Prediction of ARrhythmic Events With Positron Emission Tomography (PAREPET)

October 8, 2020 updated by: JOHN CANTY, State University of New York at Buffalo

Hibernating Myocardium and Sudden Cardiac Death

The hypothesis of PAREPET is that hibernating myocardium (viable myocardium with reduced resting flow) and/or viable but denervated myocardium can predict the risk of sudden death in subjects with ischemic cardiomyopathy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Currently available electrophysiological approaches are limited in their ability to identify the majority of patients with CAD and LV dysfunction that succumb to sudden cardiac death (SCD). Half of the patients developing SCD are not inducible at electrophysiological testing underscoring the need for new ways to identify substrates leading to arrhythmic death. Viable chronically dysfunctional with reduced resting flow, or hibernating myocardium, not amenable to revascularization appears to be a major risk factor for subsequent cardiac death and is present in up to 60% of patients with ischemic cardiomyopathy. Cause specific mortality data is limited but appears to be arrhythmic rather than from fatal myocardial infarction or progressive heart failure. Revascularization improves survival but most patients with hibernating myocardium are managed medically due to prohibitive procedural risks or technical limitations. Basic studies in swine with hibernating myocardium demonstrate SCD arising from VT/VF in the absence of myocardial scar or heart failure. The central hypothesis of this proposal is that the presence of hibernating myocardium as opposed to scar identifies a large subset of patients with ischemic cardiomyopathy that are at high risk for SCD. We further hypothesize that this risk is related to inhomogeneity in sympathetic innervation arising from chronic repetitive ischemia. PAREPET is a prospective observational study that will enroll patients with coronary disease, Class I-III heart failure and an ejection fraction ≤35%. Using positron emission tomography (PET), the frequency and amount of hibernating myocardium will be quantified in patients that are not candidates for coronary revascularization. Three Specific Aims are proposed. Aim 1 will determine whether imaging the mismatch between viability (preserved 18F-2-deoxyglucose) and reduced resting flow (13NH3) can predict an increased risk of SCD (or ICD discharge for VT/VF as a surrogate end-point) in hibernating myocardium. Aim 2 will image norepinephrine uptake using 11C-hydroxyephedrine to determine whether inhomogeneity in myocardial sympathetic innervation predicts SCD risk better than viability testing. Aim 3 will identify whether the substrate identified by PET is stable after an aborted SCD event by evaluating temporal changes in function, viability and sympathetic innervation in patients with an ICD. Our long-term objective is to develop better approaches to identify patients with CAD who are most likely to benefit from primary prevention of SCD with placement an ICD.

Study Type

Observational

Enrollment (Actual)

257

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
    • New York
      • Buffalo, New York, United States, 14214
        • SUNYBuffalo

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

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Residents of Western New York referred for an implantable cardiac defibrillator, transthoracic echocardiography, and/or coronary angiography

Description

Inclusion Criteria:

  • LV EF ≤35% (by nuclear imaging, cardiac catheterization or echocardiography)
  • Coronary artery disease documented by cardiac catheterization, a history of definite myocardial infarction, or reversible ischemia on nuclear imaging
  • New York State Heart Association functional Class I-III heart failure
  • Not a candidate for surgical or percutaneous coronary revascularization at the time of enrollment

Exclusion Criteria:

  • History of resuscitated sudden cardiac death, sustained ventricular tachycardia, appropriate implantable cardiac defibrillator (ICD) discharge, or unexplained syncope
  • Myocardial infarction within 30 days
  • Coronary artery bypass grafting within 1 year
  • Percutaneous intervention within 3 months
  • Claustrophobia or physical limitation that would preclude PET scanning
  • Pregnancy
  • Tricyclic antidepressant drug therapy
  • Comorbidities that would be expected to result in noncardiac death within 2 years
  • Inability to provide informed consent

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ischemic Cardiomyopathy
Subjects with ischemic cardiomyopathy [pre-enrollment left ventricular ejection fraction ≤0.35, with coronary artery disease documented by cardiac catheterization, a history of definite myocardial infarction, or reversible ischemia on nuclear imaging] who are considered eligible to receive an implantable cardiac defibrillator for the primary prevention of sudden cardiac death.
Radiation: Positron Emission Tomography
Quantification of cardiac function using positron emission tomography and: a)11C-meta-hydroxyephedrine [HED, 20 mCi (740 MBq)] to quantify sympathetic nerve function, b) 13N-ammonia [NH3, 20 mCi (740 MBq)] for regional perfusion, and c) 18F-2-deoxyglucose [FDG; 6.5 mCi (241 MBq)] administered during a hyperinsulinemic-euglycemic clamp to assess viability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sudden Cardiac Death
Time Frame: every 3 months
Adjudicated sudden cardiac death and implantable cardiac defibrillator therapy for fast ventricular tachycardia (>240 bpm) or ventricular fibrillation.
every 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac Death
Time Frame: every 3 months
Sudden cardiac death and adjudicated non-sudden cardiac death
every 3 months

Collaborators and Investigators

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

Sponsor

State University of New York at Buffalo

Investigators

  • Principal Investigator: John M Canty, MD, State University of New York at Buffalo
  • Principal Investigator: James A Fallavollita, MD, State University of New York at Buffalo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2004

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

July 20, 2011

First Submitted That Met QC Criteria

July 20, 2011

First Posted (Estimate)

July 22, 2011

Study Record Updates

Last Update Posted (Actual)

October 12, 2020

Last Update Submitted That Met QC Criteria

October 8, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HL76252

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ischemic Cardiomyopathy

Clinical Trials on Positron Emission Tomography

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe