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.

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.

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.

Vein of Marshall ethanol infusion: First-step or adjunctive choice for perimitral atrial tachycardia?

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.

Lambl's excrescence and the safety of radiofrequency ablation for atrial fibrillation.

BACKGROUND: Lambl's excrescences (LEs) are excrescences with an extremely low incidence, mainly ultrasound diagnosed. Increasingly, LEs are detected by transesophageal echocardiography before catheter ablation, which raises safety concerns on whether LEs were associated with an embolism event during or after ablation, but clinical data are still lacking. METHODS AND RESULTS: We consecutively recruited 8081 patients with atrial fibrillation who underwent radiofrequency catheter ablation in Beijing Anzhen Hospital from Jan 1, 2017 to Dec 31, 2019. Total 21 patients (0.3%) were diagnosed as LEs with an average age of 70.8 ± 8.9 years, and 38.1% were male. Persistent atrial fibrillation (PeAF) and paroxysmal atrial fibrillation (PAF) accounted for 57.1% (12 cases) and 42.9% (nine cases), respectively. LEs were mostly frequently observed on the aortic valve (18 cases, 75%) and mitral valve (six cases, 25%). Precisely, the noncoronary cusp is ranked first in terms of the LEs presence (seven cases, 29.2%), followed by the right coronary cusp (six cases, 25.0%), the left coronary cusp (five cases, 20.8%), the anterior mitral valve (four cases, 16.7%), and the posterior mitral valve (two cases, 8.3%). During the ablation for LEs patients, the average procedure time was 96.0 ± 22.4 min; the average fluoroscopy time was 4.2 ± 0.8 min; the average total ablation time was 20.6 ± 5.6 min; and the mean hospital stay was 3.3 ± 0.6 days. No patients suffered from serious complications during the procedure. Furthermore, no cardiovascular event was observed during a follow-up of 19.1 ± 11.8 months. CONCLUSIONS: There was no clear association between LEs with intraoperative embolism events or cardiovascular events during the follow-up period.

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.

Effectiveness of ethanol infusion into the vein of Marshall combined with a fixed anatomical ablation strategy (the "upgraded 2C3L" approach) for catheter ablation of persistent atrial fibrillation.

INTRODUCTION: Linear ablation in addition to pulmonary vein antrum isolation (PVAI) has failed to improve the success rate for persistent atrial fibrillation (PeAF), due to incomplete block of ablation lines, especially in the mitral isthmus (MI). METHODS AND RESULTS: The study enrolled 191 patients (66 in group 1 and 125 in group 2). In group 1, ethanol infusion into the vein of Marshall was first performed, followed by radiofrequency (RF) applications targeting bilateral PVAI and bidirectional block in the roofline, cavotricuspid isthmus, and MI. In group 2, PVAI and the three linear ablations were completed using only RF energy. MI block was achieved in 63 (95.5%) and 101 (80.8%) patients in groups 1 and 2, respectively (p = .006). Patients in group 1 had shorter ablation time for left pulmonary vein antrum (8.15 vs. 12.59 min, p < .001) and MI (7.0 vs. 11.8 min, p < .001) and required less cardioversion (50 [78.5%] vs. 113 [90.4%], p = .007). During the 12-month follow-up, 58 (87.9%) patients were free from atrial fibrillation/atrial tachycardia in group 1 compared with 81 (64.8%) in group 2 (p < .001). In multivariate cox regression, the "upgraded 2C3L" procedure is associated with a lower recurrence rate (hazard ratio = 0.27, 95% confidence interval = 0.12-0.59). CONCLUSION: Compared with the conventional "2C3L" approach, the "upgraded 2C3L" approach has higher effectiveness for ablation of PeAF.

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.

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.

Pravastatin alleviates intracellular calcium dysregulation induced by Interleukin-6 via the mitochondrial ROS pathway in adult ventricular myocytes.

Acute inflammation often contributes to the increased arrhythmogenesis in the cardiomyocytes. We investigated the protective effects of pravastatin on calcium disorders induced by acute administration of pro-inflammatory cytokines in isolated ventricular myocytes and its underlying mechanisms. Wild-type mice were intraperitoneally injected for five days with either pravastatin 20 mg/kg per day or an equal volume of normal saline. Cytosol Ca2+ handling was studied in freshly isolated ventricular myocytes after acute exposure of interleukin-6 (IL-6) (1 ng/ml) for 120 min by Ionoptix and confocal microscopy. Acute administration of clinically relevant concentrations of IL-6 disturbed calcium handling in ventricular myocytes, which presented as decreased amplitudes, prolonged decay times of Ca2+ transients, and reduced sarcoplasmic reticulum (SR) calcium stores. The frequency of spontaneous Ca2+ release, including calcium sparks and spontaneous calcium waves, was dramatically enhanced in the setting of IL-6. Notably, the pretreatment of pravastatin alleviated disturbed Ca2+ cycling, reduced spontaneous Ca2+ leakage induced by IL-6. Mitochondrial ROS pathway may constitute the underlying mechanism of the protective effects of pravastatin. Pravastatin protected the cardiomyocytes against calcium disorders induced by IL-6 via the mitochondrial ROS pathway, which suggests that pravastatin may represent a promising auxiliary therapeutic strategy for cardiac injury under acute inflammation.

Physical activity and atrial tachyarrhythmia recurrence in atrial fibrillation patients after catheter ablation.

BACKGROUND: The association between physical activity (PA) and atrial tachyarrhythmia (AT) recurrence after ablation for atrial fibrillation (AF) remains unclear. METHODS: We consecutively enrolled 496 patients treated with AF ablation therapy in Beijing Anzhen Hospital. After excluding six patients with valvular heart disease, seven patients with congenital heart disease, 33 patients lost to follow-up, and 14 patients who did not provide PA level during follow-ups, 436 patients had their PA level assessed by the International Physical Activity Questionnaire-Short Form before ablation and each time of follow-up. The association between PA level (measured at the time closest to AT recurrence, or the end of 12-month follow-up if no AT recurrence), as well as active PA during follow-up, and postablation AT recurrence was tested by multivariate logistic regression. RESULTS: Of the enrolled patients, 134 (30.7%) patients experienced AT recurrence in the first 12 months postablation. Compared to patients with low PA, patients with moderate or high PA had a lower risk of AT recurrence (odds ratio [OR] = .44; 95% confidence interval [CI], .25-.80; P = .01 for patients with moderate PA; and OR = .43 [95% CI, .21-.85], P = .02 for patients with high PA). Compared to patients without active PA, patients with active PA had a lower risk of AT recurrence (OR = .44 [95% CI, .27-.70], P < .01). CONCLUSIONS: Moderate and high PA are associated with a lower risk of AT recurrence after AF ablation. Active PA during follow-up is also associated with a significantly lower risk of AT recurrence in the postablation AF population.

Effectiveness and safety of atrial fibrillation ablation in females.

BACKGROUND: Existing data on the effectiveness and safety of atrial fibrillation (AF) ablation in females are limited to studies of small sample size, lacking longer term follow-up or adjustment for potential confounders. METHODS: A total of 6421 patients (2072 females) undergoing a first AF ablation procedure after enrollment in the Chinese Atrial Fibrillation Registry (China-AF) study between August 2011 and December 2017 were analyzed. We evaluated the effectiveness (recurrence of documented [symptomatic or not] atrial tachyarrhythmia (AT)) and the safety (incidence of procedure-related complications) of AF ablation in female patients compared to male patients. Sensitivity analyses based on routine data were also utilized to avoid potential sex differences in reporting of AF symptoms. RESULTS: Females were about 5 years older than males at the time of ablation (mean age 63.4 ± 9.5 vs 58.3 ± 10.8, P < .0001). A higher proportion of female patients had paroxysmal AF (74.3% vs 56.7%, P < .0001), hypertension (69.7% vs 61.3%, P < .0001), and hyperlipidemia (57.2% vs 52.9%, P = .001). Female sex was found to be an independent risk factor of AT recurrence in multivariate analyses (HR = 1.26, 95% CI 1.15-1.38, P < .0001). These findings were confirmed in sensitivity analyses using only Holter data. Female sex was also associated with a higher risk of periprocedural complications after adjustment for baseline variables (OR = 1.41, 95% CI 1.03-1.94, P = .03). CONCLUSIONS: Female sex is an independent risk factor of AT recurrence and periprocedural complications after AF ablation.

