Adverse Remodeling of the Electrophysiological Response to Ischemia–Reperfusion in Human Heart Failure Is Associated With Remodeling of Metabolic Gene Expression

BACKGROUND—Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia–reperfusion although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute ischemia–reperfusion in heart failure and its potential causes, including the remodeling of metabolic gene expression. METHODS AND RESULTS—We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to ischemia–reperfusion, with greater action potential duration shortening (P