Re-evaluating serum angiotensin-converting enzyme in sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, which mainly affects the lungs and lymph nodes, as well as extrapulmonary organs. Its incidence, and prevalence rate, and disease course largely vary with regions and populations globally. The clinical manifestations of sarcoidosis depend on the affected organs and the degree of severity, and the diagnosis is mainly based on serum biomarkers, radiographic, magnetic resonance, or positron emission tomography imaging, and pathological biopsy. Noncaseating granulomas composing T cells, macrophages, epithelioid cells, and giant cells, were observed in a pathological biopsy, which was the characteristic pathological manifestation of sarcoidosis. Angiotensin-converting enzyme (ACE) was first found in the renin-angiotensin-aldosterone system. Its main function is to convert angiotensin I (Ang I) into Ang II, which plays an important role in regulating blood pressure. Also, an ACE insertion/deletion polymorphism exists in the human genome, which is involved in the occurrence and development of many diseases, including hypertension, heart failure, and sarcoidosis. The serum ACE level, most commonly used as a biomarker in diagnosing sarcoidosis, in patients with sarcoidosis increases. because of epithelioid cells and giant cells of sarcoid granuloma expressing ACE. Thus, it serves as the most commonly used biomarker in the diagnosis of sarcoidosis and also aids in analyzing its therapeutic effect and prognosis in patients with sarcoidosis.

Impact of age on characteristics, performance measures and outcomes of inpatients for heart failure in Beijing, China.

AIMS: This study aims to provide representative information on heart failure (HF) patients in China, especially older adults aged ≥75 years. We aim to clarify the age-related discrepancies in performance measures and the modifying effect of age on the impact of HF patients' characteristics on clinical outcomes. METHODS AND RESULTS: All HF patients admitted into five tertiary and four secondary hospitals of the Capital Medical University were divided into two groups according to age: 1419 (53.3%) were <75 years, and 1244 (46.7%) were ≥75 years. Older HF patients were more likely to be women, with higher left ventricular ejection fraction, with co-morbidities including chronic obstructive pulmonary disease/asthma, anaemia, chronic kidney disease, stroke/transient ischemic attack (TIA), atrial fibrillation/atrial flutter, hypertension, and coronary artery disease, while obesity, diabetes mellitus, hypercholesterolaemia and valvular heart disease were more prevalent among younger HF patients. Left ventricular ejection fraction assessment was performed in a similar proportion of patients in the younger and older groups (81.7% vs. 80.5%, P = 0.426), while B-type natriuretic peptide/N terminal pro brain natriuretic peptide was tested in a lower proportion in the younger group (84.8% vs. 89%, P = 0.001). At discharge, HF with reduced ejection fraction patients were less likely to receive beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, or combined beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy in the older group (49.74% vs. 63.2%, P = 0.002; 52.9% vs. 64.7%, P = 0.006; and 28.57% vs. 45.5%, P < 0.001, respectively) but were equally likely to receive mineralocorticoid receptor antagonists in the two age groups (80.8% vs. 84.1%, P = 0.322). Older patients with HF had higher risk of in-hospital and 1 year mortality (2.7% vs. 1.3%, P = 0.011; 21.7% vs. 12.5%; P < 0.001, respectively). Higher body mass index was associated with better outcomes in both age groups. New York Heart Association functional class IV and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were independent predictors of 1 year mortality. The associations between patients' characteristics and risk of mortality were not modified by age. CONCLUSIONS: HF patients aged ≥75 years had distinct clinical profiles, received worse in-hospital therapies and experienced higher in-hospital and 1 year mortality.

Stentless at ostium: a novel approach for treating ostial left anterior descending or left circumflex coronary artery lesions with drug-coated balloons.

BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.

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

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

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.

Clinical Characteristics and Contemporary Prognosis of Ventricular Septal Rupture Complicating Acute Myocardial Infarction: A Single-Center Experience.

Objectives: Ventricular septal rupture (VSR) is a rare but lethal complication of acute myocardial infarction (AMI). We conducted a retrospective analysis of the clinical characteristics of VSR patients and explored the risk factors for long-term mortality. Methods: In this single-center cohort study, 127 patients diagnosed with post-AMI VSR between May 2012 and April 2019 were included. Demographic, clinical, operative, and outcome data were collected. The 30-day and long-term mortality were outcomes of interest. Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The mean age of the VSR cohort was 66.6 ± 8.7 years, 67 (52.8%) were males. Among the 127 patients, 78 patients (61.4%) were medically managed, 31 (24.4%) patients underwent percutaneous transcatheter closure (TCC), and 18 (14.2%) patients received surgical repair. The median follow-up time was 1129 days [interquartile range: 802-2019 days]. The 30-day mortality of the medically managed group, percutaneous TCC group, and surgical management group was 93.6, 22.6, and 11.1%, respectively; and the long-term mortality was 96.2, 25.8, and 22.2%, respectively. VSR repair treatment including surgical management (HR 0.01, 95% CI 0.001-0.09, p < 0.001) and percutaneous TCC (HR 0.09, 95% CI 0.03-0.26, p < 0.001) was associated with a better prognosis, and cardiogenic shock (CS) (HR 9.30, 95% CI 3.38-25.62, p < 0.001) was an independent risk factor of long-term mortality. Conclusions: The prognosis of VSR patients without operative management remains poor, especially in those complicated with CS. Timely and improved surgery treatment is needed for better outcomes in VSR patients.

A strategy of idarucizumab for pericardial tamponade during perioperative period of atrial fibrillation ablation.

OBJECTIVE: To investigate theoptimal idarucizumab (dabigatran antagonist) usage strategy for patients with acute pericardial tamponade receiving uninterrupted dabigatran during catheter ablation for atrial fibrillation (AF). METHODS: Ten patients presenting acute pericardial tamponade while receiving uninterrupted dabigatran during catheter ablation for AF in Beijing Anzhen Hospital from January 2019 to July 2020 were enrolled and retrospectively analyzed. A "wait and see" strategy of idarucizumab was carried out for all patients; in brief, idarucizumab was applied following pericardiocentesis, comprehensive evaluation of bleeding and hemostasis. RESULTS: There were five males, five paroxysmal AF, and the average age of the patients was 64.0 ± 9.8 years. Among the 10 patients, four were treated with dabigatran 110 mg, six were treated with dabigatran 150 mg, and one was simultaneously given clopidogrel. The average time from pericardial tamponade to the last dose of dabigatran was 8.2 ± 3.4 h. All patients underwent pericardiocentesis successfully, and the average drainage volume was 322.5 ml (220.0 ± 935.0 ml). For reversal anticoagulation, six patients received protamine, and five patients received idarucizumab. Of the five patients who were treated with idarucizumab, four presented exact hemostasis, except for one patient who underwent continuous drainage and finally received surgery repair. The average time to restart anticoagulation was 1.1 ± 0.3 days after the procedure, and no rebleeding, embolism or deaths were observed. CONCLUSION: The "wait and see" strategy of idarucizumab for acute pericardial tamponade during the perioperative period of catheter ablation for AF may be safe and feasible.

Catheter ablation of atrial fibrillation in situs inversus dextrocardia: Challenge, improved procedure, outcomes, and literature review.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF-CA) in patients with situs inversus dextrocardia (SID) can be challenging because of the contrary anatomy and associated anomalies. Cases and literature regarding AF-CA in SID are rare and provide little information. Our study aims to present an improved procedure, ablation strategies, and evaluate the safety and outcomes of AF-CA in patients with AF and SID. METHODS: A total of 10 patients with AF-SID (mean age, 60.4 ± 15.7 years; six paroxysmal AF, four persistent atrial fibrillation [PeAF]) were enrolled. For the improved procedure, images obtained by preacquired computed tomography and three-dimensional electroanatomical mapping, integrating intracardiac echocardiography, and x-ray imaging data are necessary to optimize the transseptal puncture and ablation procedure. RESULTS: All patients successfully underwent 13 AF-CA procedures without complications, including three patients received repeat procedures. However, two PeAF patients presented sick sinus syndrome (SSS) after the AF-CA procedure, and one underwent permanent pacemaker implantation therapy during hospitalization. During the follow-up period (6-72 months), the outcomes were not favorable: three patients (30%) maintained sinus rhythm (SR) after the initial procedure; after repeated procedures, the overall SR rate was 40% (four patients). CONCLUSION: With the improved strategy, AF-CA can be safely and effectively performed with low radiation exposure in patients with SID. However, the long-term outcomes were not favorable, even when managed at a tertiary center by a team of specialists. Moreover, patients with PeAF might also have masked SSS, which should be carefully considered.

Promising xenograft animal model recapitulating the features of human pancreatic cancer.

BACKGROUND: Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer (PC). There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling. AIM: To create a new xenograft animal model that can faithfully recapitulate the features of human PC. METHODS: Interleukin 2 receptor subunit gamma (IL2RG) gene knockout Syrian hamster was created and characterized. A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically. Tumor growth, local invasion, remote organ metastasis, histopathology, and molecular alterations of tumor cells and stroma were compared over time. RESULTS: The Syrian hamster with IL2RG gene knockout (named ZZU001) demonstrated an immune-deficient phenotype and function. ZZU001 hamsters faithfully recapitulated most features of human PC, in particular, they developed metastasis at multiple sites. PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes, whereas PC tissues derived from immune-deficient mice did not present such features. CONCLUSION: ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice. ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.

Maternal arrhythmia in structurally normal heart: Prevalence and feasibility of catheter ablation without fluoroscopy.

BACKGROUND: Data on management of maternal arrhythmia among Chinese were limited. Radiofrequency catheter ablation (RFCA) proved to be a reliable treatment choice for sustained tachyarrhythmia but it has rarely been performed during pregnancy due to radiation exposure. OBJECTIVE: To investigate the incidence of idiopathic sustained maternal arrhythmia and the feasibility of RFCA in the pregnant patients without fluoroscopy. METHODS: From January of 2015 to December of 2018, the medical records on pregnancy-related admissions in Beijing Anzhen Hospital (Beijing, China) were retrospectively analyzed. Patients who had sustained tachyarrhythmia episodes without structural heart disease were identified. Catheter ablation was performed in those with drug resistant and severely frequent tachyarrhythmia under the guidance of electroanatomical mapping system and intracardiac echocardiography catheter (ICE), if appropriate. RESULTS: During the study period, 12 584 consecutive pregnant women were admitted for pregnancy-related reasons, 156 (1.2%) of them were identified as sustained maternal tachyarrhythmia. Twenty-eight patients (age 21-37 years) received catheter ablation because the arrhythmias were drug resistant and severely frequent. The RFCA was successfully performed in all patients with zero fluoroscopy after 72.4 ± 24.7 min. Transseptal puncture was performed in 11 patients under the guidance of ICE. In a median of 37 (interquartile range [IQR]: 34-39) weeks' pregnancy, 28 healthy fetuses were delivered. No cardiac-related adverse event occurred during delivery. During later follow-up, all patients were free of arrhythmia, and all the infants were well developed. CONCLUSION: Sustained maternal tachyarrhythmia is not uncommon in the clinical practice. To those with drug resistant and severely frequent arrhythmia, RFCA with zero fluoroscopy could be safely performed with acceptable efficacy.

Prevalence of modifiable risk factors and relation to stroke and death in patients with atrial fibrillation: A report from the China atrial fibrillation registry study.

BACKGROUND: Lifestyle and risk factor management may improve outcomes in patients with atrial fibrillation (AF). We aim to evaluate the prevalence of modifiable risk factors and how these factors impact clinical outcomes in patients with AF. METHODS AND RESULTS: Data on 17 898 AF cohort patients with AF enrolled between 2011 and 2016 was analyzed. A healthy lifestyle was defined as not smoking, not drinking, a healthy body mass index (BMI), untreated total cholesterol less than 200 mg/dL, untreated blood pressure (BP) less than 120/80 mm Hg, and untreated fasting plasma glucose (FPG) less than 100 mg/dL. The association between risk factors and risk of the composite endpoint of all-cause mortality and nonfatal ischemic stroke were assessed using Cox proportional hazards regression model. Only 4.0% of patients achieved a healthy lifestyle. In multivariate analysis, current smoking, a low BMI, not well-controlled FPG were independently and significantly associated with higher risk of all-cause mortality and nonfatal ischemic stroke, with corresponding hazard ratio (HR) estimates 1.22 (95% confidence interval [CI], 1.00-1.47), HR = 1.72 (95% CI, 1.34-2.20), and HR = 1.25 (95% CI, 1.06-1.46), respectively. High BP was also associated with higher risk with the outcomes (HR = 1.15, 95% CI, 1.00-1.34). Compared with patients with no risk factor, those who failed to maintained or achieved optimal risk factor control had a progressively higher risk of death and nonfatal ischemic stroke (HR for 1 risk factor = 1.44; 95% CI, 1.07-1.92; and more than 2 risk factors = 1.75; 95% CI, 0.99-3.09). CONCLUSIONS: Maintenance of well-controlled risk factors may substantially lower the risk of death and ischemic stroke in patients with AF.

