Improving sudden cardiac death risk stratification by evaluating electrocardiographic measures of global electrical heterogeneity and clinical outcomes among patients with implantable cardioverter-defibrillators: rationale and design for a retrospective, multicenter, cohort study

  • Jonathan W. Waks
  • Christopher Hamilton
  • Saumya Das
  • Ashkan Ehdaie
  • Jessica Minnier
  • Sanjiv Narayan
  • Mark Niebauer
  • Merritt Raitt
  • Christine Tompkins
  • Niraj Varma
  • Sumeet Chugh
  • Larisa G. Tereshchenko



Implantable cardioverter-defibrillators (ICDs) improve survival of systolic heart failure (HF) patients who are at risk of sudden cardiac death (SCD). We recently showed that electrocardiographic (ECG) global electrical heterogeneity (GEH) is independently associated with SCD in the community-dwelling cohort and developed GEH SCD risk score. The Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study is a retrospective multicenter cohort designed with two goals: (1) validate an independent association of ECG GEH with sustained ventricular tachyarrhythmias and appropriate ICD therapies and (2) validate GEH ECG risk score for prediction of sustained ventricular tachyarrhythmias and appropriate ICD therapies in systolic HF patients with primary prevention ICD.


All records of primary prevention ICD recipients with available data for analysis are eligible for inclusion. Records of ICD implantation in patients with inherited channelopathies and cardiomyopathies are excluded. Raw digital 12-lead pre-implant ECGs will be used to measure GEH (spatial QRST angle, spatial ventricular gradient magnitude, azimuth, and elevation, and sum absolute QRST integral). The primary endpoint is defined as a sustained ventricular tachyarrhythmia event with appropriate ICD therapy. All-cause death without preceding sustained ventricular tachyarrhythmia with appropriate ICD therapy will serve as a primary competing outcome. The study will draw data from the academic medical centers.


We describe the study protocol of the first multicenter retrospective cohort of primary prevention ICD patients with recorded at baseline digital 12-lead ECG.


Findings from this study will inform future trials to identify patients who are most likely to benefit from primary prevention ICD.

Trial registration

URL: Unique identifier: NCT03210883.


Sudden cardiac death Implantable cardioverter-defibrillators Electrocardiogram Vectorcardiogram Ventricular arrhythmias Risk stratification 



Global electrical heterogeneity


Implantable cardioverter-defibrillator


Sudden cardiac death




Left ventricular ejection fraction


Ventricular tachycardia


Ventricular fibrillation


Spatial ventricular gradient


American Heart Association


Compliance with ethical standards

The multicenter study has been approved by the OHSU Institutional Review Board (IRB).

Conflict of interests

The Johns Hopkins University owns the patent US8880159 B2 “Methods for determining risk of ventricular arrhythmia” (Inventor LGT; 100% assigned to the Johns Hopkins University; not licensed).

Supplementary material

10840_2018_342_MOESM1_ESM.pdf (91 kb)
ESM 1 (PDF 90 kb)
10840_2018_342_MOESM2_ESM.pdf (64 kb)
ESM 2 (PDF 63 kb)
10840_2018_342_MOESM3_ESM.pdf (111 kb)
ESM 3 (PDF 111 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jonathan W. Waks
    • 1
  • Christopher Hamilton
    • 2
  • Saumya Das
    • 3
  • Ashkan Ehdaie
    • 4
  • Jessica Minnier
    • 2
    • 5
  • Sanjiv Narayan
    • 6
  • Mark Niebauer
    • 7
  • Merritt Raitt
    • 8
  • Christine Tompkins
    • 9
  • Niraj Varma
    • 7
  • Sumeet Chugh
    • 4
  • Larisa G. Tereshchenko
    • 1
    • 2
    • 10
  1. 1.Beth Israel Deaconess Medical CenterBostonUSA
  2. 2.Knight Cardiovascular InstituteOregon Health and Science UniversityPortlandUSA
  3. 3.Massachusetts General HospitalBostonUSA
  4. 4.Cedars-Sinai Medical CenterLos AngelesUSA
  5. 5.OHSU-PSU School of Public HealthOregon Health and Science UniversityPortlandUSA
  6. 6.Stanford University School of MedicinePalo AltoUSA
  7. 7.Cleveland Clinic FoundationClevelandUSA
  8. 8.VA Portland Health Care SystemPortlandUSA
  9. 9.University of ColoradoAuroraUSA
  10. 10.PortlandUSA

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