Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF

TL;DR

This paper reviews how heart metabolism differs in healthy individuals and those with heart failure, proposing new ways to measure and treat these conditions.

Contribution

The paper introduces a dynamic functional profiling approach to assess cardiac metabolic flexibility for personalized treatment.

Findings

HFrEF involves mitochondrial dysfunction and lipotoxicity, while HFpEF is driven by comorbidities and microvascular issues.

Biomarkers like ketones, acylcarnitines, and amino acids reflect metabolic flux in heart failure.

Dynamic profiling using tests like mixed-meal or exercise can improve risk stratification and therapy.

Abstract

Cardiac metabolic flexibility is a key determinant of myocardial energetic resilience. In heart failure with reduced ejection fraction (HFrEF), intrinsic mitochondrial dysfunction and lipotoxicity compromise oxidative capacity. In contrast, heart failure with preserved ejection fraction (HFpEF) is orchestrated primarily by systemic comorbidities and coronary microvascular dysfunction, which decouple glycolysis from glucose oxidation. This review integrates these distinct pathophysiologies into a comprehensive biomarker framework. Beyond core hemodynamic markers, we detail indices of metabolic flux (ketones, acylcarnitines, branched-chain amino acids), endothelial injury, and fibrosis. We further prose a shift from static, isolated measurements to dynamic functional profiling using standardized challenges (e.g., mixed-meal or exercise tests) to quantify metabolic suppression and recovery kinetics. This structured hierarchy enables phenotype-tailored risk stratification and guides mechanism-based precision therapies in the era of personalized medicine.

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