Rasmussen aneurysm: A forgotten complication of tuberculosis in the COVID-19 era.

COVID-19 pandemic has led to an overwhelming healthcare system causing a delay in management of other infectious diseases such as tuberculosis. Rasmussen aneurysm (RA) appears in chronic cavitary tuberculosis. We report here, three cases of pulmonary tuberculosis complicated by RA admitted to Department 1 of Abderrahmane Mami hospital in Tunisia. Data were collected from June 2020 to September 2021. All patients presented with hemoptysis. Sputum was positive for the acid-fast bacilli. Computed tomographic pulmonary angiography showed RA. Only one patient underwent emergent glue embolization. These cases give an insight into the importance of timely therapeutic care for tuberculosis.

Healthcare utilization and clinical outcomes after ablation of atrial fibrillation in patients with and without insertable cardiac monitoring.

BACKGROUND: Compared with short-term electrocardiogram (ECG) monitors, insertable cardiac monitors (ICMs) have been shown to increase atrial fibrillation (AF) detection rates and the opportunity to treat recurrent AF in patients postablation. OBJECTIVE: To examine healthcare utilization and clinical outcomes following AF ablation, in patients with vs without ICM. METHODS: Retrospective analysis pooling Optum Clinformatics and Medicare Fee-for-service 5% Sample claims databases. Patients with an AF ablation between January 1, 2011, and March 31, 2018 who received an ICM implant within 1 year pre-/postablation were propensity score matched 1:3 to patients without ICM. Outcomes included AF-related healthcare utilization, medication use, and occurrence of composite severe cardiovascular events (stroke / transient ischemic attack, major bleeds, systemic embolism, AF- or heart failure-related hospitalization, or death). RESULTS: A total of 1000 ICM patients and 2998 non-ICM patients were included. During mean follow-up of 33 ± 16 months postablation, ICM patients experienced significantly fewer severe cardiovascular events (1.09 ± 2.22 vs 1.37 ± 4.19, P = .008) and associated costs ($20,757 vs $29,106, P = .0005). ICM patients had a greater number of AF-related clinic visits (16.8 vs 11.6 visits, P < .0001) and were more likely to receive a repeat ablation (38.7% vs 32.4%, P = .0003). Total all-cause costs during follow-up were not statistically different. Discontinuation of oral anticoagulation was higher in ICM patients at 1 year (44% vs 31%, P < .0001) and 2 years (73% vs 64%, P = .0012). CONCLUSION: A shift from acute, reactive care to routine outpatient management was observed in patients with long-term ECG monitoring. Results suggest closer patient management in patients with long-term monitoring after an AF ablation and an improvement in outcomes, at similar overall cost.

Atrial Fibrillation-Mediated Cardiomyopathy.

AF-mediated cardiomyopathy (AMC) is an important reversible cause of heart failure that is likely underdiagnosed in today's clinical practice. AMC describes AF either as the sole cause for ventricular dysfunction or exacerbating ventricular dysfunction in patients with existing cardiomyopathy or heart failure. Studies suggest that irreversible ventricular and atrial remodeling can occur in AMC, making timely diagnosis and intervention critical to optimize clinical outcome. Clinical correlation between AF onset/burden and progression of cardiomyopathy/heart failure symptoms provides strong evidence for the diagnosis of AMC. Cardiac MRI, continuous cardiac monitoring, and biomarkers are important diagnostic tools. From the therapeutic standpoint, early data suggest that AF ablation may improve long-term outcomes in AMC patients compared with medical rate and rhythm control. Patients with more AF burden and less severe underlying structural heart disease are more likely to experience left ventricle function recovery with successful AF ablation. Despite recent advances, significant knowledge gaps exist in our understanding of the epidemiology, mechanisms, diagnosis, management strategies, and prognosis of AMC.

Emergency Department Visits for Atrial Fibrillation in the United States: Trends in Admission Rates and Economic Burden From 2007 to 2014.

