Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure With Improved Ejection Fraction.

Min KH, Go AS, Lee K, Parikh RV, Horiuchi KM, Ambrosy AP, Tan TC, Srikanth K, Hamilton SA, Svetlichnaya J, Solomon SD, Inciardi RM, Vardeny O, Vasti E, Sandhu AT, Ku IA, Adatya S, Bhatt AS. Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure With Improved Ejection Fraction. Journal of the American College of Cardiology. 2025 Aug 5; 86(5):338-350, DOI: 10.1016/j.jacc.2025.05.040.

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Abstract:

BACKGROUND: The prevalence of heart failure with improved ejection fraction (HFimpEF) is anticipated to increase with the availability and implementation of novel pharmacotherapy for heart failure with reduced ejection fraction (HFrEF). However, there are limited data on contemporary epidemiology, management, and outcomes for this clinical entity. OBJECTIVES: The aim of this study was to describe epidemiology, guideline-directed medical therapy (GDMT), and outcomes among patients with HFimpEF across a large, diverse, multisite integrated health care delivery system. METHODS: Patients who were diagnosed with incident HFrEF between January 2013 and December 2022 across the Kaiser Permanente Northern California integrated health care delivery system were identified. Rates of incident HFimpEF, defined as HFrEF with a follow-up ejection fraction > 40% and with > 10% absolute left ventricular ejection fraction improvement within 12 months of incident HFrEF diagnosis, were identified. GDMT was examined at the time of incident HFrEF and HFimpEF and in the year following HFimpEF. Rates of worsening heart failure events and death were examined and compared among those with HFimpEF vs persistent HFrEF. RESULTS: In total, 28,292 patients with newly diagnosed HFrEF (mean left ventricular ejection fraction 31.1% ± 7.4%) were identified, of whom 8,656 (30.6%) experienced HFimpEF within 12 months. Use of GDMT marginally decreased in most medication categories after incident HFimpEF during the study period. Rates of worsening heart failure were 17.4 per 100 person-years (95% CI: 16.9-18.0 per 100 person-years) among patients with HFimpEF vs 34.1 per 100 person-years (95% CI: 33.5-34.6 per 100 person-years) among patients with persistent HFrEF (HR: 0.58; 95% CI: 0.55-0.61 per 100 person-years). Rates of death were 5.7 per 100 person-years (95% CI: 5.4-6.0 per 100 person-years) and 11.0 per 100 person-years (95% CI: 10.7-11.3 per 100 person-years) among patients with HFimpEF and those with persistent HFrEF, respectively (HR: 0.52; 95% CI: 0.49-0.56). Withdrawal of GDMT was modestly associated with greater clinical risk. CONCLUSIONS: A significant percentage of patients with HFrEF experience improvement in ejection fraction, transitioning to HFimpEF, yet remain at significant clinical risk. Further research is needed to evaluate the impact of sustained GDMT adherence and therapeutic optimization on outcomes in patients with HFimpEF.