear to randomised, 52-week, phase II, double- therapy with insulin glargine and exenatide: impair cognitive function, although, the blind, parallel-treatment trial. Lancet 2009; real world outcomes in patients with type 2 next day, subjective well being is affected. 373(9662): 473–481. diabetes. Curr Med Res Opin 2012; 28(3): ‘These nocturnal events may, however, 5. Marre M, Shaw J, Brandle M, Bebakar 439–446. contribute to the development of impaired WM, Kamaruddin NA, et al. Liraglutide, a 15. Thong KY, Jose B, Sukumar N, Cull awareness of hypoglycaemia’, Dr Frier once-daily human GLP-1 analogue, added ML, et al. Safety, efficacy and tolerabil- to a sulphonylurea over 26 weeks produces ity of exenatide in combination with insu- noted. greater improvements in glycaemic and lin in the Association of British Clinical Age affects hypoglycaemic awareness, weight control compared with adding rosigl- Diabetologists nationwide exenatide audit. with younger patients being able to tolerate itazone or placebo in subjects with Type 2 Diabetes Obes Metab 2011; 13(8): 703–710. lower glucose levels without cognitive diabetes (LEAD-1 SU). Diabetes Med 2009; 16. Vilsboll T, Rosenstock Y, Yki-Jarvinen H, et dysfunction, while older patients, over 26(3): 268–278. al. Efficacy and safety of sitagliptin when the age of 65 years have less time for 6. Nauck MA, Frid A, Hermansen K, Shah added to insulin therapy in patients with corrective action and generally experience NS, et al. Efficacy and safety comparison type 2 diabetes. Diabetes Obes Metab 2010; of liraglutide, glimepiride, and placebo, all 12(2): 167–177. wider cognitive dysfunction, including in combination with metformin, in type 2 17. Bain SC, De Vries JH, Rodbard HW. visual disturbances, inco-ordination and diabetes: the LEAD (liraglutide effect and Adding insulin detemir (IDet) to liraglutide impaired balance.23 ‘These symptoms action in diabetes)-2 study. Diabetes Care and metformin improves glycaemic control could be perceived by the attending 2009; 32(1): 84–90. with sustained weight reduction and low physician as a transient ischaemic attack 7. Russell-Jones D, Vaag A, Schmitz O, Sethi hypoglycaemia rate: 52-week results. EASD or early dementia and not correlated to BK, Lalic N, et al. Liraglutide vs insulin 2011 congress abstract. low glucose levels’, Prof Freir warned. glargine and placebo in combination with 18. Arnolds S, Dellweg S, Clair J, et al. Further metformin and sulfonylurea therapy in type improvement in post prandial glucose Hypoglycaemia provokes profound 2 diabetes mellitus (LEAD-5 met+SU): a control with addition of exenatide or sitag- haemodynamic changes through randomised controlled trial. Diabetologia liptin to combination therapy with insulin sympatho-adrenal activation, resulting in 2009; 52(10): 2046–2055. glargine and metformin: a proof-of-concept the profuse secretion of catecholamines.24 8. Zinman B, Gerich J, Buse JB, Lewing A, study. Diabetes Care 2010; 33(7): 1509– This can provoke ECG-abnormalities; Schwartz S, et al. Efficacy and safety of 1515. prolongation of the QT interval, and the human glucagon-like peptide-1 analog 19. Bus JB, Bergenstol RM, Glass LC, et liraglutide in combination with metformin al. Use of twice daily exenatide in Basal abnormalities in AV conduction (due also and thiazolidinedione in patients with type Insulin-treated patients with type 2 diabetes: to a fall in plasma potassium), which are 2 diabetes (LEAD-4 Met+TZD). Diabetes a randomised controlled trial. Arch Intern associated with a risk of life-threatening Care 2009; 32(7): 1224–1230. Med 2011; 154(2): 103–112. cardiac arrhythmias. 9. Pratley R, Nauck M, Bailey T, et al. One 20. Fonseca V, Baron M, Shao Q, Dejager S. Hypoglycaemic events adversely year of liraglutide treatment offers sustained Sustained efficacy and reduced hypogly- affect quality of life and ‘having and more effective glycaemic control and caemia during one year of treatment with events, increases the fear of having weight reduction compared with sitagliptin, vildagliptin added to insulin in patients with both in combination with metformin, in type 2 diabetes. Horm Metab Res 2008; further events’. Dr Frier said. The rate patients with type 2 diabetes: a randomised, 40(6): 427–430. of hypoglycaemic events induced by parallel group, open-label trial. Int J Clin 21. Elashoff M, Elashoff M, Matveyenko AV, incretin-based therapies is trivial, as these Pract 2011; 65(4): 397–407. Gier B, Elashoff R, Butler PC. Pancreatitis, drugs promote glucose-dependent insulin 10. Bergenstal RM, Wysham C, Macconell L, pancreatic and thyroid cancer with GLP-1- secretion’, Prof Frier concluded. et al. Efficacy and safety of exentatide based therapies. Gastroenterology 2011; once-weekly versus sitagliptin or pioglita- 141(1): 150–156. Peter Wagenaar, Glenda Hardy, Julia Aalbers zone as an adjunct to metformin for treat- 22. UK Hypoglycaemia Study Group ment of type 2 diabetes (DURATION-2): Diabetologia. Risk of hypoglycaemia in References a randomised trial. Lancet 2010; 9739: types 1 and 2 diabetes: effects of treatment 1. Butler AE, Janson J, Bonner-Weir S, et al. 431–439. modalities and their duration. Diabetologia Beta-cell deficit and increased beta-cell 11. Buse JB, Drucker DJ, Taylor KL. 2007; 50(6): 1140–1147. apoptosis in humans with type 2 diabetes. Duration-1: exenatide once weekly products 23. McAulay V, Deary IJ, Frier BM. Symptoms Diabetes 2003; 52(1): 102–110. sustained glycaemic control and wigth loss of hypoglyacamia in people with diabetes. 2. Meier JJ, Kjems LL, Veldhuis JJ, et al. over 52 weeks Diabetes Care 2010; 33(6): Diabet Med 2001; 18(9): 690-705. Postprandial suppression of glucagon secre- 1255–1261. 24. Frier BM, Schernthaner G, Heller SR. tion depends on intact pulsatile insulin 12. Buse JB, Nauck MA, Forst T, Sheu WHH, Hypoglycaemia and cardiovascular risks. secretion: further evidence for the intraislet Hoogwerf BJ, et al. Efficacy and safe- Diabetes Care 2001; 34: 5132–137. For people with type 2 diabetes Do more than lower blood glucose. Grab diabetes by the rootsTM
Victoza® is the fi rst and only human GLP-1 analogue with 97 % homology to natural GLP-1
1-3 Reductions in HbA1C
1-3 Reductions in weight
1-3 Reductions in systolic blood pressure
4 Improvements in beta-cell function
References: 1. Nauck M, et al; for the LEAD-2 Study Group. Effi cacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination with Metformin, in Type 2 Diabetes. The LEAD (Liraglutide Effect and Action in Diabetes)-2 study. Diabetes Care. 2009;32(1):84-90. 2. Gallwitz B, et al. Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time. Int J Clin Pract. 2010;64(2):267-276. 3. Garber A, et al; on behalf of the LEAD-3 (Mono) Study Group. Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes, Obes Metab. 2011; 13: 348-356. 4. Chang AM, et al. The GLP-1 Derivative NN2211 Restores ß-cell Sensitivity to Glucose in Type 2 Diabetic Patients After a Single Dose. Diabetes. 2003;52:1786-1791.
Proprietary Name: Victoza®. Scheduling Status: S4 Composition: Liraglutide 6 mg/ml. Indications: As an adjunct to diet and exercise to achieve glycaemic control in patients with type 2 diabetes mellitus. Registration Number: 43/21.13/0781. For full prescribing information refer to package insert approved by the medicines regulatory authority.
Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. 2nd Floor, Building A, 345 Rivonia Boulevard, Edenburg, Rivonia, Sandton 2128, South Africa. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO/5281/January/2012/ver1 www.servier.com
SLOW the beat Improve the outcome
Coralan® specifically reduces Coralan® has powerful Coralan® improves outcomes in heart rate without affecting anti-anginal and heart failure patients with a heart cardiac contraction 1, conduction 2 anti-ischaemic efficacy3 rate above 70bpm - SHIFT 4 or blood pressure 3
For full prescribing information, refer to package insert approved by medicines regulatory authority.
S3 CORALAN® 5 mg Tablets. Ivabradine 5 mg. Reg. No. A39/7.1.4/0410 S3 CORALAN® 7,5 mg Tablets. Ivabradine 7,5 mg. Reg. No. A39/7.1.4/4011 NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE: SERVIER LABORATORIES SOUTH AFRICA (Pty) Ltd. Reg. No. 72/14307/07. Building Number 4, Country Club Estate, 21 Woodlands Drive, Woodmead 2191. PO Box 930, Rivonia 2128, Republic of South Africa. TEL: +27(0) 861 700 900. FAX: +27(0)11 525 3401.
