Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis

Lili Zhang, Magid Awadalla, Syed S Mahmood, Anju Nohria, Malek Z O Hassan, Franck Thuny, Daniel A Zlotoff, Sean P Murphy, James R Stone, Doll Lauren Alexandra Golden, Raza M Alvi, Adam Rokicki, Maeve Jones-O'Connor, Justine V Cohen, Lucie M Heinzerling, Connor Mulligan, Merna Armanious, Ana Barac, Brian J Forrestal, Ryan J Sullivan, Raymond Y Kwong, Eric H Yang, Rongras Damrongwatanasuk, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Javid J Moslehi, Otavio R Coelho-Filho, Sarju Ganatra, Muhammad A Rizvi, Gagan Sahni, Carlo G Tocchetti, Valentina Mercurio, Michael Mahmoudi, Donald P Lawrence, Kerry L Reynolds, Jonathan W Weinsaft, A John Baksi, Stephane Ederhy, John D Groarke, Alexander R Lyon, Michael G Fradley, Paaladinesh Thavendiranathan, Tomas G Neilan, Lili Zhang, Magid Awadalla, Syed S Mahmood, Anju Nohria, Malek Z O Hassan, Franck Thuny, Daniel A Zlotoff, Sean P Murphy, James R Stone, Doll Lauren Alexandra Golden, Raza M Alvi, Adam Rokicki, Maeve Jones-O'Connor, Justine V Cohen, Lucie M Heinzerling, Connor Mulligan, Merna Armanious, Ana Barac, Brian J Forrestal, Ryan J Sullivan, Raymond Y Kwong, Eric H Yang, Rongras Damrongwatanasuk, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Javid J Moslehi, Otavio R Coelho-Filho, Sarju Ganatra, Muhammad A Rizvi, Gagan Sahni, Carlo G Tocchetti, Valentina Mercurio, Michael Mahmoudi, Donald P Lawrence, Kerry L Reynolds, Jonathan W Weinsaft, A John Baksi, Stephane Ederhy, John D Groarke, Alexander R Lyon, Michael G Fradley, Paaladinesh Thavendiranathan, Tomas G Neilan

Abstract

Aims: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.

Methods and results: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.

Conclusion: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Keywords: Cardiovascular magnetic resonance; Immune checkpoint inhibitor; Myocarditis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
Patient cohort of immune checkpoint inhibitor-associated myocarditis. CMR, cardiovascular magnetic resonance; ICI, immune checkpoint inhibitors; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; STIR, short tau inversion recovery.
Figure 2
Figure 2
Representative late gadolinium enhancement pattern. Representative late gadolinium enhancement images from patients with immune checkpoint inhibitor-associated myocarditis, showing a patient with no late gadolinium enhancement (A); a patient with sub-endocardial/transmural late gadolinium enhancement (B); a patient with sub-epicardial late gadolinium enhancement (C); a patient with mid-myocardial late gadolinium enhancement (D); a patient with diffuse late gadolinium enhancement (E); and a patient with mixed late gadolinium enhancement (sub-epicardial, mid-myocardial, and transmural) (F). Regions of late gadolinium enhancement are highlighted using white arrows.
Figure 3
Figure 3
Locally Weighted Scatterplot Smoothing method demonstrating the relationship between the time from admission to cardiovascular magnetic resonance and the presence of late gadolinium enhancement. CMR, cardiovascular magnetic resonance; LGE, late gadolinium enhancement.
Figure 4
Figure 4
Kaplan–Meier curves for major adverse cardiovascular events by late gadolinium enhancement (A), T2-weighted STIR imaging for oedema (B), and pathological fibrosis (C). LGE, late gadolinium enhancement.
Take home figure
Take home figure
Proposal algorithm for diagnosing immune checkpoint inhibitor-associated myocarditis.BNP, B-type natriuretic peptide; CMR, cardiovascular magnetic resonance; ECG, electrocardiogram; ICI, immune checkpoint inhibitors; LGE, late gadolinium enhancement.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7205467/bin/eurheartj_41_18_1733_f5.jpg

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