Anatomic Correlates of Mitral Systolic Anterior Motion in Transposition of the Great Arteries Following Atrial Switch Operation

Introduction:We sought to investigate whether the development of sub-pulmonic systolic anterior motion(SAM)may be inherent to the anatomy of the the mitral valve(MV)or affected by external factors,such as a dilated right ventricle or chest abnormalities in d-looped transposition of the great arteries post atrial switch operation(d-TGA/AtS).Methods:Analysis was performed of clinical and cardiac imaging studies acquired on 19 adult patients with d-TGA/AtS(age 42±6 years old,56%male)between 2015–2019.Echocardiography data included mitral apparatus anatomy,and CT/MRI data included biventricular dimensions,function,and Haller index(HI)for pectus deformity.Results:Patients with leaflet SAM(n=6)compared to patients without SAM(n=13)had higher MV protrusion height(2.3±0.5 vs.1.5±0.4 cm,p≤0.01)and longer anterior MV leaflet length(3.1±0.4 cm vs.2.6±0.3 cm p≤0.05),when compared to those without.CT/MRI showed higher sub-pulmonic left ventricular ejection fraction(LVEF)in the SAM group(71%±8%vs.54%±7%,respectively).RV size and function,significant chest deformity(HI>3.5),presence of a ventricular lead pacemaker,and septal thickness did not play a role in development of SAM.Conclusions:An elongated mitral apparatus is associated with the development of SAM,and the development of left ventricular outflow tract obstruction(LVOTO),in d-TGA/AtS.LV hyperkinesia is associated with SAM.Systemic RV dimensions,septal thickness,and degree of chest deformity did not differ significantly between subjects with SAM and those without.

Emotions,Perceptions and Health Behaviors of Adult Congenital Heart Disease Patients during COVID-19 in New York City

Background:Adults with congenital heart disease(ACHD)have increased prevalence of mood and anxiety disorders.There are limited data regarding the influence of the COVID-19 pandemic on the mental health and health behaviors of these patients.Objective:The purpose is to evaluate the perceptions,emotions,and health behaviors of ACHD patients during the COVID-19 pandemic.Methods:In this cross-sectional study of ACHD patients,we administered surveys evaluating self-reported emotions,perceptions and health behaviors.Logistic regressions were performed to determine the adjusted odds of displaying each perception,emotion and health behavior based on predictor variables.Results:Ninety-seven patients(mean age 38.3 years,46.4%female,85.6%moderate or complex lesion)completed the survey.The majority of patients reported feeling moderately or very sad(63.1%),and 48.4%of patients identified themselves as feeling moderately or very anxious.The majority of patients perceived their risk of COVID-19 as moderate or high.Females were more likely to report feeling sad and anxious(95%CI 1.06–10.96,p-value 0.039,and 95%CI 1.44–15.30,p-value=0.012,respectively),and were associated with higher odds of having a perceived increased risk of COVID-19(95%CI 1.33–10.59,p-value 0.012).There was no association between ACHD anatomic or physiologic classification and perceptions,emotions and health behaviors.Conclusions:Females were more likely to report feeling sad,anxious and an increased risk of COVID-19 in comparison to males.These findings indicate the need for mental health support and promotion of health behaviors during the pandemic amongst all ACHD patients,regardless of underlying condition.

Red blood cell distribution width in heart failure: A narrative review

The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence suggests that RDW assessment not only predicts the risk of adverse outcomes(cardiovascular and all-cause mortality, hospitalization for acute decompensation or worsened left ventricular function) in patients with acute and chronic heart failure(HF), but is also a significant and independent predictor of developing HF in patients free of this condition. Regarding the biological interplay between impaired hematopoiesis and cardiac dysfunction, many of the different conditions associated with increased heterogeneity of erythrocyte volume(i.e., ageing, inflammation, oxidative stress, nutritional deficiencies and impaired renal function), may be concomitantly present in patients with HF, whilst anisocytosis may also directly contribute to the development and worsening of HF. In conclusion, the longitudinal assessment of RDW changes over time may be considered an efficient measure to help predicting the risk of both development and progression of HF.

Progress and challenges in CRISPR-mediated therapeutic genome editing for monogenic diseases

There are an estimated 10000 monogenic diseases affecting tens of millions of individuals worldwide.The application of CRISPR/Cas genome editing tools to treat monogenic diseases is an emerging strategy with the potential to generate personalized treatment approaches for these patients.CRISPR/Cas-based systems are programmable and sequence-specific genome editing tools with the capacity to generate base pair resolution manipulations to DNA or RNA.The complexity of genomic insults resulting in heritable disease requires patientspecific genome editing strategies with consideration of DNA repair pathways,and CRISPR/Cas systems of different types,species,and those with additional enzymatic capacity and/or delivery methods.In this review we aim to discuss broad and multifaceted therapeutic applications of CRISPR/Cas gene editing systems including in harnessing of homology directed repair,non-homologous end joining,microhomology-mediated end joining,and base editing to permanently correct diverse monogenic diseases.