Urea-modulated UT-B urea transporter internalization is clathrin- and caveolae-dependent in infantile hemangioma-derived vascular endothelial cells.

The aim of this study was to investigate the manner of urea-modulated UT-B urea transporter (UT) internalization in infantile hemangioma-derived vascular endothelial cells (HemECs). The immunohistochemistry assay was performed to identify infancy hemangioma-derived endothelial cell line (XPTS-1) cells. Cell toxicity was detected with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Quantitative real-time polymerase chain reaction and Western blot analysis were measured to analyze the expression of UT-B. UT-B internalization was observed by confocal microscopy. The clathrin inhibitor chlorpromazine (CPZ) and caveolin endocytic disrupter methyl-ß-cyclodextrin (MßCD) were used in XPTS-1 cells transfected with UT-B-GFP to repress endocytosis. Urea-promoted UT-B expression in a concentration-dependent manner in an infantile XPTS-1 cell line. CPZ and MßCD significantly inhibited UT-B protein internalization. The pretreatment of UT-B-GFP cells with adaptor protein2 (AP2)-µ2-siRNA and caveolin-siRNA significantly inhibited UT-B protein internalization. Our findings suggested that urea-mediated UT-B UT internalization is clathrin and caveolae dependent in infantile HemECs.

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.

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

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

Characteristics of Right-Sided Accessory Pathways Associated With Right Cardiac Veins.

BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.

Small Left Ventricle in Patients With Atrial Fibrillation Is Associated With Increased Cardiovascular Risk.

BACKGROUND: It is still unclear whether small left ventricle (LV) is an adverse structural prognostic feature in patients with atrial fibrillation (AF). OBJECTIVES: The purpose of this study was to evaluate the association between small LV and risk of cardiovascular events in AF population. METHODS: From the China-AF registry, 7,764 patients with AF were enrolled and divided into groups with normal, small, and large LV size based on left ventricular end-diastolic dimension (LVEDD) measurement per the American Society of Echocardiography references. Cox models were used to assess the association between LV size or LVEDD with composite cardiovascular events (cardiovascular death, ischemic stroke or systemic embolism, or major bleeding). RESULTS: There were 308 (4.0%) participants assessed with small LV who were older, with lower body mass and blood pressure, and fewer comorbidities, and 429 (5.5%) were identified with large LV. Compared with the normal LV group, small LV and large LV were significantly associated with higher incidence of composite cardiovascular events (adjusted HR [aHR]: 1.54 [95% CI: 1.07-2.20] for small LV; aHR: 1.36 [95% CI: 1.02-1.81] for large LV) and cardiovascular death (aHR: 1.94 [95% CI: 1.14-3.28] for small LV; aHR: 1.83 [95% CI: 1.24-2.69] for large LV). Small LV was also associated with increased risk of major bleeding [aHR: 2.21 [95% CI: 1.01-4.86]). A U-shaped relationship between LVEDD and composite cardiovascular events was identified (Pnonlinear < 0.001). CONCLUSIONS: In a prospective AF cohort, small LV was independently associated with an increased risk of cardiovascular events, which needed consideration in risk stratification and management for patients with AF. (ChiCTR-OCH-13003729).