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A combined filtration system was investigated for the first time in the present work. A reactive filter was immersed in a steel melt containing artificially generated endogenous inclusions. After extracting the filter, the melt was poured through a second filter and into a crucible where it cooled down. The second filter had a pure aluminum oxide flame-sprayed coating, in order to prevent reactions and only remove pre-existing inclusions. It was observed that the immersion of a reactive, coated filter generally resulted in larger inclusions. When no casting was performed, or when the second filter was omitted, smaller remaining inclusions were found. Calcium aluminate based coatings resulted in the creation of new multiphase inclusions (and less alumina). Although these results cannot be directly compared with state-of-the-art industrial filtration procedures, active filtration seems so far the most promising approach to produce steel of improved quality. In addition, filters with a calcium aluminate-based coating might be interesting in the production of steel with tailored inclusions for special applications.

Summary: Background: Type 1 diabetes is a complex heterogenous autoimmune disease without therapeutic interventions available to prevent or reverse the disease. This study aimed to identify transcriptional changes associated with the disease progression in patients with recent-onset type 1 diabetes. Methods: Whole-blood samples were collected as part of the INNODIA study at baseline and 12 months after diagnosis of type 1 diabetes. We used linear mixed-effects modelling on RNA-seq data to identify genes associated with age, sex, or disease progression. Cell-type proportions were estimated from the RNA-seq data using computational deconvolution. Associations to clinical variables were estimated using Pearson's or point-biserial correlation for continuous and dichotomous variables, respectively, using only complete pairs of observations. Findings: We found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Significant associations of the gene expression changes were found with ZnT8A autoantibody positivity. Rate of change in the expression of 16 genes between baseline and 12 months was found to predict the decline in C-peptide at 24 months. Interestingly and consistent with earlier reports, increased B cell levels and decreased neutrophil levels were associated with the rapid progression. Interpretation: There is considerable individual variation in the rate of progression from appearance of type 1 diabetes-specific autoantibodies to clinical disease. Patient stratification and prediction of disease progression can help in developing more personalised therapeutic strategies for different disease endotypes. Funding: A full list of funding bodies can be found under Acknowledgments.

Recent advances in microfluidic engineering allow the creation of microenvironments in which human cells can be cultured under (patho-)physiological conditions with greater reality than standard plastic tissue culture plates. Microfluidic devices, also called Organs-on-Chip (OoC), allow complex engineering of the cellular compartment, yielding designs in which microfluidic flow can be precisely controlled. However, it is important that cellular physiology is not only controlled but can also be monitored in these devices. Here, we integrated oxygen and pH sensors into microfluidics, allowing close monitoring of the extracellular flux from the cells, enabling constant assessment of features such as glycolysis and mitochondrial oxidative phosphorylation in situ. Using human-induced pluripotent stem cells (hiPSCs) as an exemplar of a highly metabolic and relatively challenging cell type to maintain, we showed that monitoring the extracellular environment allowed rapid optimization of the seeding protocol. Based on the measurements, we implemented earlier and more frequent media refreshment to counteract the rapid acidification and depletion of oxygen. The integrated sensors showed that hiPSCs in the devices exhibited mitochondrial and glycolytic capacity similar to that measured with the Seahorse extracellular flux system, the most widely used standard for these types of assays in conventional cell culture. Under both conditions, hiPSCs showed greater reliance on glycolysis than mitochondrial OXPHOS and the absolute values obtained were similar. These results thus pave the way for the assessment of cell metabolism in situ under conditions of fluidic flow with the same precision and relevance as current standard static cell cultures.

Combined Oxidative Phosphorylation Deficiency 8 (COXPD8) is an autosomal recessive disorder causing lethal childhood-onset hypertrophic cardiomyopathy. Homozygous or compound heterozygous mutations in the nuclear-encoded mitochondrial alanyl-tRNA synthetase 2 (AARS2) gene underly the pathology. We generated induced pluripotent stem cells (hiPSCs) from two patients carrying the heterozygous compound c.1774 C>T, c.2188 G>A and c.2872 C>T AARS2 mutations, as well as a related healthy control carrying the c.2872 C>T AARS2 mutation. All hiPSC-lines expressed pluripotency markers, maintained a normal karyotype, and differentiated towards the three germ layer derivatives in vitro. These lines can be used to model COXPD8 or mitochondrial dysfunction.

Objectives: We sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [ 15 O]H 2 O positron-emission tomography (PET) perfusion imaging., Background: CTO 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., Methods: A total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [ 15 O]H 2 O 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., Results: This 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)., Conclusions: The present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [ 15 O]H 2 O 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 Perspective: What is new? What are the clinical implications?, Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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

