Registry of Unexplained Cardiac Arrest

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by University of British Columbia
Sponsor:
Collaborators:
Heart and Stroke Foundation of Ontario
Boston Scientific Corporation
Medtronic
Information provided by (Responsible Party):
Andrew Krahn, University of British Columbia
ClinicalTrials.gov Identifier:
NCT00292032
First received: February 14, 2006
Last updated: April 13, 2015
Last verified: April 2015
  Purpose

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.


Condition Phase
Cardiac Arrest
Long QT Syndrome
Brugada Syndrome
Catecholaminergi Polymorphic Ventricular Tachycardia
Idiopathic VentricularFibrillation
Early Repolarization Syndrome
Arrhythmogenic Right Ventricular Cardiomyopathy
Phase 3

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Developing and Testing Algorithms for Diagnostics and Treatments in Survivors of Unexplained Cardiac Arrest [ Time Frame: 25 years ] [ Designated as safety issue: No ]
    Long Term follow up data on survivors of cardiac arrest Long term monitoring of high risk patients and familymembers with an Injectable Cardiac Monitor 24 hour holter monitoring during provocative testing with epinephrine infusion and ambulatory activities to detect subclinical repolarization


Biospecimen Retention:   Samples With DNA

blood


Estimated Enrollment: 1000
Study Start Date: May 2004
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Detailed Description:

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:

  1. 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.
  2. Long term cardiac monitoring for (3 years) in select heigh-risk patients with an injectable cardiac monitor to detect potential substrate and/ore triggers for sudden death.
  3. DNA/plasma collection and biobanking for stratified whole exome sequencing.
  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Unexplained cardiac arrest patients, and first degree relatives of 1) UCA patients 2) patients with known primary electrical disease or 3) unexplained sudden death before age 60

Criteria

Inclusion Criteria:

  • Cardiac arrest requiring cardioversion or defibrillation.
  • Syncope with documented polymorphic ventricular tachycardia felt to be responsible for the index event.
  • First degree relative of an index case of UCA undergoing clinical testing.
  • First degree relative of a family member with UCA or sudden death before age 35 with a negative autopsy for cause of death, presumed arrhythmic.
  • First degree relative of a family member with UCA or sudden death with objective evidence of primary electrical disease, such as a diagnostic electrocardiogram (ECG), exercise test, drug infusion, or genetic testing.

Exclusion Criteria:

  • Coronary artery disease (stenosis > 50%)
  • Reduced left ventricular function (left ventricular ejection fraction [LVEF] < 50%)
  • Event managed without an implantable cardioverter defibrillator [ICD] (for follow-up portion)
  • Unwilling or unable to provide clinical follow-up (for follow-up portion)
  • Comorbidity making survival of > 1 year unlikely
  • Persistent resting QTc > 460 msec for males and 480 msec for females
  • Reversible cause of cardiac arrest such as marked hypokalemia (< 2.8 mmol/l) or drug overdose sufficient in gravity without other cause to explain the cardiac arrest
  • Hemodynamically stable sustained monomorphic ventricular tachycardia with a QRS morphology consistent with recognized forms of idiopathic ventricular tachycardia (outflow tract or apical septal)
  • Brugada's sign with e2 mm ST elevation in V1 and/or V2
  • Unwilling or unable to provide consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00292032

Contacts
Contact: Andrew D Krahn, MD 604-682-2344 ext 63260 akrahn@mail.ubc.ca
Contact: Karen A Gibbs, RN 604-682-2344 ext 63260 kgibbs@providencehealth.bc.ca

Locations
Canada, British Columbia
University of British Columbia Recruiting
Vancovuer, British Columbia, Canada, V6E 1M7
Contact: Andrew D Krahn, MD    604-682-2344 ext 63260    akrahn@mail.ubc.ca   
Contact: Karen A Gibbs, RN    604-682-2344 ext 63260    kgibbs@providencehealth.bc.ca   
Principal Investigator: Andrew D Krahn, MD         
Sponsors and Collaborators
University of British Columbia
Heart and Stroke Foundation of Ontario
Boston Scientific Corporation
Medtronic
Investigators
Principal Investigator: Andrew D Krahn, MD University of British Columbia
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrew Krahn, principal investigator, University of British Columbia
ClinicalTrials.gov Identifier: NCT00292032     History of Changes
Other Study ID Numbers: R-04-099, 10076
Study First Received: February 14, 2006
Last Updated: April 13, 2015
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
cardiac arrest
diagnosis
genetics
testing

Additional relevant MeSH terms:
Long QT Syndrome
Arrhythmogenic Right Ventricular Dysplasia
Brugada Syndrome
Cardiomyopathies
Heart Arrest
Syndrome
Tachycardia
Tachycardia, Ventricular
Ventricular Fibrillation
Arrhythmias, Cardiac
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Disease
Genetic Diseases, Inborn
Heart Defects, Congenital
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 25, 2015