Bad Oeynhausen, Germany
Bad Oeynhausen, Germany

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Sossalla S.,University of Gottingen | Fluschnik N.,University of Gottingen | Ort K.R.,University of Gottingen | Neef S.,University of Gottingen | And 8 more authors.
Circulation Research | Year: 2010

Rationale: Heart failure (HF) is known to be associated with increased Ca/calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed CaMKIIδ expression in end-stage failing human hearts (dilated and ischemic cardiomyopathy) and the functional effects of CaMKII inhibition on contractility. Methods and Results: Expression analysis revealed that CaMKIIδ, both cytosolic δC and nuclear δB splice variants, were significantly increased in both right and left ventricles from patients with dilated or ischemic cardiomyopathy versus nonfailing. Experiments with isometrically twitching trabeculae revealed significantly improved force frequency relationships in the presence of CaMKII inhibitors (KN-93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an improved sarcoplasmic reticulum (SR) Ca2+ loading. This was confirmed in isolated myocytes by a reduced SR Ca2+ spark frequency and hence SR Ca2+ leak, resulting in increased SR Ca 2+ load when inhibiting CaMKII. Ryanodine receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated by CaMKII thereby contributing to SR Ca2+ leak, was found to be markedly reduced in KN-93-treated trabeculae. Interestingly, CaMKII inhibition did not influence contractility in nonfailing sheep trabeculae. Conclusions: The present study shows for the first time that CaMKII inhibition acutely improves contractility in human HF where CaMKIIδ expression is increased. The mechanism proposed consists of a reduced SR Ca2+ leak and consequently increased SR Ca2+ load. Thus, CaMKII inhibition appears to be a possible therapeutic option for patients with HF and merits further investigation. © 2010 American Heart Association. All rights reserved.


Wohrle J.,University of Ulm | Zadura M.,Heart and Diabetes Center | Mobius-Winkler S.,University of Leipzig | Leschke M.,Pneumology and Angiology | And 7 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: This study sought to assess the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in an international, multicenter, prospective, large-scale registry study. Background: In small randomized trials, PCB angioplasty was superior to uncoated balloon angioplasty for treatment of bare-metal stent (BMS) and drug-eluting stent (DES) restenosis. Methods: Patients treated with SeQuent Please PCBs were included. The primary outcome measure was the clinically driven target lesion revascularization (TLR) rate at 9 months. Results: At 75 centers, 2,095 patients with 2,234 lesions were included. The TLR rate was 5.2% after 9.4 months. Definite vessel thrombosis occurred in 0.1%. PCB angioplasty was performed in 1,523 patients (72.7%) with DES or BMS restenosis and 572 patients (27.3%) with de novo lesions. The TLR rate was significantly lower in patients with PCB angioplasty for BMS restenosis compared with DES restenosis (3.8% vs. 9.6%, p < 0.001). The TLR rate did not differ for PCB angioplasty of paclitaxel-eluting stent and non-paclitaxel-eluting sten restenosis (8.3% vs. 10.8%, p = 0.46). In de novo lesions (small vessels), the TLR rate was low and did not differ between PCB angioplasty with and without additional BMS implantation (p = 0.31). Conclusions: PCB angioplasty in an all-comers, prospective, multicenter registry was safe and confirmed in a large population the low TLR rates seen in randomized clinical trials. PCB angioplasty was more effective in BMS restenosis compared with DES restenosis, with no difference regarding the type of DES. © 2012 American College of Cardiology Foundation.


Zittermann A.,Heart and Diabetes Center | Kuhn J.,Ruhr University Bochum | Ernst J.B.,Heart and Diabetes Center | Becker T.,Heart and Diabetes Center | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Several cohort studies have reported U-shaped or inverse J-shaped associations between circulating 25-hydroxyvitamin D [25OHD] and clinical outcomes. Objective: We aimed to investigate in cardiac surgical patients the association of preoperative 25OHD and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels with the risk of major adverse cardiac and cerebrovascular events (MACCE). Design: A prospective cohort study of adult cardiac surgical patients in 2012-2013 was used. Setting: The study was conducted at the Heart and Diabetes Center North Rhine-Westphalia, Germany. Patients: A total of 3371 adult patients participated in the study. Intervention: None Measurements: The main outcome measure was MACCE until discharge. We categorized vitamin D metabolite levels into subgroups and performed multivariable-adjusted logistic regression analysis to estimate odds ratios (ORs) of MACCE. Moreover, we performed multiple regression analysis to assess the association of 25OHD and circulating 1,25(OH)2D3 with preoperative parameters. Results: As compared with patients in the 25OHD reference category (75-100 nmol/L), the multivariable-adjusted odds ratios (OR) of MACCE was significantly higher in patients with deficient 25OHD levels (< 30 nmol/L) (OR = 2.06 [95%CI: 1.24-3.43]), but was comparable in patients with 25OHDlevels-100 nmol/L (OR=1.16 [95% CI: 0.56-2.37]). Poor kidney function was an important predictor of high 25OHD (-100 nmol/L) and low 1,25(OH)2D3 levels. 1,25(OH)2D3 was not independently associated with the incidence of MACCE. Conclusions: In cardiac surgical patients, deficient but not high 25OHD levels are independently associated with the risk of MACCE. Cohort studies should consider potential interrelationships between kidney function, circulating vitamin D metabolite levels, and clinical outcome. © 2015 by the Endocrine Society.


News Article | December 16, 2016
Site: www.prweb.com

1,25-Dihydroxyvitamin D (1,25[OH]2D) is the active, hormonal form of vitamin D. Circulating 1,25(OH)2D levels are regulated by serum calcium and phosphate concentrations; this is mediated by the calcium-regulating hormones. In the human body, 1,25(OH)2D has a broad range of actions which include endocrine, autocrine and paracrine properties. Due to its picomolar concentrations and its lipophilic nature, 1,25(OH)2D is a difficult analyte and represents a challenge to the analytical biochemist with respect to quantification. Until recently, relatively large sample volumes and extensive purification and separation steps were required to quantify 1,25(OH)2D. In this webinar, sponsored by DiaSorin, participants will learn the clinical relevance of circulating 1,25(OH)2D. Besides the well-known suppression of circulating 1,25(OH)2D in chronic kidney disease, it will become evident that circulating 1,25(OH)2D is also reduced in other diseases. In the clinical setting, however, there are still several gaps in the present knowledge on circulating 1,25(OH)2D. This webinar will delve into these gaps, which include incomplete data about the effect of activated vitamin D; the influence of dosing and initial 25OHD level on circulating 1,25(OH)2D; and the effect of different diseases on circulating 1,25(OH)2D. Attendees will learn the clinical conditions that would benefit from follow-up measurement for 1,25 dihydroxyvitamin D, as well as better understand why active vitamin D therapy should be accompanied by measuring 1,25 dihydroxyvitamin D. The speaker for this webinar will be Dr. Armin Zittermann, head of the Center for Clinical Studies in Thoracic and Cardiovascular Surgery at the Heart and Diabetes Center. As a nutritionist and head of the Center for Clinical Studies in Thoracic and Cardiovascular Surgery at the Heart and Diabetes Center in Bad Oeynhausen, Germany, Zittermann’s research focuses on the prevalence and the consequences of insufficient levels of vitamin D in humans, in particularly in patients with cardiovascular diseases. Zittermann also lectures at the Institute of Nutrition and Food Sciences at the University of Bonn on specific aspects of food security. LabRoots hosted the webinar December 7, which is now available on demand. To read full event details, learn about P.A.C.E continuing education credits, or to register for free, click here. About DiaSorin Headquartered in Italy and listed in the FTSE Italia Mid Cap Index, DiaSorin is a global leader in the In Vitro Diagnostics (IVD) field. For over 40 years the Company has been developing, producing and marketing reagent kits for IVD worldwide. Through constant investments in research and development, and using its own distinctive expertise in the field of immunodiagnostics to deliver a high level of innovation, DiaSorin offers today the broadest range of specialty tests available in the immunodiagnostics market and new tests in the molecular diagnostics markets, which identify DiaSorin Group as the IVD “diagnostics specialist.” About LabRoots LabRoots is the leading scientific social networking website and producer of educational virtual events and webinars. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the world’s largest series of virtual events within the Life Sciences and Clinical Diagnostics community.


