Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy

Steven A Muller; Alessio Gasperetti; Laurens P Bosman; Amand F Schmidt; Annette F Baas; Ahmad S Amin; Arjan C Houweling; Arthur A M Wilde; Paolo Compagnucci; Mattia Targetti; Michela Casella; Leonardo Calò; Claudio Tondo; Pim van der Harst; Folkert W Asselbergs; J Peter van Tintelen; Marish I F J Oerlemans; Anneline S J M Te Riele

doi:10.1016/j.jacc.2023.05.005

Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy

J Am Coll Cardiol. 2023 Jul 18;82(3):214-225. doi: 10.1016/j.jacc.2023.05.005. Epub 2023 May 18.

Authors

Steven A Muller¹, Alessio Gasperetti², Laurens P Bosman³, Amand F Schmidt⁴, Annette F Baas⁵, Ahmad S Amin⁶, Arjan C Houweling⁷, Arthur A M Wilde⁶, Paolo Compagnucci⁸, Mattia Targetti⁹, Michela Casella⁸, Leonardo Calò¹⁰, Claudio Tondo¹¹, Pim van der Harst³, Folkert W Asselbergs¹², J Peter van Tintelen¹³, Marish I F J Oerlemans³, Anneline S J M Te Riele¹⁴

Affiliations

¹ Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands.
² Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Division of Medicine, Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA; Department of Clinical Electrophysiology and Cardiac Pacing, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
³ Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁴ Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Amsterdam University Medical Centers, Department of Cardiology, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁶ Amsterdam University Medical Centers, Department of Cardiology, University of Amsterdam, Amsterdam, the Netherlands.
⁷ Amsterdam University Medical Centers, Department of Human Genetics, University of Amsterdam, Amsterdam, the Netherlands.
⁸ Cardiology and Arrhythmology Clinic, University Hospital "Ospedali Riuniti," Ancona, Italy.
⁹ Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
¹⁰ Department of Cardiology, Policlinico Casilino, Rome, Italy.
¹¹ Department of Clinical Electrophysiology and Cardiac Pacing, Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
¹² Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Amsterdam University Medical Centers, Department of Cardiology, University of Amsterdam, Amsterdam, the Netherlands; Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom.
¹³ Netherlands Heart Institute, Utrecht, the Netherlands; Department of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
¹⁴ Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands. Electronic address: [email protected].

PMID: 37210036
DOI: 10.1016/j.jacc.2023.05.005

Abstract

Background: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Methods: A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with "possible ARVC" (only genetic or familial predisposition) and "borderline ARVC" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).

Results: At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05).

Conclusions: Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.

Keywords: ARVC; family screening; predictors; screening interval; ventricular arrhythmia.

Publication types

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

MeSH terms

Arrhythmogenic Right Ventricular Dysplasia* / diagnosis
Arrhythmogenic Right Ventricular Dysplasia* / epidemiology
Arrhythmogenic Right Ventricular Dysplasia* / genetics
Electrocardiography / methods
Humans
Netherlands
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding