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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. OBJECTIVES: The study compared the performance for detection and grading of coronary stenoses using artificial intelligence-enabled quantitative coronary computed tomography angiography (AI-QCT) analyses to core lab-interpreted coronary computed tomography angiography (CTA), core lab quantitative coronary angiography (QCA), and invasive fractional flow reserve (FFR). BACKGROUND: Clinical reads of coronary CTA, especially by less experienced readers, may result in overestimation of coronary artery disease stenosis severity compared with expert interpretation. AI-based solutions applied to coronary CTA may overcome these limitations. METHODS: Coronary CTA, FFR, and QCA data from 303 stable patients (64 ± 10 years of age, 71% male) from the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia) trial were retrospectively analyzed using an Food and Drug Administration-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. RESULTS: Disease prevalence was high, with 32.0%, 35.0%, 21.0%, and 13.0% demonstrating ≥50% stenosis in 0, 1, 2, and 3 coronary vessel territories, respectively. Average AI-QCT analysis time was 10.3 ± 2.7 minutes. AI-QCT evaluation demonstrated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94%, 68%, 81%, 90%, and 84%, respectively, for ≥50% stenosis, and of 94%, 82%, 69%, 97%, and 86%, respectively, for detection of ≥70% stenosis. There was high correlation between stenosis detected on AI-QCT evaluation vs QCA on a per-vessel and per-patient basis (intraclass correlation coefficient = 0.73 and 0.73, respectively; P < 0.001 for both). False positive AI-QCT findings were noted in in 62 of 848 (7.3%) vessels (stenosis of ≥70% by AI-QCT and QCA of

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.

OBJECTIVE This study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Whether APCs differ based on lesion severity and diabetes status is unknown. RESEARCH DESIGN AND METHODS We retrospectively evaluated 303 subjects from the Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia (CREDENCE) trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (≥50% stenosed) or nonobstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs, including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low-density NCP (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP), and percentage of atheroma volume (PAV; PV normalized for vessel volume). The relationship between APCs, stenosis severity, and diabetes status was assessed. RESULTS Among the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the cohort with diabetes, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (P = 0.004). Patients with diabetes and nonobstructive disease had greater PV (P = 0.02), PAV (P = 0.02), NCP (P = 0.03), PAV NCP (P = 0.02), diseased vessels (P = 0.03), and maximum stenosis (P = 0.02) than patients without diabetes with nonobstructive disease. APCs were similar between patients with diabetes with nonobstructive disease and patients without diabetes with obstructive disease. Diabetes status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and nonobstructive lesions. CONCLUSIONS Patients with diabetes and nonobstructive stenosis had an association to similar APCs as patients without diabetes who had obstructive stenosis. Among patients with nonobstructive disease, patients with diabetes had more total PV and NCP.

Objectives: This study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Background: Whether APCs differ based on lesion severity and diabetic status is unknown. Methods: We retrospectively evaluated 303 subjects from the CREDENCE trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (>50% stenosed) or non-obstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low density noncalcified plaque (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP) and percent atheroma volume (PAV; plaque volume normalized for vessel volume). The relationship between APCs, stenosis severity and diabetic status was assessed. Results: Among the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the diabetic cohort, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (p=0.004). Patients with diabetes and nonobstructive disease had greater PV (p=0.02), PAV (p=0.02), NCP (p=0.03), PAV NCP (p=0.02), diseased vessels (p=0.03), and max stenosis (p=0.02) than nondiabetic patients with nonobstructive disease. APCs were similar between diabetics with non-obstructive disease and non-diabetic patients with obstructive disease. Diabetic status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and non-obstructive lesions. Conclusions: Patients with diabetes and non-obstructive stenosis had an association to similar APCs as patients without diabetes who have obstructive stenosis. Among patients with non-obstructive disease, patients with diabetes had more total PV and NCP.

Background: A pathophysiological interplay exists between plaque morphology and coronary physiology. Machine learning (ML) is increasingly being applied to coronary computed tomography angiography (CCTA) for cardiovascular risk stratification. We sought to assess the performance of a ML score integrating CCTA-based quantitative plaque features for predicting vessel-specific ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by positron emission tomography (PET). Methods: This post-hoc analysis of the PACIFIC trial (Prospective Comparison of Cardiac Positron Emission Tomography/Computed Tomography [CT]‚ Single Photon Emission Computed Tomography/CT Perfusion Imaging and CT Coronary Angiography with Invasive Coronary Angiography) included 208 patients with suspected coronary artery disease who prospectively underwent CCTA‚ [ 15 O]H 2 O PET, and invasive FFR. Plaque quantification from CCTA was performed using semiautomated software. An ML algorithm trained on the prospective NXT trial (484 vessels) was used to develop a ML score for the prediction of ischemia (FFR≤0.80), which was then evaluated in 581 vessels from the PACIFIC trial. Thereafter, the ML score was applied for predicting impaired hyperemic MBF (≤2.30 mL/min per g) from corresponding PET scans. The performance of the ML score was compared with CCTA reads and noninvasive FFR derived from CCTA (FFR CT ). Results: One hundred thirty-nine (23.9%) vessels had FFR-defined ischemia, and 195 (33.6%) vessels had impaired hyperemic MBF. For the prediction of FFR-defined ischemia, the ML score yielded an area under the receiver-operating characteristic curve of 0.92, which was significantly higher than that of visual stenosis grade (0.84; P CT (0.93; P =0.34). Quantitative percent diameter stenosis and low-density noncalcified plaque volume had the greatest ML feature importance for predicting FFR-defined ischemia. When applied for impaired MBF prediction, the ML score exhibited an area under the receiver-operating characteristic curve of 0.80; significantly higher than visual stenosis grade (area under the receiver-operating characteristic curve 0.74; P =0.02) and comparable with FFR CT (area under the receiver-operating characteristic curve 0.77; P =0.16). Conclusions: An externally validated ML score integrating CCTA-based quantitative plaque features accurately predicts FFR-defined ischemia and impaired MBF by PET, performing superiorly to standard CCTA stenosis evaluation and comparably to FFR CT .

Objectives: This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia. Background: Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). Methods: A total of 539 patients who underwent CCTA and [ 15O]H 2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. Results: During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm 3, CPV >110 mm 3, NCPV >85 mm 3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). Conclusions: Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

Publisher Copyright: © 2022 The Authors Objectives: To determine whether coronary computed tomography angiography (CCTA) scanning, scan preparation, contrast, and patient based parameters influence the diagnostic performance of an artificial intelligence (AI) based analysis software for identifying coronary lesions with ≥50% stenosis. Background: CCTA is a noninvasive imaging modality that provides diagnostic and prognostic benefit to patients with coronary artery disease (CAD). The use of AI enabled quantitative CCTA (AI-QCT) analysis software enhances our diagnostic and prognostic ability, however, it is currently unclear whether software performance is influenced by CCTA scanning parameters. Methods: CCTA and quantitative coronary CT (QCT) data from 303 stable patients (64 ± 10 years, 71% male) from the derivation arm of the CREDENCE Trial were retrospectively analyzed using an FDA-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. The algorithm's diagnostic performance measures (sensitivity, specificity, and accuracy) for detecting coronary lesions of ≥50% stenosis were determined based on concordance with QCA measurements and subsequently compared across scanning parameters (including scanner vendor, model, single vs dual source, tube voltage, dose length product, gating technique, timing method), scan preparation technique (use of beta blocker, use and dose of nitroglycerin), contrast administration parameters (contrast type, infusion rate, iodine concentration, contrast volume) and patient parameters (heart rate and BMI). Results: Within the patient cohort, 13% demonstrated ≥50% stenosis in 3 vessel territories, 21% in 2 vessel territories, 35% in 1 vessel territory while 32% had 400 mg/ml 95.2%; p = 0.0287) in the context of low injection flow rates. On a per patient basis there were no significant differences in AI diagnostic performance measures across all measured scanner, scan technique, patient preparation, contrast, and individual patient parameters. Conclusion: The diagnostic performance of AI-QCT analysis software for detecting moderate to high grade stenosis are unaffected by commonly used CCTA scanning parameters and across a range of common scanning, scanner, contrast and patient variables. Condensed abstract: An AI-enabled quantitative CCTA (AI-QCT) analysis software has been validated as an effective tool for the identification, quantification and characterization of coronary plaque and stenosis through comparison to blinded expert readers and quantitative coronary angiography. However, it is unclear whether CCTA screening parameters related to scanner parameters, scan technique, contrast volume and rate, radiation dose, or a patient's BMI or heart rate at time of scan affect the software's diagnostic measures for detection of moderate to high grade stenosis. AI performance measures were unaffected across a broad range of commonly encountered scanner, patient preparation, scan technique, intravenous contrast and patient parameters. publishersversion published

Objectives: This study aimed to investigate the performance of computed tomography derived fractional flow reserve based interactive planner (FFRCT planner) to predict the physiological benefits of percutaneous coronary intervention (PCI) as defined by invasive post-PCI FFR. Background: Advances in FFRCT technology have enabled the simulation of hyperemic pressure changes after virtual removal of stenoses. Methods: In 56 patients (63 vessels) invasive FFR measurements before and after PCI were obtained and FFRCT was calculated using pre-PCI coronary CT angiography. Subsequently, FFRCT and invasive coronary angiography models were aligned allowing virtual removal of coronary stenoses on pre-PCI FFRCT models in the same locations as PCI was performed. Relationships between invasive FFR and FFRCT, between post-PCI FFR and FFRCT planner, and between delta FFR and delta FFRCT were evaluated. Results: Pre PCI, invasive FFR was 0.65 ± 0.12 and FFRCT was 0.64 ± 0.13 (p =.34) with a mean difference of 0.015 (95% CI: −0.23–0.26). Post-PCI invasive FFR was 0.89 ± 0.07 and FFRCT planner was 0.85 ± 0.07 (p CT were 0.23 ± 0.12 and 0.21 ± 0.12 (p =.09) with a mean difference of 0.025 (95% CI: −0.20–0.25). Significant correlations were found between pre-PCI FFR and FFRCT (r = 0.53, p CT planner (r = 0.41, p =.001), and between delta FFR and delta FFRCT (r = 0.57, p CT planner tool demonstrated significant albeit modest agreement with post-PCI FFR and change in FFR values after PCI. The FFRCT planner tool may hold promise for PCI procedural planning; however, improvement in technology is warranted before clinical application.

Determining the anatomic severity and extent of coronary artery disease (CAD) by means of coronary computed tomography angiography (CCTA) and its effect on perfusion using myocardial perfusion imaging (MPI) form the pillars of the non-invasive imaging assessment of CAD. This review will 1) focus on CCTA and [15O]H2O positron emission tomography MPI as stand-alone imaging modalities and their combined use for detecting CAD, 2) highlight some of the lessons learned from the PACIFIC trial (Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve (FFR) (NCT01521468)), and 3) discuss the use of [15O]H2O PET MPI in the clinical work-up of patients with a chronic coronary total occlusion (CTO).

Purpose To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). Methods Fifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress. Results CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P r = 0.36; P 15O]H2O PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR. Conclusion CMR measurements of stress MBF and MFR showed modest agreement to those obtained with [15O]H2O PET. Nevertheless, stress MBF and MFR were concordant between CMR and [15O]H2O PET in 77% and 80% of vascular territories, respectively.

Contains fulltext : 229194.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 +/- 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to >/=70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

ObjectiveThe study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT).MethodsThis is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (ResultsThe cohort was 64.4±10.2 years and 29% women. Overall, patients >65 had more PV and CP than patients 65 had more CP than younger patients in both obstructive (29.2 mm3 vs 48.2 mm3; p3 vs 49.4 mm3; pConclusionAI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment.

Introduction: Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. This study evaluated the impact of CTO percutaneous coronary intervention (PCI) on absolute perfusion in remote myocardium. Methods: A total of 164 patients underwent serial [ 15 O]H 2 O positron emission tomography (PET) perfusion imaging at baseline and 3 months after successful CTO PCI to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in remote myocardium subtended by non-target collateral donor coronary arteries. Results: Absolute perfusion indices in the CTO and remote myocardium showed a positive linear correlation before (hMBF: r=0.75, p-1 ·g -1 , p Conclusions: Baseline and post-PCI perfusion indices in remote and CTO myocardium were positively correlated. An overall increase in remote myocardial perfusion was observed following CTO PCI and the absolute perfusion increase in the CTO territory was an independent predictor of remote myocardial perfusion improvement. Successful CTO PCI impacts coronary hemodynamics in the closely interlinked CTO and remote myocardium.

Aims The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI). Methods and results In this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58–76%) for SPECT, 81% (72–87%) for PET, and 66% (56–75%) for MRI. Specificity was 61% (48–72%) for SPECT, 65% (53–76%) for PET, and 62% (49–74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68–81%) did not statistically differ from SPECT (65%, 58–72%, P = 0.03) and MRI (64%, 57–72%, P = 0.052). Using FFR Conclusion In this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.

Objectives: This study evaluated myocardial viability as well as global and regional functional recovery after successful chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) using sequential quantitative cardiac magnetic resonance (CMR) imaging. Background: The patient benefits of CTO PCI are being questioned. Methods: In a single high-volume CTO PCI center patients were prospectively scheduled for CMR at baseline and 3 months after successful CTO PCI between 2013 and 2018. Segmental wall thickening (SWT) and percentage late gadolinium enhancement (LGE) were quantitatively measured per segment. Viability was defined as dysfunctional myocardium (50%, N = 26 [4%], −0.08 ± 1.09 mm, p < 0.01). Patients with ≥2 CTO segments viability showed more SWT increase in the CTO territory compared to patients with 0–1 segment viability (0.49 ± 0.93 vs. 0.12 ± 0.98 mm, p = 0.03). Conclusions: Detection of dysfunctional myocardial segments without extensive scar (≤50% LGE) as a marker for viability on CMR aids in identifying patients with significant regional functional recovery after CTO PCI.

Contains fulltext : 209423.pdf (Publisher’s version ) (Open Access) OBJECTIVES: The aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)-derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BACKGROUND: In addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. METHODS: Patients with suspected coronary artery disease underwent coronary CTA and [(15)O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA-derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow

Background: Risk stratification is crucial to improve tailored therapy in patients with suspected coronary artery disease (CAD). This study investigated the ability of targeted proteomics to predict presence of high-risk plaque or absence of coronary atherosclerosis in patients with suspected CAD, defined by coronary computed tomography angiography (CCTA). Methods: Patients with suspected CAD (n = 203) underwent CCTA. Plasma levels of 358 proteins were used to generate machine learning models for the presence of CCTA-defined high-risk plaques or complete absence of coronary atherosclerosis. Performance was tested against a clinical model containing generally available clinical characteristics and conventional biomarkers. Findings: A total of 196 patients with analyzable protein levels (n = 332) was included for analysis. A subset of 35 proteins was identified predicting the presence of high-risk plaques. The developed machine learning model had fair diagnostic performance with an area under the curve (AUC) of 0·79 ± 0·01, outperforming prediction with generally available clinical characteristics (AUC = 0·65 ± 0·04, p < 0·05). Conversely, a different subset of 34 proteins was predictive for the absence of CAD (AUC = 0·85 ± 0·05), again outperforming prediction with generally available characteristics (AUC = 0·70 ± 0·04, p < 0·05). Interpretation: Using machine learning models, trained on targeted proteomics, we defined two complementary protein signatures: one for identification of patients with high-risk plaques and one for identification of patients with absence of CAD. Both biomarker subsets were superior to generally available clinical characteristics and conventional biomarkers in predicting presence of high-risk plaque or absence of coronary atherosclerosis. These promising findings warrant external validation of the value of targeted proteomics to identify cardiovascular risk in outcome studies. Fund: This study was supported by an unrestricted research grant from HeartFlow Inc. and partly supported by a European Research Area Network on Cardiovascular Diseases (ERA-CVD) grant (ERA CVD JTC2017, OPERATION). Funders had no influence on trial design, data evaluation, and interpretation.

Aims Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. Methods and results A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P Conclusion A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

Background and aims Both plasma low-density lipoprotein (LDL) cholesterol levels and risk for premature cardiovascular disease are extremely elevated in patients with homozygous familial hypercholesterolemia (HoFH), despite the use of multiple cholesterol lowering treatments. Given its inborn nature, atherosclerotic plaques are commonly observed in young HoFH patients. Whether intensive lipid lowering strategies result in plaque regression in adolescent patients is unknown. Methods Two HoFH patients with null/null LDLR variants, who participated in the R1500-CL-1629 randomized clinical trial (NCT03399786) evaluating the LDL cholesterol lowering effect of evinacumab (a human antibody directed against ANGPTL3; 15 mg/kg intravenously once monthly), were included in this study. Patients underwent coronary computed tomography angiography (CCTA) before randomization and after 6 months of treatment. Results Both patient A (aged 12) and B (aged 16) were treated with a statin, ezetimibe and weekly apheresis. Evinacumab decreased mean pre-apheresis LDL cholesterol levels from 5.51 ± 0.75 and 5.07 ± 1.45 mmol/l to 2.48 ± 0.31 and 2.20 ± 0.13 mmol/l and post-apheresis LDL levels from 1.45 ± 0.26 and 1.37 ± 39 mmol/l to 0.80 ± 0.16 and 0.78 ± 0.13 mmol/l in patient A and B, respectively. Total plaque volumes were reduced by 76% and 85% after 6 months of evinacumab treatment in patient A and B, respectively. Conclusions We describe two severely affected young HoFH patients in whom profound plaque reduction was observed with CCTA after intensive lipid lowering therapy with statins, ezetimibe, LDL apheresis, and evinacumab. This shows that atherosclerotic plaques possess the ability to regress at young age, even in HoFH patients.

Objectives: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. Background: The clinical benefit of CTO PCI is questioned. Methods: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [ 15O]H 2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min −1 · g −1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. Results: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus −1 · g −1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min −1 · g −1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min −1 · g −1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04). Conclusions: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Background: This study aimed to investigate the diagnostic value of comprehensive on-site coronary computed tomography angiography (CCTA) using stenosis and plaque measures and subtended myocardial mass (V sub) for fractional flow reserve (FFR) defined hemodynamically obstructive coronary artery disease (CAD). Additionally, the incremental diagnostic value of off-site CT-derived FFR (FFR CT) was assessed. Methods: Prospectively enrolled patients underwent CCTA followed by invasive FFR interrogation of all major coronary arteries. Vessels with ≥30% stenosis were included for analysis. On-site CCTA assessment included qualitative and quantitative stenosis (visual grading and minimal lumen area, MLA) and plaque measures (characteristics and volumes), and V sub. Diagnostic value of comprehensive on-site CCTA assessment was tested by comparing area under the curves (AUC). In vessels with available FFR CT, the incremental value of off-site FFR CT was tested. Results: In 236 vessels (132 patients), MLA, positive remodeling, non-calcified plaque volume, and V sub were independent on-site CCTA predictors for hemodynamically obstructive CAD (p < 0.05 for all). V sub/MLA 2 outperformed all these on-site CCTA parameters (AUC = 0.85) and V sub was incremental to all other CCTA predictors (p = 0.02). In subgroup analysis (n = 194 vessels), diagnostic performance of FFR CT and V sub/MLA 2 was similar (AUC 0.89 and 0.85 respectively, p = 0.25). Furthermore, diagnostic performance significantly albeit minimally increased when FFR CT was added to on-site CCTA assessment (ΔAUC = 0.03, p = 0.02). Conclusions: In comprehensive on-site CCTA assessment, V sub/MLA2 demonstrated greatest diagnostic value for hemodynamically obstructive CAD and V sub was incremental to all evaluated CCTA indices. Additionally, adding FFR CT only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to FFR CT. Several novel indices have been proposed to increase the diagnostic performance of coronary computed tomography angiography (CCTA). The diagnostic value of comprehensive on-site CCTA assessment using qualitative and quantitative stenosis and plaque measures and subtended myocardial mass (V sub) for fractional flow reserve (FFR) defined hemodynamically obstructive CAD was assessed in 236 vessels with ≥30% stenosis (132 patients). V sub/MLA 2 demonstrated greatest diagnostic value and V sub was incremental to all evaluated CCTA indices. The addition of off-site CT-derived FFR (FFR CT, in 192 vessels) only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to off-site assessment using FFR CT.

Funding Acknowledgements Type of funding sources: None. Background Inflammation is a key component in the atherosclerotic process, initiating and sustaining plaques and serving as a trigger for plaque rupture leading to myocardial infarction. Coronary computed tomography angiography (CCTA) derived pericoronary adipose tissue attenuation (PCATa) has been proposed as surrogate marker for coronary inflammation and might improve risk assessment on top of CCTA derived cardiovascular risk-factors: atherosclerotic burden and plaque vulnerability. Purpose To assess the prognostic value of PCATa beyond atherosclerotic burden and high-risk plaques (HRPs). Methods A total of 543 patients who underwent CCTA because of suspected CAD were included. CCTA assessment comprised coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and HRPs, total plaque volume (TPV), non-calcified plaque volume (NCPV), and PCATa. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Prognostic thresholds were determined for quantitative CCTA variables. Results During a median follow-up of 6.6 [interquartile range: 4.7-7.8] years, the endpoint was observed in 42 (20 MI/22 death) patients. CACS >83, obstructive CAD, HRPs, TPV >269mm3, and NCPV >83mm3 were associated with shorter time to the endpoint with unadujsted hazard ratio’s (HR) of 5.37 (95% confidence interval (CI): 2.56-11.29), 5.70 (95% CI: 2.40-13.55), 3.31 (95% CI: 1.80-6.07), 7.76 (95% CI: 3.59-16.81), and 6.77 (95% CI: 3.24-14.16), respectively (p -74.4 Hounsfield units was associated with worse prognosis (unadjusted HR: 1.99, 95% CI: 1.04-3.79, p = 0.037), whereas PCATa of the LAD and Cx were not associated with prognosis. PCATa of the RCA remained a significant predictor of death and non-fatal MI corrected for CCTA variables and clincal chacteristics associated with the endpoint (adjusted HR: 2.11, 95% CI: 1.11-4.04, p = 0.024). Conclusion Coronary inflammation determined by PCATa of the RCA provides incremental prognostic value beyond clinical characteristics and comprehensive CCTA assessment. Abstract Figure. Take-home figure

Background A myocardial ischemic burden (IB) of 10% is used to denote high-risk patients with coronary artery disease (CAD). This threshold has primarily been assessed by single-photon emission computed tomography. Differences in the pharmacokinetics of the utilized traces, higher resolution of positron emission tomography (PET), and lastly differences in assessment of IB might lead to a higher prognostic threshold for quantitative PET. Purpose To determine a [15O]H2O PET derived IB to identify low (annualized event rate (AER) Methods 623 patients who underwent [15O]H2O PET because of suspected CAD and in whom follow-up was obtained were included. The IB was defined as the percentage of myocardium with a hyperemic blood flow (hMBF) ≤2.3 ml/min/g and by a coronary flow reserve (CFR) of ≤2.5. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Time-dependent ROC curves were constructed for the prediction of the endpoint within the first 5-years, based on these curves thresholds were selected for which specificity was maximized and sensitivity was at least 80%. Patients were classified as having a high IB if their respective IBs were above the prognostic thresholds and as having a low IB if not. Results During a median follow-up of 6.7 years, 34 (6%) patients died and 28 (4%) experienced a MI resulting in 62 (10%) endpoints. An IB of 24% and 28% for hMBF and CFR, respectively, was found to be the optimal threshold to define prognosis. Patients with a high hMBF or high CFR IB had worse outcome compared to patients with a low IB (log-rank p Conclusion An IB of 24% and 28% for hMBF and CFR was found to be the optimal prognostic threshold. Both measurements can be used to determine patients outcome. However combining hMBF and CFR IB results leads to a further refinement of risk-stratification allowing for the identification of low (concordant low or discordant IB result) and high (concordant high IB result) risk CAD patients. Funding Acknowledgement Type of funding source: None

