Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker

Area of Science:

• Biochemistry
• Cardiology
• Metabolomics

Background:

• Skeletal muscle metabolic and structural changes are observed in heart failure (HF) patients, impacting muscle endurance.
• Reduced muscle endurance (RME) is a common symptom in both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).
• Understanding the distinct metabolomic profiles associated with RME in HFpEF versus HFrEF is crucial for identifying underlying pathophysiological differences.

Purpose of the Study:

• To establish metabolomic phenotypes for patients with RME in HFpEF compared to HFrEF.
• To investigate the potential of Kynurenine (Kyn) as a biomarker for RME in heart failure patients.

Main Methods:

• Prospective study including 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC).
• Evaluated isokinetic muscle function, echocardiography, spiroergometry, and serum metabolite concentrations using liquid chromatography tandem mass spectrometry.
• Analyzed amino acids (AA), acylcarnitines (ACs), and Kynurenine (Kyn) levels.

Main Results:

• HF patients exhibited reduced amino acids (AAs) compared to HC, with specific perturbations in HFpEF and HFrEF.
• Elevated Kyn and acylcarnitines (ACs) were found in both HFpEF and HFrEF patients.
• HFpEF with RME showed reduced ACs, while HFrEF with RME displayed distorted AA metabolism. Kyn demonstrated potential as a biomarker for RME in HF (AUC 0.83).

Conclusions:

• RME in HFpEF and HFrEF presents with distinct metabolomic profiles, indicating varied pathophysiological mechanisms.
• Kynurenine (Kyn) may serve as a promising biomarker for identifying reduced muscle endurance in heart failure patients.