JULY/AUGSUT 2023 VOL 34 NO 3 • Prognost ic value of myocardial scar cardiomyopathy • Trends and outcomes of cardiovascular disease admissions in Niger ia • Two decades of implantable cardioverter def ibr i l lator implantat ion • Prevalence and r isk factors for elevated blood pressure in South Afr ica • Creat ing blood conservat ion for a cardiothoracic surgical hospi tal • Assessment of papi l lary muscle free strain in hypertrophic cardiomyopathy • Electr ic cardioversion in pat ients treated wi th oral ant icoagulants • Permanent His bundle pacing using a Biotronik stylet-dr iven lead CardioVascular Journal of Afr ica (off icial journal for PASCAR) www.cvja.co.za
PERINDOPRIL TERT-BUTYLAMINE / AMLODIPINE 4 mg/5 mg 4 mg/10 mg 8 mg/5 mg 8 mg/10 mg For further product information contact PHARMA DYNAMICS Email info@pharmadynamics.co.za CUSTOMER CARE LINE +27 21 707 7000 www.pharmadynamics.co.za PEARLOC 4 mg/5 mg, 4 mg/10 mg, 8 mg/ 5 mg, 8 mg/10 mg. Each tablet contains 4, 8 mg perindopril tert -butylamine respectively and 5, 10 mg amlodipine respectively. S3 A50/7.1.3/0230, 0231, 0232, 0233. For full prescribing information, refer to the professional information approved by SAHPRA, February 2021. 1) Data on file. 2) Bahl VK, et al. Management of hypertension with fixed combination of perindopril and amlodipine in daily clinical practice. Results from the STRONG prospective, observational, multicentre study. American Journal of Cardiovascular Drugs 2009(3):135-142. 3) Bertrand ME. Perindopril/Amlodipine combination: an optimal synergy for cardiovascular protection. European Heart Journal supplements 2009;11(supplement E):E22-E25. 3) Telejko E, Perindopril arginine: Benefits of a new salt of the ACE inhibitor perindopril. Current Medical Research and Opinion 2007;23(5):953-960. PCD1045/05/2023. FORMULARY LISTINGS1 DISCOVERY HEALTH Exec/Comp Core/Saver/Priority Keycare MPL MMAP MRP MMI 4 mg/ 5 mg 4 mg/ 10 mg 8 mg/ 5 mg 8 mg/ 10 mg * All plans excluding the low chronic and restrictive formulars. Bahl VK, et al. reported PERINDOPRIL/AMLODIPINE, an optimal synergy for: • Significant BP reductions2 • Improved tolerability2 and According to Bertrand ME. PERINDOPRIL/AMLODIPINE, an optimal synergy for: • Reduction of CV events3 PERINDOPRIL TERT-BUTYLAMINE 8 mg IS EQUIVALENT TO PERINDOPRIL ARGININE 10 mg4
ISSN 1995-1892 (print) ISSN 1680-0745 (online) Cardiovascular Journal of Afr ica www.cvja.co.za CONTENTS INDEXED AT SCISEARCH (SCI), PUBMED, PUBMED CENTRAL AND SABINET Vol 34, No 3, JULY/AUGUST 2023 EDITORS Editor-in-Chief (South Africa) PROF PAT COMMERFORD Assistant Editor PROF JAMES KER (JUN) Regional Editor DR A DZUDIE Regional Editor (Kenya) DR F BUKACHI Regional Editor (South Africa) PROF R DELPORT EDITORIAL BOARD PROF PA BRINK Experimental & Laboratory Cardiology PROF R DELPORT Chemical Pathology PROF MR ESSOP Haemodynamics, Heart Failure & Valvular Heart Disease DR OB FAMILONI Clinical Cardiology DR V GRIGOROV Invasive Cardiology & Heart Failure PROF J KER (SEN) Hypertension, Cardiomyopathy, Cardiovascular Physiology DR J LAWRENSON Paediatric Heart Disease PROF A LOCHNER Biochemistry/Laboratory Science DR MT MPE Cardiomyopathy PROF DP NAIDOO Echocardiography PROF B RAYNER Hypertension/Society PROF MM SATHEKGE Nuclear Medicine/Society PROF YK SEEDAT Diabetes & Hypertension PROF H DU T THERON Invasive Cardiology INTERNATIONAL ADVISORY BOARD PROF DAVID CELEMAJER Australia (Clinical Cardiology) PROF KEITH COPELIN FERDINAND USA (General Cardiology) DR SAMUEL KINGUE Cameroon (General Cardiology) DR GEORGE A MENSAH USA (General Cardiology) PROF WILLIAM NELSON USA (Electrocardiology) DR ULRICH VON OPPEL Wales (Cardiovascular Surgery) PROF PETER SCHWARTZ Italy (Dysrhythmias) PROF ERNST VON SCHWARZ USA (Interventional Cardiology) SUBJECT EDITORS Nuclear Medicine and Imaging DR MM SATHEKGE Heart Failure DR G VISAGIE Paediatric DR S BROWN Paediatric Surgery DR DARSHAN REDDY Renal Hypertension DR BRIAN RAYNER Surgical DR F AZIZ Adult Surgery DR J ROSSOUW Epidemiology and Preventionist DR AP KENGNE Pregnancy-associated Heart Disease PROF K SLIWA-HAHNLE 131 FROM THE EDITOR’S DESK P Commerford CARDIOVASCULAR TOPICS 132 Prognostic value of myocardial scar in ischaemic and non-ischaemic cardiomyopathy using cardiac magnetic resonance imaging R Laymouna • E El-Sharkawy • S El-Tahan • M Elfiky 140 Trends and outcomes of cardiovascular disease admissions in Lagos, Nigeria: a 16-year review AC Mbakwem • CE Amadi • JN Ajuluchukwu • OA Kushimo 150 Clinical profile and outcomes of young patients treated with implantable cardioverter defibrillators at a South African tertiary hospital: a review of two decades of implantable cardioverter defibrillator implantation and follow up P Mkoko • K Solomon • A Chin 157 Prevalence and associated risk factors for elevated blood pressure in young adults in South Africa S Naidoo • J Fabian • SA Norris 164 Creating blood conservation for a cardiothoracic surgical hospital: when you have to start from scratch! C Indelen • YU Kizmaz • A Erkilinc • AE Altinay • A Shander • MK Kirali 169 Assessment of papillary muscle free strain in hypertrophic cardiomyopathy and hypertension-induced left ventricular hypertrophy C Yildiz • A Koyuncu • L Ocal • MO Gursoy • E Oflar • G Kahveci 175 Combined systolic velocities using tissue Doppler imaging could predict the severity of cirrhosis: a prospective cohort study I Dönmez • E Acar
