The Impact of Coronary Revascularization on Absolute Myocardial Blood Flow as Assessed by Stress Myocardial Positron Tomography

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.