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Background Deep learning image reconstructions (DLIR) have been recently introduced as an alternative to filtered back projection (FBP) and iterative reconstruction (IR) algorithms for computed tomography (CT) image reconstruction. The aim of this study was to evaluate the effect of DLIR on image quality and quantification of coronary artery calcium (CAC) in comparison to FBP. Methods One hundred patients were consecutively enrolled. Image quality–associated variables (noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)) as well as CAC-derived parameters (Agatston score, mass, and volume) were calculated from images reconstructed by using FBP and three different strengths of DLIR (low (DLIR_L), medium (DLIR_M), and high (DLIR_H)). Patients were stratified into 4 risk categories according to the Coronary Artery Calcium - Data and Reporting System (CAC-DRS) classification: 0 Agatston score (very low risk), 1–99 Agatston score (mildly increased risk), Agatston 100–299 (moderately increased risk), and ≥ 300 Agatston score (moderately-to-severely increased risk). Results In comparison to standard FBP, increasing strength of DLIR was associated with a significant and progressive decrease of image noise (p < 0.001) alongside a significant and progressive increase of both SNR and CNR (p < 0.001). The use of incremental levels of DLIR was associated with a significant decrease of Agatston CAC score and CAC volume (p < 0.001), while mass score remained unchanged when compared to FBP (p = 0.232). The underestimation of Agatston CAC led to a CAC-DRS misclassification rate of 8%. Conclusion DLIR systematically underestimates Agatston CAC score. Therefore, DLIR should be used cautiously for cardiovascular risk assessment. Key Points • In coronary artery calcium imaging, the implementation of deep learning image reconstructions improves image quality, by decreasing the level of image noise. • Deep learning image reconstructions systematically underestimate Agatston coronary artery calcium score. • Deep learning image reconstructions should be used cautiously in clinical routine to measure Agatston coronary artery calcium score for cardiovascular risk assessment.

Pathologic hypertrophy of the cardiac muscle is a commonly encountered phenotype in clinical practice, associated with a variety of structural and non-structural diseases. Coronary microvascular disease is considered to play an important role in the natural history of this pathological phenotype. Non-invasive imaging modalities, most prominently positron emission tomography and cardiac magnetic resonance, have provided insights into the pathophysiological mechanisms of the interplay between hypertrophy and the coronary microvasculature. This article summarizes the current knowledge on coronary microvascular dysfunction in the most frequently encountered forms of pathologic hypertrophy.

Aim The current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). Methods Data from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., Results A total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. Conclusion A single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.

Cardiac masses represent infrequent findings in cardiac CT and the differential diagnosis includes normal variants, non-neoplastic cardiac masses, imaging artefacts, and benign and malignant cardiac tumours. Given its exceptional spatial resolution and by enabling tissue attenuation characterization with the aid of contrast agents, cardiac CT can provide accurate assessment of the location, the extent, the morphological features of masses, and facilitate diagnosis as an adjunct to other imaging modalities. Standard coronary CT angiography image acquisition can be employed, and modification of the timing of injected contrast agent can improve the diagnostic accuracy of the modality. The most common cardiac masses include thrombi, myxomas, and metastatic tumours. Thrombi are commonly encountered in the left atrial appendage or left ventricle, and are characterized by low attenuation. Benign neoplastic masses appear pedunculated with narrow base to the myocardium, while malignant tumours have a more infiltrative pattern with broad attachments.

Background: Medical 3D printing is being increasingly employed for pre-procedural planning and simulation. One important application is in occluder device sizing for left atrial appendage (LAA) closure. Studies have demonstrated clinical utility of 3D printed anatomical models for LAA closure. Artificial intelligence-based segmentation has been applied to multiple cardiovascular diseases, including to LAA segmentation. However, to our knowledge, there has not been a comparison of artificial intelligence-based deep learning segmentation (DLS) where there was a clinical 3D printed model of the left atrium and appendage. Methods: Thirty-nine patients had 3D printed models requested by the interventional cardiologist (IC). Standard segmentation (SS) was performed by a trained engineer and approved by a cardiovascular imager (CI). The models were 3D printed using flexible resin and desktop inverted vat photopolymerization technology. The effort expended throughout the workflow was meticulously documented. Thirty-four of the 39 patients underwent left atrial appendage occlusion using the 3D printed model for device sizing. The 34 patients who underwent a procedure using the 3D printed model were followed for 6 months for major adverse events, device embolization, procedure related myocardial infarction (MI), procedural stroke, new pericardial effusion, pericardial effusion requiring intervention, surgical conversion, and peri-procedural death. All 39 patients also underwent DLS using a commercial software and metrics including segmentation time, segmented volume, DICE index were assessed compared to the SS. A Bland-Altman and regression/correlation analysis was also conducted. Results: The mean SS time was 72.3 minutes whereas the mean DLS time was 3.5 minutes. The DLS closely matched the SS with a mean DICE index of 0.96. The average number of devices attempted was 1.3. The DLS was highly correlated with the SS volume data (r = 0.99). Bland-Altman analysis showed a negative bias (-5.31%) in the volume difference data. There were no long-term complications in the 34 patients who underwent procedure using the 3D printed model for occluder device sizing. Conclusions: We have successfully demonstrated the performance of a commercial DLS algorithm compared to CI approved SS for left atrial appendage occluder device sizing using a clinical 3D printed model.

We present the management of an anomalous coronary artery originating from the opposite sinus of Valsalva with comprehensive diagnostic workup including noninvasive coronary computed tomography (CT) derived fractional flow reserve (FFR) and invasive dobutamine-volume challenge-FFR/intravascular ultrasound. After surgical operation, treatment success was quantified by anatomical and functional analysis in postoperative CT. (Level of Difficulty: Advanced.).

Purpose To assess the prognostic value of regional quantitative myocardial flow measures as assessed by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). Methods We retrospectively included 150 consecutive patients with suspected CAD who underwent clinically indicated 13 N-ammonia PET-MPI and who did not undergo revascularization within 90 days of PET-MPI. The presence or absence of a decreased global myocardial flow reserve (i.e., MFR Results Over a median follow-up of 50 months (IQR 38–103), 30 events occurred in 29 patients. Kaplan–Meier analysis showed significantly reduced event-free and overall survival in MFR groups 2 and 3 compared to MFR group 1 (log-rank: p = 0.015 and p = 0.013). In a multivariable Cox regression analysis, decreased regional MFR was an independent predictor for MACE (adjusted HR 3.44, 95% CI 1.17–10.11, p = 0.024) and all-cause death (adjusted HR 4.72, 95% CI 1.07–20.7, p = 0.04). Conclusions A decreased regional MFR as assessed by 13 N-ammonia PET-MPI confers prognostic value by identifying patients at increased risk for future adverse cardiac outcomes and all-cause death.

Congenital heart disease (CHD) is a group of structural defects of the heart and the great vessels, and one of the leading causes of death among infants and young adults. Several gene variants are involved in diverse mechanisms of cardiac and vessel development and could thus be considered candidate mutated genes for a congenital heart defect or a specific variant could predispose a person to CHD. In the present study, variants in four such genes are investigated for the first time in a group of young Greek CHD patients: the NFKB1 gene polymorphism (–94ins/ delATTG), rs28362491, NKX2-5 gene polymorphism rs2277923, GATA4 gene polymorphism rs11785481 and RANKL gene polymorphism rs4531631. A total of 43 CHD patients and 100 healthy adults were included in the study. The polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) method was used to genotype the aforementioned polymorphisms of NFKB1, NKX2-5, GATA4 and RANKL. The association analysis identified that there was a protective association between CHD and the A allele of rs2277923 polymorphism (p = 0.004). The D allele of the rs28362491 polymorphism is also a likely risk factor for causing CHD (p = 0.006). The differences of the rs4531631 and rs11785481 variant contribution had no statistical significance between the groups (p >0.05). In conclusion, our results revealed that the rs28362491 and rs2277923 gene polymorphisms, but not the rs4531631 and rs11785481 polymorphisms, may contribute to CHD risk in a cohort of Greek CHD patients.

Objectives Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI). Methods Sixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell’s c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%). Results CAVi correlated moderately with stress MBF and MFR (R = 0.50, p < 0.001, and R = 0.39, p = 0.002). Mean stress MBF and MFR were lower in patients with low (i.e., ≤ 20.2 mm3/g, n = 24) versus high (i.e., > 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82–0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively). Conclusions CAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone. Key Points • Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from13N-ammonia positron emission tomography myocardial perfusion imaging. • CAVi is independently associated with abnormal stress myocardial blood flow. • CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia.

Pathologic hypertrophy of the cardiac muscle is a commonly encountered phenotype in clinical practice, associated with a variety of structural and non-structural diseases. Coronary microvascular disease is considered to play an important role in the natural history of this pathological phenotype. Non-invasive imaging modalities, most prominently positron emission tomography and cardiac magnetic resonance, have provided insights into the pathophysiological mechanisms of the interplay between hypertrophy and the coronary microvasculature. This article summarizes the current knowledge on coronary microvascular dysfunction in the most frequently encountered forms of pathologic hypertrophy.

OBJECTIVE To evaluate the impact of adaptive statistical iterative reconstruction-V (ASIR-V) on the accuracy of ultra-low-dose coronary artery calcium (CAC) scoring. MATERIALS AND METHOD One-hundred-and-three patients who underwent computed tomography (CT) for CAC scoring were prospectively included. All underwent standard scanning with 120-kilovolt-peak (kVp) and with 80- and 70-kVp tube voltage. ASiR-V was applied to the 80- and 70-kVp scans at different levels. The 120-kVp scans reconstructed with filtered back projection served as the standard of reference. Recently published novel kVp-adapted thresholds were used for calculation of CAC scores from 80- and 70-kVp scans and the resulting CAC scores were compared against the standard of reference. Patients were stratified into six CAC score risk categories: 0, 1-10, 11-100, 101-400, 401-1000, and >1000. RESULTS Increasing levels of ASIR-V led to an increasing underestimation of CAC scores with bias ranging from -128 to -118 and from -205 to -198 for the 80- and 70-kVp scans, respectively, when compared with the standard of reference. Reconstruction with 20% and 40% ASIR-V for the 80- and 70-kVp scans, respectively, yielded noise levels comparable to the standard of reference. Nevertheless, a change in risk-class was observed in 29 (28.6%) and 46 (44.7%) patients, exclusively to a lower risk-class, when CAC scores were derived from these reconstructions. CONCLUSION ASIR-V leads to noise reduction in CT scans acquired with low tube-voltages. However, ASIR-V introduces substantial inaccuracies and marked underestimation of ultra-low-dose CAC scoring as compared with standard-dose CAC scoring despite normalization of noise.

BACKGROUND Coronary computed tomography angiography (CCTA)-based transluminal attenuation gradient (TAG) was suggested to determine the functional significance of a stenosis. However, evidence that TAG acquired by wide-volume scanners can assess the hemodynamic significance of stenosis assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is lacking. Moreover, coronary cross-sectional area may influence TAG. Hence, we aimed at assessing the diagnostic value of TAG to predict ischemia in SPECT-MPI and the correlation between TAG and the transluminal cross-sectional area gradient (TCG). METHODS Patients undergoing CCTA and SPECT-MPI for suspected coronary artery disease were included. TAG and TCG were calculated measuring the mean vessel attenuation and the cross-sectional area along major coronary vessels at 5-mm intervals. RESULTS A total of 255 coronary arteries of 87 patients were included. TAG and TCG did not discriminate between coronary arteries with or without ischemia as assessed by SPECT-MPI (p = .44 and p = .25, respectively). The area under the curve to predict ischemia was not increased by adding TAG (0.88, 95% CI 0.83-0.92) or TCG (0.87, 95% CI 0.81-0.90) to CCTA alone (0.85, 95% CI 0.80-0.89). There was a significant correlation between TAG and TCG (r = 0.43; p

Background Advances in three-dimensional reconstruction techniques and computational fluid dynamics of coronary CT angiography (CCTA) data sets make feasible evaluation of endothelial shear stress (ESS) in the vessel wall. Purpose To investigate the relationship between CCTA-derived computational fluid dynamics metrics, anatomic and morphologic characteristics of coronary lesions, and their comparative performance in predicting impaired coronary vasodilating capability assessed by using PET myocardial perfusion imaging (MPI). Materials and Methods In this retrospective study, conducted between October 2019 and September 2020, coronary vessels in patients with stable chest pain and with intermediate probability of coronary artery disease who underwent both CCTA and PET MPI with oxygen 15-labeled water or nitrogen 13 ammonia and quantification of myocardial blood flow were analyzed. CCTA images were used in assessing stenosis severity, lesion-specific total plaque volume (PV), noncalcified PV, calcified PV, and plaque phenotype. PET MPI was used in assessing significant coronary stenosis. The predictive performance of the CCTA-derived parameters was evaluated by using area under the receiver operating characteristic curve (AUC) analysis. Results There were 92 coronary vessels evaluated in 53 patients (mean age, 65 years ± 7; 31 men). ESS was higher in lesions with greater than 50% stenosis versus those without significant stenosis (mean, 15.1 Pa ± 30 vs 4.6 Pa ± 4 vs 3.3 Pa ± 3; P = .004). ESS was higher in functionally significant versus nonsignificant lesions (median, 7 Pa [interquartile range, 5-23 Pa] vs 2.6 Pa [interquartile range, 1.8-5 Pa], respectively; P ≤ .001). Adding ESS to stenosis severity improved prediction (change in AUC, 0.10; 95% CI: 0.04, 0.17; P = .002) for functionally significant lesions. Conclusion The combination of endothelial shear stress with coronary CT angiography (CCTA) stenosis severity improved prediction of an abnormal PET myocardial perfusion imaging result versus CCTA stenosis severity alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kusmirek and Wieben in this issue.

Candida albicans is the most prevalent and pathogenic fungal infection of the urinary tract. Although fungal urinary tract infections occur less frequently than bacterial infections, their incidence has increased during the last decades. Prematurity, parenteral nutrition, corticosteroids, immunosuppressive factors, surgical procedures, and prolonged antibiotic therapy are common predisposing factors. We report a case of candidal renal mycetomas in a 10-month-old female infant without immunodeficiency who developed candidal infection after surgical treatment for bilateral vesico-ureteric reflux. The renal candidiasis was treated successfully with fluconazole and echinocandin. The occurrence of mycetomas or fungus balls in patients who are immunocompetent is extremely rare. To the best of our knowledge, this is the second case report of mycetomas occurring in immunocompetent pediatric patients.

Objective The purpose of this study was to quantify the reduction in radiation dose achievable by using the optimal z-axis coverage in coronary computed tomography (CT) angiography (CCTA) on a latest-generation 256-slice scanner. Methods A total of 408 scans were reviewed that were performed on a wide-range detector scanner allowing up to 16-cm z-axis coverage (adjustable in 2-cm increments). For each CCTA study, we assessed the radiation dose (ie, dose-length product and volume CT dose index) and measured the minimum z-axis coverage necessary to cover the complete cardiac anatomy. We calculated the potential radiation dose savings achievable through reduction of the z-axis coverage to the minimum necessary. Results The majority of the CCTA scans were performed with a z-axis coverage of 16 cm (n = 285, 69.9%), followed by 14 cm (n = 121, 29.7%) and 12 cm (n = 2, 0.5%). In the group that was scanned with a collimation of 16 cm, radiation dose could have been reduced by 12.5% in 55 patients, 25% in 195 patients, and 37.5% in 33 patients when using optimal z-axis coverage for CCTA. In the group that was scanned with a collimation of 14 cm, radiation dose could have been reduced by 14.3% in 90 patients, and 28.6% in 30 patients, whereas in the group that was scanned with a collimation of 12 cm, dose could have been reduced by 16.7% in 2 patients. Conclusions Using correct z-axis coverage in CCTA on a latest-generation 256-slice scanner yields average dose reductions of 22.0% but may be as high as 37.5%.

Given the current increase in the incidence of coronary artery disease in younger women as well as the high lifetime risk of developing an x-ray-induced malignancy in this population, we aimed at assessing chest radiation in 206 women ≤55 years old undergoing coronary calcium scoring (CACS) by using a Monte Carlo simulation tool. Our data indicate that the simulated radiation dose of the female breast during CACS depends substantially on the starting position of the x-ray tube, with an almost 2 times excess of breast radiation exposure being measured during anterior-posterior tube positioning. Thus, an additional technical feature taking into account the position of the x-ray tube when acquisition is triggered might be an important tool to reduce radiation exposure of the female breast during CACS.

A surface 12-lead electrocardiogram (ECG) is widely available, fast, inexpensive, and safe. However, its value to predict a true myocardial scar in patients with ischemic cardiomyopathy (ICM) has not been studied extensively yet. This study was conducted to assess whether Q waves on resting surface 12-lead ECG are predictive of non-viable myocardium in patients with ICM. We analyzed resting ECGs of 149 patients with ICM undergoing cardiac positron emission tomography (PET) with 13N-ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) at our institution. Pathological Q waves and QS complexes were assigned to one of three coronary artery territories and compared to the PET findings. Myocardial scar was defined as 2 or more contiguous myocardial segments with an average (matched) reduction of NH3 and FDG uptake

The human pathophysiology of stunned, hibernating and scarred myocardium in ischemic cardiomyopathy is a subject of controversy. While the “smart heart” theory postulates that reduced myocardial blood flow (MBF) at rest is responsible for myocytes switching to a state of hibernation, other theories suggest that a reduced myocardial flow reserve (MFR) may be the cause. We included 110 patients with ischemic cardiomyopathy. Based on quantitative myocardial perfusion assessment and viability imaging with 13N-NH3 and 18F-FDG positron emission tomography, respectively, as well as wall motion assessment from echocardiography, myocardial tissue was characterized as remote (i.e., normal myocardium), stunned (i.e., dysfunctional but viable myocardium with normal rest perfusion), hibernating (i.e., dysfunctional but viable myocardium with impaired rest perfusion), or scarred myocardium (i.e., non-viable myocardium). Compared to remote myocardium, dysfunctional but viable myocardium (including stunned and hibernating) had reduced rest MBF (0.89 mL/min/g vs. 0.79 and 0.76 mL/min/g, respectively; p

Positron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. In 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. Across myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min−1·g−1, sensitivity and specificity were 96% and 12%, respectively. Quantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min−1·g−1, viability testing by FDG-PET may be safely deferred.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Correlation of coronary artery tree geometry and clinical parameters with the distribution, complexity and severity of coronary artery disease: a pilot study using multislice CT coronary angiography” (MIS 5047882) Background Development and progression of coronary atherosclerosis is complex and not yet fully understood. Accumulative evidence supports the notion that coronary artery disease (CAD) results from an interaction of systemic factors, such as dyslipidemia, with local hemodynamic factors that regulate the site-specific predilection of atherosclerosis, particularly low endothelial shear stress (ESS). Since low ESS develops in geometrically irregular regions of the coronary tree for a given arterial blood flow, geometrical factors affect atherosclerotic plaque distribution and vulnerability. However, the correlation of coronary geometric features with the complexity and severity of CAD has not been fully elucidated. Purpose GEOMETRY-CTA is a prospective, non-randomized, observational study that aims to investigate the correlation of coronary artery geometrical features with the complexity and severity of CAD using Coronary Computed Tomography Angiography (CCTA). The prognostic value of a CCTA-derived geometric risk score will also be assessed. Methods The study aims to recruit 100 consecutive patients with suspected CAD and low/intermediate pre-test probability. Coronary geometrical characteristics such as angulation of coronary bifurcations, tortuosity, coronary artery volume index (CAVi) and vessel-length will be assessed with multi-planar reformation and volume rendering techniques, and integrated into a single geometric risk score. The extent and vulnerability of plaque burden will be calculated using several anatomical scoring systems such as the Leiden CTA risk score, CT-SYNTAX score, and CT-adapted Gensini score. Patients will be prospectively followed for 12 months after enrollment. Results The primary objective of the study is to evaluate the correlation of the geometric risk score with CAD severity and plaque vulnerability. We also hypothesize that wider bifurcation angles and lower CAVi augmenting the atherosclerosis-prone environment and predict higher CAD extent and complexity. Conclusion The present study aims to introduce a quantitative, non-invasive imaging biomarker expressing CAD severity and investigate its prognostic value in regards to adverse cardiovascular events. The derived index will be available for incorporation in larger national prospective studies for further cardiovascular risk stratification.

