When the data from 2 large multicenter registries, including a total of 3615 symptomatic patients, were com- bined, the estimated diagnostic sensitivity for the CAC score to predict obstructive CAD on invasive angiography was 85%, with a specificity of 75%.218 In a recent meta-analysis of 18 studies, which included 10 355 symptomatic patients, the presence of nonzero CAC score had a pooled sensitivity and specificity of 98% and 40%, respectively, for detection of significant CAD on invasive coronary angiography.174 Although the diagnostic sensitivity of CAC to detect obstructive CAD is fairly high, the frequency of false nega- tive exams (ie, significant CAD in the absence of CAC) is not well established. In small single-center studies, perfusion defects on nuclear MPI or high-grade coronary stenosis on coronary angiography can be present in 0% to 39% of symptomatic patients with a calcium score of zero.219 223 In the recent large, multicenter, CONFIRM (Coronary CT An- giography Evaluation For Clinical Outcomes: An Interna- tional Multicenter Registry) registry, CCTA showed mild, nonobstructive CAD in 13%, stenosis $50% in 3.5%, and stenosis $70% in 1.4% of the 10 037 symptomatic patients without known CAD who had a CAC score of zero.214 Documentation of obstructive CAD without CAC occurs more often in younger patients in whom atherosclerotic plaque has not advanced to the stage of calcification. Previous official documents from the AHA and ACCF218 concluded that patients considered to be at low risk of coronary disease by virtue of atypical cardiac symptoms may benefit from CAC testing to help in ruling out the presence of obstructive coronary disease 218 or that coronary calcium assessment may be reasonable for the assessment of symp- tomatic patients, especially in the setting of equivocal tread- mill or functional testing (Class IIb, LOE: B). 