Coronary Artery Disease
Conditions
Keywords
coronary artery disease, exercise, regadenoson, positron emission tomography
Brief summary
This is a single-center study of subjects undergoing clinically indicated heart scans for evaluation of known or suspected heart disease. We will also include 10 healthy subjects without known heart disease. We would like to study stress testing of the heart using exercise and a medication called regadenoson. Imaging of the heart will be performed.
Detailed description
Regadenoson is stress agent approved by the FDA for use with myocardial perfusion imaging with technetium-99m single photon emission computed tomography (SPECT) in patients that are unable to exercise adequately. We would like to study Regadenoson in conjunction with Exercise Rubidium-82 positron emission tomography myocardial perfusion imaging (PET MPI). Regadenoson is not approved by FDA for use with Rubidium-82 PET MPI. Also, we would like to study a novel stress protocol of Regadenoson combined with symptom limited exercise stress (not FDA approved). The objectives of this study are to assess the tolerability and safety of combined symptom limited exercise stress test with Lexiscan (Lexercise PET) compared to Lexiscan alone (Lexiscan PET), to assess image quality of Lexercise compared to Lexiscan PET and to compare relative and absolute myocardial perfusion imaging with Lexercise compared to Lexiscan PET to identify CAD.
Interventions
DRUGExercise plus Regadenoson (Lexercise)
Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography
DRUGRegadenoson (Lexiscan)
Regadenoson Rubidium-82 Positron Emission Tomography
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* Age \> 18 years * Clinically indicated N-13 ammonia PET study or ten healthy volunteers * Known coronary artery disease (prior percutaneous coronary intervention, prior coronary artery bypass surgery or Q wave MI on ECG) or intermediate to high pretest likelihood of CAD * Able to exercise on a treadmill * Able and willing to provide informed consent to participate in the study
Exclusion criteria
* Contraindications to exercise stress testing such as, unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure \< 90 or \> 200 mmHg, respectively), or \> 1st degree atrioventricular block in the absence of a functioning pacemaker. * Subject requires emergent cardiac medical intervention or catheterization after the clinical study. * Documented myocardial infarction (MI) ≤ 30 days prior to enrollment. * History of percutaneous coronary intervention (PCI) ≤ 4weeks prior to enrollment. * History of coronary artery bypass graft (CABG) ≤ 8 weeks prior to enrollment. * History of heart transplantation. * Allergy or intolerance to aminophylline or regadenoson * Known severe or oxygen dependent bronchoconstrictive or bronchospastic lung disease \[e.g., asthma, wheezing, chronic obstructive pulmonary disease (COPD), etc.\]. * Severe LV dysfunction, with ejection fraction of \< 30% * Serious non-cardiac medical illness (e.g., disseminated malignancy, severe neurological dysfunction at time of baseline PET study) or a social situation which will preclude research study participation * History of Seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Combined Exercise and Regadenoson Stress | Day of the research scan during the stress test | 1. Count of subjects with ischemic ECG changes is reported 2. Count of subjects with systolic blood pressure decrease \> 20 mm Hg is reported 3. Count of subjects with abnormal serum troponin T levels is reported 4. Radiation dose to the staff will be measured using personal dosimeters after the Lexiscan as well as the Lexercise PET study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image Quality: Heart to Liver Ratio of Counts | Week 1 (day of the clinical scan), and Week 2 (day of the research scan) | Sub-diaphragmatic activity: Heart to Liver Ratio was measured on the rubidium-82 and N-13 ammonia scans. Since this measure is a ratio it has no units. Mean and Standard Deviation of Ratio is reported for each group. This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects. |
| Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET | Week 1 (day of the clinical scan), and Week 2 (day of the research scan) | Left ventricular ejection fraction (LVEF) at stress was measured at Stress scan 1 (regadenoson) and Stress scan 2 (regadenoson or exercise + regadenoson). This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects. |
| Peak Stress Myocardial Blood Flow | Week 1 (day of the clinical scan), and Week 2 (day of the research scan) | Myocardial Blood Flow Measured at Peak Hyperemia With Regadenoson or Immediately After Exercise + Regadenoson This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects. |
Countries
United States
Participant flow
Recruitment details
43 subjects consented for the study and 41 subjects completed the study. One subject did not come for the study procedures. One subject could not cooperate with imaging and was moving during the rest scan. Regadenoson scan was not performed.
Participants by arm
| Arm | Count |
|---|---|
| Regadenoson Regadenoson Rubidium-82 Positron Emission Tomography
Regadenoson: Regadenoson Rubidium-82 Positron Emission Tomography | 11 |
| Exercise + Regadenoson Exercise plus Regadenoson Rubidium-82 Positron Emission Tomography
Exercise plus Regadenoson: Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography | 30 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Movement during rest scan. | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Regadenoson | Total | Exercise + Regadenoson |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 11 | 57 years STANDARD_DEVIATION 15 | 54 years STANDARD_DEVIATION 15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 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 | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 31 Participants | 22 Participants |
| Region of Enrollment United States | 11 Participants | 41 Participants | 30 Participants |
| Sex: Female, Male Female | 3 Participants | 17 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 24 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 30 |
| other Total, other adverse events | 0 / 11 | 0 / 30 |
| serious Total, serious adverse events | 0 / 11 | 0 / 30 |
Outcome results
Primary
Safety and Tolerability of Combined Exercise and Regadenoson Stress
1. Count of subjects with ischemic ECG changes is reported 2. Count of subjects with systolic blood pressure decrease \> 20 mm Hg is reported 3. Count of subjects with abnormal serum troponin T levels is reported 4. Radiation dose to the staff will be measured using personal dosimeters after the Lexiscan as well as the Lexercise PET study.
