In dogs with chronic AV-block, alternating preload significantly increased beat-to-beat variability in ventricular repolarization compared to acute AV-block (2.2±1.1 ms vs 0.45±0.14 ms, P<0.01).
In a canine model of chronic AV block, beat-to-beat variability in ventricular repolarization is driven by preload changes and mediated by stretch-activated channels, unmasking latent risk for Torsade de Pointes.
Absolute Event Rate: 2.2% vs 0.45%
p-value: p=<0.01
BACKGROUND: Beat-to-beat variability in ventricular repolarization (BVR) associates with increased arrhythmic risk. Proarrhythmic remodeling in the dog with chronic AV-block (CAVB) compromises repolarization reserve and associates with increased BVR, which further increases upon dofetilide infusion and correlates with Torsade de Pointes (TdP) arrhythmias. It was hypothesized that these pro-arrhythmia-associated increases in BVR are induced by beat-to-beat variability in preload. METHODS AND RESULTS: Left ventricular monophasic action potential duration (LVMAPD) was recorded in acute (AAVB) and CAVB dogs, before and after dofetilide infusion. BVR was quantified as short-term variability of LVMAPD. The PQ-interval was controlled by pacing: either a constant or an alternating preload pattern was established, verified by PV-loop. The effect of the stretch-activated channel blocker, streptomycin, on BVR was evaluated in a second CAVB group. At alternating preload only, BVR was increased after proarrhythmic remodeling (0.45±0.14 ms AAVB vs. 2.2±1.1 ms CAVB, P<0.01). At CAVB, but not at AAVB, dofetilide induced significant proarrhythmia. Preload variability augmented the dofetilide-induced BVR increase at CAVB (+1.5±0.8 ms vs. +0.9±0.9 ms, P=0.058). In the second group, the increase in baseline BVR by alternating preload (0.3±0.03 ms to 1.0±0.8 ms, P<0.01) was abolished by streptomycin (0.5±0.2 ms, P<0.05). CONCLUSIONS: In CAVB dogs, the inverse relation between BVR and repolarization reserve originates from an augmented sensitivity of ventricular repolarization to beat-to-beat preload changes. Stretch-activated channels appear to be involved in the mechanism of BVR. (Circ J 2016; 80: 1336-1345).
Stams et al. (Fri,) conducted a other in Chronic atrioventricular block. Alternating preload pattern vs. Acute atrioventricular block was evaluated on Beat-to-beat variability in ventricular repolarization (BVR) (p=<0.01). In dogs with chronic AV-block, alternating preload significantly increased beat-to-beat variability in ventricular repolarization compared to acute AV-block (2.2±1.1 ms vs 0.45±0.14 ms, P<0.01).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: