Long-term follow-up analysis of a highly characterized arrhythmogenic cardiomyopathy cohort with classical and non-classical phenotypes–a real-world assessment of a novel prediction model: does the subtype really matter

AIMS: To provide long-term outcome data on arrhythmogenic cardiomyopathy (ACM) patients with non-classical forms [left dominant ACM (LD-ACM) and biventricular ACM (Bi-ACM)] and an external validation of a recently proposed algorithm for ventricular arrhythmia (VA) prediction in ACM patients. METHODS AND RESULTS: Demographic, clinical, and outcome data were retrieved from all ACM patients encountered at our institution. Patients were classified according to disease phenotype (R-ACM; Bi-ACM; LD-ACM). Overall and by phenotype long-term survival were calculated; the novel Cadrin-Tourigny et al. algorithm was used to calculate the a priori predicted VA risk, and it was compared with the observed outcome to test its reliability. One hundred and one patients were enrolled; three subgroups were defined (R-ACM, n = 68; Bi-ACM, n = 14; LD-ACM, n = 19). Over a median of 5.41 (2.59-8.37) years, the non-classical form cohort experienced higher rates of VAs than the classical form [5-year freedom from VAs: 0.58 (0.43-0.78) vs. 0.76 (0.66-0.89), P = 0.04]. The Cadrin-Tourigny et al. predictive model adequately described the overall cohort risk [mean observed-predicted risk difference (O-PRD): +6.7 (-4.3, +17.7) %, P = 0.19]; strafing by subgroup, excellent goodness-of-fit was demonstrated for the R-ACM subgroup (mean O-PRD, P = 0.99), while in the Bi-ACM and LD-ACM ones the real observed risk appeared to be underestimated [mean O-PRD: -20.0 (-1.1, -38.9) %, P < 0.0001; -22.6 (-7.8, -37.5) %, P < 0.0001, respectively]. CONCLUSION: Non-classical ACM forms appear more prone to VAs than classical forms. The novel prediction model effectively predicted arrhythmic risk in the classical R-ACM cohort, but seemed to underestimate it in non-classical forms.