Ti3C2 mediates the NiFe-LDH layered electrocatalyst to enhance the OER performance for water splitting.

Oxygen evolution reaction (OER) is a very complex process with slow reaction kinetics and high overpotential, which is the main limitation for the commercial application of water splitting. Thus, it is of necessary to design high-performance OER catalysts. NiFe based layered double hydroxides (NiFe-LDHs) have recently gained a lot of attention due to their high reaction activity and simple manufacturing process. In this study, a novel electrocatalyst based on NiFe-LDH was constructed by introducing Ti3C2, which was utilized to modulate the structural and electronic properties of the electrocatalysts. Structural examinations reveal that the Ti3C2 of 2D structure successfully dope the NiFe-LDHs nanosheets, forming NiFe-LDH/Ti3C2 heterojunctions. Firstly, the heterojunction substantially reduces the charge transfer resistance, promoting the electron migration between the LDH nanosheets. Secondly, theoretical calculations demonstrate that the energy barrier between the rate-determining step from *OH to *O is lowered, favoring the formation of the reaction intermediates and thus the occurrence of OER. As a result, the composite electrocatalyst exhibits a low overpotential of 334 mV at a current density of 10 mA/cm2 and a small Tafel slope of 55 mV/dec, which are superior to those of the NiFe-LDH by 11.2 % and 38.5 %, respectively. This study provides inspiration for promoting the performances of NiFe based electrocatalysts by utilizing 2D materials.

Two-Dimensional SnS Mediates NiFe-LDH-Layered Electrocatalyst toward Boosting OER Activity for Water Splitting.

NiFe-layered double hydroxides (NiFe-LDHs), as promising electrocatalysts, have received significant research attention for hydrogen and oxygen generation through water splitting. However, the slow oxidation kinetics of NiFe-LDH, due to the limited number of active sites and the low conductivity, hinders the improvement of the water-splitting efficiency. Therefore, to overcome the obstacles, two-dimensional (2D) SnS was first explored to tailor the prepared NiFe-LDH via the hydrothermal method. A NiFe-LDH/SnS heterojunction is built, which is observed from the microstructural investigations. SnS incorporation could greatly improve the conductivity of the NiFe-LDH sheets, which was reflected by the reduced charge transfer resistance. Moreover, SnS layers modulated the electronic environment around the active sites, favoring the adsorption of intermediates during the oxygen evolution reaction (OER) process, which was verified by density functional theory calculations. A synergistic effect induced by the NiFe-LDH/SnS heterostructure promoted the OER activities in electrical, electronic, and energetic aspects. Consequently, the as-prepared NiFe-LDH/SnS electrocatalyst greatly improved the electrocatalytic performance, exhibiting 20% and 27% reductions in the overpotential and Tafel slope compared with those of pristine NiFe-LDH, respectively. The results provide a strategy for regulating NiFe-based electrocatalysts by using emerging 2D materials to enhance water-splitting efficiency.

Fecal calprotectin: A novel predictor of ulcerated esophageal injury after atrial fibrillation catheter ablation.

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.

Use of intracardiac echocardiography in vein of Marshall ethanol infusion for ablation of persistent atrial fibrillation.

BACKGROUND: Few methods have been reported to demonstrate real-time effects during vein of Marshall (VOM) ethanol infusion in persistent atrial fibrillation (PeAF). OBJECTIVE: This study was to evaluate the impact of left atrial (LA) monitoring using intracardiac echocardiography (ICE) during VOM ethanol infusion. METHODS: Seventy-four consecutive patients with PeAF who underwent VOM ethanol infusion followed by radiofrequency (RF) ablation were included. Patients with findings on ICE consistent with echogenic streaming in the LA and with increased myocardial local echogenicity along the VOM area were placed into one group (group A) and those without into the other group (group B). Outcomes between the 2 groups were compared. RESULTS: Forty-six patients (62%) were placed into group A. A new ethanol-induced low-voltage area in group A was larger than that in group B (8.5 cm2 [5.5-10.2 cm2] and 4.0 cm2 (2.4-6.3 cm2]; P < .001). The RF ablation time required to achieve MI block was reduced in group A patients (263.0 seconds [196.0-351.0 seconds] vs 417.0 seconds [315.0-709.5 seconds] in group B patients; P < .001). MI block was achieved in 46 patients (100%) via an endocardial approach in group A and 27 patients (96.4%) in group B (extra coronary sinus ablation in 4 patients). One patient developed clinically significant pericardial effusions and required pericardiocentesis in group B. CONCLUSION: Presence of increased myocardial local echogenicity at the ridge and consistent echogenic streaming in the LA detected by ICE-based imaging during VOM ethanol infusion suggests increased ablated tissue in that region and lower RF ablation time during ablation for PeAF.

Feasibility and safety of left bundle branch area pacing for patients with stable coronary artery disease.

Aims: Stable coronary artery disease (CAD) is a prevalent comorbidity among patients requiring pacemaker implantation. This comorbidity may have an impact on the safety and prognosis of traditional right ventricular pacing (RVP). Left bundle branch area pacing (LBBaP) is a new physiological pacing modality. Our aim was to investigate the feasibility and safety of LBBaP in patients with the stable CAD. Methods: This study included 309 patients with symptomatic bradycardia who underwent LBBaP from September 2017 to October 2021. We included 104 patients with stable CAD (CAD group) and 205 patients without CAD (non-CAD group). Additionally, 153 stable CAD patients underwent RVP, and 64 stable CAD patients underwent His-bundle pacing (HBP) were also enrolled in this study. The safety and prognosis of LBBaP was assessed by comparing pacing parameters, procedure-related complications, and clinical events. Results: During a follow-up period of 17.4 ± 5.3 months, the safety assessment revealed that the overall rates of procedure-related complications were similar between the stable CAD group and the non-CAD group (7.7% vs. 3.9%). Likewise, similar rates of heart failure hospitalization (HFH) (4.8% vs. 3.4%, stable CAD vs. non-CAD) and the primary composite outcome including death due to cardiovascular disease, HFH, or the necessity for upgrading to biventricular pacing (6.7% vs. 3.9%, stable CAD vs. non-CAD), were observed. In stable CAD patients, LBBaP demonstrated lower pacing thresholds and higher R wave amplitudes when compared to HBP. Additionally, LBBaP also had significantly lower occurrences of the primary composite outcome (6.7% vs. 19.6%, P = 0.003) and HFH (4.8% vs. 13.1%, P = 0.031) than RVP in stable CAD patients, particularly among patients with the higher ventricular pacing (VP) burden (>20% and >40%). Conclusion: Compared with non-CAD patients, LBBaP was found to be attainable in stable CAD patients and exhibited comparable mid-term safety and prognosis. Furthermore, in the stable CAD population, LBBaP has demonstrated more stable pacing parameters than HBP, and better prognostic outcomes compared to RVP.

Patient-specific iPSC-derived cardiomyocytes reveal aberrant activation of Wnt/ß-catenin signaling in SCN5A-related Brugada syndrome.

BACKGROUND: Mutations in the cardiac sodium channel gene SCN5A cause Brugada syndrome (BrS), an arrhythmic disorder that is a leading cause of sudden death and lacks effective treatment. An association between SCN5A and Wnt/ß-catenin signaling has been recently established. However, the role of Wnt/ß-catenin signaling in BrS and underlying mechanisms remains unknown. METHODS: Three healthy control subjects and one BrS patient carrying a novel frameshift mutation (T1788fs) in the SCN5A gene were recruited in this study. Control and BrS patient-specific induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts using nonintegrated Sendai virus. All iPSCs were differentiated into cardiomyocytes using monolayer-based differentiation protocol. Action potentials and sodium currents were recorded from control and BrS iPSC-derived cardiomyocytes (iPSC-CMs) by single-cell patch clamp. RESULTS: BrS iPSC-CMs exhibited increased burden of arrhythmias and abnormal action potential profile featured by slower depolarization, decreased action potential amplitude, and increased beating interval variation. Moreover, BrS iPSC-CMs showed cardiac sodium channel (Nav1.5) loss-of-function as compared to control iPSC-CMs. Interestingly, the electrophysiological abnormalities and Nav1.5 loss-of-function observed in BrS iPSC-CMs were accompanied by aberrant activation of Wnt/ß-catenin signaling. Notably, inhibition of Wnt/ß-catenin significantly rescued Nav1.5 defects and arrhythmic phenotype in BrS iPSC-CMs. Mechanistically, SCN5A-encoded Nav1.5 interacts with ß-catenin, and reduced expression of Nav1.5 leads to re-localization of ß-catenin in BrS iPSC-CMs, which aberrantly activates Wnt/ß-catenin signaling to suppress SCN5A transcription. CONCLUSIONS: Our findings suggest that aberrant activation of Wnt/ß-catenin signaling contributes to the pathogenesis of SCN5A-related BrS and point to Wnt/ß-catenin as a potential therapeutic target.

Patient-specific iPSC-derived cardiomyocytes reveal variable phenotypic severity of Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation. METHODS: 26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol. FINDINGS: D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na+ channel function and irregular Ca2+ signaling, when compared to controls. Importantly, the phenotype severity observed in AMC iPSC-CMs was milder than that of proband iPSC-CMs, an observation exacerbated by flecainide. Interestingly, the iPSC-CMs of the proband exhibited markedly decreased Ca2+ currents in comparison with control and AMC iPSC-CMs. CRISPR/Cas9-mediated genome editing to correct D356Y in proband iPSC-CMs effectively rescued the arrhythmic phenotype and restored Na+ and Ca2+ currents. Moreover, drug screening using established BrS iPSC-CM models demonstrated that quinidine and sotalol possessed antiarrhythmic effects in an individual-dependent manner. Clinically, venous and oral administration of calcium partially reduced the malignant arrhythmic events of the proband in mid-term follow-up. INTERPRETATION: Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca2+ currents might be a compensatory mechanism to resist arrhythmogenesis in BrS AMCs. FUNDING: National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).

False Tendons in the Left Ventricle: Implications for Successful Ablation of Left Posterior Fascicular Tachycardias.

BACKGROUND: The anatomical substrate for left posterior fascicular ventricular tachycardia (LPF-VT) is still unclear. OBJECTIVES: The purpose of this study is to describe the endocavitary substrate of the re-entrant loop of LPF-VT. METHODS: A total of 26 consecutive patients with LPF-VT underwent an electrophysiology study and radiofrequency ablation. RESULTS: Intracardiac echocardiography imaging observed a 100% prevalence of false tendons (FTs) at the left posterior septal region in all patients, and 3 different types of FTs could be classified according to their location. In 22 patients, a P1 potential could be recorded via the multielectrode catheter from a FT. In 4 patients without a recorded P1 during LPF-VT, the earliest P2 potentials were recorded from a FT in 3 patients, and from a muscular connection between 2 posteromedial papillary muscles in 1 patient. Catheter ablation focused on the FTs with P1 or earliest P2 (in patients without P1) was successful in all 26 patients. After 19 ± 8.5 months of follow-up, no patients had recurrence of LPF-VT. CONCLUSIONS: FTs provide an electroanatomical substrate for LPF-VT and a "culprit FT" may be identified as the critical structure bridging the macro-re-entrant loop. Targeting the "culprit FT" is a novel anatomical ablation strategy that results in long-term arrhythmia-free survival.

The specific value of upgrading to left bundle branch area pacing in patients with pacing-induced cardiomyopathy or non-pacing-induced cardiomyopathy related upgrade status: A retrospective study.

