Genetic Risk Assessment of Defibrillator Events

Study Overview
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Brief Summary
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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.

Official Title
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Genetic Risk Assessment of Defibrillator Events: A Prospective Multicenter Observational Study

Conditions
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Sudden Cardiac Death, Arrhythmias, Congestive Heart Failure, Cardiomyopathy

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiomyopathy patients with ICDs<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shock-Free Survival | Time to first appropriate shock from an Implantable Cardioverter-Defibrillator | Up to 5 years | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sudden Cardiac Death, Arrhythmias, Congestive Heart Failure, Cardiomyopathy, Single Nucleotide Polymorphisms, Genomics