Showing papers by "Heart and Diabetes Center North Rhine-Westphalia published in 2013"

Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery

Abstract: Aims A significant proportion of cardiac surgical patients develop critical post-operative complications. We aimed to investigate the association of pre-operative 25-hydroxyvitamin D (25(OH)D) levels with major cardiac and cerebrovascular events (MACCE) in cardiac surgical patients. Methods and results From January 2010 to August 2011, we consecutively measured circulating 25(OH)D in 4418 operated patients. Of the study cohort, 38.0% had deficient 25(OH)D values ( 100 nmol/L. The incidence of MACCE was 11.5%. In multivariable-adjusted logistic regression models, the odds ratio of MACCE at deficient, inadequate, and high 25(OH)D levels was 2.23 [95% confidence interval (CI): 1.31–3.79], 1.73 (95% CI: 1.01–2.96) and 2.34 (95% CI: 1.12–4.89), respectively, compared with 25(OH)D levels of 75–100 nmol/L. A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay. Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75–100 nmol/L. Conclusion Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE. Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels >100 nmol/L. Trial registration information: Clinicaltrials.gov identifier number: [NCT01552382][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01552382&atom=%2Fehj%2Fearly%2F2013%2F01%2F11%2Feurheartj.ehs468.atom

The European Association for Cardio-Thoracic Surgery (EACTS) database: an introduction

Abstract: OBJECTIVES: Continuous monitoring of surgical outcomes through benchmarking and the identification of best practices has become increasingly important. A structured approach to data collection, coupled with validation, analysis and reporting, is a powerful tool in these endeavours. However, inconsistencies in standards and practices have made comparisons within and between European countries cumbersome. The European Association for Cardio-Thoracic Surgery (EACTS) has established a large international database with the goals of (i) working with other organizations towards universal data collection and creating a European-wide repository of information on the practice of cardio-thoracic surgery, and (ii) disseminating that information in scientific, peer-reviewed articles. We report on the process of data collection, as well as on an overview of the data in the database. METHODS: The EACTS Database Committee met for the first time in Monaco, September 2002, to establish the ground rules for the process of setting up the database. Subsequently, data have been collected and merged by Dendrite Clinical Systems Ltd. RESULTS: As of December 2008, the database included 1 074 168 patient records from 366 hospitals located in 29 countries. The latest submission from the years 2006–08 included 404 721 records. The largest contributors were the UK (32.0%), Germany (20.9%) and Belgium (7.3%). Isolated coronary bypass surgery was the most frequently performed operation; the proportion of surgical workload that comprised isolated coronary artery bypass grafting varied from country to country: 30% in Spain and almost 70% in Denmark. Isolated valve procedures constituted 12% of all procedures in Norway and 32% in Spain. Baseline demographics showed an increase in the mean age and the percentage of patients that were female over time. Remarkably, the mortality rates for all procedures declined over the period analysed, to 2.2% (95% confidence interval [CI] 2.2–2.3%) for isolated coronary bypass, 3.4% (95% CI 3.3–3.5%) for isolated valve and 6.2% (95% CI 6.0–6.5%) for bypass + valve procedures. CONCLUSION: The EACTS database has proven to be an important step forward in providing opportunities for monitoring cardiac surgical care across Europe. As the database continues to expand, it will facilitate research projects, establish benchmarking standards and identify potential areas for quality improvements.

Everolimus in Heart Transplantation: An Update

Abstract: The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

Acute Macrovascular Dysfunction in Patients With Type 2 Diabetes Induced by Ingestion of Advanced Glycated β-Lactoglobulins

Abstract: OBJECTIVES Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T), 90 (T90), and 180 (T180) min. RESULTS Following the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 ( P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 ( P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in Ne-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage. CONCLUSIONS In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

Balloon expandable sheath for transfemoral aortic valve implantation: a viable option for patients with challenging access.

Abstract: Background and Objectives Transcatheter aortic valve replacement (TAVR) via femoral access is a new option for patients with severe aortic valve stenosis considered to be at high risk for conventional open-heart surgery This procedure requires peripheral arteries that are able to accommodate the large sheaths required for valve delivery We present a series of patients with suboptimal vascular conditions, who received a self-expandable vascular sheath Methods and Results From January 2009 to September 2011, a total of 96 patients (43% male) were treated with the 18F Medtronic CoreValve (Medtronic, Minneapolis, MN, USA) The patients' average age was 825 ± 46 years, and the mean EuroSCORE was 29% In eight cases, vascular conditions were inadequate either due to advanced atherosclerotic disease (n = 5, 625%), or an arterial diameter ≤7 mm (n = 3, 375%) Instead of the standard 18F sheath, a balloon-expandable transfemoral introducer (SoloPath™-Introducer, Onset Medical Corporation, Irvine, CA, USA) was delivered and removed without complications in all but one (875%) patient In the last case, rupture of the right femoral artery occurred after removal of the sheath with the need of vascular surgery Conclusion The SoloPath sheath is a feasible alternative to conventional sheaths for transfemoral TAVR patients with difficult femoral vascular access

Predicting the Optimal Basal Insulin Infusion Pattern in Children and Adolescents on Insulin Pumps

Abstract: OBJECTIVE We aimed at developing and cross-validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy (CSII). RESEARCH DESIGN AND METHODS We used the German/Austrian DPV-Wiss database for quality control and scientific surveys in pediatric diabetology and retrieved all CSII patients <20 years of age (November 2009). A total of 1,248 individuals from our previous study were excluded (dataset 1), resulting in 6,063 CSII patients (dataset 2) (mean age 10.6 ± 4.3 years). Only the most recent basal insulin infusion rates (BRs) were considered. BR patterns were identified and corresponding patients sorted by unsupervised clustering. Logistic regression analysis was applied to calculate the probabilities for each BR pattern. Equations were based on both independent datasets separately, and probabilities for BR patterns were cross-validated using typical test patients. RESULTS Of the 6,063 children, 5,903 clustered in one of four major circadian BR patterns, confirming our previous study. The oldest age-group (mean age 12.8 years) was represented by 2,490 patients (42.18%) with a biphasic dawn-dusk pattern (BC). A broad single insulin maximum at 9–10 p.m. (F) was unveiled by 853 patients (14.45%) (mean age 6.3 years). Logistic regression analysis revealed that age, to a lesser extent duration of diabetes, and partly sex predicted BR patterns. Cross-validation revealed almost identical probabilities for BR patterns BC and F in the two datasets but some variation in the remaining two BR patterns. CONCLUSIONS Reconfirmation of four key BR patterns in two very large independent cohorts supports that these patterns are realistic approximations of the circadian distribution of insulin needs in children with type 1 diabetes. Prediction of an optimal pattern a priori can improve initiation and clinical follow-up of CSII in children and adolescents. In addition, these BR patterns represent valuable information for insulin-infusion algorithms in closed-loop CSII.

Meta-analysis of three observational studies of amlodipine/valsartan in hypertensive patients with additional risk factors

Abstract: Objectives. In this study, the effectiveness of amlodipine/valsartan single-pill combination was assessed in hypertensive patients with diabetes, metabolic risk or overweight. Methods. Data from 12,265 patients treated with amlodipine/valsartan from three studies were analyzed in a meta-analysis. These studies focused on (i) non-diabetic hypertensive patients suffering from abdominal obesity; (ii) hypertensive patients with at least one metabolic risk factor; and (iii) hypertensive patients with type 2 diabetes mellitus. The observation periods were 16 weeks for the first two and 24 weeks for the latter cohort. Results. At start of observation, the mean blood pressure was 162.3 mmHg (systolic) and 93.5 mmHg (diastolic). A total of 7.4% of patients were aged ≥ 80 years. At end of the observation, a normalized blood pressure was present in 38.8% of patients. No appreciable differences in blood pressure reduction were evident between the study groups. In both age subgroups (< 80 years and ≥ 80 years)...

