Perfusion Measurements of the Myocardium

Cardiovascular disease is the leading cause of mortality in the USA, with coronary artery disease (CAD) accounting for about half of these deaths. While invasive coronary angiography (ICA) is considered by most people to be the gold standard for the diagnosis of CAD, noninvasive testing is often the initial approach. In many cases an examination to detect physiologic evidence of coronary ischemia is chosen as such tests, having less risk of morbidity and mortality than ICA, more accurately depict the functional significance of any CAD that might be present. Among the common tests chosen is stress radionuclide myocardial perfusion imaging (MPI) , using either single photon emission computed tomography with a 201Tl-or a 99mTc-based (sestamibi or tetrofosmin) radiopharmaceutical or positron emission tomography (PET) that uses either 82Rb or 13N-ammonia. The basic principle by which MPI assesses CAD is by evaluating heterogeneity and homogeneity of coronary flow reserve. Through complex mechanisms involving physical forces, autonomic neural tone, circulating catecholamines, chemical mediators, myocardial metabolites, and other factors, there is tight autoregulation of coronary blood flow that matches blood supply to myocardial oxygen demand, with the normal autoregulation impaired in the setting of atherosclerotic disease. While arterial narrowing can often be compensated for at rest through these autoregulatory mechanisms, with application of “stress” through exercise, positive inotropic agents, or coronary arterial vasodilating agents, the ability to augment coronary blood flow is measured. As myocardial perfusion tracers are identified from nature or artificially designed to be taken up by myocytes in proportion to coronary blood flow, distribution of nuclear gamma or PET camera detected radiotracer counts in the different myocardial walls represents the homogeneity or heterogeneity of coronary blood flow to myocytes that have sufficient structural integrity and metabolic activity to take up and retain tracer. The diagnostic accuracy of radionuclide MPI in relation to ICA detected anatomic stenoses is high, with a sensitivity of 87–89 %, a specificity of 73–75 % (ranges related to mode of stress), and a normalcy rate of 91 %. Accuracy is further improving with increased use of PET and with techniques that can overcome artifacts such as attenuation correction. The introduction of new tracers, such as 18F-flurpiridaz – a PET tracer under phase III investigation – promises even better images and accuracy. Recent developments to assess quantitative blood flow – coronary flow reserve and absolute blood flow in ml/min/g – will further improve the diagnostic accuracy and clinical utility of MPI, including the ability to overcome false-negative MPI images in the setting of balanced ischemia and by identifying earlier disease. Perhaps more important has been the consistently shown robust ability of radionuclide MPI to risk stratify patients such that lower risk patients who require only medical therapy and risk factor reduction can be distinguished from those who might benefit from an invasive evaluation with revascularization. Ancillary data such as left ventricular (LV) function from ECG-gated SPECT further enhance diagnostic and prognostic capabilities. At the same time, it is recognized that complementary noninvasive imaging modalities can enhance radionuclide MPI. Cardiac MRI is a developing alternative imaging modality to assess coronary blood flow. The superior anatomic detail with MRI, including the potential to distinguish subendocardial versus subepicardial blood flow may, with hybrid PET/MRI cameras under development, complement radionuclide MPI and provide a more comprehensive evaluation of coronary blood flow in health and disease. Complementary multidetector CT technology can add further by providing assessment of plaque morphology. New nuclear camera technology promises to not only improve image quality but also to increase efficiency through markedly decreased procedure times that improve patient comfort and allow lower radiation exposure. Improving our ability to assess coronary perfusion with imaging should make a significant contribution to improving cardiovascular diagnostics by noninvasive means.