Extracellular Matrix Marker of Arrhythmia Risk (EMMA)
Recruitment status was Recruiting
The primary objective of this study is to assess whether serum levels of MMP 2, 9, and evaluation of the genomic promoter sequence polymorphisms, correlate with episodes of VT/VF in patients who have implantable cardioverter defibrillator devices.
Death, Sudden, Cardiac
Device: 2 ARM Event vs. Non-Event
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||The Role of MMP-9 and MMP-2 in Risk Stratification for VT/VF in Patients With Implanted Cardioverter Defibrillator Devices.|
|Study Start Date:||September 2006|
|Estimated Study Completion Date:||September 2008|
Subject with an ICD event of pacing or shock vs. subjects without an event
Device: 2 ARM Event vs. Non-Event
Comparison of MMP Levels and Genetic Promoter Sequence in event (pacing or shock) vs. non-event subjects
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.
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.
|Contact: Suzanne Adams, RN MPHfirstname.lastname@example.org|
|Contact: Shaw Natan, MDemail@example.com|
|United States, Pennsylvania|
|Jefferson Heart Institute||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Suzanne Adams, RN MPH 215-955-8848 firstname.lastname@example.org|
|Principal Investigator: David J. Whellan, MD MHS FACC|
|Sub-Investigator: Shaw Natan, MD|
|Sub-Investigator: Arnold Greenspon, MD|
|Sub-Investigator: Behzad Pavri, MD|
|Sub-Investigator: Reginald Ho, MD|
|Sub-Investigator: Arthur M. Feldman, MD PhD|
|Principal Investigator:||David J. Whellan, MD MHS FACC||Thomas Jefferson University|