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Damage control

Dr. Davinder Jassal has set a new standard for detecting cardiac injury caused by drugs used to fight breast cancer. Now he hopes to stop those drugs from hurting the heart in the first place

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Winnipeg Health Region
Wave, July / August 2012

Penny Copeland's story begins as it does for so many women with breast cancer.

In 2007, while showering, the 44-year-old Winnipegger discovered a lump a bit bigger than a pea in her right breast.

"It was about one and a half centimeters across. It felt huge to me." Dread and fear came next.

Copeland, whose mother had breast cancer, knew immediately what she faced. "I never assumed it was anything other than breast cancer," says the mother of two.

A mammogram confirmed her fears.

Every woman with breast cancer receives surgical treatment, with either a lumpectomy or mastectomy followed by radiation and chemotherapy to prevent the cancer from spreading. And this was the case with Copeland. She had a mastectomy and reconstructive surgery that rebuilt her breast using fat from her belly. Cancer had spread to one lymph node, which surgeons also removed. Chemotherapy and radiation were also ordered.

But this is where Copeland's story veers from the typical breast cancer plot.

Through breast cancer tissue analysis, Copeland tested positive for HER2 (human epidermal growth factor receptor type 2), a protein that promotes cancer cell growth. HER2- positive breast cancers are generally more aggressive and grow faster than other types of breast cancers. An estimated 25 to 30 per cent of women with breast cancer are HER2- positive, and all of them are candidates to receive treatment with a relatively new drug called Trastuzumab (Herceptin).

Approved by the United States Federal Drug Administration in 1998, Herceptin is considered a wonder treatment for patients with aggressive breast cancers because it specifically targets fast-growing cancer cells and reduces the chance of breast cancer recurrence by half.

But the drug has some serious risks, too.

While effective in knocking out cancer cells in HER2- positive patients, it can also cause heart damage. Research shows that Herceptin, when used with chemotherapy including anthracyclines, can weaken the heart muscle and cause heart dysfunction in up to 25 per cent of women.

As a result, doctors are cautious about using Herceptin and monitor the patient closely with cardiac imaging. All women with breast cancer who receive Herceptin, are monitored with serial multi-gated acquisition (MUGA) scans. These scans, which are essentially an X-ray, assess the pumping function of the heart. When the pumping function drops to less than 40 per cent, Herceptin is stopped and the patient is referred to a cardiologist for further management of this heart failure syndrome.

Enter Dr. Davinder Jassal, Associate Professor of Medicine, Radiology and Physiology at the University of Manitoba's Faculty of Medicine, Principal Investigator of the Cardiovascular Imaging Laboratory at St. Boniface Hospital Research, and Medical Director of the Winnipeg Health Region's Coronary Care Units.

Born in Thompson, raised in Winnipeg and trained at the University of Manitoba and Harvard, Dr. Jassal is a rare breed: He is a physician who sees heart patients and also conducts leading edge cardiac research and clinical trials. "I have the best of both worlds," Jassal says. "I like seeing patients in my clinic but I also have the research bug," he says, adding that his dual life gives him a first-hand opportunity to see his research at the benchtop translated into better care and even prevention at the bedside.

At any given time, Jassal and his team of student researchers at the Cardiovascular Imaging Laboratory, located on the fourth floor of the Campbell G Maclean Building, will have a dozen or more research projects on the go, all designed to provide more insight into the heart and how it functions.

To carry out this work, Jassal depends on the latest imaging equipment technology, including echocardiography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI).

While Jassal's work covers a lot of ground, one of his main areas of interest involves research into the damage to the heart caused by breast cancer treatments, or more precisely, how to prevent the damage from occurring in the first place.

As he explains, scientists discovered soon after Herceptin was approved that it could cause potential heart problems when used in conjunction with chemotherapy. "That's why I call Herceptin a double-edged sword. It's good for cancer, bad for the heart," he says.

In 2005, Jassal embarked on a research project aimed at answering some of the big questions around the issue of breast cancer treatment and heart damage.

Among other things, he wanted to know whether women treated at CancerCare Manitoba were experiencing Herceptin mediated heart dysfunction, whether any damage that did occur could be detected sooner, and whether anything could be done to protect the heart from being damaged at all.

The first phase of this research looked at the experiences of 152 women with breast cancer at CancerCare Manitoba during 2006 and 2007. The study revealed that 36 women developed heart failure, which suggested that as many as one in four women can be affected by this drug. The findings conclusively confirmed earlier research results in animal studies. The results took researchers one step closer to understanding heart failure in cancer patients and another step forward in helping discover preventive care.

But it was during the follow-up to this initial phase of research that Jassal would make an important discovery, one that would change the way many oncologists may treat their patients.

While breast cancer patients undergoing chemotherapy with Herceptin are monitored with MUGA scans to keep close tabs on the heart's pumping function, the problem is they can only see the damage after it has happened. Jassal wondered if imaging technologies like tissue Doppler imaging using echocardiography (essentially using ultrasound to measure cardiac function) and cardiac magnetic resonance imaging could get clearer pictures of the heart sooner.

In 2008, Jassal began testing his hypothesis on mice treated with Herceptin. After just one treatment of Herceptin, tissue Doppler imaging using echocardiography was able to detect early changes in cardiac function as compared to traditional methods. Jassal then began a clinical trial to see if similar results would apply in women with breast cancer.

Copeland was one of the participants in that clinical trial. As she was undergoing treatment with Herceptin and chemotherapy, she was given a regular MUGA scan, blood tests, tissue Doppler imaging using echocardiography and cardiac magnetic resonance imaging at baseline, three months into treatment, six months and one year into treatment. Researchers in Jassal's lab compared images, looking for changes in heart function.

This 2008 clinical trial confirmed Jassal's earlier findings in mouse models. Of the 42 women in the study, 10 (25 per cent) developed some heart damage. While traditional MUGA scans detected damage after six months of treatment, tissue Doppler imaging revealed small changes in the heart's pumping function at just three months and before any serious damage occurred.

This was a major breakthrough for Jassal and his team and for breast cancer patients around the world. The results had the potential to have a major impact on cancer and heart care. Instead of waiting to treat the damage caused by Herceptin, Jassal's findings opened the door for the early detection of heart failure as compared to traditional methods. The ultrasound test is non-invasive and has been proven to give doctors a potential three-month head start to prevent any potential heart damage in breast cancer patients.

The story also turned out well for Penny Copeland. As a research subject undergoing a multitude of scans and under the watchful eye of Jassal and his team, Copeland's mind was set at ease. "It was reassuring," she says. "I wish everybody could have that many tests to protect them."

In the end, Herceptin didn't hurt her heart. And today, at 50 years of age, she is cancer free.

Jassal's quest, meanwhile, continues. Having developed a way to detect heart damage in breast cancer patients sooner using tissue Doppler imaging, he is now turning his attention to preventing any damage from occurring in the first place. He and his Winnipeg team of researchers have joined forces with cardiologist Dr. Ian Patterson at the University of Alberta in Edmonton for a new clinical trial.

The trial involves about 50 women with breast cancer from Winnipeg and Edmonton and will be completed in 2014. During the study, one third of the women getting cancer treatment will receive beta-blockers, one third will receive ACE-inhibitors and a third will receive a placebo prior to receiving chemotherapy and Herceptin. Both beta-blockers and ACE-inhibitors are used to treat different heart problems like high blood pressure, congestive heart failure and heart arrhythmias, among other conditions. The hope is to determine whether any of these medications can prevent damage to the heart.

As part of the study, patients will receive doses of the heart medications in conjunction with chemotherapy with the hope of preventing heart damage of any kind. Researchers will also perform an array of imaging tests, as performed in previous studies, to monitor heart function and damage caused by Herceptin.

The goal, says Jassal, is to discover whether the drugs in question could be used as a kind of "magical pill" to block the cardiac effects of Herceptin.

Robin Summerfield is a Winnipeg writer.

*   *   * 

Bio: Dr. Davinder Jassal

  • Dr. Davinder Jassal was born in Thompson, Manitoba.
  • Received an International Baccalaureate diploma from Winnipeg's Sisler High School.
  • Graduated from the University of Manitoba with an MD in 1998.
  • From 1998 to 2004, Jassal completed a residency in internal medicine at the University of Manitoba and a residency in cardiology at Dalhousie University in Halifax, Nova Scotia.
  • Completed a clinical and research fellowship in cardiac imaging, specializing in ECHO, CT and MRI at Massachussetts General Hospital, Harvard Medical School in Boston, MA.
  • In 2006, returned to Winnipeg and the Faculty of Medicine at the University of Manitoba in the Department of Internal Medicine's Cardiology Section.
  • He is an Associate Professor of Cardiology, Oncology, Radiology and Physiology. Jassal is also the Director of the University of Manitoba's Cardiology Residency Training Program.
  • He is the Prinicipal Investigator of the Cardiac Imaging Laboratory within the Institute of Cardiovascular Sciences at St. Boniface Hospital Research.
  • He holds a new investigator award from the Heart and Stroke Foundation.
  • He is Medical Director of the Winnipeg Health Region's Coronary Care Units.

Source: St. Boniface Hospital Research

*   *   *

Heart research

Winnipeg cardiologist and researcher Dr. Davinder Jassal is currently focussing on three main themes of research:

Marathon runners

While the positive long-term health effects of exercise on the cardiovascular system are well documented, less is known about how extreme exertion, like a 26-mile marathon, affects the heart. Although it is a statistically small number, marathoners have been known to drop dead after or even during a race. Jassal wondered if the extreme endurance race actually harmed the heart and caused heart failure. That was and continues to be the basic starting point of his marathon research.

