Clinical trial NCT02931331: Coronary Revascularization Assessed by Stress PET
Official title: The Impact of Coronary Revascularization on Absolute Myocardial Blood Flow as Assessed by Stress Myocardial Positron Tomography
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Stenoses
Myocardial Ischemia
Coronary Artery Stenosis
Coronary Disease
Coronary Occlusion
Lead sponsor: Ochsner Health System
Sponsor class: OTHER
Collaborators: name: Bracco Corporate
First posted: 2016-10-13
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals who undergo cardiac stress PET and subsequently undergo coronary angiography and mechanical revascularization. Mechanical revascularization is defined as PCI and/or coronary artery bypass grafting (CABG).

Brief summary: Regional absolute myocardial blood flow during stress (sMBF) as measured by Positron Emission Tomography (PET) improves post mechanical revascularization provided there is a baseline stress induced perfusion defect. Coronary revascularization performed on regions without a stress induced perfusion defect does not increase the sMBF.

Detailed description: 1.0 HYPOTHESIS Regional absolute myocardial blood flow during stress (sMBF) as measured by Positron Emission Tomography (PET) improves post mechanical revascularization provided there is a baseline stress induced perfusion defect. Coronary revascularization performed on regions without a stress induced perfusion defect does not increase the sMBF.

2.0 BACKGROUND Angiographic severity of coronary artery stenosis has historically been the primary guide to mechanical revascularization and/or medical management of coronary artery disease. Studies have shown that in patients with stable coronary artery disease (CAD) percutaneous coronary intervention (PCI) based on angiographic stenosis severity does not reduce coronary events more than initial medical treatment. In contrast, randomized trials of PCI report better outcomes when guided by fractional flow reserve (FFR) than when guided by angiographic severity or when compared to initial medical treatment.

Several potential explanations have been proposed for these conflicting views. Revascularization procedures may not alter the natural history of multicentric plaque rupture determined by complex arterial vascular biology. CAD exists diffusely in addition to segmental stenosis, so that localized mechanical intervention may fail to alter long-term disease progression or outcome. Additionally, anatomic severity on coronary angiography may not reflect the physiologic severity that directly determines ischemia, left ventricular function, and prognosis. Invasive physiologic criteria such as fractional flow reserve (FFR) can be utilized during invasive angiography to further educate decision making about whether to perform PCI, however FFR is performed in only 6% of percutaneous coronary interventions (PCI) in the United States. Consequently, percent stenosis on coronary angiography remains the main determinant when deciding to proceed with PCI.

It is well established that coronary angiography is frequently unable to adequately characterize the hemodynamic impact of coronary stenoses. In particular, percent stenosis does not predict or reliably relate to maximum flow capacity or coronary flow reserve (CFR). Studies have clearly demonstrated that the anatomical assessment of the hemodynamic significance of coronary stenoses determined by visual modalities such as coronary angiography or computed tomography coronary angiography (CTCA) does not correlate well with the functional assessment of FFR. It is plausible, therefore, that when epicardial vessels are targeted for revascularization based on percent stenosis, this intervention may not lead to a significant improvement in myocardial blood flow and in fact could be detrimental.

Myocardial perfusion by positron emission tomography (PET) is a well-established and validated tool for assessing myocardial perfusion and quantifying absolute myocardial blood flow. As such, cardiac PET serves as an ideal technology for quantifying changes in flow after revascularization procedures. Noninvasive myocardial perfusion imaging by positron emission tomography (PET) combines high spatial resolution (down to secondary or tertiary coronary branches) with quantitative measures of rest and stress myocardial perfusion in absolute units to compute absolute coronary flow reserve (CFR). Quantitative myocardial perfusion by PET has an extensive and technically robust literature, with over 250 papers including almost 15,000 subjects in the past 25 years.

Furthermore, there is robust data demonstrating prognostic information obtained from stress myocardial perfusion imaging. However, as counterintuitive and antithetical to modern practice as it seems, there are no prospective studies demonstrating that mechanical revascularization on patients with moderate or high risk perfusion scans alters prognosis. In fact, the ongoing International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial seeks to determine this very question. This study seeks to determine the regional effects of mechanical revascularization on patients with abnormal cardiac PET stress tests who were referred to angiography.

