LVEF trajectory in HFimpEF and its association with prognosis

Abstract Background The 2021 revised Universal Definition of Heart Failure (HF) introduced the subgroup known as HF with improved ejection fraction (HFimpEF), aiming to establish a standardized definition for left ventricular ejection fraction (LVEF) improvement and emphasize the importance of longitudinally assessment of LVEF. However, there remains an insufficient characterization of the association between serial LVEF trajectory before and after impEF, and outcomes in HFimpEF. Purpose We aim to delineate the LVEF trajectory in patients with impEF and to discern specific LVEF trajectory pattern that portends an unfavorable prognosis. Methods We conducted a retrospective analysis by including hospitalized HF patients with baseline LVEF ≤ 40% and satisfactory serial echocardiographic follow-ups. ImpEF was defined as a follow-up LVEF measurement of > 40% with a ≥10-point increase from baseline. Longitudinal LVEF trajectories for patients with impEF (before and after LVEF improvement) were plotted according to the clinical outcome of all-cause death using Loess curves. LVEF changes over time were analyzed by unconditional non-linear mixed-effects modeling, and compared between the groups of patients who died and those who survived using conditional non-linear mixed-effects modeling. Results Among the initial 923 patients with reduced LVEF, 517 had impEF. According to Loess curves and non-linear mixed-effects analysis, LVEF trajectory of impEF differed according to the clinical outcome of death. For patients who suffered all-cause death, there was a comparatively limited improvement in LVEF followed by a more rapid plateauing and decline, exhibiting an inverted U-shaped pattern with lower LVEF values towards both ends of the distribution. Conclusions In HFimpEF, an inverted U-shaped trajectory of LVEF, characterized by limited initial improvement followed by subsequent decline, is associated with poorer prognosis. Serial LVEF monitoring in patients with HFimpEF could help with early identification of at-risk patients.Graphical Abstract