HYPERTROPHIC CARDIOMYOPATHY (HCM) IS A RELAtivelycommondisorder(occurringinapproximately 1 in 500 adults in the general population) and has the widely recognized clinical findings of massive myocardial hypertrophy and dynamic left ventricular outflow tract obstruction. Once thought to be a disease of unknown etiology, HCM is now recognized as a genetic disorder often caused by a mutation in at least 1 of 12 genes that encode the proteins of the cardiac sarcomere. Knowledge about HCM has changed dramatically over the past few decades, by virtue of increased recognition of this disorder due to heightened awareness of the disease and wider use of noninvasive imaging modalities. Initially, HCM was thought to be a deadly disease of the young, because patients presented with severely limiting symptoms (dyspnea, angina, and syncope) or even sudden cardiac death. However, patients with HCM can present with a wide spectrum of cardiac manifestations. The degree of hypertrophy is highly variable, ranging from only mild hypertrophy to severe massive hypertrophy, with a variable time course of onset. The dynamic left ventricular outflow tract obstruction is only a part of the complex pathophysiologic process affecting these patients, and other abnormalities such as diastolic dysfunction, myocardial ischemia, mitral regurgitation, and cardiac arrhythmias play important roles. Although HCM was once thought to be a disease with an extremely poor prognosis, the majority of patients with HCM are asymptomatic throughout life, and the survival of population-based series of these patients is comparable to that of an age-matched, sex-matched control population. Despite the relatively benign course for the majority of patients with HCM, this disease continues to be the most common cause of sudden death in young individuals (including trained athletes) and may cause sudden death in patients of all ages. Sudden death results primarily from ventricular arrhythmias that, in turn, are likely related to an abnormal substrate of disorganized muscle cell structure and a multitude of possible inciting events, such as ischemia, abnormal autonomic milieu, atrial arrhythmias, or bradycardia. However, these devastating events occur infrequently and thus pose a tremendous management dilemma for clinicians. Implantable cardiac defibrillators (ICDs) are an effective therapy to prevent sudden death in patients with HCM, but there is no method to consistently identify patients at high risk of sudden death. Data from retrospective studies have identified risk factors associated with an increased incidence of sudden death. These risk factors are only clinical surrogates used to attempt to identify an abnormal underlying substrate or triggers of arrhythmia. The positive predictive values of any 1 of these risk factors is less than 20% to 25%. In addition, although the negative predictive value of the risk factors are near 90%, some patients (approximately 3%-5%) without identifiable risk factors die suddenly. In this issue of JAMA, Maron and colleagues present important timely data on the relationship between clinical risk profile and the use and efficacy of ICD intervention in patients with HCM. The authors report data from a multicenter registry study of ICDs implanted in 506 patients with HCM, who underwent follow-up for a mean of approximately 4 years. In these relatively young patients (mean age, 42 years) in whom ICDs were implanted for either secondary prevention or primary prevention, ICD interventions appropriately terminated serious ventricular arrhythmias in 20% of patients. The intervention rates were 11% per year for secondary prevention and 4% per year for primary prevention. Patients who had received an ICD for only a single risk factor had a similar likelihood of appropriate ICD intervention (ie, device discharge) as did patients with 2 or more risk factors. The measured risk factors included (1) a family history of sudden death due to hypertrophic cardiomyopathy, (2) massive left ventricular hypertrophy, (3) nonsustained ventricular tachycardia on Holter monitoring, and