When she was only 45, Maggie Thiesen, a Calgary mother of four, developed congestive heart failure, a condition whereby the heart becomes too weak to efficiently pump blood to other organs, causing swelling in the tissues. Over the next three years, her condition got progressively worse, to the point where she couldn't walk more than two blocks without huffing and puffing. Maggie was headed for the heart transplant waiting list, but in January 2008, she became the first Canadian patient to receive the HeartNet, an experimental device that would help her ailing heart pump properly. The device is just one of many recent, lifesaving breakthroughs in cardiovascular research. Canadian Living asked a number of noted cardiovascular specialists from across the country about this and other key advances.
Q: More than 500,000 Canadians have congestive heart failure. How does the HeartNet stop or slow progression of the disease?
A: The device is an expandable nickel titanium net that puts gentle pressure on the heart, causing it to shrink over time. "The goal is for the heart to get smaller and stronger," enabling it to pump blood more efficiently, says Dr. Debra Isaac of the Foothills Medical Centre in Calgary, where Maggie’s operation took place.
The concept of wrapping a device around the heart to restrain growth isn't new, but previous efforts have been hampered by the fact that they involved major open-heart surgery. This procedure, in which the device is inserted through a small incision between the ribs under the left breast, is minimally invasive and can be tolerated by patients with very sick hearts. "Putting on the device after we make the incision takes only 20 minutes," says Isaac. "Our patients recover so well they are out of hospital in three days."
By preventing progression to endstage heart failure, the HeartNet could dramatically reduce the need for heart transplants. That's what happened to Maggie. Since the operation, her condition has improved significantly. She can now walk her dog for a half an hour without feeling short of breath. "I have more energy and want to do more," she says. "If I do things in moderation, I feel great."
Isaac is leading the Canadian arm of an international clinical trial to compare the effectiveness of the device against conventional drug therapies. At least 50 patients will be enrolled in centres in Montreal, Toronto, London, Ont., Calgary and Vancouver. "It’s very satisfying to be involved on the cutting edge of a new treatment that could turn things around for these patients," says Isaac.
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Q: Some people are genetically predisposed to develop heart disease at an early age. Is there a way to identify these people and begin preventive treatment before serious problems develop?
A: At least one Canadian researcher is on this track. Dr. Ruth McPherson, director of the Lipid Clinic and AtheroGenetics Laboratory at the University of Ottawa Heart Institute (UOHI), has identified a common genetic variation on chromosome 9 that increases the risk of developing premature heart disease. McPherson’s research team used a technique known as genome-wide scanning to compare the DNA of 1,800 Ottawa patients with premature heart disease to the DNA of 1,800 healthy Ottawa seniors and to pinpoint crucial differences.
McPherson's landmark 2007 study showed that about 25 per cent of Caucasian Canadians carry two copies of this flawed stretch of DNA, which increases their heart disease risk by 50 per cent. A further 50 per cent of Caucasians carry one copy, which increases their risk by 25 per cent. This discovery could lead to better genetic tests to assess future heart disease risk, allowing people to take preventive action through exercise, diet and drugs. "Within five years we hope to have a simple blood test that uses up to 10 genetic variants to give an accurate assessment of heart disease risk," she says.
Q: Time is of the essence when someone has a heart attack. Are there any systemwide efforts in Canada to speed up the response time to get treatment?
A: That's also in the works at the UOHI. When a person in Ottawa calls 911 complaining of chest pain, a crew of advanced care paramedics is immediately dispatched. These paramedics are trained to interpret the results of an electrocardiogram and recognize the deadliest form of attack, known as a STEMI (ST-Elevation Myocardial Infarction). If a STEMI is detected, paramedics bypass emergency departments and route the patient directly to the UOHI, where a team performs an emergency angioplasty (a procedure using a balloon to clear blocked arteries).
A 2008 study in the New England Journal of Medicine showed that such a streamlined approach cut the death rate in half, from 10 per cent to less than five per cent. "Patients leave the hospital sooner and they also have fewer complications," says Dr. Michel Le May of the UOHI, who authored the study.
The citywide emergency system cuts the "door-to-balloon time" – the time from hospital arrival to first balloon inflation – to only 69 minutes (the average for patients referred through emergency departments is 123 minutes).