References: 1. Vilaine JP et al. J Cardiovasc Pharmacol 2003;42:688-696. 2. Camm A et al. Drugs R&D 2003;4:83-89. 3. Borer J et al. Circulation 2003;107:817-823. 4. Swedberg K et al. Lancet 2010;376:875-885. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 295
Drug Trends in Cardiology
New ESC heart failure guidelines with South African expert comment
The new ESC heart failure guidelines, an eplerenone in patients with systolic heart failure in the light of the new update of the 2008 version, was released heart failure (HF-REF) and mild scientific evidence from recent clinical at the ESC Heart Failure Congress in symptoms. This broadens the indication trials. The purpose is to improve the Belgrade this weekend. This is the first for a MRA to essentially all HF-REF clinical outcomes from contemporary time the guidelines have been presented remaining symptomatic, despite adequate interventions with improvement in both at the Heart Failure Congress as opposed treatment with a beta-blocker and ACE morbidity and mortality. This comes at to at the annual European Society of inhibitor or ARB. A further innovation a price since stringent application of the Cardiology (ESC) Congress. is the recommendation that ivabradine recommendations has cost implications Major updates are in the provision be added to an ACE inhibitor, beta- on the already financially strained of new algorithms for the diagnosis of blocker (at maximum tolerated doses) healthcare systems all over the world. patients with suspected heart failure, and MRA to HF-REF patients in sinus Local adaptations of these guidelines treatment for systolic heart failure rhythm with a persistently high heart are mandatory and should be sensitive to patients with reduced ejection fraction beat above 70 beats/min (Table 2). local circumstances. For the majority of (HF-REF), and the management of acute The new guidelines devote substantial patients, the logical approach is to ensure heart failure.1,2 The diagnostic algorithm space to co-morbidities, given their access to the ‘maximum’ recommended recognises the increasing importance of importance in relation to symptoms and pharmacological intervention as the cardiac MRI and includes mid-regional progress, and therapeutic decision making. minimum standard of care. proBNP as a ‘rule-out’ blood test in In this way, the guidelines recognise that Special investigations in the setting of patients with acute heart failure. heart failure and left ventricular systolic heart failure have been re-emphasised, The pharmacological therapy section dysfunction (LVSD) may alter therapies which leads to further increase in cost. of the guideline has been updated to for co-morbidities and that co-morbidities The escalation of therapy depends on specifically relate the treatment to clinical may also influence the use of heart failure special investigations over and above the outcome effects and provides the level of therapies. symptom response. evidence supporting a use of the particular Co-morbidities such as chronic The main changes, as presented by agent (Table 1). The cornerstone use of obstructive pulmonary disease (COPD), the chairperson of the Task Force for the ACE inhibitors has been acknowledged diabetes, hypertension, kidney dysfunction review committee of the 2012 ESC heart with a class I, level A recommendation as and cardiorenal syndrome are discussed failure guidelines committee, John JV has the use of the ARBs (also class I, level and guidelines presented. Recent evidence McMurray, are the following: A). ‘ARBs, as they become generically has also pointed to the value of physicians An expanded indication for mineralo- available, can also be regarded as a managing patients with chronic heart corticoid (aldosterone) receptor antag- cornerstone therapy, particularly as drug failure and co-morbidities.3 onists (MRAs) adherence is such an important issue’, Dr The use of MRAs following the use Erik Klug (cardiologist, Johannesburg) Comment from Dr Martin Mpe of ACEI/ARB and beta-blockers in noted at the recent Physicians Congress Cardiologist in private practice, Pretoria symptomatic patients implies a revisit held in Cape Town. and a member of the CVJA editorial board on the wider use of eplerenone. In these 2012 guidelines, there is a Spironolactone has an unpleasant side new indication for the mineralocorticoid/ The update of the 2008 guidelines is effect of gynaecomastia in a significant aldosterone receptor antagonists (MRA), intended to advance the treatment of number of users, which may be more
TABLE 1. PHARMACOLOGICAL TREATMENTS INDICATED IN POTENTIALLY ALL PATIENTS WITH SYMPTOMATIC (NYHA FUNCTIONAL CLASS II–IV) SYSTOLIC HEART FAILURE Recommendations Classa Levelb An ACE inhibitor is recommended, in addition to a beta-blocker, for all patients with an EF ≤ 40% to reduce the risk of heart IA failure hospitalisation and the risk of premature death. A beta-blocker is recommended, in addition to an ACE inhibitor (or ARB if ACE inhibitor not tolerated), for all patients with an IA EF ≤ 40% to reduce the risk of heart failure hospitalisation and the risk of premature death. An MRA is recommended for all patients with persisting symptoms (NYHA class II–IV) and an EF ≤ 35%, despite treatment IA with an ACE inhibitor (or an ARB if an ACE inhibitor is not tolerated) and a beta-blocker, to reduce the risk of heart failure hospitalisation and the risk of premature death. ACE = angiotensin converting enzyme; ARB = angiotensin receptor blocker; EF = ejection fraction; MRA = mineralocorticoid receptor antago- nist; NYHA = New York Heart Association. aClass of recommendation; bLevel of evidence. 296 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
TABLE 2. OTHER TREATMENTS WITH LESS CERTAIN BENEFITS IN PATIENTS WITH SYMPTOMATIC (NYHA CLASS II–IV) SYSTOLIC HEART FAILURE Recommendations Classa Levelb ARB Recommended to reduce the risk of heart failure hospitalisation and the risk of premature death in patients with an EF ≤ 40% and I A unable to tolerate an ACE inhibitor because of cough (patients should also receive a beta-blocker and an MRA). Recommended to reduce the risk of heart failure hospitalisation in patients with an EF ≤ 40% and persisting symptoms (NYHA I A class II–IV), who are unable to tolerate an MRA, despite treatment with an ACE inhibitor and a beta-blocker.c Ivabradine Should be considered to reduce the risk of heart failure hospitalisation in patients in sinus rhythm with an EF ≤ 35%, a heart rate IIa B remaining ≥ 70 beats/min, and persisting symptoms (NYHA class II–IV) despite treatment with an evidence-based dose of beta- blocker (or maximum tolerated dose below that), ACE inhibitor (or ARB), and an MRA (or ARB).d May be considered to reduce the risk of heart failure hospitalisation in patients in sinus rhythm with an EF ≤ 35% and a heart rate IIb C ≥ 70 beats/min who are unable to tolerate a beta-blocker. Patients should also receive an ACE inhibitor (or ARB) and an MRA (or ARB).d Digoxin May be considered to reduce the risk of heart failure hospitalisation in patients in sinus rhythm with an EF ≤ 45% who are unable IIb B to tolerate a beta-blocker (ivabradine is an alternative in patients with a heart rate ≥ 70 beats/min). Patients should also receive an ACE inhibitor (or ARB) and an MRA (or ARB). May be considered to reduce the risk of heart failure hospitalisation in patients with an EF ≤ 45% and persisting symptoms IIb B (NYHA class II–IV) despite treatment with a beta-blocker, ACE inhibitor (or ARB), and an MRA (or ARB). H-ISDN May be considered as an alternative to an ACE inhibitor or ARB, if neither is tolerated, to reduce the risk of heart failure IIb B hospitalisation and risk of premature death in patients with an EF ≤ 45% and dilated LV (or EF ≤ 35%). Patients should also receive a beta-blocker and an MRA. May be considered to reduce the risk of heart failure hospitalisation and risk of premature death in patients in patients with an EF IIb B ≤ 45% and dilated LV (or EF ≤ 35%) and persisting symptoms (NYHA class II–IV) despite treatment with a beta-blocker, ACE inhibitor (or ARB), and an MRA (or ARB). PUFAs An n-3 PUFAe preparation may be considered to reduce the risk of death and the risk of cardiovascular hospitalisation in patients IIb B treated with an ACE inhibitor (or ARB), beta-blocker and an MRA (or ARB). ACE = angiotensin converting enzyme; ARB = angiotensin receptor blocker; CHARM-Added = Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity-Added; EF = ejection fraction; H-ISDN = hydralazine and isosorbide dinitrate; MRA = mineralocorticoid receptor antagonist; NYHA = New York Heart Association; PUFA = polyunsaturated fatty acid. aClass of recommendation; bLevel of evidence; CIn the CHARM-Added trial, candesartan also reduced cardiovascular mortality; dEuropean Medecines Agency has approved ivabradine for use in patients with a heart rate ≥ 70 beats/min; ePreparation studied in cited trial; the GISSI-HF trial had no EF limit. in combination with the use of digoxin. indirect cost of death. The emergence of transcatheter valve I would imagine that there will be a New information on the role of interventions significant increase in the use of coronary revascularisation in systolic This is a further reflection of the evolution eplerenone with the perceived benefit of heart failure in the practice of medicine and cardiology a better side-effect profile. The changing epidemics in coronary in particular. I find these exciting but A new indication for the sinus node artery disease risk factors, especially in the the economic realities dampen one’s inhibitor ivabradine developing world, will mean an increase enthusiasm. There may be a balance in This agent will enjoy much wider use in in invasive interventions in the heart the future as these interventions become a substantial number of patients, given failure population as well. Infrastructural more widely used and readily available. the qualifying criteria for use. I would and human resource development are also Julia Aalbers hope that the pricing will improve with imperative for the standard of care to be increase in the number of prescriptions. adequate in the not-so-distant future. 1. ESC guidelines for the diagnosis and treat- ment of acute and chronic heart failure An expanded indication for cardiac Recognition of the growing use of 2012. Eur Heart J. Doi 10.1093/eurheartj/ resynchronisation therapy (CRT) ventricular assist devices (VADs) ehs104.. With the proper selection of patients, This is idealistic and will still not be a 2. ESC Press Conference, Belgrade, 20 May there is still a significant proportion of widely available treatment avenue. This is 2012. patients who qualify for CRT. The cost of course of major importance where the 3. Boom NK, Lee DS, Tu JV. Comparison of processes of care and clinical outcomes for implication is a given, but in the long indication for appropriate use is met. The patients newly hospitalised for heart failure run, this is cost saving in comparison to cost implication as well as availability attended by different physician specialists. the cost of repeated hospitalisations and remain deterrents for most nations. Am Heart J 2012; 163: 252–259. HEALTHCARE More than 1 million patients worldwide treated with Xarelto ® Leading the way in new THR and TKR10 in ORAL anticoagulation .* More than 75 000 patients enrolled 10654/FPFC/CVJA Clinical Trial Programme
Study Programme Dosage n Main Outcome Measures Outcome
E f fi c a c y : Superior effi cacy Rivaroxaban 4,541 Composite of deep vein thrombosis (DVT), vs enoxaparin, NEJM Venous thromboembolism (VTE) prevention in total 10 mg OD 2008 hip replacements. non-fatal pulmonary embolism (PE), comparable safety. and all-cause mortality Superior effi cacy of long Safety: term (5 week) prophylaxis Rivaroxaban with rivaroxaban vs short 2,509 Major bleeding THE LANCET Venous thromboembolism prevention in total hip 10 mg OD term (2 week) prophylaxis 2008 replacements - extended prophylaxis. with enoxaparin, comparable safety.
Superior effi cacy Rivaroxaban 2,531 vs enoxaparin, NEJM Venous thromboembolism prevention in total knee 10 mg OD 2008 replacements. comparable safety.
Superior effi cacy Rivaroxaban 3,148 vs enoxaparin, THE LANCET Venous thromoboembolism prevention in total knee 10 mg OD 2009 replacements - compared to enoxaparin 30mg BD. comparable safety.
◆ Xarelto® 10 OD is approved for clinical use for VTE prevention in adult patients undergoing major orthopaedic surgery of the lower limbs. OD = once daily.
Study Programme Dosage n Main Outcome Measures Outcome
E f fi c a c y :
Composite of VTE (DVT and/or PE) and VTE Rivaroxaban related death PRESENTED ~8,000 Study completed ACC Prevention of venous thromboembolism in 10 mg OD Safety: 2011 hospitalised medically ill patients. Major and clinically relevant non-major bleeding
E f fi c a c y : Rivaroxaban 15 mg BID, 3,464 Symptomatic recurrent VTE Study completed NEJM Treatment of acute symptomatic deep vein 2010 thrombosis. fi rst 3 weeks Safety: Continue with Major and clinically relevant non-major bleeding To be presented Rivaroxaban 20 mg OD 4,300 Study completed ACC Treatment of acute pulmonary embolism with or 2012 without symptomatic DVT.