Purpose Misalignment between positron emission tomography (PET) datasets and attenuation correction (AC) maps is a potential source of artifacts in myocardial perfusion imaging (MPI). We assessed the impact of adenosine on the alignment of AC maps derived from magnetic resonance (MR) and PET datasets during MPI on a hybrid PET/MR scanner. Methods Twenty-eight volunteers underwent adenosine stress and rest 13N-ammonia MPI on a PET/MR. We acquired Dixon sequences for the creation of MRAC maps. After reconstruction of the original non-shifted PET images, we examined MRAC and PET datasets for cardiac spatial misalignment and, if necessary, reconstructed a second set of shifted PET images after manually adjusting co-registration. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were compared between shifted and non-shifted PET images. Additionally, we measured the amount of cranial movement of the heart (i.e., myocardial creep) after termination of adenosine infusion. Results Realignment was necessary for 25 (89.3%) stress and 12 (42.9%) rest PET datasets. Median SRS, SSS, and SDS of the non-shifted images were 6 (IQR = 4–7), 12 (IQR = 7–18), and 8 (IQR = 2–11), respectively, and of the shifted images 2 (IQR = 1–6), 4 (IQR = 7–18), and 1 (IQR = 0–2), respectively. All three scores were significantly higher in non-shifted versus shifted images (all p r = 0.541, p = 0.005). Conclusion Misalignment of MRAC and PET datasets commonly occurs during adenosine stress MPI on a hybrid PET/MR device, potentially leading to an increase in false-positive findings. Our results suggest that myocardial creep may substantially account for this and prompt for a careful review and correction of PET/MRAC data.

BACKGROUND AND AIMS: We aimed to characterize the spatial proximity of plaque destabilizing features local endothelial shear stress (ESS), minimal luminal area (MLA), plaque burden (PB), and near-infrared spectroscopy (NIRS) lipid signal in high- vs. low-risk plaques. METHODS: Coronary arteries imaged with angiography and NIRS-intravascular ultrasound (IVUS) underwent 3D reconstruction and computational fluid dynamics calculations of local ESS. ESS, PB, MLA, and lipid core burden index (LCBI), for each 3-mm arterial segment were obtained in arteries with large lipid-rich plaque (LRP) vs. arteries with smaller LRP. The locations of the MLA, minimum ESS (minESS), maximum ESS (maxESS), maximum PB (maxPB), and maximum LCBI in a 4-mm segment (maxLCBI(4mm)) were determined along the length of each plaque. RESULTS: The spatial distributions of minESS, maxESS, maxPB, and maxLCBI(4mm), in reference to the MLA, were significantly heterogeneous within and between each variable. The location of maxLCBI(4mm) was spatially discordant from sites of the MLA (p

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 onbehalf EVINCI-SMARTOOL Background/Objectives: The relationship between biomechanical characteristics of a coronary lesion with myocardial blood flow has not been studied. We investigated the relationship between local endothelial shear stress (ESS) and computed tomography coronary angiography (CTCA)-derived anatomical and plaque characteristics data with impaired vasodilating capability assessed by positron emission tomography myocardial perfusion imaging (PET-MPI). Methods A total of 92 coronary vessels of 53 patients who have undergone both CTCA and PET-MPI with 15O-water or 13N-ammonia were analysed. PET was considered abnormal when > 1 contiguous segments showed both stress Myocardial Blood Flow (MBF) ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or Results ESS was weakly correlated with total PV (rho = 0.273, p = 0.008), non-calcified PV (rho = 0.247, p = 0.017) and the volume of necrotic core (rho = 0.242, p = 0.02). ESS increased progressively with stenosis severity (p ≤ 0.001). ΕSS was also higher in functionally significant vs. non-significant lesions (10.4 [8.04-54.4] Pa vs. 3.9 [2.32-7.29] Pa, p ≤0.001). Addition of ESS to stenosis severity improved prediction (Δ[AUC]:0.113, 95% CI: 0.055 to 0.171, p = 0.0001) of functionally significant lesions. Conclusion There is a weak positive association between lesion-specific ESS and plaque volume. ESS increases progressively with stenosis severity and is higher in functionally significant lesions by PET-MPI. The addition of ESS to CTCA-anatomical information improves prediction of an abnormal PET-MPI result.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 Background Computed Tomography Coronary Angiography (CTCA) is a non-invasive imaging modality, used effectively for anatomo-functional assessment of coronary artery disease (CAD). Machine learning (ML) processes can effectively allow the extraction of useful information from multidimensional feature spaces for evaluation of coronary lesions. Purpose To investigate the ability of ML for predicting impaired myocardial blood flow (MBF) by combining computational fluid dynamics (CFD) derived parameters with quantitative plaque burden, plaque morphology and anatomical characteristics obtained from CTCA. Methods 53 patients (31 male, mean age 64.7 ± 7.1 years) with intermediate pre-test likelihood of CAD who underwent CTCA and PET-MPI were included. PET was considered positive when > 1 contiguous segment demonstrated MBF ≤ 2.3 mL/g/min for 15O-water or ≤ 1.79 for 13N-ammonia respectively. CFD derived parameters such as a previously validated, virtual functional assessment index (vFAI), segmental endothelial shear stress (ESS), as well as anatomical and plaque characteristics were assessed. Seven classifiers were implemented and internally validated using 5-fold cross validation, repeated 1000 times. Using sequential forward selection (SFS), the highest rank features combination, based on appearances in the highest mean area under curve (AUC) classification scheme, was selected and features performance was evaluated following exhaustive search (ES). Results 92 coronary segments were analyzed and 34 features derived from CTCA were extracted. Classifiers performance are depicted in Figure A. k-NN was the best classifier with AUCmean = 0.791 (SENSmean= 0.622, SPECmean = 0.840, p Conclusion ML analysis is feasible for predicting with reasonable specificity abnormal MBF by PET, using a combination of CFD derived parameters and anatomical features. vFAI as a single characteristic was a specific predictor of impaired MBF, whilst in combination with stenosis severity, maintained almost the same AUC and specificity values and resulted in improved sensitivity. On the other hand, addition of lumen area to vFAI, increases the AUC and provides a relatively good specificity but low sensitivity. Abstract Figure 1

