Coronary Artery Vasculopathy in Pediatric Heart Transplant Patients (CFR-OHT)

Early Detection of Coronary Artery Vasculopathy in Pediatric Heart Transplant Patients: A Prospective Assessment Using Coronary Flow Reserve and Contrast-Enhanced Cardiac MRI

Heart transplantation is a life-sustaining therapy that allows patients with either congenital or acquired heart disease and severe cardiac dysfunction to survive. Over time, however, the transplanted heart can develop problems. One of the more common and troubling problems is the development of stenoses, or narrowings, within the coronary arteries. These narrowings, technically referred to as coronary artery vasculopathy (CAV for short), account for the single most common cause of death or need for repeat heart transplant in persons more than one year post-transplant. Traditionally, CAV has been diagnosed at cardiac catheterization using coronary angiography (where dye is directly injected into the coronary blood vessels and viewed using special x-ray equipment called fluoroscopy). There is no good treatment for CAV aside from treatment of symptoms and listing for repeat heart transplantation. The goal of this study is to test several newer methods of diagnosing CAV. The first is called coronary flow reserve (catheterization test). The second is called Endo-PAT (a finger probe test) and the third is called contrast-enhanced cardiac MRI (MRI test, only for patients 12 and older). The older method (coronary angiography) will still be used in all cases, in addition to the new tests The goal is, one day, to be able to diagnose patients with CAV earlier in the course, prior to a patient's development of abnormal angiograms. If this can be done, it is possible that better therapies will be able to be used to stop or even reverse the development of CAV, perhaps reducing, or at least delaying, the need for repeat heart transplantation.

Study Overview

• Status: Completed
• Conditions: Orthotopic Heart Transplant
• Intervention / Treatment: Drug: Adenosine

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of MIchigan-Congenital Heart Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age 1 - 25 years who are status-post OHT (≤18 years at the time of transplantation) and undergoing routine post-transplant surveillance catheterization for endomyocardial biopsy and coronary angiography

Exclusion Criteria:

• The presence of sick sinus syndrome or 2nd or 3rd degree atrioventricular block (without a functioning implanted pacemaker)
• Hemodynamically significant valvular disease
• Severe asthma or bronchospasm, known severe CAV
• Pulmonary hypertension.
• Patients taking digoxin
• Verapamil and dipyridamole are also excluded given known interactions with adenosine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Arm	Drug: Adenosine; Administration of intravenous adenosine infusion over 3 minutes (0.14 ml/kg, 3mg/ml concentration, total dose).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Flow Reserve (CFR)	Ratio of peak to baseline coronary flow velocity (CFV)	Baseline testing (acute only), 3 minutes of adenosine infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gadolinium Enhancement by Cardiac MRI	Categorical measure - yes or no; number of participants with gadolinium enhancement	Baseline MRI only

Collaborators and Investigators

• Sponsor: Bryan Goldstein
• Investigators: Principal Investigator: Bryan Goldstein, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: October 19, 2011
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Orthotopic Heart Transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: HUM23585

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No