Immune Checkpoint Inhibitors and the Heart

Abstract

Immune checkpoint inhibitors (ICIs) represent a break-through treatment for a large number of cancer types. This treatment is increasingly being recommended. ICIs are prescribed for primary tumours and for metastases, adjuvant/neo-adjuvant therapy. Thus, there is an increased need for expertise in the field, including the ways of response and toxicities related to them. ICIs become toxic because of the removal of self-tolerance, which in turn induces autoimmune processes that affect every organ. However, when relating to the heart, it has been noticed to be leading to acute heart failure and even death caused by various mechanisms, such as: myocarditis, pericarditis, arrhythmia, and Takotsubo cardiomyopathy. This review aims to address the above issues by focusing on the latest findings on the topic, by adding some insights on the mechanism of action of ICIs with a special focus on the myocardial tissue, by providing information on clinical manifestations, diagnosis and (wherever possible) treatment of the cardiotoxic events related to this therapy. The information is expanding and in many cases, the articles we found refer mainly to case-presentations and studies conducted on small populations. However, we consider that it is worthwhile to raise awareness of this new treatment, especially since it is widely now and it provides a significant increase in the survival rate in patients who receive it.

ICIs-Related Cardiotoxicity in Different Types of Cancer

“…Tumor-intrinsic factors partook of the tumor-extrinsic mechanisms of ICIs-related cardiotoxicity through their effect on the interaction between the host immune system and the tumor [ 92 , 96 ]. The interval of time required for cardiotoxicity to occur has not yet been precisely indicated [ 97 , 98 ], so further work is required to elucidate this. There are still many unanswered questions about the effect of patient-intrinsic factors on ICIs-related cardiotoxicity because the mechanisms differ, even in patients treated with the same agent.…”

Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitor Therapy: A Comprehensive Review

“…93 The 2017 consensus statement of the Society for Immunotherapy of Cancer’s Toxicity Management Working Group recommended permanent discontinuation of ICIs in patients with cardiotoxicity grade 4; however; it suggests a rechallenge in stabilized patients with grade 3 cardiotoxicity. 94,95…”

Cardiotoxicity induced by immune checkpoint inhibitor: The complete insight into mechanisms, monitoring, diagnosis, and treatment

“…Zooming into cardiac events, myocarditis accounted for 14.1% of cases, followed by pericarditis with 13.6% and conduction abnormalities in 6.86% of cases ( 5 ). Myocarditis has a histological picture depicted with CD3, CD4+, CD8+ lymphocytes and macrophages infiltrating the myocardium ( 21 ). The symptoms of myocarditis mimic that of acute heart failure and consist of chest pain, dyspnea, pulmonary edema, arrhythmias, elevated (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP), etc., ( 8 , 14 , 22 ).…”