Evolving Natural History of Left Ventricular Ejection Fraction Recovery and Relapse in Heart Failure With Reduced Ejection Fraction

BACKGROUND: Patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF; LVEF) may achieve recovery of LVEF. The trends in achieving LVEF recovery across time and the risk and clinical predictors of subsequent LVEF relapse remain understudied. The purpose of this study is to describe the contemporary natural history of LVEF recovery and relapse in HFrEF. METHODS: In this retrospective cohort study, an HFrEF cohort (LVEF ≤ 40%; n = 42,329) and an LVEF recovery cohort (HFrEF with improvement in LVEF to ≥ 50%; n = 10,877) were followed longitudinally to assess LVEF recovery and relapse, respectively, including in an analysis that stratified patients based on 3 distinct guideline-directed medical therapy (GDMT) eras. RESULTS: Coinciding with advances in GDMT, the probability of achieving LVEF recovery increased greatly across GDMT eras, with an estimated median time to recovery in the 2009-2015, 2016-2020 and 2021-2024 eras of 7 years (95% CI, 6.7-7.3), 3.9 years (95% CI, 3.7-4.0), and 1.8 years (95% CI, 1.7-1.9), respectively (P < 0.005). In the 2021-2024 era, an estimated 71.8% (95% CI, 69.4-74.2) of patients achieved LVEF recovery within 3 years. Nevertheless, the probability of sustaining LVEF recovery did not improve across GDMT eras, with an estimated 46.2% (95% CI, 44.9-47.4) of patients experiencing LVEF relapse within 5 years. A higher area deprivation index was independently associated with a lower probability of LVEF recovery and a higher risk of LVEF relapse. CONCLUSIONS: Patients with HFrEF are more likely to achieve LVEF recovery in the current era of GDMT compared with prior eras, but they are not less likely to experience LVEF relapse. Socioeconomic status independently influences prognosis beyond biological factors.