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Despite some caveats: a normal myocardial perfusion result is still a strong value!

A normal myocardial perfusion [single photon emission computed tomography (SPECT)] (MPS) is consistent with a low probability of haemodynamically relevant coronary stenosis, an excellent prognosis, and a warranty period of up to 2 years. These facts have been demonstrated extensively in thousands of patients. However, we all know the sobering effect of disappointment when a patient with normal myocardial perfusion is diagnosed with severe triple vessel disease. In these cases, we are going back to see if we have missed anything, if the stress test was really adequate, if the perfusion was absolutely normal, and if there were any discordant findings besides the perfusion findings (typical angina during the stress test, ischaemic electrocardiogram (ECG) changes, transient ischaemic dilation, and increased tracer uptake in the lungs). Yokota et al. describe 133 patients who had normal perfusion findings on MPS but had persistent or worsening chest pain after the test. They underwent subsequent coronary angiography and fractional flow reserve (FFR) testing. These 133 (2%) patients are part of 6603 consecutive patients who had normal perfusion on MPS and underwent the evaluation at the Isala Hospital, Zwolle, in the Netherlands between 2009 and 2014. Of these 6603 patients, only 47 (0.7%) had lesions with an FFR <_ 0.80 and therefore were haemodynamically relevant. The authors conclude, that in selected patients with normal MPS and persistent angina complaints, the prevalence of functionally relevant coronary artery disease (CAD) is very low. These low rates of relevant CAD in patients with normal MPS in patients with chest pain are reassuring, especially in the era in which we often use complimentary information of anatomic and functional testing. How to deal with a normal perfusion and a high calcium score? How to deal with normal perfusion and an obvious stenosis on coronary computed tomography angiography? We still have to learn how to best integrate and weight all the information and variables that may be provided by a contemporary (hybrid) test: pre-test likelihood of CAD, historical and stress test variables, calcium score, coronary computed tomography angiography findings, myocardial perfusion, myocardial blood flow, and ejection fraction. In the current study, it would have been useful to know the baseline characteristics of all 6603 patients with normal MPS and to compare the patients with vs. without persistent symptoms. However, as mentioned by the authors, the lack of this information is one of the several limitations of the study. In addition, the patient group with relevant stenosis is very small (n = 22). As a consequence, the power to detect differences between patients with vs. without relevant stenosis is too low. But still, looking at potential discordant findings, one might think to recognize some hints or slight differences between these groups (Table 1 in the paper of Yokota et al.): patients with relevant stenosis ‘tended’ (in part far away from statistical significance) to have a higher pre-test probability of CAD, to have more often typical angina, ischaemic ECG changes during the stress test, and to have higher calcium scores than patients without relevant stenosis. Ischaemic ECG—changes during physical stress testing in patients with normal perfusion seem to have some prognostic relevance, since the magnitude of ST-depression was a predictor of the composite endpoint of cardiac death, myocardial infarction (MI), or revascularization in a large study of almost 5000 patients. These patients had an intermediate-risk treadmill score (including ST-segment depression in 45% of patients) but with normal perfusion images they were still at low risk for subsequent cardiac death. During pharmacologic stress, the relevance of ECG changes with ST depression is less clear. In a very recent meta-analysis, the rate of cardiac death or MI was increased in patients with transient ischaemic dilation of the left ventricle and normal perfusion, primarily amongst patients with diabetes mellitus, known CAD, and ischaemia. If a coronary calcium score is available it can not only be used for prognostic but also diagnostic purposes. Absent coronary calcifications (calcium score = 0) are consistent with a negative predictive value of 99.5% to exclude coronary stenosis. Normal myocardial perfusion and absent coronary calcium are therefore