Understanding the Risk of Sudden Death in Families: Cascade Screening in CPVT

Nickname: To be determined

Principal Investigators

Dr. Shubhayan Sanatani, Associate Professor, Division of Cardiology, Department of Pediatrics, University of British Columbia

Funding

Heart and Stroke Foundation of Canada (2015 – 2018)

Participating Centres

Multiple international sites. Specific centres to be confirmed.

Background

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited heart rhythm disorder that causes sudden unexpected death (SUD) in young, apparently healthy individuals. CPVT occurs in at least 1 in 10,000 individuals (in Canada, ~4,000 patients), is typically diagnosed in childhood, and has a reported mortality of 50% by age 30. In a person diagnosed with CPVT, the standard therapy is medication and activity restriction, often starting in childhood and continuing for decades; implantable defibrillators are also commonly used. These treatments are associated with significant failure rates and long-term complications. At the same time, some individuals with the genetic susceptibility show no signs of CPVT; we do not know the risk of SUD in these asymptomatic carriers.

At present, we have no risk prediction models for CPVT and the role of family screening and genetic testing in risk stratification has not been studied systematically in a large population of patients. Therefore, all patients are treated in the same way – to prevent SUD – regardless of symptoms or risk of SUD. Understanding the risk continuum, including the contribution of the family history to patient outcome, is a critical gap in CPVT management.

Objectives

  1. To understand the family history, including genotype and phenotype, of CPVT.
  2. To lay the foundation for a risk stratification model by evaluating factors associated with CPVT, including demographics, family history, clinical presentation and genetics.

Methodology

The PI will collaborate with members of the international Pediatric and Congenital Electrophysiology Society (PACES), with confirmed participation from over 30 pediatric electro¬physiology sites. Over the course of three years, the study will enroll approximately 100 pediatric probands with CPVT and >2 first-degree relatives per proband. Detailed information on demographics, diagnostic tests, clinical events, family history, and treatments received will be collected at baseline and annual follow-up visits and entered into the International Pediatric CPVT Registry. The study will also collect and store blood samples to couple the registry to a biobank for future research.

Significance

Currently, without an understanding of individual risk for SUD, all patients with CPVT are treated similarly using treatments with significant side-effects and limited effectiveness. By identifying the role of family history and other risk factors in CPVT on an international scale, the study can lay the groundwork for development of risk stratification model and tools to guide individualized patient and family-specific treatments for CPVT. This study will ultimately create a novel pediatric registry established by some of the world’s top researchers in this field of study.