Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of mechanical function.Personalized computational modeling provides a novel framework for integrating and interpreting the combined role of atrial electrophysiology and mechanics in AF development and sustenance.Coronary computed tomography angiography data were segmented using a threshold-based approach and the smoothed voxel representation was discretized into a high-resolution tetrahedral finite element (FE) mesh.To estimate the complex left atrial fiber architecture, individual fiber fields were generated according to morphological data on the endo-and epicardial surfaces based on local solutions of Laplace's equation and transmurally interpolated to all tetrahedral elements.Personalized geometrical models included the heterogeneous thickness distribution of the left atrial myocardium and subsequent discretization led to high-fidelity tetrahedral FE meshes.The novel algorithm for (automated) incorporation of the left atrial fiber architecture provided a realistic estimate of the atrial microstructure and was able to qualitatively capture all important fiber bundles.The established modeling pipeline provides a robust framework for the rapid development of personalized model cohorts and facilitates simulations of atrial electromechanics.
A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.
Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT‐CMR). Here, we develop a CMR‐compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D‐printed chamber and perfusion circuit re‐established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT‐CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT‐CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT‐CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT‐CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic‐like state. A contiguous stack of 313 5‐μm histological sections at and a 100‐μm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT‐CMR data were obtained. A CMR‐compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.
Background: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling. Methods: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y). Results: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m 2 ; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m 2 ; P <0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m 2 and RVESVi ≤82 mL/m 2 . RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P <0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm 2 /m 2 ; P <0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality ( P =0.03) over a median of 9.5 years of follow-up. Conclusions: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m 2 confers optimal chances of normalization of RV function.
Studies finding perioperative hyperglycaemia is associated with adverse patient outcomes in surgical procedures spurred the development of blood glucose guidelines at many institutions. In this trial, we will assess the implementation of a clinical decision support tool that is integrated into the intraoperative portion of our electronic health record and provides real-time best practice recommendations for intraoperative insulin dosing in surgical patients at high risk for hyperglycaemia.
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