Etiology of heart failure across the ejection fraction spectrum and association with mortality – insight from the HEart failuRe ObsErvational Study (HEROES)

PURPOSE: The associations between heart failure (HF) etiology in patients with HF with preserved ejection fraction (HFpEF), HF with mildly reduced ejection fraction (HFmrEF), HF with reduced ejection fraction (HFrEF) and all-cause mortality are inconsistent. We performed a comparative assessment of the different HF etiologies and their impact on the long-term prognosis. PATIENTS AND METHODS: Hospitalized patients and outpatients were enrolled in the HEart failuRe ObsErvational Study (HEROES), a prospective, multicenter cohort study. Patients were categorized according to HF etiology (ischemic, valvular, hypertensive, arrhythmic, and other) and HF subtype. Follow-up included all-cause mortality. RESULTS: Among included 1,210 patients (26.5% HFpEF, 21.7% HFmrEF, 51.8% HFrEF, 41.2% ischemic, 11.6% hypertensive, 11.3% arrhythmic, 10.7% valvular, and 25.5% other etiologies), over a median follow-up of 14.7 months (interquartile range 11.6-18.4), 183 deaths (15.1%) were observed. Considering ischemic etiology as the reference, the adjusted hazard ratios (HRs) for all-cause mortality were: HFpEF - arrhythmic 1.00 [0.35-2.88], hypertensive 0.42 [0.14-1.30], valvular 0.54 [0.17-1.67], other 1.03 [0.25-4.29], P=0.40; HFrEF - arrhythmic 0.76 [0.26-2.32], hypertensive 1.65 [0.60-4.65], valvular 0.80 [0.32-2.04], other 0.79 [0.47-1.35], P=0.30. In HFmrEF, ischemic etiology conferred the best survival, with significantly higher risks for arrhythmic (aHR 5.30 [1.57-17.92]), hypertensive (4.33 [1.33-14.11]), and valvular (6.82 [1.95-23.82]) groups, P<0.001. CONCLUSIONS: In our study, etiology exerts minimal independent influence on mortality in HFpEF and HFrEF, and HFmrEF exhibited marked divergence, with ischemic etiology conferring the best survival and significantly higher risks for arrhythmic, hypertensive, and valvular groups.