E f fi c a c y : NEJM Rivaroxaban Symptomatic recurrent VTE 2010 1,197 Study completed Continued treatment of deep vein thrombosis or 20 mg OD Safety: pulmonary embolism. Major bleeding
Rivaroxaban E f fi c a c y : NEJM 20 mg OD or 011 14,269 Composite of stroke and non-CNS Study completed 2 Prevention of stroke and embolism in atrial Rivaroxaban 15 mg systemic embolism fi brillation. OD 30-49 ml/min CrCl Safety: PRESENTED Rivaroxaban 15 mg OD 1,280 Composite of major and clinically relevant Study completed ISTH non-major bleeding 2011
E f fi c a c y : Composite of CV death, MI and stroke Rivaroxaban 2.5 mg BID Study completed ~16,000 NEJM Anti-Xa therapy to lower cardiovascular events in Rivaroxaban 5 mg BID Safety: 2011 addition to Aspirin with or without thienopyridine therapy in subjects with acute coronary syndrome. Major bleeding events not associated with CABG surgery
OD = once daily BID = twice daily CrCl = creatinine clearance. Rivaroxaban 2.5 mg, Rivaroxaban 5 mg, Rivaroxaban 15 mg and Rivaroxaban 20 mg are in Clinical Development; and thus not recommended for clinical use in all Indications under investigation. The most extensive Phase III Clinical Trial Programme of any new oral anticoagulant **
www.thrombosisadviser.com
*THR - total hip replacement. TKR - total knee replacement. **http://clinicaltrial.gov RECORD1: Eriksson BI, et al. N Engl J Med. 2008; 358(26):2765-2775. RECORD2: Kakkar AK, et al. Lancet. 2008; 372(9632):29-37. RECORD3: Lassen MR, et al. N Engl J Med. 2008; 358(26):2776-2786. RECORD4: Turpie AGG, et al. Lancet. 2009; 373(9676):1673-1680. MAGELLAN: http://clinicaltrials.gov/ct2/show/NCT00571649. EINSTEIN DVT and EXT: Einstein Investigators. N Engl J Med. 2010. EINSTEIN PE: http://clinicaltrials.gov/ct2/show/NCT00439777. ROCKET AF: Patel, et al. N Engl J Med. 2011. J-ROCKET AF: http://clinicaltrials.gov/ct2/show/NCT00973323. ATLAS ACS TIMI 51: http://clinicaltrials.gov/ct2/show/NCT00809965. For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority (MCC) S4 XARELTO® 10 (Film-coated tablets). Reg.No.: 42/8.2/1046. Each fi lm-coated tablet contains rivaroxaban 10 mg. PHARMACOLOGICAL CLASSIFICATION: A.8.2 Anticoagulants. INDICATION: Prevention of venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery of the lower limbs. HCR: Bayer (Pty) Ltd, Reg. No.: 1968/011192/07, 27 Wrench Road, Isando, 1609. Tel: 011 921 5044 Fax: 011 921 5041 DATE: February 2012 L.ZA.GM.02.2012.0377 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 299
EINSTEIN-PE study results, with South African expert comment
Rivaroxaban has been shown to be as included patients treated with LMWH, relevant non-major bleeding was the same, effective as initial and long-term treatment fondaparinux or unfractionated heparin for overall major bleeding episodes did differ, with enoxaparin and warfarin for pulmonary more than 48 hours or if they had already with 26 (1.1%) occurring in the rivaroxaban embolism (PE), with a potentially improved received more than a single dose of a vitamin group and 52 (2.2%) in the standard-therapy risk profile benefit.1 The results of the K antagonist before randomisation. Also group. This difference had a standard Einstein-PE study were announced at the patients who had undergone thrombectomy deviation of 0.49 (95% confidence interval recent American College of Cardiology or other surgical procedures were excluded. of 0.31–0.79) and was significant (p = meeting in Chicago and simultaneously Patients with contra-indications to vitamin 0.003). Within this latter group was included published in the March issue of New K were also excluded, as were patients with other non-fatal episodes in critical sites, and England Journal of Medicine 2012. active bleeding or at high risk of bleeding, a large proportion of the differences within Commenting on the study results, Dr contra-indicating anti-coagulant therapy. the group of major bleeds was made up of Harry Buller, Academic Medical Centre, Randomisation was stratified according intra-cerebral bleeds, which occurred in one Amsterdam pointed out that in the to country and the attending physician’s patient (< 0.1%) with rivaroxaban, and 10 overall EINSTEIN-DVT and EINSTEIN- intention-to-treat duration of three, six or (0.4%) with standard therapy. PE programme of 10 000 patients, there 12 months. Importantly, standard therapy Will this study change therapy? The was a very convincing 50% lower rate was well controlled and time in therapeutic important considerations are firstly efficacy, of major bleeding, particularly intra- range (TTR) of the target INR (2–3) was and in this regard rivaroxaban is non-inferior cranial haemorrhage and retroperitoneal 62.7%. The TTR percentage did vary from to standard therapy. Second is safety, and bleeds with rivaroxaban compared with 57.8% during the first month, to 72.7% certainly with regard to major bleeding the difficult-to-manage warfarin standard during month 11. In the rivaroxaban group, episodes, it is superior, although the therapy. ‘One of the patient groups who adherence to therapy was above 80%. numbers are small. Third is the issue of cost. particularly benefited with regard to major In the study, rivaroxaban demonstrated If it is priced too high, the cost efficacy may bleeding with rivaroxaban was those over 75 efficacy comparable to that of the current make this therapy non-justifiable and this years of age’, Dr Buller noted. standard therapy in reducing the primary may prove to be an obstacle. Fourthly, some The EINSTEIN-PE study was been endpoint of recurrent symptomatic VTE, patients do not like injecting themselves heralded as a landmark study in the a composite of symptomatic deep-vein and may prefer to take a tablet that has been field of pulmonary embolism and marks thrombosis and non-fatal or fatal pulmonary proven to be equally efficacious. a turning point in its management. It is embolism (2.1 vs 1.8%, respectively; p Bayer is to be congratulated, however, the largest-ever study of PE, recruiting = 0.003 for non-inferiority). Rivaroxaban on successfully completing an arduous 4 833 patients from 36 countries, including also demonstrated similar safety results study without any pre-knowledge as to what South Africa. compared to current standard of care for the outcome would be. This study adds Designed as a non-inferiority study, oral the principal safety outcome measuring significantly to our knowledge of these rivaroxaban was given as 15 mg bid for a composite of major and non-major new drugs and offers different options for three weeks, followed by 20 mg daily. This clinically relevant bleeding events the treatment of pulmonary embolus in the was compared to the standard treatment (10.3 vs 11.4%, respectively; p = 0.23). future. of subcutaneous injections for five to 10 Importantly, rivaroxaban treatment resulted days with a low-molecular weight heparin in a significant reduction in major bleeding Julia Aalbers (LMWH) and an oral vitamin K antagonist events (1.1 vs 2.2%, respectively; p = 0.003) (warfarin) for the prevention of recurrent compared to the current standard therapy. thromboembolism. Acute coronary events were low (0.6%) ‘Rivaroxaban was given as monotherapy, and were equally distributed between the which was a very brave step and it is the first two groups. study to really bite the bullet with regard to its challenge of conventional LMWH 1. The Einstein investigators. N Engl J Med therapy’, Dr Buller said. Rivaroxaban, an 2012: 366: 1287–1297. oral factor Xa inhibitor, has already been shown in phase III trials to be as effective Prof Guy Richards (University of the as standard anticoagulant therapy for the Witwatersrand) comments on the treatment of deep-vein thrombosis and importance of the EINSTEIN-PE study stroke prevention in atrial fibrillation and for South African clinicians is currently registered in South Africa for This is an interesting study, the first the prevention of venous thromboembolism assessing utilisation of one of the new orally in patients undergoing major orthopaedic available anticoagulants to treat pulmonary surgery of the lower limbs. embolism. The outcomes were similar with The EINSTEIN-PE study recruited a regard to prevention of recurrence but there broad spectrum of patients with PE with and were differences with regard to safety. without deep-vein thrombosis. Exclusions Whereas overall major or clinically HEALTHCARE 300 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
The role of aspirin in cardiovascular disease prevention
Prof Gordon T McInnes, University of suggests that once you initiate, you should showed that 28% of the CVD subjects Glasgow, Scotland continue for life.’ While it can be and involved were resistant. This would dilute Acetylsalicylic acid (aspirin) may have often is used in combination with other apparent benefits and may be responsible been around for over 100 years, but treatments, it remains the foundation of for the modest nature of the benefits seen this ‘cheap and cheerful’ agent continues any antiplatelet approach. in primary prevention.’ to surprise with new indications for its Turning to aspirin’s longer-term use There are also gender differences in use. Prof Gordon McInnes feels that post MI and in chronic stable angina, primary prevention in that aspirin appears this ‘old drug with new tricks’ has an Prof McInnes noted that there was good to reduce ischaemic stroke but not MI in important ongoing role to play in both evidence of benefit. ‘Twelve trials have women. The picture may be reversed in the primary and secondary prevention of shown that post MI, it prevents 36 serious men. cardiovascular disease (CVD). He was vascular events per 100 patients per two Discontinuation of aspirin in patients speaking at a meeting hosted by Bayer years, while 55 trials have shown that in with a history of ischaemic events is Healthcare in Johannesburg in May. coronary heart disease (CHD) with no nonetheless associated with a major ‘Aspirin was developed in 1897 and is MI, there is a 37% reduction in serious increased risk of non-fatal MI or CHD still going strong, with new indications vascular events. Seven trials have shown death within 30 days. ‘This is evidence for its use continuing to appear’, he said. benefit in acute ischaemic stroke, with for continuation and suggests that patients ‘We think we’re civilised, but we’re nine serious vascular events prevented should never discontinue aspirin therapy doing a lot of things wrong and driving per 1 000 patients per three weeks. The without careful consultation with medical ourselves to an early grave’, he warned. early introduction of aspirin is therefore professionals’, Prof McInnes advised. As the developing world, including South recommended.’ Africa, adopts Westernised lifestyles, ‘The evidence for more intensive Other benefits the tsunami of CVD previously seen in therapy with additional agents is weak, There has been some good news in recent Europe and North America is sweeping but we’re still awaiting the results of years, with high-quality data indicating through Asia and Africa, with 80% of ongoing trials in this regard. Twenty-one that aspirin reduces the risk of large cases now seen in low- and middle- trials also support the use of maintenance bowel cancer. A meta-analysis of 51 income countries. aspirin in transient ischaemic attack and trials showed substantial reductions in CVD accounts for 30% of all deaths, ischaemic stroke.’ cancer death, incident cancer and spread 12 million worldwide per year. ‘It’s the Not all the news is good, though. Prof of cancer, suggesting that ‘an aspirin a number one killer on the planet. Over and McInnes feels that there is, sadly, not day keeps cancer away’. ‘A decreased above that, there are 20 million survivors much benefit in atrial fibrillation, with risk of type 2 diabetes may also be added of a stroke or myocardial infarction (MI) only one trial having shown positive to the list of clinical benefits of aspirin’, each year, which makes it important to results. ‘Aspirin’s days as a protective said Prof McInnes, ‘although these data look at preventing subsequent events. agent in this setting are gone, especially are somewhat less compelling.’ Aspirin has a role to play in both primary with the advent of the newer agents that So what does all this mean for primary and secondary prevention.’ are safer than warfarin.’ prevention? Prof McInnes feels that All forms of vascular disease have However, the news is good where it is important to do an in-depth risk the same underlying process and central peripheral vascular disease is concerned. assessment to guide decision making but to this is the role of platelets – their Aspirin is associated with a 23% that in patients over 50 years, there is adhesion, activation and aggregation. reduction in serious vascular events and, indeed clear benefit that becomes even Antiplatelet treatments such as aspirin are importantly, improved symptoms more apparent as age increases, especially therefore very important. when one factors in cancer. Primary prevention ‘The provision of aspirin in people Secondary prevention In this context, the evidence is less clear at increased vascular risk provides the In the secondary prevention of CVD, cut than that for secondary prevention. greatest benefit and has the lowest cost aspirin’s role is clear and straightforward. ‘The most recent meta-analysis published by far of any preventive measures, apart According to the Antithrombotic by Berger et al.2 showed a 50% or higher from smoking cessation’, he concluded. Trialists’ Collaboration study published risk of major bleeding with only modest ‘After all these years, aspirin still hits the in the Lancet in 2009,1 it reduces the risk risk reduction in MI, stroke, CV death target.’ of any vascular event by 19%, non-fatal and all death. There is also conflicting MI by 31%, stroke by 19% and vascular evidence around the use of aspirin for Peter Wagenaar mortality by 9%. ‘So there are benefits primary CVD prevention in diabetics. across the board!’ ‘However, the POPADAD3 and JPAD4 1. Antithrombotic trialists’ (ATT) collabora- When it comes to acute coronary trials, which produced these conflicting tion. Lancet 2009; 373: 1849–1860. syndrome, aspirin’s benefits have been findings, were underpowered and 2. Berger JS, et al. Am Heart J 2011; 162: 115–124. shown in 15 trials. It prevents 30 serious imprecise, so clinical benefit cannot be 3. Belch J, et al. Br Med J 2008; 337: 1030– vascular events per 1 000 patients per ruled out.’ 1034. week, with the low risk of only one major Another reason for the conflicting 4. Ogawa H, et al. J Am Med Assoc 2008; 300: bleed per 1 000 patients per year. ‘There evidence in primary prevention is the 2134–2141. is some debate around how long it should phenomenon of aspirin resistance. ‘A 5. Krasopoulos G, et al. Br Med J 2008; 336: be taken for, but much of the evidence meta-analysis by Kraspoulos et al.,5 195–198. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e1
Case Report
Severe haemoptysis due to subclavian arteritis A LIOULIAS, P MISTHOS, J KOKOTSAKIS, P DROSOS, N KARAGIANNIDIS, D PAVLOPOULOS, M MITSELOU
Abstract A chest computed tomography (CT) scan revealed a Severe haemoptysis due to infective subclavian arteritis has, solid intraparenchymal mass at the apex of the left lung. CT to our knowledge, never been documented. We report a case angiography showed a giant intrapulmonary haematoma due to of subclavian arterial vasculitis that eroded into the left lung a subclavian artery leak (Figs 1, 2). apex, causing a large intraparenchymal mycotic pseudo- An emergency left lateral thoracotomy was performed. The aneurysm. The patient presented with high fever and blood apex of the lung was separated from the rest of the lung with expectoration. An emergent left lateral thoracotomy was a linear staple. The subclavian artery was controlled distal performed. The inflamed segment of the subclavian artery to its origin at the aortic arch. The lung apex was dissected was resected and continuity was restored with a reversed extrapleuraly until the subclavian artery was seen. The subclavian saphenous vein graft. The postoperative course was unevent- artery was distally controlled just before its exit at the thoracic ful and the patient was discharged on the 10th postoperative outlet above the first rib. Resection of the subclavian artery was day. technically demanding because several branches that originate distal to the vertebral artery were difficult to find and control. Keywords: haemoptysis, subclavian artery, arteritis, lung Submitted 8/6/10, accepted 26/11/10 Cardiovasc J Afr 2012; 23: e1–e2 www.cvja.co.za DOI: 10.5830/CVJA-2010-096
Seven cases of haemoptysis as the presenting symptom of a subclavian aneurysm have been published.1-7 However, severe haemoptysis due to infective subclavian arteritis has, to our knowledge, never been documented. We report a case of subclavian arterial vasculitis that eroded into the left lung apex, causing a large intraparenchymal mycotic pseudo-aneurysm. The patient presented with high fever and blood expectoration.
Case report A 17-year-old male presented with high-grade fever, which he had had for the previous three weeks, retrosternal pain, and multiple episodes of severe haemoptysis during the preceding two days. He was a heroin addict and used the subclavian vessels as vascular access. He reported that one month previously, injection at that location was accompanied by severe pain at the area of the thoracic outlet. Fig. 1. CT angiography on the transverse plane, show- ing a giant intrapulmonary haematoma (arrow) due to a subclavian artery leak. Thoracic Surgery Department, Sismanogleio General Hospital, Athens, Greece A LIOULIAS, MD, PhD P MISTHOS, MD, PhD, [email protected] J KOKOTSAKIS, MD, PhD P DROSOS, MD D PAVLOPOULOS, MD Third Department of Pneumonology, Sismanogleio General Hospital, Athens, Greece N KARAGIANNIDIS, MD, PhD Department of Anaesthesia, Sismanogleio General Hospital, Athens, Greece Fig. 2. CT angiography on the coronal plane, showing a giant intrapulmonary haematoma (arrow) due to a subcla- M MITSELOU, MD vian artery leak. e2 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
tomography may demonstrate changes in the size or appearance of the infected artery or show peri-arterial nodularity, air or pus in the arterial wall. Arteriography is not specific but may show atheromatous disease or a saccular or multiloculated aneurysm in an otherwise normal vessel, suggesting a local infection.6 The accepted management of bacterial arteritis is intravenous antibiotic therapy, excision and debridement of the artery and the mycotic false aneurysm if present, and where possible, extra- anatomical vascular reconstruction along an uncontaminated path. Surgical treatment for patients with subclavian arteritis should be considered in cases of unremitting infection after adequate antibiotic treatment, or rupture, and to avoid embolus formation or thrombosis. In our case, emergency surgical management was indicated because the recurrent severe haemoptysis had to be controlled. A variety of techniques are used with different surgical approaches and arterial repair. Surgical approaches include supra- Fig. 3. The surgical specimen showing the ruptured clavicular incision, axillary incision, median sternotomy with a subclavian artery and left lung apex associated with a transverse incision along the second rib bed, and posterolateral giant pulmonary haematoma. thoracotomy, or a combination of all of these, depending on the Macroscopically the surgical specimen showed the ruptured location of the aneurysm. subclavian artery running into the left lung apex and associated with a giant pulmonary haematoma (Fig 3). The continuity of Conclusion the subclavian artery was restored with a reversed saphenous In our case, a left posterolateral thoracotomy was performed vein graft, which was harvested before the thoracotomy. The through the fourth intercostal space with the patient under blood loss was estimated to be approximately 350 cm3. The anaesthesia, using double-lumen endotracheal intubation. postoperative course was uneventful and the patient was It provided a good approach to perform the excision and discharged on the 10th postoperative day. reconstruction of the subclavian artery and to perform a concomitant left upper lobectomy. A reversed saphenous vein Discussion bypass graft was used to reduce the risk of secondary blood-borne An infected artery may rupture in the absence of aneurysmal infection, which is associated with using prosthetic materials.9 dilatation.7 The pathogenesis, however, remains unclear in many cases. The commonest site of endarterial infection is the References abdominal aorta.8 Infection of the main intrathoracic arteries 3 1. Saliou C, Badia P, Duteille F, D’Attellis N, Ricco JB, Barbier J. is rarely reported and may present as haemoptysis, or it may Mycotic aneurysm of the left subclavian artery presented with hemop- 4 mimic a bronchogenic carcinoma. In our case, the infected site tysis in an immunosuppressed man: case report and review of literature. had been used as an injection site. The infection caused the J Vasc Surg 1995; 21(4): 697–702. vascular wall to erode into the left lung and the intrapulmonary 2. Iijima K, Kuribayashi R, Sakarada T, Sekine S, Aida H, Abe T. [A left artery to rupture. subclavian arterial aneurysm ruptured into the left lung – a case report]. Early diagnosis is important because untreated mycotic Nippon Kyobu Geka Gakkai Zasshi 1992; 40(3): 440–443. subclavian arterial disease has a dismal outcome. Therefore a high 3. Takagi H, Mori Y, Umeda Y, Fukumoto Y, Yoshida K, Shimokawa K, Hirose H. Proximal left subclavian artery aneurysm presenting hemop- index of suspicion must be maintained. Moreover, haemoptysis tysis, hoarseness, and diplopia: repair through partial cardiopulmonary due to subclavian arteritis has not been documented before. bypass and perfusion of the left common carotid artery. Ann Vasc Surg Numerous organisms can cause infection in the arterial wall but 2003; 17(4): 461–463. the most frequent is Salmonella, which is found in 36% of cases. 4. Boundy K, Bignold LP. Syphilitic aneurysm of the right subcla- It has a predilection for larger, diseased blood vessels. Other vian artery presenting with hemoptysis. Aust NZ J Med 1987; 17(5): organisms known to cause such infection are staphylococci, 533–535. 5. Deulofeu Fontanillas F, Barbeta Sánchez E, Bernet Vidal M, Sentis streptococci, Escherichia coli, Pseudomonas, Bacteroides, Criville M, Pujol Farriols R. [Massive hemoptysis secondary to Haemophilus, Clostridia and Enterobacter klebsiella. mycotic aortic aneurysm]. Ann Med Interna 1989; 6(7): 373–375. Predisposing factors to infective endarteritis include pre-existing 6. Wu MH, Lai WW, Lin MY, Chou NS. Massive hemoptysis caused by atherosclerosis, aneurysms, diabetes, immunosuppression or a ruptured subclavian artery aneurysm. Chest 1993; 104(2): 612–613. active vasculitis. 7. Mii S, Ienaga S, Motohiro A, Okadome K. An unusual symptom of An early diagnosis allows both prompt, appropriate antibiotic subclavian artery aneurysm: hemoptysis. J Vasc Surg 1991; 14(2): treatment and timely surgical intervention before invasive 243–245. 8. Oz MC, Brener BJ, Budas JA, et al. A ten-year experience with bacte- pathogens destroy the arterial wall. Early diagnosis may be aided rial aortitis. J Vasc Surg 1989; 10: 439–449. by greater awareness and improved radiological techniques such 9. Visrutaratna P, Charoenkwan P, Saeteng S. Mycotic aneurysm of the as ultrasonography, computer-aided tomography and digital left subclavian artery: CT findings. Singapore Med J 2006; 47(1): subtraction angiography. In particular, enhanced computed 77–79. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e3
Case Report
The dangerous fifth chamber: congenital left atrial appendage aneurysm KURSAT M Tigen, CEM Dogan, AHMET Guler, SUZAN Hatipoglu, MEHMET Yanartas, CEVAT Kirma
Abstract atrium, and there was dynamic blood flow within the aneurysm Aneurysms of the left atrial appendage are extremely rare. (Fig. 2). Enlargement of the left atrial appendage can be congeni- Because of the potential risk of embolism, the patient was tal or acquired. Dysplasia of the left atrial muscles leads referred to surgery for resection of the aneurysm. Following a to congenital left atrial appendage aneurysm and usually median sternotomy, surgical exploration confirmed the diagnosis presents as atrial tachyarrhythmia or embolic events in of an LAA aneurysm (Fig. 3). The aneurysm was resected the second or third decade of life. We report a case of an without extracorporeal circulation. The anatomical features of asymptomatic 12-year-old child with a congenital left atrial the resected LAA were consistent with the echocardiographic appendage aneurysm. Transthoracic and transoesophageal images. The patient’s postoperative course was uneventful. echocardiography demonstrated a large left atrial appendage aneurysm without thrombus or spontaneous echo-contrast. Discussion The patient was successfully treated with surgical resection Aneurysm of the LAA is a very rare condition and can be of the aneurysm. categorised into two groups; congenital or acquired. Acquired Keywords: congenital, left atrial appendage aneurysm LAA aneurysms are associated with increased left atrial pressure as a result of rheumatic valve disease or mitral regurgitation. The Submitted 7/2/11, accepted 6/9/11 cause of congenital aneurysms of the LAA is dysplasia of the Cardiovasc J Afr 2012; 23: e3–e4 www.cvja.co.za pectineal muscles.1 DOI: 10.5830/CVJA-2011-051 Symptoms associated with aneurysms of the LAA are supraventricular tachyarrhythmia, such as atrial fibrillation or flutter and paroxysmal atrial tachycardia, embolic events, heart Case report failure and angina pectoris. Atrial tachyarrhythmia, which is A 12-year-old female without symptoms and previous history the most common cause for presentation, could be explained of disease was referred to our clinic because of a chest X-ray by irritation of the enlarged LAA or congenital defects of the demonstrating a prominent convexity of the left upper heart conduction system. Embolic events such as cerebrovascular border in the position of the left atrial appendage (LAA). The infarcts are related to stasis caused by the increase in LAA physical examination was normal and an electrocardiograph volume and subsequent thrombus formation. More rarely in (ECG) showed normal sinus rhythm. Laboratory findings were within the normal range. Transthoracic echocardiography (TTE) revealed a huge LAA aneurysm resembling a fifth cardiac chamber and normal ventricular and valvular function (Fig. 1). For better determination of the aneurysm, transoesophageal echocardiography (TEE) was performed. This revealed a 6.2 × 4.4-cm LAA aneurysm with a left atrial connection. There was no spontaneous echo-contrast or thrombus in the LAA and left
Department of Cardiology, Kartal Kosuyolu Heart Education and Research Hospital, Istanbul, Turkey KURSAT M TIGEN, MD CEM DOGAN, MD AHMET GULER, MD, [email protected] Suzan Hatipoglu, MD CEVAT KIRMA, MD Department of Cardiovascular Surgery, Kartal Kosuyolu Fig. 1. Apical four-chamber view of TTE demonstrating a Heart Education and Research Hospital, Istanbul, Turkey large LAA aneurysm resembling a fifth cardiac chamber. MEHMET YANARTAS, MD LA: left atrium, LV: left ventricle, LAA: left atrial append- age. e4 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Fig. 3. A: Intra-operative image of the large LAA aneu- rysm. B: Postoperative image of the resected material.
LAA aneurysms should be treated even if the patient is asymptomatic because they could be the source of arrhythmias and life-threatening thromboembolic complications. The surgical treatment of congenital aneurysm of the LAA is resection with or without extracorporeal circulation.
Conclusion A left atrial appendage aneurysm is a rare but potentially dangerous entity. Because of the risk of embolic complications, resection is advised when possible. Fig. 2. Modified transoesophageal four-chamber, two- dimensional (A), and colour flow (B) views showing a References huge LAA aneurysm with a broad left atrial connective neck. There was no spontaneous echo-contrast or throm- 1. Chowdhury UK, Seth S, Govindappa R, Jagia P, Malhotra P. Congenital bus in the LAA and left atrium, and there was dynamic left atrial appendage aneurysm: a case report and brief review of litera- blood flow within the aneurysm. LA: left atrium, LV: left ture. Heart Lung Circ 2009; 18(6): 412‒416. ventricle, LAA: left atrial appendage. 2. Zhang PF, Zhang M, Zhang W, Yao GH, Wu SM, Zhang Y. Giant aneu- rysm of the left atrial appendage: detected by real-time 3-dimensional the literature, there are also reports of patients presenting with echocardiography. Tex Heart Inst J 2010; 37(1): 129‒130. positional hypotension and tachycardia.2 3. Foale RA, Gibson TC, Guyer DE, Gillam L, King ME, Weyman AE. An echocardiographic image of an LAA aneurysm could be Congenital aneurysms of the left atrium: recognition by cross-ectional confused with cystic tumours of the mediastinum, pericardial echocardiography. Circulation 1982; 66: 1065–1069. cysts, herniation of the left atrium through a pericardial defect, 4. Comess KA, Labate DP, Winter JA, Hill AC, Miller DC. Congenital anomalous pulmonary venous drainage, and secondary causes left atrial appendage aneurysm with intact pericardium: diagnosis by transesophageal echocardiography. Am Heart J 1990; 120: 992–996. 3-5 of LAA enlargement. TEE, computed tomography and cardiac 5. Gold JP, Afifi HY, Ko W, Horner N, Hahn R. Congenital giant aneu- magnetic resonance imaging provide detailed information on the rysms of the left atrial appendage: diagnosis and management. J Card structure and composition of the LAA aneurysm. Surg 1996; 11: 147–150. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e5
Case Report
Corrected transposition of the great arteries with previously unreported cardiac anomalies AHMET KAYA, IBRAHIM HALIL TANBOGA, MUSTAFA KURT, TURGAY IŞIK, MESUT OZGOKCE, SELIM TOPÇU, ENBIYA AKSAKAL
Abstract threatening late complications in this patient group.4 The corrected transposition of the great arteries is a rare In the medical literature, there is no evidence of any patient congenital cardiac anomaly characterised by atrio-ventricu- with corrected transposition combined with atrial septal defect lar and ventriculo-arterial discordance and is related to the (ASD), pulmonary stenosis, situs inversus totalis, right arcus largest incidence of cardiological complications. We report aorta and coronary artery anomalies. We report here, for the first on a 40-year-old woman with congenitally corrected trans- time, a case of CTGA with all of these anomalies. position of the great arteries, situs inversus, atrial septal defect, pulmonary stenosis, right arcus aorta and coronary Case report artery anomalies. A 40-year-old woman was admitted to the cardiology clinic Keywords: corrected transposition, congenital heart disease, with chest pain and worsening dyspnoea. She had no history cardiovascular imaging of cardiac disorder or risk factors for coronary artery disease. Her blood pressure and pulse rate were normal at 125/80 Submitted 16/4/11, accepted 6/9/11 mmHg and 60 beats/min, respectively. Auscultation revealed a Cardiovasc J Afr 2012; 23: e5–e7 www.cvja.co.za grade III holosystolic murmur, which was best heard at the left DOI: 10.5830/CVJA-2011-049 sternal border. There was no diastolic murmur. The laboratory examinations (blood count, biochemistry) were within normal Congenital cardiac anomalies are present in between ranges, and electrocardiography (ECG) demonstrated regular approximately 3.7 and eight of every 1 000 live-birth infants. sinus rhythm. The corrected transposition of the great arteries (CTGA), Transthoracic echocardiography (TTE) showed atrio- characterised by atrioventricular and ventriculo-arterial ventricular and ventriculo-arterial discordance and also revealed discordance and normal atrial situs, occurs in approximately 0.5 that the aorta was on the right side, anteriorly located. The final to 1.4% of all congenital cardiac diseases.1 diagnosis was congenitally corrected transposition of the great Most patients have one or more associated cardiac anomalies, arteries. TTE further revealed a normal systemic (morphological and the presence or absence of these anomalies significantly alters right) ventricular ejection fraction of 60%, and a normal the natural history.2 Peri-membranous ventricular septal defect (VSD) and pulmonary stenosis (PS), which may result from an aneurysm of the interventricular septum, an associated fibrous tissue tag, or a discrete ring of tissue in the subvalvular area, are the most common associated defects.3 VSD occurs in 70% of patients and PS in 40%.2 Systemic ventricular dysfunction, tricuspid regurgitation, heart blocks and arrhythmias are life-
Department of Cardiology, Erzurum Regional Education and Research Hospital Erzurum, Turkey AHMET KAYA, MD, [email protected] IBRAHIM HALIL TANBOGA, MD MUSTAFA KURT, MD TURGAY IŞIK, MD Department of Radiology, Medical Faculty, Atatürk University Erzurum, Turkey MESUT OZGOKCE, MD Department of Cardiology, Medical Faculty, Atatürk University Erzurum, Turkey SELIM TOPÇU, MD Fig. 1. TEE showing a discrete ring. PV: pulmonary valve, ENBIYA AKSAKAL, MD Ao: aorta, PA: pulmonary artery. e6 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Fig. 4. Left and right heart catheterisation. Right ventricu- lography showing prominent trabeculations, which are characteristic of a morphological right ventricle. RV: right ventricle, Ao: aorta.
to further evaluate the cardiac morphology and coronary Fig. 2. TEE showing inter-atrial septal defect with intra- anatomy. The results of MRI corroborated the findings on cardiac shunting. ASD: atrial septal defect. echocardiography (Fig. 3). The patient underwent right and left heart catheterisation, pulmonary (morphological left) ventricular ejection fraction which showed increased right-side pressures (130 mmHg). of 55%. There was ventricular inversion with anatomical Systemic ventricular end-diastolic pressures were normal. preservation of the atrial and venous drainages, and the right Systemic ventriculography revealed a heavily trabeculated ventricle (RV) was dilated. ventricular chamber with an outflow tract leading to the aortic Transoesophageal echocardiography (TEE) showed there valve, which is an indication of a morphological right ventricle was significant pulmonary obstruction associated with a (Fig. 4) and D-transposition. discrete ring of tissue in the subvalvular area (Fig. 1) and that There was no angiographic evidence of significant systemic the transpulmonary gradient pressure was high (81 mmHg). atrio-ventricular valvular regurgitation, but there was intra- Additionally, there was an inter-atrial septal defect associated cardiac shunting on the inter-atrial septum. Selective coronary with intra-cardiac left-to-right shunting (Fig. 2). angiography revealed the circumflex artery originating from the Cardiac magnetic resonance imaging (MRI) was performed right coronary artery, and a normal course of the left anterior descending and right coronary arteries (Fig. 5).
Fig. 3. Cardiac magnetic resonance imaging showing CTGA, right arcus aorta and situs inversus. RV: right Fig. 5. Circumflex artery originating from the right coro- ventricle, LV: left ventricle, Ao: aorta, PA: pulmonary nary artery. CX: circumflex artery, RCA: right coronary artery. artery. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e7
The patient was referred for cardiovascular surgery but she approach, with unexpected anatomy being associated with higher refused and has been followed up medically. morbidity and mortality rates,7 so clinicians must be careful to identify these anomalies in a timely manner. Discussion This case presents a unique feature rarely described in the Conclusion medical literature, namely, the combination of several congenital A single case of CTGA combined with ASD, pulmonary stenosis anomalies. CTGA may remain asymptomatic for several years and situs inversus has been reported before.8 Our report, however, in individuals without associated cardiopathies and may only demonstrates the combination of ASD, pulmonary stenosis, right be seen on ECG or X-ray due to the unusual position of the arcus aorta and coronary artery anomalies in a case of CTGA ventricles. Over time, systemic ventricular failure may develop involving situs inversus. We believe that this combination is due to pressure overload, causing fatigue and dyspnoea.1 extremely rare. To our knowledge, this is the first case of its kind In this anomaly, the right atrium enters the morphological reported in the medical literature. left ventricle, which leads to the pulmonary artery, and the left atrium communicates with the morphological right ventricle, References which leads to the aorta. Therefore, atrio-ventricular and ventriculo-arterial discordance exists, and although blood flows 1. Roger PO, Panayotis A, Ronaldo V, et al. Corrected transposition of the great arteries: late clinical presentation, in the fifth decade of life. Arq in the normal direction, it passes through the ‘wrong’ ventricular Bras Cardiol 2008; 91: 4. chamber. This ‘double discordance’ results in the term CTGA, 2. Warnes CA. Transposition of the great arteries. Circulation 2006; 114: which is, in essence, a misnomer.5 It is also called L-transposition 2699–2709. because the morphological right ventricle is in the levoposition. 3. Taçoy G, Kula S, Cemri M. An unusual appearance: a heart in the heart The aorta is also usually, but not universally, anterior and to in a patient with congenitally corrected transposition of great arteries. the left, and the great arteries may be side by side. Because the Anadolu Kardiyol Derg 2009; 9: 5–9. tricuspid valve always enters a morphological right ventricle, 4. Ikeda U, Furuze M, Suzuku O, et al. Long-term survival in aged patients with corrected transposition of the great arteries. Chest 1992; it too is on the left side in the systemic circulation and is more 101: 1382–1385. 2 appropriately termed the systemic atrio-ventricular valve. In our 5. Warnes CA. Congenitally corrected transposition: the uncorrected case, the morphological right ventricle was in the dextroposition, misnomer. J Am Coll Cardiol 1996; 27: 1244–1245. the aorta was anterior and to the right, and the great arteries were 6. Donald SC, Bruce MB, Margaret HL, et al. Congenitally corrected side by side (in the D-transposition) (D-CTGA). transposition of the great arteries: imaging with 16-MDCT. Am J Coronary artery anomalies in congenitally corrected Radiol 2007: 188. transposition of the great arteries have seldom been reported in 7. Ismat FA, Baldwin HS, Karl TR, et al. Coronary anatomy in congeni- tally corrected transposition of the great arteries. Int J Cardiol 2002; the medical literature due to the rarity of this disorder and the 86: 207–216. 6 relatively small number of patients in each reported series. The 8. Sefidbar M, Ludin H, Burckhardt D. Corrected d-transposition in situs coronary arteries usually course to their respective ventricles. inversus with atrial septal defect and pulmonary stenosis. Z Kardiol; Significant coronary artery abnormalities may affect the surgical 1973; 62(4): 360–365. e8 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
Case Report
Rocking mitral annuloplasty ring PRASHANTH PANDURANGA, MOHAMMED K MUKHAINI
Abstract inside the left atrium. There was severe A2 prolapse with no Dehiscence of a mitral annuloplasty ring is a rare occur- chordal rupture seen. His left ventricle measured 62 mm in rence. We present a young patient with long-standing gross diastole and 44 mm in systole, with an ejection fraction of 60%. dehiscence of a Duran annuloplasty ring secondary to suture The patient was repeatedly advised to have the mitral valve dehiscence, occurring three years after mitral valve surgery. surgery redone but he declined. He was doing well without any It was detected by transthoracic echocardiography. This case symptoms or haemolysis at the two-year follow up. emphasises the importance of clinical and echocardiographic follow-up examinations after mitral valve surgery to detect Discussion any unexpected complications. Mitral valve annuloplasty with flexible rings is a safe and stable Keywords: Duran annuloplasty ring, dehiscence, mitral regur- reconstructive procedure in which preservation of spatial motility gitation and configuration of the annulus allows a more physiologically natural valve repair with improvement of ventricular function. Submitted 16/7/10, accepted 12/9/11 In one study, five-year significant MR-free survival was 75.1 ± Cardiovasc J Afr 2012; 23: e8–e10 www.cvja.co.za 4.6% for the group of patients with Carpentier rings and 82.4 DOI: 10.5830/CVJA-2011-055 ± 4.5% for the group with Duran rings, with no significant difference.1 In another study using Duran rings, freedom from Dehiscence of a mitral annuloplasty ring is rare. We describe re-operation at seven years was 98% for both ischaemic and 2 a young patient with long-standing dehiscence of a Duran degenerative MR. annuloplasty ring, which on transthoracic echocardiography was Post mitral valve repair, early recurrent MR is usually seen rocking. procedure related [incomplete initial repair, suture dehiscence
Case report A 21-year-old man with mitral valve prolapse and severe symptomatic mitral regurgitation (MR) had undergone minimally invasive mitral valve repair three years earlier. Through an upper-J mini-sternotomy into the fourth right intercostal space, under standard moderate hypothermic cardiopulmonary bypass, he had undergone anterior leaflet (A2 segment) chordal shortening, followed by the placement of a 31-mm Duran flexible mitral ring, using interrupted sutures. Post-operatively as well as at his first annual echocardiographic Fig. 1. Transthoracic echocardiography in the parasternal examination, he showed no MR. He was followed up in the long-axis (A) and short-axis (B) views showing gross dehiscence of the Duran mitral annuloplasty ring (arrow- cardiology clinic and was doing well, with no symptoms. On heads). LA, left atrium; LV, left ventricle; MV, mitral valve. cardiac auscultation, however, there was the appearance of a pansystolic murmur, which had not been noted after the surgery. There was no history of endocarditis or trauma. Transthoracic and transoesophageal echocardiographic studies revealed a rocking Duran annuloplasty ring in the left atrium, with severe eccentric, posterolateral-directed MR (Figs 1, 2). The Duran ring had completely detached from the mitral annulus except at the lateral commissural area and was flail
Department of Cardiology, Royal Hospital, Muscat, Sultanate of Oman Fig. 2. Transoesophageal echocardiography showing PRASHANTH PANDURANGA, MD, MRCP (UK), prashanthp_69@ dehiscence of the Duran mitral annuloplasty ring along yahoo.co.in with the disrupted sutures (A). Colour Doppler (B) show- ing the severe eccentric mitral regurgitation jet. LA, left MOHAMMED K MUKHAINI, MD, FRCPC, FACC atrium; AML, anterior mitral leaflet. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e9
(ring or leaflet), residual cleft/prolapse or residual annular dilatation of the anterior and posterior mitral ring segments, dilatation, systolic anterior motion of the mitral valve causing together with asymmetrical ventricular dilatation, causing left ventricular outflow tract obstruction, rupture of previously tethering and therefore MR.13 It was noted that annuloplasty shortened or transferred chordae, elongations or ruptures of using flexible rings may not completely remodel the native valve chordae from previously shortened papillary muscles, flail and, in particular, neglect the insertion area of the anterior mitral or perforated leaflet]. Late failure however is usually valve leaflet. related (progressive degenerative disease, valvular retractions, Silberman et al.14 analysed long-term outcomes in 169 or endocarditis).3,4 patients who had undergone mitral valve annuloplasty and In their study, Dumont et al.3 observed that suture dehiscence coronary artery bypass grafting. Over a mean clinical follow was the most common cause (42%) for procedure-related up of almost 58 months, 34% in the patient group with flexible early failure of mitral valve repair, occurring at the sites of rings had residual MR to a moderate or greater degree, compared leaflet resection and at the annuloplasty ring. This early suture with 15% in the group with rigid rings. Therefore we feel that dehiscence can occur due to a fragile mitral annulus, superficial a rigid or semi-rigid ring would cause significant reduction sutures, regurgitation due to leaflet problem causing undue in the antero-posterior diameter and thus reduce residual MR, stress on the rings, or increased tension on suture lines,3 and due compared to a using flexible ring. to endocarditis5 or blunt chest trauma.6,7 This underscores the Another novel surgical procedure with promising results is importance of the creation of a tension-free repair, especially the use of biodegradable annuloplasty rings, which remodel in large posterior leaflet resection. A sliding repair to reduce the shape, reinforce the repair, restore the function of the atrio- tension on the suture lines is suggested.3 ventricular valves, and maintain the three-dimensional dynamic Clinically, dehiscence of the annuloplasty ring can result motion and geometry of the mitral valve annulus.15 in significant MR, heart failure or haemolysis.8 Our patient had gross dehiscence of the Duran ring secondary to suture dehiscence, occurring very late after surgery (without a history Conclusion of endocarditis or chest trauma), which is uncommon. Late The exact cause for such late suture dehiscence in our patient is dehiscence of an annuloplasty ring at one year has previously not known, but the above drawbacks of the flexible ring would been reported.5 have played a significant role. In our patient, ring dehiscence as well as its attachment to the lateral commissural area of the annulus was clearly demonstrated References with transthoracic and transoesophageal echocardiography. Recently, three-dimensional transoesophageal echocardiography 1. Chung CH, Kim JB, Choo SJ, et al. Long-term outcomes after mitral ring annuloplasty for degenerative mitral regurgitation: Duran ring has been reported to provide detailed anatomical information in versus Carpentier-Edwards ring. J Heart Valve Dis 2007; 16: 536–544. 