Paradoxical association between programmed ventricular stimulation (PVS) induction threshold and arrhythmic events: the EP VSTIM Risk Registry

Background/Introduction Programmed ventricular stimulation (PVS) during electrophysiological study (EPS) remains a cornerstone of arrhythmic risk assessment in patients with structural heart disease. The conventional paradigm suggests that easier arrhythmia inducibility (requiring fewer extra-stimuli) indicates higher substrate vulnerability and greater clinical risk. However, the independent prognostic value of induction threshold for predicting spontaneous arrhythmic events remains uncertain. Purpose To investigate the correlation between PVS induction threshold and 12-month arrhythmic events in ICD recipients. Methods This retrospective analysis included 66 consecutive patients from the EP VSTIM Risk Registry who underwent comprehensive PVS protocols prior to ICD implantation. PVS was performed using standardized protocols with progressively aggressive stimulation: S2 (single extra-stimulus), S3 (double extra-stimuli), and S4+ (triple extra-stimuli or burst pacing). The primary endpoint was any documented ventricular arrhythmic event during 12-month follow-up, including sustained monomorphic or polymorphic VT, non-sustained VT, or appropriate ICD interventions (anti-tachycardia pacing or shock delivery). Statistical analyses included Chi-square test, Fisher's exact test, logistic regression, and Cochran-Armitage trend test. Results Among 66 patients, 54 (81.8%) had positive PVS (inducible VT/VF). Induction threshold distribution was: S2 n=4 (7.4%), S3 n=16 (29.6%), S4+ n=34 (63.0%). Monomorphic VT was the predominant induced rhythm (77.8%). During follow-up, 9 patients (16.7%) experienced arrhythmic events, including 4 VT episodes requiring shock therapy. Unexpectedly, event rates increased with higher induction thresholds: S2 0.0% (0/4 patients), S3 6.2% (1/16 patients), S4+ 23.5% (8/34 patients), demonstrating a clear dose-response pattern. Although this trend did not achieve statistical significance (Chi-square p=0.202), logistic regression revealed a substantial effect size (OR 5.15, 95% CI 0.66-40.17, p=0.117), and trend analysis approached significance (p=0.084). The lack of statistical significance was primarily attributable to limited sample size and low event rate. Conclusions This study reveals a paradoxical association whereby patients requiring more aggressive PVS protocols (S4+) demonstrated the highest 12-month arrhythmic event rates, contradicting traditional risk stratification paradigms. This finding suggests that induction threshold may reflect overall disease severity and substrate heterogeneity rather than focal arrhythmia vulnerability. The observed pattern warrants validation in larger prospective cohorts and highlights the need for comprehensive multivariate risk models incorporating clinical, imaging, and electrophysiological parameters beyond induction threshold alone.