Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
Bibliographical noteFunding Information:
This work was supported by the Canadian Heart Rhythm Society George Mines Traveling Fellowship to Dr Cadrin-Tourigny; the Montreal Heart Institute Foundation Bal du Coeur bursary to Dr Cadrin-Tourigny; The Marvin and Philippa Carsley Chair of medicine to Drs Cadrin-Tourigny, Tadros, and Talajic. The Johns Hopkins Arrhythmogenic Right Ventricular Dysplasia (ARVD) Program is supported by the Dr Francis P. Chiaramonte Private Foundation, the Leyla Erkan Family Fund for ARVD Research, 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. The Johns Hopkins ARVD and Zurich ARVC Programs are also supported by a joint grant from the Leonie-Wild Foundation. The Dutch ARVC program is supported by the Dutch Heart Foundation (CVON2018-30 PREDICT2, CVON eDETECT 2015-12) and the Netherlands Organization for Scientific Research (NWO)—travel grant 040.11.586 to Dr James. Dr Asselbergs is supported by UCL Hospitals NIHR biomedical research center. The Zurich ARVC Program is supported by the Georg und Bertha Schwyzer Winiker Foundation, the Baugarten Foundation, and the Swiss Heart Foundation. The Canadian ARVC registry is supported by the Heart in Rhythm Organization (Dr Krahn, Principal Investigator) receiving support from the Canadian Institutes of Health Research (RN380020—406814). The Nordic ARVC registry is supported by the Norwegian Research Council (grant No. 288438, Dr Haugaa), the Swedish Heart-Lung Foundation (grant No. 20180444, Dr Platonov), the Swedish Healthcare system (ALF-grant No. 46702, Dr Platonov and ALF-grant LIO-796561 Dr Svensson). This work is also supported by a grant from the Fondation Leducq to Dr Calkins.
Dr Calkins is a consultant for Medtronic Inc and St. Jude Medical/Abbott. Dr Calkins receives research support from Boston Scientific Corp. C. Tichnell and Dr James receive salary support from this grant. Dr James has received funding for an invited lecture from Abbott. Dr Tandri receives research support from Abbott. Dr Saguner received lecture honoraria from Boston Scientific Corp. Dr Zimmerman receives salary support from Siemens Healthcare. Dr Yap has research grants from Medtronic and Biotronik and is consultant for Boston Scientific. Dr Judge is a consultant for 4D Molecular Therapeutics, ADRx, Pfizer, and Blade Therapeutics and receives research support from Eidos Therapeutics and Array Biopharma. Dr Chelko receives laboratory supplies from Novartis. Dr Krahn receives research and consulting fees from Medtronic. The other authors report no conflicts.
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