Time frame: Day of the research scan during the stress test
Population: Radiation dose to staff was not measured due to logistical difficulties.Three subjects had blood pressure changes in the Regadenoson (Lexiscan) arm; 3 subjects showed ischemic ECG changes in the exercise + regadenoson (Lexercise) arm; and, none of the subjects showed abnormal troponin levels.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regadenoson (Lexiscan) | Safety and Tolerability of Combined Exercise and Regadenoson Stress | Count of ischemic ECG changes | 0 Participants |
| Regadenoson (Lexiscan) | Safety and Tolerability of Combined Exercise and Regadenoson Stress | Count of subjects systolic blood pressure decrease | 3 Participants |
| Regadenoson (Lexiscan) | Safety and Tolerability of Combined Exercise and Regadenoson Stress | Count of subjects with abnormal troponin | 0 Participants |
| Exercise + Regadenoson (Lexercise) | Safety and Tolerability of Combined Exercise and Regadenoson Stress | Count of ischemic ECG changes | 3 Participants |
| Exercise + Regadenoson (Lexercise) | Safety and Tolerability of Combined Exercise and Regadenoson Stress | Count of subjects systolic blood pressure decrease | 0 Participants |
| Exercise + Regadenoson (Lexercise) | Safety and Tolerability of Combined Exercise and Regadenoson Stress | Count of subjects with abnormal troponin | 0 Participants |
Secondary
Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET
Left ventricular ejection fraction (LVEF) at stress was measured at Stress scan 1 (regadenoson) and Stress scan 2 (regadenoson or exercise + regadenoson). This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.
Time frame: Week 1 (day of the clinical scan), and Week 2 (day of the research scan)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regadenoson (Lexiscan) | Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET | Stress 1 Scan | 58 percentage of LVEF | Standard Deviation 15 |
| Regadenoson (Lexiscan) | Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET | Stress 2 Scan | 59 percentage of LVEF | Standard Deviation 15 |
| Exercise + Regadenoson (Lexercise) | Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET | Stress 1 Scan | 60 percentage of LVEF | Standard Deviation 14 |
| Exercise + Regadenoson (Lexercise) | Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET | Stress 2 Scan | 62 percentage of LVEF | Standard Deviation 14 |
Secondary
Image Quality: Heart to Liver Ratio of Counts
Sub-diaphragmatic activity: Heart to Liver Ratio was measured on the rubidium-82 and N-13 ammonia scans. Since this measure is a ratio it has no units. Mean and Standard Deviation of Ratio is reported for each group. This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.
Time frame: Week 1 (day of the clinical scan), and Week 2 (day of the research scan)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regadenoson (Lexiscan) | Image Quality: Heart to Liver Ratio of Counts | Stress Scan 1 | 1.23 mean ratio | Standard Deviation 0.55 |
| Regadenoson (Lexiscan) | Image Quality: Heart to Liver Ratio of Counts | Stress Scan 2 | 1.25 mean ratio | Standard Deviation 0.57 |
| Exercise + Regadenoson (Lexercise) | Image Quality: Heart to Liver Ratio of Counts | Stress Scan 1 | 1.11 mean ratio | Standard Deviation 0.58 |
| Exercise + Regadenoson (Lexercise) | Image Quality: Heart to Liver Ratio of Counts | Stress Scan 2 | 1.37 mean ratio | Standard Deviation 0.82 |
Secondary
Peak Stress Myocardial Blood Flow
Myocardial Blood Flow Measured at Peak Hyperemia With Regadenoson or Immediately After Exercise + Regadenoson This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.
Time frame: Week 1 (day of the clinical scan), and Week 2 (day of the research scan)
Population: Myocardial blood flow could not be accurately measured in one subject from each arm. Therefore we report information on 10/11 subjects in Regadenoson arm and 29/30 subjects in the Exercise + Regadenoson arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regadenoson (Lexiscan) | Peak Stress Myocardial Blood Flow | Stress 1 Scan | 1.82 mL/gm/min | Standard Deviation 0.73 |
| Regadenoson (Lexiscan) | Peak Stress Myocardial Blood Flow | Stress 2 Scan | 1.85 mL/gm/min | Standard Deviation 0.85 |
| Exercise + Regadenoson (Lexercise) | Peak Stress Myocardial Blood Flow | Stress 1 Scan | 2.04 mL/gm/min | Standard Deviation 0.58 |
| Exercise + Regadenoson (Lexercise) | Peak Stress Myocardial Blood Flow | Stress 2 Scan | 2.34 mL/gm/min | Standard Deviation 0.82 |