High-risk coronary artery disease, but normal myocardial perfusion: A matter of concern?

Abstract

Use of non-invasive cardiac imaging is recommended in numerous clinical scenarios in order to provide diagnostic and prognostic information to guide clinical decision making. Stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is well validated and has proven value in identifying patients at high risk of a serious cardiac event, whereas a normal MPI study confers a benign prognosis with a low annual serious cardiac event rate of 0.6% per year. However, there has always been concern that MPI can miss high-risk coronary artery disease (CAD) as in patients with balanced ischemia due to flow-limiting three-vessel CAD or left main stenosis, while this group is particularly prone to adverse cardiac events and may have benefit of revascularization. In the current issue of the journal, Nakanishi et al studied the prevalence and predictors of high-risk CAD in patients with normal MPI. Subsequent invasive coronary angiography was performed within 60 days after normal MPI in 580 patients in two centers. High-risk CAD was defined as 3 vessels with C70% stenosis, 2 vessels with C70% stenosis including proximal left anterior descending, or left main with C50% stenosis. Overall, 36% in this highly selected group of patients had evidence of anatomically obstructive CAD, with high-risk CAD in 7.2% of all patients. Predictors for high-risk CAD were the presence of mild/equivocal perfusion defects, transient ischemic left ventricle dilatation or abnormal ejection fraction, and a pre-test probability ofC66%. AlthoughMPI can miss both high-risk CAD and stenoses in small coronary arteries, the charm of the paper by Nakanishi et al is that they focused on high-risk CAD.Although their number of false-negative MPI with 7.2% of patients high-risk CAD is impressive, it should be realized that these 42 patients are selected from a total of 25,698 patients with normal MPI (0.16%). Moreover, since the angiographic presence of high-risk CAD in their study was not proven by fractional flow reserve (FFR) measurements, probably a substantial part of these stenoses was functionally not significant. Several previous studies suggested that MPI may underestimate high-risk CAD in selected patients. Berman et al demonstrated in 101 patients with proven left main stenosis (by invasive angiography) that 13% had normal perfusion by visual analysis. Lima et al demonstrated similar findings for 143 patients with severe threevessel CAD, in which one-fifth had normal MPI results. There are several potential reasons for SPECT-MPI missing high-risk CAD. Visual analysis of MPI images provides information on relative rather than absolute perfusion for each myocardial region. Therefore, global but uniform reduction in coronary vasodilator reserve may result in a homogeneous decreased distribution of radiotracer, potentially leading to false-negative MPI results. Several other reasons for false-negative MPI findings include insufficient coronary vasodilatation due to unrecognized ingestion of caffeine-containing products, attenuation and motion artifacts and plateauing of myocardial tracer uptake at high flow rates. Finally, a false-negative MPI may be in fact not false negative, since invasive angiography, without functional measurement of the stenosis, may overestimate the functional severity.