Coronary Artery Disease
Conditions
Keywords
Atherosclerosis, Cardiovascular disease, Myocardial ischemia, Imaging, Nuclear medicine, Radiology
Brief summary
The overall goal of this project is to compare the absolute quantification of myocardial perfusion done by using CT myocardial perfusion imaging (CT-MPI) and the coronary flow measured by using CT Fractional Flow Reserve analysis (CT-FFR) to the gold standard represented by PET myocardial perfusion imaging (PET-MPI).
Detailed description
Participants will be patients who are scheduled to undergo PET Myocardial Perfusion Imaging, which is the traditional method for evaluating patients with suspected blockages or narrowing of the heart vessels (coronary artery disease) causing impaired blood to flow to the heart muscle (myocardium). The purpose of the study is to determine and compare the newest heart imaging equipment which allows the non-invasive evaluation of coronary anatomy, coronary flow and myocardial perfusion in patients with suspected or proven coronary artery disease (CAD) with the actual gold-standard for quantitative myocardial perfusion assessment. In order to achieve this aim, the study team will compare heart scan results from a computed tomography (CT) Myocardial Perfusion Imaging (CT-MPI) scan and CT-Fractional Flow Reserve (FFR) with the actual standard clinical care represented by a PET Myocardial Perfusion Imaging (PET-MPI) study.
Interventions
DIAGNOSTIC_TESTPET-MPI Protocol
Patients with suspected CAD who are referred to a clinical PET-MPI will undergo the standard clinical protocol applied in the Emory Nuclear Medicine department.
DIAGNOSTIC_TESTCT-MPI
For the CT-MPI, dynamic volume CT myocardial perfusion applying the dynamic shuttle mode will be used to rapidly cover the entire cardiac anatomy during infusion of a contrast medium bolus for monitoring bolus passage through the left ventricular myocardium. The dynamic shuttle mode consists of an image acquisition during rapid, yet smooth back-and-forth movement of the CT scanner table, so that contrast media bolus passage can be evaluated within the entire left ventricle in a time-resolved fashion. This scan acquisition will be performed during pharmacologically induced stress and during rest conditions. CT-MPI studies will be contrast medium enhanced by 50-70 ml of iodinated contrast agent, administered at a flow rate of 5 mL/s. The CT examinations are scheduled within 90 days of the standard clinical PET examination.
DIAGNOSTIC_TESTCoronary CT angiography (CCTA) for CT-FFR calculation
Coronary CT angiography (CCTA) will be performed for delineation of the coronary arteries, detection of potential coronary stenosis and FFR calculation. CCTA will be performed at rest following administration of intravenous contrast agent (50-70 mL of iodinated contrast material at a flow rate of 4-5 mL/s). A total radiation dose of approximately 8 millisievert (mSv) has expected to be administered with the stress/rest protocol to the patient. The total amount of contrast agent will not exceed 140 ml. The CT examinations are scheduled within 90 days of the standard clinical PET examination.
DRUGRegadenoson
Pharmacological stress testing for the CT-MPI scan will be performed with a single injection of 0.4 mg of regadenoson (Lexiscan).