Background Coronary computed tomography angiography (CCTA) derived parameters linked to severity and extent of atherosclerosis are associated with prognosis in patients with coronary artery disease (CAD). Furthermore, coronary inflammation, by determining pericoronary adipose tissue CT-attenuation (PCATa), can be assessed on CCTA as well and has been proposed as promising prognostic marker. Objective To assess the prognostic value of PCATa on top of traditional CCTA derived atherosclerotic parameters. Methods A total of 543 patients who underwent CCTA because of suspected CAD and in whom follow-up was obtained were included. CCTA assessment comprised; coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRP), total plaque volume (TPV), non-calcified plaque volume (NCPV), and PCATa. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Optimal prognostic thresholds were determined for quantitative CCTA variables. Univariable Cox regression analyses were performed to determine clinical characteristics and CCTA variables associated with the endpoint, a subsequent multivariable Cox regression analysis that included variables associated with the endpoint was used to determine independent predictors of the endpoint. An additional Cox regression analysis was performed to test the incremental prognostic value of CCTA variables over clinical characteristics, significance of each sequentially added variable was tested using the likelihood ratio test. Results During a median follow-up time of 6.6 [interquartile range: 4.7–7.8] years, a total of 42 (20 MI/22 death) (8%) patients suffered an endpoint. CACS >83.2, obstructive CAD, HRP, TPV >269mm3, and NCPV >83mm3 were all associated with occurrence of the endpoint with unadujsted hazard ratio's (HR) of; 5.37, 5.70, 3.31, 7.76, and 6.77, respectively (p Conclusion Coronary inflammation of the RCA determined by PCATa provides incremental prognostic value on top of traditional CCTA parameters linked to extent and severity of CAD. Figure 1. Cox regression analysis demonstrating the incremental prognostic value of sequentially added CCTA variables over clinical characteristics tested for significance using the likelihood ratio test. Funding Acknowledgement Type of funding source: None

Aims This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD). Methods and results In this retrospective study, 539 patients referred for hybrid [15O]H2O PET-CT imaging because of suspected CAD were investigated. PET was used to determine myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenoses and high-risk plaque (HRP) morphology. Patients were followed up for the occurrence of all-cause death and non-fatal myocardial infarction (MI). During a median follow-up of 6.8 (interquartile range 4.8–7.8) years, 42 (7.8%) patients experienced events, including 23 (4.3%) deaths, and 19 (3.5%) MIs. Annualized event rates for normal vs. abnormal results of PET MBF, CCTA-derived stenosis, and HRP morphology were 0.6 vs. 2.1%, 0.4 vs. 2.1%, and 0.8 vs. 2.8%, respectively (P, Graphical Abstract Graphical Abstract

OBJECTIVES This study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)-defined coronary artery disease (CAD).BACKGROUND QFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking.METHODS A total of 208 (624 vessels) patients underwent technetium -99m tetrofosmin SPECT and [15O]H2O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels).RESULTS QFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively.CONCLUSIONS In this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFRdefined significant CAD compared with perfusion imaging by SPECT or PET. (J Am Coll Cardiol Img 2020;13:1976-85) (c) 2020 by the American College of Cardiology Foundation.

Key PointsQuestionAre atherosclerotic plaque measurements associated with physiologic measures of invasive fractional flow reserve? FindingsIn this analysis of the CREDENCE clinical trial that included 612 patients, nonobstructive and obstructive measures of atherosclerotic plaque were significantly associated with invasive fractional flow reserve. A comprehensive set of atherosclerotic plaque features improved the accuracy of classifying vessel-specific reduced fractional flow reserve vs rest/stress myocardial perfusion imaging measurements. MeaningUsing coronary computed tomographic angiography for detection of atherosclerotic plaque features associated with coronary physiology may improve diagnostic certainty and guide clinical management of symptomatic patients.ImportanceStress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement. ObjectiveTo compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR. Design, Setting, and ParticipantsControlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018. InterventionsPatients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve. Main Outcomes and MeasuresThe primary end point was invasive FFR of 0.80 or less. ResultsOf the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (>= 2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P

Aims To evaluate the prognostic value of global and regional quantitative [15O]H2O positron emission tomography (PET) perfusion. Methods and results In this retrospective study, 648 patients with suspected or known coronary artery disease (CAD) who underwent [15O]H2O PET were followed for the occurrence of death and myocardial infarction (MI). Global and regional hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) were obtained from [15O]H2O PET. During median follow-up of 6.9 (5.0–7.9) years, 64 (9.9%) patients experienced the composite of death (36–5.6%) and MI (28–4.3%). Impaired global hMBF ( Conclusion Global and regional hMBF and CFR were all prognostic factors for death and MI. However, for both global and regional perfusion, hMBF remained the only independent prognostic factor after adjusting for the combined use of hMBF and CFR. Additionally, integrating global and regional perfusion did not increase prognostic performance compared to either regional or global perfusion alone.

Background: Scan quality can have a significant effect on the diagnostic performance of non-invasive imaging techniques. However, the extent of its influence has scarcely been investigated in a head-to-head manner. Methods: Two-hundred and eight patients underwent CCTA, SPECT, and PET prior to invasive fractional flow reserve measurements. Scan quality was classified as either good, moderate, or poor. Results: Distribution of good, moderate, and poor quality scans was; CCTA; 66%, 22%, 13%; SPECT; 52%, 38%, 9%; PET; 86%, 13%, 1%. Good quality CCTA scans possessed a higher specificity (75% vs. 31%, p = 0.001), positive predictive value (PPV, 71% vs. 51%, p = 0.050), and accuracy (80% vs. 60%, p = 0.009) compared to moderate quality scans, while sensitivity (94%) and negative predictive value (NPV, 88%) were similar to moderate and poor quality scans. Sensitivity (76%), NPV (84%), and accuracy (85%) of good quality SPECT scans was superior to those of moderate (41% p = 0.001, 56% p = 0.010, 70% p = 0.010) and poor quality (30% p = 0.003, 65% p = 0.069, 63% p = 0.038). Specificity (92%) and PPV (87%) of good quality SPECT scans did not differ from scans of diminished quality. Good quality PET scans exhibited high sensitivity (84%), specificity (86%), NPV (88%), PPV (81%) and accuracy (85%), which was comparable to scans of lesser quality. Good quality CCTA, SPECT, and PET scans demonstrated a similar diagnostic accuracy (p = 0.247). Conclusion: Diagnostic performance of CCTA, and SPECT is hampered by scan quality, while the diagnostic value of PET is not affected. Good quality CCTA, SPECT, and PET scans possess a high diagnostic accuracy.

Objectives This study sought to compare Doppler flow velocity reserve (CFRDoppl) and thermodilution-derived coronary flow reserve (CFRthermo) head-to-head with the gold standard for quantification of myocardial perfusion, [15O]H2O positron emission tomography (PET). Background Coronary flow reserve (CFR) is an important parameter for assessing coronary vascular function. To date, 2 techniques are available for invasive assessment of CFR: Doppler flow velocity and thermodilution. Although these techniques have been compared with each other, neither has been compared with [15O]H2O PET perfusion imaging. Methods CFR was assessed in 98 vessels of 40 consecutive stable patients with suspected coronary artery disease. Patients underwent [15O]H2O PET, followed by invasive angiography in conjunction with simultaneous measurements of fractional flow reserve, CFRDoppl, and CFRthermo. Both normal and obstructed arteries were included. Results The quality of Doppler flow velocity traces was significantly lower than that of thermodilution curves (p Conclusions Coronary flow reserve, determined using Doppler flow velocity, has superior agreement with [15O]H2O PET in comparison with CFRthermo.

Background: Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity. Objectives: This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively. Methods: Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR. Results: Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively). Conclusions: PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity.

Item does not contain fulltext Aims: Guidelines recommend the use of fractional flow reserve (FFR) to guide percutaneous coronary intervention. For this purpose, physiological lesion assessment without adenosine may have a similar diagnostic accuracy as FFR. We aimed to investigate the performances of FFR, resting instantaneous wave-free ratio (iFR), and resting Pd/Pa compared with [15O]H2O positron emission tomography (PET) perfusion imaging. Methods and results: [15O]H2O PET and intracoronary pressure measurements were evaluated in 320 coronary arteries (of which 136 coronary stenoses) in 129 stable patients. The primary analysis consisting of the area-under-the-receiver-operating-characteristic curve for impaired PET hyperaemic myocardial blood flow (MBF)

Noninvasive assessment of coronary artery disease remains a challenging task, with a large armamentarium of diagnostic modalities. Myocardial perfusion imaging (MPI) is widely used for this purpose whereby cardiac positron emission tomography (PET) is considered the gold standard. Next to relative radiotracer distribution, PET allows for measurement of absolute myocardial blood flow. This quantification of perfusion improves diagnostic accuracy and prognostic value. Cardiac hybrid imaging relies on the fusion of anatomical and functional imaging using coronary computed tomography angiography and MPI, respectively, and provides incremental value as compared with either stand-alone modality.

Scan quality directly impacts the diagnostic performance of non-invasive imaging modalities as reported in a substudy of the PACIFC-trial: “Impact of Scan Quality on the Diagnostic Performance of CCTA, SPECT, and PET for Diagnosing Myocardial Ischemia Defined by Fractional Flow Reserve” [1]. This Data-in-Brief paper supplements the hereinabove mentioned article by presenting the diagnostic performance of CCTA, SPECT, and PET on a per vessel level for the detection of hemodynamic significant coronary artery disease (CAD) when stratified according to scan quality and vascular territory. Keywords: Coronary artery disease, Fractional flow reserve, Coronary computed tomography angiography, Single photon emission computed tomography, Positron emission tomography

Background: Multiple crossing techniques in chronic total occlusion (CTO) percutaneous coronary intervention have been developed. This study compared recovery of quantitative myocardial blood flow (MBF) after different CTO percutaneous coronary intervention techniques. Methods: Consecutive patients with [ 15 O]H 2 O positron emission tomography perfusion imaging before and 3 months after successful CTO percutaneous coronary intervention between 2013 and 2018 were included. Changes in hyperemic MBF, coronary flow reserve, and perfusion defect size were compared between antegrade wire escalation, retrograde wire escalation, antegrade dissection and reentry (ADR), and retrograde dissection and reentry. Results: One hundred ninety-three patients were treated with antegrade wire escalation (N=90), retrograde wire escalation (N=24), ADR (N=35), and retrograde dissection and reentry (N=44). Increase in hyperemic MBF (1.19±0.77, 0.94±0.65, 1.09±0.63, and 1.02±0.75 mL·min -1 ·g -1 , respectively; P =0.40) and coronary flow reserve (1.34±1.08, 1.14±1.09, 1.31±0.96, and 1.24±0.99, respectively; P =0.84) and decrease in defect size (3.2±2.1, 3.0±2.2, 2.7±2.1, and 2.9±1.9 segments, respectively; P =0.77) were comparable between the 4 approaches. In addition, recovery of hyperemic MBF was less pronounced after subintimal crossing with knuckle-wire-technique compared with CrossBoss in controlled ADR and retrograde dissection and reentry (0.93±0.69 versus 1.54±0.65 mL·min -1 ·g -1 , P =0.02), and less after reentry using subintimal tracking and reentry in ADR compared with controlled ADR (Stingray) or limited antegrade subintimal tracking (0.60±0.53 versus 1.18±0.54 [ P =0.04] and versus 1.49±0.57 mL·min -1 ·g -1 , [ P Conclusions: Recovery of hyperemic MBF, coronary flow reserve, and perfusion defect size after CTO percutaneous coronary intervention was comparable between different approaches. Although sometimes necessary to cross a complex CTO lesion, subintimal knuckle wiring and subintimal tracking and reentry resulted in less hyperemic MBF improvement compared with other subintimal crossing and reentry techniques.

Background The patient benefits after chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. Purpose The present study explored the relationships between baseline ischemic burden findings and subsequent changes in absolute myocardial perfusion after CTO PCI. Methods Consecutive patients underwent serial [15O]H2O positron emission tomography perfusion imaging prior and 3 months after successful CTO PCI. Change in perfusion defect size (in myocardial segments), quantitative (hyperemic) myocardial blood flow (MBF) and coronary flow reserve (CFR) in the CTO area were compared between patients with a limited (0–1 segment), moderate (2–3 segments) and large perfusion defect (≥4 segments). Results 193 patients were included, with 15, 61 and 117 patients having a limited, moderate and large perfusion defect at baseline. Hyperemic MBF and CFR were lower in a large perfusion defect compared to smaller defects (all comparisons p Conclusions Patients with a CTO and a larger perfusion defect have more severe hyperemic MBF and CFR levels. Major reductions in ischemic burden can be achieved by CTO PCI, with more defect size reduction in patients with a larger perfusion defect, whereas hyperemic MBF and CFR significantly improve irrespective of starting values before PCI. Acknowledgement/Funding None

