Lipoprotein binding to anionic biopolyelectrolytes and the effect of glucose on nanoplaque formation in arteriosclerosis and Alzheimer's disease.

Arteriosclerosis with its clinical sequelae (cardiac infarction, stroke, peripheral arterial occlusive disease) and vascular/Alzheimer dementia not only result in far more than half of all deaths but also represent dramatic economic problems. The reason is, among others, that diabetes mellitus is an independent risk factor for both disorders, and the number of diabetics strongly increases worldwide. More than one-half of infants in the first 6months of life have already small collections of macrophages and macrophages filled with lipid droplets in susceptible segments of the coronary arteries. On the other hand, the authors of the Bogalusa Heart Study found a strong increase in the prevalence of obesity in childhood that is paralleled by an increase in blood pressure, blood lipid concentration, and type 2 diabetes mellitus. Thus, there is a clear linkage between arteriosclerosis/Alzheimer's disease on the one hand and diabetes mellitus on the other hand. Furthermore, it has been demonstrated that distinct apoE isoforms on the blood lipids further both arteriosclerotic and Alzheimer nanoplaque formation and therefore impair flow-mediated vascular reactivity as well. Nanoplaque build-up seems to be the starting point for arteriosclerosis and Alzheimer's disease in their later full clinical manifestation. In earlier work, we could portray the anionic biopolyelectrolytes syndecan/perlecan as blood flow sensors and lipoprotein receptors in cell membrane and vascular matrix. We described extensively molecular composition, conformation, form and function of the macromolecule heparan sulfate proteoglycan (HS-PG). In two supplementary experimental settings (ellipsometry, myography), we utilized isolated HS-PG for in vitro nanoplaque investigations and isolated human coronary artery segments for in vivo tension measurements. With the ellipsometry-based approach, we were successful in establishing a direct connection on a molecular level between diabetes mellitus on the one side and arteriosclerosis/Alzheimer's disease on the other side. Application of glucose at a concentration representative for diabetics and leading to glycation of proteins and lipids, entailed a significant increase in arteriosclerotic and Alzheimer nanoplaque formation. IDLapoE4/E4 was by far superior to IDLapoE3/E3 in plaque build-up, both in diabetic and non-diabetic patients. Recording vascular tension of flow-dependent reactivity in blood substitute solution and under application of different IDLapoE isoforms showed an impaired vasorelaxation for pooled IDL and IDLapoE4/E4, thus confirming the ellipsometric investigations. Incubation in IDLapoE0/E0 (apoE "knockout man"), however, resulted in a massive flow-mediated contraction, also complemented by strongly aggregated nanoplaques. In contrast, HDL was shown to present a powerful protection against nanoplaque formation on principle, both in the in vitro model and the in vivo scenario on the endothelial cell membrane. The competitive interplay with LDL is highlighted through the flow experiment, where flow-mediated, HDL-induced vasodilatation remains untouched by additional incubation with LDL. This is due to the four times higher affinity for the proteoglycan receptor of HDL as compared to LDL. Taken together, the studies demonstrate that while simplistic, the ellipsometry approach and the endothelial-mimicking proteoglycan-modified surfaces provide information on the initial steps of lipoprotein-related plaque formation, which correlates with findings on endothelial cells and blood vessels, and afford insight into the role of lipoprotein deposition and exchange phenomena at the onset of these pathophysiologies.

A simplified minimally invasive approach to mitral valve surgery - optimal access under direct vision.

With increasing enthusiasm in minimally invasive surgery, several approaches and access are being performed with great precision. In this report, we illustrate and describe a minimal invasive approach to mitral valve surgery with optimal access under direct vision, the indications and patient selection, the surgical techniques, its advantages over the other approaches, and its simplicity and reproducibility.

Trends and outcomes in heart transplantation: the Berlin experience.

Heart transplantation is an established procedure with acceptable, predictable long-term results and good quality of life for more than 20 years. However, it is only available for a limited number of patients. The fate of the patients is determined by the side effects of immunosuppressive drugs, increased tumor incidence and chronic vascular transplant disease. Patients living 10 to 20 years after heart transplantation show physical status equal to that of patients with various chronic illnesses. They suffer from chronic side effects of long-term medication and mainly report fears of renal insufficiency followed by osteoporosis-associated pain, cortisone-induced myopathy and risk for tumors. Only moderate psychological impairment is reported despite somatic problems. In the period 10-20 years post-heart transplantation, there is even a surprising increase in emotional well-being. The 20-year survivors are active and satisfied with daily life. They experience their own life as meaningful and have good partner, family and social relations. Heart transplantation, the most ambitious project in medicine in the 20th century has been made a reality. Its development has the strongest impact on cardiac surgery, immunology, pharmacology, medical logistics, defining life and death, ethics in medicine, acceptance of medical progress by the public and by health care systems. It has  provided a strong  solidarity among politicians, sociologists, physicians and citizens. Ethical concerns will last and will make heart transplantation an important, yet temporary episode in human medicine. It has stimulated research and development of mechanical circulatory support systems as an alternative to treat end-stage heart failure.

Surgical treatment concepts for end-stage congenital heart diseases.

It is anticipated that as many as 10-20% of patients alive with anatomical congenital heart lesions may eventually develop heart failure. Most of these patients have undergone previous palliative or corrective surgeries. The Fontan procedure, although it has helped many patients with single-ventricle physiology to become hemodynamically functional, it is associated with  protein-losing entropathy, intractable atrial arryhythmia and systemic ventricular dysfunction. In patients with transposition of the great arteries, physiological or intra-atrial repair techniques (Mustard and Senning) or anatomical correction (arterial switch) have been used. The majority of these patients are clinically well throughout their adult life but, as a consequence of the potential for right ventricular failure, some may develop cardiac insufficiency. Although long-term survival and quality of life in children and adults with complex congenital heart disease have remarkably improved due to advances in operative techniques and perioperative management, as well as the increasing experience of congenital heart surgeons, a growing number of these patients eventually develop end-stage heart failure and will require another treatment. Surgical options for treatment of these patients are limited. Heart transplantation has become a well-established treatment option for children as well as adults with end-stage congenital heart  disease. Because of organ donor shortage, another option is mechanical circulatory assist device implantation, either as a bridge to transplantation, or as a permanent therapy.

Tuberculous meningitis in a lung transplanted patient.

A 57-year-old female lung transplant recipient developed tuberculosis after quadruple maintenance immunosuppression for acute cellular rejection with respiratory compromise. Deteriorating neurological status led to cerebral imaging and lumbar puncture, which showed Mycobacterium tuberculosis. Tuberculous meningitis with elevated intracranial pressure was treated for 2 weeks on a neurosurgical ward, and intensive care therapy was necessary for another 2 weeks. Complete neurological recovery was achieved after 3 months.

Gender-specific predictors of early mortality after coronary artery bypass graft surgery.

BACKGROUND: Female gender is a risk factor for early mortality after coronary artery bypass graft surgery (CABG). Yet, the causes for this excess mortality in women have not been fully explained. OBJECTIVES: To analyse gender differences in early mortality (30 days post surgery) after CABG and to identify variables explaining the association between female gender and excess mortality, taking into account preoperative clinical and psychosocial, surgical and postoperative risk factors. METHODS: A total of 1,559 consecutive patients admitted to the German Heart Institute Berlin (2005-2008) for CABG were included in this prospective study. A comprehensive set of prespecified preoperative, surgical and postoperative risk factors were examined for their ability to explain the gender difference in early mortality. RESULTS: Early mortality after CABG was higher in women than in men (6.9 vs. 2.4 %, HR 2.91, 95 % CI 1.70-4.96, P < 0.001). Women were older than men (+4.7 years, P < 0.001), had lower self-assessed preoperative physical functioning (-16 points on a scale from 0 to 100, P < 0.001), and had higher rates of postoperative low cardiac output syndromes (6.6 vs. 3.3 %, P = 0.01), respiratory insufficiency (9.4 vs. 5.3 %, P = 0.006) and resuscitation (5.2 vs. 1.8 %, P = 0.001). The combination of these factors explained 71 % of the gender difference in early mortality; age and physical functioning alone accounted for 61 %. Adjusting for these variables, HR for female gender was 1.36 (95 % CI 0.77-2.41, P = 0.29). CONCLUSIONS: Age, physical function and postoperative complications are key mediators of the overmortality of women after aortocoronary bypass surgery. Self-assessed physical functioning should be more seriously considered in preoperative risk assessment particularly in women.

Argatroban anticoagulation for heparin induced thrombocytopenia in patients with ventricular assist devices.

BACKGROUND: Patients receiving implantation of ventricular assist devices (VAD) suffer a high incidence of heparin induced thrombocytopenia (HIT); the occurrence of this condition is associated with increased complications and worse outcomes. We report our experience in the management of patients who were diagnosed with HIT either before (HITpre) or after (HITpost) implantation of VAD with argatroban, a direct thrombin inhibitor. METHODS: This retrospective analysis assessed data of VAD patients diagnosed with HIT at Deutsches Herzzentrum Berlin between November 2005 and April 2009. Argatroban dose requirements, anticoagulation efficacy and adverse events (death, thromboembolism, bleeding) were recorded. Procedural success (discharge from the hospital, heart transplantation, or recovery of the failing heart) was also assessed. RESULTS: Twenty-seven patients were identified (11 HITpre, 16 HITpost). Argatroban was effective in obtaining adequate anticoagulation with a reduced dose regimen (0.02-0.42 mcg/Kg/min starting dose; 0.02-1.5 mcg/Kg/min maintenance dose). We noted 5 thromboembolic complications (18%), 6 cases of major bleeding (22%) and 5 deaths (18%), all cause composite adverse end point occurring in 40% of patients. Procedural success was obtained in 81% of patients (92% HITpre, 69% HITpost). As compared to historical controls of patients treated with lepirudin in the period 2000-2005, results were significantly improved. CONCLUSION: Argatroban anticoagulation is feasible in patients with HIT after VAD implantation, without increasing bleeding risk. Its impact in terms of survival should be reviewed also in the light of the technological improvements of assist devices.

Impact of heart transplantation in infancy and adolescence on quality of life and compliance.

INTRODUCTION: Young patients who undergo heart transplantation in their early childhood or adolescence are confronted with typical developmental problems, which affect their specific adjustment to heart transplantation. This study aims at evaluating patients' health related quality of life and at determining the degree and sources of non-compliant behavior with its somatic and psychosocial consequences. METHODS: The study sample consists of 38 patients, who received heart transplantation between the age of 1 and 18 and are now between 16 and 34 years old. All participants received self-rating instruments: The Short-Form Health Survey (SF-36), Giessen Subjective Complaints List (GBB), Medication Experience Scale for Immunosuppressants (MESI), and Health Questionnaire for Children and Young People (KIDSCREEN-27). Patient´s scores were compared to the scores of the specific norm sample. Further assessment was done by semi-structured interviews directed at psychosocial outcome, compliance, relationship to family and peer-group and integration into the work environment. RESULTS: In comparison to healthy controls the patients showed a significantly reduced quality of life (SF-36) in all psychological and nearly all somatic domains. Patients emphasized a very close and satisfying relationship to their parents and pronounced overall social support. Almost 50% of the patients reported some reduced medical compliance and 20% are to be seen as a high risk group for noncompliance, simultaneously characterized by poor physical and mental status. CONCLUSION: Young adult transplant patients are to be carefully evaluated for psychosocial risks to avoid noncompliance and reduced quality of life in long-term follow up.

The future of heart valve banking and of homografts: perspective from the Deutsches Herzzentrum Berlin.

Ever since the early days of homograft implantation in 1956, and the introduction into clinical practice by Ross and Barrat Boyes, homograft heart valves have proven to have many advantages. Its disadvantages became evident during long-term follow up. Factors, such as donor and recipient morbidity, tissue banking techniques, and the often complex surgical technique required to implant, are of great influence on the long term results. Because of European Directives, legally binding quality assurance regulations have been introduced in homograft banks. However, still not all processing methods have been scientifically sub-structured on their effects on the final product and its durability. The donor shortage has stimulated researchers and industries to develop and improve mechanical and biological valve substitutes such as the stentless bioprostheses. In general, candidates for homograft valve implantation include patients with: endocarditis, congenital defects and women who wish to become pregnant. For each category of patients different implantation techniques are required. The results of homograft banking and homograft transplantation in the German Heart Institute Berlin are satisfactory. Freedom of re-infection rate after homograft implantation is 91.9% +/- 3.6% after 15 years. Current developments show an increased interest in tissue engineered as well as in de- and re-cellularization of heart valve homografts. The advantages and disadvantages of the several processing techniques have not yet been proven in long term clinical results. For homograft bankers these developments pose as a challenge to join forces and to initiate cooperate projects aimed at scientific and organizational development.

Cardiovascular tissue banking in Europe.

INTRODUCTION: In the past 50 years, human cardiovascular tissue allografts, also called homografts, have been implanted into patients with different valvular diseases. The use of these allografts and  the number of cardiovascular tissue banks and their respective techniques increased. We conducted a survey to establish the quantity of allografts processed, and issued by, European tissue banks. The survey also included the collection of other relevant statistics. METHODS: In 2011, the Foundation of European Tissue Banks collected data from 19 different cardiovascular tissue banks in 11 European countries. RESULTS: From  2007 to 2010 the  data show a decrease in the number of hearts received, from 1700 to 1640 in 18 tissue banks; the average number of hearts received for cardiovascular tissue processing decreased from 113 to 91. The number of heart valves issued for transplantation increased from 1272 in 2007 to 1486 in 2010. The average rate of discard because of microbiological contamination was 20.7%, while 4.2% of the grafts were not used because of positive serology. Half of the tissue banks issued arterial grafts, while 3 banks also issued veins and pericardium. An overview of decontamination methods shows considerable methodological differencesbetween 17 cardiovascular tissue banks. CONCLUSIONS: From the experience in Europe, it can be concluded that cardiovascular tissue banks have an established place in the domain of cardiovascular surgery. The statistics show fluctuating data concerning the demand for human cardiovascular allografts and methodological questions. There is room for growth and improvement with respect to validation of decontamination methods.

State of the art in cardiovascular perfusion: now and in the next decade.

The development and improvement of cardiopulmonary bypass technology is an ongoing process. During the past decade, a number of publications on improvements and best practices have appeared, especially in the areas of biocompatibility, materials sciences, instrumentation, monitoring of physiological parameters and knowledge base (education and evidence-based medicine). Biocompatibility may be defined not only as an inherent property of a particular composition of matter, but also as a set of properties concerning shape, finish, fabrication techniques and choice of application. Materials in use for cardiopulmonary bypass have changed and coated components have been used frequently. Improvements in the area of instrumentation were achieved by adaptation of conventional cardiopulmonary bypass circuits. Miniaturization and re-design of cardiopulmonary bypass circuits (so-called minimized perfusion circuits or minimal extracorporeal circulation circuits) have made cardiopulmonary bypass technology less traumatic. A team approach, including the cardiac surgeon, the anesthesiologist and the cardiovascular perfusionist, was deemed beneficial in order to achieve further improvements. Next to choice of technology and material for a given operation, adjunct measures such as pharmaceutical treatment and blood conservation strategies need to be taken into consideration. Monitoring of variables during cardiopulmonary bypass has made some progress, while the knowledge base has expanded due to studies on best practices. For the immediate future, sound scientific knowledge and intelligent monitoring tools will allow cardiopulmonary bypass to be tailored to individual patients' needs.

[Improvements in implantable mechanical circulatory support systems : literature overview and update]. / Fortschritte bei implantierbaren mechanischen Kreislaufunterstüzungssystemen : Literaturübersicht und Update.

In recent years, ventricular assist devices (VAD) supporting the left (LVAD), the right (RVAD) or both ventricles (BVAD) have rapidly emerged as the standard of care for advanced heart failure patients. Both the numbers and ages of patients in which they are used are rising worldwide, especially when used as a permanent support (bridge to destination, BTD). Due to the continuing lack of donor organs, these devices now represent a viable alternative to bridge patients to transplantation (BTT), with a 1-year survival rate of 86%. BTD, especially in long-term support, might be a valid, and the sole, option for those patients in whom heart transplantation is contraindicated. Patient selection, pre- and intra-operative preparation, as well as the timing of VAD implantation are important factors critical to successful circulatory support. While BTT remains the goal in the majority of patients, the number of permanent VADs (i. e. BTD) is rising significantly. Although explantation of a VAD system as a bridge to recovery (BTR) can be considered in only a small number of patients, it represents a very special part of this therapy modality.

Fast-track pulmonary conditioning before urgent cardiac surgery in patients with insufficiently treated chronic obstructive pulmonary disease.

