Assessing the impact of atrial fibrillation on symptoms and quality of life in hypertrophic cardiomyopathy.

Introduction: In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) has historically been regarded to have a deleterious impact on clinical course, strongly associated with progressive heart failure (HF) symptoms. However, there is a paucity of information regarding the impact of AF on HCM employing validated quality of life (QoL) surveys. Therefore, we evaluated the impact of AF on QoL utilizing patient reported outcome measures (PROMs).

Hybrid Convergent Procedure for the Treatment of Persistent and Long-Standing Persistent Atrial Fibrillation: Results of CONVERGE Clinical Trial.

Background: The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment.

Methods: One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA.

Appropriate Implantable Cardioverter-Defibrillator Therapies Delivered 5 Years After End of Service.

We present the case of a 57-year-old man with a primary prevention internal cardioverter-defibrillator for severe nonischemic cardiomyopathy. At the time of elective replacement indicator, systolic function had fully recovered, and his generator was not changed. Nearly 5 years post-elective replacement indicator he received appropriate internal cardioverter-defibrillator therapies during a myocardial infarction.

Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage. Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking.

Methods: Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years.

T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow.

Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP cells.

Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs.

Innate lymphoid cells (ILCs) are critical mediators of mucosal immunity, and group 1 ILCs (ILC1 cells) and group 3 ILCs (ILC3 cells) have been shown to be functionally plastic. Here we found that group 2 ILCs (ILC2 cells) also exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ (IFN-γ). Interleukin 12 (IL-12) and IL-18 regulated this conversion, and during viral infection, ILC2 cells clustered within inflamed areas and acquired an ILC1-like phenotype.

IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity.

Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rβ2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12.

Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection.

Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss.

Adverse structural remodeling of the left ventricle and ventricular arrhythmias in patients with depressed ejection fraction.

Background: The relationship of life-threatening ventricular arrhythmias to specific patterns of adverse LV remodeling has not been reported. We examined the relationship of ventricular tachycardia and/or fibrillation (VT/VF) to the pattern of left ventricular (LV) structural remodeling and to the degree of LV dysfunction in patients with a low ejection fraction (EF).

Methods And Results: Data from 127 patients with a low EF (≤0.

A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure.

IL-21 is required for optimal antibody production and T cell responses during chronic Toxoplasma gondii infection.

Previous studies have indicated that Il21r (-/-) mice chronically infected with Toxoplasma gondii display a defect in serum IgG; however, the basis for this antibody defect was not defined and questions remain about the role of IL-21 in promoting the production of IL-10, which is required to limit infection-induced pathology during toxoplasmosis. Therefore, Il21 (-/-) mice were challenged with T. gondii to determine whether IL-21 impacts the parasite-specific CD8(+) T cell response, its contribution to thymus-dependent antibody production after infection, and balance between protective and pathogenic responses.

The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology.

Interferon-γ (IFN-γ) promotes a population of T-bet(+) CXCR3(+) regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology. Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T-bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar population emerged that limited T cell responses and was dependent on IFN-γ in the periphery but on IL-27 at mucosal sites.

Infection with Toxoplasma gondii alters lymphotoxin expression associated with changes in splenic architecture.

B cell responses are required for resistance to Toxoplasma gondii; however, the events that lead to production of class-switched antibodies during T. gondii infection have not been defined. Indeed, mice challenged with the parasite exhibited an expansion of T follicular helper cells and germinal center B cells in the spleen.

The immunobiology of IL-27.

Like many cytokines, IL-27 has pleiotropic properties that can limit or enhance ongoing immune responses depending on context. Thus, under certain circumstances, IL-27 can promote TH1 differentiation and has been linked to the activation of CD8(+) T cells and enhanced humoral responses. However, IL-27 also has potent inhibitory properties and mice that lack IL-27 mediated signaling develop exaggerated inflammatory responses in the context of infection or autoimmunity.

Cutting edge: dendritic cell-restricted antigen presentation initiates the follicular helper T cell program but cannot complete ultimate effector differentiation.

Follicular helper T (T(FH)) cells are critical for germinal center (GC) formation. The processes that drive their generation and effector potential remain unclear. In this study, we define requirements for MHC class II APCs in murine T(FH) cell formation by either transiently ablating or restricting Ag presentation to dendritic cells (DCs).

IL-6 mediates the susceptibility of glycoprotein 130 hypermorphs to Toxoplasma gondii.

IL-6 and IL-27 are closely related cytokines that play critical but distinct roles during infection with Toxoplasma gondii. Thus, IL-6 is required for the development of protective immunity to this pathogen, whereas IL-27 is required to limit infection-induced pathology. Paradoxically, these factors both signal through gp130, but little is known about how the signals downstream of gp130 are integrated to coordinate the immune response to infection.

IL-6 promotes NK cell production of IL-17 during toxoplasmosis.

Previous studies have implicated T cell production of IL-17 in resistance to Toxoplasma gondii as well as the development of immune-mediated pathology during this infection. Analysis of C57BL/6 and C57BL/6 RAG(-/-) mice challenged with T. gondii-identified NK cells as a major innate source of IL-17.

Strategy to eliminate inappropriate shocks secondary to T-wave oversensing in a biventricular ICD.

T-wave oversensing represents a common cause of inappropriate shocks in patients with implanted cardiac defibrillators. This case report demonstrates a strategy of device programming using V-V pace delay (sequential rather than simultaneous biventricular pacing) to eliminate T-wave oversensing without decreasing sensitivity to detect true tachyarrhythmia.

Maintenance of tolerance by regulation of anti-myeloperoxidase B cells.

Anti-neutrophil cytoplasmic autoantibodies directed toward myeloperoxidase or proteinase 3 are detected in sera of patients with small vessel vasculitis and participate in the pathogenesis of this disease. Autoantibodies develop when self-reactive B cells escape the regulation that ensures self-tolerance. In this study, regulation of anti-myeloperoxidase B cells was examined in mice that express an anti-myeloperoxidase Vkappa1C-Jkappa5 light-chain transgene, which confers anti-myeloperoxidase specificity when combined with a variety of heavy chains.

With a little help from their friends: interleukin-21, T cells, and B cells.

T follicular cells help B cells generate high-affinity antibodies. Two papers in this issue of Immunity (Nurieva et al., 2008, and Vogelzang et al.