Ignite Creation Date:
2024-05-06 @ 10:40 AM
Last Modification Date:
2024-10-26 @ 12:34 PM
Study NCT ID:
NCT03324308
Status:
WITHDRAWN
Last Update Posted:
2024-02-16
First Post:
2017-10-17
Brief Title:
Dynamic Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
The Safety Feasibility and Accuracy of Dynamic Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease
Status:
WITHDRAWN
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Redesign of Study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Coronary artery computed tomographic angiography CTA is a widely used highly accurate technique for the detection of coronary artery disease CAD with sensitivity and negative predictive values of over 90 1-4 Patients with normal CTA findings have an excellent prognosis and do not require further testing for CAD 5 However like invasive coronary angiography QCA CTA is an anatomic test and unless lesions are very severe 90 stenosis cannot reliably predict the impairment of flow functional significance of intermediate grade stenoses
For this reason in approximately 15-25 of patients additional functional testing may be required after CTA usually in the form of stress testing 6-8 Stress testing is commonly done by exercise or pharmacologic stress with electrocardiographic monitoring and often imaging of myocardial perfusion by nuclear scintigraphy MPI or detection of abnormal contraction by echocardiography This requires a separate procedure entailing time expense and limited risk Furthermore in patients with previously known CAD CTA alone is not an adequate test because in most cases there are multiple lesions that are possible sources of ischemia
Over the last 10 years these investigators and others around the world have developed a method of imaging myocardial perfusion by CT CTP This test is an adjunct to the usual Cardiac Computed Tomography Angiography CCTA procedure and can be done immediately thereafter using conventional pharmacologic stress agents It has demonstrated accuracy in many single center trials and in this large multicenter study the CORE320 trial 910 which showed a high accuracy in predicting the combined results of QCA plus MPI testing and a second multicenter trial established non-inferiority of myocardial CTP compared with nuclear stress testing 1112 Additionally this investigator group has published a direct comparison of diagnostic performance of myocardial CTP imaging and SPECT myocardial perfusion imaging and demonstrated superior diagnostic performance of CTP imaging compared with SPECT for the diagnosis of significant disease on invasive angiography 13
CTP images can be acquired with two different approaches static or dynamic In the CORE320 study the CTP protocol used static acquisition method The static CTP method samples a snapshot of the iodine distribution in the blood pool and the myocardium over a short period of time targeting either the upslope or the peak of contrast bolus The notion behind this is that at the upslope of the contrast the difference in attenuation value of the ischemic and remote myocardium is at the maximum which enables for qualitative and semi-quantitative assessment of myocardial perfusion defects The static CTP however does not allow for direct quantification of the myocardial blood flow MBF One of the drawbacks of static CTP lies in the acquirement of only one sample of data and the possibility of mistiming of the contrast bolus that results in poor contrast-to-tissue ratios by missing the peak attenuation 14 Output and flow rate of the contrast material may affect bolus timing In addition the acquisition of data from sequential heartbeats affects the attenuation gradient and may result in a heterogeneous iodine distribution mimicking perfusion defects 15 Furthermore the static CTP is limited in detection of balanced ischemia where the perfusion of the entire myocardium is impaired and therefore there is no reference remote myocardium for comparison for semi-quantitative or qualitative static methods of CTP interpretation
Dynamic CT perfusion imaging uses serial imaging over time to record the kinetics of iodinated contrast in the arterial blood pool and myocardium This technique allows for multiple sampling of the myocardium and the blood pool and creating time attenuation curves TAC by measuring the change in CT attenuation over time Mathematical modelling of TACs permits for direct quantification of MBF Despite its advantages the use of dynamic CTP were limited in the past A high temporal resolution and high number of detectors are required for dynamic CTP to allow for entire myocardial coverage and in order to obtain multiple consecutive images at high heart rates1617 But the main challenge of dynamic CTP acquisition was the high radiation dose associated with this technique Nevertheless with the introduction of the cutting-edge 320 detector CT scanning systems with fast gantry rotation the issue of the cardiac coverage is eliminated17 The second-generation 320-row scanners also permit the quantification of the MBF with dynamic CTP acquisition with relatively low-dose of radiation1819
