Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis

Abstract

Background: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.

Objectives: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.

Methods: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.

Results: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.

Conclusions: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.

Keywords: Lake Louise Criteria; T1 mapping; T2 mapping; cardiovascular magnetic resonance; immune checkpoint inhibitor; major adverse cardiovascular event; myocarditis.

Conflict of interest statement

Funding Support and Author Disclosures Dr. Thavendiranathan was supported, in part, through the Canadian Institutes of Health Research New Investigator Award (FRN 147814) and a Canada Research Chair in Cardio-Oncology. This work is supported by the New York Academy of Medicine's Glorney-Raisbeck Award to Dr. Mahmood. Dr. Sullivan was supported, in part, through the National Institutes of Health (NIH)/National Cancer Institute (RO1CA229851, UH2CA207355, RO1CA193970). Dr. C.L. Chen, and Dr. D. Gupta were supported, in part, through the NIH/National Cancer Institute P30CA008748. Dr. Neilan was supported, in part, through the Kohlberg Foundation, the NIH/National Heart, Lung, and Blood Institute (RO1HL130539, RO1HL137562, and K24HL150238), and the NIH/Harvard Center for AIDS Research (P30 AI060354). Dr. Thavendiranathan has received Speakers Bureau fees from Amgen, Takeda, and BI. Dr. Mahmood has received consulting fees from OMR Globus, Alpha Detail, and Opinion Research Team. Dr. Nohria has received research grant support from Amgen; and has served a consultant for Takeda Oncology. Dr. Heinzerling has received consulting, advisory board, and speaker fees from MSD, BMS, Roche, Novartis, Amgen, and Curevac. Dr. Sullivan has served as a consultant for Merck and Novartis. Dr. Groarke has received research support from Amgen. Dr. Neilan has received advisory fees from Parexel, BMS, H3 Biomedicine, AbbVie, and Intrinsic Imaging. Dr. Neilan has received grant support from AstraZeneca. Dr. Wintersperger has received research support and speaker honoraria from Siemens Healthineers (the University Health Network has a master research agreement with Siemens Healthineers); and is an inventor of the IG fitting method owned by the University Health Network (US10314548B2). Dr. Yang has received research funding from CSL Behring. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1:. Multi-contrast and parametric CMR imaging in patient with confirmed ICI myocarditis (1.5T).

(a) Representative short axis T2-weighted SPAIR without focal signal abnormality; (b) Mid-ventricular short axis MOLLI T1-map demonstrates diffusely elevated T1 values (local normal reference: 1006±24ms) while (c) same slice T2-map demonstrate normal global T2 values (local normal reference: 52±3ms); (d) Post-contrast LGE imaging demonstrates faint mid-myocardial enhancement (arrow) in the mid-ventricular anteroseptum; (e) 3-chamber cine bSSFP image demonstrates a pericardial effusion (*); (f-h) coronary CT angiography performed for exclusion of possible coronary artery disease demonstrated calcified and non-calcified changes (predominately in LAD; f) without significant coronary artery stenosis.

Figure 2.. Kaplan–Meier curves of MACE free survival in patients with normal and abnormal T1 values (left panel) and T2 values (right panel).

Abnormal values were defined as above mean+2SD of the site, CMR vendor/field strength specific reference ranges.

Figure 3.. Receiver-Operating-Characteristic (ROC) curves for major adverse cardiovascular events for cardiovascular magnetic resonance T1 and T2 mapping.

T1/T2 values were converted to z-scores for combined analysis.

Central Illustration:. A proposed approach to CMR assessment of ICI myocarditis with incorporation of parametric mapping techniques.

Arrowheads delineate band-like subepicardial late gadolinium enhancement (LGE), block arrows highlight elevated signal intensity on T2 weighted image, and (*) demonstrates the presence of pericardial effusion on a cine bSSFP image.