Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Eur Heart J. 2022 Aug 21;43(32):3041-3052. doi: 10.1093/eurheartj/ehac289.

Authors

Paloma Jordà^{1

2

3}, Laurens P Bosman⁴, Alessio Gasperetti⁵, Andrea Mazzanti^{6

7

8}, Jean Baptiste Gourraud⁹, Brianna Davies¹⁰, Tanja Charlotte Frederiksen^{11

12}, Zoraida Moreno Weidmann¹³, Andrea Di Marco¹⁴, Jason D Roberts^{15

16

17}, Ciorsti MacIntyre¹⁸, Colette Seifer¹⁹, Antoine Delinière²⁰, Wael Alqarawi²¹, Deni Kukavica^{6

7

8}, Damien Minois⁹, Alessandro Trancuccio^{6

7

8}, Marine Arnaud⁹, Mattia Targetti²², Annamaria Martino²³, Giada Oliviero²³, Daniel C Pipilas²⁴, Corrado Carbucicchio²⁵, Paolo Compagnucci²⁶, Antonio Dello Russo²⁶, Iacopo Olivotto²², Leonardo Calò²³, Steven A Lubitz²⁴, Michael J Cutler²⁷, Philippe Chevalier²⁰, Elena Arbelo^{2

3

28

29}, Silvia Giuliana Priori^{6

7

8}, Jeffrey S Healey^{15

16}, Hugh Calkins⁵, Michela Casella³⁰, Henrik Kjærulf Jensen^{11

12}, Claudio Tondo^{25

31}, Rafik Tadros¹, Cynthia A James⁵, Andrew D Krahn¹⁰, Julia Cadrin-Tourigny¹

Affiliations

¹ Cardiovascular Genetics Center, Montreal Heart Institute, Université de Montréal, Montréal, QC, Canada.
² Arrhythmia Section, Cardiology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
³ Institut d'Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁴ Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁵ Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
⁶ Department of Molecular Medicine, University of Pavia, Pavia, Italy.
⁷ Department of Molecular Cardiology, IRCCS Istituti Clinici Scientifici Maugeri, Pavia, Italy.
⁸ Department of Molecular Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
⁹ Department of Cardiology, Centre Hospitalier Universitaire Nantes, Nantes, France.
¹⁰ Centre for Cardiovascular Innovation, Division of Cardiology, University of British Columbia, Vancouver, BC, Canada.
¹¹ Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.
¹² Department of Clinical Medicine, Health, Aarhus University, Aarhus N, Denmark.
¹³ Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Universitat Autònoma de Barcelona, CIBERCV, Barcelona, Spain.
¹⁴ Arrhythmia Unit, Department of Cardiology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁵ Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
¹⁶ Division of Cardiology, Hamilton Health Sciences, Hamilton, ON, Canada.
¹⁷ Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada.
¹⁸ Cardiac Electrophysiology Service, Quenn Elisabeth II Health Sciences Center, Dalhousie University, Halifax, NS, Canada.
¹⁹ St-Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
²⁰ National Reference Center for Inherited Arrhythmias of Lyon, Louis Pradel Cardiovascular Hospital, Hospices Civils de Lyon, Lyon, France.
²¹ Cardiac Electrophysiology Service, Ottawa Heart Institute, University of Ottawa, Ottawa, ON, Canada.
²² Cardiomyopathy Unit, Department of Cardiology, Careggi University Hospital, Florence, Italy.
²³ Department of Cardiology, Policlinico Casilino, Rome, Italy.
²⁴ Cardiovascular Research Center and Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MA, USA.
²⁵ Department of Clinical Electrophysiology and Cardiac Pacing Centro Cardiologico Monzino, IRCCSC, Milan, Italy.
²⁶ Department of Biomedical Sciences and Public Health, Cardiology and Arrhythmology Clinic, University Hospital Umberto I-Salesi-Lancisi, Marche Polytechnic University, Ancona, Italy.
²⁷ Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT, USA.
²⁸ Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
²⁹ European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart.
³⁰ Department of Clinical, Special and Dental Sciences, Cardiology and Arrhythmology Clinic, University Hospital Umberto I-Salesi-Lancisi, MarchePolytechnic University, Ancona, Italy.
³¹ Department of Biomedical, Surgical and Dentistry Sciences, University of Milan, Milan, Italy.

Abstract

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus.

Methods and results: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%.

Conclusion: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC.

Keywords: Arrhythmogenic right ventricular cardiomyopathy; Genetic cardiomyopathies; Implantable cardioverter-defibrillator; Risk stratification; Sudden cardiac death; Ventricular arrhythmias.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arrhythmias, Cardiac / etiology
Arrhythmogenic Right Ventricular Dysplasia* / complications
Arrhythmogenic Right Ventricular Dysplasia* / diagnosis
Arrhythmogenic Right Ventricular Dysplasia* / therapy
Death, Sudden, Cardiac / epidemiology
Death, Sudden, Cardiac / etiology
Death, Sudden, Cardiac / prevention & control
Defibrillators, Implantable* / adverse effects
Humans
Retrospective Studies
Risk Factors

Grants and funding

R01 HL139731/HL/NHLBI NIH HHS/United States