Cardiac Dysfunction and Arrhythmias
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.
…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).
…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 Netherlands in 2020 is estimated to be 48,000 patients, we predict that a number of old patients will be excluded from surgery and become candidates for percutaneously introduced aortic valves. Another approach of aortic valve implantation using a minimally invasive surgical procedure through the apex of the left ventricle is developed in cooperation with the Department of Cardiothoracic Surgery.
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.