The role of exhaled breath acetone and BNP in predicting outcomes in advanced heart failure

Introduction With the advent of new therapies, there is increasing interest in understanding cardiac metabolism in heart failure (HF). Ketone bodies may act as an alternative energy source for myocardial metabolism, and acetone serves as a marker of ketogenic activity. In this context, Exhaled Breath Acetone (EBA) has emerged as a biomarker for HF diagnosis and chronic HF prognosis. However, its role as a predictor of adverse outcomes in advanced HF remains uncertain. B-Type Natriuretic Peptide (BNP), conversely, is a biomarker of myocardial stress, playing a critical role in HF diagnosis and prognosis. Since EBA and BNP reflect distinct physiological pathways, EBA might complement BNP as a prognostic marker in HF. Objective To evaluate the prognostic value of EBA in combination with BNP as a predictor of death or urgent heart transplantation (HT) among patients with HF in hemodynamic profile C(wet and cold).A secondary objective was to assess the association of these biomarkers with overall mortality. Methods This prospective, observational, single-center study included patients with advanced HF in a quaternary care hospital. Exhaled air samples were collected upon hospital admission and analyzed using spectrophotometry by reaction with salicylaldehyde. Cox proportional hazards multivariate analysis was employed to assess the predictive value of EBA for adverse outcomes and Kaplan Meier curves were built. Results From Jan 2019 to Aug 2023, 287 patients were enrolled. The median EBA level was 5.8 (2.4–11.7) µg/L, and the median BNP level was 1708 (1033–2775) pg/mL. EBA levels were significantly higher in patients who had the primary outcome of death or urgent HT [6.6 (2.8–13.15) vs. 4.6 (2.08–9.05) µg/L, p=0.014]. (Figure 1). The AUC of EBA for death or urgent HT was 0.585(0.519–0.651), p < 0.001 and 4.3ug/L was the best cutoff to predict the primary endpoint. EBA levels > or =4.3µg/L were associated with an increased risk of death or urgent HT [HR=1.42, 95% CI(1.03–1.96), p=0.003].When EBA > or =4.3µg/L was combined with BNP > or = 2214pg/mL, the risk of the primary outcome was increased in 2.5-fold [HR=2.5, 95% CI(1.64–3.97), p<0.001],even after adjusting for other independent predictors: BNP (p<0.001), systolic blood pressure (p=0.002), urea (p=0.022), and sodium (p<0.001).This combination also increased the risk of overall mortality [HR=3.0, 95% CI(1.73–5.20), p<0.001].Figure 2 depicts Kaplan-Meier curves of death or urgent HT according with levels of EBA and BNP at admission. Patients with high levels of both biomarkers had higher cumulative incidence of death or urgent HT in six months. (Log-rank test, p < 0.001). Conclusion The combination of elevated EBA and BNP levels significantly increased the risk of death or urgent HT, as well as overall mortality. These findings suggest that EBA, a biomarker of metabolism in HF, may provide additional prognostic value to BNP in patients with advanced HF.