By comparison, the Lauer score incorporates clinical vari- ables, which results in more effective classification of low- risk (,1% annual mortality rate) patients.248 3.2.2.5. Exercise Echocardiography and Exercise Nuclear MPI Evidence from thousands of patients evaluated in multiple large registries and clinical trials and meta-analyses confirm that a normal exercise echocardiogram or exercise nuclear MPI is associated with a very low risk of death due to cardiovascular causes or AMI.111,265,304 The extent and sever- ity of inducible abnormalities in wall motion or perfusion are directly correlated with the degree of risk. For nuclear MPI, reversible perfusion defects encompassing 10% of the myo- cardium (determined either semiquantitatively with summed scores or quantitatively) to assess defect extent and severity are considered moderately abnormal, and reversible perfusion defects encompassing $15% of the myocardium are consid- ered severely abnormal.277,305,306 Other findings also indica- tive of elevated risk include a reduction in reduced post-stress LVEF $5% or a global LVEF ,45%, transient ischemic LV dilation, increased lung or right ventricular uptake, or abnor- mal coronary reserve (detected on myocardial perfusion PET). For echocardiography, a wall motion abnormality extending beyond 2 to 3 segments as well as the presence of change in .1 coronary territory are suggestive of higher risk. For both tests, multiple defects in different coronary territo- ries with either moderately reduced perfusion (or $10% of the myocardium) or inducible wall motion abnormalities with transient ischemic dilatation are suggestive of severe CAD. Currently, the National Institutes of Health National Heart, Lung, and Blood Institute sponsored ISCHEMIA trial is under way and is comparing the effectiveness of a conserva- tive versus catheterization-based initial management strategy for patients with moderate severe ischemia. 