Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Richard T. Carrick*, Anneline S.J.M. Te Riele, Alessio Gasperetti, Laurens Bosman, Steven A. Muller, Catherine Pendleton, Crystal Tichnell, Brittney Murray, Sing Chien Yap, Maarten P. van den Berg, Arthur Wilde, Katja Zeppenfeld, Allison Hays, Stefan L. Zimmerman, Harikrishna Tandri, Julia Cadrin-Tourigny, Peter van Tintelen, Hugh Calkins, Cynthia A. James, Katherine C. Wu

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown. METHODS: This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates. RESULTS: Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (-1200/day) and nonsustained ventricular tachycardia (-14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator's ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%. CONCLUSIONS: Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.

Original languageEnglish
Pages (from-to)e011207
JournalCirculation. Arrhythmia and electrophysiology
Issue number11
Publication statusPublished - 1 Nov 2022

Bibliographical note

Funding Information:
Dr Calkins consults for Medtronic, Inc, Biosense Webster, Pfizer, StrideBio, and Abbott. B. Murray consults for MyGeneCounsel. Dr James consults for Pfizer, Inc, Tenaya, Inc, and StrideBio, Inc. Drs Calkins, James, and C. Tichnell receive research support from Boston Scientific Corp. Dr Tandri receives research support from Abbott. Dr Yap consults for Boston Scientific Corp. Dr Wilde consults for LQTherapeutics and ARMGO. The other authors report no conflicts.

Funding Information:
This research was funded by multiple generous sources, including the Johns Hopkins Cardiology National Institutes of Health (NIH) T32HL007227 training grant (Dr Carrick), the Leonie-Wild Foundation, the Wilton W. Webster Fellowship from the Heart Rhythm Society (Dr Gasperetti), the Netherlands Heart Foundation grant 2015T058 and University Medical Center Utrecht Fellowship Clinical Research Talent, and the Young Talent Program CVON2012-10 PREDICT (Dr te Riele) and PREDICT2 (Dr Wilde and Dr van Tintelen). We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Netherlands Heart Foundation, grant numbers: CVON2012-10 PREDICT, CVON2015-12 eDETECT (Early Detection of Disease in Cardiomyopathy Mutation Carriers). The Netherlands Arrhythmogenic Cardiomyopathy (ACM) Registry is supported by the Netherlands Heart Institute (project 06901). The Johns Hopkins Arrhythmogenic Right Ventricular Dysplasia (ARVD) Program is supported by the Leyla Erkan Family Fund for ARVD Research, the Dr Francis P. Chiramonte Private Foundation, the Dr Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins, the Bogle Foundation, the Healing Hearts Foundation, the Campanella family, the Patrick J. Harrison Family, the Peter French Memorial Foundation, and the Wilmerding Endowments.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.


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