C-P bond formation of cyclophanyl-, and aryl halides via a UV-induced photo Arbuzov reaction : a versatile portal to phosphonate-grafted scaffolds

A new versatile method for the C-P bond formation of (hetero)aryl halides with trimethyl phosphite via a UV-induced photo-Arbuzov reaction, accessing diverse phosphonate-grafted arenes, heteroarenes and co-facially stacked cyclophanes under mild reaction conditions without the need for catalyst, additives, or base is developed. The UV-induced photo-Arbuzov protocol has a wide synthetic scope with large functional group compatibility exemplified by over 30 derivatives. Besides mono-phosphonates, di- and tri-phosphonates are accessible in good to excellent yields. Mild and transition metal-free reaction conditions consolidate this method's potential for synthesizing pharmaceutically relevant compounds and precursors of supramolecular nanostructured materials.Peer reviewe

Phrenic nerve palsy during ablation of atrial fibrillation using a 28-mm cryoballoon catheter: predictors and prevention

Purpose: The purposes of this study were to determine whether predictors of phrenic nerve palsy (PNP) exist and to test whether a standardized ablation protocol may prevent PNP during cryoballoon (CB) ablation using the 28mm CB. Methods: Three-dimensional (3D) geometry of the pulmonary veins (PV) and their relationship to the superior vena cava (SVC) was analyzed. Phrenic nerve (PN) stimulation was performed during ablation of the right-sided PVs with a 28-mm CB. The freezing cycle was immediately terminated in case of loss of PN capture. Results: Sixty-five patients (age, 58 ± 11years; ejection fraction, 0.59 ± 0.06; left atrial size, 40 ± 5mm) with paroxysmal atrial fibrillation were included. No persistent PNP was observed. Transient PNP occurred in 4 of 65 patients (6%). PN function normalized within 24h in all four patients. A short distance between the right superior PV and the SVC was significantly associated with PNP, but left atrial and 3D PV anatomy were not. Low temperature early during the freezing cycle (<−41°C at 30s) predicted PNP with a sensitivity and a specificity of 100 and 98%, respectively. Conclusion: The anatomical relationship between the right superior PV and the SVC is a preprocedural predictor for the development of transient PNP, and low temperature early during ablation at the right superior PV is a sensitive warning sign of impending PNP. Despite the use of the 28mm CB, transient PNP occurred in 6% of patients undergoing CB ablatio

Quantitative assessment of a second-generation cryoballoon ablation catheter with new cooling technology—a perspective on potential implications on outcome

Purpose: The purpose of this study was to assess the differences in cooling behavior between the first-generation cryoballoon (CB-1G) and the second-generation cryoballoon (CB-2G) quantitatively to understand the freezing capabilities and to benefit from the improved efficacy of the CB-2G in patients with atrial fibrillation. Methods: We analyzed quantitatively the ice formation of the CB-1G and CB-2G catheters in vitro in a 37°C warm water bath during freezing for 60, 120, 180, 240, and 300s, respectively. Results: The mean-covered surface area and the relative coverage of the ice spots on the CB-2G were significantly different from the spots on the CB-1G for the 28-mm CBs but not for the 23-mm CBs. Whereas for the CB-1G, the ice formation was discontiguous with four isolated ice spots; the CB-2G showed a contiguous ice cap covering the entire distal part including the pole of the balloon. No homogeneous cooling behavior could be observed at the equatorial level with both catheters. Temporal differences on the ice formation could be observed for the 28-mm CB-2G but not for the 23-mm CB-2G. Conclusion: The new-generation CB-2G showed more powerful and homogeneous cooling behavior, especially for the 28-mm CB. Whether this translates into higher long-term success rates is currently unknown. The impact of the more effective cooling and the longer dissolving duration of the ice cap of the new-generation CB-2G on procedural safety needs to be investigated

High-sensitivity cardiac Troponin T delta concentration after repeat pulmonary vein isolation

Introduction: Difference between high-sensitivity cardiac troponin T concentrations (hs-cTnT) before and after ablation procedure (delta concentration) reflects the amount of myocardial injury. The aim of the study was to investigate hs-cTnT prognostic power for predicting atrial fibrillation (AF) recurrence after repeat pulmonary vein isolation (PVI) procedure. Materials and methods: Consecutive patients with paroxysmal AF undergoing repeat PVI using a focal radiofrequency catheter were included in the study. Hs-cTnT was measured before and 18-24 hours after the procedure. Standardized 3, 6 and 12-month follow-up was performed. Cox-regression analysis was used to identify predictors of AF recurrence. Results: A total of 105 patients undergoing repeat PVI were analysed (24% female, median age 61 years). Median (interquartile range) hs-cTnT delta after repeat PVI was 283 (127 - 489) ng/L. After a median follow-up of 12 months, AF recurred in 24 (23%) patients. A weak linear relationship between the total radiofrequency energy delivery time and delta hs-cTnT was observed (Pearson R2 = 0.31, P = 0.030). Delta Hs-cTnT was not identified as a significant long-term predictor of AF recurrence after repeated PVI (P = 0.920). Conclusion: This was the first study evaluating the prognostic power of delta hs-cTnT in predicting AF recurrence after repeat PVI. Delta hs-cTnT does not predict AF recurrence after repeat PVI procedures. Systematic measurement of hs-cTnT after repeat PVI does not add information relevant to outcome

Effective reduction of fluoroscopy duration by using an advanced electroanatomic-mapping system and a standardized procedural protocol for ablation of atrial fibrillation: ‘the unleaded study'

Aims It is recommended to keep exposure to ionizing radiation as low as reasonably achievable. The aim of this study was to determine whether fluoroscopy-free mapping and ablation using a standardized procedural protocol is feasible in patients undergoing pulmonary vein isolation (PVI). Methods and results Sixty consecutive patients were analysed: Thirty consecutive patients undergoing PVI using Carto3 were treated using a standardized procedural fluoroscopy protocol with X-ray being disabled after transseptal puncture (Group 1) and compared with a set of previous 30 consecutive patients undergoing PVI without a specific recommendation regarding the use of fluoroscopy (Group 2). The main outcome measures were the feasibility of fluoroscopy-free mapping and ablation, total fluoroscopy time, total dose area product (DAP), and procedure time. Sixty patients (age 60 ± 10 years, 73% male, ejection fraction 0.55 ± 0.09, left atrium 42 ± 8 mm) were included. In Group 1, total fluoroscopy time was 4.2 (2.6-5.6) min and mapping and ablation during PVI without using fluoroscopy was feasible in 29 of 30 patients (97%). In Group 2, total fluoroscopy time was 9.3 (6.4-13.9) min (P < 0.001). Total DAP was 13.2 (6.2-22.2) Gy*cm2 in Group 1 compared with 17.5 (11.7-29.7) Gy*cm2 in Group 2 (P = 0.036). Total procedure time did not differ between Groups 1 (133 ± 37 min) and 2 (134 ± 37 min, P = 0.884). Conclusion Performing mapping and ablation guided by an electroanatomic-mapping system during PVI without using fluoroscopy after transseptal puncture using a standardized procedural protocol is feasible in almost all patients and is associated with markedly decreased total fluoroscopy duration and DA

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation

Objective Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the α-subunit of the human cardiac voltage-dependent sodium channel (hNav1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever. Methods The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration. Results The biophysical characterization of the channels carrying the F1344S mutation revealed a 10mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5°C further shifted the mid-point activation by 18mV and significantly changed the slope factor in Nav1.5/F1344S mutant channels from − 6.49 to − 10.27mV. Conclusions Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotyp

Fluoroscopy-free recrossing of the interatrial septum during left atrial ablation procedures

Aim: The purpose of this is to evaluate the safety and feasibility of recrossing the interatrial septum in case of inadvertent loss of or need for repeated left atrial access using a simple electroanatomical landmark without the use of fluoroscopy. Methods: Twenty-five consecutive patients undergoing pulmonary vein isolation (PVI) for paroxysmal (n = 12) or persistent (n = 13) atrial fibrillation ablation were included. All procedures were performed using an electroanatomical mapping system (Carto 3, Biosense Webster, Diamond Bar, USA). After fluoroscopy-guided double transseptal puncture and fast anatomical mapping of the left atrium, a reconstruction of the transseptal access was created by retracting the mapping catheter into the sheath to the level of the inferior vena cava. After completing the left sided ablation, both sheaths and catheters were withdrawn to the inferior vena cava. Recrossing was then attempted by fellows (EF) and experienced operators (EO) using the reconstruction of the transseptal access in a standard right anterior oblique (RAO) and left anterior oblique (LAO) projection without the use of fluoroscopy. Results: Using the described technique, EP fellows and experienced operators could recross the interatrial septum without fluoroscopy in all patients. Median time needed for recrossing was 14s (interquartile range (IQR) 7-20). Median recrossing times did not differ significantly between EF and EO (14 (IQR 8-26.5s) versus 12 (IQR 6.5-17.5s), p = 0.26). In five (20%) procedures, recrossing was necessary during the procedure after intermittent mapping of the right atrium or inadvertent catheter dislodgment. Conclusion: Adding a simple and fast anatomical reconstruction of the transseptal access to the standard left atrial mapping procedure allows for easy and fluoroscopy-free recrossing of the interatrial septum during atrial fibrillation ablation and further reduces radiation exposure

Atrial substrate characterization based on bipolar voltage electrograms acquired with multipolar, focal and mini-electrode catheters.

BACKGROUND Bipolar voltage (BV) electrograms for left atrial (LA) substrate characterization depend on catheter design and electrode configuration. AIMS The aim of the study was to investigate the relationship between the BV amplitude (BVA) using four catheters with different electrode design and to identify their specific LA cutoffs for scar and healthy tissue. METHODS AND RESULTS Consecutive high-resolution electroanatomic mapping was performed using a multipolar-minielectrode Orion catheter (Orion-map), a duo-decapolar circular mapping catheter (Lasso-map), and an irrigated focal ablation catheter with minielectrodes (Mifi-map). Virtual remapping using the Mifi-map was performed with a 4.5 mm tip-size electrode configuration (Nav-map). BVAs were compared in voxels of 3 × 3 × 3 mm3. The equivalent BVA cutoff for every catheter was calculated for established reference cutoff values of 0.1, 0.2, 0.5, 1.0, and 1.5 mV. We analyzed 25 patients (72% men, age 68 ± 15 years). For scar tissue, a 0.5 mV cutoff using the Nav corresponds to a lower cutoff of 0.35 mV for the Orion and of 0.48 mV for the Lasso. Accordingly, a 0.2 mV cutoff corresponds to a cutoff of 0.09 mV for the Orion and of 0.14 mV for the Lasso. For healthy tissue cutoff at 1.5 mV, a larger BVA cutoff for the small electrodes of the Orion and the Lasso was determined of 1.68 and 2.21 mV, respectively. CONCLUSION When measuring LA BVA, significant differences were seen between focal, multielectrode, and minielectrode catheters. Adapted cutoffs for scar and healthy tissue are required for different catheters

Reduction of ST-elevation myocardial infarction in Canton Ticino (Switzerland) after smoking bans in enclosed public places—No Smoke Pub Study

Background: Second-hand smoke increases the risk of acute myocardial infarction. Canton Ticino (CT) first introduced a smoking ban in public places in 2007. This offered the opportunity to assess the long-term impact of a smoking ban on the incidence of ST-elevation myocardial infarctions (STEMI) compared with a population where the law was not yet implemented. Methods: We assessed the incidence of STEMI hospitalizations per 100 000 inhabitants both during 3 years before and after the ban application in CT and in Canton Basel City (CBC), where this law was not yet applied. Data were obtained from the codified hospital registry (ICD-10 codes). Results: In CT, the mean incidence of STEMI admissions during the 3 pre-ban years (123.7) was significantly higher than the incidence of admissions in each of the 3 post-ban years (92.9, 101.6 and 89.6 respectively; P <.024). Analysing population subsets, a post-ban reduction was observed among ≥65-year-old people of both sexes in each of the 3 post-ban years and in the <65-year age group during the first post-ban year (P = 0.02). Conversely, the mean incidence of STEMI hospitalizations in CBC (92.4) didn't change significantly in each of the 3 post-ban years (83.9, 83.3 and 79.5, P = NS) during the same period. However, a significant long-term reduction in STEMI admissions was observed in CBC among the male group with ≥65 years (P < 0.01). Conclusion: Our work suggests a significant impact of the smoke-free policy on the number of annual STEMI. Specific population subsets (i.e. ≥65-year-old females) were particularly affected by the smoking ban, showing a significant reduction in STEMI hospitalization