Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review
Walid Shalata1, Amjad Abu-Salman2, Rachel Steckbeck3
1The Legacy Heritage Center & Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel.
Abstract:
Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to fight tumor cells. However, immune checkpoint inhibitors have several immune-related adverse effects. Many cases have come to light recently of cardiotoxicity as a result of treatment with these drugs. Cardiotoxicity from immune checkpoint inhibitors is unique due to its rarity and high mortality rate. Patients with this toxicity may present with myocarditis, pericarditis, Takotsubo cardiomyopathy, conduction disorders, and others within just a few weeks of starting immune checkpoint inhibitors. We present here a review of the current research on immune checkpoint inhibitors, their associated cardiotoxicities, the timing of presentation of these conditions, lab tests and histology for each condition, and finally the treatment of patients with cardiotoxicity. We observe a positive skew in the onset of presentation, which is significant for the treating physician.
Insights
Immune checkpoint inhibitors (ICIs) can cause rare but fatal cardiotoxicity. This review details ICI-related heart conditions, their presentation timing, diagnosis, and treatment for better clinical management.
Area of Science:
- Oncology
- Immunology
- Cardiology
Background:
- Immune checkpoint inhibitors (ICIs) are increasingly used to treat various cancers by enhancing T-cell responses.
- ICIs target inhibitory proteins like CTLA-4 and PD-1/PD-L1, augmenting anti-tumor immunity.
- Adverse effects, particularly cardiotoxicity, are a significant concern with ICI therapy.
Purpose of the Study:
- To review current research on immune checkpoint inhibitor-associated cardiotoxicity (ICIAc).
- To detail the clinical presentation, diagnostic methods, and treatment strategies for ICIAc.
- To analyze the temporal patterns of ICIAc onset.
Main Methods:
- Comprehensive literature review of studies on ICIs and cardiotoxicity.
- Analysis of case reports and clinical trial data.
- Synthesis of information on diagnostic markers and histological findings.
Main Results:
- ICIAc encompasses conditions like myocarditis, pericarditis, and cardiomyopathy, often presenting early in treatment.
- Diagnosis involves clinical evaluation, ECG, cardiac biomarkers, and imaging.
- A notable positive skew in the onset of symptoms was observed.
Conclusions:
- ICIAc is a rare but severe complication of ICI therapy with a high mortality rate.
- Early recognition and prompt management are crucial for improving patient outcomes.
- Understanding the timing of presentation aids in timely diagnosis and intervention.
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