Impact of phenotypic profile and genotype on ventricular tachycardia ablation outcomes in hypertrophic cardiomyopathy

Background

Although hypertrophic cardiomyopathy (HCM) has a prevalence of 0.2%, and monomorphic ventricular tachycardia (VT) being the most frequent VA subtype (82% off all episodes in ICD carriers), data on genotype, phenotype and outcomes after VT-ablation are limited.

Objectives

To characterize phenotype, arrhythmic substrate, and clinical outcomes after VT-ablation in genotyped HCM patients.

Methods

Consecutive HCM patients undergoing a first VT ablation procedure, between 2012 and 2024, in a high volume centre were included. Clinical records, multimodal-imaging (echocardiography, LGE-CMR, CT), procedural data, bail-out strategies, and outcome data were analysed.

CT and MRI segmentations, and LV AHA 16 segment models were generated and aligned with electroanatomic voltage maps to correlate findings (figure 1).

Results

Of 1,277 patients undergoing VT-ablation, 9 (0.7%) had a HCM phenotype: all were male and the median age was 59 [45–61] years. Six out of nine presented a pathogenic MYBPC3 variant, and the median LVEF was 42% [35.5–52.5]. The maximal wall thickness (WT) was 21.0 mm [20.0–24.0], a median of 6 [5–9] AHA segments had a maximal WT above 15 mm, and a median of 8 [7–12] segments had LGE presence.

Electroanatomical voltage maps showed a median of 4 [2–6], 9 [7–13], and 12 [7–13] segments with BV <1.5 mV, <3.0 mV, and UV <8.3 mV, respectively (figure 2).

Segments harbouring VT-related sites (defined based on pace-mapping, activation mapping and entrainment and VT-termination sites) had a WT of 17 mm [14.3–19.6], all but one had LGE and 17/23 BV <1.5 mV[AM1] .

During a median follow-up of 38 months [6–83], VT recurred in 7 of 9 patients with a median time to recurrence of 72 days [60-110], requiring re-ablation or bailout strategies in 4 out of 7 (stellate ganglion blockade in 2, surgical substrate resection in 3, and STAR in 2) all being patients with MYBPC3 variant. Six patients died or underwent heart transplantation (5 of 6 with MYBPC3 variants); two died during index VT ablation admission (uncontrollable VT, surgical complication).Two patients underwent heart transplantation, and 3 died, with a median time to death of 23 months [11-83] (one due to an infection during a post-transplant lymphoproliferative disorder, and two due to progressive heart failure).

Conclusion

Unselected HCM patients requiring VT ablation showed extensive hypertrophy, LGE and voltage reduction despite wall thickening which together with a high prevalence of MYBPC3 variants, may explain poor ablation outcome and a high mortality.