Exhaled breath acetone: a non-invasive marker of disease severity across the spectrum of heart failure

<i>Background.</i>Increased exhaled breath acetone (EBA) concentrations might reflect impaired myocardial energetics and haemodynamic stress. We investigated the relation of EBA and cardiac structure, function, and exercise capacity in patients with or at risk of heart failure (HF).<i>Methods.</i>We enrolled outpatients with HF and reduced (<50%, HFrEF) or preserved (>50%, HFpEF) left ventricular ejection fraction (LVEF) and subjects with cardiovascular risk factors and/or structural heart disease without established HF. All participants underwent clinical and laboratory evaluation, resting transthoracic echocardiography, and a combined cardiopulmonary-echocardiographic stress test with EBA monitoring at rest (EBA_rest) and during exercise (EBA_ex).<i>Results.</i>Patients with HFpEF (<i>n</i>= 62) were older and more often female than those at risk of HF (<i>n</i>= 50) or with HFrEF (<i>n</i>= 41). EBA_rest(1.5, interquartile range (IQR) 1.0-3.1 vs 0.9, IQR 0.7-1.2 mcg l^-1) and EBA_ex(2.4, IQR 1.5-4.4 vs 1.1, IQR 0.9-2.1 mcg l^-1; all<i>p</i>< 0.0001) were significantly higher in patients with HF compared to others. Among HF patients, those in the highest EBA_resttertile had lower LVEF, greater echocardiographic signs of congestion, higher NT-proBNP levels, and lower peak oxygen consumption, indicating impaired exercise capacity. In multivariate regression, NT-proBNP (<i>p</i>= 0.0004) and the slope of minute ventilation to carbon dioxide production (<i>p</i>= 0.0013) were independent predictors of EBA_rest(adjusted<i>R</i>²= 0.458).<i>Conclusions.</i>EBA concentrations are higher in patients with HF compared to those without, regardless of LVEF, and are associated with markers of disease severity. Further studies are needed to determine whether EBA measurement can aid in HF diagnosis and management.