The Role of Electrophysiology Testing in Survivors of Unexplained Cardiac Arrest

NCT ID: NCT03079414

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2025-06-01

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.

Conditions

Sudden Cardiac Death

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Unexplained Aborted Cardiac Arrest

Survivors of sudden cardiac death with no identifiable etiology following initial diagnostic workup.

Invasive Electrophysiology Study

Intervention Type: PROCEDURE

Invasive electrophysiology studies will be performed using four catheters placed in the right ventricular apex, the coronary sinus, the His bundle region, and the high right atrium. Standard induction protocols for supraventricular and ventricular arrhythmias will be utilized in the absence and presence of isoproterenol. Long-short ventricular extra-stimuli will also be delivered to screen for bundle branch reentrant ventricular tachycardia. The study is considered observational as the participating sites perform electrophysiology studies in this patient population as part of standard clinical care.

Interventions

Invasive Electrophysiology Study

Invasive electrophysiology studies will be performed using four catheters placed in the right ventricular apex, the coronary sinus, the His bundle region, and the high right atrium. Standard induction protocols for supraventricular and ventricular arrhythmias will be utilized in the absence and presence of isoproterenol. Long-short ventricular extra-stimuli will also be delivered to screen for bundle branch reentrant ventricular tachycardia. The study is considered observational as the participating sites perform electrophysiology studies in this patient population as part of standard clinical care.

Intervention Type: PROCEDURE

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Western University, Canada

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason D Roberts, MD MAS

Role: PRINCIPAL_INVESTIGATOR

Western University

Andrew D Krahn, MD

Role: STUDY_DIRECTOR

University of British Columbia

Melvin M Scheinman, MD

Role: STUDY_DIRECTOR

University of California, San Francisco

Locations

UCLA Medical Center

Los Angeles, California, United States

UC San Diego Health System

San Diego, California, United States

UCSF Medical Center

San Francisco, California, United States

Stanford University

Stanford, California, United States

Queen's Medical Center

Honolulu, Hawaii, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Regions Hospital

Saint Paul, Minnesota, United States

Oregon Health & Science University

Portland, Oregon, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Utah

Salt Lake City, Utah, United States

Inova Heart and Vascular Institute

Falls Church, Virginia, United States

University of Calgary

Calgary, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

University of British Columbia

Vancouver, British Columbia, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Laval University

Québec, Quebec, Canada

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Countries

United States; Canada; Israel

References

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: BACKGROUND

PMID: 19597050 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1960318 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29759522 (View on PubMed)

Other Identifiers

108939

Identifier Type: -

Identifier Source: org_study_id