Molecular aspects of arrhythmias associated with cardiomyopathies

Abstract

The increased risk of sudden cardiac death in patients with myocardial hypertrophy and heart failure is the result of remodeling that occurs in both the myocyte and interstitial compartments of the heart. Action potential prolongation is a hallmark of hypertrophied and failing myocardium and is a consequence of differential expression and function of membrane currents and transporters. Functional downregulation of K currents in the ventricle is a recurring theme in hypertrophy and failure; the reduction in the density of the transient outward current (I(to)) is the most consistent observation, whereas data on the density of the inward (I(K1)) and the delayed rectifier (I(K)) currents are more contradictory. The altered intracellular Ca handling of the myopathic hearts prolongs the decay of the L-type Ca current and favors extrusion of cytosolic Ca2+ via the Na+-Ca2+ exchanger. The interaction between such altered membrane currents and a changed neurohumoral milieu creates a substrate that is highly susceptible to potentially lethal ventricular arrhythmias.