Heart failure improvement, remission and recovery: patients characteristics and prognostic implications

Background

Heart failure with improved ejection fraction (HFimpEF) is increasingly recognized as a distinct heart failure (HF) phenotype, yet its definition remains heterogeneous. Traditional definitions rely exclusively on improvement in left ventricular ejection fraction (LVEF), whereas a recent expert consensus framework incorporates LVEF together with clinical and biochemical parameters, potentially identifying phenotypes with different prognostic implications.1-4

Purpose

To compare patient characteristics and outcomes across contemporary HFimpEF definitions, contrasting historical LVEF-based definitions with a multidimensional consensus-based approach, and to compare prognosis with persistent HF and matched individuals without HF.

Methods

We analyzed patients with HF with reduced/mildly reduced (HFrEF/HFmrEF) ejection fraction and ≥2 longitudinal registrations from the Swedish Heart Failure Registry (SwedeHF). Patients with HFrEF were classified as with HFimpEF according to the definitions proposed by the European Society of Cardiology (ESC), American College of Cardiology (ACC), and Universal Definition (UD), or as not improving.1-3 Separately, patients with HFrEF or HFmrEF were classified according to a recent consensus framework, integrating EF, NYHA functional class, and NT-proBNP levels to define improved HF (impHF), HF in remission (remHF), recovered HF (recHF).4 Patient characteristics, predictors of improvement, and outcomes were compared with patients with non-improving HF and with non-HF controls matched 3:1 by sex, year of birth, and county of residence.

Results

Among 3,814 HFrEF patients and 4,125 HFrEF/HFmrEF patients, those fulfilling improvement criteria (median time 359 days, IQR 179-773) by any definition were younger, more likely female, had shorter HF duration, fewer comorbidities, and greater reductions in NT-proBNP as compared with patients with persistent HF. Longer HF duration, older age, device therapy and comorbidities were associated with a lower likelihood of HF improvement.

Over a median follow-up of 1.8 years [IQR 0.8-3.2], as compared with patients with persistent HF, those fulfilling criteria for impHF based on ACC, ESC or UD definitions had ≈70–80% lower crude risk of cardiovascular death or HF hospitalization (CVM/HHF) but a ≈2.5-fold higher risk as compared with 8205 matched non-HF controls. In contrast, recent consensus-based remHF and recHF phenotypes showed >90% and >95% lower crude risk of CVM/HHF, respectively, with no significant excess risk of CVM or all-cause mortality compared with 4764 matched non-HF controls. Results were overall consistent after adjustments.

Conclusions

LVEF-only definitions identify partial recovery with significant residual risk, whereas multidimensional consensus-based definitions capture patients with near-normal prognosis, supporting their use for refined risk stratification and personalized HF management.Improved HF definitionsFor image description, please refer to the figure legend and surrounding text.OutcomesFor image description, please refer to the figure legend and surrounding text.