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. 2024 Apr;39(4):299-309.
doi: 10.1007/s00380-023-02356-4. Epub 2024 Feb 17.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Jorge Dahdal  1   2 , Frank Bakker  1 , Johan Svanerud  3 , Ibrahim Danad  4 , Roel S Driessen  1 , Pieter G Raijmakers  5 , Hendrik J Harms  6 , Adriaan A Lammertsma  5 , Tim P van de Hoef  4 , Yolande Appelman  1 , Niels van Royen  7 , Paul Knaapen  1 , Guus A de Waard  8
Affiliations

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Jorge Dahdal et al. Heart Vessels. 2024 Apr.

Abstract

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Keywords: FFR; NHPR; Positron emission tomography; RFR; dPR.

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Conflict of interest statement

The present work is a researcher-driven investigation, and neither of the authors nor the institutions involved have received any funding for this purpose. JS is the Chief Executive Officer of Coroventis and acted as an unsubsidized corelab for the analysis of dPR and RFR, while being blinded to any patient data, including angiograms, PET scans, hyperemic pressure traces, and FFR results. NvR and TvdH have received speaker fees and institutional research grants from Abbott and Philips. The remaining authors have no conflicts of interest or disclosures to report.

Figures

Fig. 1
Fig. 1
Results of [15O]H2O PET myocardial perfusion in hyperemia in a 75-year-old woman with suspected CAD. In the center, PET vessel-specific hyperemic myocardial blood flow, and myocardial perfusion reserve. Ischemic regional myocardial blood flow and perfusion reserve values were observed in the LAD territory, whilenormal perfusion was demostrated in the LCx territory. The patient had a normal perfusion during rest (not shown). In the left panel, the aortic and distal rest intracoronary pressure of the LAD are plotted. The yellow rectangle represents the period in which dPR is computed (ratio between the mean distal and the mean aortic pressure during the diastolic period). RFR is an immediate pressure ratio, the lowest during the whole cardiac cycle; represented by the dashed blue line (RFR is the average of this instantaneous ratio in 5 cardiac cycles). Abnormal results of dPR and RFR in LAD were concordant with results of the PET scan. The right panel shows a pressure recording for the LCx, with normal pressure ratios in this vessel. In the coronary angiogram the white asterisk highlights a severe proximal lesion of the LAD. PET Positron emission tomography, RFR resting full-cycle ratio, dPR diastolic pressure ratio, FFR fractional flow reserve, MBF myocardial blood flow, MPR myocardial perfusion reserve
Fig. 2
Fig. 2
Frequency distribution of the physiological indices and diameter of coronary stenoses (N = 136). Histograms of the distributions of A RFR, B dPR, C FFR, and D diameter stenoses. Only in vessels with ≥ 30% diameter stenosis. RFR resting full-cycle ratio, dPR diastolic pressure ratio, FFR fractional flow reserve
Fig. 3
Fig. 3
Correlation between physiologic indices and PET values, only stenoses included (N = 136). Scatter plots shows correlations between the different pressure indices and A–C PET hMBF and D–F MPR in stenoses group. Spearman’s rho reported in each graphic. PET Positron emission tomography, RFR resting full-cycle ratio, dPR diastolic pressure ratio, FFR fractional flow reserve
Fig. 4
Fig. 4
Diagnostic performance of physiological indices, only stenoses included (N = 136). Diagnostic performance of RFR, dPR, and FFR using A PET hMBF and B MPR as reference standards for regional myocardial ischemia in coronary stenoses. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy are reported with their respective 95% confidence interval. Cohen’s kappa coefficient is shown. Significance testing was performed between the test accuracy of each pressure indices; p values are shown only if < 0.05. PET Positron emission tomography, RFR resting full-cycle ratio, dPR diastolic pressure ratio, FFR fractional flow reserve, hMBF hyperemic myocardial blood flow, MPR myocardial perfusion reserve, PPV positive predictive value, NPV negative predictive value
Fig. 5
Fig. 5
ROC Analysis using PET-derived parameters as the reference standard, only stenosis included. A ROC curves for RFR, dPR, and FFR predicting PET hMBF in the stenoses group and their respective AUCs are presented. B ROC curves for physiological indices are shown using PET MPR as reference. ROC receiver operating characteristic, PET positron emission tomography, RFR full-cycle ratio, dPR diastolic pressure ratio, FFR fractional flow reserve, MBF myocardial blood flow, MPR myocardial perfusion reserve, AUC area under the curve. * There were non-significant differences between the ROC AUC values of the indices using on De Long Test (RFR vs dPR, p = 0.91; RFR vs FFR, p = 0.5; and dPR vs FFR, p = 0.56). ** There were non-significant differences between the ROC AUC values of the indices using on De Long Test (RFR vs dPR, p = 0.93; RFR vs FFR, p = 0.54; and dPR vs FFR, p = 0.59)
Fig. 6
Fig. 6
PET myocardial perfusion in FFR and NHPR subgroups. Boxplot represents the hMBF and the MPR in the different subgroups based on the pressure indices. Significance testing was performed between each subgroup; p values are shown only if < 0.05. PET Positron emission tomography, RFR resting full-cycle ratio, dPR diastolic pressure ratio, FFR fractional flow reserve, MBF myocardial blood flow, MPR myocardial perfusion reserve
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