Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.

<h4>Background</h4>There is an urgent need to better understand the diverse presentations, risk factors, and outcomes of immune checkpoint inhibitor (ICI)-associated cardiovascular toxicity. There remains a lack of consensus surrounding cardiovascular screening, risk stratification, and...

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Main Authors: Jennifer M Kwan, Miles Shen, Narjes Akhlaghi, Jiun-Ruey Hu, Ruben Mora, James L Cross, Matthew Jiang, Michael Mankbadi, Peter Wang, Saif Zaman, Seohyuk Lee, Yunju Im, Attila Feher, Yi-Hwa Liu, Shuangge S Ma, Weiwei Tao, Wei Wei, Lauren A Baldassarre
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0314555
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author Jennifer M Kwan
Miles Shen
Narjes Akhlaghi
Jiun-Ruey Hu
Ruben Mora
James L Cross
Matthew Jiang
Michael Mankbadi
Peter Wang
Saif Zaman
Seohyuk Lee
Yunju Im
Attila Feher
Yi-Hwa Liu
Shuangge S Ma
Weiwei Tao
Wei Wei
Lauren A Baldassarre
author_facet Jennifer M Kwan
Miles Shen
Narjes Akhlaghi
Jiun-Ruey Hu
Ruben Mora
James L Cross
Matthew Jiang
Michael Mankbadi
Peter Wang
Saif Zaman
Seohyuk Lee
Yunju Im
Attila Feher
Yi-Hwa Liu
Shuangge S Ma
Weiwei Tao
Wei Wei
Lauren A Baldassarre
author_sort Jennifer M Kwan
collection DOAJ
description <h4>Background</h4>There is an urgent need to better understand the diverse presentations, risk factors, and outcomes of immune checkpoint inhibitor (ICI)-associated cardiovascular toxicity. There remains a lack of consensus surrounding cardiovascular screening, risk stratification, and clinical decision-making in patients receiving ICIs.<h4>Methods</h4>We conducted a single center retrospective cohort study including 2165 cancer patients treated with ICIs between 2013 and 2020. The primary outcome was adverse cardiovascular events (ACE): a composite of myocardial infarction, coronary artery disease, stroke, peripheral vascular disease, arrhythmias, heart failure, valvular disease, pericardial disease, and myocarditis. Secondary outcomes included all-cause mortality and the individual components of ACE. We additionally conducted an imaging substudy examining imaging characteristics from echocardiography (echo) and cardiac magnetic resonance (CMR) imaging.<h4>Results</h4>In our cohort, 44% (n = 962/2165) of patients experienced ACE. In a multivariable analysis, dual ICI therapy (hazard ratio [HR] 1.23, confidence interval [CI] 1.04-1.45), age (HR 1.01, CI 1.00-1.01), male sex (HR 1.18, CI 1.02-1.36), prior arrhythmia (HR 1.22, CI 1.03-1.43), lung cancer (HR 1.17, CI 1.01-1.37), and central nervous system (CNS) malignancy (HR 1.23, CI 1.02-1.47), were independently associated with increased ACE. ACE was independently associated with a 2.7-fold increased risk of mortality (P<0.001). Dual ICI therapy was also associated with a 2.0-fold increased risk of myo/pericarditis (P = 0.045), with myo/pericarditis being associated with a 2.9-fold increased risk of mortality (P<0.001). However, the cardiovascular risks of dual ICI therapy were offset by its mortality benefit, with dual ICI therapy being associated with a ~25% or 1.3-fold decrease in mortality. Of those with echo prior to ICI initiation, 26% (n = 115/442) had abnormal left ventricular ejection fraction or global longitudinal strain, and of those with echo after ICI initiation, 28% (n = 207/740) had abnormalities. Of those who had CMR imaging prior to ICI initiation, 43% (n = 9/21) already had left ventricular dysfunction, 50% (n = 10/20) had right ventricular dysfunction, 32% (n = 6/19) had left ventricular late gadolinium enhancement, and 9% (n = 1/11) had abnormal T2 imaging.<h4>Conclusion</h4>Dual ICI therapy, prior arrhythmia, older age, lung and CNS malignancies were independently associated with an increased risk of ACE, and dual ICI therapy was also independently associated with an increased risk of myo/pericarditis, highlighting the utmost importance of cardiovascular risk factor optimization in this particularly high-risk population. Fortunately, the occurrence of myo/pericarditis was relatively uncommon, and the overall cardiovascular risks of dual ICI therapy appeared to be offset by a significant mortality benefit. The use of multimodal cardiac imaging can be helpful in stratifying risk and guiding preventative cardiovascular management in patients receiving ICIs.
