A novel mutation in hERG gene associated with azithromycin-induced acquired long QT syndrome.

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.

Comparison of strategies for catheter ablation of left posterior fascicular ventricular tachycardia.

AIMS: Traditional ablation strategies including targeting the earliest Purkinje potential (PP) during left posterior fascicular (LPF) ventricular tachycardia (VT) or linear ablation at the middle segment of LPF during sinus rhythm are commonly used for the treatment of LPF-VT. Catheter ablation for LPF-VT targeting fragmented antegrade Purkinje (FAP) potential during sinus rhythm is a novel approach. We aimed to compare safety and efficacy of different ablation strategies (FAP ablation vs. traditional ablation) for the treatment of LPF-VT. METHODS AND RESULTS: Consecutive patients with electrocardiographically documented LPF-VT referred for catheter ablation received either FAP ablation approach or traditional ablation approach. Electrophysiological characteristics, procedural complications, and long-term clinical outcome were assessed. A total of 189 consecutive patients who underwent catheter ablation for LPF-VT were included. Fragmented antegrade Purkinje ablation was attempted in 95 patients, and traditional ablation was attempted in 94 patients. Acute ablation success with elimination of LPF-VT was achieved in all patients. Left posterior fascicular block occurred in 11 of 95 (11.6%) patients in the FAP group compared with 75 of 94 (79.8%) patients in the traditional group (P < 0.001). Fragmented antegrade Purkinje ablation was associated with significant shorter procedure time (94 ± 26 vs. 117 ± 23 min, P = 0.03) and fewer radiofrequency energy applications (4.1 ± 2.4 vs. 6.3 ± 3.5, P = 0.003) compared with the traditional group. One complete atrioventricular block and one left bundle branch block were seen in the traditional group. Over mean follow-up of 65 months, 89 (93.7%) patients in the FAP group and 81 (86.2%) patients in the traditional group remained free of recurrent VT off antiarrhythmic drugs (P = 0.157). CONCLUSION: Left posterior fascicular-ventricular tachycardia ablation utilizing FAP and traditional ablation approaches resulted in similar acute and long-term procedural outcomes. Serious His-Purkinje injury did occur infrequently during traditional ablation. The use of FAP ablation approach was associated with shorter procedure time and fewer radiofrequency energy applications, especially for non-inducible patients.

Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm.

AIMS: The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm. METHODS AND RESULTS: This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT. CONCLUSION: Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.

Discovery of Natural Ursane-type SENP1 Inhibitors and the Platinum Resistance Reversal Activity Against Human Ovarian Cancer Cells: A Structure-Activity Relationship Study.

Platinum-resistant ovarian cancer is one of the most common and refractory gynecologic cancers around the world. The SENP1/JAK2 (small ubiquitin-like modifier-specific protease 1/Janus activating kinase 2) axis activation has been proposed as a critical mechanism in platinum-resistant ovarian cancer, and as such, SENP1 inhibitors become a feasible alternative to reverse platinum resistance. In this work, 29 commercially available natural ursane-type aglycones were tested for their SENP1 inhibitory activities, among which 12 aglycones showed IC50 activity at the concentration below 5 µM. Pomolic acid and tormentic acid were identified as potent SENP1 inhibitors with the IC50 values of 5.1 and 4.3 µM, respectively. The structure-activity relationship (SAR) of ursane-type SENP1 inhibitors was evaluated. A molecular docking model of the SENP1-tormentic acid complex was obtained and applied to describe the SAR. Moreover, the combinations of cisplatin with pomolic acid (IC50 = 3.69 µM, combination index (CI) = 0.23) and tormentic acid (IC50 = 2.40 µM, CI = 0.30) exhibited potent platinum-resistant reversal activities to cisplatin only (IC50 = 28.23 µM) against the human ovarian cancer SKOV3 cells. The data suggested a potential for pomolic acid and tormentic acid to be promising compounds for in vivo studies of platinum-resistant ovarian cancer with SENP1 activation.