Elsewhere, hospitals in Calgary and Vancouver are also helping to shorten the time to treatment by transmitting electrocardiograms from the ambulance to emergency physicians.
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Q: Do shift workers experience additional health issues because of interrupted sleep patterns?
A: This is a growing concern and one being addressed by Dr. Michael Sole of the University Health Network (UHN) in Toronto. He has found that chronic sleep cycle disruption can seriously enlarge and damage the heart. In a 2008 study, Sole showed that when hamsters’ sleep cycles are chronically out of sync with external stimuli such as light and darkness, the animals die at a younger age with cardiomyopathy (an enlarged heart) and severe kidney disease. When sleep cycles are normalized, the harmful effects are reversed.
Sole's research shows that renewal and repair of heart tissues occur mainly during sleep at night. "Cell renewal and remodelling is a rhythmic process that is dependent on synchronicity between the external environment and the body’s internal clock," says Sole, a cardiologist at the UHN’s Peter Munk Cardiac Centre. "Disrupting the daynight sleep cycle interrupts the renewal process, and that interruption leads to tissue disease. Heart muscle cells become impaired and die, and are replaced by scar tissue."
His findings have disturbing implications for the nearly 30 per cent of Canadians who work irregular shifts. Sole advises these people to maintain a consistent schedule for a month or more if possible, so that their body has time to adjust its internal clock. Healthy sleep – seven to eight hours – is as important to heart health as nutrition and exercise, he says.
This research could be particularly worrisome for people who already have heart disease or high blood pressure for whom a regular day-night sleep pattern is especially important. "I'd be very concerned about a patient with heart problems doing shift work," he says.
Q: More and more patients are getting stents to prop open narrowed arteries following a balloon angioplasty. Are these devices safe?
Yes, increasingly so.
Dr. Michael Kutryk of St. Michael's Hospital in Toronto has come up with a way to harness the body's ability to heal the area of the blood vessel damaged during an angioplasty procedure. He has developed a coronary stent coated with antibodies that attract endothelial progenitor cells (EPC) circulating in the bloodstream. EPCs are involved in the repair of damaged blood vessels; they evolve into endothelial cells that line blood vessels and allow blood to flow smoothly.
The new device offers key advantages over the commonly used drug-eluting stents (those coated with a drug to prevent renarrowing of the artery). Results from a 2008 European study suggest that these new antibody-coated stents promote faster blood vessel healing and reduce the risk of blood clots by rapidly forming a protective endothelial layer over the stent. And while patients treated with drug-eluting stents must take bloodthinning medications for the first year after angioplasty to prevent blood clots, the new stent eliminates the need for this medication. "With antibody-coated stents, the risk of blood clotting is as low as can be," says Kutryk. "That’s important because 50 per cent of patients who develop blood clots after angioplasty will die."
Angioplasty procedures using this new invention have been performed on more than 20,000 patients at 250 medical centres worldwide. At St. Michael’s Hospital in Toronto, Kutryk had performed 18 procedures by mid-November on patients who were allergic to blood-thinning medications or who were actively bleeding and therefore could not use them (and so were inelligible for drug-eluting stents). Without the new stent, most would not tolerate open-heart surgery. Kutryk expects the device to be approved for wide use in Canada within two years.
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Q: Heart bypass operations are still considered major surgery; is there a less invasive alternative?
A: Yes there is. Dr. Marc Ruel of the UOHI has introduced a new, minimally invasive multivessel bypass procedure in which he does grafts on a beating heart through a tiny "keyhole" incision. In this innovative procedure, called Multi-Vessel Small Thoroctomy (MVST), the surgeon makes a small incision (not much larger than a paper clip) between the ribs and uses specially designed precision tools to move the heart into position. MVST is especially suitable for patients who need to return to physically demanding jobs soon after surgery, and for those with complex medical issues that put them at higher risk for surgical complications such as stroke, internal bleeding – even death.
"We’ve done this on close to 100 patients in Ottawa of all ages, from their late 30s to mid-80s,” says Ruel. “The results are very good and the recovery can be quite rapid," with patients usually leaving hospital within four days and returning to work within a month.
Ruel has trained surgeons at the Sunnybrook Health Sciences Centre in Toronto and Laval University Hospital in Quebec in this new technique.
Q: We've heard that stem cells are the key to fixing a damaged heart. How far along is this research and when will it be widely available?
A: The research is advancing at a quick pace, thanks in part to Dr. Gordon Keller, director of the McEwen Centre for Regenerative Medicine at the UHN in Toronto. Keller has discovered the elusive "recipe" for three of the major cell types of the human heart from embryonic stem cells.
He begins by adding a cocktail of growth factors and other molecules to stem cells to develop early-stage heart cells, also known as heart progenitor cells. He then coaxes these cells to make millions of cardiac muscle cells (beating cells, which pump blood), endothelial cells (which line blood vessels) and vascular smooth muscle cells (which form blood vessels). "You can see the heart muscle cells contracting in the petri dish, which is spectacular," says Keller.
The plan is to eventually produce a large supply of these heart cells to attempt to replace damaged heart tissue.
Keller's team is also doing experiments attempting to make comparable heart cells from reprogrammed human skin. This would transform human skin cells into early-stage heart cells, thus avoiding organ rejection in tissue transplants. He plans to work with tissue engineers in Toronto to combine lab-cultured heart cells with supportive scaffolding to create pieces of artificial heart tissue that would then be grafted onto the heart. Keller believes these cardiac patches would be more effective than transplanting the cells alone.
It will likely be several years before results of these animal studies are known and even longer for this approach to reach your local hospital.
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Q: Gene therapies are also getting a lot of attention. In the field of heart disease, what’s coming down the pipeline?
A: Researchers are testing treatments that combine genes and stem cells – with the idea that the synergistic benefits of this combined therapy are better than those of either the gene or stem cell therapies alone.
Dr. Duncan Stewart of the Ottawa Health Research Institute (OHRI) developed the world’s first experimental gene plus cell therapy for pulmonary arterial hypertension, a devastating heart-lung disease affecting mainly young women, in which the vessels that carry blood from the heart to the lungs become damaged. The new treatment involves adding a gene that makes nitric oxide (which stimulates the growth and repair of blood vessels) into stemlike cells called endothelial progenitor cells, which circulate in the bloodstream. He then injects these souped-up cells into the lungs. "We're seeing improved lung function in these patients, and the safety looks excellent," says Stewart, a cardiologist and CEO of the OHRI.
Both gene therapy and stem cell treatments have been tested separately in heart attack patients, with only limited success. One reason for this, suggests Stewart, is that the stemlike cells circulating in the blood of patients with heart disease don’t produce enough nitric oxide.
Stewart is now set to launch a three-year clinical trial in which investigators will be injecting heart attack patients in Ottawa, Montreal and Toronto with stemlike cells that contain the nitric oxide gene. This strategy, he adds, holds tremendous promise in the field of cardiovasclar research. "Unlike drug treatments, it could potentially restore functional tissue in regions of the heart that otherwise would form only scar tissue."
Q: Some patients with a faulty aortic valve – the valve controlling blood flow from the heart to the rest of the body – are too sick for surgery. Are there other alternatives?
A: Yes. A good example is a procedure pioneered by Dr. John Webb of the Providence Heart and Lung Institute at St. Paul's Hospital in Vancouver. This minimally invasive technique, known as a percutaneous (through the skin) valve replacement, replaces the aortic valve in patients who aren't candidates for open-heart surgery. Without a valve replacement, most of these patients would die within three to five years.
In this new procedure, Webb inserts a replacement aortic valve (attached to a catheter) through an incision on the upper thigh and threads it along an artery into the heart. Unlike open-heart surgery, the procedure does not require cracking the ribs and breastbone, stopping the heart or putting the patient on a heart-lung machine.
Webb has performed this procedure on more than 150 patients, and trained doctors at hospitals in Canada (including Laval Hospital in Quebec City, McGill University Health Centre in Montreal, and the UHN's Toronto General Hospital) and the U.S. and Europe.
The results have been excellent. "The success rate is over 95 per cent," says Webb. "It’s very exciting to see patients who had no options have their valve disease cured in a matter of hours and leave hospital in a few days," whereas about 30 per cent of them would have died within a month after conventional open-heart surgery. Webb predicts that not only high-risk patients but also many others who need a new aortic valve may one day be candidates for this procedure.
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