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spelling doaj-art-70ecc61b83694e568be00d77ca0c8f142024-12-10T05:31:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031455510.1371/journal.pone.0314555Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.Jennifer M KwanMiles ShenNarjes AkhlaghiJiun-Ruey HuRuben MoraJames L CrossMatthew JiangMichael MankbadiPeter WangSaif ZamanSeohyuk LeeYunju ImAttila FeherYi-Hwa LiuShuangge S MaWeiwei TaoWei WeiLauren A Baldassarre<h4>Background</h4>There is an urgent need to better understand the diverse presentations, risk factors, and outcomes of immune checkpoint inhibitor (ICI)-associated cardiovascular toxicity. There remains a lack of consensus surrounding cardiovascular screening, risk stratification, and clinical decision-making in patients receiving ICIs.<h4>Methods</h4>We conducted a single center retrospective cohort study including 2165 cancer patients treated with ICIs between 2013 and 2020. The primary outcome was adverse cardiovascular events (ACE): a composite of myocardial infarction, coronary artery disease, stroke, peripheral vascular disease, arrhythmias, heart failure, valvular disease, pericardial disease, and myocarditis. Secondary outcomes included all-cause mortality and the individual components of ACE. We additionally conducted an imaging substudy examining imaging characteristics from echocardiography (echo) and cardiac magnetic resonance (CMR) imaging.<h4>Results</h4>In our cohort, 44% (n = 962/2165) of patients experienced ACE. In a multivariable analysis, dual ICI therapy (hazard ratio [HR] 1.23, confidence interval [CI] 1.04-1.45), age (HR 1.01, CI 1.00-1.01), male sex (HR 1.18, CI 1.02-1.36), prior arrhythmia (HR 1.22, CI 1.03-1.43), lung cancer (HR 1.17, CI 1.01-1.37), and central nervous system (CNS) malignancy (HR 1.23, CI 1.02-1.47), were independently associated with increased ACE. ACE was independently associated with a 2.7-fold increased risk of mortality (P<0.001). Dual ICI therapy was also associated with a 2.0-fold increased risk of myo/pericarditis (P = 0.045), with myo/pericarditis being associated with a 2.9-fold increased risk of mortality (P<0.001). However, the cardiovascular risks of dual ICI therapy were offset by its mortality benefit, with dual ICI therapy being associated with a ~25% or 1.3-fold decrease in mortality. Of those with echo prior to ICI initiation, 26% (n = 115/442) had abnormal left ventricular ejection fraction or global longitudinal strain, and of those with echo after ICI initiation, 28% (n = 207/740) had abnormalities. Of those who had CMR imaging prior to ICI initiation, 43% (n = 9/21) already had left ventricular dysfunction, 50% (n = 10/20) had right ventricular dysfunction, 32% (n = 6/19) had left ventricular late gadolinium enhancement, and 9% (n = 1/11) had abnormal T2 imaging.<h4>Conclusion</h4>Dual ICI therapy, prior arrhythmia, older age, lung and CNS malignancies were independently associated with an increased risk of ACE, and dual ICI therapy was also independently associated with an increased risk of myo/pericarditis, highlighting the utmost importance of cardiovascular risk factor optimization in this particularly high-risk population. Fortunately, the occurrence of myo/pericarditis was relatively uncommon, and the overall cardiovascular risks of dual ICI therapy appeared to be offset by a significant mortality benefit. The use of multimodal cardiac imaging can be helpful in stratifying risk and guiding preventative cardiovascular management in patients receiving ICIs.https://doi.org/10.1371/journal.pone.0314555
spellingShingle Jennifer M Kwan
Miles Shen
Narjes Akhlaghi
Jiun-Ruey Hu
Ruben Mora
James L Cross
Matthew Jiang
Michael Mankbadi
Peter Wang
Saif Zaman
Seohyuk Lee
Yunju Im
Attila Feher
Yi-Hwa Liu
Shuangge S Ma
Weiwei Tao
Wei Wei
Lauren A Baldassarre
Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.
PLoS ONE
title Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.
title_full Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.
title_fullStr Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.
title_full_unstemmed Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.
title_short Adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors.
title_sort adverse cardiovascular events and cardiac imaging findings in patients on immune checkpoint inhibitors
url https://doi.org/10.1371/journal.pone.0314555
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