Patient-specific in silico 3D coronary model in cardiac catheterisation laboratories

Coronary artery disease is caused by the buildup of atherosclerotic plaque in the coronary arteries, affecting the blood supply to the heart, one of the leading causes of death around the world. X-ray coronary angiography is the most common procedure for diagnosing coronary artery disease, which uses contrast material and x-rays to observe vascular lesions. With this type of procedure, blood flow in coronary arteries is viewed in real-time, making it possible to detect stenoses precisely and control percutaneous coronary interventions and stent insertions. Angiograms of coronary arteries are used to plan the necessary revascularisation procedures based on the calculation of occlusions and the affected segments. However, their interpretation in cardiac catheterisation laboratories presently relies on sequentially evaluating multiple 2D image projections, which limits measuring lesion severity, identifying the true shape of vessels, and analysing quantitative data. In silico modelling, which involves computational simulations of patient-specific data, can revolutionise interventional cardiology by providing valuable insights and optimising treatment methods. This paper explores the challenges and future directions associated with applying patient-specific in silico models in catheterisation laboratories. We discuss the implications of the lack of patient-specific in silico models and how their absence hinders the ability to accurately predict and assess the behaviour of individual patients during interventional procedures. Then, we introduce the different components of a typical patient-specific in silico model and explore the potential future directions to bridge this gap and promote the development and utilisation of patient-specific in silico models in the catheterisation laboratories

Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies

Some metabolic diseases, such as diabetes and hyperlipidemia, are associated with a state of inflammation, which adversely affects cardiovascular health. Emerging evidence suggests that long-term hyperactivation of innate immune cells and their bone marrow progenitors, termed trained immunity, functions to accelerate atherosclerosis and its complications in cardiometabolic diseases. This review will focus on how trained immunity is established, particularly through metabolic and epigenetic reprogramming, to cause persistent and deleterious changes in immune cell function, even after the original stimulus has been corrected or removed. Understanding the mechanisms driving maladaptive trained immunity and its fundamental contribution to cardiovascular disease might enable the development of novel disease-modifying therapeutics for the reduction in cardiovascular risk in diabetes, hyperlipidemia, and related cardiometabolic states

Multimodal cardiovascular magnetic resonance quantifies regional variation in vascular structure and function in patients with coronary artery disease: Relationships with coronary disease severity

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) of the vessel wall is highly reproducible and can evaluate both changes in plaque burden and composition. It can also measure aortic compliance and endothelial function in a single integrated examination. Previous studies have focused on patients with pre-identified carotid atheroma. We define these vascular parameters in patients presenting with coronary artery disease and test their relations to its extent and severity.</p> <p>Methods and Results</p> <p>100 patients with CAD [single-vessel (16%); two-vessel (39%); and three-vessel (42%) non-obstructed coronary arteries (3%)] were studied. CAD severity and extent was expressed as modified Gensini score (mean modified score 12.38 ± 5.3). A majority of carotid plaque was located in the carotid bulb (CB). Atherosclerosis in this most diseased segment correlated modestly with the severity and extent of CAD, as expressed by the modified Gensini score (R = 0.251, P < 0.05). Using the AHA plaque classification, atheroma class also associated with CAD severity (rho = 0.26, P < 0.05). The distal descending aorta contained the greatest plaque, which correlated with the degree of CAD (R = 0.222; P < 0.05), but with no correlation with the proximal descending aorta, which was relatively spared (R = 0.106; P = n. s.). Aortic distensibility varied along its length with the ascending aorta the least distensible segment. Brachial artery FMD was inversely correlated with modified Gensini score (R = -0.278; P < 0.05). In multivariate analysis, distal descending aorta atheroma burden, distensibility of the ascending aorta, carotid atheroma class and FMD were independent predictors of modified Gensini score.</p> <p>Conclusions</p> <p>Multimodal vascular CMR shows regional abnormalities of vascular structure and function that correlate modestly with the degree and extent of CAD.</p

Visualization of Activated Platelets by Targeted Magnetic Resonance Imaging Utilizing Conformation-Specific Antibodies against Glycoprotein IIb/IIIa

Ruptured atherosclerotic plaques, lined with activated platelets, constitute an attractive target for magnetic resonance imaging (MRI). This study evaluated whether microparticles of iron oxide (MPIO) targeting ligand-induced binding sites (LIBS) on the activated conformation of glycoprotein IIb/IIIa could be used to image platelets. MPIO (size: 1 μm) were conjugated to anti-LIBS or control single-chain antibody. Following guidewire injury to mouse femoral artery, platelet adhesion was present after 24 h. Mice were perfused with anti-LIBS-MPIO (or control MPIO) via the left ventricle and 11.7-tesla MRI was performed on femoral arteries ex vivo. A 3D gradient echo sequence attained an isotropic resolution of 25 μm. MPIO binding, quantified by MRI, was 4-fold higher with anti-LIBS-MPIO in comparison to control MPIO (p < 0.01). In histological sections, low signal zones on MRI and MPIO correlated strongly (R2 = 0.72; p < 0.001), indicating accurate MR quantification. In conclusion, anti-LIBS-MPIO bind to activated platelets in mouse arteries, providing a basis for the use of function-specific single-chain antibody-MPIO conjugates for molecular MRI, and represent the first molecular imaging of a conformational change in a surface receptor. This presents an opportunity to specifically image activated platelets involved in acute atherothrombosis with MRI

Predictive Ecology and Management of Phyllosphere Microbial Communities Through Cross-Scale Synthesis

In this article, we summarize the main takeaways from a symposium and hybrid virtual and in-person participatory discussion focused on the challenges of scale in understanding the ecology and management of phyllosphere microbial communities. We provide an overview of the confounding effects of spatial scale on inference in microbial ecology, the spatial organization of microbial interactions in the phyllosphere, advances and remaining gaps in measuring phyllosphere colonization across scales, and the epidemiology in the phyllosphere. We hope to motivate further discussion and the development and adoption of creative approaches to solving the challenges of scale to enhance fundamental understanding and practical management of the phyllosphere microbiomes

How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction?

Aims Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation. Methods and results In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2-95.8] to 36.7 (IQR: 22.7-59.5), P 40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: −0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: −0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR − pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm3 of stent), P: 0.01] were associated with a potentially deleterious increase in IMR. Conclusion Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burde