Heart failure is a clinical syndrome resulting from various cardiovascular diseases of different aetiologies and pathophysiology. These varying pathologies involve several complex mechanisms that lead to the activation of the neurohumoral system, inflammation, angiogenesis, apoptosis, fibrosis, and eventually adverse cardiac remodelling associated with a progressive decline in cardiac function. Once a diagnosis is made, the cardiac function has a gradual decline characterised by multiple hospital admissions. It is therefore imperative to identify patients at different stages of the heart failure continuum to better risk stratify and initiate optimal management strategies. Biomarkers may play a role in the diagnosis, prognostication, and monitoring response to treatment. This review discusses the epidemiology of heart failure and biomarkers commonly used in clinical practice such as natriuretic peptides and cardiac troponins. In addition, we provide a brief overview of novel biomarkers and genetic coding and non-coding biomarkers used in the management of patients with heart failure. We also discuss barriers that hinder the clinical application of novel biomarkers. Finally, we appraise the value of polygenic risk scoring, focusing on sub-Saharan Africa.

Aims: In sub-Saharan Africa (SSA), the clinical profile and in-hospital outcomes of adults with acute heart failure (HF) based on left ventricular ejection fraction (LVEF) categories are unknown. This study aimed to describe the prevalence and clinical characteristics of patients admitted with acute HF based on LVEF categories and their association with in-hospital outcomes. Methods: Four hundred six consecutive patients with acute HF were enrolled in this prospective study between February and November 2023. The patients were stratified into three categories: HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary outcome measure was all-cause in-hospital mortality. The prevalence and outcomes of various LVEF phenotypes were evaluated in adult patients with acute HF. Results: The mean age of the patients was 54.94 ± 15.83 years, of whom 207 (51%) were female (P = 0.004). Two hundred fifty-seven (63.3%) patients had HFrEF, 62 (15.3%) had HFmrEF, and 87 (21.4%) had HFpEF. Patients with HFpEF were older and predominantly female and had a higher median global longitudinal score and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < 0.001). The all-cause in-hospital mortality was 3.4% [95% confidence interval (CI): 2.0–6.0] without significant variation across LVEF phenotypes (P = 0.70). In the multivariable model after adjusting for age and sex, higher C-reactive protein levels [odds ratio (OR): 1.02; 95% CI: 1.00–1.03; P = 0.009], elevated neutrophil–lymphocyte ratio (OR: 1.15; 95% CI: 1.03–1.29; P = 0.012), elevated serum potassium (OR: 3.41; 95% CI: 1.23–9.43; P = 0.018), moderate aortic regurgitation (AR) (OR: 12.80; 95% CI: 1.12–101.29; P = 0.016) and severe AR (OR: 34.49; 95% CI: 3.77–353.47; P = 0.002) were observed. Low diastolic blood pressure was associated with a reduced mortality risk (OR: 0.94; 95% CI: 0.89–0.99; P = 0.045). Conclusions: In our study, HFrEF was the predominant phenotype, and each phenotype exhibited distinct clinical and biomarker profiles. All-cause in-hospital mortality was low and did not differ significantly across the phenotypes. Independent predictors of mortality included markers of inflammation, electrolyte imbalance and moderate-to-severe AR. These findings highlight the need for targeted risk stratification and management strategies to improve the outcomes in this population.

Introduction Low Low-dose triple single pill combination therapy is recommended for hypertension treatment. However, the efficacy and safety of these combinations in low- and middle-income countries (LMICs) remain unclear. Aim We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose triple single pill combination therapy in controlling blood pressure (BP) in LMICs. Methods We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomised controlled trials (RCTs) comparing low-dose triple single pill combination therapy with standard care for hypertension management up to 29 January 2025. Mean differences (MD) were computed for continuous outcomes and risk ratio (RR) with 95% confidence intervals (CI) for binary outcomes. Results Three RCTs comprising 1758 patients, of whom 752 (43%) received low-dose triple single pill combination therapy, were included. The proportion of patients that achieved target BP at six weeks was higher with this therapy (RR 1.89; 95% CI 1.29, 2.75; P < 0.001). Compared with standard care, it significantly reduced SBP (MD − 5.30 mmHg; 95% CI − 9.55, − 0.92; P = 0.017), DBP (MD − 3.50 mmHg; 95% CI − 4.95, − 2.05; P < 0.001), and urine albumin-to-creatinine ratio (RR 0.59; 95% CI 0.44, 0.80; P < 0.001). No significant differences in adherence, withdrawal, or adverse effects were observed between groups. Conclusion In this meta-analysis, the use of a low-dose triple single pill combination in hypertensive patients in LMICs led to earlier and sustained blood pressure control and reduced urine albumin-to-creatinine ratio, with a safety profile comparable to standard care. PROSPERO registration: Number: CRD42025647884, Date: 15 February 2025 Graphic Abstract

