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.

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.

A novel esophageal retractor with eccentric balloon during atrial fibrillation ablation.

BACKGROUND: Due to the anatomically adjacent relationship between the left atrium (LA) and esophagus, energy delivery on the posterior wall of LA is limited. The aim of this study was to evaluate the feasibility of a novel esophageal retractor (SAFER) with an inflatable C-curve balloon during atrial fibrillation (AF) ablation. METHOD: Nine patients underwent AF ablation assisted with the SAFER. After inflation, the esophagus was deviated laterally away from the intended ablation site of the posterior wall under local anesthesia. The extent of mechanical esophageal deviation (MED) was evaluated under fluoroscopy, defined as the shortest distance from the trailing esophageal edge to the closest point of the ablation line. Gastroscopy was performed before and after ablation. The target ablation index used in all LA sites including the posterior wall was 400-450 after effective MED. All adverse events during the periprocedural period were recorded. RESULTS: The mean deviation distance achieved 16.2 ± 9.6 mm away from the closest ablation point of the pulmonary vein lesion set. With respect to the individual left and right pulmonary vein lesion sets, the deviation distance was 19.7 ± 11.5 and 12.7 ± 6.8 mm, respectively. The extent of deviation was 0 to 5 mm, 5.1 to 10 mm, or >10 mm in 0(0%), 7(38.9%), and 11(61.1%), respectively. Procedural success was achieved in all patients without acute reconnection. There was only one esophageal complication which manifested as esophageal erosion and this patient experienced throat pain possibly related to the SAFER retractor with no clinical sequelae. CONCLUSION: Esophageal deviation with the novel eccentric balloon is a novel feasible choice during AF ablation, enabling adequate energy delivery to the posterior wall of LA. Additional prospective randomized controlled studies are required for further validation.

[The role of mother-child relationship in the association between maternal parenting stress and emotional and behavioral problems in preschool children]. / æ¯å­å ³ç³»åœ¨æ¯äº²å »è‚²åŽ‹åŠ›ä¸Žå­¦é¾„å‰å„¿ç«¥æƒ ç»ªè¡Œä¸ºé—®é¢˜å ³è”ä¸­çš„ä½œç”¨.

OBJECTIVES: To study the moderating effect of mother-child relationship in the association between maternal parenting stress and emotional and behavioral problems in preschool children, and to provide reference for the prevention and control of emotional and behavioral problems in preschool children. METHODS: Using a stratified cluster sampling method, 2 049 preschool children were surveyed from November to December 2021, who sampled from 12 kindergartens in Wuhu City, Anhui Province. The emotional and behavioral problems of preschool children were assessed with the Strength and Difficulties Questionnaire. Pearson correlation analysis was used to evaluate the relationship of maternal parenting stress and mother-child relationship with children's emotional and behavioral problems. The PROCESS Macro was used to analyze the moderating effect of conflicted and dependent mother-child relationships in the association between maternal parenting stress and emotional and behavioral problems in these preschool children. RESULTS: Among these preschool children, maternal parenting stress was positively correlated with the scores of emotional symptoms, conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001); intimate mother-child relationships were negatively correlated with the scores of conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001); conflicted and dependent mother-child relationships were positively correlated with the scores of emotional symptoms, conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001). After controlling for relevant confounding factors, conflicted mother-child relationship (ß=0.05, P=0.001) and dependent mother-child relationship (ß=0.04, P=0.012) were found to have a moderating effect on the association between maternal parenting stress and total difficulty scores in these preschool children. CONCLUSIONS: Negative mother-child relationships play a moderating role in the association between maternal parenting stress and emotional and behavioral problems in preschool children. Prevention of emotional and behavioral problems in preschool children should focus on reducing maternal parenting stress and improving negative mother-child relationships.

Effects of intensive blood pressure control on cardiovascular and cognitive outcomes in patients with atrial fibrillation: insights from the SPRINT trial.

