207 re-defining arrhythmogenic cardiomyopathy: characterization and long-term prognostic implications

Abstract Background Arrhythmogenic dilated cardiomyopathy (AR-DCM) combines phenotypical aspects of dilated cardiomyopathy (DCM) and risk of sudden cardiac death (SCD), typical of the arrhythmogenic form (ACM). However, AR-DCM is often ambiguously defined leaving clinicians uncertain on how to identify these high-risk patients. The aims of the study were to re-define AR-DCM based on outcome related arrhythmic markers and to test the usefulness of the novel AR-DCM definition in identifying arrhythmogenic genotypes (i.e., LMNA, FLNC, RBM20, and desmosomal genes). Materials and methods Consecutive DCM patients with genetic evaluation and Holter ECG monitoring or telemetry in two referral institution were analyzed. The arrhythmic markers tested to define AR-DCM were: SCD or major ventricular arrhythmias (MVA), unexplained syncope, rapid nonsustained ventricular tachycardia (nsTV), ≥1000 premature ventricular contractions/24 hours, or ≥50 ventricular couplets/24 hours. Patients were labeled as Early AR-DCM if criteria were met within 12 months from enrolment. The primary endpoint was a composite of SCD/MVA; the secondary endpoint was a composite of all-cause mortality/heart transplant/LVAD implantation (D/HTx/LVAD). Results Among the 743 DCM patients included, 290 had disease-related variants (39%), 94 (30%) of these carried arrhythmogenic genotype. Early AR-DCM was identified in 429 (58%) patients. During a median follow-up of 7.0 [2.2-13.8] years, among arrhythmic markers the occurrence of syncope and/or nsVT within 12 months from enrolment were the only arrhythmic markers independently associated with SCD/MVA (Figure), while the occurrence of early MVA and/or nsTV emerged as the strongest long-term predictors of D/ HTx/LVAD. Family history of MVA was also independently associated with primary and secondary endpoints, and together with MVA, nsTV or unexplained syncope increased the agreement between AR-DCM and arrhythmogenic genotypes in 1 out 2 patients. Conclusions A combination of early (i.e., within 1 year from diagnosis) MVA or nsVT or unexplained syncope might be proposed as a clinically useful new definition of AR-DCM, especially if associated to family history of MVA. This definition in fact allows clinicians to anticipates worse long-term arrhythmic and global outcomes, and to accurately identify malignant arrhythmogenic genotypes.