The Prognosis of Baseline Mitral Regurgitation in Patients with Transcatheter Aortic Valve Implantation

International audienceMitral regurgitation (MR) is the most common valvular lesion in transcatheter aortic valve implantation (TAVI) recipients. This study aims to assess the long-term prognostic impact of baseline MR in TAVI patients. Methods: Adult patients who underwent TAVI were identified in the French National Hospital Discharge Database. All-cause and cardiovascular mortality, stroke, and rehospitalization with heart failure (HF) were compared in TAVI patients with and without baseline MR and tricuspid regurgitation (TR), respectively; the associations of MR and TR with the outcomes were assessed by Cox regression. Results: Baseline MR was identified in 8240 TAVI patients. Patients with baseline MR have higher yearly incidence of all-cause mortality (HR: 1.192, 95% confidence interval CI: 1.125–1.263), cardiovascular mortality (HR: 1.313, 95%CI: 1.210–1.425), and rehospitalization for heart failure (HF) (HR: 1.411, 95%CI: 1.340–1.486) compared to those without, except for stroke rate (HR: 0.988, 95%CI: 0.868–1.124). Neither baseline MR nor TR was an independent risk predictor for all-cause mortality or cardiovascular mortality in TAVI patients. Baseline MR was independently associated with rehospitalization for HF in TAVI patients. Conclusions: Baseline MR and TR were associated with increased all-cause and cardiovascular mortality post-TAVI, however, neither of them was independent predictor for all-cause or cardiovascular mortality

Yearly Incidence of Stroke and Bleeding in Atrial Fibrillation with Concomitant Hyperthyroidism: A National Discharge Database Study

Background: Hyperthyroidism is associated with atrial fibrillation (AF), and the latter is a major risk factor for stroke. Aim: We aimed to investigate the yearly incidence of stroke and bleeding in AF patients with and without concomitant hyperthyroidism from the French National Hospital Discharge Database. Methods: Admissions with AF between January 2010 and December 2019 were retrospectively identified and retrieved from the French national database. Incidence rates of ischaemic stroke and bleeding were compared in AF patients with and without concomitant hyperthyroidism. The associations of risk factors with ischaemic stroke were assessed by Cox regression. Results: Overall 2,421,087 AF patients, among whom 32,400 had concomitant hyperthyroidism were included in the study. During the follow-up (mean: 2.0 years, standard deviation SD: 2.2 years), the yearly incidence of ischaemic stroke was noted to be 2.6 (95% confidence interval CI: 2.5–2.8) in AF patients with concomitant hyperthyroidism, and 2.3 (95%CI: 2.3–2.4) in non-thyroid AF patients. Hyperthyroidism was noted as an independent risk factor for ischaemic stroke (adjusted hazard ratio aHR: 1.133, 95%CI: 1.080–1.189) overall, particularly within the first year of hyperthyroidism diagnosis (aHR 1.203, 95%CI 1.120–1.291), however, the association became non-significant in subsequent years (aHR 1.047, 95%CI 0.980–1.118). Major bleeding incidence was lower in the hyperthyroid AF group in comparison to the non-thyroid AF group (incidence ratio: 5.1 vs. 5.4%/year, p < 0.001). The predictive value of CHA(2)DS(2)VASc and HAS-BLED scores for ischaemic stroke and bleeding events, respectively, did not differ significantly between AF patients with or without concomitant hyperthyroidism. Conclusions: Hyperthyroidism seems to be an independent risk factor of ischaemic stroke in AF patients, particularly within the first year of hyperthyroidism diagnosis

Distinct regulatory effects of myeloid cell and endothelial cell Nox2 on blood pressure

Background -Hypertension due to increased renin angiotensin system (RAS) activation is associated with elevated reactive oxygen species (ROS) production. Previous studies implicate NADPH oxidase (Nox) proteins as important ROS sources during RAS activation, with different Nox isoforms being potentially involved. Among these, Nox2 is expressed in multiple cell types including endothelial cells, fibroblasts, immune cells and microglia. Blood pressure (BP) is regulated at central nervous system, renal and vascular levels but the cell-specific role of Nox2 in BP regulation is unknown. Methods -We generated a novel mouse model with a Floxed Nox2 gene and used Tie2-Cre, LysM Cre or Cdh5-CreERT2 driver lines to develop cell-specific models of Nox2 perturbation to investigate its role in BP regulation. Results -Unexpectedly, Nox2 deletion in myeloid but not endothelial cells resulted in a significant reduction in basal BP. Tie2-CreNox2 knockout (KO) mice (in which Nox2 was deficient in both endothelial cells and myeloid cells) and LysM Cre Nox2KO mice (in which Nox2 was deficient in myeloid cells) both had significantly lower BP than littermate controls whereas basal BP was unaltered in Cdh5-CreERT2 Nox2 KO mice (in which Nox2 is deficient only in endothelial cells). The lower BP was attributable to an increased NO bioavailability which dynamically dilated resistance vessels in vivo under basal conditions, without change in renal function. Myeloid-specific Nox2 deletion had no effect on angiotensin II-induced hypertension which, however, was blunted in Tie2-CreNox2KO mice along with preservation of endothelium-dependent relaxation during angiotensin II stimulation. Conclusions -We identify a hitherto unrecognized modulation of basal BP by myeloid cell Nox2 whereas endothelial cell Nox2 regulates angiotensin II-induced hypertension. These results identify distinct cell-specific roles for Nox2 in BP regulation

Effectiveness and Safety of Apixaban in over 3.9 Million People with Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: There is a plethora of real-world data on the safety and effectiveness of direct-acting oral anticoagulants (DOACs); however, study heterogeneity has contributed to inconsistent findings. We compared the effectiveness and safety of apixaban with those of other direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKA e.g., warfarin). Methods: A systematic review and meta-analysis was conducted retrieving data from PubMed, SCOPUS and Web of Science from January 2009 to December 2021. Studies that evaluated apixaban (intervention) prescribed for adults (aged 18 years or older) with AF for stroke prevention compared to other DOACs or VKAs were identified. Primary outcomes included stroke/systemic embolism (SE), all-cause mortality, and major bleeding. Secondary outcomes were intracranial haemorrhage (ICH) and ischaemic stroke. Randomised controlled trials and non-randomised trials were considered for inclusion. Results: In total, 67 studies were included, and 38 studies were meta-analysed. Participants taking apixaban had significantly lower stroke/SE compared to patients taking VKAs (relative risk (RR) 0.77, 95% confidence interval (CI) 0.64–0.93, I2 = 94%) and dabigatran (RR 0.84, 95% CI 0.74–0.95, I2 = 66%), but not to patients administered rivaroxaban. There was no statistical difference in mortality between apixaban and VKAs or apixaban and dabigatran. Compared to patients administered rivaroxaban, participants taking apixaban had lower mortality rates (RR 0.83, 95% CI 0.71–0.96, I2 = 96%). Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52–0.65, I2 = 90%), dabigatran (RR 0.79, 95% CI 0.70–0.88, I2 = 78%) and rivaroxaban (RR 0.61, 95% CI 0.53–0.70, I2 = 87%). Conclusions: Apixaban was associated with a better overall safety and effectiveness profile compared to VKAs and other DOACs.</jats:p

The Prognosis of Baseline Mitral Regurgitation in Patients with Transcatheter Aortic Valve Implantation

Mitral regurgitation (MR) is the most common valvular lesion in transcatheter aortic valve implantation (TAVI) recipients. This study aims to assess the long-term prognostic impact of baseline MR in TAVI patients. Methods: Adult patients who underwent TAVI were identified in the French National Hospital Discharge Database. All-cause and cardiovascular mortality, stroke, and rehospitalization with heart failure (HF) were compared in TAVI patients with and without baseline MR and tricuspid regurgitation (TR), respectively; the associations of MR and TR with the outcomes were assessed by Cox regression. Results: Baseline MR was identified in 8240 TAVI patients. Patients with baseline MR have higher yearly incidence of all-cause mortality (HR: 1.192, 95% confidence interval CI: 1.125–1.263), cardiovascular mortality (HR: 1.313, 95%CI: 1.210–1.425), and rehospitalization for heart failure (HF) (HR: 1.411, 95%CI: 1.340–1.486) compared to those without, except for stroke rate (HR: 0.988, 95%CI: 0.868–1.124). Neither baseline MR nor TR was an independent risk predictor for all-cause mortality or cardiovascular mortality in TAVI patients. Baseline MR was independently associated with rehospitalization for HF in TAVI patients. Conclusions: Baseline MR and TR were associated with increased all-cause and cardiovascular mortality post-TAVI, however, neither of them was independent predictor for all-cause or cardiovascular mortality

Quadrotor UAV flight control via a novel saturation integral backstepping controller

In this paper, in order to reduce the influence on quadrotor flight from different external disturbances, a novel nonlinear robust controller is designed and used in the quadrotor system. At first, a nonlinear dynamic model of the quadrotor is formulated mathematically. Then, a quadrotor flight controller is designed with the method of classical backstepping control (CBC) and the nonlinear system using this controller is proved to be asymptotically stabilized by the Lyapunov stability theory when there is no external disturbance. At last, a new nonlinear robust controller established by the introduction of both the saturation function and the integral of error into CBC is designed and named as saturation integral backstepping control (SIBC). The boundedness of the nonlinear system under external disturbances is verified by the uniformly ultimately bounded theorem of the nonvanishing perturbation. The numerical simulations of hovering and trajectory tracking are carried out using MATLAB/SIMULINK taking the external disturbances into consideration. In addition, a series of outdoor flight experiments were completed on the actual experimental equipments of quadrotor UAV under the time-varying disturbance from wind. According to the simulation and flight experiment results, the proposed SIBC strategy shows a superior robustness than CBC and integral backstepping control (IBC) strategy