Author Correction: Controlling an organic synthesis robot with machine learning to search for new reactivity.

Change history: Owing to the misidentification of compound 22 in the original Letter, changes have been made to Fig. 5, Extended Data Fig. 2 and the main text; see accompanying Amendment.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Controlling an organic synthesis robot with machine learning to search for new reactivity.

The discovery of chemical reactions is an inherently unpredictable and time-consuming process1. An attractive alternative is to predict reactivity, although relevant approaches, such as computer-aided reaction design, are still in their infancy2. Reaction prediction based on high-level quantum chemical methods is complex3, even for simple molecules. Although machine learning is powerful for data analysis4,5, its applications in chemistry are still being developed6. Inspired by strategies based on chemists' intuition7, we propose that a reaction system controlled by a machine learning algorithm may be able to explore the space of chemical reactions quickly, especially if trained by an expert8. Here we present an organic synthesis robot that can perform chemical reactions and analysis faster than they can be performed manually, as well as predict the reactivity of possible reagent combinations after conducting a small number of experiments, thus effectively navigating chemical reaction space. By using machine learning for decision making, enabled by binary encoding of the chemical inputs, the reactions can be assessed in real time using nuclear magnetic resonance and infrared spectroscopy. The machine learning system was able to predict the reactivity of about 1,000 reaction combinations with accuracy greater than 80 per cent after considering the outcomes of slightly over 10 per cent of the dataset. This approach was also used to calculate the reactivity of published datasets. Further, by using real-time data from our robot, these predictions were followed up manually by a chemist, leading to the discovery of four reactions.

Publisher Correction: Controlling an organic synthesis robot with machine learning to search for new reactivity.

The chemical structure formatting in Fig. 5 has been corrected online.

[Research progress on induced hepatic stellate cell ferroptosis in prevention and treatment of liver fibrosis].

Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

O-GlcNAcylation of RAB10 promotes hepatocellular carcinoma progression.

Ras-related protein Rab-10 (RAB10) is involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Here, we found RAB10, O-GlcNAc transferase (OGT), and O-GlcNAcylation were upregulated in HCC. In addition, RAB10 protein level was prominently positively correlated with the expression of OGT. O-GlcNAcylation modification of RAB10 was then investigated. Here we showed that RAB10 interacts directly with OGT in HCC cell lines, Meanwhile, O-GlcNAcylation enhanced RAB10 protein stability. Furthermore, knockdown of OGT suppressed aggressive behaviors of HCC in vitro and in vivo, while elevated RAB10 reversed these. Taken together, these results indicated that OGT mediated O-GlcNAcylation stabilized RAB10, thus accelerating HCC progression.

Automated Library Generation and Serendipity Quantification Enables Diverse Discovery in Coordination Chemistry.

Library generation experiments are a key part of the discovery of new materials, methods, and models in chemistry, but the question of how to generate high quality libraries to enable discovery is nontrivial. Herein, we use coordination chemistry to demonstrate the automation of many of the workflows used for library generation in automated hardware including the Chemputer. First, we explore the target-oriented synthesis of three influential coordination complexes, to validate key synthetic operations in our system; second, the generation of focused libraries in chemical and process space; and third, the development of a new workflow for prospecting library formation. This involved Bayesian optimization using a Gaussian process as surrogate model combined with a metric for novelty (or serendipity) quantification based on mass spectrometry data. In this way, we show directed exploration of a process space toward those areas with rarer observations and build a picture of the diversity in product distributions present across the space. We show that this effectively "engineers" serendipity into our search through the unexpected appearance of acetic anhydride, formed in situ, and solvent degradation products as ligands in an isolable series of three Co(III) anhydride complexes.

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.

Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

Fascicular ventricular tachycardia arising from the left side His and its adjacent region: a subset of upper septal idiopathic left ventricular tachycardia.

AIMS: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics. METHODS AND RESULTS: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences. CONCLUSIONS: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region.

Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation.

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.

Impact of pre-ablation left appendage flow velocities on long term recurrence of catheter ablation for paroxysmal atrial fibrillation.

