Extracellular Matrix Marker of Arrhythmia Risk (EMMA)
Death, Sudden, Cardiac
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Role of Matrix Metaloproteinase(MMP)9 and MMP 2 in Risk Stratification for Ventricular Tachycardia/Fibrillation in Patients With Implanted Cardioverter Defibrillator (ICD) Devices.|
- MMP-2 [ Time Frame: At time of enrollment ] [ Designated as safety issue: No ]Serum MMP-2 levels determined by Aushon Biosystems Searchlight® Protein Array Analysis.
- MMP-9 [ Time Frame: At time of enrollment ] [ Designated as safety issue: No ]Serum MMP-9 levels determined by Aushon Biosystems Searchlight® Protein Array Analysis.
Biospecimen Retention: Samples Without DNA
|Study Start Date:||September 2006|
|Study Completion Date:||September 2008|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
ICD pacing or shock event
Subjects who experienced a device treatment, defined as a pacing event or a shock event
No ICD pacing or shock event
Subjects who did not experience a treatment defined as a pacing event or a shock event
Sudden cardiac death (SCD) is responsible for 300,000-450,000 deaths per year in the United States. While it is well known that patients with both ischemic and non-ischemic cardiomyopathy (ICM, NICM) are at increased risk for SCD, there is little beyond ejection fraction which has proven useful as a noninvasive predictor to risk stratify these patients.
Myocardial scar has been validated as an arrhythmic substrate in ischemic populations; the majority of successful ablations for lethal ventricular arrhythmias are performed on tissues in peri-infarct regions. Scar provides an anatomic electrical boundary where peri-infarct zones may lead to areas of slow conduction due to the disruption of inter-myocyte electrical conduction.
Myocardial scar is a less organized collagen deposition which disrupts the typical cardiac extracellular matrix. The collagen matrix provides mechanical support to the myocardium dictating ventricular shape, size and stiffness. While typically relatively dormant, the fibrillar collagen matrix reflects a dynamic relationship between collagen synthesis mediated by fibroblasts and collagen degradation performed by matrix metalloproteinases (MMP).
A marker for scar burden or a marker which could assess a patient's predilection to form scar after either an ischemic or non-ischemic insult may be useful in further risk stratifying this population. Since MMP levels may fluctuate in the course of ischemic or nonischemic injury a static promoter sequence which confers a higher level of MMP expression to an ischemic or nonischemic insult may prove to be a reliable marker. Functional polymorphisms of the MMP-9 gene promoters have been shown in multivariate analysis to be an independent predictor of cardiac mortality regardless of the mechanism of heart failure.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00376532
|United States, Pennsylvania|
|Jefferson Heart Institute|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||David J. Whellan, MD MHS FACC||Thomas Jefferson University|