Genetic Risk Assessment of Defibrillator Events

Congestive Heart Failure Clinical Trial

— GRADE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02045043
• Other study ID #: GRADE
• Secondary ID: R01HL077398
• Status: Completed
• Phase: N/A
• First received: January 22, 2014
• Last updated: January 22, 2014
• Start date: March 2002
• Est. completion date: June 2012

Study information

• Verified date: January 2014
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1807
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Arrhythmias
• Cardiomyopathies
• Cardiomyopathy
• Congestive Heart Failure
• Death, Sudden, Cardiac
• Heart Failure
• Sudden Cardiac Death

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Massuchetts General Hospital	Boston	Massachusetts
United States	Mid Ohio Cardiology	Columbus	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Iowa	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Blanco RR, Austin H, Vest RN 3rd, Valadri R, Li W, Lassegue B, Song Q, London B, Dudley SC, Bloom HL, Searles CD, Zafari AM. Angiotensin receptor type 1 single nucleotide polymorphism 1166A/C is associated with malignant arrhythmias and altered circulatin — View Citation

Bloom HL, Shukrullah I, Veledar E, Gutmann R, London B, Dudley SC. Statins Decrease Oxidative Stress and ICD Therapies. Cardiol Res Pract. 2010;2010:253803. doi: 10.4061/2010/253803. Epub 2010 Mar 25. — View Citation

Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, MacRae CA, Dudley SC, Shalaby AA, Weiss R, McNamara DM, London B, Ellinor PT. Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm. 2012 Mar;9(3):390-6. doi: 10.1016/j.hrthm.2011.10.016. Epub 2011 Oct 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Shock-Free Survival	Time to first appropriate shock from an Implantable Cardioverter-Defibrillator	Up to 5 years	No
Secondary	Survival	Time to death from any cause	Up to 5 years	No
Secondary	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	No
Secondary	Appropriate Shock Frequency	The number of appropriate shocks per year	Up to 5 years	No