COEUR COEUR AN N UA L R EPORT
2004
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ANNUAL REPORT 2004
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COEUR ANNUAL REPORT
2004
Erasmus MC Rotterdam The Netherlands
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Contents a
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C O E U R Annual Report 2004
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Preface
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Mission
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Abbreviations
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Organization
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Input Personnel Funding
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Education PhD training program MSc training program Electives for medical students
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Research Research themes Research groups PhD students Doctorate degrees Publications Patents Awards & Grants
12 25 36 50 52 82 83
Lectures Inaugural & farewell lectures COEUR lectures
86 87
Communication Website Cri du COEUR
89 89
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C O E U R Annual Report 2004
3
Preface a
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Cardiovascular Research School Erasmus University Rotterdam (COEUR) Participating institutes Cardiology Cardiothoracic Surgery Pharmacology Pediatric Cardiology Neurology Radiology Biochemistry Hematology Anesthesiology Internal Medicine Surgery -
Executive Board Prof. Maarten L. Simoons, chairman Prof. Ad J.J.C. Bogers Prof. A.H. Jan Danser Prof. Wim A. Helbing Prof. Peter J. Koudstaal (Vascular Neurology) Prof. Gabriel P. Krestin Prof. Jos M.J. Lamers Dr. Frank W.G. Leebeek (Thrombosis and Hemostasis) Prof. Don Poldermans Dr. Anton H. van den Meiracker (Vascular Medicine) Prof. Hero van Urk (Vascular Surgery) Prof. N. (Klaas) Bom, scientific director Dr. Jan Willem de Jong, education officer
Scientific Advisory Board Prof. Jos R.T.C. Roelandt, chairman Prof. Jan H.J. Hoeijmakers, KNAW Research School MGC Prof. Albert Hofman, KNAW Research School NIHES Prof. M.G. Myriam Hunink, Erasmus MC Research Committee Prof. Huib A.P. Pols, KNAW Research School Molecular Medicine Prof. Harry A.J. Struijker Boudier, KNAW Research School CARMA Prof. Wiek H. van Gilst, ICIN a
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Prof. Maarten L. Simoons, chairman COEUR
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C O E U R Annual Report 2004
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COEUR, the cardiovascular research school at Erasmus MC, continues to grow. This continuing success has been possible through the endeavors of basic and clinical investigators, including 132 research fellows/PhD students by the end of 2004. A PhD was awarded to 20 candidates (promovendi), who successfully completed their research projects and defended their theses. We would like to single out Pedro Lemos and Miklos Kertai, who received their PhD diploma cum laude. COEUR research led to 364 publications, an increase by 22% compared to the preceding year. COEUR was pleased to see the appointments of both Dr. Don Poldermans (Anesthesiology/ Vascular Surgery) and Dr. Luc Jordaens (Cardiology) as professor. The Department of Anesthesiology joined COEUR, which now includes a total of eleven departments at Erasmus MC. It comprises all research conducted within the Departments of Cardiology, Cardiothoracic Surgery, Pediatric Cardiology and Pharmacology as well as the cardiovascular research conducted in the Departments of Anesthesiology, Biochemistry, Hematology, Internal Medicine, Neurology, Radiology and Surgery. This is a true collaboration, as will be evident from the updated list of research projects, organized in six themes. Sixteen out of 55 projects (29%) involve two or more departments at Erasmus MC. Part of the research is conducted in collaboration with other research schools, including NIHES and Molecular Medicine. In 2004 more than ₠ 6.0 million was awarded to COEUR projects through special funds from international,
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national and institutional sources. Part of COEUR’s mission is to train investigators and future leaders in cardiovascular research. To this end six new PhD training courses were organized, while members of our staff also participated in national PhD courses related to cardiovascular research. Electives were organized again for second-year medical students. In 2003 and 2004, much effort was put into preparation of a program of Master of Science Clinical Research. We were pleased to see that the NederlandsVlaamse Accreditatie Organisatie (NVAO) accredited this program, and we look forward to enrolling the first MSc students in 2005. An Annual Report is rather factual, including descriptions of research programs, publication lists, honors received and other important facts. Yet, together they may conceal the true message. In our six research programs, we see exciting developments related to molecular and systemic biology, and pharmacology, of the cardiovascular system; to atherosclerosis; to heart failure and stroke; to new exciting modalities in clinical epidemiology, congenital heart disease in infants and adults as well as surgical, interventional and device therapy. It is a pleasure indeed to work with so many gifted, enthusiastic and often original investigators. It is a particular pleasure to recognize again that COEUR research contributes to improve the quality of life of patients with diseases of the heart and/or blood vessels. Prof. Maarten L. Simoons, chairman COEUR C O E U R Annual Report 2004
5
Mission a
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Organization a
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COEUR’s mission is to conduct and promote worldclass cardiovascular research, and to train future leaders in the cardiovascular field, ultimately aiming at improved quality of life of the general population and, in particular, new and better perspectives for patients with diseases of the blood vessels and the heart. To achieve this mission, COEUR is structured to conduct innovative research and to provide high quality training in research related to the cardiovascular system. The research programs include a wide spectrum of disciplines, all focused on elements of cardiovascular disease, including cardiac vascular (molecular) biology, (patho)physiology, pharmacology, biomedical engineering and clinical epidemiology, leading to prevention, detection, diagnosis and management of cardiovascular disease. COEUR recognizes the need for an interactive, multi-disciplinary approach to achieve optimal results, encouraging national and international collaboration.
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C O E U R Annual Report 2004
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Abbreviations
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CARMA – CArdiovasculaire Research school Maastricht Amsterdam COEUR – Cardiovasculaire Onderzoekschool Erasmus Universiteit Rotterdam [Cardiovascular Research School Erasmus University Rotterdam] ECTS – European Credit Transfer System Erasmus MC – Erasmus University Medical Center Rotterdam EUR - Erasmus University Rotterdam Fte – Full Time Equivalent ICIN – Interuniversitair Cardiologisch Instituut Nederland [Netherlands Interuniversitary Cardiology Institute] KNAW – Koninklijke Nederlandse Academie voor Wetenschappen [Royal Netherlands Academy of Arts and Sciences] LUMC – Leids Universitair Medisch Centrum [Leiden University Medical Center] MGC – Medisch Genetisch Centrum [Medical Genetic Center] NIHES – Netherlands Institute for HEalth Sciences NVAO – Nederlands-Vlaamse Accreditatie Organisatie [Netherlands-Flemish Accreditation Organization] NWO – Nederlandse organisatie voor Wetenschappelijk Onderzoek [Netherlands Science Foundation] STW – Stichting Technische Wetenschappen [Technical Sciences Foundation]
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The COEUR organogram below depicts the representation of the participating departments in the Executive Board, the advisory role of the Scientific Advisory Board, and the chain of commands from the Board of Directors, Erasmus MC, to the education and research project leaders in various themes. In May 2004, the Department of Anesthesiology joined COEUR, appointing Prof. Don Poldermans as its representative in the Executive Board. COEUR departments
Anesthesiology Biochemistry
Board of Directors, Erasmus MC
Cardiology
Cardiothoracic Surgery Hematology
COEUR Scientific Advisory Board
COEUR Executive Board
Internal Medicine Neurology
Pediatric Cardiology Pharmacology
Management Team
Radiology
Scientific Director
Surgery
Scientific Secretariat
Theme I
Theme 2
Theme 3
Theme 4
Theme 5
Theme 6
Clinical Epidemiology
Congenital Heart Disease
Surgical-, Interventional- and Device Therapy
Imaging & Diagnostics
Vascular Medicine, Atherosclerosis, Heart Failure and Stroke
Cardiac and Vascular Biology, and Pharmacology
C O E U R Annual Report 2004
7
Input of personnel and funds a
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Personnel
PhD training program
COEUR faculty invested much time in research and education. As of 2004, the research school included 132 fellows/PhD students. Project leaders Prof. Hans Jansen and Prof. Pramod R. Saxena retired. The EUR Trustfonds has appointed Dr. Don Poldermans (Anesthesiology/Surgery) to Professor of Perioperative Cardiovascular Care, and Dr. Luc Jordaens (Cardiology) to Professor of Experimental and Clinical Electrophysiology of the Heart.
COEUR provides thorough and institutionalized training for fellows/PhD students (promovendi) to become independent scientists. Research electives are part of the curriculum at Erasmus MC to become a medical doctor. A special program for excellent and motivated students offers the possibility to become Master of Science in Clinical Research at Erasmus MC. The PhD program by COEUR provides the final training for students with a basic training in medicine, but also in related fields. The PhD students take part in individual training programs, under close guidance by their supervisors.
Funding Funds for special projects increased from M₠ 3.7 (2003) to M₠ 6.0 (2004). About half of the PhD students were funded directly by Erasmus MC and Erasmus University Rotterdam. Substantial indirect government funding was obtained through ICIN, KNAW, NWO and STW, whereas the remainder was provided by charity organisations and the industry. Some details are presented in the Awards & Grants section. COEUR research funding for special research projects, granted in 2004. € 1 = University and hospital funds; € 2 = KNAW (ICIN), NWO and STW funds; € 3 = Funds from charities, industry et cetera.
Theme
€1
€2
€3
50,000 261,000
682,000
882,000
2
615,000
133,000
3
175,000
923,000
4
250,000
1
260,000
6 Total
119,000 1,475,000
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Education
216,000 736,000
2,220,000
C O E U R Annual Report 2004
3,085,000
3rd party funding direct funding
indirect funding
Funding source of COEUR PhD students (n=132).
The table provides a breakdown of new funds— totalling ₠ 6,043,000—for special projects. The grants do not include the substantial industrial donations in the form of equipment and materials. Furthermore, excluded are also the substantial sums raised to conduct phase II and phase III clinical trials by the contract research organization Cardialysis, which is formally independent of, but closely related to Cardiology. Due to the extensive collaboration with groups outside COEUR, also regarding fund raising, the figures mentioned should be regarded as indicative. For overhead costs, the Erasmus MC provided ₠ 44,000 in 2004. The participating departments contributed ₠ 110,000 to cover salaries and running expenses, e.g. 1.7 fte salaries, printing costs of PhD Training Brochure and Annual Report, organization PhD courses, and accreditation MSc program. COEUR acknowledges the sponsorship of the Netherlands Heart Foundation, which contributed to the printing cost of some course books. The Executive Board distributed ₠ 46,000, obtained from Erasmus MC Breedtestrategie funds, for equipment.
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This program consists of three components: A. A number of (mandatory) training courses, offered by Erasmus MC; B. Elective COEUR courses, to suit the needs of individual PhD students (see below), complemented by monthly research seminars; C. A series of courses, organized by other Erasmus MC research schools and by other organizations in the Netherlands, in which COEUR trainees may participate. PhD students were required to complete at least twelve modules of one week each, or equivalent (18 ECTS), during their 3- to 4-year training period.
A. Erasmus MC training program COEUR PhD students often take part in the centrally organized Erasmus MC training program, which includes the courses Biostatistics, English and Animal Experimentation. B. COEUR courses and seminars COEUR organized the following PhD courses focusing on methodology for cardiovascular research: Date ’04
Course/participants
Organizers
Mar 22-25
Atherosclerosis research (33 participants)
de Crom (Cell Biology/Surgery), Krams (Cardiology)
Mar 29-Apr 2
Cardiovascular imaging and diagnostics (45 pp) Design of cardiovascular trials (24 pp) Neurovascular diseases (16 pp) Heart-failure research (29 pp) Congenital heart disease (14 pp)
Pattynama (Radiology), van der Steen (Cardiology), de Feyter (Cardiology/Radiology) Boersma, Scholte op Reimer, Simoons (Cardiology) Koudstaal, Dippel, van Kooten (Neurology) Balk, Duncker (Cardiology) Bogers (Cardiothoracic Surgery), Helbing (Pediatric Cardiology), Meijboom (Cardiology)
Apr 5-8 Oct 4-8 Oct 11-15 Sep 22-Oct 1
C O E U R Annual Report 2004
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The courses were attended by COEUR PhD students and MD residents, but also by promovendi from other Erasmus MC departments and sister universities. To the participant numbers given above, single-day participants should be added. New PhD students/fellows were encouraged to take part in at least six of the twelve COEUR courses, offered in a two-year cycle, to get an Date ’04 Jan 23 Feb 20 Mar 26 Apr 16 May 28
Jun 25 Sep 24 Oct 22 Nov 26 Dec 17
Research seminar Cardiac and vascular biology, and pharmacology Hypertension and stroke Cardiovascular imaging Revascularization therapy for atherosclerosis Cardiology of the right ventricle Tetralogy of Fallot as an experiment of nature Cardiovascular epidemiology Molecular signaling in cardiac health and disease Atherosclerosis and heart failure Electrophysiology Myocardial imaging
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overview of the methodologies used in COEUR. An extensive PhD Training Brochure was prepared for COEUR promovendi. The electronic version is available on www.coeur.nl/education.html. In 2004, COEUR started a series of research seminars, which took place in the Netherlands Architecture Institute. An average of 30 COEUR PhD students, MD residents and faculty members participated. Topics and organizers: Organizers/chair Danser/Teunissen (Pharmacology), Lamers (Biochemistry) Koudstaal (Neurology), van den Meiracker (Internal Medicine) Krestin (Radiology) van Urk (Surgery), van der Giessen (Cardiology) Helbing (Pediatric Cardiology), Bogers (Cardiothoracic Surgery), Meijboom (Cardiology) Boersma (Cardiology), Dippel (Neurology) Lamers (Biochemistry), Duckers (Cardiology), Duncker (Cardiology) Balk, Boersma (Cardiology) Jordaens (Cardiology) Pattynama (Radiology), de Feyter (Cardiology/ Radiology), van der Steen (Cardiology)
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C. Other courses The third major training component encompasses courses outside the cardiovascular research school, e.g. the national cardiovascular PhD courses in Papendal/Arnhem, coorganized by COEUR (Duncker, Krams). During October 18-22, 2004, concurrent courses took place on Vascular biology and Cardiac function and adaptation.
MSC training program In collaboration with the Departments of Internal Medicine, Hematology, Pediatrics and Epidemiology, COEUR has launched a new training program for excellent medical students, to become Master of Science in Clinical Research. In April 2004, the Nederlands-Vlaamse Accreditatie Organisatie (NVAO) has accredited this MSc program at the Erasmus University Rotterdam.
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Electives for medical students The departments participating in COEUR organized a broad range of educational activities in the medical curriculum Erasmus Arts 2007. Thirty 2nd-year medical students elected for the COEUR training program Cardiovascular Diseases, which took place during June 7 - July 2, 2004. Research projects for a period of 21 weeks for 4thyear medical students were part of the curriculum mentioned; student-researchers received a warm welcome at COEUR departments. Its international networks enabled students to arrange fellowships and clinical internships abroad, and to participate in international student exchange programs. Through the years, education in cardiovascular disease ranks among the best courses in the curriculum, as judged by Erasmus MC students.
Programs and snapshots are available on www.coeur.nl/archive.html.
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C O E U R Annual Report 2004
C O E U R Annual Report 2004
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Research a
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Research themes Cardiovascular research, as coordinated by COEUR, is organized in six themes: THEME 1 - CARDIAC AND VASCULAR BIOLOGY, AND PHARMACOLOGY Program code: EMC 05-01-43-01-01 Coordinators: Danser, Duncker, Lamers Modulation of vascular tone Calcitonin gene-related peptide (CGRP), probably the main factor initiating migraine headache, dilates blood vessels via CGRP receptors. The Department of Pharmacology has, for the first time in human blood vessels, demonstrated
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the endogenous receptor for the angiotensin metabolite angiotensin-(1-7). The Mas receptor and the AT1 receptor form a constitutive heterooligomeric complex that is unaffected by the presence of agonists or antagonists of the two receptors. In vivo, Mas acts as an antagonist of the AT1 receptor; mice lacking the Mas gene show enhanced Ang II-mediated vasoconstriction in mesenteric microvessels. Pathophysiology of lipid metabolism Basic research on this topic was discontinued due to the retirement of several senior investigators. The results are being published in the international literature and in theses. Clinical
“Calcitonin gene-related peptide receptors are operative in the porcine carotid circulation.” Uday Arulmani. Academic thesis, Erasmus University Rotterdam, 2004 the existence of multiple CGRP receptor subtypes. Furthermore, in collaboration with the Department of Cardiothoracic Surgery, it was observed that angiotensin II (Ang II) is capable of dilating human coronary microarteries. This effect depends on stimulation of angiotensin II type 2 (AT2) receptors, and involves both NO and bradykinin. AT2 receptors counteract the well-known constrictor effects of Ang II, and their stimulation may underlie, at least in part, the beneficial cardiovascular effects of reninangiotensin system blockers. On the other hand these beneficial effects may also be mediated by the receptor Mas, which were identified as 12
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research related to lipid disorders continued in theme 2. Cardiovascular repair and remodeling Early post-infarct remodeling of the non-infarcted area of the pig heart appears associated with decreased expression of the sarcoplasmic reticulum Ca2+ pump, partial breakdown of troponin I (TnI), likely at a calpain cleavage site 193, and depressed contractility measured in individual cardiomyocytes. TnI proteolysis is correlated with depressed contractile function. Future experiments will address the hypothesis that the chronic neurohumoral activation
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VASCULAR PHARMACOLOGY OF MIGRAINE The headache during a migraine attack is most probably the result of cranial vasodilatation. Therefore, study of the pharmacological mechanisms underlying this vasomotion is pivotal for the understanding and better treatment of migraine. Current research focuses on the study of human isolated blood vessels, obtained from the Departments of Neurosurgery (middle meningeal artery) and Cardiothoracic Surgery (coronary artery and saphenous vein), used to study potential cardiovascular side effects of antimigraine drugs. In addition, we have recently started investigations on the influence of female sex steroids on the occurrence of migraine. In this project, we study the influence of estrogen and progesterone on vasodilatation in response to CGRP (calcitonin generelated peptide, the putative peptide causing cranial vasodilatation during migraine) in an in vivo rat model, allowing a continuous measurement of the diameter of cranial blood vessels. A second project is based on the finding that mutations in the gene encoding the P/Q type calcium channel, are involved in migraine. We will study the influence of this calcium channel on the release of CGRP in transgenic mice, containing the same mutations that were demonstrated in migraine patients. The results of these studies will provide more insight into the pathophysiology of migraine, as well as new avenues for the development of antimigraine drugs. In 2004, the research on the Vascular Pharmacology of Migraine was awarded with the Migraine & Women’s Health Research Award of the American Headache Society, as well as the prestigious VENI award of NWO. a a a Dr. Antoinette Maassen van den Brink (Pharmacology) that occurs after a myocardial infarction, is responsible for increased susceptibility of TnI to calpain by increasing diastolic free Ca2+ level and TnI phosphorylation. The experiments may underscore the rational basis for the treatment of infarcted patients with beta-blockers and ACE inhibitors, which is known to improve left
ventricular function, slows progression of heart failure and reduces risk of sudden death. Increased myocardial mass, such as occurs during left ventricular remodeling, requires vascular adaptations to maintain a healthy wellperfused myocardium. Insufficient structural adaptations can lead to recurrent myocardial C O E U R Annual Report 2004
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hypoperfusion and may thus contribute to the transition from asymptomatic ventricular dysfunction to overt heart failure. Recently, the Experimental Cardiology Laboratory found perturbations in oxygen supply to occur in the post-infarct hypertrophied heart during treadmill exercise, which was associated with an increased metabolic vasodilator influence on the coronary microvessels via K+ATP channels. Interestingly,
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despite increased circulating endothelin levels during exercise, the coronary vasoconstrictor influence of endothelin was abolished in remodeled hearts reflecting an adaptive response, likely at the endothelin receptor level, to minimize the perturbation. New programs have been initiated to investigate the modulation of angiogenesis, myogenesis and tissue engineering. Although
THEME 2: ACROSS FRONTIERS OF DISCIPLINES Cardiovascular disease is the leading cause of illness and death in the Netherlands. Therefore, it is not surprising that COEUR has a strong clinical research theme. Theme 2 (Vascular Medicine, Atherosclerosis, Heart Failure and Stroke) indeed contains a large number of clinical research groups. The first great scientific triumph of this century—the decoding of the human genome—was based on the large-scale collaboration in the Human Genome Project. This approach might have been contagious, as suggested by the joint enterprise of our clinical research groups that work together to develop and investigate novel diagnostic and therapeutic strategies: We will improve the prognosis of our patients! A course of events enhanced our clinical research possibilities. Vascular medicine is a new specialization of internal medicine. In addition to clinical challenges, vascular medicine united our hypertension, dyslipidemia, and diabetes mellitus research. In 2005, PhD students will start working on joint research projects of the microcirculation and genetics of diabetes (DiaGene study). The candidate pathways of the latter large-scale molecular study will be assessed in collaboration with specialists from different COEUR departments. Coagulation disorders in young patients with arterial thrombosis are assessed in the ATTAC study, which is a good example of collective action to identify cases. This study is ahead of schedule and most clinical research groups of COEUR are involved. The Departments of Vascular Medicine and Cardiology work together on identifying patients, who inherited cardiovascular disease. This has already resulted in new methods for multilocus analyses. These recent initiatives illustrate that COEUR offers PhD students innovative research across the frontiers of internal medicine, hematology, cardiology, and neurology. Moreover, our Clinical Epidemiology Department enables us to extend our case-control and pedigree work to a large population-based sample (ERGO or the Rotterdam Study), and our clinical research groups have a large tradition of clinical trials. a a a Dr. Eric J.G. Sijbrands, Internal Medicine 14
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atherosclerosis affects large parts of the coronary and other arteries, major lesions typically occur at predilection places, such as the origins of the arterial side branches and at the vessel wall curvatures. Apparently, biomechanical factors like wall and shear stress interact with risk factors; in this way, they are important determinants for the localization and development of atherosclerotic lesions. The mechanisms are investigated how biomechanical factors translate into vascular lesions, both at the level of gene expression and at the level of inflammation. THEME 2 - VASCULAR MEDICINE, ATHEROSCLEROSIS, HEART FAILURE AND STROKE Program code: EMC 05-01-43-01-02 Coordinators: Koudstaal, Leebeek, Simoons, van den Meiracker This theme has a predominantly clinical focus, complementing basic research in theme 1. Hypertension Hypertension can be considered as a disturbance of blood pressure regulation. The Department of Internal Medicine and its Section of Geriatric Medicine analyze the effect of ageing on vascular and cardiac structure and blood pressure regulation in a large cohort of elderly subjects with a history of falls. Angiotensin II sensitivity was found to increase in subjects with familial hypercholesterolemia. This interaction could provide an explanation for the frequently
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observed association between dyslipidemia and hypertension. Furthermore, angiotensin II itself may accelerate the process of atherosclerosis by inducing oxidative stress and modulating inflammation making this interaction even more appealing. Future studies will address mechanisms underlying the increased sensitivity to angiotensin II in conditions like hypercholesterolemia, and insulin resistance syndromes at the level of vascular wall. Aldosterone, apart from its effects on renal sodium handling, may induce (peri)vascular fibrosis and thereby accelerating cardiac and renal damage. In subjects with type 1 and type 2 diabetes mellitus with overt nephropathy, the effect of spironolactone on proteinuria, renal function and neurohormones is currently under investigation. Semicarbizide-sensitive amine-oxidase (SSAO) is supposed to contribute to vascular damage especially in diabetes mellitus. Recent studies have shown that one gene encodes for SSAO and a vascular adhesion protein (VAP). Laboratory studies have been started to explore regulation of the enzyme in adipocyte cultures, like the vascular smooth muscle cells an important soured of SSAO activity. Atherosclerosis In 2003 a large clinical trial of secondary prevention with an ACE inhibitor was completed including over 12,000 patients, with four to five years follow up. The overall results confirmed C O E U R Annual Report 2004
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a 20% reduction of cardiovascular death and myocardial infarction in patients receiving the ACE inhibitor, compared with placebo. Additional analyses in 2004 support the concept that the improved outcome in these patients is partly related to reduction in blood pressure, but also to direct vascular effects of the ACE inhibitor, including improvement of endothelial function. In patients with coronary artery disease risk can only partly be predicted from clinical factors. The Department of Cardiology demonstrated that this risk prediction can be significantly improved through the introduction of biomarkers, which reflect more closely the pathophysiology, including different aspects of vascular inflammation, thrombosis and measurements of myocardial necrosis and cardiac function. In heart–transplant recipients, allograft vasculopathy is an important cause of morbidity and mortality. Although the precise mechanism of this vasculopathy is unknown, both immunologic, like cytokine activation, and non-immunologic mechanisms are involved. In particular, relationships between cytokine activation and course of vasculopathy are investigated.
Clinical research at the Department of Radiology: Studies on magnetic resonance imaging.
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Stroke Within the setting of the Rotterdam Study, a large prospective population-based study, participants are extensively screened at baseline for cardiovascular risk factors and carefully followed during many years. Over 600 cases of stroke have developed to date. Research is focused
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on vascular inflammation (e.g. CRP, interleukines), vascular calcifications, endocrine factors, genetic aspects, and blood coagulation. Major sequellae of stroke are also studied, such as dementia and aphasia. In 2004, a new multicenter clinical trial that compares different treatment strategies has been initiated. Another program is focused on the diagnosis and management of subarachnoid hemorrhage. Highlights are the comparison of CT angiography and conventional angiography in the diagnosis of intracranial aneurysms and a sophisticated decision analysis for management of unruptured aneurysms. Thrombosis and hemostasis In order to define the role of the hemostasis process in the pathogenesis of arterial thrombosis, the Department of Hematology investigated the genetic variability in the genes involved in blood coagulation and fibrinolysis on ischemic stroke, coronary artery disease and peripheral vascular disease. Several variations in hemostasis molecules have been identified, resulting from genetic polymorphisms and post-translational modifications that contribute to the development of arterial thrombosis. Increased functional levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are associated with the risk of ischemic stroke. Also the role of genetic and functional variations in platelet receptors, such as the P2Y12 ADP receptor, which is of main importance for platelet aggregation, is under investigation. A proteomics-based research program on fibrin C O E U R Annual Report 2004
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formation and degradation and its role in arterial thrombosis has recently been started. Furthermore, a pharmacokinetic and clinical study on FVIII/vWillebrand factor concentrate in patients with severe von Willebrand disease is carried out. The Department of Hematology is
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techniques within cardiovascular medicine is a core activity of COEUR biomedical engineering. Developments range from fundamental to clinical applications: Improved intravascular diagnosis of the vascular wall, including morphological and
THEME 3 - CARDIOVASCULAR IMAGING AND DIAGNOSTICS Program code: EMC 05-01-43-01-03 Coordinators: de Feyter, Pattynama, van der Steen This theme includes fundamental research of new diagnostic modalities and the evaluation of clinical application of such methods. The strong interrelation between fundamental research on the one hand, and clinical application on the other, guarantees minimal lag time to introduce new promising methods into the clinical arena. By the same token, the inherent cooperation serves to provide relevant clinical feedback to improve the effectiveness in the developmental study groups. Biomedical engineering, echocardiography Development of new or improved diagnostic 18
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“Sirolimus-eluting stent implantation for unselected patients is safe and effective in reducing major adverse cardiac events in the ‘real world’.” Pedro Alves Lemos Neto. Academic thesis, Erasmus University Rotterdam, 2004
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“Comparison of the X-ray spectra entering the patient to those leaving the patient allows to apply extra filtering for optimal imaging, with the lowest patient dose.” Ad den Boer. Academic thesis, Erasmus University Rotterdam, 2004 involved in several studies on venous thrombotic disorders and pulmonary embolism, using newly developed anticoagulants.
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functional imaging, and vulnerable plaque detection; Ultrasound contrast agents for myocardial perfusion imaging, enhanced boundary detection and local drug delivery; Development and clinical evaluation of ultrasound transducers for real-time 3D imaging, for transesophageal imaging and for nonlinear imaging (superharmonic imaging); 3D imaging of coronary arterial lumen and wall and determination of blood velocity profile take place in coronary patients, to study wall composition, vasomotion and arterial remodeling in relation to rheological factors, action of vasoactive agents and wall shear stress and to assess stenting (accuracy of placement and long–term effects); Finally, development of a camera for real-time oxygenation imaging during thoracic surgery.
Study topics in clinically applied imaging and diagnostics include, among others, the
noninvasive imaging with magnetic resonance (MR) imaging and multidetector computed tomography (MsCT) of the heart, the vessels and the vessel wall (plaque composition characterization, imaging of the ‘vulnerable’ plaque). Other, more experimental imaging modalities include intravascular MR imaging, MR spectroscopy, Raman spectroscopy, optical coherence tomography and invasive temperature mapping of the vessel wall. Cardiac non-invasive MR and CT imaging Clinical projects include: Implementation and evaluation of MSCT to non-invasively detect significant coronary stenoses in patients with a wide spectrum of ischemic manifestations; Development of algorithms to quantify MSCT coronary stenoses; Evaluation of MSCT coronary plaque imaging: Identification, characterization and prognostic implications; Implementation and evaluation of MR-cardiac imaging to identify and quantify infarct size, left ventricular function and myocardial viability; Development of stress MR-techniques to detect myocardial ischemia. a
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THEME 4 - SURGICAL-, INTERVENTIONAL- AND DEVICE THERAPY OF CARDIOVASCULAR DISEASE Program code: EMC 05-01-43-01-4 Coordinators: Bogers, Jordaens, Serruys, van der Giessen, van Urk The technology and clinical strategy for surgical, interventional and device therapy is evolving rapidly. COEUR investigators have contributed significantly to this development, and will continue to do so. Several techniques and devices were designed, developed and evaluated in the preclinical laboratories, and subsequently introduced and tested in the clinical setting of interventional cardiology. Practice is gradually shifting towards early intervention after presentation of a patient with an acute syndrome. But also therapies for more difficult patients, who were only recently regarded ineligible, are being introduced and evaluated. This requires both development of biological tools to improve healing after injury (e.g. angiogenesis, myogenesis, wound healing) as well as development, validation, and evaluation of new catheter-based techniques to study and treat vulnerable atherosclerotic plaques before these become hemodynamically significant, as well as chronic occlusions in arteries. The research C O E U R Annual Report 2004
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line ‘Experimental interventional cardiology’ is a typical example of the constant interplay between preclinical lab and clinical interventional cardiology. The surgical projects are dedicated to clinical research in support of the introduction and development of innovative cardiac and vascular surgical techniques.
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Electrophysiogical studies Treatment of arrhythmias by ablation and/or device is evolving rapidly. In the recently built facilities at COEUR, Clinical Electrophysiology addresses the following research topics: Improved ablation of atrial arrhythmias with cryo-therapy and other energy sources; Management of atrial fibrillation, particularly in elderly patients, often with heart failure and in adult congenital heart disease; Evaluation of biventricular pacing in patients a
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Interventional cardiology Projects in the clinical catheterization laboratories are aimed at finding new methods
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“A new treatment is emerging for the diabetic patient, aimed at targeting multiple inflammatory and metabolic pathways that lead to the progression of atherosclerosis.” C. Akis Arampatzis. Academic thesis, Erasmus University Rotterdam, 2004 of percutaneous revascularization for patients with coronary artery disease, as well as noncoronary interventions (e.g. patent foramen ovale, left ventricular assist). The research and educational programs of clinical and experimental interventional cardiology are: Systemic pharmacological studies; Local drug delivery; The development and evaluation of new technology (stents, imaging); Imaging and procedural guidance (e.g. magnet navigation).
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with impaired conduction and heart failure; Assessment of implantable cardioverter defibrillators; Introduction of real-time imaging during procedures, and integration with electrophysiological and echocardiographic signals.
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In 2004, research on brachytherapy, to prevent restenosis, was discontinued, because the drugeluting stent proved to be a much more promising alternative approach. 20
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Endovascular intervention Endovascular repair of abdominal aortic aneurysms (EVAR) exists now since almost 15 years. It has created an unprecedented change in the daily practice of vascular surgeons and interventional radiologists. The results are still a matter of debate, but it is clear that EVAR is here to stay! Endovascular PTA and stenting of carotid artery stenoses (CAST) is still considered to be experimental, but several randomised
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“In-stent restenosis and acute myocardial infarction could be seen as two ‘boundaries’ of drug-eluting stent utilization.” Francesco Saia. Academic thesis, Erasmus University Rotterdam, 2004 controlled trials are underway, and the published experience sofar is encouraging: It is certainly not unthinkable that CAST will replace carotid endarterectomy in the foreseeable future. In the meantime, other endovascular techniques and materials are tested and improved. The Departments of Vascular Surgery, Interventional Radiology, Vascular Neurology and Neurophysiology are participating in several of these trials (DREAM-trial, ICSS). They are actively involved in research projects that are directly related to these problems. Carotid plaque imaging (MRI), cerebral protection devices (filters, etc.) and neuropsychological tests are incorporated in these studies. The possibility of measuring (wall) shear stress in order to predict the behavior (and potentially: rupture) of abdominal aortic aneurysms is a new and exiting addition to these research projects. Cardiosurgical research The role of new ultrasound methodology (transesophageal and 3D echocardiography) is evaluated in allograft-, autograft- and reconstructive valve surgery during and after the operation. Outcomes-research focuses on the late results of mechanical valve surgery, hypertrophic cardiomyopathy and diseases of the aorta, and to clinical decision making.
THEME 5 - CONGENITAL HEART DISEASE Program code: EMC 05-01-43-01-05 Coordinators: Bogers, Helbing, Meijboom Congenital heart disease results from multifactorial causes, including genetic alterations, and may lead to important structural abnormalities. These abnormalities may result in increased cardiac pressure and/or volume load, which may be accompanied by chronic hypoxemia. Abnormal loading conditions and/or chronic hypoxemia may persist after surgical therapy or catheter intervention. Management of congenital heart disease has improved significantly in the last decades, which has resulted in improved survival into adulthood of patients with congenital heart disease, and thus in a growing number of adult patients. Many of these patients have residual cardiac loading abnormalities, the prognosis of which is often unclear. In particular, abnormal loads are commonly imposed on the right ventricle. Residual abnormalities may cause heart failure, rhythm disturbances and may affect quality of life. Evidence–based medical treatment of impending heart failure in congenital heart disease is often lacking. Guidelines for timing of catheter intervention and surgical therapy lack sufficient evidence and often are not generally C O E U R Annual Report 2004
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accepted. The lack of evidence is in part caused by problems to assess cardiac function in the normal right ventricle and in structurally abnormal hearts with conventional imaging techniques. The theme aims to improve clinical decision making and therapy by continous research in these fields. Current research project include: Outcome of surgery for congenital heart disease; Stratified treatment of PA, VSD with SPCAs; Aspects of coronary artery development; Medical and psychosocial aspects of quality of life in congenital heart disease; Diagnosis, assessment and catheter intervention for congenital heart disease; Myocardial protein changes and hemodynamics in experimental RV pressure overload; Hemodynamic and genetic factors contributing to heart failure after Fontan operation; RV function long-term after correction of tetralogy of Fallot; 3D echocardiography in congenital heart disease; Congenital heart disease and pregnancy. a
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During the last decades, our understanding of cardiovascular diseases has considerably increased, and major improvements have been achieved in patient management and outcome. One of the challenges for contemporary cardiovascular medicine is to rationally implement the available therapies in clinical practice, in the appropriate patients at the appropriate time (evidence-based medicine). The mission in theme 6 is to improve clinical decision making in cardiovascular medicine by: The use of quantitative, statistical methods for assessment of short- and long-term prognosis, and prognostic factors; Development of diagnostic and prognostic prediction models; Assessment outcomes after cardiovascular events, disability and quality of life, including psychosocial sequelae; Assessment of the effects of treatment modalities on these outcomes; Developing clinical decision models and algorithms; Studying the relation between (use of) decision models, algorithms and treatment guidelines and outcome; Study the short- and long-term prognosis of (subgroups of) patients with acute or chronic a
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“The microsimulation method provides an important adjunct to standard statistical methods in determining the outcome of patients after aortic valve replacement.” John P.A. Puvimanasinghe. Academic thesis, Erasmus University Rotterdam, 2004
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Development of advanced stenting procedures.
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THEME 6 - CARDIOVASCULAR CLINICAL EPIDEMIOLOGY Program code: EMC 05-01-43-01-06 Coordinators: Boersma, Dippel
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cardiovascular diseases in relation to applied treatment; Develop diagnostic and prognostic stratification models for asymptomatic individuals at suspected high risk of cardiovascular diseases, as well as for patients with established cardiovascular diseases; Develop clinical decision models that aim at optimal treatment of patients with established cardiovascular diseases, tailored to estimated benefits, risks and costs; Study the relation between the application in clinical practice of treatment guidelines
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and outcome in patients with established cardiovascular diseases; Identify and study prevalence of psychological risk factors for adverse clinical outcome and impaired health-related quality of life in patients with established heart disease.
Research strategy Discussions on all six research themes regarding future directions and collaboration took place in 2004. The minutes are available on www.coeur.nl/ archive.html. Various initiatives will be further explored in the near future, e.g. for theme 2.
“Statin use is associated with a reduction in the incidence of perioperative and late cardiac events, irrespective of cholesterol levels.” Miklos D. Kertai. Academic thesis, Erasmus University Rotterdam, 2004
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DISTRESSED PERSONALITY PREDICTS DEATH OR MYOCARDIAL INFARCTION AFTER STENTING In collaboration with their cardiological colleagues, Dr. Susanne S. Pedersen and Dr. Ruud A.M. Erdman (Cardiology/Psychology) investigated the effect of type D (the distressed) personality on the occurrence of adverse events at follow-up in patients with ischemic heart disease, following percutaneous coronary intervention with stents. Type D defines those who tend to experience increased negative emotions and who do not express these emotions in social interactions. The sirolimus-eluting stent is a new advent in cardiac event, but it has not been shown to confer any benefits on death or myocardial infarction (MI). Consecutive patients with ischemic heart disease, enrolled in the RESEARCH registry, filled in the type D Personality Scale 6 months following percutaneous coronary intervention. The primary endpoint was a composite of death and MI. Type D patients were at a cumulative increased risk of a composite of death and myocardial infarction at 9 months compared with non-type D patients. Type D personality remained an independent predictor of a composite of death and MI adjusting for all other variables. Thus, Type D is an independent predictor of mortality or MI in patients optimally treated with the latest advent in interventional cardiology. The risk associated with type D is similar to that of traditional cardiovascular risk factors. a
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The above is a popularized summary of a published paper (S.S. Pedersen et al. J. Am. Coll. Cardiol. 2004;44:997-1001).
PhD course coordinator Prof. Peter J. Koudstaal starting his introductory lecture on stroke.
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Research groups – ultimo 2004 Hematology Pediatric Cardiology
Biochemistry
Internal Medicine Radiology Anesthesiology
Cardiology
Pharmacology Neurology Vascular Surgery
Cardiothoracic Surgery
COEUR PhD student affiliation (n=132).
RESEARCH GROUPS THEME 1 Pathogenesis and therapy of hypertension and heart failure, with special emphasis on the reninangiotensin system, its local function(s) and the synthesis of its components at tissue sites Project leader AHJ Danser Advisor PR Saxena Postdocs JJ Saris, AWRH Teunissen PhD students WW Batenburg, W Chai, JHM van Esch Molecular biology of atherosclerosis: Studies in transgenic mice Project leader R de Crom Staff JF Hamming Advisors F Grosveld, H van Urk PhD student BME Mees Genetic basis of angiogenesis and vascular proliferative diseases Project leader HJ Duckers Advisors DJGM Duncker, F Grosveld, EG Nabel PhD student MM Noordeloos
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Cardiac (mal)adaptation to stress and damage Project leader DJGM Duncker Staff R de Crom, HJ Duckers, HMM van Beusekom Advisor WJ van der Giessen Postdoc D Merkus PhD students MC de Waard, J Houtgraaf, B Houweling, OC Manintveld Stem-cell and growth-factor therapy for patients with heart failure or refractory angina Project leaders DJGM Duncker, WJ van der Giessen Staff HMM van Beusekom Advisors JF Jongkind, GP Krestin, APWM Maat, ML Simoons PhD students AD Moelker, EJ van den Bos Circulatory aspects of anesthesia and ventilation Project leaders DAMPJ Gommers, J van Bommel Staff H Boersma Advisors AJJC Bogers, J Klein, B Lachmann, D Poldermans, HW Tilanus PhD students EAJ Boudesteijn, MP Buise, YLJM Deryck, D dos Reis Miranda, F Grüne, HC Rettig Experimental atherosclerosis: Shear-stress related gene expression and inflammation in plaque progression Project leader R Krams Staff R de Crom Advisors AJJC Bogers, DJGM Duncker, F Grosveld, PW Serruys, AFW van der Steen PhD students KL Cheng, F Helderman, VD Segers Molecular biology of heart failure: Genomic and proteomic analysis of disease-related proteins as basis for development of novel therapeutic strategies Project leader JMJ Lamers Staff W Sluiters, AJM Verhoeven Advisor H Jansen PhD students GJ Botma, D van Deursen 26
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Pharmacology of migraine: The role of serotonin, calcitonin gene-related peptide and noradrenaline receptors Project leader A Maassen van den Brink Staff HS Sharma Advisors CJJ Avezaat, AJJC Bogers, PR Saxena Postdoc U Arulmani PhD students S Gupta, S Mehrotra Angiogenesis and tissue remodeling in the pathogenesis of cardiovascular and pulmonary diseases Project leader HS Sharma Staff I Garrelds Advisors AJJC Bogers, HC Hoogsteden, PR Saxena, PJ Sterk PhD students VKT Alagappan, AR Kranenburg Interaction between different peptide systems Project leader T Walther Advisor AHJ Danser Postdoc S Heringer-Walther PhD students F Gembardt, Y Wang RESEARCH GROUPS THEME 2 Development of transplant coronary artery disease in relation to post–transplant cytokine profiles Project leaders AHMM Balk, W Weimar PhD student Vacancy Pathogenesis of hypertension Project leaders F Boomsma, AH van den Meiracker Staff FWM de Rooij Advisor HAP Pols PhD students JHW Rutten, NAJ van der Linde
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Causes and consequences of stroke Project leaders MMB Breteler, PJ Koudstaal Staff DWJ Dippel, F van Kooten, EG Visch-Brink Advisors AJ Beekman, A Hofman, FWG Leebeek, CM van Duijn PhD students MJ Bos, LML de Lau, P Naarding, M van Oijen
Role of hemostasis in arterial thrombosis Project leader FWG Leebeek Staff MPM de Maat, DC Rijken,HHDM van Vliet Advisors DWJ Dippel, PJ Koudstaal, B Löwenberg PhD students T Bongers, ELE de Bruijne, AHC Guimarães, GR Rudež
Management and prevention of stroke Project leaders DWJ Dippel, PJ Koudstaal Staff EJ van Dijk, F van Kooten Advisors DJGM Duncker, MGM Hunink, A van der Lugt, EG Visch-Brink PhD students H El Hachioui, EJ van Breda
Management of hemorrhagic and thrombotic disorders Project leader FWG Leebeek Staff MC Kappers-Klunne, HHDM van Vliet Advisors HR Büller, MPM de Maat, B Löwenberg, DC Rijken, P Sonneveld PhD students JJA Auwerda, MJHA Kruip
Circulatory aspects of living related kidney transplantation Project leader DAMPJ Gommers Staff SJ Verbrugge Advisors JNM IJzermans, J Klein PhD student IRAM Mertens zur Borg
Genetics of dyslipidemias, diabetes mellitus, and atherosclerosis Project leader EJG Sijbrands Staff AH Bootsma, GM Dallinga-Thie, JG Langendonk, BA van Acker Advisors J Lindemans, HAP Pols PhD student KCMC Koeijvoets
Arterial stiffness in older adults Project leaders A Hofman, MADH Schalekamp Staff TJM van der Cammen, JCM Witteman PhD student FUS Mattace Raso
Acute coronary syndromes Project leader ML Simoons Staff H Boersma, APJ Klootwijk, FWG Leebeek, M van der Ent Advisors P Armstrong, GJ Laarman, JCM Witteman PhD students A de Torbal, MT Dirksen, T Lenderink
Subarachnoid hemorrhage Project leaders PJ Koudstaal, F van Kooten Staff DWJ Dippel, D Hasan Advisors CJJ Avezaat, H Bijvoet, HZ Flach, A van der Lugt PhD student MJ van der Jagt
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Monitoring of patients with acute disorders Project leader ML Simoons Staff JA Kors, SH Meij, N van der Putten PhD student SP Nelwan Cardiovascular aging Project leader TJM van der Cammen Advisors HAP Pols, BHC Stricker PhD student N van der Velde
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RESEARCH GROUPS THEME 3 MRI and CT Project leaders Staff Advisor Postdocs PhD students
PJ de Feyter, PMT Pattynama PA Wielopolski GP Krestin K Nieman, RJM van Geuns T Baks, F Cademartiri, WB Meijboom, NRA Mollet
Contrast agents Project leader Staff Advisors Postdoc PhD students
N de Jong FJ ten Cate J Klein, AFW van der Steen JET van Wamel JMG Borsboom, M Emmer
Transducers Project leaders Staff Advisors PhD students
N de Jong, AFW van der Steen CT Lancée N Bom, JRTC Roelandt BJ Krenning, E Merks, E Vlaanderen, MM Voormolen
Peripheral imaging and diagnostics Project leader PMT Pattynama Staff JW Kuiper, LC van Dijk, PA Wielopolski PhD student J van Holten Interventional cardiology and intravascular imaging Project leader PW Serruys Staff R Krams, WJ van der Giessen Advisors PJ de Feyter, H van Urk PhD students GA Rodríguez Granillo, M Valgimigli, CAG Van Mieghem
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Clinical echocardiography Project leader FJ ten Cate Staff N Bruining Advisors JJ Bax, AJJC Bogers, D Poldermans, JRTC Roelandt, ML Simoons Postdocs ML Geleijnse, E Vourvouri PhD students E Biagini, V Rizello, C van der Lee Neurovascular imaging and diagnostics Project leader A van der Lugt Staff DWJ Dippel, PA Wielopolski Advisors GP Krestin, PMT Pattynama PhD students C. de Monyé, TT de Weert, HZ Flach, M Ouhlous Oxygenation imaging Project leader AFW van der Steen PhD student F Wieringa Intravascular ultrasound techniques Project leader AFW van der Steen Staff D Goertz Advisor PW Serruys PhD students RA Baldewsing, ME Frijlink, JA Schaar, AG ten Have, S van der Meer
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RESEARCH GROUPS THEME 4 Surgical aspects of acute and chronic cardiovascular disease and heart failure Project leader AJJC Bogers Staff JJM Takkenberg, LMB Vaessen Advisors J Klein, HG Stassen, W Weimar PhD students P Athanassopoulos, JA Bekkers, JM Hartman, P Havlik, C Kik, RJM van Thiel Lung surgery and lung transplantation Project leader AJJC Bogers Staff H de Bruin, AP Kappetein, J Kluin PhD students Ö Birim, APWM Maat, NP van der Kaaij Novel strategies in clinical electrophysiology Project leader L Jordaens Staff PA Janse, APJ Klootwijk, J Res Advisor JRTC Roelandt PhD students GJ Kimman, JM Mekel, M Rivero-Ayerza, MF Scholten, DAMJ Theuns, AS Thornton
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Novel aspects of interventional cardiology Project leader PW Serruys Staff G Sianos Advisors PJ de Feyter, JRTC Roelandt PhD students Y Ozaki, K Tsuchida Experimental interventional cardiology Project leader WJ van der Giessen Staff HMM van Beusekom Advisors DJGM Duncker, PW Serruys PhD student SH Hofma Hyperplasia after surgery Project leader H van Urk Staff RG Statius van Eps, MRHM van Sambeek, CHA Witters Advisor PMT Pattynama PhD students P Fungaloi, MTC Hoedt, I Toonder, WB van Gent RESEARCH GROUPS THEME 5
Interventional radiology Project leader PMT Pattynama Staff LC van Dijk Advisor H van Urk PhD student JM Hendriks Drug-eluting stents Project leader PW Serruys Staff A den Boer, WJ van der Giessen PhD students J Aoki, HM García García, A Hoye, ATL Ong, K Tanabe
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Outcome of surgery for congenital heart disease Project leaders AJJC Bogers, WA Helbing Staff AP Kappetein, JW Roos-Hesselink, JJM Takkenberg, ADJ ten Harkel, L van Osch-Gevers Advisor AC Gittenberger-Groot PhD students G Bol Raap, PL de Jong, I Eralp Quality of life with congenital heart disease, pediatric cohort Project leaders WA Helbing, EM Utens Advisor FC Verhulst PhD students WB de Koning, A Spijkerboer
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Diagnosis, assessment and catheter intervention for congenital heart disease Project leaders WA Helbing, M Witsenburg Staff M Dalinghaus, FJ Meijboom, JJM Takkenberg, ADJ ten Harkel, L van Osch-Gevers Advisors AJJC Bogers, JMJ Lamers, ML Simoons PhD students MJ Faber, D Robbers-Visser, WJBW van den Berg, AE van den Bosch Quality of life with congenital heart disease, adult cohort Project leaders FJ Meijboom, ML Simoons Staff JW Roos-Hesselink, JJM Takkenberg, EM Utens PhD student Vacancy Congenital heart disease and pregnancy Project leaders JW Roos-Hesselink, EAP Steegers Staff CJM de Groot Advisor ML Simoons PhD student Sing-Chien Yap RESEARCH GROUPS THEME 6 Perioperative risk evaluation and management using a computerized risk model and cardioprotective medical therapy Project leaders H Boersma, D Poldermans Advisors J Klein, HAP Pols, JRTC Roelandt, H van Urk PhD students D Mathioudakis, PG Noordzij, A Oberthür, L Visser Treatment strategies and outcome in patients with coronary artery disease Project leaders H Boersma, ML Simoons Staff JP Ottervanger, RT van Domburg Advisor F Zijlstra PhD students A Breeman, MJ van der Vlugt, CM Westerhout
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Evaluation of the applicability and clinical application of European treatment guidelines of patients with cardiovascular diseases (Euro Heart Survey Programme) Project leaders H Boersma, ML Simoons Staff JW Deckers, B Mulder, WJM Scholte op Reimer Advisors H Crijns, JPG Tijssen, F Zijlstra PhD students P Engelfriet, MJ Lenzen, R Nieuwlaat Use of simulation models for clinical practice in cardiology and cardiac surgery Project leaders H Boersma, JJM Takkenberg Postdoc J Puvimanasinghe PhD student Vacancy Clinical decision making in cardiac surgery Project leaders AJJC Bogers, JJM Takkenberg Staff AP Kappetein, LA van Herwerden PhD student Vacancy Prognosis, diagnosis and decision making in stroke Project leader DWJ Dippel Staff F van Kooten Advisors JDF Habbema, JF Koudstaal, E Steyerberg PhD students M Dirks, E Maasland, AD Wijnhoud Psychological sequelae of patients with coronary disease Project leaders RAM Erdman, RT van Domburg Postdoc S Pedersen PhD student Vacancy Cardiac risk evaluation and modification in patients with peripheral artery disease Project leader D Poldermans Staff H Boersma Advisors JJ Bax, J Klein, H van Urk PhD students H Feringa, R Kuyper, O Schouten C O E U R Annual Report 2004
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PhD students and thesis topics - ultimo 2004 a
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Theme 1 - Cardiac and Theme Vascular Biology, and Pharmacology
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Thesis topic
Promotor(s)
Copromotor(s)
Funding source1
VKT Alagappan
Pulmonary vascular remodeling and function
PR Saxena
HS Sharma
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WW Batenburg
AT2 receptors, NO and S-nitrosothiols: Their importance for coronary vasodilation
AHJ Danser
GJ Botma
Mechanisms in the transcriptional regulation of hepatic lipase gene expression
H Jansen
AJM Verhoeven
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EAJ Boudesteijn
J Klein, D Poldermans
DAMPJ Gommers
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J Klein, HW Tilanus
J van Bommel
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W Chai
Circulatory aspects of xenon anesthesia Microvascular perfusion- and oxygenation-directed anesthetic management in gastric tube reconstruction The effects of aldosterone on isolated human and rat myocardial tissue
KL Cheng
Shear stress and gene expression
AFW van der Steen
YLJM Deryck
The aortic-to-radial artery pressure relationship
J Klein
MC de Waard
Role of NO in cardiovascular control in health and disease
DJGM Duncker
R de Crom
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D dos Reis Miranda Circulatory aspects of mechanical ventilation according to the open lung concept
J Klein, AJJC Bogers
DAMPJ Gommers
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F Gembardt
AHJ Danser
T Walther
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S Gupta
Interaction between different peptide systems Changes of effective downstream pressure in cerebral perfusion under influence of anesthetics and vasoactive drugs Pharmacology of human blood vessels
PR Saxena
A Maassen van den Brink
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F Helderman
Arterial adaptation described by a stress model
AFW van der Steen
R Krams
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J Houtgraaf
The effect of ageing on cardiovascular disease
DJGM Duncker
3
B Houweling
Alterations in the regulation of pulmonary vascular tone after myocardial infarction
DJGM Duncker
3
AR Kranenburg
Airway remodelling and gene expression
PR Saxena, PR Sterk
OC Manintveld
Preconditioning windows in ischemic heart disease
DJGM Duncker
BME Mees
eNOS and angiogenesis
H van Urk
R de Crom
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S Mehrotra
Molecular cloning of noradrenaline and CGRP-receptor
PR Saxena
HS Sharma
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F Grüne
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Theme 1 - Cardiac and Theme Vascular Biology, and Pharmacology - cont’d Name
Thesis topic
Promotor(s)
Copromotor(s)
Funding source1
AD Moelker
Regeneration of infarcted myocardium by stem cells
DJGM Duncker
WJ van der Giessen
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MM Noordeloos
Hemoxygenase and cardiovascular disease
DJGM Duncker
HJ Duckers
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HC Rettig
Neuraxial blockade for pain relieve
J Klein
H Boersma
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VD Segers
Inflammation and atherosclerosis
AFW van der Steen
R Krams
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EJ van den Bos D van Deursen
DJGM Duncker
JHM van Esch
Cell therapy for myocardial regeneration The coordinate regulation of HDL-related genes by E-box binding transcription factors Renin-angiotensin system and oxidative stress
Y Wang
Overexpression of C-type natriuretic peptide in transgenic animals
AHJ Danser
H Jansen, JMJ Lamers
2 AJM Verhoeven
AHJ Danser
1 T Walther
1 1 Funding source: University and hospital (1); ICIN, NWO, KNAW, STW (2); Charity, industry etc. (3)
Theme 2 - Vascular Medicine, Atherosclerosis, Heart Failure and Stroke
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Name
Thesis topic
Promotor(es)
Copromotor(es)
Funding source1
JJA Auwerda
Hemostatic disorders in multiple myeloma
P Sonneveld
FWG Leebeek
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T Bongers
ADAMTS13 in arterial thrombosis
B Löwenberg
FWG Leebeek
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MJ Bos
Causes of stroke
MMB Breteler, PJ Koudstaal
ELE de Bruijne
Thrombin-activatable fibrinolysis inhibitor and arterial thrombosis
B Löwenberg
LML de Lau
Parkinson disease
MMB Breteler, PJ Koudstaal
A de Torbal
Acute myocardial infarction: Insights in its incidence and prognosis
ML Simoons
H Boersma
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MT Dirksen
Reperfusion injury in human heart
ML Simoons
GJ Laarman
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H El Hachioui
Management and prevention of stroke
PJ Koudstaal
EG Visch-Brink
3
AHC Guimarães
Role of hemostasis in arterial thrombosis
B Löwenberg
FWG Leebeek
3
KCMC Koeijvoets
Secondary genetic factors determining the burden of hypercholesterolemia
HAP Pols
EJG Sijbrands
1
MJHA Kruip
Diagnostic strategies for pulmonary embolism
HR Büller, B Löwenberg
FWG Leebeek
1
T Lenderink
Development and clinical application of risk models in acute coronary syndromes
ML Simoons
H Boersma
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Thesis topic
FUS Mattace Raso Arterial stiffness in older adults
Promotor(s)
Copromotor(s)
Funding source1
A Hofman, MADH Schalekamp
TJM van der Cammen JCM Witteman
1
SJ Verbrugge
1
IRAM Mertens zur Borg P Naarding
Circulatory aspects of living related kidney transplantation
J Klein, JNM IJzermans
Vascular factors in depression
PJ Koudstaal, AJ Beekman
SP Nelwan
Evaluation of reduced lead sets for reconstruction of the 12-lead ECG
ML Simoons
JA Kors
1
GR Rudež
Platelet gene polymorphisms and arterial thrombosis
B Löwenberg
FWG Leebeek, MPM de Maat
1
JHW Rutten
Natriuretic peptides as biomarker
HAP Pols
AH van den Meiracker
1
EJ van Breda
Paracetamol treatment of acute stroke
PJ Koudstaal
DWJ Dippel
3
MJ van der Jagt
Intracranial aneurysms and subarachnoid hemorrhage: Clinical studies on diagnosis and treatment
PJ Koudstaal, CJJ Avezaat
F van Kooten
1
NAJ van der Linde
Nitrous oxide, blood pressure and kidney function: Interaction with the reninangiotensin system and the sympathic nervous system
HAP Pols
AH van den Meiracker
3
N van der Velde
Falls, medication and cardiovascular aging
BHC Stricker
TJM van der Cammen
1
M van Oijen
Causes and consequences of cerebral silent infarcts and white lesion matter
MMB Breteler, PJ Koudstaal
2 1 Funding source: University and hospital (1); ICIN, NWO, KNAW, STW (2); Charity, industry etc. (3)
Theme 3 - Cardiovascular Imaging and Diagnostics Name
Thesis topic
Promotor(es)
T Baks
Cardiac viability using MRI
PJ de Feyter
1,3
RA Baldewsing
Intravascular ultrasound modulography of vulnerable plaques
AFW van der Steen
2
E Biagini
Predictive echocardiography
D Poldermans, ML Simoons
JMG Borsboom
Advanced detection strategies for ultrasound contrast agents
N de Jong, AFW van der Steen
2
F Cademartiri
Multislice computed tomography coronary angiography Diagnostic accuracy of CT angiography with a 16-slice multi detector CT-scanner for the screening of atherosclerotic lesions in the carotid and vertebrobasilar arteries Atherosclerotic plaque characterization
GP Krestin, PJ de Feyter
1
C de Monyé TT de Weert
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Copromotor(es)
FJ ten Cate
Funding source1
3
GP Krestin
A van der Lugt
1
PMT Pattynama
A van der Lugt
1
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Thesis topic
Promotor(s)
M Emmer
Medical microbubbles
N de Jong
HZ Flach
Complications of carotid intervention assessed with DW-MRI
GP Krestin
ME Frijlink
Harmonic intravascular ultrasound
AFW van der Steen
2
BJ Krenning
Ultrafast echocardiography and 3-D reconstruction
JRTC Roelandt
2
WB Meijboom
PJ de Feyter
3
N de Jong, N Bom
2
NRA Mollet
Non-invasive visualization of coronary vessels with multislice CT Instantaneous non-invasive ultrasonic measurement of volume within a fluid-filled cavity Clinical effectiveness of multislice CT coronary angiography
PJ de Feyter, PMT Pattynama
1
M Ouhlous
Atherosclerotic plaque imaging with MRI
PMT Pattynama
A van der Lugt
1
V Rizzello
Myocardial viability: Beyond improvement of function
D Poldermans, JRTC Roelandt
JJ Bax
3
GA Rodríguez Granillo
Novel imaging techniques to detect the vulnerable plaque
PW Serruys, PJ de Feyter
3
JA Schaar
Intravascular palpography: A new method to diagnose vulnerable plaque
AFW van der Steen, PW Serruys
3
AG ten Have
Intravascular thermography for vulnerable plaque detection
AFW van der Steen
2
M Valgimigli
Detection and treatment of vulnerable plaque
PW Serruys
3
C van der Lee
Hypertrophic cardiomyopathy
ML Simoons
S van der Meer
UCA for diagnosis and therapy
AFW van der Steen
J van Holten
MRI of metallic stents
PMT Pattynama
applications of spiral computed tomography coronary angiography in CAG Van Mieghem Clinical interventional cardiology
Copromotor(s)
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Funding source1 2
A van der Lugt
FJ ten Cate
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1 2
LC van Dijk
1
PW Serruys, PJ de Feyter
3
E Vlaanderen
Development of an ultrasound measurement system of vibrations for the diagnosis of low back disorders
N de Jong
2
MM Voormolen
3D-echocardiography
N de Jong
1,2
F Wieringa
Novel imaging techniques: From pulse oximeter towards ‘SpO2 camera’
AFW van der Steen
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Funding source: University and hospital (1); ICIN, NWO, KNAW, STW (2); Charity, industry etc. (3)
Name
E Merks
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Theme 3 - Cardiovascular Imaging and Diagnostics - cont’d
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Thesis topic
Promotor(es)
Copromotor(es)
Funding source1
J Aoki
Treatment of ischemic heart disease, using the drug-eluting stent
PW Serruys
WJ van der Giessen
3
chemokine system in heart failure and reperfusion injury, in relation to acute P Athanassopoulos The rejection and transplant coronary artery disease after heart transplantation
AJJC Bogers, W Weimar
LMB Vaessen
1
JA Bekkers
Evaluation of clinical treatment of aorta problems
AJJC Bogers
Ö Birim
AJJC Bogers
AP Kappetein
1
P Fungaloi
Assessment of preoperative conditions and postoperative complications in patients operated for non-small cell lung cancer Photodynamic therapy for prevention of intima hyperplasia at the anastomosis location during arteriovenous entry surgery
H van Urk
RG Statius van Eps
3
HM García García
Stenting of chronic total occlusions
PW Serruys
3
JM Hartman
Postoperative supraclavicular duplex of the LIMA in CABG surgery
AJJC Bogers
1
P Havlik
Mechanical design of instruments for mitral annuloplasty
HG Stassen, AJJC Bogers
1
JM Hendriks
H van Urk, PMT Pattynama
1
H van Urk
3
C Kik
Carotis stenting End-to-end versus end-to-side distal anastomosis during femoropopliteal bypass surgery Vascular response and clinical results of drug-eluting stents Contemporary percutaneous coronary intervention for complex lesions: The treatment of chronic total occlusions and bifurcations in the drug-eluting era Evaluation of electrophysiological treatment during heart surgery (MAZE operations)
AJJC Bogers
1
GJ Kimman
New insights in arrhythmias arising in the triangle of Koch
L Jordaens, JRTC Roelandt
1
APWM Maat
Oncological lung surgery
AJJC Bogers
1
JM Mekel
Improved risk stratification for the prevention of sudden cardiac death
L Jordaens
1
ATL Ong
Drug eluting stents, paclixatel, sirolimus
PW Serruys
3
Y Ozaki
Clinical application of intracoronary ultrasound and quantitative coronary angiography to assess coronary intervention and atherosclerosis
PW Serruys, JRTC Roelandt
3
M Rivero-Ayerza
Role of imaging techniques in clinical electrophysiology
L Jordaens
3
MF Scholten
Innovations in the treatment of atrial fibrillation
L Jordaens
1
K Tanabe
Refined assessment of vascular responses to drug-eluting stents
PW Serruys
WJ van der Giessen
3
DAMJ Theuns
Implantable cardioverter-defibrillator: More than defibrillation
L Jordaens
APJ Klootwijk
3
SH Hofma A Hoye
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Name
MTC Hoedt
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Funding source: University and hospital (1); ICIN, NWO, KNAW, STW (2); Charity, industry etc. (3)
Theme 4 - Surgical-, Interventional- and Device Therapy of Cardiovascular Disease
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PW Serruys
WJ van der Giessen
1
PW Serruys
WJ van der Giessen
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Theme 4 - Surgical-, Interventional- and Device Therapy of Cardiovascular Disease - cont’d Name
Thesis topic Prevention of sudden death and heart failure in a population after acute myocardial infarction Importance of geometry for anastomoses in relation to hemodynamics and shear stress Percutaneous coronary intervention in complex lesions using the magnetic navigation system
Promotor(s)
AJJC Bogers
3
WB van Gent
Ischemia reperfusion as a risk factor for the development of chronic transplant dysfunction after lung transplantation The SEPS trial: Conservative versus scopic surgical treatment of the ulcus cruris venosum
H van Urk
1
RJM van Thiel
Metabolic aspects of cardiac surgery
AJJC Bogers
1
AS Thornton I Toonder K Tsuchida NP van der Kaaij
Copromotor(s)
L Jordaens
1
H van Urk
CHA Witters
1
PW Serruys
WJ van der Giessen
3
1 Funding source: University and hospital (1); ICIN, NWO, KNAW, STW (2); Charity, industry etc. (3)
Theme 5 - Congenital Heart Disease
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Funding source1
Name
Thesis topic
Promotor(es)
Copromotor(es)
Funding source1
G Bol Raap
Surgical treatment of congenital heart disease
AJJC Bogers
AP Kappetein
1
PL de Jong
Pulmonary atresia with ventricular septal defect and systemic-pulmonary collateral arteries. Basic and clinical aspects of multistaged surgical correction
AJJC Bogers
1
WB de Koning
Quality of life with congenital heart disease, medical aspects
WA Helbing
1
I Eralp
The role of epicardium in cardiac development
AJJC Bogers, AC Gittenberger-de Groot
1
MJ Faber
WA Helbing, JMJ Lamers
D Robbers-Visser
Right ventricular response in physiological and pathological increase in loading conditions Genetic susceptibility and determinants of heart failure after Fontan operation
Sing-Chien Yap
Statin therapy for valve disease
ML Simoons
JW Roos-Hesselink
3
A Spijkerboer
Quality of life with congenital heart disease, pediatric cohort
WA Helbing, FC Verhulst
EM Utens
3
WJBW van den Berg
Early diagnosis of right ventricular failure during long-term follow up after surgical repair of tetralogy of Fallot
WA Helbing
AE van den Bosch
The clinical usefulness of real-time transthoracic echocardiography in the diagnosis and management of patients with congenital heart disease
ML Simoons, AJJC Bogers
C O E U R Annual Report 2004
M Dalinghaus
WA Helbing
1 3
1 FJ Meijboom
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Theme 6 - Cardiovascular Clinical Epidemiology
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1 Funding source: University and hospital (1); ICIN, NWO, KNAW, STW (2); Charity, industry etc. (3)
Name
Thesis topic
Promotor(es)
Copromotor(es)
Funding source1
A Breeman M Dirks P Engelfriet H Feringa R Kuyper
F Zijlstra PJ Koudstaal JPG Tijssen, B Mulder D Poldermans D Poldermans
H Boersma DWJ Dippel H Boersma H Boersma H Boersma
3 2 3 3 3
ML Simoons
H Boersma, WJM Scholte op Reimer
1
PJ Koudstaal
DWJ Dippel
1
D Mathioudakis
Treatment of patients with multivessel coronary artery disease Expanding thrombolysis for ischemic stroke Treatment and outcome of congenital heart disease Cardiac risk assessment and management of patients undergoing surgery Use of handheld echo device in perioperative care Evaluation of the application and applicability of (European) treatment guidelines on heart failure, valvular heart disease, coronary revascularization and stable angina Computerized risk factor education and monitoring after TIA or minor stroke The use of a hand-held echocardiographic device for perioperative cardiac evaluation
R Nieuwlaat
Management of atrial fibrillation and valvular heart disease in Europe
H Crijns
H Boersma
3
PG Noordzij
D Poldermans, J Klein
H Boersma
1
J Klein, D Poldermans
H Boersma
1
D Poldermans, H van Urk
H Boersma
1
MJ van der Vlugt
The value of routine preoperative testing in cardiac risk assessment before noncardiac surgery Perioperative risk evaluation and management using a computerized risk model and cardioprotective medical therapy Perioperative myocardial ischemia an cytokine response in patients undergoing high-risk surgery: The influence of statins Early discharge after acute myocardial infarction
ML Simoons
H Boersma
3
L Visser
Perioperative risk evaluation and management using a computerized risk model and cardioprotective medical therapy
J Klein, D Poldermans
CM Westerhout
Risk stratification of acute coronary syndromes
ML Simoons
H Boersma
3
AD Wijnhoud
Transcranial Doppler ultrasonography and stroke
PJ Koudstaal
DWJ Dippel
3
MJ Lenzen E Maasland
A Oberthür O Schouten
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J Klein, D Poldermans
1
1
The number of PhD students increased from 122 (2003) to 132 (2004).
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Doctorate degrees a
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C. Akis Arampatzis, MD. Novel percutaneously based therapies for complex coronary atherosclerosis. Promotores: Prof. Patrick W. Serruys (Cardiology) & Prof. Pim J. de Feyter (Cardiology/Radiology), copromotor: Dr. Peter C. Smits (Cardiology). June 23, 2004. Uday Arulmani, MSc. Calcitonin gene-related peptide and migraine: Implications for therapy. Promotor: Prof. Pramod R. Saxena (Pharmacology). June 11, 2004. Manolis Bountioukos, MD. Dobutamine stress echocardiography: Beyond traditional uses. Promotor: Prof. Don Poldermans (Surgery/Cardiology), copromotores: Dr. Jeroen J. Bax (LUMC) & Dr. H. (Eric) Boersma (Cardiology). December 15, 2004. Marinel N. Cavelaars, MSc. Ambulatory blood pressure monitoring - Effects of physical activity. Promotor: Prof. Jan H. van Bemmel (Bioinformatics), copromotores: Dr. Anton H. van den Meiracker (Internal Medicine) & Dr. Joke H.M. Tulen (Psychiatry). May 26, 2004. Inge de Koning, MSc. The value of screening instruments in the diagnosis of poststroke dementia. Promotor: Prof. Peter J. Koudstaal (Neurology), copromotor: Dr. Diederik W.J. Dippel (Neurology). December 17, 2004. Ad den Boer, BSc. Radiation safety in interventional procedures. Promotor: Prof. Jos R.T.C. Roelandt (Cardiology), copromotor: Dr. Wim J. van der Giessen (Cardiology). February 13, 2004. Tom den Heijer, MD. Causes and correlates of brain atrophy. Promotores: Prof. Monique M.B. Breteler & Prof. Albert Hofman (Epidemiology). April 14, 2004 [prepared in Neurology]. Suzanne J.C. Doesborgh, MSc. Assessment and treatment of linguistic deficits in aphasic patients. Promotor: Prof. Peter J. Koudstaal (Neurology). May 19, 2004. Miklos D. Kertai, MD (cum laude). Travelling beyond the current frontiers: Perioperative and long-term cardiac risk assessment and management in patients undergoing major surgery. Promotor: Prof. Don Poldermans (Surgery/Anesthesiology), copromotor: Dr. H. (Eric) Boersma (Cardiology). May 12, 2004. Pedro Alves Lemos Neto, MD (cum laude). Unrestricted utilization of sirolimus-eluting stents in the ‘real world’. The rapamycin-eluting stent evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry. Promotor: Prof. Patrick W. Serruys (Cardiology), copromotor: Dr. Wim J. van der Giessen (Cardiology). April 28, 2004.
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Jessica T. Lie, MSc. The role of plasma phospholipid transfer protein (PLTP) in the development of atherosclerosis. Studies in genetically modified mice. Promotor: Prof. Hans Jansen (Biochemistry/Internal Medicine), copromotores: Dr. Rini de Crom (Cell Biology/ Surgery) & Dr. Aad van Tol (Biochemistry). September 15, 2004. Adriaan Moelker, MSc. Evaluation of acoustic noise in magnetic resonance imaging. Promotor: Prof. Peter M.T. Pattynama (Radiology). June 30, 2004. Peggy C. Palanchon, MSc. Ultrasound harmonic classification of microemboli. Promotores: Prof. Nico de Jong (Cardiology) & Prof. Jan Klein (Anesthesiology). September 22, 2004. Michiel A.B. Postema, MSc. Medical bubbles. Promotores: Prof. Nico de Jong & Prof. Anton F.W. van der Steen (Cardiology). September 17, 2004 [University of Twente, Enschede]. Niels D. Prins, MD. Cerebral small vessel disease in dementia and depression - A prospective population-based MRI study. Promotores: Prof. Monique M.B. Breteler (Epidemiology) & Prof. Peter J. Koudstaal (Neurology). March 24, 2004. John P.A. Puvimanasinghe, MD. Prognosis after aortic valve replacement with mechanical valves and bioprostheses: Use of meta-analysis and microsimulation. Promotores: Prof. Ad J.J.C. Bogers (Cardiothoracic Surgery) & Prof. J. Dick F. Habbema (Public Health), copromotor: Dr. J.J.M. (Hanneke) Takkenberg (Cardiothoracic Surgery). June 9, 2004. Jolien W. Roos-Hesselink, MD. Congenital heart diseases at adult age. Promotores: Prof. Maarten L. Simoons (Cardiology) & Prof. Ad J.J.C. Bogers (Cardiothoracic Surgery), copromotor: Dr. Folkert J. Meijboom (Cardiology). June 23, 2004. Franscesco Saia, MD. Redefining the boundaries of drug-eluting stent utilization: From in-stent restenosis to acute myocardial infarction. Promotores: Prof. Patrick W. Serruys (Cardiology) & Prof. Pim J. de Feyter (Cardiology/Radiology). September 22, 2004. Ewoud J. van Dijk, MD. Causes of cerebral small vessel disease. Promotores: Prof. Monique M.B. Breteler (Epidemiology) & Prof. Peter J. Koudstaal (Neurology). May 26, 2004. Mary-Lou van Goor, MD. Genetically determined coagulation disorders in ischemic stroke. Promotor: Prof. Peter J. Koudstaal (Neurology), copromotor: Dr. Diederik W.J. Dippel (Neurology). November 3, 2004. The number of theses defended increased from 16 (2003) to 20 (2004).
C O E U R Annual Report 2004
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1. Abizaid A, Costa MA, Blanchard D, Albertal M, Eltchaninoff H, Guagliumi G, Geert-Jan L, Abizaid AS, Sousa A, Wuelfert E, Wietze L, Sousa JE, Serruys PW,
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of the arterial revascularization therapies study trial).
related peptide (CGRP) receptor antagonist BIBN4096BS
Heart Survey on diabetes and the heart. European Heart
American Journal of Cardiology. 2004;94:627-631.
on alpha-CGRP-Induced regional haemodynamic
Journal. 2004;25:1880-1890.
7. Arampatzis CA, Hoye A, Lemos PA, Saia F, Tanabe K,
changes in anaesthetised rats. Basic and Clinical
Morice MC. Sirolimus-eluting stents inhibit neointimal
Degertekin M, Sianos G, Smits PC, van der Giessen
hyperplasia in diabetic patients - Insights from the
WJ, McFadden E, van Domburg R, de Feyter P, Serruys
RAVEL Trial. European Heart Journal. 2004;25:107-112.
PW. Elective sirolimus-eluting stent implantation
Weimar W, Bogers A. Peripheral blood dendritic cells
2. Adam S, van Bommel J, Pelka M, Dirckx M, Jonsson D,
Pharmacology and Toxicology. 2004;94:291-297. 13. Athanassopoulos P, Vaessen LMB, Maat A, Balk A,
19. Batenburg WW, de Vries R, Saxena PR, Danser AHJ. LS-nitrosothiols: endothelium-derived hyperpolarizing factors in porcine coronary arteries? Journal of Hypertension. 2004;22:1927-1936.
for multivessel disease involving significant LAD
in human end-stage heart failure and the early post-
20. Batenburg WW, Garrelds IM, Bernasconi CC, Juillerat-
Klein J. Propofol-induced injection pain: Comparison of
stenosis: One-year clinical outcomes of 99 consecutive
transplant period: evidence for systemic Th1 immune
Jeanneret L, van Kats JP, Saxena PR, Danser AHJ.
a modified propofol emulsion to standard propofol with
patients-the Rotterdam experience. Catheterization and
responses. European Journal of Cardio-Thoracic Surgery.
Angiotensin II type 2 receptor - Mediated vasodilation
2004;25:619-626.
in human coronary microarteries. Circulation. 2004;109:
premixed lidocaine. Anesthesia and Analgesia. 2004;99: 1076-1069. 3. Adriaensen M, Kock M, Stijnen T, van Sambeek M, van
Cardiovascular Interventions. 2004;63:57-60. 8. Arampatzis CA, Lemos PA, Hoye A, Saia F, Tanabe K,
14. Bakker SLM, de Leeuw FE, den Heijer T, Koudstaal PJ,
2296-2301.
van der Giessen WJ, Smits PC, McFadden E, de Feyter P,
Hofman A, Breteler MMB. Cerebral haemodynamics in
Urk H, Pattynama PMT, Hunink MGM. Peripheral arterial
Serruys PW. Elective sirolimus-eluting stent implantation
the elderly: The Rotterdam study. Neuroepidemiology.
PR, Danser AHJ. Mediators of bradykinin-induced
disease: Therapeutic confidence of CT versus digital
for left main coronary artery disease: Six-month
2004;23:178-184.
vasorelaxation in human coronary microarteries.
subtraction angiography and effects on additional
angiographic follow-up and 1-year clinical outcome.
imaging recommendations. Radiology. 2004;233:385-391.
Catheterization and Cardiovascular Interventions.
der Steen AFW. A finite element model for performing
2004;62:292-296.
intravascular ultrasound elastography of human
Saxena PR, Danser AHJ. Bradykinin-induced relaxation of
atherosclerotic coronary arteries. Ultrasound in Medicine
coronary microarteries: S-nitrosothiols as EDHF? British
and Biology. 2004;30:803-813.
Journal of Pharmacology. 2004;142:125-135.
4. Albrecht T, Blomley M, Bolondi L, Claudon M, Correas JM, Cosgrove D, Greiner L, Jager K, de Jong N, Leen E,
9. Ariesen MJ, Algra A, Koudstaal PJ, Rothwell PM, van
15. Baldewsing RA, de Korte CL, Schaar JA, Mastik F, van
21. Batenburg WW, Garrelds IM, van Kats JP, Saxena
Hypertension. 2004;43:488-492. 22. Batenburg WW, Popp R, Fleming I, de Vries R, Garrelds IM,
Lencioni R, Lindsell D, Martegani A, Solbiati L, Thorelius L,
Walraven C. Risk of intracerebral hemorrhage in patients
Tranquart F, Weskott HP, Whittingham T. Guidelines for
with arterial versus cardiac origin of cerebral ischemia
the use of contrast agents in ultrasound. Ultraschall in
on aspirin or placebo - Analysis of individual patient
Steen AFW. Finite element modeling and intravascular
Steendijk P, van der Wall EE, Schalij MJ. Left ventricular
der Medizin. 2004;25:249-256.
data from 9 trials. Stroke. 2004;35:710-714.
ultrasound elastography of vulnerable plaques:
dyssynchrony predicts response and prognosis after
parameter variation. Ultrasonics. 2004;42:723-729.
cardiac resynchronization therapy. Journal of the
5. Amfilochiadis AA, Papageorgiou PC, Kogan N, Boomsma
10. Arulmani U, Heiligers JPC, Garrelds IM, Sanchez-
16. Baldewsing RA, de Korte CL, Schaar JA, Mastik F, van der
Lopez A, Willems EW, Villalon CM, Saxena PR.
sympathoadrenal effects of ‘new pressor protein’ related
Effects of sumatriptan on capsaicin-induced carotid
Dijk LC, Pattynama PMT, Poldermans D, Bouchier-
to human blood coagulation factor XII fragment. Journal
haemodynamic changes and CGRP release in
Hayes DJ, van Urk H, van Sambeek M. Comparison of
MIM, Boersma E, Schalij MJ, van der Wall EE, Dion RA.
anaesthetized pigs. Cephalalgia. 2004;24:717-727.
catecholamine hormone release in patients undergoing
Restrictive annuloplasty and coronary revascularization
carotid artery stenting or carotid endarterectomy.
in ischemic mitral regurgitation results in reverse left
6. Aoki J, Ong ATL, Arampatzis CA, Vijaykumar M, Granillo
11. Arulmani U, MaassenVanDenBrink A, Villalon CM,
GAR, Disco CMC, Serruys PW. Comparison of three-year
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future ischemic cardiac events. International Journal of
Journal of Haematology. 2004;124:343-347. Boontje NM, Dekkers DH, Stienen GJ, Lamers JM, Duncker
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prognostic clinical study using thermography to predict
of coronary heart disease: the Rotterdam Study. British 328. van der Velden J, Merkus D, Klarenbeek BR, James AT,
342. Vantrimpont P, van Dalen BM, van Riemsdijk-van
336. Van Kerckhoven R, van Veghel R, Saxena PR, Schoemaker
and Lung Transplantation. 2004;23:171-177.
apolipoprotein E, lacunar infarcts, and white matter
RG. Pharmacological therapy can increase capillary
343. Ver Elst KMM, van Vliet HDM, Kappers-Klunne MC,
lesions. Annals of Neurology. 2004;55:570-575.
density in post-infarction remodeled rat hearts.
Leebeek FWG. In vitro studies, pharmacokinetic studies
Cardiovascular Research. 2004;61:620-629.
and clinical use of a high purity double virus inactivated
330. van Dijk EJ, Vermeer SE, de Groot JC, van de Minkelis J, Prins ND, Oudkerk M, Hofman A, Koudstaal PJ, Breteler
337. van Rijen EHM, Utens E, Roos-Hesselink JW, Meijboom
348. Vijayakumar M, Lemos PA, Hoye A, Ong ATL, Aoki J, Granillo GR, McFadden EP, Sianos G, Hofma SH, Smits
artery disease in octogenarians. American Journal of Cardiology. 2004;94:909-913. 349. Villalon CM, Centurion D, Willems EW, Arulmani
FVIII/VWF concentrate (Immunate) in the treatment of
U, Saxena PR, Valdivia LF. 5-HT1B receptors and
MMB. Arterial oxygen saturation, COPD, and cerebral
FJ, van Domburg RT, Roelandt J, Bogers A, Verhulst FC.
von Willebrand disease. Thrombosis and Haemostasis.
alpha(2A/2C)-adrenoceptors mediate external carotid
small vessel disease. Journal of Neurology Neurosurgery
Medical predictors for psychopathology in adults with
2004;92:67-74.
vasoconstriction to dihydroergotamine. European
and Psychiatry. 2004;75:733-736.
operated congenital heart disease. European Heart
331. van Dockum WG, Ten Cate FJ, ten Berg JM, Beek AM, Twisk JWR, Vos J, Hofman MBM, Visser CA, van
Journal. 2004;25:1605-1613. 338. van Sambeek MR, Hendriks JM, Tseng L, van Dijk LC, van
Rossum AC. Myocardial infarction after percutaneous
Urk H. Sac enlargement without endoleak: When and
transluminal septal myocardial ablation in hypertrophic
how to convert and technical considerations. Seminars in
obstructive cardiomyopathy: Evaluation by contrast-
Vascular Surgery. 2004;17:284-287.
enhanced magnetic resonance imaging. Journal of the American College of Cardiology. 2004;43:27-34. 332. van Goor MPJ, Alblas CL, Leebeek FWG, Koudstaal PJ,
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339. van Wamel A, Bouakaz A, Bernard B, Ten Cate F, de
344. Verheye S, De Meyer GRY, Krams R, Kockx MM, van Damme LCA, Gourabi BM, Knaapen MWM, van
Journal of Pharmacology. 2004;484:287-290. 350. Vogel MW, Entius CAC, Pattynama PMT. Monitoring
Langenhove G, Serruys PW. Intravascular thermography:
tissue coagulation during thermoablative treatment
Immediate functional and morphological vascular
by using a novel magnetic resonance imaging contrast
findings. European Heart Journal. 2004;25:158-165. 345. Verheye S, van Langenhove G, van Es GA, Serruys P. The
agent. Investigative Radiology. 2004;39:661-665. 351. Voko Z, Hollander M, Koudstaal PJ, Hofman A, Breteler
percutaneous assessment of regional and acute coronary
MMB. How do American stroke risk functions perform
Jong N. Radionuclide tumour therapy with ultrasound
hot unstable plaques by thermographic evaluation
in a Western European population? Neuroepidemiology.
contrast microbubbles. Ultrasonics. 2004;42:903-906.
(PARACHUTE) study: a prospective reproducibility and
2004;23:247-253.
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352. Voormolen MM, Bouakaz A, Krenning BJ, Lancee CT, Ten Cate FJ, de Jong N. Feasibility of 3D harmonic contrast imaging. Ultrasonics. 2004;42:739-743. 353. Walsh EK, Huang H, Wang Z, Williams J, de Crom R, van
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and positioning on hemodynamic responses during
stent deployment in diabetic patients. Circulation.
carbon dioxide pneumoperitoneum for laparoscopic donor
2004;109:867-873.
nephrectomy - A prospective controlled clinical study.
Kohlmann T, Niero M, Cook SA, Crickx B, Herdman MJ,
of myocardial oxygen consumption in transgenic mice
Frech F, Van Assche D. A new instrument for assessing
overexpressing vascular eNOS. American Journal of
quality of life in atopic dermatitis: international
Physiology-Heart and Circulatory Physiology. 2004;287:
development of the Quality of Life Index for Atopic
H2115-H2121.
Dermatitis (QoLIAD). British Journal of Dermatology. 2004;150:274-283. 360. Wiegman A, de Groot E, Hutten BA, Rodenburg J, Gort J,
C. Angiotensin deficiency in mice leads to dilated
Bakker HD, Sijbrands EJG, Kastelein JJP. Arterial intima-
cardiomyopathy. European Journal of Pharmacology.
media thickness in children heterozygous for familial
2004;493:161-165.
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Clinical and angiographic predictors of restenosis after
Haperen R, Thompson CI, Lefer DJ, Hintze TH. Control
Schulze K, Heringer-Walther S, Schultheiss HP, Tschope
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359. Whalley D, McKenna SP, Dewar AL, Erdman RA,
354. Walther T, Steendijk P, Westermann D, Hohmann C,
hypercholesterolaemia. Lancet. 2004;363:369-370.
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2004;18:919-923.
The number of publications present in the public domain (Web of Science and PubMed/Medline) increased from 293 (2003) to 364 (2004). The number of publications by COEUR investigators that have been cited at least 100 times, increased from 103 to 110. The lists are available on www.coeur.nl.html. Three papers were ‘citation classics’, i.e. they have been cited more than 1,000 times:
361. Wiegman A, Hutten BA, de Groot E, Rodenburg J, Bakker
HP, Siems WE. Biochemical analysis of neutral
HD, Buller HR, Sijbrands EJG, Kastelein JJP. Efficacy
endopeptidase activity reveals independent catabolism
and safety of statin therapy in children with familial
of atrial and brain natriuretic peptide. Biological
hypercholesterolemia - A randomized controlled trial.
Mylecharane EJ, Saxena PR, Humphrey PPA. International
Chemistry. 2004;385:179-184.
Journal of the American Medical Association. 2004;292:
Union of Pharmacology classification of receptors for 5-
331-337.
hydroxytryptamine (serotonin). Pharmacological Reviews.
Schultheiss HP, Siems WE. Relation of ANP and BNP to
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Surgical Endoscopy and Other Interventional Techniques.
355. Walther T, Stepan H, Pankow K, Becker M, Schultheiss
356. Walther T, Stepan H, Pankow K, Gembardt F, Faber R,
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362. Witte DR, Taskinen MR, Perttunen-Nio H, van Tol A,
Treatment of sufferer’s head with crocodile (2500 BC). U. Arulmani, Thesis, 2004
Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR,
1994;46:157-203 [cited 1,749x].
Livingstone S, Colhoun HM. Study of agreement between
for enhanced neutral endopeptidase activity and
LDL size as measured by nuclear magnetic resonance and
Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet.
resistance of BNP to neutral endopeptidase in the fetus.
gradient gel electrophoresis. Journal of Lipid Research.
1999;353:9-13 [cited 1,120x].
M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F,
British Journal of Obstetrics and Gynaecology. 2004;111:
2004;45:1069-1076.
Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W,
Falotico R. A randomized comparison of a sirolimus-eluting
Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne
stent with a standard stent for coronary revascularization. New England Journal of Medicine. 2002;346:1773-1780 [cited
363. Zhang Z, van den Bos EJ, Wielopolski PA, de Jong-Popijus
357. Wassen F, Klootwijk W, Kaptein E, Duncker DJ, Visser TJ,
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Lechat P, Jordaens L et al. The Cardiac Insufficiency
Hot papers The journal Medisch Contact (January 7, 2005) analyzed frequently cited Dutch medical research. It identified the following two publications by COEUR investigators as ‘hot papers’:
their N-terminal fragments in fetal circulation: evidence
452-455.
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Morice M, Serruys PW, Sousa JE, Fajadet J, Hayashi EB, Perin
M, Duncker DJ, Krestin GP. High-resolution magnetic
P, Belardi J, Sigwart U, Colombo A, Goy JJ,
Kuiper G. Characteristics and thyroid state-dependent
resonance imaging of iron-labeled myoblasts using a
van den Heuvel P, Delcan J, Morel MA. A comparison of
regulation of iodothyronine deiodinases in pigs.
standard 1.5-T clinical scanner. Magma. Epub: Oct 28,
balloon-expandable-stent implantation with balloon
Endocrinology. 2004;145:4251-4263.
2004.
bngioplasty in patients with coronary-artery disease.
A, van Geuns RJ, de Feyter PJ. Coronary angiography with
zur Borg I, Lim A, Verbrugge SJC, IJzermans JNM,
New England Journal of Medicine. 1994;331:489-495 [cited
multi-slice computed tomography. Lancet. 2001;357:599-603
Klein J. Effect of intraabdominal pressure elevation
2,356x].
[cited 134x].
358. West NEJ, Ruygrok PN, Disco CMC, Webster MWI, Lindeboom WK, O’Neill WW, Mercado NF, Serruys PW.
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503x]. a
Nieman K, Oudkerk M, Rensing BJ, van Ooijen P, Munne
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Awards and Grants a
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Kipshidze NN, Serruys PW (Eds). Handbook of cardiovascular cell transplantation. Martin Dunitz, London. 2004.
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Serruys PW, Lemos PA (Eds). Sirolimus-eluting stents. Taylor & Francis, London, 2004.
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Waksman R, Serruys PW (Eds). Handbook of the vulnerable plaque. Martin Dunitz, London. 2004.
Patent applications a
Baartmans HLG (NL), Lancée CT (NL), Bom N (NL), McMorrow GJ (US). Instantaneous ultrasonic echo measurement of
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beams. Publication number GB2391625, Publications GB2391625 and WO2004017834, February 11, 2004. Frinking PJ (CH), de Jong N (NL). Method and apparatus for ultrasound contrast imaging. Publication number US6752762, publications US6752762 and WO0042916, June 22, 2004. a
Frinking PJA (CH), de Jong N (NL), Cespedes I (US). Ultrasound contrast imaging. Publication number US6726629, publications AU2068299, TW410305, US6726629, WO9935967 and ZA9900281, April 27, 2004.
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Meij SH (NL), Nelwan SP (NL), Tabbara B (US). A system for adaptively deriving ECG chest lead signal data. Publication number and publications US2004030256 and WO2004041083, February 12, 2004, and May 21, 2004, respectively.
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Pols HAP (NL), Uiterlinden AG (NL), van Leeuwen JPTH (NL). Method for determining susceptibility to heart disease by screening polymorphisms in the vitamin D receptor gene. Publication number US6808881, October 10, 2004.
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MARIE CURIE EARLY STAGE TRAINING PROGRAM COEUR applied to the European Union for a large grant, to act as a host institution for Early Stage Trainees. The application, which has to be carried out in two steps, listed six multidisciplinary PhD projects and nine shorter research projects. Medio 2005 a decision can be expected on this overly popular part of the FP6 program. COEUR’s application can be downloaded from www.coeur.nl/fellow.html.
bladder urine volume with a limited number of ultrasound
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Prof. Luc Jordaens preparing Research seminar.
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Hall of Fame K.L. Cheng, MSc ICIN has awarded PhD student Caroline Cheng ₠ 250 for her Excellent presentation of in vivo shear stress data, obtained in the Hemodynamics Laboratory (Cardiology). M. de Kraker The organizers of the EACT/EST Joint Meeting in Leipzig presented the Thoracic Young Investigator’s Award to student Marjolein de Kraker (Cardiothoracic Surgery), for her presentation on CT scan and myasthenia gravis. M.J. Faber, MD For his pressure-overload presentation, PhD student Matthijs Faber (Pediatric Cardiology/ Biochemistry) was awarded the Basic Science Poster Prize at the Annual Scientific Meeting of the Association for European Paediatric Cardiology. M.E. Frijlink, MSc For harmonic imaging studies, PhD student Martijn Frijlink (Cardiology) received the Student Poster Award at the 2004 International IEEE Ultrasound Ferroelectrics and Frequency Control Symposium, Montreal. A.V. Hernández, MD, MSc PhD student Adrián V. Hernández (Public Health/ Cardiology) was finalist in the Young Investigators Awards in Population Sciences during the 2004 European Society of Cardiology Conference, Munich. He was awarded with ₠ 500 and a diploma.
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G.P. Krestin, MD, PhD Board member Prof. Gabriel Krestin (Radiology) was named President of the European Society for Magnetic Resonance in Medicine and Biology. A. Maassen van den Brink, PhD The American Headache Society honored project leader Dr. Antoinette Maassen van den Brink (Pharmacology) with the Migraine and Women’s Health Research Award ($ 20,000), to study female hormones and calcitonin-related peptide. NWO awarded her a VENI grant, which includes ₠ 200,000 to study genes involved in migraine. K. Nieman, MD, PhD At the 2004 Spring meeting of the Dutch Cardiological Society, Dr. Koen Nieman was finalist for the Einthoven Dissertation Prize, sponsored by Sanofi-Synthélabo. In 2003, he defended cum laude his thesis, prepared in Cardiology/Radiology. J.R.T.C. Roelandt, MD, PhD Scientific Advisory Board chairman Prof. Jos Roelandt presented the Wenckebach Lecture at the 2004 Fall meeting of the Netherlands Cardiological Society. P.R. Saxena, MD, PhD The EUR awarded retiring Prof. Pramod Saxena (Pharmacology) with the prestigious Ad Fontes Medal. J.A. Schaar, MD The Netherlands Heart Foundation presented PhD student Johannes Schaar (Cardiology) with the Best Poster Prize during the ‘Wetenschapsdag’ (Science Day) in Leiden.
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P.W. Serruys, MD, PhD The Swiss Cardiological Society presented project leader Prof. Patrick Serruys (Cardiology) with the Gruentzig Award. A. van der Lugt, MD, PhD Project leader Dr. Aad van der Lugt (Radiology) received a Clinical Fellowship (₠ 136,000) from ZonMW, to detect vulnerable plaque in carotid artery with multislice CT. N. van der Velde, MD PhD student Nathalie van der Velde (Geriatrics/ Internal Medicine), who studies cardiovascular aging, received the Best Poster Prize at the 7th International Congress on Geriatrics, Vienna.
A selection of grants H. Boersma, PhD The Netherlands Heart Foundation subsidized project leader Dr. Eric Boersma (Cardiology) with a Research grant of ₠ 216,000 for epidemiological studies on beta-blockers and statins. N. Bom, PhD STW allotted scientific director Prof. Klaas Bom (Cardiology) a ₠ 400,000 Research grant for volume measurements with non-linear echography in the Experimental Echocardiography Laboratory. P.J. de Feyter, MD, PhD ZonMW provided project leader Prof. Pim de Feyter (Cardiology/Radiology) with a ₠ 387,000 Health Technology Assessment grant to compare multislice computed tomography with invasive coronary angiography. 84
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D.W.J. Dippel, MD, PhD Project leader Dr. Diederik Dippel (Neurology) et al. received a ZonMW grant (₠ 350,000) to reimplement thrombolysis for acute ischemic stroke. D.J. G.M. Duncker, MD, PhD et al. The European Space Agency allotted a Research grant of ₠ 170,000 to project leaders Prof. Dirk Duncker and Dr. Wim van der Giessen (Cardiology) for their study on vascular endothelial cells in microgravity. M.J. Faber, MD PhD student Matthijs Faber (Pediatric Cardiology/ Biochemistry) received a Research grant (₠ 10,000) from the TerMeulen Fund, to study myofilament protein changes in hypertrophy at the Johns Hopkins NHLBI Proteomics Center. W.A. Helbing, MD, PhD Board member Prof. Wim Helbing (Pediatric Cardiology) received a ₠ 200,000 Research grant from the Sophia Research Foundation (SSWO) and the Academic Medical Center Utrecht (UMCU) to study heart failure in young Fontan patients. R. Krams, MD, PhD For therapy of the vulnerable plaque, Erasmus MC granted project leader Dr. Rob Krams (Cardiology) ₠ 50,000 in the Translational research program. F.W.G. Leebeek, MD, PhD The Translational research program (Erasmus MC) allotted Board member Dr. Frank Leebeek et al. (Internal Medicine, Biostatistics/Epidemiology & Neurology) ₠ 136,000 for their ADAMTS13 stroke project.
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D. Merkus, PhD et al. The Netherlands Heart Foundation provided postdoc Dr. Daphne Merkus and project leader Prof. Dirk Duncker (Cardiology) with a Research grant of ₠ 130,000, to study coronary adaptations to hypertrophy. P.W. Serruys, MD, PhD Glaxo provided project leader Prof. Patrick Serruys (Cardiology) with an Educational grant of ₠ 1,000,000. A.H. van den Meiracker, MD, PhD For ‘Doelmatigheidsonderzoek’ (Suitability research), Erasmus MC granted Board member Dr. Ton van den Meiracker (Internal Medicine) ₠ 125,000 to study (NT-pro) BNP during acute dyspnea. In addition, he received a ₠ 205,000 Research grant from the Netherlands Kidney Foundation for his investigations on non-dipping blood pressure and impaired renal function. W.J. van der Giessen, MD, PhD et al. ICIN/KNAW provided project leader Dr. Wim van der Giessen (Cardiology) et al. with a Research grant of ₠ 75,000 for stem-cell investigations. Together with Prof. Gabriel Krestin (Radiology), he received ₠ 125,000 from Erasmus MC Translational research coffers, for MRI bone marrow cell transplantation studies.
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J.J. van Wenzel, PhD et al. In a joint effort of Cardiology and Radiology, Drs. Jolanda van Wenzel, Cees Slager and Aad van der Lugt ended 2nd postion in the ICIN grant application competition. They obtained a ₠ 150,000 Research grant for carotid shear-stress studies. E. Visch-Brink, MD, PhD et al. ZonMW provided Dr. Evy Visch-Brink (Neurology) with a Research grant (₠ 60,000) to implement results of the RATS study on aphasia treatment in stroke patients. OHRA subsidized her RATS2 study with a ₠ 133,000 Research grant, to be spent in collaboration with Prof. Peter Koudstaal. T. Walther, PhD Project leader Thomas Walther (Pharmacology) received Research grants from the Sonnenfeltstiftung (₠ 18,000) and EURNEST (KP6, ₠ 87,000) for his studies on autoimmune-antibodies and on the maternal food intake/offspring cardiovascular outcome-relation, respectively. P.A. Wielopolski, PhD et al. For MRI-based tracking of transferred cells, Dr. Piotr Wielopolski (Radiology) and Dr. Timo ten Hagen (Oncology) received ₠ 50,000 from Erasmus MC Translational research coffers. Prof. Dirk Duncker (Cardiology) and Prof. Gabriel Krestin (Radiology) also participate in this research.
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Inaugural and farewell lectures
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On March 19, 2004, Dr. Dirk J.G.M. Duncker (Cardiology), Professor of Experimental Cardiology, delivered his inaugural lecture Aanpassingsvermogen van het hart: zegen of zorg?
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Dr. Thomas Brand, Cell and Molecular Biology Institute for Biochemistry and Biotechnology, Technical University Braunschweig, Braunschweig, Germany. Molecular analysis of cardiac development. Chair: Dr. Hari S. Sharma (Pharmacology). May 12, 2004. Prof. William M. Chilian, Department of Physiology, Louisiana State University, New Orleans, Louisiana. Acute and chronic adaptations of the coronary circulation to ischemia. Chair: Prof. Dirk J.G.M. Duncker (Cardiology). April 28, 2004.
On June 15, 2004, retiring Professor Pramod R. Saxena (Pharmacology) delivered his farewell lecture Four decades in pharmacology: An adventurous journey from India to the Netherlands. On behalf of the EUR, dean Prof. Paul J. van der Maas presented the Ad Fontes Medal.
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On June 11, 2004, Dr. Don Poldermans (Anesthesiology/Surgery), Professor of Perioperative Cardiovascular Care, gave his inaugural lecture Perioperatieve cardiovasculaire zorg Risico en zorg op maat.
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COEUR lectures a
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Prof. Mat J.A.P. Daemen, Department of Pathology, CARIM, University of Maastricht. Molecular markers of plaque instability. Chair: Dr. Rob Krams (Cardiology). October 6, 2004. Dr. Thomas S. Hatsukami, Division of Surgery, University of Washington School of Medicine, Seattle, Washington. Magnetic resonance of carotid atherosclerosis. Chair: Prof. Hero van Urk (Surgery). September 1, 2004. Prof. William R.E. Jamieson, Department of Cardiovascular Surgery, University of British Columbia, Vancouver. Bioprosthetic heart valve replacement: Past, present, future. Chair: Prof. Ad J.J.C. Bogers (Cardiothoracic Surgery). June 8, 2004. Dr. Nassir F. Marrouche, Center for Atrial Fibrillation, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio. Ablation of pulmonary veins guided by echocardiography. Chair: Dr. Luc Jordaens (Cardiology). June 10, 2004. NB: Dr. Jordaens presented the lecture, because Dr. Marouche’s clinical expertise was needed at the Thoraxcenter Electrophysiology Laboratory.
Snapshots of these lectures are available on www.coeur.nl/arc_lectsymp.html. COEUR lecturer Prof. William Chilian (left).
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Wetenschapsdag Hartstichting
Website
On April 15, 2004, the Netherlands Heart Foundation celebrated its 40th birthday in Leiden with a ‘Science Day’, which included presentations by COEUR as a cardiovascular research school and by COEUR investigators (see picture).
The website www.coeur.nl was increasingly used to disseminate news, programs and reports of the research school. It contains information on, e.g.: Calendar (Special lectures, Research seminars, Courses, Thesis defense); Education (PhD training brochure, MSc program, Student electives); Research (Themes, Strategy, Project groups, PhD projects); Fellowships (Cardiovascular funding offered by various organizations); Archive (Past Educational Programs, Course evaluations, Special Lectures and Seminars, Publications, Addenda & Corrigenda Annual Reports).
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In 2004, the number of visits and hits increased by 23 and 86%, respectively. Kilobytes downloaded increased 8-fold.
Cri du COEUR
PhD student Johannes A. Schaar explaining his award-winning poster to Education officer Dr. Jan Willem de Jong.
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The information bulletin Cri du COEUR was distributed at quarterly intervals by E-mail and in printed form. Cri du COEUR contained up-to-date information for PhD students, postdocs and faculty on coming events (thesis defense!), funding possibilities, programs, awards received et cetera. Please, consult www.coeur.nl/archive.html for the pdf files. From the Introductions (see p. 90):
PhD course coordinator Dr. Aggie H.M.M. Balk lectures on heart failure.
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Cri du COEUR, January 2004 “Within six months after its recognition by the Royal Academy of Arts and Sciences (KNAW), COEUR has set out a tremendous range of activities. All 120 (!) current COEUR PhD students have now been traced down and a system has been set up to evaluate their individual research and education on a regular basis.” Prof. A.H. Jan Danser, Pharmacology COEUR Board member
Cri du COEUR, July 2004 “I am very pleased to announce the participation of the Department of Anesthesiology in COEUR. Our research activities focus on ventilation, anesthesia and analgesia, with great interest in the cardiovascular aspects of these topics. Specifically, we wish to further explore perioperative cardiovascular care, microcirculation and qualification and quantification of emboli by echo techniques in relation to our established research areas.” Prof. Jan Klein, Chairman, Anesthesiology
Cri du COEUR, April 2004 “Through research seminars, mutual discussions and COEUR lectures, this exchange of information is rapidly increasing in pace, especially among our 126 PhD students, Both teachers and students have expressed great enthusiasm for the variety of courses offered so far, which is heart-warming. And apparently good news spreads quickly! It seems that larger colloquium rooms will be required in the future.” Prof. N. (Klaas) Bom, COEUR Scientific director
Cri du COEUR, October 2004 “Despite its relatively short period of existence in its renewed form, COEUR has already provided a surplus value, with regard to expansion of our research and the training of our PhD students and fellows.” Dr. Anton H. van den Meiracker, Internal Medicine, COEUR Board member
Conclusions In the first issue of Cri du COEUR (May 2003), the dean referred to the new research school as the “fledgling”. We may conclude that the (ugly?) duckling is turning into a fair swan. Participation in COEUR has grown, with an increased number of PhD students attending courses organized by an enthousiastic and ambitious staff. Within the prestigious Erasmus MC, COEUR is becoming a powerhouse of scientific pursuit and training. Collectively, the departments involved provide a scholarly arena that offers PhD students, postdocs and faculty with prime opportunities for interdisciplinary collaboration, and an intellectual environment that addresses a variety of cardiovascular subjects from bench to bedside. Maarten Simoons, chairman Klaas Bom, director Jan Willem de Jong, secretary 90
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Edited by: Prof. N. (Klaas) Bom, scientific director Dr. Jan Willem de Jong, education officer/secretary Prof. Maarten L. Simoons, chairman Photography: Contributions from various sources are greatfully acknowleged Lay out: Ms. Maud E. van Nierop Production and publication: COEUR Secretariat, Erasmus MC Printing: Drukkerij Gebroeders Peters BV Contact: Thoraxcenter, Room Ba 573 Erasmus MC P.O. Box 2040 3000 CA Rotterdam The Netherlands Phone: +31-10-4635312 E-mail:
[email protected] Website: www.coeur.nl
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This Annual Report was prepared with the secretarial assistance of Ms. Linda Smit, who succeeded Ms. Willeke Korpershoek in December 2004.
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