BACKGROUND: Atrial fibrillation (AF) is an increasingly prevalent public health problem and one of the most common causes of emergency department (ED) visits. We aimed to investigate the trends in ED visits and hospital admissions for AF. METHODS AND RESULTS: This is a repeated cross-sectional analysis of ED visit-level data from the Nationwide Emergency Department Sample for 2007 to 2014. We identified adults who visited EDs in the United States, with a principal diagnosis of AF. A sample of 864 759 ED visits for AF, representing a weighted total of 3 886 520 ED visits, were analyzed. The annual ED visits for AF increased by 30.7% from 411 406 in 2007 (95% confidence interval, 389 819-432 993) to 537 801 (95% confidence interval, 506 747-568 855) in 2014. Patient demographics remained consistent, with an average age of 69 to 70 years and slight female predominance (51%-53%) throughout the study period. Hospital admission rates were stable at ≈70% between 2007 and 2010, after which they gradually declined to 62% in 2014 (Ptrend=0.017). Despite the decline in hospital admission rates, AF hospitalizations increased from 288 225 in 2007 to 333 570 in 2014 because of the increase in total annual ED visits during the study. The adjusted annual charges for admitted AF patients increased by 37% from $7.39 billion in 2007 to $10.1 billion in 2014. CONCLUSIONS: Annual ED visits and hospital admissions for AF increased significantly between 2007 and 2014, despite a reduction in admission rates. These data emphasize the need for widespread implementation of effective strategies aimed at improving the management of patients with AF to reduce hospital admissions and the economic burden of AF.

Quantitative in vivo mapping of myocardial mitochondrial membrane potential.

BACKGROUND: Mitochondrial membrane potential (ΔΨm) arises from normal function of the electron transport chain. Maintenance of ΔΨm within a narrow range is essential for mitochondrial function. Methods for in vivo measurement of ΔΨm do not exist. We use 18F-labeled tetraphenylphosphonium (18F-TPP+) to measure and map the total membrane potential, ΔΨT, as the sum of ΔΨm and cellular (ΔΨc) electrical potentials. METHODS: Eight pigs, five controls and three with a scar-like injury, were studied. Pigs were studied with a dynamic PET scanning protocol to measure 18F-TPP+ volume of distribution, VT. Fractional extracellular space (fECS) was measured in 3 pigs. We derived equations expressing ΔΨT as a function of VT and the volume-fractions of mitochondria and fECS. Seventeen segment polar maps and parametric images of ΔΨT were calculated in millivolts (mV). RESULTS: In controls, mean segmental ΔΨT = -129.4±1.4 mV (SEM). In pigs with segmental tissue injury, ΔΨT was clearly separated from control segments but variable, in the range -100 to 0 mV. The quality of ΔΨT maps was excellent, with low noise and good resolution. Measurements of ΔΨT in the left ventricle of pigs agree with previous in in-vitro measurements. CONCLUSIONS: We have analyzed the factors affecting the uptake of voltage sensing tracers and developed a minimally invasive method for mapping ΔΨT in left ventricular myocardium of pigs. ΔΨT is computed in absolute units, allowing for visual and statistical comparison of individual values with normative data. These studies demonstrate the first in vivo application of quantitative mapping of total tissue membrane potential, ΔΨT.

Seroprevalence and risk factors for peste des petits ruminants in sheep and goats in Djibouti.