AIMS: Left bundle branch area pacing (LBBaP) upgrade can improve cardiac function and clinical outcomes in patients with pacing-induced cardiomyopathy (PICM), but the specific value of LBBaP upgrade, especially compared with the cardiac function level before right ventricular pacing (RVP) in patients with PICM and non-pacing-induced cardiomyopathy-related upgrade status (Non-PICMUS) is still unknown. METHODS: This study retrospectively enrolled 70 patients with LBBaP upgrade (38 patients with PICM and 32 patients with Non-PICMUS). All upgrade patients experienced three stages: before RVP (Pre-RVP), before LBBaP upgrade (Pre-LBBaP), and after LBBaP upgrade (Post-LBBaP). QRS duration (QRSd), lead parameters, echocardiographic indicators, and clinical outcomes evaluation were recorded at multiple time points. RESULTS: At the follow-up of 12 months, for PICM patients, left ventricular ejection fraction (LVEF) significantly increased from 36.6% ± 7.2% to 51.3% ± 8.7% Post-LBBaP (p < .001), and left ventricular end-diastolic diameter (LVEDD) significantly decreased from 61.5 ± 6.4 mm to 55.2 ± 6.5 mm Post-LBBaP (p < .001), but they both failed to restore the level Pre-RVP (both p < .001). For PICM patients, New York Heart Association (NYHA) classification, the number of moderate-to-severe heart failure (NYHA III-IV), and diuretics using rate after the LBBaP upgrade also could not restore to the level Pre-RVP (all p < .001). At the follow-up of 12 months, Non-PICMUS patients after the LBBaP upgrade had no significant improvement in LVEF, LVEDD, and NYHA classification (all p > .05). CONCLUSION: LBBaP upgrade effectively improved the cardiac function and clinical outcomes in PICM patients, but its effectiveness seemed to be limited as the deteriorated cardiac function cannot be completely reversed. For Non-PICMUS patients, the cardiac function and clinical outcomes Post-LBBaP had no significant improvement.

Overexpression of KCNJ2 enhances maturation of human-induced pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Although human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising cell resource for cardiovascular research, these cells exhibit an immature phenotype that hampers their potential applications. The inwardly rectifying potassium channel Kir2.1, encoded by the KCNJ2 gene, has been thought as an important target for promoting electrical maturation of iPSC-CMs. However, a comprehensive characterization of morphological and functional changes in iPSC-CMs overexpressing KCNJ2 (KCNJ2 OE) is still lacking. METHODS: iPSC-CMs were generated using a 2D in vitro monolayer differentiation protocol. Human KCNJ2 construct with green fluorescent protein (GFP) tag was created and overexpressed in iPSC-CMs via lentiviral transduction. The mixture of iPSC-CMs and mesenchymal cells was cocultured with decellularized natural heart matrix for generation of 3D human engineered heart tissues (EHTs). RESULTS: We showed that mRNA expression level of KCNJ2 in iPSC-CMs was dramatically lower than that in human left ventricular tissues. KCNJ2 OE iPSC-CMs yielded significantly increased protein expression of Kir2.1 and current density of Kir2.1-encoded IK1. The larger IK1 linked to a quiescent phenotype that required pacing to elicit action potentials in KCNJ2 OE iPSC-CMs, which can be reversed by IK1 blocker BaCl2. KCNJ2 OE also led to significantly hyperpolarized maximal diastolic potential (MDP), shortened action potential duration (APD) and increased maximal upstroke velocity. The enhanced electrophysiological maturation in KCNJ2 OE iPSC-CMs was accompanied by improvements in Ca2+ signaling, mitochondrial energy metabolism and transcriptomic profile. Notably, KCNJ2 OE iPSC-CMs exhibited enlarged cell size and more elongated and stretched shape, indicating a morphological phenotype toward structural maturation. Drug testing using hERG blocker E-4031 revealed that a more stable MDP in KCNJ2 OE iPSC-CMs allowed for obtaining significant drug response of APD prolongation in a concentration-dependent manner. Moreover, KCNJ2 OE iPSC-CMs formed more mature human EHTs with better tissue structure and cell junction. CONCLUSIONS: Overexpression of KCNJ2 can robustly enhance maturation of iPSC-CMs in electrophysiology, Ca2+ signaling, metabolism, transcriptomic profile, cardiomyocyte structure and tissue engineering, thus providing more accurate cellular model for elucidating cellular and molecular mechanisms of cardiovascular diseases, screening drug-induced cardiotoxicity, and developing personalized and precision cardiovascular medicine.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