Background Quantitative flow ratio (QFR) uses fast computational algorithms based on 3-dimensional quantitative coronary angiography and estimation of contrast flow velocity during invasive coronary angiography (ICA) to obtain QFR values equivalent to fractional flow reserve (FFR). Objective To compare the diagnostic performance of QFR with coronary computed tomography angiography (CCTA), single-photon emission tomography (SPECT), and positron emission tomography (PET) for diagnosing myocardial ischemia defined by FFR. Method QFR computation was attempted in 109 patients (286 vessels without a subtotal/total lesion) of the 208 patients included in the PACIFIC-trial. Patients underwent 256-slice CCTA, Tetrofosmin SPECT, and [15O]H2O PET prior to ICA in conjunction with 3 vessel FFR measurements. ICA images were obtained without the use of a dedicated QFR acquistion protocol. QFR was calculated using a fixed empiric hyperemic flow velocity (fQFR) as well as using a patient specific flow velocity based on contrast passage through the coronary (cQFR). All analysis were performed on a per vessel level. Results Fixed QFR computation succeeded in 152 (53%) vessels while cQFR analysis was successful in 140 (49%) vessels. A good correlation between FFR and fQFR/cQFR was observed (R=0.774, p Table 1 % (95% Confidence Interval) fQFR n=152 cQFR (n=140) CCTA (n=152) SPECT (n=150) PET (n=149) Sensitivity 76 (59–89) 71 (53–86) 70 (51–84) 30 (16–49) 76 (58–89) Specificity 94 (88–98) 93 (86–97) 73 (64–81) 96 (90–99) 80 (72–87) Negative Predictive Value 93 (88–96) 92 (86–95) 90 (84–94) 83 (79–86) 92 (86–96) Positive Predictive Value 79 (64–89) 74 (59–85) 42 (33–51) 67 (42–84) 52 (42–62) Accuracy 90 (84–94) 88 (81–93) 72 (65–79) 81 (74–87) 79 (72–85) Figure 1. Conclusion Fixed QFR and cQFR correlate well with FFR with a high diagnostic accuracy as result. QFR outperformed CCTA, SPECT, and PET for the diagnosis of myocardial ischemia on a per vessel basis with the important footnote that fQFR and cQFR could only be computed in 53%, and 49% of the vessels.

Background Management of patients with suspected coronary artery disease (CAD) can be optimized with prognostic information derived from non-invasive imaging such as positron emission tomography (PET) perfusion imaging and coronary computed tomography angiography (CCTA). The aim of the present study was to determine the incremental prognostic value of combined functional testing using PET perfusion imaging and anatomical testing using CCTA-derived stenosis severity and morphological assessment of CCTA-derived plaque morphology. Methods In this retrospective study, 539 patients referred for hybrid [15O]H2O PET – CCTA imaging because of suspected CAD were investigated. PET perfusion imaging was used to determine hyperemic myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenosis and high-risk plaque morphology. Major adverse coronary events (MACE) included all-cause death, non-fatal myocardial infarction (MI), urgent revascularization and late non-urgent revascularization (i.e. not guided by initial diagnostic work-up with non-invasive imaging). Kaplan Meier analysis and Cox proportional hazard regression were used to evaluate the independent prognostic value of PET-derived MBF, CCTA-derived stenosis and CCTA-derived high-risk plaque. Results During a mean follow-up of 6.8 [4.8–7.9] years, 79 (14.7%) patients experienced MACE, including 23 (4.3%) deaths, 19 (3.5%) MIs, 8 (1.5%) urgent revascularizations and 29 (5.4%) late non-urgent revascularizations. Annualized event rates for normal vs. abnormal results of PET perfusion imaging, CCTA-derived stenosis and high-risk plaque morphology were 1.2% vs 4.1%, 0.6% vs 4.4%, and 1.7% vs 5.6%, respectively (p MACE-free survival stratified by PET-CT Conclusion PET-derived myocardial blood flow and CCTA-derived stenosis severity and high-risk plaque morphology are independent long-term predictors of adverse cardiac events and provide incremental prognostic value. Combined functional, anatomical and morphological assessment may allow for improved risk stratification in patients with suspected CAD.

Background A low coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as a factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive coronary artery disease (CAD). Objective To elucidate the association of V/M with non-invasively obtained MBF parameters by means of [15O]H2O positron emission tomography (PET), as well as its correlations with invasively measured fractional flow reserve (FFR), overall and specifically in vessel with non-obstructive CAD. Methods This is a substudy of the PACIFIC trial, in which 208 patients underwent CCTA, and [15O]H2O PET prior to invasive coronary angiography (ICA) in conjunction with 3 vessel FFR measurements. Patient specific V/M was calculated for 152 patients. Matched vessel specific hyperemic MBF (hMBF), coronary flow reserve (CFR), FFR, and patient specific V/M were available for 431 vessels. The median V/M (20.71 mm3/g) was used to divide the study population into a group with a low V/M ( Results Overall, a higher percentage of vessels with an abnormal hMBF (34% vs. 19%, p=0.009), lower FFR values (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p=0.016), and a higher number of positive FFR values (20% vs. 9%, p=0.004) were observed among vessels in the low V/M group. Furthermore, a weak correlation between V/M, global hMBF (R=0.179, p=0.027), and global CFR (R=0.163, p=0.045) as well as a weak significant association with vessel specific hMBF (p=0.027), and FFR (p Conclusion Overall, vessels with an abnormal hMBF, and positive FFR measurements were more frequently observed in patients with a low V/M compared to those with a high V/M. Furthermore, V/M weakly correlated with global hMBF as well as with CFR and was associated with vessel specific hMBF and FFR. However, there was no correlation between V/M and global nor vessel specific blood flow parameters in the absence of obstructive CAD, notwithstanding a weak association of V/M with FFR within this group was noted.

Background Multiple techniques in chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) have been developed to cross CTOs. Purpose To compare recovery of quantitative myocardial blood flow (MBF) after different CTO PCI techniques. Methods Consecutive patients with [15O]H2O positron emission tomography perfusion imaging before and three months after successful CTO PCI were included. Change in quantitative hyperemic MBF, coronary flow reserve (CFR) and perfusion defect size were compared between antegrade wire escalation (AWE), retrograde wire escalation (RWE), antegrade dissection and reentry (ADR) and retrograde dissection and reentry (RDR), and further between specific subintimal crossing and reentry techniques. Results 193 patients were treated with AWE (N=90), RWE (N=24), ADR (N=35) and RDR (N=44). Significant improvements (all p Conclusions Recovery of hyperemic MBF, CFR, and perfusion defect size was significant after CTO PCI and comparable between different crossing techniques. Improvement of hyperemic MBF was inferior after using the knuckle-wire subintimal crossing technique and STAR compared to other subintimal crossing and reentry techniques. Acknowledgement/Funding None

