Direct Oral Anticoagulants versus Vitamin K Antagonists in Cirrhotic Patients with Atrial Fibrillation: Update of Systematic Review and Meta-Analysis.

BACKGROUND: Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC). OBJECTIVE: This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC. METHODS: A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3. RESULTS: Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08). CONCLUSION: DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.

TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway.

Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.

Cerebral hemodynamics and brain functional activity during lower body negative pressure.

INTRODUCTION: Exposure to high +Gz acceleration forces on a centrifuge or in an aircraft can severely decrease cerebral blood perfusion and cause rapid G-induced loss of consciousness. However, milder acceleration may gradually reduce cerebral blood flow and affect cognitive function in subtler ways. This study used lower body negative pressure (LBNP) to mimic +Gz circulatory effects in order to study cerebral hemodynamics and brain function. METHODS: Subjects were 15 healthy men, 19-21 yr of age. They were exposed to LBNP at two levels for 5 min each separated by a 10-min recovery period. The conditions were low (LO), -4.00 kPa (-30 mmHg) and high (HI), -6.67 kPa (-50 mmHg).Variables measured before, during, and after LBNP included cerebral blood flow velocity (CBFV) in the middle cerebral artery, blood oxygen saturation (SaO2), heart rate (HR), blood pressure, P300 of event-related EEG potentials, reaction time, and tracking error. RESULTS: LO significantly reduced CBFV at 4 and 5 min, increased HR, and decreased the amplitude of P300, but none of the other variables changed from baseline. In contrast, HI produced significant changes in most variables: CBFV decreased at 2 min and then fell further at 4 and 5 min, HR increased, and SaO2 decreased. Significant neurocognitive changes included increased latency and reduced amplitude of P300, slower reaction time, and greater tracking error. CONCLUSION: The higher level of LBNP used here reduced cerebral perfusion sufficiently to impair neurocognitive function. This model may be useful for further studies of these and other variables under closely controlled conditions.

[Changes of human cerebral blood flow velocity and blood oxygen saturation under lower body negative pressure in upright seated position].

Objective. To investigate the effect of lower body negative pressure (LBNP) in upright seated position on cerebral blood flow velocity, heart rate (HR), and blood oxygen saturation (SaO2) in human. Method. Fifteen young men were selected as subjects. Blood flow velocity in middle cerebral artery (VMCA), HR and SaO2 were measured at 0.5, 1, 2, 3, 4, and 5 min during LBNP and 1, 3, 5 min after -4.00 kPa and -6.67 kPa LBNP in upright seated position respectively. Result. Under -4.00 kPa LBNP, VMCA slowed down at 4, 5 min during LBNP (P<0.05), and HR speeded up at 3, 4, 5 min during LBNP (P<0.05). There were no significant changes of SaO2. Under -6.67 kPa LBNP, VMCA became slow at 2, 3 min (P<0.05), and at 4 and 5 min (P<0.01) during LBNP. At 1 min after release of LBNP, VMCA did not recover, after which it recovered to control level. HR significantly increased (P<0.01) and SaO2 decreased at 5 min (P<0.05) during LBNP. Conclusion. LBNP can cause blood pooling in lower body so that VMCA and brain blood volume decrease. Then it causes loss of consciousness. The results of this experiment may provide experimental data for diagnosis of flight syncope and orthostatic intolerance.