Search

Background: The applicability of quantitative flow ratio (QFR), a nonhyperemic, invasive coronary angiography-derived computation of fractional flow reserve (FFR), has not been studied in coronary artery bypass grafts. We sought to explore the correlation and diagnostic agreement between QFR and FFR in saphenous vein grafts (SVGs)., Methods and Results: A total of 129 prospectively included patients (mean age 73±8 years, 84% male) with prior coronary artery bypass grafting underwent invasive coronary angiography and pressure-derived functional assessment in 150 nonoccluded SVGs. QFR dedicated angiography images of the SVGs were acquired and used for offline QFR computation. The diagnostic performance of QFR was compared with 2-dimensional quantitative coronary angiography, using FFR as a reference. A threshold of ≤0.80 was used to define functional significance. QFR was successfully computed in 140 (93%) SVGs. We found a significant correlation between QFR and FFR (r=0.72, P <0.001). FFR indicated significant disease in 43 (31%) SVGs, whereas QFR analysis showed significant lesions in 53 (38%) bypass grafts. QFR exhibited a higher sensitivity and diagnostic accuracy compared with angiographic lesion assessment (84% versus 63%, P =0.030 and 83% versus 74%, P =0.036, respectively), whereas specificity did not differ (82% versus 79%, P =0.466). Lastly, QFR demonstrated a higher area under the receiver operating curve than quantitative coronary angiography (0.90 versus 0.82, P =0.008) for the detection of FFR-defined significant vein graft disease., Conclusions: This study shows the potential applicability of contemporary QFR computation in venous bypass grafts with a moderate correlation and good diagnostic accuracy compared with functional assessment using FFR.

Background: Fractional flow reserve (FFR) has emerged as the invasive gold standard for assessing vessel-specific ischemia. However, FFR measurements are influenced by the hydrostatic effect, which might adversely impact the assessment of ischemia., Aims: This study aimed to investigate the impact of hydrostatic pressure on FFR measurements by correcting for the height and comparing FFR with [ 15 O]H 2 O positron emission tomography (PET)-derived relative flow reserve (RFR)., Methods: The 206 patients were included in this analysis. Patients underwent coronary computed tomography angiography (CCTA), [ 15 O]H 2 O PET, and invasive coronary angiography with routine FFR in every epicardial artery. Height differences between the aortic guiding catheter and distal pressure sensor were quantified on CCTA images. An FFR ≤ 0.80 was considered significant., Results: The study found a reclassification in 7% of the coronary arteries. Notably, 11% of left anterior descending (LAD) arteries were reclassified from hemodynamically significant to nonsignificant. Conversely, 6% of left circumflex (Cx) arteries were reclassified from nonsignificant to significant. After correcting for the hydrostatic pressure effect, the correlation between FFR and PET-derived RFR increased significantly from r = 0.720 to r = 0.786 (p = 0.009). The average magnitude of correction was +0.05 FFR units in the LAD, -0.03 in the Cx, and -0.02 in the right coronary artery., Conclusion: Hydrostatic pressure has a small but clinically relevant influence on FFR measurements obtained with a pressure wire. Correcting for this hydrostatic error significantly enhances the correlation between FFR and PET-derived RFR., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs., Objectives: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCT ISCHEMIA ) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE)., Methods: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed. In both studies, symptomatic patients with suspected stable coronary artery disease had prospectively undergone coronary computed tomography angiography (CTA), myocardial perfusion imaging (MPI), SPECT, or PET, fractional flow reserve by CT (FFR CT ), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCT ISCHEMIA model was