Clinical significance and contributing factors of long-term variability in induced ventricular tachyarrhythmias

Introduction: Ventricular arrhythmias induced during electrophysiologic study (EPS) may vary over time, making arrhythmia induction studies unreliable. The aim of this prospective study was to clarify the clinical significance of long-term variability in induced arrhythmias and to elucidate factors determining this variability. Methods and Results: Three noninvasive EPSs were performed 1, 13, and 25 months after implantation of a cardioverter defibrillator in 40 patients with ventricular tachyarrhythmias, without a change in their antiarrhythmic drug regimens. The induced ventricular arrhythmias were categorized into five grades. Long-term variability, which was defined as a variation in the grades during the three EPSs, was observed in 23 patients (group A) and not in the remaining 17 patients (group B). During the 2-year period, spontaneous sustained ventricular arrhythmias developed in 15 patients (65%) in group A but in only 4 patients (24%) in group B (P = 0.01). Inducibility of sustained tachyarrhythmias was not associated with emergence of spontaneous arrhythmias. All patients also underwent thallium-201 and iodine-123-metaiodobenzylguanidine (MIBG) scans to evaluate the extent of the regions showing normal thallium uptake with reduced MIBG uptake. Group A patients showed greater thallium/MIBG mismatched regions than did group B patients (P = 0.01). Logistic regression analysis revealed that long-term variability (relative risk [RR] 7.55, P = 0.03), amiodarone therapy (RR 0.14, P = 0.04), and left ventricular ejection fraction <35% (RR 6.26, P = 0.04) were independent predictors of spontaneous arrhythmia occurrence. Conclusion: In patients with ventricular tachyarrhythmias, long-term variability in induced arrhythmias, but not the inducibility of arrhythmias, is associated with a higher incidence of spontaneous arrhythmias. Regional cardiac sympathetic denervation may be an important mechanism of this variability. These results also may explain why inducibility-based antiarrhythmic drug testing does not predict patient prognosis.