Comprehensive quantification of fuel use by the failing and nonfailing human heart

The heart consumes circulating nutrients to fuel lifelong contraction,but a comprehensive mapping of human cardiac fuel use is lacking. We usedmetabolomics on blood from artery, coronary sinus, and femoral vein in 110patients with or without heart failure to quantify the uptake and release of277 metabolites, including all major nutrients, by the human heart and leg.The heart primarily consumed fatty acids and, unexpectedly, little glucose;secreted glutamine and other nitrogen-rich amino acids, indicating activeprotein breakdown, at a rate ~10 times that of the leg; and releasedintermediates of the tricarboxylic acid cycle, balancing anaplerosis fromamino acid breakdown. Both heart and leg consumed ketones, glutamate, andacetate in direct proportionality to circulating levels, indicating thatavailability is a key driver for consumption of these substrates. Thefailing heart consumed more ketones and lactate and had higher rates ofproteolysis. These data provide a comprehensive and quantitative picture ofhuman cardiac fuel use.