Mechanisms Underlying Arrhythmogenesis Associated with Heart Failure

The hallmark of electrophysiologic remodeling in heart failure is arrhythmogenic prolongation of the action potential. Downregulation of repolarizing K⁺ currents and bioenergetic pathways are hallmarks of electrophysiological remodeling. Ion transport and mitochondrial bioenergetic transcripts are tightly co-regulated, with a predicted increase in electrical instability in the failing myocardium. Cardiac resynchronization therapy (CRT) significantly shortens the action potential particularly in myocytes isolated from the lateral wall of the left ventricle during dyssynchronous contraction. This partial normalization of the electrical phenotype may provide an explanation for the reduced risk for arrhythmias and better prognosis after CRT.