Novel dual-reference approach facilitates the activation mapping and catheter ablation of premature atrial complexes with non-pulmonary vein and non-superior vena cava origins.

AIMS: Activation mapping of premature atrial complexes (PACs) proves challenging due to interference by mechanical bumping and non-targeted ectopies. This study aims to compare the mapping efficacy, instant success, and long-term recurrence of catheter ablation for PACs with non-pulmonary vein (PV) and non-superior vena cava (SVC) origins between the novel dual-reference approach (DRA) and the routine single-reference approach (SRA) of mapping. METHODS AND RESULTS: Patients with symptomatic, drug-refractory PACs, or frequent residual PACs after atrial tachyarrhythmia ablation were enrolled. During activation mapping, the coronary sinus (CS) catheter was used as the only timing reference in the SRA group. In the DRA group, another catheter, which was spatially separated from the CS catheter, was used as the second reference. The timing difference between the two references was used to discriminate the targeted PACs from the uninterested rhythms. Procedural parameters and long-term recurrence were compared. A total of 188 patients (109 in SRA and 79 in DRA) were enrolled. The baseline characteristics were similar. Compared with the SRA group, the DRA group had less repeated mapping (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.004), shorter mapping (15 ± 6 vs. 23 ± 7 min, P < 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P > 0.999), higher instant success (96.2 vs. 87.2%, P = 0.039), and lower recurrence rate (15.2 vs. 29.3%, hazard ratio 1.943, P = 0.033) during a 24-month follow-up. CONCLUSION: As a novel strategy, the DRA shortens the procedural time and improves both instant and long-term success of PAC ablation, serving as a promising approach in mapping PACs with non-PV and non-SVC origins.

[Simulation Results and Analysis of Electric Field Distribution in Myocardial Tissue under Circular Electrode Electric Pulse Ablation].

As a new energy source for atrial fibrillation ablation, electric pulse ablation has higher tissue selectivity and biosafety, so it has a great application prospect. At present, there is very limited research on multi-electrode simulated ablation of histological electrical pulse. In this study, a circular multi-electrode ablation model of pulmonary vein will be built on COMSOL5.5 platform for simulation research. The results show that when the voltage amplitude reaches about 900 V, it can make some positions achieve transmural ablation, and the depth of continuous ablation area formed can reach 3 mm when the voltage amplitude reaches 1 200 V. When the distance between catheter electrode and myocardial tissue is increased to 2 mm, a voltage of at least 2 000 V is required to make the depth of continuous ablation area reach 3 mm. Through the simulation of electric pulse ablation with ring electrode, the research results of this project can provide reference for the voltage selection in the clinical application of electric pulse ablation.

[Simulation and Experiment of Electric Field Distribution of Non-invasive Pelvic Floor Electric Stimulation Therapeutic Apparatus].

This study analyzes the difference between non-invasive and invasive pelvic floor electric stimulation therapeutic apparatus. Through establishing the resistance network model of human pelvic floor muscle group, using circuit loop analysis and simulation, the current and voltage distribution are obtained, and the conclusions are listed as follows: Since invasive electrode has a central symmetry, pelvic floor muscles have equipotential areas and unable to form the current loop. Non-invasive electrodes don't have this problem. With the same stimulation conditions, non-invasive stimulation intensity of the superficial pelvic floor muscle is the highest, followed by the middle and the deep layer. While the invasive electrode stimulates the superficial and deep pelvic floor muscles moderately, the middle pelvic floor muscles some parts strongly, some parts weakly. The results of in vitro experiments show that the tissue impedance is very small, and the non-invasive electrical stimulation is well conducted into the tissue, which is consistent with the analysis and simulation results.

Current evidence on the safety and efficacy of combined atrial fibrillation ablation and left atrial appendage closure.

PURPOSE OF REVIEW: Combined atrial fibrillation (AF) ablation and left atrial (LA) appendage (LAA) closure (LAAC) has been practiced for management of both the symptoms and the high stroke risk of AF. The purpose of this review is to review recent evidence regarding the combined procedure. RECENT FINDINGS: Newly acquired long-term data of combined AF ablation and LAAC supplied satisfactory evidence on the safety and efficacy of the combined procedure. Studies also showed LA structural remodeling following combined procedure was mainly affected by sinus rhythm status post catheter ablation, not by LAAC. A cost-effectiveness study revealed that combined procedure was a cost-effective therapeutic option in symptomatic AF patients with high stroke and bleeding risk. Due to recent evidence of high incidences of LAA thrombus formation after LAA electrical isolation (LAAEI) and benefit of LAAC after LAAEI, an extended combined procedure of standard AF ablation plus LAAEI and LAAC was considered as a potential therapeutic option for persistent AF patients with high stroke risk. SUMMARY: In conclusion, combined AF ablation and LAAC serve as a promising option for patients with symptomatic AF and high risk of stroke and/or bleeding.

Value of detecting peri-device leak and incomplete endothelialization by cardiac CT angiography in atrial fibrillation patients post Watchman LAAC combined with radiofrequency ablation.

OBJECTIVES: To explore the value of detecting the peri-device leak (PDL) and device endothelialization after left atrial appendage closure (LAAC) by cardiac computed tomography (CT) in patients with atrial fibrillation (AF), who underwent Watchman LAAC combined with radiofrequency ablation of atrial fibrillation (AFCA). METHODS: Patients with symptomatic drug-refractory atrial fibrillation at high risk of stroke (CHA2 DS2 -VASc Score ≥ 2), who underwent Watchman LAAC combined with AFCA in our center from March 2017 to December 2018 were enrolled. Maximum diameter of LAA orifice was determined by preoperative CCTA. A standardized view of Watchman device was obtained by postoperative CCTA multiplannar reconstruction to evaluate the PDL and device endothelialization. RESULTS: Approximately 84 patients post successful LAAC and AFCA were enrolled in this study. The satisfactory LAA occlusion rate was 100%. There was no death, bleeding, stroke, and device-related thrombus (DRT) events. At 6-month postprocedure, CCTA images evidenced complete endothelialization in 44 patients (no contrast enhancement in LAA); contrast enhancement in LAA and visible PDL in 33 patients; contrast enhancement in LAA but without PDL in seven patients (incomplete device endothelialization). Maximum diameter of LAA orifice could independently predict the occurrence of PDL (odds ratio, 1.31; 95% confidence interval, 1.11-1.55; p = .002), sensitivity was 69.7% and specificity was 80.4% with the cutoff value of maximum diameter of LAA orifice more than 28.2 mm on predicting PDL. CONCLUSIONS: CCTA is feasible to evaluate PDL and device endothelialization after LAAC. The maximum diameter of LAA orifice derived from CT can independently predict the occurrence of post-LAAC PDL.

[CT Image-based Surgery Assist System for Left Atrial Appendage Occlusion].

At present, the standard left atrial appendage occlusion procedure mainly involves two-dimensional imaging methods such as X-ray fluoroscopy and transesophageal echocardiography to guide the operation, which will lead to underestimation of the three dimensional structure of the left atrial appendage and the surrounding tissue, thus adversely affects the surgery. To solve this problem, a surgery assist system for left atrial appendage occlusion based on preoperative cardiac CT images is developed. The proposed system realizes the left atrial appendage parameter measurement based on cardiac CT image, and realizes the calculation of optimal delivery sheath trajectory and three-dimensional simulation of the delivery sheath movement on the basis of a novel delivery sheath trajectory model. The system is expected to provide precise guidance for left atrial appendage occlusion, improve the success rate and safety of the operation, and at the same time help reduce the difficulty of learning the operation, and facilitate the promotion of left atrial appendage occlusion.

Utility of Circadian Variability Patterns in Differentiating Origins of Premature Ventricular Complexes.

BACKGROUND: Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns. METHODS: We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally. RESULTS: In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns. CONCLUSIONS: The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.

Combined Therapy of Catheter Ablation and Left Atrial Appendage Closure for Patients with Atrial Fibrillation: A Case-Control Study.

AIM: The feasibility and safety of performing the combined procedure of catheter ablation (CA) and left atrial appendage closure (LAAC) for atrial fibrillation (AF) have been reported by observational studies without controls. The aim of this study was to compare the procedural and long-term outcomes of combined procedures with isolated CA or LAAC. METHODS AND RESULTS: This study included patients who underwent combined CA and LAAC (combined group), CA alone (CA-only group), or LAAC alone (LAAC-only group). Propensity score matching was used to select controls from the CA-only and LAAC-only groups. Each group contained 76 subjects. The procedures were successfully performed in all the patients. Procedure-related complications of the combined group included one pericardial effusion and two groin haematomas, which did not differ significantly with those of the CA-only group (3.9% vs. 2.6%, P=0.650) or the LAAC-only group (3.9% vs. 2.6%, P=0.650), respectively. The AF-free rate of the combined group was comparable with that of the CA-only group after a mean of 2 years follow-up (67.1% vs. 69.7%, P=0.727). Compared with the LAAC-only group, the combined group achieved similar complete occlusion rate at implant (94.7% vs. 93.4%) and at 45 days (82.9% vs. 85.5%). At the end of follow-up, ischemic stroke and bleeding events of the combined group were low (3.9%) and were comparable with those of the CA-only group (5.3%) and the LAAC-only group (2.6%). CONCLUSIONS: The combination of AF-CA and LAAC is safe and efficacious compared with single procedures alone.

EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation.

Angiotensin II (Ang-II)-induced fibroblast differentiation plays an important role in the development of atrial fibrosis and atrial fibrillation (AF). Here, we show that the expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is increased in atrial muscle and atrial fibroblasts in patients with AF, accompanied by significant atrial fibrosis and atrial fibroblast differentiation. In addition, EZH2 is induced in murine models of atrial fibrosis. Furthermore, either pharmacological GSK126 inhibition or molecular silencing of EZH2 can inhibit the differentiation of atrial fibroblasts and the ability to produce ECM induced by Ang-II. Simultaneously, inhibition of EZH2 can block the Ang-II-induced migration of atrial fibroblasts. We found that EZH2 promotes fibroblast differentiation mainly through the Smad signaling pathway and can form a transcription complex with Smad2 to bind to the promoter region of the ACTA2 gene. Finally, our in vivo experiments demonstrated that the EZH2 inhibitor GSK126 significantly inhibited Ang-II-induced atrial enlargement and fibrosis and reduced AF vulnerability. Our results demonstrate that targeting EZH2 or EZH2-regulated genes might present therapeutic potential in AF.

Incidence, impact and predictors of residual device patency after left atrial appendage closure with the LACbes device.

BACKGROUND: The residual device patency (RDP) after left atrial appendage closure (LAAC) with the LACbes device has not been specifically explored in atrial fibrillation (AF) patients. This study aims to explore the incidence, impact and predictors of RDP detected by cardiac computed tomography angiography (CCTA) post LAAC. METHODS: AF patients implanted with the LACbes device were prospectively enrolled. CCTA device surveillance was performed at 3 months post-procedure. Major adverse events (MAEs), including stroke/transient ischemic attack, major bleeding and all-cause death, were evaluated. RESULTS: Among 141 patients with CCTA surveillance, 56 (39.7%) showed no visible leak and 85 (60.3%) showed RDP. During the median follow-up of 443 [232, 706] days, the presence of RDP was not associated with an increased risk of MAEs (adjusted hazard ratio [HR]: 4.07, 95% confidence interval [CI]: 0.49-34.24, p = 0.196), while peri-device leak (PDL) at the lobe was associated with heightened risks of MAEs (adjusted HR: 6.85, 95% CI: 1.62-28.89, p = 0.009). In patients with PDL at the lobe, antiplatelet after 6 months (HR: 0.20, 95% CI: 0.05-0.91, p = 0.038) was independent protective predictor of MAEs. Besides, current smoking (odds ratio [OR]: 7.52, 95% CI: 2.68-21.08, p < 0.001) and maximum diameter of LAA orifice (OR: 1.16, 95% CI: 1.00-1.34, p = 0.048) were independent predictors of PDL at the lobe. CONCLUSIONS: Presence of PDL at the device lobe detected by CCTA at 3-month post LAAC with LACbes is associated with unfavorable prognosis in AF patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03788941.

Prognostic Impact of Left Atrial Appendage Patency After Device Closure.

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.

Accuracy of the Injection-Based Occlusion Tool Utilizing Saline and Glucose Solution in Cryoballoon Ablation Guided by a Novel Dielectric Imaging System.

Introduction: The aim of this study is to assess the accuracy of the injection-based occlusion (IBO) tool utilizing saline and glucose solution in verifying pulmonary vein (PV) occlusion during cryoballoon ablation guided by a novel dielectric system (KODEX-EPD system). Methods: In this retrospective study, we enrolled 34 consecutive patients with paroxysmal atrial fibrillation (AF) who underwent their initial cryoballoon ablation procedure guided by the KODEX-EPD system. PV occlusion was firstly assessed by the IBO tool utilizing saline or glucose solution and then verified by direct contrast angiography. Patients were divided into two groups according to the fluid used in the IBO tool: the Saline Group and the Glucose Group. Results: The overall procedure time and fluoroscopy time were comparable between the Saline Group and the Glucose Group (113.7 ± 18.3 vs. 108.4 ± 15.9 min; p = 0.375 and 10.1 ± 3.7 vs. 9.3 ± 3.5 min; p = 0.559). The IBO tool was utilized a total of 138 times in the Saline Group and 135 times in the Glucose Group. When assessing PV occlusion, the IBO tool using saline demonstrated a sensitivity of 92.6% and a specificity of 95.2% compared to angiography. Similarly, the IBO tool utilizing glucose solution showed a sensitivity of 93.2% and a specificity of 96.1%. Conclusions: The IBO tool utilizing non-contrast fluid, saline and glucose solution, demonstrates a high level of sensitivity and specificity in accurately predicting PV occlusion during cryoablation procedures. Both the saline and glucose solutions used in the IBO tool show promising results in effectively assessing PV occlusion.

Sex Differences in the Combined Ablation and Left Atrial Appendage Closure: Results From LAACablation Registry.

Background: More than 40% of left atrial appendage closure (LAAC) procedures were combined with atrial fibrillation (AF) ablation in China. Objectives: This study aimed to assess the sex differences in the combined radiofrequency catheter ablation and LAAC procedures. Methods: Data from the LAACablation (Left Atrial Appendage Closure in Combination With Catheter Ablation) registry, which enrolled AF patients who underwent the combined procedure between 2018 and 2021, were analyzed. Procedural complications, long-term outcomes, and quality of life (QoL) were compared between sexes. Results: Of 931 patients, 402 (43.2%) were women. Compared with men, women were older (age 71.3 ± 7.4 years vs 68.7 ± 8.1 years; P < 0.001), presented more often with paroxysmal AF (52.5% vs 42.7%; P < 0.003), and had higher CHA2DS2-VASc scores (4.1 ± 1.5 vs 3.1 ± 1.5; P < 0.001), but received less often linear ablation and had shorter total procedural times and radiofrequency catheter ablation times. Women had similar rates of total and major procedural complications but presented with a higher incidence of minor complications than men (3.7% vs 1.3%; P = 0.027). Follow-up over 1,812 patient-years revealed similar adverse events between women and men, including all-cause death (HR: 0.89; 95% CI: 0.43-1.85; P = 0.754), thromboembolic events (HR: 1.17; 95% CI: 0.54-2.52; P = 0.697), major bleeding (HR: 0.96; 95% CI: 0.38-2.44; P = 0.935), and their composite (HR: 0.85; 95% CI: 0.56-1.28; P = 0.434). The recurrence rates of atrial tachyarrhythmia were also comparable between sexes presenting either paroxysmal or persistent AF. Women were seen with greater QoL impairment at baseline, but the sex gap narrowed at 1-year follow-up. Conclusions: In AF patients who underwent the combined procedure, women had similar procedural safety and long-term efficacy to men and presented greater QoL improvement. (Left Atrial Appendage Closure in Combination With Catheter Ablation [LAACablation]; NCT03788941).