BACKGROUND: Despite undergoing a single ablation, many patients with paroxysmal atrial fibrillation (PAF) experience a gradually increasing recurrence rate. This study aims to examine the relationship between left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV) profiles and 3-year recurrence of AF after ablation. METHODS: We conducted a prospective study of 658 consecutive PAF patients who underwent their first ablation between January 2018 and December 2019. We collected the clinical and echocardiographic characteristics of the patients. LAAeV and LAAfV were obtained from a transesophageal echocardiogram (TEE) before catheter ablation. Patients were followed at regular intervals to monitor for the primary outcome of AF recurrence. RESULTS: After a median follow-up period of 35.3 months (range, 10.7-36.3), 288 patients (43.8%) experienced AF recurrence after catheter ablation. Patients who experienced AF recurrence had decreased LAAeV and LAAfV (LAAeV: 56.5 ± 21.2 vs. 59.6 ± 20.7 cm/s, p = .052; LAAfV: 47.5 ± 17.9 vs. 51.7 ± 18.2, p = .003). Kaplan-Meier analysis showed that patients in the low LAAeV (<55 cm/s) group had a poorer event-free survival rate than those in the high LAAeV (≥55 cm/s) group (log-rank p = .012). Patients with LAAfV <48 cm/s had a significantly higher risk of AF recurrence than those with LAAfV ≥48 cm/s (log-rank p = .003). In the multivariable model, low LAAfV pre-ablation in TEE-guided was significantly independently associated with 3-year recurrence after single radiofrequency ablation in patients with PAF, along with LA dimension and duration of AF. CONCLUSION: This study found an independent association between low LAAfV pre-ablation in TEE-guided and 3-year recurrence after single radiofrequency ablation in patients with PAF.

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.

Spontaneous formation of autocatalytic sets with self-replicating inorganic metal oxide clusters.

Here we show how a simple inorganic salt can spontaneously form autocatalytic sets of replicating inorganic molecules that work via molecular recognition based on the {PMo12} ≡ [PMo12O40]3- Keggin ion, and {Mo36} ≡ [H3Mo57M6(NO)6O183(H2O)18]22- cluster. These small clusters are able to catalyze their own formation via an autocatalytic network, which subsequently template the assembly of gigantic molybdenum-blue wheel {Mo154} ≡ [Mo154O462H14(H2O)70]14-, {Mo132} ≡ [MoVI72MoV60O372(CH3COO)30(H2O)72]42- ball-shaped species containing 154 and 132 molybdenum atoms, and a {PMo12}⊂{Mo124Ce4} ≡ [H16MoVI100MoV24Ce4O376(H2O)56 (PMoVI10MoV2O40)(C6H12N2O4S2)4]5- nanostructure. Kinetic investigations revealed key traits of autocatalytic systems including molecular recognition and kinetic saturation. A stochastic model confirms the presence of an autocatalytic network involving molecular recognition and assembly processes, where the larger clusters are the only products stabilized by the cycle, isolated due to a critical transition in the network.

Pore "Softening" and Emergence of Breathability Effects of New Keplerate Nano-Containers.

The self-assembly of porous molecular nanocapsules offer unique opportunities to investigate a range of interesting phenomena and applications. However, to design nanocapsules with pre-defined properties, thorough understanding of their structure-property relation is required. Here, we report the self-assembly of two elusive members of the Keplerate family, [Mo132 Se60 O312 (H2 O)72 (AcO)30 ]42- {Mo132 Se60 } 1 and [W72 Mo60 Se60 O312 (H2 O)72 (AcO)30 ]42- {W72 Mo60 Se60 } 2, that have been synthesised using pentagonal and dimeric ([Mo2 O2 Se2 ]2+ ) building blocks and their structures have been confirmed via single crystal X-ray diffractions. Our comparative study involving the uptake of organic ions and the related ligand exchange of various ligand sizes by the {Mo132 Se60 } and previously reported Keplerates {Mo132 O60 }, {Mo132 S60 } based on the ligand exchange rates, revealed the emergence of increased "breathability" that dominates over the pore size as we transition from the {Mo132 S60 } to the "softer" {Mo132 Se60 } molecular nano-container.

Water-soluble Self-assembled {Pd84 }Ac Polyoxopalladate Nano-wheel as a Supramolecular Host.

