Non-Cardiac Comorbidities in Acute Heart Failure: Phenotype-Specific Insights from Sub-Saharan Africa

Background: Non-cardiac comorbidities (NCCs) are key determinants of outcomes in patients hospitalized with acute heart failure (HF). However, data from sub-Saharan Africa (SSA) on the prevalence and their prevalence across HF phenotypes, HF with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF), and their impact on in-hospital outcomes remain limited. Methods: We consecutively evaluated patients admitted with acute HF at Charlotte Maxeke Johannesburg Academic Hospital, South Africa, between February and November 2023. Ten NCCs were assessed, and the patients were stratified by comorbidity burden. The primary outcomes were all-cause in-hospital mortality and the length of hospital stay. Logistic and linear regression analyses, complemented by propensity score-based inverse probability weighting, were used to identify predictors of outcomes. Results: Of the 406 patients included (mean age 54.9 ± 15.8 years; 51% women; 63.3% had HFrEF, 15.3% HFmrEF, and 21.4% HFpEF. The most common NCCs were diabetes, 47%; chronic kidney disease (CKD), 46%; obesity, 45%; and anaemia, 33%. Two-thirds had ≥2 NCCs, and 11.3% had four or more NCCs. Obesity and anaemia were more frequent in the patients with HFmrEF/HFpEF. Patients with a high burden (≥ 3 NCCs) were older and had worse renal function and higher body mass index. The median hospital stay was 8 days (IQR: 5-12) and in-hospital mortality was 3.4%, with a non-significant trend across NCCs groups. Higher heart rate was associated with longer length of stay (β = +0.05 days; 95% confidence interval (CI): 0.006-0.092; p = 0.025), whereas the use of renin-angiotensin system inhibitors (RASi) (β = -1.84 days; 95% CI: -3.78, -0.12; p = 0.049) and the presence of thyroid disorders β = -4.10 days; 95% CI: -7.75, -0.45; p = 0.028) were associated with shorter hospitalization. Lower KCCQ score with higher mortality (aOR 1.009; 95% CI: 1.003-1.015; p = 0.005) and higher N-terminal proB-type natriuretic peptide (NT-proBNP) levels (aOR 1.00007; 95% CI: 1.0002-1.00013; p = 0.014) were independently associated with increased mortality. Multivariable and sensitivity analyses showed no statistically significant associations between overall comorbidity burden and in-hospital outcomes. Conclusions: Among adults hospitalized with acute HF in South Africa, NCCs are highly prevalent, their overall burden was not independently associated with in-hospital outcomes. Clinical and functional markers, lower KCCQ and higher NT-proBNP predicted in-hospital mortality, while higher heart rate was linked to longer hospitalization. Conversely, the use of RASi, and the presence of thyroid disorders are associated with shorter hospital stays. These findings emphasize the complex interplay between multimorbidity, functional status, and treatment patterns in acute HF and highlight the importance of integrated, context-specific management strategies in SSA.