Cardiotoxicity in Cancer Therapy: Prevention & Treatment
Research and real-world experience have shown that certain cancer treatments can exert cardiotoxic effects, but routine screening and monitoring can detect and minimize cancer therapy-related cardiotoxicity.1-11
Cardiotoxicity has been observed in patients receiving anthracyclines, HER2-targeted therapies, tyrosine kinase inhibitors, and radiotherapy.4-6,8 Immune checkpoint inhibitors (ICIs) have been linked to fulminant myocarditis, which is possibly due to acute cardiotoxicity.6,9
“Anthracyclines cause irreversible apoptosis and fibrosis of myocardial tissues, and cardiotoxic effects can occur many years after the initial treatment,” said Jina Sohn, MD, a cardiologist at Keck Medicine of the University of Southern California in Los Angeles.
“[I]mmunotherapies, particularly tyrosine kinase inhibitors, have shown vascular effects that may indirectly result in adverse cardiac effects, including myocardial infarctions, atrial fibrillation, and severe hypertension,” Dr Sohn added.10
“Studies have shown the effects of radiation dose — not only to the heart as a whole, but also to specific cardiac substructures — on the risk of future cardiovascular events, and this is informing how radiotherapy is administered,” noted Anju Nohria, MD, director of the cardio-oncology program at Dana-Farber Brigham Cancer Center in Boston.
Risk Assessment and Prevention
To minimize the risk of cardiotoxicity from cancer treatment, providers should remain aware of the potential cardiotoxicities of various cancer therapies and screen patients for traditional cardiovascular risk factors and preexisting cardiovascular disease, both of which should be treated aggressively if detected, Dr Nohria advised.
The 2022 European Society of Cardiology (ESC) guidelines for cardio-oncology recommend assessing baseline patient risk using the Heart Failure Association-International Cardio-Oncology Society cardiovascular toxicity risk assessment.6 Patients’ medical history, including past cardiovascular issues, cancer history, and past cancer therapies, should also be evaluated. The JACC: CardioOncology expert panel recommendations, released in 2024, also advise that cancer patients undergo a baseline cardiovascular risk assessment.11
Such risk assessments “primarily focus on characterizing potential cardiotoxicities associated with particular cancer therapeutic classes, establishing the risk of patients to develop these cardiotoxicities based on their preexisting cardiovascular disease and prior cancer treatment history, and recommend CV [cardiovascular] imaging, ECG, and biomarker data to help with diagnosis of cardiotoxicities and risk stratification prior to starting cancer therapy,” explained Adam Potter, MD, PhD, a physician scientist, Director of Cardio-Oncology, and Program Director of the Cardio-Oncology fellowship at The Ohio State University Wexner Medical Center in Columbus.6,11
Both the ESC and the JACC expert panel also advise that patients be given information on maintaining a healthy lifestyle ahead of treatment.6,11 Emerging data point to shared risk factors for cancer and cardiovascular disease, including hypertension, smoking, diabetes, and social determinants of health.6,11,12
In addition, cancer and cardiovascular disease have shared mechanisms, such as chronic inflammation, clonal hematopoiesis of indeterminate potential, and metabolic dysregulation.6,11,12
“Once the overall risk has been determined, this framework can help guide the oncology team to determine when to refer to a cardio-oncologist, whether to proceed with the planned cancer treatment, what appropriate cardiac surveillance may be indicated for the patient while receiving potentially cardiotoxic cancer therapy, and what approach should be taken if a patient were to develop cardiotoxicity,” said Dr Potter.
“[T]he 2022 ESC cardio-oncology guidelines recommend that ACEi [angiotensin-converting enzyme inhibitors]/ARBs [angiotensin II receptor blockers], beta blockers, and statins can be considered for primary prevention in cancer patients receiving cardiotoxic therapy that are at high and very high risk of developing cardiotoxicities,” Dr Potter continued. “Additionally, there is more recent data suggesting that SGLT2i [SGLT2 inhibitors] may have a cardioprotective role in cancer patients as well, reducing the risk of cancer therapy-related cardiac dysfunction [and] acute heart failure exacerbations, [and leading to] fewer hospitalizations and improved mortality.”