Despite the occurrence of peste des petits ruminants (PPR) in all other countries in the Horn of Africa, which engage in free animal movement, to date, PPR has not been reported in Djibouti. The objective of this study was to estimate the seroprevalence of PPR and its associated risk factors in sheep and goats in that country. A cross-sectional method was used with proportional sampling to allocate the number of small ruminants to be sampled from each of the country's regions (Ali Sabieh, Arta, Dikhil, Djibouti, Obock and Tadjourah). From a total of 1,516 serum samples tested, using a competitive enzyme-linked immunosorbent assay (cELISA), 91 were positive, with an overall 6% (95% confidence interval [CI] = 4.8-7.2) prevalence of antibodies to the PPR virus (PPRV). Antibodies to PPRV were detected in small ruminants from all the regions, excluding Obock. Seroprevalence was highest in the Tadjourah region (8.92%), whereas the lowest prevalence was observed in the Djibouti region (1.28%). The species, age and sex of the animals and the herd size were identified as risk factors for PPR seropositivity. The risk of goats testing positive for PPRV antibodies was2.95 (CI = 1.39-6.35) times that of sheep. Moreover, the risk of animals younger than two years testing positive for PPRV antibodies was 2.29 (CI = 1.47-3.56) times that of animals older than two years. Similarly, it was shown that female animals were more frequently infected (odds ratio [OR] = 3.82; CI = 1.51 to 9.67) than their male counterparts. In addition, small ruminants from small herds/flocks were more likely to be seropositive (OR = 2.06; CI = 1.10-3.83) than those from medium-sized herds/flocks. The present study revealed, for the first time, the widespread occurrence of PPRV antibodies in small ruminants in Djibouti with low prevalence.

Bien que présente dans tous les autres pays de la corne d'Afrique où la libre circulation des animaux est de mise, la peste des petits ruminants (PPR) n'a jamais été notifiée à Djibouti. Les auteurs présentent les résultats d'une étude visant à estimer la prévalence sérologique de la PPR ainsi que les facteurs de risque qui lui sont associés chez les ovins et les caprins du pays. Il a été fait appel à une méthodologie transversale afin de prélever un échantillon proportionnel représentatif des effectifs de petits ruminants de chaque région du pays (Ali Sabieh,Arta, Dikhil, Djibouti, Obock et Tadjourah). Au total, 91 des 1 516 prélèvements de sérum testés au moyen d'une épreuve immuno-enzymatique de compétition (ELISAc) ont donné des résultats positifs, soit une prévalence globale d'animaux possédant des anticorps dirigés contre le virus de la peste des petits ruminants(VPPR) de 6 % (intervalle de confiance [IC] à 95% de 4,8 à 16,2). La présence d'anticorps vis-à-vis du VPPR chez des petits ruminants a été détectée dans toutes les régions à l'exclusion d'Obock. La prévalence sérologique la plus élevée a été observée à Tadjourah (8,92 %) tandis que la plus faible concernait la région de Djibouti (1,28 %). Les facteurs de risque associés à la présence d'anticorps contre la PPR étaient l'espèce, l'âge et le sexe des animaux, ainsi que la taille du troupeau. La probabilité de détection d'anticorps vis-à-vis du PPRV était 2,95 fois plus élevée chez les chèvres que chez les moutons (IC de 1,39 à 6,35). De plus, la probabilité de trouver des anticorps contre le VPPR était 2,29 fois plus élevée chez les jeunes de moins de deux ans que chez les animaux âgés de plus de deux ans (IC de 1,47 à 3,56). De même, l'infection était plus fréquente chez les femelles que chez les mâles (rapport de cotes ou odds ratio [OR] de 3,82 ;IC compris entre 1,51 et 9,67). Enfin, la probabilité d'être porteur d'anticorps était plus élevée chez les petits ruminants élevés dans des troupeaux ou cheptels de petite taille (OR de 2,06 ; IC de 1,10 à 3,83) que chez ceux appartenant à des troupeaux ou cheptels de taille moyenne. Cette étude fait état pour la première fois de la présence sur une vaste partie du territoire de Djibouti de petits ruminants porteurs d'anticorps dirigés contre le VPPR, à une prévalence relativement faible.