AIMS: Patients with atrial fibrillation (AF) have an increased risk of cardiovascular events and dementia, even if anticoagulated. Hypertension is highly prevalent in AF population; however, the optimal blood pressure (BP) target for AF patients remains unknown. METHODS AND RESULTS: We conducted subgroup analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) to examine whether AF modified the treatment effects of intensive BP control on cardiovascular and cognitive outcomes using Cox proportional hazards regression and likelihood ratio tests. Among 9361 randomized participants, 778 (8.3%) had baseline AF, and 695 (89.3%) completed at least one follow-up cognitive assessment. Intensive BP control reduced the similar relative risk of cardiovascular events irrespective of the presence of AF, with all interaction P-values > 0.05. Patients with AF experienced a greater absolute risk reduction in the composite primary cardiovascular outcome (12.3 vs. 5.6 events per 1000 person-years) with intensive treatment, compared with those without AF. However, intensive BP control increased the risk of probable dementia in patients with AF [hazard ratio (HR), 2.22; 95% confidence interval (CI), 1.03-4.80], while reducing the dementia risk in patients without AF (HR, 0.75; 95% CI, 0.60-0.95; P = 0.009 for interaction). There were no significant interactions between the presence of AF and intensive BP treatment for mild cognitive impairment. CONCLUSION: Patients with AF experienced greater absolute cardiovascular benefits with intensive BP treatment, but may need to be cautious of an increased risk of dementia. This post hoc analysis should be considered as hypothesis generating and merit further study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

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).

Evaluation of Safety and Effectiveness of Catheter Ablation of Atrial Fibrillation in Patients Aged ≥80 Years.

AIMS: The prevalence and incidence of atrial fibrillation (AF) significantly increase with age. Catheter ablation is already recommended in the guidelines for this selected elderly population. This study aimed to explore the safety and effectiveness of AF catheter ablation in patients aged ≥80 years. METHODS: The data were based on the China-AF study. Patients with AF aged ≥80 years who received catheter ablation from August 2011 to December 2020 were selected. Catheter ablation included bilateral circumferential pulmonary vein antrum isolation with or without additional linear ablation. Patients were followed up every 6 months. Arrhythmia-free curves were generated using Kaplan-Meier analysis. Cox proportional hazards regression models were used to analyse the predictors for post-ablation recurrence. RESULTS: A total of 270 patients were included in the study. Many patients had comorbidities: 73.7% had hypertension and 29.3% had diabetes mellitus. All patients achieved successful bilateral circumferential pulmonary vein antrum isolation. Total complications were noted in nine of 270 (3.3%) patients and nine of 286 (3.1%) ablation procedures. After the first ablation procedure, 74% of the whole cohort-78% patients with paroxysmal AF, and 66% patients with persistent AF - were free from atrial tachyarrhythmia at follow-up to 12 months. Patients with persistent AF, longer AF duration, and history of ischaemic stroke were more likely to have AF recurrence. CONCLUSION: Patients with AF aged ≥80 years, although with many comorbidities, had low complication rates and favourable outcomes after catheter ablation. Catheter ablation was a safe and effective treatment to achieve sinus rhythm in the selected elderly patients.

Ethanol infusion into the vein of Marshall for recurrent perimitral atrial tachycardia after catheter ablation for persistent atrial fibrillation.

BACKGROUND: Catheter ablation of perimitral atrial tachycardia (PMAT) is challenging. Epicardial conduction of the Marshall bundle (MB) across the mitral isthmus (MI) remains an important cause of recurrent tachycardia. The role of ethanol infusion into the vein of Marshall (EI-VOM) for PMAT has not been fully elucidated. METHODS: The study enrolled 28 consecutive patients with recurrent PMAT after atrial fibrillation (AF) ablation. Conventional PMAT (group 1, n = 15) and MB-related PMAT (group 2, n = 13) were diagnosed by detailed activation mapping and entrainment mapping. VOM venography and EI-VOM were first performed, and additional ablation was performed if necessary. RESULTS: The VOM was accessible in 24 (85.7%) patients (12 [80%] in group 1 and 12 [92.3%] in group 2). Patients with MB-related PMAT were more responsive to EI-VOM (as shown by PMAT termination or tachycardia cycle length prolongation) (92.4% vs 53.3%, P = .038). In the 16 patients requiring additional ablation after EI-VOM, all residual MI conduction gaps were located on the annular side of the MI. At the end of the procedure, MI bidirectional block was achieved in 14 (93.3%) patients in group 1 and in 12 (92.3%) patients in group 2 (P = 1.000). After a mean follow-up of 7.5 ± 3.1 months, three (10.7%) patients had recurrent AT. CONCLUSIONS: EI-VOM is feasible and effective in the treatment of PMAT after AF ablation, especially in patients with MB-related PMAT.

Picophytoplankton identification by flow cytometry and high-throughput sequencing in a clean reservoir.

Understanding picophytoplankton variations that play important roles in the material circulation and energy flow are critical to assessing overall status of waterbody, especially for clean reservoirs which remain a relatively stable community structure and high species diversity due to lower nitrogen and phosphorus nutrients. However, their response to key environmental factors and tightly acting microbial remains poorly understood. Traditional quantification methods are limited, such as chlorophyll-a, turbidity and microscope. There are still many defects with present molecular analysis. In this study, a flow cytometric analysis and high-throughput sequencing combination methodology was developed and tested on clean water from a reservoir, by a monthly dynamic for a vegetative period April-September in 2019 to improve the accuracy of dynamic monitoring for the picophytoplankton system. More species of Pico-Cyanobacteria and Pico-Eukaryotes were discovered. The increased percentage of pigment compounds from 8.2% to 76.3% proves the effective reduce of heterotrophic disturbing and enrichment of target populations. Picophytoplankton that was previously neglected due to their low relative abundance has once again entered the scope of our eyes. Phytoplankton were divided into three categories. The first one was the highly abundant and frequently present taxa, the second one was the low-abundance but highly-transient population, and the third one was the low abundance and stable group. Synechococcus, Emiliania, Tetraselmis and Thalassiosira were dominant picophytoplankton and displayed obvious temporal and spatial distribution characteristics. Pico-PE rich Cyanobacteria and Nano-Eukaryotes with high transience abnormally increased in summer. Temperature, ammonia-N, nitrate-N, turbidity and total nitrogen were most influencing factors, while some picophytoplankton with special physiological structure showed distinct competitive advantages in the microbial community. As for the off-flavor compounds, the concentration of 2-methylisoborneol and geosmin were high even 66.7% and 20.8% of the samples exceeded their olfactory threshold. Chrysochromuina, Planktothrix and Microcystis might be the potential producers.

New-Onset Atrial Fibrillation and Adverse In-Hospital Outcome in Patients with Acute Pulmonary Embolism.

Atrial fibrillation (AF) can be secondary to acute pulmonary embolism (PE). This study aimed to investigate the prognostic impact of new-onset AF on patients with acute PE. In this study, 4,288 consecutive patients who were diagnosed with acute PE were retrospectively screened. In total, 77 patients with acute PE and new-onset AF were analyzed. Another 154 acute PE patients without AF were selected as the age- and sex-matched control group. Adverse in-hospital outcome comprised one of the following conditions: all-cause death, endotracheal intubation, cardiopulmonary resuscitation, and intravenous catecholamine therapy. The patients with new-onset AF had higher prevalence of congestive heart failure, higher simplified PE severity index (sPESI), higher creatinine, and larger left atrium diameter. The incidences of adverse in-hospital outcomes were 10.4 and 2.6% in patients with new-onset AF and no AF, respectively (p = 0.02). Patients with sPESI ≥ 1 had higher incidence of adverse in-hospital outcomes than those with sPESI = 0 (9.4 vs. 0.9%, p < 0.01). The area under the receiver operating characteristic curve of sPESI and sPESI + AF (adding 1 point for new-onset AF) scores in assessing the adverse in-hospital outcome were 0.80 (95% confidence interval [CI]: 0.68-0.93) and 0.84 (95% CI: 0.72-0.96), respectively. In multivariable analysis, sPESI ≥ 1 (odds ratio, 8.88; 95% CI: 1.10-72.07; p = 0.04) was an independent predictor of adverse in-hospital outcome. However, new-onset AF was not an independent predictor. In the population studied, sPESI is an independent predictor of adverse in-hospital outcomes, whereas new-onset AF following acute PE is not, but it may add predictive value to sPESI.

Left-sided accessory pathways successfully ablated from the aortomitral continuity region: distinctive atrial activation patterns and anatomic concerns.