3.0 Study Design and Population This is a prospective, single center study from the Ochsner Medical Center. Adult patients with a stress induced perfusion defect on myocardial PET scanning who undergo mechanical revascularization will be asked to undergo a subsequent myocardial PET scan after mechanical revascularization is completed. Socio-demographic data will also be collected from the participant's electronic medical record.

4.0 Study Procedures All participants eligible for inclusion will be identified and asked to enroll with a goal of 50 participants. All Individuals will have already had an initial cardiac PET stress test (PET 1) followed by mechanical revascularization as part of their routine medical care. Enrolled participants will then be asked to perform a second cardiac PET stress test (PET 2) within 12 weeks of their revascularization procedure(s). The stress agents, radiotracer and protocol of PET 1 and PET 2 will be identical and have been described in previous studies.

5.0 Measurements Baseline absolute coronary flow and CFR will be obtained for each major coronary artery territory \[left anterior descending (LAD), left circumflex (LCx), right coronary (RCA)\] using FDA-approved software. Vessels will be divided into two groups: 1) those in which the baseline perfusion defect matched the revascularized territory and 2) those in which there was no baseline defect in the revascularized territory. The change in pre-vascularization and post-vascularization myocardial blood flow will be compared between the two groups. Chart review and participant interviews will include patient demographics, complete medical history, physical examination, laboratory data, 12-lead electrocardiogram (ECG), Canadian Cardiovascular Society grading of angina pectoris, and procedure reports for LHC and revascularization procedures.

6.0 Statistical Analysis Paired t-test of the average change in absolute myocardial flow between the matched and unmatched revascularized territories will be performed using SPSS software. Participant groups will be compared using Student's t-test (for normally distributed variable) or Wilcoxon's rank-sum test (for other variables) for continuous variables and the X2 test or Fisher's exact test for categorical variables. A P value of less than 0.05 will be considered statistically significant. Multiple logistic regressions will be used to determine the association between revascularization and sMBF.

7.0 Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants or Others This study deviates from standard of care in that one additional, not clinically indicated PET stress test, will be performed soon after mechanical revascularization. Adverse events or unanticipated problems will be reported to Robert Bober, MD or Fahad Javed, MD at 504-842-2420 and the Internal Review Board as directed by Ochsner Medical Center IRB rules and regulations. Furthermore, after the first 25 patients have completed PET 2, review of adverse events and unanticipated problems will be reviewed by a safety monitoring committee comprised of 3 cardiologists who are not involved with study.

8.0 Radiation Risks Participants who enroll in the study will receive additional ionizing radiation. The effective dose of a cardiac PET scan is 5mSV or less. This is about 1/10 or 10% of the occupational exposure allowed for a radiation worker. This is also about twice the annual amount of natural background radiation exposure.

9.0 Study Withdrawal/Discontinuation Participants opting to withdraw from the study will not have the PET 2 performed.

10.0 Privacy/Confidentiality Issues All hard copies of participant data will be kept securely the PET department where only PET and research staff has access. All PET workstations are encrypted and password protected. All participant data and PET results will be de-identified of individual health information.

11.0 Follow-up and Record Retention This study is estimated to take approximately 9 months to obtain a total of 50 participants. Hard copies of PET scans are kept securely the PET department where only PET and research staff has access. The electronic PET data is encrypted and password protected. Only study personnel will have access to the files.

Eligibility criteria: Inclusion Criteria:

* Individuals who undergo cardiac stress PET and subsequently undergo coronary angiography and mechanical revascularization. Mechanical revascularization is defined as PCI and/or coronary artery bypass grafting (CABG).
* Adults ≥18 and able to give informed consent.

Exclusion Criteria:

* Individuals with acute ST-elevation myocardial infarction (\< 3 days)
* Individuals where absolute flow data is not available on the initial PET stress.
* Individuals who are unable to perform PET scanning secondary to hemodynamic instability.
* Individuals who are medically noncompliant with post revascularization drug therapy.
* Women who are pregnant at the time of PET2

Primary outcomes:
measure: Absolute Myocardial Flow (CC/Min/GM)
timeFrame: Within 12 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
Study officials:
affiliation: Ochsner Health System
name: Robert Bober, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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