The Role of Electrophysiology Testing in Survivors of Unexplained Cardiac Arrest (EPS ARREST)

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.

Study Overview

• Status: Completed
• Conditions: Sudden Cardiac Death
• Intervention / Treatment: Procedure: Invasive Electrophysiology Study

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.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada
      • University of British Columbia
    • Vancouver, British Columbia, Canada
      • British Columbia Children's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • QEII Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal Heart Institute
    • Quebec City, Quebec, Canada
      • Laval University
• Israel
  • Tel-Aviv, Israel
    • Tel-Aviv Sourasky Medical Center
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • San Diego, California, United States, 92037
      • UC San Diego Health System
    • San Francisco, California, United States, 94143-0124
      • UCSF Medical Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Unexplained Aborted Cardiac Arrest; Survivors of sudden cardiac death with no identifiable etiology following initial diagnostic workup.

Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arrhythmic culprit for aborted cardiac arrest	Identification of an arrhythmic culprit for aborted cardiac arrest using an invasive electrophysiology study.	Assessed immediately upon testing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of bundle branch reentrant ventricular tachycardia	Prevalence of bundle branch reentrant ventricular tachycardia among survivors of unexplained cardiac arrest.	Assessed immediately upon testing
Prevalence of supraventricular tachycardia associated with hemodynamic collapse	Prevalence of inducible supraventricular tachycardia during invasive electrophysiology study among survivors of unexplained cardiac arrest.	Assessed immediately upon testing
Prevalence of a latent/cryptic accessory pathway	Prevalence of a latent/cryptic accessory pathway among survivors of unexplained cardiac arrest.	Assessed immediately upon testing.

Collaborators and Investigators

• Sponsor: Western University, Canada
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Jason D Roberts, MD MAS, Western University; Study Director: Andrew D Krahn, MD, University of British Columbia; Study Director: Melvin M Scheinman, MD, University of California, San Francisco

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): June 1, 2025

Study Registration Dates

• First Submitted: March 2, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Genetics; Sudden Cardiac Death; Electrophysiology Study; Cardiac Arrhythmia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Death, Sudden; Heart Arrest; Death, Sudden, Cardiac; Death
• Other Study ID Numbers: 108939

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no current plan to share IPD with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No