8 8 patients with mitral ring dehiscence. Kronzon et al. reported 2. Makhija Z, Desai J. Early and mid-term functional and survival benefits eight patients with ring dehiscence and they observed that in ischemic versus degenerative mitral valve repair using Duran flexible dehiscence occurred mainly in a posterior or lateral location. ring: a single surgeon series. Interact CardioVasc Thorac Surg 2009; 9: There was only one anterior dehiscence. 471–475. The reasons postulated for increased occurrence of posterior 3. Dumont E, Gillinov AM, Blackstone EH, et al. Reoperation after mitral valve repair for degenerative disease. Ann Thorac Surg 2007; dehiscence of the ring are: the posterior annulus is in the far 84: 444‒450. surgical field, thus limiting the view while suturing, performance 4. Agricola E, Oppizzi M, Maisano F, et al. Detection of mechanisms of of a more superficial suturing posteriorly by the surgeon to avoid immediate failure by transesophageal echocardiography in quadrangu- the circumflex artery, or due to calcifications and fibrosis of the lar resection mitral valve repair technique for severe mitral regurgita- mitral annulus, which are more prevalent posteriorly, making it tion. Am J Cardiol 2003; 91: 175–179. less amenable to suturing.8 In our patient it was a circumferential 5. Alexioua C, Doukasa G, Swanevelderb J, Sosnowski A. Late dehis- dehiscence, but it was in the lateral commissural location, which cence of a mitral annuloplasty band in an asymptomatic patient: the value of follow-up with echocardiography. Eur J Cardiothorac Surg is uncommon. 2004; 25: 642. Recently, it has been observed that saddle-shaped mitral 6. Ramakrishna H. Incidental TOE finding – Carpentier mitral annulo- rings, compared to presently available flat rings, may reduce plasty ring dehiscence during heart transplantation. Ann Card Anaesth systolic strain in both the radial and circumferential directions, 2008; 11: 49–50. leading to reduction in loading on the suture lines and potentially 7. Kolowca M, Domaradzki W, Biernat J, et al. Mitral annuloplasty ring improving repair durability and preventing dehiscence.9,10 In dehiscence after blunt chest trauma. Kardiol Pol 2007; 65: 575–576. another study, complete rings increased the non-planarity angle 8. Kronzon I, Sugeng L, Perk G, et al. Real-time 3-dimensional transesophageal echocardiography in the evaluation of post-operative of the mitral valve (making the native mitral annulus less saddle mitral annuloplasty ring and prosthetic valve dehiscence. J Am Coll shaped), compared with partial rings. Neither of the two types of Cardiol 2009; 53: 1543–1547. rings was found to restore the non-planarity angle to the normal 9. Jensen MO, Jensen H, Smerup M, et al. Saddle-shaped mitral valve range.11 annuloplasty rings experience lower forces compared with flat rings. In a meta-analysis, Chee et al.12 observed that flexible Circulation 2008; 118: S250–255. annuloplasty rings demonstrated comparable outcomes for 10. Padala M, Hutchison RA, Croft LR, et al. Saddle shape of the mitral annulus reduces systolic strains on the P2 segment of the posterior patients with MR secondary to degenerative mitral valve disease, mitral leaflet. Ann Thorac Surg 2009; 88: 1499–1504. compared to semi-rigid/rigid annuloplasty rings. With regard 11. Mahmood F, Subramaniam B, Gorman JH 3rd, et al. Three-dimensional to ischaemic MR, it was observed that there was continued echocardiographic assessment of changes in mitral valve geometry after global and regional left ventricular remodelling with subsequent valve repair. Ann Thorac Surg 2009; 88: 1838–1844. e10 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
12. Chee T, Haston R, Togo A, Raja SG. Is a flexible mitral annuloplasty plasty. J Am Soc Echocardiogr 2009; 22: 1256–1264. ring superior to a semi-rigid or rigid ring in terms of improvement in 14. Neirotti R, Cikirikcioglu M, Della Martina A, Le Goff P, Kalangos A. symptoms and survival? Interact Cardiovasc Thorac Surg 2008; 7: New technology: valve repair using biodegradable rings. Rev Bras Cir 477–484. Cardiovasc 2008; 23: 556–561. 13. Magne J, Pibarot P, Dumesnil JG, Sénéchal M. Continued global left 15. Silberman S, Klutstein MW, Sabag T, et al. Repair of ischemic mitral ventricular remodeling is not the sole mechanism responsible for the regurgitation: comparison between flexible and rigid annuloplasty late recurrence of ischemic mitral regurgitation after restrictive annulo- rings. Ann Thorac Surg 2009; 87: 1721–1727. AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e11
Case Report
Repair of a right coronary artery arising from the pulmonary artery ADEM GULER, MEHMET ALI SAHIN, CELALETTIN GUNAY, ARTAN JAHOLLARI, HARUN TATAR
Abstract Transthoracic echocardiography revealed advanced We present here the fourth patient in the literature, over the hypokinesia of the posterior, inferior and mid-basal septum, age of 50 years old, with an abnormal right coronary artery minimal mitral regurgitation and decreased left ventricular arising from the pulmonary artery, who was successfully ejection fraction (45%). The left ventricle’s internal diameter in treated with surgery. Pre-operative computerised tomogra- diastole (LVIDd) was 57 mm. phy (CT) angiography revealed an abnormal right coronary Coronary angiography revealed markedly dilated and tortuous artery arising from the pulmonary artery. The right coro- coronary arteries. The right coronary artery arose from the nary artery was surgically transposed from the pulmonary pulmonary trunk and had collateral filling from the left coronary artery to the ascending aorta with the aid of cardiopulmo- system. Computerised tomography (CT) angiography was nary bypass. The patient had an uneventful postoperative applied for anatomical imaging and ARCAPA was confirmed course and the corrected anatomy was documented by post- (Fig. 1). The ectopic ostium of the RCA was from the right operative CT angiography. anterior pulmonary cusp.
Keywords: anomalous right coronary artery, coronary malfor- Surgical technique mation, ARCAPA After a median sternotomy and pericardiotomy, cannulas for Submitted 13/4/10, accepted 12/9/11 cardiopulmonary bypass (CPB) were placed into the right atrium Cardiovasc J Afr 2012; 23: e11–e13 www.cvja.co.za and ascending aorta. The left anterior descending artery (LAD) DOI:10.5830/CVJA-2011-054 was markedly dilated and tortuous. The aorta and pulmonary
Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary malformation.1 In contrast to the Bland–Garland–White syndrome (anomalous left coronary artery from the pulmonary artery, ALCAPA), most patients with ARCAPA remain asymptomatic.2,3 Although the course of the disease has been considered benign, case reports of sudden cardiac death do exist. Successful surgical repair basically depends on re-establishment of a bi-coronary system.4 We present here the fourth case in the literature of a patient over the age of 50 years who was treated successfully with surgery.
Case report A 51-year-old man had been admitted to hospital with a history of syncope and complaints of palpitations and dyspnoea on effort since childhood. No pathology was found on physical examination. There was no murmur on cardiac auscultation. The ECG revealed Q waves and negative T waves in the inferior leads. The chest X-ray was normal. Cardiac enzymes were within the normal range.
Department of Cardiovascular Surgery, Gülhane Military Medical Academy, Etlik, Ankara, Turkey ADEM GULER, MD MEHMET ALI SAHIN, MD, [email protected] CELALETTIN GUNAY, MD Fig. 1. Pre-operative CT angiography (three-dimensional ARTAN JAHOLLARI, MD reconstruction) showing the abnormal right coronary artery arising from the pulmonary artery. RCA: right coro- HARUN TATAR nary artery, Ao: aorta, PA: pulmonary artery. e12 CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 AFRICA
trunk were separated from each other. After institution of CPB, an aortic cross clamp was applied and cold crystalloid cardioplegia was administered. The origin of the anomalous right coronary artery arising from the right anterior aspect of the main pulmonary trunk was dissected and transected from the pulmonary trunk. The defect on the pulmonary trunk was repaired with a primary closure. A hole was created with a 5-mm punch slightly to the left anterior aspect of the ascending aorta, and the right coronary artery was anastomosed there. A standard decannulation procedure was performed. After sternal and wound closure, the patient was transferred to the cardiac surgical intensive care unit, and the following day to the postoperative ward. After an uneventful postoperative course, the patient was discharged on the sixth postoperative day. During the follow up, the patient was asymptomatic. No change in cardiac enzymes was observed. The corrected anatomy was documented by postoperative CT angiography (Fig. 2). At 24 months after the procedure, the patient had a normal treadmill test and echocardiography revealed a hypokinetic inferior septum, increased left ventricle ejection fraction (54%), minimal mitral regurgitation and a LVIDd of 54 mm.
