Heart failure with improved ejection fraction (HFimpEF) was associated with better outcomes than persistent heart failure with reduced ejection fraction (HFrEF) in both women and men, according to research published Oct. 15 in JACC: Heart Failure. Although women were more likely to experience HFimpEF within 12 months, compared with men, they had higher rates of worsening heart failure (WHF) events, including hospitalizations, emergency department or observation stays and urgent HF visits.

Investigators Yilin Liang, MD, MPH, et al., identified 28,292 adults (mean age, 69 years; 35% women; mean LVEF, 31%) within the Kaiser Permanente Northern California health system with incident HFrEF (LVEF ≤40%) between 2013 and 2022. Among the 9,849 women and 18,443 men, women were older (mean age, 72 vs. 68 years; p<0.001) and more likely to be White (62% vs. 60%) and less likely to be Hispanic.

Women also were more likely to have documented stress-induced cardiomyopathy at baseline (4.7% vs. 0.5%) and had a higher median LVEF at the time of incident HF (33% vs. 31%) than men. In contrast, women were less likely to have alcohol use disorder, prior ASCVD and cardiometabolic comorbidities including peripheral artery disease and diabetes.

Results showed that 35% of all patients experienced HFimpEF, defined by the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure as a subsequent measurement of LVEF >40%. HFimpEF occurred more frequently in women than men (37% vs. 35%; risk difference [RD], 2%; p<0.001), and the difference increased following adjustment for age, baseline EF and clinical covariates (adjusted RD, 3.8%; p<0.001).

In the 12-month landmark cohort of 21,907 participants, patients with HFimpEF had a lower adjusted risk of WHF or all-cause death than those with persistent HFrEF among both women and men (adjusted hazard ratio [aHR], 0.68 and 0.63, respectively; p for interaction=0.10).

Guideline-directed medical therapy use was generally similar between women and men with HFimpEF and declined in both sexes after HFimpEF was achieved.

However, among patients with HFimpEF, women experienced higher rates of WHF than men, with the difference persisting after adjustment for clinical covariates.

"We believe this finding has important clinical implications among females with HFimpEF," write Liang and colleagues. "For one, LVEF alone may not adequately measure or reflect risk of adverse outcomes among females. Females at a given LVEF may have more systolic dysfunction than males at a similar LVEF. Future studies should incorporate non-EF markers of risk, such as functional capacity and comorbidity burden, when assessing differences among males and females with HFimpEF and to further guide management in females with HFimpEF."

"Interesting questions remain: what does 'improved' LVEF mean in men vs women with HF, and should LVEF thresholds be defined differently between the sexes?" write Carolyn S.P. Lam, MBBS, PhD, and Li Shen, MD, PhD, in an accompanying editorial comment. "Whether the LVEF threshold for HFimpEF should be sex-calibrated, or the change in LVEF indexed to a sex-specific normal, is testable, and the imaging archives that generated this cohort could begin to answer it."