Cardiovascular Complications of Immune Checkpoint Inhibitors

Jang Seok^*
*Correspondence: Jang Seok, Department of Precision Medicine,, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea, Email:

Introduction

Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer therapy by enhancing the body's immune system to target and eliminate cancer cells. Medications such as pembrolizumab, nivolumab and ipilimumab have demonstrated significant efficacy in treating a variety of cancers, including melanoma, non-small cell lung cancer and renal cell carcinoma. These agents work by blocking inhibitory signals in the immune system, thus unleashing a more robust immune response against tumors. However, despite their impressive success in oncology, ICIs are not without risks immune-related Adverse Events (irAEs) are a known complication and while they often affect organs like the skin, liver and gastrointestinal system, the cardiovascular system can also be adversely impacted. Cardiovascular complications associated with ICIs, though relatively rare, can range from mild to life-threatening conditions, including myocarditis, pericarditis, arrhythmias and vasculitis. These complications represent a significant challenge in both the diagnosis and management of patients receiving ICI therapy. As such, a better understanding of the pathophysiology, clinical manifestations and management strategies for these cardiovascular toxicities is essential for improving patient care and outcomes [1].

Description

The pathophysiology of cardiovascular complications induced by ICIs is not yet fully understood. ICIs function by blocking immune checkpoints such as PD-1/PD-L1 and CTLA-4, which normally act to regulate T-cell activation and prevent autoimmunity. By inhibiting these checkpoints, ICIs enhance T-cell activity, leading to a more vigorous immune response against tumors. Unfortunately, this increased immune activity may also result in the activation of autoreactive T-cells that mistakenly attack normal tissues, including the heart. It is hypothesized that some shared antigens between tumor cells and cardiac tissue may increase the risk of such immune-mediated damage. For instance, certain proteins expressed on both cancer cells and cardiac myocytes may serve as targets for immune cells, resulting in inflammation and damage to the heart muscle [2].

The clinical presentation of cardiovascular toxicities following ICI therapy can vary greatly, ranging from mild symptoms such as fatigue or chest pain to severe, life-threatening events like myocarditis or arrhythmias. Myocarditis, the inflammation of the heart muscle, is the most commonly reported cardiovascular complication and occurs in approximately 1% of patients treated with ICIs. Symptoms of myocarditis include fatigue, chest pain, shortness of breath and arrhythmias, which can progress to severe outcomes such as cardiogenic shock and death if left untreated. Other cardiovascular manifestations include pericarditis (inflammation of the pericardium), which can lead to chest pain and pericardial effusion and arrhythmias, including atrial fibrillation and ventricular tachycardia. In rare cases, ICI therapy has been associated with Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, which mimics acute coronary syndrome but is not associated with coronary artery blockage. Vasculitis, inflammation of the blood vessels, can also occur, leading to conditions like temporal arteritis and cerebral vasculitis [3].

The diagnosis of ICI-related cardiovascular toxicities requires careful clinical evaluation. Symptoms of heart-related irAEs are often nonspecific and can overlap with other conditions, making early diagnosis challenging. Elevated cardiac biomarkers, such as troponin and B-type Natriuretic Peptide (BNP), are commonly used to identify myocardial injury. An Electro Cardio Gram (ECG) may reveal arrhythmias or conduction abnormalities. Additionally, cardiac imaging modalities such as echocardiography and Cardiac Magnetic Resonance imaging (CMR) can provide insights into myocardial function and inflammation. In some cases, an endomyocardial biopsy may be necessary to confirm the diagnosis of myocarditis. The diagnosis of these complications often requires a multidisciplinary approach, with collaboration between oncologists, cardiologists and immunologists [4].

The management of cardiovascular toxicities associated with ICIs begins with the immediate cessation of the offending therapy. Discontinuing ICI treatment is crucial to prevent further immune-mediated damage. In cases of severe myocarditis or other significant cardiovascular toxicities, high-dose corticosteroids are the standard treatment to suppress the overactive immune response. Additional immunosuppressive agents, such as infliximab or intravenous immunoglobulin, may be considered in refractory cases. Supportive care, including management of heart failure, arrhythmias and other complications, may require hospitalization and intensive monitoring. Involvement of cardiology specialists is essential for optimal management and careful consideration of immunosuppressive therapy is necessary to balance the risks of further cardiovascular damage with the need to control the immune response [5].

Conclusion

Immune checkpoint inhibitors have significantly advanced the treatment landscape for various cancers, offering hope to patients with otherwise limited therapeutic options. However, like all potent therapies, ICIs come with the risk of immune-related adverse events, including serious cardiovascular complications. Myocarditis, pericarditis, arrhythmias and vasculitis are some of the most concerning cardiovascular side effects, with the potential to cause significant morbidity and even mortality. Early recognition of these toxicities is critical to improving patient outcomes and prompt management, including the cessation of ICIs and the use of immunosuppressive therapies, is necessary to mitigate the effects. As the use of ICIs continues to expand, greater awareness of their cardiovascular complications will be essential for safe and effective patient management. Ongoing research into the underlying mechanisms of these toxicities, as well as improved diagnostic and treatment strategies, is crucial for enhancing the care of cancer patients undergoing immunotherapy. A multidisciplinary approach involving oncologists, cardiologists and other healthcare professionals is vital to ensure that the benefits of ICIs outweigh the risks of cardiovascular complications, allowing patients to reap the full potential of this transformative cancer treatment.

Acknowledgement

None.

Conflict of Interest

None.

References

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