Prognoseabschätzung und Prognoseverbesserung von kardiovaskulären Erkrankungen im perioperativen Umfeld der modernen Herzmedizin

Mit den von mir in dieser Habilitationsschrift vorgestellten Arbeiten habe ich versucht, anhand einer Auswahl meiner bisherigen Projekte den Gesamtablauf von Patienten mit schwerwiegenden kardiovaskulären Erkrankungen im perioperativen Umfeld zu erfassen und ausgewählte Studien in einzelnen Bereichen dieses komplexen Themenschwerpunktes darzustellen. Wichtig ist mir anzumerken, dass dies natürlich nur eine Auswahl sein kann, jedoch können diese einzelnen Bausteine dazu beitragen, den Verlauf eines Patienten an unterschiedlichen Stellen im perioperativen Kontext zu unterschiedlichen Zeitpunkten positiv zu beeinflussen. Aufgrund der Vielfältigkeit der kardiologisch-internistischen Beeinflussungsoptionen in diesem in großen Teilen akutmedizinischen Kontext ist es mir außerdem wichtig darzustellen, dass eben diese Auswahl dazu beigetragen hat, auch zukünftige, aktuell von mir bearbeitete Forschungsprojekte zu entwickeln und weiter voranzutreiben. So haben sich aus jedem Projekt zum Teil mehrere neue Ansätze ergeben. Diese Projekte wurden in der Diskussion zum Teil schon aufgegriffen, weitere möchte ich im Kommenden kurz darstellen, wobei auch diese wiederum nur Bausteine sind, um den kardiologischen Gesamtprozess in diesem Kontext in einzelnen Aspekten zu verbessern. Die Komplexität der einzelnen Bereiche zeigt die Notwendigkeit der spezialisierten Behandlung dieser Patienten in einem interdisziplinären Team, in dem sowohl kardiologische als auch herzchirurgische Betrachtungen wichtig für die Gesamtstrategie der Behandlung sind. Dies ist sowohl für den Patienten optimal als auch eine Bereicherung der ärztlichen Ausbildung von Kollegen aus verschiedenen Fachbereichen ohne starre Departmentsgrenzen. Wie wichtig diese Zusammenarbeit ist wird zum Teil erst erkennbar, wenn diese Zusammenarbeit nicht mehr besteht [83]. Im Rahmen der gesamthaften Patientenbetrachtung im Sinne des Value based Healthcare wird dieser Bereich zukünftig immer wichtiger werden, insbesondere bei schwerstkranken Patienten ohne die Möglichkeit einer tiefgreifenden ambulanten Voruntersuchung, sowohl im kardiologischinterventionellen als auch im herzchirurgisch-operativen Kontext als auch an anderen Schnittstellen zwischen internistischer und chirurgischer Behandlungsoption

Acute aortic dissection: pathogenesis, risk factors and diagnosis

Acute aortic dissection is a rare but life-threatening condition with a lethality rate of 1 to 2% per hour after onset of symptoms in untreated patients. Therefore, its prompt and proper diagnosis is vital to increase a patient's chance of survival and to prevent grievous complications. Typical symptoms of acute aortic dissection include severe chest pain, hypotension or syncope and, hence, mimic acute myocardial infarction or pulmonary embolism. Advanced age, male gender, long-term history of arterial hypertension and the presence of aortic aneurysm confer the greatest population attributable risk. However, patients with genetic connective tissue disorders such as Marfan, Loeys Dietz or Ehlers Danlos syndrome, and patients with bicuspid aortic valves are at the increased risk of aortic dissection at a much younger age. Imaging provides a robust foundation for diagnosing acute aortic dissection, as well as for monitoring of patients at increased risk of aortic disease. As yet, easily accessible blood tests play only a small role but have the potential to make diagnosis and monitoring of patients simpler and more cost-effective

