Extracellular Matrix Marker of Arrhythmia Risk (EMMA)
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/5/2014 |
| Start Date: | September 2006 |
| End Date: | September 2008 |
| Contact: | Suzanne Adams, RN MPH |
| Email: | suzanne.adams@jefferson.edu |
| Phone: | 215-955-8848 |
The Role of MMP-9 and MMP-2 in Risk Stratification for VT/VF in Patients With Implanted Cardioverter Defibrillator Devices.
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.
evaluation of the genomic promoter sequence polymorphisms, correlate with episodes of VT/VF
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.
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.
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.
Inclusion Criteria:
- LVEF of ≤ 35% measured within 6 months of ICD implantation
- NYHA class II-IV at the time of ICD implantation
- ICD implantation at least 1 year prior to enrollment
Exclusion Criteria:
- Status post heart transplant
- Known malignancy in the past 2 years.
- Recent procedure, intervention or surgery within the past 90 days
- Acute MI, CABG, or PTCA/stent within the past 2 months.
- Active rheumatoid arthritis or pulmonary or hepatic fibrosis.
- Taking chronic steroid therapy for a medical condition Currently pregnant Enrolled in
a concurrent study that may confound the results of this study
We found this trial at
1
site
Click here to add this to my saved trials