LncRNA H19 alleviates sepsis-induced acute lung injury by regulating the miR-107/TGFBR3 axis.

OBJECTIVE: Acute lung injury (ALI) increases sepsis morbidity and mortality. LncRNA H19 plays a critical role in sepsis. miR-107 is highly-expressed and TGFß type III receptor (TGFBR3) is poorly-expressed in sepsis, yet their roles in sepsis development require further investigation. This study aimed to investigate the mechanism of H19 in alleviating sepsis-induced ALI through the miR-107/TGFBR3 axis. METHODS: Mice were intravenously injected with Ad-H19 adenovirus vector or control vector one week before establishing the mouse model of cecal ligation and puncture (CLP). Pulmonary microvascular endothelial cells (PMVECs) were transfected with oe-H19 or oe-NC plasmids and then stimulated by lipopolysaccharide (LPS). Lung injury was assessed via hematoxylin-eosin staining, measurement of wet-to-dry (W/D) ratio, and TUNEL staining. Levels of H19, miR-107, and TGFBR3 were determined by RT-qPCR. Apoptosis of PMVECs was evaluated by flow cytometry. Levels of Bax and Bcl-2 in lung tissues and PMVECs were measured using Western blot. Total protein concentration and the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) were quantified. Levels of TNF-α, IL-1ß, IL-6, and IL-10 in BALF, lung tissues, and PMVECs were measured by ELISA. Cross-linking relationships among H19, miR-107 and TGFBR3 were verified by dual-luciferase and RIP assays. RESULTS: H19 was poorly-expressed in CLP-operated mice. H19 overexpression attenuated sepsis-induced ALI, which was manifested with complete alveolar structure, decreased lung injury score and lung W/D ratio, and inhibited apoptosis in CLP-operated mice, which was manifested with decreased number of TUNEL-positive cells and Bax level and increased Bcl-2 level. CLP-operated mice had increased concentration of total protein and number of total cells, neutrophils, and macrophages in BALF, which was nullified by H19 overexpression. H19 overexpression declined levels of TNF-α, IL-1ß, and IL-6 and elevated IL-10 levels. H19 inhibited LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production. H19 targeted TGFBR3 as the ceRNA of miR-107. miR-107 overexpression or silencing TGFBR3 partially averted the inhibition of H19 overexpression on LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production. CONCLUSION: LncRNA H19 inhibited LPS-induced PMVEC apoptosis and pro-inflammatory cytokine production and attenuated sepsis-induced ALI by targeting TGFBR3 as the ceRNA of miR-107.

Discovery of novel triazole compounds as selective IL-1ß releasement inhibitors.

Inflammation and immunity are closely related to the occurrence and development of a variety of immune diseases. Although IL-1ß has been identified as a key cytokine in many immune diseases, safe and specific small molecular IL-1ß releasement inhibitors are still scarce and urgently required in clinic. The investigation prospect of triazoleis limited by its complicated pharmacological effect which exhibited inferior effects on IL-1ß and TNF-α. Herein, 36 novel derivatives were designed and synthesized, and nearly half of the derivatives exhibited much better selectivity on IL-1ß releasement inhibition as well as keep similar inhibitory activities to lead compound. In 20 µM, compound 19 exhibited IL-1ß releasement inhibitory activity (IC50 = 5.489 µM) which closed to the original compound, and 4.5-fold superior selectivity (SI = 4.71) to the lead compound (SI = 0.82). A probable SAR model of triazole derivatives for IL-1ß releasement inhibition and selectivity was also proposed, which might promote the discovery of more effective and specific IL-1ß releasement inhibitors in the future.

Electrical isolation of the superior vena cava using second-generation cryoballoon in patients with atrial fibrillation.

