Repolarization Gradients Alter Post-infarct Ventricular Tachycardia Dynamics in Patient-Specific Computational Heart Models

Eric Sung, Adityo Prakosa, Natalia Trayanova
Johns Hopkins University


Background: The post-infarct ventricular tachycardia (VT) substrate is characterized by structural and electrical heterogeneities. Repolarization heterogeneity contributes to VT arrhythmogenesis but the impact of repolarization gradients on post-infarct VT dynamics is not well-characterized.

Objective: The goal of this study is to assess the effects of repolarization gradients on post-infarct VT dynamics using patient-specific heart models.

Methods: 3D late gadolinium-enhanced magnetic resonance images were acquired from 7 patients with ischemic heart disease. Baseline models were reconstructed along with the patient-specific scar and infarct border zone distributions. Models with physiological action potential duration (APD) gradients along apicobasal (AB) and transmural (TM) axes were reconstructed. Rapid pacing from the right ventricular apex was applied to induce VTs. For models with APD gradients, two pacing protocols were applied: (1) exact timed stimulus that matched the timing of corresponding baseline protocols and (2) earliest timed stimulus with premature stimuli delivered as early as possible. The resultant VT dynamics (inducibility, re-entry pathway, and the exit site) were assessed.

Results: Ten VTs were induced across all baseline models. Repolarization gradients did not significantly impact VT inducibility (7 VTs induced, p<0.05). However, repolarization gradients altered the re-entry pathway in all models and exit site location in 5/7 models due to modulations in unidirectional conduction block. Both AB and TM APD gradients alone were also sufficient for inducing these changes in VT dynamics. Lastly, APD gradients revealed multiple distinct morphologies that used similar conducting channels in the patient-specific substrate.

Conclusion: These results highlight how the interplay between repolarization gradients and the patient-specific substrate can have consequences on VT dynamics. Thus, repolarization gradients induced physiologically or pharmacologically could impact post-infarct VT dynamics and should be considered during VT ablation procedures to improve therapeutic efficacy.