Long-term cerebral thromboembolic complications of transapical endocardial resynchronization therapy

Purpose: Cardiac resynchronization therapy (CRT) is an established therapeutic option in selected heart failure patients (pts). However, the transvenous left ventricular (LV) lead implantation remains ineffectual in a considerable number of pts. Transapical LV (TALV) lead implantation is an alternative minimally invasive, surgical, endocardial implantation technique. The aim of the present prospective study is to determine the long-term outcome, including the cerebral thromboembolic complications, of pts

Prehistoric uses of circumpolar mineral resources: Insights and emerging questions from Arctic archaeology

Background. There are little comparative data on catheter ablation of paroxysmal atrial fibrillation (AF) using the contact force radiofrequency (CF-RF) catheter versus the second-generation cryoballoon (CB2). Methods and results. This is a single center, retrospective, nonrandomized study of 98 patients with symptomatic, drug-refractory paroxysmal AF who underwent their first PVI ablation using either the CB2 (n=40) or CF-RF (n=58). The mean age was 60 years with 63% men, a mean LA size of 42 mm. The procedure duration (74±17 versus 120±49 minutes p<0.05) was shorter for CB2 group; the fluoroscopy time (14±17 versus 16±5 minutes, p=0.45) was similar. Complete PVI was achieved in 96% of patients with RF-CF and 98% with CB2. Phrenic nerve palsies (2 transient and 1 persistent) occurred exclusively in the CB2 group and 1 severe, nonlethal complication (pericardial tamponade) occurred in the CF-RF group. At 24-month follow-up, the success rate, defined as freedom from AF/atrial tachycardia (AT) after a single procedure without antiarrhythmic drug, was comparable in CF-RF group and CB2 group (65.5% versus 67%, resp., log rank p=0.54). Conclusion. Both the CB2 and the RF-CF ablation appeared safe; the success rate at 2 years was comparable between both technologies

Pulmonary Vein Isolation Without Left Atrial Mapping

Background: One of the crucial points during in most approaches developed for ablation of atrial fibrillation (AF) is the ability to identify the pulmonary vein (PVs) and to accurately locate their ostia. Objectives: The purpose of this case series was to investigate a simplified method for fusion of the multislice computer tomography (CT) derived 3D dataset with the electroanatomical map in order to facilitate the mapping procedure. Methods: In 5 consecutive patients (4 male) referred for catheter ablation of symptomatic drug-refractory paroxysmal atrial fibrillation contrast enhanced computer tomography was performed before the procedure and imported into an electroanatomical mapping system (Carto XP) using CartoMerge Image Integration Module. During the procedure a multipolar mapping catheter (Quick Star DS, Biosense Webster, Diamond Bar, CA, USA) was introduced to the coronary sinus (CS) to align the CSCT shell to the proper position. The CS potentials provided information to identify the ostium of the CS to achieve a more accurate fusion of the images. No mapping points were taken in the left atrium. The feasibility of the method was characterized by the distance of mapping points. Mapping, registration and outcome data were compared with a cohort of patients undergoing MRI image integration. Result: The mean distance between the mapping points taken in the CS by the Quick Star catheter and the CS CT surface was suitable (mean±SD, 1.4±0.3 mm). Full electrical isolation of the pulmonary veins could be achieved in all patients. The mean procedure and fluoroscopy time were 39 ± 22 and 134 ±38 min respectively, significantly decreased as compared to the MRI cohort. Conclusions: Highly accurate CT image and the electroanatomical map (EAM) fusion can be obtained by the Carto 3D electromanatomical mapping system using CS as the key anatomical structure for registration. Using this technique the mapping time of the left atrium can be reduced

Energy Policies in the European Union

textabstractBackground: Coronary sinus lead placement for transvenous left ventricular (LV) pacing in cardiac resynchronization therapy (CRT) has a significant failure rate at implant and a considerable dislocation rate during follow-up. For these patients epicardial pacing lead implantation is the most frequently used alternative. Recent data support endocardial lead implantation through the atrial septum and the mitral valve, because this method provides further hemodynamic advantages. On the other hand transseptal CRT carries a significant risk for device related infective endocarditis of the mitral valve. The aim of this prospective, nonrandomized study was to demonstrate the feasibility of a fundamentally new approach for endocardial LV lead implantation. Methods: We performed 12 transapical LV lead implantations in 10 end-sta