BACKGROUND: The safety and efficacy of superior vena cava (SVC) isolation using second-generation cryoballoon (CB) ablation remain unknown. METHODS: A total of 26 (3.2%) patients with SVC-related paroxysmal atrial fibrillation (AF) from a consecutive series of 806 patients who underwent second-generation CB were included. Pulmonary vein isolation was initially achieved by CB ablation. If the SVC trigger was determined, the electrical isolation of SVC isolation was performed using the second-generation CB. RESULTS: Real-time SVC potential was observed in all patients. Isolation of the SVC was successfully accomplished in 21 (80.8%) patients. The mean number of freeze cycles in each patient was 2.1 ± 1.1. The mean time to isolation and ablation duration were 22.5 ± 14.2 seconds and 94.5 ± 22.3 seconds, respectively. A transient phrenic nerve (PN) injury was observed in five patients (19.2%). There were two patients (7.7%) experienced reversible sinus node injury during the first application. During a mean follow-up period of 13.2 ± 5.8 months, four patients (15.4%) had atrial arrhythmia recurrences. CONCLUSION: Isolation of SVC using the second-generation 28-mm CB is feasible when SVC driver during AF is identified. Vigilant monitoring of PN function during CB ablation of SVC is needed to avoid PN injury.

Comfort With Touch and Influencing Factors Among Chinese Midwives: A Cross-sectional Survey.

The aim of this study was to identify comfort with touch (CT) and influencing factors among Chinese midwives. Midwives (N = 252) from 7 hospitals in Guangdong, China, were asked to complete a self-report questionnaire between November 2018 and April 2019. The questionnaire included the Nurses' Comfort with Touch Scale (NCTS), the Nurses' Perceived Professional Benefits (NPPB) Scale, the Maslach Burnout Inventory-General Survey (MBI-GS), and a self-designed demographic questionnaire. Multivariate linear regression was used to identify influencing factors for CT. Mean NCTS total score was 88.90 ± 14.40, and the mean item score was 5.23 ± 0.91, which indicated a respectable score. Within the NCTS, CT was highest in the comfort support category (5.32 ± 0.29) whereas CT was lowest in the physical comfort category (4.28 ± 0.28). Multivariate regression analysis demonstrated that CT among Chinese midwives was associated with positive experiences or feelings surrounding the patient-nurse relationship (B = 3.239, P < .001), perceived professional benefit (PPB, positive professional identity) (B = 0.240, P < .001), emotional exhaustion (B = -0.414, P < .001), depersonalization (negative attitude toward the work setting) (B = -0.773, P < .001), and personal accomplishment (evaluation of self-worth) (B = 0.170, P = .015). Touch training and educational programs are recommended for Chinese midwives to enhance awareness and acceptance of touch care. In addition, promoting positive patient-nurse relationships, improving PPB, and reducing burnout are recommended to enhance CT among Chinese midwives. Because of the size and racial homogeneity of the sample, further studies are recommended to identify CT and influencing factors in a larger, more diverse population of midwives worldwide.

Stigma and Its Influence on Patients With Temporary Ostomy: A Cross-sectional Survey.

PURPOSE: The purpose of this study was to explore stigma and its influencing factors in Chinese patients with a temporary ostomy. DESIGN: Cross-sectional, descriptive. SUBJECTS AND SETTING: Convenience sampling was used to recruit 170 patients living with a temporary ostomy for at least 2 weeks. Participants were recruited from 3 general hospitals in Guangdong province, located in southeastern China. METHODS: Respondents completed a questionnaire that included ostomy-related sociodemographic questionnaire, the Social Impact Scale, and the Stoma Self-Efficacy Scale. Multivariate linear regression was used to identify factors influencing stigma. RESULTS: Of the 170 questionnaires distributed, 159 (93.5%) respondents who sufficiently completed responses were included in the final analysis. The average score of the Social Impact Scale was 61.63 (SD = 8.39), reflecting a moderate level of stigma, and 27 (17%) experienced high levels of stigma. Multivariate regression analysis revealed that stigma was associated with family relationships (B = 6.139, P = .000), age when ostomy was created (B = -4.038, P = .000), and self-efficacy (B = -0.080, P = .002). CONCLUSIONS: The level of stigma in Chinese patients with temporary ostomies is moderate. Multivariate regression analysis identified family relationship, age, and self-efficacy as the main factors that influenced stigma in patients with temporary ostomy.

Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress.

CONTEXT: Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. OBJECTIVE: We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. MATERIALS AND METHODS: We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0-50 µM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. RESULTS: Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC50 = 5.4-6.1 µM for A549 and 3.9-5.7 µM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. CONCLUSION: UA232 induced apoptosis through the ER stress pathway, and showed stronger growth-inhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.

Ablation of ventricular arrhythmias with predominant monophasic "R" waves in precordial leads from the left sinus of Valsalva: Electrocardiographic and electrophysiologic characteristics.

BACKGROUND: While the left sinus of Valsalva (LSV) is a frequent origin of ventricular arrhythmias (VAs). Uncommonly, VAs with right bundle branch block (RBBB) morphology may be successfully terminated from the LSV. OBJECTIVE: We aimed to investigate the electrocardiographic and electrophysiologic characteristics of VAs with RBBB which were successfully eliminated from the LSV. METHODS: We identified patients with VAs successfully ablated from the LSV from January 2014 to December 2017 and compared electrophysiologic characteristics and ablation sites of those VAs with RBBB versus a control group of patients with left bundle branch block morphology. RESULTS: We identified 18 patients with RBBB and predominant "R" waves in the precordial leads. In 12 (66.7%) patients, a small "s" wave in lead V2 and positive "R" in the remaining pericardial leads could be seen. Overall, a single "V" potential was seen in 72.2% of patients in the study group, while discrete potentials were recorded in 80% of the patients in the control group. The majority (88.9%) of the VAs could only be terminated at the nadir of the LSV in the study group. After mean follow-up of 33 ± 14 months, 93.8% and 92% were free of VAs after initial ablation in study and control group, respectively (P = 0.99). CONCLUSION: Some VAs with predominant monophasic "R" wave in precordial leads could be terminated from LSV, especially a small "s" wave in lead V2 was recorded. The nadir of LSV is highly successful for RBBB VAs and single electrogram was recorded at the target for most of the cases.

Procedural findings and clinical outcome of second-generation cryoballoon ablation in patients with variant pulmonary vein anatomy.

INTRODUCTION: The procedural findings and clinical outcome of second-generation cryoballoon (CB2) ablation in patients with variant pulmonary vein (PV) anatomy have not been fully investigated. METHODS: A total of 424 consecutive patients who underwent PV isolation with CB2 were included. Computed tomographic (CT) scan was performed in all patients before the procedure. The study population was divided into common PV, accessory PV, and nonvariant PV groups according to the CT scan. Procedural findings and clinical outcome between the three groups were compared. RESULTS: Variant PV anatomy was observed in 118 of 424 (27.8%) patients. PV isolation was successfully achieved in all patients in three groups with low rates of need for touch-up ablation (P = 0.974). Total procedure time was longer in the accessory PV group compared with nonvariant PV group (53.7 ± 12.9 vs 49.5 ± 8.8 minutes; P < 0.001). More number of applications per patient were required in accessory PV group compared with the nonvariant PV and common PV groups (7.5 ± 2.1 vs 6.5 ± 1.6, P < 0.001; 7.5 ± 2.1 vs 6.8 ± 1.4, P = 0.027, respectively). No significant difference in phrenic nerve (PN) injury was observed between the three groups (P = 0.693). During mean follow-up duration of 16.1 ± 3.3 months, there was no significant difference in rates of atrial fibrillation (AF) recurrences in the three groups (13 of 43 common PV group, 21 of 75 accessory PV group, and 80 of 306 nonvariant PV group, P = 0.178). CONCLUSION: Variant PV patterns are common in patients undergoing ablation for drug-resistant AF. CB2 ablation appears to be a reasonable strategy in the setting of the variant PV anatomy with a small increase in procedure time and the number of cryoapplications.

Predictors of hemoptysis in the setting of pulmonary vein isolation using the second-generation cryoballoon.

INTRODUCTION: To assess the predictors of hemoptysis using second-generation cryoballoon (CB). METHODS: Thirty patients with hemoptysis after second-generation CB ablation and 60 age-, gender-, and body mass index-matched controls were recruited. Anatomic parameters were obtained from preprocedural cardiac computed tomography (CT). Pulmonary vein isolation was performed with 28-mm balloon using single 3-minute freeze technique. RESULTS: Clinical and procedural characteristics were similar between the groups. A shorter distance between left superior PV (LSPV) and left main bronchus (LMB) was associated with hemoptysis (7.8 ± 4.3 mm vs. 12.5 ± 3.5 mm, P < 0.001), whereas no significant difference in the distance between right superior PV (RSPV) and right main bronchus (RMB) was found between groups (11.9 ± 3.5 mm vs. 12.9 ± 4.6 mm, P = 0.089). Additionally, the mean thickness of the connective tissue interposed between RSPV and RMB was significantly thicker than that between LSPV and LMB in both groups (both P < 0.001). A stepwise logistic multivariate analysis identified only the LMB-LSPV distance as an independent predictor of hemoptysis (odd ratio [OR] 2.676; 95% CI 1.121-4.843, P < 0.001). A cutoff value ≤ 9.5 mm predicted hemoptysis after CB ablation with 93.8% sensitivity and 75.0% specificity. CONCLUSION: Hemoptysis is a relatively rare event following second-generation CB ablation. The bronchi location obtained from CT aids in identifying high-risk population for the complication.

Electrocardiographic and electrophysiologic differentiation between atriofascicular, long atrioventricular, and short atrioventricular decrementally conducting accessory pathways.

Aims: We aimed to examine the electrocardiographic and electrophysiologic characteristics of anterograde-conducting decremental accessory pathways (DAP) and to identify surrogate criteria to distinguish short atrioventricular (SAV) DAP from atriofascicular (AF) AP and long atrioventricular (LAV) DAP. Methods and results: We identified all patients with DAPs and analysed electrocardiographic and electrophysiologic characteristics. Distal insertion sites were examined using existing criteria, including V-H interval, ventricular activation at the right ventricular apex, and around tricuspid annulus during antidromic atrioventricular re-entrant tachycardia (A-AVRT) or complete pre-excitation and evaluated the AV node-like properties according to the response to adenosine and radiofrequency ablation. Out of 45 patients with DAPs, 28 (62.2%) had SAV-DAP (13 with definite AF-AP, 2 with definite LAV-DAP, 2 indeterminate). In all, 50% of SAV-DAPs and 53.3% of AF-AP/LAV-DAPs had 'rS' pattern in lead III. Longer QRS duration (159.9 ± 17.4 ms vs. 139.2 ± 14.3 ms, P < 0.0001) during full pre-excitation or A-AVRT differentiated SAV-DAP from AF-AP. The QRS-V(His) interval was longer for those with SAV-DAP compared vs. AF-AP/LAV-DAP (45.3 ± 2.4 ms vs. 22.9 ± 2.5 ms, P < 0.0001) and a cut-off value of 33.0 ms differentiated the two (sensitivity 81.3%, specificity 87.5%). Conclusion: The majority of the SAV-DAPs are located at the TA free wall. An 'rS' pattern in lead III is frequently seen in SAV-DAP as well as AF-AP/LAV-DAPs. Measuring the QRS-V(His) interval would be helpful to distinguish SAV-DAP from AF-AP/LAV-DAP.

