Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center

Abstract

Background: Arrhythmogenic cardiomyopathy (AC) is an inheritable progressive heart disease with high risk of life-threatening ventricular arrhythmia (VA). We aimed to explore the prevalence of VA as presenting event in patients with AC over two decades, symptoms preceding VA and compare the clinical presentations and rate of AC-diagnosis over time. Methods: We included consecutive AC-patients from our tertiary referral center. We recorded clinical history, VA (aborted cardiac arrest, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator therapy), cardiac symptoms preceding VA in AC, and compared the history of patients diagnosed before and after implementation of genetic testing. Results: We included 179 consecutive AC-patients and mutation-positive family members (95 [53%] probands, 84 [45%] female, 49 ± 17 years), 33 (18%) diagnosed before and 146 (82%) after genetic testing became available. VA led to the AC-diagnosis in 46 (26%), and was less prevalent after implementation of genetic testing (17[52%] vs. 29[20%], p < 0.001), also when adjusted for proband status (Adjusted OR 2.7, 95% CI 1.1–6.7, p = 0.03). Yearly rate of AC-diagnosis increased after implementation of genetic testing in probands (2.7 ± 1.3 vs. 6.8 ± 4.3, p = 0.01) and family members (0.7 ± 1.1 vs. 7.7 ± 5.9, p = 0.002). Most patients with VA (92%) reported cardiac symptoms prior to event, and exercise-induced syncope was the strongest marker of subsequent VA (Adjusted OR 5.3, 95% CI 1.7–16.4, p = 0.004). Conclusion: VA led to AC-diagnosis in 46% of probands and was preceded by cardiac symptoms in the majority of cases. Yearly rate of AC-diagnoses increased after the implementation of genetic testing and life-threatening presentation of AC-disease seemed to decrease.