Ginkgo biloba extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway.

OBJECTIVE: The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1ß, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2. RESULTS: The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1ß in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group. CONCLUSION: EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction.

Luteolin decreases atherosclerosis in LDL receptor-deficient mice via a mechanism including decreasing AMPK-SIRT1 signaling in macrophages.

Lipid metabolism dysfunction and inflammatory infiltration into arterial walls are associated with the initiation and progression of atherosclerosis. Luteolin has been reported to possess anti-inflammatory actions and protect against tumor necrosis factor-α (TNF-α)-induced vascular inflammation, monocyte adhesion to endothelial cells and the formation of lipid-laden macrophages in vitro. However, the role of luteolin in atherosclerosis and the associated vascular inflammatory remains to be elucidated. The aim of the present study was to investigate the effects of luteolin on plaque development, lipid accumulation and macrophage inflammation low-density lipoprotein receptor-deficient (LDLR-/-) mice with atherosclerosis, as well as the underlying mechanisms in ox-induced THP-1-derived macrophages. Firstly, 9-week-old male C57BL/6 mice were fed a standard chow diet, western diet or western diet supplemented with 100 mg/kg luteolin for 14 weeks. The results of histological staining revealed that 100 mg/kg dietary luteolin ameliorated western diet-induced atherosclerotic plaque development and lipid accumulation in the abdominal aorta. Furthermore, total cholesterol, triglyceride and LDL-cholesterol levels were decreased in the plasma of western diet + luteolin mice compared with those fed with a western diet alone. Quantitative polymerase chain reaction analysis revealed that dietary luteolin inhibited the expression of cluster of differentiation 68, macrophage chemoattractant protein 2 and inflammatory cytokines, including interleukin-6 (IL-6) and TNF-α. Mechanistically, luteolin decreased the total cholesterol level as well as macrophage chemokine and inflammatory cytokine expression in THP-1-derived macrophages via AMP-activated protein kinase (AMPK)-Sirtuin (SIRT)1 signaling following induction with oxidized low-density lipoprotein. The results of the present study suggest that luteolin prevents plaque development and lipid accumulation in the abdominal aorta by decreasing macrophage inflammation during atherosclerosis, which is mediated by mechanisms including AMPK-SIRT1 signaling.

Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction.

Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD. Melatonin attenuated obesity-induced myocardial oxidative stress and apoptosis and promoted the secretion of C1q/tumour necrosis factor-related protein 3 (CTRP3) by adipose tissue. And depletion of circulating CTRP3 largely abolished melatonin-mediated cardio-protection. Melatonin-mediated secretion of adipocyte-derived CTRP3 activated NF-E2-related factor 2 (Nrf2), which were largely abrogated by knocking down CTRP3 in adipocytes or Nrf2 in cardiomyocytes. Nrf2 activation was mediated by miR-200a, and a miR-200a antagomir offset the effects of melatonin-conditioned medium on Nrf2 expression. Our results indicate that melatonin can be used to treat and prevent obesity-related HFpEF.

Acute administration of tumour necrosis factor-α induces spontaneous calcium release via the reactive oxygen species pathway in atrial myocytes.

