[Short-term efficacy and safety of cardiac contractility modulation in patients with heart failure].

Objective: To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure. Methods: This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded. Results: CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions: CCM has better short-term safety and efficacy in patients with heart failure.

A case of endocardial dissection caused by Micra implantation.

BACKGROUND: Leadless pacemakers are a recent technological advancement. It has many advantages, but there are still a few serious complications. CASE PRESENTATION: This article reports the case of a patient with an endocardial tear and dissection caused by contact with the tip of the Micra cup during surgery and summarises the relevant data. CONCLUSIONS: This case report details the occurrence and management of the incident and provides some guidance for future clinical management.

Identification of a Novel Target Implicated in Chronic Obstructive Sleep Apnea-Related Atrial Fibrillation by Integrative Analysis of Transcriptome and Proteome.

Objective: This study aimed to identify a newly identified target involved in atrial fibrillation (AF) linked to chronic obstructive sleep apnea (COSA) through an integrative analysis of transcriptome and proteome. Methods: Fifteen beagle canines were randomly assigned to three groups: control (CON), obstructive sleep apnea (OSA), and OSA with superior left ganglionated plexi ablation (OSA+GP). A COSA model was established by intermittently obstructing the endotracheal cannula during exhalation for 12 weeks. Left parasternal thoracotomy through the fourth intercostal space allowed for superior left ganglionated plexi (SLGP) ablation. In vivo open-chest electrophysiological programmed stimulation was performed to assess AF inducibility. Histological, transcriptomic, and proteomic analyses were conducted on atrial samples. Results: After 12 weeks, the OSA group exhibited increased AF inducibility and longer AF durations compared to the CON group. Integrated transcriptomic and proteomic analyses identified 2422 differentially expressed genes (DEGs) and 1194 differentially expressed proteins (DEPs) between OSA and CON groups, as well as between OSA+GP and OSA groups (1850 DEGs and 1418 DEPs). The analysis revealed that differentially regulated DEGs were primarily enriched in mitochondrial biological processes in the CON-vs.-OSA and OSA-vs.-GP comparisons. Notably, the key regulatory molecule GSTZ1 was activated in OSA and inhibited by GP ablation. Conclusion: These findings suggest that GSTZ1 may play a pivotal role in mitochondrial damage, triggering AF substrate formation, and increasing susceptibility to AF in the context of COSA.

Feasibility study of cryoballoon ablation for atrial fibrillation with KODEX-EPD: a single center experience.

To evaluate the feasibility of cryoballoon (CB) ablation of atrial fibrillation (AF) under the guidance of a new three-dimensional (3D) mapping system KODEX-EPD. 40 patients scheduled for CB ablation of AF in the first affiliated Hospital of Xinjiang Medical University from August 2021 to July 2022 were randomly divided into two groups: KODEX-EPD 3D mapping system guidance group (KODEX group, n = 20) and conventional two-dimensional perspective group (standard group, n = 20). The ablation time, operation time, fluoroscopy time, fluoroscopy dose, contrast agent dosage and follow-up data were compared between the two groups. Besides, the feasibility and accuracy of the dielectric sensing system in evaluating pulmonary vein (PV) occlusion in patients with AF during CB ablation were verified. All pulmonary veins were being isolated. The ablation time (36.40 ± 6.72 min vs 35.15 ± 6.29 min, P > 0.05) and the operation time (64.20 ± 11.82 min vs 66.00 ± 13.18 min, P > 0.05) were not statistically different in the two groups. The standard group has longer fluoroscopy time, dose and contrast medium dosage. There were significant differences in fluoroscopy time (532.30 ± 72.83 s vs 676.25 ± 269.33 s, P < 0.05), fluoroscopy dose (110.00 ± 28.64 mGy vs 144.68 ± 66.66 mGy, P < 0.05), and contrast medium dosage (71.90 ± 5.97 ml vs 76.05 ± 5.93 ml, P < 0.05) between the two groups. The learning curves of the first 5 patients and the last 15 patients in the KODEX group were compared. There was no statistical difference in the ablation time (36.80 ± 8.56 min vs 36.27 ± 6.34 min, P > 0.05) or the operation time (69.00 ± 5.00 min vs 62.60 ± 13.10 min, P > 0.05); however, compared to the first 5 patients, fluoroscopy time (587.40 ± 38.34 s vs 513.93 ± 73.02 s, P < 0.05), fluoroscopy dose (147.85 ± 35.19 mGy vs 97.39 ± 8.80 mGy, P < 0.05) and contrast medium dosage (79.60 ± 1.14 ml vs 69.33 ± 4.45 ml, P < 0.05) were significantly decreased. Using pulmonary venography as the gold standard, the sensitivity, specificity of the completely occlusion in KODEX group was 93.6% (95% CI 85-97.6%) and 69.6% (95% CI 54-81.8%); and the sensitivity, specificity of the small leak in KODEX group was 93.1% (95% CI 82.4-97.8%) and 82.0% (95% CI 65.9-91.9%). During an average follow-up of (9.90 ± 1.06) months, there was no statistical difference in arrhythmia recurrence and antiarrhythmic drugs taking after CB ablation between the two groups (P > 0.05). Using the KODEX-EPD system, the CB ablation procedure can correctly evaluate the PV occlusion, and significantly reduce fluoroscopy exposure and contrast medium without significantly increasing the operation time.

Feasibility, safety and effectiveness of mapping system assisted conduction system pacing: a single-center prospective study.

To assess pacing and electrophysiological parameters, as well as mid-term outcomes, among patients undergoing His bundle pacing (HBP) guided by KODEX-EPD (a novel mapping system). Consecutive patients undergoing conduction system pacing (CSP) for bradycardia indications were evaluated. Procedural and fluoroscopic times and pacing characteristics were compared between conventional fluoroscopy (the standard group, N = 20 cases) and KODEX-EPD mapping system guided group (the KODEX group, N = 20cases) at CSP implantation and all patients were followed at 6-month. HBP was achieved in all patients (the standard group 20/20 and the KODEX group 20/20). There was no difference in the mean procedure time between the two groups (63.7 ± 9.3 vs. 78.2 ± 25.1 min, p = 0.33). Compared with the standard group, the KODEX group significantly reduced the intraoperative X-ray exposure time (3.8 ± 0.5 vs. 19.3 ± 5.1 min, p < 0.05) and X-ray dose (23.6 ± 5.4 vs. 120.2 ± 38.3 mGy, p < 0.05). There were no significant differences in atrial impedance (643.0 ± 98.8 vs. 591.5 ± 92.1 Ω, p = 0.09), atrial sensing (2.9 ± 0.8 vs. 2.5 ± 0.8 mV, p = 0.08), ventricular sensing (12.8 ± 2.4 vs. 13.3 ± 3.3 mV, p = 0.63),atrial pacing threshold (1.0 ± 0.2 vs. 1.0 ± 0.1 V/0.4 ms, p = 0.81) and ventricular pacing threshold (1.0 ± 0.2 vs. 0.9 ± 0.1 V/0.4 ms, p = 0.63) between two groups, There were statistical differences in ventricular impedance (640.0 ± 80.3 vs. 702.0 ± 86.1 Ω, p < 0.05). There was no statistical significance in pacing parameters between the two groups at 6 months after procedure (p > 0.05). During the 6-months follow-up period, no adverse events occurred in the two groups. It can be concluded that KODEX-EPD can safely guide His bundle branch pacing lead implantation with reduced fluoroscopic time and dose without lengthening the procedure time.

Renal denervation alleviates chronic obstructive sleep apnea-induced atrial fibrillation via inhibition of atrial fibrosis and sympathetic hyperactivity.

OBJECTIVE: Previous studies have reported that renal denervation (RDN) prevents the occurrence of atrial fibrillation (AF) related to obstructive sleep apnea (OSA). However, the effect of RDN on chronic OSA (COSA)-induced AF is still unclear. METHODS: Healthy beagle dogs were randomized into the OSA group (sham RDN + OSA), OSA-RDN group (RDN + OSA), and CON group (sham RDN + sham OSA). The COSA model was built via repeated apnea and ventilation rounds for 4 h each day lasting 12 weeks, and RDN was employed after 8 weeks of modeling. All dogs were implanted Reveal LINQ™ to detect spontaneous AF and AF burden. Circulating levels of norepinephrine, angiotensin II, and interleukin-6 were determined at baseline and end of the study. In addition, measurements of the left stellate ganglion, AF inducibility, and effective refractory period were conducted. The bilateral renal artery and cortex, left stellate ganglion, and left atrial tissues were collected for molecular analysis. RESULTS: Of 18 beagles, 6 were randomized to each of the groups described above. RDN remarkably attenuated ERP prolongation and AF episodes and duration. RDN markedly suppressed the LSG hyperactivity and atrial sympathetic innervation, decreased the serum concentrations of Ang II and IL-6, further inhibited fibroblast-to-myofibroblast transformation via the TGF-ß1/Smad2/3/α-SMA pathway, and reduced the expression of MMP-9, thus decreasing OSA-induced AF. CONCLUSIONS: RDN may reduce AF by inhibiting sympathetic hyperactivity and AF in a COSA model.

Right ventriculography improves the accuracy of leadless pacemaker implantation in right ventricular mid-septum.

BACKGROUND: Implanting leadless pacemakers in the right ventricular (RV) apex is prone to causing pericardial tamponade and myocardial perforation. OBJECTIVE: To investigate the feasibility and safety of right ventriculography-guided implantation of Micra™ leadless pacemaker (Micra™, Medtronic, Minneapolis, MN, USA) in the RV mid-septum. METHODS: One hundred eight consecutive patients who underwent Micra™ implantation intended in the mid-septum were enrolled and randomized (3:1) into the radiography group (n = 81) with assistance of right ventriculography to illustrate the RV septum and the non-radiography group (n = 27). All subjects underwent a postoperative computed tomography (CT) scan to determine the Micra™ location. The Micra™ location assessed by CT image was compared between the two groups to confirm the accuracy of the intended pacing site. The duration of the procedure, X-ray radiation dose, and time were also compared between the two groups. RESULTS: Reconstructed CT 3-D cardiac images found the Micra™ location in the intended mid-septum in 13 patients (48.1%, 13/27) in the non-radiography group and 76 patients (93.8%, 76/81) in the radiography group (P < 0.0001 between two groups). There was no significant difference in procedure interval between the two groups while the X-ray radiation dose (564.86 ± 112.44 vs. 825.85 ± 156.12 mGy, P < 0.0001), X-ray exposure time (7.79 ± 1.43 vs. 12.03 ± 2.86 min, P < 0.0001), and the number of fluoroscopy re-positioning (2.79 ± 1.03 vs. 6.41 ± 1.82, P < 0.0001) were significantly less in the radiography group than in the non-radiography group. No implantation-related complications were observed in both groups. CONCLUSION: Right ventriculography increases the accuracy of Micra™ implantation in the mid-septum and reduces X-ray exposure. TRIAL REGISTRATION: The trial registration number (ChiCTR2100051374) and date (09/22/2021).

In Vitro Drug Screening Using iPSC-Derived Cardiomyocytes of a Long QT-Syndrome Patient Carrying KCNQ1 & TRPM4 Dual Mutation: An Experimental Personalized Treatment.

Congenital long QT syndrome is a type of inherited cardiovascular disorder characterized by prolonged QT interval. Patient often suffer from syncopal episodes, electrocardiographic abnormalities and life-threatening arrhythmia. Given the complexity of the root cause of the disease, a combination of clinical diagnosis and drug screening using patient-derived cardiomyocytes represents a more effective way to identify potential cures. We identified a long QT syndrome patient carrying a heterozygous KCNQ1 c.656G>A mutation and a heterozygous TRPM4 c.479C>T mutation. Implantation of implantable cardioverter defibrillator in combination with conventional medication demonstrated limited success in ameliorating long-QT-syndrome-related symptoms. Frequent defibrillator discharge also caused deterioration of patient quality of life. Aiming to identify better therapeutic agents and treatment strategy, we established a patient-specific iPSC line carrying the dual mutations and differentiated these patient-specific iPSCs into cardiomyocytes. We discovered that both verapamil and lidocaine substantially shortened the QT interval of the long QT syndrome patient-specific cardiomyocytes. Verapamil treatment was successful in reducing defibrillator discharge frequency of the KCNQ1/TRPM4 dual mutation patient. These results suggested that verapamil and lidocaine could be alternative therapeutic agents for long QT syndrome patients that do not respond well to conventional treatments. In conclusion, our approach indicated the usefulness of the in vitro disease model based on patient-specific iPSCs in identifying pharmacological mechanisms and drug screening. The long QT patient-specific iPSC line carrying KCNQ1/TRPM4 dual mutations also represents a tool for further understanding long QT syndrome pathogenesis.

Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats.

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.

Ganglionated Plexi Ablation Suppresses Chronic Obstructive Sleep Apnea-Related Atrial Fibrillation by Inhibiting Cardiac Autonomic Hyperactivation.

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.

Enhanced atrial internal-external neural remodeling facilitates atrial fibrillation in the chronic obstructive sleep apnea model.

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.

Histopathological substrate of the atrial myocardium in the progression of obstructive sleep apnoea-related atrial fibrillation.

BACKGROUND: Obstructive sleep apnoea (OSA) is closely related to atrial fibrillation (AF), and OSA-induced atrial structural remodelling is the basis of AF maintenance. However, the process of atrial structural remodelling during the progression of acute OSA to chronic OSA is still unclear. OBJECTIVE: To investigate changes in the atrial myocardium in acute sleep apnoea (6 h) and chronic sleep apnoea (12 weeks) by echocardiography, atrial myocardium morphology analysis, PAS staining, TUNEL staining, Masson's trichrome staining and analyses of ultrastructural changes. METHODS: Eighteen adult beagle dogs under general anaesthesia were used to establish an OSA model. The animals were divided into the control group, acute OSA group and chronic OSA group, and there were six animals in each group. Cardiac ultrasounds of dogs from the three groups were examined. Left and right atrial muscle tissues were taken for HE staining, PAS staining, TUNEL staining, Masson's trichrome staining and transmission electron microscopy. RESULTS: In the acute OSA model, the left atrial diameter of the dogs began to increase 3 h after ventilation, and this difference was more obvious at 6 h. The morphology of the myocardial cells did not change significantly, but mitochondrial swelling was observed in some atrial myocytes at 3 h. In the chronic OSA model, the left atrial diameter gradually increased, the volume of the right and left atria increased, the glycogen and collagen volume fractions and apoptosis ratio were significantly increased in atrial myocytes, mitochondria swelling and lengthening occurred in some atrial myocytes, the matrix became lighter, the mitochondrial ridge density decreased and the myofilament arrangement was disordered. The disc was distorted and not continuous, and there was some cardiomyocyte necrosis. CONCLUSION: With the prolongation of apnoea, the atrium gradually enlarges, myocardial cells become disordered, glycogen aggregates, the number of necrotic cells increases, fibrosis worsens, mitochondrial abnormalities occur and the arrangement of the discs are disordered, providing a basis for the maintenance of AF.

Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure.

Heart failure (HF) leads to a progressive increase in morbidity and mortality rates. This study aimed to explore the transcriptional landscape during HF and identify differentially expressed transcripts (DETs) and alternative splicing events associated with HF. We generated a dog model of HF (n = 3) using right ventricular pacemaker implantation. We performed full-length transcriptome sequencing (based on nanopore platform) on the myocardial tissues and analyzed the transcripts using differential expression analysis and functional annotation methods [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses]. Additionally, we estimated the expression of the selected genes by quantitative real-time PCR (qRT-PCR) and detected the proportion of immune cells using flow cytometry. We found that increased B-type natriuretic peptide reduced ejection fraction, and apparent clinical signs were observed in the dog model of HF. We identified 67,458 transcripts using full-length transcriptome sequencing. A total of 785 DETs were obtained from the HF and control groups. These DETs were mainly enriched in the immune responses, especially Th1, Th2, and Th17 cell differentiation processes. Furthermore, flow cytometry results revealed that the proportion of Th1 and Th17 cells increased in patients with HF compared to controls, while the proportion of Th2 cells decreased. Differentially expressed genes in the HF and control groups associated with Th1, Th2, and Th17 cell differentiation were quantified using qRT-PCR. We also identified variable splicing events of sarcomere genes (e.g., MYBPC3, TNNT2, TTN, FLNC, and TTNI3). In addition, we detected 4,892 transcription factors and 406 lncRNAs associated with HF. Our analysis based on full-length transcript sequencing provided an analysis perspective in a dog model of HF, which is valuable for molecular research in an increasingly relevant large animal model of HF.

Diabetes Mellitus is Associated with Severe Infection and Mortality in Patients with COVID-19: A Systematic Review and Meta-analysis.

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.

Elevated ß1-Adrenergic Receptor Autoantibody Levels Increase Atrial Fibrillation Susceptibility by Promoting Atrial Fibrosis.

OBJECTIVE: Beta 1-adrenergic receptor autoantibodies (ß1ARAbs) 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 ß1ARAb levels increase AF susceptibility by promoting atrial fibrosis. METHODS: A total of 70 patients with paroxysmal AF were continuously recruited. The serum levels of ß1ARAb and circulating fibrosis biomarkers were analyzed by ELISA. Linear regression was used to examine the correlations of ß1ARAb levels with left atrial diameter (LAD) and circulating fibrosis biomarker levels. Furthermore, we established a rabbit ß1ARAb overexpression model. We conducted electrophysiological studies and multielectrode array recordings to evaluate the atrial effective refractory period (AERP), AF inducibility and electrical conduction. AF was defined as irregular, rapid atrial beats > 500 bpm for > 1000 ms. Echocardiography, hematoxylin and eosin staining, Masson's trichrome staining, and picrosirius red staining were performed to evaluate changes in atrial structure and detect fibrosis. Western blotting and PCR were used to detect alterations in the protein and mRNA expression of TGF-ß1, collagen I and collagen III. RESULTS: Patients with a LAD ≥ 40 mm had higher ß1ARAb levels than patients with a smaller LAD (8.87 ± 3.16 vs. 6.75 ± 1.34 ng/mL, P = 0.005). ß1ARAb levels were positively correlated with LAD and circulating biomarker levels (all P < 0.05). Compared with the control group, the rabbits in the immune group showed the following: (1) enhanced heart rate, shortened AERP (70.00 ± 5.49 vs. 96.46 ± 3.27 ms, P < 0.001), increased AF inducibility (55% vs. 0%, P < 0.001), decreased conduction velocity and increased conduction heterogeneity; (2) enlarged LAD and elevated systolic dysfunction; (3) significant fibrosis in the left atrium identified by Masson's trichrome staining (15.17 ± 3.46 vs. 4.92 ± 1.72%, P < 0.001) and picrosirius red staining (16.76 ± 6.40 vs. 4.85 ± 0.40%, P < 0.001); and (4) increased expression levels of TGF-ß1, collagen I and collagen III. CONCLUSION: Our clinical and experiential studies showed that ß1ARAbs participate in the development of AF and that the potential mechanism is related to the promotion of atrial fibrosis.

Association of Obesity Measures with Atrial Fibrillation Recurrence After Cryoablation in Patients with Paroxysmal Atrial Fibrillation.

