1. A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy
- Author
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Miron, A. (Anastasia), Lafreniere-Roula, M. (Myriam), Steve Fan, C.-P. (Chun-Po), Armstrong, K.R. (Katey R.), Dragulescu, A. (Andreea), Papaz, T. (Tanya), Manlhiot, C. (Cedric), Kaufman, B. (Beth), Butts, R.J. (Ryan J.), Gardin, L. (Letizia), Stephenson, E.A. (Elizabeth A.), Howard, T.S. (Taylor S.), Aziz, P.F. (Pete F.), Balaji, S. (Seshadri), Ladouceur, V.B. (Virginie Beauséjour), Benson, L.N. (Lee N.), Colan, S.D. (Steven), Godown, J. (Justin), Henderson, H.T. (Heather T.), Ingles, J. (Jodie), Jeewa, A. (Aamir), Jefferies, J.L. (John L.), Lal, A.K. (Ashwin K.), Mathew, J. (Jacob), Jean-St-Michel, E. (Emilie), Michels, M. (Michelle), Nakano, S.J. (Stephanie J.), Olivotto, I. (Iacopo), Parent, J.J. (John J.), Pereira, A. (A.), Semsarian, C. (Christopher), Whitehill, R.D. (Robert D.), Wittekind, S.G. (Samuel G.), Russell, M.W. (Mark W.), Conway, J. (Jennifer), Richmond, M.E. (Marc E.), Villa, C. (Chet), Weintraub, R.G. (Robert G), Rossano, J.W. (Joseph W.), Kantor, P.F. (Paul F.), Ho, C.Y. (Carolyn Y.), Mital, S. (Seema), Miron, A. (Anastasia), Lafreniere-Roula, M. (Myriam), Steve Fan, C.-P. (Chun-Po), Armstrong, K.R. (Katey R.), Dragulescu, A. (Andreea), Papaz, T. (Tanya), Manlhiot, C. (Cedric), Kaufman, B. (Beth), Butts, R.J. (Ryan J.), Gardin, L. (Letizia), Stephenson, E.A. (Elizabeth A.), Howard, T.S. (Taylor S.), Aziz, P.F. (Pete F.), Balaji, S. (Seshadri), Ladouceur, V.B. (Virginie Beauséjour), Benson, L.N. (Lee N.), Colan, S.D. (Steven), Godown, J. (Justin), Henderson, H.T. (Heather T.), Ingles, J. (Jodie), Jeewa, A. (Aamir), Jefferies, J.L. (John L.), Lal, A.K. (Ashwin K.), Mathew, J. (Jacob), Jean-St-Michel, E. (Emilie), Michels, M. (Michelle), Nakano, S.J. (Stephanie J.), Olivotto, I. (Iacopo), Parent, J.J. (John J.), Pereira, A. (A.), Semsarian, C. (Christopher), Whitehill, R.D. (Robert D.), Wittekind, S.G. (Samuel G.), Russell, M.W. (Mark W.), Conway, J. (Jennifer), Richmond, M.E. (Marc E.), Villa, C. (Chet), Weintraub, R.G. (Robert G), Rossano, J.W. (Joseph W.), Kantor, P.F. (Paul F.), Ho, C.Y. (Carolyn Y.), and Mital, S. (Seema)
- Abstract
Background: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. Methods: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy <18 years of age at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest, and aborted SCD, that is, appropriate shock following primary prevention implantable cardioverter defibrillators. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with 10 repeated 4-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized by using the c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe [Sarcomeric Human Cardiomyopathy Registry], n=285). Results: Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated sudden cardiac arrests, and 14 aborted SCD). Risk predictors included age at diagnosis, documented nonsustained ventricular tachycardia, unexplained syncope, septal diameter z-score, left ventricular posterior wall diameter z score, left atrial diameter z score, peak left ventricular outflow tract gradient, and presence of a pathogenic variant. Unlike in adults, left ventricular outflow tract gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic mode
- Published
- 2020
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