Heart failure (HF) is associated with substantial morbidity and mortality. Metabolic abnormalities are increasingly recognized as integral to HF pathophysiology and may provide incremental value for phenotyping and prediction of outcomes. However, a comprehensive synthesis of metabolic alterations and their prognostic implications remains limited. This scoping review aimed to map metabolic changes in HF, describe analytical methods, and evaluate their diagnostic and prognostic relevance for clinical risk assessment. Methods: We systematically searched PubMed, Scopus, Web of Science, Cochrane Central, and grey literature from January 2010 to December 2024 to identify studies evaluating metabolic profiling in patients with HF. Two independent reviewers screened studies using predefined inclusion criteria and data were extracted using a customized charting form. Discrepancies were resolved by consensus or a third reviewer. We reported and synthesized findings narratively in accordance with scoping review methodology. Results: Seventy-two studies (66 observational and 6 randomized) were included, encompassing HF phenotypes including HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The analytical approaches included mass spectrometry and nuclear magnetic resonance (¹H-NMR) platforms. The main metabolite classes that demonstrated prognostic significance were amino acids, acylcarnitines, and lipids, and gut-derived metabolites, which were associated with mortality, HF hospitalization, or disease progression. Several studies reported incremental prognostic value beyond conventional biomarker; however, most were exploratory, with modest sample sizes, limited external validation, and heterogeneous methodologies. Conclusions: Metabolomic profiling identifies biologically relevant alterations predicted worse clinical outcomes in HF and may complement existing risk assessment strategies. Nevertheless, standardized workflows and large prospective validation studies are required before clinical implementation can be considered.

Background: Non-cardiac comorbidities (NCCs) are highly prevalent among patients hospitalized for acute heart failure (HF). However, data from sub-Saharan Africa (SSA) on their distribution across HF phenotypes and association with in-hospital outcomes remain limited. Methods: We prospectively enrolled adults hospitalized with acute HF at a tertiary centre in South Africa between February and November 2023. Ten NCCs were assessed and patients were categorized according to comorbidity burden. The primary outcomes were all-cause in-hospital mortality and length of stay. Multivariable regression and sensitivity analyses were performed to identify predictors of outcomes. Results: Of the 406 patients (mean age 54.9 ± 15.8 years; 51% women), HF with reduced ejection fraction (HFrEF) accounted for 63%, HF with mildly reduced ejection fraction (HFmrEF) for 15%, and HF with preserved ejection fraction (HFpEF) for 21%. The most common NCCs were diabetes (47%), chronic kidney disease (CKD) (46%), obesity (45%), and anaemia (33%). Two-thirds had ≥2 NCCs. The median hospital stay was 8 days (IQR: 5–12) and in-hospital mortality was 3.4% (p > 0.05 across NCC groups). Higher heart rate predicted longer hospitalization, while renin angiotensin system inhibitor (RASi) therapy was associated with shorter stay. Lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score (adjusted odds ratio [aOR] 1.009; 95% confidence interval [CI]: 1.003–1.015) and higher log-transformed NT-proBNP were independently associated with increased in-hospital mortality (aOR 1.85; 95% CI: 1.07–3.50; p = 0.026). Total comorbidity burden was not independently associated with length of stay or in-hospital mortality. Conclusions: Non-cardiac comorbidities are common in acute HF in SSA, and functional status and clinical markers were the strongest predictors of length of stay and in-hospital mortality.

Cardiovascular disease is a significant cause of morbidity and mortality for individuals living with type 2 diabetes mellitus (T2DM). These patients have double the risk of atherosclerotic cardiovascular disease (ASCVD) compared with the general population. Furthermore, approximately a third of T2DM patients live with established ASCVD. The traditional ‘glucocentric’ approaches to managing T2DM have failed to mitigate the burden of ASCVD. In recent years, some cardiovascular outcome trials of the sodium glucose-2 cotransporter inhibitors (SGLT2i) and the glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated an ability to reduce secondary cardiovascular events significantly. These therapies have ushered in an era of ‘thinking beyond HbA1c’ when treating T2DM patients. There is now a renewed focus on assessing patients for ASCVD risk and adding these novel therapies early to mitigate the adverse cardiovascular events that have become familiar to this population. While the exact physiological mechanisms underlying these clinical benefits are not yet explicitly defined, both the glycaemic benefits and other pleiotropic effects improve the metabolic milieu. This review will discuss the burden of cardiovascular disease (CVD) in T2DM and present a summary of these new antidiabetic drug classes proven to reduce CVD in T2DM.