Left Ventricular Assist Device Flow Pattern Analysis Using a Novel Model Incorporating Left Ventricular Pulsatility

Our current understanding of flow through the circuit of left ventricular assist device (LVAD), left ventricle and ascending aorta remains incompletely understood. Computational fluid dynamics, which allow for analysis of flow in the cardiovascular system, have been used for this purpose, although current simulation models have failed to fully incorporate the interplay between the pulsatile left ventricle and continuous-flow generated by the LVAD. Flow-through the LVAD is dependent on the interaction between device and patient-specific factors with suboptimal flow patterns evoking increased risk of LVAD-related complications. Computational fluid dynamics can be used to analyze how different pump and patient factors affect flow patterns in the left ventricle and the aorta. Computational fluid dynamics simulations were carried out on a patient with a HeartMate II. Simulations were also conducted for theoretical scenarios substituting HeartWare HVAD, HeartMate 3 (HM3) in continuous mode and HM3 with Artificial Pulse. An anatomical model of the patient was reconstructed from computed tomography (CT) images, and the LVAD outflow was used as the inflow boundary condition. The LVAD outflow was calculated separately using a lumped-parameter-model of the systemic circulation, which was calibrated to the patient based on the patient-specific ventricular volume change reconstructed from 4 dimensional computed tomography and pulmonary capillary wedge pressure tracings. The LVADs were implemented in the lumped-parameter-model via published pressure head versus flow (H-Q) curves. To quantify the flushing effect, virtual contrast agent was released in the ascending aorta and its flushing over the cycles was quantified. Shear stress acting on the aortic endothelium and shear rate in the bloodstream were also quantified as indicators of normal/abnormal blood flow, especially the latter being a biomarker of platelet activation and hemolysis. LVAD speeds for the HVAD and HM3 were selected to match flow rates for the patient’s HMII (9,000 RPM for HMII, 5,500 RPM for HM3, and 2,200 RPM for HVAD), the cardiac outputs were 5.81 L/min, 5.83 L/min, and 5.92 L/min, respectively. The velocity of blood flow in the outflow cannula was higher in the HVAD than in the two HeartMate pumps with a cycle average (range) of 0.92 m/s (0.78–1.19 m/s), 0.91 m/s (0.86–1.00 m/s), and 1.74 m/s (1.40–2.24 m/s) for HMII, HM3, and HVAD, respectively. Artificial pulse increased the peak flow rate to 9.84 L/min for the HM3 but the overall cardiac output was 5.96 L/min, which was similar to the continuous mode. Artificial pulse markedly decreased blood stagnation in the ascending aorta; after six cardiac cycles, 48% of the blood was flushed out from the ascending aorta under the continuous operation mode while 60% was flushed under artificial pulse. Shear stress and shear rate in the aortic arch were higher with the HVAD compared to the HMII and HM3, respectively (shear stress: 1.76 vs. 1.33 vs. 1.33 Pa, shear rate: 136 vs. 91.5 vs. 89.4 s–1). Pump-specific factors such as LVAD type and programmed flow algorithms lead to unique flow patterns which influence blood stagnation, shear stress, and platelet activation. The pump-patient interaction can be studied using a novel computational fluid dynamics model to better understand and potentially mitigate the risk of downstream LVAD complications

Relationship between adiposity and admixture in African-American and Hispanic-American women.

ObjectiveThe objective of this study was to investigate whether differences in admixture in African-American (AFA) and Hispanic-American (HA) adult women are associated with adiposity and adipose distribution.DesignThe proportion of European, sub-Saharan African and Amerindian admixture was estimated for AFA and HA women in the Women's Heath Initiative using 92 ancestry informative markers. Analyses assessed the relationship between admixture and adiposity indices.SubjectsThe subjects included 11 712 AFA and 5088 HA self-identified post-menopausal women.ResultsThere was a significant positive association between body mass index (BMI) and African admixture when BMI was considered as a continuous variable, and age, education, physical activity, parity, family income and smoking were included covariates (P<10(-4)). A dichotomous model (upper and lower BMI quartiles) showed that African admixture was associated with a high odds ratio (OR=3.27 (for 100% admixture compared with 0% admixture), 95% confidence interval 2.08-5.15). For HA, there was no association between BMI and admixture. In contrast, when waist-to-hip ratio (WHR) was used as a measure of adipose distribution, there was no significant association between WHR and admixture in AFA but there was a strong association in HA (P<10(-4); OR Amerindian admixture=5.93, confidence interval=3.52-9.97).ConclusionThese studies show that: (1) African admixture is associated with BMI in AFA women; (2) Amerindian admixture is associated with WHR but not BMI in HA women; and (3) it may be important to consider different measurements of adiposity and adipose distribution in different ethnic population groups

Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Echogenicity as a surrogate for bioresorbable everolimus-eluting scaffold degradation: analysis at 1-, 3-, 6-, 12- 18, 24-, 30-, 36- and 42-month follow-up in a porcine model

The objective of the study is to validate intravascular quantitative echogenicity as a surrogate for molecular weight assessment of poly-l-lactide-acid (PLLA) bioresorbable scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California). We analyzed at 9 time points (from 1- to 42-month follow-up) a population of 40 pigs that received 97 Absorb scaffolds. The treated regions were analyzed by echogenicity using adventitia as reference, and were categorized as more (hyperechogenic or upperechogenic) or less bright (hypoechogenic) than the reference. The volumes of echogenicity categories were correlated with the measurements of molecular weight (Mw) by gel permeation chromatography. Scaffold struts appeared as high echogenic structures. The quantification of grey level intensity in the scaffold-vessel compartment had strong correlation with the scaffold Mw: hyperechogenicity (correlation coefficient = 0.75; P < 0.01), upperechogenicity (correlation coefficient = 0.63; P < 0.01) and hyper + upperechogenicity (correlation coefficient = 0.78; P < 0.01). In the linear regression, the R2 for high echogenicity and Mw was 0.57 for the combination of hyper and upper echogenicity. IVUS high intensity grey level quantification is correlated to Absorb BVS residual molecular weight and can be used as a surrogate for the monitoring of the degradation of semi-crystalline polymers scaffolds

Nosocomial Transmission of Coronavirus Disease 2019: A Retrospective Study of 66 Hospital-acquired Cases in a London Teaching Hospital

COVID-19 can cause deadly healthcare-associated outbreaks. In a major London teaching hospital, 66/435 (15%) of COVID-19 inpatient cases between 2 March and 12 April 2020 were definitely or probably hospital-acquired, through varied transmission routes. The case fatality was 36%. Nosocomial infection rates fell following comprehensive infection prevention and control measures

The "Solar Model Problem" Solved by the Abundance of Neon in Stars of the Local Cosmos

The interior structure of the Sun can be studied with great accuracy using observations of its oscillations, similar to seismology of the Earth. Precise agreement between helioseismological measurements and predictions of theoretical solar models has been a triumph of modern astrophysics (Bahcall et al. 2005). However, a recent downward revision by 25-35% of the solar abundances of light elements such as C, N, O and Ne (Asplund et al. 2004) has broken this accordance: models adopting the new abundances incorrectly predict the depth of the convection zone, the depth profiles of sound speed and density, and the helium abundance (Basu Antia 2004, Bahcall et al. 2005). The discrepancies are far beyond the uncertainties in either the data or the model predictions (Bahcall et al. 2005b). Here we report on neon abundances relative to oxygen measured in a sample of nearby solar-like stars from their X-ray spectra. They are all very similar and substantially larger than the recently revised solar value. The neon abundance in the Sun is quite poorly determined. If the Ne/O abundance in these stars is adopted for the Sun the models are brought back into agreement with helioseismology measurements (Antia Basu 2005, Bahcall et al. 2005c).Comment: 13 pages, 3 Figure

Lattice potentials and fermions in holographic non Fermi-liquids: hybridizing local quantum criticality

We study lattice effects in strongly coupled systems of fermions at a finite density described by a holographic dual consisting of fermions in Anti-de-Sitter space in the presence of a Reissner-Nordstrom black hole. The lattice effect is encoded by a periodic modulation of the chemical potential with a wavelength of order of the intrinsic length scales of the system. This corresponds with a highly complicated "band structure" problem in AdS, which we only manage to solve in the weak potential limit. The "domain wall" fermions in AdS encoding for the Fermi surfaces in the boundary field theory diffract as usually against the periodic lattice, giving rise to band gaps. However, the deep infrared of the field theory as encoded by the near horizon AdS2 geometry in the bulk reacts in a surprising way to the weak potential. The hybridization of the fermions bulk dualizes into a linear combination of CFT1 "local quantum critical" propagators in the bulk, characterized by momentum dependent exponents displaced by lattice Umklapp vectors. This has the consequence that the metals showing quasi-Fermi surfaces cannot be localized in band insulators. In the AdS2 metal regime, where the conformal dimension of the fermionic operator is large and no Fermi surfaces are present at low T/\mu, the lattice gives rise to a characteristic dependence of the energy scaling as a function of momentum. We predict crossovers from a high energy standard momentum AdS2 scaling to a low energy regime where exponents found associated with momenta "backscattered" to a lower Brillioun zone in the extended zone scheme. We comment on how these findings can be used as a unique fingerprint for the detection of AdS2 like "pseudogap metals" in the laboratory.Comment: 42 pages, 5 figures; v2, minor correction, to appear in JHE