Therapeutic efficacy of ECs Foxp1 targeting Hif1α-Hk2 glycolysis signal to restrict angiogenesis.

Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

Niobium carbide MXenzyme-Driven comprehensive cholesterol regulation for photoacoustic image-guided and anti-inflammatory photothermal ablation in atherosclerosis.

Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls. They release inflammatory molecules that attract additional immune cells, leading to further macrophage recruitment and plaque development. In this study, we develop an osteopontin (OPN) antibody-conjugated niobium carbide (Nb2C-aOPN) MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment. This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux. Nb2C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties, including catalase, superoxide dismutase, peroxidase and glutathione peroxidase, and acts as a scavenger for reactive oxygen and nitrogen species. The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux, leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2. This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.

Sonosynthetic Cyanobacteria Oxygenation for Self-Enhanced Tumor-Specific Treatment.

Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well-known low penetration depth of external light. Here, ultrasound-mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound-induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof-of-concept sonosynthesis (sonoafterglow-induced photosynthesis) in cancer therapy. Chlorin e6, a typical small-molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue-penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia-inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis.

Piezocatalytic Schottky Junction Treats Atherosclerosis by a Biomimetic Trojan Horse Strategy.

The atherosclerotic vulnerable plaque is characterized by the foamy macrophage burden, involving impaired cholesterol efflux and deficient efferocytosis. Correspondingly, piezocatalytic therapy is an emerging solution for eliminating the foamy macrophage burden with satisfactory spatiotemporal controllability and deep penetration depth. Herein, a biomimetic Trojan horse (Au-ZnO@MM) is engineered by coating the macrophage membrane (MM) onto the surface of a rod-like Au-ZnO Schottky Junction to effectively relieve the atherosclerotic progression. These Trojan horses with the coating of MM are actively transported into subsistent foamy macrophages and generate abundant reactive oxygen species (ROS) via ultrasound-activated piezocatalysis. ROS-initiated autophagy and mitochondrial dysfunction induce substantial cell apoptosis, alleviating the burden of subsistent foamy macrophages. The resulting apoptotic fragments further significantly facilitate cholesterol excretion and trigger efferocytosis of intraplaque fresh macrophages. Ultimately, the biomimetic Au-ZnO@MM piezocatalyst not only inhibits the foaming capacity of macrophages, but also improves the function of removing cell debris, which can stabilize atherosclerotic vulnerable plaque. Meanwhile, the plasmon resonance effect of integrated gold nanoparticles enables favorable photoacoustic molecular imaging for real-time image-guided atherosclerotic therapy. This proposed biomimetic Trojan horse strategy provides the paradigm of employing ultrasound-activated piezocatalytic methodology for enhanced atherosclerotic theranostics.

Soluble PILRα: A novel plasma biomarker for atrial fibrillation progression and recurrence after catheter ablation.

BACKGROUND: We aimed to identify plasma biomarkers of atrial fibrillation (AF) progression and recurrence after catheter ablation. METHODS: Using AF gene profiling data from GEO database, a weighted gene co-expression network analysis (WGCNA) was conducted to determine the most significant module and hub genes associated with AF. Subsequently, 318 consecutively admitted patients who had undergone radiofrequency catheter ablation were enrolled in this study. RESULTS: WGCNA results revealed that paired immunoglobulin-like type 2 receptor alpha (PILRA) was the only black module gene highly correlated with clinical traits. Plasma soluble PILRα (sPILRα) levels were elevated in patients with AF and significantly elevated in patients with persistent versus paroxysmal AF (4.64 ± 2.74 vs. 3.04 ± 1.56 ng/mL, p < 0.001). Elevated sPILRα level was an independent risk factor for AF progression even after adjusting for traditional factors (adjusted odds ratio: 3.06, 95 % confidence interval [CI]: 1.88-5.27, p < 0.001) and AF recurrence after catheter ablation in patients with persistent AF (adjusted hazards ratio: 4.41, 95 % CI: 1.22-15.92, p = 0.023). CONCLUSIONS: WGCNA screening of GEO microarray gene profiling data showed PILRA expression levels to be correlated with AF progression and recurrence after catheter ablation in patients with persistent AF.

[Clinical application and effectiveness of patellar tunnel locator in medial patellofemoral ligament reconstruction surgery].

