Segmental volume-weighted unipolar voltage: a novel parameter for localization of non-ischemic fibrosis and disease progression in dilated cardiomyopathy and ventricular arrythmias

Background Patients with dilated cardiomyopathy (DCM) or non-dilated left ventricular cardiomyopathy (NDLVC) undergoing ablation for ventricular arrhythmias (VA) represent a heterogeneous population, and clinical courses differ significantly depending on the underlying aetiology. Prior studies have described predominant anteroseptal and inferolateral involvement based on late gadolinium enhancement (LGE) or low unipolar voltage (UV), typically using a single cut-off value. In this study, we propose a novel parameter, segmental vwUV, and hypothesize that segmental analysis of vwUV, as a surrogate for the amount and regional distribution of non-ischemic fibrosis, can refine patient characterization and improve prognostication in DCM/NDLVC patients undergoing VA ablation. Methods DCM/NDLVC patients referred for electroanatomical mapping and VA ablation at three centers were included. Segmental vwUV was calculated using the AHA 17-segment model. Patients were followed for VA recurrence and mortality. Results A total of 125 patients (57 ± 14 years, LVEF 39 ± 13%) were enrolled. Genetic testing was performed in all but 2 patients, identifying a (likely) pathogenic mutation in 45 (36%). Based on the location of segments with the greatest reduction in segmental vwUV (cut-offs derived from normal controls) and the involvement of neighboring segments, patients were classified into: (1) no vwUV reduction (n=10, 8%), (2) septal (n=53, 42%), (3) lateral (n=44, 35%), (4) apical (n=9, 7%), or (5) remote involvement (n=9, 7%). Distribution of vwUV per segment according to dominant substrate location is illustrated in Figure 1. LVEF was comparable across groups (2)–(5). Complete procedural success was most frequently achieved in the apical-dominant group (75%) compared with the other location groups (lateral 51%, septal 42%, remote 38%). Over a median follow-up of 35 (IQR 12–63) months, 29 patients (23%) died or required LV assist device (LVAD) implantation or heart transplantation (HTx), and 59 (46%) experienced VA recurrence. Kaplan–Meier analysis demonstrated that septal-dominant and remote-involvement patterns were associated with poor LVAD/HTx-free and VA-free survival, whereas the no-segmental-vwUV-reduction and apical-dominant groups showed excellent outcomes (log-rank P<0.01). Conclusion Segmental vwUV is a novel surrogate maker for segmental distribution of non-ischemic fibrosis. It allows for more detailed characterization and prognostication of DCM/NDLVC patients with VA and may serve as an important tool for substrate delineation and procedural strategy.