Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Vein of Marshall ethanol infusion: First-step or adjunctive choice for perimitral atrial tachycardia?

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.

Incidence and risk factors of post-operative cognitive decline after ablation for atrial fibrillation.

BACKGROUND: Catheter ablation is widely used in atrial fibrillation (AF) management. In this study, we are aimed to investigate the incidence of postprocedural cognitive decline in a larger population undergoing AF ablation under local anesthesia, and to evaluate the associated risk factors. METHODS: This study included 287 patients with normal cognitive functions, with 190 ablated AF patients (study group) and 97 AF patients who are awaiting ablation (practice group). We assessed the neuropsychological function of each patient for twice (study group: 24 h prior to ablation and 48 h post ablation; practice group: on the day of inclusion and 72 h later but before ablation). The reliable change index was used to analyze the neuropsychological testing scores and to identify postoperative cognitive dysfunction (POCD) at 48 h post procedure. Patients in the study group accepting a 6-month follow up were given an extra cognitive assessment. RESULTS: Among the ablated AF patients, 13.7% (26/190) had POCD at 48 h after the ablation procedure. Multivariable analysis revealed that, a minimum intraoperative activated clotting time (ACT) < 300 s (OR 3.82, 95% CI 1.48-9.96, P = 0.006) and not taking oral anticoagulants within one month prior to ablation(OR 10.35, 95% CI 3.54-30.27, P < 0.001) were significantly related to POCD at 48 h post-ablation. In 172 patients of the study group accepting a 6-month follow up, there were 23 patients with POCD at 48 h post-ablation and 149 patients without POCD. The global cognitive scores were decreased in 48 h post-operation tests (0 ± 1 vs - 0.15 ± 1.10, P < 0.001) and improved significantly at 6 months post-operation (0 ± 1 vs 0.43 ± 0.92, P < 0.001). In the 23 patients with POCD at 48 h after the procedure, global cognitive performance at 6 months was not significantly different compared with that at baseline (- 0.05 ± 1.25 vs - 0.19 ± 1.33, P = 0.32), while 13 of them had higher scores than baseline level. CONCLUSIONS: Incident of POCD after ablation procedures is high in the short term. Inadequate periprocedural anticoagulation are possible risk factors. However, most POCD are reversible at 6 months, and a general improvement was observed in cognitive function at 6 months after ablation.

Catheter ablation of atrial fibrillation in patients with autoimmune disease: A propensity score matching study based on the China Atrial Fibrillation Registry.

BACKGROUND: Evidence on outcomes of catheter ablation (CA) for atrial fibrillation (AF) in patients with autoimmune disease (AD) is limited. HYPOTHESIS: Patients with AD had worse outcomes after CA procedures for AF. METHODS: A retrospective analysis was performed in patients undergoing AF ablation between 2012 and 2021. The risk of recurrence after ablation was investigated in patients with AD and a 1:4 propensity score matched non-AD group. RESULTS: We identified 107 patients with AD (64 ± 10 years, female 48.6%) who were matched with 428 non-AD patients (65 ± 10 years, female 43.9%). Patients with AD exhibited more severe AF-related symptoms. During the index procedure, a higher proportion of AD patients received nonpulmonary vein trigger ablation (18.7% vs. 8.4%, p = 0.002). Over a median follow-up of 36.3 months, patients with AD experienced a similar risk of recurrence with the non-AD group (41.1% vs. 36.2%, p = 0.21, hazard ratio [HR]: 1.23, 95% confidence interval [CI]: 0.86-1.76) despite a higher incidence of early recurrences (36.4% vs. 13.5%, p = 0.001). Compared with non-AD patients, patients with connective tissue disease were at an increased risk of recurrence (46.3% vs. 36.2%, p = 0.049, HR: 1.43, 95% CI: 1.00-2.05). Multivariate Cox regression analysis showed that the duration of AF history and corticosteroid therapy were independent predictors of postablation recurrence in patients with AD. CONCLUSIONS: In patients with AD, the risk of recurrence after ablation for AF during the follow-up was comparable with non-AD patients, but a higher risk of early recurrence was observed. Further research into the impact of AD on AF treatment is warranted.

Catheter ablation versus medical therapy for atrial fibrillation with prior stroke history: a prospective propensity score-matched cohort study.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS: In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Cell atlas of CCl 4-induced progressive liver fibrosis reveals stage-specific responses.

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis, a major cause of morbidity and mortality worldwide. However, there are currently no effective anti-fibrotic therapies available, especially for late-stage patients, which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cell-specific responses in different fibrosis stages. To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes, we generated a single-nucleus transcriptomic atlas encompassing 49 919 nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride (CCl 4)-induced progressive liver fibrosis. Integrative analysis distinguished the sequential responses to injury of hepatocytes, hepatic stellate cells and endothelial cells. Moreover, we reconstructed cell-cell interactions and gene regulatory networks implicated in these processes. These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions, dysfunction for clearance by apoptosis of activated hepatic stellate cells, accumulation of pro-fibrotic signals, and the switch from an anti-angiogenic to a pro-angiogenic program during CCl 4-induced progressive liver fibrosis. Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

Complexation of fluorescent tetraphenylthiophene-derived ammonium chloride to poly(N-isopropylacrylamide) with sulfonate terminal: aggregation-induced emission, critical micelle concentration, and lower critical solution temperature.

Amphiphilic polymers with hydrophilic poly(N-isopropylacylamide) (PNIPAM) shell connecting hydrophobic tetraphenylthiophene (TP) core, which has the novel aggregation-induced emission (AIE) property, by ionic bonds were prepared to explore the AIE-operative emission responses toward critical micelle concentration (CMC) and lower critical solution temperature (LCST). To exercise the idea, ammonium-functionalized TP2NH(3)(+) and sulfonate-terminated PNIPAM were separately prepared and mixed in different molar ratios to yield three amphiphilic TP-PNIPAMn complexes for the evaluations of CMC and LCST by fluorescence responses. The nonemissive dilute aqueous solutions of TP-PNIPAMn became fluorescent when increasing concentrations above CMC. Heating micelles solution to temperatures above LCSTs causes further enhancement on the emission intensity. The fluorescence responses are explained by the extent of aggregation in the micelles and in the globules formed at room temperature and at high temperatures, respectively.

A simple and easily implemented risk model to predict 1-year ischemic stroke and systemic embolism in Chinese patients with atrial fibrillation.

BACKGROUND: Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients. METHODS: From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA2DS2-VA score (excluding female sex from the CHA2DS2-VASc score). RESULTS: Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA2DS2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA2DS2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). CONCLUSION: In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA2DS2-VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. TRIAL REGISTRATION: www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Improving the Supercapacitor Performance by Dispersing SiO2 Microspheres in Electrodes.

This paper describes a simple, reproducible, and scalable procedure for the preparation of a SiO2-containing supercapacitor with high cycle stability. A carbon mesoporous material (CMM) with a high specific surface area, CMK-3, was adopted as an electric double-layer capacitor (EDLC) active material for the preparation of electrodes for the supercapacitor. The optimized SiO2 content decreased as the microsphere diameter decreased, and the optimal specific capacitance was obtained with 6 wt % SiO2 microspheres (100 nm size). The capacitance improved from 133 to 298 F/g. The corresponding capacitance retention rate after 1000 cycles increased from 68.04 to 91.53%. In addition, the energy density increased from 21.05 to 26.25 Wh/kg with a current density of 1 A/g. Finally, similar results based on active carbon, CeO2/CMK-3, and graphene/CNT/MnOv composite electrodes demonstrated that the proposed method exhibits wide compatibility with diverse electrode materials.