Combined Radiofrequency Ablation and Left Atrial Appendage Closure in Atrial Fibrillation and Systolic Heart Failure.

BACKGROUND: Managing patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF. METHODS: AF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison. RESULTS: Among 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415-4.449, p = 0.002) and with the respective rates predicted by risk scores. CONCLUSIONS: Combining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

Safety and efficacy of ablation for atrial fibrillation in combination with left atrial appendage occlusion in octogenarians.

BACKGROUND: Catheter ablation (CA) combined with left atrial appendage occlusion (LAAO) is a feasible approach for atrial fibrillation (AF) patients. Its role in octogenarians with AF is unclear. HYPOTHESIS: In AF patients over 80 years, CA combined with LAAO is a feasible way in restoring sinus rhythm and preventing stroke. METHODS: This is a single-center retrospective study. Patients who underwent CA and LAAO in a single procedure between March 2018 and December 2020 were included. Efficacy endpoints included procedural success rate, AF recurrence rate, and thromboembolic events. Safety endpoints included pericardial effusion/cardiac tamponade, device-related thrombus (DRT), all-cause death, and major bleeding. RESULTS: Five hundred and five patients (mean age 69.5 ± 7.7 years; 230 [45.5%] female) were included, with 46 (9.1%) patients aged ≥80 years old (octogenarian group). Prevalence of paroxysmal AF (25 [54.3%] vs. 207 [45.1%], p < 0.001) and CHA2DS2VASc score (4.1 ± 1.3 vs. 3.1 ± 1.4, p < 0.0001) were higher in octogenarian patients. There were six cases (1.2%) of pericardial effusion (all in nonoctogenarian patients). At 3 months postprocedure, 437 patients underwent TEE/CT. Thirty-two (80%) octogenarian patients and 308 (77.6%) nonoctogenarian patients had no peri-device leak. After a mean follow-up of 26.9 ± 9.1 months, AF was documented in 10 (21.7%) patients in octogenarian group and in 103 (22.4%) patients in nonoctogenarian group (p = 0.99). The annual thromboembolic risk was 2.1% and 0.8% in the octogenarian group and nonoctogenarian group, respectively. Death occurred in 16 nonoctogenarian patients. One major bleeding was recorded in the octogenarian group. CONCLUSIONS: The combination of CA and LAAO in a single procedure is a feasible treatment option in octogenarians with comparable efficacy and safety profile.

Higher Sodium Channel Excitability in Cardiac Purkinje Fibers: Implications for Multifocal Ectopic Purkinje-Related Premature Contractions.

BACKGROUND: Multifocal ectopic Purkinje-related premature contractions (MEPPCs) are associated with SCN5A variants. However, it is not well understood why Purkinje fibers, but not ventricular myocardium, play a predominant role in arrhythmogenesis. OBJECTIVES: This study sought to explore the underlying mechanisms of MEPPC. METHODS: Whole-cell patch-clamp and molecular biology techniques were used in the present study. RESULTS: Clinical data from one patient with R814W variant showed MEPPC syndrome, which is well responsive to amiodarone. Compared with canine ventricular myocytes, Purkinje cells (PCs) had significantly larger sodium current (INa), leftward shift of INa activation and inactivation curves, suggesting higher sodium channel excitability in PCs. Real-time polymerase chain reaction and Western blot analysis showed that the mRNA and protein expression of NaVß1 and NaVß3 was higher in canine Purkinje fibers than in ventricular myocardium. INa in heterologous Chinese hamster ovary cell expression system co-expressing NaV1.5 and NaVß1/NaVß3 exhibited similar biophysical properties of INa in PCs. R814W variant shifted INa activation in a hyperdepolarized direction, caused a larger window current, and generated an outward-gating pore current at depolarized voltages. Coexpression of NaVß1/NaVß3 with Nav1.5-R814W further left-shifted INa activation and caused an even larger window current and gating pore current, suggesting higher susceptibility of Purkinje fibers to R814W variant. Amiodarone inhibited INa, shifted its inactivation to more negative voltages, and significantly decreased the window current. CONCLUSIONS: A higher expression of ß1 and ß3 subunits contributes to higher sodium channel excitability in cardiac Purkinje fibers, making them more susceptible to MEPPC.

Case report: Intrapericardial thrombus aspiration in early stage of pericardial thrombosis for cardiac tamponade complicating percutaneous left atrial appendage closure.

Introduction: Pericardial thrombosis that complicates pericardial bleeding is a life-threatening emergency in interventional cardiology, and surgery remains the only definitive treatment option. We report the first case of successful intrapericardial thrombus aspiration using a dedicated thrombus aspiration catheter in the early stage of pericardial thrombosis. Case report: A 76-year-old woman with non-valve atrial fibrillation underwent percutaneous left atrial appendage (LAA) closure for secondary prevention of stroke. A 24-mm Watchman device was deployed under fluoroscopic guidance. Post-deployment angiography revealed LAA perforation, which led to the rapid onset of cardiac tamponade. Emergency pericardiocentesis was performed and the deep-seated device was redeployed at a more proximal position to seal the distal perforation. Pericardial bleeding was controlled after the drainage of 400 ml of blood. However, the patient re-developed cardiac tamponade following a period of stability. The patient was diagnosed with early-stage pericardial thrombosis based on echocardiographic findings of a hypoechoic effusion in the pericardial space. Thrombus aspiration using a pigtail catheter and long sheath failed; however, we performed successful intrapericardial thrombus aspiration using a dedicated thrombus aspiration catheter. We drained 120 ml of sludge-like blood, and the patient underwent successful conservative management without surgical intervention. Conclusion: This case report highlights the potential usefulness of a percutaneous intrapericardial thrombus aspiration technique using a dedicated thrombus aspiration catheter in selected patients with early-stage pericardial thrombosis, as a less invasive alternative to cardiac surgery.

Inhibition of Wdr5 Attenuates Ang-II-Induced Fibroblast-to-Myofibroblast Transition in Cardiac Fibrosis by Regulating Mdm2/P53/P21 Pathway.

Cardiac fibrosis is an important pathological process in many diseases. Wdr5 catalyzes the trimethylation of lysine K4 on histone H3. The effects of Wdr5 on the cardiac fibrosis phenotype and the activation or transformation of cardiac fibroblasts were investigated by Ang-II-infused mice by osmotic mini-pump and isolated primary neonatal rat cardiac fibroblasts. We found that the Wdr5 expression and histone H3K4me3 modification were significantly increased in Ang-II-infused mice. By stimulating primary neonatal rat cardiac fibroblasts with Ang II, we detected that the expression of Wdr5 and H3K4me3 modification were also significantly increased. Two Wdr5-specific inhibitors, and the lentivirus that transfected Sh-Wdr5, were used to treat primary mouse cardiac fibroblasts, which not only inhibited the histone methylation by Wdr5 but also significantly reduced the activation and migration ability of Ang-II-treated fibroblasts. To explore its mechanism, we found that the inhibition of Wdr5 increased the expression of P53, P21. Cut&Tag-qPCR showed that the inhibition of Wdr5 significantly reduced the enrichment of H3K4me3 in the Mdm2 promoter region. For in vivo experiments, we finally proved that the Wdr5 inhibitor OICR9429 significantly reduced Ang-II-induced cardiac fibrosis and increased the expression of P21 in cardiac fibroblasts. Inhibition of Wdr5 may mediate cardiac fibroblast cycle arrest through the Mdm2/P53/P21 pathway and alleviate cardiac fibrosis.