The diagnostic end- point of nuclear MPI is reduction in myocardial perfusion after stress. Nonperfusion high-risk markers include a mark- edly abnormal ECG, extensive stress-induced wall motion abnormalities, reduced post-stress left ventricular ejection fraction (LVEF) $5% or global LVEF (rest or post-stress) ,45%, transient ischemic LV dilation, increased lung or right ventricular uptake, or abnormal coronary flow reserve with myocardial perfusion PET.183 186 The diagnostic accuracy for detection of obstructive CAD of exercise and pharmacological stress nuclear MPI has been studied extensively in multiple meta-analyses, systematic reviews, RCTs, and large, multicenter, observational regis- tries.91,114,132,147,148,152,155,156,175 From these reports, the uncor- rected diagnostic sensitivity ranged from 82% to 88% for exercise and 88% to 91% for pharmacological stress nuclear MPI. The uncorrected diagnostic specificity ranged from 70% to 88% and 75% to 90% for exercise and pharmacological stress nuclear MPI, respectively. Diagnostic image quality is affected in obese patients, as well as in women and men with large breasts. Reductions in breast tissue artifact have been reported with the use of the Tc-99m agents as well as with attenuation-correction algo- rithms or prone imaging.187 190 For myocardial perfusion SPECT, global reductions in myocardial perfusion, such as in the setting of left main or 3-vessel CAD, can result in balanced reduction and an underestimation of ischemic burden. Myocardial perfusion PET is characterized by high spatial resolution of the photon attenuation corrected images with Rubidium or 13 N-ammonia used as myocardial blood flow tracers. Although less well studied than myocardial perfusion SPECT, a meta-analysis of 19 studies suggests that PET has a slightly higher (uncorrected) sensitivity for detection of CAD,191,192 including in women and obese patients.193 2.2.3.4. Pharmacological Stress CMR Wall Motion/Perfusion In recent years, more centers have used pharmacological stress CMR in the diagnostic evaluation of SIHD patients. 