Delayed Diagnosis and Recovery of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis on VA-ECMO Support.
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ABSTRACT:
SUBMITTER: Ramayya T
PROVIDER: S-EPMC9830207 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Delayed Diagnosis and Recovery of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis on VA-ECMO Support.
Ramayya Tarun T Mitchell Joshua D JD Hartupee Justin C JC Lavine Kory K Ridley Clare H CH Kotkar Kunal D KD Jimenez Jesus J Lin Chieh-Yu CY Alvarez-Cardona Jose A JA Krone Ronald K RK Campbell Courtney M CM
JACC. CardioOncology 20221220 5
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Project description:BackgroundImmune checkpoint inhibitors (ICIs) are effective antineoplastic agents but can cause adverse effects in many organ systems. Cardiovascular toxicities include arrhythmias, myocarditis, heart failure, takotsubo syndrome, pericarditis, coronary artery disease, and vasculitis.Case summaryA 66-year-old woman with Stage 3C2 endometrial carcinoma presented for her second cycle of pembrolizumab, carboplatin, and paclitaxel. She subsequently suffered cardiac arrest and was brought to the emergency department. Spontaneous circulation returned following resuscitation, but she was haemodynamically unstable. An electrocardiogram revealed complete heart block. Initial management included intubation, vasopressor support, and transcutaneous pacing before transfer to the catheterization lab. Coronary angiography revealed no coronary artery disease. Right heart catheterization confirmed severe cardiogenic shock despite inotropic support and a temporary transvenous pacemaker in place. A micro-axial flow pump (Impella CP) was implanted for deteriorating cardiogenic shock. She was treated with high-dose corticosteroids (dexamethasone 190 mg i.v.) for suspected ICI-associated myocarditis, with significant improvement in cardiac function. The Impella was weaned and removed on Day 5. Cardiac magnetic resonance imaging showed elevated T1 and T2 signal intensities, consistent with the 2018 Lake Louise Criteria for myocarditis. The complete heart block was resolved, but a leadless pacemaker was implanted due to pre-existing conduction abnormalities.DiscussionEarly recognition of ICI-associated myocarditis can be achieved with biochemical testing, electrocardiography, imaging, and expedited investigation of alternative causes for cardiac decompensation. Our case demonstrates that temporary left ventricular assist devices can support cardiac output for patients in cardiogenic shock due to ICI-associated myocarditis, allowing for recovery following high-dose corticosteroids.
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Project description:BackgroundImmune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy with growing indications for treatment of various malignancies. Immune checkpoint inhibitors are monoclonal antibodies that block inhibitory pathways in immune cells, including cytotoxic T lymphocyte antigen-4 (CTLA4), programmed death 1 receptor (PD1), and programmed cell death ligand-1 (PDL1), to activate the immune system. However, these agents can disrupt self-tolerance and lead to immune-related adverse events. Fulminant myocarditis, a feared complication of ICIs, can be highly fatal, and there is a need for effective treatment options.Case summaryA 70-year-old patient with recurrent metastatic disease of urothelial carcinoma subsequently developed fulminant myocarditis after receiving eight cycles of pembrolizumab. He developed cardiogenic shock and required inotropes and a percutaneous microaxial flow pump placement for temporary mechanical circulatory support. He received methylprednisolone initially and then was started on second-line immunosuppression agents, ruxolitinib and abatacept, for steroid-refractory myocarditis. Abatacept is thought to inhibit activation of T-cell CTLA4 and PD1/PDL1 pathways and reverse ICI-activated pathways. Ruxolitinib is a Janus kinase inhibitor that impairs immune activation through suppressing cytokine sensing and production and T-cell activation. After these treatments, the patient subsequently clinically improved and his myocarditis resolved.DiscussionThis case highlights ICI myocarditis refractory to corticosteroids leading to treatment with second-line immunosuppression. As immunotherapies are increasingly applied to a broader range of cancers, further research is needed to evaluate the optimal treatment strategy for ICI-related myocarditis and other immune-related adverse events.
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