The effectiveness and feasibility of using multi-lead ECG monitoring combined with a programmed intracavitary ECG to complete left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBaP) as an alternative method for delivering physiological pacing, is difficult for many primary hospitals that lack the electrophysiological multichannel recorder to carry out. We hope to find a simple and feasible method that combines the multi-lead surface electrocardiogram (ECG) monitoring and the intracavity ECG of the pacing programmer to achieve LBBaP. METHODS: A total of 50 patients with bradycardia indications who attempted permanent pacemaker implantation were included in this study. We referred to multi-lead surface ECG monitoring and pacing system analyzer (PSA), combined with the nine-zone pacing method of the LBBaP, to complete LBBaP. We assessed multiple parameters to verify whether the LBBaP was successfully achieved and used univariable analysis of variance for repeated measures to judge the feasibility and effectiveness of LBBaP without the electrophysiological multichannel recorder. RESULTS: LBBaP was successfully archived without the electrophysiological multichannel recorder in 44 of 50 patients (88%). In the study, paced QRS duration and the stimulus to peak left ventricular activation time (Sti-LVAT) were 117.04 ± 10.34 ms and 71.10 ± 7.91 ms and had no significant changes in the 3-month follow-up. The unipolar pacing threshold and R-wave amplitudes were 0.85 ± 0.32 V and 10.36 ± 5.24 mV at baseline respectively, which also showed stability during the 1-month and 3-month follow-up. During the 3-month follow-up, no lead-related complication was recorded. CONCLUSION: It is effective and feasible to achieve LBBaP combining the multi-lead ECG monitoring and the intracavitary ECG of PSA without the electrophysiological multichannel recorder, which could be an alternative to perform LBBaP.

Feasibility and safety of both His bundle pacing and left bundle branch area pacing in atrial fibrillation patients: intermediate term follow-up.

PURPOSE: His bundle pacing (HBP) improves heart failure (HF) in atrial fibrillation (AF) pacing-dependent patients with a potential for a progressively increased threshold. HBP with right ventricular pacing (RVP) as a backup is always the preferred choice; however, RVP may induce HF. His Purkinje system pacing (HPSP) includes HBP and left bundle branch area pacing (LBBAP). LBBAP maintains left ventricular synchrony but has not been proven to be safe over the long term. We assessed the feasibility and safety of both HBP and LBBAP in AF pacing-dependent patients and compared the parameters of both leads at baseline and at the 6-month follow-up. METHODS: A total of 16 AF patients in our center, who successfully attempted both HBP and LBBAP, were prospectively enrolled unless only one of these treatment statuses was attained. The electrocardiogram characteristics, leading parameters, echocardiography results, and clinical outcomes were assessed. RESULTS: Thirteen out of 16 patients achieved both HBP and LBBAP successfully in the same AF pacing-dependent patients. In symptomatic HF patients with preserved left ventricular ejection fraction (LVEF) (n = 10), the left ventricular end-diastolic diameter (LVEDD) was reduced from 51.8 ± 4.4 to 48.3 ± 3.1 mm (p = 0.01) with the use of diuretics, either reduced or stopped (n = 7). During the follow-up, one patient in the group without HF had an increased HBP threshold and developed HF symptoms. His HF symptoms disappeared when switched into LBBAP mode. Another patient in the group with HF got his LVEF elevated by HBP for 3 months by utilizing left bundle branch block(LBBB)correction and continued to increase when switched into LBBAP for another 3 months due to an increased HBP correction threshold. The average unipolar pacing threshold of LBBAP was lower than that of HBP. No perforation or dislodgement occurred in our study. CONCLUSION: Both HBP and LBBAP could be attempted successfully in the same AF patients when one of the two modes could be adopted and switched according to the clinical feasibility. Compared with HBP, LBBAP yielded better and more stable parameters but showed comparable effects during the 6-month follow-up.

Intracardiac echocardiography is a safe and effective alternative to transesophageal echocardiography for left atrial appendage thrombus evaluation at the time of atrial fibrillation ablation: The ICE-TEE study.

BACKGROUND: Intracardiac echocardiography (ICE) technology has been increasingly accepted as an integral part of atrial fibrillation (AF) ablation procedures. It is still unknown whether ICE can routinely replace transesophageal echocardiography (TEE) for routine thrombus screening in non-selective AF patients. OBJECTIVE: To assess whether ICE can routinely replace TEE in screening for left atrial (LA)/left atrial appendage (LAA) thrombus in general patients undergoing catheter ablation for AF. METHODS: A total of 2003 consecutive patients undergoing AF ablation were included. 1155 patients (ICE group) received intra-procedural ICE examination for LA/LAA thrombus screening, while 848 patients (TEE group) received pre-procedure TEE examination. The incidence of thrombus, peri-procedure complications, and hospital efficiency were assessed. RESULTS: The LA and LAA were adequately visualized in all patients. Five patients in the ICE group and 15 patients in the TEE group were found to have LAA thrombus. The incidence of major periprocedural thrombo-embolic events was comparable between two groups (0.2% vs. 0.1%, p = .76), none were due to undetected LA/LAA thrombus. Other major periprocedural complications occurred at similar rates in both groups, while post-procedure fever was less common in the ICE group (12.7% vs. 17.4%, p < .001). Procedure times and hospital length of stay were both shorter in the ICE group (142 min [87-197 min] vs. 150 min [95-205 min], and 3[2-4] day vs. 4[3-5] day, respectively, both p < .001). CONCLUSIONS: ICE can replace TEE for atrial thrombus screening in AF patients undergoing ablation without increased complications. An "ICE replacing TEE" workflow can also reduce the incidence of postoperative fever and improve hospital efficiency.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

Establishment of an induced pluripotent stem cell line (ZJULLi004-A) from a hypertrophic cardiomyopathy patient carrying MYBPC3/c.3764C>A mutation.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease characterized by left ventricular hypertrophy and a high risk of sudden death. In this study, a skin biopsy was obtained from a HCM patient harboring a heterozygous missense mutation (c.3764C>A; p.A1225D) in the myosin binding protein C3 (MYBPC3) gene. The isolated fibroblasts were reprogrammed using non-integrated Sendai viral method to establish the patient-specific induced pluripotent stem cell (iPSC) line. The established iPSC line displayed normal morphology and karyotype, expressed pluripotency markers, and can differentiate into three germ layers in vivo.

Generation of an induced pluripotent stem cell line (ZJULLi003-A) from a hypertrophic cardiomyopathy patient carrying MYH7/c.4384G > A mutation.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiovascular disease characterized by left ventricular hypertrophy and cardiomyocyte disarray. In this study, a skin biopsy was obtained from a HCM patient, who carried a missense mutation (c.4384G > A; p.E1462K) in the myosin heavy chain 7 (MYH7) gene. The skin fibroblasts were subsequently reprogrammed with a non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical morphology and normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.

Generation of an induced pluripotent stem cell line from a long QT syndrome patient carrying KCNH2/1956C > A mutation.

Long QT syndrome (LQT) is an inherited primary arrhythmic disorder characterized by prolonged QT interval on the surface electrocardiogram and life-threatening arrhythmia. In this study, a skin biopsy was obtained from an LQT type 2 (LQT2) patient, who carried a nonsense mutation (c.1956C > A; p.Y652X) in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. The skin fibroblasts were reprogrammed by non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical embryonic stem cell-like morphology, exhibited normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.

Catheter ablation for persistent atrial fibrillation with left ventricular systolic dysfunction: Who is the best candidate?

