Exhaled breath acetone as a metabolic marker of early urgent heart transplant listing in patients with heart failure requiring inotropic support: a prospective cohort study

Aims Risk stratification in inotrope-dependent heart failure(HF) patients remains challenging, particularly at hospital admission. Exhaled breath acetone (EBA), a noninvasive marker of ketone metabolism, may help to identify those in need of advanced therapy. We evaluated the role of EBA on the risk of listing for urgent heart transplant(HT) or death. Methods and Results In this prospective single-center study, 287 patients admitted in hemodynamic profile C had exhaled air samples collected, analyzed by spectrophotometry, and were followed for 6 months. Cox multivariable models were applied, and cumulative incidence curves generated and an exploratory classification and regression tree (CART) analysis also performed. Median EBA was 5.8 (2.4–11.7) µg/L and patients reaching the primary outcome had higher EBA levels compared with those without events [6.8 (2.8–13.6) vs. 3.9 (2.0–8.5) µg/L; p=0.002]. In a multivariate model, EBA was shown to be an independent predictor of the combined primary outcome. Discriminatory performance was modest (AUC 0.607). EBA ≥4.3 µg/L was associated with a 1.49-fold increased risk of being listed urgent HT or of death (HR 1.49, 95% CI 1.08–2.06; p=0.016) and when combined with elevated BNP, risk increased further (HR 2.73, 95% CI 1.74–4.27; p<0.001). CART analysis showed that EBA further refined risk stratification among patients with elevated BNP levels and normal sodium concentrations. EBA was associated with urgent HT listing (p=0.032), but not with mortality alone (p=0.095). Conclusion In HF patients on inotropes, higher EBA levels were associated with increased risk of listing for urgent HT or death.