CONTENTS Vol 34, No 3, JULY/AUGUST 2023 FINANCIAL & PRODUCTION CO-ORDINATOR ELSABÉ BURMEISTER Tel: 021 976 8129 Fax: 086 664 4202 Cell: 082 775 6808 e-mail: elsabe@clinicscardive.com PRODUCTION EDITOR SHAUNA GERMISHUIZEN Tel: 021 785 7178 Cell: 083 460 8535 e-mail: shauna@clinicscardive.com CONTENT MANAGER MICHAEL MEADON (Design Connection) Tel: 021 976 8129 Fax: 0866 557 149 e-mail: michael@clinicscardive.com The Cardiovascular Journal of Africa, incorporating the Cardiovascular Journal of South Africa, is published 10 times a year, the publication date being the third week of the designated month. COPYRIGHT: Clinics Cardive Publishing (Pty) Ltd. LAYOUT: Jeanine Fourie – TextWrap PRINTER: Tandym Print/Castle Graphics ONLINE PUBLISHING & CODING SERVICES: Design Connection & Active-XML.com All submissions to CVJA are to be made online via www.cvja.co.za Electronic submission by means of an e-mail attachment may be considered under exceptional circumstances. Postal address: PO Box 1013, Durbanville, RSA, 7551 Tel: 021 976 8129 Fax: 0866 644 202 Int.: +27 21 976 8129 e-mail: info@clinicscardive.com Electronic abstracts available on Pubmed Audited circulation Full text articles available on: www.cvja. co.za or via www.sabinet.co.za; for access codes contact elsabe@clinicscardive.com Subscription: To subscribe to the online PDF version of the journal, e-mail elsabe@clinicscardive.com • R500 per issue (excl VAT) • R2 500 for 1-year subscription (excl VAT) The views and opinions expressed in the articles and reviews published are those of the authors and do not necessarily reflect those of the editors of the Journal or its sponsors. In all clinical instances, medical practitioners are referred to the product insert documentation as approved by the relevant control authorities. REVIEW ARTICLE 181 Electric cardioversion in patients treated with oral anticoagulants: embolic material in the left atrial appendage J Karwowski • J Rekosz • M Solecki • R Mączyńska-Mazuruk • K Wrzosek • J Sumińska-Syska • M Dłużniewski CASE REPORT 190 Permanent His bundle pacing using a Biotronik stylet-driven lead: feasibility and early outcomes from a single centre B Vezi • A Olujimi • M Ngatcha • A Bonny • J Ragadu PUBLISHED ONLINE (Available on www.cvja.co.za and in PubMed)
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 AFRICA 131 From the Editor’s Desk Cardiovascular disease (CVD)-related admissions are on the increase in Africa. Amadi and colleagues report (page 140) that in a study carried out in a tertiary hospital over a 16-year period in Lagos, Nigeria, that CVD admissions are not only common in Nigeria, but there was also a temporal exponential increase in both the admission and death rates, most likely reflecting the epidemiological transition in that country. Notably, the median age of the patients was 56.6 (46.0–68.0) years. As has been noted previously, the transition seems to be associated with presentation of the conditions at a younger age. Naidoo and colleagues, in a study of young black Africans living in urban South Africa (page 157), have shown a high prevalence of elevated blood pressure (EBP), particularly in males, and that an overwhelming proportion who had EBP at 22 years continued to have EBP six years later. In addition, EBP in females was associated with a history of gestational hypertension and injectable contraceptive use, while in males EBP was associated with haematuria. Albuminuria, a surrogate marker for vascular and renal target-organ damage, was associated with EBP with profound implications for premature cardiovascular and all-cause mortality, while also providing opportunities for lifestyle and therapeutic interventions to mitigate risk. Specialist electrophysiological services are not widely available in Africa and it is pleasing to see that they appear to be increasing and usage is being documented. In this, the first reported case series from Africa, Vezi and co-authors document their experience with His bundle pacing (HBP) for a variety of indications (page 190). They stress the importance of HBP in resource-limited countries. It is important to recognise that these excellent results may be influenced by operator experience. In young patients without atherosclerotic coronary artery disease, the aetiology of sudden cardiac death (SCD) has been described in Europe and North America. However, there are important regional variations and there are limited data on the aetiology and outcome of SCD in South Africa. Mkoko and colleagues (page 150) sought to determine the profile and outcomes of young patients treated with implantable cardioverter defibrillators (ICDs) at a South African tertiary hospital. In this single-centre study from South Africa, arrhythmogenic right ventricular cardiomyopathy and repaired congenital heart disease were the leading causes of SCD in patients younger than 35 years treated with secondary-prevention ICDs. Primaryprevention ICDs were frequently implanted for idiopathic dilated cardiomyopathy. Appropriately, the authors point out the limitations of their study. Pat Commerford Editor-in-Chief Professor PJ Commerford
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 132 AFRICA Cardiovascular Topics Prognostic value of myocardial scar in ischaemic and non-ischaemic cardiomyopathy using cardiac magnetic resonance imaging Reem Laymouna, Eman El-Sharkawy, Salah El-Tahan, Mohamed El-Fiky Abstract Aim: The aim of this research was to evaluate the prognostic value of myocardial scar using cardiac magnetic resonance (CMR) imaging in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM). Methods: One hundred and fifty-four patients with either ICM or NICM underwent CMR with late gadolinium enhancement sequences for assessment of left ventricular ejection fraction (LVEF), and detection and quantification of any myocardial scar using three methods: manual, number of segments involved, and percentage of scarred myocardium. Patients were followed up for at least six months for clinical cardiac events. Results: Patients were divided into two groups: group I, patients with ICM (58%) and group II, those with NICM (42%). Clinical presentation ranged from eventless (10%) to chest pain (18%), heart failure (15%), hospitalisation (35%), syncope (1%), ventricular tachycardia (< 1%) and cardiac arrest (< 1%). The scar mass was larger in size in group I (17 ± 15%) than in group II (8 ± 13%). A direct relationship was observed between scar size and event severity (p < 0.001). An inverse relationship between LVEF and event severity was found in group I (p < 0.001) but not in group II (p = 0.128). Conclusion: Myocardial scar size was a strong predictor of clinical outcome in both the ICM and NICM patients. LVEF was less reliable in predicting morbidity in cardiomyopathy patients. Keywords: ischaemic cardiomyopathy, non-ischaemic cardiomyopathy, cardiac MRI, myocardial scar Submitted 12/8/21; accepted 2/7/22 Published online 23/9/22 Cardiovasc J Afr 2023; 34: 132–139 www.cvja.co.za DOI: 10.5830/CVJA-2022-040 Cardiac muscle is a unique muscle type to perform a specific function: conducting electrical activity to both ventricles simultaneously to contract and relax in a synchronised