Alexandra Kiss

Cerebral microembolization during atrial fibrillation ablation: Comparison of different single-shot ablation techniques

BACKGROUND Clinically silent cerebral ischemia (SCI) detected by diffusion-weighted MRI has been reported in 5-40% of patients undergoing pulmonary vein isolation (PVI). Although initial reports suggested a high rate of SCI with phased radiofrequency (RF) ablation on use of the pulmonary vein ablation catheter (PVAC), the incidence was subsequently markedly reduced in consequence of procedural modifications in recent studies. We analyzed cerebral microembolization as assessed with transcranial Doppler during phased RF ablation and with two other single-shot AF ablation technologies: the cryoballoon (CB) and the nMARQ™ multipolar irrigated RF ablation system. METHODS AND RESULTS A total of 89 patients (mean age: 57, SD: 12years; 62 males) with paroxysmal or persistent AF underwent PVI. Phased RF was used according to the initial protocol in 7 patients (PVAC Group I), with procedural modifications and a newer (14.4) version of the RF generator in 37 patients (PVAC Group II) and with the most recent (version 15.1) generator in 18 patients (PVAC Group III). Ablation was performed with the CB in 13 and with the nMARQ system in 14 patients. The number of microemboli (mean+(SD)) detected in the middle cerebral arteries was 2703 (918) in PVAC Group I, 1087 (542) in PVAC Group II, 719 (469) in PVAC Group III, 1057 (784) with CB and 2166 (1047) with nMARQ (p<0.01). CONCLUSION Significant decreases in MES counts were observed thanks to the procedural modifications and newer RF generator with phased RF. High MES counts comparable to those with the initial phased RF resulted from the use of nMARQ.

Predictors of cerebral microembolization during phased radiofrequency ablation of atrial fibrillation: Analysis of biophysical parameters from the ablation generator

BACKGROUND Pulmonary vein isolation with phased radiofrequency current and use of a pulmonary vein ablation catheter (PVAC) has recently been associated with a high incidence of clinically silent brain infarcts on diffusion-weighted magnetic resonance imaging and a high microembolic signal (MES) count detected by transcranial Doppler. OBJECTIVE The purpose of this study was to investigate the potential correlation between different biophysical parameters of energy delivery (ED) and MES generation during PVAC ablation. METHODS MES counts during consecutive PVAC ablations were recorded for each ED and time stamped for correlation with temperature, power, and impedance data from the GENius 14.4 generator. Additionally, catheter-tissue contact was characterized by the template deviation score, calculated by comparing the temperature curve with an ideal template representing good contact, and by the respiratory contact failure score, to quantify temperature variations indicative of intermittent contact due to respiration. RESULTS A total of 834 EDs during 48 PVAC ablations were analyzed. A significant increase in MES count was associated with a lower average temperature, a temperature integral over 62°C, a higher average power, the total energy delivered, higher respiration and template deviation scores (P <.0001), and simultaneous ED to the most proximal and distal poles of the PVAC (P <.0001). CONCLUSION MES generation during ablation is related to different indicators of poor electrode-tissue contact, the total power delivered, and the interaction between the most distal and the most proximal electrodes.

Intracardiac Hemostasis and Fibrinolysis Parameters in Patients with Atrial Fibrillation

Aims To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. Patients and Methods Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. Results Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. Conclusions None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level.

Lymphoid metastasis of rat My2/De leukemia

By grafting spontaneous leukemia tumor cells, the myeloid My2/De leukemia rat model was established. Death was caused by impaired functions of heavily infiltrated organs. In vitro culturing of tumor cells, blood and bone marrow counts and cytochemic reactions indicated the leukemic the origin resembling human myeoloblastic leukemia. Metastatic spread was followed after i.v. and i.p. injection, and by implantation of leukemia cells under the renal capsule of rats. Primary tumor and metastasis formation was visualized by (18)FDG or (11)C-methionine administration and MiniPET. The accumulation of radiotracers was measured in different organs and expressed as Differential Absorption Ratios (DARs). Subrenal implantation of My2/De cells resulted in their appearance in other abdominal organs and in parathymic lymph nodes. The release of tumor cells from the primary kidney to the peritoneum was mimicked by the i.p. administration of ink particles. Ink particles deposited in the abdominal organs and in the thoracal lymph nodes, preferentially in parathymic lymph nodes, confirming the notion of lymphatic spread of metastasis.

Cerebral micro-embolization during pulmonary vein isolation: Relation to post-ablation silent cerebral ischemia

BACKGROUND High incidences of silent cerebral ischemia (SCI) have been revealed by diffusion-weighted magnetic resonance imaging (DW MRI) after pulmonary vein isolation (PVI) for atrial fibrillation. A high number of mostly gaseous micro-embolic signals (MESs) was detected by transcranial Doppler (TCD) during PVI. In this investigation the possible relationship between MESs detected intraoperatively by TCD and new SCI on DW MRI post-ablation is reported. METHODS 27 consecutive atrial fibrillation patients (6 female, age median: 64 interquartile range: 13.23) undergoing PVI with the pulmonary vein ablation catheter, pre- and post-ablation DW MRI and intra-operative MES detection by TCD were included in the study. Procedures were performed on a therapeutic international normalized ratio (2-3) and with a target activated clotting time ≥ 350 s in all patients. DW MRI scans performed pre- and post-ablation revealed new SCI in 6 out of 27 (22%) patients. RESULTS The median (interquartile range) MES count recorded during the whole procedure was 1642 (912) in patients with and 1019 (529) in those without SCI (p = 0.129). The number of MESs recorded during pulmonary vein angiography was significantly higher in patients as compared to those without a new lesion on the post-ablation DW MRI: 257 (249) vs. 110 (71), respectively (p = 0.0009). On mul-tivariate logistic regression, the total MES count was predictive of SCI in patients older than 68 years. CONCLUSIONS Micro-embolus generation detected by TCD during pulmonary vein angiography significantly correlates with new SCI on DW MRI post-ablation.

MICAN, a new fluorophore for vital and non-vital staining of human cells

Fluorescence time-lapse microscopy is in connection with the invasive properties of fluorochrome applied, and with the toxicity of the excitation energy and wavelength of the dye itself. Experiments with the newly synthesized fluorescent dye 1-N-methylamino-5-isocyanonaphthalene (MICAN) served to test its cytotoxicity on human HaCaT keratinocyte cell cultures. Experiments related to staining capability were performed with paraformaldehyde (PFA) fixed cells and observed with fluorescence microscope. It was assumed that the fluorophore 1-amino-5-isocyanonaphthalene (ICAN) and especially its N-methylamino derivative MICAN, containing condensed aromatic rings could serve as a nonselective fluorescent dye capable to stain cellular structures of fixed, living, damaged and dead cells. This notion was confirmed by the MICAN staining of cytoplasmic proteins primarily rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SEM) and less efficiently nuclear proteins suggesting the involvement of staining of subcellular structures involved in protein synthesis. MICAN was not only well tolerated by living cells but turned out to be a strong heterochromatin and RER staining agent. This led to the development of a MICAN staining protocol for native and living samples. Relative to other fluorescent dyes, MICAN is not only useful but also cost-effective. Toxicology tests were performed using 30, 10, 5, 0.5 μg/ml MICAN concentrations. Time-lapse videomicroscopy at near-infrared (NIR) illumination has been used for the examination of MICAN effect on cell division. It was found that MICAN as a vital stain had no significant harmful effect on HaCaT cells. MICAN turned out to be a non-toxic, highly quantum-efficient vital stain with minimal, or no photobleaching, and can be applied to co-stain with propidium-iodide due the strong spectral separation.

Gadolinium induced effects on mammalian cell motility, adherence and chromatin structure

The toxicity of gadolinium is reduced by chelating agents that render this heavy metal into contrast complexes used for medical magnetic resonance imaging. However, the dissociation of gadolinium chelates is known to generate Gd3+ ions, the cellular toxicity of which has not been tested in details. The cytotoxic effects of Gd(III) ions were evaluated by monitoring the proliferation, measuring the cellular motility and following chromatin changes in various cell lines upon Gd3+ treatment. Measurements applied long-term scanning microscopy and a perfusion platform that replaced the medium with test solutions, bypassed physical contact with the cell culture during experiments, and provided uninterrupted high time-resolution time-lapse photomicrography for an extended period of time. Genotoxicity specific chromatin changes characteristic to Gd(III) were distinguished in human skin keratinocytes (HaCaT), human limbal stem cells (HuLi), colorectal adenocarcinoma (CaCO2), murine squamous carcinoma (SCC) and Indian muntjac (IM) cell lines. Characteristic features of Gd(III) toxicity were: loss of cellular motility, irreversible attachment of cells to the growth surface and cell death. Injury-specific chromatin changes manifested at micromolar Gd3+ concentrations as premature chromatin condensation and highly condensed sticky chromatin patches. Gd(III) concentration- and cell type-dependent reduction of normal adherence, as well as premature chromatin condensation confirmed apoptosis. The risk related to the release of toxic Gd3+ ions from gadolinium complexes and their effects on mono- and multi-layer cellular barriers have to be reconsidered when these chelated complexes are used as contrasting agents especially in relation to possible blood–brain barrier damages.

REDUCTION IN EMBOLIC EVENTS WITH MULTIPOLAR DUTY-CYCLED RADIOFREQUENCY ISOLATION OF THE PULMONARY VEINS USING THE MODIFIED VERSION OF THE GENIUS™ ABLATOR

Backround: High incidence (up to 40%) of clinically silent cerebral ischemia (SCI) on diffusion-weighted (DW) MRI has been consistently demonstrated after pulmonary vein isolation (PVI) using duty-cycled radiofrequency (RF) ablation with a multipolar circular ablation catheter (PVAC) . Our group has also demonstrated a significantly higher number of microembolic singnals (MES) on Transcranial Doppler (TCD) with PVAC as compared to cryoballoon ablation (CBA). Power and temperature handling algorhythms of the GENiusTM RF generator used for PVAC ablations have recently been modified to avoid temperature overshoots aiming at a reduced thrombogenic potential. We compared the incidence of microembolization during PVAC ablation with the old versus the modified version of the GENiusTM generator as assessed by TCD. In addition, we investigated the incidence of new silent cerebral lesions on DW MRI using the modified generator and an agressive periprocedural anticoagulation protocol.