GRADE: Genetic Risk Assessment of Defibrillator Events

Sponsor

University of Iowa (Other)

Overall Status

Completed

CT.gov ID

NCT02045043

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

1,807

Enrollment

Locations

123

Duration (Months)

301.2

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
Sudden Cardiac Death Arrhythmias Congestive Heart Failure Cardiomyopathy

Study Design

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 :

Mar 1, 2002

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Cardiomyopathy patients with ICDs

Outcome Measures

Primary Outcome Measures

Shock-Free Survival [Up to 5 years]
Time to first appropriate shock from an Implantable Cardioverter-Defibrillator

Secondary Outcome Measures

Survival [Up to 5 years]
Time to death from any cause
Transplant- and VAD-Free Survival [Up to 5 years]
Time to occurence of death from any cause, cardiac transplantation, or Ventricular Assist Device placement (whichever comes first)
Appropriate Shock Frequency [Up to 5 years]
The number of appropriate shocks per year

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30322
2	Massuchetts General Hospital	Boston	Massachusetts	United States	02114
3	The Ohio State University	Columbus	Ohio	United States	43210
4	Mid Ohio Cardiology	Columbus	Ohio	United States	43214
5	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
6	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15240