Assessing ventricular arrhythmic risk in non-ischemic cardiomyopathy: a comparative analysis of late gadolinium enhancement and grey zone scar methods

Background Myocardial scar is associated with arrhythmic events in non-ischemic cardiomyopathy (NICM). Various CMR-based methods exist to quantify scar tissue, including late gadolinium enhancement (LGE) and gray zone analysis, but it's yet unknown which best predicts arrhythmic events in this population. Purpose To determine the LGE and gray zone quantitative method that best predicts ventricular arrhythmias in NICM. Methods Single-centre retrospective study with NICMLGE positive patients. Quantitative analysis was performed by measuring LGE mass (absolute and relative to the total myocardial mass), gray zone scar (GZS) and total scar (TS) masses. LGE was assessed with the reference region of interest (ROI) method (intensity 5 standard deviations [5SD] above remote myocardium), the full width at half maximum (FWHM) and manually selected single intensity threshold. GZS was defined as non-LGE area with intensity above 2SD of the reference ROI. TS was defined as the total mass with intensity above 2SD of reference ROI. Two composite endpoints were selected: Major Ventricular Arrhythmic Event (MVAE) was defined as sudden cardiac death (SCD), appropriate implantable cardioverter-defibrillator (ICD) shock, ventricular fibrillation (VF) or sustained ventricular tachycardia (SVT) and Total Ventricular Arrhythmic Events (TVAE), including MVAE and, additionally, non-sustained ventricular tachycardia (NSVT). Results This cohort included 213 NICM, LGE-positives patients, age 63.6±8.7 years, male sex (81%), mean indexed left ventricular end-diastolic volume (LVEDVi) 116.2±23.1 mL, and mean left ventricular ejection fraction (LVEF) of 33.7±8.9%. After 5.3 [IQR 3.9-6.8] years, TVAE and MVAE endpoints occurred in 44 (21%) and 17 (8%) patients, respectively. Variables with the highest discriminative value, according to Harrell’s C index (C-i), for the TVAE were 5SD-LGE (HR 1.03 [1.02-1.05], p=<0.001, C-i 0.62), 2SD-GZS (HR 1.03 [1.01- 1.05], p=0.01, C-i 0.61) and TS (HR 1.02 [1.01-1.03], p=<0.001, C-i 0.63). For MVAE, 5-SD LGE had a similar association compared with TVAE (C-i 0.66); whereas both 2SD-GZS (C-i 0.71) and TS (C-i 0.7) had a stronger association (Figure). 5SD-LGE relative mass was not statistically significant for MVAE (Figure). To note, scar assessing quantitative methods based on scar identification were not predictors of arrhythmic events. In a multivariate analysis adjusted for other well-known prognostic measures such as LVEF, LVEDVi and LV global longitudinal strain (LV-GLS), 5SD-LGE, 2SD-GZS and TF were independently associated with both endpoints (Table). Conclusion The quantification of myocardial scar in patients with NICM and LGE, including grey zone analysis as absolute mass values, showed a stronger predictive value for MVAE compared to LGE percentage alone. The absolute masses from grey zone analysis and scar tissue, along with 5SD-LGE, were linked to a higher risk of MVAE and TVAE, independently of LVEF, LVEDVi, and LV-GLS.