Registry of Unexplained Cardiac Arrest

NCT ID: NCT00292032

Last Updated: 2020-11-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1529 participants

Study Classification

OBSERVATIONAL

Study Start Date

2004-05-31

Study Completion Date

2020-08-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Keywords

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cardiac arrest diagnosis genetics testing

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cardiac Arrest Survivors or Post Mortem Unexplained Cardiac

Probands - Unexplained Cardiac Arrest Survivors and Post Mortem Unexplained Cardiac Arrest Cases

No interventions assigned to this group

First Degree Family Members

First Degree Family Members of those affected by Sudden Unexplained Cardiac Arrest

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kingston Health Sciences Centre

OTHER

Sponsor Role collaborator

Quebec Heart Institute

OTHER

Sponsor Role collaborator

The Queen Elizabeth Hospital

OTHER

Sponsor Role collaborator

St. Boniface Hospital

OTHER

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role collaborator

Vancouver Island Health Authority

OTHER

Sponsor Role collaborator

Provincial Health Services Authority

OTHER

Sponsor Role collaborator

Montreal Heart Institute

OTHER

Sponsor Role collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role collaborator

University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Andrew Krahn

Principal Iinvestigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andrew D Krahn, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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University of British Columbia

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

References

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Krahn AD, Gollob M, Yee R, Gula LJ, Skanes AC, Walker BD, Klein GJ. Diagnosis of unexplained cardiac arrest: role of adrenaline and procainamide infusion. Circulation. 2005 Oct 11;112(15):2228-34. doi: 10.1161/CIRCULATIONAHA.105.552166. Epub 2005 Oct 3.

Reference Type RESULT
PMID: 16203906 (View on PubMed)

Krahn AD, Healey JS, Chauhan V, Birnie DH, Simpson CS, Champagne J, Gardner M, Sanatani S, Exner DV, Klein GJ, Yee R, Skanes AC, Gula LJ, Gollob MH. Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER). Circulation. 2009 Jul 28;120(4):278-85. doi: 10.1161/CIRCULATIONAHA.109.853143. Epub 2009 Jul 13.

Reference Type RESULT
PMID: 19597050 (View on PubMed)

Davies B, Bartels K, Hathaway J, Xu F, Roberts JD, Tadros R, Green MS, Healey JS, Simpson CS, Sanatani S, Steinberg C, Gardner M, Angaran P, Talajic M, Hamilton R, Arbour L, Seifer C, Fournier A, Joza J, Krahn AD, Lehman A, Laksman ZWM. Variant Reinterpretation in Survivors of Cardiac Arrest With Preserved Ejection Fraction (the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry) by Clinicians and Clinical Commercial Laboratories. Circ Genom Precis Med. 2021 Jun;14(3):e003235. doi: 10.1161/CIRCGEN.120.003235. Epub 2021 May 7.

Reference Type DERIVED
PMID: 33960826 (View on PubMed)

Cheung CC, Davies B, Gibbs K, Laksman ZW, Krahn AD. Patch monitors for arrhythmia monitoring in patients for suspected inherited arrhythmia syndrome. J Cardiovasc Electrophysiol. 2021 Mar;32(3):856-859. doi: 10.1111/jce.14917. Epub 2021 Feb 15.

Reference Type DERIVED
PMID: 33512057 (View on PubMed)

Mellor G, Laksman ZWM, Tadros R, Roberts JD, Gerull B, Simpson CS, Klein GJ, Champagne J, Talajic M, Gardner M, Steinberg C, Arbour L, Birnie DH, Angaran P, Leather R, Sanatani S, Chauhan VS, Seifer C, Healey JS, Krahn AD. Genetic Testing in the Evaluation of Unexplained Cardiac Arrest: From the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry). Circ Cardiovasc Genet. 2017 Jun;10(3):e001686. doi: 10.1161/CIRCGENETICS.116.001686.

Reference Type DERIVED
PMID: 28600387 (View on PubMed)

Steinberg C, Padfield GJ, Champagne J, Sanatani S, Angaran P, Andrade JG, Roberts JD, Healey JS, Chauhan VS, Birnie DH, Janzen M, Gerull B, Klein GJ, Leather R, Simpson CS, Seifer C, Talajic M, Gardner M, Krahn AD. Cardiac Abnormalities in First-Degree Relatives of Unexplained Cardiac Arrest Victims: A Report From the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry. Circ Arrhythm Electrophysiol. 2016 Sep;9(9):e004274. doi: 10.1161/CIRCEP.115.004274.

Reference Type DERIVED
PMID: 27635072 (View on PubMed)

Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, Champagne J, Healey JS, Gibbs K, Talajic M, Gardner M, Bennett MT, Steinberg C, Janzen M, Gollob MH, Angaran P, Yee R, Leather R, Chakrabarti S, Sanatani S, Chauhan VS, Krahn AD. Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry. Circ Arrhythm Electrophysiol. 2016 Jan;9(1):e003619. doi: 10.1161/CIRCEP.115.003619.

Reference Type DERIVED
PMID: 26783233 (View on PubMed)

Krahn AD, Healey JS, Chauhan VS, Birnie DH, Champagne J, Sanatani S, Ahmad K, Ballantyne E, Gerull B, Yee R, Skanes AC, Gula LJ, Leong-Sit P, Klein GJ, Gollob MH, Simpson CS, Talajic M, Gardner M. Epinephrine infusion in the evaluation of unexplained cardiac arrest and familial sudden death: from the cardiac arrest survivors with preserved Ejection Fraction Registry. Circ Arrhythm Electrophysiol. 2012 Oct;5(5):933-40. doi: 10.1161/CIRCEP.112.973230. Epub 2012 Sep 3.

Reference Type DERIVED
PMID: 22944906 (View on PubMed)

Krahn AD, Healey JS, Simpson CS, Chauhan VS, Birnie DH, Champagne J, Gardner M, Sanatani S, Chakrabarti S, Yee R, Skanes AC, Leong-Sit P, Ahmad K, Gollob MH, Klein GJ, Gula LJ, Sheldon RS. Sentinel symptoms in patients with unexplained cardiac arrest: from the cardiac arrest survivors with preserved ejection fraction registry (CASPER). J Cardiovasc Electrophysiol. 2012 Jan;23(1):60-6. doi: 10.1111/j.1540-8167.2011.02185.x. Epub 2011 Sep 28.

Reference Type DERIVED
PMID: 21955300 (View on PubMed)

Derval N, Simpson CS, Birnie DH, Healey JS, Chauhan V, Champagne J, Gardner M, Sanatani S, Yee R, Skanes AC, Gula LJ, Leong-Sit P, Ahmad K, Gollob MH, Haissaguerre M, Klein GJ, Krahn AD. Prevalence and characteristics of early repolarization in the CASPER registry: cardiac arrest survivors with preserved ejection fraction registry. J Am Coll Cardiol. 2011 Aug 9;58(7):722-8. doi: 10.1016/j.jacc.2011.04.022.

Reference Type DERIVED
PMID: 21816308 (View on PubMed)

Other Identifiers

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10076

Identifier Type: OTHER

Identifier Source: secondary_id

R-04-099

Identifier Type: -

Identifier Source: org_study_id