Percutaneous left atrial appendage closure with SeaLA device in non-valvular atrial fibrillation.

OBJECTIVES: The clinical efficacy and safety of a novel left atrial appendage (LAA) occluder of the SeaLA closure system in patients with nonvalvular atrial fibrillation (NVAF) were reported. BACKGROUND: Patients with NVAF are at a higher risk of stroke compared to healthy individuals. Left atrial appendage closure (LAAC) has emerged as a prominent strategy for reducing the risk of thrombosis in individuals with NVAF. METHODS: A prospective, multicenter study was conducted in NVAF patients with a high risk of stroke. RESULTS: The LAAC was successfully performed in 163 patients. The mean age was 66.93 ± 7.92 years, with a mean preoperative CHA2DS2-VASc score of 4.17 ± 1.48. One patient with residual flow >3 mm was observed at the 6-month follow-up, confirmed by TEE. During the follow-up, 2 severe pericardiac effusions were noted, and 2 ischemic strokes were observed. Four device-related thromboses were resolved after anticoagulation treatment. There was no device embolism. CONCLUSIONS: The LAAC with the SeaLA device demonstrates encouraging feasibility, safety, and efficacy outcomes.

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.

Efficacy and safety of a novel hexaspline pulsed field ablation system in patients with paroxysmal atrial fibrillation: the PLEASE-AF study.

AIMS: Pulsed field ablation (PFA) is an emerging non-thermal ablative modality demonstrating considerable promise for catheter ablation of atrial fibrillation (AF). However, these PFA trials have almost universally included only Caucasian populations, with little data on its effect on other races/ethnicities. The PLEASE-AF trial sought to study the 12-month efficacy and the safety of a multi-electrode hexaspline PFA catheter in treating a predominantly Asian/Chinese population of patients with drug-refractory paroxysmal AF. METHODS AND RESULTS: Patients underwent pulmonary vein (PV) isolation (PVI) by delivering different pulse intensities at the PV ostium (1800 V) and atrium (2000 V). Acute success was defined as no PV potentials and entrance/exit conduction block of all PVs after a 20-min waiting period. Follow-up at 3, 6, and 12 months included 12-lead electrocardiogram and 24-h Holter examinations. The primary efficacy endpoint was 12-month freedom from any atrial arrhythmias lasting at least 30 s. The cohort included 143 patients from 12 hospitals treated by 28 operators: age 60.2 ± 10.0 years, 65.7% male, Asian/Chinese 100%, and left atrial diameter 36.6 ± 4.9 mm. All PVs (565/565, 100%) were successfully isolated. The total procedure, catheter dwell, total PFA application, and total fluoroscopy times were 123.5 ± 38.8 min, 63.0 ± 30.7 min, 169.7 ± 34.6 s, and 27.3 ± 10.1 min, respectively. The primary endpoint was observed in 124 of 143 patients (86.7%). One patient (0.7%) developed a small pericardial effusion 1-month post-procedure, not requiring intervention. CONCLUSION: The novel hexaspline PFA catheter demonstrated universal acute PVI with an excellent safety profile and promising 12-month freedom from recurrent atrial arrhythmias in an Asian/Chinese population with paroxysmal AF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05114954.

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.

Catheter ablation of atrial fibrillation using FireMagic TrueForce ablation catheter: The TRUEFORCE trial.

BACKGROUND: The use of contact force (CF) sensing catheters has provided a revolutionary improvement in catheter ablation (CA) of atrial fibrillation (AF) in the past decade. However, the success rate of CA for AF remains limited, and some complications still occur. METHODS: The TRUEFORCE trial (Catheter Ablation of Atrial Fibrillation using FireMagic TrueForce Ablation Catheter) is a multicenter, prospective, single-arm objective performance criteria study of AF patients who underwent their first CA procedure using FireMagic TrueForce ablation catheter. RESULTS: A total of 120 patients (118 with paroxysmal AF) were included in this study, and 112 patients included in the per-protocol analysis. Pulmonary vein isolation (PVI) was achieved in 100% of the patients, with procedure and fluoroscopy time of 146.63 ± 40.51 min and 12.89 ± 5.59 min, respectively. Freedom from recurrent atrial arrhythmia after ablation was present 81.25% (95% confidence interval [CI]: 72.78%-88.00%) of patients. No severe adverse events (death, stroke/transient ischemic attack [TIA], esophageal fistula, myocardial infarction, thromboembolism, or pulmonary vein stenosis) were detected during the follow-up. Four (4/115, 3.33%) adverse events were documented, including one abdominal discomfort, one femoral artery hematoma, one coughing up blood, and one postoperative palpitation and insomnia. CONCLUSIONS: This study demonstrated the clinical feasibility of FireMagic force-sensing ablation catheter in CA of AF, with a satisfactory short- and long-term efficacy and safety.

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.

Integrated Pipeline of Rapid Isolation and Analysis of Human Plasma Exosomes for Cancer Discrimination Based on Deep Learning of MALDI-TOF MS Fingerprints.

Plasma exosomes have shown great potential for liquid biopsy in clinical cancer diagnosis. Herein, we present an integrated strategy for isolating and analyzing exosomes from human plasma rapidly and then discriminating different cancers excellently based on deep learning fingerprints of plasma exosomes. Sequential size-exclusion chromatography (SSEC) was developed efficiently for separating exosomes from human plasma. SSEC isolated plasma exosomes, taking as less as 2 h for a single sample with high purity such that the discard rates of high-density lipoproteins and low/very low-density lipoproteins were 93 and 85%, respectively. Benefitting from the rapid and high-purity isolation, the contents encapsulated in exosomes, covered by plasma proteins, were well profiled by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS). We further analyzed 220 clinical samples, including 79 breast cancer patients, 57 pancreatic cancer patients, and 84 healthy controls. After MS data pre-processing and feature selection, the extracted MS feature peaks were utilized as inputs for constructing a multi-classifier artificial neural network (denoted as Exo-ANN) model. The optimized model avoided overfitting and performed well in both training cohorts and test cohorts. For the samples in the independent test cohort, it realized a diagnosed accuracy of 80.0% with an area under the curve of 0.91 for the whole group. These results suggest that our integrated pipeline may become a generic tool for liquid biopsy based on the analysis of plasma exosomes in clinics.

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.

scRNA-seq of ovarian follicle granulosa cells from different fertility goats reveals distinct expression patterns.

The new technology of high-throughput single-cell RNA sequencing (10 × scRNA-seq) was developed recently with many advantages. However, it was not commonly used in farm animal research. There are few reports for the gene expression of goat ovarian follicle granulosa cells (GCs) during different developmental stages. In the current investigation, the gene expression of follicle GCs at different stages from two populations of Ji'ning grey goats: high litter size (HL; ≥3/L; 2 L) and low litter size (LL; ≤2 /L; 2 L) were analysed by scRNA-seq. Many GC marker genes were identified, and the pseudo-time showed that GCs developed during the time course which reflected the follicular development and differentiation trajectory. Moreover, the gene expression difference between the two populations HL versus LL was very clear at different developmental stages. Many marker genes differentially expressed at different developmental stages. ASIP and ASPN were found to be highly expressed in the early stage of GCs, INHA, INHBA, MFGE8 and HSD17B1 were identified to be highly expressed in the growing stage of GCs, while IGFBP2, IGFBP5 and CYP11A1 were found to be highly expressed in late stage. These marker genes could be used as reference genes of goat follicle GC development. This investigation for the first time discovered the gene expression patterns in goat follicle GCs in high- or low-fertility populations (based on litter size) by scRNA-seq which may be useful for uncovering the oocyte development potential.

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.

A New Formula for Estimating the True QT Interval in Left Bundle Branch Block.

INTRODUCTION: QT prolongation is an independent risk factor for cardiac mortality. Left bundle branch block (LBBB) is more common in patients as they age. Widening of the QRS in LBBB causes false QT prolongation and thus makes true QT assessment difficult. We aimed to develop a simple formula to achieve a good estimate of the QT interval in the presence of LBBB. METHODS AND RESULTS: To determine the effect of QRS duration on the QT interval, QRS and QT were measured in sinus rhythm and during right ventricular apical pacing in 62 patients (age 55 ± 11 years, 60% male) undergoing electrophysiology studies. A QT formula for LBBB (QT-LBBB) was derived based on the effect of increased QRSLBBB on QTLBBB . The predictive accuracy of the QT-LBBB formula was then tested in 22 patients (age 66 ± 13 years, 64% male) with intermittent LBBB with comparisons to prior QT formulae and JT index. On average, the net increase in QRSLBBB constituted 92% of the net increase in QTLBBB . A new formula, QT-LBBB = QTLBBB - (0.86 * QRSLBBB - 71), which takes the net increase in QRSLBBB into account, best predicted the QT interval with heart rate corrected QTc in the test set of LBBB ECGs when compared to the baseline value and prior formulae. CONCLUSION: The QT-LBBB formula developed in this study best estimates the true QT interval in the presence of LBBB. It is simple and therefore can be easily utilized in clinical practice.

