Anthony Becker

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.

Reversal of IFN-γ, oxLDL and prolactin serum levels correlate with clinical improvement in patients with peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is characterized by acute onset of heart failure of unknown aetiology. We aimed to identify mechanisms involved in initiation and progression of the disease.

Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort

AIMS The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. METHODS AND RESULTS Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. CONCLUSION Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in this setting, HIV-related cases of CAD remain at historically low levels.

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.

Acute coronary syndromes in treatment-naive black south africans with human immunodeficiency virus infection

BACKGROUND HIV patients on protease inhibitors have greater risk of acute coronary syndromes (ACS) but little is known about treatment-naïve patients. METHODS AND RESULTS Authors conducted a prospective single-center study from Soweto, South Africa, comparing the clinical and angiographic features of treatment-naïve HIV positive and negative patients with ACS. Between March 2004 and February 2008, 30 consecutive treatment-naïve HIV patients with ACS were compared to the next HIV-negative patient as a 1:1 control. HIV patients were younger (43 +/- 7 vs. 54 +/- 13, P = 0.004) and, besides smoking (73% vs. 33%, P = 0.002), had fewer risk factors than the control group with less hypertension (23% vs. 77%, P = 0.0001), diabetes (3% vs. 23%, P = 0.05), LDL hyperlipidemia (2.2 +/- 0.9 vs. 3.0 +/- 1.2, P = 0.006), and other coronary risk factors (7% vs. 53%, P = 0.0001). HDL was lower in the HIV group (0.8 +/- 0.3 vs. 1.1 +/- 0.4, P = 0.001). Atherosclerotic burden was lower in the HIV group with more normal infarct-related arteries (47% vs. 13%, P = 0.005) but a higher degree of large thrombus burden (43% vs. 17%, P = 0.02). Stents were used to a similar degree in HIV and control patients (30% vs. 37%, P = 0.78) with more target lesion revascularization in the HIV group (56% vs. 0%, P = 0.008). CONCLUSION Treatment-naïve HIV patients with ACS are younger and have fewer traditional risk factors than HIV-negative patients. HIV patients have less atherosclerotic but higher thrombotic burden which may imply a prothrombotic state in the pathogenesis of ACS in these patients.

The Thrombotic Profile of Treatment-Naive HIV-Positive Black South Africans With Acute Coronary Syndromes

Background: Patients with human immunodeficiency virus (HIV) infection on protease inhibitors (PIs) have a heightened risk of arterial thrombosis but little is known about treatment-naive patients. Methods/Results: Prospective study from South Africa comparing thrombotic profiles of HIV-positive and -negative patients with acute coronary syndrome (ACS). A total of 30 treatment-naive HIV-positive patients with ACS were compared to 30 HIV-negative patients with ACS. Patients with HIV were younger; and besides smoking (73% vs 33%) and low high-density lipoprotein (HDL; 0.8 ± 0.3 vs 1.1 ± 0.4), they had fewer risk factors. Thrombophilia was more common in HIV-positive patients with lower protein C (PC; 82 ± 22 vs 108 ± 20) and higher factor VIII levels (201 ± 87 vs 136 ± 45). Patients with HIV had higher frequencies of anticardiolipin (aCL; 47% vs 10%) and antiprothrombin antibodies (87% vs 21%). Conclusion: Treatment-naive HIV-positive patients with ACS are younger, with fewer traditional risk factors but a greater degree of thrombophilia compared with HIV-negative patients.

Antiphospholipid antibodies in black south africans with hiv and acute coronary syndromes: prevalence and clinical correlates

BackgroundHIV infection is associated with a high prevalence of antiphospholipid antibodies (aPL) and increased thrombotic events but the aetiopathogenic link between the two is unclear.FindingsProspective single centre study from Soweto, South Africa, comparing the prevalence of aPL in highly active anti-retroviral therapy (HAART) naïve HIV positive and negative patients presenting with Acute Coronary Syndromes (ACS). Between March 2004 and February 2008, 30 consecutive black South African HIV patients with ACS were compared to 30 black HIV negative patients with ACS. The HIV patients were younger (43 ± 7 vs. 54 ± 13, p = 0.004) and besides smoking (73% vs. 33%, p = 0.002) and lower HDL levels (0.8 ± 0.3 vs. 1.1 ± 0.4, p = 0.001) had fewer risk factors than the control group. HIV patients had a higher prevalence of anticardiolipin (aCL) IgG (47% vs. 10%, p = 0.003) and anti-prothrombin (aPT) IgG antibodies (87% vs. 21%, p < 0.001) but there was no difference in the prevalence of the antiphospholipid syndrome (44% vs. 24%, p = N/S) and aPL were not predictive of clinical or angiographic outcomes.ConclusionsTreatment naïve black South African HIV patients with ACS are younger with fewer traditional coronary risk factors than HIV negative patients but have a higher prevalence and different expression of aPL which is likely to be an epiphenomenon of the HIV infection rather than causally linked to thrombosis and the pathogenesis of ACS.