Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity

Angela Y. Higgins; Amit Arbune; Aaron Soufer; Elio Ragheb; Jennifer M. Kwan; Jerome Lamy; Mariana Henry; Jason R. Cuomo; Ahmad Charifa; Cesia Gallegos; Sarah Hull; Jessica Shank Coviello; Anna S. Bader; Dana C. Peters; Steffen Huber; Hamid R. Mojibian; Albert J. Sinusas; Harriet Kluger; Lauren A. Baldassarre

doi:10.1371/journal.pone.0246764

Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity

Angela Y. Higgins, Amit Arbune, Aaron Soufer, Elio Ragheb, Jennifer M. Kwan, Jerome Lamy, Mariana Henry, Jason R. Cuomo, Ahmad Charifa, Cesia Gallegos, Sarah Hull, Jessica Shank Coviello, Anna S. Bader, Dana C. Peters, Steffen Huber, Hamid R. Mojibian, Albert J. Sinusas, Harriet Kluger, Lauren A. Baldassarre

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Background Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. Methods We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. Results Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of −9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at −12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (r_s = −0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (r_s = −0.29, p = 0.22) or GLS (r_s = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. Conclusion In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

Original language	English
Article number	e0246764
Journal	PLoS ONE
Volume	16
Issue number	2 February 2021
DOIs	https://doi.org/10.1371/journal.pone.0246764
State	Published - Feb 2021

Bibliographical note

Publisher Copyright:
© 2021 Higgins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

LB, grant #18CDA34110361, American Heart Association. https://www.heart.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 2) HK, grant # R01 CA227473, National Cancer Institute. https://www.cancer.gov/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
National Childhood Cancer Registry – National Cancer Institute
American the American Heart Association	R01 CA227473
National Center for Advancing Translational Sciences (NCATS)	UL1TR001863

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0246764

Cite this

Higgins, A. Y., Arbune, A., Soufer, A., Ragheb, E., Kwan, J. M., Lamy, J., Henry, M., Cuomo, J. R., Charifa, A., Gallegos, C., Hull, S., Coviello, J. S., Bader, A. S., Peters, D. C., Huber, S., Mojibian, H. R., Sinusas, A. J., Kluger, H., & Baldassarre, L. A. (2021). Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity. PLoS ONE, 16(2 February 2021), Article e0246764. https://doi.org/10.1371/journal.pone.0246764

@article{a7b6dfa5d06b4598a87a415aecfd5d5b,

title = "Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity",

abstract = "Background Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. Methods We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. Results Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5\% ± 19.1 and 50\% had a normal LVEF (≥53\%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of −9.8\%± 4.2\%. In patients with a normal LVEF, the average GLS remained depressed at −12.3\%± 2.4\%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = −0.64, p 0.002). Sixteen patients (80\%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = −0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45\%) met full Updated Lake Louise Criteria and 85\% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65\%) were treated for ICI-associated myocarditis and, of these, 54\% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or \% LGE (0.15) and recovery of LVEF with treatment. Conclusion In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.",

author = "Higgins, \{Angela Y.\} and Amit Arbune and Aaron Soufer and Elio Ragheb and Kwan, \{Jennifer M.\} and Jerome Lamy and Mariana Henry and Cuomo, \{Jason R.\} and Ahmad Charifa and Cesia Gallegos and Sarah Hull and Coviello, \{Jessica Shank\} and Bader, \{Anna S.\} and Peters, \{Dana C.\} and Steffen Huber and Mojibian, \{Hamid R.\} and Sinusas, \{Albert J.\} and Harriet Kluger and Baldassarre, \{Lauren A.\}",

note = "Publisher Copyright: {\textcopyright} 2021 Higgins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2021",

month = feb,

doi = "10.1371/journal.pone.0246764",

language = "English",

volume = "16",

number = "2 February 2021",

}

Higgins, AY, Arbune, A, Soufer, A, Ragheb, E, Kwan, JM, Lamy, J, Henry, M, Cuomo, JR, Charifa, A, Gallegos, C, Hull, S, Coviello, JS, Bader, AS, Peters, DC, Huber, S, Mojibian, HR, Sinusas, AJ, Kluger, H & Baldassarre, LA 2021, 'Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity', PLoS ONE, vol. 16, no. 2 February 2021, e0246764. https://doi.org/10.1371/journal.pone.0246764

TY - JOUR

T1 - Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity

AU - Higgins, Angela Y.

AU - Arbune, Amit

AU - Soufer, Aaron

AU - Ragheb, Elio

AU - Kwan, Jennifer M.

AU - Lamy, Jerome

AU - Henry, Mariana

AU - Cuomo, Jason R.

AU - Charifa, Ahmad

AU - Gallegos, Cesia

AU - Hull, Sarah

AU - Coviello, Jessica Shank

AU - Bader, Anna S.

AU - Peters, Dana C.

AU - Huber, Steffen

AU - Mojibian, Hamid R.

AU - Sinusas, Albert J.

AU - Kluger, Harriet

AU - Baldassarre, Lauren A.

N1 - Publisher Copyright: © 2021 Higgins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/2

Y1 - 2021/2

N2 - Background Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. Methods We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. Results Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of −9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at −12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = −0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = −0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. Conclusion In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

AB - Background Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. Methods We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. Results Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of −9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at −12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = −0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = −0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. Conclusion In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

UR - https://www.scopus.com/pages/publications/85101396227

UR - https://www.scopus.com/inward/citedby.url?scp=85101396227&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0246764

DO - 10.1371/journal.pone.0246764

M3 - Article

C2 - 33606757

AN - SCOPUS:85101396227

SN - 1932-6203

VL - 16

JO - PLoS ONE

JF - PLoS ONE

IS - 2 February 2021

M1 - e0246764

ER -

Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this