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. 2022 Dec 21;13(1):13.
doi: 10.3390/biom13010013.

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

Patrick A Gladding  1   2 , Maxine Cooper  1 , Renee Young  1 , Suzanne Loader  1 , Kevin Smith  3 , Erica Zarate  4 , Saras Green  4 , Silas G Villas Boas  4 , Phillip Shepherd  5 , Purvi Kakadiya  5 , Eric Thorstensen  6 , Christine Keven  6 , Margaret Coe  6 , Mia Jüllig  7 , Edmond Zhang  8 , Todd T Schlegel  9   10
Affiliations

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

Patrick A Gladding et al. Biomolecules. .

Abstract

Background: Multi-omics delivers more biological insight than targeted investigations. We applied multi-omics to patients with heart failure 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) and solid-phase microextraction (SPME) volatilomics in plasma and urine. HFrEF was defined using left ventricular global longitudinal strain, ejection fraction and NTproBNP. A consumer breath acetone (BrACE) sensor validated results in n = 73.

Results: 28 metabolites were identified by GCMS, 35 by LCMS and 4 volatiles by SPME 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), 2-oxovaleric and cis-aconitic acid, involved with ketone metabolism and mitochondrial energetics. BrACE > 1.5 ppm discriminated HF from other cardiac pathology (AUC 0.8, 95% CI 0.61 to 0.92, p < 0.0001).

Conclusion: Breath acetone discriminated HFrEF from other cardiac pathology using a consumer sensor, but was not cardiac specific.

Keywords: heart failure with reduced ejection fraction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
HFrEF = heart failure reduced ejection fraction, CCHF = chronic compensated heart failure, SPME = Solid-phase microextraction, GCMS = Gas chromatography mass spectrometry, LCMS = Liquid chromatography mass spectrometry.
Figure 1
Figure 1
SPME plasma NTproBNP ≥ 35 pmol/L. Log10 transformed t-test p values for individual metabolites with p-value threshold for multiplicity (horizontal line) (left). Acetone was the only VOC reaching statistical significance (right).
Figure 2
Figure 2
SPME urine NTproBNP > 211 pmol/L. Log10 transformed t-test p-values for individual metabolites with p-value threshold for multiplicity (horizontal line) (left). Single VOC reaching statistical significance (right).
See this image and copyright information in PMC

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