Insights into human cardiac lipid dynamics through comprehensive arteriovenous lipidomics

Free fatty acids (FFAs) are the adult heart's primary energy substrate, but human cardiac lipid exchange remains incompletely characterized. We assessed cardiac lipid import and export using arteriovenous lipidomics in a prospective observational study of 59 fasting patients undergoing catheter ablation for atrial arrhythmias. Paired arterial and coronary sinus plasma samples underwent targeted lipidomics, detecting 1,464 lipid species across 20 classes; 851 species were analyzed. Paired comparisons used separate Benjamini-Hochberg corrections for classes and species. The heart showed net uptake of FFAs (-122.4 μmol/L; 95% confidence interval [CI], -146.0 to -98.8; q = 1.49 × 10⁻¹³) and nonsignificant triglyceride uptake. Lysophosphatidylcholine was released (+4.32 μmol/L; 95% CI, 2.45 to 6.19; q = 2.12 × 10⁻⁴); no other class met q < 0.05. Thirty-two species met q < 0.05. Release from other classes offset FFA and triglyceride uptake on average, yielding a positive aggregate acyl-chain-equivalent difference (+28.2 μmol acyl-chain equivalents/L), although the CI included both uptake and release (95% CI, -112.8 to 169.2; P = 0.690). This study characterizes distinct patterns of cardiac lipid exchange under fasting conditions and provides a basis for studies in heart failure and broader cardiometabolic disease. Further studies are warranted to identify the sources of released lipids and explore cardiac lipid handling in the fed state.