Aim      To study the role of myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with heart failure with preserved ejection fraction (HFpEF) in stratifying the risk of HFpEF progression during 12 months of follow-up.Material and methods  The study included 58 patients with non-obstructive coronary artery disease and HFpEF. Concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using an enzyme-linked immunosorbent assay. MFR and MBF were determined by dynamic single-photon emission computed tomography of the myocardium.Results At 12 months, the patients were divided into two groups: group 1 (n=11) included patients with an unfavorable course of HFpEF, group 2 (n=47) included patients with a favorable course. A multivariate analysis showed that NT-proBNP concentrations (odds ratio (OR), 3.23; 95% confidence interval (CI), 1.76-6.78; p=0.008) and MFR (OR, 8.09; 95% CI, 5.12-19.98; p<0.001) were independent predictors of adverse outcomes. According to ROC analysis, values of MFR ≤1.62 (area under the curve (AUC)=0.827; p<0.001) and NT-proBNP ≥760.5 pg/ml (AUC=0.708; p=0.040) can be considered as markers for HFpEF progression. Furthermore, the combined measurement of NT-proBNP concentration and MFR had a higher prognostic significance (AUC, 0.954; p<0.001).Conclusion      Values of NT-proBNP and MFR can be used as noninvasive markers for an unfavorable course of HFpEF, and their combined measurement increases the prognostic significance.