The Effect of Frailty on the Efficacy and Safety of Intensive Blood Pressure Control: A Post Hoc Analysis of the SPRINT Trial.

BACKGROUND: Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control. METHODS: Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. RESULTS: A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59-2.77] and 1.85 [95% CI, 1.46-2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52-1.60) versus 0.30 (95% CI, 0.16-0.59), respectively; Pinteraction=0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment. CONCLUSIONS: Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events.

Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.

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.

Data-driven classification of left atrial morphology and its predictive impact on atrial fibrillation catheter ablation.

INTRODUCTION: Various left atrial (LA) anatomical structures are correlated with postablative recurrence for atrial fibrillation (AF) patients. Comprehensively integrating anatomical structures, digitizing them, and implementing in-depth analysis, which may supply new insights, are needed. Thus, we aim to establish an interpretable model to identify AF patients' phenotypes according to LA anatomical morphology, using machine learning techniques. METHODS AND RESULTS: Five hundred and nine AF patients underwent first ablation treatment in three centers were included and were followed-up for postablative recurrent atrial arrhythmias. Data from 369 patients were regarded as training set, while data from another 140 patients, collected from different centers, were used as validation set. We manually measured 57 morphological parameters on enhanced computed tomography with three-dimensional reconstruction technique and implemented unsupervised learning accordingly. Three morphological groups were identified, with distinct prognosis according to Kaplan-Meier estimator (p < .001). Multivariable Cox model revealed that morphological grouping were independent predictors of 1-year recurrence (Group 1: HR = 3.00, 95% CI: 1.51-5.95, p = .002; Group 2: HR = 4.68, 95% CI: 2.40-9.11, p < .001; Group 3 as reference). Furthermore, external validation consistently demonstrated our findings. CONCLUSIONS: Our study illustrated the feasibility of employing unsupervised learning for the classification of LA morphology. By utilizing morphological grouping, we can effectively identify individuals at different risks of postablative recurrence and thereby assist in clinical decision-making.

Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice.

Eupatilin is a pharmacologically active flavonoid with a variety of biological activities, such as anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic and cardioprotective effects. However, whether eupatilin has protective effects on doxorubicin-induced cardiotoxicity remains unknown. Thus, this study aimed to investigate the role of eupatilin in doxorubicin-induced cardiotoxicity. Mice were exposed to a single dose of doxorubicin (15 mg/kg) to generate doxorubicin-induced cardiotoxicity or normal saline as a control. To explore the protective effects, mice were intraperitoneally injected with eupatilin daily for 7 days. Then, we examined the changes in cardiac function, inflammation, apoptosis, and oxidative stress to evaluate the effects of eupatilin on doxorubicin-induced cardiotoxicity. Additionally, RNA-seq analysis was introduced to explore the potential molecular mechanisms. Eupatilin ameliorated doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and cardiomyocyte apoptosis and ameliorated doxorubicin-induced cardiac dysfunction. Mechanistically, eupatilin activated the PI3K-AKT signaling pathway, as evidenced by RNA-seq analysis and Western blot analysis. This study provides the first evidence that eupatilin ameliorates doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and apoptosis. Pharmacotherapy with eupatilin provides a novel therapeutic regimen for doxorubicin-induced cardiotoxicity.

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.

Evaluation of an algorithm-guided photoplethysmography for atrial fibrillation burden using a smartwatch.

BACKGROUND: Wearable devices based on the PPG algorithm can detect atrial fibrillation (AF) effectively. However, further investigation of its application on long-term, continuous monitoring of AF burden is warranted. METHOD: The performance of a smartwatch with continuous photoplethysmography (PPG) and PPG-based algorithms for AF burden estimation was evaluated in a prospective study enrolling AF patients admitted to Beijing Anzhen Hospital for catheter ablation from September to November 2022. A continuous Electrocardiograph patch (ECG) was used as the reference device to validate algorithm performance for AF detection in 30-s intervals. RESULTS: A total of 578669 non-overlapping 30-s intervals for PPG and ECG each from 245 eligible patients were generated. An interval-level sensitivity of PPG was 96.3% (95% CI 96.2%-96.4%), and specificity was 99.5% (95% CI 99.5%-99.6%) for the estimation of AF burden. AF burden estimation by PPG was highly correlated with AF burden calculated by ECG via Pearson correlation coefficient (R2 = 0.996) with a mean difference of -0.59 (95% limits of agreement, -7.9% to 6.7%). The subgroup study showed the robust performance of the algorithm in different subgroups, including heart rate and different hours of the day. CONCLUSION: Our results showed the smartwatch with an algorithm-based PPG monitor has good accuracy and stability in continuously monitoring AF burden compared with ECG patch monitors, indicating its potential for diagnosing and managing AF.

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.

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.

OTUB1 alleviates NASH through inhibition of the TRAF6-ASK1 signaling pathways.

