Arrythmia Clinical Trial
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.
Assess whether serum levels of MMP 2 and or MMP 9 correlate with episodes of ventricular tachycardia or fibrillation in patients who have implantable cardioverter defibrillator devices.
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.
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Observational Model: Case Control, Time Perspective: Prospective
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