Aissaoui N.,Heart and Diabetes Center | Aissaoui N.,European Georges Pompidou Hospital | Morshuis M.,Heart and Diabetes Center | Schoenbrodt M.,Heart and Diabetes Center | And 4 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2013

Background: Management of right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is not evidence based. Temporary circulatory assistance has recently been reported to be of value for managing postoperative RV failure after LVAD implantation, but only in small series of patients or isolated case reports. We report here our experience with the use of temporary right ventricular assist devices (RVADs) in LVAD recipients. Methods: Forty-five of the 488 (9%) patients undergoing LVAD implantation between 2001 and 2011 at the Clinic for Thoracic and Cardiovascular Surgery in Bad Oeynhausen had RV failure requiring temporary RVAD. We analyzed preoperative data, complications, mortality at 6 months, and risk factors of death. Results: The LVAD patients receiving temporary RVAD were younger than the 443 recipients of LVAD alone. They were more likely to have mechanical ventilation and haemofiltration and their Michigan right ventricular risk score was higher. The LVAD patients with temporary RVAD had a higher mortality at 6 months: 53%, versus 25% for patients receiving LVAD only (P <.001). The univariate risk factors for death were high blood urea nitrogen and C-reactive protein concentrations, preoperative mechanical ventilation, preoperative hemofiltration, destination therapy, the use of temporary RVAD, and the development of RV failure. Multivariate analyses did not identify predictors of death. Conclusions: The development of RV failure in LVAD recipients is a serious problem associated with high mortality. Temporary RV mechanical support is an acceptable way to manage postoperative RV failure in these severely ill LVAD recipients. © 2013 by The American Association for Thoracic Surgery.


Stirban A.,Heart and Diabetes Center | Stirban A.,Profil Institute for Metabolic Research GmbH | Pop A.,Heart and Diabetes Center | Tschoepe D.,Heart and Diabetes Center
Diabetic Medicine | Year: 2013

Aims: In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. Methods: In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. Results: Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. Conclusions: In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible. © 2013 Diabetes UK.


Dahm J.B.,Heart and Vascular Center Neu Bethlehem | van Buuren F.,Heart and Diabetes Center
Indian Heart Journal | Year: 2010

Transradial access is associated with enhanced patients' comfort, significant lower complication rates in diagnostic coronary angiography and better immediate and long-term outcomes after transradial percutaneous coronary interventions. Access failure has been reported to occur in less than 3-7% of cases due to anatomical circumstances (e.g., anomalous radial branching patterns, tortuosity e.g. radial loops, and small radial artery diameters). Radial coronary angiography and angioplasty entail a secondary learning curve of at least 150 cases in order to become familiar and comfortable with this technique. In contrast to previous established techniques (e.g. Sones-arteriotomy), the patient should be positioned in a comfortable supine position with his right arm next to his hip and the interventionist next to the right side of the patient. 19 gauge needles and 0.018 inch wires enhance the chance of successful cannulation the radial artery. A spasmolytic cocktail (3 mg Dinitrate, 3 mg verapamil, at least 3.000 U Heparine) should always be given intraarterially. Longer sheaths (> 13 cm) are not necessary. Essential for easy passage of the vertebralian artery and the common brachio-cephalic trunc (as the most dangerous part of the procedure) in order to reach the ascending aorta, the patient should be asked for a deep inspiration and/or dorsoflexion of his head. An Amplatz-II catheter can be used for LCA, RCA and in some cases for LV-angiogram. The sheath should always be removed immediately and hemostasis achieved by radial compression (e.g. clamp). There is a close relationship between access failure respective radial spasm or occlusions and anatomical circumstances (i.e., hypoplastic radial artery, radioulnar loop, or small radial diameters: radial diameter-to-catheter ration < 1.0; assessment by Duplex). Although the radial access can be used in the majority of patients, the use is limited in patients with very small radial diameters and/or with complex lesions (e.g kissing balloon, etc).


Dahm J.B.,Heart and Vascular Center Neu Bethlehem | van Buuren F.,Heart and Diabetes Center
Indian Heart Journal | Year: 2010

Before ten years, radial artery was discovered as a useful vascular access site for percutaneous coronary procedures. It has the advantage of reduced access site complications but is associated with specific technical challenges in comparison with the transfemoral approach. Although earlier data from a meta-analysis indicated higher procedure failure rates with radial - as compared to femoral access (7.2 vs. 2.4%), more recent data from prospective multicenter studies and large meta analysis showed significantly better outcomes with radial access versus femoral access in contemporary, real-world clinical settings of percutaneous cardiovascular procedures (e.g. PREVAIL-, PRESTO-ACS-studies). This includes also challenging coronary procedures in acute coronary syndromes (NSTEMI and STEMI) where the radial access was associated with fewer bleeding complications leading to better long-term outcomes. Transradial procedure failures can sometimes be due to variation in radial artery anatomy (e.g. vessel diameter, anomalous branching patterns, tortuosity) or risk factors for radial spasms (e.g. smoking, anxiety, vessel diameter, age, gender). Postprocedural radial occlusions (0.6-1.2%) seems strongly be related to these anatomical variances, which possibly may be reduced by the use of smaller catheter, however 5 French lumen diameter guiding catheter include limitations regarding treating options in complex coronary lesion. In conclusion, the transradial access for coronary angiography and interventions is not only to enhance patients comfort, but shows significant better long term results due to less bleeding complications as compared to the femoral access.


Beck C.,Heart and Diabetes Center | Laser K.T.,Heart and Diabetes Center | Haas N.A.,Heart and Diabetes Center
Catheterization and Cardiovascular Interventions | Year: 2010

Since March 2008, the new Amplatzer duct occluder II (ADO II) has been used clinically for PDA closure in Europe. We report an interesting case of a 21/2-year-old girl with a 3-mm conical shape PDA (type A PDA) who underwent uneventful implantation of 3/4 ADO II with complete closure by angiography and echocardiographic control at the end of the procedure. To our surprise, echocardiography 24 hr later revealed a moderate secondary shunt due to kinking of the aortic retention disk of the device with the central waist and the pulmonary retention disk still in correct position. The persistent shunt was closed 1 year later in the cath lab with a 9/6 Nit-Occlud device. To our knowledge, this is the first reported late complication directly related to the device. © 2010 Wiley-Liss, Inc.


Aslan I.,Heart and Diabetes Center | Fischer M.,Heart and Diabetes Center | Laser K.T.,Heart and Diabetes Center | Haas N.A.,Heart and Diabetes Center
Cardiology in the Young | Year: 2013

Eosinophilic myocarditis is a rare disease occurring mainly in adulthood. It is generally known to be caused by autoimmune diseases, parasitic infections, hypersensitivity to drugs or substances, and after vaccinations. We describe the case of a 15-year-old adolescent, who presented initially with flu-like symptoms, as well as syncope. Subsequently, catecholaminergic treatment had to be initialised because of cardiac failure. Peripheral eosinophil count was normal at admission and at the time of endomyocardial biopsy. The biopsy, however, proved the diagnosis of eosinophilic myocarditis, but the causative agent remained unclear despite intensive diagnostic work-up. Cardiac magnetic resonance imaging showed signs of acute myocardial oedema and a delayed enhancement in the basal inferolateral segments consistent with acute myocarditis. Under treatment with corticosteroids, angiotensin-converting enzyme inhibitor, and warfarin, we accomplished a rapid and complete recovery of cardiac function and histology. This unique case of eosinophilic myocarditis is rare in childhood. The differential diagnosis and diagnostic pathway is discussed, and a review of the literature and therapeutic options based on the literature is performed. © 2012 Cambridge University Press.

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