Objective: To evaluate the operability and effectiveness of a self-developed patellar bone canal locator (hereinafter referred to as "locator") in the reconstruction of the medial patellofemoral ligament (MPFL). Methods: A total of 38 patients with recurrent patellar dislocation who met the selection criteria admitted between January 2022 and December 2022 were randomly divided into study group (the patellar canal was established with a locator during MPFL reconstruction) and control group (no locator was used in MPFL reconstruction), with 19 cases in each group. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, body mass index, disease duration, patella Wiberg classification, constituent ratio of cartilage injury, Caton index, tibia tubercle-trochlear groove, and preoperative Lysholm score, Kujal score, Tegner score, visual analogue scale (VAS) score, and so on. The Lysholm score, Kujal score, Tegner score, and VAS score were used to evaluate knee joint function before operation and at 3 days,1 month, 3 months, and 6 months after operation. The ideal prepatellar cortical thickness and canal length were measured before operation, and the actual prepatellar cortical thickness and canal length after operation were also measured, and D1 (the distance between the ideal entrance and the actual entrance), D2 (the ideal canal length minus the actual canal length), D3 (the ideal prepatellar cortical thickness minus the actual prepatellar cortical thickness) were calculated. Results: Patients in both groups were followed up 6-8 months (mean, 6.7 months). The incision length and intraoperative blood loss in the study group were smaller than those in the control group, but the operation time was longer than that in the control group, the differences were significant ( P<0.05). There was no complication such as incision infection, effusion, and delayed healing in both groups, and no further dislocation occurred during follow-up. One patient in the study group had persistent pain in the anserine area after operation, and the symptoms were relieved after physiotherapy. The VAS score of the two groups increased significantly at 3 days after operation, and gradually decreased with the extension of time; the change trends of Lysholm score, Kujal score, and Tegner score were opposite to VAS score. Except that the Lysholm score and Kujal score of the study group were higher than those of the control group at 3 days after operation, and the VAS score of the study group was lower than that of the control group at 3 days and 1 month after operation, the differences were significant ( P<0.05), there was no significant difference in the scores between the two groups at other time points ( P>0.05). Patellar bone canal evaluation showed that there was no significant difference in preoperative simulated ideal canal length, prepatellar cortical thickness, and postoperative actual canal length between the two groups ( P>0.05). The postoperative actual prepatellar cortical thickness of the study group was significantly smaller than that of the control group ( P<0.05). D1 and D3 in the study group were significantly higher than those in control group ( P<0.05), but there was no significant difference in D2 between the two groups ( P>0.05). Conclusion: The locator can improve the accuracy of MPFL reconstruction surgery, reduce the possibility of intraoperative damage to the articular surface of patella and postoperative patellar fractures.

Plasma myeloperoxidase: association with atrial fibrillation progression and recurrence after catheter ablation.

Background: Myeloperoxidase (MPO), released by activated neutrophils, is significantly increased in atrial fibrillation (AF). MPO may play a role in the progression of atrial fibrillation and further involved in AF recurrence after catheter ablation. We compared plasma MPO levels in paroxysmal and persistent AF and explored their role in AF recurrence after catheter ablation. Methods: Plasma MPO levels were measured in consecutive patients with paroxysmal AF (n = 225) and persistent AF (n = 106). Samples of patients were collected from the femoral vein during catheter ablation and all patients included were followed up after catheter ablation. Results: Plasma MPO levels increased from paroxysmal AF to persistent AF patients (56.31 [40.33-73.51] vs. 64.11 [48.65-81.11] ng/ml, p < 0.001). MPO significantly correlated with left atrium volume (LAV) and there existed a significant interaction between the two in relation to AF recurrence (p for interaction <0.05). During a median follow-up of 14 months, 28 patients with paroxysmal AF (12.44%) and 27 patients with persistent AF (25.47%) presented with recurrence after catheter ablation. The percentage of recurrence increased stepwise with increasing tertiles of MPO levels in both paroxysmal AF and persistent AF. MPO levels remained independently associated with AF recurrence after adjusting for potential confounding variables. Conclusion: MPO levels were higher in persistent AF than in paroxysmal AF and MPO was positively correlated with LAV in AF. Elevated MPO levels may predispose a switch in AF phenotype and AF recurrence after catheter ablation.

Different electrophysiological characteristics of cavo-tricuspid isthmus dependent atrial flutter guided by robotic magnetic navigation in patients with and without prior cardiac surgery.

BACKGROUD: Cavo- tricuspid isthmus dependent atrial flutter (CTI- AFL) is a common atrial arrhythmia in patients with prior cardiac surgery (postsurgical AFL) and without prior cardiac surgery (nonsurgical AFL). However, there is only limited data regarding the eletrophysiological differences between the CTI- AFL in the postsurgical patients and the nonsurgical patients. HYPOTHESIS: We aimed to investigate the differences in clinical and electrophysiological characteristics between the postsurgical group and nonsurgical group and to evaluate the acute and long-term outcomes after ablation guided by robotic magnetic navigation (RMN) in both the groups. Methods Fourty-two consecutive patients with nonsurgical AFL and 21 with postsurgical AFL were retrospectively analyzed in our center. Electrocardiographic (ECG) analysis and three-dimensional electrophysiological study were performed in all the patients. RESULTS: The results revealed that only 55.6% of postsurgical patients with proven counterclockwise (CCW) AFL presented with a typical ECG suggesting this mechanism. In contrast, 86.1% of nonsurgical patients demonstrated a typical ECG pattern for CCW AFL. In addition, we employed a reverse "U-curve" to facilitate radiofrequency delivery when ablating near the inferior vena cava ostium in the present study. Compared with the nonsurgical group, electroanatomical mapping showed the mean AFL cycle length was significantly longer (253.3 ± 40.4 vs. 234.1 ± 24.2 ms, p = 0.03) and the right atrium volume was larger (114.8 ± 26.0 vs. 97.5 ± 19.1 mL, p = 0.004) in the postsurgical group. Additionally, the procedural time (75.9 ± 21.3 vs. 61.6 ± 26.6 minutes, p = 0.03) and ablation time (53.0 ± 21.4 vs. 36.7 ± 25.6 minutes, p = 0.02) are much longer in the postsurgical group. However, the navigation index in the postsurgical group was significantly smaller (0.35 ± 0.08 vs. 0.43 ± 0.13, p = 0.01). Moreover, the acute and long-term success rates were comparable between the two groups. CONCLUSIONS: Catheter ablation of CTI-AFL with and without prior cardiac surgery guided by RMN are associated with high acute and long-term success rates, despite the procedural and ablation times are much longer in the postsurgical patients. However, ECG characteristics of the tachycardia may be misleading as they are more often atypical in patients after cardiac surgery.

Initial experience of a novel method for electrical isolation of the superior vena cava using cryoballoon in patients with atrial fibrillation.

BACKGROUND: Damage to the sinus node (SN) has been described as a potential complication of superior vena cava (SVC) isolation. There have been reports of permanent SN injury requiring pacemaker implantation during isolation of the SVC. HYPOTHESIS: It is safe and effective to isolate SVC with the second-generation 28-mm cryoballoon by using a novel method. METHODS: Forty-three patients (including six redo cases) with SVC-related atrial fibrillation (AF) from a consecutive series of 650 patients who underwent cryoballoon ablation were included. After pulmonary vein isolation was achieved, if the SVC trigger was identified, the SVC was electrically isolated using the cryoballoon. First, the cryoballoon was inflated in the right atrium (RA) and advanced towards the SVC-RA junction. After total occlusion was confirmed by dye injection with total retention of contrast in the SVC, the SVC-RA junction was determined. Next, the cryoballoon was deflated, advanced into SVC, then reinflated, and pulled back gently. The equatorial band of the cryoballoon was then set slightly (4.32 ± 0.71 mm) above the SVC-RA junction for isolation of the SVC. RESULTS: Real-time SVC potential was observed in all patients during ablation. The mean time to isolation was 24.5 ± 10.7 s. The SVC was successfully isolated in all patients. The mean number of freeze cycles was 2.5 ± 1.4 per patient, and the mean ablation time was 99.8 ± 22.7 s. A transient phrenic nerve (PN) injury occurred in one patient (2.33%). There were no SN injuries. Freedom from AF rates at 6 and 12 months was 97.7% and 93.0%, respectively. CONCLUSIONS: This novel method for SVC isolation using the cryoballoon is safe and feasible when the SVC driver during AF is determined and could avoid SN injury. PN function should still be carefully monitored during an SVC isolation procedure.

Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients.

BACKGROUND: The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. OBJECTIVES: This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. RESULTS: Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P < 0.001). We categorized these patients with diabetes into MPO level or activity tertile subgroups. Significant differences in the plaque progression ratio and prominent changes in the minimal lumen diameter, stenosis diameter and coronary artery stenosis score were observed across the tertile subgroups of MPO levels and activities (all P < 0.01). Moreover, serum MPO levels and activities correlated significantly with these indices of coronary artery disease severity after adjustment for other risk factors. Multivariable regression analyses revealed that serum MPO levels and activities remained independently associated with plaque progression, in addition to smoking, hypertension and CRP levels (all P < 0.05). CONCLUSIONS: Serum MPO levels and activities are significantly associated with coronary atherosclerotic plaque progression in patients with type 2 diabetes.

Prognostic Implications of Left Atrial Spontaneous Echo Contrast with Catheter Ablation of Nonvalvular Atrial Fibrillation Patients with Left Atrial Dilation.

Background: Left atrial spontaneous echo contrast (LASEC) can be detected by transesophageal echocardiography (TEE) before the catheter ablation of atrial fibrillation (AF), especially in patients with left atrial (LA) dilation. Whether LASEC has prognostic value in predicting the procedure outcomes in patients with an enlarged atrium is unknown. The prognostic implications of LASEC with the catheter ablation of AF patients with LA dilation will be evaluated in this study. Methods: AF patients scheduled to undergo catheter ablation in Ruijin Hospital, Shanghai, China, between January 2018 and June 2020 were screened for this prospective study. All patients underwent TEE before the procedure. Patients with a left atrial diameter (LAD; 45 mm ≤ LAD < 50 mm) and left atrial volume (LAV ≥ 120 mL) were enrolled in this study. The endpoint was AF/atrial tachycardia (AT) recurrence-free survival following a 3-month blanking period after the catheter ablation. All patients were followed up for 18 months. Results: This study included 123 AF patients, who were divided into the LASEC (n = 73) and no LASEC (n = 50) groups. Baseline patient characteristics were similar in the two groups. At the end of 18 months of follow-up, AF/AT recurrence-free survival was achieved in 33 (45.2%) and 34 (68.0%) patients in the LASEC and no LASEC groups, respectively (p = 0.013). In survival analysis, the LASEC group was also associated with a poor outcome of catheter ablation (log-rank test, p = 0.011; Cox regression, p = 0.015, HR = 2.058, 95%CI = 1.151−3.679). Meanwhile, during the follow-up AF/AT recurrence was observed in 30 (57.7%) and 15 (71.4%) cases in the mild and severe SEC groups, respectively. Ischemic stroke occurred in two patients in the LASEC group. Conclusions: LASEC could be a predictor of the recurrence of AF/AT after catheter ablation in AF patients with LA dilation. The higher the degree of LASEC, the worse the prognosis.

[Epidemiological and clinical characteristics analysis of 681 cases of thoracolumbar osteoporotic vertebral compression fractures].

Objective: To investigate the epidemiological and clinical characteristics of patients with thoracolumbar osteoporotic vertebral compression fracture (OVCF) treated by percutaneous vertebroplasty (PVP). Methods: The clinical and imaging data of 681 patients with thoracolumbar OVCF treated with PVP between January 2017 and December 2021 were collected. The epidemiological and clinical characteristics of the patients with thoracolumbar OVCF in single center were summarized from the aspects of demographic distribution (mainly including gender, age), fracture characteristic analysis [including pathological segments, bone mineral density, and body mass index (BMI)], and operation related results (including the distribution of unilateral and bilateral puncture and bone cement injection, postoperative effectiveness analysis and refracture). Results: Of the 681 patients, 134 (19.68%) were male and 547 (80.32%) were female, with a male-to-female ratio of 1∶4.08. The age ranged from 53 to 105 years, with an average of 75.3 years. The age group of 60-90 years old had the largest number of patients (91.04%); the high incidence age group of men was 70-90 years old (13.95%), and that of women was 60-80 years old (72.98%). A total of 836 vertebrae were involved, and the morbidity of thoracolumbar vertebrae (T 11-L 1) was the highest (56.34%, 471/836). The main type of fracture was compression fracture (92.58%, 774/836) and Kümmell disease (7.42%, 62/836). There were 489 cases (71.81%) of osteoporosis, including 66 males and 423 females, with a male-to-female ratio of 1∶6.42. There was significant difference in distribution of bone mineral density between male and female groups ( Z=-5.810, P<0.001). BMI showed 206 cases (30.25%) of underweight, 347 (50.95%) cases of normal, 58 cases (8.52%) of overweight, 42 cases (6.17%) of obese, and 28 cases (4.11%) of extremely obese. The difference in BMI distribution between male and female groups was significant ( Z=-2.220, P=0.026). Of 836 vertebral bodies, 472 (56.46%) were punctured unilaterally and 364 (43.54%) bilaterally. Most of the vertebral bodies (49.88%, 417/836) were injected with 5.0-6.9 mL bone cement, and most of them were distributed in thoracolumbar and lumbar vertebral bodies (T 11-L 3). The visual analogue scale (VAS) score and Oswestry disability index (ODI) of patients with unilateral puncture and bilateral puncture significantly improved at 6 months after operation ( P<0.001), and also the difference was significant between the two groups in the difference of pre- and post-operation ( P<0.001). There were 628 cases (92.22%) with the first occurrence of OVCF, and 53 cases (7.78%) with two or more times of OVCF, all of which were female patients, and 26 cases (49.06%) occurred in the adjacent segment of the previous PVP operation. Conclusion: Female were more than male in OVCF patients. Thoracolumbar vertebral body has the highest morbidity. Patients with low BMI are more likely to have osteoporosis, and patients with high BMI have a higher risk of compression fracture. The amount of bone cement injected through bilateral puncture was greater than that through unilateral puncture.

The feasibility of using remote magnetic navigation system as the primary technological training tool for novice cardiac electrophysiology operators in the catheter ablation of left-sided accessory pathway.

BACKGROUND: For novice operators, mastering catheter ablation of left-sided accessory pathway (LSAP) in a short duration of time without compromising efficacy and safety remains a challenge. In this study an attempt to shorten the learning curve by using robotics via a remote magnetic navigation (RMN) system was performed. METHODS: Novice physician fellows without prior catheter ablation experience initiated their process of learning LSAP ablation using the Niobe™ RMN system. Their procedure parameters were recorded and compared with experienced operators using RMN and manual catheter navigation (MCN). RESULTS: Novice operators quickly shortened the total procedure time after their first five procedures. In subsequent procedures, no significant difference in procedure time, fluoroscopy exposure or ablation time was observed between novice and experienced RMN operators. When compared to MCN operators, novice operators avoided excessive radiation exposure beginning with their first RMN procedure, while lower fluoroscopy doses were noted after five procedures. It was observed that procedure parameters did not differ significantly according to LSAP location. CONCLUSION: The RMN system is a practical and easy to use tool for novice electrophysiology operators to quickly master LSAP ablation, without compromising efficacy or safety. Additionally, when compared to MCN it also protects the operators and patients from excessive radiation exposure during the procedure.

Remifentanil versus Dexmedetomidine in Cardiac Surgery Patients with Noninvasive Ventilation Intolerance: Protocol for the REDNIVI Trial.

BACKGROUND: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. METHODS: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. CONCLUSIONS: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. CLINICAL TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

Comparison of the Mid-Term Outcomes of Robotic Magnetic Navigation-Guided Radiofrequency Ablation versus Cryoballoon Ablation for Persistent Atrial Fibrillation.

Introduction: Currently, numerous ablation techniques are available for atrial fibrillation (AF), in addition to manual radio frequency ablation. The aim of this prospective, non-randomized concurrent controlled trial was to compare the mid-term efficacy and procedural outcomes of persistent AF (PerAF) using cryoballoon (CB) and robotic magnetic navigation (RMN). Methods: Two hundred PerAF patients were assigned, in a 1:1 ratio, to undergo catheter ablation using RMN (RMN group) or CB (CB group). The primary endpoint was freedom from AF recurrence following a 3-month period after the index ablation. The secondary endpoint was peri-procedural outcomes, including the total procedure time, left atrial procedure time, fluoroscopy time, and fluoroscopy dose. The Two-step cluster analysis was used to determine the efficacy of RMN and CB between the different groups. The Cox proportional hazard model and restricted cubic spline were used to determine predictors for AF recurrence. Results: At the mean follow-up of 28.1 ± 9.7 months, the primary endpoint was achieved in 71 PerAF patients in the RMN group and in 62 PerAF patients in the CB group (71% vs. 62%, p = 0.158). Compared with CB, RMN-guided ablation led to a longer procedure time (p < 0.001), but with less radiation (p < 0.001). Cluster analysis returned two clusters of patients and RMN was favorable for one cluster (p = 0.037), in which more patients presented with diabetes mellitus and smaller left atria. Conclusions: For patients with PerAF, CB is generally equivalent to RMN-guided ablation with regard to overall efficacy. RMN-guided ablation could be favorable in specific patient populations presenting with diabetes mellitus and smaller left atria.

