A spatiotemporal atlas of cholestatic injury and repair in mice.

Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response. Cholangiocytes express genes related to recruitment and differentiation of lipid-associated macrophages, which generate feedback signals enhancing ductular reaction. Moreover, cholangiocytes express high TGFß in association with the conversion of liver progenitor-like cells into cholangiocytes during injury and the dampened proliferation of periportal hepatocytes during recovery. Notably, Atoh8 restricts hepatocyte proliferation during 3,5-diethoxycarbonyl-1,4-dihydro-collidin damage and is quickly downregulated after injury withdrawal, allowing hepatocytes to respond to growth signals. Our findings lay a keystone for in-depth studies of cellular dynamics and molecular mechanisms of cholestatic injuries, which may further develop into therapies for cholangiopathies.

Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

Association between performance measures and clinical outcomes in patients with heart failure in China: Results from the HERO study.

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.

VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification.

In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-like family member 1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.

Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. SS AIMS: To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. METHODS: Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. RESULTS: Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64-0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. CONCLUSIONS: The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.

Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Impact of Sodium-Glucose Cotransporter 2 Inhibitor on Recurrence After Catheter Ablation for Atrial Fibrillation in Patients With Diabetes: A Propensity-Score Matching Study and Meta-Analysis.

BACKGROUND: The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and atrial fibrillation (AF) recurrence after catheter ablation among patients with diabetes and AF remains unclear. METHODS AND RESULTS: Patients with AF undergoing initial catheter ablation with a history of diabetes from the China AF registry were included. Patients using SGLT2i were identified and matched by propensity score with non-SGLT2i patients in a 1:3 ratio. The main outcome was AF recurrence during the 18-month follow-up. A total of 138 patients with diabetes with SGLT2i therapy and 387 without SGLT2i were analyzed. AF recurrence occurred in 37 patients (26.8%) in the SGLT2i group and 152 patients (39.3%) in the non-SGLT2i group during a total of 593.3 person-years follow-up. The SGLT2i group was associated with lower AF recurrence compared with the non-SGLT2i group (hazard ratio, 0.63 [95% CI, 0.44-0.90], P=0.007). A total of 4 studies were analyzed in our meta-analysis demonstrating that SGLT2i was associated with lower AF recurrence after catheter ablation (odds ratio, 0.61 [95% CI, 0.54-0.69]; P<0.001, I2=0.0%). CONCLUSIONS: Our prospective study coupled with a meta-analysis demonstrated a lower risk of AF recurrence with the use of SGLT2i among patients with diabetes after AF ablation.

Live birth of chimeric monkey with high contribution from embryonic stem cells.

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.

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.

Identification of atrial fibrillation phenotypes at low risk of stroke in patients with CHA2DS2-VASc ≥2: Insight from the China-AF study.

OBJECTIVE: Patients with atrial fibrillation (AF) are highly heterogeneous, and current risk stratification scores are only modestly good at predicting an individual's stroke risk. We aim to identify distinct AF clinical phenotypes with cluster analysis to optimize stroke prevention practices. METHODS: From the prospective Chinese Atrial Fibrillation Registry cohort study, we included 4337 AF patients with CHA2 DS2 -VASc≥2 for males and 3 for females who were not treated with oral anticoagulation. We randomly split the patients into derivation and validation sets by a ratio of 7:3. In the derivation set, we used outcome-driven patient clustering with metric learning to group patients into clusters with different risk levels of ischemic stroke and systemic embolism, and identify clusters of patients with low risks. Then we tested the results in the validation set, using the clustering rules generated from the derivation set. Finally, the survival decision tree was applied as a sensitivity analysis to confirm the results. RESULTS: Up to the follow-up of 1 year, 140 thromboembolic events (ischemic stroke or systemic embolism) occurred. After supervised metric learning from six variables involved in CHA2 DS2 -VASc scheme, we identified a cluster of patients (255/3035, 8.4%) at an annual thromboembolism risk of 0.8% in the derivation set. None of the patients in the low-risk cluster had prior thromboembolism, heart failure, diabetes, or age older than 70 years. After applying the regularities from metric learning on the validation set, we also identified a cluster of patients (137/1302, 10.5%) with an incident thromboembolism rate of 0.7%. Sensitivity analysis based on the survival decision tree approach selected a subgroup of patients with the same phenotypes as the metric-learning algorithm. CONCLUSIONS: Cluster analysis identified a distinct clinical phenotype at low risk of stroke among high-risk [CHA2 DS2 -VASc≥2 (3 for females)] patients with AF. The use of the novel analytic approach has the potential to prevent a subset of AF patients from unnecessary anticoagulation and avoid the associated risk of major bleeding.

Systolic Blood Pressure Time in Target Range and Incident Atrial Fibrillation in Patients With Hypertension: Insights From the SPRINT Trial.

BACKGROUND: Systolic blood pressure (SBP) time in target range (TTR) indicates the mean value, exposure time, and variability in blood pressure over time. The prognostic value of SBP TTR for incident atrial fibrillation (AF) in patients with hypertension is unclear. METHODS: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. SBP target ranges for intensive and standard arms were defined as 110 to 130 and 120 to 140 mm Hg, respectively. TTR was calculated by linear interpolation method using SBP from months 0 to 3. We used Cox proportional regression models to assess the association of SBP TTR with incident AF. RESULTS: Among 7939 participants included in this analysis, 187 incident AF cases occurred during follow-up. After multivariable adjustment, a 10% increase in SBP TTR was independently associated with a 7% lower risk of incident AF (hazard ratio, 0.93 [95% CI, 0.88-0.97]; P=0.003). The restricted spline curve depicted a linear and inverse relationship between SBP TTR and incident AF. Sensitivity analyses generated consistent results when calculating TTR over a longer period or setting target range as 110 to 140 mm Hg for the whole population. CONCLUSIONS: Higher SBP TTR independently predicts a lower risk of incident AF. Efforts to attain SBP within 110 to 140 mm Hg over time may be an effective strategy to prevent AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.

Genetic Evidence for Causal Association Between Atrial Fibrillation and Dementia: A Mendelian Randomization Study.

Background The knowledge gap regarding whether the correlation between atrial fibrillation (AF) and dementia in observational studies is causation or driven by other shared risk factors remains substantially unfilled. Methods and Results We performed a comprehensive 2-sample Mendelian randomization study to evaluate the causal effect of AF on overall dementia and its subtypes, including vascular dementia, Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. The primary results in inverse variance-weighted analyses were further validated by various Mendelian randomization sensitivity analyses. Additionally, we conducted multivariable Mendelian randomization to examine 10 candidate mediators of the causal association of AF and dementia. Genetic predisposition to AF was modestly associated with an increased risk of overall dementia (odds ratio, 1.140 [95% CI, 1.023-1.271]; P=0.018) and strongly associated with vascular dementia (odds ratio, 1.350 [95% CI, 1.076-1.695]; P=0.010). Genetically predicted AF indicated neutral effects on Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. In multivariable Mendelian randomization analysis, the total effect of AF on overall dementia was remarkably attenuated by adjusting for genetic effect for ischemic stroke (odds ratio, 1.068 [95% CI, 0.953-1.197]; P=0.259) and low cardiac output (odds ratio, 1.046 [95% CI, 0.926-1.181]; P=0.475), indicating that the causal association of genetically predicted AF with dementia was potentially mediated by ischemic stroke and low cardiac output. The causal effect of genetically predicted AF on dementia was independent of cerebral small-vessel disease and brain volume phenotypes. Conclusions Our findings provided novel evidence supporting the causal effect of genetically predicted AF on dementia mediated by ischemic stroke and low cardiac output. Future clinical trials are warranted to evaluate the potential role of appropriate AF management in dementia prevention.