manner, and pumping the blood to the whole body with a proper myocardial reserve to meet the varying physiological body situations.1 Therefore, evaluation of the myocardial muscle function using only left ventricular ejection fraction (LVEF) would be inaccurate. However, assessment of the myocardium on the tissue level to determine how healthy it is would be expected to provide more precise data regarding the ability to conduct, contract and relax properly. Tissue characterisation using cardiac magnetic resonance (CMR) provides more knowledge about the pathological processes occurring in different types of cardiomyopathy, hence, more prognostic information about each type of cardiomyopathy.2 Gadolinium contrast has a large molecular size that under normal conditions allows it to distribute in the extracellular space without penetrating the intact myocardial cells.3 However, in certain pathological circumstances, either the extracellular space may increase, such as in some non-ischaemic cardiomyopathy (NICM), or the myocardial cell membrane may be disrupted, as in ischaemic cardiomyopathy (ICM), leading to an increase in the amount of gadolinium distribution and gadolinium enhancement.4,5 Different types of cardiomyopathies exhibit different patterns of late enhancement,6,7 which open up entirely new possibilities in the differential diagnosis in patients with ventricular dysfunction. Late gadolinium enhancement (LGE) is based on differences in extracellular space in different areas of the myocardium, therefore it is more useful when the fibrosis is regional, for example, myocarditis, myocardial infarction scar, sarcoidosis and hypertrophic cardiomyopathy.6,7 Currently, there is no uniform approved way to quantify the myocardial scar size in cardiac magnetic resonance imaging (MRI) LGE sequences. Several methods have been used, such as number of segments with scar, manual planimetry of the enhanced myocardium, and automatic quantification using signal thresholding techniques to determine scar borders. For the last approach, most often the full width at half-maximum (FWHM) technique and two-standard deviations (2-SD) technique were used, as described originally by Kim et al.8 for myocardial infarction. Our study aim was to evaluate the prognostic value of myocardial scar using CMR on the clinical outcome in patients Cardiology and Angiology Department, Alexandria University, Alexandria, Egypt Reem Laymouna, PhD, r_hamdy10@alexmed.edu.eg Eman El-Sharkawy, MB BCh, MSc, PhD Salah El-Tahan, MB BCh, MSc, PhD Mohamed El-Fiky, MB BCh, MSc, PhD International Cardiac Centre Scan, Alexandria, Egypt Reem Laymouna, PhD Eman El-Sharkawy, MB BCh, MSc, PhD Salah El-Tahan, MB BCh, MSc, PhD
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 AFRICA 133 with ICM and NICM and compare it to the prognostic value of the LVEF in the same study population. Methods This study included 154 patients who were diagnosed to have cardiomyopathy (both ischaemic and non-ischaemic) using cardiac MRI (1.5 tesla). The patients were either referred from heart failure clinics or recruited directly after having been diagnosed by cardiac MRI. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol got the approval of the Committee of Ethics of the Alexandria University. CMR was performed using the 1.5-T machine. Sequences were ECG-triggered and performed in breath-hold technique using a body array coil. Myocardial function was assessed with cine steady-state free-precession (SSFP) pulse sequences that were acquired in stacks of short-axis slices covering the whole left ventricle with eight to 10 contiguous sections. LGE was acquired 10 minutes after intravenous gadolinium contrast (0.2 mmol/kg) by using a gradient-spoiled turbo fast low-angle shot sequence with phase-sensitive inversion recovery technique in four- and two-chamber views and a series of left ventricular short axes (section thickness 6 mm). The cardiac MRI study analysis included (1) ventricular function assessment (LVEF) though volume measurements in short-axis cine images; (2) detection of any myocardial scar or fibrosis using short-axis, two-, three- and four-chamber LGE images; (3) quantification of myocardial scar/fibrosis using three methods: manual quantification of the LGE mass in each slice of the short-axis LGE sequence; number of segments involved in the scar tissue (segments involving LGE); percentage of the scarred myocardium (summation of the percentage of the scarred myocardium in each segment of the 17 myocardial segments in relation to the total left ventricular mass). All 154 patients were followed up for at least six months for any clinical cardiac events. These events were scaled according to severity, from one (less severe) to seven (most severe); ranging from mild chest pain (non-acute coronary syndrome), mild dyspnoea (New York Heart Association stage I–II), and including hospital admission due to decompensated heart failure and up to syncope, documented ventricular arrhythmia and sudden cardiac arrest/death, respectively. Follow-up details were collected from hospital records and arranged phone calls with patients. Statistical correlation between the amount of the scarred myocardium in both ICM and NICN patients and the severity of the clinical events during the period of the follow up was performed. If any patient had experienced more than one event, the most serious one was considered the main event for this patient. Details of clinical events were collected from hospital records. Additional phone calls were arranged to get more details about the patient’s symptoms. Statistical analysis Data were fed into the computer and analysed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). The Kolmogorov–Smirnov test was used to verify the normality of distribution of variables. The Spearman coefficient was used to correlate between quantitative variables. Significance of the obtained results was judged at the 5% level. Results One hundred and fifty-four patients were included in the study, and 87 patients (56%) were male and 69 (44%) were female, with a mean age of 61 ± 15 years (range 20–87). The time of the clinical follow up was variable, with a minimum of six months and a mean of 10 months (from six to 40 months). Our patients were divided into two groups; 89 (58%) were