Registry of Unexplained Cardiac Arrest
The project will evaluate a standardized testing protocol in detecting the cause of cardiac arrest and familial sudden death in patients with apparently unexplained cardiac arrest. The testing is directed at the detection of rare genetic conditions that result in palpitations, blackouts and sudden death in patients and their family members. Genetic testing will be performed to validate the clinical findings.
Long QT Syndrome
Catecholamine Sensitive Polymorphic Ventricular Tachycardia
Idiopathic Ventricular Fibrillation
Early Repolarization Syndrome
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)|
|Study Start Date:||May 2004|
|Estimated Study Completion Date:||June 2013|
Arrhythmias caused by congenital or acquired abnormalities of cardiac K+ or Na+ channels are increasingly recognized as a cause of syncope and sudden death. Cardiac arrest in the absence of overt structural heart disease was previously considered idiopathic ventricular fibrillation (IVF). The list of causes of "unexplained" cardiac arrest (UCA) now encompasses K+ related abnormalities (Long and Short QT, Andersen's), Na+ related (Long QT3, Brugada), Ca++ related (Catecholaminergic Polymorphic Ventricular Tachycardia-CPVT), and latent cardiomyopathy. These underlying causes of cardiac arrest are overtly familial in 30-60% of cases. Clinical detection of the underlying phenotype is crucial to direct appropriate treatment, genetic testing and screening of family members.
Phenotype recognition of the range of these rare genetic conditions includes non-invasive and invasive testing to demonstrate the hallmarks of each individual condition, and exclude common causes such as ischemic or idiopathic forms of cardiomyopathy. The outcomes from this type of testing have not been assessed in a systematic fashion in patients with UCA or their family members. Phenotype-genotype correlation is necessary to develop optimal diagnostic testing in probands and screening techniques in their family members, which will result in disease-specific therapy. Genetic testing of patients with an overt phenotype demonstrates a potentially causative mutation in 50-75% of LQTS patients, and 20% of Brugada's Syndrome patients. Despite recognized mutations with phenotypic expression models, 30-80% of patients will have negative gene screening despite overt or latent clinical disease.
The proposed project is evaluating a systematic approach to clinical assessment and genetic screening of patients and families with UCA and suspected inherited arrhythmias involving:
- A multicenter registry of UCA patients, their family members and referred patients with familial sudden death undergoing standardized testing for evidence of primary electrical disease (PED). The single center pilot experience at the applicant's institution has proven feasibility, and has been accepted for publication in Circulation, indicating novelty. Ten centers across Canada have agreed to participate. The target is to enroll 200 UCA probands, 100 family members and 100 1st degree relatives of autopsy negative unexplained sudden death victims.
- DNA testing of affected individuals involving testing for LQTS, Brugada's Syndrome and CPVT. This project will partner with Dr. Michael Gollob at University of Ottawa for DNA sequencing.
|Contact: Andrew D Krahn, MDfirstname.lastname@example.org|
|Contact: Bonnie M Spindler, RN||519-685-8500 ext email@example.com|
|London Health Sciences Center||Recruiting|
|London, Ontario, Canada, N6A 5A5|
|Contact: Andrew D Krahn, MD 519-663-3746 ext 1 firstname.lastname@example.org|
|Contact: Bonnie M Spindler, RN 519-685-8500 ext 34748 email@example.com|
|Principal Investigator: Andrew D Krahn, MD|
|Principal Investigator:||Andrew D Krahn, MD||University of Western Ontario, Canada|