Abstract 562: Comprehensive Arteriovenous Metabolomics in the Human Heart

Abstract

Introduction: Despite broad interest in the role of metabolism in the pathogenesis of heart failure, a definitive account of fuel use by the beating human heart in situ is lacking. We therefore determined the uptake and release of over 270 metabolites by simultaneous sampling of arterial, coronary sinus, and femoral venous blood in 100 patients. Methods: We enrolled 100 patients (60% male, 12% diabetic, age = 63.6 +/- 13.5 years, BMI = 29.75 +/- 6.1, EF = 57.14 +/- 6.48) undergoing ablation of atrial fibrillation. We used liquid chromatography-mass spectrometry to quantify over 270 metabolites in plasma from coronary sinus, femoral vein, and arterial blood. We also measured O 2 and CO 2 concentration, as well as atrial pressure. Results: We detected uptake or release of 77 metabolites by the heart and 136 metabolites across the leg (p <0.05 after Benjamini-Hochberg correction). We determined the cardiac extraction of all major fuel sources, including 29 fatty acids, 11 amino acids, lactate, acetoacetate, and 3-hydroxybutyrate. Several patterns emerge: first, while the leg extracts glucose (FV/A = 0.95, q = 4.7x10-14) and releases lactate (FV/A = 1.11, q = 2.87x10-14), the heart extracts lactate (CS/A = 0.95, q = 3.77x10-9) and neither extracts nor secretes glucose. Second, while the leg releases nearly all fatty acid and amino acid species, the heart consumes most fatty acids and certain non-essential amino acids. Third, extraction of unsaturated acylcarnitines correlates with left atrial pressure (p<0.01). Finally, we find a significant positive correlation between myocardial O2 consumption and extraction of ketones (p < 0.01), but not other major cardiac fuels. Conclusion: We present the most comprehensive study to date of metabolite use and secretion by the human heart. We find the heart to be an avid consumer of fatty acids and ketone bodies, but less so of glucose and essential amino acids. Consumption of ketones increases with O2 consumption, suggesting that ketones may be a preferential fuel source under high work loads. Extraction of certain acylcarnitines increases with left atrial pressure, indicating metabolic reprogramming under high filling pressures. In summary, we provide the first comprehensive model of fuel use by the beating human heart in situ.