in-vitro-microfluidic-disease-model-to-study-whole-blood-endothelial

In Vitro Microfluidic Disease Model to Study Whole Blood-Endothelial Interactions and Blood Clot Dynamics in Real-Time

The formation of blood clots involves complex interactions between endothelial cells, their underlying matrix, various blood cells, and proteins. The ...

VU University medical center

The implanted prosthetic heart valve (PHV) size is vital for the evaluation of suspected PHV dysfunction and in case of reoperation or valve-in-valve transcatheter approaches. The labeled size is not always known, and discrepancies exist between manufacturers' labeled sizes and true sizes. Reproducible methods for noninvasive PHV size assessment are lacking. We determined the reliability and agreement of PHV size measurements using multidetector-row computed tomography (MDCT) and provide reference values of MDCT measurements compared with manufacturer specifications. In vitro, 15 different PHV types in available sizes (total n = 63) were imaged. In vivo, available MDCT acquisitions of patients with PHVs were retrospectively gathered in 2 centers, and 230 patients with 249 PHVs were included. Inner valve area and area-derived diameter were measured in all PHVs. For mechanical PHVs, the inner diameter was also measured. Data were analyzed using the intraclass correlation coefficient and Bland-Altman plots and related to manufacturer specifications. Measurements could be obtained for all PHV types, except the Björk-Shiley (n = 7) because of severe valve-related artifacts hampering the image quality. Intrarater and interrater reliability was excellent for biological and mechanical PHVs (intraclass correlation coefficients ≥0.903). Agreement was good for all measurements with an overall maximal mean difference (95% confidence interval) of -2.61 mm(2) (-37.9 to 32.7), -0.1 mm (-1.1 to 1.0), and 0 mm (-0.4 to 0.3) for valve area, area-derived diameter, and inner diameter, respectively. MDCT reliably discriminated consecutive PHV sizes as labeled by the manufacturer because the absolute ranges for the measurements never overlapped. In conclusion, MDCT allows assessment of the implanted PHV size with excellent reliability and agreement and can discriminate between PHV sizes for contemporary prostheses. MDCT can be used to noninvasively identify the manufacturer-labeled PHV size.

Reliability, Agreement, and Presentation of a Reference Standard for Assessing Implanted Heart Valve Sizes by Multidetector-Row Computed Tomography.

Echocardiography and fluoroscopy are the main techniques for prosthetic heart valve (PHV) evaluation, but because of specific limitations they may not identify the morphological substrate or the extent of PHV pathology. Cardiac computed tomography (CT) and magnetic resonance imaging (MRI) have emerged as new potential imaging modalities for valve prostheses. We present an overview of the possibilities and pitfalls of CT and MRI for PHV assessment based on a systematic literature review of all experimental and patient studies. For this, a comprehensive systematic search was performed in PubMed and Embase on March 24, 2015, containing CT/MRI and PHV synonyms. Our final selection yielded 82 articles on surgical valves. CT allowed adequate assessment of most modern PHVs and complemented echocardiography in detecting the obstruction cause (pannus or thrombus), bioprosthesis calcifications, and endocarditis extent (valve dehiscence and pseudoaneurysms). No clear advantage over echocardiography was found for the detection of vegetations or periprosthetic regurgitation. Whereas MRI metal artifacts may preclude direct prosthesis analysis, MRI provided information on PHV-related flow patterns and velocities. MRI demonstrated abnormal asymmetrical flow patterns in PHV obstruction and allowed prosthetic regurgitation assessment. Hence, CT shows great clinical relevance as a complementary imaging tool for the diagnostic work-up of patients with suspected PHV obstruction and endocarditis. MRI shows potential for functional PHV assessment although more studies are required to provide diagnostic reference values to allow discrimination of normal from pathological conditions. 

Multimodality Imaging Assessment of Prosthetic Heart Valves.

Two-dimensional video-assisted thoracic surgery (2D-VATS) has gained its position in daily practise. Although very useful, its two-dimensional view has its drawbacks when performing pulmonary resections. We report our first experience with 3-dimensional video-assisted surgery (3D-VATS). Advantages and differences with 2D-VATS and robotic surgery (RS) are discussed.

Feasibility of 3-dimensional video-assisted thoracic surgery (3D-VATS) for pulmonary resection.

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients.

Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension.

The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis.

Article	Year
Reliability, Agreement, and Presentation of a Reference Standard for Assessing Implanted Heart Valve Sizes by Multidetector-Row Computed Tomography. The American journal of cardiology\| PubMed ID: 25935442	2015
Multimodality Imaging Assessment of Prosthetic Heart Valves. Circulation. Cardiovascular imaging\| PubMed ID: 26353926	2015
Feasibility of 3-dimensional video-assisted thoracic surgery (3D-VATS) for pulmonary resection. Annals of surgical innovation and research\| PubMed ID: 26478741	2015
Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension. American journal of physiology. Lung cellular and molecular physiology\| PubMed ID: 27190061	2016
Quality of initial anticoagulant treatment and risk of CTEPH after acute pulmonary embolism. PloS one\| PubMed ID: 32343741	2020

Petr Symersky

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