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.

Overexpression of MD1 ameliorates pathological myocardial remodeling in diabetic cardiomyopathy by TLR4/STAT3 signaling pathway.

Diabetic cardiomyopathy (DCM) is characterized by oxidative damage and inflammatory responses. Myeloid differentiation protein 1 (MD1) exhibits antioxidant and anti-inflammatory properties. However, the specific role of MD1 in DCM has yet to be elucidated. This study aims to investigate the role of MD1 in DCM and to elucidate the underlying mechanisms. We utilized a gain-of-function approach to explore the involvement of MD1 in DCM. Diabetes was induced in MD1-transgenic (MD1-TG) mice and their wild-type (WT) counterparts via streptozotocin (STZ) injection. Additionally, a diabetes cell model was established using H9c2 cells exposed to high glucose levels. We conducted comprehensive evaluations, including pathological analyses, echocardiography, electrocardiography, and molecular assessments, to elucidate the underlying mechanisms of MD1 in DCM. Notably, MD1 expression was reduced in the hearts of STZ-induced diabetic mice. Overexpression of MD1 significantly improved cardiac function and markedly inhibited ventricular pathological hypertrophy and fibrosis in these mice. Furthermore, MD1 overexpression resulted in a substantial decrease in myocardial reactive oxygen species (ROS) accumulation, mitigating myocardial oxidative stress and reducing the levels of inflammation-related markers such as IL-1ß, IL-6, and TNF-α. Mechanistically, MD1 overexpression inhibited the activation of the TLR4/STAT3 signaling pathway, as demonstrated in both in vivo and in vitro experiments. The overexpression of MD1 significantly impeded pathological cardiac remodeling and improved cardiac function in STZ-induced diabetic mice. This effect was primarily attributed to a reduction in ROS accumulation and mitigation of myocardial oxidative stress and inflammation, facilitated by the inhibition of the TLR4/STAT3 signaling pathway.

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.

Immunomagnetic capture and traceless release of native tumor-derived exosomes from human plasma for exploring interaction with recipient cells by aptamer-functionalized nanoflowers.

BACKGROUND: Tumor-derived exosomes (TEXs) play an important role in the development process of cancer, which can transport a large number of carcinogenic molecules to normal cells, and subsequently promote tumor metastasis. However, TEXs that were utilized in most of previous researches were obtained from the cell medium of tumor cell lines, which cannot reflect the physiological state of primary cells in vivo. Isolation of native TEXs from human plasma with intact function is contributed to exploring the interaction between TEXs and recipient cells for understanding their true biological functions. RESULTS: We developed a strategy that involves both capture and release processes to obtain native TEXs from plasma of cancer patients. An MoS2-based immunomagnetic probe (Fe3O4@MoS2-Au-Aptamer, named as FMAA) with the advantages of high surface area, magnetic response and abundant affinity sites was designed and synthesized to capture TEXs through recognizing high-expression tumor-associated antigens of EpCAM. With the assistance of complementary sequences of EpCAM, TEXs were released with non-destruction and no residual labels. According to NTA analysis, 107-108 TEXs were recovered from per mL plasma of breast cancer patients. The interaction between native TEXs and normal epithelial cells confirms TEXs could induce significant activation of autophagy of recipient cells with co-culture for 12 h. Proteomics analysis demonstrated a total of 637 proteins inside epithelial cells had dynamic expression with the stimulation of TEXs and 5 proteins in the pathway of autophagy had elevated expression level. SIGNIFICANCE: This work not only obtains native TEXs from human plasma with non-destruction and no residual labels, but also explores the interaction between TEXs and recipient cells for understanding their true biological functions, which will accelerate the application of TEXs in the field of biomarkers and therapeutic drugs.

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.