Clinical and forensic examinations of glycaemic marker methylglyoxal by means of high performance liquid chromatography–tandem mass spectrometry

Abstract: The postmortem determination of hyperglycaemic coma is quite difficult because of the lack of morphological findings and the difficult interpretation of biochemical parameters. Methylglyoxal (MG) is a reactive oxoaldehyde, which is mainly derived from glycolysis. An electrospray ionisation liquid chromatography–tandem mass spectrometric procedure for the determination of methylglyoxal in human serum and postmortem blood was developed. It involves protein precipitation with perchloric acid and a derivatisation step with 2,3-diaminonaphthalene. The assay was validated according to international guidelines. Serum samples from diabetics obtained at a diabetes clinic and from non-diabetics were used to assess data about reference concentrations in human serum. The assay showed linearity within the physiological concentrations in serum (5–500 ng/ml). Intraday imprecision at three concentrations was 10.3, 9.2 and 8.3 %, and interday imprecision was 15.3, 14.2 and 9.4 %; the limit of detection was 1.3 ng/ml, and limit of quantification, 3.2 ng/ml. One hundred and eighteen clinical (100 diabetics, 18 non-diabetics) and 98 forensic samples (84 non-diabetics, 14 in a status of hyperglycaemic coma) were measured. During life, diabetics showed significantly (p < 0.001) higher serum concentrations of MG than non-diabetics. After death, concentrations of MG increased significantly (p < 0.001). However, there was no correlation between the sum formula of Traub in vitreous humour and MG femoral blood concentrations (R = 0.237). This indicates that MG concentrations in the deceased cannot distinguish deaths due to a hyperglycaemic coma from other causes of death.

Antiestrogens suppress effects of transforming growth factor-β in breast cancer cells via the signaling axis estrogen receptor-α and Y-box Binding Protein-1.

Abstract: Background: Multifunctional Y-box Binding Protein-1 (YB1) is correlated with a poor outcome in breast cancer. We found YB1 expression to be regulated by antiestrogens commonly used in the hormonal therapy of breast cancer and known as activators of Transforming Growth Factor-β (TGFβ). Thus, a putative influence of YB1 on TGFβ signaling should be investigated. Materials and Methods: The effect of YB1 on TGFβ signaling was monitored by expression analysis and reporter gene assays in breast cancer cells overexpressing YB1 and treated with antiestrogens. Results: Antiestrogen-mediated inhibition of estrogen receptor-α led to a suppression of YB1 protein synthesis. On the other hand, YB1 was found to be an enhancer of TGFβ signaling. Conclusion: High levels of YB1 expression lead to a stimulation of TGFβ pathways, thereby counteracting antihormonal breast cancer therapy and representing a putative resistance mechanism. Antiestrogens such as tamoxifen and fulvestrant are successfully used in the endocrine therapy of estrogen receptor (ER)-positive breast cancer. It has been shown that besides direct antagonistic effects on the ER and its target gene expression, antiestrogens can also activate the transforming growth factor-β (TGFβ) system in tumor cells (1-3). Enhanced secretion and activation of TGFβ typically act as an inhibitory autocrine feedback in early tumor stages but can switch to tumor-promoting functions in later stages e.g. by inducing invasion, angiogenesis and local immunosuppression (4, 5). Thus, malignant cells can even benefit from increased levels of activated TGFβ during antihormonal therapy, a mechanism probably contributing to the development of resistance to antiestrogens (6-8). The DNA- and RNA-binding protein Y-box binding protein-1 (YB1) exerts pleiotropic functions in cells by regulating target genes at the level of transcription and translation (9). In breast cancer, YB1 is described as a proliferative factor, correlated with higher relapse frequencies and reduced overall survival (10-12). In addition, YB1 functionality includes the regulation of anti- therapeutic mechanisms, e.g. by induction of the multidrug resistance gene ABCB1 (10). In the course of a cDNA microarray analysis to study differential gene expression during antiestrogen treatment of the MCF-7 human breast cancer cell line, we found that YB1 regulated by both tamoxifen and fulvestrant. These findings raised the question of whether YB1 is also involved in the numerous antiestrogen-induced alterations of TGFβ expression and signaling in breast cancer cells, and if so, how it could possibly influence TGFβ-related cancer progression in general. In the present work, we show that overexpression of YB1 amplifies TGFβ signal pathway activities in breast cancer cells, probably a further way for this factor to enhance tumor progression and to counteract antiestrogen-driven therapeutic effects.

Delayed coronary ischemia after transfemoral aortic valve implantation.

Abstract: Transcatheter aortic valve implantation (TAVI) offers a less invasive treatment alternative to surgical aortic valve replacement for high-risk patients. Although the procedure can be performed at low risk, life-threatening complications may arise in single cases during or even months after the procedure. Here, the details are presented of two patients who underwent TAVI by a transfemoral approach with Medtronic CoreValve prostheses and suffered myocardial ischemia months later. The patients' anatomy with small aortic root, narrow sinus of Valsalva and small distance between the annulus base and coronary arteries and/or the relative oversizing of the CoreValve prosthesis with a high positioning may have contributed to this late complication. Hence, caution is mandatory in this type of patient, with exact pre-procedural planning and close follow up required.

