Heterogeneity of ejection fraction recovery in acute heart failure with reduced ejection fraction: a phenotype-based analysis from a nationwide registry
I Kim, J H Cho, H J Lee, H Kim, E J Kim, J H Lee, M C Cho, H J Cho, B S Yoo, S M Kang, D J ChoiAbstract
Background
Predictors of left ventricular ejection fraction (EF) recovery after acute heart failure (AHF) with reduced EF (HFrEF) remains incompletely understood. Phenotype-based approaches may provide deeper insights into this heterogeneity beyond conventional clinical classifications. This study aimed to characterize clinical phenotypes associated with EF recovery in patients hospitalized with AHF and HFrEF using a nationwide registry.
Methods
We analyzed patients with AHF and baseline HFrEF enrolled in the Korean HF III (KorHF III) registry. Among 7,351 patients with AHF from 47 tertiary university hospitals in South Korea, 1,264 HFrEF patients with baseline and follow-up echocardiography were finally included for the analysis. EF recovery was defined as the absolute change in left ventricular EF during follow-up echocardiographic assessment. To explore baseline factors associated with subsequent EF change, univariable linear regression analyses were performed using EF change as a continuous outcome. Based on the regression-derived determinants, patients were classified into distinct clinical phenotypes reflecting differences in age, ischemic burden, cardiac structure, and hemodynamic reserve, using baseline variables only. EF recovery was then systematically compared across the resulting phenotypes.
Results
Four distinct phenotypes were identified. Cluster 1 (Elderly Remodeling) was characterized by advanced age, lower baseline EF, enlarged left ventricular dimensions, and limited EF recovery (mean ΔEF 17.2 ± 13.6%). Cluster 2 (Ischemic Burden), predominantly composed of patients with prior myocardial infarction and lower systolic blood pressure (sBP), demonstrated the most constrained EF improvement (mean ΔEF 8.8 ± 10.8%). Cluster 3 (Preserved Structure) showed relatively younger age, higher baseline EF, smaller left ventricular size, and moderate EF recovery (mean ΔEF 15.8 ± 12.9%), consistent with preserved structural reserve. In contrast, Cluster 4 (Hemodynamic Resilience)—characterized by younger age, lower baseline EF but higher sBP and hemoglobin levels—exhibited the greatest degree of EF recovery (mean ΔEF 24.2 ± 13.0%). Mean EF improvement differed substantially across phenotypes, highlighting marked heterogeneity in myocardial recovery potential.
Conclusions
In a large nationwide cohort of patients with AHF and HFrEF, EF recovery was highly heterogeneous and could be effectively stratified using phenotype-based classification derived from regression-identified determinants. These findings underscore the importance of hemodynamic and structural reserve in myocardial recovery and may inform personalized risk stratification and post-discharge management strategies in acute HFrEF patients.For image description, please refer to the figure legend and surrounding text.