Key result
Longer baseline QTc and increased contractility linked to dofetilide-induced TdP in dogs with AV block.
Why the study?
Despite combining multiple risk factors for Torsade de Pointes, approximately 33% of dogs with chronic atrioventricular block are resistant to dofetilide-induced arrhythmia.
What baseline factors are associated with dofetilide-induced Torsade de Pointes in the CAVB dog model?
What baseline factors are associated with dofetilide-induced Torsade de Pointes in the CAVB dog model?
Absolute Event Rate: 407% vs 338%
p-value: p=<0.05
In a CAVB dog model, baseline prolonged repolarization and increased contractility predict susceptibility to dofetilide-induced Torsade de Pointes.
Body weight may modulate TdP inducibility in CAVB dogs; leaves open relevance for human arrhythmia risk stratification.
The dog with chronic atrioventricular block (CAVB) combines a number of risk factors associated with Torsade de Pointes (TdP) arrhythmias. Nevertheless, approximately 33% of the animals are resistant to dofetilide-induced TdP arrhythmia. Of a group of 78 experimentally identical CAVB dogs, we compared TdP inducible vs. non-inducible animals for a set of basic, and cardiac electrical and mechanical parameters. Body weight, but not sex or age, is associated with TdP inducibility. Of the cardiac parameters, longer ventricular repolarization duration and increased contractility at baseline are associated with dofetilide-induced TdP arrhythmias. Differences in cardiac parameters disappeared upon dofetilide infusion. We discuss that prolonged repolarization and increased contractility may be early indications of calcium-mediated early after depolarization that may develop into TdP arrhythmias.
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Bavel et al. (2025) studied Chronic atrioventricular block (CAVB) and Torsade de Pointes (TdP) arrhythmia (n=78). Baseline prolonged repolarization and increased contractility vs. Non-inducible dogs was evaluated on Baseline QTc interval (ms) (p=<0.05). In dogs with chronic atrioventricular block, longer baseline ventricular repolarization (QTc 407 vs 338 ms) and increased contractility were significantly associated with dofetilide-induced Torsade de Pointes arrhythmias.
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