Hypertrophic Cardiomyopathy Registry: The rationale and design of an international, observational study of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease with a frequency as high as 1 in 200. In many cases, HCM is caused by mutations in genes encoding the different components of the sarcomere apparatus. Hypertrophic cardiomyopathy is characterized by unexplained left ventricular hypertrophy, myofibrillar disarray, and myocardial fibrosis. The phenotypic expression is quite variable. Although most patients with HCM are asymptomatic, serious consequences are experienced in a subset of affected individuals who present initially with sudden cardiac death or progress to refractory heart failure. The Hypertrophic Cardiomyopathy Registry study is a National Heart, Lung, and Blood Institute-sponsored 2,750-patient, 44-site, international registry and natural history study designed to address limitations in extant evidence to improve prognostication in HCM (NCT01915615). In addition to the collection of standard demographic, clinical, and echocardiographic variables, patients will undergo state-of-the-art cardiac magnetic resonance for assessment of left ventricular mass and volumes as well as replacement scarring and interstitial fibrosis. In addition, genetic and biomarker analyses will be performed. The Hypertrophic Cardiomyopathy Registry has the potential to change the paradigm of risk stratification in HCM, using novel markers to identify those at higher risk.

Funding evidence: the National Institute of Neurological Disorders and Stroke Clinical Trials Program.

The goal of the National Institute of Neurological Disorders and Stroke (NINDS) Clinical Trials Program is to foster clinical trials that will provide the evidence needed to inform clinical care. The NINDS currently supports clinical research in over 150 neurological disorders. The rapid pace of preclinical discovery and the diversity of neurological diseases, however, present challenges for clinical trials. There is a growing number of potential interventions to be tested in clinical trials. The NINDS Clinical Trials program is therefore exploring ways of making drug selection for clinical trials more evidence-based. Additionally, NINDS supports pilot clinical trials that focus on the timely and efficient testing of agents to determine if resource-intensive comparative efficacy trials are warranted. In concert with the National Institutes of Health Roadmap, NINDS is planning to expand clinical trials infrastructure. This infrastructure is intended to enable the conduct of clinical trials for rare diseases and diseases without previous trials experience and facilitate the recruitment of a broad range of participants. Rigorous programs to select agents, and design and monitor clinical trials will encourage the efficient use of this clinical trials infrastructure and will ensure that NINDS-funded studies meet the highest scientific and ethical standards.