A universal nanoreactor triggering butterfly effect for encouraging Fenton/Fenton-like reactions and chemodynamic therapy.

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M(n+1)+) to low-valent ions (Mn+) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H2O2 conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M(n+1)+ to Mn+ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H2O2 and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe3O4 and MoS2, thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine.

Nanomedicine alleviates doxorubicin-induced cardiotoxicity and enhances chemotherapy synergistic chemodynamic therapy.

Doxorubicin (DOX) is widely used in clinic as a broad-spectrum chemotherapy drug, which can enhance the efficacy of chemodynamic therapy (CDT) by interfering tumor-related metabolize to increase H2O2 content. However, DOX can induce serious cardiomyopathy (DIC) due to its oxidative stress in cardiomyocytes. Eliminating oxidative stress would create a significant opportunity for the clinical application of DOX combined with CDT. To address this issue, we introduced sodium ascorbate (AscNa), the main reason is that AscNa can be catalyzed to produce H2O2 by the abundant Fe3+ in the tumor site, thereby enhancing CDT. While the content of Fe3+ in heart tissue is relatively low, so the oxidation of AscNa had tumor specificity. Meanwhile, due to its inherent reducing properties, AscNa could also eliminate the oxidative stress generated by DOX, preventing cardiotoxicity. Due to the differences between myocardial tissue and tumor microenvironment, a novel nanomedicine was designed. MoS2 was employed as a carrier and CDT catalyst, loaded with DOX and AscNa, coating with homologous tumor cell membrane to construct an acid-responsive nanomedicine MoS2-DOX/AscNa@M (MDA@M). In tumor cells, AscNa enhances the synergistic therapy of DOX and MoS2. In cardiomyocytes, AscNa could effectively reduce the cardiomyopathy induced by DOX. Overall, this study enhanced the clinical potential of chemotherapy synergistic CDT.

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.

Development and validation of a novel nomogram for predicting recurrent atrial fibrillation after cryoballoon ablation.

Background: Few studies have explored the use of machine learning models to predict the recurrence of atrial fibrillation (AF) in patients who have undergone cryoballoon ablation (CBA). We aimed to explore the risk factors for the recurrence of AF after CBA in order to construct a nomogram that could predict this risk. Methods: Data of 498 patients who had undergone CBA at Ruijin Hospital, Shanghai Jiaotong University School of Medicine, were retrospectively collected. Factors such as clinical characteristics and biophysical parameters during the CBA procedure were collected for the selection of variables. Scores for all the biophysical factors-such as time to pulmonary vein isolation (TTI) and balloon temperature-were calculated to enable construction of the model, which was then calibrated and compared with the risk scores. Results: A 36-month follow-up showed that 177 (35.5%) of the 489 patients experienced AF recurrence. The left atrial volume, TTI, nadir cryoballoon temperature, and number of unsuccessful freezes were related to the recurrence of AF (P < .05). The area under the curve (AUC) of the nomogram's time-dependent receiver operating characteristic curve was 77.6%, 71.6%, and 71.0%, respectively, for the 1-, 2-, and 3-year prediction of recurrence in the training cohort and 77.4%, 74.7%, and 68.7%, respectively, for the same characteristics in the validation cohort. Calibration and data on the nomogram's clinical effectiveness showed it to be accurate for the prediction of recurrence in both the training and validation cohorts as compared with established risk scores. Conclusion: Biophysical parameters such as TTI and cryoballoon temperature have a great impact on AF recurrence. The predictive accuracy for recurrence of our nomogram was superior to that of conventional risk scores.

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.

Robotic magnetic navigation-guided pulmonary vein isolation in an atrial fibrillation patient with dextrocardia situs inversus: techniques and potential advantages.

BACKGROUND: Dextrocardia with situs inversus (DSI) is a very rare congenital anomaly. Catheter manipulation and ablation of atrial fibrillation (AF) in patients with this anatomical variant is challenging for the operators. This case report presents a safe and effective AF ablation guided by the robotic magnetic navigation (RMN) system in combination with intracardiac echocardiograhy (ICE) in a patient with DSI. CASE PRESENTATION: A 64-year-old male with DSI was referred for catheter ablation of symptomatic, drug-refractory paroxysmal AF. One transseptal access was achieved via the left femoral vein under the guidance of ICE. The three-dimensional reconstruction of the left atrium and the pulmonary veins (PVs) were performed by the magnetic catheter using the CARTO and the RMN system. Then, the electroanatomic map and pre-acquired CT images were merged. Finally, bilateral circumferential ablation lines were delivered around the ipsilateral PV ostia to achieve complete PV isolation (PVI). CONCLUSIONS: This case demonstrates that AF catheter ablation under the guidance of the RMN system using ICE is feasible and safe in a patient with DSI. Moreover, the combination of these technologies broadly facilitates treatment of patients with complex anatomy, while reducing the risk of complications.

Highly sensitive H2O2-scavenging nano-bionic system for precise treatment of atherosclerosis.

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 µmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

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.

Early recurrence after cryoballoon versus radiofrequency ablation for paroxysmal atrial fibrillation: mechanism and implication in long-term outcome.

BACKGROUND: Early recurrence (ER) after catheter ablation for atrial fibrillation (AF) has been considered as a common phenomenon but its mechanism and implication in long-term outcome has not been fully elucidated. We aimed to clarify the relation between post-ablation inflammation and ER after cryoballoon ablation (CBA) or radio-frequency ablation (RFA) and evaluate the clinical significance of ER. METHODS: A total of 154 patients with paroxysmal AF undergoing ablation were consecutively recruited, including 90 patients undergoing RFA (RF group) and 64 patients undergoing CBA (CB group). Myocardial injury and inflammation biomarkers were analyzed before and 6 h, 24 h and 48 h after ablation. Acute early recurrence (AER), non-acute early recurrence (NAER) and late recurrence (LR) was defined as recurrence of atrial tachyarrhythmia during 0-3, 4-90 days and beyond a 90-day blanking period after ablation. RESULTS: Cardiac troponin I was significantly higher in CB group while C reactive protein (CRP) and Ratio Neutrophil/Lymphocyte were more elevated in RF group. Higher CRP level after RFA was significantly associated with AER in RF group and lower CRP level after CBA was predictive of AER in CB group. In addition, average cryoablation duration was positively correlated with CRP level after CB group. Cox regression revealed that NAER and left atrial diameter were associated with LR in RF group, while AER and NAER were predictive of LR after CBA. CONCLUSIONS: Post-ablation inflammation was greater in RFA than in CBA. Excessive inflammatory response may be an important factor of AER after RFA. AER after CBA was related with lower inflammation and predictive of LR. Further investigations are still warranted to address on these findings.

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.

Long-term outcomes of a time to isolation - based strategy for cryoballoon ablation compared to radiofrequency ablation in patients with symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon ablation (CBA) is one of the most commonly used technologies designed for pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF), although the dosing of CBA remains controversial. We evaluated the long-term efficacy and safety of a novel individualized strategy of CBA compared to radiofrequency ablation (RFA) for patients with PAF. METHODS: In this observational study, symptomatic patients with drug-refractory paroxysmal AF were prospectively consented and enrolled in four centers, being assigned either to the CBA or RFA arm for ablation. In the CBA group, we used a time to isolation (TTI) - based dosing protocol. The primary endpoint was the recurrence of atrial arrhythmia >30 s following a 90-day blanking period. The secondary endpoint was procedure-related complications and procedure parameters. RESULTS: A total of 500 patients were recruited in either the CBA group (n = 247) or the RFA group (n = 253) between January 2017 and July 2018. After a median follow-up of 778 days, the atrial tachyarrhythmia-free survival was 71.7% in the CBA group and 67.0% in the RFA group. CBA and RFA displayed similar major or minor complication occurrence, while the former had a significantly shorter procedure duration (82.5 min vs. 141.1 min, p < .001) and left atrial dwell time (60.1 min vs. 109.9 min, p < .001) but longer fluoroscopy exposure (13.8 min vs. 8.1 min, p < .001). CONCLUSION: Compared to RFA, our TTI-based CBA dosing protocol showed comparable efficacy and safety, with a significantly reduced procedure duration in patients with PAF.