diagnosed with ICM and 65 (42%) with NICM. The NICM subgroup included a variety of different aetiologies of cardiomyopathies: 41 patients were diagnosed to have dilated cardiomyopathy (DCM), seven with Takotsubo cardiomyopathy, five with left ventricular non-compaction, four with apical non-obstructive hypertrophic cardiomyopathy (HCM), three with amyloidosis, two with sarcoidosis, two with arrhythmogenic left ventricular dysplasia and one patient with endomyocardial fibrosis. Of the 154 patients, 52 (34%) had LVEF < 45% (28 patients in group I and 24 in group II) and 102 (66%) patients had LVEF ≥ 45% (61 patients in group I and 41 in group II). All the 154 patients were followed up clinically for at least six months. The clinical presentation ranged from eventless (no events) in 16 patients (six in group I, 10 in group II), chest pain in 28 (18%) patients (19 in group I, nine in group II), heart failure in 23 (15%) (12 in group I, 11 in group II), hospitalisation in 54 (35%) patients (35 in group I, 19 in group II), syncope in 14 (1%) (six in group I, eight in group II), ventricular tachycardia in nine (< 1%) patients (five in group I, four in group II) and cardiac arrest in 10 (< 1%) patients (six in group I, four in group II). Our main concern in this study was to determine whether there was a relationship between the scar size detected in the LGE CMR and the severity of clinical presentation of the patient during the follow up. In our study, a direct relationship between the absolute size of the myocardial scar (g) and event severity was observed (p < 0.001, rs = 0.464), as shown in Table 1 and Fig 1. When the two subgroups were compared, the scar mass was larger in size in group I (19.5 ± 18.9 g) than in group II (11.3 ± 19.9 g) but still with a linear relationship between scar size and event severity (p < 0.001) in both groups (Fig. 1). The size of the scar was also assessed by the total number of segments involved in the scar. Again, there was a significant direct relationship between the number of segments involved in this scar and event severity in both subgroups (group I, p < 0.001, rs = 0.490; group II, p < 0.001, rs = 0.536). The third method to evaluate the myocardial scar mass was through calculation of the percentage of myocardial scar to the total myocardial mass (by estimating the percentage of scar tissue in each segment of the 17 myocardial segments separately, each myocardial segment representing 1/17th of the total myocardial mass). The mean scar percentage was 17 ± 15% in the ICM patients and 8 ± 13% in the NICM patients. There was also a direct relationship observed between the estimated percentage of scarred myocardium and event severity (group I, p < 0.001, rs = 0.468; group II, p < 0.001, rs = 0.558) (Fig. 2).
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 134 AFRICA Regarding the left ventricular systolic function assessed by LVEF, there was an inverse relationship between the LVEF and event severity in the ICM group (p = 0.013, rs = –0.263) (Fig. 3). This was different from the results of the NICM group where there was no significant correlation between the LVEF and event severity (p = 0.128, rs = 0.180). Discussion Many of the recent research studies concerned with myocardial scar were designed to assess the presence or absence of this scar and its relationship with sudden cardiac arrest and/or malignant ventricular arrhythmias, hence the indication for implantable cardioverter–defibrillator (ICD) insertion, paying less attention to the rest of the clinical spectrum of the outcome.8 In our study, we were not only interested in sudden cardiac arrest as the main outcome. The wider spectrum of clinical events is thought to provide more data on expected clinical pattern, hence, treatment plans and expected quality of life in cardiomyopathy patients. A linear relationship was clearly observed between the size of the myocardial scar (using any of the three methods) and the severity of the clinical event. More serious cardiac events such as hospitalisation due to heart failure, serious arrhythmias and Table 1. Analysis of scar mass, actual number of scar segments, percentage of scar and LVEF in groups I and II Event Scar mass (g), mean ± SD Number of scar segments, mean ± SD Percentage of scar, mean ± SD LVEF (%), mean ± SD Total* Group I* Group II* Total* Group I* Group II* Total* Group I* Group II* Total Group I* Group II No events 0.3 ± 0.4 0.4 ± 0.4 0.2 ± 0.3 0.5 ± 0.7 0.8 ± 0.8 0.3 ± 0.7 1.5 ± 2.1 2.5 ± 2.2 0.9 ± 2.0 52.4 ± 14.6 62.2 ± 8.6 46.5 ± 14.5 Chest pain 0.9 ± 0.8 1.3 ± 0.7 0.2 ± 0.4 1.3 ± 1.1 1.7 ± 0.9 0.3 ± 0.7 5.4 ± 4.7 7.4 ± 4.2 1.0 ± 2.1 59 ± 10.5 61.8 ± 8.1 53.0 ± 13 Heart failure 1.4 ± 1.9 2.0 ± 1.8 0.8 ± 1.8 2.1± 2.2 2.6 ± 1.7 1.6 ± 2.7 8.4 ± 11.0 11.8 ± 10.6 4.8 ± 10.7 46.1 ± 13.1 51.3 ± 13 40.5 ± 11 Hospitalisation 4.1 ± 3.0 4.7 ± 2.9 2.8 ± 3 5.5 ± 3.5 5.9 ± 2.7 4.8 ± 4.7 23.9 ±17.8 27.9 ± 16.9 16.6 ± 17.7 44.4 ± 14.9 41.8 ± 12.9 49.1 ± 17.3 Syncope 1.4 ± 1.2 1.9 ± 1.1 1.0 ± 1.2 2.5 ± 1.9 3.1 ± 1.10 2.1 ± 1.9 8.2 ± 7.2 11.3 ± 6.6 5.9 ± 7.2 51.6 ± 19.3 54.8 ± 15.8 49.3 ± 22.3 Ventricular tachycardia 1.7 ± 1.3 1.6 ± 1.2 1.8 ± 1.5 2.4 ± 1.7 2.2 ± 1.3 2.6 ± 2.2 9.8 ± 7.5 9.4 ± 7.3 10.3 ± 8.8 49.7 ± 16.2 53.6 ± 10.5 44.8 ± 22.3 Arrest 2.7 ± 1.8 3.3 ± 1.8 1.9 ± 1.8 3.3± 1.7 3.8 ± 1.5 2.5 ± 1.9 15.9 ± 10.8 19.1 ± 10.8 11.0 ± 10.3 60.9 ± 10.5 58.7 ± 13.3 64.3 ± 4.0 *Statistical significance with event severity. 90 80 70 60 50 40 30 20 10 0 Scar mass Event severity 1 2 3 4 5 6 7 rs = 0.464* p < 0.001* 120 100 80 60 40 20 0 Scar mass Event severity 1 2 3 4 5 6 7 rs = 0.542* p < 0.001* 100 80 60 40 20 0 Scar mass Asympt CP HF HA Syncope VT Arrest Event 120 100 80 60 40 20 0 Scar mass Asympt CP HF HA Syncope VT Arrest Event * * * * * * Fig. 1. Relationship between event severity and scar mass; A and C for group I, and B and D for group II. Asympt, asymptomatic; CP, chest pain; HF, heart failure; HA, hospitalisation; VT, ventricular tachycardia. A C B D
