Comorbidity patterns and mortality in HFpEF: A retrospective longitudinal cohort study.

Background: Comorbid conditions (CCs) in heart failure with preserved ejection fraction (HFpEF) are associated with poor prognosis, but the influence of their duration on mortality remains unclear. We examined how pre-admission comorbidity duration affects long-term mortality after HFpEF hospitalization. Methods: This retrospective study included adults hospitalized for HFpEF at 17 hospitals (2010-2022) with follow-up through July 2024. Twelve individual and four system-based comorbidities present at admission were classified by duration: new (<0.5 years), early (0.5-<3 years), intermediate (3-<6 years), and long-term (>6 years). Mortality was further stratified by Get With The Guidelines-Heart Failure (GWTG) score (1, 2, ≥3) and discharge SGLT2i prescription. Cox regression and restricted cubic splines estimated risk. Results: Among 9256 patients (mean age 77.8 years; 54.1 % female; 40.2 % rural), 64.1 % died over a median follow-up of 2.7 years. Comorbidity prevalence ranged from 6.0 % (neurological) to 73.4 % (hypertension), with durations from 0.5 years (obesity) to 5 years (diabetes). Most comorbidities increased mortality risk (HRs 1.06-1.25), highest for neurological disease, CKD, stroke, and anemia. Risk rose within 3 years of comorbidity onset, then stabilized, consistent across age, sex, and residential status. Associations persisted across GWTG strata. SGLT2i therapy attenuated mortality risk for most comorbidities, though residual risk remained for stroke, CKD, chronic lung, and neurological disease. Conclusions: In HFpEF, comorbidities are common and associated with higher mortality, especially within the first 3 years. Prognostic effects persisted across GWTG strata, while SGLT2i therapy attenuated these risks, highlighting the importance of early detection and optimized therapy.