Abstract 17165: Myocardial Iron Depletion In Patients With Heart Failure Is Associated With Mitochondrial Dysfunction And Attenuation Of Citrate Synthase Activity

Introduction: Very little is known about the determinants and consequences of abnormal iron (Fe) content in the failing human myocardium. Hypothesis: We hypothesized that myocardial Fe deficiency (ID) in heart failure (HF) is associated with impaired mitochondrial function of Fe-regulated enzymes of respiratory chain (RC) and Krebs (TCA) cycle. Methods: LV samples were obtained from 90 consecutive patients undergoing transplantation (HF: LVEF 23±8%, age 53±11y, 83% males, 46% CAD, 24 % diabetes) and from 38 HF-free organ donors (CON: LVEF 57±12%, age 42±15y, 50% males, 14% with diabetes). Activities of citrate synthase (CS, Krebs cycle) and RC enzymes NADH-cytochrome c oxidoreductase (NCCR), succinate cytochrome c oxidoreductase (SCCR) and cytochrome c oxidase (COX) were measured in homogenates. Total Fe was measured by ICP-MS after microwave-assisted digestion of lyophilized samples. Results: Compared to CON, HF patients had lower total myocardial Fe (156±41 vs 200±38 μg/g dry weight, p Conclusions: Myocardial Fe content is systematically diminished in advanced HF and is associated with mitochondrial dysfunction, in particular with reduced CS activity. These relations may reflect Fe-dependent regulation of aconitase (TCA cycle enzyme) and may influence the utilization of energetic substrates.