Kemi Tibazarwa

Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): a cohort study

BACKGROUND The Heart of Soweto Study aims to increase our understanding of the characteristics and burden imposed by heart disease in an urban African community in probable epidemiological transition. We aimed to investigate the clinical range of disorders related to cardiovascular disease in patients presenting for the first time to a tertiary-care centre. METHODS From Jan 1 to Dec 31, 2006, we recorded data for 4162 patients with confirmed cases of cardiovascular disease (1593 newly diagnosed and 2569 previously diagnosed and under treatment) who attended the cardiology unit at the Chris Hani Baragwanath Hospital in Soweto, South Africa. We developed a prospectively designed registry and gathered detailed clinical data relating to the presentation, investigations, and treatment of all 1593 patients with newly diagnosed cardiovascular disease. FINDINGS Most patients were black Africans (n=1359 [85%]), and the study population contained more women (n=939 [59%]) than men. Women were slightly younger than were men (mean 53 [SD 16] years vs 55 [15] years; p=0.031), with 399 (25%) patients younger than 40 years. Heart failure was the most common primary diagnosis (704 cases, 44% of total). Moderate to severe systolic dysfunction was evident in 415 (53%) of 844 identified cases of heart failure, 577 (68%) of which were attributable to dilated cardiomyopathy or hypertensive heart disease, or both. Black Africans were more likely to be diagnosed with heart failure than were the rest of the cohort (739 [54%] vs 105 [45%]; odds ratio [OR] 1.46, 95% CI 1.11-1.94; p=0.009) but were less likely to be diagnosed with coronary artery disease (77 [6%] vs 88 [38%]; OR 0.10, 0.07-0.14; p<0.0001). Prevalence of cardiovascular risk factors was very high, with 897 (56%) patients diagnosed with hypertension (190 [44%] of whom were also obese). Only 209 (13%) patients had no identifiable risk factors, whereas 933 (59%) had several risk factors. INTERPRETATION We noted many threats to the present and future cardiac health of Soweto, including a high prevalence of modifiable risk factors for atherosclerotic disease and a combination of infectious and non-communicable forms of heart disease, with late clinical presentations. Overall, our findings provide strong evidence that epidemiological transition in Soweto, South Africa has broadened the complexity and spectrum of heart disease in this community. This registry will enable continued monitoring of the range of heart disease.

Evaluation of Bromocriptine in the Treatment of Acute Severe Peripartum Cardiomyopathy A Proof-of-Concept Pilot Study

Background— Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM. Methods and Results— A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P=0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM-Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P=0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival. Conclusions— In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly.

A time bomb of cardiovascular risk factors in South Africa: results from the Heart of Soweto Study "Heart Awareness Days"

BACKGROUND There is strong anecdotal evidence that many urban communities in Sub-Saharan Africa are in epidemiologic transition with the subsequent emergence of more affluent causes of heart disease. However, data to describe the risk factor profile of affected communities is limited. METHODS During 9 community screening days undertaken in the predominantly Black African community of Soweto, South Africa (population 1 to 1.5 million) in 2006-2007, we examined the cardiovascular risk factor profile of volunteers. Screening comprised a combination of self-reported history and a clinical assessment that included calculation of body mass index (BMI), blood pressure and random blood glucose and total cholesterol levels. RESULTS In total, we screened a total of 1691 subjects (representing almost 0.2% of the total population). The majority (99%) were Black African, there were more women (65%) than men and the mean age was 46+/-14 years. Overall, 78% of subjects were found to have >or=1 major risk factor for heart disease. By far the most prevalent risk factor overall was obesity (43%) with significantly more obese women than men (23% versus 55%: OR 1.76 95% CI 1.62 to 1.91: p<0.001). A further 33% of subjects had high blood pressures (systolic or diastolic) and 13% an elevated (non-fasting) total blood cholesterol level: no statistically significant differences between the sexes were found. There was a positive correlation between increasing BMI and other risk factors including elevated systolic (r(2)=0.046, p<0.001) and diastolic blood pressure (r(2)=0.032, p<0.001) with overweight subjects three times more likely to have concurrent hypercholesterolemia (OR 3.3, 95% CI 2.1 to 5.3: p<0.01). CONCLUSIONS These unique pilot data strongly suggest a high prevalence of related risk factors for heart disease in this urban black African population in epidemiologic transition. Further research is needed to confirm our findings and to determine their true causes and potential consequences.

