Electrophysiological remodeling in heart failure

Abstract

Heart failure affects nearly 6 million Americans, with a half-million new cases emerging each year. Whereas up to 50% of heart failure patients die of arrhythmia, the diverse mechanisms underlying heart failure-associated arrhythmia are poorly understood. As a consequence, effectiveness of antiarrhythmic pharmacotherapy remains elusive. Here, we review recent advances in our understanding of heart failure-associated molecular events impacting the electrical function of the myocardium. We approach this from an anatomical standpoint, summarizing recent insights gleaned from pre-clinical models and discussing their relevance to human heart failure.

Figure 1. Cardiac conduction system

(© Carolina Biological Supply Company, Used with permission)

Figure 2. Anisotropic conduction between subendocardial and subepicardial layers of LV

In normal heart, impulse conduction is favored in the physiological direction of subendocardium (SEN) to subepicardium (SEP) and relatively disfavored from SEP to SEN. Electrical remodeling in heart failure, including AP prolongation and a diminished transmural gradient of APD30, abolishes directionally preferential conduction.