Differences In Tissue Injury and Ablation Outcomes In Atrial Fibrillation Patients - Manual versus Robotic Catheters.

Abstract: Robots have gained their place in almost all areas of our daily life. Robotic systems have been introduced for ablation therapies associated with the hope of automation of procedures, increase in precision of lesion placement, improved energy transmission to the tissue and reduction in radiation exposure of the patients and the interventionalist. Finally, they may be associated with higher comfort for the operator by transferring his work into the control room and thereby supersede wearing sterile and radiation protective clothing. Systems providing a remote mechanical replacement of the operators´ hands have been introduced as well as systems guiding the catheter tip by external magnets. Guiding of the catheter tip has major impact on contact to the tissue and thereby modifies energy transmission. This may be advantageous in terms of higher catheter stability and modification of contact towards a more constant than intermittent type of contact. However, increasing contact bears the risk of mechanical perforation and excessive energy delivery. Many clinical studies have been conducted evaluating novel remotely guiding techniques in atrial fibrillation ablation procedures. Although only a few of them are prospectively randomized, reduction in fluoroscopy exposure has been found in most of the trials. Data on outcome is less uniform. It seems that remote navigation does not improve outcomes and on the other hand does not increase complication rates. However, large prospectively randomized trials conducted by operators well skilled not only in manual but also in remote techniques would be needed to compare outcomes particularly in terms of decrease in complication rates. Finally, the type of navigation chosen actually is and probably will remain a question of personal preference.

Sleep Disordered Breathing and the Pathogenesis of Atrial Fibrillation.

Abstract: This review illustrates the importance of sleep disordered breathing in evolution and progression of atrial fibrillation. While in early years associations were mainly attributed to the impact of hypoxemia and hypertension, nowadays multiple, additional pathways have been investigated or are currently under investigation. Sleep disordered breathing has been shown to have a direct impact on mechanical and electrical remodeling. In addition hypercapnia and negative intrathoracic pressure seem to alter atrial electrophysiology. Finally, impacts on inflammation and metabolic dysregulation display the complex interplay between breathing disorders and evolution and progression of atrial fibrillation.

Mitral chordae myxoma-chordae replacement with a premeasured gore-tex loop using a minimally invasive video-assisted approach.

Abstract: Cardiac myxomas are one of the most common types of primary cardiac tumors and are associated with embolization, angina, and sudden death. Most cardiac myxomas arise from the fossa ovalis, while those that arise from the mitral valve are exceedingly rare and those that arise from the chordae are even rarer. We report the case of a 28-year-old Caucasian woman who suffered from a brain infarction. A duplex ultrasound showed no cerebrovascular stenosis or occlusion, but an echocardiogram revealed a left ventricle pedunculated mobile mass (5 mm in diameter) that was attached to the mitral valve chordae tendineae. We elected cardiac surgery to resect the cardiac tumor and to avoid further embolic events. The traditional surgical strategy—mitral valve replacement through full sternotomy—has many disadvantages, particularly for young women. Therefore we desided to use the Premeasured Gore-Tex chordal loop method followed by annuloplasty using a minimally invasive video-assisted approach. Exploration of the mitral valve showed a globular tumor involving the anterior mitral leaflet chordae tendineae, which was removed along with the involved chordae tendineae. Histopathological examination of the tissue revealed a benign polypoid myxoma. The patient had an uneventful recovery and has remained symptom-free. Echocardiography one week after surgery showed satisfactory valve function. We believe our surgical treatment was the most appropriate option for this case and it resulted in an excellent medical outcome and improved the quality of life, including only a small lateral scar without the need for teratogenic anticoagulants.

