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

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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% (<i>p</i> > 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; <i>p</i> = 0.026). Total comorbidity burden was not independently associated with length of stay or in-hospital mortality. <b>Conclusions:</b> 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.