Prognostic markers of all-cause mortality in patients with atrial fibrillation: data from the prospective long-term registry of the German Atrial Fibrillation NETwork (AFNET).

Aims: Atrial fibrillation (AF) is associated with a high risk of cardiovascular and non-cardiovascular death, even on anticoagulation. It is controversial, which conditions-including concomitant diseases and AF itself-contribute to this mortality. To further clarify these questions, major determinants of long-term mortality and their contribution to death were quantified in an unselected cohort of AF patients.

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy.

Use of vitamin K antagonists for secondary stroke prevention depends on the treating healthcare provider in Germany - results from the German AFNET registry.

Background: Anticoagulation using vitamin K antagonists (VKAs) significantly reduces the risk of recurrent stroke in stroke patients with atrial fibrillation (AF) and is recommended by guidelines.

Methods: The German Competence NETwork on Atrial Fibrillation established a nationwide prospective registry including 9,574 AF patients, providing the opportunity to analyse AF management according to German healthcare providers.

Results: On enrolment, 896 (9.

Morbidity and treatment in patients with atrial fibrillation and chronic kidney disease.

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality but there are few studies available about atrial fibrillation, the most frequent arrhythmia in CKD, and the applied treatment. Based on the prospective German Competence NETwork on Atrial Fibrillation, data of 3138 patients with atrial fibrillation were analyzed and categorized by their estimated glomerular filtration rate (stages 1-3 and 4 plus 5). With advanced CKD, significantly more patients suffered from a more severe form of atrial fibrillation.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging.

The Registry of the German Competence NETwork on Atrial Fibrillation: patient characteristics and initial management.

Aims: The aim of this study was to describe the characteristics of patients with atrial fibrillation (AF) enrolled in the Central Registry of the German Competence NETwork on Atrial Fibrillation (AFNET) and to assess current medical practice in patients treated at various levels of medical care in Germany.

Methods And Results: From February 2004 to March 2006, 9582 ambulatory and hospitalized patients with ECG-documented AF were enrolled by 194 participating study centres from all levels of medical care in Germany. Clinical type of AF was reported as paroxysmal in 2893, persistent in 1873, and permanent in 3134 patients or classified as a first episode in 1035 patients.

Regulation of IFN-gamma production by B effector 1 cells: essential roles for T-bet and the IFN-gamma receptor.

This manuscript systematically identifies the molecular mechanisms that regulate the ability of B cells to produce the critical type 1 cytokine, IFN-gamma. B cells produce IFN-gamma in response to IL-12 and IL-18 and when primed by Th1 cells. We show that development of IFN-gamma-producing B cells by either Th1 cells or IL-12/IL-18 is absolutely dependent on expression of the IFN-gammaR and the T-box transcription factor, T-bet.

SH2D1A regulates T-dependent humoral autoimmunity.

The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a family of chromosome 1-encoded cell surface molecules with costimulatory functions mediated in part by the adaptor protein SH2D1A (SLAM-associated protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of lupus, including the development of hypergammaglobulinemia, autoantibodies including anti-double stranded DNA, and renal disease. This protection did not reflect grossly defective T or B cell function per se because SH2D1A-deficient mice were susceptible to experimental autoimmune encephalomyelitis, a T cell-dependent disease, and they were capable of mounting normal T-independent antigen-specific immunoglobulin responses.

Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.

B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production.

CpG DNA redirects class-switching towards "Th1-like" Ig isotype production via TLR9 and MyD88.

Unmethylated CpG-containing DNA plays a critical role in immunity via the augmentation of Th1 but suppression of Th2 T cell responses. We describe here that CpG motifs also redirect isotype production by murine B cells to "Th1-like" Ig isotypes (IgG2a, IgG2b, and IgG3) while suppressing Th2 isotypes (IgG1 and IgE). Using genetically mutant B cells, we find that the IgG2a, IgG2b and IgG3 isotypes are transcriptionally regulated via the promotion of class-switching, in a manner critically dependent upon TLR9 and MyD88.

An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.

Background & Aims: Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease.

Susceptibility of mast cell-deficient W/Wv mice to pristane-induced experimental lupus nephritis.

In many models of organ-specific autoimmune diseases, mast cells provide a critical cellular link between autoantibodies and end-organ inflammation, both initiating and propagating disease. However, their role in systemic autoimmunity remains speculative. We therefore examined the role of mast cells in a murine model of systemic immune complex-related autoimmune disease, lupus nephritis, expecting to observe the development of humoral autoimmunity in the absence of end-organ disease.

Modulation of Th1 activation and inflammation by the NF-kappaB repressor Foxj1.

Forkhead transcription factors play key roles in the regulation of immune responses. Here, we identify a role for one member of this family, Foxj1, in the regulation of T cell activation and autoreactivity. Foxj1 deficiency resulted in multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell proliferation in autologous mixed lymphocyte reactions.

T-bet regulates T-independent IgG2a class switching.

The IgG2a Ig subclass plays a critical role in the pathogenesis of humoral autoimmunity and protection against pathogens. The T-box transcription factor T-bet has been implicated as a critical mediator of class-switch recombination (CSR) to IgG2a, but its relative importance to this process in various immune contexts remains incompletely defined. We report here that, surprisingly, T-bet is selectively required for IgG2a class switching in response to T-independent, but not T-dependent, stimuli.

Transvenous defibrillation leads: high incidence of failure during long-term follow-up.

Introduction: Patients with implantable cardioverter defibrillators (ICD) critically depend on correct functioning of their system. The aim of this study was to determine the incidence and clinical presentation of transvenous ICD lead failures during long-term follow-up.

Methods And Results: The study group consisted of 261 consecutive patients who received Medtronic right ventricular polyurethane transvenous leads (models 6884, 6966, 6936) between 1990 and 1998 as part of an abdominal (n = 70) or pectoral (n = 191) ICD system.

Pulmonary vein bigeminy: electrophysiological characteristics and results of catheter ablation.

Unlabelled: Pulmonary vein bigeminy is the pair of a second, late and ectopic pulmonary vein potential following atrial far-field activation and a first passive pulmonary vein potential during sinus rhythm. The aim of this study was to determine the electrophysiological characteristics of pulmonary vein bigeminy and to evaluate its relevance as a trigger for paroxysmal atrial fibrillation.

Methods And Results: Pulmonary vein bigeminy was recorded in 8 of 45 patients (18%) who underwent mapping of pulmonary veins for ablation of focal atrial fibrillation.

Further analysis of the T-cell subsets and pathways of murine cardiac allograft rejection.

The present study examined the role of CD4+ and CD8+ T cells in cardiac allograft rejection when either the direct or indirect pathway was eliminated for the CD4+ portion of the response. To study the pathways in vivo, we used genetically altered mouse strains that lack class II antigens as either the donors or recipients for cardiac transplantation. In contrast to earlier published studies, which used different strain combinations, we found that either CD4- or CD8-depletion prolonged cardiac allograft survival moderately, but not indefinitely, in an MHC-mismatched, minor-matched combination.