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 AFRICA 135 sudden cardiac arrest were detected more often in patients with a larger scar size in both groups (p < 0.001) (Figs 4–6). It was observed that serious cardiac events were less often seen in patient with a mean scar mass of < 5.4–8.4%. On the contrary, patients who had experienced sudden cardiac arrest had a mean scar mass of 15.9% and patients with ventricular tachycardia had a mean scar mass of 9.8% (Table 1). It was also interesting that hospitalisation with decompensated heart failure was significantly more frequent in patients with a high scar mass, especially in ICM patients with a mean scar mass of 27.9%. This may be explained that the scar mass in ICM patients was directly reflecting the severity of the baseline coronary artery disease and the number of territories involved. Another finding that may support this theory is that the mean LVEF for those patients was < 45%. Neilan et al.9 demonstrated that for every 1% of left ventricular mass increase in scar size, the risk of cardiovascular death or ventricular arrhythmia increased by 15%. This relationship was similar whether scar size was measured using the 2-SD method [hazard ratio (HR) 1.15; 95% confidence interval (CI): 1.12–1.18] or the FWHM method (HR 1.16; 95% CI: 1.12–1.20). When only arrhythmic events were considered, the extent of the scar was again associated with higher event risk (HR 1.17 for each 1% absolute increase in scar size; 95% CI: 1.12–1.22). Similar results were reported by Gulati et al.,10 where for each percentage scar extent, the risk of all-cause mortality was increased by 11% (HR 1.11; 95% CI: 1.06–1.16) and the risk for arrhythmic events was increased by 10% (HR 1.10; 95% CI: 1.05–1.16). Li et al.11 aimed to develop a risk score [LGE-based prediction of sudden cardiac death (SCD) risk in non-ischaemic dilated cardiomyopathy (NIDCM) (ESTIMATED)] based on LGE in CMR to predict SCD in patients with NIDCM and LVEF ≤ 35%. They followed up 395 patients with NIDCM for three years for SCD events. The estimated score (constructed by the LGE extent > 14%, syncope, atrial flutter/fibrillation, non-sustained ventricular tachycardia, advanced atrioventricular block, and age ≤ 20 or > 50 years) showed good calibrations for SCD prediction.11 From the score, 20.3% of primary-prevention patients were categorised as high risk (≥ three points), 28.1% as intermediate risk (two points) and 51.6% as low risk (zero to one point) for three-year SCD events (45.9 vs 20.1 vs 5.1%, p < 0.0001). The three-year SCD events were also well in agreement with the score stratification in patients without ICDs.11 Their study suggested LGE-based (ESTIMATED) risk score to be validated in providing refined SCD prediction. The score may help to identify candidates for primary-prevention ICDs in patients with NIDCM.11 80 70 60 50 40 30 20 10 0 % of scar Event severity 1 2 3 4 5 6 7 rs = 0.468* p < 0.001* 80 70 60 50 40 30 20 10 0 % of scar Event severity 1 2 3 4 5 6 7 rs = 0.558* p < 0.001* 80 70 60 50 40 30 20 10 0 % of scar Asympt CP HF HA Syncope VT Arrest Event * 80 60 40 20 0 % of scar Asympt CP HF HA Syncope VT Arrest Event * * ** ** * * Fig. 2. Relationship between event severity and scar percentage; A and C for group I, and B and D for group II. Asympt, asymptomatic; CP, chest pain; HF, heart failure; HA, hospitalisation; VT, ventricular tachycardia. A C B D
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 136 AFRICA Our study included both the ischaemic and non-ischaemic spectrum, studied independently and also compared to each other. Moreover, the follow up included a wider spectrum of clinical events ranging from mild chest pain or shortness of breath, passing through hospitalisation due to decompensated heart failure and up to malignant arrhythmia and sudden cardiac arrest. We were concerned about the clinical pattern of the patients regarding their morbidity, hospitalisation and quality of life. The mean LVEF was 51 ± 14% (18–77) in group I (32% of group I with LVEF < 45% and 69% with LVEF > 45%) and 48 ± 16% (9–77) in group II (37% of group II with LVEF < 45% and 63% with LVEF > 45%). There was a statistically significant linear relationship between left ventricular systolic dysfunction represented by LVEF and event severity in group I (p = 0.013). On the other hand, for group II patients, there was no clear relationship between LVEF and event severity (p = 0.150). In this non-ischaemic group, the main predictor of cardiac events was scar mass. For example, in the four patients in group II who experienced sudden cardiac arrest, the LVEF was > 45% but with a high scar mass average (13.99 ± 13.77 g). It was also observed in group I that the lower LVEF was more linked with hospitalisation due to decompensated heart failure (63% of the hospital admissions had LVEF < 45%). On the other hand, most of the patients with no events or mild chest pain or dyspnoea had LVEF > 45%. This could be explained by the fact that in ischaemic patients, the amount of scarred myocardium was directly linked to the severity of the underlying coronary artery disease, and the amount of scar mass and its distribution may also indicate the number of coronary territory affected. In non-ischaemic patients, the preserved LVEF is misleading because it does not indicate the degree of underlying myocardial pathology. However, LGE in cardiac MRI is more precise in tissue characterisation and spotting unhealthy myocardium that is usually a substrate for serious arrhythmogenic events and subsequently sudden cardiac arrest, even in cases of preserved LVEF.12 In the report by Dokainish et al.,13 they had a similar outcome to ours when they evaluated the prognostic implications of left ventricular systolic and diastolic dysfunction early post-acute ST-segment elevation myocardial infarction. Patients with LVEF ≤ 45% and restrictive diastolic function (RDF) were at greatly increased risk of major adverse cardiovascular events (MACE) (HR 8.85, 95% CI: 4.21–18.60) compared to patients with LVEF ≥ 45% and without RDF. RDF remained a strong predictor for MACE in patients with LVEF ≥ 45% (HR 4.38, 95% CI: 1.52–12.60), and in multivariate models adjusted for LVEF, left ventricular end-systolic volume and clinical variables. 90 80 70 60 50 40 30 20 10 0 LVEF Event severity 1 2 3 4 5 6 7 rs = 0.263* p < 0.013* 90 80 70 60 50 40 30 20 10 0 LVEF Event severity 1 2 3 4 5 6 7 rs = 0.180 p < 0.150 80 60 40 20 0 LVEF Asympt CP HF HA Syncope VT Arrest Event 80 60 40 20 0 LVEF Asympt CP HF HA Syncope VT Arrest Event Fig. 3. Relationship between event severity and LVEF; A and C for group I, and B and D for group II. Asympt, asymptomatic; CP, chest pain; HF, heart failure; HA, hospitalisation; VT, ventricular tachycardia. A C B D
