There are a whole host of drugs that can cause cardiovascular complications.

Exploring the link between cancer treatment and heart disease

At 48, Colleen Schindler-Lynch was diagnosed with HER2-positive, an aggressive form of breast cancer. To treat it, she underwent surgery in September 2015, then two rounds of chemotherapy that fall and winter. Following chemo, she got 30 rounds of radiation.

By June 2016, the Toronto resident’s life was getting back to normal. In fact, she says she felt phenomenal.

“I was out power-walking everywhere,” says Ms. Schindler-Lynch. She was even steadily shedding the 20 pounds that she had gained from chemotherapy.

But while Ms. Schindler-Lynch was busy beating cancer, her heart function had dropped as much as 15 per cent during her chemotherapy. It’s something that she, as a cancer patient, would normally not be aware of. “I didn’t feel any different,” she says.

Her reduced heart function was caught as a result of a pioneering clinical trial investigating the connection between cancer treatment and cardiovascular disease.

For cancer patients like Ms. Schindler-Lynch, chemotherapy can be a lifesaver. But it can also be toxic to the heart and can cause cardiovascular disease.

Dr. Paaladinesh (Dinesh) Thavendiranathan is a cardiologist at Toronto General Hospital and the director of the Cardiotoxicity Prevention Program at the Ted Rogers Centre for Heart Research at the Peter Munk Cardiac Centre in Toronto. Dr. Thavendiranathan is at the forefront of cardio-oncology, a new field within cardiology that is focused on recognizing, preventing and treating cardiovascular complications of cancer therapy.

Twenty years ago, cancer treatments didn’t work as well as today’s molecular targeted therapies. If patients had high-risk cancer, they were going to die from it, and the focus was to improve survival by months or a few years, Dr. Thavendiranathan says.

“That has changed because of the significant advances in cancer therapy,” he says. “Now, a woman with early stage breast cancer has about an 87 per cent [chance] that they’ll live past five years. So now all the potential side effects from the cancer therapy have become important, because you can have a breast cancer survivor who now develops heart disease.”

Certain classes of drugs used to treat cancer, such as anthracyclines and trastuzumab, can cause heart failure in a small percentage of patients, says Dr. Thavendiranathan. Radiation therapy can cause disease to the muscles as well as the arteries of the heart. There’s also a group of drugs called tyrosine kinase inhibitors that can cause artery disease and VEGF (vascular endothelial growth factor) inhibitors can cause high blood pressure. There is also a new class of drugs called immune check-point inhibitors that can cause inflammation of the heart called myocarditis.

“So there are a whole host of drugs that can cause cardiovascular complications,” he says.

About two to five per cent of breast cancer patients will develop heart failure during cancer therapy, Dr. Thavendiranathan says, and patients who receive radiation therapy have a 20-30 per cent higher chance of developing vascular disease in the long term. Also, one in five will develop some vascular disease in the long term. Up to 50 per cent of patients may develop high blood pressure from VEGF inhibitors.

In Ms. Schindler-Lynch’s case, her chemotherapy concluded with the use of trastuzumab. Through a referral from her oncologist, she was able to participate in one of Dr. Thavendiranathan’s clinical trials, called EMBRACE MRI. This trial looks at advanced methods for early identification of heart dysfunction in women with breast cancer who are receiving treatment.

During the trial, Ms. Schindler-Lynch got regular heart MRIs and echocardiograms to measure her heart performance. Tests showed her heart function had dropped as much as 15 per cent several months into the yearlong use of trastuzumab.

Because of this loss in function, she was put on a medication that makes it easier for her heart to pump, preventing it from deteriorating further. This would then allow her to complete her planned cancer therapy.

Ms. Schindler-Lynch says she was “ecstatic” about being able to take part in the trial. “We would not have even known I had decreased heart function had it not been for Dinesh and the trial.”

The EMBRACE MRI trial – funded through donor support and the Canadian Institutes of Health Research – is focused on 136 women with HER2-positive breast cancer, says Dr. Thavendiranathan, who is the study’s principal investigator with radiologist Dr. Bernd Wintersperger.

The patients, who are women in their early 30s to late 70s from all over the world, are monitored with heart MRIs and blood work every three months for 18 months from just before initiating cancer therapy to its completion.

Through MRI, researchers look for markers in the heart that are normally not measured in patients receiving cancer therapy. These markers include inflammation, edema (water in the heart muscle) and fibrosis (scarring within the heart muscle), markers that can be early signals that they have heart injury.

Dr. Thavendiranathan says they’re also looking at genetic markers and new blood protein markers that may also help identify patients who may be at risk of developing heart or vascular disease.

EMBRACE MRI is one of three trials Dr. Thavendiranathan is involved in that investigate cancer and heart disease. In the SPARE HF trial, researchers want to learn whether they can prevent heart damage if they put patients on protective medications.

The SPARE HF trial, which began in May 2018, involves 112 cancer patients – men and women from diverse backgrounds with many different types of cancers – who are being treated with anthracyclines. These patients receive a cardiac MRI to assess their heart function before they start their drug therapy, and they stay on a cholesterol-lowering statin or placebo during the course of their treatment. MRIs are repeated after treatment is completed to assess if a change in heart function has occurred.

The SPARE HF study was developed by Dr. Thavendiranathan and Dr. Eitan Amir, an oncologist at the Princess Margaret Cancer Centre in Toronto. Dr. Amir says he’s been a big supporter of Dr. Thavendiranathan’s work since 2013, and that Princess Margaret is a major referral stream for the studies.

“This is an example of collaboration which has worked very well,” Dr. Amir says. “There are some exciting things happening in this space, and hopefully [we] will be one of the leaders going forward in showing the world how to best manage these patients.”

Dr. Thavendiranathan is also leading the North American arm of the SUCCOUR international multicenter study. This study is focused on looking at two advanced imaging techniques by cardiac ultrasound (echocardiography) to detect early heart damage. One method is referred to as 3D echocardiography while the other is called strain imaging. Once early heart damage is identified, the investigators quickly start heart protective medications with the hope of preventing subsequent heart failure.

Dr. Thavendiranathan notes that cardiovascular disease is a growing problem because of our aging population and the many different drugs being used to treat cancer. But he stresses that it’s important to put these cardiovascular risks into perspective.

“Sometimes we forget that the problem that the patient has is their cancer,” he says. “Cardiovascular disease is a potential [problem]. Therefore the overall focus should still remain on the best cancer therapy with interventions to minimize the cardiovascular risk.”

Dr. Christine Brezden-Masley is president of the Canadian Cardiac Oncology Network and a medical oncologist at St. Michael’s Hospital in Toronto. She says that Dr. Thavendiranathan’s work has moved the field forward.

“It’s important that cardiologists and oncologists continue to work together to ensure that we figure out who is at risk,” says Dr. Brezden-Masley, who has been a co-investigator on the SPARE HF and EMBRACE trials.

“We can cure cancer, but we also have to save their hearts.”

This article originally appeared in the 2018 issue of the Peter Munk Cardiac Centre magazine. Read it here.