Extracellular Matrix Marker of Arrhythmia Risk (EMMA) (EMMA)

May 5, 2014 updated by: Thomas Jefferson University

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19107
    - Jefferson Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMP-2 Time Frame: At time of enrollment	Serum MMP-2 levels determined by Aushon Biosystems Searchlight® Protein Array Analysis.	At time of enrollment
MMP-9 Time Frame: At time of enrollment	Serum MMP-9 levels determined by Aushon Biosystems Searchlight® Protein Array Analysis.	At time of enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Jefferson University

Collaborators

Medtronic

Investigators

Principal Investigator: David J. Whellan, MD MHS FACC, Thomas Jefferson University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

September 14, 2006

First Submitted That Met QC Criteria