In this study the investigators aim to evaluate the feasibility safety and accuracy of the low-radiation dose dynamic myocardial CT perfusion compared to static CTP approach to detect hemodynamically significant coronary artery disease
For this reason in approximately 15-25 of patients additional functional testing may be required after CTA usually in the form of stress testing 6-8 Stress testing is commonly done by exercise or pharmacologic stress with electrocardiographic monitoring and often imaging of myocardial perfusion by nuclear scintigraphy MPI or detection of abnormal contraction by echocardiography This requires a separate procedure entailing time expense and limited risk Furthermore in patients with previously known CAD CTA alone is not an adequate test because in most cases there are multiple lesions that are possible sources of ischemia
Over the last 10 years these investigators and others around the world have developed a method of imaging myocardial perfusion by CT CTP This test is an adjunct to the usual Cardiac Computed Tomography Angiography CCTA procedure and can be done immediately thereafter using conventional pharmacologic stress agents It has demonstrated accuracy in many single center trials and in this large multicenter study the CORE320 trial 910 which showed a high accuracy in predicting the combined results of QCA plus MPI testing and a second multicenter trial established non-inferiority of myocardial CTP compared with nuclear stress testing 1112 Additionally this investigator group has published a direct comparison of diagnostic performance of myocardial CTP imaging and SPECT myocardial perfusion imaging and demonstrated superior diagnostic performance of CTP imaging compared with SPECT for the diagnosis of significant disease on invasive angiography 13
CTP images can be acquired with two different approaches static or dynamic In the CORE320 study the CTP protocol used static acquisition method The static CTP method samples a snapshot of the iodine distribution in the blood pool and the myocardium over a short period of time targeting either the upslope or the peak of contrast bolus The notion behind this is that at the upslope of the contrast the difference in attenuation value of the ischemic and remote myocardium is at the maximum which enables for qualitative and semi-quantitative assessment of myocardial perfusion defects The static CTP however does not allow for direct quantification of the myocardial blood flow MBF One of the drawbacks of static CTP lies in the acquirement of only one sample of data and the possibility of mistiming of the contrast bolus that results in poor contrast-to-tissue ratios by missing the peak attenuation 14 Output and flow rate of the contrast material may affect bolus timing In addition the acquisition of data from sequential heartbeats affects the attenuation gradient and may result in a heterogeneous iodine distribution mimicking perfusion defects 15 Furthermore the static CTP is limited in detection of balanced ischemia where the perfusion of the entire myocardium is impaired and therefore there is no reference remote myocardium for comparison for semi-quantitative or qualitative static methods of CTP interpretation
Dynamic CT perfusion imaging uses serial imaging over time to record the kinetics of iodinated contrast in the arterial blood pool and myocardium This technique allows for multiple sampling of the myocardium and the blood pool and creating time attenuation curves TAC by measuring the change in CT attenuation over time Mathematical modelling of TACs permits for direct quantification of MBF Despite its advantages the use of dynamic CTP were limited in the past A high temporal resolution and high number of detectors are required for dynamic CTP to allow for entire myocardial coverage and in order to obtain multiple consecutive images at high heart rates1617 But the main challenge of dynamic CTP acquisition was the high radiation dose associated with this technique Nevertheless with the introduction of the cutting-edge 320 detector CT scanning systems with fast gantry rotation the issue of the cardiac coverage is eliminated17 The second-generation 320-row scanners also permit the quantification of the MBF with dynamic CTP acquisition with relatively low-dose of radiation1819
In this study the investigators aim to evaluate the feasibility safety and accuracy of the low-radiation dose dynamic myocardial CT perfusion compared to static CTP approach to detect hemodynamically significant coronary artery disease
Detailed Description:
This will be a prospective study comparing the low-dose dynamic vs static CTP combined with the CTA for detecting hemodynamically significant coronary artery stenosis The aim of the study is to assess the feasibility safety and accuracy of low-dose dynamic CTP following CTA