Background Quantification of absolute myocardial perfusion using positron emission tomography (PET) augments diagnostic performance and aids risk stratification in patients with coronary artery disease (CAD). Similar to PET, cardiac magnetic resonance imaging (CMR) allows for quantification of absolute myocardial blood flow (MBF). To date, quantitative CMR perfusion has not been compared with [15O]H2O PET, which is considered to be the gold standard for quantification of MBF. Purpose The purpose of this study was to compare CMR measurements of absolute myocardial perfusion to those obtained using [15O]H2O PET. Methods Fifty-one patients with stable CAD underwent [15O]H2O PET followed by CMR within 7 days. Late gadolinium enhancement was used to rule out presence of scar tissue. CMR perfusion imaging was performed using a single bolus dual sequence technique. Myocardial perfusion was quantified for the three main vascular territories at rest and during vasodilator stress. Results Pooled CMR estimates of absolute MBF correlated well with PET (r=0.79; p Per vessel – CMR vs PET perfusion Conclusions Resting MBF, stress MBF and CFR measurements correlated poorly with [15O]H2O PET. Nevertheless, stress MBF and CFR were concordant between CMR and [15O]H2O PET in 79% and 75% of vascular territories, respectively. Acknowledgement/Funding None

Purpose To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). Methods Fifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress. Results CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P

BACKGROUND: The benefits of chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial perfusion, as compared with PCI of hemodynamically significant non-CTO lesions. METHODS: Consecutive patients with a preserved left ventricular ejection fraction (≥50%) and a CTO or non-CTO lesion, in whom [15 O]H2 O positron emission tomography was performed prior and after successful PCI, were included. Change in quantitative (hyperemic) myocardial blood flow (MBF), coronary flow reserve (CFR) and perfusion defect size (in myocardial segments) were compared between CTOs and non-CTO lesions. RESULTS: In total 92 patients with a CTO and 31 patients with a non-CTO lesion were included. CTOs induced larger perfusion defect sizes (4.51 ± 1.69 vs. 3.23 ± 2.38 segments, P < 0.01) with lower hyperemic MBF (1.30 ± 0.37 vs. 1.58 ± 0.62 mL·min-1 ·g-1 , P < 0.01) and similarly impaired CFR (1.66 ± 0.75 vs. 1.89 ± 0.77, P = 0.17) compared with non-CTO lesions. After PCI both hyperemic MBF and CFR increased similarly between groups (P = 0.57 and 0.35) to normal ranges with higher hyperemic MBF values in non-CTO compared with CTO (2.89 ± 0.94 vs. 2.48 ± 0.73 mL·min-1 ·g-1 , P = 0.03). Perfusion defect sizes decreased similarly after CTO PCI and non-CTO PCI (P = 0.14), leading to small residual defect sizes in both groups (1.15 ± 1.44 vs. 0.61 ± 1.45 segments, P = 0.054). CONCLUSIONS: Myocardial perfusion findings are slightly more hampered in patients with a CTO before and after PCI. Percutaneous revascularization of CTOs, however, improves absolute myocardial perfusion similarly to PCI of hemodynamically significant non-CTO lesions, leading to satisfying results.

Objective Next to myocardial perfusion, single-photon emission computed tomography (SPECT) also allows for assessment of non-perfusion parameters such as transient ischemic dilatation (TID) and a reduction of ejection fraction (EF) with stress imaging. The present study aimed to evaluate the diagnostic value of TID and EF reserve for the detection of significant multivessel coronary artery disease (CAD). Methods A total of 206 patients with suspected stable coronary artery disease prospectively underwent gated stress-rest 99mTc-tetrofosmin SPECT and invasive coronary angiography with routine fractional flow reserve (FFR) measurements, regardless of imaging results. Left ventricular (LV) volumes, TID and EF reserve were assessed and compared with FFR defined severity of CAD. Results According to FFR, 92 (45%) patients had significant CAD, whereas 25 (12%) showed two vessel disease and 22 (11%) showed three vessel disease (3-VD). With an increasing extent of CAD, TID values and EF reserve did not significantly change (p = 0.07 and p = 0.42 for trend, respectively). Conversely, absolute LV volumes and EF differed significantly among groups of CAD severity (p < 0.01 for all trends). Conclusion SPECT derived TID and EF reserve did not differ between patients with high risk CAD (3-VD) and low risk or no significant CAD. Therefore the present results advocate exert caution when using these ancillary findings in clinical practice.

Objectives The randomized clinical VANISH (Impact of Vascular Reparative Therapy on Vasomotor Function and Myocardial Perfusion: A Randomized [15O]H2O PET/CT Study) trial was conducted to assess quantitative myocardial blood flow (MBF) during resting, hyperemia, and cold pressor testing (CPT) with positron emission tomographic perfusion imaging after the implantation of a bioresorbable everolimus-eluting scaffold compared with a drug-eluting stent. Background Long-term resorption of the bioresorbable everolimus-eluting scaffold reinstates normal vessel geometry, allowing natural regeneration of the newly formed endothelium with revival of vasomotor function. Methods Sixty patients (18 to 65 years of age) with single-vessel disease and type A or B1 lesions were randomized in a 1-to-1 fashion. Approximately 1 month, 1 year, and 3 years after device implantation, patients underwent [15O]H2O cardiac positron emission tomography. The primary endpoint was the interaction of device type and evolution over time of hyperemic MBF, coronary flow reserve, or CPT reserve. At 3-year follow-up, control invasive coronary angiography with optical coherence tomography was performed. Results Fifty-nine (98%), 56 (93%), and 51 (85%) patients successfully completed 1-month, 1-year, and 3-year follow-up positron emission tomography, respectively, and no culprit vessel events were registered during follow-up time. The primary study endpoint (i.e., interaction between device type and time) was nonsignificant for hyperemic MBF, CPT reserve, and coronary flow reserve (p > 0.05 for all). In all patients, hyperemic MBF decreased from 1 to 3 years (p = 0.02), while coronary flow reserve was lower at 3-year follow-up compared with 1-month and 1-year follow-up (p = 0.03 for both). After 3 years, percentage area stenosis measured with optical coherence tomography was higher within the bioresorbable everolimus-eluting scaffold compared with the drug-eluting stent (p = 0.03). Conclusions The hypothesized beneficial effects of scaffold resorption did not translate to improved MBF during maximal hyperemia or endothelium-dependent vasodilation by CPT.