BACKGROUND Obesity increases the risk of atrial fibrillation (AF) recurrence after ablation. This study explored the relationship between various obesity indexes and risk of recurrence after cryoablation of paroxysmal AF (PAF). MATERIAL AND METHODS Our prospective study included 100 patients with PAF who underwent first cryoablation. Physical examination and fasting blood lipids levels were measured at baseline. Seven obesity indexes were determined: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-hip ratio (WHR), cardiometabolic index (CMI), lipid accumulation product (LAP), and body adiposity index (BAI). AF recurrence was confirmed by electrocardiograms and Holter monitor at follow-up visits after the initial 3-month blanking period. Receiver operating characteristic (ROC) curves were drawn to assess the abilities of obesity indicators in predicting AF recurrence. Multivariable Cox regression analysis was used to examine independent predictors of AF recurrence. RESULTS During a mean follow-up of 13.4 months, 31 patients (31.0%) had recurrent AF. Patients with recurrence had higher BMI, WC, WHtR, LAP, and BAI compared with those without recurrence. ROC analysis indicated the potential predictive value of BAI with an AUC of 0.657 (95% confidence interval [CI]: 0.534-0.779), followed by WC, WHtR, LAP, and BMI (all P<0.05). Diagnosis-to-ablation time (HR 1.034, 95% CI: 1.002-1.068), left atrial diameter (HR 1.147, 95% CI: 1.026-1.281), and WC (HR 1.026, 95% CI: 1.000-1.053) were independent predictive factors for AF recurrence after multivariable adjustment. CONCLUSIONS In this study population, WC appears to be a potential indicator for the prediction of recurrence in patients with PAF after cryoablation.

Low-Level Vagus Nerve Stimulation Reverses Obstructive Sleep Apnea-Related Atrial Fibrillation by Ameliorating Sympathetic Hyperactivity and Atrial Myocyte Injury.

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.

The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation / 中华内科杂志

Objective:To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF).Methods:This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke.Results:Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion:Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

Expression of Galectin-7 in squamous cell carcinoma of the cervix and its association with HPV 16 infection / 临床与实验病理学杂志

Purpose To study the expression of Galectin-7 in squamous carcinoma of the cervix and its correlation with HPV 16 infec-tion in Uyghur and Han women. Methods The expression of Galectin-7 in paraffin-embedded cervical tissues collected from Uyghur women including 21 patients with cervicitis and 49 patients with squamous carcinoma of the cervix and Han women including 25 patients with cervicitis and 29 patients with squamous cervical cancer was evaluated by immunohistochemical SP method. The infection of HPV 16 was evaluated by PCR amplification of HPV DNA from the corresponding cervical tissue samples. The expression of levels of Galec-tin-7 in cervical tissues was analyzed according to the corresponding integrated optical density ( IOD) value of Galectin-7 in cervical le-sions with professional image analysis software Image-Pro Plus (IPP) 6. 0. Results PCR detection of HPV 16 in Uyghur patients from Kashghar showed that 20 patients were positive and 29 cases were negative for HPV 16 in squamous cervical cancer patients whereas in patients with cervicitis, only 5 cases were positive, 16 cases were negative for HPV 16. Furthermore the detection of HPV 16 in Han patients showed that 2 cases were positive and 27 cases was negative in patients with squamous cervical cancer patients, and all the ca-ses were negative for HPV 16 in patients with cervicitis. The expression of Galectin-7 in squamous cervical cancer tissues was signifi-cantly lower than that in the cervicitis patients (P<0. 05). The expression of Galectin-7 in HPV 16 positive squamous cervical cancer patients was significantly lower than that in HPV 16 negative patients ( P<0. 05 ) . There was no obvious correlation between the ex-pression levels of Galectin-7 in squamous cervical cancer patients with the differentiation degree and disease oneset age both in Uyghur and Han patients. Conclusion Compared with cervicitis tissues, Galectin-7 expression in squamous cervical cancer is down-regulated in Uyghur women from Kashghar region implying that the expression of Galectin-7 may play a certain role in the occurrence and develop-ment of squamous cervical cancer, and its detection has a certain reference value for the diagnosis of cervical cancer for Uyghur women.