Targeted Quantitative Plasma Metabolomics Identifies Metabolite Signatures that Distinguish Heart Failure with...

Area of Science:

• Cardiovascular Medicine
• Metabolomics
• Biomarker Discovery

Background:

• Heart failure (HF) presents as two main phenotypes: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).
• Developing distinct biomarkers is crucial for phenotype-specific HF diagnosis and treatment strategies.
• This study aimed to identify plasma metabolic signatures differentiating HF phenotypes using quantitative metabolomics.

Purpose of the Study:

• To identify and validate plasma metabolic signatures that distinguish between HFrEF and HFpEF.
• To extend current knowledge of metabolic alterations in human HF.
• To explore potential links between metabolic signatures and HF severity.

Main Methods:

• Quantitative, targeted LC/MS plasma metabolomics was performed on 787 samples from HFrEF, HFpEF, and control groups.
• Analysis included 90 metabolites: 28 amino acids, 8 organic acids, and 54 acylcarnitines.
• Proteomic profiling using an OLINK panel was conducted on a subset of samples.

Main Results:

• Elevated unsaturated medium/long-chain acylcarnitines were observed in HFrEF compared to HFpEF and controls.
• Specific amino acid derivatives (e.g., ADMA) were elevated in HF, with ADMA uniquely in HFpEF.
• Ketone body 3-hydroxybutyrate (3-HBA) and C4-OH carnitine were uniquely elevated in HFrEF, correlating with NT-proBNP levels.

Conclusions:

• Distinct plasma metabolic signatures can differentiate between HFrEF and HFpEF.
• Metabolic reprogramming, particularly ketogenic pathways, appears unique to HFrEF.
• These identified metabolites may serve as future biosignatures for guiding HF phenotype-specific therapeutics.