Author + information
- Received February 3, 2019
- Revision received May 7, 2019
- Accepted May 10, 2019
- Published online July 15, 2019.
- Elizabeth S. DeWitt, MDa,b,
- Stephanie F. Chandler, MDa,b,
- Robyn J. Hylind, MS, CGCa,b,
- Virginie Beausejour Ladouceur, MDa,b,
- Elizabeth D. Blume, MDb,
- Christina VanderPluym, MDb,
- Andrew J. Powell, MDb,
- Francis Fynn-Thompson, MDc,
- Amy E. Roberts, MDb,
- Stephen P. Sanders, MDb,d,
- Vassilios Bezzerides, MD, PhDa,b,
- Neal K. Lakdawala, MDe,
- Calum A. MacRae, MD, PhDe and
- Dominic J. Abrams, MD, MBAa,b,∗ ()
- aInherited Cardiac Arrhythmia Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
- bDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
- cDepartment of Cardiovascular Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
- dDepartment of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
- eCardiovascular Genetics Program, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Dominic Abrams, Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115.
Background Arrhythmogenic cardiomyopathy (ACM) is a variably penetrant disease increasingly identified in young patients.
Objectives This study sought to describe the diverse phenotype, genotype, and outcomes in pediatric and adolescent patients.
Methods Records from 1999 to 2016 were reviewed for individuals age <21 years with a consistent personal or family history. Patients were categorized by right ventricular (RV), left dominant (LD), or biventricular subtypes using 2010 Task Force Criteria or proposed features of LD disease, encompassing electrocardiographic, structural, histological, and arrhythmic characteristics. Genetic variants classified as pathogenic and/or likely pathogenic by 2015 American College of Medical Genetics and Genomics criteria in recognized disease-associated genes were included.
Results Manifest disease was evident in 32 patients (age 15.1 ± 3.8 years), of whom 22 were probands, including 16 RV, 7 LD, and 9 biventricular ACM. Nondiagnostic features were seen in 5 of 15 family members. RV disease was associated with cardiac arrest and ventricular tachycardia (p = 0.02) and prevalence of PKP2 variants (p < 0.01), whereas biventricular disease was associated with a younger age of onset (p = 0.02). LD ACM was associated with variants in DSP and LMNA, and biventricular ACM with more a diverse etiology in desmosomal genes. Cardiac arrest was observed in 5 probands (age 15.3 ± 1.9 years) and ventricular tachycardia in 10 (age 16.6 ± 2.7 years), 6 probands, and 4 family members. Features suggestive of myocardial inflammation were seen in 6 patients, with ventricular tachycardia and/or cardiac arrest in 3 patients. Cardiac transplantation was performed in 10 patients. There were no deaths. In RV and biventricular disease, electrocardiographic preceded imaging features, whereas the reverse was seen in LD disease.
Conclusions ACM in the young has highly varied phenotypic expression incorporating life-threatening arrhythmia, heart failure, and myocardial inflammation. Increased awareness of early onset, aggressive disease has important implications for patient management and familial screening.
- arrhythmogenic right ventricular cardiomyopathy
- diagnostic criteria
The Inherited Cardiac Arrhythmia Program is funded by the generous philanthropic support of the Mannion and Roberts families. Dr. Lakdawala has acted as a consultant for Array BioPharma and Myokardia. Dr. MacRae is supported by a grant from the Leducq Foundation. Dr. Abrams has acted as a consultant for Audentes Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received February 3, 2019.
- Revision received May 7, 2019.
- Accepted May 10, 2019.
- 2019 American College of Cardiology Foundation
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