Transvenous Closure of Patent Foramen Ovale: Preliminary Results with a New Self-Expanding Nitinol Wire Mesh in a Swine Model

Objectives. The transvascular closure of patent foramen ovale (PFO) with self-expanding devices carries the risk of left atrial thrombus formation related to material protruding into the left atrium. Thus, we developed a novel device with flat left atrial disc geometry. We evaluated feasibility, handling, and biocompatibility in a porcine animal model. Methods. Implantation of an Occlutech Figulla PFO device was performed in 10 mini pigs using fluoroscopy and intra-cardiac ultrasound after transseptal puncture of the interatrial septum. Angiographic follow-up was performed after six and twelve weeks. Results. Implantation was successful in 100%. There were no further implant related complications. One procedure related death occurred, as one animal died of ventricular tachycardia due to mispunture of the interatrial septum. Angiographic studies showed no residual shunt during follow-up. Histopathological evaluation could demonstrate partial neoendothelialization after 6 weeks with completion after 12 weeks. The devices were incorporated into connective tissue containing fibro muscular cells. An only mild inflammatory reaction was detected locally related to the polyester fibers. Conclusion. In terms of feasibility and handling, the new device does not seem to be inferior to other presently used implantation systems. Good biocompatibility was demonstrated with rapid and complete neoendothelialization

eine systematische Übersicht der aktuellen Literatur

Objectives: Transcatheter aortic valve implantation (TAVI) promises effective treatment for high-risk elderly patients with symptomatic severe aortic stenosis (AS). However, the adop-tion of TAVI must be justified and guarantee long-term performance. Systematic reviews are a core methodology in evidence-based health economics for judging medical effectiveness. In this work, the methodology was applied to provide objective evidence on the efficacy and safety of TAVI at 1-year follow-up and to assess whether TAVI confers a survival benefit compared to medical therapy. Methods: In accordance with the toolkit of the “German Scientific Working Group Technol-ogy Assessment for Health Care” (GSWG), two independent systematic literature reviews on the safety and efficacy of TAVI procedures and medical therapy of AS were conducted in major bibliographic databases. Preestablished inclusion criteria were defined that were consis-tent for both reviews. For each review, an initial screening of identified articles regarding ti-tles and abstracts was followed by a full-text screening. Data from eligible articles was ex-tracted and evaluated according to GSWG checklists followed by a qualitative synthesis of information. Results: The systematic literature search identified 12 primary publications (derived from 1,849 citations) for TAVI (number of patients [n]=1,049) and 11 publications (derived from 189 citations) for medical therapy of AS (n=946) that fulfilled the inclusion criteria. The mean overall procedural success rate for included TAVI interventions was 93.3%. The mean combined procedural, post-procedural, and cumulative in-hospital/30-day mortality was 11.4% (n=116; range 5.3%–23%). For transvascular (TV) TAVI procedures, the mean inhospital/30-day mortality was significantly lower than for transapical (TA) TAVI procedures (9.5% versus 14%) (p-value=0.03). Major vascular complications occurred on average in 3.1% of all patients included in this review, particularly when the TV access route was chosen the incidence was up to 33.3%. Mean incidence of stroke was 4.4%. One year after TAVI, the mean overall survival rate was 75.9% (range 64.1%–87%) compared with 62.4% (range 40%–84.8%) for medically treated patients (p-value Conclusion: Based on the best available data, in patients with symptomatic severe AS, TAVI demonstrates an improved 1-year survival compared with medical treatment. The survival benefit of TV-TAVI over medical therapy elucidated from this systematic literature review is +16.8% and therefore, in good congruence with the recently published results from the ran-domized PARTNER U.S. trial (+20%).Ziele: Kathetergeführte Aortenklappenimplantationen (TAVI) versprechen eine effektive Behandlung von älteren Hochrisikopatienten mit symptomatischer schwerer Aortenstenose (AS). Allerdings muss die Einführung von TAVI gut begründet sein und langfristigen Erfolg garantieren. Systematische Reviews sind ein anerkannte Methodik in der evidenzbasierten Gesundheitsökonomie für die Beurteilung medizinischer Wirksamkeit. In dieser Arbeit wurde diese Methodik angewendet, um die Wirksamkeit und Unbedenklichkeit von TAVI bis zum 1-Jahres-Follow-up objektiv zu belegen und den Überlebensvorteil von TAVI im Vergleich zur medikamentösen Therapie zu beurteilen. Methoden: In Übereinstimmung mit dem Toolkit der "German Scientific Working Group Technology Assessment for Health Care" (GSWG), wurden zwei unabhängige systematische Übersichtsarbeiten über die Unbedenklichkeit und Wirksamkeit von TAVI und medikamentöser Therapie in großen bibliographischen Datenbanken durchgeführt . A priori Einschlusskriterien wurden konsistent für beide Beurteilungen definiert. Es erfolgte ein erstes Screening der identifizierten Artikel anhand der Überschriften und Abstracts gefolgt von einem Volltext-Screeing. Daten aus relevanten Publikationen wurde extrahiert, gemäß GSWG Checklisten evaluiert. Dann erfolgte eine qualitative Synthese der Informationen. Ergebnisse: Durch die systematische Literaturrecherche wurden 12 Primärpublikationen (abgeleitet aus 1.849 Zitationen) für TAVI (Anzahl der Patienten [n] = 1.049) und 11 Primärpublikationen (abgeleitet aus 189 Zitaten) für die medizinische Therapie von AS (n = 946) identifiziert, die alle Einschlusskriterien erfüllten. Die mittlere prozedurale Erfolgsrate für TAVI Interventionen betrug 93,3%. Die mittlere kombinierte prozedurale, post-prozedurale und kumulative Krankenhaus/30-Tages- Letalität betrug 11,4% (n = 116; range 5,3% -23%). Für transvaskuläre (TV) TAVI Verfahren war die durchschnittliche Krankenhaus/30-Tages- Letalität signifikant niedriger als für transapikale (TA) TAVI Verfahren (9,5% versus 14%) (p-Wert = 0,03). Schwerwiegende vaskuläre Komplikationen traten im Durchschnitt in 3,1% aller in diesem Review einbezogenen Patienten auf, insbesondere wenn der TV Zugangsweg gewählt wurde betrug die Inzidenz bis zu 33,3%. Die mittlere Inzidenz von Schlaganfällen betrug 4,4%. Ein Jahr nach TAVI betrug die mittlere Überlebensrate 75,9% (Range 64,1% -87%), verglichen mit 62,4% (Range 40% -84,8%) für medikamentös behandelte Patienten (p-Wert Fazit: Auf Basis der besten verfügbaren Daten, bei Patienten mit symptomatischer schwerer AS, zeigt TAVI eine verbesserte 1-Jahres-Überlebensrate im Vergleich mit der medikamentösen Standardtherapie. Der aus diesem systematischen Review abgeleitete Überlebensvorteil von TV-TAVI versus medikamentöser Therapie beträgt +16,8% und stimmt gut überein mit den kürzlich veröffentlichten Ergebnissen aus der randomisierten PARTNER US Studie (+20%)

