Myocardial Blood Flow Reserve Research Articles

Determining Hemodynamically Significant Coronary Artery Disease: Patient-Specific Cutoffs in Quantitative Myocardial Blood Flow Using [15O]H2O PET Imaging

Determining Hemodynamically Significant Coronary Artery Disease: Patient-Specific Cutoffs in Quantitative Myocardial Blood Flow Using [¹⁵O]H₂O PET Imaging

Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

Association of cardiac mechanical dyssynchrony indices with data of dynamic single-photon emission computed tomography of the myocardium: the role of the time interval between the stress test and recording

Introduction. According to ECG-synchronized myocardial perfusion imaging (MPI) mechanical dyssynchrony (MD) is a sensitive marker of impaired myocardial perfusion. However, its direct comparison with indicators of myocardial blood flow reserve (MFR) according to single-photon emission computed tomography (SPECT) was not carried out. Traditional MPI protocols imply a long gap between stress test and image acquisition, during which stress-induced changes may pass. It is potentially possible to reduce the time interval down to 5 minutes.Aim: To investigate the relationship between early and delayed MD indices and the data of MFR by means of SPECT.Material and Methods. The study included 20 patients with suspected coronary heart disease, preserved left ventricular ejection fraction (&gt; 55%) and without obstructive coronary artery lesions (&lt; 50%) according to multislice computed coronary angiography. All patients underwent dynamic SPECT (dSPECT) according to a two-day rest/stress protocol. Gated MPI was performed 60 minutes after radiopharmaceutical administration. Myocardial blood flow and reserve, as well as phase histogram standard deviation (PSD, degree) and phase histogram bandwidth (HBW, degree) from 5 minutes after radiopharmaceutical administration were obtained from the dSPECT data by postprocessing. Perfusion data as well as MD indices (PSD, HBW) were obtained from delayed images. Based on dSPECT data, patients were divided into 2 groups: with preserved (MFR ≥ 2.0) and reduced (MFR &lt; 2.0) myocardial blood flow reserve.Results. Correlation analysis showed that MD indices on stress test in early scan had a stronger association with MFR (PSD ρ = –0.68, p &lt; 0.001; HBW ρ = –0.68, p = 0.001) compared to those in delayed scan (PSD ρ = –0.38, p = 0.019; HBW ρ = –0.44, p = 0.005). According to multivariate regression analysis, PSD on stress test at early scan was the only independent predictor of reduced MFR (OR 1.29 (1.1; 1.53)). Stress PSD &gt; 22° obtained at early scanning had a sensitivity of 81% and specificity of 87% (AUC = 0.86, p &lt; 0.001) in predicting of reduced MFR.Conclusion. Left ventricular mechanical dyssynchrony indices obtained by early post-stress gated MPI have a stronger association with myocardial blood flow reserve indices.

Comparing various AI approaches to traditional quantitative assessment of the myocardial perfusion in [82Rb] PET for MACE prediction

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [82\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{82}$$\\end{document}Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model (p<0.001\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p<0.001$$\\end{document}), where the best AUC of 73.9% (CI 72.5–75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3–74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE.

Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions

ObjectivesWe sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BackgroundCTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. MethodsA total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. ResultsThis study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). ConclusionsThe present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. Clinical perspectiveWhat is new?•CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization.•We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H2O PET imaging, whereas coronary flow reserve was comparable between sexes.•The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI.What are the clinical implications?•Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients.•These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes.•Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI.

Comparison of machine learning-based CT fractional flow reserve with cardiac MR perfusion mapping for ischemia diagnosis in stable coronary artery disease.

