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Hall Plan

Hallenplan Biomedica 2017

Day 2 // Session 3, Blauwe Zaal

Cardiac Monitoring

Dr. Claudia Goettsch

Dr. Claudia Goettsch (Chairman)

Universtiy Hospital RWTH Aachen, DE

Scientific Group Leader

Curriculum vitae

06/2016
Research group leader RWTH Aachen University Hospital
Department of Internal Medicine I
Research focus: Cardiovascular calcification

06/2011 – 5/2016
Senior Postdoctoral Research Fellow, Harvard University Medical School
Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine
Brigham and Women’s Hospital, Boston, MA, USA
Research focus: Cardiovascular calcification

09/2007 – 05/2011
Junior group leader, Lab manager
Technical University, Dresden
Division of Endocrinology, Diabetes and Bone Diseases
Department of Internal Medicine
Research focus: Bone-vascular-axis

10/2006 – 08/2007
Maternity leave

02/2007
PhD defense
Title: “Regulation of oxidative stress by biomechanical forces and high fat diet in the cardiovascular system”
magna cum laude

08/2003 – 09/2006
PhD student
Department of Vascular Endothelium and Microcirculation, Medical Faculty, Technical University Dresden, Germany,
PhD program “Metabolism and Endothelium”
Mentor: Prof. Dr. rer. nat. Henning Morawietz

09/1998 – 07-2003
Study of Nutritional Science
Friedrich Schiller University Jena, Germany

01/07/2003
Diploma (Dipl. Trophologe)

Abstract

Pathological calcific mineral deposition within the soft tissue has emerged as a predictor of and contributor to cardiovascular (CV) morbidity and mortality. Evidence suggests that coronary artery calcification particularly when present as microcalcification, reduces plaque integrity and triggers rupture and subsequent acute myocardial infarction, a global health threat and socio-economic burden. In addition, calcific aortic valve disease causes aortic stenosis and chronic heart failure. Particularly, patients with chronic kidney disease (CKD) are highly susceptible for vascular and valvular calcification and thus harbor a higher risk for CV complications due to calcification compared to non-CKD patients. Although this disorder causes several devastating clinical problems medical therapies remain unavailable. It is well accepted that the pattern/density of plaque calcification is an essential variable in addition to the calcification volume to predict cardiac events. Clinical data showed an inverse correlation of CV morbidity and the density of calcification present within the arterial plaque. Computational modelling suggests that microcalcifications in the fibrous cap may promote destabilization of the plaque. Recently, we could show that calcification morphology and collagen density – a classical characteristic of plaque vulnerability - are interlinked. We found that extracellular vesicles (EV) released from calcifying smooth muscle cells are the smallest nidus for microcalcification formation and maturation. On a molecular level, we demonstrated that sortilin, a lysosomal sorting receptor, regulates the calcification competence of these EVs. Sortilin regulated the loading of the calcification protein “tissue nonspecific alkaline phosphatase” (TNAP) into EVs, thereby conferring their calcification potential. In an atherosclerotic mouse model of Ldlr-deficiency, sortilin-deficiency reduced aortic calcification but did not alter bone mineralization. Future studies of cardiovascular calcification may need to recreate aspects of the in vivo situation in order to assess the importance of intercellular communication and interactions between cells and the extracellular matrix. This requires a detailed understanding of the tissue to be modeled including cell populations, extracellular matrix components, biomechanics, and true pathologic endpoints. Calcification research, therefore, requires a truly multi-disciplinary approach in order to connect these various aspects of the disease.

Dr. Arthur Bouwman

10:15 - The clinical perspective of monitoring vital instability

Dr. Arthur Bouwman

Catharina Ziekenhuis, NL

Anesthetist

Curriculum vitae

Arthur Bouwman started his medical training in the University of Groningen. After his graduation in 2001 he started his clinical work in the intensive care unit of the Leiden University Medical Center and became involved in a research project that focused on hemodynamic monitoring and fluid management in intensive care patients. In 2002 he started his residency training in anesthesiology, which he combined with his PhD on the cardioprotective properties of inhalational anesthetics. In an experimental lab model he investigated signal transduction pathways involved in anesthetic-induced cardioprotection against ischemia and reperfusion injury. He particularly focused on the interaction of protein kinase C, reactive oxygen species and ATP-sensitive mitochondrial potassium channels in the healthy and also diabetic rat heart. He finished his PhD in 2006 and in 2010 he started to work as anesthesiologist in the VU University Medical Center and focused on cardiothoracic anesthesia. He continued his research and focused on perioperative cardiovascular function, myocardial perfusion and hemodynamic monitoring in surgical patients under anesthesia using contrast-enhanced echocardiography, transoesophageal echocardiography combined with invasive and non-invasive hemodynamic monitoring modalities. He received several research grants and supervised several PhD students. In 2013 he change positions and moved his clinical practice and research to the Catharina Hospital in Eindhoven.  His special interest for cardiothoracic anesthesia remained and continued his research interest in advanced perioperative hemodynamic monitoring techniques and decision support in collaboration with Professor Erik Korsten. Smart cardiovascular monitoring systems that detect patient deterioration in an early time-frame and supports clinical decision making is now his main focus. 

Abstract

Clinical decision making in the perioperative period is frequently guided by information derived from cardiovascular monitoring technology, which improved peri-procedural care and safety. These monitoring techniques are traditionally restricted towards high acuity departments taking care of the most critically ill patients. After recovery of cardiovascular stability these patients are transferred to lower acuity settings or the general ward.

Current clinical practice however is challenged by a patient population that is older, more diseased and undergo more extensive procedures while hospital resources remain unchanged.  Combined with the notion that patient deterioration in most cases can be detected long before critical incidents requiring ICU admittance occur, the clinical interest for solutions to guide clinical decision making in patients at risk has increased. Many hospitals included early warning systems combined with rapid response teams in their clinical practice to allow early intervention in case of deterioration. The reported impact of early warning systems on outcome are variable, and relate the used risk score, level of adherence and specific interventions coupled to the early warning system. Technology developments made less invasive and  more unobtrusive technologies available that allow continuous vital signs monitoring for a larger group of patients in a wide range of care settings, even in the general ward environment. While trend monitoring cardiovascular vital signs may better detect patient deterioration in an early time frame, these large amounts of  continuously generated vital sign data needs to be adapted in the clinical work flow with respect to data responsibility, data interpretation and clinical decision making. This implicates that ultimately integration of smart algorithms based on analytics in clinical practice is warranted to exploit the full potential of these large vital sign datasets for predictive risk assessment and clinical decision support on vital instability.

Dr. Virginie D'Orio

10:25 - Telemonitoring in heart failure

Dr. Virginie D'Orio

CHU of Liège, BE

Department of Cardiology

Curriculum vitae

2014
Certification : ECMO and other circulatory and respiratory support
University Pierre et Marie Curie, Paris

2015
Cardiology Specialist (Ulg)

2009
Medical doctor (Ulg)

Abstract

Chronic Heart Failure is a major public health problem in industrialized countries.  Despite improvement of medical practice, the prognosis remains poor with hight rate of mortality and morbidity. The hospitalization costs are in perpetual increase.

To improve the outcomes in heart failure, home monitoring is in continued development from many years, to decrease hospitalisation rates, mortality and to improve patient quality of live. The approach has been integrated in the recent Heart Failure Guidelines form the European Society of Cardiology.

Telemonitoring is the use of communication technology to monitor clinical status of the patient, by collecting data without the need for face-to-face contact. The aim is to efficiently enhance communication between patients and medical practitioner and has the potential to improve outcomes through early intervention.

Telemonitoring holds particular promise for patients with heart failure: it can lead to early detection of deterioration in their health status, with an increase in weight, heart rate, blood pressure or symptoms over a period of days. A system of frequent monitoring can alert clinicians to this early signs and symptoms of decompensation, providing the opportunity for intervention before patients become severely ill and require hospitalization.

Moreover, patients’ participation in communicating information about their clinical parameters and health status on a daily basis could have a favorable effect on their health behavior, including adherence to medical recommendations. Some informations can be add to the program: the involvement of the patient in his own treatment is a part of the multidisciplinary approach, which also improve survival.

Some studies didn’t show improvement of mortality or hospitalisation, other did. It  makes sense that simple monitoring doesn’t modify the curse of the disease unless action results. Some population have higher risk of new acute decompensation of chronic heart failure that we could avoid, maybe we should focus on this population to be more effective.

Lars Mulder

10:35 - LifeTec Group - Enabling medical innovation using realistic assessment, lifelike training, and business acceleration

Lars Mulder

LifeTec Group, NL

Director of Operations

Curriculum vitae

In 2002 Lars Mulder graduated as Biomedical Engineer in cardiovascular regenerative medicine from the
Eindhoven University of Technology and in 2007 obtained his PhD in Dentistry and Orthopedics from the
Universiteit van Amsterdam. He moved back to Eindhoven for a 2.5-year postdoctoral research position about
CT imaging of bone disease and treatment in the Orthopedic Biomechanics group of the TU/e.

He joined HemoLab BV in 2010 and in 2012 he was co-founder of LifeTec Group BV with its goal to
assess, develop, and commercialize innovative healthcare technology and related services. Has held positions as project manager and Manager Orthopedics and is currently Director of Operations at LifeTec Group.

In 2016 he was co-founder of Meliora Medical BV, a spin-off company of LifeTec Group and the TU/e
aiming to develop and commercialize innovative treatment for spinal afflictions. The first product is a motionpreserving
artificial disc prosthesis to surgically treat chronic neck and back pain.

Abstract

The vision of LifeTec Group is that everyone should be able to benefit from the availability of the best quality (bio)medical products; patients to get the best treatment for their condition and clinicians to be able to give their patients just that. LifeTec Group applies three modes to make a difference. First, as a preclinical contract research organization, LifeTec assesses the performance and safety of medical innovations. We believe that this has to be done in a setting that represents the true clinical situation as realistically as possible. With LifeTec’s heart valve testing platforms, isolated beating heart platforms, and isolated ex vivo blood vessel platforms all cardiological and cardiac surgery products and therapies can be assessed. LifeTec’s ex vivo osteochondral platform allows realistic assessment of cartilage and bone disease treating products. Next to that LifeTec’s expertise and pragmatic approach is applied to all sorts of clinical domain technologies. All of LifeTec’s platform technology can be considered alternatives to animal studies. Second, as a technology and training provider, LifeTec’s applies its platforms as training platforms to train clinicians to correctly use new technologies before operating on patients or to extend their skills with existing procedures. Third, as an acceleration provider, LifeTec supports start-ups, growing companies, multinationals exploring new avenues, and investors by performing technological and commercial feasibility studies, network building, adopting new technologies, and making expertise and facilities available. All to propel the technology and the companies forward so to increase the chances for innovative technology to reach the market. An example of this is the recent founding of Meliora Medical, a joint spin-off of LifeTec Group and the Eindhoven University of Technology to develop and commercialize an innovative technology to serve as artificial intervertebral disc prosthesis to successfully treat chronic neck and back pain while preserving freedom of motion.

Linda Eerikäinen

10:45 - Towards continuous unobtrusive atrial fibrillation monitoring with wrist-worn photoplethysmography

Linda Eerikäinen

Eindhoven University of Technology, NL

Doctoral candidate at Department of Electrical Engineering

Curriculum vitae

Linda Eerikäinen completed her B.Sc. in Biomedical Engineering in Aalto University, Helsinki, Finland, and continued her studies in T.I.M.E. double degree program receiving the M.Sc. in Biomedical Engineering in 2015 from Aalto University and Politecnico of Milan, Italy. Her graduation project, which was carried out at GE Healthcare Finland, was about electroencephalogram-based seizure detection in patients in the intensive care. In February 2015, Linda started as a Ph.D. candidate in Eindhoven University of Technology, the Netherlands, in the Biomedical Diagnostics research group within Signal Processing Systems, Department of Electrical Engineering. The topic of her Ph.D. research is cardiac arrhythmia monitoring, focusing in particular on wearable solutions. The project is in collaboration with Philips Research and Catharina Hospital Eindhoven.

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia affecting 1.5-4 % of the general population in the Western countries. AF increases the risk of stroke, congestive heart failure, hospitalization, and death, and has become one of the most important health issues in our society. The arrhythmia develops from paroxysmal, i.e., occasional manifestations, through persistent to permanent. AF can be asymptomatic, and therefore remain undiagnosed before it has been already developed to persistent or has led to a stroke. The prevalence of AF is increasing, and its medical, social, and economic aspects are expected to worsen in the coming decades.

The diagnostic methods for detecting AF vary in costs, invasiveness, and detection sensitivity. The Holter monitoring, which is an electrocardiogram recording usually performed for 24 or 48 hours, is an essential tool in the diagnosis of AF. However, rare episodes of arrhythmia, such as paroxysmal AF, might not occur during the measurement period and are therefore missed. The highest sensitivity for diagnosing paroxysmal AF is reached with implantable devices that monitor continuously for long-term, but these devices, which require the insertion by surgical procedures, are costly.

Photoplethysmography (PPG) is an optical measurement to detect blood volume changes in the human tissue. The measurement principle can be used in wearable applications and provides means to detect heart rate from the blood volume changes. In AF, the heart rate is irregularly irregular. The irregularity can be evaluated from the pulse intervals extracted from the PPG signal. In 24-hour measurements, rhythm irregularities were evaluated in 30-second windows and windows containing AF were detected with 97% sensitivity. The wrist-worn device can be worn for long periods and therefore could provide means to detect also the rare episodes of paroxysmal AF. In addition, wrist-worn PPG could be used as a low-cost method for screening high risk populations for asymptomatic AF. The final diagnosis could be further confirmed with traditional methods. The earlier AF is detected, the earlier the treatment can start. This can prevent the progression of the disease, reduce the risk of stroke and other adverse events, thus leading to lower healthcare costs and longer life expectancy of the patient.

Dr. Claudia Goettsch

10:55 - Role of microcalcification in cardiovascular disease

Dr. Claudia Goettsch

Universtiy Hospital RWTH Aachen, DE

Scientific Group Leader

Curriculum vitae

06/2016
Research group leader RWTH Aachen University Hospital
Department of Internal Medicine I
Research focus: Cardiovascular calcification

06/2011 – 5/2016
Senior Postdoctoral Research Fellow, Harvard University Medical School
Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine
Brigham and Women’s Hospital, Boston, MA, USA
Research focus: Cardiovascular calcification

09/2007 – 05/2011
Junior group leader, Lab manager
Technical University, Dresden
Division of Endocrinology, Diabetes and Bone Diseases
Department of Internal Medicine
Research focus: Bone-vascular-axis

10/2006 – 08/2007
Maternity leave

02/2007
PhD defense
Title: “Regulation of oxidative stress by biomechanical forces and high fat diet in the cardiovascular system”
magna cum laude

08/2003 – 09/2006
PhD student
Department of Vascular Endothelium and Microcirculation, Medical Faculty, Technical University Dresden, Germany,
PhD program “Metabolism and Endothelium”
Mentor: Prof. Dr. rer. nat. Henning Morawietz

09/1998 – 07-2003
Study of Nutritional Science
Friedrich Schiller University Jena, Germany

01/07/2003
Diploma (Dipl. Trophologe)

Abstract

Pathological calcific mineral deposition within the soft tissue has emerged as a predictor of and contributor to cardiovascular (CV) morbidity and mortality. Evidence suggests that coronary artery calcification particularly when present as microcalcification, reduces plaque integrity and triggers rupture and subsequent acute myocardial infarction, a global health threat and socio-economic burden. In addition, calcific aortic valve disease causes aortic stenosis and chronic heart failure. Particularly, patients with chronic kidney disease (CKD) are highly susceptible for vascular and valvular calcification and thus harbor a higher risk for CV complications due to calcification compared to non-CKD patients. Although this disorder causes several devastating clinical problems medical therapies remain unavailable. It is well accepted that the pattern/density of plaque calcification is an essential variable in addition to the calcification volume to predict cardiac events. Clinical data showed an inverse correlation of CV morbidity and the density of calcification present within the arterial plaque. Computational modelling suggests that microcalcifications in the fibrous cap may promote destabilization of the plaque. Recently, we could show that calcification morphology and collagen density – a classical characteristic of plaque vulnerability - are interlinked. We found that extracellular vesicles (EV) released from calcifying smooth muscle cells are the smallest nidus for microcalcification formation and maturation. On a molecular level, we demonstrated that sortilin, a lysosomal sorting receptor, regulates the calcification competence of these EVs. Sortilin regulated the loading of the calcification protein “tissue nonspecific alkaline phosphatase” (TNAP) into EVs, thereby conferring their calcification potential. In an atherosclerotic mouse model of Ldlr-deficiency, sortilin-deficiency reduced aortic calcification but did not alter bone mineralization. Future studies of cardiovascular calcification may need to recreate aspects of the in vivo situation in order to assess the importance of intercellular communication and interactions between cells and the extracellular matrix. This requires a detailed understanding of the tissue to be modeled including cell populations, extracellular matrix components, biomechanics, and true pathologic endpoints. Calcification research, therefore, requires a truly multi-disciplinary approach in order to connect these various aspects of the disease.

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