Aunque la peste de pequeños rumiantes (PPR) está presente en todos los demás países del Cuerno de África que participan de la libre circulación de animales, a día de hoy no se ha notificado su presencia en Djibouti. Los autores describen un estudio destinado a estimar la seroprevalencia de la enfermedad y sus factores de riesgo en los ovinos y caprinos de este último país. Para ello se utilizó un método transversal, asignando a cada una de las regiones del país (Ali Sabieh, Arta, Dikhil, Djibouti, Obock y Tadjoura) un número proporcional de muestras que extraer de la población de pequeños rumiantes. De un total de 1516 muestras de suero analizadas con un ensayo inmunoenzimático de competición (ELISAc), 91 resultaron positivas, lo que supone una prevalencia global de anticuerpos contra el virus de la PPR del 6% (intervalo de confianza [IC] al 95% = 4,8­7,2). Se detectaron anticuerpos en pequeños rumiantes de todas las regiones con la salvedad de Obock. El máximo nivel de seroprevalencia se registró en la región de Tadjoura (un 8,92%), mientras que el nivel más bajo se observó en la de Djibouti (un 1,28%). Como factores de riesgo de seropositividad se encontraron la especie, la edad y el sexo del animal, así como el tamaño del rebaño. El riesgo de seropositividad, o presencia de anticuerpos contra el virus de la PPR, era 2,95 veces mayor en los caprinos (IC = 1,39­6,35) que en los ovinos. Por otra parte, el riesgo de que los ejemplares de menos de 2 años resultaran positivos era 2,29 veces superior (IC = 1,47­3,56) al de los animales de más edad. Análogamente, quedó demostrado que las hembras resultaban infectadas con más frecuencia (razón de posibilidades [odds ratio: OR] = 3,82; IC = 1,51 a 9,67) que los machos homólogos. Además, los pequeños rumiantes de rebaños de escaso tamaño tenían mayor probabilidad de resultar seropositivos (OR = 2,06; IC = 1,10­3,83) que los de rebaños de mediano tamaño. El estudio puso de manifiesto, por primera vez, la presencia extendida, pero con escasa prevalencia, de anticuerpos contra el virus de la PPR en los pequeños rumiantes de Djibouti.

Statistical analysis of dislocations and dislocation boundaries from EBSD data.

Electron BackScatter Diffraction (EBSD) is often used for semi-quantitative analysis of dislocations in metals. In general, disorientation is used to assess Geometrically Necessary Dislocations (GNDs) densities. In the present paper, we demonstrate that the use of disorientation can lead to inaccurate results. For example, using the disorientation leads to different GND density in recrystallized grains which cannot be physically justified. The use of disorientation gradients allows accounting for measurement noise and leads to more accurate results. Misorientation gradient is then used to analyze dislocations boundaries following the same principle applied on TEM data before. In previous papers, dislocations boundaries were defined as Geometrically Necessary Boundaries (GNBs) and Incidental Dislocation Boundaries (IDBs). It has been demonstrated in the past, through transmission electron microscopy data, that the probability density distribution of the disorientation of IDBs and GNBs can be described with a linear combination of two Rayleigh functions. Such function can also describe the probability density of disorientation gradient obtained through EBSD data as reported in this paper. This opens the route for determining IDBs and GNBs probability density distribution functions separately from EBSD data, with an increased statistical relevance as compared to TEM data. The method is applied on deformed Tantalum where grains exhibit dislocation boundaries, as observed using electron channeling contrast imaging.

Catheter Ablation for Cardiac Arrhythmias: Utilization and In-Hospital Complications, 2000 to 2013.

OBJECTIVES: This study sought to investigate the utilization of and in-hospital complications in patients undergoing catheter ablation in the United States from 2000 to 2013 by using the National Inpatient Sample and Nationwide Inpatient Sample. BACKGROUND: Catheter ablation has become a mainstay in the treatment of a wide range of cardiac arrhythmias. METHODS: This study identified patients 18 years of age and older who underwent inpatient catheter ablation from 2000 to 2013 and had 1 primary diagnosis of any of the following arrhythmias: atrial fibrillation, atrial flutter, supraventricular tachycardia, or ventricular tachycardia. RESULTS: An estimated total of 519,951 (95% confidence interval: 475,702 to 564,200) inpatient ablations were performed in the United States between 2000 and 2013. The median age was 62 years (interquartile range: 51 to 72 years), and 59.3% of the patients were male. The following parameters showed increasing trends during the study period: annual volume of ablations, number of hospitals performing ablations, mean age and comorbidity index of patients, rate of ≥1 complication, and length of stay (p < 0.001 for each). Substantial proportions (27.5%) of inpatient ablation procedures were performed in low-volume hospitals and were associated with an increased risk for complications (odds ratio: 1.26; 95% confidence interval: 1.12 to 1.42; p < 0.001). Older age, greater numbers of comorbidities, and complex ablations for atrial fibrillation and ventricular tachycardia were independent predictors of in-hospital complications and in-hospital mortality. In addition, female sex and lower hospital volumes were independent predictors of complications. CONCLUSIONS: From 2000 to 2013, there was a substantial increase in the annual number of in-hospital catheter ablation procedures, as well as the rate of periprocedural complications nationwide. Low-volume centers had a significantly higher rate of complications.

Management of Periprocedural and Early Pericardial Effusions With Tamponade Following Ablation of Atrial Fibrillation With Uninterrupted Factor Xa Inhibitors: A Case Series.

INTRODUCTION: Because of the absence of a dedicated reversal agent, the outcome of pericardial effusion (PE) following procedures performed with uninterrupted apixaban or rivaroxaban is unknown. We report the characteristics of PEs presenting with tamponade in patients undergoing AF ablation with uninterrupted factor Xa inhibition (FXaI) to understand their management and prognosis. METHODS AND RESULTS: We performed a multicenter cross-sectional survey in 10 centers across the United States. Patient data were obtained by chart review. In all patients the procedure was performed with uninterrupted FXaI. A total of 16 PEs requiring intervention were reported from 5 centers. Two patients were on apixaban 5 mg BD, the remaining on rivaroxaban 20 mg OD. Eleven PEs occurred in the periprocedural setting, and 5 PEs occurred from 1 to 28 days after the procedure. Pericardiocentesis and drainage were performed in all cases. Protamine and 4-factor prothrombin complex concentrate (4F-PCC) were given in all periprocedural cases. Two patients required surgery: in one case coagulation of the pericardial blood prevented effective drainage, and in the other bleeding was secondary to a steam pop-induced atrial tear. None of the postprocedural cases required FXaI reversal and the dose of rivaroxaban was temporarily reduced. No fatal outcomes or thromboembolic events were reported. CONCLUSION: Pericardiocentesis and drainage with FXaI reversal proved effective in the management of acute PEs with tamponade occurring periprocedurally in patients undergoing AF ablation with uninterrupted FXaI. Early postprocedural effusions can be treated with pericardiocentesis without the need of a reversal agent.

Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer's disease models.

Alzheimer's disease (AD) brains exhibit plaques and tangles in association with inflammation. The non-receptor tyrosine kinase Abl is linked to neuro-inflammation in AD. Abl inhibition by nilotinib or bosutinib facilitates amyloid clearance and may decrease inflammation. Transgenic mice that express Dutch, Iowa and Swedish APP mutations (TgAPP) and display progressive Aß plaque deposition were treated with tyrosine kinase inhibitors (TKIs) to determine pre-plaque effects on systemic and CNS inflammation using milliplex® ELISA. Plaque Aß was detected at 4months in TgAPP and pre-plaque intracellular Aß accumulation (2.5months) was associated with changes of cytokines and chemokines prior to detection of glial changes. Plaque formation correlated with increased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1α, IL-1ß) and markers of immunosuppressive and adaptive immunity, including, IL-4, IL-10, IL-2, IL-3, Vascular Endothelial Growth Factor (VEGF) and IFN-γ. An inverse relationship of chemokines was observed as CCL2 and CCL5 were lower than WT mice at 2months and significantly increased after plaque appearance, while soluble CX3CL1 decreased. A change in glial profile was only robustly detected at 6months in Tg-APP mice and TKIs reduced astrocyte and dendritic cell number with no effects on microglia, suggesting alteration of brain immunity. Nilotinib decreased blood and brain cytokines and chemokines and increased CX3CL1. Bosutinib increased brain and blood IL-10 and CX3CL1, suggesting a protective role for soluble CX3CL1. Taken together these data suggest that TKIs regulate systemic and CNS immunity and may be useful treatments in early AD through dual effects on amyloid clearance and immune modulation.