The Manitoba Marathon provided all the research subjects he needed. For the past six years, Jassal has studied runners using two imaging techniques, echocardiography and cardiac magnetic resonance (CMR) imaging, and blood testing that look for changes in bio-markers (biochemical evidence in the blood that indicate heart damage). The amateur runners were put through a battery of tests before the race, immediately after the marathon and one week later. "The bottom line, all across the board, was that the right side of the heart balloons out and stops pumping blood efficiently to the lungs," he says.

The good news?

"All of the runners had (heart) injury to the right side but it was all transient damage," says Jassal.

Within one week of running the marathon, runners were retested and their hearts were completely back to normal. The study, which was published in the American Journal of Cardiology in 2009, was an international sensation. Jassal's work was picked up by local, national and international media around the globe. He has follow-up marathon research studies in the queue including a study of halfmarathon runners and multiple marathon runners. More recently, Jassal has tweaked his cardiac marathon research focus. He is currently studying the impact of marathons on pregnant runners.

Women's health

Jassal is currently investigating the effects of pregnancy on the heart using echocardiography and cardiac magnetic resonance imaging. The study, called Cardiac Hemodynamic Imaging and Remodeling During Pregnancy (CHIRP) hopes to expand our understanding of how women's hearts are taxed during pregnancy. Researchers know that pregnancy causes many changes, including the enlargement of all four chambers of the heart and a 40 per cent increase in cardiac output (pumping of blood).

Through his research, Jassal hopes to determine the "range of normal structural and functional changes of the heart during a healthy pregnancy using magnetic resonance imaging." Knowing the normal range will help physicians better treat pregnant women who fall outside the range of normal, and possibly help prevent permanent heart damage.

Sleep apnea

An estimated five per cent of North Americans have obstructive sleep apnea (OSA), a sleep-related disorder characterized by an obstruction in the upper airway. OSA often causes pauses in breathing during sleep. Oxygen sleep masks - which provide continuous positive airway pressure (CPAP) - have been shown to help prevent cardiac-related deaths caused by sleep apnea and enhance quality of life. Using blood testing, echocardiography and cardiac magnetic resonance imaging, Jassal studied how sleep apnea affects the heart in patients using CPAP. Patients in his study underwent tests before CPAP treatment, and at the three-, six- and 12-month marks. The results, published in CHEST this year, demonstrated that in OSA patients who were compliant with CPAP therapy, their hearts favorably remodeled and demonstrated improved pumping function when studied with echocardiography and cardiac magnetic resonance imaging.

 *   *   *

Five tips for a healthy heart

Dr. Davinder Jassal offers the following suggestions to help keep your heart healthy.

Stop smoking

In addition to causing many types of cancer, tobacco smoke is also one of the causes of coronary heart disease (heart attacks). Smoking is connected to plaque build-up in the arteries, increased risk of blood clots and high blood pressure, and reduces the amount of oyxgen carried in the blood. For help quitting smoking, go to Smoker's Helpline at www.smokershelpline.ca.

Eat healthy

Everyone's diet should include plenty of fruits, vegetables, whole grains, unsaturated oils and lean protein. Daily servings depend on age and sex. It's also helpful to cut out junk food and fast food. Eat whole, unprocessed foods as much as possible. Reduce salt and sugar intake. Eat in moderation. For helpful tips and some sound, healthy eating principles, check out Canada's Food Guide.

Reduce stress

While the connection between increased stress and heart disease and stroke isn't 100 per cent clear, it is believed prolonged stress can lead to higher blood cholesterol and higher blood pressure. It may also be connected to a narrowing of the arteries. Prolonged stress can lead to depression and anxiety, and it also makes it more difficult to lead a healthy lifestyle including eating well, getting lots of sleep and being active.

Get moving, get active

Active and fit people are less likely to suffer from heart disease or have heart attacks or strokes. Regular aerobic activity increases blood flow and improves circulation and strengthens your heart and cardiovascular system - all things that make a healthy heart. Adults should get a minimum of 30 minutes of aerobic exercise every day or 150 minutes per week.

Know your numbers: weight, blood pressure and cholesterol

Visit your doctor regularly and get your blood pressure and cholesterol checked. Weigh yourself regularly to keep on top of weight gain before five extra pounds become 10, and so forth. Keeping track of your numbers and keeping your numbers in check will keep your heart healthy and prevent cardiovascular disease, heart attacks and strokes.

Sources: Dr. Davinder Jassal; Heart and Stroke Foundation of Canada; Health Canada; Canadian Society for Exercise Physiology

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