Interleukin-5 alleviates cardiac remodelling via the STAT3 pathway in angiotensin II-infused mice.

Interleukin-5 (IL-5) has been reported to be involved in cardiovascular diseases, such as atherosclerosis and cardiac injury. This study aimed to investigate the effects of IL-5 on cardiac remodelling. Mice were infused with angiotensin II (Ang II), and the expression and source of cardiac IL-5 were analysed. The results showed that cardiac IL-5 expression was time- and dose-dependently decreased after Ang II infusion, and was mainly derived from cardiac macrophages. Additionally, IL-5-knockout (IL-5-/-) mice were used to observe the effects of IL-5 knockout on Ang II-induced cardiac remodelling. We found knockout of IL-5 significantly increased the expression of cardiac hypertrophy markers, elevated myocardial cell cross-sectional areas and worsened cardiac dysfunction in Ang II-infused mice. IL-5 deletion also promoted M2 macrophage differentiation and exacerbated cardiac fibrosis. Furthermore, the effects of IL-5 deletion on cardiac remodelling was detected after the STAT3 pathway was inhibited by S31-201. The effects of IL-5 on cardiac remodelling and M2 macrophage differentiation were reversed by S31-201. Finally, the effects of IL-5 on macrophage differentiation and macrophage-related cardiac hypertrophy and fibrosis were analysed in vitro. IL-5 knockout significantly increased the Ang II-induced mRNA expression of cardiac hypertrophy markers in myocardial cells that were co-cultured with macrophages, and this effect was reversed by S31-201. Similar trends in the mRNA levels of fibrosis markers were observed when cardiac fibroblasts and macrophages were co-cultured. In conclusions, IL-5 deficiency promote the differentiation of M2 macrophages by activating the STAT3 pathway, thereby exacerbating cardiac remodelling in Ang II-infused mice. IL-5 may be a potential target for the clinical prevention of cardiac remodelling.

Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Impact of left atrial appendage orifice diameter on the safety and efficacy of left atrial appendage closure using the LAmbre device.

BACKGROUND: The diameter and shape of the left atrial appendage (LAA) orifices may influence occluder selection and the outcomes of left atrial appendage closure (LAAC) procedure. This study aimed to evaluate the impact of LAA orifice diameter on the safety and efficacy of LAAC using the LAmbre device. METHODS: A total of 133 patients with nonvalvular atrial fibrillation (AF) who underwent LAAC with the LAmbre device between June 2018 and June 2020 were included in this study. The patients were categorized into two groups based on the maximal diameter of the LAA orifice: the large LAA group (n = 45) with a maximal orifice diameter of ≥31 mm, and the normal LAA group (n = 88) with a maximal orifice diameter of <31 mm. The study assessed periprocedural characteristics and long-term clinical follow-up. RESULTS: Successful implantation of the LAmbre device was observed in all patients. The incidence of periprocedural peridevice leakage (PDL) was significantly higher in the large LAA group (P < 0.001), while the incidence of acute pericardial effusion (PE) during the procedure was comparable between the two groups (P = 1.000). After a mean follow-up period of 4.8 ± 1.7 years, three patients in the large LAA group developed delayed PE, while no patients in the normal LAA group did (P = 0.037). Additionally, a larger LAA maximal orifice diameter was associated with a higher prevalence of PDL (P = 0.001) and PE (including both acute and delayed PE) (P = 0.027). The optimal cutoff value of the LAA maximal orifice diameter for predicting PDL and PE after LAAC with the LAmbre device was determined to be 30 mm. CONCLUSION: The findings suggest that the LAmbre device is a safe and feasible option for occluding the LAA, regardless of its orifice diameter. However, it is important to note that a larger LAA orifice diameter may increase the risk of PDL and delayed PE.

Visfatin aggravates transverse aortic constriction-induced cardiac remodelling by enhancing macrophage-mediated oxidative stress in mice.

Previous studies have reported that visfatin can regulate macrophage polarisation, which has been demonstrated to participate in cardiac remodelling. The aims of this study were to investigate whether visfatin participates in transverse aortic constriction (TAC)-induced cardiac remodelling by regulating macrophage polarisation. First, TAC surgery and angiotensin II (Ang II) infusion were used to establish a mouse cardiac remodelling model, visfatin expression was measured, and the results showed that TAC surgery or Ang II infusion increased visfatin expression in the serum and heart in mice, and phenylephrine or hydrogen peroxide promoted the release of visfatin from macrophages in vitro. All these effects were dose-dependently reduced by superoxide dismutase. Second, visfatin was administered to TAC mice to observe the effects of visfatin on cardiac remodelling. We found that visfatin increased the cross-sectional area of cardiomyocytes, aggravated cardiac fibrosis, exacerbated cardiac dysfunction, further regulated macrophage polarisation and aggravated oxidative stress in TAC mice. Finally, macrophages were depleted in TAC mice to investigate whether macrophages mediate the regulatory effect of visfatin on cardiac remodelling, and the results showed that the aggravating effects of visfatin on oxidative stress and cardiac remodelling were abrogated. Our study suggests that visfatin enhances cardiac remodelling by promoting macrophage polarisation and enhancing oxidative stress. Visfatin may be a potential target for the prevention and treatment of clinical cardiac remodelling.

Delayed pericardial effusion or tamponade following left atrial appendage closure: A single-center experience.

BACKGROUND: Pericardial effusion or pericardial tamponade (PE/PT) is a relatively common complication of left atrial appendage closure (LAAC). However, delayed PE/PT is rare with limited data. The aim of the study was to analyze the incidence and clinical consequences of delayed PE/PT following LAAC. METHODS: Patients with nonvalvular AF who were successfully implanted with LAAC devices from October 2014 to April 2021 were consecutively screened. Subjects experiencing delayed PE/PT after LAAC were included. All treatment sessions of the subjects were recorded in detail. After discharge, the patients were followed up for clinical outcomes. RESULTS: A total of 748 patients with successful LAAC [nitinol cage device (475 Watchman 2.5), nitinol plug device (131 ACP and 142 LAmbre)] were screened. Six patients experienced delayed PE/PT (1 Watchman, 2 ACP, 3 LAmbre). The incidence of delayed PE/PT was higher in patients with a nitinol plug device (1.8% vs. 0.2%, P = 0.027). Bloody PE only occurred in patients with a nitinol plug device (5/273, 1.8%). All the patients accepted pericardiocentesis and discontinuing antithrombotic medication, and none of the patients died or needed cardiac surgery. All patients were followed up for 810 (598, 1174) days after discharge. None of them developed constrictive pericarditis or thromboembolic or major bleeding events. CONCLUSION: Delayed PE/PT is rare but can occur, and the incidence of delayed bloody PE/PT for the nitinol plug device was higher than that for the nitinol cage device. The strategy of emergency pericardiocentesis combined with discontinuing antithrombotic medication may be effective for delayed bloody PE/PT.

Interactions between climate warming, herbicides, and eutrophication in the aquatic food web.

Understanding the interactive effects of multiple environmental stressors on biological communities is crucial for effective environmental management and biodiversity conservation. Here, we present the results of an outdoor mesocosm experiment examining how an aquatic food web responds to the individual and combined effects of climate warming, heat waves, nutrient enrichment, and herbicide exposure. To assess ecosystem functioning, we examined energy flow, using stable isotope analysis integrated with the bioenergetics food web approach to quantify energy fluxes among trophic levels. Our results revealed that the combined effects of these stressors altered the pattern of energy fluxes within the food web. Under warming conditions, there was an increase in energy flux from producers and primary consumers to secondary consumers. However, we did not observe a significant increase in energy flux in primary consumers, potentially due to enhanced top-down control. Nutrient enrichment increased energy flux from producers to higher trophic levels while simultaneously decreasing detrital energy flux. Herbicide exposure did not significantly affect herbivory energy flux but did reduce detritivory energy flux, particularly from detritus to primary consumers. The interactive effects we observed were primarily antagonistic or additive, although we also detected reversed and synergistic effects. The responses to multiple stressors varied across different energy flow pathways, leading to an asymmetric response. Furthermore, our results also revealed significant differences in the effects of constant warming and heat waves, either alone or in combination with water pollution. The asymmetric response of energy flow pathways and the prevalence of antagonistic effects present significant challenges for ecosystem restoration. Together, our findings provide novel and clear evidence of the complex mechanisms by which the coexistence of stressors can differently affect the pathways of energy flux across trophic levels in aquatic ecosystems. Regulatory strategies for ecosystems should comprehensively consider responses at multi-trophic levels using a network perspective, especially in the face of combinations of global and local stressors.

Safety and efficacy of low-dose non-vitamin K antagonist oral anticoagulants versus warfarin after left atrial appendage closure with the Watchman device.

BACKGROUND/PURPOSE: Anticoagulant therapy is suggested within 45 days after Watchman device implantation for stroke prevention in patients with atrial fibrillation (AF). A previous study demonstrated that non-vitamin K antagonist oral anticoagulants (NOACs) were a feasible peri- and postprocedural alternative to warfarin. The present study aimed to compare the safety and efficacy of using different anticoagulants (low-dose NOACs vs. warfarin) within 45 days after Watchman device implantation in a Chinese population. METHODS: Patients with successful Watchman device implantation from October 2014 to June 2020 were included. All patients received anticoagulants within 45 days after the procedure, and those patients were divided into three groups according to the type of postprocedural anticoagulants. Transesophageal echocardiography follow-up was performed 45 days post procedure to assess residual flow and the occurrence of device-related thrombus (DRT). RESULTS: A total of 368 patients were enrolled in the study. The study population was divided into three groups: the warfarin group (n = 77), the dabigatran group (n = 165) and the rivaroxaban group (n = 126). Periprocedural major bleeding was higher in the warfarin group (2.6% vs. 0% vs. 0%, P = 0.043), while minor bleeding was comparable among the groups (3.9% vs. 1.2% vs. 0.8%, P = 0.230). No periprocedural transient ischemic attack/stroke occurred. At follow-up, the incidence of DRT was higher in the warfarin group than in the other groups (4.2% vs. 0.6% vs. 0.8%; P = 0.116), but the difference was not statistically significant. The rates of thromboembolic and bleeding events were similar in the three groups. CONCLUSION: The safety and efficacy of low-dose dabigatran and rivaroxaban were comparable to those of warfarin within 45 days after Watchman device implantation in a Chinese population.

LPS induces cardiomyocyte necroptosis through the Ripk3/Pgam5 signaling pathway.

Necroptosis is a new type of cell death. However, the role of necroptosis in LPS-related cardiomyocyte damage has not been fully understood. The aim of our study is to explore the molecular mechanism underlying inflammation-mediated cardiomyocyte necroptosis. H9C2 cardiomyocyte cell line was treated with LPS. Then, cell viability and necroptosis were measured through qPCR and ELISA. Pathway analysis was performed to verify whether Ripk3/Pgam5 signaling pathway is implicated into the regulation of cardiomyocyte necroptosis. The results demonstrated that LPS reduced cardiomyocyte viability and activated necroptosis. At the molecular levels, oxidative stress and inflammation were triggered by LPS and these alterations may contribute to the activation of necroptosis. Finally, we found that Ripk3/Pgam5 signaling pathway was activated by LPS in cardiomyocyte and this signaling pathway may explain the regulatory mechanism underlying LPS-mediated necroptosis. Altogether, our results demonstrated that septic cardiomyopathy is associated with an activation of necroptosis through the Ripk3/Pgam5 signaling pathway.

Percutaneous Left Atrial Appendage Closure Confirmed by Intra-Procedural Transesophageal Echocardiography under Local Anesthesia: Safety and Clinical Efficacy.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) is usually performed under general anesthesia (GA) guided by transesophageal echocardiography (TEE), or under local anesthesia (LA) guided by intracardiac echocardiography (ICE). GA is known to carry some disadvantages. It is sometimes technically challenging to obtain adequate imaging of the left atrial appendage (LAA) with LAAC guided by ICE. This study aimed to assess the safety and clinical efficacy of LAAC guided by TEE under LA in patients with non-valvular atrial fibrillation (AF). METHODS: A total of 159 patients (70.5 ± 8.2 years; 66% male) with AF who had a high risk of stroke and bleeding or who had contraindications for oral anticoagulation underwent LAAC under LA. TEE or computed tomography (CT) follow-up was scheduled approximately 6 weeks after the procedure. Patients were followed to assess ischemic stroke and major bleeding events. RESULTS: The LAA was successfully occluded in 152 patients (95.6%). There were 2 (1.3%) periprocedural major adverse events. A total of 142 patients (93.4%) finished TEE or CT follow-up. Thrombus formation as seen on the device was documented in 2 patients. All of the LAAs were completely sealed with the absence of flow or with minimal flow. The median follow-up period was 522 days, resulting in a total of 216 patient-years. Ischemic stroke occurred in 4 patients. The annual ischemic stroke rate was 1.9/100 person-years. Major bleeding occurred in 2 patients. The annual major bleeding rate was 1.9/100 person-years. CONCLUSIONS: In this study, percutaneous LAAC using TEE under LA was safe and showed encouraging results for stroke prevention and major bleeding reduction.

Left atrial appendage closure with zero fluoroscopic exposure via intracardiac echocardiographic guidance.

BACKGROUND/PURPOSE: Left atrial appendage closure (LAAC) is conventionally guided by fluoroscopy and transesophageal echocardiography. We introduce an LAAC technique without fluoroscopy exposure using intracardiac echocardiography (ICE) and electroanatomic mapping system (EAMS) under local anesthesia. METHODS: Seven non-valvular atrial fibrillation patients who underwent LAAC with the LAmbre devices under the ICE and EAMS guidance were compared to 7 patients following the conventional approach by propensity score matching. ICE probe was advanced into the left atrium (LA) to guide sizing and device implantation following the orthogonal tri-axial technique (Axis-X: from left pulmonary veins [PVs] to LAA; Axis-Y: from right PV ostium to LAA; Axis-Z: from lower LA to LAA). RESULTS: The mean diameters of ostia and landing zone were 21.4 ± 3.9 mm and 20.4 ± 4.2 mm, respectively. LAmbre devices with a mean umbrella diameter of 23.7 ± 4.2 mm and cover disc diameter of 29.4 ± 3.6 mm were successfully implanted and acute complete LAA sealing without peri-device leak (PDL) were achieved in all cases. Neither fluoroscopy exposure nor contrast consumption was recorded. No procedure related complications were documented. The mean procedural time and PDLs at follow-ups were comparable to those in the conventional group. No stroke or thromboembolic events were documented. CONCLUSION: The fluoroscopy exposure could be minimized, even to zero, in the ICEguided LAAC procedures feasibly and safely using LAmbre devices. The orthogonal triaxial technique is considered efficacious and safe for the procedures.

Combination of left atrial appendage closure and catheter ablation in a single procedure for patients with atrial fibrillation: Multicenter experience.

BACKGROUND/PURPOSE: Experience in procedures combining left atrial appendage (LAA) closure (LAAC) and catheter ablation (CA) was scarce in Chinese nonvalvular atrial fibrillation (AF) patients with high risks for stroke and bleeding. We aimed to investigate the efficacy and safety of the combination therapy with LAAC and AF CA in a single procedure based on the multicenter data and medium-term follow-up results. METHODS: A total of 122 AF patients with a mean CHA2DS2-VASc score of 4.3 ± 1.4 and HAS-BLED score of 3.3 ± 1.0 were enrolled. The Watchman (n = 83) devices were implanted either before or after AF ablations in the same procedure, while the Amplatzer Cardiac Plug (ACP, n = 39) devices were implanted immediately after CA. AF recurrence and transesophageal echocardiography results were evaluated. RESULTS: All devices were successfully implanted and acute complete LAA occlusions were achieved in 115 (94.3%) of patients. Neither acute nor chronic peri-device leaks greater than 5 mm were detected. Oral anticoagulation was held in all patients but two with asymptomatic device-related thrombi, which were resolved after prolonged anticoagulation. AF-free success rate without antiarrhythmic drugs was 76.2% after a mean follow-up of 11.5 ± 6.8 months. No serious complications were observed during the follow-up. CONCLUSION: The combination therapy with LAAC and AF ablation in a single procedure was efficacious and safe in the Chinese symptomatic AF population with high risk for stroke and bleeding.

Association of Left Atrial Appendage Voltage with Ischemic Stroke in Patients with Atrial Fibrillation.

