Coronary Artery Disease
Conditions
Brief summary
The broad, long-term objective of this pilot study is to develop an optimal, clinically usable, non-invasive evaluation of Coronary Artery Disease (CAD) in the setting of stable angina which provides both anatomic and functional information. Patients already scheduled to undergo Invasive coronary catheterization (ICA) for the clinical indication of angina will be recruited to under go stress-rest Positron Emission Tomography-Coronary CT Angiography-Fractional Flow Reserve (PET-cCTA-cFFR)
Detailed description
This is a single cohort, technology assessment study. Thirty-five patients presenting with stable angina and a moderate pretest likelihood for CAD who are already scheduled to undergo invasive coronary angiography (ICA) for the clinical indication of angina will be recruited to undergo a cCTA examination with FFR followed immediately by regadenoson stress-rest PET on the same PET/CT scanner. Sensitivity, specificity, NPV, PPV of CTA-cFFR will be obtained using the reference standard of standard of care ICA with FFR for each epicardial coronary artery. Segmental stress PET MBF will be compared to presence or absence of a coronary artery stenosis ≥ 50% diameter on CCTA and ICA.
Interventions
DIAGNOSTIC_TESTPET-cCTA-cFFR
patients presenting with stable angina and a moderate pretest likelihood for CAD who are already scheduled to undergo ICA for the clinical indication of angina will be recruited to undergo PET-cCTA-cFFR
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* 18-90 years of age, of either sex * Patients presenting with stable angina and a moderate pretest likelihood for CAD and scheduled to undergo ICA for the clinical indication of angina. Subjects will undergo this study within 45 days prior to the cardiac catheterization. This study can also be performed 45 days after the cardiac catheterization if the patient had no interventions.
Exclusion criteria
* Prior history of stenting, coronary artery bypass graft surgery, or myocardial infarction, unstable angina, atrial fibrillation, second or third degree atrioventricular block, class IV heart failure * Iodine allergy * Renal dysfunction (creatinine above normal laboratory limits) * Symptomatic asthma * Women who are pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Flow-limiting Coronary Artery Stenosis on CT | Day 1 - Day of Scan | CT presence of flow limiting stenosis (≤ 0.8) as determined by CT-FFR in comparison to invasive coronary artery (ICA) FFR. CT-FFR was determined in the following myocardial segments: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). The number of coronary artery stenoses as determined by CT (CT-FFR ≤ 0.8) was measured. |
| Association Between Stress Myocardial Blood Flow (MBF) on PET and Coronary Artery Stenosis on CCTA | Day 1 - Day of Scan | Association between N-13 Ammonia PET MBF (mL/g/min) during stress and presence or absence of coronary artery stenosis ≥ 50% diameter on CCTA as determined by measurement in each epicardial coronary artery. The MBF values during stress were categorized as normal or abnormal. Normal MBF is defined as \>1.8 mL/g/min. MBF and percent diameter stenosis were determined in the following myocardial segments: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Instant Wave Free Ratio (iFR) | Day of invasive coronary catheterization - within 2 weeks of imaging | The instant wave Free Ratio (iFR) was measured during the patient's clinically scheduled invasive coronary catheterization. Normal iFR was defined as ≥ 0.90. |
| N-13 Ammonia PET Global Myocardial Blood Flow (MBF) Stress | Day 1 - Day of Scan | Myocardial Blood Flow was measured by N-13 Ammonia positron emission tomography (PET) during stress following injection of regadenoson. |
| Correlation of Myocardial Blood Flow (MBF) by PET to Fractional Flow Reserve (FFR) by CT. | Day 1 - Day of Scan | Correlation of CT-FFR and N-13 Ammonia PET MBF (mL/g/min) during stress as determined by measurement in each epicardial coronary artery. Values were determined in the following myocardial segments: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). |
| N-13 Ammonia PET Global Myocardial Flow Reserve (MFR) | Day 1 - Day of Scan | Myocardial flow reserve (MFR) is a ratio between myocardial blood flow (MBF) during stress and at rest, as determined by positron emission tomography (PET). Normal MFR was defined as \> 2.0. |
| N-13 Ammonia PET Global Myocardial Blood Flow (MBF) Rest | Day 1 - Day of Scan | Myocardial Blood Flow (MBF) was measured by N-13 Ammonia positron emission tomography (PET) at rest. |
| CT-Fractional Flow Reserve (CT-FFR) Global | Day 1 - Day of Scan | CT-FFR was calculated using a computational flow/AI FFR program (Siemens). Normal CT-FFR was defined as \>0.80. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PET-cCTA-cFFR Patients presenting with stable angina and a moderate pretest likelihood for coronary artery disease (CAD) who are already scheduled to undergo invasive coronary catheterization (ICA) for the clinical indication of angina will be recruited to undergo a Coronary CT Angiography (cCTA) examination with Fractional Flow Reserve (FFR) followed immediately by regadenoson stress-rest N-13 Ammonia Positron Emission Tomography (PET) on the same PET/CT scanner. Patients will undergo their clinically scheduled ICA with FFR within 2 weeks of the imaging procedures.
Patients will receive two single intravenous injections of 10-12 mCi each of the PET radiotracer N-13 Ammonia, one during rest and one during stress. Stress imaging will occur 30-40 minutes prior to rest imaging. Patients will undergo PET/CT imaging immediately post N-13 Ammonia injection. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Radiotracer production failed. Patient received an intervention so did not qualify to come back. | 1 |
Baseline characteristics
| Characteristic | PET-cCTA-cFFR |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 64.6 years STANDARD_DEVIATION 7.1 |
| Hypertension No | 2 Participants |
| Hypertension Yes | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 7 Participants |
| Smoking No | 9 Participants |
| Smoking Yes | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Association Between Stress Myocardial Blood Flow (MBF) on PET and Coronary Artery Stenosis on CCTA
Association between N-13 Ammonia PET MBF (mL/g/min) during stress and presence or absence of coronary artery stenosis ≥ 50% diameter on CCTA as determined by measurement in each epicardial coronary artery. The MBF values during stress were categorized as normal or abnormal. Normal MBF is defined as \>1.8 mL/g/min. MBF and percent diameter stenosis were determined in the following myocardial segments: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA).