Paroxysmal AF catheter ablation with a contact force sensing catheter: results of the prospective, multicenter SMART-AF trial.

BACKGROUND: Catheter ablation is important for treatment of paroxysmal atrial fibrillation (PAF). Limited animal and human studies suggest a correlation between electrode-tissue contact and radiofrequency lesion generation. OBJECTIVES: The study sought to assess the safety and effectiveness of an irrigated, contact force (CF)-sensing catheter in the treatment of drug refractory symptomatic PAF. METHODS: A prospective, multicenter, nonrandomized study was conducted. Enrollment criteria included: ≥3 symptomatic episodes of PAF within 6 months of enrollment and failure of ≥1 antiarrhythmic drug (Class I to IV). Ablation included pulmonary vein isolation with confirmed entrance block as procedural endpoint. RESULTS: A total of 172 patients were enrolled at 21 sites, where 161 patients had a study catheter inserted and 160 patients underwent radiofrequency application. Procedural-related serious adverse events occurring within 7 days of the procedure included tamponade (n = 4), pericarditis (n = 3), heart block (n = 1, prior to radiofrequency application), and vascular access complications (n = 4). By Kaplan-Meier analyses, 12-month freedom from atrial fibrillation/atrial flutter/atrial tachycardia recurrence was 72.5%. The average CF per procedure was 17.9 ± 9.4 g. When the CF employed was between investigator selected working ranges ≥80% of the time during therapy, outcomes were 4.25 times more likely to be successful (p = 0.0054; 95% confidence interval: 1.53 to 11.79). CONCLUSIONS: The SMART-AF trial demonstrated that this irrigated CF-sensing catheter is safe and effective for the treatment of drug refractory symptomatic PAF, with no unanticipated device-related adverse events. The increased percent of time within investigator-targeted CF ranges correlates with increased freedom from arrhythmia recurrence. Stable CF during radiofrequency application increases the likelihood of 12-month success. (THERMOCOOL® SMARTTOUCH® Catheter for Treatment of Symptomatic Paroxysmal Atrial Fibrillation; NCT01385202).

Incidence and predictors of atrial fibrillation and its impact on long-term survival in patients with supraventricular arrhythmias.

AIMS: To determine the incidence and predictors of atrial fibrillation (AF) and its impact on survival in patients with other forms of supraventricular arrhythmias (SVAs) including atrial flutter (AFL), atrial tachycardia (AT), atrioventricular reentrant (AVRT), and AV nodal reentrant tachycardia (AVNRT). We hypothesized that SVA may increase risk of AF and concomitant AF may influence long-term survival. METHODS AND RESULTS: All patients who underwent catheter ablation for SVA from 2000 to 2010 were included in this study. The patients were identified retrospectively and the vital status determined prospectively. Observed survival in the study cohort was compared with survival rates in the age- and sex-matched general population. The study group included 1573 patients (mean age 50.5 ± 18 years, 47% female) with AVNRT (38.5%), AFL (29.6%), AVRT (22.6%) and AT (9.3%). The patients were followed for a mean of 35 months (median 23 months). Atrial fibrillation was documented in 424 patients (27%) with a higher incidence in males (35 vs. 18%). Atrial fibrillation was present in 19.6% of patients before the ablation and developed in 9.07% after ablation. Atrial fibrillation commonly occurred in patients with AFL (57.5%), AT (27.4%), AVRT (13.5%), and AVNRT (9.7%). Older age, prolonged PR interval, dilated left atrium, low left ventricular ejection fraction and presence of AFL were independent predictors for concomitant AF. Long-term survival was worse in the presence of AF. CONCLUSION: The incidence of AF is high in patients with other forms of SVA. The most common association is between AFL and AF. Long-term survival is decreased in those who have concomitant AF, although AF did not emerge as an independent predictor of mortality when adjusted for other covariates.

New classification scheme for atrial fibrillation symptom severity and burden.

