Building a sturdy foundation for childhood cancer survivors to reduce risk of major adverse cardiovascular events (MACE)

Imagine your body as a house; over time it will need maintenance to keep its systems functioning properly. If something catastrophic occurs, such as an earthquake, your home might need more skilled and dedicated commitment to its infrastructure. Cancer is like that earthquake. Necessary treatments such as chemotherapy and radiation therapy can often act as aftershocks, further weakening the body and causing problems in the future if not addressed.

Radiation therapy, for instance, may damage blood vessels and heart tissue, leading to inflammation and scarring that compromise heart function over time. Similarly, chemotherapy can injure healthy heart cells, potentially increasing the risk of cardiovascular diseases such as heart failure and stroke in survivors.

As years pass, the cumulative effects of these treatments become more evident, increasing childhood cancer survivors' risk of major adverse cardiovascular events (MACE) compared to the general population. MACE includes cardiomyopathy, heart attack, stroke and any cardiovascular deaths. Regular cardiovascular screenings such as echocardiograms and electrocardiograms are crucial to mitigate these risks. These screenings allow early detection of damage, like an inspector identifying issues in a house before they worsen, helping to preserve survivors' long-term heart health.

Treatment toxicity increases risk of major cardiovascular events

It is through a foundation of knowledge that researchers today such as Greg Armstrong, MD, MSCE, Department of Epidemiology and Cancer Control chair know that exposure to certain necessary cancer treatments, such as chest radiation and anthracycline chemotherapy is associated with cardiac-related morbidity and mortality.

 “Curing cancer is the priority,” Armstrong said, “So, we're trying to reduce radiation and anthracycline doses or even eliminate them for certain cancers. In some cases, however, those treatments are absolutely necessary.”

In a study led by Armstrong and first-author Rawan Hammoud, MD, a former St. Jude postdoctoral fellow, investigators discovered that by age 50, survivors experience a cumulative rate of MACE of 17.7%, compared to just 0.9% in the general population. Childhood cancer survivors are therefore nearly 20 times more likely to experience MACE compared to the average person. The study was recently published in The Lancet Oncology.

Treatment toxicity can increase the likelihood of MACE, but researchers and clinicians at St. Jude aim to reduce these risks. Strategies include using cardioprotective drugs such as dexrazoxane and advancing novel immunotherapies to lower cardiovascular risk while ensuring effective cancer treatment.

The study points out that while aging childhood cancer survivors face a higher risk of cardiovascular complications than the general population, they can take key steps to safeguard their cardiovascular health, such as screening and proactive care.

Minor heart complications predict later major problems

The study used the St. Jude Lifetime Cohort Study (St. Jude LIFE) to track the frequency of MACE in survivors. Through St. Jude LIFE, patients treated as far back as the hospital’s first year (1962) are invited to return to St. Jude for evaluation every five years. With this data, researchers delved into the complexities of the long-term needs of childhood cancer survivors. 

The investigators found that less severe adverse cardiovascular events, including asymptomatic arrhythmias and asymptomatic ventricular dysfunction, were associated with a higher risk of future MACE among survivors. These were only detectible by screening with an electrocardiogram (ECG) or echocardiography (echo). Without these screenings, survivors would not have known they were at risk.

The risk of an early cardiovascular issue growing into a major issue shows the need for early and regular cardiovascular screenings for childhood cancer survivors. Proactively detecting and managing emerging conditions could mitigate the risk of progression to severe cardiovascular complications later in life. To enhance detection and intervention efforts, the researchers suggest integrating advanced health tracking technology, such as wearable devices for long-term monitoring, into survivorship care plans.

Echocardiogram and ejection fraction analysis for cardiovascular risk assessment

When survivors treated at St. Jude return for St. Jude LIFE, they receive an echocardiogram to evaluate their risk for both minor cardiovascular issues and MACE. Researchers use the ejection fraction, a measurement of how well the heart pumps blood, to monitor the organ’s function. Individuals with an ejection fraction between 40% and 50% have abnormal heart function but are often asymptomatic. Therefore, without this screening, their heart problems could go unnoticed and unaddressed, leading to more severe issues.

Longitudinal data regarding ejection fraction shows that even though these individuals may not have symptoms of heart failure at their initial screening evaluation, they have a higher risk of developing it in the future. Armstrong explains, “When analyzing an echocardiogram, individuals may not show signs of heart failure, even though they have an abnormal ejection fraction. This abnormal yet asymptomatic state suggested a doubled risk of developing heart failure later.”

Additionally, individuals with mildly reduced ejection fraction may be good candidates for early intervention rather than just monitoring. For example, taking heart failure medications prior to the onset of symptoms may mitigate their future heart failure risk.

Moving forward, the research calls for prioritizing cardiovascular screenings and personalized care plans. 

“Clinicians need to be aware of guidelines indicating that cancer survivors are at higher risk than the general population,” Armstrong said. “They should screen survivors appropriately and maintain a low threshold for referral to a cardiologist.”

Cancer survivorship is marked by resilience and adaptation. The aftermath of intensive treatments shows the need for proactive monitoring and personalized care. Beyond routine screenings and monitoring technologies, there is an opportunity for survivors to not just manage but prevent adverse health outcomes.