BACKGROUND: Tachycardia-induced cardiomyopathy is poorly recognized pre-ablation. It remains unclear of better patient selection and timing for catheter ablation in persistent atrial fibrillation (PerAF) with heart failure (HF). METHODS: Consecutive patients with PerAF and left ventricular ejection fraction (LVEF) <50% referred for AF ablation were retrospectively included. The impact of LV size, heart rate (HR), and LVEF pre-ablation were analyzed for assessing LV systolic function recovery, defined as LVEF increase of ≥20% or to a value ≥55% after ablation. RESULTS: A total of 120 patients (2017-2020) were included. After 19 ±14 months post ablation, LVEF improvement was similar in patients with normal or dilated LV (18.3 ± 9.4% vs. 16.1 ± 10.8%, P = .25), rapid or controlled HR (19.5 ± 10% vs. 16.1 ± 10%, P = .09), but higher in HFrEF (HF with reduced EF) than HFmrEF (HF with midrange EF) (21.6 ± 10.3% vs. 14.9 ± 9.3%, P < .01). There was more LV systolic function recovery in those with normal to moderate LV dilation (80%, odds ratio [OR] 15.22, P < .01), HR ≥80 bpm (79%, OR 5.38, P < .01) and HFmrEF (80%, OR 4.03, P < .01). The overall AF freedom was similar between normal and dilated LV (59% vs. 62%, P = .95), rapid and controlled HR (67% vs. 56%, P = .18), and HFmrEF and HFrEF (65% vs. 50%, P = .19). CONCLUSION: Catheter ablation is effective independent of LV dilation, rate control or HFrEF. Patients with normal to moderate LV dilation, resting HR ≥80 bpm and HFmrEF may be candidates for early PerAF ablation to achieve LVEF normalization.

Preliminary experience of permanent left bundle branch area pacing using stylet-directed pacing lead without delivery sheath.

BACKGROUND: Left bundle branch area pacing (LBBAP) aims to capture the cardiac conduction system in area of the left bundle branch. Currently, LBBAP is mainly performed using lumen-less pacing leads (LLLs) with preshaped sheath. However, the data on LBBAP with stylet-driven leads (SDLs) without sheath is limited. OBJECTIVE: This study presents the feasibility, safety, and pacing characteristics of LBBAP using SDLs without the support of sheath. METHODS: A total of 25 patients with bradycardia indications who received LBBAP implantation with an attempt of SDL (FINELINE II 4471 lead, Boston Scientific, MA, US) between August 2020 and April 2021 at Sir Run Run Shaw Hospital were included in this retrospective cohort study. Twenty of them finally were paced with SDL in priority (SDL-LBBAP group). Twenty propensity score matching patients who underwent LBBAP with LLL (Select Secure 3830 lead, Medtronic, MN, US) and 20 right ventricular septal pacing (RVSP) with regular active fixation lead respectively in the same period (the LLL-LBBAP group and RVSP group) were compared using ECG characteristics, pacing parameters and complications during 6-month follow-up. RESULTS: LBBAP was successful with SDL in 23 of 25 patients (92%) and 20 of them were paced with SDL first. In the SDL-LBBAP group, the average age was 70.4 ± 8.2 years, and 55% of patients were male. Paced QRS duration and the stimulus to peak left ventricular activation time (Sti-LVAT) in SDL-LBBAP group were similar with those in LLL-LBBAP group and significantly shorter than those in RVSP group (126.1±14.1 ms vs. 124.8±10.9 ms, p = 1.00; 77.7 ± 11.2 ms vs. 73.5 ± 9.3 ms, P = .75; 126.1 ± 14.1 ms vs. 147.7 ± 22.5 ms, P<.001; 77.7 ± 11.2 ms vs. 97.0 ± 13.2 ms, P<.001). The pacing threshold and R-wave amplitude of SDL-LBBAP group were 0.53 ± 0.18V and 11.53 ± 3.63 mV at baseline respectively, which were comparable with the other two groups. During the 6-month follow-up, the pacing parameters remained stable and no lead-related complications were recorded. CONCLUSION: It is feasible and safe to use stylet-directed pacing lead for permanent LBBAP without a delivery sheath. Similar to LLL, LBBAP using SDL showed stable parameters and narrower paced QRS duration compared with RVSP, which could be an alternative to LLL in LBBAP.