Silent Cerebral Events/Lesions Related to Atrial Fibrillation Ablation: A Clinical Review

Brain magnetic resonance imaging (MRI) has identified a high incidence of cerebral ischemia in asymptomatic patients after atrial fibrillation (AF) ablation (silent). Detection of cerebral ischemic events on MRI is based on acute hyperintense lesions on diffusion‐weighted imaging. In the literature, the incidence is related to specifications of MRI and depends on the definition applied. In comparative studies, silent cerebral events (SCE, diffusion‐weighted MRI [DWI] positive only) appear to be approximately 3 times more common compared to using a definition of silent cerebral lesions (SCL; without fluid attenuated inverse recovery sequence [FLAIR] positivity). Whereas the FLAIR sequence may turn positive within days after the ischemic event, SCE definition is highly sensitive for early phases of ischemic brain damage. SCE/SCL appear to represent cerebral ischemic infarcts and determine the “embolic fingerprint” of a specific ablation technology and strategy used. The optimum time point for detecting SCE is early after AF ablation (24–72 hours), whereas detection of SCL can only be performed within the first 2–7 days (due to delay of FLAIR positivity). Different technology‐, procedure‐, and patient‐related parameters have been identified to play a role in the multifactorial genesis of SCE/SCL. In recent years, evidence has been gathered that there may be differences of SCE/SCL rates depending upon the ablation technology used, but small patient numbers and a large number of potential confounders hamper all studies. As major findings of recent studies, mode of periprocedural and intraprocedural anticoagulation has been identified as a major predictor for incidences of SCE/SCL. Whereas procedural characteristics related to higher SCE/SCL‐rates may be modified, unchangeable patient‐related factors should be taken into account for future individualized risk assessment. Novel ablation devices introduced into the market should be tested for their potential embolic fingerprint and refinements of ablation procedures to reduce their embolic potential should be prompted. The knowledge of “best practice” in terms of low SCE/SCL rates has prompted changes in work‐flow, which have been implemented into ablation procedures using novel ablation devices. So far, no study has linked SCE/SCL to neuropsychological decline and the low number of AF‐ablation‐associated events needs to be weighted against the multitude of preexisting asymptomatic MRI‐detected brain lesions related to the course of AF itself. Future studies are needed to evaluate if more white matter hyperintensities due to AF may be prevented by AF ablation (producing only a small number of SCE/SCL).     

Complete Revascularization in Patients Undergoing Multivessel PCI is an Independent Predictor of Improved Long‐term Survival

Background: The prognostic relevance of complete revascularization (CR) in patients with multivessel coronary artery disease (MV‐CAD) has been established so far for surgical treatment strategies rather than for percutaneous coronary revascularization (PCI). In addition, different definitions of CR have further complicated the interpretation of clinical studies. Methods: Procedural characteristics and long‐term overall survival were assessed in 679 consecutive “all‐comer” patients, who underwent PCI in at least two main vessels. We adapted three definitions of CR from the coronary artery bypass grafting (CABG) trials. CR was achieved if following MV‐PCI one of the three criteria was met: (1) no residual stenosis in a main coronary vessel, (2) no residual stenosis in any coronary segment, or (3) no residual stenosis in the left anterior descending (LAD) and at least one further main branch. The main objective was the evaluation of predictors of incomplete revascularization and the prognostic impact of CR in MV‐PCI patients. Results: CR was achieved in 76%, 67%, and 95%, respectively, (definitions 1–3). Patients without CR were older, had a lower ejection fraction, and presented more often with acute coronary syndromes (ACS). Clinical long‐term follow‐up regarding survival was available in 664 patients (98%) with a mean follow‐up of 2.5 ± 1.6 years. Independent of the specific definition, CR was associated with a reduced long‐term mortality by approximately 50%. After adjusting for relevant baseline parameters, only absence of residual stenosis in all coronary segments remained as an independent predictor of long‐term prognosis (hazard ratio [HR]= 0.51, 95% confidence interval [CI]: 0.28–0.93; P = 0.025). Conclusions: CR of all coronary segments is associated with improved overall survival after MV‐PCI. (J Interven Cardiol 2010;23:256–263)     

Noninvasive Mapping of Human Atrial Fibrillation

Introduction: Invasive high-density mapping of atrial fibrillation (AF) has revealed different patterns of atrial activation ranging from single wavefronts to disorganized activation with multiple simultaneous wavefronts. Whether or not similar activation patterns can also be observed using body surface recordings is currently unknown, and was consequently evaluated in this study.
Methods and Results: Surface electrocardiographic mapping was performed in 14 patients (age 68 ± 14 years) with persistent AF (AF duration 12 ± 18 months). A total of 56 electrocardiographic leads were placed on the chest over the atria on the front (n = 40) and on the back (n = 16). Using 240-second recordings, wavefront propagation maps were automatically computed and visually classified as either type I (single wavefront), II (single wavefront with wave breakages and splitting), or III (multiple simultaneous wavefronts). Almost half of the patients (n = 6) presented most predominantly type III atrial activation, while six patients mostly presented type I activation. The rest of the patients (n = 2) presented mixed type I and type III activations. This classification showed to be highly reproducible over 4 minutes.
Conclusions: Using electrocardiographic body surface mapping during AF, interindividual differences of atrial fibrillatory activation can be observed. The surface activation pattern during AF shows an excellent short-term reproducibility.     