New method for cardiac resynchronization therapy: Transapical endocardial lead implantation for left ventricular free wall pacing

Coronary sinus lead placement for transvenous left ventricular (LV) pacing in cardiac resynchronization therapy (CRT) has a significant failure rate at implant and a significant dislocation rate during follow-up. For these patients, epicardial pacing lead implantation is the most frequently used alternative. The aim of this case report is to describe

Evaluation of Isolation Area, Myocardial Injury and Left Atrial Function Following High-Power Short-Duration Radiofrequency or Second-Generation Cryoballoon Ablation for Atrial Fibrillation

This randomized study aims to compare the left atrial (LA) lesion size, function, and tissue damage following pulmonary vein isolation (PVI) by high-power short-duration (HPSD) radiofrequency (RF) and second-generation cryoballoon (CB2) ablation. We enrolled 40 patients with paroxysmal atrial fibrillation who underwent PVI by HPSD RF (n = 21) or CB2 (n = 19). Every patient underwent LA CT angiography and transthoracic echocardiography (TTE) to assess the LA anatomy and function. Biomarker levels (hs-cTnT, hs-CRP, LDH) were compared pre- and post-procedurally. Pre- and post-ablation high-density mapping (HDM) was performed. The isolation area was defined under 0.2 mV bipolar voltage (low voltage area, LVA). We calculated the post-PVI LVA/LA surface ratio using LA CT-HDM merge images. At 3-month follow-up, TTE was performed to assess the changes in LA function. Post-ablation hs-cTnT level was significantly higher in the RF group (RF: 1249 ± 469 ng/L, CB2: 995 ± 280 ng/L, p = 0.024). Post-PVI hs-CRP (RF: 9.53 ± 10.30 mg/L, CB2: 12.36 ± 5.76 mg/L, p = 0.034) and LDH levels (RF: 349.9 ± 65.6 U/L, CB2: 451.6 ± 91.3 U/L, p p = 0.022). LA function did not change significantly after the PVI procedure. Our data indicate that second-generation cryoballoon ablation produces a significantly larger LA lesion size compared to “point-by-point” HPSD radiofrequency. Both techniques preserve LA function. The myocardial component of tissue loss appears to be higher using HPSD radiofrequency ablation, with less collateral damage

Rational design of balanced dual-targeting antibiotics with limited resistance

Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds, ULD1 and ULD2, belonging to a novel chemical class, almost equipotently inhibit bacterial DNA gyrase and topoisomerase IV complexes and interact with multiple evolutionary conserved amino acids in the ATP-binding pockets of their target proteins. ULD1 and ULD2 are excellently potent against a broad range of gram-positive bacteria. Notably, the efficacy of these compounds was tested against a broad panel of multidrug-resistant Staphylococcus aureus clinical strains. Antibiotics with clinical relevance against staphylococcal infections fail to inhibit a significant fraction of these isolates, whereas both ULD1 and ULD2 inhibit all of them (minimum inhibitory concentration [MIC] ≤1 μg/mL). Resistance mutations against these compounds are rare, have limited impact on compound susceptibility, and substantially reduce bacterial growth. Based on their efficacy and lack of toxicity demonstrated in murine infection models, these compounds could translate into new therapies against multidrug-resistant bacterial infections

Cardioverter defibrillator implantation without induction of ventricular fibrillation: a single-blind, non-inferiority, randomised controlled trial (SIMPLE).

International audienceDefibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384. Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25). Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office)

Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death: Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study

BACKGROUND: Population‐based studies suggest that genetic factors contribute to sudden cardiac death (SCD). METHODS AND RESULTS: In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy‐arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single‐nucleotide polymorphisms (SNPs) in 3 genes coding G‐protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter‐defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, a community‐based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11‐1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18‐2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26‐1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05‐1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10‐2.13]) genetic models. CONCLUSIONS: GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community‐based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933