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.

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.

The persistent thrombus: complications, diagnosis, and novel treatment intervention.

OBJECTIVE: To review the findings and discuss the implications of the topic of pharmacomechanical thrombolysis in pediatric patients with persistent thrombus. DESIGN: A pediatric case presentation with a brief literature review on treatment of venous thrombosis and pharmacomechanical thrombolysis. INTERVENTIONS: None. MAIN RESULTS: Thrombotic events refractory to standard medical and surgical care remain a life-threatening clinical challenge in the pediatric population. Research on persistent deep venous thrombosis and treatment modalities is limited. We present a pediatric patient with a history of malignant osteosarcoma who was diagnosed with deep venous thrombosis. Despite appropriate anticoagulation therapy, the thrombus remained persistent. Pharmacomechanical thrombolysis was utilized and proved to be an effective method in providing diagnosis and treatment. CONCLUSION: Pharmacomechanical thrombolysis is a valuable and effective method in providing diagnosis and treatment of persistent thrombus.

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.

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

AIM: 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. METHODS AND RESULTS: Serum markers related to cardiac function, apoptosis, oxidative stress, remodelling, inflammation and the nursing hormone prolactin were analyzed in PPCM patients and healthy controls. The kinetics of these markers were compared between patients who improved cardiac function (IMP) and those patients who did not improve (NIMP), over 6 months follow-up. All patients received ACE-inhibitors, beta-blockers and diuretics. Baseline levels of TGF-beta-1 were significantly lower, MMP-9 and VEGF were not different; all other markers were significantly higher in PPCM compared with controls. Only baseline NT-proBNP levels were higher in NIMP compared with IMP. After 6 months, NT-proBNP, oxLDL and IFN-gamma were significantly lower in IMP and the decrease in oxLDL, IFN-gamma and prolactin was significant in IMP but not in NIMP. Significant correlations were observed between the kinetics of NT-proBNP, oxLDL, prolactin and IFN-gamma in PPCM patients. CONCLUSION: Baseline NT-proBNP and the failure to decrease oxLDL, IFN-gamma and prolactin are associated with poor outcome in PPCM, suggesting a potential role of these factors in the pathophysiology of PPCM and for risk stratification of PPCM patients.

Mapping the emergence of heart disease in a black, urban population in Africa: the Heart of Soweto Study.

BACKGROUND: There is increasing evidence that many populations in the developing world are in "epidemiologic transition" with the subsequent emergence of more "affluent" disease states. The "Heart of Soweto Study" will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. METHODS: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of 1 million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of >12,000 "prevalent" cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of >5000 "incident" cases. Sub-studies of the relationship between HIV status and HD and the optimal management of chronic heart failure will also be performed. RESULTS: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a "developing world" community in epidemiologic transition. Initially documented population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. CONCLUSION: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard.

Bulk segregant analysis using single nucleotide polymorphism microarrays.

Bulk segregant analysis (BSA) using microarrays, and extreme array mapping (XAM) have recently been used to rapidly identify genomic regions associated with phenotypes in multiple species. These experiments, however, require the identification of single feature polymorphisms (SFP) between the cross parents for each new combination of genotypes, which raises the cost of experiments. The availability of the genomic polymorphism data in Arabidopsis thaliana, coupled with the efficient designs of Single Nucleotide Polymorphism (SNP) genotyping arrays removes the requirement for SFP detection and lowers the per array cost, thereby lowering the overall cost per experiment. To demonstrate that these approaches would be functional on SNP arrays and determine confidence intervals, we analyzed hybridizations of natural accessions to the Arabidopsis ATSNPTILE array and simulated BSA or XAM given a variety of gene models, populations, and bulk selection parameters. Our results show a striking degree of correlation between the genotyping output of both methods, which suggests that the benefit of SFP genotyping in context of BSA can be had with the cheaper, more efficient SNP arrays. As a final proof of concept, we hybridized the DNA from bulks of an F2 mapping population of a Sulfur and Selenium ionomics mutant to both the Arabidopsis ATTILE1R and ATSNPTILE arrays, which produced almost identical results. We have produced R scripts that prompt the user for the required parameters and perform the BSA analysis using the ATSNPTILE1 array and have provided them as supplemental data files.

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.

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

BACKGROUND: HIV infection is associated with a high prevalence of antiphospholipid antibodies (aPL) and increased thrombotic events but the aetiopathogenic link between the two is unclear. FINDINGS: Prospective 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. CONCLUSIONS: Treatment 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.