Procalcitonin in inflammatory bowel disease: Drawbacks and opportunities

The measurement of procalcitonin has recently become a mainstay for the diagnosis and therapeutic management of severe bacterial infections, especially those sustained by Gram-negative bacteria. Therefore, the aim of this article is to provide a narrative overview on the potential role of procalcitonin measurement in patients with inflammatory bowel disease(IBD). According to the available scientific literature, the clinical significance of procalcitonin for diagnosing IBD or monitoring disease activity remains elusive, and its association with disease severity is confined to a limited number of case-control studies, with low sample size. Nevertheless, literature data also suggests that a supranormal procalcitonin serum concentration(i.e., > 0.5 ng/m L) may reflect the presence of a number of infective complications in IBD, especially bacterial enterocolitis, bacterial gastroenteritis, intraabdominal abscess, postsurgical infection and sepsis. Rather than for diagnosing or assessing disease activity, the measurement of this biomarker may hence retain practical clinical significance for early prediction, timely diagnosis and therapeutic monitoring of many IBDassociated infections and complications.

On the Volume Conservation of the Immersed Boundary Method

The immersed boundary(IB)method is an approach to problems of fluid-structure interaction in which an elastic structure is immersed in a viscous incompressible fluid.The IB formulation of such problems uses a Lagrangian description of the structure and an Eulerian description of the fluid.It is well known that some versions of the IB method can suffer from poor volume conservation.Methods have been introduced to improve the volume-conservation properties of the IB method,but they either have been fairly specialized,or have used complex,nonstandard Eulerian finite-difference discretizations.In this paper,we use quasi-static and dynamic benchmark problems to investigate the effect of the choice of Eulerian discretization on the volume-conservation properties of a formally second-order accurate IB method.We consider both collocated and staggered-grid discretization methods.For the tests considered herein,the staggered-grid IB scheme generally yields at least a modest improvement in volume conservation when compared to cell-centered methods,and in many cases considered in this work,the spurious volume changes exhibited by the staggered-grid IB method are more than an order of magnitude smaller than those of the collocated schemes.We also compare the performance of cell-centered schemes that use either exact or approximate projection methods.We find that the volumeconservation properties of approximate projection IB methods depend strongly on the formulation of the projection method.When used with the IB method,we find that pressure-free approximate projection methods can yield extremely poor volume conservation,whereas pressure-increment approximate projection methods yield volume conservation that is nearly identical to that of a cell-centered exact projection method.

Simulating an Elastic Ring with Bend and Twist by an Adaptive Generalized Immersed Boundary Method

Many problems involving the interaction of an elastic structure and a viscous fluid can be solved by the immersed boundary(IB)method.In the IB approach to such problems,the elastic forces generated by the immersed structure are applied to the surrounding fluid,and the motion of the immersed structure is determined by the local motion of the fluid.Recently,the IB method has been extended to treatmore general elasticity models that include both positional and rotational degrees of freedom.For such models,force and torque must both be applied to the fluid.The positional degrees of freedomof the immersed structuremove according to the local linear velocity of the fluid,whereas the rotational degrees of freedom move according to the local angular velocity.This paper introduces a spatially adaptive,formally second-order accurate version of this generalized immersed boundary method.We use this adaptive scheme to simulate the dynamics of an elastic ring immersed in fluid.To describe the elasticity of the ring,we use an unconstrained version of Kirchhoff rod theory.We demonstrate empirically that our numerical scheme yields essentially second-order convergence rates when applied to such problems.We also study dynamical instabilities of such fluid-structure systems,and we compare numerical results produced by our method to classical analytic results from elastic rod theory.

Efficient Variable-Coefficient Finite-Volume Stokes Solvers

We investigate several robust preconditioners for solving the saddle-point linear systems that arise from spatial discretization of unsteady and steady variablecoefficient Stokes equations on a uniform staggered grid.Building on the success of using the classical projection method as a preconditioner for the coupled velocitypressure system[B.E.Griffith,J.Comp.Phys.,228(2009),pp.7565–7595],as well as established techniques for steady and unsteady Stokes flow in the finite-element literature,we construct preconditioners that employ independent generalized Helmholtz and Poisson solvers for the velocity and pressure subproblems.We demonstrate that only a single cycle of a standard geometric multigrid algorithm serves as an effective inexact solver for each of these subproblems.Contrary to traditional wisdom,we find that the Stokes problem can be solved nearly as efficiently as the independent pressure and velocity subproblems,making the overall cost of solving the Stokes system comparable to the cost of classical projection or fractional step methods for incompressible flow,even for steady flow and in the presence of large density and viscosity contrasts.Two of the five preconditioners considered here are found to be robust to GMRES restarts and to increasing problem size,making them suitable for large-scale problems.Our work opens many possibilities for constructing novel unsplit temporal integrators for finite-volume spatial discretizations of the equations of low Mach and incompressible flow dynamics.