To our knowledge, this is the first study analyzing the prognostic value of regional perfusion assessed by the CZT camera in predicting vessel-related events, in patients with suspected or known CAD and angiographic correlation. Our data highlight that regional ITPD is a significant predictor of vessel-related events. The prognostic significance of stress perfusion abnormalities assessed by the CZT camera in the prediction of adverse cardiac events has been extensively addressed. All published data confirmed that the presence of a normal scan is associated with a good outcome, whereas the degree of myocardial perfusion defect is a good predictor of cardiovascular events [
10‐
13]. Engbers et al. [
22] in 2017 demonstrated, in a very large cohort of 4057 patients with suspected CAD undergoing MPI with a CZT SPECT camera, that cardiovascular events occurred more in patients with abnormal than in those with normal MPI. Moreover, the events were more frequent along with the increase in the extension of reversible defects, as well as differences in terms of AER, were observed between small and large total perfusion defects. In a recent prospective registry of patients with suspected or known CAD [
23], it has been demonstrated that the extent of global stress perfusion abnormalities detected by CZT SPECT had the best accuracy in predicting cardiovascular death and myocardial infarction. In particular, a summed stress score of >8 was a strong predictor of future adverse events, and the presence of ischemia involving > 10% of the myocardium was also associated with all-cause death and late revascularization. Similarly, Lima et al. [
11] demonstrated that in 2930 patients with known or suspected CAD, the event rates were higher in patients showing greater extension of perfusion defects and ischemia. Accordingly, in our study population, patients experiencing cardiovascular events during the follow-up had a greater extent and severity of myocardial perfusion abnormalities. In our population, LVEF was not associated with events, data explained by the relatively normal values of LVEF in our study cohort. While previous studies [
11,
23] outlined the prognostic value of myocardial perfusion abnormalities assessed by CZT cameras, no studies performed a regional analysis evaluating the potential interplay between the perfusion results and angiographic findings. In the current study, we analyzed the role of the regional TPD automatically provided by the software. Our findings are not greatly different from those reported by Gimelli et al. [
23], considering that TPD and ITPD are derived from summed stress and summed difference score, respectively. Our results demonstrate that both regional stress TPD and ITPD were significantly higher in vessels with vessel-related events compared to those without. In particular, we found that an ITPD threshold of 2.0% provided the best trade-off between sensitivity and specificity for identifying vessel-related events, and this threshold resulted in an independent predictor of a vessel-related event at multivariable analysis. A previous report [
24] investigated the relationship between the prognostic value of CZT MPI and the presence of obstructive CAD on coronary angiography, demonstrating that patients with abnormal MPI findings and no obstructive CAD showed similar prognosis to patients with obstructive CAD and normal MPI. These per-patient results are consistent with our per-vessel analysis in which vessels with CAD < 50% and ITPD ≥ 2.0% had similar AER as compared to vessels with CAD ≥ 50% and ITPD < 2.0%. However, in our study, the presence of ITPD ≥ 2.0% even in absence of significant CAD was associated with a higher AER and a lower event-free survival as compared to vessels with ITPD < 2.0%. Similar results were found using PET/CT by Zampella et al. [
25] in a recent study evaluating the prognostic role of ITPD in predicting lesion-related outcomes in patients with suspected CAD. The combined evaluation of multiple parameters derived from MPI such as regional coronary atherosclerosis and vascular function showed incremental value in predicting the occurrence of lesion-related events in the presence of significant CAD. Accordingly, in our study, it emerged that by combining anatomic information from coronary angiography with MPI findings, a better risk stratification can be provided. Thus, the potential integration of multiple parameters to optimize risk stratification of patients with these noninvasive techniques is desirable to increase the usefulness of regional assessment for prognostic evaluation of patients with suspected or known CAD.