Utilization of steerable sheath improves the efficiency of atrial fibrillation ablation guided by robotic magnetic navigation compared with fixed-curve sheath.

BACKGROUND: The objective of this study was to assess the impact of steerable sheaths compared with fixed-curve sheaths on the procedural outcomes of atrial fibrillation (AF) ablation guided by robotic magnetic navigation (RMN). METHODS AND RESULTS: In this retrospective case-control study, 110 patients scheduled for AF catheter ablation were enrolled and divided into two groups. Fifty-five patients (paroxysmal, 70%) were treated with RMN-guided ablation utilizing a steerable sheath and another 55 patients (paroxysmal, 70%) were ablated with RMN using a fixed-curve sheath. Clinical characteristics were similar between the two groups. Compared with the fixed-curve sheath group, the steerable sheath group procedure time (111.9 ± 25.2 vs. 90.4 ± 20.7 min, p < .001) and radiofrequency (RF) time (35.9 ± 9.0 vs. 30.5 ± 7.4 min, p < .001) were significantly shortened. Additionally, the navigation index was significantly improved (0.41 ± 0.06 vs. 0.48 ± 0.08, p < .001) in the steerable sheath group. By employing a large catheter loop for targeting the right pulmonary veins (PVs), the steerable sheath group significantly reduced the RF delivery time (15.0 ± 3.0 vs. 12.0 ± 2.1 min, p < .001) during right-side PV isolation (PVI). However, total fluoroscopy time was similar between the two groups (5.6 ± 2.6 vs. 5.0 ± 2.0 min, p > .05). Acute PVI success rates were similar between the two groups. No major or minor complications occurred in either group. CONCLUSION: Appropriate utilization of steerable sheath technology can improve the efficiency of AF ablation guided by RMN, primarily by reducing the total procedure and RF delivery times of right-side PVI without compromising safety.

Plasma protein profiling analysis in patients with atrial fibrillation before and after three different ablation techniques.

Background: There are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources. Objectives: We evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation. Methods: Blood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein-protein interaction network and module analysis were conducted using Cytoscape software. Results: Of 181 proteins, 42 proteins in the cryoballoon group, 46 proteins in the radiofrequency balloon group, and 43 proteins in the radiofrequency group significantly changed after ablation. Most of the proteins altered significantly on the first day after ablation. Altered proteins were mainly involved in cytokine-cytokine receptor interaction. Both balloon-based ablations showed a similar shift toward enhancing cell communication and regulation of signaling while inhibiting neutrophil chemotaxis. However, radiofrequency ablation presented a different trend. Seed proteins, including osteopontin, interleukin-6, interleukin-10, C-C motif ligand 8, and matrix metalloproteinase-1, were identified. More significant proteins associated with hemorrhage and coagulation were selected in balloon-based ablations by machine learning. Conclusion: Plasma protein response after three different ablations in patients with AF mainly occurred on the first day. Radiofrequency balloon ablation shared similar alteration in protein profile as cryoballoon ablation compared with radiofrequency ablation, suggesting that lesion size rather than energy source is the determinant in pathophysiological responses to the ablation.

Differences in D-dimer blood concentration in atrial fibrillation patients with left atrial thrombus or severe left atrial spontaneous echo contrast.