Clinical impact of repolarization changes in supine versus upright body position

Background: The impact of postural changes on various electrocardiography (ECG) characteristics has only been assessed in a few small studies. This large prospective trial was conducted to confirm or refute preliminary data and add important results with immediate impact on daily clinical practice. Methods: ECGs in supine and upright position from 1028 patients were analyzed. Evaluation was made according to changes in T-wave vector and direction, ST-segment deviation, heart rate, QT interval and QTc interval was performed. Findings were correlated with the medical history of patients. Results: Positional change from supine to upright resulted in a significantly increased heart rate (8.05 ± 7.71 bpm) and a significantly increased QTc interval after Bazetts (18 ± 23.45 ms) and Fridericas (8.84 ± 17.30) formula. In the upright position significantly more T-waves turned negative (14.7%) than positive (5.7%). ST elevation was recorded in only 0.4% and ST depression in not more than 0.2% of all patients. Conclusions: The majority of the patients do not show significant morphological changes in their ECG by changing the body position from supine to upright. Changes of QTc time instead, are significant and the interval might be overestimated in upright. Therefore assessment of the QTc interval should strictly be done in a supine position

A proposal for early dosing regimens in heart transplant patients receiving thymoglobulin and calcineurin inhibition

There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation

The putative Tumor Suppressor VILIP-1 Counteracts Epidermal Growth Factor-Induced Epidermal-Mesenchymal Transition in Squamous Carcinoma Cells

Epithelial-mesenchymal transition (EMT) is a crucial step for the acquisition of invasive properties of carcinoma cells during tumor progression. Epidermal growth factor (EGF)-treatment of squamous cell carcinoma (SCC) cells provokes changes in the expression of lineage markers, morphological changes, and a higher invasive and metastatic potential. Here we show that chronic stimulation with EGF induces EMT in skin-derived SCC cell lines along with the down-regulation of the epithelial marker E-cadherin, and of the putative tumor suppressor VILIP-1 (visinin-like protein 1). In esophageal squamous cell carcinoma and non-small cell lung carcinoma the loss of VILIP-1 correlates with clinicopathological features related to enhanced invasiveness. VILIP-1 has previously been shown to suppress tumor cell invasion via enhancing cAMP-signaling in a murine SCC model. In mouse skin SCC cell lines the VILIP-1-negative tumor cells have low cAMP levels, whereas VILIP-1-positive SCCs possess high cAMP levels, but low invasive properties. We show that in VILIP-1-negative SCCs, Snail1, a transcriptional repressor involved in EMT, is up-regulated. Snail1 expression is reduced by ectopic VILIP-1-expression in VILIP-1-negative SCC cells, and application of the general adenylyl cyclase inhibitor 2′,3′-dideoxyadenosine attenuated this effect. Conversely, EGF-stimulation of VILIP-1-positive SCC cells leads to the down-regulation of VILIP-1 and the induction of Snail1 expression. The induction of Snail is inhibited by elevated cAMP levels. The role of cAMP in EMT was further highlighted by its suppressive effect on the EGF-induced enhancement of migration in VILIP-1-positive SCC cells. These findings indicate that VILIP-1 is involved in EMT of SCC by regulating the transcription factor Snail1 in a cAMP-dependent manner

Protocol of the Berlin Long-term Observation of Vascular Events (BeLOVE): a prospective cohort study with deep phenotyping and long-term follow up of cardiovascular high-risk patients

INTRODUCTION: The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations. METHODS AND ANALYSIS: A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes. ETHICS AND DISSEMINATION: The study was approved by the Charité-Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations. STUDY REGISTRATION: First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021

Praxisbeispiel aus der AMEOS Gruppe: Transformation des Einkaufs als Wertetreiber im Klinikumfeld

Das Gesundheitssystem ist aufgrund der Corona-Krise besonders gefordert. Während Klinik-Kapazitäten ausgebaut und Hygienekonzepte angepasst werden, wird auch der Bereich Einkauf &amp; Logistik mit neuen Aufgaben konfrontiert, um in der Krise eine sichere Klinikversorgung zu gewährleisten. Die AMEOS Gruppe hat als zentrale Leistungseinheit für Einkaufsthemen die KH Einkauf GmbH gegründet.</jats:p

Erfahrungsbericht: Lieferengpässe und deren Auswirkungen auf das Gesundheitswesen

Lieferengpässe aufgrund der COVID-19-Pandemie belasten die gesamte Wirtschaft weltweit, darunter auch das Gesundheitswesen. Infolgedessen wird die deutsche Wirtschaft stark ausgebremst. Die erwartete Erholung der weltweiten Lieferketten verzögert sich weiterhin.</jats:p