Background: Hypertrophic cardiomyopathy (HCM) 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 HCM to guide SCD prevention strategies. Methods: In an international multi-center observational cohort study, phenotype-positive patients with isolated HCM <18 years 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 (SCA), and aborted SCD, i.e. appropriate shock following primary prevention ICD. 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 ten repeated four-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 using c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe, 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 SCA, 14 aborted SCD). Risk predictors included age at diagnosis, documented non-sustained ventricular tachycardia, unexplained syncope, septal diameter z-score, LV posterior wall diameter z-score, LA diameter z-score, peak LV outflow tract (LVOT) gradient, and presence of a pathogenic variant. Unlike adults, LVOT gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated patients with and without SCD events with a c-statistic of 0.75 and 0.76 respectively and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72 respectively). Conclusions: Our study provides a validated SCD risk prediction model with over 70% prediction accuracy and incorporates risk factors that are unique to pediatric HCM. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision-making for ICD insertion. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT04036799
Background: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients. Methods: In an international cohort study with 20 centers, phenotype-positive children with primary HCM <18 years at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response, and new or worsened ST-T wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of an abnormal exercise test with transplant and SCD event-free survival. Results: Of 724 eligible patients, 630 underwent at least one exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8yrs (IQR 4.7yrs); 78% were male, 39% were receiving beta-blockers. 175 (28%) had an abnormal test. Patients with an abnormal test had more severe septal hypertrophy, higher left atrial diameter z-scores, higher resting LV outflow tract gradient, and higher frequency of myectomy compared to those with a normal test (p<0.05). Compared to those with a normal test, an abnormal test was independently associated with a lower 5-year transplant-free survival (97% vs. 88% respectively, p=0.005). Those with exercise-induced ischemia were most likely to experience all-cause death or transplant [Hazard ratio (HR) 4.86, CI 1.69-13.99], followed by those with an abnormal blood pressure response (HR 3.19, CI 1.32-7.71). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (HR 3.32, CI 1.27-8.70). Exercise-induced ectopy was not associated with survival. Conclusions: Exercise abnormalities are common in childhood HCM. An abnormal exercise test was independently associated with lower transplant-free survival especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.
Introduction: Right ventricular pacing is associated with pacemaker induced cardiomyopathy and lesser degrees of pacing-induced LV dysfunction (PIVD) manifested by a reduction in left ventricular ejection fraction (LVEF). Our objective was to determine whether apical 4 chamber strain (A4C) by echocardiography can identify patients at risk of PIVD before LVEF declines.Methods and Results: A retrospective chart review of patients (0-21 years) who had a pacemaker with a ventricular lead placed between 2011 and 2017 was performed.Patients were divided into group A (LVEF <55% and/or >10% decline in LVEF within 12 months of pacemaker placement) and group B. Data have collected before and 1 and 12 months postpacemaker implantation. There were 30 patients in the group A and 60 in group B. At 1 and 12 months postpacemaker implantation, the LVEF was significantly lower while the A4C and QRS duration on electrocardiogram were significantly higher in the group A. While the LVEF and A4C became markedly abnormal in group A as early as 1 month, the A4C did not seem to demonstrate such marked abnormalities in group B. However, a sub-analysis of patients in the group A with preserved LVEF at 1 month demonstrated significant worsening in their A4C at that time.Conclusion: Myocardial deformation imaging may be a clinically useful tool for the prediction of a decline in LV systolic function following pacemaker implantation.Abnormalities in A4C seem to appear before LVEF decline and as soon as 1-month postpacemaker implantation. K E Y W O R D S cardiomyopathy, deformation, dysfunction, electrocardiogram, pacemaker, pediatric
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