Registry of Unexplained Cardiac Arrest

November 12, 2020 updated by: Andrew Krahn, University of British Columbia

Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)

The CASPER will collect systematic clinical assessments of patients and families within the multicenter Canadian Inherited Heart Rhythm Research Network. Unexplained Cardiac Arrest patients and family members will undergo standardized testing for evidence of primary electrical disease and latent cardiomyopathy along with clinical genetics screening of affected individuals based on an evident or unmasked phenotype.

Study Overview

Status

Completed

Conditions

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 1500 UCA probands, 1st degree family members. 1st degree relatives of autopsy negative unexplained sudden death victims.
  2. Long term cardiac monitoring for (3 years) in select high-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.

Study Type

Observational

Enrollment (Actual)

1529

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6E 1M7
        • University of British Columbia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cardiac Arrest Survivors or Post Mortem Unexplained Cardiac
Probands - Unexplained Cardiac Arrest Survivors and Post Mortem Unexplained Cardiac Arrest Cases
First Degree Family Members
First Degree Family Members of those affected by Sudden Unexplained Cardiac Arrest

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Developing and Testing Algorithms for Diagnostics and Treatments in Survivors of Unexplained Cardiac Arrest
Time Frame: 25 years
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
25 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

Unity Health Toronto
University of Calgary
Queen's University
Ottawa Heart Institute Research Corporation
Provincial Health Services Authority
Montreal Heart Institute
The Queen Elizabeth Hospital
Vancouver Island Health Authority
St. Boniface Hospital
Quebec Heart Institute

Investigators

  • Principal Investigator: Andrew D Krahn, MD, University of British Columbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

August 30, 2020

Study Completion (Actual)

August 30, 2020

Study Registration Dates

First Submitted

February 14, 2006

First Submitted That Met QC Criteria

February 14, 2006

First Posted (Estimate)

February 15, 2006

Study Record Updates

Last Update Posted (Actual)

November 16, 2020

Last Update Submitted That Met QC Criteria

November 12, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-04-099
  • 10076 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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