The study will enroll patients who have documented coronary artery disease and an indication for coronary angiography or CT angiography Referred patients will be assessed for eligibility through phone calls followed by in-person interviews Patents will be provided with the informed consent forms for CTA-CTP and iodine contrast if it is determined that participants are eligible for the study Patients have the right to refuse to participate in the study and in that case participants will receive the regular care per clinical guidelines Baseline information will be collected from the patients after participants consent to participate in the study Baseline data collection will happen at the same day that the patients will undergo CTA-CTP The CTA-CTP acquisition takes less than 60 minutes after the patient is on the CT scanner table Patient preparation time before patient is brought on the CT scanner depends on patients heart rate and the time that takes to reduce patients heart rate to a level that is appropriate for CTA-CTP acquisition The blood sample will be obtained from the patients at the same day as CTA-CTP acquisition Patients will be discharged to home at the same day participants undergo CTA-CTP
b Study duration and number of study visits required of research participants There will be only one visit required for the purposes of the study during which the CTA-CTP acquisition will be completed baseline information will be collected and the blood samples will be drawn The study participants will be contacted through phone 3-days after CTA-CTP acquisition for follow-up
CT Imaging protocol
Patients will have two 18-20 gauge intravenous lines placed one preferably in an antecubital vein for contrast administration The patient will be hydrated with normal saline intravenously 250 - 500 ml prior to CT scanning The patient will lie supine on the scanner table and be attached to a 12 lead electrocardiographic monitor and an automated blood pressure monitor Baseline ECG heart rate and blood pressure will be recorded and reviewed by one of the study investigators Due to resultant artifacts from precordial leads the 12 ECG leads and electrodes will be removed and rhythm monitoring will continue using the 3 lead system attached to the scanners monitoring system during scanning A physician will be present at all times during adenosine infusion and CT imaging Patients may receive an oral andor intravenous dose of metoprolol up to one hour prior to the CT If the heart rate is 60 beats per minute 75 mg max 80 mg of metoprolol will be given orally If Heart rate remains 60 beats per minute at the scan acquisition then intravenous beta blocker metoprolol propranolol or landiolol 25 - 50 mg every 5 minutes will be administered to achieve a heart rate between 60 beats per minute as blood pressure tolerates under the supervision of a physician Scout images for determining scanning range will be obtained in the anterior-posterior and lateral views Patients with systolic blood pressure 110 will receive sublingual fast acting short lasting nitrates eg nitroglycerin isosorbide dinitrate Patients will then be asked to hold their breath approximately 10-15 seconds and non-contrast CT imaging will be performed starting just cranial to the coronary ostia and extending just caudal to the apex of the heart in order to obtain a coronary calcium score CT angiogram will be performed to evaluate the coronaries and myocardial perfusion at rest Blood pressure will be checked and intravenous adenosine infusion 014 mgkgmin will begin with continuous heart rate and rhythm monitoring After 5 minutes of adenosine infusion contrast-enhanced CT perfusion imaging will be performed during a 4-5 mlsec intravenous iodinated contrast ISOVUE-370 infusion Total contrast dose for the entire protocol will not exceed 140 ml and will be based on patients body size Patients will be asked to hold their breath during scanning Immediately following completion of the scan the adenosine infusion will be discontinued A twelve lead ECG and blood pressure measurement will be repeated after discontinuation of adenosine and reviewed by a physician Intravenous hydration will be continued during recovery with normal saline for a total volume for the entire post scan of 250 to 500 ml if deemed appropriate by the supervising physician
320-Detector CT Protocol for Combined Coronary Angiography and Perfusion Imaging
1 Coronary calcium scan will be performed using the following protocol
No contrast
CT Imaging tube voltage 120kV tube current 140 Milliampere mA gantry rotation speed 035 seconds slice thickness 05 mm rows 256-320 range 128-160 mm X-ray tube will be on for a total of 035 seconds Estimated radiation dose 15 Millisievert mSv
2 Rest coronary arterial imaging Rest perfusion and coronary arterial imaging will be performed during a 4-5 mlsec intravenous iodinated contrast ISOVUE-370 infusion The rest CTA-dynamic CTP images will be started using a test bolus acquisition and accurate quantification of optimum timing for dynamic CTP and boost CTA acquisition and will continue for 20-30 sec using a ECG triggering method to allow acquiring the images only within 70-80 of the R-R interval but not continuously The parameters for the dynamic CTP image acquisition are the followings For the heart rate of 60 bpm the tube voltage will be 80 kV and the tube current will be 100mA Other parameters are gantry rotation0275 range120mm The CTA and static CTP imaging will be performed as a boost scan during the dynamic CTP with the same tube voltage 80kV but the tube current of 600mA within 70-80 of R-R interval The boost timing will be quantified from test bolus acquisition The average radiation dose for rest CTA and rest dynamic and static CTP acquisition is 369mSv
3 Stress Myocardial Perfusion imaging 20 minutes after rest image acquisition Blood pressure will be checked and intravenous adenosine infusion will begin with continuous heart rate and rhythm monitoring After 5 minutes of adenosine infusion contrast-enhanced CT perfusion imaging will be performed during a 4-5 mlsec intravenous iodinated contrast ISOVUE-370 infusion The stress dynamic CTP images will be started using a test bolus acquisition and accurate quantification of optimum timing for dynamic CTP and boost CTA acquisition and will continue for 20-30 sec using a ECG triggering method to allow acquiring the images only within 70-80 of the R-R interval but not continuously The parameters for the stress dynamic CTP image acquisition are the followings For the heart rate of 80 bpm the tube voltage will be 80 kV and the tube current will be 100mA Other parameters are gantry rotation0275 range120mm The stress static CTP imaging will be performed as a boost scan during the stress dynamic CTP with the same tube voltage 80kV but the tube current of 600mA within 70-80 of R-R interval The boost timing will be quantified from test bolus acquisition The average radiation dose for stress dynamic and static CTP acquisition is 517mSv
The estimated average radiation dose for the entire cardiac computed protocol is 1055 mSv and shall not exceed 15mSv Beta-blockers will be used to control the heart rate and thus maintain the radiation dose as low as reasonably achievable The total contrast dose will not exceed 140 ml Depending on patient size 50-70 ml of iodinated contrast will be used for each of rest and stress scans
In the event that the CT raw data are not readable at the Johns Hopkins University a copy of the raw data anonymized without patient identifiers will be transferred to Toshiba Medical Systems for engineering support of image reconstruction in these isolated cases Toshiba Medical Systems will perform the image reconstruction and return the raw data and the reconstructed image data to the Johns Hopkins University for image analysis
Within 3 weeks of the CT the CT will be reviewed for non-cardiac findings by a locally qualified institutionally approved cardiologist and reported to the patients clinical physician and patient in a timely fashion preferably prior to or during the 30-day follow-up
c Blinding including justification for blinding or not blinding the trial if applicable
Dynamic and static CTP images will be analyzed separately and when analyzing the CTP images with each method the readers will be blinded to the results the other method However the readers will have access to the results for CTA interpretation while reading the CTP images with either of static or dynamic methods
d Justification of why participants will not receive routine care or will have current therapy stopped
The study will be only enrolling patients with an indication for CTA or invasive coronary angiography and will undergo these tests So routine care will be delivered to the participants
7 Study Statistics
a Primary outcome variable The primary outcome measures will be feasibility safety and accuracy of dynamic CTP-CTA compared to static CTP-CTA to detect hemodynamically significant coronary artery stenosis The hemodynamically significant coronary artery stenosis will be defined as having at least one vessel with a 50 stenosis associated with perfusion defect in static CTP images
At the index visit failure to complete the CTP protocol will constitute an incomplete study and such patients will be excluded from the per protocol analysis All patients completing the CTP protocol and providing informed consent will be included in per-protocol analyses All data from all consented patients who do not complete the CTP protocol will be included in the intent-to-diagnose analysis
Descriptive statistics will be given for all variables including indications for the test demographics patient history CTA test information dynamic and static CTP information Categorical variables will be summarized as counts and percentages All continuous variables will be summarized as means- the standard deviation followed by the median minimum and maximum and 25th 75th percentiles where needed
