Epidemiology, clinical characterization, and outcomes for heart failure with improved ejection fraction
Authors: Min K H M , Lee K L , Parikh R V P , Horiuchi K M H , Ambrosy A P A , Tan T C T , Hamilton S H , Vardeny O V , Vasti E V , Sandhu A T S , Axelrod A A , Go A S G , Adatya S A , Bhatt A S B 
Published: October 2024

Abstract

Background
Contemporary guidelines propose a new classification of heart failure with improved ejection fraction (HFimpEF). The prevalence of HFimpEF is expected to increase with the implementation of guideline-directed medical therapy (GDMT); however, there are limited data on the epidemiology of and outcomes for this novel clinical entity.

Purpose
We describe the prevalence, GDMT use and outcomes among patients with HFimpEF within a large, integrated healthcare delivery system.

Methods
We identified adults ≥18 years with incident HF with reduced EF (HFrEF ≤40%) between January 2013 and December 2018 from a large, integrated healthcare system serving &gt;4.5 million members. HFimpEF was defined as known HFrEF with a follow-up EF measurement &gt;40% within 12 months after incident HFrEF. Among HFimpEF patients, we examined GDMT use at discharge after incident HFrEF, incident HFimpEF, and at 6- and 12-months post-HFimpEF. From 12 months post initial HFrEF diagnosis, we calculated incidence rates of subsequent worsening HF (WHF) events (i.e., HF-related hospitalization, emergency department or urgent outpatient visits adjudicated using validated natural language processing-based algorithms) and all-cause death through December 31, 2019. We compared rates between patients with HFimpEF and those with persistent HFrEF (i.e., having all LVEF measurements within 12 months of incident HFrEF ≤40%) using Cox proportional hazards models adjusted for the EF value at incident HFrEF.

Results
Among 12,639 patients with incident HFrEF, 4,124 (33%) experienced HFimpEF within 12 months. Among patients with HFimpEF, use of β-blockers (82%) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers (86%) was high, while angiotensin receptor-neprilysin inhibitor (1.2%) or mineralocorticoid receptor antagonist (28.2%) use was low. β-blockers, ACEi/ARB, and MRA use declined after incident HFimpEF (Figure, Panel A). Rates of WHF were 19.7 (95% Confidence Interval [CI]: 18.7 to 20.6) per 100 person-years among patients with HFimpEF vs. 40.0 (95% CI: 38.5 to 41.5) among patients with persistent HFrEF (hazard ratio [HR]: 0.55, 95% CI: 0.49 to 0.62; Figure, Panel B). Rates of death were 5.2 (95% CI: 4.7 to 5.7) and 8.4 (95% CI: 7.8 to 9.1) per 100 person-years among HFimpEF and persistent HFrEF, respectively (HR: 0.59, 95% CI: 0.52 to 0.67). Among patients with HFimpEF, those with an absolute EF improvement of ≥20% were less likely to experience WHF (HR: 0.82, 95% CI: 0.67 to 0.99) and death (HR: 0.85, 95% CI: 0.69 to 1.04) compared with those with &lt;20% improvement.

Conclusions
One in three patients experienced improvement in EF within 12 months of initial HFrEF diagnosis. HFimpEF is associated with a reduced risk of WHF events and death, although these patients remain at significant clinical risk. Further research is necessary to assess the potential impact of sustained adherence to GDMT and therapeutic optimization on HFimpEF patient outcomes.