Diagnostic value of the International Society of Cardio-Oncology (IC-OS) definition for suspected immune checkpoint inhibitor-associated myocarditis

Abstract

The diagnosis of immune checkpoint inhibitor-associated myocarditis (ICI-M) is challenging. Recently, the International Society of Cardio-Oncology (IC-OS) proposed an empirical definition of ICI-M; however, this definition has never been validated. We aimed to assess the diagnostic value at admission of the IC-OS definition in a cohort of patients with suspected ICI-M and to determine whether the addition of other criteria to this definition would improve its performance. Between May 2017 and November 2021, all patients with suspected ICI-M were consecutively included in a multicenter cohort. The final diagnosis was the one recorded in the patient's electronic medical record, established within one month of hospital discharge by the expert cardio-oncology team that managed the patient. Of the 68 patients included, 45 patients presented with ICI-M. The sensitivity, specificity, and positive and negative likelihood ratios of the IC-OS definition were 93% (95% CI: 82%–99%), 70% (95% CI: 47%–87%), 3.1 (95% CI: 1.7–5.7), and 0.1 (95% CI: 0–0.3), respectively. A delay in the onset of the first events < 3 months after the introduction of ICIs was the only variable that was both significantly associated with the final diagnosis of ICI-M and did not already meet the criteria of the IC-OS definition (72% vs. 52%, P = 0.03). By including this variable as a new minor criterion and increasing the number of minor criteria for defining ICI-M to 3, the specificity increased from 70% to 83% (P = 0.08), and the sensitivity remained unchanged (93%). The IC-OS definition for the diagnosis of ICI-M showed excellent sensitivity and moderate specificity. The latter could be increased by a modified definition including the time of the onset of the first events < 3 months after the introduction of ICIs (Fig. 1).