Enhanced susceptibility for acquired Torsade de Pointes arrhythmias in the dog with chronic, complete AV block is related to cardiac hypertrophy and electrical remodeling

Background-Chronic, complete AV block (CAVB) in the dog leads to ventricular hypertrophy, which has been described as an independent risk factor for arrhythmias. In this model, we examined (1) whether the short- and long-term electrical adaptations predispose to acquired torsade de pointes arrhythmias (TdP) and (2) the nature of the structural and functional adaptations involved. Methods and Results-We determined (I) endocardial right (RV) and left (LV) ventricular APD, Delta APD (LV APD-RV APD), presence of EADs at 0 weeks (acute: AAVB), and CAVE (6 weeks) and inducibility of TdP by pacing and d-sotalol (n=10); (2) steady-state and dynamic LV hemodynamics at 0 and 6 weeks (n=6); (3) plasma neurohumoral levels in time (n=7); (4) structural parameters of the LV and RV of CAVE dogs (n=6) compared with sinus rhythm (SR) dogs (n=6); and (5) expression of ventricular mRNA atrial natriuretic factor (ANF) in CAVE (n=4) and SR (n=4) dogs. Compared with AAVB, CAVE led to nonhomogeneous prolongation of LV and RV APD and different sensitivity for d-sotalol, leading to EADs (4 of 14 versus 9 of 18, P<0.05), increased Delta APD (45+/-30 versus 125+/-60 ms, P<0.05), and induction of TdP in most dogs (0% versus 60%, P<0.05). CAVE led to biventricular hypertrophy, whereas LV function was similar in AAVB and CAVE. The neurohumoral levels were transiently elevated. The LV and RV collagen and the capillary/fiber ratio remained normal, whereas ventricular ANF mRNA was not detectable. Conclusions-The electrical remodeling occurring after CAVE predisposes the heart to acquired TdP, whereas the structural changes (hypertrophy) are successfully aimed at maintaining cardiac function.