BACKGROUND: Low atrial voltage is associated with an increased risk of stroke. The relationship between left atrial appendage voltage (LAAV) and ischemic stroke remains unknown. Low LAAV may predict the prevalence of ischemic stroke in patients with atrial fibrillation (AF). METHODS: A total of 1108 patients with AF referred for catheter ablation were consecutively included from January 2015 to May 2018. The patients were divided into stroke and control groups based on previous ischemic stroke by neuroimaging criteria. LAAV was measured with a circular mapping catheter in sinus rhythm after ablation. Variables were compared, and logistic regression was performed to assess the relationship between LAAV and stroke. RESULTS: A total of 120 patients (10.8%) had a history of ischemic stroke. The patients in the stroke group were older and had higher percentages of hypertension, diabetes mellitus and coronary/vascular disease. The CHA2DS2-VASc score was higher and left atrial diameter was larger in the patients with stroke. More left atrial appendage thrombi and spontaneous echo contrast were detected in the stroke group. LAAV was significantly lower in the stroke group compared with the controls (5.3 ± 1.8 mV vs. 6.5 ± 1.8 mV; p < 0.001). Multivariate logistic regression revealed that a lower LAAV was associated with increased stroke prevalence [odds ratio = 0.75; 95% confidence interval (CI) 0.65-0.87; p < 0.001]. LAAV had a predictive value, with an area under the curve of 0.83 (95% CI 0.79-0.87; p < 0.001). With an optimal cut-off value of 5.2 mV for LAAV, the sensitivity and specificity were 75% and 74%, respectively. CONCLUSIONS: Lower LAAV in AF patients was associated with increased ischemic stroke prevalence. Whether LAAV is related to incident stroke requires further studies.

Optimal combination strategy of left atrial appendage closure plus catheter ablation in a single procedure in patients with nonvalvular atrial fibrillation.

BACKGROUND: The efficacy and safety of combining left atrial appendage closure (LAAC) plus atrial fibrillation (AF) catheter ablation (CA) in a single procedure has been established, but the optimal combination strategy has not been thoroughly elucidated to date. OBJECTIVE: We aimed to investigate the impact of different combination strategies on clinical outcomes. METHODS: Eighty-two consecutive patients with symptomatic AF (mean CHA2 DS2 -VASc score 4.4 ± 1.4, mean HAS-BLED score 3.5 ± 1.0) were enrolled. LAAC with the Watchman device was performed either before (occlusion-first group, N  =  52) or after (ablation-first group, N  =  30) CA. Procedural and clinical data were retrospectively analyzed to evaluate the advantages of each strategy. RESULTS: Complete device occlusions were achieved in 92.3% and 90.0% of patients, respectively (P  =  0.719). Neither acute nor chronic peridevice leak greater than 5 mm was detected. Oral anticoagulants were held in all patients, except two (one in each group) with asymptomatic device-related thrombi. AF-free success rates were comparable between groups with a mean follow-up of 11.2 ± 7.3 months (75.0% vs. 70.0%, log-rank P  =  0.311). The new peridevice leak rate was significantly lower in the occlusion-first group (7.7% vs. 26.7%, P  =  0.019). Multivariate logistic regression demonstrated that the combination strategy was independently associated with the new peridevice leak (P  =  0.025, OR 13.3). CONCLUSIONS: Both occlusion-first and ablation-first strategies were efficacious and safe as combined procedures in patients with nonvalvular AF; however, the occlusion-first strategy was associated with lower new peridevice leak rates at follow-up.

Clinical outcomes of combined catheter ablation and left atrial appendage closure in elderly patients with nonvalvular atrial fibrillation.

BACKGROUND: Catheter ablation (CA) combined with left atrial appendage closure (LAAC) has emerged as a promising method to relieve symptoms while reducing the incidence of stroke in selected high-risk patients with atrial fibrillation (AF). HYPOTHESIS: We aimed to investigate the clinical outcomes of combined CA and LAAC in elderly patients. METHODS: A total of 316 patients with symptomatic drug-refractory AF who underwent combined CA and LAAC between January 2016 and December 2020 were retrospectively included. Baseline characteristics, periprocedural complications, and clinical events during follow-up were recorded and compared between patients aged ≥ 75 years (n = 66) and <75 years (n = 250). RESULTS: Pulmonary vein isolation and satisfactory LAAC were achieved in all patients. No patients experienced death or stroke/transient ischemic stroke periprocedurally. After a median follow-up of 12.2 (6.7-24.4) months and 11.9 (5.5-23.6) months, the rate of sinus rhythm maintenance was comparable between the two groups (≥75 years: 78.8% vs. <75 years: 80.8%; log-rank test, p = 0.674). The median follow-up periods for clinical outcomes were 27.9 (9.3-44.8) months and 25.2 (10.8-45.7) months, respectively. In patients aged ≥ 75 years, one suffered ischemic stroke, and one experienced major bleeding event. In patients aged < 75 years, four had ischemic stroke, and eight had major bleeding events. Two patients aged < 75 years died during follow-up, while none of the patients aged ≥ 75 years died. CONCLUSIONS: Combining CA and LAAC was feasible, safe and effective in elderly patients with AF.

Left atrial appendage closure in patients with left atrial appendage thrombus guided by intracardiac echocardiography.

BACKGROUND: Data regarding left atrial appendage closure (LAAC) in patients with left atrial appendage (LAA) thrombus are limited. Recently published cases have mostly been guided by transesophageal echocardiography. Intracardiac echocardiography (ICE) is now widely used during LAAC procedures. OBJECTIVE: This is the first study to report the feasibility of LAAC in patients with LAA thrombus guided by ICE. METHODS: Patients with persistent LAA thrombus despite anticoagulation or contraindications to anticoagulation who underwent a modified ICE-guided LAAC procedure between June 2021 and April 2023 were included. Periprocedural events and clinical outcomes during follow-up were recorded. RESULTS: A total of 12 patients (mean age 65 ± 7 years; 92% male) were included: 10 with persistent LAA thrombus and 2 with contraindications to anticoagulation. Most of the thrombus was at the apex (n = 6), followed by the body (n = 3) and the ostium (n = 3). A LAmbre device was used and successfully implanted in all patients with the guidance of ICE. No thrombotic material was retrieved from patients with the protection of cerebral protection device (n = 11). No patient experienced severe periprocedural complications. All patients completed transesophageal echocardiography follow-up, and no device-related thrombus or peridevice leak > 3 mm was detected. None of the patients experienced stroke/transient ischemic attack, systemic embolism, or major bleeding events during a median follow-up of 147 days (interquartile range 80-306 days). CONCLUSION: LAAC using the LAmbre device guided by ICE may be feasible in patients with LAA thrombus when performed by experienced operators.

Crocin alleviates neurotoxicity induced by bupivacaine in SH-SY5Y cells with inhibition of PI3K/AKT signaling.

BACKGROUND: Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. OBJECTIVE: The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. METHOD: Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. RESULT: Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3ß. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. CONCLUSION: These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity.

Outcomes of Focal Pulsed Field Ablation for Paroxysmal Supraventricular Tachycardia.

BACKGROUND: Pulsed field ablation (PFA) is primarily used for treatment of atrial fibrillation as it provides better safety and efficacy. However, there are limited data available on the use of PFA for paroxysmal supraventricular tachycardia (PSVT). The study sought to describe the outcomes of PSVT ablation with a novel focal contact force (CF)-sensing PFA. METHODS: In this first-in-human pilot study, a focal CF-sensing PFA catheter was used for mapping and ablation navigated with an electroanatomic mapping system (EAMS). Pulsed field energy was delivered as biphasic/bipolar electrical pulse trains with 2000 V/delivery. CF was controlled from 2 g to 10 g during PFA. RESULTS: Procedural acute success was achieved without general anaesthesia or conscious sedation in all 10 patients, including 7 patients diagnosed with typical atrioventricular nodal re-entrant tachycardias and 3 patients with orthodromic reciprocating tachycardias. Successful target ablation time was 2.0 ± 0.5 seconds per patient, and the acute procedural success at the first single site was achieved in 5 patients. The mean skin-to-skin procedure time was 79.4 ± 15 minutes, PFA catheter dwell time was 50.1 ± 14 minutes, and fluoroscopy time was 6.2 ± 7 minutes. Maintenance of sinus rhythm was observed in all patients within 6-month follow-up. No serious adverse events occurred in any subjects during PFA or during the 6-month follow-up. CONCLUSIONS: A focal CF-sensing PFA catheter could effectively, rapidly, and safely ablate PSVT in conscious patients. CLINICAL TRIAL REGISTRATION: NCT05770921.

Polymorphisms but not mutations of the KCNQ1 gene are associated with lone atrial fibrillation in the Chinese Han population.

