Arjun Khunger1, Lucas Battel2, Ashna Wadhawan1, Aditi More1, Ankita Kapoor3, Nikhil Agrawal4. 1. Department of Internal Medicine, Memorial Hospital West, Pembroke Pines, FL, USA. 2. Department of Medicine, Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, UB Office of Graduate Medical Education, 955 Main Street, Suite 7230, Buffalo, NY, 14203-1121, USA. 3. Department of Medicine, Rochester General Hospital, Rochester, USA. 4. Department of Medicine, Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, UB Office of Graduate Medical Education, 955 Main Street, Suite 7230, Buffalo, NY, 14203-1121, USA. nikhilag@buffalo.edu.
Abstract
PURPOSE OF REVIEW: The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity. RECENT FINDINGS: Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data. It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancer patients undergoing ICI therapy.
PURPOSE OF REVIEW: The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity. RECENT FINDINGS: Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data. It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancerpatients undergoing ICI therapy.
Authors: Dongqing Chen; Conagh Kelly; Tatt Jhong Haw; Janine M Lombard; Ina I C Nordman; Amanda J Croft; Doan T M Ngo; Aaron L Sverdlov Journal: Curr Heart Fail Rep Date: 2021-11-03