Validation of a four-extrastimulus programmed ventricular stimulation protocol for arrhythmic risk stratification in repaired tetralogy of Fallot

Introduction The usefulness of electrophysiological study (EPS) for arrhythmic risk stratification in patients with tetralogy of Fallot (ToF) has been demonstrated using sequential stimulation protocols such as that described by Josephson (1). However, evidence regarding shortened protocols, such as the four-extrastimulus (4-ES) approach (2), is lacking in this setting. Purpose To determine the prognostic value of ventricular inducibility using a four-extraestimulus (4-ES) EPS protocol in identifying patients with ToF at risk of sustained ventricular arrhythmias (SVA). Methods We retrospectively included 41 adults with repaired ToF who underwent EPS (2008–2025) using programmed ventricular stimulation (PVS) following the 4-ES protocol at two right ventricular sites without isoproterenol. SVA (≥30 s or requiring cardioversion) defined inducibility. Clinical SVA during follow-up was analysed using Firth-penalised Cox models and Kaplan–Meier survival estimates. The diagnostic performance of the protocolol was assessed with ROC curves. Results Forty-one repaired ToF patients (mean age 43 ± 11.3 years, 83% male) were included. SVA were inducible in 18 (43.9%) using the 4-ES protocol: 16 sustained monomorphic ventricular tachycardia (SMVT) (88.9%) and two polymorphic VT. A second arrhythmia was induced in five patients (29.4%). An ICD was implanted in 17 of the 18 inducible patients (94.4%). During a median follow-up of 1.4 years (IQR 0.47–2.87), clinical SVA occurred exclusively in inducible patients (5/18; 27.8%), all SMVT, whereas none occurred in the non-inducible group (log-rank p = 0.015). Median time to first event was 1.76 years (IQR 0.73–7.39). Inducibility was associated with a significantly increased risk of SVA (HR 13.6; 95% CI 1.5–180.4; p = 0.017) and showed 100% sensitivity and 63.9% specificity. Recurrent VT occurred in two patients (4.8%). Antitachycardia pacing was effective in three cases, and ablation was required in two, one for arrhythmic storm. Two patients (4.8%) died from non-arrhythmic causes. Conclusion PVS using a 4-ES protocol identified a high-risk subgroup among repaired ToF patients, with all SVA confined to inducible cases and none among non-inducible ones. The 4-ES protocol showed excellent negative predictive value and may enhance risk stratification efficiency while avoiding unnecessary ICD implantation. These findings support its feasibility and prognostic relevance, warranting validation in larger multicentre studies.