Background: Patients (pts) with DCM and genetic mutations who present with VT have poor outcomes
Objective: Elucidate the true character and distribution of VT substrate in DCM pts with VT using histology
Methods: 7 pts (all male, median age 63) with pathogenic variants (3 LMNA, TTN, MYBPC3, MYH7, RBM20) underwent high-density mapping and ablation 343 [IQR29-609] days before death (n=6) or transplantation (n=1). 5mm slices were stained for fibrosis (0.01mm/pi). As a surrogate for tissue heterogeneity, length of contact between fibrosis and viable myocardium (VM) was calculated.
Results: All pts were classified as having an anteroseptal substrate based on substrate and activation mapping. Pts had a median of 3 VTs; in 6 pleomorphic VTs were seen; 6 pts remained inducible or recurred within 2 days. Median fibrotic burden, after ablation, was 25%. 48% of segments had diffuse transmural fibrosis, 28% subendocardial, 13% midwall and 5% subepicardial fibrosis. Basal segments were more affected (median fibrosis 29% vs 24% in mid and 17% in apical) with higher heterogeneity (17mm
-1 vs. 15mm
-1 and 13mm
-1). Anteroseptal segments showed similar fibrosis quantity and heterogeneity compared to inferior (30% vs. 29%; 17mm
-1 vs. 17mm
-1. The tissue in targeted segment not reached by ablation had higher fibrosis quantity and heterogeneity than those not targeted: 29% vs. 18%; and 18mm
-1 vs. 13mm
-1.
Conclusion: Neither the concept of purely “midwall” nor anteroseptal/inferolateral substrate applies. Targeted segments show higher amount and heterogeneity of fibrosis suggesting specific features may be required to sustain VT. Current ablation techniques are unlikely to control VT in pts with inherited DCM.