In patients receiving anthracycline therapy, dexrazoxane and liposomal anthracyclines have demonstrated benefit in preventing cardiotoxicity and are approved for patients with a high risk of chemotherapy-related cardiac dysfunction who have received large cumulative doses of anthracyclines.6,9,11
Dexrazoxane has also been found to “safely mitigate anthracycline cardiotoxicity without reducing cancer treatment efficacy or increasing the risk of secondary malignancies” in pediatric patients, Dr Nohria noted.7,13
In patients treated with anthracyclines and HER2-targeted therapy, meta-analyses have shown a significant benefit with renin-angiotensin-aldosterone system inhibition, beta blockers, and mineralocorticoid receptor antagonists in preventing left ventricular ejection fraction (LVEF) reduction.6,8
These studies have produced mixed results, with some findings demonstrating no difference in LVEF decline between statin and placebo groups and other research showing a small but significant difference between groups.11,14
“From a clinical perspective, the available data, while encouraging, does not conclusively support the universal use of these medications as cardioprotective agents for the primary prevention of cardiotoxicity, but they can be considered in the right patient population, and potentially with additional data from future RCTs [randomized clinical trials], this will become more well defined,” Dr Potter said.
Monitoring for Cardiotoxicity
JACC recommendations and ESC guidelines recommend routine follow-up and surveillance for cardiotoxicity during and after cancer treatment, utilizing echocardiography to assess LVEF and global longitudinal strain (GLS).6,11
“Strain imaging for improved detection of subclinical ventricular dysfunction has been well established in multiple populations and etiologies,” she noted.15 For example, a meta-analysis of 21 studies demonstrated the prognostic value of GLS in predicting chemotherapy-related cardiac dysfunction in patients with various cancers.16
“Cardiac MRI and multigated acquisition nuclear imaging are also useful tools for following LVEF closely, and cardiac biomarkers such as troponin and B-type natriuretic peptide can aid in the detection of subclinical LV dysfunction,” Dr Sohn added.6
Referral to a cardio-oncologist is recommended for patients with a high risk of developing cardiotoxicity prior to the initiation of cancer therapy and for those who develop cardiovascular symptoms or cardiotoxicities after starting treatment, Dr Potter said. Patients who develop moderate-to-severe cardiac dysfunction related to cancer treatment should receive guideline-directed medical treatment for heart failure, and the cancer therapy may need to be paused or discontinued.6
“Early detection and treatment of cardiotoxicity can both improve CV outcomes and permit safe continuation of cancer therapy,” Dr Nohria emphasized.
Treatment Implications
While the treatment recommendations for cancer therapy-related cardiotoxicity are extensive and depend on the causative therapy, the experts interviewed for this article shared several key points from the ESC guidelines and JACC recommendations.6,11
For patients receiving HER2 antagonists who have mild or moderate asymptomatic cardiotoxicity, treatment can be safely continued with cardioprotective therapies and close cardiovascular monitoring.In most of these cases, cardiac function remains stable or improves after completion of HER2 therapy, Dr Nohria stated.
Myocarditis due to cardiotoxicity with ICIs can be lethal, but “early detection, interruption of ICI therapy, and treatment with high-dose steroids can alter the prognosis in some patients,” she said.6
When radiotherapy cannot be omitted from the treatment plan, cardioprotective strategies may include modification of the dose and volume and the use of heart-sparing strategies such as intensity-modulated radiotherapy, certain breathing techniques, and image-guided radiotherapy.6,11
For patients who experience cancer therapy-related cardiac dysfunction with LVEF that has declined to less than 50%, guideline-directed therapy with an ACEi, ARB, angiotensin receptor-neprilysin inhibitor, SGLT2i, mineralocorticoid receptor antagonist, and/or a beta blocker, with or without diuretic therapy, should be considered as detailed in the 2022 ACC/AHA/HFSA guideline, and survivors who received radiation therapy or systemic cardiotoxic therapies should undergo an annual cardiovascular risk factor assessment and optimization, Dr Potter said.6,11,17
Remaining Needs
According to Dr Potter, the primary needs within cardio-oncology are more randomized controlled trials to evaluate the best treatment approach for patients who develop cancer therapy-related cardiotoxicity, and studies that help better define the optimal biomarkers and imaging modalities to predict cardiotoxicity and guide surveillance during cancer treatment.
Dr Potter also cited the need for ongoing education of cardiologists and hematologists/oncologists regarding the possible cardiotoxicities related to cancer treatment, the specific cancer therapies and preexisting cardiovascular conditions associated with an increased risk of cardiotoxicity, and when to refer patients to a cardio-oncologist for further evaluation.
Disclosures: Dr Nohria disclosed relationships with AstraZeneca, Regeneron, Takeda Oncology, and Bristol Myers Squibb. Dr Sohn and Dr Potter reported that they have no relevant financial disclosures. Some study authors disclosed conflicts of interest. Please see the original references for complete disclosures.
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