Identification of Risk Factors for Arrhythmia in Children and Adolescents With Hypertrophic Cardiomyopathy

Patients with HCM have an increased incidence of sudden death, particularly younger individuals. However, HCM has markedly variable clinical presentations, and the risk of sudden death and arrhythmia events (AE) differs significantly from one patient to another. Several risk factors for AE have been proposed. These risk factors have been defined in predominantly adult HCM populations. Little data is available defining risk factors for sudden death in a carefully defined HCM population composed of only children and adolescents. Those at highest risk may benefit from implantable defibrillator (ICD) therapy. However, the universal application of ICD therapy is not without significant morbidity and mortality.

Traditional risk factors for sudden death (SD) in adult HCM patients include a family history of SD, young age, non-sustained ventricular tachycardia (VT) on Holter monitoring, increased ventricular septal thickness (ST), abnormal blood pressure (BP) response to exercise and syncope.

The purpose of this study will be to 1) to determine whether risk factors for and mechanisms of AE in adults have predictive value in children, and 2) in particular, whether ventricular septal thickness and inducible ventricular tachycardia at electrophysiologic study (EPS) would identify a subgroup of children that might benefit most from ICD implantation.

Clinical features that will be examined as potential AE predictors included: age at presentation to the NIH; family history of SD; pre-syncope or syncope; exercise-induced hypotension; ventricular septal thickness; LV outflow obstruction; elevated LV end diastolic pressure; QRS duration; QT interval; VT on ambulatory electrocardiographic monitoring; myocardial ischemia on stress nuclear perfusion imaging; inducible VT; intra-cardiac conduction intervals; and ventricular refractory periods. Statistical significance for the time-to-event analyses will be assessed using the logrank statistic for dichotomous variables and Cox's score statistic for continuous variables.

We anticipate that this study will improve risk stratification in children and adolescents with HCM, enhance our ability to predict AE, and refine guidelines for ICD therapy in children.

• Children and adolescents (less than or equal to 21 years) with HCM who had been evaluated in the Cardiology Branch, National Heart Lung and Blood Institute between 1977 and 2002. HCM was diagnosed by echocardiographic demonstration of a hypertrophied non-dilated left ventricle (LV) in the absence of another cause of LV hypertrophy. All patients participated in protocols approved by the NHLBI Institutional Review Board, and provided informed written consent to participate. The patients participated in the following protocols: 98-H-0102, 77-H-0082, 99-H-0150, 01-H-0007, 96-H-0144, 94-H-0001, 84-H-0232, 98-H-0100, and 99-H-0065.