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to return for imaging.
| Arm | Measure | Group | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|---|
| PET-cCTA-cFFR | Association Between Stress Myocardial Blood Flow (MBF) on PET and Coronary Artery Stenosis on CCTA | Diameter Stenosis ≥50% | Abnormal MBF Stress | 9 Coronary arteries |
| PET-cCTA-cFFR | Association Between Stress Myocardial Blood Flow (MBF) on PET and Coronary Artery Stenosis on CCTA | Diameter Stenosis ≥50% | Normal MBF Stress | 7 Coronary arteries |
| PET-cCTA-cFFR | Association Between Stress Myocardial Blood Flow (MBF) on PET and Coronary Artery Stenosis on CCTA | Diameter Stenosis <50% | Abnormal MBF Stress | 17 Coronary arteries |
| PET-cCTA-cFFR | Association Between Stress Myocardial Blood Flow (MBF) on PET and Coronary Artery Stenosis on CCTA | Diameter Stenosis <50% | Normal MBF Stress | 27 Coronary arteries |
p-value: 0.2522Fisher Exact
Primary
Number of Flow-limiting Coronary Artery Stenosis on CT
CT presence of flow limiting stenosis (≤ 0.8) as determined by CT-FFR in comparison to invasive coronary artery (ICA) FFR. CT-FFR was determined in the following myocardial segments: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). The number of coronary artery stenoses as determined by CT (CT-FFR ≤ 0.8) was measured.
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to come back.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| PET-cCTA-cFFR | Number of Flow-limiting Coronary Artery Stenosis on CT | 8 Coronary arteries |
Secondary
Correlation of Myocardial Blood Flow (MBF) by PET to Fractional Flow Reserve (FFR) by CT.
Correlation of CT-FFR and N-13 Ammonia PET MBF (mL/g/min) during stress as determined by measurement in each epicardial coronary artery. Values were determined in the following myocardial segments: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA).
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to return for imaging.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PET-cCTA-cFFR | Correlation of Myocardial Blood Flow (MBF) by PET to Fractional Flow Reserve (FFR) by CT. | 0.284 Pearson correlation coefficient (r) |
p-value: 0.028Pearson's correlation test
Secondary
CT-Fractional Flow Reserve (CT-FFR) Global
CT-FFR was calculated using a computational flow/AI FFR program (Siemens). Normal CT-FFR was defined as \>0.80.
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to come back.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PET-cCTA-cFFR | CT-Fractional Flow Reserve (CT-FFR) Global | All Participant Analyzed | 0.90 Ratio | Standard Deviation 0.09 |
| PET-cCTA-cFFR | CT-Fractional Flow Reserve (CT-FFR) Global | Participants with Normal CT-FFR | 0.93 Ratio | Standard Deviation 0.05 |
| PET-cCTA-cFFR | CT-Fractional Flow Reserve (CT-FFR) Global | Participants with Abnormal CT-FFR | 0.73 Ratio | Standard Deviation 0.02 |
Secondary
Instant Wave Free Ratio (iFR)
The instant wave Free Ratio (iFR) was measured during the patient's clinically scheduled invasive coronary catheterization. Normal iFR was defined as ≥ 0.90.
Time frame: Day of invasive coronary catheterization - within 2 weeks of imaging
Population: iFR was done for 8 coronary arteries in 7 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PET-cCTA-cFFR | Instant Wave Free Ratio (iFR) | 0.92 Ratio | Standard Deviation 0.05 |
Secondary
N-13 Ammonia PET Global Myocardial Blood Flow (MBF) Rest
Myocardial Blood Flow (MBF) was measured by N-13 Ammonia positron emission tomography (PET) at rest.
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to come back.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PET-cCTA-cFFR | N-13 Ammonia PET Global Myocardial Blood Flow (MBF) Rest | 0.94 mL/g/min | Standard Deviation 0.23 |
Secondary
N-13 Ammonia PET Global Myocardial Blood Flow (MBF) Stress
Myocardial Blood Flow was measured by N-13 Ammonia positron emission tomography (PET) during stress following injection of regadenoson.
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to come back.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PET-cCTA-cFFR | N-13 Ammonia PET Global Myocardial Blood Flow (MBF) Stress | 1.88 mL/g/min | Standard Deviation 0.45 |
Secondary
N-13 Ammonia PET Global Myocardial Flow Reserve (MFR)
Myocardial flow reserve (MFR) is a ratio between myocardial blood flow (MBF) during stress and at rest, as determined by positron emission tomography (PET). Normal MFR was defined as \> 2.0.
Time frame: Day 1 - Day of Scan
Population: One participant did not undergo imaging. Radiotracer production failed. Patient received an intervention so did not qualify to come back.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PET-cCTA-cFFR | N-13 Ammonia PET Global Myocardial Flow Reserve (MFR) | Participants with Normal MFR | 2.31 Ratio | Standard Deviation 0.31 |
| PET-cCTA-cFFR | N-13 Ammonia PET Global Myocardial Flow Reserve (MFR) | All Participants Analyzed | 2.05 Ratio | Standard Deviation 0.45 |
| PET-cCTA-cFFR | N-13 Ammonia PET Global Myocardial Flow Reserve (MFR) | Participants with Abnormal MFR | 1.67 Ratio | Standard Deviation 0.33 |