Sponsors
Siemens Medical Solutions
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Referred for a clinically indicated CT-MPI for CAD assessment * Must provide written informed consent prior to any study-related procedures being performed * Must be willing to comply with all clinical study procedures
Exclusion criteria
* Pregnant or nursing females. The possibility of pregnancy will be excluded by testing (serum or urine ßHCG) within 24 hours before study agent administration, or if the woman has previous surgical sterilization, or if the woman is post-menopausal, with minimum one (1) year history without menses. * Currently taking or has taken within 48 hours the following excluded medications: * ActoPlus Met (Pioglitazone + metformin) * Avandamet (Rosiglitazone + metformin) * Fortamet (metformin) * Glucovance (Glyburide +metformin) * Glucophage (metformin) * Glucophage extended-release (XR) (metformin) * Glumetza (metformin) * Janumet (Sitagliptin + metformin) * Metformin * Metaglip (Glipizide + metformin) * Riomet (metformin) * Acute psychiatric disorder * Unwilling to comply with the requirements of the protocol * Previously entered this study * Known hypersensitivity to iodinated contrast material, beta-blockers, or pharmaceutical stressors used in this study * Suffers from claustrophobia * Impaired renal function (GFR \< 45 ml/min) * Acute hypotension (\<100 mm Hg systolic) * 2nd or 3rd degree atrioventricular (AV) block
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Blood Flow | Day of PET-MPI Scan, and Day of CT-MPI and CT-FFR Scans (up to 90 days) | The absolute quantification of myocardial perfusion between CT-MPI and PET-MPI is compared. Myocardial perfusion is quantified using appropriate tracer kinetic models resulting myocardial blood flow mL/g/min. |
| Coronary Flow Per CT-FFR | Day of CT-MPI and CCTA scans | Coronary flow is measured using the CT-FFR calculation with the CCTA scans. CT-FFR measures blood flow through coronary arteries and is used clinically to quantify the severity of CAD to determine further interventions. CT-FFR is the ratio between the blood flow (BF) in a diseased artery and a normal artery. Clinically, the CT-FFR calculation is only useful in patients with intermediate stenosis because stenosis below intermediate results in a value that is near zero and the calculation cannot be performed when stenosis is complete. The normal range for CT-FFR is greater than 0.80, values of 0.76 to 0.80 are borderline while values of 0.75 or less are associated with a high likelihood of reduced blood flow (ischemia). |
| Sensitivity of Myocardial Perfusion Abnormalities Diagnosis | Day 1 (day of scans) | The accuracy of detection of myocardial perfusion abnormalities is compared between PET-MPI, CT-MPI, CCTA, and CT-FFR approach. Diagnostic accuracy using CT-MPI, CCTA and CT-FFR is calculated as sensitivity (true positives) with PET as the reference standard. |
| Specificity of Myocardial Perfusion Abnormalities Diagnosis | Day 1 (day of scans) | The accuracy of detection of myocardial perfusion abnormalities is compared between PET-MPI, CT-MPI, CCTA, and CT-FFR approach. Diagnostic accuracy using CT-MPI, CCTA and CT-FFR is calculated as specificity (true negatives) with PET as the reference standard. |
| Area Under the Curve (AUC) for Detection of Myocardial Perfusion Abnormalities | Day 1 (day of scans) | The accuracy of detection of myocardial perfusion abnormalities is compared between PET-MPI, CT-MPI, CCTA, and CT-FFR approach. Diagnostic accuracy using CT-MPI, CCTA and CT-FFR is calculated as overall AUC with PET as the reference standard. The AUC examines the overall accuracy of a diagnostic test. Higher AUC indicates greater accuracy in detecting myocardial perfusion abnormalities with 1.0 being 100% accurate. An AUC value of 0.5 indicates that the test is as accurate as random chance. |
| Sensitivity of Coronary Stenosis Diagnosis | Day 1 (day of scans) | The accuracy of detection of coronary stenosis is compared between PET-MPI, CT-MPI, and CCTA with CT-FFR approach. Diagnostic accuracy is calculated as sensitivity (true positives) with CCTA as the reference standard. |
| Specificity of Coronary Stenosis Detection | Day 1 (day of scans) | The accuracy of detection of coronary stenosis is compared between PET-MPI, CT-MPI, and CCTA with CT-FFR approach. Diagnostic accuracy is calculated as specificity (true negatives) with CCTA as the reference standard. |
| Area Under the Curve for Detection of Coronary Stenosis | Day 1 (day of scans) | The accuracy of detection of coronary stenosis is compared between PET-MPI, CT-MPI, and CCTA with CT-FFR approach. Diagnostic accuracy is calculated as overall AUC with CCTA as the reference standard. The AUC examines the overall accuracy of a diagnostic test. Higher AUC indicates greater accuracy in detecting coronary stenosis with 1.0 being 100% accurate. An AUC value of 0.5 indicates that the test is as accurate as random chance. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Emory University Hospital in Atlanta, Georgia, USA. Participant enrollment began June 16, 2021 and all follow-up assessments were completed by September 24, 2024.