Epicardial connections and bi-atrial tachycardias: From anatomy to clinical practice.

Bi-atrial tachycardia (BiAT) is not rare after extensive atrial ablation or cardiac surgery. The complexity of bi-atrial reentrant circuits poses a great challenge for clinical practice. With recent advances in mapping technologies, we are now able to characterize atrial activation in detail. However, given the involvement of both atria and multiple epicardial conductions, endocardial mapping for BiATs is not easy to understand. Knowledge of the atrial myocardial architecture is the foundation for the clinical management of BiATs; as it is required to understand the possible mechanism of the tachycardia and identify the optimal target of ablation. In this review we summarize current knowledge about the anatomy of interatrial connections as well as other epicardial fibers and discuss the interpretation of electrophysiological findings and ablation strategies for BiATs.

Very-early symptomatic recurrence is associated with late recurrence after radiofrequency ablation of atrial fibrillation.

AIMS: After radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), the effect of very-early (within 48 h) symptomatic recurrence (VESR) on late (after 3 months of RFCA) recurrence (LR) has been seldomly reported. We aimed to explore the relationship between VESR and LR among post-RFCA patients. METHODS AND RESULTS: This was a single-centre prospective cohort study that enrolled 6887 AF patients who received the first RFCA procedure from June 2018 to December 2021 at Beijing Anzhen Hospital. Patients were divided into four groups based on VESR and early (from 48 h to 3 months after RFCA) recurrence (ER): Group A (no VESR, no ER); Group B (VESR but no ER); Group C (ER but no VESR); and Group D (both VESR and ER). Three hundred and thirty (4.79%) patients experienced VESR (Groups B and D). With an average follow-up of 14.7 months after grouping, the Kaplan-Meier curve showed that LR risk in VESR patients was higher than in other patients (log-rank, P < 0.001), and the difference was significant in both paroxysmal (log-rank, P < 0.001) and persistent (log-rank, P < 0.001) AF patients (P for interaction = 0.118). In multivariate analysis, Groups B, C, and D were associated with a 2.161-, 5.409-, and 7.401-fold increase in the risk of LR, respectively. What is more, compared with Group A, VESR-atrial tachycardia and VESR-AF were related to a 3.467- and 5.564-fold LR risk, respectively. In VESR patients, classification based on ER and VESR modes improved the prediction potential of LR risk. CONCLUSION: Very-early symptomatic recurrence is associated with an increased risk of LR.

Effectiveness of mHealth interventions for improving hypertension control in uncontrolled hypertensive patients: A meta-analysis of randomized controlled trials.

The benefits of mHealth interventions in uncontrolled hypertension are unclear. To determine whether mHealth effectively improves the control rate of uncontrolled hypertension. PubMed, Web of Science, EMBASE, Scopus, and Cochrane Library were searched for randomized controlled trials (RCTs) from January 2007 to September 2022. The intervention group consisted of mHealth intervention, and the control group was usual care. Random-effects meta-analysis models were used to assess pooled mHealth intervention effects and CIs. The primary outcome was the blood pressure (BP) control rate of uncontrolled hypertension. The secondary outcome was the change of BP. Thirteen RCTs were included in this meta-analysis, of which eight reported the successful BP control rate, 13 reported the change of systolic blood pressure (SBP), and 11 reported the change in diastolic blood pressure (DBP). The mean age of trial participants ranged from 47.7 to 66.9 years old, with a female composition ratio of 40.0%-66.1%. The duration of follow-up ranged from 3 to 18 months. This study showed a more robust effect size for improving BP control rate by mHealth interventions than usual care (57.5% vs. 40.8% of successful control rate; odds ratio [OR], 2.19 [95% CI, 1.32-3.62]). Furthermore, mHealth significantly reduced SBP by 4.45 mm Hg and DBP by 2.47 mm Hg, and subgroup analysis did not observe the major source of heterogeneity. This meta-analysis found that mHealth could significantly improve the uncontrolled hypertension control rate and might be a feasible, acceptable, and effective tool for uncontrolled hypertension management.

Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT MIND Trial.

BACKGROUND: The prognostic value of systolic blood pressure (SBP) time in target range (TTR) on cognitive outcomes among adults with hypertension remains unclear. METHODS: We performed secondary analysis of SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension), which compared intensive (<120 mm Hg) versus standard (<140 mm Hg) SBP intervention in hypertensive individuals. TTR was calculated from baseline to month 3 using 110 to 130 mm Hg and 120 to 140 mm Hg as target range for the intensive and standard groups, respectively. Cognitive outcomes included probable dementia, mild cognitive impairment, and the composite of probable dementia or mild cognitive impairment. Cox regression models were used to evaluate the relationship between SBP-TTR and cognitive outcomes. RESULTS: A total of 8298 patients were included. Participants with higher TTR were younger and less likely to be women or to have a history of cardiovascular disease. After adjustment of baseline demographics, medical history, and mean SBP, a 1-SD (31.5%) increase in TTR was independently associated with a 14% lower risk of probable dementia (hazard ratio, 0.86 [95% CI, 0.76-0.98]; P=0.023). Sensitivity analysis showed consistent results when combining target range as 110 to 140 mm Hg. However, there was no significant association between SBP-TTR and mild cognitive impairment. CONCLUSIONS: In this post hoc analysis of SPRINT MIND, SBP-TTR was an independent predictor of probable dementia beyond mean SBP. Maintaining SBP within 110 to 140 mm Hg over time may be beneficial for dementia prevention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.

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.

Epicardial Roof-Dependent Macro-Re-Entrant Tachycardia After Ablation of Atrial Fibrillation: Electrophysiological Characteristics and Ablation.

BACKGROUND: Epicardial roof-dependent macro-re-entrant tachycardias (epi-RMAT) after catheter ablation of persistent atrial fibrillation are not rare but the prevalence and characteristics remain unclear. OBJECTIVES: The purpose of this study was to investigate the prevalence, electrophysiological characteristics and ablation strategy of recurrent epi-RMATs after ablation of atrial fibrillation. METHODS: A total of 44 consecutive patients with 45 roof-dependent RMATs after atrial fibrillation ablation were enrolled. High-density mapping and appropriate entrainment were performed to diagnose epi-RMATs. RESULTS: Epi-RMAT was identified in 15 patients (34.1%). Under the right lateral view, the activation pattern can be briefly classified into clockwise re-entry (n = 4), counterclockwise re-entry (n = 9), and bi-atrial re-entry (n = 2). Five (33.3%) had a pseudofocal activation pattern. All epi-RMATs had continuous slow or no conduction zone with a mean width of 21.3 ± 12.3 mm traversing both pulmonary antra, and 9 (60.0%) had missing cycle length of >10% actual cycle length. Compared with endocardial RMAT (endo-RMAT), epi-RMAT required longer ablation time (9.60 ± 4.98 minutes vs 3.68 ± 3.42 minutes; P < 0.001), more floor line ablation (93.3% vs 6.7%; P < 0.001), and electrogram-guided posterior wall ablation (78.6% vs 3.3%; P < 0.001). Electric cardioversion was required in 3 patients (20.0%) with epi-RMATs, whereas all endo-RMATs were terminated by radiofrequency applications (P = 0.032). Posterior wall ablation was performed under esophagus deviation in 2 patients. We did not observe a significant difference in the recurrence of atrial arrhythmias between patients with epi-RMATs and endo-RMATs after the procedure. CONCLUSIONS: Epi-RMATs are not uncommon after roof or posterior wall ablation. An explicable activation pattern with a conduction obstacle in the dome and appropriate entrainment is critical for the diagnosis. The effectiveness of posterior wall ablation may be restricted by the risk of esophagus impairment.

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.