Diagnostic Delay in Arrhythmogenic Cardiomyopathy

Aims: Diagnosis of arrhythmogenic cardiomyopathy (ACM) may be challenging, as it comprises diverse phenotypes (right-dominant, biventricular, left-dominant) and each may overlap with other clinical entities. The issue of differential diagnosis with conditions mimicking ACM has been previously highlighted, however, a systematic analysis of ACM diagnostic delay, and of its clinical implications, is lacking. Methods: Data of all ACM patients from 3 Italian Cardiomyopathy Referral Centres were reviewed to assess time from first medical contact to definitive ACM diagnosis; a significant diagnostic delay was defined as a time to ACM diagnosis ≥2 years. Baseline characteristics and clinical course of patients with and without diagnostic delay were compared. Results: Of 174 ACM patients, 31% experienced diagnostic delay, with a median time to diagnosis of 8 years (20% in right-dominant ACM, 33% in left-dominant and 39% in biventricular). Patients with diagnostic delay, as compared to those without, more frequently exhibited an ACM phenotype with left ventricular (LV) involvement (74% vs. 57%, p=0.04) and a specific genetic background (none had plakophilin-2 variants). The most common initial (mis)diagnoses were dilated cardiomyopathy (51%), myocarditis (21%) and idiopathic ventricular arrhythmia (9%). At follow-up, all-cause mortality was greater in those with diagnostic delay (p=0.03). Conclusions: Diagnostic delay is common in patients with ACM, particularly in the presence of LV involvement, and is associated with greater mortality at follow-up. Clinical suspicion and increasing use of tissue characterization by cardiac magnetic resonance in specific clinical settings are of key importance to timely identify ACM.