Numerical simulation of the flow around the ahmed vehicle model

The unsteady flow around the Ahmed vehicle model is numerically solved for a Reynolds number of 4.25 million based on the model length. A viscous and incompressible fluid flow of Newtonian type governed by the Navier-Stokes equations is assumed. A Large Eddy Simulation (LES) technique is applied together with the Smagorinsky model as Subgrid Scale Modeling (SGM) and a slightly modified van Driest near-wall damping. A monolithic computational code based on the finite element method is used, with linear basis functions for both pressure and velocity fields, stabilized by means of the Streamline Upwind Petrov-Galerkin (SUPG) scheme combined with the Pressure Stabilizing Petrov- Galerkin (PSPG) one. Parallel computing on a Beowulf cluster with a domain decomposition technique for solving the algebraic system is used. The flow analysis is focused on the near-wake region, where the coherent macro structures are estimated through the second invariant of the velocity gradient (or Q-criterion) applied on the time-average flow. It is verified that the topological features of the timeaverage flow are independent of the averaging time T and grid-size.Fil: Franck, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Tecnologica Nacional; ArgentinaFil: Nigro, Norberto Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Storti, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: D'elia, Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

Purpose: Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. Methods: Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. Results: A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45–6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45–9.10); p < 0.001] and body mass index [OR = 1.27 (1.14–1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36–96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61–0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62–0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43–28); p = 0.039]. There wasn’t significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001). Conclusion: In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs’ overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival

Heart rate distribution in paced and non-paced patients with severe recurrent reflex syncope and tilt-induced asystole: Findings from the BIOSync CLS study

Background: Undiagnosed sinus or atrioventricular node dysfunction may bias estimation of the real efficacy of cardiac pacing in preventing vasovagal reflex syncope. We assessed this hypothesis in the BIOSync CLS trial which showed that dual-chamber pacing with closed loop stimulation (CLS) remarkably reduced recurrences of syncope. Methods and results: In the study patients aged 40 years or older with ≥2 episodes of loss of consciousness in the last year and an asystolic response to Tilt-Table test were randomized to pacing ON (DDD-CLS mode) or pacing OFF (ODO mode). We utilized the available pacemaker diagnostic data in a total of 103 patients (52 pacing ON, 51 pacing OFF) to generate cumulative distribution charts for heart rate (HR) and percentage of pacing. At 12 months, we did not find evidence of suspected sinus or atrioventricular node dysfunction. Beats were similarly distributed between groups (p = 0.96), with an average HR of 76 ± 8 bpm (pacing ON) versus 77 ± 7 bpm (pacing OFF). In the active group, the median percentage of atrial and ventricular pacing was 47% and 0%, respectively. Intolerance to high pacing rates was reported in only one patient (1.6%) and was easily resolved by reprogramming the maximum CLS pacing rate. Conclusions: We did not find evidence of suspected sinus or atrioventricular node dysfunction in the BIOSync CLS patients. The benefit of pacing should be ascribed to pacing prevention of pure vasovagal episodes. CLS algorithm modulated pacing rates over a wide frequency range, consistently competing with sinus node

Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments

The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure.Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement.Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders

Worsening of Cardiomyopathy Using Deflazacort in an Animal Model Rescued by Gene Therapy

We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV) 2/8 by a single intraperitoneal injection into BIO14.6 Syrian hamsters at ten days of age to rescue the phenotype. We then treated the hamsters with deflazacort. Treatment was administered to half of the hamsters that had received the AAV and the other hamsters without AAV, as well as to normal hamsters. Both horizontal and vertical activities were greatly enhanced by deflazacort in all groups. As in previous experiments, the AAV treatment alone was able to preserve the ejection fraction (70±7% EF). However, the EF value declined (52±14%) with a combination of AAV and deflazacort. This was similar with all the other groups of affected animals. We confirm that gene therapy improves cardiac function in the BIO14.6 hamsters. Our results suggest that deflazacort is ineffective and may also have a negative impact on the cardiomyopathy rescue, possibly by boosting motor activity. This is unexpected and may have significance in terms of the lifestyle recommendations for patients

