Dynamic ejection fraction improvement drives prognosis in heart failure with improved ejection fraction
S Ravichandran, R V Parikh, A P Ambrosy, A S Go, T S Tan, G Manthripragada, S Solomon, O Vardeny, D Ouyang, A T Sandhu, M Vaduganathan, M P Porras, A S BhattAbstract
Background/Introduction
Heart failure with improved ejection fraction (HFimpEF) is a distinct clinical phenotype in which patients experience improvement in ejection fraction (EF) after initial diagnosis of HF with reduced EF (HFrEF). However, baseline EF and magnitude of EF improvement vary substantially in HFimpEF.
Purpose
To evaluate the association of baseline EF at incident HFrEF and magnitude of EF improvement at incident HFimpEF with clinical outcomes in patients with HFimpEF.
Methods
We developed a cohort of patients in a learning health system serving ~4.5 million members, with incident HFrEF from 2013 to 2024 and 1-year follow-up. HFimpEF was defined as HFrEF with a followup EF > 40% within 1 year of incident HFrEF, in accordance with the ACC/AHA definition. Patients with HFimpEF were categorized into 3 subgroups: (1) baseline EF <30% with any degree of absolute EF improvement, (2) baseline EF ≥30% with ≤15% absolute change in EF, and (3) baseline EF ≥30% with >15% absolute change in EF. The primary outcome was a composite of HF hospitalization and all-cause mortality. Associations between HFimpEF subgroups and the primary composite outcome were evaluated with nested Cox proportional hazards models, adjusted for age, sex, and cardiovascular comorbidities.
Results
Among 15,030 patients with HFimpEF, 4283 (28%) had baseline EF < 30% and any improvement in EF, 4951 (33%) had baseline EF ≥ 30% and ≤ 15% absolute improvement and 5796 (39%) had baseline EF ≥ 30% and >15% absolute improvement. Median EF improvement was 30% (IQR 24%-35%), 10% (IQR 7%-14%), and 22.5% (IQR 20%-26.5%) in these groups, respectively. GDMT rates were highest in those with lower baseline EF. Among those with HFimpEF who were alive at 1 year with subsequent follow-up (n=11,860), lower baseline EF was modestly associated with a higher risk of worsening HF (WHF) or death (aHR 1.06, 95% CI: 1.03-1.09 per 10% lower baseline EF). Each 10% absolute increase in EF was associated with an 18% lower risk for WHF or death (aHR 0.82, 95% CI: 0.81-0.84), adjusted for age, sex, and comorbidities. Greater magnitude of EF improvement was associated with a lower cumulative incidence of WHF or death, regardless of baseline EF.
Conclusion(s)
In a large, diverse U.S. cohort with HFimpEF, greater EF improvement—accompanied by higher use of GDMT—was strongly associated with improved outcomes, regardless of baseline EF. These findings support early initiation of GDMT and suggest that EF trajectory and magnitude of improvement may be more prognostically informative than absolute EF thresholds alone.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.