Genetic Risk Assessment of Defibrillator Events (GRADE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02045043
Recruitment Status : Completed
First Posted : January 24, 2014
Last Update Posted : January 24, 2014
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Barry London, University of Iowa

Brief Summary:

Arrhythmias remain a major health problem, causing at least 250,000 deaths annually in the United States. Pharmacological treatments often do more harm than good, and device therapies are limited by high cost and effects on quality of life. Ion channel mutations cause rare inherited arrhythmopathies, but account for only a small fraction of patients with life- threatening arrhythmias and sudden death. Most arrhythmias occur during myocardial ischemia, following myocardial infarction, and in patients with poor left ventricular (LV) function of any etiology. Aside from ejection fraction (EF), few clinically useful indicators to stratify the risk of sudden death have been identified. The role of subtle difference in ion channel expression and/or structure in predisposing patients to arrhythmias and modulating the risk of sudden death is unknown.

In this study, we are prospectively testing whether polymorphisms in ion channels and ion channel modifying genes are associated with arrhythmias in a population with internal cardioverter-defibrillators (ICDs) and poor LV function. We will test the hypothesis that functional polymorphisms in the coding sequences and promoter regions of cardiac genes (e.g. ion channels, beta-adrenergic receptors) predispose individuals to arrhythmias and /or heart failure progression.

We hope to identify genetic predictors for the common forms of sudden cardiac death. This would allow the identification of a subpopulation of heart failure patients that would benefit most from ICD placement.

Condition or disease
Sudden Cardiac Death Arrhythmias Congestive Heart Failure Cardiomyopathy

Study Type : Observational
Actual Enrollment : 1807 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetic Risk Assessment of Defibrillator Events: A Prospective Multicenter Observational Study
Study Start Date : March 2002
Primary Completion Date : June 2012
Study Completion Date : June 2012

Cardiomyopathy patients with ICDs

Primary Outcome Measures :
  1. Shock-Free Survival [ Time Frame: Up to 5 years ]
    Time to first appropriate shock from an Implantable Cardioverter-Defibrillator

Secondary Outcome Measures :
  1. Survival [ Time Frame: Up to 5 years ]
    Time to death from any cause

  2. Transplant- and VAD-Free Survival [ Time Frame: Up to 5 years ]
    Time to occurence of death from any cause, cardiac transplantation, or Ventricular Assist Device placement (whichever comes first)

  3. Appropriate Shock Frequency [ Time Frame: Up to 5 years ]
    The number of appropriate shocks per year

Biospecimen Retention:   Samples With DNA
Blood was obtained for DNA (all subjects) and serum (subgroup of subjects)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects 18 years of age and over with a cardiomyopathy, an ejection fraction less than or equal to 30%, and an implantable cardioverter defibrillator

Inclusion Criteria:

  • An ICD placed during the last 5 years, or a planned ICD within 1 month
  • Age 18 or older
  • Left Ventricular Ejection fraction < or = 30%
  • Ability to give informed consent

Exclusion Criteria:

  • Patient refuses or is unable to give consent
  • A life expectancy <6 months from a non-cardiac life threatening disease
  • Ongoing Class IV heart failure symptoms despite treatment
  • History of cardiac transplant or left ventricular assist device

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02045043

United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massuchetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Mid Ohio Cardiology
Columbus, Ohio, United States, 43214
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, United States, 15240
Sponsors and Collaborators
University of Iowa
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Barry London, MD PhD University of Iowa

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Barry London, Director, Division of Cardiovascular Medicine, University of Iowa Identifier: NCT02045043     History of Changes
Other Study ID Numbers: GRADE
R01HL077398 ( U.S. NIH Grant/Contract )
First Posted: January 24, 2014    Key Record Dates
Last Update Posted: January 24, 2014
Last Verified: January 2014

Keywords provided by Barry London, University of Iowa:
Sudden Cardiac Death
Congestive Heart Failure
Single Nucleotide Polymorphisms

Additional relevant MeSH terms:
Heart Failure
Death, Sudden, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Heart Arrest
Death, Sudden