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

AIM: Radiofrequency ablation (RFA) 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. PFA generator generated a bipolar and biphasic waveform (± 1000 V) with a duration of 100 ms from the tip of PFA catheter. 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 seconds for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 seconds at targets and 3.2 ± 2.9 seconds at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 minutes, and PFA catheter dwell time was 29.4 ± 7.8 minutes. 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 short-term follow-up. CONCLUSIONS: PFA 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 APs 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.

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.

Unipolar Electrogram-Guided versus Lesion Size Index-Guided Catheter Ablation in Patients with Paroxysmal Atrial Fibrillation.

Background: This research explores the relationship between the unipolar electrogram (UP-EGM) and lesion size index (LSI) in different regions of continuous circular lesions (CCLs) and to assess the safety and efficacy of UP-EGM-guided versus LSI-guided radiofrequency catheter ablation (RFCA) in patients with paroxysmal atrial fibrillation (PAF). Methods: A total of 120 patients with drug-refractory PAF who underwent index RFCA were scheduled to be consecutively included from March 2020 to April 2021. All the patients were randomly divided 1:1 into two groups: the UP-EGM group and the LSI group. The first-pass PVI rate, acute PVI rate, and the sinus rhythm maintenance rate were compared. Results: A total of 120 patients with PAF were included in the study: the UP-EGM group (n = 60) and the LSI group (n = 60). All the LSI values in the UP-EGM group were less than those in the corresponding regions in the LSI group (all p < 0.001). There were no significant differences in the first-pass PVI rate and acute PVI rate between the two groups. After a mean follow-up period of 11.31 ± 1.70 months, the sinus rhythm maintenance rate in the UP-EGM group was comparable to that in the LSI group (90% vs. 91.7%, p = 0.752). Conclusion: UP-EGM-guided and LSI-guided RFCA are both effective and safe in patients with PAF. However, UP-EGM may be more suitable than LSI for guiding individual RFCA.

Anti-fibrotic mechanism of SPP1 knockdown in atrial fibrosis associates with inhibited mitochondrial DNA damage and TGF-ß/SREBP2/PCSK9 signaling.

Atrial fibrosis occurs frequently with structural heart disease and is considered as a major cause of arrhythmia. Microarray-based profiling predicted the differential expression of SPP1 in atrial fibrosis. Herein, we aimed to analyze the role of shRNA-mediated SPP1 knockdown in the progression of atrial fibrosis as well as the downstream mechanism. In vivo model in mice and in vitro HL-1 cell model of atrial fibrosis were developed by the angiotensin II (Ang II) method, where SPP1 expression was validated by RT-qPCR. Gain- and loss-of-function experiments were performed in Ang II-induced mice and HL-1 cells to evaluate the effect of the SPP1/TGF-ß/SREBP2/PCSK9 axis on cell viability, apoptosis, collagen production and mitochondrial DNA (mtDNA) damage in atrial fibrosis. Expression of SPP1, TGF-ß, SREBP2 and PCSK9 was increased in Ang II-induced mice and HL-1 cells. Silencing of SPP1 inhibited the occurrence of atrial fibrosis, as reflected by attenuated cell viability and collagen production as well as increased cell apoptosis. Conversely, upregulated SPP1 enhanced atrial fibrosis, which was related to upregulation of TGF-ß. In addition, TGF-ß elevated the expression of SREBP2, which promoted mtDNA damage and the consequent atrial fibrosis by augmenting the expression of PCSK9. This study uncovers previously unrecognized pro-fibrotic activities of SPP1 in atrial fibrosis, which is achieved through activation of the TGF-ß/SREBP2/PCSK9 signaling pathway and promotion of mtDNA damage.

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.

Left Atrial Spontaneous Echo Contrast and Ischemic Stroke in Patients Undergoing Percutaneous Left Atrial Appendage Closure.

Objectives: Spontaneous echo contrast (SEC) in the left atrium (LA) is frequently observed in atrial fibrillation (AF) patients and may lead to thromboembolic events. We aimed to investigate both periprocedural and long-term stroke risks associated with LA SEC in AF patients undergoing percutaneous left atrial appendage closure (LAAC). Methods: A total of 408 consecutive AF patients treated with LAAC between March 2015 and February 2019 were divided into two groups based on preprocedural transesophageal echocardiography: the study group (moderate/severe LA SEC; n = 41) and the control group (none, mild, or mild to moderate LA SEC; n = 367). To attenuate the observed imbalance in baseline covariates, a propensity score matching technique was used. Results: No periprocedural stroke/transient ischemic attack (TIA) was documented. The incidence of device-related thrombus was higher in the study group than in the control group (8.8 vs. 1.3%; P = 0.025). The mean follow-up period was 3.2 ± 1.1 years, during which 8 patients (2.2%) in the control group and 4 (9.8%) in the study group experienced stroke/TIA (P = 0.024). Moderate/severe LA SEC was identified as an independent predictor of stroke/TIA in both the original population (HR = 5.71, 95% CI 1.47-22.19, P = 0.012) and the matched population (HR = 9.79, 95% CI 1.44-66.86, P = 0.020). Conclusions: LA SEC did not show a relationship with periprocedural stroke events in patients undergoing percutaneous LAAC. However, moderate/severe LA SEC increased the incidence of device-related thrombus and the risk of late stroke/TIA.

ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis.

BACKGROUND: Precursor of nerve growth factor (proNGF) was previously considered biologically inactive; however, it has recently been identified as having important roles in the pathology of cancer development. AIM: This study aimed to explore the therapeutic effects of proNGF siRNA on the proliferation, invasion, and anoikis of pancreatic cancer cells and determine the functions of proNGF. METHODS: Pancreatic ductal adenocarcinoma (PDAC) and paired paracancerous tissue samples were collected from 60 patients for evaluation of proNGF expression by immunohistochemistry staining, qPCR, and western blotting. PDAC cell proliferation, migration, apoptosis, and anoikis following proNGF siRNA knockdown were investigated in two pancreatic cancer cell lines, Panc-1 and Bxpc-3, using BrdU incorporation assays, EdU staining, Ki-67 immunofluorescence (IF) staining, wound-healing assays, transwell invasion assays, and EthD-1 IF staining. Autophagy-related proteins were also measured by western blotting. RESULTS: Levels of proNGF protein were higher in pancreatic cancer tissues and cells lines than those in paracancerous tissues and normal pancreatic duct epithelial cells, respectively. In vitro, ProNGF knockdown by siRNA led to significantly reduced cell proliferation, remarkably inhibited wound-healing, and reduced the number of invaded PDAC cells in migration and transwell assays. Treatment with proNGF siRNA also downregulated ATG5 and Beclin 1 protein levels, increased those of P62, and increased EthD-1 staining in PDAC cells. CONCLUSION: ProNGF expression is elevated in PDAC tissues and cell lines, and proNGF siRNA can inhibit cell proliferation, migration, and invasion, and promote anoikis of pancreatic cancer cells, in which decreased proNGF may participate.