Circulating Levels of Interleukin-1 Family Cytokines in Overweight Adolescents

Objectives. Obesity and related diseases are dramatically increasing problems, particularly in children and adolescents. We determined circulating levels of different interleukin (IL)-1 family members in normal weight and overweight adolescents. Methods. Seventy male, Caucasian adolescents (13–17 years) were recruited. Thirty-five had a body-mass index (BMI) above the 90th age-specific percentile. IL-1α, IL-1β, IL-1 receptor antagonist (IL-1ra), and IL-18 were determined using multiplex-technology. Results. IL-18 concentrations were higher in the overweight group compared to normal weight (161.6 ± 40.7 pg/ml versus 134.7 ± 43.4 pg/ml, P = .009). Concentrations of circulating IL-1β levels were below the detection threshold. IL-18 (R2:0.355, P < .01) and IL-1ra (R2:0.287, P < .05) correlated with BMI, whereas IL-1α did not. Conclusions. Accumulating data indicate the importance of the endocrine function of adipose tissue for the pathophysiological consequences of obesity-related co-morbidities. Since IL-18 is involved in the pathogenesis of different cardiovascular diseases, we conclude that IL-18 may represent a link between obesity and related co-morbidities in children and adolescents

Impact of Short-Term Systemic Hypoxia on Phagocytosis, Cytokine Production, and Transcription Factor Activation in Peripheral Blood Cells

Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4+ T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB

Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation

Background. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. Methods: As a substudy of the optimization with intracoronary, ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography tinder identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. Results: With respect to the ACE gene polymorphism, there were three subgroups: DID genotype (48 patients), ID (83 patients) and 11 (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 mumol/l/s in the DD subgroup, 0.29 mumol/l/s in the ID

Elevated Plasma Levels of Interleukin-12p40 and Interleukin-16 in Overweight Adolescents

Introduction. Obesity during adolescence is an increasing problem for both the individual and health care systems alike. In Western world countries, childhood adiposity has reached epidemic proportions. It is known that elevated levels of proinflammatory cytokines can be found in the plasma of obese patients. In this study, we sought to determine the relation between IL-12p40, IL-12p70, and Interleukin-16 (IL-16) in overweight adolescents. Materials and Methods. Seventy-nine male Caucasian adolescents aged 13-17 years were included in this study. Thirty-seven of them had a body mass index (BMI) above the 90th age-specific percentile. Il-12p40, IL-12p70, and IL-16 were measured from plasma using Luminex multiplex technology. Results. Both IL-12p40 and IL- 16 concentrations were significantly increased in overweight subjects compared to normal weight controls (IL-12p40: 1086.6 pg/mL +/- 31.7 pg/mL SEM versus 1228.6 pg/mL +/- 43.5 pg/mL SEM;IL-16 494.0 pg/mL +/- 29.4 pg/mL SEM versus 686.6 pg/mL +/- 52.5 pg/mL SEM, P < 0.05 and P < 0.01, resp.). No differences were found for IL-12p70. Conclusions. Based on these results, we believe that the increased levels of IL-12p40 and IL-16 are associated with an ongoing inflammatory response in obese individuals and could lead to the development of disease conditions related to obesity

Cardiotrophin-1 Induces Tumor Necrosis Factor α Synthesis in Human Peripheral Blood Mononuclear Cells

Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) α and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNFα in PBMC of healthy volunteers. CT-1 induced in PBMC TNFα protein in the supernatant and TNFα mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNFα protein was achieved with 100 ng/mL CT-1 after 3–6 hours and maximal TNFα mRNA induction after 1 hour. ELISA data were confirmed using immunofluorescent flow cytometry. Inhibitor studies with actinomycin D and brefeldin A showed that both protein synthesis and intracellular transport are essential for CT-1 induced TNFα expression. CT-1 caused a dose dependent nuclear factor (NF) κB translocation. Parthenolide inhibited both NFκB translocation and TNFα protein expression indicating that NFκB seems to be necessary. We revealed a new mechanism for elevated serum TNFα concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut