April Flowers for redOrbit.com – Your Universe Online
A new study led by the Faculty of Medicine & Dentistry at the University of Alberta significantly improves understanding of how widely used drugs in pulmonary arterial hypertension (PAH) affect the heart health of patients who use them.
The findings of this study, published in a recent issue of Circulation Research, a journal of the American Heart Association, reveal that the medications most often prescribed for PAH could block the function of an important cardiac hormone. This would decrease the strength of the contraction in the right heart chambers, creating a potentially important yet unrecognized adverse effect.
PAH causes a progressive narrowing and restriction of the blood flow through the lungs, putting a significant strain in the right chamber (ventricle) of the heart that pushes blood through the lungs. The right ventricle eventually fails, causing a cascading effect of heart failure leading to death.
An increased level of endothelin — a hormone that constricts blood vessels throughout the body — in the lungs is one cause of the narrowing blood vessels. Very expensive and commonly used drugs called endothelin receptor antagonists (ERA) block the endothelin actions. ERAs are currently prescribed by cardiologists around the world to treat PAH patients. However, the effects of these drugs on the right ventricle have not been examined prior to this study.
Cardiologist Evengelos Michelakis and cardiac surgeon Jayan Nagendran led the research team of cardiologists, cardiac surgeons, pathologists and scientists who studied human hearts from 50 PAH patients and laboratory models. Though ERAs do not have significant effects on normal hearts because the endothelin levels are low, in the diseased hearts of PAH patients it´s a different story as the thickened right ventricles usually have significantly increased levels of endothelin.
The results of this study suggest that the increase of endothelin may be beneficial for the hearts of PAH sufferers, as endothelin is known to increase the contraction strength of the heart muscle. As the right ventricle has to work harder pushing blood through the narrowed vessels, endothelin could help it function better. ERAs, however, block endothelin. According to the study, ERAs also decrease the contraction strength of the diseased right ventricles.
“These new findings — that ERAs have direct effects on the right chambers of the heart — have important implications for treated patients,” said Nagendran. “For example, PAH patients treated with ERAs can develop fluid retention (swelling), which is currently treated with diuretics. As fluid retention can be a result of decreased right ventricle function, the new findings suggest that this could be a previously unrecognized important adverse effect of these drugs.” In other words, ERAs may have a beneficial effect on the lung blood vessels, but they may also have unwanted effects on the heart.
“While this does not mean that PAH patients should stop using these drugs, this new research sheds more light on the overall mechanism of action of these drugs in PAH patients,” explained Michelakis. “It may also help physicians to better approach the treatment of PAH patients and design clinical studies to validate these new findings in large populations.”
Though PAH mostly effects younger women, patients of both sexes and all ages can be affected. Survival rates of PAH patients is similar to that of metastatic breast cancer, but the annual cost of treatment for PAH can be more than double that of metastatic breast cancer — sometimes reaching as much as $200,000 per patient per year.