Exhaled breath acetone for predicting cardiac and overall mortality in chronic heart failure patients

Abstract

Aims Exhaled breath acetone (EBA) has been described as a new biomarker of heart failure (HF) diagnosis. EBA concentration increases according to severity of HF and is associated with poor prognosis, especially in acute decompensated HF. However, there are no data on chronic HF patients. The aim is to evaluate the role of EBA for predicting cardiac and overall mortality in chronic HF patients. Methods and results In GENIUS-HF cohort, chronic patients were enrolled between August 2012 and December 2014. All patients had left ventricular ejection fraction ≤ 50%, and the diagnosis was established according to Framingham criteria. After consent, patients were submitted to clinical evaluation and exhaled breath collection. EBA identification and quantitative determination were done by spectrophotometry. The clinical characteristics associated with acetone were identified. All participants were followed for 18 months to assess cardiac and overall mortality. Around 700 participants were enrolled in the current analysis. Patients were 55.4 ± 12.2 years old, 67.6% male patients, and 81% New York Heart Association I/II with left ventricular ejection fraction of 32 ± 8.6%. EBA median concentration was 0.6 (0.3-1.2) ug/L. Acetone levels increased with the number of symptoms of HF and were associated with right HF signs/symptoms and liver biochemical changes. EBA at highest quartile (EBA > 1.2ug/L) was associated with a significantly worse prognosis (log rank test, P < 0.001). Cox proportional multivariable regression model revealed that EBA > 1.20ug/L was an independent predictor of cardiac (P = 0.011) and overall (P = 0.010) mortality in our population. Conclusions This study shows that EBA levels reflect clinical HF features, especially right HF signs/symptoms. EBA is an independent predictor of cardiac and overall mortality in chronic HF patients.

Novel Oxidative Stress Biomarkers with Risk Prognosis Values in Heart Failure

“…While EBA is also detected in patients with other diseases such as diabetes mellitus, lung cancer, and allergic asthma, it may still have potential in differentiating underlying HF [ 98 ]. EBA concentrations were also higher in more severe right sided-venous engorgement, suggesting that hepatic congestion may contribute to ketosis generation [ 99 ].…”

“…Patients with lower EBA levels and pentane upon initial hospital admission have been shown to have a significantly higher likelihood of survival [ 100 ]. A recent study of 695 patients with chronic HF concluded that higher EBA levels were independently correlated with cardiac and overall mortality over a follow-up period of 18 months [ 99 , 101 ]. With advances in metabolomics, EBA is indeed a promising biomarker with good correlation with HF severity and prognosis.…”

Ketones and the Heart: Metabolic Principles and Therapeutic Implications

“…Elevated concentrations of exhaled breath acetone are associated with poor outcomes in HFrEF. 60,61 Elevated ßOHB concentration also predicts outcomes in patients with arrhythmogenic cardiomyopathy. 9 In a prospective study, risk of HFrEF and HFpEF correlated with elevated ßOHB concentrations.…”

Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue

“…As mentioned, in patients with congestive HF, circulating ketone bodies are usually elevated, and their levels increase with worsening systolic myocardial function, commensurate with neurohormonal activation and with increasing atrial pressures and with the degree of venous congestion, partly ascribable to elevated FFA mobilization in response to heightened neurohormonal stimulation [ 9 , 46 , 47 ]. Acetone can be measured reliably in exhaled breath, acetoacetate in urine, and β-OHB in urine or via a finger-stick method by using portable devices, which renders them useful for routine clinical practice [ 48 , 49 , 50 ].…”

“…Thus, ketone bodies may constitute useful biomarkers of the severity of HF and its prognosis [ 40 , 46 , 47 ].…”