Participants by arm
| Arm | Count |
|---|---|
| Three Imaging Techniques: PET-MPI, CT-MPI, and CT-FFR Participants referred for a clinical positron emission tomography myocardial perfusion imaging (PET-MPI), the gold standard for evaluating patients with suspected coronary blockages or coronary artery disease, also attend a study visit where they have computed tomography (CT) myocardial perfusion imaging (CT-MPI) and coronary CT angiography for calculation of CT fractional flow reserve (CT-FFR) imaging performed for analysis of myocardial perfusion. The CT examinations are scheduled within 90 days of the standard clinical PET examination. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Three Imaging Techniques: PET-MPI, CT-MPI, and CT-FFR |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 55.9 years STANDARD_DEVIATION 9 |
| Body Mass Index (BMI) | 34.9 kg/m^2 STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Curve (AUC) for Detection of Myocardial Perfusion Abnormalities
The accuracy of detection of myocardial perfusion abnormalities is compared between PET-MPI, CT-MPI, CCTA, and CT-FFR approach. Diagnostic accuracy using CT-MPI, CCTA and CT-FFR is calculated as overall AUC with PET as the reference standard. The AUC examines the overall accuracy of a diagnostic test. Higher AUC indicates greater accuracy in detecting myocardial perfusion abnormalities with 1.0 being 100% accurate. An AUC value of 0.5 indicates that the test is as accurate as random chance.
Time frame: Day 1 (day of scans)
Population: This analysis includes participants with a PET-MPI result available. PET-MPI data were lost for two participants during an equipment move.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Area Under the Curve (AUC) for Detection of Myocardial Perfusion Abnormalities | 1.00 probabliity of accurate detection |
| PET-MPI - Rest | Area Under the Curve (AUC) for Detection of Myocardial Perfusion Abnormalities | 0 probabliity of accurate detection |
| PET-MPI - Stress | Area Under the Curve (AUC) for Detection of Myocardial Perfusion Abnormalities | 0.97 probabliity of accurate detection |
Primary
Area Under the Curve for Detection of Coronary Stenosis
The accuracy of detection of coronary stenosis is compared between PET-MPI, CT-MPI, and CCTA with CT-FFR approach. Diagnostic accuracy is calculated as overall AUC with CCTA as the reference standard. The AUC examines the overall accuracy of a diagnostic test. Higher AUC indicates greater accuracy in detecting coronary stenosis with 1.0 being 100% accurate. An AUC value of 0.5 indicates that the test is as accurate as random chance.
Time frame: Day 1 (day of scans)
Population: This analysis includes participants with a PET-MPI result available. PET-MPI data were lost for two participants during an equipment move.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Area Under the Curve for Detection of Coronary Stenosis | 0.83 probabliity of accurate detection |
| PET-MPI - Rest | Area Under the Curve for Detection of Coronary Stenosis | 0.83 probabliity of accurate detection |
| PET-MPI - Stress | Area Under the Curve for Detection of Coronary Stenosis | 1 probabliity of accurate detection |
Primary
Coronary Flow Per CT-FFR
Coronary flow is measured using the CT-FFR calculation with the CCTA scans. CT-FFR measures blood flow through coronary arteries and is used clinically to quantify the severity of CAD to determine further interventions. CT-FFR is the ratio between the blood flow (BF) in a diseased artery and a normal artery. Clinically, the CT-FFR calculation is only useful in patients with intermediate stenosis because stenosis below intermediate results in a value that is near zero and the calculation cannot be performed when stenosis is complete. The normal range for CT-FFR is greater than 0.80, values of 0.76 to 0.80 are borderline while values of 0.75 or less are associated with a high likelihood of reduced blood flow (ischemia).
Time frame: Day of CT-MPI and CCTA scans
Population: Only one participant met clinical guidelines for the calculation of CT-FFR by having intermediate stenosis. One participant had stenosis too high to calculate CT-FFR while the remaining 18 participants had too little stenosis for an informative calculation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Coronary Flow Per CT-FFR | 1.29 ratio |
Primary
Myocardial Blood Flow
The absolute quantification of myocardial perfusion between CT-MPI and PET-MPI is compared. Myocardial perfusion is quantified using appropriate tracer kinetic models resulting myocardial blood flow mL/g/min.
