Myocardial metabolism evaluation and ketones utilization in the failing human heart

Background: Under normal circumstances, free fatty acids (FFAs) are the predominant energetic substrate of the heart. In experimental and end-stage models of heart failure (HF) a quantitative switch from a predominance of FFAs utilization to the more energy favourable ketone bodies has been demonstrated. The aim of this study was to identify and quantify the heart substrates utilization in mild to moderate human HF. Methods: β-hydroxybutyrate, lactate, triacyclglycerols, glucose and FFAs concentrations in arterial, coronary sinus (CS), and central venous beds were measured after an overnight fast to derive myocardial substrates utilization in HF patients and controls scheduled for cardiac device implanting procedures. Results: A total of 15 HF patients and 11 controls were enrolled. Arterial and CS metabolites concentration were similar between the groups. A significant reduction in the myocardial FFAs extraction was showed in HF patients compared to controls (HF 0.07 +- 0.23 mmol/L vs non-HF 0.25 +- 0.16 mmol/L, p=0.03), together with an inverse association between FFAs and neurohormonal and echocardiographic HF hallmarks. Opposite, β-hydroxybutyrate, lactate, triacyclglycerols and glucose extractions were relatively unchanged between groups. The net cardiac extraction of β-hydroxybutyrate was directly associated to HF duration. When diabetic and non-diabetic patients were compared among HF population, the results were substantially similar, with a slight trend in reduction of FFAs net extraction (HF 0.03 +- 0.30 mmol/L vs non-HF 0.26 +- 0.12 mmol/L, p=0.09). Conclusions: In our study ketone bodies utilization was unchanged between mild to moderate HF patients and controls. We showed a reduced myocardial FFAs extraction consistent with a downregulation of beta-oxidation in the failing heart in HF population. Future studies are needed to clarify mechanisms that regulate the metabolic switch and its timing.