Polyoxopalladates (POPs) are a class of self-assembling palladium-oxide clusters that span a variety of sizes, shapes and compositions. The largest of this family, {Pd84 }Ac , is constructed from 14 building units of {Pd6 } and lined on the inner and outer torus by 28 acetate ligands. Due to its high water solubility, large hydrophobic cavity and distinct 1 H NMR fingerprint {Pd84 }Ac is an ideal molecule for exploring supramolecular behaviour with small organic molecules in aqueous media. Molecular visualisation studies highlighted potential binding sites between {Pd84 }Ac and these species. Nuclear Magnetic Resonance (NMR) techniques, including 1 H NMR, 1 H Diffusion Ordered Spectroscopy (DOSY) and Nuclear Overhauser Spectroscopy (NOESY), were employed to study the supramolecular chemistry of this system. Here, we provide conclusive evidence that {Pd84 }Ac forms a 1 : 7 host-guest complex with benzyl viologen (BV2+ ) in aqueous solution.

Outcome of catheter ablation for paroxysmal atrial fibrillation in patients with stable coronary artery disease.

BACKGROUND: Atrial fibrillation (AF) and stable coronary artery disease (SCAD) frequently coexist. This study aimed to assess the long-term outcome of catheter ablation in patients with paroxysmal AF and SCAD. METHODS: In total, 12,104 patients with paroxysmal AF underwent catheter ablation in the Chinese Atrial Fibrillation Registry between 2011 and 2019 were screened. A total of 441 patients with SCAD were matched with patients without SCAD in a 1:4 ratio. The primary endpoint was AF recurrence after single ablation. The composite secondary endpoints were thromboembolism, coronary events, major bleeding, all-cause death. RESULTS: Over a mean follow-up of 46.0 ± 18.9 months, the recurrence rate in patients with SCAD was significantly higher after a single ablation (49.0% vs. 41.9%, p = .03). The very late recurrence rate of AF in the SCAD group was also significantly higher than that in the control group (38.9% vs. 31.2%;p = .04). In multivariate analysis, adjusted with the female, smoking, duration of AF, previous thromboembolism, COPD, and statins, SCAD was independently associated with AF recurrence (adjusted HR, 1.19 [1.02-1.40], p = .03). The composite secondary endpoints were significantly higher in the SCAD group (12.70% vs. 8.54%, p = .02), mainly due to thromboembolism events (8.16% vs. 4.41%, p < .01). CONCLUSIONS: SCAD significantly increased the risk of recurrence after catheter ablation of paroxysmal AF. The incidence of thromboembolic events after catheter ablation of paroxysmal AF in the patients with SCAD was significantly higher than that in those without SCAD.

Repeat ablation strategy for recurrent persistent atrial fibrillation: A propensity-matched score comparison between "2C3L" and "extensive ablation" approach.

BACKGROUND: Debates exist in the repeat ablation strategy for patients with recurrence presenting as persistent atrial fibrillation (AF) after initial persistent AF ablation. OBJECTIVE: To compare the outcome between the "2C3L" and "extensive ablation" approach in patients undergoing repeat procedures for recurrent persistent AF. METHODS: Propensity-score matching was performed in 196 patients with AF recurrence undergoing repeat ablation, and 79 patients treated with "2C3L" strategy were matched to 79 patients treated with "extensive ablation" strategy. The "2C3L" approach included pulmonary vein isolation, mitral isthmus, left atrial roof, and cavotricuspid isthmus ablation, while the "extensive ablation" strategy included extensive ablation of a variety of other targets aiming to terminate the AF. The primary outcome was freedom from any atrial tachyarrhythmia after 24-h ambulatory monitoring follow-up for 12 months. RESULTS: No statistically significant difference was found between the primary outcome between the "2C3L" and the "extensive ablation" group [70.9% vs. 69.6%, p = .862; 95% confidence interval (CI) -12.8 to 15.3], although the "extensive ablation" group had a significantly high proportion of AF termination (19.0% for "2C3L" vs. 41.8% for "extensive ablation" group, p = .002; 95% CI 8.5-35.9). And AF termination was not related to the primary outcome in multifactorial regression. At 40 ± 22 months after the repeat procedure, the primary outcome was also comparable (57.0 % for "2C3L" vs. 48.1% for "extensive ablation" group, p = .265; 95% CI -6.6 to 23.7). CONCLUSION: The outcome between the "2C3L" and "extensive ablation" approaches was comparable in patients undergoing repeat procedures for recurrent persistent AF.

Antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation and chronic coronary syndrome.

This study aimed to explore antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation (AF) at high risk for stroke and chronic coronary syndrome (CCS) in real-world clinical practice. Patients with AF at high risk for stroke complicated with CCS from China Atrial Fibrillation Registry (CAFR) were enrolled. The patients were divided into non-antithrombotic (Non-AT) group, oral anticoagulants (OAC) group, antiplatelet therapy (APT) group (aspirin or clopidogrel), and dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) according to their antithrombotic strategies at baseline. The patients with OAC + single antiplatelet drug (14 cases) and OAC + dual antiplatelet therapy (7 cases) were excluded for the small sample size. The primary effectiveness outcome was the composite outcome of coronary events, thromboembolism, and all-cause mortality. The primary safety outcome was major bleeding events. From 2011 to 2018, 25,512 patients were included in the CARF study, 769 patients with AF at high risk for stroke and CCS were enrolled in this study. After a follow-up of 47.4 ± 25.3 months, the incidences of primary effectiveness outcome were 44.6%, 25.7%, 43.6%, and 29.1% in the four groups, respectively (P < 0.001). The incidences of primary effectiveness and all-cause mortality were both significantly lower in the OAC group than in the Non-AT group, (25.7% vs. 44.6%, HR 0.53, 95% CI 0.39-0.73, P < 0.001) and (14.6% vs. 38.5%, HR 0.36, 95%CI 0.25-0.52, P < 0.001). In multivariate analysis, age (HR 1.03, 95%CI 1.01-1.05, P = 0.015), heart failure (HR 1.67, 95%CI 1.20-2.33, P = 0.002) and OAC (HR 0.66, 95%CI 0.47-0.91, P = 0.012) were independent factors for the composite outcome. There was no significant difference in major bleeding events between the four groups. OAC monotherapy significantly reduced the primary effectiveness composite outcome and all-cause mortality in the patients with AF at high risk for stroke complicated with CCS. However, there was no significant difference in major bleeding among the different antithrombotic strategies.Trial Registration www.chictr.org.cn (No. ChiCTR-OCH-13003729).

Thrombolytic DNT and fatality and disability rates in acute ischemic stroke: a study from Bigdata Observatory Platform for Stroke of China.

OBJECTIVE: To evaluate whether shorter door-to-needle times (DNT) with intravenous tissue plasminogen activator (tPA) for acute ischemic stroke are associated with improved 1-year outcomes in Chinese patients. METHODS: From August to September 2019, all first-ever ischemic stroke patients who were treated with intravenous tPA within 4.5 h of the time they were last known to be well from 232 hospitals in China were included. Patients were divided into four groups according to DNT time (≤ 45 min; 45-60 min; 60-90 min; > 90 min). All discharged patients would receive a telephone follow-up at 12-month after admission. Death and disability events were recorded. RESULTS: Finally, 2370 patients were analyzed. The median age was 65 years, 66.6% were male, and 2.4% were of ethnic minorities. In the 1-year follow-up, 211 patients died (8.9%; 95%CI: 7.8-10.0%). The patients (53.1%) had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year mortality (8.9% vs 8.9% [absolute difference, 0.03% {95% CI, - 0.05% to - 0.10%}, odd ratio {OR}, 1.00 {95% CI, 0.75 to 1.33}]). In addition, 385 patients (16.2%; 14.8-17.3%) out of those survivors had disability events. The patients had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year disability rate (18.9% vs 16.7% [absolute difference, 1.9% {95% CI, 1.1% to 3.0%}, odd ratio {OR}, 1.22 {95% CI, 0.89 to 1.43}]). CONCLUSIONS: The results did not show that shorter DNT for tPA administration was significantly associated with better 1-year outcomes.