Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure

Area of Science:

• Biochemistry
• Cardiology
• Metabolomics

Background:

• Multi-omics approaches provide deeper biological insights compared to targeted investigations.
• This study focused on applying multi-omics to patients diagnosed with heart failure with reduced ejection fraction (HFrEF).

Purpose of the Study:

• To investigate the metabolic profile of patients with HFrEF using comprehensive multi-omics techniques.
• To explore the potential of breath acetone as a non-invasive biomarker for HFrEF detection.

Main Methods:

• Collected plasma and urine samples from 46 HFrEF patients and 20 controls for metabolomic profiling (LC-MS/GC-MS, SPME volatilomics).
• Defined HFrEF based on left ventricular global longitudinal strain, ejection fraction, and NT-proBNP levels.
• Validated findings using a consumer breath acetone (BrACE) sensor in 73 individuals.

Main Results:

• Identified 28 metabolites via GC-MS, 35 via LC-MS, and 4 volatiles via SPME.
• Observed alterations in alanine, aspartate, glutamate, citric acid cycle, arginine biosynthesis, and glyoxylate/dicarboxylate metabolism in HFrEF patients.
• Found a correlation between plasma acetone and NT-proBNP (r=0.59), 2-oxovaleric acid, and cis-aconitic acid, indicating links to ketone metabolism and mitochondrial energetics.
• Breath acetone levels (>1.5 ppm) differentiated heart failure from other cardiac conditions (AUC=0.8).

Conclusions:

• Breath acetone, detectable by a consumer sensor, can distinguish HFrEF from other cardiac pathologies.
• While promising for screening, breath acetone is not exclusively indicative of cardiac conditions.