Clinical and Advanced MRI Techniques for Detection of Checkpoint Inhibitor Associated Myocarditis

Abstract

Purpose of Review With the advent of immune checkpoint inhibitors (ICIs), cancer treatment has been revolutionized; however, these agents are associated with immune-related adverse events, including myocarditis, which ranges from mild to fulminant in severity. Currently, there are no established guidelines in diagnosing ICI-associated myocarditis, and the gold standard test for diagnosis of myocarditis in general is invasive endomyocardial biopsy (EMB). Cardiac magnetic resonance (CMR) imaging is a noninvasive test with the advantage of providing structural, functional and tissue characterization information. Additionally, it provides high spatial and temporal resolution without exposure to ionizing radiation, iodinated contrast, or radioactive isotopes. Recent Findings With an increasing number of reported cases of ICI associated myocarditis, understanding of the disease process and associated CMR findings is growing. Diagnostic testing with cardiac biomarkers, electrocardiogram, and echocardiogram can be nonspecific and EMB can have sampling errors. CMR as a diagnostic tool can provide functional assessment of biventricular ejection fraction, myocardial strain, tissue characterization of myocardial edema and inflammation as well as fibrosis. Furthermore, with advanced parametric mapping techniques, CMR provides even more sensitive and quantitative information about myocardial inflammation and fibrosis, including measurements of extracellular volume. Summary ICI-associated myocarditis is a serious immune adverse event, and CMR plays a vital role in establishing its diagnosis, providing prognostic information, and has the potential for use as a tool for screening and serial monitoring in patients exposed to ICIs.

Emerging Role of Cardiac Magnetic Resonance Imaging in Diagnosing Myocarditis

“…In these patients, myocardial edema is detected when the T2 myocardium to muscle ratio (T2 ratio) is > 1.9, especially in lateral and septal segments. 15 Moreover, native T1 and ECV values are shown to be higher with respect to healthy individuals. 54 Myocarditis is a rare complication of RA.…”

“…In addition, with the advantage of providing absolute values, mapping technique does not require the reference with the skeletal muscle, avoiding potential false negatives, unlike the previously mentioned T1-weighted and T2-weighted images. 15,20,22 T1 mapping provides with indication of the myocardial T1 relaxation times, which are elevated in case of edema, increased extracellular space and fibrosis, as in myocarditis. 24 These sequences are acquired before and 10 minutes after contrast injection, in end diastole in 3 short axis slices: apical, mid, and basal.…”

“…They are easily removed from normal cells, while their renal secretion is slow in case of hyperemia, ruptured cell membranes, or fibrosis. 15 In evaluating LV and right ventricle (RV) systolic function, the gold standard is represented by the steady-state free precession (SSFP) cine imaging sequences, although they are not myocarditis specific. 21 In case of suspected myocarditis, tissue edema, hyperemia, and necrosis should be detected to confirm the diagnosis.…”

“…The CMR sequences that are acquired for myocarditis evaluation are summarized in Table 2. Using an ECG gating for cardiac circle synchronization 15 and a respiratory gating, almost all the sequences are acquired during breath hold, in horizontal long axis (HLA), vertical long axis (VLA), left ventricle (LV) outflow tract, and short axis (SAX). 20 The contrast agents used in CMR are gadoliniumbased GBCA; this type of contrast agents are extracellular and do not enter the cellular membrane.…”

Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review

“…When the examination was performed during the first 4 days of hospital admission, LGE was present only in 21.6% of cases, compared to 72% when cMRI was performed on day 4 of admission or later. Although a prolongation of the time from the onset of clinical symptoms to cMRI is associated with more frequent detection of LGE, such management is not recommended due to a higher risk of serious adverse events [ 52 , 74 ].…”