Echo-guided extracorporeal shock wave therapy for refractory angina improves regional myocardial blood flow as assessed by PET imaging

Abstract: Purpose: Low-intensity extracorporeal shock wave (SW) therapy (SWT) has been shown to improve symptoms and exercise tolerance in patients (pts.) with coronary artery disease (CAD) not suitable for conventional revascularization strategies. Induction of neovascularization and improvement of myocardial perfusion are mechanisms hypothetized to be involved. Methods: 43 pts. with advanced CAD (mean age 67±10 years) not suitable for catheter-based or surgical revascularization were suffering from severe stable angina pectoris (CCS class III or IV) refractory to individually optimized medical treatment underwent a series of 9 echocardiography-targeted SW applications (3 SW applications/week during weeks 1, 5, and 9). The antero-septal wall (LAD territory) was targeted in 19, the lateral wall (RCX territory) in 18, and the inferior wall (RCA territory) in 6 pts. A series of 300-500 shock waves was applied per session. Anti-anginal medication (combination of 2 or 3 drugs) was kept unchanged. Regional myocardial blood flow (MBF) was measured quantitatively by NH3-PET at baseline and 4-6 weeks after completion of SWT. Results: Complications of SWT did not occur, markers of myocardial cell damage were all negative during SWT. At follow-up, 30 pts. (64%) reported improvement of angina to a tolerable level. CCS angina class decreased from 3.1±0.6 to 2.5±0.6 (p<0.0001). Maximum ergometric workload increased from 78±53 to 90±46 watts (p=0.04). MBF in the LV region targeted by SWT improved from 119+42 mL/min/100g at baseline to 129±48 mL/min/100g at follow up (p=0.047), while there was no change in the opposite wall (136±52 vs. 137±53 ml/min/100g; p=0.9). Conclusions: SWT improves symptoms in a sizeable number of pts. with chronic refractory angina. Regional improvement of MBF in the region targeted by SWT was also documented by PET imaging. Additional studies are warranted to clarify the role of SWT in the armamentarium for this challenging patient group.

Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure - a randomized, controlled, double-blind, crossover trial

Abstract: Background: Studies confirmed Cheyne-Stokes respiration (CSR) to be associated with elevated pulmonary capillary wedge pressure (PCWP) in chronic heart failure (CHF). This study aimed to investigate the acute effects of lowering PCWP and pulmonary artery pressure (PAP) on CSR severity. Methods: 21 consecutive patients with CHF and CSR (apnea-hypopnea-index (AHI≥15/h)) underwent right heart catheterization, followed by infusion of glyceryltrinitrate (GTN), and inhalation of iloprost. Throughout the procedure PAP and PCWP was measured invasively. Afterwards maximum tolerable dosage of GTN and iloprost were randomly applied in 2 split-night procedures versus i.v. or inhalative NaCl 0.9% under full polysomnography monitoring. Results: Mean (m)PAP was significantly reduced by GTN (20.1±9.0 to 11.6±4.2mmHg, p Conclusion: GTN and Iloprost led to a significant reduction in PAP, whereas PCWP was lowered by GTN exclusively. However, acute improvement of pulmonary congestion had no impact on CSR severity. Extended treatment periods appear crucial for successful causal therapies.

The Role of Three-dimensional Rotational Angiography in Atrial Fibrillation Ablation.

Abstract: Three-dimensional (3D) imaging became the cornerstone of catheter guidance in atrial fibrillation (AF) ablation procedures during the last few years. Multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) have been the technologies of choice for pre-procedural imaging of the left atrium (LA) and the pulmonary veins to make lesions more precisely set in a highly variable and difficult to understand 3D environment. These technologies have been used not only for pre-procedural orientation but have also been overlayed to fluoroscopic views in many fluoroscopy-guided ablation procedures. As image integration into non-fluoroscopic 3D imaging systems became available, 3D reconstructions of MSCT and MRI became the standard approach in many centres. However, 3D imaging is not a cornerstone during ablation as it is not indispensable and ablation can be performed without. Although rare, some very important and key centres do not routinely use 3D imaging during ablation. Being remote to the ablation procedure, these imaging technologies may have the disadvantage of not reflecting the current status of a variable LA volume and scheduling of an additional diagnostic procedure may complicate the workflow of AF ablation procedures. Intra- procedural imaging techniques are likely to overcome both issues. Beside others, rotational angiography has been introduced for proving highly actual imaging by intra-procedural acquisition of 3D shells suitable for overlay to fluoroscopy without need for registration and image integration into 3D mapping systems registered by point-by-point electroanatomical mapping or 3D echocardiographic imaging.