Late enhancement, lasting impact: left ventricular fibrosis in arrhythmogenic right ventricular cardiomyopathy

Abstract Background The increasing use of Cardiac Magnetic Resonance (CMR) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) has revealed that a considerable number of patients show left ventricular (LV) involvement through the detection of late gadolinium enhancement (LGE). While recent studies are investigating myocardial scarring across cardiomyopathies, data on the prevalence and prognostic role of LV-LGE in ARVC—especially when quantified—remain limited. Purpose To assess the prevalence of LV-LGE in a well-defined ARVC cohort, explore related clinical, genetic, and imaging features, and evaluate its prognostic relevance. We also aimed to identify a LGE burden threshold associated with major adverse cardiovascular events (MACE). Methods We included patients with definite ARVC diagnosis according to the 2010 Revised Task Force Criteria who had undergone CMR. Clinical, genetic, imaging characteristics and outcomes were compared based on LV-LGE presence. Univariate regression analysis was performed to assess the association between LV-LGE and MACE. LGE burden was quantified using the 17-segment model; ROC analysis identified a segment-based threshold associated with MACE, defined as a composite of life-threatening ventricular arrhythmias, sudden cardiac death, cardiovascular death, heart failure, and hot-phase episodes. Results In our cohort, 105 patients (49.5%) showed evidence of LV-LGE. No significant differences were observed between groups regarding sex (p = 1) or proband status (p = 0.52). Clinically, patients with LV-LGE more frequently presented with chest pain (p < 0.001). Pathogenic or likely pathogenic mutations in Desmoplakin (DSP) and Filamin C (FLNC) were more prevalent in the LV-LGE group (p < 0.001 and p = 0.01, respectively), whereas Plakophilin-2 (PKP2) mutations were significantly more frequent in the LV-LGE–negative group (p < 0.001). Electrocardiographic findings in the LV-LGE group included low voltage in peripheral leads (p < 0.001), QRS fragmentation (p = 0.005), and a higher burden of premature ventricular contractions on 24-hour Holter monitoring (p < 0.001). On CMR, the presence of LV-LGE was associated with increased LV end-diastolic volume (93 ± 20 vs 82 ± 12 mL/m², p < 0.001) and reduced mean LV ejection fraction (54% vs 61%, p < 0.001). Over a median follow-up of 5.2 years (IQR 2.0–10.1), patients with LV-LGE experienced a higher incidence of MACE (p < 0.001). Univariate regression confirmed the association between LV-LGE and MACE (OR 2.34, 95% CI 1.3–4.0, p = 0.005). A cut-off of ≥2 LV-LGE segments demonstrated moderate predictive value for MACE (AUC 0.63). Conclusion LV-LGE is common in ARVC patients and defines a distinct subgroup with specific genetic and phenotypic characteristics. Its presence is associated with worse outcomes, and segment-based quantification may serve as an additional imaging marker in the multiparametric risk stratification assessment.