To compare the diagnostic performance of machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and cardiac magnetic resonance (MR) perfusion mapping for functional assessment of coronary stenosis. Between October 2020 and March 2022, consecutive participants with stable coronary artery disease (CAD) were prospectively enrolled and underwent coronary CTA, cardiac MR, and invasive fractional flow reserve (FFR) within 2weeks. Cardiac MR perfusion analysis was quantified by stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Hemodynamically significant stenosis was defined as FFR ≤ 0.8 or > 90% stenosis on invasive coronary angiography (ICA). The diagnostic performance of CT-FFR, MBF, and MPR was compared, using invasive FFR as a reference. The study protocol was completed in 110 participants (mean age, 62years ± 8; 73 men), and hemodynamically significant stenosis was detected in 36 (33%). Among the quantitative perfusion indices, MPR had the largest area under receiver operating characteristic curve (AUC) (0.90) for identifying hemodynamically significant stenosis, which is in comparison with ML-based CT-FFR on the vessel level (AUC 0.89, p = 0.71), with comparable sensitivity (89% vs 79%, p = 0.20), specificity (87% vs 84%, p = 0.48), and accuracy (88% vs 83%, p = 0.24). However, MPR outperformed ML-based CT-FFR on the patient level (AUC 0.96 vs 0.86, p = 0.03), with improved specificity (95% vs 82%, p = 0.01) and accuracy (95% vs 81%, p < 0.01). ML-based CT-FFR and quantitative cardiac MR showed comparable diagnostic performance in detecting vessel-specific hemodynamically significant stenosis, whereas quantitative perfusion mapping had a favorable performance in per-patient analysis. ML-based CT-FFR and MPR derived from cardiac MR performed well in diagnosing vessel-specific hemodynamically significant stenosis, both of which showed no statistical discrepancy with each other. • Both machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and quantitative perfusion cardiac MR performed well in the detection of hemodynamically significant stenosis. • Compared with stress myocardial blood flow (MBF) from quantitative perfusion cardiac MR, myocardial perfusion reserve (MPR) provided higher diagnostic performance for detecting hemodynamically significant coronary artery stenosis. • ML-based CT-FFR and MPR from quantitative cardiac MR perfusion yielded similar diagnostic performance in assessing vessel-specific hemodynamically significant stenosis, whereas MPR had a favorable performance in per-patient analysis.

Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated cadmium zinc telluride single photon emission computed tomography

BackgroundIt is clinically needed to explore a more efficient imaging protocol for single photon emission computed tomography (SPECT) myocardial blood flow (MBF) quantitation derived from cadmium zinc telluride (CZT) SPECT camera for the routine clinical utilization. MethodsOne hundred and twenty patients with matched clinical characteristics and angiographic findings who completed one-day rest/stress SPECT imaging with either the intermittently sequential imaging (ISI) protocol (two dynamic and two electrocardiography (ECG)-gated scans) or the continuous rapid imaging (CRI) protocol (two dynamic/ECG-gated scans) were included. MBF quantitation adopted residual activity correction (RAC) to correct for rest residual activity (RRA) in the stress dynamic SPECT scan for the detection of flow-limited coronary artery disease. ResultsThe CRI protocol reduced about 6.2 times shorter than the ISI protocol (25.5 min vs 157.6 min), but slightly higher than the RRA (26.7% ± 3.6% vs 22.3% ± 4.9%). With RAC, both protocols demonstrated close stress MBF (2.18 ± 1.13 vs 2.05 ± 1.10, P > 0.05) and myocardial flow reserve (MFR) (2.42 ± 1.05 vs 2.48 ± 1.11, P > 0.05) to deliver comparable diagnostic performance (sensitivity = 82.1%–92.3%, specificity = 81.2%–91.2%). Myocardial perfusion and left ventricular function overall showed no significant difference (all P > 0.26). ConclusionOne-day rest/stress SPECT with the CRI protocol and rest RAC is feasible to warrant the diagnostic performance of MBF quantitation with a shortened examination time and enhanced patient comfort. Further evaluation on the impact of extracardiac activity to regional MBF and perfusion pattern is required. Additional evaluation is needed in a patient population that is typical of those referred for SPECT MPI, including those with known or suspected coronary microvascular disease.

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

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.

Quantitative imaging of dynamic myocardial blood flow using dual‐head rapidly rotating gantry single‐photon emission computed tomography to enhance coronary artery disease diagnosis

AbstractBackgroundThis study aimed to evaluate the performance of myocardial blood flow (MBF) and myocardial flow reserve (MFR) for diagnosing coronary artery disease (CAD) using dynamic single‐photon emission computed tomography/computed tomography (SPECT/CT) with a dual‐head rapidly rotating gantry (RRG) and to compare this method with conventional myocardial perfusion imaging (MPI), which can be obtained in a one‐stop manner.MethodsA total of 93 patients with suspected or confirmed CAD who underwent RRG SPECT/CT were retrospectively enrolled. They underwent invasive coronary angiography (ICA) and conventional MPI within 3 weeks. Based on the ICA results, the performance of MBF quantitative and semi‐quantitative parameters were compared at patient and vessel levels using ≥50% and ≥75% stenosis as the criteria for CAD diagnosis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of two types of parameters.ResultsFor patient‐level analysis, the area under ROC curves (AUCs) for stress MBF (sMBF), MFR, summed stress score (SSS), and summed different score (SDS) were 0.971, 0.939, 0.612, and 0.546, respectively, for ≥50% stenosis as positive, and were 0.983, 0.932, 0.735, and 0.509, respectively, for ≥75% stenosis as positive criteria. For vessel‐level analysis, the AUCs of sMBF, MFR, SSS, and SDS were 0.981, 0.933, 0.636, and 0.560, respectively, for ≥50% stenosis as positive and were 0.984, 0.933, 0.767, and 0.583, respectively, for ≥75% stenosis as positive criteria.ConclusionsCompared with semi‐quantitative parameters of conventional MPI, MBF quantitative parameters of dual‐head RRG SPECT had higher diagnostic performance for CAD.

Hemodynamic Insights into Combined Fractional Flow Reserve and Instantaneous Wave-Free Ratio Assessment Through Quantitative [15O]H2O PET Myocardial Perfusion Imaging.

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 [15O]H2O 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 [15O]H2O 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 [15O]H2O 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 [15O]H2O PET-derived quantitative myocardial perfusion as the physiologic standard of CAD severity.

Impact of Absolute Myocardial Blood Flow Quantification on the Diagnostic Performance of PET-Based Perfusion Scans Using 82Rubidium.

Guidelines propose the inclusion of quantitative measurements from 82Rubidium positron emission tomography (RbPET) to discriminate obstructive coronary artery disease (CAD). However, the effect on diagnostic accuracy is unknown. The aim was to investigate the optimal RbPET reading algorithm for improved identification of obstructive CAD. Prospectively enrolled patients (N=400) underwent RbPET and invasive coronary angiography with fractional flow reserve and quantitative coronary angiography. Quantitative measurements (myocardial blood flow (MBF), MBF reserve, transient ischemic dilatation) by RbPET were step-wisely added to a qualitative assessment by the summed stress score based on their diagnostic accuracy of obstructive CAD by invasive coronary angiography-fractional flow reserve. Prespecified cutoffs were summed stress score ≥4, hyperemic MBF 2.00 mL/g per min, and MBF reserve 1.80, respectively. Hemodynamically obstructive CAD was defined as >90% diameter stenosis or invasive coronary angiography-fractional flow reserve ≤0.80, and sensitivity analyses included a clinically relevant reference of anatomically severe CAD (>70% diameter stenosis by invasive coronary angiography-quantitative coronary angiography). Hemodynamically obstructive CAD was present in 170/400 (42.5%) patients. Stand-alone summed stress score showed a sensitivity and specificity of 57% and 93%, respectively, while hyperemic MBF showed similar sensitivity (61%, P=0.57) but lower specificity (85%, P=0.008). With increased discrimination by receiver-operating characteristic curves (0.78 versus 0.85; P<0.001), combining summed stress score, MBF and MBF reserve showed the highest sensitivity of 77% but lower specificity of 74% (P<0.001 for both comparisons). Against anatomically severe CAD, all measures independently yielded high discrimination ≥0.90 with increased sensitivity and lower specificity by additional quantification. The inclusion of quantitative measurements to a RbPET read increases in the identification of obstructive CAD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Kiosk 7R-FA-02 - Assessment of the Effect of Patient Age and Sex on Normal Hyperemic and Baseline Myocardial Blood Flow and Myocardial Perfusion Reserve Using High-resolution Inline Quantitative Perfusion Imaging

Kiosk 7R-FA-02 - Assessment of the Effect of Patient Age and Sex on Normal Hyperemic and Baseline Myocardial Blood Flow and Myocardial Perfusion Reserve Using High-resolution Inline Quantitative Perfusion Imaging

Prognostic Role of Myocardial Flow Reserve in Heart Failure With Preserved Ejection Fraction.

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&lt;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&lt;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&lt;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.

Quantitative analysis of myocardial blood flow in surgically revascularized and not revascularized myocardial segments. A pilot PET study.

To prospectively compare changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) in multivessel coronary artery disease (MVCAD) patients undergoing incomplete revascularization (IR) versus complete revascularization (CR) by coronary artery bypass grafting (CABG). Seven male patients (age 68 ± 9years) with MVCAD underwent myocardial perfusion PET/CT with [13N]ammonia before and at least 4months after CABG. Segmental resting and stress MBF as well as MFR were measured. Resting and during stress left ventricle ejection fraction (LVEF) were also calculated. Three patients (43%) underwent CR and four (57%) IR. Among 119 myocardial segments, 101 (85%) were revascularized, and 18 (15%) were not. After CABG, stress MBF (mL/min/gr) and MFR are significantly increased in all myocardial segments, with a greater increase in the revascularized segments (p = 0.013). In both groups, LVEF significantly decreased during stress at baseline PET (p = 0.04), but not after CABG. Stress MBF and MFR significantly improve after CABG in both revascularized and not directly revascularized myocardial segments. IR strategy may be considered in patients with high surgical risk for CR.