Background Advances in CTCA imaging enable assessment of coronary plaque burden, a predictor of myocardial perfusion abnormalities and more recently, with the use of computational fluid dynamics (CFD) of endothelial shear stress (ESS), an established contributor to atherosclerotic plaque development and progression. Purpose To investigate the relationship of local endothelial shear stress (ESS) and plaque burden (PB) between them and with stenosis severity as well as their comparative performance in predicting impaired coronary vasodilating capability assessed by PET myocardial perfusion imaging (MPI). Methods 49 patients (29 males, mean age 65.3±6.3 years, intermediate pre-test likelihood of coronary artery disease, CAD), who underwent PET-MPI with 15O-water or 13N-ammonia and CTCA were included. PET was considered abnormal when >1 contiguous segment showed both stress Myocardial Blood Flow ≤2.3 mL/g/min and Myocardial Flow Reserve ≤2.5 for 15O-water or Results 85 coronary vessels were evaluated. There was a positive correlation between ESS and PB (r(total)=0.544, r(prox)=0.528, r(MLA)=0.529, r(dist)=0.474, p50% in predicting an abnormal PET MPI, (AUC: from 0.682 to 0.780, p-diff >0.5 for all comparisons). The pairwise combination of sten >50% with the ESS segments, except the distal one, increased the predictive ability of the model over stenosis alone (AUC (sten >50% + ESS(total)) = 0.80, AUC (sten >50% + ESS(prox)) = 0.797, AUC (sten >50% + ESS(MLA)) = 0.822, p-diff ≤0.01 for all comparisons, AUC (sten >50% + ESS(dist)) = 0.768, p-diff=0.07). Conclusion There is a low to moderate positive association between lesion plaque burden and ESS indices. Like PB, ESS increases progressively with stenosis severity and is higher in lesions paired with abnormal PET results. ESS is a moderate predictor of impaired vasodilating capability, performing equally with PB and stenosis severity. The addition of ESS to stenosis severity can improve prediction of an abnormal PET result. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning 2014-2020” in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach” and from p-Med GR 5002802

Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Machine learning (ML) algorithms allow extraction and process of useful information from multidimensional spaces for evaluation of coronary lesions. Purpose To investigate the ability of ML to integrate computational fluid dynamics (CFD) derived parameters with quantitative plaque burden, plaque morphology and anatomical characteristics for predicting impaired myocardial flow reserve by PET myocardial perfusion imaging (MPI). Methods 49 patients (29 male, mean age 65.3±6.3 years) with intermediate pre-test likelihood of CAD who underwent CTCA and PET-MPI were included. PET was considered positive when >1 contiguous segment demonstrated Myocardial flow reserve (MFR) ≤2.5 mL/g/min for 15O-water or ≤2.0 for 13N-ammonia respectively. CDF derived parameters such as a previously validated CT-FFR surrogate, virtual functional assessment index (vFAI), segmental endothelial shear stress (ESS), as well as anatomical and plaque characteristics were assessed. k-nearest neighbor (k-NN), support vector machines (SVM) and feedforward neural networks (FF-NN) were implemented. ML was internally validated using 5-fold cross validation, repeated 100 times. Using sequential forward selection (SFS), the 5 highest rank features based on appearances in each classification scheme were selected and following exhaustive search (ES) the best features combinations were identified. Each classifier's performance was evaluated using an area-under-receiver operating characteristic curve (AUC) analysis. Results 85 coronary segments were analyzed and 28 features derived from CTCA were extracted. The features ranking for every classifier are depicted in Figure 1. k-NN using a combination only of ESS in the proximal (ESSprox) and distal segment achieved an AUC=0.78 (Sens=0.71, Spec=0.77, p Conclusion ML analysis is feasible for predicting abnormal MFR by PET using a combination of CFD derived parameters, anatomical and morphological features. ESSprox was present in every combination of best features. As a single characteristic was a moderate predictor of impaired MFR, whilst in combination with plaque characteristics and CFD derived features resulted in improved sensitivity and specificity. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human, Resources Development, Education and Lifelong Learning 2014-2020” in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach” and from p-Med GR 5002802

Background The Cocoon septal occluder (CSO) is a new generation double disk occluder device for catheter closure of the secundum atrial septal defect (ASD). Initial clinical evaluations with the use of this device have shown quite satisfactory results but large follow-up studies are missing. In this international multicenter study, we present procedural and follow-up data from 4008 patients with secundum ASD who underwent catheter closure with the use of CSO. Methods The study cohort consisted of 1853 pediatric and 2155 adult patients with secundum ASD treated with the CSO. Patients were enrolled retrospectively from 11 international centers and were followed for a mean period of 43 months (range 12–84 months), postprocedural. Clinical, electrocardiographic, echocardiographic, procedural, and follow-up data were collected from each collaborating hospital. Results The CSO was permanently implanted in 3983 patients (99.4%). Echocardiographic evaluation at one month follow-up revealed complete closure in 99.6% of those patients who had a device implanted. Thrombus formation in one adult patient was the only major device related to procedural complication. During the follow-up period, no patient developed cardiac erosions, allergic reactions to nickel, or other major complications. Conclusions Implantation of CSO provided satisfactory procedural and follow-up results with high success and no device-related cardiac erosions and nickel allergy.

