By Sarah Handzel, BSN, RN
According to a recent estimate, approximately 400,000 children in the world receive a cancer diagnosis each year.1 Fortunately, modern diagnostic and treatment methods have substantially improved survival rates for pediatric cancer patients. However, certain cancer-targeting therapies demonstrate cardiotoxic effects. This may be exacerbated by preexisting cardiovascular disease (CVD) risk factors.
Among pediatric cancer survivors, cardiac complications are the second leading cause of morbidity and mortality, following disease relapse itself.2 As an emerging multidisciplinary subspecialty, cardio-oncology combines the latest innovations with tried-and-true techniques like ECG to screen, diagnose, and guide treatment decisions while also addressing CVD risk factors that may impact survival rates.
Cardiotoxicity and Common Pediatric Cancer Treatments
Chemotherapy regimens for pediatric patients typically involve the drug anthracycline. While the drug is effective for many, cardiotoxicity is often a dose-limiting side effect of treatment.3 Although high-dose exposure is currently defined as a doxorubicin equivalent of 250mg/m2, some pediatric patients have been shown to develop CVD at doses as low as 60mg/m2.3 The exact mechanisms of cardiotoxicity are varied, but researchers believe several cellular mechanisms, including mitochondrial dysfunction, nuclear DNA damage, and the formation of reactive oxygen species all contribute to CVD development.3
While anthracycline cardiotoxicity has been studied in detail, other newer therapies also demonstrate toxic effects. Though more research is necessary, previous studies indicate that the use of chemotherapy agents such as microtubule inhibitors, platinum-based drugs, antimetabolites, and others may lead to various side effects, including:3
- Arrhythmias
- Ischemia
- Prolonged QT segment
- Venous thromboembolism
- Ventricular dysfunction
Because of these documented adverse effects, every pediatric cancer patient and survivor should be initially evaluated for cardiovascular risk factors and regularly monitored for cardiac symptoms anytime treatment regimens include chemotherapeutic agents.
Radiation treatment to the chest area also poses a risk for pediatric patients; depending on exposure, cardiovascular structures may suffer damage, particularly if radiation doses exceed 15 gray (Gy) for direct cardiac exposure.3 Pediatric patients may develop a number of cardiac complications resulting from radiation therapy, such as:3
- Aortic root calcification
- Cerebrovascular disease
- Conduction system problems
- Coronary artery disease
- Heart failure
- Injury to heart valves
- Peripheral vascular disease
As with chemotherapy, any pediatric patient receiving radiation therapy should be regularly monitored for evidence of CVD.
How ECG Mitigates CVD Risk
Because it is inexpensive and readily available at almost all healthcare facilities, ECG remains an important screening and diagnostic tool to monitor CVD risk factors. Cardiologists working as part of the cardio-oncology team should be prepared to evaluate ECGs in conjunction with other screening tests, such as echocardiography.
The simple 12-lead ECG may reveal various markers for cardiotoxicity; depending on the results, chemotherapy or radiation therapy may need to be adjusted or even temporarily stopped.4 According to some estimates, up to 25% of children receiving treatment with anthracyclines develop ECG changes.4 Subtle changes, such as prolonged P waves or QT interval, may signal the beginning of conduction issues and should be investigated thoroughly. However, many changes reflected on ECG may only be temporary. Therefore, providers should perform other tests to verify any suspicious ECG results.
Prior to beginning chemotherapy or other treatment, providers should use ECG to detect any preexisting CVD risk factors.5 ECG should be repeated at regular intervals to monitor cardiovascular function over the course of the treatment period. Providers should also use ECG to monitor long-term risk for pediatric patients receiving treatment, as cancer survivors as a group are more likely to develop CVD issues over time.
Updated Pediatric Guidelines Reflect ECG Monitoring Best Practices
While various international guidelines direct ECG monitoring and other interventions for adults receiving cancer treatment, until recently there have been no guidelines addressing monitoring for cardiac risk factors in children. In late 2022, experts from Australia and New Zealand published a Delphi consensus approach spanning 11 separate domains of cardio-oncology care.2
The 11 domains included in the guidelines reflect efforts to better define, identify, and manage at-risk pediatric cancer patients during the course of their treatment. Physicians should first compare the patient's health history to high-risk criteria, such as history of treatment with anthracycline at a doxorubicin equivalent dose of 250mg/m2 or higher, or preexisting heart disease or family history of heart disease. Once the physician identifies high-risk patients, further domains define the minimum set of techniques, which they should use to further investigate the patient's risk.
Other domains concern surveillance measures for patients receiving specific antineoplastics or specific ECG changes, such as QT prolongation.2 The study authors hope these guidelines will help standardize medical care for pediatric cancer patients who also have cardiovascular risk factors.
ECG remains an essential tool for evaluating CVD risk factors in pediatric cancer patients and survivors due to its widespread availability, relatively little expense, and ease of use. Thanks to the new pediatric guidelines, physicians now have a direction for standardizing monitoring and treatment across this patient population. Cardiologists should be prepared to further investigate any ECG abnormalities using other screening or diagnostic tests as necessary to ensure patient safety and promote the most positive outcomes possible.
Resources
- "Childhood Cancer Statistics." ACCO, November 17, 2022. https://www.acco.org/childhood-cancer-statistics/#:~:text=Globally%2C%20approximately%20400%2C000%20children%20are,Picture%20your%20old%20elementary%20school.
- Toro C, Flemingham B, Jessop S, et al. Cardio-oncology recommendations for pediatric oncology patients: An Australian and New Zealand Delphi consensus. JACC: Advances. 2022;1(5):100155. https://www.sciencedirect.com/science/article/pii/S2772963X22002332?via%3Dihub#tbl1.
- Brickler M, Raskin A, Ryan TD. Current state of pediatric cardio-oncology: A review. Children (Basel). 2022;9(2):127. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870613/.
- Spînu Ștefan, Cismaru G, Boarescu PM, et al. ECG markers of cardiovascular toxicity in adult and pediatric cancer treatment. Dis Markers. 2021;2021:6653971. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837776/.
- Alexander R Lyon, Teresa López-Fernández, Liam S Couch, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC), European Heart Journal, Volume 43, Issue 41, 1 November 2022, Pages 4229–4361, https://doi.org/10.1093/eurheartj/ehac244
Sarah Handzel, BSN, RN, has been writing professionally since 2016 after spending over nine years in clinical practice in various specialties.
The opinions, beliefs and viewpoints expressed in this article are solely those of the author and do not necessarily reflect the opinions, beliefs and viewpoints of GE Healthcare. The author is a paid consultant for GE Healthcare and was compensated for creation of this article.
