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Dynamic Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease

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ClinicalTrials.gov Identifier: NCT03324308
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : December 16, 2019
Sponsor:
Collaborator:
Toshiba Medical Systems Corporation, Japan
Information provided by (Responsible Party):
Johns Hopkins University

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 (9,10) 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 (11,12). 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 rates(16,17). 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 eliminated(17). The second-generation 320-row scanners also permit the quantification of the MBF with dynamic CTP acquisition with relatively low-dose of radiation(18,19).

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.


Condition or disease Intervention/treatment Phase
Coronary Artery Disease Ischemia Diagnostic Test: Computed Tomography Angiography Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: The Safety, Feasibility and Accuracy of Dynamic Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease
Actual Study Start Date : March 30, 2018
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Interventional Group

Participants undergoing dynamic computed tomography myocardial perfusion imaging.

Intervention: Diagnostic Test: Dynamic Computed Tomography Angiography Imaging

Diagnostic Test: Computed Tomography Angiography
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. Patients will have two 18-20 gauge intravenous lines placed for contrast administration. The following image sequences will be completed: coronary calcium scan (non-contrast), rest coronary arterial imaging (with 4-5 mL/sec intravenous ISOVUE-370 infusion), stress myocardial perfusion imaging 20 minutes after rest acquisition imaging (blood pressure will be checked then an infusion of adenosine will be started for a total of 5 minutes; after 5 minutes of adenosine infusion, CT perfusion imaging will be performed during a 4-5 mL/sec ISOVUE-370 infusion). Total estimated radiation dose: 10.551 mSv.
Other Names:
  • Myocardial Computed Tomography Perfusion - Static
  • Myocardial Computed Tomography Perfusion - Dynamic




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (Safety and tolerability) [ Time Frame: 30 days post procedure ]
    Occurrence of treatment emergent adverse events including allergic reactions, adverse reactions to pharmacologic stress agents, contrast induced nephropathy


Secondary Outcome Measures :
  1. The Area Under Receiver Operating Characteristics Curve (AUC) of combined CTA-dynamic CTP for detection of hemodynamically significant coronary artery stenosis at the patient level [ Time Frame: At the day of procedure ]
    At the patient level: The Area Under Receiver Operating Characteristics Curve (AUC) of combined CTA-dynamic CTP for detection of hemodynamically significant coronary artery stenosis by combined CTA-static CTP defined as at least one vessel with ≥50% stenosis with an associated perfusion defect in static CTP.

  2. The Area Under Receiver Operating Characteristics Curve (AUC) of dynamic CTP for detection of a perfusion defect at the patient level [ Time Frame: At the day of procedure ]
    At the patient level: The Area Under Receiver Operating Characteristics Curve (AUC) of dynamic CTP for detection of a perfusion defect compared to static CTP.

  3. The Area Under Receiver Operating Characteristics Curve (AUC) of combined CTA-dynamic CTP for detection of hemodynamically significant coronary artery stenosis at the vessel level. [ Time Frame: At the day of procedure ]
    At the vessel level: The Area Under Receiver Operating Characteristics Curve (AUC) of combined CTA-dynamic CTP for detection of hemodynamically significant coronary artery stenosis by combined CTA-static CTP defined a coronary artery lesion with ≥50% stenosis with an associated perfusion defect in the same artery in static CTP.

  4. The Area Under Receiver Operating Characteristics Curve (AUC) of dynamic CTP for detection of a perfusion defect at the vessel level. [ Time Frame: At the day of procedure ]
    At the vessel level: The Area Under Receiver Operating Characteristics Curve (AUC) of dynamic CTP for detection of a perfusion defect compared to static CTP.

  5. Total length of stay (hours) [ Time Frame: 1-7 days after the procedure ]
    Total length of stay including hospital stay if admitted (hours).

  6. Duration of exam (hours) [ Time Frame: 24 hours after initiation of exam ]
    Time from initiation to completion of CCTA and CTP testing (hours)

  7. Interpretation time (hours) [ Time Frame: 1-4 hours after initiation of test interpretation ]
    Time to interpret the test (hours)

  8. Frequency of interpretable images [ Time Frame: At the day of procedure ]
    Frequency of the studies with the adequate image quality for interpretation of dynamic CTP images

  9. Frequency of interpretable myocardial segments [ Time Frame: At the day of procedure ]
    Frequency of the myocardial segments with adequate dynamic CTP image quality for interpretation

  10. The inter-reader reproducibility of dynamic CTP image interpretation [ Time Frame: 1-7 days after the exam ]
    The inter-reader reproducibility of dynamic CTP image interpretation using Concordance Correlation Coefficient