developed in the derivation cohort of the CREDENCE study, and its diagnostic performance for coronary ischemia (FFR ≤0.80) was evaluated in the CREDENCE validation cohort and PACIFIC-1. Its prognostic value was investigated in PACIFIC-1., Results: In CREDENCE validation (n = 305, age 64.4 ± 9.8 years, 210 [69%] male), the diagnostic performance by area under the receiver-operating characteristics curve (AUC) on per-patient level was 0.80 (95% CI: 0.75-0.85) for AI-QCT ISCHEMIA , 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFR CT , and 0.65 (95% CI: 0.59-0.71; P < 0.001) for MPI. In PACIFIC-1 (n = 208, age 58.1 ± 8.7 years, 132 [63%] male), the AUCs were 0.85 (95% CI: 0.79-0.91) for AI-QCT ISCHEMIA , 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFR CT , 0.89 (95% CI: 0.84-0.93; P = 0.262) for PET, and 0.72 (95% CI: 0.67-0.78; P < 0.001) for SPECT. Adjusted for clinical risk factors and coronary CTA-determined obstructive stenosis, a positive AI-QCT ISCHEMIA test was associated with aHR: 7.6 (95% CI: 1.2-47.0; P = 0.030) for MACE., Conclusions: This newly developed coronary CTA-based ischemia model using coronary atherosclerosis and vascular morphology characteristics accurately diagnoses coronary ischemia by invasive FFR and provides robust prognostic utility for MACE beyond presence of stenosis., Competing Interests: Funding Support and Author Disclosures This project has been supported by the Foundation “De Drie Lichten” in the Netherlands. Dr Nurmohamed has received grants from the Dutch Heart Foundation (Dekker 03-007-2023-0068) and grants from the European Atherosclerosis Society (2023); and is co-founder of Lipid Tools. Mr Wang, Dr Chan, Ms Crabtree, Ms Aquino, Dr Min, and Dr Earls are employees of Cleerly Inc. Dr Choi has received grant support from GW Heart and Vascular Institute; equity in Cleerly, Inc; and has received consulting fees from Siemens Healthineers. Dr Knaapen has received research grants from HeartFlow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Microvascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI)., Methods: In this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [ 15 O]H 2 O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR., Results: Among 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19)., Conclusions: Our study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In patients evaluated for obstructive coronary artery disease (CAD), guidelines recommend using either fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. This study compared [ 15 O]H 2 O PET-derived absolute myocardial perfusion between vessels with concordant and discordant FFR and iFR measurements. Methods: We included 197 patients suspected of obstructive CAD who had undergone [ 15 O]H 2 O PET perfusion imaging and combined FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF, and coronary flow reserve (CFR) were compared among 4 groups: FFR low/iFR low ( n = 79), FFR high/iFR low ( n = 22), FFR low/iFR high ( n = 22), and FFR high/iFR high ( n = 345). Predefined [ 15 O]H 2 O PET thresholds for ischemia were 2.3 mL·min -1 ·g -1 or less for hyperemic MBF and 2.5 or less for CFR. Results: Hyperemic MBF was lower in the concordant low (2.09 ± 0.67 mL·min -1 ·g -1 ), FFR high/iFR low (2.41 ± 0.80 mL·min -1 ·g -1 ), and FFR low/iFR high (2.40 ± 0.69 mL·min -1 ·g -1 ) groups compared with the concordant high group (2.91 ± 0.84 mL·min -1 ·g -1 ) ( P < 0.001, P = 0.004, and P < 0.001, respectively). A lower CFR was observed in the concordant low (2.37 ± 0.76) and FFR high/iFR low (2.64 ± 0.84) groups compared with the concordant high group (3.35 ± 1.07, P < 0.01 for both). However, for vessels with either low FFR or low iFR, quantitative hyperemic MBF and CFR values exceeded the ischemic threshold in 38% and 49%, respectively. In addition, resting MBF exhibited a negative correlation with iFR ( P < 0.001) and was associated with FFR low/iFR high discordance compared with concordant low FFR/low iFR measurements, independent of clinical and angiographic characteristics, as