Predictors of outcome in 176 South African patients with peripartum cardiomyopathy.

Objective Identify novel prognostic factors for patients with peripartum cardiomyopathy (PPCM). Design and setting Prospective cohort study conducted in a single tertiary care centre in South Africa. Patients 176 African women with newly diagnosed PPCM were studied. Interventions Clinical assessment, echocardiography and laboratory results were obtained at baseline and at 6 months. Main outcome measures Poor outcome was defined as the combined end point of death, left ventricular (LV) ejection fraction (LVEF) < 35%, or remaining in New York Heart Association (NYHA) functional class III/IV at 6 months. Complete LV recovery was defined as LVEF ≥55% at 6 months. Results Forty-five (26%) patients had a poor outcome. Multiple logistic regression analysis revealed that, after adjustment for age, NYHA functional class, LVEF and systolic blood pressure, increased left ventricular end systolic dimension (LVESD), lower body mass index (BMI) and lower total cholesterol at baseline were independent predictors of poor outcome (adjusted OR 1.09, 95% CI 1.04 to 1.15, p=0.001; OR 0.89, 95% CI 0.83 to 0.96, p=0.004, and OR 0.50, 95% CI 0.34 to 0.73, p=0.0004, respectively). Thirty (21%) of the 141 surviving patients with echocardiographic follow-up recovered LV function at 6 months. Multiple logistic regression analysis revealed that, after adjustment for NYHA functional class, LVEF and left ventricular end diastolic dimension, older age and smaller LVESD at baseline were predictors of LV recovery (OR 1.08, 95% CI 1.01 to 1.17, p=0.02 and OR 0.92, 95% CI 0.86 to 0.98, p=0.007, respectively). Conclusions This study suggests that increased LVESD, lower BMI and lower serum cholesterol at baseline may be independent predictors of poor outcome in patients with PPCM, while older age and smaller LVESD at baseline appear to be independently associated with a higher chance of LV recovery.

Long-term outcome of Peripartum cardiomyopathy in a population with high seropositivity for Human Immunodeficiency Virus

BACKGROUND Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy with a high risk of mortality. The present study assessed clinical outcome and mortality over a 2-year period in an African cohort of 80 PPCM patients. METHODS A prospective study over a 2-year period at a tertiary center, where 80 consecutive women presenting with PPCM were enrolled on first diagnosis. Patients obtained standard heart failure therapy. Detailed assessments included echocardiography, NYHA functional class, left ventricular ejection fraction (LVEF), mortality and serum levels for hemoglobin, CRP, IL-6, TNF-alpha, Fas/Apo-1, and T-cell count at each 6-month intervals for 24 months. RESULTS Baseline mean age was 30 ± 7 years; 38% were primigravidas and 34% were co-infected with HIV. NYHA functional class III-IV was present in 89% patients with a mean LVEF of 30 ± 9%. Four patients were lost to follow-up, 9 moved to remote areas, 7 were excluded due to subsequent pregnancy. The 2-year mortality rate was 28%. Eight of 80 (10%) died by 6 months. Mean LVEF of surviving patients was: 44 ± 11% at 6-months, 46 ± 13% at 12-months and 50 ± 14% at 24-months follow-up. Of the 69 patients still enrolled at 6 months 14 (20%) died over the remaining 18-month period, despite functional recovery. No statistically significant difference in LVEF and mortality was observed between PPCM patients with or without HIV co-infection. CONCLUSION The novel finding of this study is the continuous high mortality of PPCM patients occurring beyond 6 months independent of HIV infection and subsequent pregnancy. This finding strongly encourages the need for long-term clinical follow-up and management of women with PPCM.

HIV-1 infection alters CD4+ memory T-cell phenotype at the site of disease in extrapulmonary tuberculosis

HIV‐1‐infected people have an increased risk of developing extrapulmonary tuberculosis (TB), the immunopathogenesis of which is poorly understood. Here, we conducted a detailed immunological analysis of human pericardial TB, to determine the effect of HIV‐1 co‐infection on the phenotype of Mycobacterium tuberculosis (MTB)‐specific memory T cells and the role of polyfunctional T cells at the disease site, using cells from pericardial fluid and blood of 74 patients with (n=50) and without (n=24) HIV‐1 co‐infection. The MTB antigen‐induced IFN‐γ response was elevated at the disease site, irrespective of HIV‐1 status or antigenic stimulant. However, the IFN‐γ ELISpot showed no clear evidence of increased numbers of antigen‐specific cells at the disease site except for ESAT‐6 in HIV‐1 uninfected individuals (p=0.009). Flow cytometric analysis showed that CD4+ memory T cells in the pericardial fluid of HIV‐1‐infected patients were of a less differentiated phenotype, with the presence of polyfunctional CD4+ T cells expressing TNF, IL‐2 and IFN‐γ. These results indicate that HIV‐1 infection results in altered phenotype and function of MTB‐specific CD4+ T cells at the disease site, which may contribute to the increased risk of developing TB at all stages of HIV‐1 infection.

Heart Failure in Africa, Asia, the Middle East and South America: The INTER-CHF study

BACKGROUND There are few data on heart failure (HF) patients from Africa, Asia, the Middle East and South America. METHODS INTER-CHF is a prospective study that enrolled HF patients in 108 centers in 16 countries from 2012 to 2014. Consecutive ambulatory or hospitalized adult patients with HF were enrolled. Baseline data were recorded on sociodemographics, clinical characteristics, HF etiology and treatments. Age- and sex-adjusted results are reported. RESULTS We recruited 5813 HF patients: mean(SE) age=59(0.2)years, 39% female, 65% outpatients, 31% from rural areas, 26% with HF with preserved ejection fraction, with 1294 from Africa, 2661 from Asia, 1000 from the Middle-East, and 858 from South America. Participants from Africa-closely followed by Asians-were younger, had lower literacy levels, and were less likely to have health or medication insurance or be on beta-blockers compared with participants from other regions, but were most likely to be in NYHA class IV. Participants from South America were older, had higher insurance and literacy levels, and, along with Middle Eastern participants, were more likely to be on beta-blockers, but had the lowest proportion in NYHA IV. Ischemic heart disease was the most common HF etiology in all regions except Africa where hypertensive heart disease was most common. CONCLUSIONS INTER-CHF describes significant regional variability in socioeconomic and clinical factors, etiologies and treatments in HF patients from Africa, Asia, the Middle East and South America. Opportunities exist for improvement in health/medication insurance rates and proportions of patients on beta blockers, particularly in Africa and Asia.

Rationale and design of the Pan African Pulmonary hypertension Cohort (PAPUCO) study: implementing a contemporary registry on pulmonary hypertension in Africa