BACKGROUND AND AIMS: NAFLD is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance, obesity and hyperlipidemia. NASH is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation, and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases, regulates many metabolism-associated signaling pathways. However, the role of OTUB1 in NASH is unclarified. METHODS AND RESULTS: We demonstrated that mice with Otub1 deficiency exhibited aggravated high-fat diet-induced and high-fat high-cholesterol (HFHC) diet-induced hyperinsulinemia and liver steatosis. Notably, hepatocyte-specific overexpression of Otub1 markedly alleviated HFHC diet-induced hepatic steatosis, inflammatory responses, and liver fibrosis. Mechanistically, we identified apoptosis signal-regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA-sequencing analysis and immunoblot analysis. Through immunoprecipitation-mass spectrometry analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway. CONCLUSIONS: OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6-mediated ASK1 activation. Targeting the OTUB1-TRAF6-ASK1 axis may be a promising therapeutic strategy for NASH.

Empagliflozin attenuates doxorubicin-impaired cardiac contractility by suppressing reactive oxygen species in isolated myocytes.

In animal studies, sodium-glucose co-transporter-2 inhibitors-such as empagliflozin-have been shown to improve heart failure and impaired cardiac contractility induced by anthracyclines-including doxorubicin-although the therapeutic mechanism remains unclear. Moreover, abnormalities in Ca2+ handling within ventricular myocytes are the predominant feature of heart failure. Accordingly, this study aimed to investigate whether empagliflozin can alleviate Ca2+ handling disorders induced by acute doxorubicin exposure and elucidate the underlying mechanisms. To this end, ventricular myocytes were isolated from C57BL/6 mice. Contraction function, Ca2+ handling, and mitochondrial reactive oxygen species (ROS) generation were then evaluated using IonOptix or confocal microscopy. Ca2+ handling proteins were detected by western blotting. Results show that incubation with 1 µmol/L of doxorubicin for 120-min impaired cardiac contractility in isolated myocytes, which was significantly alleviated by pretreatment with 1 µmol/L of empagliflozin. Doxorubicin also markedly induced Ca2+ handling disorders, including decreased Ca2+ transients, prolonged Ca2+ transient decay time, enhanced frequency of Ca2+ sparks, and decreased Ca2+ content in the sarcoplasmic reticulum. These dysregulations were improved by pretreatment with empagliflozin. Moreover, empagliflozin effectively inhibited doxorubicin-induced mitochondrial ROS production in isolated myocytes and rescued doxorubicin-induced oxidation of Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) and CaMKII-dependent phosphorylation of RyR2. Similarly, preincubation with 10 µmol/L Mito-TEMPO mimicked the protective effects of empagliflozin. Collectively, Empagliflozin ameliorated the doxorubicin-induced contraction malfunction and Ca2+-handling disorders. These findings suggest that empagliflozin alleviates Ca2+-handling disorders by improving ROS production in the mitochondria and alleviating the enhanced oxidative CaMKII signaling pathway induced by doxorubicin.

Effects of glucagon-like peptide-1 receptor agonists on major coronary events in patients with type 2 diabetes.

AIMS: To perform a meta-analysis to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major coronary events, including myocardial infarction (MI), unstable angina and coronary revascularization, in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We systematically searched the PubMed, CENTRAL, EMBASE and clinicaltrial.gov databases to seek eligible studies with a cardiovascular endpoint comparing GLP-1RAs with a placebo in T2DM patients. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated for the outcomes. RESULTS: Nine studies, with a total of 64 236 patients, were included. GLP-1RA treatment reduced fatal and nonfatal MI by 8% (OR 0.92, 95% CI 0.86-0.99; P = 0.02, I2  = 39%). The reduction reached 15% in human-based GLP-1RA-treated patients. Similarly, once-weekly GLP-1RA treatment reduced the risk of MI by 13%. In contrast, GLP-1RA treatment did not reduce the risk of hospitalization for unstable angina (OR 1.11, 95% CI 0.97-1.28; P = 0.13, I2  = 21%). GLP-1RAs exhibited a tendency to lower the risk of coronary revascularization (OR 0.95, 95% CI 0.89-1.02; P = 0.15, I2  = 22%), but without statistical significance. Human-based GLP-1RAs decreased the risk by 11%. CONCLUSIONS: In high-risk patients with T2DM, GLP-1RAs were associated with a decrease in MI, especially the human-based and once-weekly GLP-1RAs. No benefit was seen for hospitalization for unstable angina or coronary revascularization. Further research is urgently needed to ascertain improvements in coronary events.

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.

Effect of repeat catheter ablation vs. antiarrhythmic drug therapy among patients with recurrent atrial tachycardia/atrial fibrillation after atrial fibrillation catheter ablation: data from CHINA-AF registry.