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 AFRICA 137 Fig. 6. CMR images. A and B: short-axis and two-chamber cine images, C and D: short-axis and two-chamber LGE images showing transmural myocardial scar of the basal and mid-cavity inferior and inferolateral segments (four segments), partially involving both papillary muscles. The evaluated myocardial scar mass was 28 g, representing 24% of the myocardium for a patient admitted with heart failure symptoms. A C B D Fig. 5. CMR images. A and B: four-chamber and short-axis cine images, C and D: four-chamber and short-axis LGE of left ventricular non-compaction in an asymptomatic patient (nine-month follow up) with no myocardial scar/fibrosis. LVEF was 47%. A C B D Fig. 4. CMR LGE images. A: two-chamber, B: four-chamber, C: three-chamber long axis views, D: basal, E and F: mid-cavity shortaxis views showing extensive mid-myocardial fibrosis for a patient with arrhythmogenic left ventricular cardiomyopathy, presented with multiple syncopal episodes. The Holter monitor showed frequent multifocal ventricular ectopic beats. LVEF was 54%, scar mass was 9.9 g, representing 16% of the myocardial mass detected in eight segments. A D B E C F
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 138 AFRICA Regarding non-ischaemic cardiomyopathy, Ge et al.14 investigated whether structural abnormality on CMR represented by LGE may be a predictor of MACE in patients with non-sustained ventricular tachycardia (NSVT) and ventricular tachycardia (VT)/SCD. They studied 651 patients (age 54 ± 15; 61% male) referred to CMR for ventricular arrhythmia, who were divided into two groups according to the presence of NSVT (53%) or sustained VT/aborted SCD (47%). MACE was a composite of cardiovascular death, a need for heart transplantation or left ventricular assist device and recurrent VT/ventricular fibrillation needing therapy. The mean LVEF was 54 ± 13% and LGE was present in 39% of patients (mean 9.5 ± 8%).14 A structurally abnormal heart, defined by LGE, abnormalities in wall motion or impaired systolic function was observed in 52% of patients (n = 336). A change in diagnostic impression based on CMR took place for 27% of patients with NSVT versus 40% of patients with VT/SCD (p < 0.001). A total of 122 patients experienced MACE during the follow-up period (median, 3.6 years). Structural abnormality detected on CMR was found to be an independent predictor of MACE (HR 3.65; 95% CI: 2.09–6.27; p < 0.001).14 Although each of the three methods used to quantify the myocardial scar using LGE in CMR has a different concept to calculate the size of the scar, they all showed comparable results. The manual method is a commonly used technique,15 however, it is extremely time consuming. The second method, using the total number of segments involving any LGE is theoretically less accurate as it considers one segment affected even if the late enhancement is focal or minimal. On the other hand, it is the least time-consuming method as it gives only a general impression of how many of the myocardial segments include scarred tissue. However, the third method, summation of the percentage of the scarred myocardium in each segment of the 17 myocardial segments, is less time consuming than the manual one, with considerable accuracy in representing how much of the myocardium is unhealthy. Many other methods were tested and compared for accuracy in quantifying myocardial scar. Flett et al.15 studied the reproducibility of LGE quantification techniques in three different pathological conditions: acute myocardial infarction, chronic myocardial infarction and HCM, using seven techniques. These were manual quantification, automatic methods including thresholding by 2-, 3-, 4-, 5- or 6-SD above remote myocardium, and the FWHM technique. They concluded that regardless of the underlying disease, the FWHM technique for LGE quantification gave mean LGE volume results similar to manual quantification and it was statistically the most reproducible, reducing the required sample sizes by up to a half.15 Another study by Gao et al.16 using automatic thresholding measured a 50% larger scar size going from 5-SD to 2-SD thresholds above remote myocardial signal intensity. Neilan et al.9 found that scar size was, on average, 50% greater using the 2-SD technique versus the FWHM technique (9 ± 5% by 2-SD method vs 6 ± 4% by FWHM method), however, there was close correlation between both the measurements (r = 0.92, p < 0.001), and more importantly, both methods of quantification showed robust prognostic association. Therefore, despite the different ways used to quantify myocardial scar, manual assessment is considered one of the most accurate methods. However, no one specific method has been agreed on to be the standard yet. The small number of patients included in our study, especially in each type of cardiomyopathy, is one of the limitations in our study. In addition, longer follow-up time would have added more significant predictive value. Conclusion Myocardial scar/fibrosis using CMR is a reliable parameter that can reflect the degree of diseased myocardium. The amount of scarred or fibrosed myocardium is found to be directly linked to the severity of the clinical event in both ICM and NCIM patients. The larger the scar size, the more severe was the clinical event, even with preserved LVEF. Therefore, quantification of myocardial scar/fibrosis could be used as a predictor for cardiac events, hospitalisation and SCD. LVEF is not always linked with severity of the cardiac event, especially in NICM patients. Low LVEF was mainly linked with hospitalisation in both ICM and NICM patients. References 1. ECG & Echo Learning. Clinical Echocardiography. Myocardial mechanics: structure and function of myocardial fibers. Available from: https:// ecgwaves.com/topic/structure-and-function-of-myocardial-fibersmyocardium/ 2. Treibel TA, White SK, Moon JC. Myocardial tissue characterization: histological and pathophysiological correlation. Curr Cardiovasc Imaging Rep 2014; 7(3): 9254. 3. Klein C, Nekolla SG, Balbach T, Schnackenburg B, Nagel E, Fleck E, et al. The influence of myocardial blood flow and volume of distribution on late Gd-DTPA kinetics in ischemic heart failure. J Magn Reson Imaging 2004; 20(4): 588–593. 4. Klein C, Schmal TR, Nekolla SG, Schnackenburg B, Fleck E, Nagel E. Mechanism of late gadolinium enhancement in patients with acute myocardial infarction. J Cardiovasc Magn Reson 2007; 9(4): 653–658. 5. Kelle S, Roes SD, Klein C, Kokocinski T, de Roos A, Fleck E, et al. Prognostic value of myocardial infarct size and contractile reserve using magnetic resonance imaging. J Am Coll Cardiol 2009; 54(19): 1770–1777. 6. Beek AM, Kühl HP, Bondarenko O, Twisk JW, Hofman MB, van Dockum WG, et al. Delayed contrast-enhanced magnetic resonance imaging for the prediction of regional functional improvement after acute myocardial infarction. J Am Coll Cardiol 2003; 42 (5): 895–901. 7. McCrohon JA, Moon JC, Prasad SK, McKenna WJ, Lorenz CH, Coats AJ, et al. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation 2003; 108(1): 54–59. 8. Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999; 100(19): 1992–2002. 9. Neilan TG, Coelho-Filho OR, Danik SB, Shah RV, Dodson JA, Verdini DJ, et al. CMR quantification of myocardial scar provides additive prognostic information in nonischemic cardiomyopathy. J Am Coll Cardiol Cardiovasc Imaging 2013; 6(9): 944–954. 10. Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. J Am Med Assoc
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 AFRICA 139 2013; 309(9): 896–908. 11. Li X, Fan X, Li S, Sun W, Shivkumar K, Zhao S, et al. A novel risk stratification score for sudden cardiac death prediction in middle-aged, nonischemic dilated cardiomyopathy patients: the ESTIMATED score. Can J Cardiol 2020; 36(7): 1121–1129. 12. Luo N, O’Connor CM, Chiswell K, Anstrom KJ, Newby LK, Mentz RJ. Survival in patients with nonischemic cardiomyopathy with preserved vs reduced ejection fraction. CJC Open 2021; 3(11): 1333–1340. 13. Dokainish H, Rajaram M, Prabhakaran D, Afzal R, Orlandini A, Staszewsky L, et al. Incremental value of left ventricular systolic and diastolic function to determine outcome in patients with acute ST-segment elevation myocardial infarction: the echocardiographic substudy of the OASIS-6 trial. Echocardiography 2014; 31(5): 569–578. 14. Ge Y, Antiochos P, Qamar I, Seno A, Steigner ML, Aghayev A, et al. Diagnostic impact and prognostic value of cardiac MRI in patients with ventricular arrhythmias. J Am Coll Cardiol 2020; 75(11 Supplement 1): 3665. 15. Flett AS, Hasleton J, Cook C, Hausenloy D, Quarta G, Ariti C, et al. Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. J Am Coll Cardiol Cardiovasc Imaging 2011; 4(2): 150–156. 16. Gao P, Yee R, Gula L, Krahn AD, Skanes A, Leong-Sit P, et al. Prediction of arrhythmic events in ischemic and dilated cardiomyopathy patients referred for implantable cardiac defibrillator: evaluation of multiple scar quantification measures for late gadolinium enhancement magnetic resonance imaging. Circ Cardiovasc Imaging 2012; 5(4): 448–456. Several low-dose drugs better for BP than one pill: Australian meta-analysis Researchers have found that taking three or four medications at lower doses, rather than just a single pill, may help people lower their blood pressure without increasing the risk of most negative side effects. To estimate how much benefit this kind of low-dose combination therapy offers for controlling blood pressure, a team, led by the University of New South Wales, Australia, reviewed seven previous randomised clinical trials, and also combined the results of these studies, using the statistical method known as a meta-analysis, reports Healthline. Their findings, published in Journal of the American Medical Association, Cardiology, suggest that combining low doses of three or four blood pressure-lowering medications is safe and effective as an initial treatment strategy for high blood pressure. Previously, three-drug combinations had been recommended only if people have difficulty keeping their blood pressure under control with two drugs. The seven randomised clinical trials compared low-dose combinations of three or four blood pressure-lowering drugs to treatment with a single drug, usual care, or an inactive placebo. Researchers defined low doses as half or less than half the standard dose. The clinical trials included 1 918 patients. In five of the trials, participants were followed for four to 12 weeks, and for six to 12 months in the other two trials. People treated with low-dose drug combinations saw their systolic blood pressure decrease on average by 16 to 28 mmHg over four to 12 weeks, the analysis showed. In contrast, systolic blood pressure decreased 12 to 18 mm Hg on average in the group taking one drug or receiving usual care. At six and 12 months, people receiving low-dose combination therapy continued to have greater reductions in their blood pressure compared with the one-drug or usualcare groups. Low-dose combination therapy also lowered blood pressure more than placebo. In addition, a greater percentage of people receiving low-dose combination therapy lowered their blood pressure below 140/90 mmHg, compared with those receiving one drug or usual care. This was true during the short- and longterm follow ups. According to the American Heart Association, hypertension stage two is when the blood pressure is consistently at or above 140/90 mmHg. Two-thirds of people in the clinical trials were able to control their blood pressure with low-dose combination therapy, the researchers found. However, that means that one-third would ‘require treatment intensification to achieve better control rates,’ they wrote. Overall, there was a low risk of adverse effects with low-dose combination therapy, although people taking three or four medications were more likely to experience dizziness than those treated with one drug or usual care. One limitation of the analysis is that some of the clinical trials included people who were taking blood pressurelowering medications at the start of the trial, so low-dose combination therapy was not their initial treatment. However, the authors of the study found that the results were similar when they compared people who had already been taking medications to those who started on the low-dose combination therapy. Another limitation was