Why give?

Breakthrough test shows heart metabolism in action

New imaging technique could predict heart failure
Two doctors reviewing a patients medical scan

Pioneering work in medical imaging could unravel the mystery of where the heart gets its energy. The research, led by Dr. Charles Cunningham, a senior scientist at Sunnybrook Research Institute, uses new technology to illuminate the inner workings of the heart. Eventually, the technique could be used to predict heart failure.

To beat about 100,000 times a day, the heart needs to make a special fuel called adenosine triphosphate (ATP). Until recently, ATP production has been a bit of a blind taste test. We know it’s made from glucose and fatty acids. But the actual manufacturing process remained unclear. 

A 2016 study, co-funded by Heart & Stroke donors and published in Circulation Research, detailed how Dr. Cunningham and his colleagues used a naturally occurring glucose byproduct, known as pyruvate, to map out the process. To track what’s happening within the cells, they applied a strong magnetic charge to the pyruvate then injected it into patients undergoing an MRI.

The pyruvate appeared much brighter in the resulting image, enabling the researchers to see biochemical reactions occurring within the heart — including the making of ATP.

The imaging technique is called Hyperpolarized carbon-13 MRI and it may prove useful in detecting heart failure, a chronic condition where the heart is unable to meet the body’s pumping needs. Heart failure is the end result of injury or damage to the heart. Although there is no cure, early diagnosis can help people manage their condition and live longer.

“The progression of heart failure to a later stage is very likely preceded by metabolic changes,” says Dr. Cunningham. “So if you could image those and tell which people are going down that path, you could treat them more aggressively or tailor the treatment.”

Although the mechanism needs more study, researchers have determined that heart failure changes the way the heart makes ATP. A healthy heart will use pyruvate. When the heart starts to fail, however, it relies more on fat as the main fuel, says Dr. Kim Connelly, a co-author of the study and a cardiologist at St. Michael’s Hospital in Toronto. At a later stage of heart failure, the heart reverts to using more glucose.

“It’s not a static process. [Metabolism] changes depending on how bad your heart failure is and what the cause of the heart failure is,” says Dr. Connelly. “Before this, we never had a good technique that could help tease out exactly what’s going on in terms of the heart taking up glucose and taking up fats, and what happens to them once they enter the cells in the heart and get broken down.”

Hyperpolarized carbon-13 MRI is the world's first cardiac imaging technique that could show these processes. And it could be safer than positron emission tomography (PET) scanning, which relies on radiation to diagnose heart failure. The new technique would be integrated into a regular cardiac MRI, adding only about 10 minutes to the procedure.

Dr. Cunningham plans to study metabolic imaging in people with enlarged hearts, a condition that puts them at an increased risk of heart failure. By following them he hopes to learn whether glucose metabolism can be used as a biomarker to predict disease. “I think that will answer the question as to whether it’ll be useful clinically,” he says.

The current focus is on cardiac applications, but Dr. Connelly says metabolic imaging would be useful in other areas of medicine. “There’s no reason why we can’t measure [metabolism] in the liver or kidneys, and use it to gain really valuable insight into what happens to people with kidney diseases or liver diseases, and also to tailor-make drugs. This is potentially much, much broader,” he says.

It has been more than a decade since Dr. Cunningham began working on this technique. His lab had to engineer hardware to pick up the signal, and create software that enabled the MRI scanner to capture chemical changes happening within the body while still taking a picture of the patient’s anatomy. He says most of their efforts were aimed at making the contrast agent safe.

So, how did it feel to finally see it work clinically after so many years of research and development?

“It was a good day,” Dr. Cunningham says, smiling. “It was a huge step forward. I was happy.”