Cardiovascular Centre (CVC)
Research programme
Mission statement and objectives
Heart failure has a poor prognosis. After diagnosis, short-term and long-term life expectancy (5 years) is lower than
for most cancers. The pathophysiology is complex, and many different mechanisms are involved and studied in the
programme.
Therefore, the mission of the Cardiovascular Centre is to develop new treatment strategies that will improve the prognosis
of patients with heart failure. The ultimate goal is to prevent or formulate a cure for this lethal disease.
This goal will be achieved by using advanced experimental studies including both the exploration of pathophysiological
mechanisms and the identification of molecular and cellular targets for treatment. Furthermore, state-of-the-art clinical
studies are used to prove the validity of hypotheses generated by the experimental studies.
The current intermediate goals of the research programme are to:
- Design and evaluate strategies to prevent the onset and/or progression of heart failure. In addition, to design and evaluate treatment strategies to improve clinical outcome in heart failure.
- Identify and characterise key mechanisms responsible for the progression of heart failure. These include factors at the genetic, cellular and organ levels.
- Develop and use sophisticated animal, human and in vitro models to study the cellular mechanisms of heart failure.
- Conduct large population studies to identify environmental and genetic factors that lead to a higher susceptibility for heart failure.
- Evaluate the role of atrial fibrillation, which clearly complicates the course of heart failure (and which may also cause heart failure), and to subsequently develop adequate treatment and prevention methods for atrial fibrillation in order to improve the prognosis of heart failure.
- Prevent and treat myocardial damage due to ischemia and/or reperfusion following acute myocardial infarction, in order to reduce left ventricular dysfunction and the development of heart failure.
- Pharmacologically modulate pulmonary arterial hypertension in order to prevent right ventricular adaptation.
Research Area
The heart failure research programme at the Cardiovascular Centre is divided into four sub-programmes:
1. Clinical programme on heart failure and early LV dysfunction post MI (P1)
2. Experimental programme on heart failure (P2)
3. Programme on atrial fibrillation, with a focus on atrial fibrillation in heart failure (P3)
4. Programme on congenital heart disease and pulmonary hypertension, with a focus on right ventricular failure (P4)
In many ways, the four sub-programmes share topics relevant to the central research question on heart failure. The strategy of sharing similar topics throughout the four sub-programmes reinforces the coherence of the overall research area. Important topics include:
- Heart failure and concomitant disease (P1, P2). For example, changes in cardiac function will be negatively influenced by existing renal failure and anaemia. In a similar way loss of vascular function will accelerate the loss of cardiac function. Change of cellular composition and function, not only concerning the cardiac myocyte, but also the cells of the extracellular matrix, cells of the conduction system and vascular endothelial cells are influenced by concomitant diseases in heart failure. Studies into the role of diabetes in the development of heart failure have also recently begun.
- Neurohumoral activation (P1-P4). During the development of heart failure, a complex pattern of various neurohumoral systems are activated, such as the renin-angiotensin system, the natriuretic peptide system and the sympathetic system. The CVC has a strong track record with regard to studies involving strategies for modulating neurohumoral activation in order to improve the prognosis of heart failure.
- Genetic constitution (P1-P3). Are there genetic factors that may predispose for the development of heart failure? Our aim is to identify genetic and/or environmental factors that determine the response or lack of response to therapy. By modulating these factors, we strive to improve therapy efficacy, including treatmentof atrial arrhythmias that may cause or complicate heart failure. Several CVC staff members are participating in international consortia evaluating the involvement of genes in several phenotypes related to heart failure.
- Cellular hypertrophy and cardiac remodelling (P1, P2). Post-infarction hypertrophy and left ventricular remodelling are a major cause of systolic and diastolic wall motion abnormalities leading to chronic heart failure. Cellular models of stretch-induced hypertrophy and, in vivo, post myocardial infarction or aortic-bandinginduced hypertrophy are both used in sub-programme 2. Genomic and proteomic approaches are aimed at revealing the molecular heart-specific basis for early maladaptive hypertrophy.
- Right ventricular dysfunction (P4). Right ventricular failure, due to chronic abnormal loading conditions, is a major problem in the follow up of patients with congenital heart disease. Insight into the adaptation of the heart and vasculature to these abnormal loading conditions will help to improve treatment strategies, and ultimately, to prevent early heart failure in the rapidly growing population of patients with congenital or corrected congenital heart diseases. P4 specifically focuses on right ventricular hypertrophy and failure in response to pressure or volume overload as can be observed in pulmonary hypertension and congenital heart disease.
Contact
Programme leaders
Name: Prof.Dr. W.H. van Gilst
Phone: + 31 (0)50 361 5339
e-mail Prof. van Gilst
Name: Prof.Dr. D.J. van Veldhuisen
Phone: + 31 (0)50 361 3746
e-mail Prof. van Veldhuisen
Secretariat
Name: Mrs.
M. Leaker-Bos
Phone: +31 (0)50 361 5340
e-mail Mrs. Leaker-Bos