well as hyperemic MBF (odds ratio [OR], 0.41; 95% CI, 0.26-0.65; P < 0.001). Conclusion: We found reduced myocardial perfusion in vessels with concordant low and discordant FFR/iFR measurements. However, FFR/iFR combinations often inaccurately classified vessels as either ischemic or nonischemic when compared with hyperemic MBF and CFR. Furthermore, a lower resting MBF was associated with a higher iFR and the occurrence of FFR low/iFR high discordance. Our study showed that although combined FFR/iFR assessment can be useful to estimate the hemodynamic significance of coronary lesions, these pressure-derived indices provide a limited approximation of [ 15 O]H 2 O PET-derived quantitative myocardial perfusion as the physiologic standard of CAD severity., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Aims: In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD), ischaemia detection by myocardial perfusion imaging (MPI) and an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR) in patients with prior CAD [previous percutaneous coronary intervention (PCI) and/or myocardial infarction (MI)]., Methods and Results: This PACIFIC-2 sub-study evaluated 189 CCS patients with prior CAD for inclusion. Patients underwent SPECT, PET, and CMR followed by invasive coronary angiography with fractional flow reserve (FFR) measurements of all major coronary arteries (N = 567), except for vessels with a sub-total or chronic total occlusion. Quantitative flow ratio computation was attempted in 488 (86%) vessels with measured FFR available (FFR ≤0.80 defined haemodynamically significant CAD). Quantitative flow ratio analysis was successful in 334 (68%) vessels among 166 patients and demonstrated a higher accuracy (84%) and sensitivity (72%) compared with SPECT (66%, P < 0.001 and 46%, P = 0.001), PET (65%, P < 0.001 and 58%, P = 0.032), and CMR (72%, P < 0.001 and 33%, P < 0.001). The specificity of QFR (87%) was similar to that of CMR (83%, P = 0.123) but higher than that of SPECT (71%, P < 0.001) and PET (67%, P < 0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, P < 0.001), PET (0.66, P < 0.001), and CMR (0.60, P < 0.001)., Conclusion: QFR correlated better with FFR in patients with prior CAD than MPI, as reflected in the higher diagnostic performance measures for detecting FFR-defined, vessel-specific, significant CAD., Competing Interests: Conflict of interests: J.H.R., R.A.K., and J.T. are employees of Medis Medical Imaging. J.K. received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, and Merck. P.K. received research grants from HeartFlow Inc. All others have no conflict of interests to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue., Methods: Symptomatic patients underwent [ 15 O]H 2 O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement., Results: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase., Conclusions: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase., (© 2023. The Author(s).)

Aims: Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease (CAD). This study evaluated the effects of revascularization on CFC as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging., Methods and Results: A total of 314 patients with stable CAD underwent [15O]H2O PET imaging at baseline and after myocardial revascularization to assess changes in hMBF, CFR, and CFC in 415 revascularized vessels. Using thresholds for ischaemia and normal perfusion, vessels were stratified in five CFC categories: myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC, and normal flow. Additionally, the association between CFC increase and the composite endpoint of death and non-fatal myocardial infarction (MI) was studied. Vessel-specific CFC improved after revascularization (P < 0.01). Furthermore, baseline CFC was an independent predictor of CFC increase (P < 0.01). The largest changes in ΔhMBF (0.90 ± 0.74, 0.93 ± 0.65, 0.79 ± 0.74, 0.48 ± 0.61, and 0.29 ± 0.66 mL/min/g) and ΔCFR (1.01 ± 0.88, 0.99 ± 0.69, 0.87 ± 0.88, 0.66 ± 0.91, and -0.01 ± 1.06) were observed in vessels with lower baseline