BACKGROUND: Recent studies suggest that mutation of the slow delayed rectifier potassium channel (IKs) contributes to familial atrial fibrillation (FAF). In the current study, we identified common genetic variants of KCNQ1 and explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 190 Han Chinese patients with sporadic AF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified six known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 190 LAF patients and 190 healthy controls. RESULTS: One of the SNPs in KCNQ1 was strongly associated with LAF; significant allelic association was detected rs59233444 (P = 0.013, OR = 1.469, 95% confidence interval (CI): 1.083-1.993). A multiple regression analysis indicated that rs59233444 is an independent risk factor for LAF. Twelve new variants were identified in KCNQ1, including one in the 5'-UTR, two in the 3'-UTR, six in introns, two synonymous substitutions, and one missense substitution. Variants c.1009C>T, c.1860C>T, and c.+2285C>T were not present in the 190 controls, and the others were identified in controls at various frequencies. CONCLUSIONS: rs59233444, a common SNP but not mutation in the coding regions of the KCNQ1 gene, is a risk factor for LAF in Chinese Han population.

[KCNQ1 mutation in patients with lone atrial fibrillation].

OBJECTIVE: Recent studies suggest that mutation of the slow delayed rectifier potassium channel [I(Ks)] contributes to familial atrial fibrillation (FAF). In the current study, we explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 95 Han Chinese patients with LAF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified four known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 95 LAF patients and 190 healthy controls. RESULTS: Three new variations were identified in KCNQ1 from 95 sporadic LAF including 1 in 5'UTR(c.-22T > C), 1 in exon9 synonymous mutation (c.1008C > T) and 1 in intron region (c.1590 + 31A > T). These variations were heterozygous and not presented in 190 healthy controls. Highly significant difference was detected between LAF group and control groups in rs760419 polymorphism. Logistic regression revealed that rs760419 was independent risk factor for LAF(OR = 2.056, P = 0.001). CONCLUSIONS: KCNQ1 mutation is associated with LAF and rs760419 polymorphism is a susceptible marker for LAF.

The impact of empirical Marshall vein ethanol infusion as a first-choice intraoperative strategy on the long-term outcomes in patients with persistent atrial fibrillation undergoing mitral isthmus ablation.

Background: Marshall vein ethanol infusion (MVEI) as an additional therapy to conventional catheter ablation (CA) has been proved to be efficacious in patients with persistent atrial fibrillation (PeAF). However, whether empirical MVEI could be the first-line strategy in mitral isthmus (MI) ablation has seldom been investigated. Here, we aim to compare the efficacy, safety, and long-term outcomes between provisional and empirical MVEI in PeAF patients undergoing the index MI ablation procedure. Methods: We enrolled 133 patients with PeAF either in the provisional group (n = 38, MVEI was performed when conventional endocardial and/or epicardial ablation procedures were inadequate to achieve bidirectional MI block) or in the empirical group (n = 95, MVEI was performed empirically before MI CA). Results: All of the baseline characteristics were comparable. Less spontaneous or inducible atrial tachycardias (ATs) were encountered in the empirical group of patients (P < 0.001). More epicardial ablations were applied (26.3% vs. 9.5%, P = 0.016) and a higher incidence of CA-facilitated restoration of sinus rhythm was recorded (86.8% vs. 11.7%, P < 0.001) in the provisional group of patients. Although more fluoroscopy time (6.4[4.2, 9.3] vs. 9.5[5.9, 11.6] min, P = 0.019) and radiation exposure (69.0[25.3, 160.2] vs. 122.0[62.5, 234.1] mGy, P = 0.010) were documented in the empirical group with comparable procedure time, less time (455.9 ± 192.2 vs. 366.5 ± 161.3 s, P = 0.038) was consumed to achieve bidirectional MI block during endocardial ablation in the provisional group. Incidences of procedure-related complications were similar between the two groups. During a 16.5 ± 4.4-month follow-up, the empirical group of patients showed a significantly higher rate of freedom from AT recurrence (95.8% vs. 81.6%, log-rank P = 0.003), while the rate of freedom from AF or atrial tachyarrhythmias (combining AF and AT) was similar. Both univariate (HR 0.19, 95% CI 0.05-0.64, P = 0.008) and multivariate (HR 0.25, 95% CI 0.07-0.92, P = 0.037) Cox regression analyses indicated that empirical MVEI was independently associated with lower long-term AT recurrence. Conclusion: Among patients with PeAF who underwent the index MI ablation procedure, empirical MVEI could reduce endocardial MI ablation time and provide greater long-term freedom from AT recurrence.