that the analysis included only a few clinical trials, with just two trials following patients for six to 12 months, meaning the researchers might not be able to clearly see if people on the low-dose combination therapy had fewer or more side effects than the other groups. Dr Michael Broukhim, an interventional cardiologist at Providence Saint John’s Health Centre in Santa Monica, said larger studies would be needed to clearly assess the adverse effects of low-dose combination therapy. Ideally, he would like to see a larger randomised clinical trial that compares low-dose combination therapy to taking a single pill, focused on people with high blood pressure but no related health conditions. The study also shows patients tolerate low doses of multiple medications, an approach that may work better than increasing the dose of a single medication to achieve blood pressure control. With many medications, upping the dosage increases the risk of negative side effects. continued on page 148…
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 140 AFRICA Trends and outcomes of cardiovascular disease admissions in Lagos, Nigeria: a 16-year review Amam C Mbakwem, Casmir Ezenwa Amadi, Jayne N Ajuluchukwu, Oyewole A Kushimo Abstract Background: Cardiovascular disease (CVD)-related admissions are on the increase in Nigeria and the rest of Africa. This study was carried out to highlight the burden, patterns and outcomes of CVD admissions in a tertiary hospital over a 16-year period in Lagos, Nigeria. Methods: Admissions records of patients admitted into the medical wards within the study period (January 2002 to December 2017) were reviewed and relevant information pertaining to the study objectives was retrieved for analysis. Results: There were a total of 21 369 medical admissions and 4 456 (20.8%) CVD-related admissions. A total of 3 582 medical deaths were recorded and 1 090 (30.4%) CVD-related deaths. The median age of the patients was 56.6 (46.0–68.0) years and 51.4% of these were males. Stroke, heart failure, hypertensive disease and acute coronary syndrome constituted 51.2, 36.2, 11.3 and 1.6% of all CVD admissions, respectively. There was a cumulative increase in the number of CVD admissions and deaths (p < 0.001, respectively) during the period under review. Conclusion: CVD admissions are not only common in Nigeria, but there was also a temporal exponential increase in both the admission and death rates, most likely reflecting the epidemiological transition in Nigeria. Keywords: CVD admissions, temporal patterns, stroke, heart failure Submitted 5/10/21, accepted 2/7/22 Published online 30/8/22 Cardiovasc J Afr 2023; 34: 140–148 www.cvja.co.za DOI: 10.5830/CVJA-2022-037 Cardiovascular disease (CVD), typified by stroke, coronary heart disease and heart failure, is a pre-eminent and preventable cause of death globally, accounting for an estimated 29% of all deaths.1 Over 80% of the global burden of CVD is borne by the low- and middle-income countries (LMICs). This burden of CVD is on a backdrop of the perennial high prevalence of infectious diseases and poverty-related morbidities and mortalities in these regions, constituting a double burden of disease profile.2,3 It is believed that by 2030, CVD and non-communicable diseases will be the dominant conditions in these countries.4 The rising prevalence of CVD in these LMICs is fuelled by rapid urbanisation and westernisation and its corollary of globalisation of risks (unhealthy lifestyles): increased consumption of saturated fats and sugars, high salt intake, increasing physical inactivity, smoking and unhealthy use of alcohol. These unhealthy behaviours predispose to the development of biological risk factors for CVD, such as obesity, hypertension, diabetes and dyslipidaemia.4-6 The consequence is a rising burden of CVD. In high-income countries (HIC), CVD remains the greatest contributor to mortality. However, the incidence has either plateaued or has assumed a downward trend over the past half century.7,8 This has been attributed to the success of public health policies and regulation to reduce exposure to a range of risk factors for CVD, improved medical management of these risk factors, opportunistic screening to detect asymptomatic disease, emergency care and treatment.9-11 Data in the published literature show that CVD-related admissions are quite rife, constituting about 31% of all medical admissions in the USA, with ischaemic heart disease being the major cause of admission.12 In Saudi Arabia, CVDs constitute 34.4% of hospital admissions, with stroke being the leading cause.13 In Africa about one-tenth of all medical admissions are CVD related and stroke and heart failure are the major causes.14,15 In Nigeria, studies have shown that CVD-related admissions constitute about 20% of all medical admissions.16-18 However, these studies reviewed hospital admission records spanning a few years and did not demonstrate the temporal trends in these admissions and their outcomes. In essence there is limited knowledge of CVD burden and trajectories in Nigeria. Lagos is cosmopolitan in outlook and a microcosm of Nigeria. It is the country’s economic hub and is home to over 17 million people, about 10% of the Nigerian population.19 Nigeria, like several countries in LMICs, is going through epidemiological transition characterised by the rising burden of non-communicable diseases, including CVD. There are anecdotal reports that CVD admissions are quite common in Lagos. An earlier study in the same hospital looking at hypertension-related emergency room (ER) deaths over a 20-year period showed that stroke and heart failure were the major contributors.20 However, their patterns, temporal trends and outcomes have not been well characterised. Hence the necessity to study the pattern of CVD admissions and outcomes at the Lagos University Teaching Hospital, Nigeria, over a 16-year period. Ethics approval (reference number: ADM/DCST/HREC/889) for the study was obtained from the Health Research ethics committee of the hospital. College of Medicine, University of Lagos, Lagos, Nigeria Casmir Ezenwa Amadi, MD, acetalx@yahoo.com Amam C Mbakwem, MD Jayne N Ajuluchukwu, MD Department of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria Oyewole A Kushimo, MD
RkJQdWJsaXNoZXIy NDIzNzc=