Esophageal Endoscopy Results After Pulmonary Vein Isolation Using the Single Big Cryoballoon Technique

Esophageal Effects of Single Big Cryoballoon PVI. Introduction: Reversible esophageal thermal lesions after cryoballoon pulmonary vein isolation (CB‐PVI) have been reported when using variable balloon sizes. The aim of this study was to investigate (1) the incidence of esophageal thermal lesions, and (2) esophageal temperature changes associated with CB‐PVI using the single big cryoballoon technique. Methods and Results: Thirty‐eight patients with atrial fibrillation underwent successful CB‐PVI using only the 28 mm cryoballoon. Luminal esophageal temperature (LET) was continuously monitored by 3 thermocouples. Fluoroscopic distance from cryoballoon to esophagus probe was retrospectively evaluated in RAO 30° and LAO 40° projections. All patients underwent postprocedural esophageal endoscopy. Average minimal LET was lower during freezing at inferior PVs, when compared to superior PVs: 35.4 ± 0.9 (range: 32.6 to 37.4; RSPV); 31.5 ± 7.5 (2.5 to 37.6; RIPV); 32.9 ± 5.2 (8.5 to 36.5; LSPV); and 30.3 ± 8.4°C (?6 to 36.7°C; LIPV); P = 0.001. We found steep temperature gradients over distance (1) from the cryoballoon center (LETs < 10°C confined to a distance of < 15 mm in both RAO 30° and LAO 40° projections), and (2) along the esophagus long axis, underscoring the need for multiple measurement sites. None of the patients showed esophageal thermal lesions at endoscopy after 3 ± 1 (range 1–7) days. No AEF occurred during a follow‐up of 125 ± 78 days. Conclusion: In a cohort of AF patients treated by the single big cryoballoon technique, CB‐PVI was not associated with thermal esophageal lesions. (J Cardiovasc Electrophysiol, Vol. 21, pp. 869‐874, August 2010)     

Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study

Background: Few data exist regarding antegrade selective cerebral perfusion (ASCP) and its application in newborn and juvenile patients. Clinical data suggest ASCP alone to be superior to deep hypothermic circulatory arrest (DHCA); however, the effects of moderate hypothermia during ASCP on cerebral metabolism in this patient population are still unclear. Methods: After obtaining the approval from animal investigation committee, 16 piglets were randomly assigned to circulatory arrest combined with either ASCP at 27°C or DHCA at 18°C for 90 min. Cerebral oxygen extraction fraction (COEF) from blood as well as cerebral tissue glucose, glycerol, lactate, pyruvate, and the lactate/pyruvate ratio (L/P ratio) by microdialysis were obtained repeatedly. Results: COEF was lower during cooling and rewarming, respectively, in the DHCA18 group compared to the ASCP27 group (30 ± 8 vs 56 ± 13% and 35 ± 6 vs 58 ± 7%, respectively). Glucose decreased in both the DHCA18 and ASCP27 groups during the course of cardiopulmonary bypass (CPB), but were higher in the ASCP27 group during ASCP, compared to the DHCA18 group during circulatory arrest (0.7 ± 0.1 vs 0.2 ± 0.1 mm ·l^?1, P < 0.05). Pyruvate was higher (ASCP27 vs DHCA18: 53 ± 17 vs 6 ± 2 μm ·l^?1, P < 0.05), and the L/P ratio increased during circulatory arrest in the DHCA18 group, compared to the selective perfusion phase of the ASCP27 group (DHCA18 vs ASCP27: 1891 ± 1020 vs 70 ± 28, P < 0.01). Conclusions: In this piglet model, both cerebral oxygenation and microdialysis findings suggested a depletion of cerebral energy stores during circulatory arrest in the DHCA18 group, compared to selective cerebral perfusion combined with circulatory arrest in the ASCP27 group.     

Light-induced Apoptosis: Differential Timing in the Retina and Pigment Epithelium

Apoptosis is a genetically regulated form of cell death. Individual cells show condensed nuclear chromatin and cytoplasm, and biochemical analysis reveals fragmentation of the DNA. Ensuing cellular components, apoptotic bodies, are removed by macrophages or neighboring cells. Genes involved in the regulation of apoptosis as well as stimuli and signal transduction systems, are only beginning to be understood in the retina. Therefore, we developed a new in vivo model system for the investigation of events leading to apoptosis in the retina and the pigment epithelium. We induced apoptosis in retinal photoreceptors and the pigment epithelium of albino rats by exposure to 3000 lux of diffuse, cool white fluorescent light for short time periods of up to 120 minutes. Animals were killed at different time intervals during and after light exposure. The eyes were enucleated and the lower central retina was processed for light- and electron microscopy. DNA fragmentation was analysed in situ by TdT-mediated dUTP nick-end labeling (TUNEL) or by gel electrophoresis of total retinal DNA. We observed that the timing of apoptosis in the photoreceptors and pigment epithelium was remarkably different, the pigment epithelium showing a distinct delay of several hours before the onset of apoptosis. In photoreceptors, apoptosis was induced within 90 minutes of light exposure, with the morphological appearance of apoptosis preceding the fragmentation of DNA. In the pigment epithelium, the morphological appearance of apoptosis and DNA fragmentation were coincident. Different regulative mechanisms may lead to apoptotic cell death in the retinal photoreceptors and pigment epithelium. This in vivo model system will allow measurement of dose-responses, a potential spectral dependence and the molecular background of apoptotic mechanisms in the retina.     

Antidotal Efficacy of Newly Synthesized Dimercaptosuccinic Acid (DMSA) Monoesters in Experimental Arsenic Poisoning in Mice

The efficacy of four newly synthesized monoesters of meso-2,3-dimercaptosuccinicacid (DMSA), mono-i-arnyl- (Mi-ADMS), mono-n-amyl- (Mn-ADMS),mono-i-butyl- (Mi-BDMS), and mono-n-butyl-meso-2,3-dimercaptosuccinate(Mn-BDMS) in increasing survival and arsenic elimination inexperimental arsenic poisoning was investigated. Male mice (strainNMRI) received arsenite sc (survival study: 130 µmol/kg,7 mice/group; elimination study: 85 µmol/kg (LD5) togetherwith a tracer dose of⁷³ As(III), 6 mice/group). After 30 minmice were treated with 0.7 mmol/kg of DMSA or a monoester ipor via gastric tube (ig). Control animals received saline ip.In the survival study mice were observed for 30 days. In theelimination study, the 73-arsenic content of several organs(blood, liver, heart, lung, kidneys, spleen, testes, brain,small intestine, large intestine, muscle, and skin) was measured0.5, 2, 4, 6, and 8 hr after the arsenic injection using a gammacounter. Survival increased correspondingly well with the increaseof arsenic elimination. DMSA, Mi-ADMS, Mn-ADMS, Mi-BDMS, andMn-BDMS markedly decreased arsenic content in most organs assoon as 1.5 hr after treatment. Only in small and large intestinewere higher arsenic amounts found, indicating a shift in arsenicelimination from the renal to the fecal route, and thereby suggestinga protective effect for the kidneys. Given ip, the monoestersturned out to be similarly as effective as the parent drug DMSA.Following ig treatment, the DMSA monoesters Mi-ADMS and Mn ADMSseemed to be superior to DMSA with regard to survival. The similarefficacy of the various monoesters indicates that the side chainsubstitution did not markedly change bioavailabilty and efficacy.It is concluded that the new DMSA monoesters are effective arsenicantidotes given systemically or orally.     

Staphylococcus aureus isolates from blood and anterior nares induce similar innate immune responses in endothelial cells

To evaluate the possibility to distinguish virulent from non‐virulent isolates, gene expression in human umbilical vein endothelial cells (HUVEC) induced by invasive and colonizing isolates of Staphylococcus aureus was compared. Gene expression in HUVEC was analyzed by microarray analysis after 4 h of infection with Staphylococcus aureus, isolated from healthy nasal carriers (n = 5) and from blood of septic patients (n = 5), to explore possible differences between the groups of bacteria in interaction with HUVEC. All isolates were spa‐typed to disclose strain relatedness. Moreover, the isolates were characterized with DNA microarray to determine the presence of virulence genes and to investigate the potential genes of importance in HUVEC interaction. The expression of 41 genes was up‐regulated, and four were down‐regulated in HUVEC by all isolates. Most of the up‐regulated genes encode cytokines, chemokines, interferon‐induced proteins, proteins regulating apoptosis and cell proliferation. There was no difference in the gene expression pattern between HUVEC infected with invasive or colonizing isolates. Furthermore, there was no difference in the presence of bacterial virulence genes between the two groups. In conclusion, our data indicate that S. aureus isolates induce comparable expression patterns in HUVEC, irrespective of invasiveness or presence of virulence genes.