ANIMA: Association Network Integration for Multiscale Analysis

Contextual functional interpretation of -omics data derived from clinical samples is a classical and difficult problem in computational systems biology. The measurement of thousands of datapoints on single samples has become routine but relating ‘big data’ datasets to the complexities of human pathobiology is an area of ongoing research. Complicating this is the fact that many publically available datasets use bulk transcriptomics data from complex tissues like blood. The most prevalent analytic approaches derive molecular ‘signatures’ of disease states or apply modular analysis frameworks to the data. Here we show, using a network-based data integration method using clinical phenotype and microarray data as inputs, that we can reconstruct multiple features (or endophenotypes) of disease states at various scales of organization, from transcript abundance patterns of individual genes through co-expression patterns of groups of genes to patterns of cellular behavior in whole blood samples, both in single experiments as well as in a meta-analysis of multiple datasets

Sport and Arrhythmogenic Right Ventricular Cardiomyopathy

Sudden deaths have been reported in sportspersons and have been related to physical activity. It is possible that exercise may be a trigger of potentially lethal arrhythmias in susceptible individuals or may be the factor that converts a defect of genotype to an abnormal and arrhythmogenic phenotype. Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)may be at higher risk of sports-related arrhythmias and sudden death. In the South African ARVC registry,56% of patients were involved in regular sport participation. Various potential mechanisms linking sport and exercise to arrhythmias in patients with ARVC may exist

A cost-effectiveness tool to guide the prioritization of interventions for rheumatic fever and rheumatic heart disease control in African nations

Author Summary: Rheumatic heart disease is a major cause of cardiovascular morbidity and mortality in Africa. Although there are effective medications and surgical procedures for rheumatic heart disease, they are under-used. What is more, these interventions can be expensive--even if they are feasible and effective. Unfortunately, there are currently very few economic studies on rheumatic heart disease, leaving ministries of health with little guidance on how to choose among various interventions and allocate resources to control programs. Our study describes the methods and data we used to develop a cost-effectiveness analysis tool that was intended specifically for decision-making in African countries. In our study, we also illustrate, in a hypothetical low-income African country, how the tool could be used. In our illustrative example, a prevention-oriented approach would save money in the long term, although other interventions could be cost-effective and feasible if enough financial resources were present. These findings contrast with previous studies and make a strong case that rheumatic heart disease prevention could be a high-priority intervention in Africa. We are making our tool publicly available and anticipate that ministries of health will use it as they develop or expand their rheumatic heart disease control programs

Pregnancy-associated heart failure: a comparison of clinical presentation and outcome between hypertensive heart failure of pregnancy and idiopathic peripartum cardiomyopathy

AIMS: There is controversy regarding the inclusion of patients with hypertension among cases of peripartum cardiomyopathy (PPCM), as the practice has contributed significantly to the discrepancy in reported characteristics of PPCM. We sought to determine whether hypertensive heart failure of pregnancy (HHFP) (i.e., peripartum cardiac failure associated with any form of hypertension) and PPCM have similar or different clinical features and outcome. Methods and RESULTS: We compared the time of onset of symptoms, clinical profile (including electrocardiographic [ECG] and echocardiographic features) and outcome of patients with HHFP (n = 53; age 29.6 ± 6.6 years) and PPCM (n = 30; age 31.5 ± 7.5 years). The onset of symptoms was postpartum in all PPCM patients, whereas it was antepartum in 85% of HHFP cases (p<0.001). PPCM was more significantly associated with the following features than HHFP (p<0.05): twin pregnancy, smoking, cardiomegaly with lower left ventricular ejection fraction on echocardiography, and longer QRS duration, QRS abnormalities, left atrial hypertrophy, left bundle branch block, T wave inversion and atrial fibrillation on ECG. By contrast, HHFP patients were significantly more likely (p<0.05) to have a family history of hypertension, hypertension and pre-eclampsia in a previous pregnancy, tachycardia at presentation on ECG, and left ventricular hypertrophy on echocardiography. Chronic heart failure, intra-cardiac thrombus and pulmonary hypertension were found significantly more commonly in PPCM than in HHFP (p<0.05). There were 5 deaths in the PPCM group compared to none among HHFP cases (p = 0.005) during follow-up. CONCLUSION: There are significant differences in the time of onset of heart failure, clinical, ECG and echocardiographic features, and outcome of HHFP compared to PPCM, indicating that the presence of hypertension in pregnancy-associated heart failure may not fit the case definition of idiopathic PPCM

Clinical characteristics and causes of heart failure, adherence to treatment guidelines, and mortality of patients with acute heart failure: Experience at Groote Schuur Hospital, Cape Town, South Africa

Background. There is limited information on acute heart failure (AHF) and its treatment in sub-Saharan Africa.Objective. To describe the clinical characteristics and causes of heart failure (HF), adherence to HF treatment guidelines, and mortality of patients with AHF presenting to Groote Schuur Hospital (GSH), Cape Town, South Africa.Methods. This sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUS-HF) was a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to GSH and entered into the existing registry after publication of the primary THESUS-HF article in 2012. The patients were classified into prevalent (existing) or incident (new) cases of HF.Results. Of the 119 patients included, 69 (58.0%) were female and the mean (standard deviation) age was 49.9 (16.3) years. The majority of prevalent cases were patients of mixed ancestry (63.3%), and prevalent cases had more hypertension (70.0%), diabetes mellitus (36.7%), hyperlipidaemia (33.3%) and ischaemic heart disease (IHD) (36.7%) than incident cases. The top five causes of HF were cardiomyopathy (20.2%), IHD (19.3%), rheumatic valvular heart disease (RHD) (18.5%), cor pulmonale (11.8%) and hypertension (10.1%), with the remaining 20.1% consisting of miscellaneous causes including pericarditis, toxins and congenital heart disease. Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of beta-blocker, aldosterone antagonist and digoxin use. Rehospitalisation within 180 days occurred in 25.2% of cases. In-hospital mortality was 8.4% and the case fatality rate at 6 months was 26.1%.Conclusion. In Cape Town, the main causes of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is serious under-use of beta-blockers, aldosterone antagonists and digoxin. Emphasis on the rigorous application of treatment guidelines is needed to reduce readmission and mortality.

The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

<p>Abstract</p> <p>Background</p> <p>The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV).</p> <p>Methods</p> <p>A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer.</p> <p>Results</p> <p>The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11).</p> <p>Conclusion</p> <p>The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.</p