Introduction Pulmonary hypertension (PH) is a devastating, progressive disease with increasingly debilitating symptoms and usually shortened overall life expectancy due to a narrowing of the pulmonary vasculature and consecutive right heart failure. Little is known about PH in Africa, but limited reports suggest that PH is more prevalent in Africa compared with developed countries due to the high prevalence of risk factors in the region. Methods and analysis A multinational multicentre registry-type cohort study was established and tailored to resource-constraint settings to describe disease presentation, disease severity and aetiologies of PH, comorbidities, diagnostic and therapeutic management, and the natural course of PH in Africa. PH will be diagnosed by specialist cardiologists using echocardiography (right ventricular systolic pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure), usually accompanied by shortness of breath, fatigue, peripheral oedema and other cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per guidelines (European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines). Additional investigations such as a CT scan, a ventilation/perfusion scan or right heart catheterisation will be performed at the discretion of the treating physician. Functional tests include a 6 min walk test and the Karnofsky Performance Score. The WHO classification system for PH will be applied to describe the different aetiologies of PH. Several substudies have been implemented within the registry to investigate specific types of PH and their outcome at up to 24 months. Data will be analysed by an independent institution following a data analyse plan. Ethics and dissemination All local ethics committees of the participating centres approved the protocol. The data will be disseminated through peer-reviewed journals at national and international conferences and public events at local care providers.

The 12-lead ECG in peripartum cardiomyopathy

Background The value of the 12-lead electrocardiogram (ECG) to provide prognostic information in the deadly and disabling syndrome peripartum cardiomyopathy (PPCM) is unknown. Aims To determine the prevalence of major and minor ECG abnormalities in PPCM patients at the time of diagnosis, and to establish whether there are ECG correlates of persistent left ventricular dysfunction and/or clinical stability at six months of follow up, where available. Methods Twelve-lead ECGs were performed at the point of diagnosis on 78 consecutive women presenting with PPCM to two tertiary centres in South Africa and 44 cases (56%) at the six-month follow up. Blinded Minnesota coding identified major ECG abnormalities and minor ECG changes. Results The cohort mainly comprised young women of black African ancestry (90%) [mean age 29 ± 7 years and median body mass index 24.3 (IQR: 22.7–27.5) kg/m2]. The majority of cases (n = 70; 90%) presented in sinus rhythm (mean heart rate 100 ± 21 beats/min). At baseline, at least one ECG abnormality/variant was detected in 96% of cases. Major ECG abnormalities and minor changes were detected in 49% (95% CI: 37–60%) and 62% (95% CI: 51–74%) of cases, respectively; the most common being T-wave changes (59%), p-wave abnormality (29%) and QRS-axis deviation (25%). Of the 44 cases (56%) reviewed at six months, normalisation of the 12-lead ECG occurred in 25%; the most labile ECG features being heart rate (mean reduction of 27 beats/min; p < 0.001) and abnormal QRS axis (36 vs 14%; p = 0.014). On an adjusted basis, major T-wave abnormalities on the baseline 12-lead ECG were associated with lower left ventricular ejection fraction (LVEF) at baseline (average of –9%, 95% CI: –1 to –16; p = 0.03) and at six months (–12%; 95% CI: –4 to –24; p = 0.006). Similarly, baseline ST-segment elevation was also associated with lower LVEF at six months (–25%; 95% CI: –0.7 to –50; p = 0.04). Conclusions In this unique study, we found that almost all women suffering from PPCM had an ‘abnormal’ 12-lead ECG. Pending more definitive studies, the ECG appears to be a useful adjunctive tool in both screening and prognostication in resource-poor settings.

Peripartum Cardiomyopathy in Africa: Challenges in Diagnosis, Prognosis, and Therapy

Peripartum cardiomyopathy (PPCM) is a form of heart failure affecting women of childbearing age, which can be associated with considerable mortality and chronic debilitating disease. Most patients present with acute postpartal heart failure that resembles the clinical presentation of idiopathic dilated cardiomyopathy. Historically, patients with PPCM have shown high rates of rapid recovery, with 6-month recovery rates averaging at 50%. However, recent prospective long-term follow-up of patients with PPCM in developing societies suggest recovery occurring only well into the second year after diagnosis, and recovery is poorly predicted by baseline left ventricular function. Beyond any potentially inherent factors contributing to poorer outcomes of patients with PPCM in developing societies, prognosis in these settings will continue to lag behind as the challenges faced to optimizing diagnosis remain immense. New insights into the role of inflammatory, apoptotic, and other genetic pathways may improve prognosis through the early detection and more targeted treatment of PPCM.