The frequency of the primary safety outcomes death myocardial infarction unstable angina ventricular tachycardia asystole severe bradycardia allergic skin reactions allergic respiratory reactions hypotension anaphylaxis and contrast induced nephropathy will all be summarized 95 binomial confidence intervals for the proportions of these outcomes will be calculated The additional safety outcomes involving CTP complications will be summarized with frequencies and 95 confidence intervals for proportions Radiation dose and efficiency measures durations involving the CTP procedure will be summarized overall with median and 25th and 75th percentiles Also minima and maxima will be provided The investigators may explore possible associations between patient characteristics demographics gender age prior histories or indications and the binary safety outcomes using contingency table methods t tests or Wilcoxon Rank Sum as appropriate Associations between radiation dose and patient characteristics may be explored with nonparametric methods The investigators may also explore possible relationships between the CTA stenosis categories 0 1-49 50-100 and the dynamic and static CTP results The occurrence of clinical events recorded at 30-day chart review will be related to the category of CTP final results Normal Probably Normal Equivocal Probably Abnormal and Abnormal using methods for contingency tables which incorporate the natural ordering of CTP categories
The frequency of the studies with the adequate image quality for interpretation of dynamic CTP images will be reported as a measure is feasibility This feasibility index will be also reported at the myocardial segment level and the frequency of Left Ventricular LV segments with adequate dynamic CTP image quality will be reported
The inter- and intra-reader reproducibility of dynamic CTP interpretation will be assessed using kappa statistics intra-class correlation coefficients and Bland-Altman plot as appropriate
The accuracy of the dynamic CTP for detection of hemodynamically significant coronary artery stenosis will be based on the area under the receiver operating characteristic ROC curve AUC with the static CTP results as the comparator The correlation of the dynamic vs static CTP will be also assessed in the categorical Chi-squared test and continuous Spearmans correlation coefficient scale
The study will enroll patients who have documented coronary artery disease and an indication for coronary angiography or CT angiography Referred patients will be assessed for eligibility through phone calls followed by in-person interviews Patents will be provided with the informed consent forms for CTA-CTP and iodine contrast if it is determined that participants are eligible for the study Patients have the right to refuse to participate in the study and in that case participants will receive the regular care per clinical guidelines Baseline information will be collected from the patients after participants consent to participate in the study Baseline data collection will happen at the same day that the patients will undergo CTA-CTP The CTA-CTP acquisition takes less than 60 minutes after the patient is on the CT scanner table Patient preparation time before patient is brought on the CT scanner depends on patients heart rate and the time that takes to reduce patients heart rate to a level that is appropriate for CTA-CTP acquisition The blood sample will be obtained from the patients at the same day as CTA-CTP acquisition Patients will be discharged to home at the same day participants undergo CTA-CTP
b Study duration and number of study visits required of research participants There will be only one visit required for the purposes of the study during which the CTA-CTP acquisition will be completed baseline information will be collected and the blood samples will be drawn The study participants will be contacted through phone 3-days after CTA-CTP acquisition for follow-up
CT Imaging protocol
Patients will have two 18-20 gauge intravenous lines placed one preferably in an antecubital vein for contrast administration The patient will be hydrated with normal saline intravenously 250 - 500 ml prior to CT scanning The patient will lie supine on the scanner table and be attached to a 12 lead electrocardiographic monitor and an automated blood pressure monitor Baseline ECG heart rate and blood pressure will be recorded and reviewed by one of the study investigators Due to resultant artifacts from precordial leads the 12 ECG leads and electrodes will be removed and rhythm monitoring will continue using the 3 lead system attached to the scanners monitoring system during scanning A physician will be present at all times during adenosine infusion and CT imaging Patients may receive an oral andor intravenous dose of metoprolol up to one hour prior to the CT If the