Pulmonary vein isolation with real-time pulmonary vein potential recording using second-generation cryoballoon: Procedural and biophysical predictors of acute pulmonary vein reconnection.

OBJECTIVE: The study sought to evaluate the procedural and biophysical factors related to acute pulmonary vein isolation (PVI) guided by real-time pulmonary vein (PV) potential recordings. METHODS: A total of 180 consecutive patients with drug-resistant atrial fibrillation (AF) undergoing CB2 (second-generation version of cryoballoon) ablation were enrolled. Real-time monitoring of PV potentials was obtained using an inner lumen spiral mapping catheter. RESULTS: Acute isolation was achieved in all PVs without touch-up ablation. Real-time assessment of PV disconnection was possible in 611 of 711 (85.9%) PVs. A total of 617 (86.8%) PVs were isolated during the initial freeze. Longer time cycle integration (TCI) (TTI * freeze cycle, TCI) (254.6 ± 112.8 seconds vs 74.1 ± 59.7 seconds, P < 0.001), time to isolation (TTI) (94.3 ± 34.0 seconds vs 46.3 ± 26.2 seconds, P < 0.001), higher nadir temperature (-45.5 ± 5.3°C vs -50.4 ± 5.5°C, P < 0.001), longer time to -40°C (77.3 ± 22.7 seconds vs 55.7 ± 23.2 seconds, P < 0.001), faster interval rewarming time at 0°C (9.4 ± 4.3 seconds vs 12.4 ± 4.9 seconds, P = 0.008), and total balloon rewarming time (38.1 ± 11.6 seconds vs 47.7 ± 14.0 seconds, P = 0.003) were observed in PVs with acute reconduction. TTI ≤ 65 seconds predicted absence of acute reconnection with 84.2% sensitivity and 75.7% specificity, whereas TCI ≤ 119 seconds presented 94.7% sensitivity and 80.2% specificity. At a mean follow-up of 4.7 ± 1.4 months, 82.2% of patients were free of AF. None of those with PV reconnections suffered from AF recurrences. CONCLUSIONS: The ablation using CB2 is effective in achieving acute PVI. Real-time assessment of PVI could be achieved during CB application in 86% of PVs. The incidence of spontaneous PV reconnection is very low, observed in just 3% of isolated PVs. TTI ≤ 65 seconds and TCI ≤ 119 seconds predicted absence of acute PV reconnection. Although they may identify effective cryoapplications in the acute phase, their performance still needs to be verified in the long term.

"Crosstalk" technique: A comparison between two generations of cryoballoon catheter.

INTRODUCTION: The "Crosstalk" technique: if pulmonary vein isolation (PVI) of the superior one is not achieved due to a gap in the inferior part, it could be done during inferior vein cryoablation. This maneuver minimizes the total energy delivery time and number of lesions. We aimed to correlate the likelihood of crosstalk phenomenon with certain anatomic characteristics. METHODS: A total of 676 patients undergoing a first ablation procedure for paroxysmal or persistent atrial fibrillation (470 first-generation cryoballoon [CB] and 206 second-generation CB) between June 2014 and December 2016 were included. RESULTS: "Crosstalk" phenomenon occurred in 32 patients (18 first-generation CB, 14 second-generation CB). Compared to 54 control patients without crosstalk, the angle between left superior pulmonary vein (LSPV) and left atrial (LA) roof-plane, left pulmonary common ostia were significant parameters associated with crosstalk (odds ratio [OR] = 1.20, ±95% confidence interval [CI]: 1.11-1.31, P < 0.001; OR = 5.67, ±95% CI: 1.08-28.69, P = 0.04). As for angle between LSPV and LA roof-plane, the cut-off value was 28.68° with a sensitivity of 72.22%, a specificity of 81.25%, and an area under the receiver operating characteristic curve of 0.87 to predict the possibility of crosstalk technique application to get isolated in LSPV. Among the crosstalk group, there was no statistical difference between first-generation CB and second-generation CB in pulmonary anatomic characteristics. CONCLUSION: Crosstalk technique can be effective in patients with AF undergoing CB ablation using with both first and second-generation CBs. Anatomic characteristics predictive of crosstalk include a left common ostia and smaller angle between the LSPV and LA roof-plane.

