Bioinformatics analysis reveals the potential common genes and immune characteristics between atrial fibrillation and periodontitis.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) and periodontitis, both classified under chronic inflammatory diseases, share common etiologies, including genetic factors and immune pathways. However, the exact mechanisms are still poorly understood. This study aimed to explore the potential common genes and immune characteristics between AF and periodontitis. METHODS: Gene expression datasets for AF and periodontitis were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis was used to identify common genes in the training set. Functional analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were conducted to elucidate the underlying mechanisms. Hub genes were further screened based on expression levels, receiver operating characteristic (ROC) curves, and least absolute shrinkage and selection operator (LASSO) regression. Then, based on the expression levels and ROC values of the hub genes in the validation set, the target genes were identified. Finally, immune cell infiltration analysis was performed on the AF and periodontitis datasets in the training set using the "CIBERSORT" R package. The relationships between target genes, infiltrating immune cells, and inflammatory factors were also investigated. In addition, AF susceptibility, atrial fibrosis, inflammatory infiltration, and RGS1 protein expression in rat models of periodontitis were assessed through in vivo electrophysiology experiments, Masson's trichrome staining, hematoxylin-eosin staining, immunohistochemistry, and western blotting, respectively. RESULTS: A total of 21 common genes were identified between AF and periodontitis among the differentially expressed genes. After evaluating gene expression levels, ROC curves, and LASSO analysis, four significant genes between AF and periodontitis were identified, namely regulator of G-protein signaling 1 (RGS1), annexin A6 (ANXA6), solute carrier family 27 member 6 (SLC27A6), and ficolin 1 (FCN1). Further validation confirmed that RGS1 was the optimal shared target gene for AF and periodontitis. Immune cell infiltration analysis revealed that neutrophils and T cells play an important role in the pathogenesis of both diseases. RGS1 showed a significant positive correlation with activated memory CD4 T cells and gamma-delta T cells and a negative correlation with CD8 T cells and regulatory T cells in both training sets. Moreover, RGS1 was positively correlated with classical pro-inflammatory cytokines IL1ß and IL6. In periodontitis rat models, AF susceptibility, atrial fibrosis, and inflammatory infiltration were significantly increased, and RGS1 expression in the atrial tissue was upregulated. CONCLUSION: A common gene between AF and periodontitis, RGS1 appears central in linking the two conditions. Immune and inflammatory responses may underlie the interaction between AF and periodontitis.

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.

Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999-2002.

BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD. METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association. RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.

Increased ß1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.

BACKGROUND: Autoimmune disorder is the emerging mechanism of atrial fibrillation (AF). The ß1-adrenergic receptor antibody (ß1-AAb) is associated with AF progress. Our study aims to investigate whether ß1-AAbs involves in atrial vulnerable substrate by mediating Ca2+ mishandling and atrial fibrosis in autoimmune associated AF. METHODS: Active immunization models were established via subcutaneous injection of the second extracellular loop (ECL2) peptide for ß1 adrenergic receptor (ß1AR). Invasive electrophysiologic study and ex vivo optical mapping were used to evaluate the changed electrophysiology parameters and calcium handling properties. Phospho-proteomics combined with molecular biology assay were performed to identify the potential mechanisms of remodeled atrial substrate elicited by ß1-AAbs. Exogenous ß1-AAbs were used to induce the cellular phenotypes of HL-1 cells and atrial fibroblasts to AF propensity. RESULTS: ß1-AAbs aggravated the atrial electrical instability and atrial fibrosis. Bisoprolol alleviated the alterations of action potential duration (APD), Ca2+ transient duration (CaD), and conduction heterogeneity challenged by ß1-AAbs. ß1-AAbs prolonged calcium transient refractoriness and promoted arrhythmogenic atrial alternans and spatially discordant alternans, which were partly counteracted through blocking ß1AR. Its underlying mechanisms are related to ß1AR-drived CaMKII/RyR2 activation of atrial cardiomyocytes and the myofibroblasts phenotype formation of fibroblasts. CONCLUSION: Suppressing ß1-AAbs effectively protects the atrial vulnerable substrate by ameliorating intracellular Ca2+ mishandling and atrial fibrosis, preventing the process of the autoimmune associated AF.

Postcardiac injury syndrome caused by radiofrequency catheter ablation of persistent atrial fibrillation: severe pulmonary arterial hypertension with severe tricuspid regurgitation: a rare case report and literature review.

BACKGROUND: Postcardiac injury syndrome (PCIS) is an easy-to-miss diagnosis, but it is not an uncommon complication. The phenomenon of echocardiography (ECHO) showing both severe pulmonary arterial hypertension (PAH) and severe tricuspid regurgitation (TR) is indeed rare in PCIS after extensive radiofrequency ablation. CASE PRESENTATION: A 70-year-old male was diagnosed with persistent atrial fibrillation. The patient received radiofrequency catheter ablation due to his atrial fibrillation being refractory to antiarrhythmic drugs. After the anatomical three-dimensional models were created, ablations were performed on the left and right pulmonary veins, roof linear and bottom linear of the left atrium, and the cavo-tricuspid isthmus. The patient was discharged in sinus rhythm (SR). After 3 days, he was admitted to the hospital for gradually worsening dyspnea. Laboratory examination showed a normal leukocyte count with an increased percentage of neutrophils. The erythrocyte sedimentation rate, C-reactive protein concentration, interleukin-6, and N-terminal pro-B-type natriuretic peptide were elevated. ECG exhibited SR, V1-V4 of precordial lead P-wave amplitude which was increased but not prolonged, PR segment depression, and ST-segment elevation. Computed tomography angiography of the pulmonary artery revealed that the lung had scattered high-density flocculent flakes and a small amount of pleural and pericardial effusion. Local pericardial thickening was seen. ECHO showed severe PAH with severe TR. Diuretics and vasodilators did not relieve the symptoms. Tumors, tuberculosis, and immune system diseases were all excluded. Considering the patient's diagnosis of PCIS, the patient was treated with steroids. The patient recovered on the 19th day post ablation. The patient's condition was maintained until 2 years of follow-up. CONCLUSIONS: The phenomenon of ECHO showing severe PAH with severe TR is indeed rare in PCIS. Due to the lack of diagnostic criteria, such patients are easily misdiagnosed, leading to a poor prognosis.

Epicardial implantation of a lumenless active fixation lead in a neonate.

BACKGROUND: We present a case of epicardial pacemaker implantation in a low birth weight newborn using a lumenless active fixation lead. RESULTS: We found that superior pacing parameters can be obtained by implanting a lumenless active fixation lead into the epicardium, but more evidence is needed to support this hypothesis.

Weight-adjusted waist index is not superior to conventional anthropometric indices for predicting type 2 diabetes: a secondary analysis of a retrospective cohort study.

BACKGROUND: Weight-adjusted waist index (WWI) is a new anthropometric indicator to assess adiposity. Current knowledge regarding its association with type 2 diabetes mellitus (T2DM) is limited. This present study aims to evaluate the association of WWI with the risk of T2DM in the Japanese population, and to compare its predictive ability with body mass index (BMI) and waist circumference (WC). METHODS: This was a secondary analysis of a retrospective cohort study involving 15,464 participants. Participants were divided into quartiles based on baseline WWI levels. Cox regression model, Kaplan-Meier curve, and smooth curve fitting were used to explore the relationship between WWI and T2DM. The discriminative ability of obesity indices in predicting T2DM was compared by the receiver operating characteristic (ROC) curve. RESULTS: After a mean follow-up of 6.05 years, 373 participants were diagnosed with T2DM. In fully adjusted models, the risk of incident T2DM was 1.96 times higher for each 1-unit increment in WWI levels (95% CI: 1.61-2.39, P < 0.001). Smooth curve fitting analysis showed a linear positive association between baseline WWI and new-onset T2DM. Subgroup analysis showed consistent results which subjects in the 4th WWI quartile had the highest risk of developing T2DM in different age, gender, and BMI groups. WWI did not exhibit better predictive ability compared with BMI and WC in the results of ROC curve. CONCLUSION: WWI, a new metabolic index, can be used to predict new-onset T2DM in the Japanese population. However, its predictive capability was not superior to conventional anthropometric indices.

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.

Aging-induced atrial fibrosis in If current change and its effect on atrial fibrillation in dogs.

BACKGROUND: Atrial fibrillation (AF) is a very common type of cardiac arrhythmia that threatens public health. Aging is an independent AF risk factor. However, the mechanism of age-related AF remains unclear. METHODS: A total of 36 Beagle dogs were selected and divided into three groups (12 in each group): two groups were 9-year-old aged dogs, and one group was 4-year-old adult dogs. Electrophysiological testing was employed to determine if modeling is successful. Patch-clamp technique was employed to measure the If current. The expression of protein and mRNA related to If current were also tested. Collagen deposition was observed with the use of Masson staining. RESULTS: Aging resulted in a higher collagen deposition percentage in the left atrium. The hyperpolarization-activated cyclic nucleotide-gated (HCN)2 and HCN4 expressions were increased in the atria and pulmonary veins but decreased in the sinus node of the aged group. Moreover, in the aged group, the left atrium mRNA expressions of Kcnd2 (Potassium voltage-gated channel subfamily D member 2), Kcnh2, Kcnq1, Kcnj2, Kcnj11, and CACNA1H were significantly downregulated. The aged AF group also demonstrated sustained AF and significant changes in electrophysiological characteristics. The If current demonstrated an increased amplitude and was easier to activate in the aged AF group than in younger group. Finally, AF occurrence exacerbated aging-induced cardiac fibrosis, thereby aggravating the above-listed symptoms. CONCLUSION: With age, the increase in atrial fibrosis affected the expression of the ion channels, thereby modulating the If current. Moreover, AF also further exacerbated the degree of atrial fibrosis.

Association between lipoprotein(a) and thromboembolism in patients with non-valvular atrial fibrillation: a cross-sectional study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized risk factor for ischemic stroke (IS); however, its role in thromboembolism in patients with non-valvular atrial fibrillation (NVAF) remains controversial. We aimed to assess the association of Lp(a) and IS and systemic embolism (SEE) in NVAF patients. METHODS: In total, 16,357 patients with NVAF were recruited from the First Affiliated Hospital of Xinjiang Medical University from January 1, 2009, to December 31, 2021, and were divided into groups based on Lp(a) quartiles. Logistic regression models analyzed the association between Lp(a), IS, and SEE. The restriction cubic spline was used to assess the potential nonlinear relationship between Lp(a), IS, and SEE. We conducted subgroup analyses and estimated the multiplicative interaction between the stratified variables and Lp(a) to investigate whether the association between Lp(a) and IS and SEE was affected by age, sex, anticoagulants, and CHA2DS2-VASc score. RESULTS: We identified 1319 IS and 133 SEE events. After correcting for CHA2DS2-VASc score and other potential confounders, each 1-standard deviation (SD) increase in log-Lp(a) was related to a 23% increased risk of IS (odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.07-1.41). NVAF patients in the highest Lp(a) quartile were 1.23-fold more likely to have IS than those in the lowest quartile (OR, 1.23; 95% CI, 1.04-1.45). A positive linear relationship between Lp(a) and IS risk was observed (P for nonlinear = 0.341). In the fully adjusted model, subjects had a 1.78-fold increased risk of SEE for each 1-SD increase in log-Lp(a) (OR, 2.78; 95% CI, 1.78-4.36). Subjects in the highest Lp(a) quartile had a 2.38-fold elevated risk of SEE (OR, 3.38; 95% CI, 1.85-6.19) compared with the lowest quartile. Furthermore, Lp(a) had a nonlinear relationship with the risk of SEE (P for nonlinear = 0.005). CONCLUSIONS: Elevated Lp(a) concentration was significantly associated with IS and SEE, suggesting that Lp(a) may be an emerging biomarker that can help clinicians identify patients at high risk of thromboembolism in this population.

Incidence, Risk Factors, and Prognosis of Tricuspid Regurgitation After Cardiac Implantable Electronic Device Implantation: A Systematic Review and Meta-analysis.

