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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL077398 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cardiomyopathy patients with ICDs |
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| Measure | Description | Time Frame |
|---|---|---|
| Shock-Free Survival | Time to first appropriate shock from an Implantable Cardioverter-Defibrillator | Up to 5 years |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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Subjects 18 years of age and over with a cardiomyopathy, an ejection fraction less than or equal to 30%, and an implantable cardioverter defibrillator
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| Name | Affiliation | Role |
|---|---|---|
| Barry London, MD PhD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States | ||
| Massuchetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22004663 | Background | 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. | |
| 22939041 | Result | 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 circulating miR-155 levels in patients with chronic heart failure. J Card Fail. 2012 Sep;18(9):717-23. doi: 10.1016/j.cardfail.2012.06.531. Epub 2012 Aug 9. |
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| ID | Term |
|---|---|
| D016757 | Death, Sudden, Cardiac |
| D001145 | Arrhythmias, Cardiac |
| D006333 | Heart Failure |
| D009202 | Cardiomyopathies |
| ID | Term |
|---|---|
| D006323 | Heart Arrest |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D003645 | Death, Sudden |
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Blood was obtained for DNA (all subjects) and serum (subgroup of subjects)
| Up to 5 years |
| Appropriate Shock Frequency | The number of appropriate shocks per year | Up to 5 years |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| Mid Ohio Cardiology | Columbus | Ohio | 43214 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| VA Pittsburgh Healthcare System | Pittsburgh | Pennsylvania | 15240 | United States |
| 20369058 | Result | 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. |
| 26231842 | Derived | Aleong RG, Mulvahill MJ, Halder I, Carlson NE, Singh M, Bloom HL, Dudley SC, Ellinor PT, Shalaby A, Weiss R, Gutmann R, Sauer WH, Narayanan K, Chugh SS, Saba S, London B. Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function. J Am Heart Assoc. 2015 Jul 31;4(8):e001566. doi: 10.1161/JAHA.114.001566. |
| 25682436 | Derived | AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; Genetic Risk Assessment of Defibrillator Events Investigators. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study). Am J Cardiol. 2015 Apr 1;115(7):924-31. doi: 10.1016/j.amjcard.2015.01.020. Epub 2015 Jan 15. |
| D003643 |
| Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |