The continuous heart failure spectrum: moving beyond an ejection fraction classification.

Area of Science:

• Cardiology
• Clinical Trials
• Pathophysiology

Background:

• Randomized clinical trials historically selected heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to increase statistical power.
• This approach has led to an oversimplified view of HF, with classifications like HF with reduced LVEF (HFrEF), HF with preserved LVEF (HFpEF), and HF with mid-range LVEF (HFmrEF) implying distinct diseases based on arbitrary cut-offs.

Purpose of the Study:

• To challenge the current paradigm of classifying heart failure based solely on left ventricular ejection fraction (LVEF).
• To propose a new framework for understanding heart failure as a heterogeneous syndrome with a spectrum of phenotypes and dynamic disease progression.

Main Methods:

• Pathophysiological reasoning to critique LVEF-based classification.
• Conceptual framework proposing HF as a spectrum of phenotypes with overlapping and distinct characteristics.

Main Results:

• Current LVEF-based classifications oversimplify the complex nature of heart failure.
• Heart failure is a heterogeneous syndrome characterized by dynamic functional and structural changes, leading to diverse disease trajectories.

Conclusions:

• Reclassifying heart failure based on LVEF cut-offs is scientifically inadequate.
• Recognizing HF as a spectral disease will enable novel patient stratification and inform the design of future clinical trials.
• Future research should focus on deeper understanding beyond LVEF for improved HF management and therapeutic development.