The Potential Cardiotoxicity of Immune Checkpoint Inhibitors
Abstract
:1. Autoimmune Myocarditis
2. Takotsubo-like Syndrome
3. Pericardial Involvement
4. Arrythmias
5. Accelerated Atherosclerosis and Increased Risk of Cardiovascular Events
6. Vasculitis
7. Clinical Implications and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug Name | Molecular Target | Common Indications by FDA Approval |
---|---|---|
Ipilimumab | CTLA-4 | Melanoma, NSCLC, hepatocellular carcinoma, renal cell carcinoma, malignant pleural mesothelioma |
Nivolumab | PD-1 | Melanoma, NSCLC, colorectal cancer, esophageal cancer, gastric cancer, hepatocellular carcinoma, renal cell carcinoma, Hodgkin’s lymphoma, Urothelial carcinoma |
Pembrolizumab | PD-1 | NSCLC, triple negative breast cancer, cervical cancer, cutaneous SCC, esophageal cancer, gastric cancer, head and neck SCC, hepatocellular carcinoma, melanoma, Merkel cell carcinoma, primary mediastinal large B-cell lymphoma, renal cell carcinoma, urothelial carcinoma |
Atezolizumab | PD-L1 | hepatocellular carcinoma, melanoma, NSCLC, urothelial carcinoma |
Avelumab | PD-L1 | Merkel cell carcinoma, renal cell carcinoma, urothelial carcinoma |
Durvalumab | PD-L1 | NSCLC, small cell lung cancer |
ECG | Circulating Biomarkers | Echocardiography | CMR | Other | |
---|---|---|---|---|---|
Autoimmune- mediated myocarditis | Can range from normal ECG to tachycardia, ST-T changes, conduction abnormalities or arrythmias. | Troponin and BNP are usually elevated, but may also be normal. CPK may be elevated with concomitant myositis. | Findings may range from normal function to reduced systolic and/or diastolic function. Reduction in GLS may be an early marker to myocardial injury. Pericardial effusion may be present. | May demonstrate myocardial inflammation and necrosis in T1 and T2 sequences, with characteristic late gadolinium enhancement. | Endomyocardial biopsy will show predominant lymphocytic infiltration. |
Takotsubo-like syndrome | May mimic acute coronary syndrome, with ischemic chages | BNP elevation may be significantly higher than troponin elevation. | Acute LV systolic dysfunction. Classically apical akinesia (“apical ballooning”) | Left ventricular impairment without evidence of active myocarditis. | Diagnosis can be done only after excluding acute coronary syndrome. |
Pericardial involvement | May range from normal to typical PR depression or diffused ST-T changes. | When troponin is elevated, concomitant myocardial involvement should be suspected. | May demonstrate pericardial effusion. | May demonstrate active pericardial inflammation. | |
Myocardial infarction | New ischemic changes (sg, ST elevation/ depression or T-wave inversion) | Troponin elevation. | Usually, new regional-wall motion abnormality will be present. | May demonstrate regional-wall motion abnormality and characteristic mid-wall late gadolinium enhancement. | Coronary angiography for invasive diagnosis. |
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Nardi Agmon, I.; Itzhaki Ben Zadok, O.; Kornowski, R. The Potential Cardiotoxicity of Immune Checkpoint Inhibitors. J. Clin. Med. 2022, 11, 865. https://doi.org/10.3390/jcm11030865
Nardi Agmon I, Itzhaki Ben Zadok O, Kornowski R. The Potential Cardiotoxicity of Immune Checkpoint Inhibitors. Journal of Clinical Medicine. 2022; 11(3):865. https://doi.org/10.3390/jcm11030865
Chicago/Turabian StyleNardi Agmon, Inbar, Osnat Itzhaki Ben Zadok, and Ran Kornowski. 2022. "The Potential Cardiotoxicity of Immune Checkpoint Inhibitors" Journal of Clinical Medicine 11, no. 3: 865. https://doi.org/10.3390/jcm11030865