Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study.

PURPOSE Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min-1*g-1 [IQR 2.18-3.08] vs. 2.20 mL*min-1*g-1 [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR scanner

BACKGROUND Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET). METHODS We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMR$_{stress}$) and rest. RESULTS Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMR$_{stress}$ were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMR$_{stress}$: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMR$_{stress}$ and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004). CONCLUSIONS The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study

PURPOSE Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min$^{-1}$*g$^{-1}$ [IQR 2.18-3.08] vs. 2.20 mL*min$^{-1}$*g$^{-1}$ [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Electricity, Heat, and Gas Sector Data for Modeling the German System

Diese Dokumentation beschreibt Daten zum deutschen Strom- Wärme- und Gassektor und ermöglicht eine modellgestützte Abbildung dieser Energiesysteme. Die Aufbereitung der Daten erfolgte im Rahmen des vom BMWi geförderten Forschungsprojekts LKD-EU (Langfristige Planung und kurzfristige Optimierung des Elektrizitätssystems in Deutschland im europäischen Kontext, FKZ 03ET4028C). In Zusammenarbeit mit dem Deutschen Institut für Wirtschaftsforschung (DIW), der Arbeitsgruppe Wirtschafts- und Infrastrukturpolitik (WIP) der Technischen Universität Berlin (TUB), dem Lehrstuhl für Energiewirtschaft (EE2), der Technischen Universität Dresden (TUD) und dem House of Energy Markets & Finance der Universität Duisburg-Essen (UDE). Ziel des Dokumentes ist es, Referenzdaten zur Verfügung zu stellen, die den aktuellen Zustand des deutschen Energiesystems repräsentieren. Das Bezugsjahr ist 2015. Diese Dokumentation trägt dazu bei, die Transparenz in der Verfügbarkeit von Daten zum deutschen Energiesystem zu erhöhen.This data documentation describes a data set of the German electricity, heat, and natural gas sectors compiled within the research project ‘LKD-EU’ (Long-term planning and short-term optimization of the German electricity system within the European framework: Further development of methods and models to analyze the electricity system including the heat and gas sector). The project is a joined effort by the German Institute for Economic Research (DIW Berlin), the Workgroup for Infrastructure Policy (WIP) at Technische Universität Berlin (TUB), the Chair of Energy Economics (EE2) at Technische Universität Dresden (TUD), and the House of Energy Markets & Finance at University of Duisburg-Essen. The project was funded by the German Federal Ministry for Economic Affairs and Energy through the grant ‘LKD-EU’, FKZ 03ET4028A. The objective of this paper is to document a reference data set representing the status quo of the German energy sector. We also update and extend parts of the previous DIW Data Documentation 75 (Egerer et al. 2014). While the focus is on the electricity sector, the heat and natural gas sectors are covered as well. With this reference data set, we aim to increase the transparency of energy infrastructure data in Germany. On the one hand, this documentation presents sources of original data and information used for the data set. On the other hand, it elaborates on the methodologies which have been applied to derive the data from respective sources in order to make it useful for modeling purposes and to promote a discussion about the underlying assumptions. Furthermore, we briefly discuss the underlying regulations with regard to data transparency in the energy sector. Where not otherwise stated, the data included in this report is given with reference to the year 2015 for Germany

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Absence of genetic isolation across highly fragmented landscape in the ant Temnothorax nigriceps

Background Human activities, including changes in agricultural landscapes, often impact biodiversity through habitat fragmentation. This potentially reduces genetic exchange between previously connected populations. Using a combination of nuclear and mitochondrial markers, we investigated (i) genetic diversity and population structure at multiple spatial scales and (ii) colony genetic structure and queen mating frequency in the ant species Temnothorax nigriceps in a highly anthropized environment. Results Although the results highlighted genetic structure on a European spatial scale, they did not reveal an impact of fragmentation on a regional scale, and we did not observe any genetic population structure on a regional scale. Across all populations, regardless of their geographical location, colony structure suggested monogyny (a single queen per colony) and monandry (single mating). However, nestmates were more related than expected, indicating that large-scale dispersal does not fully prevent genetic isolation. Conclusions Despite living in fragmented patches of habitat, populations of Temnothorax nigriceps are apparently genetically not isolated at a regional scale. However, large-scale dispersal alone does not prevent genetic isolation. The ecological requirements of T. nigriceps may explain their resilience to habitat fragmentation by allowing them to survive in very small patches of suitable habitat. The deeper investigation of the diversity of functional habitats for this species should allow to appreciate better the mechanisms permitting this species to overcome the negative impacts of fragmentation

Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography.

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges

Myocardial creep-induced misalignment artifacts in PET/MR myocardial perfusion imaging

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 < 0.05). The difference in SDS correlated moderately but significantly with the amount of myocardial creep (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

Coronary artery lumen volume index as a marker of flow-limiting atherosclerosis-validation against 13 N-ammonia positron emission tomography

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 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 from 13N-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. Keywords: Computed tomography angiography; Myocardial ischemia; Positron emission tomograph