One in five people suffer from heart failure: the heart fails to pump blood correctly. This eventually leads to death, but UCL researchers and doctors may have found a treatment.
The heart is a muscle with four ventricles. It functions like a double pump. Blood pumped from the two right ventricles takes on oxygen in the lungs and returns to the two left ventricles. At each beat, the heart pumps blood to irrigate the rest of the body. For one reason or another, the heart can stop to pump blood correctly. This is heart failure (HF). As populations age and life expectancy increases, the prevalence of HF is also increasing. In Belgium alone, it affects almost 200,000 people and 15,000 new case are diagnosed each year.
An enlarged heart
Half of HFs are due to a defect in filling the ventricles. These are HFs with ‘preserved ejection fraction’. The heart doesn’t slacken enough to pump correctly. The cause? ‘Arterial hypertension or obesity make the heart work harder’, explains Prof. Jean-Luc Balligand, an internist at Saint-Luc University Hospital and director of the UCL Pharmacology and Therapeutic Centre (Pôle de pharmacologie et thérapeutique). ‘Eventually, this extra work thickens the heart’s walls and changes their elasticity (hypertrophic remodelling). The ventricles become incapable of filling correctly to take in the volume of blood required by the body. The sufferer first feels the effects of HF during exertion and, in the end, at rest.’ He or she has a one-in-two chance of dying within five years of the diagnosis.
Invaluable receptors
Currently, no treatment exists for this type of heart failure; at best, we can act on the risk factors (hypertension, obesity, etc.). But this might change owing to the research of Prof. Balligand and his team. ‘A few years ago we identified beta-3 adrenergic receptors in human heart muscle.’ In humans, these are also found:
- on the surface of endothelial cells (which regulate blood vessel dilation);
- on the surface of bladder muscle cells, which turned out to be quite important;
- in brown fat.
‘Our laboratory experiments demonstrated that beta-3 adrenergic receptors, once we activate them in the heart muscle cells, protect against hypertrophic remodelling. Therefore, we assume they would prevent it in individuals at risk of HF. Maybe they could even reverse it in those already suffering from HF. But we now have drugs that can activate these beta-3 adrenergic receptors.’
From bladder to heart
One of these drugs, mirabegron, has been prescribed in Belgium since 2014 for incontinence caused by a hyperactive bladder. By activating beta-3 adrenergic receptors in the bladder muscle, mirabegron helps it fill up more and thus to need emptying less often.
Prof. Balligand thought of testing the drug’s virtues on heart muscle cells—if it works on the bladder, why not the heart? Moreover, mirabegron had already passed all market approval requirements, including clinical trials that proved it’s non-toxic and safe. If it proved effective at treating HF, it would be immediately available for such use, which would be great news for millions around the world.
UCL-coordinated European study
Convinced by these arguments, the European Commission allocated €5.5 million to Prof. Balligand to organise a European study that would verify and measure the impact of mirabegron in the prevention of heart failure with preserved ejection fraction. ‘We’ll first recruit around 300 patients with heart hypertrophy and at risk of heart failure. Next, we’ll put them on mirabegron and monitor them for a year.’ In addition to heart size and structure, doctors will also monitor:
- possible fibrosis of heart walls;
- patient cardiovascular fitness (on a bicycle);
- metabolic parameters (blood pressure, insulin, triglycerides, etc.).
In parallel, two secondary studies will examine whether mirabegron has any impact on brown fat (to reduce excessive weight) and endothelium (blood vessel dilation). If so, it would benefit the entire cardiovascular system.
Candice Leblanc
A Glance at Jean-Luc Balligand's bio
