Heart Failure With Improved Ejection Fraction (HFimpEF): Current Evidence, Clinical Implications, and Future Directions

Q: What is the clinical evidence from this study?

Study design: Review. Population: Heart failure with improved ejection fraction (HFimpEF). Intervention: Guideline-directed medical therapy (GDMT) vs. Treatment withdrawal or de-escalation.

Q: What does this research mean for the field?

Heart failure with improved ejection fraction represents a state of functional remission rather than a definitive cure, requiring indefinite continuation of guideline-directed medical therapy to prevent recurrent systolic dysfunction. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Teresa Fernández Moreno; Franciszek Kukliński; Małgorzata Knapp; Karol Adam Kamiński; José A. Barrabés; Agnieszka Tycińska

doi:10.20883/medical.e1676

September 30, 2026Journal of Medical ScienceOpen Access

Heart Failure With Improved Ejection Fraction (HFimpEF): Current Evidence, Clinical Implications, and Future Directions

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Key result

GDMT withdrawal in HFimpEF triggers relapse in ~44% of patients within 6 months.

Why the study?

Heart failure with improved ejection fraction (HFimpEF) has emerged as a distinct clinical phenotype representing functional remission rather than cure, carrying important clinical implications for continuing guideline-directed medical therapy and device therapy decision-making alongside remaining knowledge gaps.

Does the indefinite continuation of guideline-directed medical therapy prevent recurrent systolic dysfunction and reduce adverse cardiovascular events compared to treatment withdrawal in patients with heart failure with improved ejection fraction (HFimpEF)?

Key Points

To review current evidence on the definition, epidemiology, pathomechanisms, imaging markers, and therapeutic management of heart failure with improved ejection fraction (HFimpEF).
Conducted a descriptive narrative review of published clinical studies and registry data evaluating HFimpEF phenotypes, left ventricular ejection fraction (LVEF) trajectories, and treatment strategies.
HFimpEF occurs in approximately 20% to over 50% of patients with initial heart failure with reduced ejection fraction, with most LVEF improvement developing within the first 12–24 months.
Approximately 70% of patients maintain an LVEF >40% on subsequent imaging, while the remainder experience transient recovery followed by recurrent systolic dysfunction.
Withdrawal or de-escalation of guideline-directed medical therapy is associated with high rates of recurrent systolic function deterioration, justifying indefinite continuation of disease-modifying therapy.

Structured PICO

Does the indefinite continuation of guideline-directed medical therapy prevent recurrent systolic dysfunction and reduce adverse cardiovascular events compared to treatment withdrawal in patients with heart failure with improved ejection fraction (HFimpEF)?

P

Population

Patients with heart failure with reduced ejection fraction (baseline LVEF ≤40%) who achieve an LVEF improvement of at least 10% to >40% following therapy.

I

Intervention

Continuation of guideline-directed medical therapy (GDMT), including neurohormonal blockers, angiotensin receptor-neprilysin inhibitors (sacubitril/valsartan), SGLT2 inhibitors (dapagliflozin), and nonsteroidal mineralocorticoid receptor antagonists (finerenone).

C

Comparator

Withdrawal or de-escalation of guideline-directed medical therapy.

O

Outcome

Maintenance of reverse remodeling, LVEF trajectories, relapse of LV systolic dysfunction, all-cause mortality, cardiovascular death, and heart failure hospitalization.

This narrative review highlights that heart failure with improved ejection fraction (HFimpEF) represents a state of functional myocardial remission rather than a definitive cure, necessitating the indefinite continuation of guideline-directed medical therapy and longitudinal monitoring to prevent relapse.

Limitations

Most existing HFimpEF studies are retrospective, observational, and single-center, limiting causal inference and generalizability.
Selection bias is common due to inclusion of patients with serial echocardiographic follow-up, potentially overestimating prevalence and favorable prognosis.
Considerable heterogeneity in the timing and frequency of non-protocol-based imaging assessments makes it difficult to identify transient HFimpEF and early relapse.
Near-exclusive reliance on echocardiographic LVEF with limited incorporation of advanced imaging (GLS, CMR) limits detection of residual myocardial dysfunction and fibrosis.
Underrepresentation of contemporary therapies and lack of systematic evaluation of treatment intensity, longitudinal changes, and adherence.
Absence of randomized clinical trials specifically designed for HFimpEF populations.
Most published studies in the existing HFimpEF literature are retrospective, observational, and often single-centre, limiting causal inference and generalizability.
Selection bias is common because only patients with serial echocardiographic follow-up are included.
Considerable heterogeneity exists in the timing and frequency of imaging assessments, which are often not protocol-based.
Near-exclusive reliance on echocardiography-derived LVEF with limited incorporation of advanced techniques such as GLS or CMR.

Implication

Supports indefinite GDMT in HFimpEF; confirms remission not cure and extends evidence against withdrawal.

Abstract

Heart failure with improved ejection fraction (HFimpEF) has emerged in recent years as a distinct clinical phenotype within the spectrum of heart failure subtypes. Current evidence supports the hypothesis that HFimpEF represents a state of functional remission rather than a definitive cure, with important clinical implications, particularly for the continuation of guideline-directed medical therapy (GDMT) and for decision-making regarding device therapies. Withdrawal or de-escalation of treatment is associated with high rates of recurrent systolic function deterioration, justifying the indefinite continuation of disease-modifying therapy. A descriptive narrative review of the available literature was performed to summarise current evidence on the definition, epidemiology, pathophysiological mechanisms, left ventricular ejection fraction (LVEF) trajectories, advanced diagnostic tools, and therapeutic considerations in HFimpEF, and to discuss the main knowledge gaps and future research directions. A better understanding of this phenotype will enable more effective risk stratification and progress towards more individualised management of patients with heart failure, with potential benefits for long-term patient outcomes and care.

Discussion

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Cite This Study

Moreno et al. (2026) conducted a review in Heart failure with improved ejection fraction (HFimpEF). Guideline-directed medical therapy (GDMT) vs. Treatment withdrawal or de-escalation was evaluated. Heart failure with improved ejection fraction represents functional remission rather than cure, with GDMT withdrawal causing relapse in ~44% of patients within 6 months.

synapsesocial.com/papers/6ae28e94cbadf70daf6c433b https://doi.org/10.20883/medical.e1676

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Heart Failure With Improved Ejection Fraction (HFimpEF): Current Evidence, Clinical Implications, and Future Directions

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Heart Failure With Improved Ejection Fraction (HFimpEF): Current Evidence, Clinical Implications, and Future Directions

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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