Sex Differences in the Prevalence, Medical Therapy, and Outcomes in Heart Failure With Improved Ejection Fraction

Heart failure with improved ejection fraction (HFimpEF) is a rapidly growing clinical entity. There is little understanding of how sex relates to the epidemiology, predictors, and trajectory of HFimpEF.

The authors aimed to describe sex-based differences in the epidemiology, guideline-directed medical therapy (GDMT) use, and clinical outcomes among patients with HFimpEF within a large, diverse health care system.

The authors identified adults with incident heart failure with reduced ejection fraction (HFrEF) (ejection fraction ≤40%) between 2013 and 2022. HFimpEF was defined as a subsequent ejection fraction measurement >40% within the following 12 months. Sex was based on self-report. Among patients with HFimpEF, the authors examined GDMT use at the time of incident HFrEF, HFimpEF, and 1 year following HFimpEF, stratified by sex. They examined the incidence of worsening heart failure (WHF) events and all-cause death 1 year postincident HFrEF. We compared event rates between patients with HFimpEF and persistent HFrEF, adjusted for demographic and clinical characteristics.

Among 28,292 patients with incident HFrEF (females: 34.8%), 35.2% experienced HFimpEF. Females were more likely to experience HFimpEF in the 12 months following HFrEF than males (36.5% vs 34.5%, P < 0.0001). Among patients with HFimpEF, GDMT use was similar among females and males and declined after incident HFimpEF in both sexes. Compared with patients with persistent HFrEF, patients with HFimpEF had better WHF outcomes and all-cause death outcomes, which was consistent by sex. However, females with HFimpEF had higher rates of WHF compared with males with HFimpEF, even when adjusted for clinical covariates.

HFimpEF is associated with improved outcomes for both females and males. However, females with HFimpEF have higher rates of WHF events compared with males.