Aims: The arrhythmogenic mechanisms of atrial fibrillation (AF) that are induced by acute inflammation, such as postoperative AF, are not well understood. We investigated the acute effects of tumour necrosis factor-α (TNF-α) that mimic acute inflammation on Ca2+ handling in isolated atrial myocytes and its underlying mechanisms. Methods and results: Cytosol Ca2+ handling and mitochondrial reactive oxygen species (ROS) production were studied in freshly isolated atrial myocytes of wild-type mice that were exposed to TNF-α (0.05 ng/mL) for 2 h by Ionoptix and confocal microscopy. The acute effects of TNF-α on Ca2+ handling were decreased amplitudes and prolonged decay times of Ca2+ transients in isolated atrial myocytes. A significant reduction in the sarcoplasmic reticulum (SR) Ca2+ content was detected in TNF-α treated cells, which was associated with increased spontaneous Ca2+ release events. In particular, physiological concentrations of TNF-α dramatically promoted the frequency of spontaneous Ca2+ waves and Ca2+ sparks, while the spark mass presented with reduced amplitudes and prolonged durations. The underlying mechanisms of pro-arrhythmic effects of TNF-α were further investigated. Acute exposure to TNF-α rapidly promoted mitochondrial ROS production that was correlated with the acute effect of TNF-α on Ca2+ handling, and enhanced the oxidation of calcium/calmodulin-dependent protein kinase II (CaMKII) and the phosphorylation of RyR2. However, the performance of ROS inhibitor, DL-Dithiothreitol (DTT), reversed Ca2+ handling disorders induced by TNF-α. Conclusion: Tumour necrosis factor-α rapidly increases spontaneous Ca2+ release and promotes atrial arrhythmogenesis via the ROS pathway, which suggests that antioxidant therapy is a promising strategy for acute inflammation related AF.

Reconstruction left atrium and isolation pulmonary veins of paroxysmal atrial fibrillation using single contact force catheter with zero x-ray exposure: A CONSORT Study.

BACKGROUND: Conventional ablation of paroxysmal atrial fibrillation (PAF) is associated with radiation risks for patients and laboratory staff. Three-dimensional (3D) mapping system capable of showing contact force (CF) and direction of catheter tip may compensate for nonfluoroscopic safety issues. OBJECTIVE: The aim of this study was to investigate the feasibility of zero x-ray exposure during reconstruction left atrium (LA) and ablation. METHODS: Single, CF catheter, and 3D mapping system were used to reconstruct LA and isolate pulmonary veins (PV) in all patients. The patients were randomly divided into 2 groups after LA angiography. In group 1, reconstruction LA and isolation PV was performed with the help of 3D system (without x-ray), whereas in group 2, x-ray and 3D system were utilized to reconstruct LA and ablate PV antrum. After ablation, Lasso catheter was used to confirm the PV isolation. All patients were followed up to 12 months. RESULTS: A total of 342 PAF patients were continuously enrolled. The basic clinical characteristics between the 2 groups had no significant difference. Parameters related to the procedure, average procedure time, ablation procedure time, average contact force (CF) applied, the percentage of time within CF settings, and average power applied during radiofrequency application showed no significant difference between the 2 groups. In group 1, the average fluoroscopy time before LA reconstruction was similar to that in group 2 (2.8 ±â€Š0.4 vs. 2.4 ±â€Š0.6 minutes, P = .75). The average fluoroscopy time during ablation was significantly lower than that in group 2 (0 vs. 7.6 ±â€Š1.3 minutes, P < .001). The total x-ray exposure dose of the procedure in group 1 was significantly lower than that in group 2 (19.6 ±â€Š9.4 vs. 128.7 ±â€Š62.5 mGy, respectively, P < .001). Kaplan-Meier analysis indicated that there were no statistical differences in the probability of freedom from atrial arrhythmia (AF/AFL/AT) recurrence at 12 months between group 1 and group 2 (P = .152). The success rate after a single ablation procedure and without drugs (Class I/III AAD) at 12 months was not significantly different between the 2 groups (67.6%, 95% confidence interval [CI]: 62%-79.5% in group 1 and 68.9%, 95% CI: 63%-80.7% in group 2, P = .207). Procedural-related adverse events showed no significant different incidence between group 1 and group 2. A multivariate logistic regression analysis of risk factors was performed to evaluate the effectiveness outcome, which demonstrated that the percentage of CF (within the investigator-selected work ranges) during therapy was significantly associated with positive outcomes (odds ratio: 3.68; 95% CI: 1.65-10.6, P = .008), whereas the LA dimension was negatively associated with effectiveness outcomes (odds ratio: 0.72; 95% CI: 0.52-0.84, P = .016). CONCLUSIONS: Reconstruction LA and isolation PV ablation using single CF-assisted catheter without x-ray exposure was both safe and effective. CF was positively associated with effective outcomes and LA dimensions negatively with effective ones.

Prophylactic Atropine Administration Prevents Vasovagal Response Induced by Cryoballoon Ablation in Patients with Atrial Fibrillation.

BACKGROUND: Cryoballoon (CB) ablation of pulmonary vein ostia often induces a vagal response. This prospective study was designed to assess the effectiveness of prophylactic intravenous administration of atropine on hemodynamic impairment induced by CB ablation in patients with atrial fibrillation. METHODS: Twenty-five patients with paroxysmal atrial fibrillation undergoing CB ablation were prospectively enrolled and assigned to one of two groups. First 12 patients (trial group) were administered 1 mg of atropine before deflation of the CB, while the following 13 patients (control group) were given atropine only after the onset of the hemodynamic variation (decrease in heart rate and/or blood pressure). Treatment was considered effective when the hemodynamic variations were restored. RESULTS: In the trial group, three patients with transient hypotension did not require supportive care throughout the procedures, and one patient with hypotension required supportive care. In the control group, hypotension, bradycardia, and mixed bradycardia with hypotension requiring supportive care occurred in six, three, and three patients, respectively. Overall, the rate of marked vagal responses was significantly lower when prophylactic atropine was administrated (4/12 patients vs 12/13 patients, respectively; P < 0.01). CONCLUSIONS: Atropine is significantly effective in the prevention of all types of vasovagal responses induced by CB ablation in patients with atrial fibrillation.

CHADS2 and CHA2DS2-VASc Scores Predict the Risk of Ischemic Stroke Outcome in Patients with Interatrial Block without Atrial Fibrillation.

AIM: To evaluate the role of CHADS2 and CHA2DS2-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF). METHODS: A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63±10 years) with IAB and without AF. IAB was defined as P-wave duration ＞120 ms using a 12-lead electrocardiogram. CHADS2 and CHA2DS2-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA. RESULTS: During the mean follow-up period of 4.9±0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2 score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562-0.715; P=0.001] and the CHA2DS2-VASc score (AUC, 0.671; 95% CI, 0.599-0.744; P＜0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2 score ≥3 (sensitivity=0.455 and specificity=0.747) and a CHA2DS2-VASc score ≥4 (sensitivity=0.564 and specificity=0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2 [hazard ratio (HR), 1.442; 95% CI, 1.171-1.774; P=0.001] and CHA2DS2-VASc (HR, 1.420; 95% CI, 1.203-1.677; P＜0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins. CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.

Usefulness of a Combination of Interatrial Block and a High CHADS2 Score to Predict New Onset Atrial Fibrillation.

Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS2 score, an AF-related risk score for ischemic stroke, with new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 ± 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS2 score as ≥ 2 points. During the mean follow-up period of 4.8 ± 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS2 score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS2 score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS2 score compared with no IAB and a low CHADS2 score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS2 score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS2 score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.

Ridge-related reentry despite apparent bidirectional mitral isthmus block.

BACKGROUND: Verification of bidirectional block is important for mitral isthmus (MI) ablation. However, recurrent perimitral reentry exists despite apparently MI block. OBJECTIVE: The purpose of this study was to identify and investigate the characteristics of the ridge breakthrough despite apparent bidirectional MI block and related reentry. METHODS: In 60 patients undergoing MI ablation and achieving the criteria of bidirectional block when assessed on the line, the pattern under differential pacing was reassessed at the ridge away from the line to check whether a breakthrough existed. Also, activation and entrainment mapping was performed in 7 patients with ridge-related reentry (RRR) to investigate its possible mechanism. RESULTS: A ridge breakthrough was found in 7 of 60 patients (11.7%) apparently fulfilling the criteria of bidirectional block. The delay from pacing artifact during distal coronary sinus pacing was shorter at the ridge than on the line (95.6 ± 11.7 ms vs 130.9 ± 15.3 ms; P < .001). In 7 patients with RRR, the left atrial endocardial activation time accounted for 58.5% ± 3.2% of the tachycardia cycle length (TCL) and wide double potential could be recorded on the line. The post-pacing interval (PPI) - TCL after entrainment at the ridge was shorter than that on the line (11.4 ± 3.9 ms vs 34.3 ± 6.6 ms; P < .001), and in 2 patients in whom entrainment from the coronary sinus was possible, the PPI - TCL was 15 and 18 ms, respectively. CONCLUSION: Apparent bidirectional MI block despite a ridge breakthrough is not uncommon and may lead to RRR, while the line is not part of the reentry.