Acute Graft Rejection, Chronic Graft Rejection, Heart Transplant
Conditions
Keywords
heart transplantation, cardiac MRI, graft rejection, nonspecific allograft dysfunction, allograft vasculopathy
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.
Interventions
DRUGRegadenoson
For use in stress myocardial perfusion imaging.
DRUGGadolinium
For use in both perfusion imaging and late gadolinium enhancement.
PROCEDURECardiac MRI
Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.
Sponsors
Astellas Pharma Inc
Paul Kim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Perfusion Reserve | Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation. | Myocardial perfusion reserve calculates the increase in myocardial perfusion after stress in comparison to rest. Outcome measure time frame specifies when the myocardial perfusion reserve was obtained in relation to date of heart-transplant for each patient. This was a one time measurement made after heart-transplantation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Ischemia/Infarction | 10 months after enrollment (when cardiac MRI was performed) | Myocardial ischemia or infarct occurring from time of enrollment (when cardiac MRI performed) over subsequent 10 month period. |
| Hospitalization for Cardiac Related Causes | 10 months after enrollment (from date of cardiac MRI) | Hospitalization for cardiac related causes after enrollment. Time frame after enrollment (date of cardiac MRI) was 10 months |
| Re-transplantation | 10 months after enrollment (from date of cardiac MRI) | Re-transplantation of the heart after enrollment (date of cardiac MRI). Measured 10 months after enrollment. |
| Late Gadolinium Enhancement | Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation. | Late gadolinium enhancement demonstrates myocardial scar by cardiac MRI. This is measured the day of the cardiac MRI scan and is a one time measurement. Time frame is measurement of late gadolinium enhancement from date of heart-transplantation. |
| Mean Segmental T1 Values of the Left Ventricle | Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation. | T1 values are obtained at the time of the cardiac MRI and indicate the amount of myocardial edema. This was a one time measurement. Outcome measure time frame indicates when T1 values of the left ventricle were obtained in relation to heart-transplantation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nonspecific Allograft Dysfunction Patients with nonspecific allograft dysfunction will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.
Regadenoson: For use in stress myocardial perfusion imaging.
Gadolinium: For use in both perfusion imaging and late gadolinium enhancement.
Cardiac MRI: Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart. | 6 |
| Normal Graft Function Patients with normal graft function will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.
Regadenoson: For use in stress myocardial perfusion imaging.
Gadolinium: For use in both perfusion imaging and late gadolinium enhancement.
Cardiac MRI: Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart. | 8 |
| Total | 14 |
Baseline characteristics
| Characteristic | Normal Graft Function | Total | Nonspecific Allograft Dysfunction |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 5 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 9 Participants | 4 Participants |
| Age, Continuous | 66 years | 64 years | 61.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment United States | 8 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 0 / 6 | 0 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 |
Outcome results
Primary
Myocardial Perfusion Reserve
Myocardial perfusion reserve calculates the increase in myocardial perfusion after stress in comparison to rest. Outcome measure time frame specifies when the myocardial perfusion reserve was obtained in relation to date of heart-transplant for each patient. This was a one time measurement made after heart-transplantation.
Time frame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nonspecific Allograft Dysfunction | Myocardial Perfusion Reserve | 1.52 arbitrary units | Standard Deviation 0.52 |
| Normal Graft Function | Myocardial Perfusion Reserve | 1.94 arbitrary units | Standard Deviation 0.37 |
Secondary
Hospitalization for Cardiac Related Causes
Hospitalization for cardiac related causes after enrollment. Time frame after enrollment (date of cardiac MRI) was 10 months
Time frame: 10 months after enrollment (from date of cardiac MRI)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nonspecific Allograft Dysfunction | Hospitalization for Cardiac Related Causes | 0 Participants |
| Normal Graft Function | Hospitalization for Cardiac Related Causes | 0 Participants |
Secondary
Late Gadolinium Enhancement
Late gadolinium enhancement demonstrates myocardial scar by cardiac MRI. This is measured the day of the cardiac MRI scan and is a one time measurement. Time frame is measurement of late gadolinium enhancement from date of heart-transplantation.
Time frame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nonspecific Allograft Dysfunction | Late Gadolinium Enhancement | 5.7 percentage of myocardium | Standard Deviation 2.6 |
| Normal Graft Function | Late Gadolinium Enhancement | 1.8 percentage of myocardium | Standard Deviation 0.8 |
Secondary
Mean Segmental T1 Values of the Left Ventricle
T1 values are obtained at the time of the cardiac MRI and indicate the amount of myocardial edema. This was a one time measurement. Outcome measure time frame indicates when T1 values of the left ventricle were obtained in relation to heart-transplantation.
Time frame: Range of 1 to 12 years after heart transplantation for subjects and an average of 4 years after heart-transplantation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nonspecific Allograft Dysfunction | Mean Segmental T1 Values of the Left Ventricle | 44.5 Percentage of myocardium | Standard Deviation 6.3 |
| Normal Graft Function | Mean Segmental T1 Values of the Left Ventricle | 38.1 Percentage of myocardium | Standard Deviation 5.9 |
Secondary
Myocardial Ischemia/Infarction
Myocardial ischemia or infarct occurring from time of enrollment (when cardiac MRI performed) over subsequent 10 month period.
Time frame: 10 months after enrollment (when cardiac MRI was performed)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nonspecific Allograft Dysfunction | Myocardial Ischemia/Infarction | 0 Participants |
| Normal Graft Function | Myocardial Ischemia/Infarction | 0 Participants |
Secondary
Re-transplantation
Re-transplantation of the heart after enrollment (date of cardiac MRI). Measured 10 months after enrollment.
Time frame: 10 months after enrollment (from date of cardiac MRI)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nonspecific Allograft Dysfunction | Re-transplantation | 0 Participants |
| Normal Graft Function | Re-transplantation | 0 Participants |