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

A new method to measure necrotic core and calcium content in coronary plaques using intravascular ultrasound radiofrequency-based analysis

Although previous intravascular ultrasound (IVUS) radiofrequency-based analysis data showed acceptable reproducibility for plaque composition, measurements are not easily obtained, particularly that of lumen contour, because of the limited IVUS resolution. The purpose of this study was to compare a new measurement method (Shin’s method) and the conventional measurement method for necrotic core and calcium content in atherosclerotic lesions using Virtual Histology-intravascular ultrasound (VH-IVUS). Fifty-seven patients with unstable angina who underwent elective percutaneous coronary intervention were included. Shin’s method focuses on catheter contour, instead of lumen contour, and vessel contour. Patients ages ranged from 46 to 88 years, and 34 were men. A total of 1,401 frames from 59 culprit lesions were assessed. There were no significant differences in the mean area and volume of necrotic core and dense calcium between the two methods. Correlation coefficients (R) were ≥0.99 for all above mentioned parameters (P < 0.001). Between methods, the absolute differences in mean area and volume of necrotic core were 0.02 ± 0.02 mm² and 0.34 ± 0.29 mm³, respectively, while for mean area and volume of dense calcium, the absolute differences were 0.04 ± 0.07 mm² and 0.36 ± 0.52 mm³, respectively. The reproducibility of Shin’s method was excellent. For area of the necrotic core and dense calcium, the means of the differences between the two measurements were nearly zero, and the reproducibility coefficients were within 1% of the means of the two measurements. Mean analysis time for both measurements was 26.8 ± 6.7 min/segment in the conventional method and 3.3 ± 0.6 min/segment in Shin’s method. Shin’s method for measurement of necrotic core and dense calcium using VH-IVUS demonstrated a good correlation with the conventional method and excellent reproducibility. Also, Shin’s method required a significantly shorter analysis time than the conventional method. Therefore, Shin’s method could replace the conventional method for necrotic core and calcium measurement in atherosclerotic lesions, and it might be useful in the catheterization laboratory for online clinical decision

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

Impact of analyzing fewer image frames per segment during offline volumetric radiofrequency-based intravascular ultrasound measurements of target lesions prior to percutaneous coronary interventions

In the present study, we evaluated the impact of a 50% reduction in number of image frames (every second frame) on the analysis time and variability of offline volumetric radiofrequency-based intravascular ultrasound (RF-IVUS) measurements in target lesions prior to percutaneous coronary interventions (PCI). Volumetric RF-IVUS data of vessel geometry and plaque composition are generally obtained by a semi-automated analysis process that includes time-consuming manual contour editing. A reduction in the number of frames used for volumetric analysis may speed up the analysis, but could increase measurement variability. We repeatedly performed offline volumetric analyses in RF-IVUS image sets of 20 mm-long coronary segments that contained 30 de novo lesions prior to PCI. A 50% reduction in frames decreased the analysis time significantly (from 57.5 ± 7.3 to 35.7 ± 3.7 min; P < 0.0001) while geometric and compositional RF-IVUS measurements did not differ significantly from measurements obtained from all frames. The variability between measurements on the reduced number of frames versus all frames was comparable to the intra-observer measurement variability. In target lesions prior to PCI, offline volumetric RF-IVUS analyses can be performed using a reduced number of image frames (every second frame). This reduces the time of analysis without substantially increasing measurement variability

Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort.

Mobocertinib, an oral, first-in-class epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for EGFR exon 20 insertions (ex20ins), achieved durable responses in adults with previously treated EGFR ex20ins+ metastatic non-small cell lung cancer (mNSCLC) in the EXCLAIM extension cohort of a phase 1/2 study (N = 96; NCT02716116). We assessed patient-reported outcomes (PROs) with mobocertinib 160 mg once daily (28-day cycles) in EXCLAIM (N = 90) with the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30) v3.0, lung cancer module (QLQ-LC13), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire, and selected PRO Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire. Median treatment duration was 6.8 (range, 0.0-18.8) months (median follow-up: 13.0 [0.7-18.8] months; data cutoff: 1 November 2020). Clinically meaningful improvements in lung cancer symptoms measured by EORTC QLQ-LC13 were observed for dyspnea (54.4% of patients), cough (46.7%), and chest pain (38.9%), evident at cycle 2 and throughout treatment (least-squares mean [LSM] changes from baseline: dyspnea, -3.2 [p = 0.019]; cough, -9.3 [p < 0.001]; chest pain, -8.2 [p < 0.001]). EORTC QLQ-C30 results indicated no statistically significant changes in global health status/quality of life (LSM change from baseline: -1.8 [p = 0.235]). On symptom scores, significant worsening from baseline was observed for diarrhea (LSM change from baseline: +34.1; p < 0.001) and appetite loss (+6.6; p = 0.004), while improvements were observed for dyspnea (LSM change from baseline: -5.1 [p = 0.002]), insomnia (-6.5 [p = 0.001]), and constipation (-5.7 [p < 0.001]). EQ-5D-5L health status was maintained. Common PRO-CTCAE symptoms were diarrhea, dry skin, rash, and decreased appetite (mostly low grade); in the first 24 weeks of treatment, 64.4% of patients had worsening diarrhea frequency and 67.8% had worsening dry skin severity. Overall, PROs with mobocertinib showed clinically meaningful improvement in lung cancer-related symptoms, with health-related quality of life maintained despite changes in some adverse event symptom scales