Although atrial fibrillation (AF) symptom severity is used to guide clinical care, a simple, standardized assessment tool is not available for routine clinical use. We sought to develop and validate a patient-generated score and classification scheme for AF-related symptom severity and burden. Atrial Fibrillation Symptom and Burden, a simple 2-part questionnaire, was designed to assess (1) AF symptom severity using 8 questions to determine how symptoms affect daily life and (2) AF burden using 6 questions to measure AF frequency, duration, and health-care utilization. The resulting score was used to classify patients into 4 classes of symptom and burden severity. Patients were asked to complete the questionnaire, a survey evaluating the questionnaire, and an Short Form-12v2 generic health-related quality-of-life form. Validation of the questionnaire included assessments of its reliability and construct and known groups validity. The strength of interrater agreement between patient-generated and blinded provider-generated classifications of AF symptom severity was also assessed. The survey had good internal consistency (Cronbach α>0.82) and reproducibility (intraclass correlation coefficient=0.93). There was a good linear correlation with health-related quality-of-life aggregates measured by Pearson correlation coefficient (r=0.62 and 0.42 vs physical component summary and mental component summary, respectively). Compared with physical and mental component summary scores, the patient-generated symptom severity classification scheme showed robust discrimination between mild and moderate severity (p<0.0001 and p=0.0009) and between moderate and severe groups (p=0.0001 and p=0.012). In conclusion, this simple patient-generated AF classification scheme is robust, internally consistent, reproducible, and highly correlated with standardized quality-of-life measures.

Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation (AF) ablation. BACKGROUND: Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation. The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown. METHODS: We performed a multicenter, observational, prospective study of a registry of patients undergoing AF ablation in 8 centers in North America. Patients taking uninterrupted periprocedural rivaroxaban were matched by age, sex, and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period. RESULTS: A total of 642 patients were included in the study, with 321 in each group. Mean age was 63 ± 10 years, with 442 (69%) males and 328 (51%) patients with paroxysmal AF equally distributed between the 2 groups. Patients in the warfarin group had a slightly higher mean HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score (1.70 ± 1.0 vs. 1.47 ± 0.9, respectively; p = 0.032). Bleeding and embolic complications occurred in 47 (7.3%) and 2 (0.3%) patients (both had transient ischemic attacks) respectively. There were no differences in the number of major bleeding complications (5 [1.6%] vs. 7 [1.9%], respectively; p = 0.772), minor bleeding complications (16 [5.0%] vs. 19 [5.9%], respectively; p = 0.602), or embolic complications (1 [0.3%] vs. 1 [0.3%], respectively; p = 1.0) between the rivaroxaban and warfarin groups in the first 30 days. CONCLUSIONS: Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy.

Impact of nonfluoroscopic MediGuide™ tracking system on radiation exposure in radiofrequency ablation procedures (LESS-RADS registry)-an initial experience.

BACKGROUND: Radiation exposure in the electrophysiology (EP) lab is a major concern to most electrophysiologists. A new technology, MediGuide™ nonfluoroscopic catheter tracking system, has been used for the first time in the USA recently. We intended to evaluate the efficacy of this novel catheter tracking system in reducing radiation exposure. METHODS: We performed a prospective observational study by comparing the radiation exposure with MediGuide™ system to that of conventional mapping systems. The first 45 EP procedures performed with the MediGuide™ system were compared to 45 matched patients undergoing similar procedures during the same time frame using conventional mapping systems (CARTO and NavX) and fluoroscopy. We collected and compared baseline characteristics, procedural variables including fluoroscopic exposure between both groups. RESULTS: Forty-five patients underwent EP procedures using the MediGuide™ technology. They were matched with an equal number of patients with conventional mapping systems. Of the 45 patients included in the study, 33 underwent right atrial flutter ablations, 5 underwent atrioventricular nodal reentrant tachycardia ablations, 4 underwent ablation of Wolf-Parkinson-White syndrome, and 3 underwent EP studies with no ablation. There were no differences in mean age, gender distribution, and body mass index between the groups. Procedure duration in the MediGuide™ group was significantly lower than the duration in the conventional group (103 vs. 142 min, p = 0.03). The fluoroscopic time was significantly less during the procedures performed with the MediGuide™ technology when compared to the control group (8 vs. 21 min, p < 0.001). No major complications occurred during the procedures in either group. CONCLUSION: MediGuide™, a new nonfluoroscopic catheter tracking system, is associated with more than a 50 % reduction in fluoroscopic time when compared to conventional mapping systems.

Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease.

Parkinson's disease (PD) is a motor disorder that involves death of dopaminergic neurons in the substantia nigra pars compacta. Parkin is an autosomal recessive gene that is mutated in early onset PD. We investigated the role of parkin and autophagic clearance in postmortem nigrostriatal tissues from 22 non-familial sporadic PD patients and 15 control samples. Parkin was insoluble with altered cytosolic expression in the nigrostriatum of sporadic PD. Parkin insolubility was associated with lack of degradation of ubiquitinated proteins and accumulation of α-Synuclein and parkin in autophagosomes, suggesting autophagic defects in PD. To test parkin's role in mediating autophagic clearance, we used lentiviral gene transfer to express human wild type or mutant parkin (T240R) with α-Synuclein in the rat striatum. Lentiviral expression of α-Synuclein led to accumulation of autophagic vacuoles, while co-expression of parkin with α-Synuclein facilitated autophagic clearance. Subcellular fractionation showed accumulation of α-Synuclein and tau hyper-phosphorylation (p-Tau) in autophagosomes in gene transfer models, similar to the effects observed in PD brains, but parkin expression led to protein deposition into lysosomes. However, parkin loss of function mutation did not affect autophagic clearance. Taken together, these data suggest that functional parkin regulates autophagosome clearance, while decreased parkin solubility may alter normal autophagy in sporadic PD.

Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation (AF) ablation. BACKGROUND: AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications. The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown. METHODS: We performed a multicenter, observational study from a prospective registry including all consecutive patients undergoing AF ablation in 8 high-volume centers in the United States. All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran, with the dose held on the morning of the procedure, were matched by age, sex, and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period. RESULTS: A total of 290 patients, including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin, were included in the study. The mean age was 60 years with 79% being male and 57% having paroxysmal AF. Both groups had a similar CHADS(2) score, left atrial size, and left ventricular ejection fraction. Three thromboembolic complications (2.1%) occurred in the dabigatran group compared with none in the warfarin group (p = 0.25). The dabigatran group had a significantly higher major bleeding rate (6% vs. 1%; p = 0.019), total bleeding rate (14% vs. 6%; p = 0.031), and composite of bleeding and thromboembolic complications (16% vs. 6%; p = 0.009) compared with the warfarin group. Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications (odds ratio: 2.76, 95% confidence interval: 1.22 to 6.25; p = 0.01) on multivariate regression analysis. CONCLUSIONS: In patients undergoing AF ablation, periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy.

Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines.

Synapse loss induced by amyloid beta (Abeta) is thought to be a primary contributor to cognitive decline in Alzheimer's disease. Abeta is generated by proteolysis of amyloid precursor protein (APP), a synaptic receptor whose physiological function remains unclear. In the present study, we investigated the role of APP in dendritic spine formation, which is known to be important for learning and memory. We found that overexpression of APP increased spine number, whereas knockdown of APP reduced spine density in cultured hippocampal neurons. This spine-promoting effect of APP required both the extracellular and intracellular domains of APP, and was accompanied by specific upregulation of the GluR2, but not the GluR1, subunit of AMPA receptors. In an in vivo experiment, we found that cortical layers II/III and hippocampal CA1 pyramidal neurons in 1 year-old APP-deficient mice had fewer and shorter dendritic spines than wild-type littermates. In contrast, transgenic mice overexpressing mutant APP exhibited increased spine density compared to control animals, though only at a young age prior to overaccumulation of soluble amyloid. Additionally, increased glutamate synthesis was observed in young APP transgenic brains, whereas glutamate levels were decreased and GABA levels were increased in APP-deficient mice. These results demonstrate that APP is important for promoting spine formation and is required for proper spine development.