Design and Synthesis of Vandetanib Derivatives Containing Nitroimidazole Groups as Tyrosine Kinase Inhibitors in Normoxia and Hypoxia.

Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16a-p)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of vandetanib. Preliminary biological tests showed that comparing with vandetanib, some target compounds exhibited excellent EGFR inhibitory activities and anti-proliferative over A549/H446 cells in hypoxia. Meanwhile, several of the above compounds demonstrated better bioactivity than vandetanib in VEGF gene expression inhibition. Owing to the excellent IC50 value (1.64 µmol/L), the inhibition ratios of 16f over A549 and H446 cells were 62.01% and 59.86% at the concentration of 0.5 µM in hypoxia, respectively. All of these results indicated that 16f was a potential cancer therapeutic agent in hypoxia and was worthy of further development.

A case report of entrapment of PentaRay catheter in the mechanical mitral valve: a known complication experienced anew.

Background: Complex atrial tachycardia (AT) is commonly observed in patients with cardiac surgery. High-density mapping is widely adopted for catheter ablation of complex AT in patients with cardiac surgery. Several case reports have described that PentaRay mapping catheter can be trapped in the mechanical valve and sheared off and successful retrieval of the spline by a snare system. We described a rare case in which PentaRay mapping catheter spline was successfully retrieved from the distal anterior tibial artery by direct syringe suction via the diagnostic catheter following entrapment in the mechanical mitral valve (MV) and rupture of the spline. Case summary: A 70-year-old female with mechanical bileaflet MV underwent catheter ablation for AT. During mapping in left atrium, the catheter was entrapped in mechanical MV and sheared off. We attempted to release the entrapped the spline by advancing the ablation catheter towards the stuck disc and pushing on the hinge portion of the disc with the catheter tip. The stuck and closed disc was opened, and the deeply entrapped spline was released. However, the entrapped PentaRay spline floated through the Valsalva sinus and strayed into the distal left anterior tibial artery. Fortunately, we successfully retrieved the spline from the distal anterior tibial artery by direct syringe suction instead of a snare system. Discussion: The possibility of the entrapment and subsequent rupture of the spline should always be considered during mapping the site close to mechanical valve. A rapid retrieval of embolized material should be carried out. If the spline strays into the distal and small artery in which the snare system is difficult to advance, a direct syringe suction via the diagnostic catheter may be attempted.

Safety and efficacy of catheter ablation of para-Hisian accessory pathway via a direct superior vena cava approach: A multicenter study.

BACKGROUND: Radiofrequency (RF) catheter ablation of para-Hisian accessory pathways (APs) can be challenging due to proximity to the conduction system. METHODS: A total of 30 consecutive patients with para-Hisian AP were enrolled for ablation in three centers, 12 (40%) of whom had previously failed attempted ablation from the inferior vena cava (IVC) approach. Ablation was preferentially performed using a superior approach from the superior vena cava (SVC) in all patients. RESULTS: The para-Hisian AP was eliminated from the SVC approach in 28 of 30 (93.3%) patients. In the remaining two patients, additional ablation from IVC was required to successfully eliminate the AP. There were two patients experienced reversible complete atrial-ventricular block and PR prolongation during the first RF application. Long-term freedom from recurrent arrhythmia was achieved in 29 (96.7%) patients over a mean follow-up duration of 15.6 ± 4.6 months. CONCLUSION: Catheter ablation of para-Hisian AP from above using a direct SVC approach is both safe and effective, and should be considered especially in patients who have failed conventional ablation attempts from IVC approach.