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.

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.

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.

Cyclized Polyacrylonitrile as a Promising Support for Single Atom Metal Catalyst with Synergistic Active Site.

Metal single atom catalysts (SAC) have been successfully used in heterogeneous catalysis but developing a scalable and economic support for SAC is still a great challenge. Here, cyclized polyacrylonitrile (CPAN) is proposed as a promising support for single atom metal catalysts. CPAN can be easily prepared from cheap industrial product polyacrylonitrile (PAN), which has excellent processability. A series of SAC on CPAN (M/CPAN, M = Ag, Cu, Ru) are designed and the catalytic activities of the as synthesized M/CPAN are investigated by the model reduction reaction of p-nitrophenol (4-NP). M/CPAN presents excellent catalytic performance with high stability and theoretical calculations elucidate that Ag/CPAN synergistically catalyze 4-NP reduction following the Langmuir-Hinshelwood (L-H) mechanism with 4-NP preferentially adsorbing at the Ag sites and H adsorbing at the bridge C sites. These results, for the first time, reveal that the single atom on CPAN can catalyze 4-NP reduction efficiently. This methodology provides a convenient route for the preparation of a variety of SAC, and this strategy is readily scalable and holds great potential in catalytic applications.

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.

Association between the rs2106261 polymorphism in the zinc finger homeobox 3 gene and risk of atrial fibrillation: Evidence from a PRISMA-compliant meta-analysis.

INTRODUCTION: Previous genome-wide studies have identified an association between the rs2106261 single-nucleotide polymorphism (SNP) in the zinc finger homeobox 3 (ZFHX3) gene and an increased risk of atrial fibrillation (AF). However, this association remains controversial, since conflicting results have been reported in previous studies. We aimed to investigate the association between the ZFHX3 rs2106261 polymorphism and susceptibility to AF. METHODS: A comprehensive literature search, of articles written in either English or Chinese, was conducted on various databases, including PubMed, Embase, Web of Science, the Cochrane library, Wan Fang, and CNKI, for studies performed up to August 1, 2020. Data were abstracted and pooled using Stata 14.0 software. A meta-analysis was performed on all selected studies based on ZFHX3 rs2106261 polymorphism genotypes. RESULTS: Nine studies, including 10,107 cases and 58,663 controls, were analyzed in the meta-analysis. In the overall population, a significant association was found between AF and the T-allelic ZFHX 3 rs2106261 SNP (odds ratio [OR] = 1.32, 95% confidence interval [CI] 1.19-1.46). In subgroup analysis, a significant association between the T-allele of rs7193343 and risk of AF in Caucasian (OR = 1.23, 95% CI 1.10-1.37) and Asian subgroups (OR = 1.58, 95% CI 1.32-1.89) was observed. However, no statistically significant association was found in African populations (OR = 1.06, 95% CI 0.95-1.19). CONCLUSION: The genetic variant rs2106261 SNP is associated with susceptibility to AF in Caucasian and Asian individuals, with Asian samples showing a stronger association. However, based on the current evidence, no association was found in African samples. Future studies, with larger sample sizes and multiple ethnicities, are still necessary.

Ibutilide Reduces Ventricular Defibrillation Threshold and Organizes Ventricular Fibrillation Activation in Canine Heart Failure Model.

PURPOSE: To compare the effects of class III antiarrhythmic agents (amiodarone vs. ibutilide) on ventricular fibrillation (VF) and hemodynamic status in a canine heart failure (HF) model. METHODS: A total of 12 beagles were used to establish the HF model by rapid pacing for 4 consecutive weeks. These canines were randomly divided into two groups based on the administration of ibutilide and amiodarone. A 12 × 12 unipolar electrode plaque was used for ventricular epicardial mapping, and a 6-electrode plunge needle was inserted for ventricular transmural mapping. The restitution curve was estimated from activation recovery intervals (ARIs) by pacing from the plaque electrodes before and after drug administration. The defibrillation threshold (DFT) and VF activation patterns, including the activation rate, cycle length (VF-CL) and the transmural dispersion of the activation rate, were evaluated and the hemodynamic parameters were mearsured and compared before and after drug administration. RESULTS: Compared to HF baseline, ibutilide administration has markedly decreased the DFT by 28% (18 ± 2 J vs. 13 ± 2.7 J, P < 0.01) without affecting the canine's hemodynamics (mean arterial pressure 91 ± 15 mmHg vs. 92 ± 17 mmHg, P > 0.05). Furthermore, VF activation pattern became more organized, and spontaneous termination was observed only after ibutilide administration. Conversely, amiodarone has significantly compromised the hemodynamic status (mean arterial pressure 92 ± 6.1 mmHg vs. 52 ± 11.6 mmHg, P < 0.05), but did not alter the DFT (17 ± 2.3 J vs. 16 ± 2.0 J, P > 0.05). Compared to pre-medication, both ibutilide and amiodarone have significantly prolonged the VERP (178 ± 9.6 ms vs. 208 ± 8.9 ms, P < 0.05; 185 ± 10.5 ms vs. 202 ± 7.5 ms, P < 0.05, respectively) and reduced the dispersion of refractoriness, the maximal slope of restitution curve, and the epicardial dispersion during pacing. Additionally, both drugs have significantly increased the VF-CL and reduced the transmural dispersion of the VF activation rate. CONCLUSIONS: Ibutilide had potential antifibrillatory properties, which was shown by decreasing the DFT and organizing the VF activation in HF, and with no apparent impact on the hemodynamic status. In contrast, intravenous amiodarone administration demonstrated prominent negative effects on the hemodynamic status possibly by affecting the myocardial contractility before and after defibrillation but did not alter the DFT.

Strategy of catheter ablation for para-Hisian premature ventricular contractions with the assistance of remote magnetic navigation.

INTRODUCTION: Catheter ablation of frequent para-Hisian premature ventricular contractions (PH-PVCs) is considered to be challenging. The purpose of this study was to evaluate the strategy, potential technical advantages, and clinical outcomes of remote magnetic navigation (RMN) in the ablation of PH-PVCs. METHODS: Fifteen consecutive patients with PH-PVCs were included in this study. Electrical mapping was initially performed in the right ventricular septum by manipulating the RMN catheter with a "U-curve." In the case of no optimal ablation site or ablation failure, the ablation catheter was directed to the left ventricular (LV) septum through a transseptal approach for further mapping and ablation by manipulating the RMN catheter with a "reverse S-curve." RESULTS: Nine of 15 patients were submitted to ablation on the right side. However, ablation success was only achieved in only three (33%) cases. Of the other 12 patients, 11 underwent LV mapping and ablation. In this subset, 9 of 11 (82%) PH-PVCs were totally eliminated on the left side. Overall, RMN-guided mapping and ablation successfully eliminated 12 (80%) of 15 idiopathic PH-PVCs. During follow-up, the reoccurrence of PVCs was reported in 1 (8%) of 12 patients. No atrioventricular block was observed during or after the procedure. CONCLUSION: RMN-guided catheter ablation for PH-PVCs is effective and safe in unselected patients. Due to the excellent reachability and contact with special morphologies of the RMN catheter on both sides of the ventricular septum, RMN can be considered an effective approach for frequent PH-PVCs.