Unplugged
One cardiologist’s quest to clear chronically clogged arteries and optimize cardiac care
June 15, 2015
Illustration: Marcio Morgado
Dr. Bradley Strauss has been performing angioplasty for more than 22 years. Angioplasty is an extremely common procedure that involves widening a blocked artery or vein with a balloon catheter and stent. The practice is effective for over 95% of patients, including people who’ve had heart attacks—acute blockages full of soft clot that can be quite easily opened up by the balloon. But in some cases angioplasty just doesn’t work, particularly in older blockages that are too hard and rigid. It drove Strauss, chief of the Schulich Heart Program and head of cardiology at Sunnybrook Health Sciences Centre, to distraction that some of his patients “had poor results” after an angioplasty, and that there was no easy solution beyond surgery. “I’m always trying to figure out why I can’t do something,” says Strauss, who is also a senior scientist at Sunnybrook Research Institute (SRI). “I spend a lot more time dwelling on failures than the cases that do well.” It’s these clinical challenges that have guided much of Strauss’s research, whether it’s figuring out how to break through an impassable blockage, questioning long-held cardiac procedures, or tracking patient recovery using a smartphone app. Ultimately, Strauss’s role as a hands-on clinician and researcher has resulted in real-world solutions at all stages of cardiac care.
It was back in 2000 that Strauss first began tackling the problem of failed angioplasties. One of the long-known problems is a particularly durable and stubborn type of material that forms slowly in the artery over weeks—and sometimes months—until it is an unmoveable mass that not even the miniscule guide wire used in angioplasty can penetrate. This chronic total occlusion, as it’s called, doesn’t typically cause a heart attack, but, at its worst, the patients can’t walk very far without gasping or their chest feels unbearably tight, and their quality of life becomes severely compromised. It’s estimated that these obstructions show up in 15% to 20% of angiograms, affecting hundreds of thousands of patients every year around the world. Since these blockages (comprised largely of collagen and calcium) cannot be pried open via angioplasty—many doctors won’t even attempt the procedure—patients usually end up on angina medications and, in severe cases, require invasive bypass surgery.
In the clinic and catheterization laboratory, Strauss had seen his share of such cases. Meanwhile, in his research laboratory, he happened to be studying an enzyme called collagenase and its role in restenosis (re-narrowing of the artery after a treatment). Collagenase is produced by the body naturally, usually as part of an immune response, and works by breaking down certain cell tissues. “I started wondering whether these enzymes that exacerbate restenosis could have a beneficial function with this hard material in arteries,” Strauss says. “It made sense when you put the two together.” After much tinkering, Strauss and his colleagues concocted a preparation of bacterial collagenase that could be injected directly into a blockage to soften the collagen. It’s been called “Drano” for the arteries, though minus the toxicity. The treatment completed a Phase 1 clinical safety trial, called CTO-1, at Sunnybrook in 2011, and the Phase 2 efficacy study (called TOSCA-5) is underway at 13 sites in Canada (of these, Sunnybrook is the highest-enrolling), as well as two in the Netherlands and two in Israel. An anticipated 90 participants will be randomized to receive one of either collagenase or a placebo after each site receives training in how to do the procedure. The study is in its early phases, but Strauss expects results by the end of 2015. In the meanwhile, he has spun off a company from his research, Matrizyme Pharma, which is charged with the commercialization of the enzyme, MZ-004.
Left: Dr. Bradley Strauss has developed a treatment to make difficult-to-treat artery blockages more amenable to minimally invasive procedures and a smartphone app to improve care during patient recovery. Right: This false-colour angiogram of a heart shows a large blockage in the left anterior descending coronary artery. No contrast medium can penetrate the solid plaque that fills the inside of the artery.
Photo (right): ©SIMON FRASER/Science Photo Library/Corbis
Martin Griedman, 69, was one of the early trial participants in TOSCA-5. Griedman had always been one of those enviably fit types. He often walked the 90 minutes home from his office. He cycled all summer. He jogged. After retiring from his stressful job running an engineering firm, Griedman kept up his fitness. But then quite suddenly, he was always out of breath. The short walk he’d done a million times to the grocery store near his condo required three or four rest stops along the way. Even just sitting still, his breathing was laboured, and he had terrible pain between his shoulders. Most terrifying was how abrupt and debilitating his physical decline was. An angiogram confirmed that he had 100% occlusion of an artery. His cardiologist attempted an angioplasty, but after an hour-and-a-half the guide wire still could not pierce the hard blockage. (The procedure can take as little as 30 minutes.) Griedman came out of the procedure deflated and worried that his only other option would be open heart surgery.
