Vascular Biology and Intervention
This programme encompasses basic, clinical (both diagnostic and therapeutic) and genetic research in the field of coronary atherosclerosis, in particular lipid metabolism, vascular biology, molecular plaque imaging, and novel therapeutic measures.
Main goal of the research in the "Vascular Biology and Intervention" programme is to enhance the link between clinical and preclinical research in atherosclerosis and restenosis by means of an integrated approach of vascular cardiology/biology by collaborative clinical and preclinical research lines. To this purpose, the collaboration in the working group Leiden Vascular Medicine (LVM) and Centre for Medical Systems Biology (CMSB) is very successful.
An important focus in this programme is on noninvasive imaging of coronary artery disease, aiming at integration of intravascular echocardiography, nuclear cardiology, magnetic resonance imaging (MRI), and multislice computed tomography (CT). Important in this programme is the future routing of patients with low, intermediate, high and very high risk of cardiovascular complications. This research is performed together with the Department of Radiology.
The MISSION! programmes are aimed to optimize of care for patients according to recent guidelines. The first of these MISSION! programmes is devoted to patients admitted with acute myocardial infarction. This guideline implementation programme includes pre-hospital, in-hospital and post-clinical phases, involving all different health care providers in the Leiden area. More recent MISSION! programmes involve patients with congestive heart failure, patients with atrial fibrillation, patients with syncope, and patients with Marfan syndrome.
In translational research on the applicability of stem cells in regenerative therapy of the damaged heart, including the type of stem cells and their routing of introduction into the heart, the Department of Cardiology participates in two national research programmes, titled BioMedical Materials (BMM) and Translationeel Adult Stamcelonderzoek (TAS). In these programmes we cooperate closely with the Departments of Hematology, Molecular Cell Biology, Immunohematology and Blood Bank, and Pharmacy.
In the Einthoven Laboratory of Vascular Medicine of the LUMC the Department of Cardiology collaborates with the Departments of Nephrology, Hematology, and Vascular Surgery. Epigenetic markers of vascular remodelling, PPARα/γ agonists to block progression of atherosclerosis, and single nucleotide polymorphisms that are associated with restenosis are subjects that are studied in this Laboratory. In a collaborative project with the Department of Endocrinology and the Department of Nephrology patients with diabetes type 2 who are asymptomatic for cardiovascular disease are tested thoroughly for cardiovascular risk factors, such as endothelial dysfunction and elevated plasma levels of C-reactive protein in a programme called DIACARM (DIAbetes CARdiovascular Risk Management).
Cardiac Dysfunction and Arrhythmias
To investigate the interrelationship between cardiac dysfunction and arrhythmias. This program consists of cardiovascular diseases due to diminished right and/or left ventricular dysfunction and due to arrhythmias.
In this programme the Department of Cardiology cooperates intensively with the Departments of Cardiothoracic Surgery, Anatomy and Embryology, Molecular Cell Biology, Hematology, Radiology and Nuclear Medicine.
In this program novel therapies for patients with heart failure are studied. Determination of interventricular and intraventricular dyssynchrony of segmental contraction has resulted in improvement of criteria for cardiac synchronization therapy. New techniques to diagnose and quantify asynchronous contraction by speckle tracking analysis and evaluation of apical and basal twist have extended the methodology to select patients for cardiac synchronization therapy, as well as assess efficacy of this therapy. Surgical therapy to treat mitral regurgitation and to reshape left ventricular geometry is assessed in close collaboration with the Department of Cardiothoracic Surgery.
Patients with drug-refractory angina pectoris receive intramyocardial injections of autologous bone marrow-derived mononucleated cells, including mesenchymal stem cells to relieve angina and improve left ventricular function. These cells are injected by transarterial catheter into myocardial areas that are hypokinetic or akinetic but display electrograms of appropriate voltage using the NOGA mapping system (in collaboration with the Department of Hematology). A recent paper in JAMA by the group of Atsma reports the results of the first randomized, placebo-controlled trial of intramyocardially injected bone marrow-derived mononucleated cells. This therapy is safe, does not cause arrhythmias, contributes to relief of angina, reduces the number of segments with stress-induced ischemia, improves myocardial perfusion, and increases left ventricular diastolic and systolic function.
In laboratory studies it is investigated in what ways bone-marrow derived mesenchymal stem cells (MSCs) could be used to regenerate damaged myocardium. In collaboration with the Department of Molecular Cell Biology, section Gene Therapy, MSCs are transfected with viral constructs containing a variety of genes that are supposed to cause differentiation of MSCs into cardiomyocytes. Characterisation of electrical properties of MSCs in various stages of differentiation is performed using extracellularly recorded potentials and by intracellular techniques, such as patch clamp. The age-dependent capacity of MSCs to differentiate into cardiomyocytes is being studied. Also the stem cell-like properties of human epicardial derived cells (EPDCs) are being studied in immuno-incompetent mice with myocardial infarction (in collaboration with the Department of Anatomy & Embryology).
The programme "Cardiac Dysfunction and Arrhythmias" includes research of atrial and ventricular arrhythmias. For complex catheter ablation procedures several imaging modalities are integrated with 3-dimensional electric mapping systems to pinpoint the anatomic structures and areas to be treated, and to improve the success of the intervention. Treatment of complex arrhythmias now also involves therapy of children with serious rhythm disturbances (in cooperation with the Department of Pediatrics) and therapy of patients with genetically determined arrhythmias (in cooperation with the Department of Clinical Genetics).
Recently, the Department of Cardiology has started aortic valve replacements by using percutaneously introduced catheters carrying the folded valve to be deployed in the aortic root. As the prevalence of aortic stenosis in the
Finally, in the research cluster entitled "Adult Congenital Heart Disease" the Department of Cardiology is a substantial part of the nation-wide registry CONCOR (CONgenitale CORvitia). Recently, CONCOR, being a nation-wide project of the Interuniversity Cardiology Institute of the Netherland (ICIN/KNAW), became accepted as the 9th pearl in the Parelsnoer Initiative, which is a national programme with the aim to collect blood, tissue and DNA for research purposes. As the group of adult patients with congenital heart disease is growing progressively, studies that are aimed to find optimal therapeutic strategies are mandatory to improve quality of life.