Arrhythmic risk stratification in patients with left ventricular ring-like scar

Abstract Background Myocardial fibrosis assessment with late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has recently emerged as an independent predictor of major adverse events in patients with non-ischemic cardiomyopathy. Several studies have examined different locations and extension degrees of LGE, and the so called "ring-like pattern" has been related with an increased incidence of ventricular arrhythmias, in patients with dilated cardiomyopathy (DCM), but also in patients with preserved systolic function. Purpose To describe clinical, electrocardiographic, echocardiographic, CMR and genetic features of the left ventricular (LV) ring-like scar phenotype and to evaluate which characteristics may be associated with the risk of sudden cardiac death (SCD). Methods Patients diagnosed with LV ring-like scar were identified at 6 referral Centres. Diagnosis was based on: 1) ring-like LGE LV pattern, defined as at least 3 contiguous segments with subepicardial/midwall LGE in the same slice with or without fatty infiltration; or 2) pathology examination of explanted hearts/autoptic cases suffering from sudden cardiac death (SCD). Moreover, patients must have an additional inclusion criterion: a positive genetic test, or ≥1 patient in the same family with an ascertained cardiomyopathy. Major adverse arrhythmic cardiac events (MAACE), defined as a composite of SCD, aborted SCD, and sustained ventricular tachycardia (SVT), were the primary study endpoint. Results The final cohort comprised 129 patients (male 59.7%, median age at diagnosis 44 years). During a median follow-up of 3.4 years (IQR 1.2 – 64.), MAACE occurred in 31 patients (24%). Nearly 70% of the patients had a likely pathogenic/pathogenic mutation, mostly in desmoplakin (DSP) and filamin-C (FLNC) genes (65% and 19%, respectively). Sex, QRS width, and LGE in LV anterior wall and/or apex, were the only independent predictors of the outcome events (HR: 0.329, 95% CI: 0.119-0.916, P = 0.033; HR: 1.036, 95% CI 1.019-1.053, P < 0.001; HR 4.270, 95% CI 1.337-13.630, P = 0.014, respectively). A significant interaction between sex and LGE in anterior wall/apex was observed, being this regions associated with MAACE only in male patients (p for interaction = 0.033). Although related to the arrhythmic endpoint at the Kaplan-Meier survival curves, neither DCM echocardiographic phenotype, nor LV ejection fraction ≤35% remained statistically associated to MAACE at the multivariate analysis. Age, genetic mutations, right ventricular involvement, proband status, LV-LGE extension (number of segments) were not statistically related to the study endpoint. Conclusions In this selected cohort of patients with LV ring-like scar and either a genetic test or family history, malignant arrhythmic events were predicted by male sex, QRS width and LGE in anterior wall and/or apex.Graphical Abstract