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Aims Low wall shear stress (WSS) is acknowledged to play a role in plaque development through its influence on local endothelial function. Also, lipid-rich plaques (LRPs) are associated with endothelial dysfunction. However, little is known about the interplay between WSS and the presence of lipids with respect to plaque progression. Therefore, we aimed to study the differences in WSS-related plaque progression between LRPs, non-LRPs, or plaque-free regions in human coronary arteries. Methods and results In the present single-centre, prospective study, 40 patients who presented with an acute coronary syndrome successfully underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) of at least one non-culprit vessel at baseline and completed a 1-year follow-up. WSS was computed applying computational fluid dynamics to a three-dimensional reconstruction of the coronary artery based on the fusion of the IVUS-segmented lumen with a CT-derived centreline, using invasive flow measurements as boundary conditions. For data analysis, each artery was divided into 1.5 mm/45° sectors. Plaque growth based on IVUS-derived percentage atheroma volume change was compared between LRPs, non-LRPs, and plaque-free wall segments, as assessed by both OCT and NIRS. Both NIRS- and OCT-detected lipid-rich sectors showed a significantly higher plaque progression than non-LRPs or plaque-free regions. Exposure to low WSS was associated with a higher plaque progression than exposure to mid or high WSS, even in the regions classified as a plaque-free wall. Furthermore, low WSS and the presence of lipids had a synergistic effect on plaque growth, resulting in the highest plaque progression in lipid-rich regions exposed to low shear stress. Conclusion This study demonstrates that NIRS- and OCT-detected lipid-rich regions exposed to low WSS are subject to enhanced plaque growth over a 1-year follow-up. The presence of lipids and low WSS proves to have a synergistic effect on plaque growth. [ABSTRACT FROM AUTHOR]

Objectives: In this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR)., Background: CT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies., Methods: At 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics., Results: ICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively., Conclusions: Dynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795)., Competing Interests: Funding Support and Author Disclosures This study was supported by unrestricted grants from Siemens Healthineers and Bayer Healthcare. Dr Nguyen’s research is supported by the National Institutes of Health (R01HL134830-01). Koen Nieman’s research is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL141712; R01HL146754). Dr Geisler has received research grants from Medtronic and Edwards Lifesciences. Dr Kitagawa has received an endowed chair position supported by Siemens Healthineers. Dr Vliegenthart has received an institutional research grant from Siemens Healthineers. Dr Hausleiter has received receiving speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences; and has served as a consultant for Edwards Lifesciences. Dr Pugliese has received research support from Siemens Healthineers. Dr Budde has received institutional research support to the Erasmus MC from Siemens Healthineers. Dr Nikolauo has received research grants from Siemens Healthineers, GE Healthcare, and Bayer Healthcare; and has served as a consultant for Siemens Healthineers; and Bayer Healthcare. Dr Sakuma has received departmental research grants from FUJIFILM Toyama Chemical Co, Ltd, and Guerbet Japan KK. Dr Klotz is a retired employee of and serves as a consultant for Siemens Healthineers. Dr Bamberg has received research grants from Siemens Healthineers and Bayer Healthcare; and has served as a consultant for Siemens Healthineers, Bayer Healthcare, and Bracco. Dr Nieman has received unrestricted institutional research support from Siemens Healthineers and HeartFlow Inc; has served as a consultant for Siemens Medical Systems USA; and holds equity in Lumen Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Identifying coronary artery disease (CAD) in atrial fibrillation (AF) patients improves risk stratification and defines clinical management. However, the value of screening for subclinical CAD with cardiac CT in AF patients is unknown. Between 2011 and 2015, 94 consecutive patients without known or suspected CAD (66 (57-73) years, 68% male), who were referred for AF evaluation, underwent a noncontrast-enhanced coronary calcium scan and a coronary computed tomography angiography (CCTA) at our center. We retrospectively evaluated the coronary calcium score, the prevalence of obstructive CAD (≥50% stenosis) determined by CCTA, compared clinical management and 5-year outcome in patients with and without obstructive CAD on CCTA, and examined the potential impact of a coronary calcium score and obstructive CAD on CCTA as a manifestation of vascular disease on the CHA2Ds2VASc score and for the cardiovascular risk stratification of AF patients. The median coronary calcium score was 57 (0-275) and 24 patients (26%) had obstructive CAD on CCTA. At baseline, patients with obstructive CAD more often used statins than those without obstructive CAD (54% vs 26%, p = 0.011). After a median clinical follow-up of 2.4 (0.5-4.5) years, patients with obstructive CAD more frequently used oral anticoagulant and/or antiplatelet drugs, statins, angiotensin-II-receptor blockers and/or angiotensin-converting-enzyme inhibitors, and less often used class I antiarrhythmic drugs than patients without obstructive CAD (all p <0.050). After a median follow-up of 5.7 (4.8-6.8) years, mortality was higher in patients with obstructive CAD than in those without obstructive CAD (29% vs 11%, log-rank test: p = 0.034). Implementation of a coronary calcium score and/or obstructive CAD on CCTA elevated the CHA2Ds2VASc score and cardiovascular risk stratification in 42 patients (p <0.001) and 47 patients (p = 0.006), respectively. In conclusion, we observed a high prevalence of obstructive CAD on CCTA in AF patients without known or suspected CAD. AF patients with obstructive CAD were managed differently and had a worse prognosis than those without obstructive CAD. Cardiac CT could enhance cardiovascular risk stratification of AF patients., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) is a noninvasive application to evaluate the hemodynamic impact of coronary artery disease by simulating invasively measured FFR based on CT data. CT-FFR is based on the assumption of a normal coronary microvascular response. We assessed the diagnostic performance of a machine-learning based application for on-site computation of CT-FFR in patients with and without diabetes mellitus with suspected coronary artery disease. The study population included 75 diabetic and 276 nondiabetic patients who were enrolled in the MACHINE consortium. The overall diagnostic performance of coronary CT angiography alone and in combination with CT-FFR were analyzed with direct invasive FFR comparison in 110 coronary vessels of the diabetic group and in 415 coronary vessels of the nondiabetic group. Per-vessel discrimination of lesion-specific ischemia by CT-FFR was assessed by the area under the receiver operating characteristic curves. The overall diagnostic accuracy of CT-FFR in diabetic patients was 83% and in nondiabetic patients 75% (p = 0.088), showing improvement over the diagnostic accuracy of coronary CT angiography, which was 58% and 65% (p = 0.223), respectively. In addition, the diagnostic accuracy of CT-FFR was similar between diabetic and nondiabetic patients per stratified CT-FFR group (CT-FFR < 0.6, 0.6 to 0.69, 0.7 to 0.79, 0.8 to 0.89, ≥0.9). The area under the curves for diabetic and nondiabetic patients were also comparable, 0.88 and 0.82 (p = 0.113), respectively. In conclusion, on-site machine-learning CT-FFR analysis improved the diagnostic performance of coronary CT angiography and accurately discriminated lesion-specific ischemia in both diabetic and nondiabetic patients suspected of coronary artery disease., (Copyright © 2018. Published by Elsevier Inc.)

Aims: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and is emerging as a biomarker of cardiac remodelling. Left ventricular assist devices (LVADs) provide unloading of the left ventricle, resulting in partial reverse remodelling. Our aim was to study GDF-15 in patients with a non-ischaemic dilated cardiomyopathy (DCM) during LVAD support., Methods and Results: We analysed circulating GDF-15 in 30 patients before and 1, 3, and 6 months after LVAD implantation and before heart transplantation or explantation. In addition, mRNA and protein expression of GDF-15 were evaluated in myocardial tissue obtained prior to and after LVAD support. Circulating GDF-15 was significantly higher before LVAD implantation as compared with healthy controls (P < 0.001). After 1 month of mechanical support, GDF-15 levels were significantly decreased compared with pre-implantation levels (P < 0.001) and remained stable thereafter. Circulating GDF-15 was significantly correlated with kidney function and the severity of myocardial fibrosis. Interestingly, GDF-15 mRNA and protein expression in the myocardium were hardly detectable., Conclusions: High circulating levels of GDF-15 in patients with end-stage non-ischaemic DCM correlate with myocardial fibrosis and kidney function and decline strongly after 1 month of mechanical unloading, remaining stable thereafter. However, cardiac mRNA and protein expression of GDF-15 are very low, suggesting that the heart is not an important source of GDF-15 production in these patients.