Immune checkpoint inhibitor-associated myocarditis: diagnostic challenges

Immune checkpoint inhibitors (ICIs), which are increasingly used in cancer pharmacotherapy, can induce myocarditis. ESC guidelines recommend cardiac MRI and myocardial biopsy as diagnostic methods, but these examinations are not readily available in all patients with suspected ICI myocarditis. One minor criterium is decline in left ventricular (LV) function, but precise details of parameters are not outlined. This may cause confusion with the diagnostic criteria for cancer therapeutic-related cardiac dysfunction (CTRCD) and may lead to difficulties in diagnosis of ICI myocarditis.

The purpose of this study was to compare echocardiographic parameters and biomarkers in ICI myocarditis and non-ICI myocarditis patients, and moreover, to evaluate their usefulness as diagnostic tools for ICI myocarditis.

Twelve patients receiving ICI therapy developed ICI myocarditis at our cancer hospital between March 2021 and November 2023. These were compared to a group of 35 patients without ICI induced myocarditis. Echocardiography was performed prior to ICI therapy (baseline) and after starting ICI therapy according to guidelines with median follow-up interval of 87 days. Echocardiographic findings and biomarkers were retrospectively analyzed.

In the ICI myocarditis group ICI therapy was discontinued, while in the non-ICI myocarditis group ICI therapy was continued. Echocardiographic parameters were compared between baseline and follow-up for each group (Table 1). In the ICI myocarditis group, there were significant decreases in LVEF and GLS and worsening of TEI index, but no significant changes in LVMI, E/e', and E/A. In the non-ICI myocarditis group, there were no significant changes in LVEF, TEI index, LVMI, E/e' and E/A, however, GLS decreased significantly.

Categorical data were compared between the two groups at follow-up (Table 2). Pericardial effusion, ECG changes, increased high-sensitivity Troponin I (hsTnI), increased BNP, and immune-related adverse effects (irAE) in other organs were significantly more prevalent in the ICI myocarditis group. However, there were no significant differences in CPK elevation, prior chemotherapy, dual ICI, prior CTRCD or CVD, and ICI-cardiotoxic combination therapy. By multinomial logistic regression analysis between the two groups, changes in hsTnI and LVEF were significant predictors to determine diagnosis, but not changes in GLS, with hsTnI being the strongest.

LVEF and hsTnI are the most useful and available tools for the diagnosis of ICI myocarditis. However, GLS is not useful, as it is also decreasing in the non-ICI myocarditis patients.

Therefore, reduction in GLS alone is not a feasible parameter for determining decline in LV function. This would differ from the approach used for the diagnosis of CTRCD.

Changes of echocardiographic indices