The causes, treatment, and outcome of acute heart failure in 1006 Africans From 9 countries

Background: Acute heart failure (AHF) in sub-Saharan Africa has not been well characterized. Therefore,wesought to describe the characteristics, treatment, and outcomes of patients admitted with AHF in sub-Saharan Africa. Methods: The Sub-Saharan Africa Survey of Heart Failure (THESUS–HF) was a prospective, multicenter, observational survey of patients with AHF admitted to 12 university hospitals in 9 countries. Among patients presenting with AHF, we determined the causes, treatment, and outcomes during 6 months of follow-up. Results: From July 1, 2007, to June 30, 2010, we enrolled 1006 patients presenting with AHF. Mean (SD) age was 52.3 (18.3) years, 511 (50.8%) were women, and the predominant race was black African (984 of 999 [98.5%]). Mean (SD) left ventricular ejection fraction was 39.5% (16.5%)... Conclusions: In African patients, AHF has a predominantly nonischemic cause, most commonly hypertension. The condition occurs in middle-aged adults, equally in men and women, and is associated with high mortality. The outcome is similar to that observed in non- African AHF registries, suggesting that AHF has a dire prognosis globally, regardless of the cause

Evaluation of Group Genetic Ancestry of Populations from Philadelphia and Dakar in the Context of Sex-Biased Admixture in the Americas

Population history can be reflected in group genetic ancestry, where genomic variation captured by the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) can separate female- and male-specific admixture processes. Genetic ancestry may influence genetic association studies due to differences in individual admixture within recently admixed populations like African Americans.We evaluated the genetic ancestry of Senegalese as well as European Americans and African Americans from Philadelphia. Senegalese mtDNA consisted of approximately 12% U haplotypes (U6 and U5b1b haplotypes, common in North Africa) while the NRY haplotypes belonged solely to haplogroup E. In Philadelphia, we observed varying degrees of admixture. While African Americans have 9-10% mtDNAs and approximately 31% NRYs of European origin, these results are not mirrored in the mtDNA/NRY pools of European Americans: they have less than 7% mtDNAs and less than 2% NRYs from non-European sources. Additionally, there is <2% Native American contribution to Philadelphian African American ancestry and the admixture from combined mtDNA/NRY estimates is consistent with the admixture derived from autosomal genetic data. To further dissect these estimates, we have analyzed our samples in the context of different demographic groups in the Americas.We found that sex-biased admixture in African-derived populations is present throughout the Americas, with continual influence of European males, while Native American females contribute mainly to populations of the Caribbean and South America. The high non-European female contribution to the pool of European-derived populations is consistently characteristic of Iberian colonization. These data suggest that genomic data correlate well with historical records of colonization in the Americas

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF)

Aims Patients with acute heart failure (HF) in Africa are rarely being treated with a hydralazine/nitrates combination. Therefore the effect of this treatment was studied here. Methods and results The study was planned to enrol 500 patients during an acute HF admission, from nine sub-Saharan African countries. Patients were randomized in a double-blind manner to receive 50 mg hydralazine/20 mg isosorbide dinitrate (HYIS) t.i.d. or matching placebo for 24 weeks followed by open label HYIS for all patients. The study was terminated after 147 patients were enrolled due mostly to issues with recruitment into a prospective, placebo-controlled study. Most patients were recruited from Mozambique, South Africa, Kenya, and Uganda. The primary endpoint of death or HF readmission through 24 weeks was neutral [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.48–2.27, P = 0.90] in the 133 randomized patients included in the analyses. There were non-signficant effects in favour of HYIS in secondary endpoints including change in dyspnoea severity at day 7 or discharge, decrease in systolic blood pressure, greater decrease in weight, and increase in 6-min walk test distance at week 24. There were also small changes in echocardiographic indices of cardiac size and function in favour or HYIS, but none was significant. Conclusion The BA-HEF trial demonstrated challenges in recruiting the expected number of patients with acute HF in a number of African countries, which highlights the need for strategic logistic support

Prevalence, clinical characteristics and outcomes of valvular atrial fibrillation in a cohort African patients with acute heart failure: insights from the THESUS-HF registry

Introduction: Rheumatic heart disease (RHD) is the commonest cause of valvular heart disease and a common cause of heart failure in sub-Saharan Africa (SSA). Atrial fibrillation (AF) complicates RHD, precipitates and worsens heart failure and cause unfavourable outcomes. We set out to describe the prevalence, clinical characteristics and outcomes of valvular atrial fibrillation in a cohort of African patients with acute heart failure (AHF). Methods: The sub-Saharan Africa Survey of Heart Failure (THESUS-HF) was a prospective, observational survey of AHF in nine countries. We collected demographic data, medical history and signs and symptoms of HF. Electrocardiograms (ECGs) were done in a standard fashion. AF was defined as either a history of AF or AF on the admission ECG. Using Cox regression models, we examined the associations of AF with all-cause death over 180 days and a composite endpoint of all-cause death or readmission over 60 days. Results: There were 1 006 patients in the registry. The mean age was 52.3 years and 50.8% were women. AF was present in 209 (20.8%) cases. Those with AF were older (57.1 vs 51.1 years), more likely to be female (57.4 vs 49.1%), had significantly lower systolic (125 vs 132 mmHg) and diastolic (81 vs 85 mmHg) blood pressure (BP), and higher heart rates (109 vs 102 bpm). Ninety-two (44%) AF patients had valvular heart disease. The presence of AF was not associated with the primary endpoints, but having valvular AF predicted death within 180 days. Conclusion: AF was present in one-fifth of African patients with AHF. Almost half of the AF patients had valvular disease (RHD) and were significantly younger and at risk of dying within six months. It is important to identify these high-risk patients and prioritise their management, especially in SSA where resources are limited

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients

BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa. RESULTS: At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible

Heart rate variability on antihypertensive drugs in black patients living in sub-Saharan Africa

BACKGROUND: Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in blacks born and living in Africa. METHODS: In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30–69 years) with uncomplicated hypertension (140–179/90–109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. RESULTS: Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (− 2.2 beats/min). R patients had reduced total (− 0.13 ms²; p = 0.0038) and low-frequency power (− 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (− 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (− 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. CONCLUSION: In native black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate

Heart rate variability on antihypertensive drugs in Black patients living in sub-Saharan Africa

Background. Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in Blacks born and living in Africa. Methods. In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. Results. Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (- 2.2 beats/min). R patients had reduced total (- 0.13 ms²; p = 0.0038) and low-frequency power (- 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (- 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (- 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. Conclusion. In native Black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iblo20status: publishe