AIM: Chronic obstructive pulmonary disease (COPD) is an important risk factor for perioperative morbidity and mortality in patients undergoing cardiac surgery. Despite high clinical relevance, current guidelines lack clear recommendations on the optimal approach for patients with insufficiently treated COPD and urgent need for cardiac surgery. The aim of the present study was to analyze the efficacy of short-term pulmonary conditioning (PC) in this subset of cardiopulmonary patients. METHODS: Eighteen patients with urgent need for cardiac surgery were treated with 1 mg budenoside twice a day, 1.25 mg salbutamol four times a day and 15 mg ambroxol three times a day. On average, patients received pulmonary conditioning for 5.1 ± 2.1 days. Lung function was assessed before and after treatment. RESULTS: Pulmonary conditioning improved forced expiratory volume in one second (FEV1) by 16% (P<0.001). Predicted FEV1 increased from 48.3 ± 13.6% at baseline to 55.4 ± 16.1% after treatment (P<0.001). Total resistance was reduced from 0.933 ± 0.418 kPa·s/L to 0.631 ± 0.344 kPa·s/L after PC (P=0.004). The percentage of patients in GOLD stages III-IV was reduced from 55.6% at baseline to 27.8% after treatment. After surgery, patients needed mechanical ventilation for 2 ± 3.4 days. One patient (5.6%) received a tracheostomy and four patients (22.2%) developed pneumonia; 30-day mortality was 5.6%. CONCLUSION: Short-term treatment with budenoside, salbutamol and ambroxol significantly improved lung function parameters. If surgery can be delayed for several days, pulmonary conditioning should be considered for patients with insufficiently treated COPD.

Transcranial Doppler sound detection of cerebral microembolism during transapical aortic valve implantation.

OBJECTIVE: Transapical aortic valve implantation (TAVI) is a new method that might reduce the surgical risk of conventional surgical aortic valve replacement in very high-risk patients. Increased downstream microembolization is expected in transapical aortic valve implantation. However, whether it usually occurs, how often, and its clinical relevance are not known. We report the results of ultrasound microembolic signal detection in the middle cerebral artery during the procedure. METHODS: Fifty patients (mean age: 80 ± 5 years; mean EuroSCORE: 36 ± 13 %) underwent transapical aortic valve implantation. Intraoperative transcranial Doppler (TCD) sound examination of both middle cerebral arteries (MCA) was used to identify high-intensity transient signals (HITS) and microembolic signals (MES) during seven phases of the procedure. Pre- and postoperative computed tomography of the brain and clinical neurological examinations were performed preoperatively and daily during the first postoperative week. RESULTS: During the procedure, HITS [right MCA: 435 ± 922 (range 9-5765); left MCA: 471 ± 996 (range 24-6432)] and MES [right MCA: 78 ± 172 (range 1-955); left MCA: 62 ± 190 (range 2-1553)] were detected in all patients. Most of the MES were recorded during valvuloplasty [right MCA: 3 ± 5.6 (range 0-31); left MCA: 2 ± 4.9 (range 0-30)] and positioning of the prosthetic valve in the aortic position [right MCA: 6 ± 5 (range 0-22); left MCA: 2 ± 6.9 (range 0-38)]. Postoperatively, there were no clinical signs of new cerebral embolism. CONCLUSIONS: Cerebral microemboli were detected by intraoperative transcranial Doppler sound examinations in all patients during transapical aortic valve implantation. Most of the signals were detected during balloon valvuloplasty and delivery of the prosthetic valve.

Onset of pulmonary stenosis after arterial switch operation for transposition of great arteries with intact ventricular septum.

INTRODUCTION: Pulmonary stenosis remains the most frequent complication and cause of reintervention after the arterial switch operation for transposition of the great arteries We investigated the onset, incidence, and outcome of pulmonary stenosis after arterial switch operation in neonates with transposition of the great arteries and intact ventricular septum. METHODS: Arterial switch operation using Lecompte maneuver was performed in 222 neonates with transposition of great arteries and intact ventricular septum. Complete medical records with serial echocardiograms were available for 174 (73%) patients and were reviewed for incidence of postoperative pulmonary stenosis defined as a thickened and doming pulmonary valve and/or a pressure gradient of >25 mmHg. RESULTS: During a mean follow-up of 14.4 ± 0.54 years, 31 children developed pulmonary stenosis. Onset of significant stenosis occurred as early as 30 days and as late as 10 years after arterial switch operation. Uncomplicated interventional balloon/stent angioplasty was performed in 11 patients with supravalvular stenosis (mean pressure gradients of 65 mmHg). Severe restenosis occurred in these patients post-angioplasty (range 2-7 years). In other 10 patientseither patch enlargement of the area involved or angioplasty were performed. Freedom from intervention was 68.6±8.7% at 1 year and 42.8.1±9.5% at 15 years and onwards. CONCLUSION: Over time, pulmonary stenosis developed after arterial switch operation. Balloon angioplasty for supravalvular pulmonary stenosis could be the initial treatment of choice owing to the high success rate. Surgical intervention is offered to those with pulmonary valve stenosis having pressure gradients of >50 mmHg, and for re-stenosis after intervention/stent implantation.