Heart failure symptoms traced to unusual source

Hundreds of thousands of Canadians struggle to survive and take in air because of heart failure. Now scientists have unravelled a new reason why that rewrites medical textbooks.

Findings by Guelph, Dalhousie team may one day help 'have a more intelligent way of choosing medications'

About 600,000 Canadians are living with heart failure, according to Heart & Stroke. (Heart and Stroke Foundation/Marketwired/Canadian Press)

Hundreds of thousands of Canadians struggle to survive and take in air because of heart failure. Now scientists in Ontario and New Brunswick have discovered a cause, involving the brain, that rewrites medical textbooks. 

It's estimated about 600,000 Canadians, among the more than 23 million worldwide, are living with heart failure.

Newly released findings uncover why heart failure labours breathing to such an extent that everyday tasks like walking become difficult. 

Many people with heart failure have shortness of breath, known in medical circles as dyspnea.

"What we were able to find is the true cause of respiratory weakness or dyspneas as being the brain," said the study's lead author, Jeremy Simpson, a professor of human health and nutritional sciences at the University of Guelph.

For cardiologists, improving survival rates in heart failure is the priority.

Twenty-five per cent of those diagnosed in Ontario won't be alive in one year, says cardiologist Dr. Peter Liu, chief scientific officer of the University of Ottawa Heart Institute.

"In heart failure, the patient definitely suffers a lot and so if there are ways in which we can improve not only the survival but also improve the quality of life I think that's really a win," Liu said.

Mouse heart and lungs, with arrows indicating obstruction points that cause heart failure and diaphram weakening. (A.J. Foster et al/Science Translational Medicine)

That's where the findings of a study in this week's issue of the journal Science Translational Medicine might come in.

Simpson and his colleagues at the University of Guelph in Ontario and Dalhousie University explored how respiratory weakness contributes to dyspnea in mice models of heart failure.

Over nearly six years of painstaking experiments, Simpson's team discovered that the diaphragm, a large muscle that helps with breathing function, doesn't work as well in mice models because of faulty signals it receives from the brain. 

What we were able to find is the true cause of respiratory weakness or  dyspneas  as being the brain.- Jeremy Simpson, University of Guelph researcher

Until now, investigators had focused on the heart and lungs. Simpson said the graduate students collected solid data that led them to cast aside conventional thinking and look at the brain's role.

"What was medically known to cause breathlessness has now been unravelled, the true mechanism revealed and importantly solutions presented," said study co-author Keith Brunt, an assistant professor of pharmacology at Dalhousie University's School of Medicine in Saint John, N.B. "Such a fundamental discovery changes the textbooks on breathlessness in heart failure."

The researchers found that a medication that fights blood pressure and a first-line heart therapy medication prevented breathing problems in mice under certain conditions.

It relates to when false signals from the brain tell the diaphragm to go into overdrive, which tires out the respiratory muscle, said Liu. 

Key mechanism

Like Liu, cardiologist Dr. Justin Ezekowitz, an associate professor at the University of Alberta in Edmonton, was not involved in the research. He is the co-director of the Canadian VIGOUR Centre, which does clinical research.

"This seems to be a really core mechanism," said Ezekowitz, a spokesman for Heart & Stroke. "I think that's why people will be interested."

Liu cautioned that even though the drugs are already available, equivalent studies need to be performed in people. How medications are distributed in mice isn't necessarily the same in us.

If it works the same way in humans, the medical community will also need to better understand what length of treatment is needed to alleviate breathlessness and how we can better balance and combine medications, Simpson said. 

Currently for instance, doctors and patients try different beta blocker medications in a process of trial and error to see what works.

"This may help us down the road to actually have a more intelligent way of choosing medications," Liu said.

The study was funded by the Ontario Thoracic Society,  the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council.