Abstract 14991: Local Prolongation of Repolarization Prevents Post Myocardial Infarction Ventricular Tachycardia

Introduction: Reentry is the predominant mechanism underlying ventricular arrhythmias in chronic myocardial infarction patients. Reentry can be prevented by prolonging effective refractory period, thereby blocking reexcitation of recently activated tissue. This is currently achieved with systemically administered class III antiarrhythmic drugs. These therapies are limited by their risk of provoking ventricular arrhythmias by off-target effects. Hypothesis: Local prolongation of repolarization in healthy myocardium adjacent to the exit site attenuates reentry and postinfarction arrhythmias. Method and results: We used a pig model and generated myocardial infarction by balloon occlusion of the left anterior descending coronary artery and performed epicardial mapping 6 weeks later during Langendorff-perfusion. Programmed stimulation induced reentry leading to ventricular premature beats and sustained ventricular tachycardia (VT). Local injection of Sotalol adjacent to the infarcted myocardium prolonged repolarization and prevented VT after programmed stimulation. To translate these experimental findings to the patient situation we used a virtual heart based on data from a patient suffering from postmyocardial infarction VTs. The patient underwent pre-ablation cardiac late gadolinium enhanced- magnetic resonance imaging followed by geometrical reconstruction of the left ventricle and computational electrophysiological modelling of VT induction. We used a rapid pacing protocol to induce VT and determined the site where the activation front exited the infarct zone and reactivated the adjacent normal myocardium. Next, we prolonged repolarization of the normal myocardium adjacent to the exit site with 50 ms and performed rapid pacing to induce VT. This only resulted in a single premature ventricular beat after which sinus rhythm restored. Conclusion: Our experimental and in silico findings show the potential of local prolongation of repolarization a novel potentially genetic anti-arrhythmic therapy in post-infarction patients.