PAREPET II: Prediction of ARrhythmic Events With Positron Emission Tomography II

Sponsor

State University of New York at Buffalo (Other)

Overall Status

Recruiting

CT.gov ID

NCT03493516

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), Lantheus Medical Imaging (Industry)

302

Enrollment

Location

72.8

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Sudden cardiac death continues to be a major contributor to mortality in patients with ischemic cardiomyopathy. While implantable defibrillators can prevent death from ventricular arrhythmias, our current approach to identify patients at highest risk primarily rests on demonstrating a reduction in left ventricular ejection fraction less than 35%. The purpose of this observational cohort study is to prospectively test whether this can be enhanced by quantifying the amount of sympathetic denervation, left ventricular end-diastolic volume or brain natriuretic peptide levels.

Condition or Disease	Intervention/Treatment	Phase
Sudden Cardiac Arrest Ischemic Cardiomyopathy Congestive Heart Failure	Diagnostic Test: PET scan quantifying sympathetic denervation using [18F]-LMI1195

Detailed Description

Using current guidelines based primarily on ejection fraction (EF), only one-quarter of patients receiving an implantable cardiac defibrillator (ICD) for the primary prevention of sudden cardiac arrest (SCA) require appropriate ICD therapy within 5 years. The NIH-sponsored PAREPET study (Prediction of ARrhythmic Events with Positron Emission Tomography, ClinicalTrials.gov, NCT01400334) identified four independent risk factors that predict SCA or ICD equivalent in patients with ischemic cardiomyopathy. Using retrospectively defined cut-points, the absence of these risk factors identified 38% of the cohort with a very low risk of SCA (<1% per year). This rate is actually lower than the 1.5-2% annual rate of SCA among patients with coronary artery disease and mild left ventricular (LV) dysfunction, who are not considered candidates for a primary prevention ICD. This proposal will prospectively determine whether these risk factors can form the basis of a clinically applicable approach to identify a subgroup of patients who are candidates for an ICD, but are at low enough risk of SCA to have an ICD safely withheld. Our long-term goal is to develop better approaches to identify patients with coronary artery disease who are most likely to benefit from prevention of SCA with placement of an implantable defibrillator.

Study Design

Study Type:

Observational

Anticipated Enrollment :

302 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prediction of ARrhythmic Events With Positron Emission Tomography II

Actual Study Start Date :

Apr 8, 2018

Anticipated Primary Completion Date :

May 4, 2023

Anticipated Study Completion Date :

May 2, 2024

Outcome Measures

Primary Outcome Measures

Sudden Cardiac Arrest Events [Through study completion, an average of 3 years]
The primary end-point will be SCA or ICD equivalent as used in PAREPET. This will consist of ICD therapies for ventricular fibrillation or ventricular tachycardia >240 bpm, and adjudicated arrhythmic death using the modified Hinkle-Thaler criteria.

Other Outcome Measures

All cause cardiac mortality [Through study completion, an average of 3 years]
Adjudicated total cardiac mortality (SCA + non-sudden cardiac death).
All appropriate ICD therapies [Through study completion, an average of 3 years]
Adjudicated appropriate ICD therapies (ICD shock and anti-tachycardia pacing) for ventricular arrhythmias. Appropriate ICD therapies will be determined from ICD device interrogation.
Hospitalization for heart failure and myocardial infarction. [Through study completion, an average of 3 years]
Interval hospitalizations for heart failure or myocardial infarction will be assessed via phone follow-up at 3 month intervals. Subjects having either will be invited to return for a repeat PET scan, echocardiogram and serum sampling to assess whether the underlying substrate for arrhythmogenesis has changed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Coronary artery disease (by cardiac catheterization or definite myocardial infarction)
ICD implantation for the primary prevention of SCA
Primary prevention patients with a Biventricular ICD
Eligible immediately when this is placed to prevent dysynchrony related to intermittent RV pacing and the native QRS duration is ≤ 130 msec in the absence of pacing.
Eligible 6 months after implantation when the native QRS duration prior to implant is >130 msec or there is persistent RV pacing.
Optimal medical therapy for heart failure.

Exclusion Criteria:

Plans for coronary revascularization (due to the independent impact on SCA)
Contraindication for PET (i.e. claustrophobia, pregnancy, physical limitation)
Tricyclic antidepressant use (inhibits norepinephrine and LMI1195 uptake)
Comorbidities limiting life expectancy <2yr.
Age <18 years or inability to provide informed consent
Primary prevention ICD/BiV recipients who have received an appropriate ICD shock prior to enrollment