Discussion Anomalous origin of the coronary arteries from the pulmonary artery is a rare congenital cardiac anomaly. Its incidence is one in 30 000 to 300 000 live births.5-8 ALCAPA is the most common form of this type of anomaly, accounting for more than 90% of cases and 0.5% of all congenital cardiac anomalies.6 ARCAPA is very rare compared to ALCAPA.7, 9 The only predictable morphological finding is an increase in Fig. 2. Postoperative CT angiography (three-dimensional the size of the left main coronary artery and its branches, and an reconstruction) showing the right coronary artery trans- 7 posed to the ascending aorta. RCA: right coronary artery, increase in the size of the RCA with thinning of its wall. As in Ao: aorta. our patient, the ectopic ostium of the RCA originates from the right anterior pulmonary cusp in the majority of cases. Right This anomaly shows different clinical signs when it becomes coronary artery dominance is usual. The flow pattern in the symptomatic. Dyspnoea develops in 17% of patients, while collateral circulation between the left coronary system and the fatigue occurs in 13%, angina in 17%, mitral regurgitation in RCA is similar to that of coronary atherosclerosis. The major 9%, congestive heart failure in 30% and cardiac arrest in 17% source of collateral circulation to the RCA is septal branches of of patients.3 Objective findings were not specific in most of the LAD.10 the cases, except in those who had angiography. Ischaemia was In this anomaly, left and right ventricular functions are not present in 40% of patients. corrupted and findings of impaired cardiac function do not In adults, this anomaly is typically diagnosed due to a cardiac occur.10 Generally there are no signs of myocardial ischaemia, murmur or during angiography performed for other reasons.10 while symptoms and clinical findings of congestive heart failure However, hidden ischaemia, revealed from a positive stress may be present only in rare paediatric cases.11 test and angina (mostly atypical angina) may develop in some In an autopsy series of nine cases, congestive heart failure patients.13 was found in a two-year-old child who died without any previous Although an ECG is helpful in the investigation of ALCAPA, symptoms, in an 11-year-old patient who died from cardiac it does not play a meaningful role in diagnosing right coronary arrest, and in a 72-year-old male patient. There were no signs artery anomaly. Generally there are no ischaemic changes and of cardiac pathology or impaired cardiac function reported in ventricular hypertrophy is usually absent or borderline. The heart the remaining six patients.7 In 30 of these 58 patients, other than silhouette in telecardiography may be slightly increased. Although the autopsy cases, the anomaly was primarily diagnosed with diagnostic findings may be present on echocardiography, there angiography. At the time of diagnosis their ages varied between has been no report in the literature of any case diagnosed one day and 90 years old.12 with only this method. Besides 12 cases diagnosed at autopsy, The real incidence of this anomaly is probably higher than three cases were diagnosed intra-operatively, 25 cases with reported because a large number of patients are asymptomatic. angiography, while in five cases, angiography was performed This is opposite to what is seen in ALCAPA. Findings of mitral after the echocardiographic findings suggested this anomaly. regurgitation and myocardial infarction, often seen in the early It is not enough to show that the right coronary artery does ages of ALCAPA, are not encountered in this anomaly. not originate from the aortic root, it is important to determine AFRICA CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012 e13
whether it originates from the pulmonary artery or not. A dilated reviex of the literature. Am Heart J 2006; 152: 1004.e9–17. left coronary artery and a wide right coronary artery observed 2. Kreutzer C, Schlicter AJ, Roman MI, Kreutzer GO. Emergency ligation on echocardiography should be the first cause of suspicion. of anomalous left coronary artery arising from the pulmonary artery. Ann Thorac Surg 2000; 69: 1591–1592. A definite diagnosis is determined with angiography. Passing 3. Radke PW, Messmer BJ, Haaher PK, Klues HG. Anomalous origin of contrast through the left coronary artery that originates from the right coronary artery: preoperative and postoperative hemodynam- the aorta and observing the passage of contrast through the ics. Ann Thorac Surg 1998; 66: 1444–1449. collaterals to the right coronary artery and finally into the 4. Bunton R, Jonas RA, Lang P, Rein AJ, Castenada AR. Anomalous pulmonary artery is diagnostic.7 origin of coronary artery from pulmonary artery: ligation versus astab- As can be seen in the literature, medical treatment was given lishment of a two coronary artery system. J Thorac Cardiovasc Surg 1987; 93: 103–108. to a few patients in whom clinical follow up was not done.14 5. Vouhe PR, Baillot-Vernant F, Trinquet F, Sidi D, de Geeter B, Khoury Usually surgical treatment is suggested, even in asymptomatic W, et al. Anomalous left coronary artery from the pulmonary artery patients. In the literature it is reported that 87% of patients in infants: which operation? When? J Thorac Cardiovasc Surg 1987; diagnosed early had surgical treatment.3 Besides the less- 94(2): 192–199. traumatic simple proximal ligation of the abnormal coronary 6. Wolf DD, Vercruysse T, Suys B, Blom N, Matthys D, Ottenkamp J. artery, in order to remove pulmonary steal, separating the Major coronary anomalies in childhood. Eur J Pediatr 2002; 161: abnormal artery from the pulmonary artery and re-implanting it 637–642. 7. Roberts WC. Major anomalies of coronary arterial origin seen in adult- into the aorta is the appropriate surgical procedure. hood. Am Heart J 1986; 111: 941–963. Surgical treatment is important for two reasons: first, providing 8. Wu QY, Xu ZH. Surgical treatment of anomalous origin of coronary two coronary systems with antegrade flow, re-implanting the artery from the pulmonary artery. Chin Med J (Engl) 2008; 121(8): aberrant artery into the aorta decreases the risk of sudden 721–724. cardiac death, and second, it removes the risk of pulmonary 9. Canale LS, Monteiro AJ, Rangel I, Wetzel E, Pinto DF, Barbosa RC, et steal phenomenon.15 In their comprehensive study, Radke et al. Surgical treatment of anomalous coronary artery arising from the al.3 reported the postoperative follow up of nine patients who pulmonary artery. Interact Cardiovasc Thorac Surg 2009; 8(1): 67–69. 10. Angelini P, Villason S, Chan AV, Diez J. Normal and anomalous coro- had surgical intervention: there had been regression in the left nary arteries in human. In: Angelini P (ed). Coronary Artery Anomalies: coronary artery dilatation after surgical correction. It was also A Comprehensive Approach. Philadelphia: Lippincott Williams and reported that symptoms and ischaemia did not disappear in two Wilkins, 1999: 49. patients with a dilated left coronary artery and slow peripheral 11. Vairo U, Marino B, de Simone G, Marcelletti C. Early congestive heart flow. failure due to origin of the right coronary artery from the pulmonary artery. Chest 1992; 102: 1610–1612. 12. Gerlish LM, Ho SY, Milo S. Three anomalies of the coronary arter- Conclusion ies co-existing in a case of pulmonary atresia with intact ventricular Although medical treatment is an option in an abnormal right septum. Int J Cardiol 1990; 29: 93–95. 13. Ladowski JS, Belvedere DA, Wuest LF. Anomalous origin of the right coronary artery (different from ALCAPA where re-implantation coronary artery from the pulmonary artery: an unusual cause of angina. into the aorta of the aberrant artery is obligatory), surgical Cardiovasc Surg 1995; 3: 81–83. correction of the anatomy is strongly supported by 14. Mahdyoon H, Brymer JF, Alam M, Khaja F. Anomalous right coronary physiopathological findings. artery from the pulmonary artery presenting with angina and aneurys- mal left ventricular dilatation. Am Heart J 1989; 118: 182–184. 15. Mintz GS, Iskandrian AS, Bemis CE, Mundth ED, Owens JS. References Myocardial ischemia in anomalous origin of the right coronary artery 1. Williams IA, Gersony W, Hellenbrand WE. Anomalous right coronary from the pulmonary trunk. Proof of a coronary steal. Am J Cardiol artery arising from the pulmonary artery: A report of 7 cases and a 1983; 51: 610–612. Today’s Prevention. Tomorrow’s Protection.
Reduce your risk of stroke and heart attack with Bayer Aspirin Cardio® 100 Why take Bayer Aspirin Cardio® 100? Aspirin, an antiplatelet agent, which slows the clotting process, is widely used among patients with cardiovascular disease, which includes heart attacks, stroke and peripheral vascular disease. 1, 2, 5, 6 During a heart attack, blood clots form in an already-narrowed artery and block the fl ow of oxygen-rich blood to the heart muscle or to parts of the brain, in the case of a stroke. 7 Studies have shown that aspirin reduced the number of strokes by 20 % and heart attacks by 30 %. It has been determined that for every 67 patients treated to protect against heart attacks and stroke, one life could be saved with low-dose aspirin therapy. 6 Doctors use different guidelines to decide who should take daily aspirin. Consult your Doctor or Pharmacist.
What are the Risk Factors for Coronary Heart Disease and Stroke? 3, 4 Major Risk Factors Include: • Cigarette smoking • Hypertension (high blood pressure) Protect • High cholesterol their passion • Diabetes mellitus for living. • Advancing age • Atrial Fibrilation Other Risk Factors Include: • Obesity • Physical Inactivity • Family History of premature coronary heart disease • Blood clotting abnormalities
Information brought to you by Bayer, the innovators of Aspirin.
References: 1. Cox D, Maree O, Dooley M, Conroy R, Byrne M, Fitsgerald DJ. Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers. 2006;2153-2158. 2. Healthwise Website. WebMD Reference from Healthwise. Last Updated: December 09,2010 3. Grundy S, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka, Housten-Millar N, Kris-Etherton P, Krumholz HM, LaRosa J, Ockene IS, Pearson TA, Reed J, Washington R, Smith SC. Primary Prevention of Coronary Heart Disease: Guidance from Framingham. A statement for healthcare professionals from the AHA task force on risk reduction. 2011;1876-1887 4. Chock AWY, O’Brien KK, Stading JA, Shea JL. Stroke risks and primary stroke prevention. 2011. The Journal of Modern Pharmacy. August 20-26 5. Package Insert for Bayer Aspirin Cardio 100 6. Weisman SM, Graham DY. Evaluation of the benefi ts and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. 2002;162:2197-2202. 7. WebMD. Heart Disease Health Centre: Low-Dose Aspirin Therapy – Topic Overview
S0 Bayer® Aspirin Cardio 100. Each tablet contains 100 mg of acetylsalicylic acid (ASA). Reg. No. 31/8/0413. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority (MCC). Bayer (Pty) Ltd, Reg.No.1968/011192/07. 27 Wrench Road, Isando, 1609. Tel (011) 921-5911. L.ZA.GM.04.2012.0409 10000141HC JUNE 2012 VOL 23 NO 5
AFRICA
www.cvja.co.za CardioVascular Journal of Africa (official journal for PASCAR)
• Global target on non-communicable diseases
• Obesity and blood pressure level of adolescents in Abeokuta
• Prevalence, awareness, treatment and control of hypertension
• Cardiovascular risk in black Africans
• Robotically controlled ablation for atrial fibrillation
• Cardiovascular disease in sub-Saharan Africa
• Effusive constrictive pericarditis
• Heart failure guidelines
• The role of aspirin in cardiovascular disease
PUBLISHED ONLINE:
Cardiovascular Journal of Africa . Vol 23, No 5, June 2012 • The dangerous fifth chamber
• Rocking mitral annuloplasty ring Printed by Durbanville Commercial Printers Tel: 021 946 4074 Tel: Printed by Durbanville Commercial Printers