Εmerging data indicate that various effects of obesity on the cardiovascular system can be evident during childhood. The aim of this study was to detect early changes in left ventricular structure and function in obese normotensive children and explore possible associations of these changes with anthropometric and biochemical parameters. Normotensive 8–11-year-old obese and normal weight children were included in the study. They all underwent anthropometric measurements, laboratory tests, and echocardiography study by conventional and tissue Doppler to assess geometric pattern and function of left ventricle. Statistically significant differences in most anthropometric and metabolic parameters were noticed between groups. Obese children showed higher left ventricular mass index (LVMI) (40.05 ± 9.44 vs. 28.31 ± 6.22), lower E/A ratio (1.76 ± 0.33 vs. 2.08 ± 0.56), and higher E/e’ (6.04 ± 1.13 vs. 5.43 ± 0.96) compared to lean peers. Waist-to-height ratio and hs-CRP correlated significantly with E/A in the obese group. Left ventricular hypertrophy was present in 47.2% of obese children and eccentric was the prominent type. Waist-to-height ratio and serum cortisol levels in plasma increased the odds of having any type of abnormal ventricular geometric pattern. Echocardiographic evaluation of left ventricle and diastolic function could be considered for obese normotensive children based on waist-to-height ratio, hs-CRP, and serum cortisol.

PurposeLeft ventricular non-compaction (LVNC) is characterized by a 2-layered myocardium composed of a noncompacted (NC) and a compacted (C) layer. The echocardiographic NC:C ratio is difficult to assess in many patients. The aim of the study was to assess the value of cardiac computed tomography (CCT) for the diagnosis of LVNC.MethodsIn this prospective controlled study, segmental analysis of transthoracic echocardiography (TTE) and prospective ECG-triggered CCT was performed in 17 patients with LVNC and 19 healthy controls. In TTE maximal NC and C thickness was measured at enddiastole and endsystole in the segment with most prominent trabeculation in short axis views. In CCT, maximal segmental NC and C thickness was measured during diastole, and NC:C ratio was determined. Spearman's correlation coefficient and receiver operating characteristic curves were calculated.ResultsThe median [IQR] radiation dose was 1.3[1.2-1.5]mSv. The CCT thickness of the C layer was significantly lower in patients with LVNC as compared to controls in the inferolateral, midventricular, lateral-, inferior-, and septal-apical segments. The CCT NC:C ratio differed significantly between LVNC and controls in the inferior-midventricular and all the apical segments. NC:C ratio correlated significantly between TTE and CCT at enddiastole (σ = 0.8) and endsystole (σ = 0.9). Using a CCT NC:C ratio ≥1.8, all LVNC patients could be identified.ConclusionLVNC can be diagnosed with ECG-triggered low-dose CCT and discriminated from normal individuals using a NC:C ratio of ≥1.8 in diastole. There is a very good correlation of NC:C ratio in TTE and CCT.

Human respiratory syncytial virus (RSV) is the leading cause of acute bronchiolitis in infants and young children. Children under the age of 2 years, hospitalized for bronchiolitis in the pediatric clinic of a tertiary hospital in northern Greece, were tested for RSV infection during two RSV seasons (2016–2017 and 2017–2018). RSV was detected in 37 of 71 (52.1%) patients, most of them younger than 6 months. Both RSV subtypes were detected – RSV-A (54.1%) and RSV-B (45.9%) – with predominance of RSV-A during the 2016–2017 and RSV-B during the 2017–2018 season. RSV-A and RSV-B sequences clustered within the ON1 and BA genotypes, respectively. Compared to the prototype strains, several amino acid substitutions were observed in the duplication region of the G gene. The study provides a first insight into the molecular epidemiology of RSV in Greece.

A reduction in left ventricular apical tracer uptake (apical thinning) is frequently observed in myocardial perfusion imaging (MPI), yet its cause remains a matter of debate, particularly in perfusion emission tomography (PET). This analysis sought to determine whether apical thinning in PET-MPI is attributable to true anatomical thinning of the left ventricular apical myocardium. We retrospectively analyzed 57 patients without any history or signs of apical myocardial infarction who underwent rest PET-MPI with 13N-ammonia and contrast-enhanced cardiac computed tomography (CT). Semi-quantitative normalized percent apical 13N-ammonia uptake at rest, myocardial blood flow (MBF), and k2 wash-out rate constants were compared to apical myocardial wall thickness measurements derived from CT and base-to-apex gradients were calculated. Apical thinning was found in 93% of patients and in 74% when analysis of normalized apical tracer uptake was confined to end-systole. No significant correlation was found between apical myocardial thickness and apical tracer uptake (r = − 0.080, P = .553), MBF (r = − 0.211, P = .115), or k2 wash-out rate (r = − 0.023, P = .872), nor between apical myocardial thickness and any gradients. A statistically significant but small difference in apical myocardial thickness was observed in patients with moderately to severely reduced apical tracer uptake vs patients with normal to mildly reduced uptake (4.3 ± 0.7 mm vs 4.7 ± 0.7 mm; P = .043). Apical thinning is a highly prevalent finding during 13N-ammonia PET-MPI that is not solely attributable to true anatomical apical wall thickness or the partial volume effect. Other factors that yet need to be identified seem to have a more prominent impact.

Objectives The aim of this study was to investigate the prognostic and clinical value of quantitative positron emission tomographic (PET) metrics in patients with ischemic heart failure. Background Although myocardial flow reserve (MFR) is a strong predictor of cardiac risk in patients without heart failure, it is unknown whether quantitative PET metrics improve risk stratification in patients with ischemic heart failure. Methods The study included 254 patients referred for stress and rest myocardial perfusion imaging and viability testing using PET. Major adverse cardiac event(s) (MACE) consisted of death, resuscitated sudden cardiac death, heart transplantation, acute coronary syndrome, hospitalization for heart failure, and late revascularization. Results MACE occurred in 170 patients (67%) during a median follow-up of 3.3 years. In a multivariate Cox proportional hazards model including multiple quantitative PET metrics, only MFR predicted MACE significantly (p = 0.013). Beyond age, symptom severity, diabetes mellitus, previous myocardial infarction or revascularization, 3-vessel disease, renal insufficiency, ejection fraction, as well as presence and burden of ischemia, scar, and hibernating myocardium, MFR was strongly associated with MACE (adjusted hazard ratio per increase in MFR by 1: 0.63; 95% confidence interval: 0.45 to 0.91). Incorporation of MFR into a risk assessment model incrementally improved the prediction of MACE (likelihood ratio chi-square test [16] = 48.61 vs. chi-square test [15] = 39.20; p = 0.002). Conclusions In this retrospective analysis of a single-center cohort, quantitative PET metrics of myocardial blood flow all improved risk stratification in patients with ischemic heart failure. However, in a hypothesis-generating analysis, MFR appears modestly superior to the other metrics as a prognostic index.

Coronary computed tomography angiography (CCTA)-based transluminal attenuation gradient (TAG) was suggested to determine the functional significance of a stenosis. However, evidence that TAG acquired by wide-volume scanners can assess the hemodynamic significance of stenosis assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is lacking. Moreover, coronary cross-sectional area may influence TAG. Hence, we aimed at assessing the diagnostic value of TAG to predict ischemia in SPECT-MPI and the correlation between TAG and the transluminal cross-sectional area gradient (TCG).Patients undergoing CCTA and SPECT-MPI for suspected coronary artery disease were included. TAG and TCG were calculated measuring the mean vessel attenuation and the cross-sectional area along major coronary vessels at 5-mm intervals.A total of 255 coronary arteries of 87 patients were included. TAG and TCG did not discriminate between coronary arteries with or without ischemia as assessed by SPECT-MPI (p = .44 and p = .25, respectively). The area under the curve to predict ischemia was not increased by adding TAG (0.88, 95% CI 0.83-0.92) or TCG (0.87, 95% CI 0.81-0.90) to CCTA alone (0.85, 95% CI 0.80-0.89). There was a significant correlation between TAG and TCG (r = 0.43; p .001).CCTA-derived TAG and TCG do not offer any value in predicting ischemia assessed by SPECT-MPI. TAG is partly affected by differences in the coronary luminal area.

IntroductionMyocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 5%–15% of all patients with acute myocardial infarction. Cardiac MR (CMR) and optical coherence tomography have been used to identify the underlying pathophysiological mechanism in MINOCA. The role of cardiac CT angiography (CCTA) in patients with MINOCA, however, has not been well studied so far. CCTA can be used to assess atherosclerotic plaque volume, vulnerable plaque characteristics as well as pericoronary fat tissue attenuation, which has not been yet studied in MINOCA.Methods and analysisMINOCA-GR is a prospective, multicentre, observational cohort study based on a national registry that will use CCTA in combination with CMR and invasive coronary angiography (ICA) to evaluate the extent and characteristics of coronary atherosclerosis and its correlation with pericoronary fat attenuation in patients with MINOCA. A total of 60 consecutive adult patients across 4 participating study sites are expected to be enrolled. Following ICA and CMR, patients will undergo CCTA during index hospitalisation. The primary endpoints are quantification of extent and severity of coronary atherosclerosis, description of high-risk plaque features and attenuation profiling of pericoronary fat tissue around all three major epicardial coronary arteries in relation to CMR. Follow-up CCTA for the evaluation of changes in pericoronary fat attenuation will also be performed. MINOCA-GR aims to be the first study to explore the role of CCTA in combination with CMR and ICA in the underlying pathophysiological mechanisms and assisting in diagnostic evaluation and prognosis of patients with MINOCA.Ethics and disseminationThe study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at national meetings and published in peer-reviewed journals.Trial registration numberNCT4186676.

Evidence to date on the unique female determinants of cardiovascular risk is inadequate. Positron Emission Tomography (PET) is considered to have the highest accuracy for the assessment of myocardial perfusion in patients with suspected coronary artery disease (CAD), but its long-term prognostic accuracy in women has not been established. A total of 619 consecutive patients (138 women, mean age 60.0 ± 11.8 years) underwent clinically indicated 13N-ammonia PET at our institution and were followed up (median 5.7 years) for major adverse cardiovascular events (MACE) including cardiac death, nonfatal myocardial infarction, hospitalization for any cardiac reason and late revascularization. During follow-up, 271 patients had at least one cardiac event, including 64 cardiac deaths and 33 nonfatal myocardial infarctions. In both women and men, abnormal myocardial perfusion was associated with reduced event-free survival (log rank p