Clinical trial NCT02597543: Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction
Official title: Stress Cardiac MRI Using Regadenoson for Evaluation of Nonspecific Allograft Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Transplant
Acute Graft Rejection
Chronic Graft Rejection
Keywords: heart transplantation
cardiac MRI
graft rejection
nonspecific allograft dysfunction
allograft vasculopathy
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Inc
First posted: 2015-11-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The investigators will use cardiac MRI to measure the myocardial perfusion reserve and amount of myocardial edema and fibrosis in heart-transplant patients with nonspecific allograft dysfunction in contrast to those with normal graft function. The investigators hypothesize that patients with nonspecific allograft dysfunction will demonstrate decreased myocardial perfusion reserve, related to microvascular allograft vasculopathy, compared to those with normal graft function.

Detailed description: Adult heart-transplant patients, excluding those with a GFR less than 30 mL/min/1.73m2, contraindications to MRI and allergies to either regadenoson or gadolinium contrast, will be enrolled over 10 months. Patients will be recruited from UC San Diego and San Diego Veterans Affairs. The investigators will specifically enroll patients with nonspecific allograft dysfunction and patients with normal graft function.

Brief protocol:

Cardiac MRI is performed. Cine images in standard views are obtained. T2 mapping sequences are performed on short axis images. For stress imaging, intravenous regadenoson is given as a 0.4 mg bolus followed by a 5 mL saline flush. After 30 seconds, short-axis images are acquired for 30 consecutive heartbeats with administration of gadolinium. Rest imaging is performed 30 minutes after stress imaging. Lastly, late gadolinium enhancement images are obtained in standard views. Images are analyzed offline by a blinded independent reader. Patients will be followed for one month after enrollment for MACE.

Eligibility criteria: Inclusion Criteria:

* Age greater than or equal to 18 years old.
* At least three months status post heart transplantation.
* Heart-transplant patients with normal graft function (left ventricular ejection fraction equal to or greater than 55%) and no prior history of clinically significant acute rejection episodes that required modification of the immunosuppressive regimen or cardiac allograft vasculopathy.
* Heart-transplant patients with nonspecific allograft dysfunction (left ventricular ejection fraction equal to or less than 50% AND decrease from post-transplant baseline ejection fraction by an absolute difference of 10% or greater, no formal diagnosis of allograft vasculopathy by coronary angiogram or coronary vascular ultrasonography, and no history of prior acute rejection episodes known to have decreased left ventricular ejection fraction to or less than 50%).

Exclusion Criteria:

* Biopsy proven acute rejection episode in the past 3 months.
* Patients with symptoms or signs of acute myocardial ischemia or recent acute coronary syndrome in the past 3 months.
* Uncontrolled obstructive ventilatory disease including asthma and COPD.
* Second or third degree AV nodal block.
* Sinus node dysfunction.
* Contraindications to MRI including pacemakers or implantable cardioverter-defibrillators.
* Renal dysfunction with an estimated GFR less than 30 mL/min/1.73m2.
* Prior adverse reaction to either regadenoson or gadolinium contrast. Prior adverse reaction to adenosine will be assessed on a case-by-case basis.
* Any invasive procedure, including endomyocardial biopsy and left coronary angiogram, performed within one week.
* Systolic blood pressure greater than 180 or less than 85 mmHg.
* Diastolic blood pressure greater than 120 or less than 40 mmHg.
* Resting heart rate greater than 120 or less than 45 beats per minute.
* Severe claustrophobia.

Primary outcomes:
measure: Myocardial Perfusion Reserve
timeFrame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
Secondary outcomes:
measure: Myocardial Ischemia/Infarction
timeFrame: 10 months after enrollment (when cardiac MRI was performed)
measure: Hospitalization for Cardiac Related Causes
timeFrame: 10 months after enrollment (from date of cardiac MRI)
measure: Re-transplantation
timeFrame: 10 months after enrollment (from date of cardiac MRI)
measure: Late Gadolinium Enhancement
timeFrame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
measure: Mean Segmental T1 Values of the Left Ventricle
timeFrame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego
state: California
Study officials:
affiliation: Stanford University
name: Paul J Kim, MD
role: PRINCIPAL_INVESTIGATOR
References:
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