Berberine ameliorates chronic intermittent hypoxia-induced cardiac remodelling by preserving mitochondrial function, role of SIRT6 signalling.

Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.

Circulating neuropeptide Y as a biomarker in postoperative atrial fibrillation cases administered off-pump coronary bypass Graft surgery.

Background and aims: Postoperative atrial fibrillation (POAF) is considered the most prevalent irregular heart rhythm after heart surgery. The cardiac autonomic nervous system significantly affects POAF, and neuropeptide Y (NPY), an abundant neuropeptide in the cardiovascular system, is involved in this autonomic regulation. The current work aimed to examine the potential association of NPY with POAF in individuals administered isolated off-pump coronary artery bypass grafting. Methods: From January 1 to May 31, 2020, we examined consecutive cases administered successful isolated off-pump coronary artery bypass grafting with no previously diagnosed atrial fibrillation (AF). Clinical characteristics and plasma samples were collected before surgery. NPY was quantified by enzyme-linked immunosorbent assay (ELISA) in peripheral blood, and POAF cases were identified through a 7-day Holter monitoring. Results: Among 120 cases with no previously diagnosed AF, 33 (27.5 %) developed POAF during hospitalization. Median NPY levels were markedly elevated in the POAF group in comparison with the sinus rhythm group (31.72 vs. 27.95, P = 0.014). Multivariable logistic regression analysis revealed age (OR = 1.135, 95%CI 1.054-1.223; P = 0.001), left atrial size (OR = 1.136, 95%CI 1.004-1.285; P = 0.043), and NPY levels in peripheral blood (OR = 1.055, 95%CI 1.002-1.111; p = 0.041) independently predicted POAF. Additionally, NPY levels were positively correlated with high-frequency (HF) (r = 0.2774, P = 0.0022) and low-frequency (LF) (r = 0.2095, P = 0.0217) components of heart rate variability. Conclusion: In summary, this study demonstrates an association between elevated NPY levels in peripheral blood before surgery and POAF occurrence.

Robust Artificial Intelligence Tool for Atrial Fibrillation Diagnosis: Novel Development Approach Incorporating Both Atrial Electrograms and Surface ECG and Evaluation by Head-to-Head Comparison With Hospital-Based Physician ECG Readers.

BACKGROUND: Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. METHODS AND RESULTS: We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. CONCLUSIONS: Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.

Long-Term Results and Risk Factors of Treatment for Post-Infarction Ventricular Septal Rupture: A Single-Center Experience.

BACKGROUND: Ventricular septal rupture (VSR) following myocardial infarction (MI) is a rare but lethal complication. We analyzed the long-term results and risk factors for survival in the treatment of VSR. METHODS: From January 2012 to December 2021, 115 consecutive patients with post-MI VSR were admitted to our hospital. Depending on different treatment methods patients were divided into following three groups: medical, transcatheter intervention, and surgical repair. During the study, relevant clinical data, operation-related conditions, and follow-up data were analyzed. The Kaplan-Meier method and log-rank test were used to determine the cumulative incidence of mortality. The independent risk factors for patient mortality were evaluated by multivariate logistic regression. RESULTS: The mean follow-up time was 43.4 ± 34.7 months. The overall in-hospital, 30-day, and long-term mortality rates were 24.3%, 38.3%, and 51.3%, respectively. In the medical group, the in-hospital and 30-day mortality rates were 46.7 % (21/45) and 82.2 % (37/45), respectively, with only three patients alive at follow-up. In the transcatheter intervention group, 30-day and long-term mortality rates were 12% and 28%, respectively. In the surgical repair group, 30-day and long-term mortality rates were 8.9% and 22.2%, respectively. Compared with the surgery-group patients, patients with transcatheter intervention had a longer time from VSR to intervention. Logistic regression analysis revealed that age, previous infarction, Killip class, serum creatinine, Troponin T, N-terminal pro-B-type natriuretic peptide, and medical strategy were risk factors for all-cause mortality. CONCLUSIONS: The 30-day and long-term outcomes of patients treated with surgical repair and transcatheter intervention were significantly better than medically treated patients.

Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma.

Sonic hedgehog (Shh)-group medulloblastoma (MB) (Shh-MB) encompasses a clinically and molecularly distinct group of cancers originating from the developing nervous system with aberrant high Shh signaling as a causative driver. We recently reported that RNF220 is required for sustained high Shh signaling during Shh-MB progression; however, how high RNF220 expression is achieved in Shh-MB is still unclear. In this study, we found that the ubiquitin E3 ligases Smurf1 and Smurf2 interact with RNF220, and target it for polyubiquitination and degradation. In MB cells, knockdown or overexpression of Smurf1 or Smurf2 promotes or inhibits cell proliferation, colony formation and xenograft growth, respectively, by controlling RNF220 protein levels, and thus modulating Shh signaling. Furthermore, in clinical human MB samples, the protein levels of Smurf1 or Smurf2 were negatively correlated with those of RNF220 or GAB1, a Shh-MB marker. Overall, this study highlights the importance of the Smurf1- and Smurf2-RNF220 axes during the pathogenesis of Shh-MB and provides new therapeutic targets for Shh-MB treatment.

Cost-effectiveness of stereotactic body radiotherapy versus conventional fractionated radiotherapy for medically inoperable, early-stage non-small cell lung cancer.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a novel radio-therapeutic technique that has recently emerged as standard-of-care treatment for medically inoperable, early-stage non-small cell lung cancer (NSCLC). In this study, we compared the cost-effectiveness of SBRT with that of conventional fractionated radiotherapy (CFRT) in patients with medically inoperable, early-stage NSCLC from the perspective of the Chinese health system. METHODS: A Markov model was developed to describe health states of patients after treatment with SBRT and CFRT. The recurrence risks, treatment toxicities, and utilities inputs were obtained from the literature. The costs were based on listed prices and real-world evidence. A simulation was conducted to determine the post-treatment lifetime years. For each treatment, the total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) per QALY were calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of the model parameters. RESULTS: In the base case analysis, SBRT was associated with a mean cost of USD16,933 and 2.05 QALYs, whereas CFRT was associated with a mean cost of USD17,726 and 1.61 QALYs. SBRT is a more cost-effective strategy compared with CFRT for medically inoperable, early-stage NSCLC, with USD 1802 is saved for every incremental QALY. This result was validated by DSA and PSA, in which SBRT remained the most cost-effective option. CONCLUSIONS: The findings suggested that, compared to CFRT, SBRT may be considered a more cost-effective strategy for medically inoperable, early-stage NSCLC.

Noncontrast cardiac computed tomography-derived mitral annular calcification scores in mitral valve disease.

BACKGROUND AND AIMS: Mitral annular calcification (MAC) by computed tomography (CT) is reported as an independent predictor of poor outcomes. However, it currently remains unclear if quantitative MAC parameters provide more value for mitral valve disease (MVD) management, therefore, we examined the prognostic value of MAC scores using noncontrast cardiac-CT in MVD patients. METHODS: Between January 2020 and December 2021, we prospectively enrolled 300 consecutive patients with MVD (MAC-present = 80 and MAC-absent = 220) undergoing preoperative cardiac-CT and mitral valve (MV) surgery. Noncontrast cardiac-CT images were used to qualitatively detect MAC (present or absent) and evaluate MAC scores. For analyses, we also collected baseline clinical data, intraoperative conversion (from MV repair to MV replacement), and follow-up arrhythmia data. RESULTS: Compared with the MAC-absent group, MAC-present patients were older (62 ± 7 vs. 58 ± 9 years, p < .001), mostly women (55% vs. 39.5%, p = .017), and also had aortic valve calcification (57.5% vs. 23.2%, p < .001), mitral stenosis (82.5% vs. 61.8%, p < .001), atrial fibrillation (30% vs. 11.8%, p < .001), and larger left atrial end-diastolic dimension (LADD, 49 [44-56] versus 46 [41-50], p = .001]. Furthermore, MAC-present patients underwent more MV replacements (61.8% vs. 82.5%, p = .001) and experienced a higher intraoperative conversion prevalence (11.8% vs. 61.3%, p < .001). Multiple logistic regression analyses showed that the female gender (odds ratio [OR]/95% confidence interval [CI]/p = 2.001/1.042-3.841/0.037) and MAC scores (OR/95% CI/p = 10.153/4.434-23.253/p < .001) were independent predictors of intraoperative conversion. During a follow-up of 263 ± 134 days, MAC-present patients had more arrhythmias (42.5% vs. 9.5%, p < .001). Also, MAC-scores (hazard ratio [HR]/95% CI/p = 6.841/3.322-14.089/p < .001) and LADD (HR/95% CI/p = 1.039/1.018-1.060/p < .001) were independently associated with arrhythmias by Cox regression analyses. CONCLUSIONS: Noncontrast cardiac CT-derived MAC-scores showed a high risk for intraoperative conversion and follow-up arrhythmias in MVD-patients.

Gut Microbiota in Patients with Postoperative Atrial Fibrillation Undergoing Off-Pump Coronary Bypass Graft Surgery.

BACKGROUND: Post-operative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery. However, the underlying mechanism is not well understood. Alterations in the gut microbiota are associated with the development of atrial fibrillation (AF). The aim of this study was to explore the relationship between gut microbiota and POAF. METHODS: Fecal samples were collected before surgery from 45 patients who underwent coronary artery bypass grafting with POAF and 90 matched patients without POAF (1:2). 16S rRNA sequencing was used to detect the microbiome profiles of 45 POAF patients and 89 matched patients (one sample in the no-POAF group was deleted owing to low quality after sequencing). Plasma 25-hydroxy vitamin D level was measured by ELISA. RESULTS: Compared to the patients without POAF, gut microbiota composition was remarkably changed in the patients with POAF, with an increase in Lachnospira, Acinetobacter, Veillonella and Aeromonas, and a decrease in Escherichia-Shigella, Klebsiella, Streptococcus, Brevundimonas and Citrobacter. Furthermore, plasma 25-hydroxy vitamin D levels were decreased in POAF patients and negatively correlated with an abundance of Lachnospira. CONCLUSIONS: The gut microbiota composition between patients with and without POAF is significantly different, implying that gut microbiota may play a role in the pathogenesis of POAF. Further studies are needed to fully clarify the role of gut microbiota in the initiation of AF.

Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1.

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.

Impact of proinflammatory epicardial adipose tissue and differentially enhanced autonomic remodeling on human atrial fibrillation.

OBJECTIVES: The mechanisms underlying atrial fibrillation are yet to be elucidated. We sought to investigate the interactions among autonomic remodeling, epicardial adipose tissue, inflammation, and atrial fibrillation. METHODS: Myocardium and adjacent epicardial adipose tissue of the left atrial appendage, right atrial appendage, and pulmonary vein muscle sleeves were obtained from 61 consecutive patients (35 with atrial fibrillation, 26 with no atrial fibrillation) during mitral valve surgeries. Patients were divided into the atrial fibrillation group and no atrial fibrillation group according to the history and Holter monitoring before surgery. Sympathetic and parasympathetic innervation were evaluated by tyrosine hydroxylase and choline acetyltransferase staining, respectively. Atrial fibrosis as well as cytokines/adipokines and related inflammatory proteins and signaling pathways in the epicardial adipose tissue were examined. RESULTS: Immunohistochemical studies revealed significantly increased tyrosine hydroxylase (+) and choline acetyltransferase (+) neural elements in the left atrial appendage and pulmonary vein muscle sleeve myocardium, as well as adjacent epicardial adipose tissue in the atrial fibrillation group, particularly the pulmonary vein muscle sleeve sites. The receiver operating curve identified a threshold ratio (tyrosine hydroxylase/choline acetyltransferase) of 0.8986 in the epicardial adipose tissue (sensitivity = 82.86%; specificity = 80.77%; area under the curve = 0.85, 95% confidence interval = 0.76-0.95, P < .0001). More patients with a higher tyrosine hydroxylase/choline acetyltransferase ratio (≥0.8986) had atrial fibrillation. Expression levels of the genes and related proteins of the ß1 adrenergic, mitogen-activated protein kinase, and nuclear factor kappa B signaling pathways were higher in patients with a higher tyrosine hydroxylase/choline acetyltransferase ratio. The tyrosine hydroxylase/choline acetyltransferase ratio also correlated with fibrosis. CONCLUSIONS: Differentially enhanced autonomic remodeling and proinflammatory and profibrotic cytokines/adipokines in the epicardial adipose tissue adjacent to the pulmonary vein muscle sleeve site may work synergistically to promote atrial fibrillation.

Surgical treatment for Behcet's disease with acute superior vena cava syndrome.

BACKGROUND AND AIM OF THE STUDY: Behcet's disease (BD) is a multisystem vasculitis with unknown etiology. The involvement of superior vena cava (SVC) is reported in less than 2% of patients with BD. METHODS: We report a patient with acute edema of neck and face associated with dyspnea as the primary manifestation. So a diagnosis of superior Vena Cava syndrome (SVCS) was made and the thickening wall of SVC was resected. An Operation was performed under cardiopulmonary bypass to remove the mass and thrombus for avoiding for pulmonary embolism. RESULTS: The diagnosis of Behcet's disease (BD) didn't not be made until the recurrent oral and genital ulceration occurred 2 weeks later. The patient taked aspirin and prednisolone orally as prescribed and no recurrence were observed during the 30 months follow-up. CONCLUSIONS: BD should be suspected in patients presenting with SVCS, when there is thickening of SVC, whether thrombosis or not. Early diagnosis and treatment are essential for management of BD.

Preventive Effect of Berberine on Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery, but the underlying factors governing POAF are not well understood. The aim of this study was to investigate the efficacy of berberine administration on POAF. METHODS: We conducted a randomized, double-blind, placebo-controlled trial with patients who underwent isolated coronary artery bypass grafting in China to study the impact of oral berberine on the incidence of POAF. A total of 200 patients who underwent coronary artery bypass grafting were randomized into the berberine group (n=100) and the placebo group (n=100). All patients underwent 7-day continuous telemetry and Holter monitoring. RESULTS: The primary outcome was the incidence of POAF at 7 days. Secondary outcomes included clinical outcomes, POAF burden, intestinal endotoxin, and serum inflammatory biomarker levels. The POAF incidence was reduced from 35% to 20% under berberine treatment (hazard ratio, 0.5 [95% CI, 0.29-0.78]; P=0.0143). Perioperative mortality and morbidity did not differ between the 2 groups. POAF burden and the dose of amiodarone were significantly reduced in the berberine group. Oral berberine significantly decreased lipopolysaccharide, CRP (C-reactive protein), and IL (interleukin)-6 levels. Elevated lipopolysaccharide after surgery has been associated with POAF. CONCLUSIONS: Our results showed that administration of berberine may be effective for reducing the occurrence of POAF after coronary artery bypass grafting. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000028839.

Efficacy of pump-controlled selective antegrade cerebral perfusion in total arch replacement: A propensity-matched analysis.

Background: Pump-controlled selective antegrade cerebral perfusion (PC-SACP) in total arch replacement (TAR) can regulate cerebral flow accurately, which might be beneficial for cerebral protection. However, the safety of PC-SACP for TAR combined with frozen elephant trunk implantation (FET) in patients with acute Type A dissections (ATAAD) is ambiguous. Methods: A total of 192 patients with ATAAD underwent TAR at our institution from October 2019 to July 2021. The patients were divided into two groups based on PC-SACP used: PC group (SACP carried out by using a separate pump, n = 35) and Control group (SACP carried out as a traditional method, n = 157). Patients under PC-SACP were propensity-score matched to patients without PC-SACP, resulting in 35 pairs of patients. Results: Preoperative characteristics, including age, gender, weight, and preoperative creatinine level, were similar between the two groups. Cardiopulmonary bypass time, cross-clamp time, circulatory arrest time, and minimum nasopharyngeal temperature did not differ between the two groups. However, SACP time (54 versus 40, P = 0.001) in the PC group was significantly longer than that in the Control group. The incidence of temporary neurologic dysfunction (5.7% versus 8.6, P = 0.643) showed a no significantly lower trend in the PC group compared with the Control group. Other clinical outcomes showed no significant intergroup differences. Conclusions: PC-SACP in TAR is safe and feasible and might be beneficial for avoiding brain injury caused by "luxury" perfusion.

Moderate Hypothermic Circulatory Arrest Model in Rats: A New Model with Hyperkalemia-Induced Cardioplegia.

BACKGROUND: Moderate hypothermic circulatory arrest (MHCA) is a safe and effective method of cardiopulmonary bypass (CPB). However, most present rat models involve a deep hypothermic circulatory arrest, which cannot exactly reflect the clinical situation. The aim of this study was to establish a novel and safe rat model of MHCA with hyperkalemia-induced cardioplegia to study the pathophysiology of potential complications. METHODS: Ten adult male Sprague-Dawley rats (age, 16-18 weeks; weight, 450-550 g) were used. The entire CPB circuit consisted of a reservoir, peristaltic pump, membrane oxygenator, heat exchanger, and hemoconcentrator, all of which were connected via silicon tubing. The prime solution was approximately 19 mL. The right jugular vein, right femoral artery, and left femoral artery were cannulated. Blood was drained from the right atrium through the right jugular vein and perfused to the rats via the left femoral artery. CPB was commenced at a full flow rate. The rats were cooled to a rectal temperature of 25°C, and cardioplegia was induced by systemic hyperkalemia. After that, MHCA was carried out for 30 min. At the same time, system self-ultrafiltration was carried out to decrease the concentration of potassium by a hemoconcentrator. The circulatory arrest was followed by reperfusion and over 30 min of rewarming. CPB carefully was terminated. Blood in the circuit slowly was centrifuged for autotransfusion. Blood gas and hemodynamic parameters were recorded at each time point before CPB, before MHCA, at 10 min after the initiation of rewarming, and after CPB. RESULTS: All CPB and MHCA procedures successfully were achieved. One rat died of respiratory failure. Cardioplegia with systemic hyperkalemia was induced by 1 mL of 10% potassium chloride injected into the reservoir, and the concentration of potassium was maintained at 17 ± 3 mmol/L. Cardiac function and blood pressure were stable after the operation. CONCLUSIONS: A novel and safe rat model of MHCA with hyperkalemia-induced cardioplegia successfully was established.

Macrophage Rmp Ameliorates Myocardial Infarction by Modulating Macrophage Polarization in Mice.

Background: Inflammation plays important roles during myocardial infarction (MI). Macrophage polarization is a major factor that drives the inflammatory process. Our previous study found that RNA polymerase II subunit 5-mediating protein (RMP) knockout in cardiomyocytes caused heart failure by impairing mitochondrial structure and function. However, whether macrophage RMP plays a role in MI has not been investigated. Methods: Macrophage RMP-knockout in combination with a mouse model of MI was used to study the function of macrophage RMP in MI. Next, we modified bone marrow-derived macrophages (BMDMs) by plasmid transfection, and the BMDMs were administered to LysM-Cre/DTR mice by tail vein injection. Immunoblotting and immunofluorescence were used to detect macrophage polarization, fibrosis, angiogenesis, and the p38 signaling pathway in each group. Results: Macrophage RMP deficiency aggravates cardiac dysfunction, promotes M1 polarization, and inhibits angiogenesis after MI. However, RMP overexpression in macrophages promotes M2 polarization and angiogenesis after MI. Mechanistically, we found that RMP regulates macrophage polarization through the heat shock protein 90- (HSP90-) p38 signaling pathway. Conclusions: Macrophage RMP plays a significant role in MI, likely by regulating macrophage polarization via the HSP90-p38 signaling pathway.

Survival and risk factors associated with surgical repair of ventricular septal rupture after acute myocardial infarction: A single-center experience.

Objective: To analyze the survival and risk factors associated with the surgical treatment of ventricular septal rupture (VSR) after acute myocardial infarction (AMI). Methods: We retrospectively analyzed 45 consecutive patients with VSR after AMI whose procedures were performed in the Department of Cardiovascular Surgery at the General Hospital of Northern Theater Command between January 2012 and December 2021. Relevant clinical data, surgery-related conditions, and follow-up data of all patients were summarized. Patients were divided into the survival group and the death group. The Kaplan-Meier method and log-rank test were used to determine the cumulative incidence of all-cause mortality. Multivariate logistic regression was used to evaluate the independent risk factors for all-cause mortality. Results: The average postoperative follow-up time was 42.1 ± 34.1 months. The overall mortality rate was 20% (9/45 patients) and the operative mortality rate was 8.9% (4/45 patients). Logistic analysis showed that the death group had higher serum creatinine (127.32 ± 47.82 vs. 82.61 ± 27.80 µmol/L, respectively; P = 0.0238) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) [8,654.00 pg/mL (6,197.00-11,949.00 pg/mL) vs. 4,268.96 pg/mL (1,800.00-7,894.00 pg/mL), respectively; P = 0.0134] levels than the survival group. The cardiopulmonary bypass time (CPB) was longer in the death group than in the survival group [131.00 min (121.00-184.00 min) vs. 119.00 min (103.00-151.50 min), respectively; P = 0.0454]. Significantly more red blood cells were transfused in the death group than in the survival group [11.60 units (6.10-16.50) vs. 3.75 units (0.00-7.00 units), respectively; P = 0.0025]. Intra-aortic balloon pump (IABP) implantation (P = 0.016) and ventilation time (P = 0.0022) were risk factors for mortality. A 1-month landmark analysis showed that compared with patients with VSR to surgical time >14 days, patients who underwent surgery within 14 days had a higher rate of all-cause mortality (25.00 vs. 3.33%; log-rank P = 0.023). Patients with VSR within 14 days also had a higher rate of residual shunts that were higher than moderate. Multivariate analysis showed that transfusion of red blood cells and NT-proBNP level were risk factors for all-cause mortality, as well as major adverse cardiovascular and cerebrovascular events. Conclusions: Surgical repair resulted in good outcomes for patients with VSR after AMI. Patients with VSR to surgical time >14 days had a lower rate of all-cause mortality. Treatment strategies for VSR should be based on the patient's condition and comprehensively determined through real-time evaluation and monitoring.

A Modified Maze Versus Cut-and-Sew Maze for Long-Standing Persistent Atrial Fibrillation Concomitant with Mitral Valve Surgery: A Propensity Score-Matched Cohort Study.

BACKGROUND: The cut-and-sew maze (CSM) procedure has an excellent efficacy for the elimination of long-standing persistent atrial fibrillation (AF) concomitant with mitral valve surgery. Because of the complexity and prolongation of cardiopulmonary bypass, CSM has not been widely used. The aim of this study was to examine a modified maze procedure that preserves the "cut-and-sew" procedure in the left atrium and uses cryoablation in the right atrium along with cavotricuspid isthmus. METHODS: From December 2013 to December 2018, 229 patients underwent CSM, and 43 underwent the modified maze procedure during mitral valve surgery. Propensity score matching analysis was used to perform selective 1:2 ratio matching of the 43 patients undergoing the modified maze procedure with 86 patients undergoing CSM. Early operative outcomes were analysed for differences. The absence of AF recurrence without the use of anti-arrhythmic drugs was calculated at 2 years by a generalised linear model analysis. RESULTS: One (1.1%) early death occurred in the CSM group, and no deaths occurred in the modified maze group (p=0.722). The aortic cross-clamp durations were 76.30±8.86 minutes for the modified maze and 92.38±10.88 for the CSM procedure (p<0.001). There were no late strokes or deaths during the 2-year follow-up. The modified maze group showed similar rates of absence of AF without the use of anti-arrhythmic drugs as the CSM group within the 2 years (p=0.332). CONCLUSION: This modified maze simplifies the "cut-and-sew" procedure and reduces operating time while retaining the efficacy of CSM.

Icariin attenuates excessive alcohol consumption-induced susceptibility to atrial fibrillation through SIRT3 signaling.

Excessive alcohol consumption has long been identified as a risk factor for adverse atrial remodeling and atrial fibrillation (AF). Icariin is a principal active component from traditional Chinese medicine Herba Epimedii and has been demonstrated to exert potential antiarrhythmic effect. The present study was designed to evaluate the effect of icariin against alcohol-induced atrial remodeling and disruption of mitochondrial dynamics and furthermore, to elucidate the underlying mechanisms. Excessive alcohol-treated C57BL/6 J mice were infected with serotype 9 adeno-associated virus (AAV9) carrying mouse SIRT3 gene or negative control virus. Meanwhile, icariin (50 mg/kg/d) was administered to the animals in the presence or absence of AAV9 carrying SIRT3 shRNA. We noted that 8 weeks of icariin treatment effectively attenuated alcohol consumption-induced atrial structural and electrical remodeling as evidenced by reduced AF inducibility and reversed atrial electrical conduction pattern as well as atrial enlargement. Furthermore, icariin-treated group exhibited significantly enhanced atrial SIRT3-AMPK signaling, decreased atrial mitoSOX fluorescence and mitochondrial fission markers, elevated mitochondrial fusion markers (MFN1, MFN2) as well as NRF-1-Tfam-mediated mitochondrial biogenesis. Importantly, these beneficial effects were mimicked by SIRT3 overexpression while abolished by SIRT3 knockdown. These data revealed that targeting atrial SIRT3-AMPK signaling and preserving mitochondrial dynamics might serve as the novel therapeutic strategy against alcohol-induced AF genesis. Additionally, icariin ameliorated atrial remodeling and mitochondrial dysfunction by activating SIRT3-AMPK signaling, highlighting the use of icariin as a promising antiarrhythmic agent in this circumstance.

Polydatin attenuates chronic alcohol consumption-induced cardiomyopathy through a SIRT6-dependent mechanism.

Polydatin has attracted much attention as a potential cardioprotective agent against ischemic heart disease and diabetic cardiomyopathy. However, the effect and mechanism of polydatin supplementation on alcoholic cardiomyopathy (ACM) are still unknown. This study aimed to determine the therapeutic effect of polydatin against ACM and to explore the molecular mechanisms with a focus on SIRT6-AMP-activated protein kinase (AMPK) signaling and mitochondrial function. The ACM model was established by feeding C57/BL6 mice with an ethanol Lieber-DeCarli diet for 12 weeks. The mice received polydatin (20 mg kg-1) or vehicle treatment. We showed that polydatin treatment not only improved cardiac function but also reduced myocardial fibrosis and dynamin-related protein 1 (Drp-1)-mediated mitochondrial fission, and enhanced PTEN-induced putative kinase 1 (PINK1)-Parkin-dependent mitophagy in alcohol-treated myocardium. Importantly, these beneficial effects were mimicked by SIRT6 overexpression but abolished by the infection of recombinant serotype 9 adeno-associated virus (AAV9) carrying SIRT6-specific small hairpin RNA. Mechanistically, alcohol consumption induced a gradual decrease in the myocardial SIRT6 level, while polydatin effectively activated SIRT6-AMPK signaling and modulated mitochondrial dynamics and mitophagy, thus reducing oxidative stress damage and preserving mitochondrial function. In summary, these data present new information regarding the therapeutic actions of polydatin, suggesting that the activation of SIRT6 signaling may represent a new approach for tackling ACM-related cardiac dysfunction.