Direct Comparison of Adjacent Endocardial and Epicardial Electrograms: Implications for Substrate Mapping

Background: Analysis of unipolar voltage maps has been used to detect epicardial scar, but data to define optimal parameters to identify scar remote from the recording site is limited. This study compares the characteristics of electrograms at endocardial sites adjacent to abnormal epicardial sites. Methods and Results: Data obtained from endocardial and epicardial electroanatomical maps of 31 patients with scar‐related ventricular tachycardia were reviewed. Five hundred twenty‐three pairs of endo‐ and epicardial points were selected according to predefined criteria. The endocardial points adjacent to epicardial scar (bipolar voltage <1.5 mV) had smaller unipolar voltage than those distant from epicardial scar (P<0.001). In multivariable analysis, unipolar voltage was the only endocardial electrogram predictor of epicardial scar (P<0.001, OR 0.94, 95% CI 0.93 to 0.97). An endocardial unipolar amplitude <4.4 mV in the right ventricular (RV) (sensitivity 93%, specificity 76%) and <5.1 mV in the left ventricular (LV) (sensitivity 91%, specificity 75%) was the optimal cutoff predicting epicardial scar. Applying these thresholds to electroanatomical maps, revealed a good match between endocardial unipolar abnormality and epicardial scar for 67% of LV and 75% of RV maps, respectively, but notably poor matches occurred in 8 (29%) maps (7 with nonischemic cardiomyopathy). Site‐by‐site correlations were better for ischemic than nonischemic cardiomyopathy. Conclusions: This study supports the contention that unipolar electrograms are capable of indicating overlying epicardial scar during endocardial mapping, but illustrates limitations that appear to differ with nonischemic as compared to ischemic cardiomyopathy. The presence of epicardial arrhythmia substrate cannot be excluded by analysis of unipolar endocardial maps in some patients

Element redistribution along hydraulic and redox gradients of low-centered polygons, Lena Delta, northern Siberia

Wetland soils affected by permafrost are extensive in subarctic and arctic tundra. However, this fact does not imply these soils have been sufficiently investigated. In particular, studies of element translocation processes are scarce. This study was conducted (i) to determine the relationship between water and redox regimes in wetland soils in the Siberian tundra, and (ii) to investigate their influence on the distribution of redox sensitive and associate elements (Mn, Fe, P). Major geomorphic units were chosen (microhigh, polygon rim and slope; microlow, polygon center) from two low-centered polygons in the Lena Delta. Within polygons, redox potential, permafrost, and water level were measured during summer in 1999 and 2000 and (related) compared with element distribution. Manganese, Fe, and P accumulations were preferentially observed in aerobic microhighs. Anaerobic conditions in the microlows lead to a mobilization of Mn, Fe, and P. The elements migrate via water and are immobilized at the microhigh, which acts as an oxidative barrier. The element pattern, indicating an upward flux via water along redox gradients, is explained by higher evapotranspiration from soils and vegetation of the microhighs (Typic Aquiturbel) compared with soils and vegetation of the microlows (Typic Historthel). However, in further research this upward transport should be validated using labeled elements

2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias: Executive summary

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias

Suppression of NLRX1 in chronic obstructive pulmonary disease

Cigarette smoke (CS) and viruses promote the inflammation and remodeling associated with chronic obstructive pulmonary disease (COPD). The MAVS/RIG-I–like helicase (MAVS/RLH) pathway and inflammasome-dependent innate immune pathways are important mediators of these responses. At baseline, the MAVS/RLH pathway is suppressed, and this inhibition must be reversed to engender tissue effects; however, the mechanisms that mediate activation and repression of the pathway have not been defined. In addition, the regulation and contribution of MAVS/RLH signaling in CS-induced inflammation and remodeling responses and in the development of human COPD remain unaddressed. Here, we demonstrate that expression of NLRX1, which inhibits the MAVS/RLH pathway and regulates other innate immune responses, was markedly decreased in 3 independent cohorts of COPD patients. NLRX1 suppression correlated directly with disease severity and inversely with pulmonary function, quality of life, and prognosis. In murine models, CS inhibited NLRX1, and CS-induced inflammation, alveolar destruction, protease induction, structural cell apoptosis, and inflammasome activation were augmented in NLRX1-deficient animals. Conversely, MAVS deficiency abrogated this CS-induced inflammation and remodeling. Restoration of NLRX1 in CS-exposed animals ameliorated alveolar destruction. These data support a model in which CS-dependent NLRX1 inhibition facilitates MAVS/RHL activation and subsequent inflammation, remodeling, protease, cell death, and inflammasome responses

miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1

As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases. © 2013 Lino Cardenas et al

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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