Prediction of ARrhythmic Events With Positron Emission Tomography (PAREPET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01400334
Recruitment Status : Completed
First Posted : July 22, 2011
Last Update Posted : December 9, 2015
Information provided by (Responsible Party):
State University of New York at Buffalo

Brief Summary:
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.

Condition or disease Intervention/treatment
Ischemic Cardiomyopathy Hibernating Myocardium Nerve; Disorder, Sympathetic Radiation: Positron Emission Tomography

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
Actual Enrollment : 257 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Hibernating Myocardium and Sudden Cardiac Death
Study Start Date : July 2004
Primary Completion Date : December 2012
Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiomyopathy
U.S. FDA Resources

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Cardiac Death [ Time Frame: every 3 months ]
    Sudden cardiac death and adjudicated non-sudden cardiac death

Biospecimen Retention:   Samples Without DNA
serum and plasma

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Residents of Western New York referred for an implantable cardiac defibrillator, transthoracic echocardiography, and/or coronary angiography

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01400334

United States, New York
Buffalo, New York, United States, 14214
Sponsors and Collaborators
State University of New York at Buffalo
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 of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: State University of New York at Buffalo Identifier: NCT01400334     History of Changes
Other Study ID Numbers: HL76252
First Posted: July 22, 2011    Key Record Dates
Last Update Posted: December 9, 2015
Last Verified: December 2015

Keywords provided by State University of New York at Buffalo:
Ischemic Cardiomyopathy
Sudden Cardiac Death
Positron Emission Tomography
Hibernating Myocardium
Denervated Myocardium

Additional relevant MeSH terms:
Death, Sudden, Cardiac
Heart Diseases
Cardiovascular Diseases
Heart Arrest
Death, Sudden
Pathologic Processes