Atrial fibrillation ablation in adults with congenital heart disease on uninterrupted oral anticoagulation is safe and efficient.

BACKGROUND: The prevalence of atrial fibrillation (AF) is significantly higher in adults with congenital heart disease (ACHD) compared to patients without congenital heart disease (CHD). As AF in ACHD patients might have significant hemodynamic consequences, rhythm control is particularly desirable but rarely achieved by antiarrhythmic drugs. The aim of this study was to investigate safety and long-term outcome of AF ablation in ACHD patients. METHODS: All ACHD patients (n = 46) that underwent AF ablation at our centre from 2013 to 2017 were included in the study. CHD was classified as simple (46%), moderate (41%) or complex (13%). The majority of patients (61%) suffered from persistent AF (paroxysmal AF 39%). Persistent AF was present in 57% of patients with simple, in 58% of patients with moderate and 83% of patients with complex CHD. All patients underwent radiofrequency (RF) ablation on uninterrupted oral anticoagulation. Pulmonary vein isolation (PVI) was performed in patients with paroxysmal AF, whereas patients with persistent AF underwent PVI and ablation of complex fractionated atrial electrograms (CFAE). RESULTS: No major complications occurred. Single-procedure success after 18 months off antiarrhythmic drugs was 61% for paroxysmal AF and 29% for persistent AF (p = 0.003). Multiple procedures (mean 2.1 ± 1.4) increased long-term success to 82% for paroxysmal AF and 48% for persistent AF (p = 0.05). Long-term ablation success was 64% for simple, 62% for moderate and 50% for complex CHD patients. CONCLUSIONS: AF ablation in ACHD patients is feasible and safe regardless of CHD complexity. Success rates in patients with paroxysmal AF are high and comparable to patients without CHD. In ACHD patients with persistent AF, success rates of ablation are markedly reduced which might be due to a different and/or more extensive (bi-)atrial substrate. In the cohort of complex ACHD patients with persistent AF as the dominant AF type, long-term success of AF ablation is limited.

Safety and outcome of very high-power short-duration ablation using 70 W for pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) in patients with paroxysmal atrial fibrillation (PAF) is effective but hampered by pulmonary vein reconnection due to insufficient ablation lesions. High-power delivery over a short period of time (HPSD) in RFA is stated to create more efficient lesions. The aim of this study was to compare intraprocedural safety and outcome of HPSD ablation to conventional power settings in patients undergoing PVI for PAF. METHODS AND RESULTS: We included 197 patients with PAF that were scheduled for PVI. An ablation protocol with 70 W and a duration cut-off of 7 s at the anterior left atrium (LA) and 5 s at the posterior LA (HPSD group; n = 97) was compared to a conventional power protocol with 30-40 W for 20-40 s (standard group; n = 100) in terms of periprocedural complications and a 1-year outcome. The HPSD group showed significantly less arrhythmia recurrence during 1-year follow-up with 83.1% of patients free from atrial fibrillation compared to 65.1% in the standard group (P < 0.013). No pericardial tamponade, periprocedural thromboembolic complications, or atrio-oesophageal fistula occurred in either group. Mean radiofrequency time (12.4 ± 3.4 min vs. 35.6 ± 12.1 min) and procedural time (89.5 ± 23.9 min vs. 111.15 ± 27.9 min) were significantly shorter in the HPSD group compared to the standard group (both P < 0.001). CONCLUSION: High-power short-duration ablation demonstrated a comparable safety profile to conventional ablation. High-power short-duration ablation using 70 W for 5-7 s leads to significantly less arrhythmia recurrences after 1 year. Radiofrequency and procedural time were significantly shortened.

Exclusion of left atrial thrombus by dual-source cardiac computed tomography prior to catheter ablation for atrial fibrillation.

OBJECTIVES: Thromboembolic complications during atrial fibrillation (AF) ablation due to mobilisation of a pre-existing thrombus formation (TF) in the left atrium (LA) are devastating. The gold standard to exclude LA TF is transesophageal echocardiography (TEE). The present study compares sensitivity and specificity of a dual-source cardiac-computed tomography (DS-CT) with TEE for TF exclusion prior to AF ablation. In addition, CT protocols with and without ECG synchronized were evaluated. METHODS: In 622 patients, DS-CT as well as TEE to exclude TF was performed less than 48 h prior to AF ablation. Mean age of patients was 60 ± 10 years (69% males, 61% paroxysmal AF). During DS-CT, 280 patients (45%) were in AF. An ECG-synchronized DS-CT was performed in 332 patients, whereas 290 patients underwent DS-CT without ECG synchronization. RESULTS: In all patients without suspected TF on DS-CT (n = 552; 88.7%), no thrombus was found on TEE. A TF was suspected on DS-CT in 70 patients, of whom only three patients showed TF on TEE. No TF was detected in the other 67 patients (Fig. 1). Overall, sensitivity for TF detection in DS-CT was 100% and specificity was 89.2% (positive predictive value 4.3%, negative predictive value 100%). The CT protocol (ECG-synchronized versus non-ECG-synchronized) had no significant influence on diagnostic accuracy. Mean dose length product during DS CT was 282 ± 287 mGy cm (synchronized) versus 136 ± 55 mGy cm (non-synchronized) with p < 0.0001. CONCLUSIONS: DS-CT is a highly sensitive method for LA thrombus detection in patients undergoing AF ablation. It delivers additional anatomic details of pulmonary veins and LA anatomy with an acceptable radiation exposure. Non-ECG-synchronized DS-CT showed a significantly lower radiation exposure, whereas diagnostic accuracy was comparable. Therefore, DS-CT might serve as primary method to exclude LA TF in patients undergoing AF ablation.

Safety of Uninterrupted Periprocedural Edoxaban Versus Phenprocoumon for Patients Who Underwent Left Atrial Catheter Ablation Procedures.

Data about the safety of edoxaban in patients who underwent left atrial (LA) radiofrequency (RF) ablation procedures are lacking. This study sought to compare the safety of uninterrupted edoxaban with uninterrupted phenprocoumon administration during LA RF ablation for atrial fibrillation and atrial tachycardia. In total, 231 patients (mean age 64 ± 11years, male 71%) who underwent LA RF ablation under continuous oral anticoagulation (OAC) with edoxaban or phenprocoumon were included in the study. Patients on uninterrupted edoxaban (60 mg or 30 mg/day for at least 4 weeks) were matched for gender, age and type of arrhythmia with 2 patients on uninterrupted phenprocoumon (international normalized ratio 2 to 3). We identified 77 consecutive patients on edoxaban and n = 154 patients on phenprocoumon. Heparin was administered periprocedurally to achieve an activated clotting time of 280 to 300 seconds. No protamine was administered periprocedurally. The primary end point was a composite of bleeding, thromboembolic events, and death. The primary end point was met in 9 patients in the edoxaban group and in 22 patients in the phenprocoumon group (p = 0.69). No patient in either group died or had a thromboembolic complication. No major bleeding complication was observed in the edoxaban group, whereas one was found in 1 patient in the phenprocoumon group (p ≥0.99). Minor bleeding complications occurred in 9 patients (12%) in the edoxaban group and in 21 patients (14%) in the phenprocoumon group (p = 0.84). Uninterrupted OAC with edoxaban appeared to be as safe as uninterrupted OAC with phenprocoumon in patients who underwent LA RF ablation procedures.

Catheter ablation of left atrial arrhythmias on uninterrupted oral anticoagulation with vitamin K antagonists: What is the relationship between international normalized ratio, activated clotting time, and procedure-related complications?

BACKGROUND: Ablation of atrial fibrillation (AF) on uninterrupted phenprocoumon reduces periprocedural thromboembolic and bleeding complications. Heparin is administered intraprocedurally to achieve activated clotting times (ACT) of 300-400 seconds. We investigated the effect of international normalized ratio (INR) on ACT and intraprocedural heparin requirements. Moreover, safety of a target ACT of 250-300 seconds was investigated. METHODS AND RESULTS: We studied 949 patients referred for AF or left atrial tachycardia ablation. Patients were divided into Group 1 (n = 249) with an INR <2 and Group 2 (n = 700) with an INR ≥2. Mean INR was 1.7 ± 0.13 in Group 1 and 2.3 ± 0.25 in Group 2. Baseline, mean, minimum and maximum ACT were significantly lower in Group 1 (138 ± 17 seconds vs. 145 ± 21 seconds; 281 ± 28 seconds vs. 288 ± 29 seconds; 251 ± 36 seconds vs. 258 ± 34 seconds; 307 ± 32 seconds vs. 316 ± 40 seconds; P <0.05). Intraprocedural heparin requirements adjusted to body weight were lower in Group 1 (127 ± 41 U/kg vs. 122 ± 40 U/kg). Weak correlations between INR and baseline, mean, minimum and maximum ACT as well as intraprocedural heparin requirements were observed. No differences regarding major or minor complications were found. INR and periprocedural anticoagulation parameters had no influence on major complications. No thromboembolic complications were observed in both groups with a target ACT value of 250-300 seconds. CONCLUSIONS: There is only a weak correlation between INR, intraprocedural ACT, and intraprocedural heparin requirements. Periprocedural target ACT of 250-300 seconds seems safe and does not increase periprocedural bleeding and thromboembolic complications in patients undergoing RF ablation on uninterrupted phenprocoumon therapy.

Safety and Feasibility of Subcutaneous Purse-String Suture of the Femoral Vein After Electrophysiological Procedures on Uninterrupted Oral Anticoagulation.

The aim of this study was to compare safety and feasibility of a subcutaneous purse-string suture (PSS) with manual compression (MC) to gain hemostasis in patients after multiple femoral venous punctures undergoing electrophysiological procedures on uninterrupted oral anticoagulation (OAK). A total of 784 patients who underwent catheter ablation for atrial fibrillation (n = 564) or (a)typical atrial flutter (n = 220) were assessed. Four hundred sixty-two patients received PSS (58.9%) and 322 patients (41.1%) received MC to gain hemostasis. All patients were on uninterrupted full-dose OAK. During the procedure, weight-adapted heparin was applied. Venous sheath diameter were 8Fr (n = 2)/11.5Fr (n = 1) for left atrial or 8Fr (n = 1)/6Fr (n = 2) for right atrial procedures. No protamine was administered at the end of the procedure. After PSS, patients' had 6 hours of bed rest compared with 10 hours after MC (sheath removal after 4 hours followed by a bandage for 6 hours). PSS was removed the following day. All patients underwent duplex sonography of the access site the following day. Using the PSS, hemostasis was achieved in 453 of 462 patients (98%). MC leads to hemostasis in all 322 patients. No difference was found between the 2 approaches regarding hematomas (<5 cm or >5 cm), arterio-venous fistulas, or pseudoaneurysms. No major complication such as ipsilateral leg ischemia, the need of vascular surgery, or deep vein thrombosis occurred. In conclusion, PSS is a safe and effective way to gain immediate hemostasis after multiple punctures of the femoral vein in patients undergoing catheter ablation on OAK. PSS avoids MC and leads to shorter patient immobilization.

Regional Lung Ventilation Analysis Using Temporally Resolved Magnetic Resonance Imaging.

