BackgroundDespite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients.MethodsThe study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina.ResultsDuring a median follow-up of 15 months (interquartile range (IQR) 11–20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) (\documentclass[12pt]{minimal}
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				\begin{document}$$p<0.001$$\end{document}p<0.001) and coronary flow reserve (CFR) (\documentclass[12pt]{minimal}
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				\begin{document}$$p<0.001$$\end{document}p<0.001) were significantly lower in the MACE group. Optimal thresholds of sMBF<3.16 and CFR<2.52 were extracted from the ROC curves, and both impaired sMBF (HR: 15.08; 95% CI 2.95–77.07;\documentclass[12pt]{minimal}
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				\begin{document}$$p=0.001$$\end{document}p=0.001) and CFR (HR: 6.51; 95% CI 1.43–29.65;\documentclass[12pt]{minimal}
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				\begin{document}$$p=0.01$$\end{document}p=0.01) were identified as prognostic factors for MACEs. Only sMBF<3.16 (HR: 11.20; 95% CI 2.04–61.41;\documentclass[12pt]{minimal}
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				\begin{document}$$p=0.005$$\end{document}p=0.005) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06,\documentclass[12pt]{minimal}
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				\begin{document}$$p=0.02$$\end{document}p=0.02; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10).ConclusionThe preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00259-023-06125-3.