Steps towards a treatment for heart failure Patients who have experienced a structural heart re-modelling, where the wall of the heart becomes thicker, are at greater risk of developing heart failure in future. The Beta3_LVH project aims to assess the efficacy of a drug called mirabegron in preventing heart failure in patients at risk of developing the disease, as Dr Nancy Van Overstraeten explains The prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise across the developed world. While patients with HFpEF are still able to pump blood relatively efficiently, there are structural and functional signs to indicate they may be at risk of developing more serious problems in future. “Despite preserved ejection fraction, cardiac remodeling can be thought of almost as an early stage in the development of heart failure when it leads to altered filling properties of the heart,” explains Dr Nancy Van Overstraeten. Based at the Université catholique de Louvain, Dr Van Overstraeten is a translational research coordinator managing the Beta3_LVH project, a multi-centric, european initiative testing a new treatment. “We are trying to demonstrate the efficacy of a drug called mirabegron, which is already on the market to treat bladder disease. This drug is known to activate the human beta3 adrenergic receptors, which are also present in the heart,” she explains.
stress-induced wall thickness decreases”, she says. Researchers are now looking to test the efficacy of mirabegron in a clinical trial. “The major points we will assess will be the left ventricular mass index and the change in diastolic function. Is the diastolic function restored after treatment?” continues Dr Van Overstraeten. “We aim to demonstrate that mirabegron can be effective in preventing heart failure.” Researchers from nine european centers are currently recruiting for the clinical trial, sponsored under a Horizon 2020 program, looking to identify people who are showing morphological signs of structural cardiac remodelling, as indicated by echocardiographic techniques. While the age range for the trial is 18-90, these signs are more common in elderly people, so they are likely to form the core of the trial group; Dr Van Overstraeten and her colleagues also aim to assess the impact of mirabegron on their quality of life. “One of the main symptoms of heart failure is that patients are tired. During exercise
The major points we will assess will be the left ventricular mass index and the change in diastolic function. Is the diastolic function restored after treatment? We aim to demonstrate that mirabegron can be effective in preventing heart failure with preserved ejection fraction Structural heart re-modelling The focus in the project is on patients who have already had a structural heart re-modelling, where the wall of the heart becomes thicker, causing it to become more rigid and its filling to be impaired. At the moment, there is no treatment available to prevent this from developing into heart failure, but Dr Van Overstraeten says that data so far on mirabegron is promising. “Preclinical data from our laboratory on animals showed that when the human beta3 adrenergic receptor is genetically expressed in the mouse heart, the
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- when they climb stairs for example, or when they do everyday physical exercise - they are tired and short of breath. So we will see if their exercise capacity is improved as a result of this treatment,” she says. This would represent a significant development, as currently there is no specific treatment available for HFpEF. Current treatment centers on reducing risk factors, such as obesity and hypertension. “This will be the first time that a drug has really been used to prevent the development of HFpEF,” says Dr Van
Overstraeten. Researchers are in contact with drug development companies, looking towards potentially using beta3 adrenoceptor agonists to prevent heart failure; however, Dr Van Overstraeten says she and her colleagues will remain focused on more fundamental research in future. “His research group is investigating new signaling pathways regulating myocardial remodeling,” she outlines. A multi-center randomized, placebocontrolled trial of mirabegron, a new beta3adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease (Beta3_LVH) Patients with cardiovascular risk factors, e.g. hypertension and obesity are at risk of developing heart failure with preserved ejection fraction (HFpEF), a highly prevalent disease in the elderly, mostly women population. There is currently no specific, defined treatment for HFpEF, beyond control of risk factors. Activation of cardiac and vascular Beta3-adrenergic receptors (B3AR) represents a new concept and a novel target for structural cardiac disease. B3AR expression and coupling were demonstrated in human myocardium and vasculature. Professor Jean-Luc Balligand Université catholique de Louvain 1, Place de l’Université B-1348 Louvain-la-Neuve (Belgium) T: + 32 2 764 52 62 E: Jl.Balligand@uclouvain.be W: http://www.beta3lvh.eu/home-
Professor Jean-Luc Balligand is Head of the FATH Pole within IREC, a practicing Physician at the Cliniques Universitaires Saint-Luc, UCL, and also teaches cardiovascular physiology and pharmacology at UCL Medical School. His research group is investigating new signaling pathways regulating myocardial remodeling.
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