OBJECTIVE: We propose a computer-aided method for regional ventilation analysis and observation of lung diseases in temporally resolved magnetic resonance imaging (4D MRI). METHODS: A shape model-based segmentation and registration workflow was used to create an atlas-derived reference system in which regional tissue motion can be quantified and multimodal image data can be compared regionally. Model-based temporal registration of the lung surfaces in 4D MRI data was compared with the registration of 4D computed tomography (CT) images. A ventilation analysis was performed on 4D MR images of patients with lung fibrosis; 4D MR ventilation maps were compared with corresponding diagnostic 3D CT images of the patients and 4D CT maps of subjects without impaired lung function (serving as reference). RESULTS: Comparison between the computed patient-specific 4D MR regional ventilation maps and diagnostic CT images shows good correlation in conspicuous regions. Comparison to 4D CT-derived ventilation maps supports the plausibility of the 4D MR maps. Dynamic MRI-based flow-volume loops and spirograms further visualize the free-breathing behavior. CONCLUSIONS: The proposed methods allow for 4D MR-based regional analysis of tissue dynamics and ventilation in spontaneous breathing and comparison of patient data. The proposed atlas-based reference coordinate system provides an automated manner of annotating and comparing multimodal lung image data.

Bridging the scales: semantic integration of quantitative SBML in graphical multi-cellular models and simulations with EPISIM and COPASI.

MOTIVATION: Biological reality can in silico only be comprehensively represented in multi-scaled models. To this end, cell behavioural models addressing the multi-cellular level have to be semantically linked with mechanistic molecular models. These requirements have to be met by flexible software workflows solving the issues of different time scales, inter-model variable referencing and flexible sub-model embedding. RESULTS: We developed a novel software workflow (EPISIM) for the semantic integration of Systems Biology Markup Language (SBML)-based quantitative models in multi-scaled tissue models and simulations. This workflow allows to import and access SBML-based models. SBML model species, reactions and parameters are semantically integrated in cell behavioural models (CBM) represented by graphical process diagrams. By this, cellular states like proliferation and differentiation can be flexibly linked to gene-regulatory or biochemical reaction networks. For a multi-scale agent-based tissue simulation executable code is automatically generated where different time scales of imported SBML models and CBM have been mapped. We demonstrate the capabilities of the novel software workflow by integrating Tyson's cell cycle model in our model of human epidermal tissue homeostasis. Finally, we show the semantic interplay of the different biological scales during tissue simulation. AVAILABILITY: The EPISIM platform is available as binary executables for Windows, Linux and Mac OS X at http://www.tiga.uni-hd.de. Supplementary data are available at http://www.tiga.uni-hd.de/supplements/SemSBMLIntegration.html. CONTACT: niels.grabe@bioquant.uni-heidelberg.de.

Investigating the effects of simulated martian ultraviolet radiation on Halococcus dombrowskii and other extremely halophilic archaebacteria.

The isolation of viable extremely halophilic archaea from 250-million-year-old rock salt suggests the possibility of their long-term survival under desiccation. Since halite has been found on Mars and in meteorites, haloarchaeal survival of martian surface conditions is being explored. Halococcus dombrowskii H4 DSM 14522(T) was exposed to UV doses over a wavelength range of 200-400 nm to simulate martian UV flux. Cells embedded in a thin layer of laboratory-grown halite were found to accumulate preferentially within fluid inclusions. Survival was assessed by staining with the LIVE/DEAD kit dyes, determining colony-forming units, and using growth tests. Halite-embedded cells showed no loss of viability after exposure to about 21 kJ/m(2), and they resumed growth in liquid medium with lag phases of 12 days or more after exposure up to 148 kJ/m(2). The estimated D(37) (dose of 37 % survival) for Hcc. dombrowskii was > or = 400 kJ/m(2). However, exposure of cells to UV flux while in liquid culture reduced D(37) by 2 orders of magnitude (to about 1 kJ/m(2)); similar results were obtained with Halobacterium salinarum NRC-1 and Haloarcula japonica. The absorption of incoming light of shorter wavelength by color centers resulting from defects in the halite crystal structure likely contributed to these results. Under natural conditions, haloarchaeal cells become embedded in salt upon evaporation; therefore, dispersal of potential microscopic life within small crystals, perhaps in dust, on the surface of Mars could resist damage by UV radiation.