Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review
by
, , , and
Walid Shalata
1,*,†
,
Amjad Abu-salman
2,†, 
Rachel Steckbeck
3,
Binil Mathew Jacob
3,
Ismaell Massalha
1 and
Alexander Yakobson
1 1
The Legacy Heritage Center & Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel
2
Cardiology Division, Soroka Medical Center, Beer Sheva 84105, Israel
3
Medical School for International Health, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this paper.
Cancers 2021, 13(20), 5218; https://doi.org/10.3390/cancers13205218
Submission received: 4 September 2021
/
Revised: 2 October 2021
/
Accepted: 8 October 2021
/
Published: 18 October 2021
(This article belongs to the Special Issue Cancer Immunotherapy and Immune-Related Adverse Events)
Simple Summary
This review article addresses the toxic effects on the heart associated with the use of certain cancer-treating drugs known as immune checkpoint inhibitors. These drugs target specific proteins in the cell cycle that are abundantly expressed in cancerous cells; however, they inadvertently damage non-cancerous tissue. In the heart, this occurs in the form of dysfunction or death of smooth muscle cells, leading to consequences such as infection, heart rhythm changes, and hormonally dependent and independent ischemia. This review examines the average and median onset of these drug toxicities as well as antidotes. One key observation is that these side effects are positively skewed, meaning they occur early in cancer treatment.
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.
