Etiology of Heart Failure Across the Ejection Fraction Spectrum and Association With Prognosis

The associations between heart failure (HF) etiology and ejection fraction (EF) category and the association between etiology and outcomes in different EF categories are poorly studied.

The aim of this study was to assess differences in etiology and their impact on outcomes in patients with heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF).

Patients enrolled in SwedeHF (Swedish Heart Failure Registry) between April 2010 and December 2023 were included. Patients were categorized according to HF etiology (ischemic, valvular, hypertensive, dilated cardiomyopathy, alcoholic cardiomyopathy, and other) and EF category. The primary outcome was the composite of time to all-cause death and first HF hospitalization. Logistic multinominal regression was used to assess the association between HF etiology and EF category, and Cox regression was used to assess the association between etiology and outcome within each EF category.

Among 73,769 patients with HF (53% HFrEF, 25% HFmrEF, and 22% HFpEF; 38% ischemic, 8% valvular, 25% hypertensive, and 29% other), ischemic etiology was independently associated with HFrEF and HFmrEF, while hypertensive and valvular etiologies were associated with HFpEF. In HFrEF, ischemic etiology was associated with the primary outcome in comparison with all other 3 etiologies. In HFmrEF, hypertensive etiology was associated with first HF hospitalization (HR: 1.10 [95% CI: 1.03-1.19]). In HFpEF, valvular etiology was associated with first HF hospitalization (HR: 1.11 [95% CI: 1.02-1.22]).

Ischemic etiology was dominant in HFrEF and HFmrEF, while valvular and hypertensive etiologies dominated in HFpEF. Etiologies most associated with death/HF hospitalization were ischemic in HFrEF, hypertensive in HFmrEF, and valvular in HFpEF.