MICROHEARTS
Better cancer treatment options mean higher survival rates, but long-term survivors risk cardiovascular disease later in life. At InvivoSciences, Ayla Annac is growing microhearts to help better understand the cardiovascular risks of cancer treatment.

Ayla Annac, CEO of InvivoSciences, is leading the next wave of cancer care and asking the one question many patients don’t consider: What happens to survivors once cancer is behind them?

As treatment methods become more effective, survivorship is on the rise. While higher survival rates seem to signify a change for the better, Annac says doctors and patients forget about their futures. Multiple studies by researchers from universities including the Mount Sinai School of Medicine and Columbia University note an increased risk of heart disease in cancer survivors, particularly survivors of breast cancer and childhood cancer. Researchers believe treatment methods such as chemotherapy and radiation therapy weaken the heart, contributing to an increased risk of cardiovascular disease beginning in the first five years after treatment.

Annac was not always interested in creating a biotech startup, but after losing her father in 1988 to heart disease following cancer, she knew she wanted to do something about this unique and underserved issue. Annac moved to the United States from Turkey in 1993 to pursue an MBA at Saint Louis University and follow a lifelong dream: her father had always wanted Annac to eventually pursue her Ph.D. in the U.S. In St. Louis, she met her co-founders, Dr. Ted Wakatsuki and Dr. Elliot Elson, both inventors. With their scientific backgrounds and Annac’s business experience and passion for cardio-oncological care, InvivoSciences was born in 2001.

Currently, the company is pioneering new technology called NuHearts. Invented by Wakatsuki and Elson, NuHearts are microhearts grown from human tissue, enabling doctors to screen drug candidates and analyze a drug’s effects and safety before treatment begins. “We and many investigators in the field believe that some patients are more sensitive to developing heart conditions such as arrhythmia and heart failure,” Annac says. “Our goal is to develop patient-specific, inexpensive diagnostic tools to monitor cardio-oncology side effects and help patients avoid expensive testing.”

According to a 2017 study conducted by researchers at the University of North Carolina at Chapel Hill, the Mount Sinai School of Medicine, and Columbia University, cardiovascular disease ranks among the leading causes of death for men and women across the general U.S. population. Among breast cancer survivors, they found that cardiovascular disease represents the number-one, non-cancer cause of death, resulting in nearly 35 percent of non-cancer deaths in survivors aged 50 or older. The risk of death increased greatly after the fifth year of cancer survivorship, and the study noted that “after year seven, breast cancer survivors had nearly twice the risk of [cardiovascular disease] mortality compared to those without breast cancer.”

Specifically, the greatest risk was linked to chemotherapy. Other studies have linked radiation therapy with increased risk of cardiovascular disease death, noting that radiation on the left side of the chest may injure cardiac muscle and increase risks. A 2018 study by researchers at the University of Arizona and Canada’s Dalhousie University also noted the link between radiation and cardiovascular disease, estimating that the heart received one to five grays (a gray is a measurement unit) of radiation during treatment. Studies by the Children’s Oncology Group found similar heightened risk of cardiovascular disease following cancer treatment in survivors of childhood cancer. Specifically, the younger a patient was during treatment, the higher the risk of potentially deadly heart disease as a survivor.

Our goal is to develop patient-specific, inexpensive diagnostic tools to monitor cardio-oncology side effects and help patients avoid expensive testing.

These numbers are alarming to Annac, who seeks to use her technology to better prepare cancer patients for life after their disease. As a mother, she was struck by the risk to survivors of childhood cancer and the dire impact on life expectancy from such risks. Addressing this cardiotoxicity could help build a future where patients and doctors are better informed of the risks of cancer treatment, and Annac aims to push technology to the next frontier to get there.

From L to R: Dr. Ted Wakatsuki, Ayla Annac, Dr. Elliot Elson, co-founders of InvivoSciences

“We have 2.5 million breast cancer survivors, which is excellent. However, we are not ready for them to have heart issues,” says Annac. “If they have a heart attack, they’re not going to think that it has anything to do with their cancer. I want to make sure they’re keeping their heart as strong as possible and stopping treatment when they need to.” She hopes the NuHearts technology will allow patients to make the best choices for their individualized treatment plans, whether that means exploring other treatment options or working with their doctor to adjust their regimen.

Generally, NuHearts use cell lines generated by outside companies, but the hearts are also being grown using samples from volunteer patients at company-approved academic institutions and hospitals. Using these cells, researchers at InvivoSciences grow a microheart in the laboratory which can then be used to analyze sensitivity to a particular drug’s cardiac side effects. The hearts provide a window into cells and tissues, giving researchers an inside view of the heartbeat’s molecular mechanisms. Each heart is approximately the size of an icon on an iPhone screen; dishes in the lab contain 96 or 384 of these tiny hearts.

Annac has always prioritized compassion. For now, Annac wants to focus on the most at-risk populations, including women, children, and the elderly, who all face higher risks of cardiovascular disease than other cancer survivor groups. She says that her intention is never to inspire fear but rather to provide information that has the potential to save lives. Through utilizing NuHearts during their treatment process, Annac hopes to empower patients to be active advocates for their best personal path to healing, adjusting drug therapy according to their heart health.

“Am I putting fear on someone who has already suffered?’” Annac asks. “But if I don’t speak about it, there’s a problem. They think they survived, they are happy, and they are not paying attention to the heart.”

NuHearts have not yet been integrated into hospitals, but InvivoSciences is in talks with pharmaceutical companies. Ultimately, Annac aims to usher in a new era where doctors and patients can work together. She does not advocate against radiation or chemotherapy, but wants patients to be informed and heart-conscious throughout their cancer journey. “Advanced cancer treatment options are excellent at producing survival, but let us not forget our hearts,” Annac says. “We are not parts; we are not cars. The highest generator of healing, love, and light is in your heart.”

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