Serial fractional flow reserve, coronary flow reserve and index of microcirculatory resistance after percutaneous coronary intervention in patients treated for stable angina pectoris assessed with PET.

Cardiac 15 O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF). The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15 O-water PET and invasive flow and pressure measurements. In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months. In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ± 0.8 vs. 3.2 ± 0.8; P < 0.001 and MFR 2.5 ± 0.8 vs. 3.4 ± 1.1; P = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ± 0.20 vs. 0.91 ± 0.06 vs. 0.91 ± 0.07; P < 0.001; CFR 2.4 ± 1.2 vs. 3.6 ± 1.9 vs. 3.6 ± 1.9; P < 0.001, whereas IMR did not change significantly: 30.3 ± 22.9 vs. 30.1 ± 25.3 vs. 31.9 ± 25.2; P = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR ( r = 0.732; P < 0.001) and an increase in MFR ( r = 0.499; P = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, ( r = -0.616; P = 0.004). Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.

Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy.

HIV infection and abacavir-containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)-derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well-validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non-HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non-abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR. Thirty-seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross-sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68-1.98] versus 2.40 mL/min per g [95% CI, 2.25-2.54]; P<0.001) and MBFR (2.18 [95% CI, 1.96-2.40] versus 2.68 [95% CI, 2.47-2.89]; P=0.002) was significantly lower in PWH than in people without HIV. In a single-arm, multicenter trial, a subset of 25 PWH who were virologically suppressed on dolutegravir/lamivudine/abacavir underwent positron emission tomography myocardial perfusion imaging at baseline and after switching to bictegravir/emtricitabine/TAF. MBFR was unchanged after switching to bictegravir/emtricitabine/TAF for a mean of 27 weeks (MBFR, 2.34 to 2.29; P=0.61), except in PWH with impaired MBFR at baseline (<2.00; N=6) in whom MBFR increased from 1.58 to 2.02 (P=0.02). PWH had reduced coronary microvascular function compared with controls without HIV. Coronary microvascular function did not improve after switching from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/TAF. URL: https://www.clinicaltrials.gov; unique identifier: NCT03656783.

Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease

Introduction: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. Methods: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. Results: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e’ septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079–1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175–19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446–4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. Conclusions: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.

The impact of coronary revascularization on coronary flow capacity assessed by serial transthoracic echocardiographic findings in patients with chronic coronary syndrome

Abstract Background Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease. This study evaluated the effects of revascularization (PCI) on CFC assessed by serial transthoracic doppler echocardiography (TDE) examinations before and after elective PCI. Methods A total of 177 patients with chronic coronary syndrome underwent stress TDE examinations of left anterior descending arteries (LAD) before and after PCI to assess changes in CFC. Resting and hyperemic diastolic peak velocity (hDPV) was used to calculate CFR. Using previously reported thresholds for ischemia and normal perfusion, vessels were stratified in four CFC categories: severely reduced, moderately reduced, minimally reduced CFC, and normal flow. The association between CFC increase and pre-procedural TDE parameters was studied. Results After PCI, fractional flow reserve (FFR) values improved in all cases (0.70, (0.62 - 0.74), P &amp;lt; 0.001), although 74 cases (41.8%) showed CFC decrease. Pre-PCI lower FFR, lower resting Pd/Pa, lower CFR, and lower hDPV were significant predictors for CFC increase after PCI. Lower baseline CFC, particularly in ischemic CFC defined as a composite of moderately, and severely reduced CFC was a predictor of CFC increase (P &amp;lt; 0.01). On multivariable analysis, pre-PCI lower hDPV, and pre-PCI ischemic CFC were independent factors predicting CFC-improvement, while pre-PCI wire-based physiological data including FFR were not significantly associated with CFC improvement. Conclusions About a half of successful LAD PCI resulted in an increase in CFC. Preprocedural TDE-derived parameters including hDPV and CFC may help identification of lesions that benefit from revascularization with respect to an increase in coronary flow capacity. Further studies are needed to elucidate the effect of CFC improvement on prognosis.Effect of preprocedural CFC after PCI

Improvement in myocardial energetics and perfusion with Liraglutide in patients with type 2 diabetes- A randomised, single centre, open label, cross-over drug trial

