Addressing Cardiovascular Complications in Cancer Immunotherapy: A Guide for Providers

The intersection of cardiovascular disease and cancer presents a significant challenge in oncology care. Both stand as leading causes of morbidity and mortality worldwide, with cancer and heart disease often competing as the top cause of death. Since the introduction of immunotherapy as a biological treatment in oncology, there have been significant improvements in patient outcomes. However, these treatments are not without their own risks, notably the emergence of cardiovascular immune-related adverse events (irAEs) with the use of immune checkpoint inhibitors. Although specific mortality rates attributed to cardiac irAEs are not well-documented, the serious nature of these events necessitates a closer look.

Cardiovascular irAEs from immune checkpoint inhibitors encompass a range of adverse events, including myocarditis, pericarditis, heart failure, and arrhythmias. The incidence of myocarditis, one of the more severe cardiovascular irAEs, ranges from 0.06% with single-agent immune checkpoint inhibitors, to 1.14% when combined with multiple-agent immune checkpoint inhibitors. These conditions carry a high morbidity and mortality risk, with myocarditis-associated case fatality rates between 20% and 30%. Most events (> 90%) happen in the first 2 to 4 months from start of therapy.

Identifying patients at risk for cardiovascular irAEs involves understanding both treatment-related and patient-specific factors. Combination therapy, pre-existing cardiovascular conditions, and specific immune checkpoint inhibitor regimens are associated with higher incidences of adverse events.

Cardio-oncology plays a crucial role in the cardiac surveillance of patients undergoing immune checkpoint inhibitors therapy, focusing on early diagnosis and management of myocarditis through biomarker monitoring to prevent fatality and enhance patient outcomes. At the Medical College of Georgia, monitoring troponin T levels is prioritized. This begins with a pretreatment assessment to establish a baseline, followed by blood draws every 15 days during the initial 8 weeks, and then monthly for the subsequent 8 weeks. Monitoring beyond that timeline is at the discretion of the oncologist. Echocardiographic monitoring is not essential due to lack of robust data.

In settings without a dedicated cardio-oncology service, collaboration between oncologists and cardiologists is vital. This partnership focuses on risk assessment, monitoring for heart complications, and patient education to mitigate risks. Key considerations include:

1. Risk Management: Early identification of patients at risk and implementing strategies to mitigate cardiovascular irAEs. These include:
   • Pre-existing Cardiovascular Disease: Patients with a history of cardiovascular disease may be at higher risk of developing myocarditis when treated with immune checkpoint inhibitors. Careful screening and management of existing cardiovascular conditions are crucial before starting therapy. These conditions include diabetes, hypertension, and heart conditions such as heart failure.
   • Baseline Assessment: Conducting thorough cardiovascular evaluations before initiating immune checkpoint inhibitors can help identify patients who may be at increased risk. This includes assessments like electrocardiograms (ECGs) and measurement of biomarkers like troponin. These assessments should be conducted as guided above and initiated at the oncologist’s office to prevent delays in care.
   • Combination Therapy Caution: The use of immune checkpoint inhibitors in combination with other immunotherapies or chemotherapies can increase the risk of myocarditis. Dosing strategies and combinations should be chosen carefully, and patients should be monitored closely for adverse effects. When selecting dosing strategies that require combinations, we recommend that patients be seen by cardio-oncologists.
   • Cardio-Oncology Referrals: Patients who require referral to cardio-oncology include those receiving dual immune checkpoint inhibitors therapy; those on combination therapy with immune checkpoint inhibitors and known cardiotoxic agents such as bevacizumab; those experiencing noncardiovascular events related to immune checkpoint inhibitor treatment, such as nephritis or myositis; and those with a history of cancer therapeutics-related cardiac dysfunction or pre-existing cardiovascular disease.
2. Monitoring and Treating Heart Complications: Regular cardiovascular assessments and prompt management of any arising complications. These include the monitoring recommendations at the Medical College of Georgia, as stated above. Troponin T monitoring can be performed at the oncologist’s office to avoid delay in care.
   • Early Detection and Symptom Reporting: Patients and health care providers should be aware of the symptoms of myocarditis, such as chest pain, shortness of breath, fatigue, and arrhythmias. Early detection and timely reporting of these symptoms can lead to prompt management, which might prevent severe complications.
   • Rapid Response and Treatment: If myocarditis is suspected, rapid intervention with high-dose corticosteroids or other immunosuppressive therapies is often necessary. Prompt discontinuation of the immune checkpoint inhibitor therapy may also be required.
   • Interdisciplinary Care: Collaboration between oncologists, cardiologists, and other health care professionals is essential for managing the risk of myocarditis effectively in patients undergoing treatment with immune checkpoint inhibitors.
     • Emergency Department: The emergency department serves as the critical first response for acute symptoms of immune checkpoint inhibitors cardiotoxicity, such as severe chest pain and arrhythmias. Emergency department teams rapidly assess and stabilize patients using diagnostics like ECGs and cardiac biomarkers and coordinate urgent care with cardiology specialists. This immediate intervention is crucial for managing life-threatening complications and ensuring patients receive specialized ongoing care.
     • Primary Care: Primary care providers are essential for the long-term monitoring and early detection of immune checkpoint inhibitors cardiotoxicity. They conduct routine health assessments, educate patients about potential cardiac side effects, and remain vigilant for symptoms reported during check-ups. Primary care plays a pivotal role in coordinating care among specialists, facilitating timely referrals to cardio-oncology, and ensuring a comprehensive approach to the patient’s health post–immune checkpoint inhibitors therapy.
3. Patient Education: Informing patients about potential cardiovascular symptoms and when to seek medical attention. Educating patients about the potential risks and symptoms of myocarditis related to immune checkpoint inhibitors therapy can empower them to seek help early if symptoms develop.

As the use of immune checkpoint inhibitors in cancer treatment continues to grow, so does the importance of understanding and managing their potential cardiovascular complications. The emerging field of cardio-oncology plays a pivotal role in this endeavor, offering a specialized perspective that enhances patient care. Through effective collaboration between cardiology and oncology; risk management; and patient education, the safety and efficacy of cancer immunotherapy can improve. Moving forward, further research and improved guidelines will be essential in optimizing outcomes for patients with cancer receiving these groundbreaking treatments.

Visit the ACCC website for more information and resources to support the management of patients being treated with immunotherapies.

The ACCC Immuno-Oncology Institute is supported by Bristol Myers Squibb and AstraZeneca.

Avirup Guha, MBBS, MPH, FAHA, FACC, FICOS, RPVI, is an assistant professor at Augusta University and leads Cardio-Oncology at the Medical College of Georgia. Dr. Guha's ongoing research, under the patronage of the American Heart Association and the Department of Defense, delves deep into the translational science concerning biological disparities between White and Black men with prostate cancer undergoing androgen deprivation therapy. He is board-certified in cardiology, cardio-oncology, echocardiography, and several other cardiac imaging modalities.