Time frame: Day of PET-MPI Scan, and Day of CT-MPI and CT-FFR Scans (up to 90 days)
Population: PET-MPI data were lost for two participants during an equipment move.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-MPI | Myocardial Blood Flow | 1.60 mL/g/min | Standard Deviation 0.43 |
| PET-MPI - Rest | Myocardial Blood Flow | 0.96 mL/g/min | Standard Deviation 0.29 |
| PET-MPI - Stress | Myocardial Blood Flow | 2.40 mL/g/min | Standard Deviation 1.09 |
Primary
Sensitivity of Coronary Stenosis Diagnosis
The accuracy of detection of coronary stenosis is compared between PET-MPI, CT-MPI, and CCTA with CT-FFR approach. Diagnostic accuracy is calculated as sensitivity (true positives) with CCTA as the reference standard.
Time frame: Day 1 (day of scans)
Population: This analysis includes participants with a PET-MPI result available. PET-MPI data were lost for two participants during an equipment move.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Sensitivity of Coronary Stenosis Diagnosis | 67 percentage of true postive cases |
| PET-MPI - Rest | Sensitivity of Coronary Stenosis Diagnosis | 67 percentage of true postive cases |
| PET-MPI - Stress | Sensitivity of Coronary Stenosis Diagnosis | 100 percentage of true postive cases |
Primary
Sensitivity of Myocardial Perfusion Abnormalities Diagnosis
The accuracy of detection of myocardial perfusion abnormalities is compared between PET-MPI, CT-MPI, CCTA, and CT-FFR approach. Diagnostic accuracy using CT-MPI, CCTA and CT-FFR is calculated as sensitivity (true positives) with PET as the reference standard.
Time frame: Day 1 (day of scans)
Population: This analysis includes participants with a PET-MPI result available. PET-MPI data were lost for two participants during an equipment move. Only one participant met clinical guidelines for the calculation of CT-FFR by having intermediate stenosis, however, the gold standard PET exam provided an incorrect diagnosis thus calculating sensitivity cannot correctly estimate the accuracy of CT-FFR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Sensitivity of Myocardial Perfusion Abnormalities Diagnosis | 100 percentage of true postive cases |
| PET-MPI - Stress | Sensitivity of Myocardial Perfusion Abnormalities Diagnosis | 100 percentage of true postive cases |
Primary
Specificity of Coronary Stenosis Detection
The accuracy of detection of coronary stenosis is compared between PET-MPI, CT-MPI, and CCTA with CT-FFR approach. Diagnostic accuracy is calculated as specificity (true negatives) with CCTA as the reference standard.
Time frame: Day 1 (day of scans)
Population: This analysis includes participants with a PET-MPI result available. PET-MPI data were lost for two participants during an equipment move. Specificity could not be calculated in the CCTA with CT-FFR Calculation study arm as there was not a participant negative for coronary stenosis per the reference standard.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Specificity of Coronary Stenosis Detection | 100 percentage of true negative cases |
| PET-MPI - Rest | Specificity of Coronary Stenosis Detection | 100 percentage of true negative cases |
Primary
Specificity of Myocardial Perfusion Abnormalities Diagnosis
The accuracy of detection of myocardial perfusion abnormalities is compared between PET-MPI, CT-MPI, CCTA, and CT-FFR approach. Diagnostic accuracy using CT-MPI, CCTA and CT-FFR is calculated as specificity (true negatives) with PET as the reference standard.
Time frame: Day 1 (day of scans)
Population: This analysis includes participants with a PET-MPI result available. PET-MPI data were lost for two participants during an equipment move. Only one participant met clinical guidelines for the calculation of CT-FFR by having intermediate stenosis, however, the gold standard PET exam provided an incorrect diagnosis thus calculating specificity cannot correctly estimate the accuracy of CT-FFR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT-MPI | Specificity of Myocardial Perfusion Abnormalities Diagnosis | 100 percentage of true negative cases |
| PET-MPI - Stress | Specificity of Myocardial Perfusion Abnormalities Diagnosis | 94 percentage of true negative cases |