AIMS: Although several studies have proved that repeat catheter ablation is beneficial to recurrent atrial tachycardia (AT)/atrial fibrillation (AF) after AF catheter ablation, the hard endpoints of the effect of catheter ablation on recurrent AT/AF patients after AF catheter ablation remains unclear. Our study aims to compare the effect of catheter ablation and drug therapy on recurrent AT/AF patients after AF catheter ablation. METHODS AND RESULTS: Four thousand nine hundred and thirteen consecutive patients with recurrent AT/AF after catheter ablation from the China-AF registry were enrolled. The patients were divided into two study groups: the repeat catheter ablation group and the medical therapy group. The primary endpoint is a composite of cardiovascular mortality or ischaemic stroke or major bleeding events. Secondary endpoints were each component of the primary endpoints and AF recurrence rate. Landmark analysis and Cox regression were used in the statistical analysis. We chose landmark 36 months as the primary landmark date. Over a median follow-up period of 40 ± 24 months, 4913 patients were divided into either the repeat ablation group or the medical therapy group. The cumulative incidence of the composite primary outcome was significantly lower in the repeat ablation group than the medical therapy group (adjusted hazard ratio = 0.56; 95% confidence interval: 0.35-0.89; P = 0.015) of landmark 36 months (2359 patients were included in medical therapy group and 704 patients were included in repeat ablation group at landmark 36 months). However, all secondary endpoints were not statistically different in the two groups, including cardiovascular mortality, ischaemic stroke, major bleeding events, and AF recurrence rate. CONCLUSION: Based on this research, in recurrent AT/AF patients after a catheter ablation procedure, compared with medical therapy, repeat catheter ablation may significantly reduce the risk of the endpoint of composite cardiovascular mortality, ischaemic stroke, and major bleeding events.

The adjunctive effect for left pulmonary vein isolation of vein of Marshall ethanol infusion in persistent atrial fibrillation.

OBJECTIVE: This study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF). METHODS AND RESULTS: A total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM. CONCLUSION: EIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.

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.

Revisiting the characteristics and ablation strategy of biatrial tachycardias: a case series and systematic review.

AIMS: To describe the role of left atrial (LA) epicardial conduction and targets of ablation in biatrial tachycardias (BiATs). METHODS AND RESULTS: Consecutive patients with BiAT diagnosed by high-density mapping and appropriate entrainment were enrolled. A systematic review of case reports or series was then performed. Biatrial tachycardia was identified in 20 patients aged 63.5 ± 11.1 years. Among them, eight had LA epicardial conduction, including four via the ligament of Marshall, two via myocardial fibres between the great cardiac vein (GCV) and LA, one via septopulmonary bundle, and one via myocardial fibres between the posterior wall and coronary sinus. Ablation was targeted at the anatomical isthmus in 14, including 5 undergoing vein of Marshall ethanol infusion and 2 undergoing ablation in the GCV. Another six underwent ablation at interatrial connections, including one with septopulmonary bundle at the fossa ovalis and five at the atrial insertions of Bachmann's bundle. After a mean follow-up of 8.7 ± 3.8 months, five patients had recurrence of atrial fibrillation/flutter. Systematic review enrolled 87 patients in previous and the present reports, showing a higher risk of impairment in atrial physiology in those targeting interatrial connections (30.4 vs. 5.0%, P < 0.001) but no significant difference in short- and long-term effectiveness. CONCLUSION: Left atrial epicardial conduction is common in BiATs and affects the ablation strategy. Atrial physiology is a major concern in selecting the target of intervention.

Electrophysiological characteristics and ablation of ventricular arrhythmias originating from the intramural basal inferior septum.

AIMS: The electrocardiographic and electrophysiological characteristics of ventricular arrhythmia (VA) arising from the intramural basal inferior septum (BIS) have not been specifically addressed to date. The aim of the current study was to characterize intramural BIS-VA and distinguish it from those with endocardial origins besides clarifying the anatomical configurations of the pyramidal space. METHODS AND RESULTS: Fifty-five consecutive patients undergoing catheter ablation of VAs from BIS were identified and divided into three groups: the left ventricular (LV)-BIS group (n = 28), right ventricular (RV)-BIS group (n = 8), and intramural group (Intra, n = 19). Compared with the LV-BIS and RV-BIS groups, patients in the Intra group presented with no adequate earliest activation time at the two-sided BIS and epicardial coronary system [right: 7.79 ± 2.38 vs. left: 7.16 ± 2.59 vs. the middle cardiac vein (MCV): 6.26 ± 1.73 ms, P = 0.173] and poor-matched pacing-produced QRS at each site. Under the intracardiac echocardiography view, the pyramidal base was the broadest part of the septum and served as the division of the two-sided BIS. Focal ablation yielded promising acute-term and long-term procedural success in the LV-BIS and RV-BIS groups. But for the Intra group, VAs disappeared only after stepwise ablation successively targeted early preferential exit. After follow-up, three patients in the Intra group had recurrent VA, and all of them were treated well by a redo procedure or drug therapy. CONCLUSION: Intramural VAs were relatively common in the BIS region in our series. Intra-procedural mapping was important to distinguish the intramural VAs from other VAs by comparing the local activation time and pacing mapping. Procedural success could be achieved by stepwise ablation on the counterpart sides of the BIS and within the MCV.

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.