Transseptal Puncture Guided by Three-Dimensional Electroanatomical Mapping: Early Experience Using a Simplified Approach in Adults with Congenital Heart Disease

Aims: The widespread use of three-dimensional (3D) mapping systems and echocardiography in the field of cardiac electrophysiology has made it possible to perform transseptal punctures (TSP) with low or no fluoroscopy. However, such attempts in adults with congenital heart disease (ACHD) who have previously undergone surgical or interventional treatment are limited. Therefore, we sought to explore the feasibility and safety of an approach to perform zero- or low-fluoroscopy TSP in ACHD patients undergoing left atrial cardiac ablation procedures. Methods and results: This study included 45 ACHD patients who underwent TSP for ablation of left-sided tachycardias (left atrium or pulmonary venous atrium). Computed tomography (CT) of the heart was performed in all patients prior to ablation. 3D mapping of the right-sided heart chambers before TSP was used to superimpose the registered anatomy, which was subsequently used for the mapping-guided TSP technique. TSP was performed with zero-fluoroscopy in 27 patients, and the remaining 18 patients had a mean fluoroscopy exposure of 315.88 ± 598.43 μGy.m2 and a mean fluoroscopy duration of 1.9 ± 5.4 min. No patient in this cohort experienced TSP-related complications. Conclusion: Our study describes a fluoroscopy-free or low-dose fluoroscopy approach for TSP in ACHD patients undergoing catheter ablation of left-sided tachyarrhythmias who had been previously treated surgically or interventionally due to congenital heart defects. By superimposing 3D electroanatomic mapping with cardiac CT anatomy, this protocol proved to be highly effective, feasible and safe

Update in the Mechanisms of Allergen-Specific Immunotheraphy

Allergic diseases represent a complex innate and adoptive immune response to natural environmental allergens with Th2-type T cells and allergen-specific IgE predominance. Allergen-specific immunotherapy is the most effective therapeutic approach for disregulated immune response towards allergens by enhancing immune tolerance mechanisms. The main aim of immunotherapy is the generation of allergen nonresponsive or tolerant T cells in sensitized patients and downregulation of predominant T cell- and IgE-mediated immune responses. During allergen-specific immunotherapy, T regulatory cells are generated, which secrete IL-10 and induce allergen-specific B cells for the production of IgG4 antibodies. These mechanisms induce tolerance to antigens that reduces allergic symptoms. Although current knowledge highlights the role of T regulatory cell-mediated immunetolerance, definite mechanisms that lead to a successful clinical outcomes of allergen-specific immunotherapy still remains an open area of research

Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy

Changes in Exercise Capacity and Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: The Impact of Sports Restriction during Follow-Up

(1) Background: Physical exercise has been suggested to promote disease progression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the exercise performance and ventricular function of ARVC patients during follow-up, while taking into account their adherence to exercise restriction recommendations. (2) Methods: This retrospective study included 49 patients (33 male, 67%) who had an exercise test at baseline and after 4.2 ± 1.6 years. Of the 49 ARVC patients, 27 (55%) were athletes, while 22 (45%) were non-athletes. Of the athletes, 12 (44%) continued intensive sports activity (non-adherent), while 15 (56%) stopped intensive physical activity upon recommendation (adherent). The maximum workload in Watts (W), percentage of the target workload (W%), and double product (DP) factor were measured for all patients. (3) Results: The non-adherent cohort had a significant decrease in physical performance (W at baseline vs. follow-up, p = 0.012; W% at baseline vs. follow-up, p = 0.025; DP-factor at baseline vs. follow-up, p = 0.012) over time. Left ventricular (LV) function (LV ejection fraction at baseline vs. follow-up, p = 0.082) showed a decreasing trend in the non-adherent cohort, while the performance of the adherent cohort remained at a similar level. (4) Conclusions: If intensive sports activities are not discontinued, exercise capacity and left ventricular function of athletes with ARVC deteriorates during follow-up. All patients with ARVC need to strictly adhere to the recommendation to cease intense sports activity in order to halt disease progression

Electroanatomical voltage mapping with contact force sensing for diagnosis of arrhythmogenic right ventricular cardiomyopathy

Background Three-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Yet, previous studies utilizing EAM have not systematically used contact-force sensing catheters (CFSC) to characterize the substrate in ARVC, which is the current gold standard to assure adequate tissue contact. Objective To investigate reference values for endocardial right ventricular (RV) EAM as well as substrate characterization in patients with ARVC by using CFSC. Methods Endocardial RV EAM during sinus rhythm was performed with CFSC in 12 patients with definite ARVC and 5 matched controls without structural heart disease. A subanalysis for the RV outflow tract (RVOT), septum, free-wall, subtricuspid region, and apex was performed. Endocardial bipolar and unipolar voltage amplitudes (BVA, UVA), signal characteristics and duration as well as the impact of catheter orientation on endocardial signals were also investigated. Results ARVC patients showed lower BVA vs. controls (p = 0.018), particularly in the subtricuspid region (1.4, IQR:0.5–3.1 vs. 3.8, IQR:2.5-5 mV, p = 0.037) and RV apex (2.5, IQR:1.5–4 vs. 4.3,IQR:2.9–6.1 mV, p = 0.019). BVA in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC 59–78%, p < 0.05 for all), with the highest performance for the subtricuspid region (AUC 78%, 95% CI:0.75–0.81, p < 0.001, negative predictive value 100%). A positive correlation between BVA and an orthogonal catheter orientation (46°-90°:r = 0.106, p < 0.001), and a negative correlation between BVA and EGM duration (r = −0.370, p < 0.001) was found. Conclusions EAM using CFSC validates previous bipolar cut-off values for normal endocardial RV voltage amplitudes. RV voltages are generally lower in ARVC as compared to controls, with the subtricuspid area being commonly affected and having the highest discriminatory power to differentiate between ARVC and healthy controls. Therefore, EAM using CFSC constitutes a promising tool for diagnosis of ARVC

Cytokine pattern and IgE regulation of human natural killer cells in atopic dermatitis, evidence for NK1 and NK2 subsets

A dysregulated, cytokine mediated response of the immune system appears to be an important pathogenic factor in allergy, however, the role of natural killer (NK) cells remained unclear so far. In the present study, peripheral blood NK cells were isolated from atopic dermatitis (AD) patients and their growth requirements, cytokine pattern and IgE regulation were determined and compared with healthy controls. IL-2 and IL-15 induced efficient proliferation, but IL-4 inhibited the growth of NK cells both in AD patients and healthy individuals. Direct fixation and permeabilization of NK cells immediately after purification demonstrated that they contain and spontaneously release low amounts of IL-4 and IFN-gamma and high amounts of IL-10 and IL-16. IL-12 or IL-15 primed NK cells, in the presence of IL-2 lead to increased IFN-gamma, but decreased IL-4 production. IL-4 primed NK cells in the presence of IL-2 showed decreased IFN-gamma production, but enhanced IL-13 production. The functional immunoglobulin isotype regulatory capacity of peripheral NK cells from AD patients was investigated by co-culturing isolated NK cells subpopulations with purified B cells. NK cells. Inhibited IgE production by B cells and this was more prominent when NK cells were primed with IL-12. These results demonstrate that NK cells can differentiate into effector subsets with NK1 and NK2 phenotypes, and NK1 cells might display an anti-allergic property by inhibition of IgE production

NK cell subsets and their role in allergy

INTRODUCTION: NK cells represent a distinct lymphocyte population with extensive cytolytic activity and a variety of other functions, including regulation of hemopoiesis, suppressor functions and immunoglobulin production. Recently, reports suggest that NK cells also display potent regulatory functions via secretion of cytokines or cell-contact-dependent mechanisms. Thus NK cells may regulate innate and adaptive immune responses and play a role in immune homeostasis. AREAS COVERED: NK cells play important roles in viral infections, autoimmunity, pregnancy, cancer and bone marrow transplantation. Although the role of NK cells in allergic diseases is poorly described, recent findings suggest their role in allergy. EXPERT OPINION: Recent developments in the study of NK cell subsets have support their role in allergic diseases that contribute to allergen-specific immune suppression, allergen-specific T(H)1 cell generation as well as IgE and other Ig production

Arrhythmogene rechtsventrikuläre Kardiomyopathie / Dysplasie: Pathogenese, Diagnose und Therapie

Zusammenfassung. Die arrhythmogene rechtsventrikuläre Kardiomyopathie / Dysplasie beschreibt eine genetische Erkrankung welche zu einer Umwandlung des Herzmuskels in Fett-und Bindegewebe, typischerweise im rechten Ventrikel führt. Biventrikuläre und linksventrikuläre Subtypen stellen zudem klinische Manifestationen dar. Mutationen in desmosomalen und nicht-desmosomalen Proteinen führen zu elektrischer und mechanischer Instabilität welche sich klinisch als initial als Rhythmusstörungen zeigen. Da die Erkrankung insbesondere junge Sportler betrifft, sind die Frühdiagnose und die adäquate Therapie von grosser Bedeutung, da die Erkrankung auch zum plötzlichen Herztod führen kann. </jats:p