AIMS: Accessory pathways (APs) successfully ablated at the aortomitral continuity (AMC) were sporadically reported but relevant data are very limited. We aimed to describe the electrophysiological characteristics of AMC-AP and the related anatomy. METHODS AND RESULTS: This study involved eight (male/female = 3/5, mean age 42.6 ± 10.5 years) patients with left-sided AP successfully ablated in the AMC region. The retrograde atrial activation sequence was analysed and compared via recordings at the His-bundle (HB), coronary sinus (CS), and roving catheter during tachycardia, and the peak of QRS from the same cardiac circle used as time reference. Of the eight patients, two received prior ablations. During tachycardia, the activation time at the proximal CS (CSp), lateral CS (CSl), and HB region averaged 120 ± 26 ms, 124 ± 29 ms, and 117 ± 21 ms following the reference, respectively (P = 0.86). The latest atrial activation was recorded in the posterior CS which averaged 135 ± 25 ms following the reference. Placing the ablation catheter to AMC via retrograde approach was attempted in all cases but stable positioning achieved in none. Via transseptal approach, the ablation catheter could be easily placed at the AMC and recorded the earliest retrograde atrial activations with 60 ± 27 ms earlier than the relatively 'earliest' CS/HB recordings, and ablation at this site successfully eliminated AP conduction. No patients had recovered AP conduction after at least 12-month follow-up. CONCLUSION: AMC-AP is featured by recording comparable retrograde atrial activation times at CSp, CSl, and HB with the latest recordings at the posterior CS. Stable placement and successful ablation in the AMC via retrograde aortic approach was difficult but can be achieved via transseptal approach.

Recombinant human arginase induces apoptosis through oxidative stress and cell cycle arrest in small cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer cases. Small cell lung cancer is characterized by frequent relapse, and current treatments lack tumor specificity. Arginine is a non-essential amino acid for human normal cells but critical to some tumor cells that cannot synthesize arginine. Therefore, arginine deprivation has become a potential therapeutic option for selected tumors. BCT-100 is a pegylated arginase that has documented anticancer activity in arginine auxotrophic tumors, such as melanoma, hepatocellular carcinoma, and acute myeloid leukemia. One of the resistance mechanisms to arginase treatment is overexpression of argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC), two important enzymes in the urea cycle. We selected 9 SCLC and 1 non-small cell lung carcinoma cell lines to determine the growth inhibition effects of BCT-100 and established that cell lines with low expression of ASS1 and OTC are relatively sensitive to BCT-100 treatment. Knocking down OTC in a H841 cell line could potentiate its sensitivity to BCT-100 treatment. Arginine concentration was sharply decreased, accompanied by apoptosis through oxidative stress as well as G1 cell cycle arrest. In addition, BCT-100 showed an anticancer effect on H446 and H510A xenograft models by lowering arginine levels and inducing apoptosis.

Long-term outcome of catheter ablation for atrial fibrillation in patients with apical hypertrophic cardiomyopathy.

INTRODUCTION: To assess the long-term outcome of catheter ablation in patients with hypertrophic cardiomyopathy (HCM), especially in patients with apical HCM (ApHCM). METHODS AND RESULTS: From 9,249 AF ablation cases, 97 patients (28 with ApHCM and 69 with non-ApHCM) were enrolled. Another 97 patients matched by age, AF type, AF duration, and left atrial diameter were selected as the control group. After a mean follow-up of (44.3 ± 29.6) months, success rate after a single procedure was 42.9% in the ApHCM patients (P  =  0.725), 36.2% in the non-ApHCM patients (P  =  0.136) versus 50.5% in the control group. After multiple procedures, success rate both in the ApHCM group (50%, P  =  0.047) and in the non-ApHCM group (50.4%, P  =  0.017) were lower than in the controls (68.0%). More patients in the ApHCM and in the non-ApHCM group suffered very late recurrence beyond 1 year after the index procedure. Left atrial diameter (hazard ratio [HR] 1.04, 95% confidential interval [CI] 1.01-1.08, P  =  0.018) and AF duration (HR 1.01, 95% CI 1.00-1.01, P  =  0.005) were independent predictors of recurrence after the index ablation. There was no difference in thromboembolic events between the HCM group and the control group (8.2% vs. 3.1%, P  =  0.082). CONCLUSIONS: Patients with ApHCM or non-ApHCM had similar success rate of AF ablation after single procedure and lower success rate after multiple procedure compared with the control group.

Transseptal puncture and catheter ablation of atrial fibrillation in patients with atrial septal occluder: initial experience of a single centre.

Aims: Catheter ablation is underutilized in atrial septal defect (ASD) patients who have undergone implantation of an atrial septal occluder (ASO). This study evaluates the feasibility and safety of catheter ablation of atrial fibrillation (AF) in this subset of patients. Methods and results: Sixteen patients (age 56 ± 12 years, 10 men) with drug-refractory AF (10 paroxysmal and 6 persistent) and previously implanted ASO were enrolled. Balloon dilatation of the closure device was performed if the native septum passage could not be achieved. For paroxysmal AF, the ablation strategy was circumferential pulmonary vein isolation (CPVI), and for persistent AF, additional linear ablation was performed. Transseptal access was achieved through the native septum in 11 patients (Group A) and through the ASO using balloon dilatation in 5 patients (Group B). Circumferential pulmonary vein isolation was achieved in all 16 patients, and linear block was achieved in all persistent patients except for 1 patient who did not achieve mitral isthmus block. The transseptal, total fluoroscopy, and procedural durations were 5 ± 3 vs. 38 ± 8 min, 31 ± 11 vs. 54 ± 15 min, and 165 ± 35 vs. 224 ± 36 min, respectively, in Group A vs. Group B, respectively (all P < 0.05). No shunt at atrial level was detected by transthoracic echocardiography at 3-month follow-up. During a follow-up of 16 ± 6 months, sinus rhythm was maintained in 12 of 16 patients. No severe complications were observed. Conclusion: In ASD patients with ASO, catheter ablation of AF is feasible, safe, and effective. The balloon dilatation technique can facilitate transseptal access through the ASO.

Elevated homocysteine increases the risk of left atrial/left atrial appendage thrombus in non-valvular atrial fibrillation with low CHA2DS2-VASc score.

Aims: To assess the association and the predictive value of plasma homocysteine (Hcy) levels with LA/LAA thrombus in non-valvular Atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Methods and results: Eight hundred and eighty-eight consecutive patients in non-valvular AF with CHA2DS2-VASc score of 0 and 1 were enrolled. All patients routinely underwent transthoracic echocardiography and transoesophageal echocardiography. A total of thirty-two patients had LA/LAA thrombus. Compared with patients without LA/LAA thrombus, plasma Hcy levels were significantly higher in patients with LA/LAA thrombus (16.5 ± 4.8 mmol/L vs. 13.4 ± 4.1 mmol/L, P = 0.009). In multivariate analysis, Hcy was independently associated with LA/LAA thrombus (OR 1.048, 95% CI 1.007-1.090, P = 0.022). Hcy demonstrated a significant predictive value with area under the curve of 0.722 (95% CI 0.662-0.781, P < 0.001). The optimal cut-off point for Hcy predicting LA/LAA thrombus was 13.5 mmol/L (sensitivity 67%, specificity 65%). Patients with Hcy ≥13.5 mmol/L had higher prevalence of LA/LAA thrombus compared with those with Hcy <13.5 mmol/L (6.1% vs. 2.1%, P < 0.001). Elevated Hcy significantly increased the risk of LA/LAA thrombus in patients with CHA2DS2-VASc score of 0 and 1 (OR 11.789, 95% CI 1.437-96.746, P = 0.022; OR 2.256, 95% CI 1.007-5.155, P = 0.048, respectively). Conclusion: Elevated plasma Hcy increases the risk of LA/LAA thrombus in non-valvular AF patients with low CHA2DS2-VASc score, thus it should be taken into account in prediction of thromboembolism.

Clinical characteristics associated with the onset of delirium among long-term nursing home residents.

BACKGROUND: Nursing home residents are frail, have multiple medical comorbidities, and are at high risk for delirium. Most of the existing evidence base on delirium is derived from studies in the acute in-patient population. We examine the association between clinical characteristics and medication use with the incidence of delirium during the nursing home stay. METHODS: This is a retrospective cohort study of 1571 residents from 12 nursing homes operated by a single care provider in Ontario, Canada. Residents were over the age of 55 and admitted between February 2010 and December 2015 with no baseline delirium and a minimum stay of 180 days. Residents with moderate or worse cognitive impairment at baseline were excluded. The baseline and follow-up characteristics of residents were collected from the Resident Assessment Instrument-Minimal Data Set 2.0 completed at admission and repeated quarterly until death or discharge. Multivariate logistic regression was used to identify characteristics and medication use associated with the onset of delirium. RESULTS: The incidence of delirium was 40.4% over the nursing home stay (mean LOS: 32 months). A diagnosis of dementia (OR: 2.54, p < .001), the presence of pain (OR: 1.64, p < .001), and the use of antipsychotics (OR: 1.87, p < .001) were significantly associated with the onset of delirium. Compared to residents who did not develop delirium, residents who developed a delirium had a greater increase in the use of antipsychotics and antidepressants over the nursing home stay. CONCLUSIONS: Dementia, the presence of pain, and the use of antipsychotics were associated with the onset of delirium. Pain monitoring and treatment may be important to decrease delirium in nursing homes. Future studies are necessary to examine the prescribing patterns in nursing homes and their association with delirium.