Because he had a particularly stubborn occlusion, Griedman was put in touch with Strauss and his team. He fit the bill perfectly and was quickly enrolled in the TOSCA-5 trial. Griedman was eager to try any treatment, however experimental, that would keep him off the operating table. In September 2014, less than a month after his failed angioplasty, Griedman was injected with a dose of collagenase that had been determined to be safe and effective during the early trial, via the wrist, through the main artery in his heart directly into the blockage. The following afternoon, the angioplasty procedure began. “Suddenly I heard the doctor say, ‘We’re through!’” recalls Griedman. “I couldn’t believe it—they got the guide wire through.” The effects were instantly noticeable, he says. “Even in recovery, I felt immediately better—stimulated, not so sluggish. Friends saw me after and said my face had a different colouring.” Griedman’s was a best-case scenario, and following six months of rehab, he is now walking three miles a day four times a week, while cycling and resistance training twice a week. “I’d say I’m 75% of where I was,” he says. If Phase 2 trials go well, then collagenase could become a standard treatment of complex chronic total occlusions, and eliminate the need for invasive cardiac surgery.
Minimizing the invasiveness and possible additional damage caused by cardiac procedures has become a running theme in Strauss’s work. He has also been studying the common practice of clot removal when a heart-attack patient undergoes an angioplasty. Decade-old studies had found that extracting the offending clot boosted survival rates in the long run, but Strauss wasn’t convinced. “We weren’t sure it was based on good science,” he says. He wondered if the effects of the procedure were really worth the potential harm caused by opening the artery to pull out the clot. “When you go in and try to open it up, some of the clot actually moves downstream to smaller vessels and may block them up,” he says, “which may extend the heart attack.” While two other recent studies have confirmed clot removal doesn’t improve lifespan among cardiac patients, Strauss’s research delves deeper into the mechanical level of what happens to heart muscles if the whole clot is left to embolize naturally downstream. He asked: if we know the procedure provides no real benefit, would not doing it cause more harm? In other words, if the whole clot is left to run its course, what’s the worst that would happen to an already damaged heart muscle?
To answer the question, he and his colleagues injected a clot directly into the artery using a preclinical model and waited to see what happened. Using magnetic resonance imaging they observed that in the short term the infarcts were a little larger, but six weeks later, the hearts had adjusted and there were no differences, except a minor amount of heart muscle wall thinning. “This suggests there is no reason to pull out the clots, because there is no long-term benefit,” he says. “Our study gives molecular evidence that this is the case.”
As important as acute on-the-table cardiac care is, Strauss’s latest project looks farther down the continuum at patient recovery—an aspect that he feels is underserved. “We know everything that happens to the patient during the procedure and directly after,” he says. “But as soon as they go home, they are off the radar.” More than 1,800 angioplasties are performed at Sunnybrook every year. “That’s a lot of phone calls,” Strauss says. “We just don’t have the resources to adequately follow up with patients in any organized way. And I think that impacts the quality of care.”
In collaboration with the Cardiac Care Network, a provincial agency responsible for improving cardiac care, Strauss’s idea for a smartphone app began taking shape in 2013. Rather than tasking a hospital staffer to follow up by phone, the app would do all the prompting and present an easy way for patients to answer questions that would determine how they’re recovering, while also allowing them to ask questions or voice concerns. The app would be loaded onto a patient’s phone (or the phone of a family member) and it would pose a series of questions at predetermined intervals (after a few days, then the following month, and so on up until six months). How do they feel? Are their symptoms abating? Are they taking their medications properly? Have they had another heart attack or cardiac event?
The app (designed for iPhone and Android operating systems) should be up and running in the next couple of months, Strauss says, and will be piloted at Sunnybrook and three other centres in Ontario. There may be some troubleshooting for elderly patients, who may not be comfortable with the technology, or people for whom English is a second language, but Strauss is confident that the technology will be successful. “It could have widespread impact and give us the opportunity to educate patients,” he says. “It’s a way to improve communication between patients and doctors. And it’s not often easy for patients to have access to the people who did the procedure.”
Breaking down barriers, both metaphorical and physical, Strauss’s research seems to advance one sweeping outcome: optimizing cardiac treatment at all stages. “I guess there’s a theme to my work,” Strauss says modestly. For people like Griedman, Strauss’s efforts have resulted in nothing short of a second chance: “He’s made me a different person,” he says. “It’s a gift, really.”
This research was funded by the Canadian Institutes of Health Research and Heart and Stroke Foundation. The Canada Foundation for Innovation and Ontario Ministry of Research and Innovation provided infrastructure support.