PURPOSE: Severe left atrial spontaneous echo contrast (SLASEC) is considered the prior stage to thrombosis and a high-risk factor for thrombotic events. Studies have suggested an effect of D-dimer blood concentration on exclusion of left atrial thrombus (LAT), but it remains unclear whether D-dimer concentrations differ between atrial fibrillation (AF) patients with SLASEC or LAT. METHODS: Nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2017 and July 2020 were screened for this prospective study. All patients underwent transesophageal echocardiography (TEE) to detect SLASEC or LAT. D-dimer concentrations were measured at the time of TEE. Clinical data including CHA2DS2-VASc score were evaluated. Major complications with thromboembolism in the SLASEC group were followed up at least 6 months after therapy. RESULTS: Among 920 consecutively enrolled nonvalvular AF patients, 30 patients with SEC grade 0, 35 patients with SLASEC, and 22 patients with LAT were included. D-dimer concentration and CHA2DS2-VASc score were significantly lower in the SLASEC group compared with the LAT group (D-dimer, 0.26±0.13 vs. 0.86±0.9 mg/L, P<0.05; CHA2DS2-VASc score, 2.3±0.9 vs. 3.1±1.5, P=0.02). The cut-off value for D-dimer concentration (0.285 mg/L) had sensitivity of 77.3% and specificity of 80.0% for prediction of LAT. D-dimer concentration showed a decreasing trend with a significant difference (0.42±0.22 vs. 0.33±0.18 mg/L, P=0.03) for 9 patients in the LAT group after complete thrombus resolution by anticoagulation treatment. No major or fatal bleeding, ischemic stroke, or systemic thromboembolism events occurred in the SLASEC group during the 6-month follow-up. CONCLUSIONS: This study demonstrated a significantly lower D-dimer concentration and CHA2DS2-VASc score in AF patients with SLASEC than in those with LAT. The D-dimer cut-off value (0.285 mg/L) can be used as an effective reference index to distinguish the pre-thrombotic state of LAT from LAT. D-dimer blood concentration may be a predictor of LAT thrombolysis.

Remote magnetic-guided ablation for three origins of idiopathic ventricular arrhythmias with right bundle branch block and superior axis.

BACKGROUND: Idiopathic ventricular arrhythmias (IVAs) with right bundle branch block (RBBB) and superior axis commonly originate from posterior mitral annulus (PMA), the left ventricular (LV) posterior fascicle (LPF), and the LV posterior papillary muscles (PPM). HYPOTHESIS: Remote magnetic navigation (RMN)-guided ablation might be safe and effective for these three origins of IVAs. METHODS: Thirty consecutive IVA patients with RBBB and superior axis (11 MPA-IVAs, 11 LPF-IVAs, and 8 PPM-IVAs) were included in this study. Electrical mapping and ablation with RMN were performed in the LV through a trans-septal approach. Navigation index, defined as the ratio of total radiofrequency (RF) time and the time from first burn to last burn, was used to determine the efficiency of RMN-guided ablation. RESULTS: The overall acute success rate was achieved in 93% (PMA, 100%; LPF, 91%; PPM, 88%; p > 0.05). No complication occurred in this study. The procedure time of PPM-IVAs group was 34 and 14 min longer when compared with MPA-IVAs and LPF-IVAs group, respectively, without an increase of X-ray time. The mean navigation index was 0.45 ± 0.20. The PPM-IVAs group had an underperforming navigation index value (0.29 ± 0.11) (p < 0.01), as longer RF time was required in the PPM-IVAs group. CONCLUSIONS: RMN-guided ablation can achieve a high acute success rate for IVAs with RBBB and superior axis. The lower navigation index for PPM-IVAs indicated that increasing the RF time and improving the catheter contact should be considered when using RMN.

Label-free proteomic analysis of serum exosomes from paroxysmal atrial fibrillation patients.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac heterogeneous rhythm disorder. It represents a major cause of mortality and morbidity, mainly related to embolic events and heart failure. Mechanisms of AF are complex and remain incompletely understood. Recent evidence suggests exosomes are membrane-coated objects released by many cell-types. Their presence in body fluids and the variable surface composition and content render them attractive as a mechanism for potential biomarkers. However, the content of serum exosomes of AF patients has not been fully delineated. METHODS: In this work, the serum exosomes from AF patients and healthy donors were used to compare changes in the exosome protein content. Exosomes were isolated from serum of AF patients and healthy donors and their purity was confirmed by Western blotting assays and transmission electron microscopy (TEM). Label-free LC-MS/MS quantitative proteomic analysis was applied to analyze protein content of serum exosomes. RESULTS: A total of 440 exosomal protein groups were identified, differentially expressed proteins were filtrated with fold change ≥ 2.0 (AF/controls protein abundance ratio ≥ 2 or ≤ 0.5) and p value less than 0.05 (p < 0.05), significantly changed in abundance group contains 39 elevated proteins and 18 reduced proteins, while consistent presence/absence expression profile group contains 40 elevated proteins and 75 reduced proteins. Bioinformatic analysis of differential exosomal proteins confirmed the significant enrichment of components involved in the anticoagulation, complement system and protein folding. Parallel-Reaction Monitoring Relative Quantitative Analysis (PRM) further suggested that AF related to complement system and protein folding. CONCLUSIONS: These results revealed the composition and potential function of AF serum exosomes, thus providing a new perspective on the complement system and protein folding to AF.