heart rate is 60 beats per minute 75 mg max 80 mg of metoprolol will be given orally If Heart rate remains 60 beats per minute at the scan acquisition then intravenous beta blocker metoprolol propranolol or landiolol 25 - 50 mg every 5 minutes will be administered to achieve a heart rate between 60 beats per minute as blood pressure tolerates under the supervision of a physician Scout images for determining scanning range will be obtained in the anterior-posterior and lateral views Patients with systolic blood pressure 110 will receive sublingual fast acting short lasting nitrates eg nitroglycerin isosorbide dinitrate Patients will then be asked to hold their breath approximately 10-15 seconds and non-contrast CT imaging will be performed starting just cranial to the coronary ostia and extending just caudal to the apex of the heart in order to obtain a coronary calcium score CT angiogram will be performed to evaluate the coronaries and myocardial perfusion at rest Blood pressure will be checked and intravenous adenosine infusion 014 mgkgmin will begin with continuous heart rate and rhythm monitoring After 5 minutes of adenosine infusion contrast-enhanced CT perfusion imaging will be performed during a 4-5 mlsec intravenous iodinated contrast ISOVUE-370 infusion Total contrast dose for the entire protocol will not exceed 140 ml and will be based on patients body size Patients will be asked to hold their breath during scanning Immediately following completion of the scan the adenosine infusion will be discontinued A twelve lead ECG and blood pressure measurement will be repeated after discontinuation of adenosine and reviewed by a physician Intravenous hydration will be continued during recovery with normal saline for a total volume for the entire post scan of 250 to 500 ml if deemed appropriate by the supervising physician
320-Detector CT Protocol for Combined Coronary Angiography and Perfusion Imaging
1 Coronary calcium scan will be performed using the following protocol
No contrast
CT Imaging tube voltage 120kV tube current 140 Milliampere mA gantry rotation speed 035 seconds slice thickness 05 mm rows 256-320 range 128-160 mm X-ray tube will be on for a total of 035 seconds Estimated radiation dose 15 Millisievert mSv
2 Rest coronary arterial imaging Rest perfusion and coronary arterial imaging will be performed during a 4-5 mlsec intravenous iodinated contrast ISOVUE-370 infusion The rest CTA-dynamic CTP images will be started using a test bolus acquisition and accurate quantification of optimum timing for dynamic CTP and boost CTA acquisition and will continue for 20-30 sec using a ECG triggering method to allow acquiring the images only within 70-80 of the R-R interval but not continuously The parameters for the dynamic CTP image acquisition are the followings For the heart rate of 60 bpm the tube voltage will be 80 kV and the tube current will be 100mA Other parameters are gantry rotation0275 range120mm The CTA and static CTP imaging will be performed as a boost scan during the dynamic CTP with the same tube voltage 80kV but the tube current of 600mA within 70-80 of R-R interval The boost timing will be quantified from test bolus acquisition The average radiation dose for rest CTA and rest dynamic and static CTP acquisition is 369mSv
3 Stress Myocardial Perfusion imaging 20 minutes after rest image acquisition Blood pressure will be checked and intravenous adenosine infusion will begin with continuous heart rate and rhythm monitoring After 5 minutes of adenosine infusion contrast-enhanced CT perfusion imaging will be performed during a 4-5 mlsec intravenous iodinated contrast ISOVUE-370 infusion The stress dynamic CTP images will be started using a test bolus acquisition and accurate quantification of optimum timing for dynamic CTP and boost CTA acquisition and will continue for 20-30 sec using a ECG triggering method to allow acquiring the images only within 70-80 of the R-R interval but not continuously The parameters for the stress dynamic CTP image acquisition are the followings For the heart rate of 80 bpm the tube voltage will be 80 kV and the tube current will be 100mA Other parameters are gantry rotation0275 range120mm The stress static CTP imaging will be performed as a boost scan during the stress dynamic CTP with the same tube voltage 80kV but the tube current of 600mA within 70-80 of R-R interval The boost timing will be quantified from test bolus acquisition The average radiation dose for stress dynamic and static CTP acquisition is 517mSv
The estimated average radiation dose for the entire cardiac computed protocol is 1055 mSv and shall not exceed 15mSv Beta-blockers will be used to control the heart rate and thus maintain the radiation dose as low as reasonably achievable The total contrast dose will not exceed 140 ml Depending on patient size 50-70 ml of iodinated contrast will be used for each of rest and stress scans
