Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment

Area of Science:

• Cardiology
• Metabolic Disease
• Pathophysiology

Background:

• Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases globally.
• The rise in cardiometabolic diseases has increased the prevalence of the cardiometabolic HFpEF (cmHFpEF) phenotype.
• cmHFpEF results from the convergence of metabolic stress, hemodynamic stress, immune activation, and systemic inflammation.

Purpose of the Study:

• To review recent advances in the biology and pathophysiology of cmHFpEF.
• To highlight key aspects including metabolic alterations, immune changes, microvascular dysfunction, inflammation, and chromatin remodeling.
• To discuss potential mechanism-based therapeutic strategies for cmHFpEF.

Main Methods:

• Literature review of recent scientific work on cmHFpEF.
• Analysis of molecular cues and pathophysiological mechanisms.
• Synthesis of current understanding and therapeutic approaches.

Main Results:

• cmHFpEF is preceded by a "metabolic cardiomyopathy" characterized by myocardial metabolic remodeling and inflammation.
• This leads to left ventricular hypertrophy, diastolic dysfunction, and atrial dilatation.
• Recent research has identified molecular underpinnings of cmHFpEF pathogenesis.

Conclusions:

• cmHFpEF is a complex syndrome driven by multiple interconnected factors.
• Understanding the molecular and pathophysiological landscape is crucial for developing effective treatments.
• Targeting specific pathways involved in metabolic alterations, inflammation, and cardiac remodeling holds therapeutic promise.