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. 2020 May 7;41(18):1733-1743.
doi: 10.1093/eurheartj/ehaa051.

Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis

Lili Zhang  1   2 , Magid Awadalla  1   2 , Syed S Mahmood  3 , Anju Nohria  4 , Malek Z O Hassan  1 , Franck Thuny  5   6   7 , Daniel A Zlotoff  2 , Sean P Murphy  1 , James R Stone  8 , Doll Lauren Alexandra Golden  1 , Raza M Alvi  1 , Adam Rokicki  1   2 , Maeve Jones-O'Connor  1 , Justine V Cohen  9 , Lucie M Heinzerling  10 , Connor Mulligan  1 , Merna Armanious  11 , Ana Barac  12 , Brian J Forrestal  12 , Ryan J Sullivan  9 , Raymond Y Kwong  13 , Eric H Yang  14 , Rongras Damrongwatanasuk  11 , Carol L Chen  15 , Dipti Gupta  15 , Michael C Kirchberger  10 , Javid J Moslehi  16 , Otavio R Coelho-Filho  17 , Sarju Ganatra  18 , Muhammad A Rizvi  19 , Gagan Sahni  20 , Carlo G Tocchetti  21 , Valentina Mercurio  21 , Michael Mahmoudi  22 , Donald P Lawrence  9 , Kerry L Reynolds  9 , Jonathan W Weinsaft  3   15 , A John Baksi  23   24 , Stephane Ederhy  25 , John D Groarke  4 , Alexander R Lyon  26   27 , Michael G Fradley  11 , Paaladinesh Thavendiranathan  28 , Tomas G Neilan  1   2
Affiliations

Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis

Lili Zhang et al. Eur Heart J. .

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.

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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.
None
See this image and copyright information in PMC

Comment in

References

    1. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJM, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–723. - PMC - PubMed
    1. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain J-F, Testori A, Grob J-J, Davidson N, Richards J, Maio M, Hauschild A, Miller WH, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen T-T, Humphrey R, Hoos A, Wolchok JD. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517–2526. - PubMed
    1. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018;378:158–168. - PubMed
    1. Tang J, Shalabi A, Hubbard-Lucey VM. Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol 2018;29:84–91. - PubMed
    1. Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N Engl J Med 2016;374:2542–2552. - PMC - PubMed

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