Background and Aim Currently, the number of patients with coronavirus disease 2019 (COVID-19) infection is increasing rapidly worldwide. In this study, we aimed to assess whether diabetes mellitus (DM) would increase the risk of severe infection and death in patients with COVID-19. Methods We systematically searched the PubMed, Web of Science, MedRxiv and COVID-19 academic research communication platform for studies reporting clinical severity and/or overall mortality data on DM in patients with COVID-19 published up to July 10, 2020. The primary outcome was to compare the severe infection rate and mortality rate in COVID-19 patients with and without DM, and to calculate the odds ratio ( OR ) and 95% confidence interval (CI). Results A total of 76 studies involving 31,067 patients with COVID-19 were included in our meta-analysis. COVID-19 patients with DM had higher severe infection and case-mortality rates compared with those without DM (21.4 vs. 10.6% and 28.5 vs. 13.3%, respectively, all p <0.01). COVID-19 patients with DM were at significantly elevated risk of severe infection ( OR = 2.38, 95% CI: 2.05–2.78, p <0.001) and mortality ( OR = 2.21, 95% CI: 1.83–2.66, p <0.001). Conclusion DM is associated with increased risk of severe infection and higher mortality in patients with COVID-19. Our study suggests that clinicians should pay more attention to the monitoring and treatment of COVID-19 patients with DM.

Beta 1-adrenergic receptor autoantibodies (β1ARAbs) have been identified as a pathogenic factor in atrial fibrillation (AF), but the underlying pathogenetic mechanism is not well understood. We assessed the hypothesis that elevated β1ARAb levels increase AF susceptibility by promoting atrial fibrosis.

Objective Autonomic imbalance plays a crucial role in obstructive sleep apnea (OSA) associated atrial fibrillation (AF). Here, we investigated the potential neural mechanism of AF induced by OSA. Methods Ten dogs were divided into control group (n = 5) and OSA group (n = 5). The chronic OSA model was established by repeat apnea-ventilation cycles for 4 hours a day for 12 weeks. During the process of model establishment, arterial blood gases, atrial effective refractory period (AERP), AF inducibility, normalized low-frequency power (LFnu), normalized high-frequency power (HFnu), and LFnu/ HFnu were evaluated at baseline, 4th week, 8th week, and 12th week. Nerve activities of left stellate ganglion (LSG) and left vagal nerve(LVN) were recorded. Tyrosine hydroxylase(TH), choline acetyltransferase(CHAT), PGP9.5, nerve growth factor(NGF), and c-Fos were detected in the left atrium, LSG, and LVN by immunohistochemistry and western blot. Moreover, high-frequency stimulations of LSG and LVN were conducted to observe the AF inducibility. Results Compared with the control group, the OSA group showed significantly enhanced neural activity of the LSG, increased AF inducibility, and shortened AERP. LFnu and LFnu/HFnu were markedly increased in the OSA group, while no significant difference in HFnu was observed. TH-positive and PGP9.5-positive nerve densities were significantly increased in the LSG and left atrium. Additionally, the protein levels of NGF, c-Fos, and PGP9.5 were upregulated both in the LSG and left atrium. AF inducibility was markedly increased under LSG stimulation without a stimulus threshold change in the OSA group. Conclusions OSA significantly enhanced LSG and left atrial neural remodeling, and hyperactivity of LSG may accelerate left atrial neural remodeling to increase AF inducibility.

Background: Previous studies have proved that low-level vagus nerve stimulation (LLVS) could suppress acute obstructive sleep apnea (OSA), which is associated with atrial fibrillation (AF).Objective: This study investigates the underlying electrophysiological, neural, and cardiomyocyte injury mechanisms on acute OSA-induced AF, examining whether LLVS can attenuate or reverse this remodeling.Methods and Results: Eighteen mongrel dogs received endotracheal intubation under general anesthesia and were randomly divided into three groups: the OSA group (simulated OSA with clamping of the trachea cannula at the end of expiration for 2min followed ventilation 8min, lasting 6h, n=6), the OSA+LLVS group (simulated OSA plus LLVS, n=6), and a control group (sham clamping the trachea cannula without stimulation, n=6). In the OSA+LLVS group, the atrial effective refractory period was significantly lengthened while the sinus node recovery time and AF duration decreased after the 4th hour, and the expression level of Cx40 and Cx43 was significantly increased compared to the OSA group. Norepinephrine, TH, and ChAT were significantly decreased in the OSA+LLVS group compared with the OSA group. Mitochondrial swelling, cardiomyocyte apoptosis, and glycogen deposition, along with a higher concentration of TNF-α, IL-6 were observed in the OSA group, and the LLVS inhibited the structural remodeling and expression of inflammatory cytokines.Conclusion: LLVS decreased the inducibility of AF partly by ameliorating sympathetic hyperactivity and atrial myocyte injury after acute OSA-induced AF.

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Background. Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. Methods and Results. CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n = 10 ), CHF group (CHF, n = 11 ), Vag group (CHF+vagotomy, n = 10 ), PNU group (CHF+PNU-282987 for 4 weeks, n = 11 ), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n = 10 ). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. Conclusion. CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.

Background: Previous studies have reported that right pulmonary artery ganglionated plexi (GP) ablation could suppress the onset of atrial fibrillation (AF) associated with obstructive sleep apnea (OSA) within 1 h.Objective: This study aimed to investigate the effect of superior left GP (SLGP) ablation on AF in a chronic OSA canine model.Methods and Results: Fifteen beagles were randomly divided into three groups: control group (CTRL), OSA group (OSA), and OSA + GP ablation group (OSA + GP). All animals were intubated under general anesthesia, and ventilation-apnea events were subsequently repeated 4 h/day and 6 days/week for 12 weeks to establish a chronic OSA model. SLGP were ablated at the end of 8 weeks. SLGP ablation could attenuate the atrial effective refractory period (ERP) reduction and decrease ERP dispersion, the window of vulnerability, and AF inducibility. In addition, chronic OSA leads to left atrial (LA) enlargement, decreased left ventricular (LV) ejection fraction, glycogen deposition, increased necrosis, and myocardial fibrosis. SLGP ablation reduced the LA size and ameliorated LV dysfunction, while myocardial fibrosis could not be reversed. Additionally, SLGP ablation mainly reduced sympathovagal hyperactivity and post-apnea blood pressure and heart rate increases and decreased the expression of neural growth factor (NGF), tyrosine hydroxylase (TH), and choline acetyltransferase (CHAT) in the LA and SLGP. After SLGP ablation, the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, cholesterol metabolism pathway, and ferroptosis pathway were notably downregulated compared with OSA.Conclusions: SLGP ablation suppressed AF in a chronic OSA model by sympathovagal hyperactivity inhibition. However, there were no significant changes in myocardial fibrosis.

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