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Prof. Dr. med. Thomas Dieterle

Department of Clinical Research
Profiles & Affiliations

Projects & Collaborations

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Functional Aging in Health and Disease - the COmPLETE Project

Research Project  | 5 Project Members

The increasing prevalence of chronic non-communicable diseases and associated risk factors contribute to earlier disability and frailty onset over the course of life in industrialized western countries. This process applies also to diseases of the cardiovascular system, including heart failure, which is a widespread syndrome in middle-aged and older people. Although life expectancy has steadily increased in past decades, the traditional curative way of thinking in medicine is unlikely to compress the disease phase to the final stage of life and thus increase the health span, which is defined as a period of relatively disease-free aging followed by a period of age-related diseases and disabilities. In the period of healthy aging, the function of the organs, including the cardiovascular system, is already deteriorating. To counteract this process and to increase the health span, the preservation or improvement of components of physical fitness (endurance capacity, muscle strength, and neuromuscular function) is thought to be an essential element. The proven, independently predictive value of the single physical fitness components for total and cardiovascular mortality confirms this assumption. However, comprehensive data regarding individual physical fitness characteristics over the course of life are not yet available. Such data is necessary for any targeted prevention program with physical activity and exercise training as crucial pillars. Furthermore, healthy reference values could be used to estimate the adaptive capacity in healthy individuals compared to patients. Therefore, the aims of the COmPLETE project are:1.To determine the trajectories of physical fitness components of healthy aging by measurement of endurance capacity, muscular strength and neuromuscular coordination in a healthy population sample between 20 and 100 years (COmPLETE-Health) and 2.To determine the health distance between healthy individuals (COmPLETE-Health) and heart failure patients (COmPLETE-Heart) on the basis of different physical fitness components (endurance capacity, muscular strength and neuromuscular coordination). We anticipate that, for the first time, a basis for targeted prevention programs will be created through better and comprehensive knowledge of the individual physical fitness to improve the health span. In addition, we are convinced that by calculating the health distance between healthy and heart failure patients, we are laying the foundation for more individual exercise therapy. The COmPLETE project could be the starting point for strengthening the in-depth diagnostics of physical fitness as a component of preventative health care.

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POC-HF - Point of care with serial NT-proBNP measurement in patients with acute decompensation of heart failure during hospitalization as a therapy-monitoring: A prospective, unblinded, randomized controlled, pilot trial

Research Project  | 4 Project Members

Background and Rationale: Despite important advances in the medical therapy of heart failure (HF), therapy monitoring is still based on signs and symptoms of this syndrome. NT-proBNP was repeatedly demonstrated to be a strong and independent predictor of morbidity and mortality in patients with HF. Only few - and conflicting - data are available on the efficacy of serial measurement of NT-proBNP as a tool for treatment monitoring in HF. In addition, these data are limited to the outpatient setting. Currently, no data are available on the effects of this approach in patients hospitalized for acute decompensated HF. Objective(s): The goal of this study is to explore whether the availability of serial NT-proBNP measurements together with safety parameters such as electrolytes and creatinine may influence treatment decision in patients with acute decompensated heart failure leading to more rapid and faster dose increase of prognostic therapies and earlier hospital discharge. Endpoint(s): Primary endpoint: The effect of therapy monitoring with NT-proBNP on the change of the NT-proBNP at discharge and the dosing of heart failure medication from admission to hospital discharge compared to the control group. Secondary endpoints: Incidence of electrolyte imbalances, renal failure, weight changes, dose and variations made to medical heart failure therapies, QoL, length of hospital stay, adverse events and mortality Inclusion / Exclusion criteria: Inclusion criteria: Informed consent as documented by the patient's signature, history of acute deterioration of signs and symptoms of chronic HF indicating acute decompensated HF (NYHA functional classes II-IV), such as dyspnea, paroxysmal nocturnal dyspnea, reduced exercise tolerance, fatigue, peripheral edema (lower leg, ankle), elevated jugular venous pressure, displacement of the apical impulse, crackles, wheezing (cardiac asthma), third/fourth heart sound, lung congestion or cardiomegaly in chest x-ray, electrocardiographic abnormalities, and an NT-proBNP >300 pg/ml Exclusion criteria: Age <18 years, NT-proBNP <1200 pg/ml with creatinine clearance <60 ml/min, pregnant or breast feeding women, lack of safe contraception, known or suspected non-compliance, drug or alcohol abuse, inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.

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THESEUS - an observational study on the use of entresto (sacubitril⁄valsartan) in clinical routine practice in Switzerland

Research Project  | 2 Project Members

Heart Failure is a common disease associated with a high mortality rate. Patients often experience severely impaired quality of life. After the introduction of the angiotensin converting enzyme (ACE) inhibitors, beta blockers and mineralocorticoid receptor antagonists, sacubitril/valsartan was the first drug demonstrating a significant reduction of mortality. So far, there is no data on the application of sacubitril/valsartan in Swiss primary care. The longitudinal, non-interventional THESEUS study will document implementation and dosing of sacubitril/valsartan over a period of 6 months in patients with heart failure in follow-up in a primary care setting in Switzerland. The THESEUS study is expected to deliver valuable real-world data on the use of sacubitril/valsartan in Swiss primary care, its tolerability and safety profile as well as its impact on the usage of healthcare resources.

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R'equip grant for Visual Sonics Vevo 770 high resolution small animal ultrasound system.

Research Project  | 4 Project Members

Gene knockout and transgenic techniques in mice and rats have contributed to the outstanding importance of small animal models of disease in cardiovascular research. Noninvasive imaging of cardiovascular function provides a means for serially assessing the effects of a gene mutation or a therapy on cardiovascular phenotype. Some phenotypic aspects can be examined postmortem (e.g. left ventricular mass), but a majority of cardiovascular phenotypic markers (e.g. left ventricular systolic/diastolic function) can only be determined in vivo . The small size and fast rate of mouse and rat hearts demand imaging equipments with a high spatial and temporal resolution not met by clinical ultrasound systems. With the current grant application we therefore request financing for a VisualSonics Vevo 770 High Frequency Ultrasound System. The Vevo 770 is a dedicated small animal imaging system fulfilling the aforementioned requirements. It offers 2-dimensional real-time ultrasound imaging with high spatial and temporal resolution with frequencies up to 60MHz, pulsed wave doppler imaging for hemodynamic assessment and tissue doppler imaging for analysis of myocardial deformation. In addition, contrast ultrasound imaging with high spatial resolution will be possible. The availability of the Vevo 770 will significantly contribute to the innovative potential of the research proposals included in this application and will allow us to initiate new research directions. In brief, this system will make possible the following main research projects: 1. Sequential contrast enhanced and high resolution ultrasound molecular imaging of inflammatory cell adhesion molecules in atherosclerosis. The Vevo 770 will be used for high resolution in vivo assessment of plaque development in murine atherosclerosis. Also, high resolution contrast enhanced molecular imaging of inflammatory markers will become possible, which constitutes a new research direction. 2. Corticotropin-releasing factor (CRF)-related peptides in ischemic heart disease, left ventricular hypertrophy (LVH) and heart failure. The Vevo 770 will be used to (a) assess the effect of CRF on LVH and development of heart failure, and (b) the cardioprotective effects of CRF-related peptides in myocardial ischemia. For both aims, high quality serial assessment with noninvasive imaging is essential. 3. Role of the tyrosine kinase receptor fetal liver kinase (Flt3) and its ligand (FL) in the myocardium. The Vevo 770 will be used for characterizing cardiac function in Flt3-knockout and FL-knockout mice under physiological and pathological (ischemic) conditions. A detailed analysis of global and regional left ventricular function with high image quality is essential in this project. 4. Role of reactive oxygen species (ROS)-producing NOX-family NADPH oxidases in diabetic cardiomyopathy (CMP). The Vevo 770 will be used to investigate the role of NOX-derived ROS in the development of diabetic CMP. LVH and diastolic dysfunction are hallmarks of diabetic CMP, and thus repetitive exact measurement of these parameters will be essential for this project. 5. Cardiac metabolic pathways in health and disease. The Vevo 770 will be used to determine the role of mammalian target of rapamycin complex 1 and 2 (mTORC1 and mTORC2) in cardiac pathways of energy metabolism and protein turnover (protein synthesis versus protein degradation by the ubiquitin proteasome pathway) in healthy mice and in models of metabolic and cardiovascular disease.