Author + information
- Received April 6, 2016
- Revision received September 8, 2016
- Accepted September 9, 2016
- Published online December 13, 2016.
- Andrea Mazzanti, MDa,
- Kevin Ng, MDa,
- Alessandro Faragli, MDa,
- Riccardo Maragna, MDa,
- Elena Chiodaroli, MDa,
- Nicoletta Orphanou, MDa,
- Nicola Monteforte, MDa,
- Mirella Memmi, PhDa,
- Patrick Gambelli, MSa,
- Valeria Novelli, PhDa,
- Raffaella Bloise, MDa,
- Oronzo Catalano, MDa,
- Guido Moro, MDa,
- Valentina Tibollo, MSa,
- Massimo Morini, MSa,
- Riccardo Bellazzi, MS, PhDb,
- Carlo Napolitano, MD, PhDa,
- Vincenzo Bagnardi, PhDc and
- Silvia G. Priori, MD, PhDa,d,∗ ()
- aMolecular Cardiology, IRCCS ICS Maugeri, Pavia, Italy
- bDepartment of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
- cDepartment of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
- dDepartment of Molecular Medicine, University of Pavia, Pavia, Italy
- ↵∗Reprint requests and correspondence:
Dr. Silvia G. Priori, Molecular Cardiology-IRCCS ICS Maugeri, Via Maugeri, 10-27100 Pavia, Italy.
Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined.
Objectives This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy.
Methods We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals.
Results A first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated.
Conclusions The high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.
This work was supported by the Ricerca Corrente of the Italian Ministry of Health. Dr. Priori has served as a scientific advisor for Medtronic and Gilead; has received unrestricted research/educational grants from Gilead and Boston Scientific; and holds equity in Audentes Rx. Dr. Napolitano holds equity in Audentes Rx. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Mazzanti and Ng contributed equally to this work.
- Received April 6, 2016.
- Revision received September 8, 2016.
- Accepted September 9, 2016.
- American College of Cardiology Foundation