  11. The intra-reader reproducibility of dynamic CTP image interpretation [ Time Frame: 1-7 days after the exam ]
    The intra-reader reproducibility of dynamic CTP image interpretation using Concordance Correlation Coefficient



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical indication for invasive coronary angiography or CT angiography
  • Documented coronary artery disease defined as presence of one or more of the following:
  • CAD documented by invasive coronary angiography or CT angiography
  • History of typical stable angina and receiving guideline-driven therapy for coronary artery disease for ≥ 1 month prior to consent
  • History of hospitalization for unstable angina with no active acute coronary syndrome within 48 hours prior to scan
  • Refractory angina defined as marked limitation of ordinary physical activity or inability to perform ordinary physical activity without discomfort, with an objective evidence of myocardial ischemia and persistence of symptoms despite optimal medical therapy, life style modification treatments, and revascularization therapies
  • Able to understand and willing to sign the Informed Consent Form.

Exclusion Criteria:

  • Known allergy to iodinated contrast media
  • History of contrast-induced nephropathy
  • History of multiple myeloma or previous organ transplantation
  • Elevated serum creatinine (> 1.5mg/dl) OR calculated creatinine clearance of < 60 ml/min (using the Cockcroft-Gault formula)
  • Atrial fibrillation or uncontrolled tachyarrhythmia, or advanced atrioventricular block (second or third degree heart block)
  • Evidence of severe symptomatic heart failure (NYHA Class III or IV); Known or suspected moderate or severe aortic stenosis
  • Previous coronary artery bypass or other cardiac surgery
  • Coronary artery intervention (PCI) within the last 6 months
  • Known or suspected intolerance or contraindication to beta-blockers including:
  • Known allergy to beta-blockers
  • History of moderate to severe bronchospastic lung disease (including moderate to severe asthma)
  • Severe pulmonary disease (chronic obstructive pulmonary disease) with the use of inhaled bronchodilators over the past year
  • Presence of any other history or condition that the investigator feels would be problematic
  • History of high radiation exposure defined as ≥2 nuclear or CT studies or ≥ 5.0 reml within 18 months prior to the scan
  • Does the patient have active acute coronary syndrome within 48 hours prior to consent?

    • Typical, prolonged (>20 minute) rest angina at admission
    • Angina equivalent symptoms compatible with ischemia plus abnormal cardiac enzymes
    • Prolonged rest chest pain (>20 minutes) resolved before admission plus prior ischemic ECG changes
    • Rest chest pain < 20 minutes relieved with nitrates in the prior 48 hours plus prior ischemic ECG changes.
    • If yes to any of the above, Calculate Thrombolysis in Myocardial Infarction (TIMI) risk score:

      • If TIMI risk score ≥ 5 OR elevated cardiac enzymes in the 72 hours prior patient is excluded.
      • If TIMI risk score is <5 and cardiac enzymes are normal patient is included.
    • If all of above are no then patient is included.
  • Implantable cardioverter-defibrillator (but not pacemakers) within the imaging field of view
  • Contraindications to vasodilator stress agents:

    • Systolic Blood Pressure (SBP)<90mmHg, -Recent use of dipyridamole and dipyridamole containing medications - -Recent use of methylxanthines (aminophylline and caffeine) - -Unstable acute Myocardial Infarction (MI) or acute coronary syndrome -
    • Profound sinus bradycardia (<40 bpm)
  • Body Mass Index greater than 30

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324308


Contacts
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Contact: Mohammad Ostovaneh 443-676-5410 mostova1@jhmi.edu
Contact: Jaclyn C Sesso, BSN 847-573-6861 jsesso1@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Unversity School of Medicine Recruiting
Baltimore, Maryland, United States, 21218
Contact: Joao Lima, MD         
Sponsors and Collaborators
Johns Hopkins University
Toshiba Medical Systems Corporation, Japan
Investigators
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Principal Investigator: Joao AC Lima, MD Johns Hopkins School of Medicine

Publications:
Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Tracy CM, Epstein AE, Darbar D, DiMarco JP, Dunbar SB, Estes NA 3rd, Ferguson TB Jr, Hammill SC, Karasik PE, Link MS, Marine JE, Schoenfeld MH, Shanker AJ, Silka MJ, Stevenson LW, Stevenson WG, Varosy PD; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Heart Rhythm Society. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2013 Jan 22;61(3):e6-75. doi: 10.1016/j.jacc.2012.11.007. Epub 2012 Dec 19.

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03324308    
Other Study ID Numbers: IRB00143208
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Johns Hopkins University:
Coronary Artery Disease
Ischemia
Computed Tomography
Myocardial perfusion
Dynamic Imaging
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes