Arresting Heart Disease

Ki Chon, left, and PhD candidate Christopher Scully.

 by Ami Albernaz

In the time it takes you to read this sentence, someone in the United States will suffer a heart attack, stroke, or other coronary event. According to the American Heart Association, heart disease takes a life every minute, making it the leading cause of death. Some who have treatable heart conditions will not know it until it’s too late, while those who suffer heart attacks will remain at greater risk of further trouble down the road. Researchers at WPI are tackling heart disease on a number of fronts, developing groundbreaking methods for early detection, assessing when surgery is warranted, and fixing damage when it occurs. Their steadfast efforts will help hearts stay healthier longer and heal better.

Stalking a Silent Killer

To most, the word “algorithm” sounds cold and abstract. But algorithms can be building blocks of life-saving technology. Take one developed by Ki Chon, head of WPI’s Department of Biomedical Engineering, which was licensed by Cleveland-based ScottCare Corporation for use in a new heart monitor. Able to detect atrial fibrillation (AF), a type of irregular heartbeat, more accurately and rapidly than existing technology, Chon’s algorithm represents a significant advance in the fight against a condition that, left untreated, can be fatal.

“You don’t know when an atrial fibrillation episode is going to happen. If you had this device, you could monitor your heart regularly.”
— Ki Chon

AF affects an estimated three million Americans, though many don’t realize they have it. In AF, the atria — the heart’s two upper chambers — beat out of sync with the ventricles. Episodes can be brief, or the condition can be chronic. Over time it can lead to congestive heart failure or stroke. In fact, people with the condition are seven times more likely to have a stroke than the general population.

Though effective medications exist, AF is notoriously difficult to detect, as it presents itself only intermittently. Even with Holter or arrhythmia monitors, which record heartbeats, infrequent occurrences are difficult for technicians who must review hours of data to spot.

“Normally a technician has to sift through data to find a certain signature,” Chon says. “Then there’s atrial flutter [a precursor to atrial fibrillation], which throws a curveball at atrial fibrillation detection. It has different characteristics; you have to train people to identify it.”

Chon combined three different statistical techniques to improve precision. While previous monitors have had accuracy rates of around 70 to 80 percent, Chon’s algorithm has been shown to accurately detect AF 95 percent of the time, based on tests with patient data provided by MIT and Beth Israel Deaconess Medical Center. Just as important, as incorporated in the new monitor marketed by ScottCare, the algorithm flags AF episodes in real-time, eliminating the need for technicians to pore over data after the fact. It even alerts patients that they should notify their doctor.

Chon says there have been a few cases in which the monitors have falsely detected AF due to motion and noise artifacts. He is now working on another algorithm that will compensate for the interference, and hopes to have it incorporated in the next generation of monitors. Further down the road, he imagines a simple device that could easily be used at home — something like a blood pressure cuff — for monitoring people without obvious AF symptoms.

“You don’t know when an AF episode is going to happen,” Chon says. “If you had this device, you could monitor your heart regularly.”

Glenn Gaudette watches Melissa Kuhn ’11 prepare a bundle of microthreads for use in his heart repair research.

New Life for Damaged Hearts

For those who’ve survived a heart attack, a serious second threat looms. Because the scar tissue that replaces damaged heart muscle does not contract, the heart pumps less blood — eventually leaving it unable to keep up with the body’s demand, and possibly leading to heart failure. Glenn Gaudette, assistant professor of biomedical engineering at WPI, is working on a revolutionary approach that would give heart muscle tissue new life — through stem cells delivered directly to the damaged area.

A number of scientists from around the world have demonstrated the promise of this sort of stem-cell therapy. Gaudette’s research focuses on mesenchymal stem cells, derived from adult bone marrow. He has found that when he engrafts these cells into damaged heart muscle, they form healthy muscle tissue. Using a scaffolding method — in which patches of biological material seeded with stem cells are placed in a damaged portion of the heart — he has been able to restore between 20 and 30 percent of the heart tissue’s normal function.

Unsatisfied with those results, he wondered if there might be a way to recover even more of the heart’s function while also making it easier to deliver the stem cells. An informal chat over coffee with colleagues George Pins, associate professor of biomedical engineering, and Marsha Rolle, assistant professor of biomedical engineering, started Gaudette on a new direction about three years ago.

“George was developing microthreads made of collagen and fibrin, which are important in the woundhealing response, and Marsha suggested putting stem cells on the end of a needle and pulling the threads through,” Gaudette recalls. “We started testing this idea.”

A WPI Faculty Advancement in Research grant allowed the team to show that stem cells could indeed grow on the threads. Subsequently, Gaudette and his colleagues have received over $600,000 from the National Institutes of Health to try to load as many stem cells as possible onto the threads and deliver the seeded threads to the right place in the heart. The latter goal came with challenges that Gaudette and his colleagues had not foreseen.

“A lot of people might think of this as a medical problem, but it really is an engineering problem.”
— Glenn Gaudette

“An Engineering Problem”

There was more to getting the threads into the damaged heart tissue than simply pulling them through with a needle. There was the chance that the stem cells would shear off, which led to the development of a sheath to cover the threads.

“A lot of people might think of this as a medical problem,” Gaudette says, “but it really is an engineering problem. There were things we didn’t think of at the outset.”

There was also the matter of bundling the threads together so that there was just the right amount for the stem cells to adhere to, and the challenge of coaxing the stem cells to attach to the bundles. In Gaudette’s lab is a device that rotates syringes containing the threads, which allows the cells to stick. The stem cell–seeded microthreads are then kept in an incubator at 37 degrees Celsius until they can be used in tests with rats. Gaudette says the preliminary data is quite promising.

“We’re still a long way from the clinic,” he acknowledges. Even so, the research marks an impressive start.

Better Prediction of Strokes

An arterial plaque — a fatty deposit made of cholesterol, fat, calcium, and other materials — may be a ticking time bomb: Under certain conditions, and without warning, it could rupture, sending debris and blood clots formed at the rupture site to the brain, causing a stroke. It takes years for these plaques to grow, and while small they usually go unnoticed. Once a plaque becomes large enough to block 70 percent of an artery, surgery is often recommended to remove it and prevent a possible rupture and stroke.

Yet, that surgery may be over-prescribed because surgeons want to err on the safe side, says Dalin Tang, professor of mathematical sciences and biomedical engineering at WPI. In fact, the literature indicates that of 20 surgeries, only one will actually prevent a stroke. All surgery entails risk, and an unnecessary endarterectomy may damage the artery and cause harm by releasing debris into the bloodstream. More precise tools to predict which plaques are likely to rupture will allow doctors to cut down on unneeded surgeries, Tang believes. He’s made finding such tools his life’s work.

With the help of a four-year, $1.4 million NIH grant awarded earlier this year (a renewal of a previous $1.1 million NIH award), Tang and colleagues at Washington University in St. Louis and the University of Washington in Seattle have been working on a model that integrates fluid dynamics, solid mechanics, and histological and medical imaging to improve prediction. Tang believes the likelihood of rupture depends on two general factors: the composition of the plaque itself and mechanical forces acting on it.

Sewing stem cell–seeded microthreads into a mouse in the surgical suite at the WPI Life Sciences and Bioengineering Center at Gatway Park are, from left, Angelica DeMartino ’10, postdoctoral researcher Zewei Tao, Glenn Gaudette, and PhD candidate Jacques Guyette.

To get a detailed picture of a plaque, in vivo, MRI data were acquired from patients and segmented to get plaque morphology and tissue components; this data is then validated with histology. They surmise that plaques covered by a thick, protective “cap” may be less likely to rupture than plaques with caps that are thin or worn away, and that plaques with larger lipid-rich cores may be more vulnerable than plaques with smaller cores. Yet blood flow and stress on the plaque also play an important role, and Tang and his colleagues believe figuring out exactly what that role is will ultimately help doctors make better decisions. “If nothing acts on the plaque, it won’t rupture,” Tang says.

In one recent study of 12 patients, Tang and colleagues found that plaques that had previously ruptured had higher plaque wall stress and flow shear stress values compared with plaques that had not ruptured. In another study of 14 patients, the researchers found that these stresses seemed to correlate with advanced plaque progression. Though more research is needed for the team to refine its model, Tang, who has been working on computational modeling for cardiovascular diseases for 27 years, is both patient and perseverant, recognizing that the challenge may be difficult, but it’s eminently worthwhile. “It’s hard to predict if a plaque will rupture,” he says. “If it were easy, people would not have died.”