This study aimed to determine the pooled incidence, risk factors, and clinical prognosis of tricuspid regurgitation (TR) deterioration after implantation of a cardiac implantable electronic device (CIED). The study was designed as a meta-analysis of randomized controlled trials and observational studies. Patients with indications for CIEDs were selected as participants and CIED implantation was the intervention. PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Science and Technology Journal Database were searched systematically to identify studies. Thirty-seven studies with 8,144 patients were included. The pooled incidence of TR deterioration of at least one grade was 25.1% (95% confidence interval [CI], 20.9-29.3; Z = 11.60; p < 0.01; I2 = 94.8%, p < 0.01). Compared with TR incidence after permanent pacemaker implantation, that after implantable cardioverter-defibrillator implantation did not significantly increase (22.68% v 29.18%; odds ratio [OR], 0.615; 95% CI, 0.271-1.339; Z =1.16; p = 0.246). The pooled incidence of TR deterioration of at least two grades was 9.4% (95% CI, 6.6-12.1; Z = 6.72; p < 0.01; I2 = 86.0%, p < 0.01). Lead interference (OR, 8.704; 95% CI,4.450-17.028; Z= 6.32; p < 0.001) and pacemaker implantation time (OR, 1.153; 95% CI, 1.082-1.229; Z = 4.37; p < 0.001) were risk factors for worsening TR. Baseline atrial fibrillation, age, baseline mild TR, and left ventricular ejection fraction were not associated with TR. All-cause mortality (>one year after pacemaker implantation) was higher in patients with TR deterioration (hazard ratio, 1.598; 95% CI, 1.275-2.002; Z = 4.07; p < 0.01; I2 = 0%). TR is a common complication after CIED implantation. Lead interference and pacemaker implantation time were risk factors for TR worsening. Compared with patients without TR deterioration after pacemaker implantation, patients with TR deterioration had a poorer prognosis.

Evaluation of safety and feasibility of leadless pacemaker implantation following the removal of an infected pacemaker.

BACKGROUND: Leadless pacemakers provide safe and effective pacing options for patients with device-related infections. This study was aimed at observing and evaluating the safety and feasibility of extracting an infected pacemaker device followed by the implantation of a leadless pacemaker in the same location for patients without systemic infection. METHODS: Between December 2019 and September 2020, following a well-planned re-implantation strategy, pacemaker electrodes were removed from patients with device infection and leadless pacemakers were immediately implanted at our center. The patients were then followed up for up to 10 months to assess the safety and practicality of the procedure. RESULTS: Pacemaker electrode removal and immediate leadless pacemaker implantation were successfully achieved in eight patients with pocket infection. After a minimum follow-up period of 1 month and a maximum follow-up of 10 months, the pacing parameters for the patients remained stable and there was no infection at the original capsular bag or in the leadless pacemaker. CONCLUSION: Direct implantation of a leadless pacemaker is safe and feasible for patients with local infection of the pacing system after removal of the electrode as an alternative to a bridge period with a temporary pacemaker. This strategy may be a better option for pacing-dependent patients.

A prospective comparison of four methods for preventing pacemaker pocket infections.

This study aims to evaluate four pacemaker pocket cleaning methods for preventing implantation-related infections. This single-center trial prospectively randomized 910 patients undergoing first-time pacemaker implantation or replacement into four pocket cleaning methods: hemocoagulase (group A, n = 228), gentamicin (group B, n = 228), hemocoagulase plus gentamicin (group C, n = 227), and normal saline (group D, n = 227). Before implanting the pacemaker battery, the pockets were cleaned with gauze presoaked in the respective cleaning solutions. Then, these patients were followed up to monitor the occurrence of infections for 1 month after implantation. Twelve implantation-related infections occurred in 910 patients (1.32%): four patients from group A (1.75%), three patients from group B (1.32%), two patients from group C (0.88%), and three patients from group D (1.32%) (P > .05). Furthermore, two patients developed bloodstream infections (0.22%), and both of these patients were associated with pocket infection (one patient was from group A, while the other patient was from group C, respectively). No cases of infective endocarditis occurred. The differences in the number of infections in these study groups were not statistically significant. The application of hemocoagulase, gentamicin, hemocoagulase plus gentamicin, or normal saline on the presoaked gauze before implantation was equally effective in preventing pocket-associated infections.

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.

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.

Prognostic value of serum amyloid A in patients with COVID-19.