Abstract Background Both the insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. In a single center, open-label, randomized, cross-over design trial we sought to compare two distinct glycaemic control strategies of targeting beta-cell dysfunction and promoting insulin secretion using Glucagon-like peptide-1 receptor agonists (GLP-1RA) -liraglutide and targeting peripheral insulin resistance using a peroxisome proliferator activated receptor-gamma agonist (PPAR-g)-pioglitazone to see which results in greater improvements in myocardial perfusion, energetics and function in patients with T2D. Methods Fifty-two T2D patients were screened. Eligible patients with no known prior cardiovascular disease were randomized in a 1:1 ratio to be administered one of the study drugs for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Thirty-three eligible participants completed both treatment periods. Participants have undergone 31phosphorus magnetic resonance spectroscopy (31P-MRS) at rest and dobutamine stress followed by the cardiac magnetic resonance (CMR) scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging (motion corrected, automated in-line perfusion mapping), velocity-encoded mitral in-flow imaging and late gadolinium enhanced imaging at 3T immediately before commencement and after completion of each treatment arm (four scans per participant). Results Clinical and biochemical characteristics, and CMR/31P-MRS results are provided in Tables 1&amp;2 respectively. Liraglutide therapy resulted in a significant reductions in the body mass index and significant improvements in glycemic control. Both drugs reduced insulin resistance indicated by a reduction in the mean triglyceride index. There were no significant changes in NTproBNP or troponin levels with either drug. Therapy with either drug did not result in a significant change in the LV end-diastolic volume, ejection fraction or global longitudinal shortening. Pioglitazone led to a significant increment in mean LV mass and LV mass index, while no significant effect in myocardial mass or mass index were detected with liraglutide. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve index. While pioglitazone treatment showed no significant effect in these parameters, an isolated improvement in the rest diastolic function was detected in this arm. Conclusions In this randomised cross-over design trial we showed for the first time that four months treatment with glucagon like protein 1 receptor agonist liraglutide results in significant improvements in myocardial stress perfusion and energetics. Pioglitazone results in an isolated improvement in rest diastolic funct

Changes in myocardial perfusion after coronary sinus reducer implantation for refractory angina - assessment using fully automated quantitative stress perfusion cardiac MRI

Abstract Introduction Previous reports show angina improvement after Coronary Sinus Reducer (CSR) implantation [1,2]. However, the mechanistic basis remains unconfirmed. Preliminary studies using semi-quantitative metrics derived from stress perfusion cardiac MRI (CMR), have suggested improved myocardial perfusion particularly in ischaemic segments [3]. To date, assessment by fully automated quantitative myocardial perfusion CMR has not been reported. Purpose To assess the effect of CSR implantation on quantitative regional myocardial blood flow in patients with refractory angina and advanced coronary artery disease (CAD). Methods Prospective cohort study of patients undergoing CSR implantation. CMR was performed at baseline and median 7 months follow-up. Automated segmentation into a 16-segment American Heart Association model was performed to quantify segmental rest and stress myocardial blood flow (MBF, ml/min/g) and myocardial perfusion reserve (MPR). Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. Wilcoxon matched-pairs sign rank tests were used to compare paired global and segmental perfusion values. A linear mixed-effects model with random slopes and intercepts was used to assess the relationship between baseline segmental MPR and associated change in MPR (ΔMPR) after CSR implantation. Results 12 patients (10M:2F; mean age 67) were included. Median Canadian Cardiovascular Society class was 3. Globally, there was no change in rest (P=0.90), stress MBF (P=0.34) or MPR (P=0.72) from baseline to follow-up. However, ΔMPR was related to the degree of baseline ischaemia (panel A). Segments with baseline MPR&amp;lt;2.45 increased in MPR whereas segments with baseline MPR ≥2.45 experienced a decrease (P=0.003, conditional R2: 0.81). In segments with MPR&amp;lt;2.45 (n=138), median ΔMPR was +0.18 (15.4%; P&amp;lt;0.0001); whereas with MPR≥2.45 (n=52) it was -0.41 (-12.7%; P=0.03; panel B). When assessed by myocardial layer, significant increases in MPR were observed in both subendocardial (+0.19 [15.6%]; P&amp;lt;0.0001) and subepicardial (+0.19 [12.3%]; P&amp;lt;0.0002) segments with baseline MPR&amp;lt; 2.45 (panel C). Conversely, in segments with baseline MPR≥2.45, there was a significant reduction in MPR in the subendocardium (-0.43 [-15.9%]; P=0.04) but not in the subepicardium (-0.36 [-9.90%]; P=0.08; panel D). Conclusion To our knowledge, this is the first study showing changes in quantitative myocardial perfusion after CSR implantation by fully automated inline quantitative perfusion CMR. Our analysis shows a relationship between baseline MPR and change in MPR after CSR implantation, supporting redistribution of perfusion into both subendocardial and subepicardial layers as potential mechanisms of action of CSR. Further studies are needed to confirm these preliminary results.