Metabolomics and a breath sensor identify acetone as a biomarker for heart failure

Abstract

Abstract Introduction Metabolomics delivers more biological and clinical insight than targeted investigations. We applied metabolomics to patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography mass spectrometry (LC-MS/GC-MS), nuclear magnetic resonance (NMR) metabolomics and solid-phase microextraction (SPME) volatilomics in plasma and urine. HFrEF was defined using left ventricular global longitudal strain (GLS) <18%, ejection fraction <50% and NTproBNP ≥35 pmol/L. A low cost consumer breath acetone (BrACE) sensor validated SPME results in 69 patients. Results 34 metabolites were identified by GCMS, 33 by LCMS and 2 volatiles by SPME (acetone, 2-pentanone in plasma and urine). Alanine, aspartate and glutamate, citric acid cycle, arginine biosynthesis, glyoxylate and dicarboxylate metabolism were altered in HFrEF. Plasma acetone correlated with NT-proBNP (r=0.59, 95% CI 0.4 to 0.7), triacylglycerol (55:9), 2-oxovaleric and cis-aconitic acid, involved with ketone metabolism and mitochondrial energetics. BrACE >1.5 ppm discriminated HF from other cardiac pathology (AUC 0.88, 95% CI 0.77 to 0.99, P<0.0001). Conclusion Breath acetone was detectable in HFrEF patients using a consumer sensor ($1/test) and although not cardiac specific, discriminated HF from other cardiac pathology. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Health Research Council of New Zealand