Growth suppressive effect of pegylated arginase in malignant pleural mesothelioma xenografts.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a difficult-to-treat global disease. Pegylated arginase (BCT-100) has recently shown anti-tumor effects in hepatocellular carcinoma, acute myeloid leukemia and melanoma. This study aims to investigate the effects of PEG-BCT-100 in MPM. METHODS: A panel of 5 mesothelioma cell lines (H28, 211H, H226, H2052 and H2452) was used to study the in vitro effects of BCT-100 by crystal violet staining. The in vivo effects of BCT-100 were studied using 211H and H226 nude mice xenografts. Protein expression (argininosuccinate synthetase, ornithine transcarbamylase, cleaved PARP, cleaved caspase 3, cyclins (A2, D3, E1 and H), CDK4 and Ki67) and arginine concentration were evaluated by Western blot and ELISA respectively. Cellular localization of BCT-100 was detected by immunohistochemistry and immunoflorescence. TUNEL assay was used to identify cellular apoptotic events. RESULTS: Argininosuccinate synthetase was expressed in H28, H226, and H2452 cells as well as 211H and H266 xenografts. Ornithine transcarbamylase was undetectable in all cell lines and xenograft models. BCT-100 reduced in vitro cell viability (IC50 values at 13-24 mU/ml, 72 h) across different cell lines and suppressed tumor growth in both 211H and H226 xenograft models. BCT-100 (60 mg/kg) significantly suppressed tumor growth (p < 0.01) with prolonged median survival (p < 0.01) in both xenograft models. Combining BCT-100 with pemetrexed or cisplatin conferred no additional benefits over single agents. Serum and intratumoral arginine levels were effectively decreased by BCT-100, associated with cytosolic accumulation of BCT-100 within tumor cells. Apoptosis (PARP cleavage in 211H xenografts; Bcl-2 downregulation, and cleavage of PARP and caspase 3 in H226 xenografts; positive TUNEL staining in both) and G1 arrest (downregulation of cyclin A2, D3, E1 and CDK4 in 211H xenografts; suppression of cyclin A2, E1, H and CDK4 in H226 xenografts) were evident with BCT-100 treatment. Furthermore, proliferative factor Ki67 was downregulated in BCT-100 treatments arms. CONCLUSIONS: BCT-100 suppressed tumor growth with prolonged median survival partially mediated by intratumoral arginine depletion resulting in apoptosis and G1 arrest in mesothelioma xenograft models. The findings provide scientific evidence to support further clinical development of BCT-100 in treatment of MPM.

Rationale and design of the Chinese Atrial Fibrillation Registry Study.

BACKGROUND: Robust data on the contemporary management of atrial fibrillation (AF) patients in China are limited. Importantly current practice in AF management has changing dramatically in recent years. Data from a large registry study will enable us to evaluate the uptake and outcomes with different therapies in a large Chinese AF population. METHODS/DESIGN: The Chinese Atrial Fibrillation Registry study (CAFR) aims to enroll 20,000 consecutive atrial fibrillation (AF) patients from 32 tertiary and non-tertiary hospitals in Beijing, China, and follow up these patients every 6 months until 2020. Key data collected includes basic sociodemographic information, symptoms and signs, medical history, results of physical examination and laboratory test, details of treatments and personal insurance status. For patients who consent, 5 ml of blood sample will be stored at -80 °C for future analyses of biomarkers. At each 6 month follow up visit, data relating to clinical outcomes will be collected. Data from a randomly selected 10 % of patients will be internally validated with their raw source data. Ischemic stroke events will be adjudicated by an independent endpoint committee. DISCUSSION: CAFR will be one of the largest registries of Asian AF patients (and the largest in Chinese AF patients), as well as providing the longest follow up. This study would provide a valuable opportunity for 'real world' clinical epidemiology with insights into the uptake (and outcomes) of contemporary AF management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OCH-13003729 . Registered 22 October 2013.