Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk

Andrea Mazzanti, Kevin Ng, Alessandro Faragli, Riccardo Maragna, Elena Chiodaroli, Nicoletta Orphanou, Nicola Monteforte, Mirella Memmi, Patrick Gambelli, Valeria Novelli, Raffaella Bloise, Guido Moro, Valentina Tibollo, Massimo Morini, Riccardo Bellazzi, Carlo Napolitano, Vincenzo Bagnardi, Silvia G. Priori

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2540-2550
Number of pages11
JournalJournal of the American College of Cardiology
Volume68
Issue number23
DOIs
Publication statusPublished - Dec 13 2016

Fingerprint

Arrhythmogenic Right Ventricular Dysplasia
Cardiac Arrhythmias
Syncope
Ventricular Tachycardia
Exercise
Sotalol
Implantable Defibrillators
Sudden Cardiac Death
Atrial Fibrillation
Therapeutics
Parturition

Keywords

  • athletes
  • genetics
  • implantable cardioverter-defibrillator
  • sudden cardiac death
  • ventricular tachycardia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Arrhythmogenic Right Ventricular Cardiomyopathy : Clinical Course and Predictors of Arrhythmic Risk. / Mazzanti, Andrea; Ng, Kevin; Faragli, Alessandro; Maragna, Riccardo; Chiodaroli, Elena; Orphanou, Nicoletta; Monteforte, Nicola; Memmi, Mirella; Gambelli, Patrick; Novelli, Valeria; Bloise, Raffaella; Moro, Guido; Tibollo, Valentina; Morini, Massimo; Bellazzi, Riccardo; Napolitano, Carlo; Bagnardi, Vincenzo; Priori, Silvia G.

In: Journal of the American College of Cardiology, Vol. 68, No. 23, 13.12.2016, p. 2540-2550.

Research output: Contribution to journalArticle

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abstract = "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.",
keywords = "athletes, genetics, implantable cardioverter-defibrillator, sudden cardiac death, ventricular tachycardia",
author = "Andrea Mazzanti and Kevin Ng and Alessandro Faragli and Riccardo Maragna and Elena Chiodaroli and Nicoletta Orphanou and Nicola Monteforte and Mirella Memmi and Patrick Gambelli and Valeria Novelli and Raffaella Bloise and Guido Moro and Valentina Tibollo and Massimo Morini and Riccardo Bellazzi and Carlo Napolitano and Vincenzo Bagnardi and Priori, {Silvia G.}",
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T2 - Clinical Course and Predictors of Arrhythmic Risk

AU - Mazzanti, Andrea

AU - Ng, Kevin

AU - Faragli, Alessandro

AU - Maragna, Riccardo

AU - Chiodaroli, Elena

AU - Orphanou, Nicoletta

AU - Monteforte, Nicola

AU - Memmi, Mirella

AU - Gambelli, Patrick

AU - Novelli, Valeria

AU - Bloise, Raffaella

AU - Moro, Guido

AU - Tibollo, Valentina

AU - Morini, Massimo

AU - Bellazzi, Riccardo

AU - Napolitano, Carlo

AU - Bagnardi, Vincenzo

AU - Priori, Silvia G.

PY - 2016/12/13

Y1 - 2016/12/13

N2 - 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.

AB - 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.

KW - athletes

KW - genetics

KW - implantable cardioverter-defibrillator

KW - sudden cardiac death

KW - ventricular tachycardia

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