Heart failure with preserved ejection fraction: controversies, challenges and future directions

Area of Science:

• Cardiology
• Internal Medicine
• Physiology

Background:

• Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of heart failure cases.
• Diagnosis is challenging due to diverse abnormalities, mimics, and normal natriuretic peptide levels in some patients.
• The heterogeneity of HFpEF contributes to diagnostic and therapeutic challenges, impacting clinical trials.

Purpose of the Study:

• To review current understanding and controversies surrounding HFpEF.
• To highlight diagnostic and therapeutic challenges in clinical practice.
• To discuss novel treatments and management strategies while identifying knowledge gaps.

Main Methods:

• Literature review of current concepts and controversies in HFpEF.
• Discussion of diagnostic challenges, including mimics and specific patient subsets.
• Exploration of potential pathophysiological mechanisms, such as nitric oxide signaling.
• Examination of novel subclassification approaches using informatics platforms.

Main Results:

• HFpEF is a heterogeneous syndrome with unclear etiology and pathophysiology.
• Dysregulated nitric oxide signaling may underlie HFpEF, leading to inflammation and endothelial dysfunction.
• Current subclassification methods aim to identify distinct patient phenotypes for targeted therapies.

Conclusions:

• HFpEF represents a significant clinical challenge due to its complexity and heterogeneity.
• Effective treatments are lacking, underscoring the need for further research into underlying mechanisms and patient stratification.
• Novel approaches in diagnostics, subtyping, and therapeutics are crucial for advancing HFpEF management.