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Objective: The objective of the study was to evaluate the prognostic role of myocardial flow reserve (MFR) and myocardial blood flow (MBF) estimates obtained with dynamic cadmium-zinc-telluride (CZT) imaging in the development and progression of heart failure with preserved ejection fraction (HFpEF) in patients with nonobstructive coronary artery disease (CAD) during a 12-month follow-up period., Patients and Methods: A total of 112 patients (70 men; median age of 62.5 [57.0; 69.0] years) with nonobstructive coronary artery disease were enrolled in the study. Dynamic CZT-SPECT, echocardiography, and coronary CT angiography studies were performed baseline., Results: Distribution of patients was performed by adverse events: group 1 comprised patients with adverse outcomes (n = 25), and group 2 comprised those without it (n = 87). Based on receiver operating characteristic analysis, the levels of MFR ≤1.62 (area under the curve [AUС], 0.884; Р < 0.001), stress-MBF ≤1.35 mL/min per gram (AUС, 0.750; Р < 0.001), and NT-proBNP ≥760.5 pg/mL (AUС, 0.764; Р = 0.001) were identified as cutoff values to predict adverse outcomes. Univariate analysis revealed that type 2 diabetes mellitus ( P = 0.044), the levels of MFR ≤1.62 ( P = 0.014), stress-MBF ≤1.35 mL/min per gram ( P = 0.012), NT-proBNP ≥760.5 pg/mL ( P = 0.018), and diastolic dysfunction ( P = 0.009) were potential risk factors for the development and progression of HFpEF. Multivariate analysis demonstrated that the values of NT-proBNP ≥760.5 pg/mL (odds ratio, 1.87; 95% confidence interval, 1.17-3.62; P = 0.027) and MFR ≤1.62 (odds ratio, 2.801; 95% confidence interval, 1.19-6.55; P = 0.018) were independent predictors of adverse outcomes., Conclusions: Our data suggest that reduced MFR ≤1.62 obtained with dynamic CZT imaging and overexpression of NT-proBNP ≥760.5 pg/mL can individuate patients at high risk of development and progression of HFpEF during a 12-month follow-up period, independently of baseline clinical parameters and imaging variables., Competing Interests: Conflicts of interest and sources of funding: This study was funded by the grant from the President of the Russian Federation (MK-4257.2022.3). The authors have no conflicts to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)