IR. Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling. Am J Physiol Heart Circ Physiol 303: H1426 -H1434, 2012. First published October 5, 2012; doi:10.1152/ajpheart.00457.2012.-Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ϳ6.3 ϫ 6.3 cm 2 field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 Ϯ 44 vs. 448 Ϯ 39 ms, at BCL ϭ 2,000 ms, P Ͻ 0.05). Dispersion of APD was increased in three failing hearts (161 Ϯ 5 vs. 86 Ϯ 19 ms, at BCL ϭ 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 Ϯ 11 vs. 98 Ϯ 8 cm/s, at BCL ϭ 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF. action potential duration; conduction abnormality; human heart failure; dispersion of repolarization; right ventricle VENTRICULAR ARRHYTHMIA AND sudden cardiac death is common in patients with heart failure (HF) (12,29). However, the understanding of the origin and nature of arrhythmia in HF remains incomplete, particularly in humans. While clinical studies that demonstrate an increased QT dispersion and prolonged interval between T wave's peak and end (1, 13, 31) suggest a link between dispersion of repolarization and arrhythmia in HF patients, studies into the mechanism of repolarization dispersion in HF are limited and report inconsistent findings. In a tachypacing-induced HF dog model, increased dispersion of left ventricular (LV) repolarization was found to be present transmurally (between endocardium and epicardium) due to a disproportionate action potential duration (APD) prolongation of the M cells. However, this was not confirmed in the human heart with advanced HF. It was found that the dispersion of repolarization from endocardium to e...