Efficacy and outcomes of S3 functional mapping for VT ablation in non-ischaemic cardiomyopathy

Background Functional substrate mapping using extra-stimuli has emerged as a promising approach to identify ventricular tachycardia (VT) ablation targets beyond those revealed by conventional mapping methods. The S3 protocol, which has been primarily validated in patients with ischaemic cardiomyopathy, may hold particular value in non-ischaemic cardiomyopathy (NICM), where smaller or intramural substrates often remain concealed during standard mapping. Purpose To asses the efficacy and effectiveness of S3 functional substrate mapping in patients with NICM undergoing VT ablation. Methods We analysed 24 consecutive NICM patients undergoing VT ablation. Isochronal late activation mapping (ILAM) and late potential (LP) identification were performed using the S3 protocol (drive train S1 followed by S2 = ERP + 30 ms and S3 = ERP + 50 ms, pacing from the right ventricle). Conducting channels (CC) were evaluated by late gadolinium enhancement cardiac MRI using ADAS 3D software and correlated with deceleration zones (DZ) and LP regions on functional maps. Outcome data were obtained through remote device monitoring, including data from 1 year before ablation to the end of follow-up. Results The cohort included 4 patients with hypertrophic cardiomyopathy, 7 with dilated cardiomyopathy, and 12 with arrhythmogenic cardiomyopathy (3 right sided (ARVC), 4 biventricular, 5 left sided (ALVC)) were included in this analysis. The mean age was 61.6 ± 17.0 years, 88 % were male, and the mean LVEF was 39.2 ± 12.9 %. Ten patients underwent epicardial ablation. Implementation of the S3 protocol significantly increased the detection of functional substrate: compared with S1 mapping, the number of DZ rose from 1.99 to 2.82 per patient (p<0.05), and LP zones from 1.91 to 2.54 (p<0.05). The proportion of MRI-defined CCs identified as DZ increased from 31% with S1 mapping to 65% with S3 mapping (p<0.05). VT isthmus identification increased from 70.6 % during S1 mapping to 82.4 % during S3 mapping, although this difference did not reach statistical significance (p = 0.69). At a median follow up of 12,4 months, VT burden decreased with 92.9 %, ATPs with 72,9% and ICD shock with 86,5%. Conclusion In NICM patients, S3 substrate mapping reveals significantly more deceleration zones and LP areas than conventional mapping, with enhanced concordance to MRI-defined CC. Outcome data parallel those observed in ischaemic cardiomyopathy, underscoring that despite distinct substrate characteristics, S3 mapping can achieve similar procedural efficacy in this population. These findings support S3 mapping as a valuable tool to unmask arrhythmogenic substrate and to guide effective ablation strategies in NICM.