Extracellular Matrix Marker of Arrhythmia Risk (EMMA)

This study has been completed.
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00376532
First received: September 14, 2006
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition
Myocardiopathies
Ischemia, Myocardial
Arrythmia
Death, Sudden, Cardiac

Study Type: Observational
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.

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • 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

Blood


Enrollment: 63
Study Start Date: September 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Inpatients or outpatients with the cardiac device of interest implanted prior to enrollment.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376532

Locations
United States, Pennsylvania
Jefferson Heart Institute
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Thomas Jefferson University
Medtronic
Investigators
Principal Investigator: David J. Whellan, MD MHS FACC Thomas Jefferson University
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00376532     History of Changes
Other Study ID Numbers: TJU 06U.282
Study First Received: September 14, 2006
Results First Received: May 5, 2014
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Cardiac Ischemia
Cardiac Arrhythmia
Defibrillator
Matrix Metalloproteinase
Genetic Polymorphism

Additional relevant MeSH terms:
Ischemia
Death, Sudden, Cardiac
Death, Sudden
Cardiomyopathies
Myocardial Ischemia
Pathologic Processes
Heart Arrest
Heart Diseases
Cardiovascular Diseases
Death
Vascular Diseases

ClinicalTrials.gov processed this record on October 19, 2014