Acute shock efficacy of the subcutaneous implantable cardioverter-defibrillator according to the implantation technique

Background: The traditional technique for subcutaneous implantable cardioverter defibrillator (S-ICD) implantation involves three incisions and a subcutaneous (SC) pocket. An intermuscular (IM) 2-incision technique has been recently adopted. Aims: We assessed acute defibrillation efficacy (DE) of S-ICD (DE ≤65 J) according to the implantation technique. Methods: We analyzed consecutive patients who underwent S-ICD implantation and DE testing at 53 Italian centers. Regression analysis was used to determine the association between DFT and implantation technique. Results: A total of 805 patients were enrolled. Four groups were assessed: IM + 2 incisions (n = 546), SC + 2 incisions (n = 133), SC + 3 incisions (n = 111), and IM + 3 incisions (n = 15). DE was ≤65 J in 782 (97.1%) patients. Patients with DE ≤65 J showed a trend towards lower body mass index (25.1 vs. 26.5; p = .12), were less frequently on antiarrhythmic drugs (13% vs. 26%; p = .06) and more commonly underwent implantation with the 2-incision technique (85% vs. 70%; p = .04). The IM + 2-incision technique showed the lowest defibrillation failure rate (2.2%) and shock impedance (66 Ohm, interquartile range: 57-77). On multivariate analysis, the 2-incision technique was associated with a lower incidence of shock failure (hazard ratio: 0.305; 95% confidence interval: 0.102-0.907; p = .033). Shock impedance was lower with the IM than with the SC approach (66 vs. 70 Ohm p = .002) and with the 2-incision than the 3-incision technique (67 vs. 72 Ohm; p = .006). Conclusions: In a large population of S-ICD patients, we observed a high defibrillation success rate. The IM + 2-incision technique provides lower shock impedance and a higher likelihood of successful defibrillation

A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation

<p>Abstract</p> <p>Background</p> <p>In recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy.</p> <p>Methods</p> <p>Thirty hamsters were divided into three groups (n = 10): Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points.</p> <p>Results</p> <p>μ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p < 0.001).</p> <p>Conclusions</p> <p>Although histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.</p

Physical activity measured by implanted devices predicts atrial arrhythmias and patient outcome: Results of IMPLANTED (Italian Multicentre Observational Registry on Patients With Implantable Devices Remotely Monitored)

Background--To determine whether daily physical activity (PA), as measured by implanted devices (through accelerometer sensor), was related to the risk of developing atrial arrhythmias during long-term follow-up in a population of heart failure (HF) patients with an implantable cardioverter defibrillator (ICD). Methods and Results--The study population was divided into 2 equally sized groups (PA cutoff point: 3.5 h/d) according to their mean daily PA recorded by the device during the 30- to 60-day period post-ICD implantation. Propensity score matching was used to compare 2 equally sized cohorts with similar characteristics between lower and higher activity patients. The primary end point was time free from the first atrial high-rate episode (AHRE) of duration 656 minutes. Secondary end points were: first AHRE 656 hours, first AHRE 6548 hours, and a combined end point of death or HF hospitalization. Data from 770 patients (65\ub115 years; 66% men; left ventricular ejection fraction 35\ub112%) remotely monitored for a median of 25 months were analyzed. A PA =3.5 h/d was associated with a 38% relative reduction in the risk of AHRE 656 minutes (72-month cumulative survival: 75.0% versus 68.1%; log rank P=0.025), and with a reduction in the risk of AHRE 656 hours, AHRE 6548 hours, and the combined end point of death or HF hospitalization (all P &lt; 0.05). Conclusions--In HF patients with ICD, a low level of daily PA was associated with a higher risk of atrial arrhythmias, regardless of the patients' baseline characteristics. In addition, a lower daily PA predicted death or HF hospitalization