Background: The recent development of artificial intelligence-guided quantitative coronary computed tomography angiography analysis (AI-QCT) has enabled rapid analysis of atherosclerotic plaque burden and characteristics., Objectives: This study set out to investigate the 10-year prognostic value of atherosclerotic burden derived from AI-QCT and to compare the spectrum of plaque to manually assessed coronary computed tomography angiography (CCTA), coronary artery calcium scoring (CACS), and clinical risk characteristics., Methods: This was a long-term follow-up study of 536 patients referred for suspected coronary artery disease. CCTA scans were analyzed with AI-QCT and plaque burden was classified with a plaque staging system (stage 0: 0% percentage atheroma volume [PAV]; stage 1: >0%-5% PAV; stage 2: >5%-15% PAV; stage 3: >15% PAV). The primary major adverse cardiac event (MACE) outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and all-cause mortality., Results: The mean age at baseline was 58.6 years and 297 patients (55%) were male. During a median follow-up of 10.3 years (IQR: 8.6-11.5 years), 114 patients (21%) experienced the primary outcome. Compared to stages 0 and 1, patients with stage 3 PAV and percentage of noncalcified plaque volume of >7.5% had a more than 3-fold (adjusted HR: 3.57; 95% CI 2.12-6.00; P < 0.001) and 4-fold (adjusted HR: 4.37; 95% CI: 2.51-7.62; P < 0.001) increased risk of MACE, respectively. Addition of AI-QCT improved a model with clinical risk factors and CACS at different time points during follow-up (10-year AUC: 0.82 [95% CI: 0.78-0.87] vs 0.73 [95% CI: 0.68-0.79]; P < 0.001; net reclassification improvement: 0.21 [95% CI: 0.09-0.38]). Furthermore, AI-QCT achieved an improved area under the curve compared to Coronary Artery Disease Reporting and Data System 2.0 (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.023) and manual QCT (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.040), although net reclassification improvement was modest (0.09 [95% CI: -0.02 to 0.29] and 0.04 [95% CI: -0.05 to 0.27], respectively)., Conclusions: Through 10-year follow-up, AI-QCT plaque staging showed important prognostic value for MACE and showed additional discriminatory value over clinical risk factors, CACS, and manual guideline-recommended CCTA assessment., Competing Interests: Funding Support and Author Disclosures Dr Nurmohamed is co-founder of Lipid Tools. Dr Stroes has received lecturing/advisory board fees from Amgen, Novartis, Esperion, Sanofi-Regeneron, and Akcea. Drs Min and Earls are employees of and hold equity in Cleerly Inc. Dr Choi has received grant support from GW Heart and Vascular Institute; holds equity in Cleerly, Inc; and has provided consulting services to Siemens Healthineers. Dr Knaapen has received research grants from HeartFlow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the potential progressiveness of mandibular asymmetry and to study factors that influence chin point deviation in patients with unilateral craniofacial microsomia (CFM). Paediatric patients with unilateral CFM with available radiologic imaging and medical photographs were included. Chin point deviation was measured on clinical photographs. A Jonckheere-Terpstra test and linear mixed model for repeated measurements assessed the relation of chin point deviation on natural growth, Pruzansky-Kaban score, and soft tissue score. A total of 110 patients were included. The linear mixed model showed no statistically significant changes of chin point deviation during growth (effect estimate -0.006°, 95% CI -0.04° to -0.03°, p = 0.74). A statistical significant relation between both the Pruzansky-Kaban and soft tissue score on chin point deviation was found (effect estimate -5.10°, 95% CI -6.45° to -3.75°, p ≤ 0.001 and effect estimate -3.42°, CI -5.86° to -0.98°, p ≤ 0.001, respectively). Within the limitations of the study it seems that craniofacial microsomia may be a non-progressive disorder, because chin point deviation did not change over time., Competing Interests: Declaration of competing interest There are no conflicts of interest in the materials or subject matter dealt with in the manuscript., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: This article provides a review of a decade of clinical research studies on clinical features, medical interventions, and surgical interventions for individuals with craniofacial microsomia (CFM). We also provide recommendations for future clinical research., Method: A systematic search of literature was conducted in Embase and PubMed/MEDLINE Ovid. All publications from 2010 to 2020 that included at least 10 individuals with CFM were considered relevant for this study., Results: A total of 91 articles were included. In the past decade, many new studies on CFM have been published providing more insight on the diagnosis and management of patients with CFM. This review encompasses findings on the clinical difficulties patients with CFM encounter, including the craniofacial and extracraniofacial characteristics of patients with CFM and its related clinical consequences on breathing, feeding, speech, and hearing., Conclusions: A considerable number of large multicenter studies have been published in recent years, providing new insights in the clinical consequences of CFM. The phenotypic variety between patients with CFM makes patient-specific treatment tailored to individual needs essential. The research and development of clinical care standards might be challenging because of the heterogeneity of CFM. Future research on clinical and patient-reported outcomes can help identify optimal treatment strategies. Cooperation between craniofacial centers, using uniform registration and outcome measurement tools, could enhance research and future care for these patients., Level of Evidence: Level IV., Competing Interests: Declaration of Competing Interest There are no conflicts of interest in the materials or subject matter dealt with in the manuscript., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.)

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

Objectives: 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 [ 15 O]H 2 O 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., Competing Interests: Funding Support and Author Disclosures Dr. Knaapen has received research grants from HeartFlow Inc. Dr. Min is employee and has an equity interest in Cleerly, Inc.; and serves on the advisory board of Arineta. Dr. Leipsic has received research grants from GE Healthcare and Edwards Lifesciences; and serves as consultant for HeartFlow Inc. and Circle CVI. Drs. Freiman, Goshen, Heitel, and Langzam are employees of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 [ 15 O]H 2 O 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 <3 segment PD reduction (p < 0.01; risk-adjusted p = 0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11 ml · min -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., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 ., Competing Interests: Declaration of competing interest Dr. Min serves as a consultant to Abbott Vascular, serves on the scientific advisory board of Arineta, and has an equity interest in MDDX. Dr. Leipsic has received research grants from GE Healthcare; and serves as a consultant and holds stock options in Circle CVI and HeartFlow. Dr. Taylor has an equity interest in and is an employee of HeartFlow. Dr. Knaapen has received unrestricted research grants from HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 [The Author/The Authors]. Published by Elsevier Inc. All rights reserved.)

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- 99 m tetrofosmin SPECT and [ 15 O]H 2 O 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 FFR-defined significant CAD compared with perfusion imaging by SPECT or PET., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)