Clinical trial NCT03079414: The Role of Electrophysiology Testing in Survivors of Unexplained Cardiac Arrest
Official title: The Role of Electrophysiology Testing in Survivors of Unexplained Cardiac Arrest
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sudden Cardiac Death
Keywords: Sudden Cardiac Death
Cardiac Arrhythmia
Electrophysiology Study
Genetics
Lead sponsor: Western University, Canada
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-03-14
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Survivors of unexplained sudden cardiac death for whom an underlying etiology remains unclear following a standard diagnostic workup, including 12-lead surface ECG, coronary artery assessment, echocardiography, cardiac MRI with late gadolinium enhancement, procainamide challenge, and exercise treadmill testing.

Brief summary: Sudden cardiac death (SCD) remains a major cause of mortality within developed nations despite aggressive efforts to reduce its societal burden. Despite extensive clinical and genetic investigations, a subgroup of cardiac arrests remain unexplained, highlighting the potential contribution of additional cardiac conditions that may not be identified with contemporary diagnostic algorithms. The EPS ARREST study aims to evaluate the role of invasive electrophysiology study within this patient population.

Detailed description: The majority of cases of SCD in older individuals occur secondary to coronary and structural heart disease, while genetic channelopathies and cardiomyopathies are prominent contributors in young adults. Among individuals that suffer aborted cardiac arrests in the absence of overt coronary and structural heart disease, diagnostic algorithms that screen for cardiac channelopathies and more subtle forms of structural heart disease have been established. Despite the extensive investigations currently utilized, a significant proportion of aborted cardiac arrests remain unexplained.

Although invasive electrophysiology studies are a cornerstone for diagnosis and management of arrhythmia disorders, they are not invariably included in the workup of cases of unexplained aborted cardiac arrest. This is largely driven by initial studies suggesting that the diagnostic yield in this context is low, however these investigations often used invasive electrophysiology studies indiscriminately in all cases of aborted cardiac arrest. Since these earlier studies, our insight and approach to SCD has evolved and it has become clear that the majority of patients do not require an invasive electrophysiology study for diagnosis. However an invasive electrophysiology study may still have an important role among these individuals when the initial workup is negative. Notably, arrhythmias that require invasive electrophysiology for diagnosis, including bundle branch reentrant ventricular tachycardia and supraventricular tachycardias associated with hemodynamic collapse, have been identified as arrhythmic culprits in this patient population.

The goal of the EPS ARREST study is to evaluate the diagnostic yield of a standardized invasive electrophysiology study among survivors of SCD when initial investigations fail to identify an underlying etiology.

Eligibility criteria: Inclusion Criteria:

1. Unexplained cardiac arrest requiring cardioversion or defibrillation
2. Willing and able to sign informed consent

Exclusion Criteria:

1. Coronary artery disease (stenosis \> 50%) and clinical findings consistent with an ischemic arrest
2. Reduced left ventricular function (left ventricular ejection fraction \< 50%) on echocardiogram or cardiac MRI.
3. Persistent resting QTc \> 460 msec for males and 480 msec for females
4. Resting QTc \< 350 msec
5. Type I Brugada ECG with \>/= 2 mm ST elevation in V1 and/or V2 (Spontaneous or Drug-Induced)
6. Polymorphic or bidirectional ventricular tachycardia observed with exertion on exercise treadmill testing
7. Clinical, electrocardiographic, and/or imaging findings consistent with a diagnosis of arrhythmogenic right ventricular cardiomyopathy
8. Myocarditis
9. Reversible cause of cardiac arrest such as marked hypokalemia (\<2.8 mmol/l) or drug overdose sufficient in severity without other cause to explain the cardiac arrest.
10. Arrhythmic mitral valve prolapse syndrome
11. Documented ventricular fibrillation initiated by a short-coupled premature ventricular contraction

Primary outcomes:
measure: Arrhythmic culprit for aborted cardiac arrest
timeFrame: Assessed immediately upon testing
Secondary outcomes:
measure: Prevalence of bundle branch reentrant ventricular tachycardia
timeFrame: Assessed immediately upon testing
measure: Prevalence of supraventricular tachycardia associated with hemodynamic collapse
timeFrame: Assessed immediately upon testing
measure: Prevalence of a latent/cryptic accessory pathway
timeFrame: Assessed immediately upon testing.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Diego
country: United States
facility: UC San Diego Health System
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: St. Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec City
country: Canada
facility: Laval University
state: Quebec
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
affiliation: Western University
name: Jason D Roberts, MD MAS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Andrew D Krahn, MD
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Melvin M Scheinman, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Wang YS, Scheinman MM, Chien WW, Cohen TJ, Lesh MD, Griffin JC. Patients with supraventricular tachycardia presenting with aborted sudden death: incidence, mechanism and long-term follow-up. J Am Coll Cardiol. 1991 Dec;18(7):1711-9. doi: 10.1016/0735-1097(91)90508-7.
citation: Roberts JD, Gollob MH, Young C, Connors SP, Gray C, Wilton SB, Green MS, Zhu DW, Hodgkinson KA, Poon A, Li Q, Orr N, Tang AS, Klein GJ, Wojciak J, Campagna J, Olgin JE, Badhwar N, Vedantham V, Marcus GM, Kwok PY, Deo RC, Scheinman MM. Bundle Branch Re-Entrant Ventricular Tachycardia: Novel Genetic Mechanisms in a Life-Threatening Arrhythmia. JACC Clin Electrophysiol. 2017 Mar;3(3):276-288. doi: 10.1016/j.jacep.2016.09.019. Epub 2016 Dec 21.