CFC (P < 0.01 for both). During a median follow-up of 3.5 (95% CI 3.1-3.9) years, an increase in CFC was independently associated with lower rates of death and non-fatal MI (HR 0.43, 95% CI 0.19-0.98, P = 0.04)., Conclusion: Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: In this study, we investigated whether increased renin angiotensin aldosterone system (RAAS) activation and endothelin-1 levels are related to coronary artery calcium (CAC) score, total plaque volume (TPV), high risk plaque, hyperemic myocardial blood flow (MBF) and coronary microvascular dysfunction (CMD)., Methods: In a prospective, observational, cross-sectional cohort, renin as a marker for RAAS activation and endothelin-1 were measured in peripheral venous blood of 205 patients (64% men; age 58 ± 8.7 years) with suspected coronary artery disease (CAD) who underwent coronary computed tomography angiography (CCTA), [ 15 O]H 2 O positron emission tomography (PET) perfusion imaging and invasive fractional flow reserve (FFR) measurements. Patients were categorized into three groups based on FFR (≤0.80) and hyperemic MBF <2.3 ml/min/g: [1] obstructive CAD (n = 92), [2] CMD (n = 26) or [3] no or non-obstructive CAD (n = 85)., Results: After correction for baseline characteristics, including RAAS inhibiting therapy, renin associated positively with CAC score and TPV, but not with hyperemic MBF (p < 0.01; p = 0.02 and p = 0.23). Patients with high risk plaque displayed higher levels of renin (mean logarithmic renin 1.25 ± 0.43 vs. 1.12 ± 0.35 pg/ml; p = 0.04), but not endothelin-1. Compared to no or non-obstructive CAD patients, renin was significantly elevated in obstructive CAD patients but not in CMD patients (mean logarithmic renin 1.06 ± 0.34 vs. 1.23 ± 0.36; p < 0.01 and 1.06 ± 0.34 vs. 1.16 ± 0.41 pg/ml; p = 0.65). Endothelin-1 did not differ between the three patient groups., Conclusions: Our report provides evidence that RAAS activity measured by renin concentration is elevated in patients with coronary atherosclerosis and high risk plaque but not in patients with CMD, whereas endothelin-1 is not related to either., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Quantitative flow ratio (QFR) computes fractional flow reserve (FFR) based on invasive coronary angiography (ICA). Residual QFR estimates post-percutaneous coronary intervention (PCI) FFR. This study sought to assess the relationship of residual QFR with post-PCI FFR., Methods: Residual QFR analysis, using pre-PCI ICA, was attempted in 159 vessels with post-PCI FFR. QFR lesion location was matched with the PCI location to simulate the performed intervention and allow computation of residual QFR. A post-PCI FFR < 0.90 was used to define a suboptimal PCI result., Results: Residual QFR computation was successful in 128 (81%) vessels. Median residual QFR was higher than post-PCI FFR (0.96 Q1-Q3: 0.91-0.99 vs. 0.91 Q1-Q3: 0.86-0.96, p < 0.001). A significant correlation and agreement were observed between residual QFR and post-PCI FFR ( R  = 0.56 and intraclass correlation coefficient = 0.47, p < 0.001 for both). Following PCI, an FFR < 0.90 was observed in 54 (42%) vessels. Specificity, positive predictive value, sensitivity, and negative predictive value of residual QFR for assessment of the PCI result were 96% (95% confidence interval (CI): 87-99%), 89% (95% CI: 72-96%), 44% (95% CI: 31-59%), and 70% (95% CI: 65-75%), respectively. Residual QFR had an accuracy of 74% (95% CI: 66-82%) and an area under the receiver operating characteristic curve of 0.79 (95% CI: 0.71-0.86)., Conclusions: A significant correlation and agreement between residual QFR and post-PCI FFR were observed. Residual QFR ≥ 0.90 did not necessarily commensurate with a satisfactory PCI (post-PCI FFR ≥ 0.90). In contrast, residual QFR exhibited a high specificity for prediction of a suboptimal PCI result., Competing Interests: Dr. Knaapen has received research grants from HeartFlow. All other authors declare that they have no conflicts of interest., (Copyright © 2021 Pepijn A. van Diemen et al.)