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.

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.

Tragus Nerve Stimulation Suppresses Post-Infarction Ventricular Arrhythmia by Modulating Autonomic Activity and Heterogeneities of Cardiac Receptor Distribution.

BACKGROUND Imbalanced cardiac autonomic control and cardiac receptors redistribution contribute to the arrhythmogenic substrate under the myocardial infarction (MI) condition. Stimulating the auricular branch of vagus nerve (AB-VNS) has been proven to reduce post-infarction ventricular arrhythmia (VAs), but its potential mechanisms were largely unknown. This study aimed to investigate whether long-term intermittent low-intensity AB-VNS could produce a protective effect on modulating autonomic activities and abnormal redistribution of autonomic nerve efferent receptors in a MI canine model. MATERIAL AND METHODS Twelve healthy beagle dogs underwent ligation of the left anterior descending coronary artery to establish a MI model and were randomized into 2 groups: an AB-VNS group, (AB-VNS for 4 weeks) and a control group (sham stimulation for 4 weeks). Dynamic electrocardiogram recording, neural recording, catecholamine concentration, and histological studies were conducted subsequently. RESULTS Compared to the control group, the AB-VNS group had significantly suppressed post-infarction VAs, reduced low frequency (LF) power and increased high frequency (HF) power. In the AB-VNS group, with the progression of reduced cardiac sympathetic activities and augmented cardiac parasympathetic activities, the catecholamine concentration in heart tissue declined in the peripheral infarction area and right ventricle (RV); tyrosine hydroxylase (TH)-positive neurons decreased in the inferior cardiac sympathetic nerve, and choline acetyltransferase (ChAT)-positive neurons increased in the cervical vagus nerve. Expression of TrkA and P75NGFR were reduced in the peripheral MI (peri-MI) and non-MI area with AB-VNS. The mRNA expression of adrenergic and nicotinic receptors (ß1-AR, ß3-AR, and CHRNA7) significantly declined in the peri-MI and non-MI area of the AB-VNS group. CONCLUSIONS Chronic intermittent low-intensity AB-VNS effectively suppressed post-infarction VAs by potentially rebalancing extracardiac intrathoracic autonomic activities, reducing excessive cardiac sympathetic denervation, and attenuating the heterogeneities of cardiac efferent nerve receptors distribution.

LDL-C/HDL-C is associated with ischaemic stroke in patients with non-valvular atrial fibrillation: a case-control study.

BACKGROUND: This study explored the relationships between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and other clinical indicators and ischaemic stroke (IS) in patients with non-valvular atrial fibrillation (NVAF) in Xinjiang. The findings could provide a theoretical and therapeutic basis for NVAF patients. METHODS: NVAF patients who were admitted to 10 medical centres across Xinjiang were divided into stroke (798 patients) and control (2671 patients) groups according to the occurrence of first acute IS. Univariate and multivariate logistic regression analysis were used to examine the independent risk factors for IS in NVAF patients. Factor analysis and principal component regression analysis were used to analyse the main factors influencing IS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory ability of LDL-C/HDL-C for predicting the occurrence of IS. RESULTS: The stroke group had an average age of 71.64 ± 9.96 years and included 305 females (38.22%). The control group had a mean age of 67.30 ± 12.01 years and included 825 females (30.89%). Multivariate logistic regression showed that the risk of IS in the highest LDL-C/HDL-C quartile (≥2.73) was 16.23-fold that of the lowest quartile (< 1.22); IS risk was 2.27-fold higher in obese patients than in normal-weight subjects; IS risk was 3.15-fold higher in smoking patients than in non-smoking patients. The area under the ROC curve of LDL-C/HDL-C was 0.76, the optimal critical value was 2.33, the sensitivity was 63.53%, and the specificity was 76.34%. Principal component regression analysis showed that LDL-C/HDL-C, age, smoking, drinking, LDL-C and hypertension were risk factors for IS in NVAF patients. CONCLUSIONS: LDL-C/HDL-C > 1.22, smoking, BMI ≥24 kg/m2 and CHA2DS2-VASc score were independent risk factors for IS in NVAF patients; LDL-C/HDL-C was the main risk factor.