In the event that the CT raw data are not readable at the Johns Hopkins University a copy of the raw data anonymized without patient identifiers will be transferred to Toshiba Medical Systems for engineering support of image reconstruction in these isolated cases Toshiba Medical Systems will perform the image reconstruction and return the raw data and the reconstructed image data to the Johns Hopkins University for image analysis
Within 3 weeks of the CT the CT will be reviewed for non-cardiac findings by a locally qualified institutionally approved cardiologist and reported to the patients clinical physician and patient in a timely fashion preferably prior to or during the 30-day follow-up
c Blinding including justification for blinding or not blinding the trial if applicable
Dynamic and static CTP images will be analyzed separately and when analyzing the CTP images with each method the readers will be blinded to the results the other method However the readers will have access to the results for CTA interpretation while reading the CTP images with either of static or dynamic methods
d Justification of why participants will not receive routine care or will have current therapy stopped
The study will be only enrolling patients with an indication for CTA or invasive coronary angiography and will undergo these tests So routine care will be delivered to the participants
7 Study Statistics
a Primary outcome variable The primary outcome measures will be feasibility safety and accuracy of dynamic CTP-CTA compared to static CTP-CTA to detect hemodynamically significant coronary artery stenosis The hemodynamically significant coronary artery stenosis will be defined as having at least one vessel with a 50 stenosis associated with perfusion defect in static CTP images
At the index visit failure to complete the CTP protocol will constitute an incomplete study and such patients will be excluded from the per protocol analysis All patients completing the CTP protocol and providing informed consent will be included in per-protocol analyses All data from all consented patients who do not complete the CTP protocol will be included in the intent-to-diagnose analysis
Descriptive statistics will be given for all variables including indications for the test demographics patient history CTA test information dynamic and static CTP information Categorical variables will be summarized as counts and percentages All continuous variables will be summarized as means- the standard deviation followed by the median minimum and maximum and 25th 75th percentiles where needed
The frequency of the primary safety outcomes death myocardial infarction unstable angina ventricular tachycardia asystole severe bradycardia allergic skin reactions allergic respiratory reactions hypotension anaphylaxis and contrast induced nephropathy will all be summarized 95 binomial confidence intervals for the proportions of these outcomes will be calculated The additional safety outcomes involving CTP complications will be summarized with frequencies and 95 confidence intervals for proportions Radiation dose and efficiency measures durations involving the CTP procedure will be summarized overall with median and 25th and 75th percentiles Also minima and maxima will be provided The investigators may explore possible associations between patient characteristics demographics gender age prior histories or indications and the binary safety outcomes using contingency table methods t tests or Wilcoxon Rank Sum as appropriate Associations between radiation dose and patient characteristics may be explored with nonparametric methods The investigators may also explore possible relationships between the CTA stenosis categories 0 1-49 50-100 and the dynamic and static CTP results The occurrence of clinical events recorded at 30-day chart review will be related to the category of CTP final results Normal Probably Normal Equivocal Probably Abnormal and Abnormal using methods for contingency tables which incorporate the natural ordering of CTP categories
The frequency of the studies with the adequate image quality for interpretation of dynamic CTP images will be reported as a measure is feasibility This feasibility index will be also reported at the myocardial segment level and the frequency of Left Ventricular LV segments with adequate dynamic CTP image quality will be reported
The inter- and intra-reader reproducibility of dynamic CTP interpretation will be assessed using kappa statistics intra-class correlation coefficients and Bland-Altman plot as appropriate
The accuracy of the dynamic CTP for detection of hemodynamically significant coronary artery stenosis will be based on the area under the receiver operating characteristic ROC curve AUC with the static CTP results as the comparator The correlation of the dynamic vs static CTP will be also assessed in the categorical Chi-squared test and continuous Spearmans correlation coefficient scale
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None