A case series of immune checkpoint inhibitor associated myocarditis - an underreported side effect?
M E Prieto, R Rauschenberg, M Wagner, A Trausch, M Cybularz-Bednarek, K Sveric, N Mangner, F Meier, K Klingel, A Linke, F M Heidrich, S JellinghausAbstract
Introduction
Early diagnosis of immune checkpoint inhibitor (ICI) associated myocarditis (ICImyocarditis) is fundamental to initiate potentially life-saving immunosuppressive therapy in time. ICImyocarditis has been reported to carry a high mortality up to 50% and to occur in 1% of ICI patients. Diagnosis is made applying the 2021 International Cardio-Oncology Society (IC-OS) consensus criteria. These require either a histologically conclusive endomyocardial biopsy (EMB) or a significantly elevated troponin (Tn) level in the presence of 1 major or at least 2 minor criteria, which include cardiac magnetic resonance imaging (cMRI), electrocardiography (ECG) and others.
Methods
32 patients’ medical records were analysed retrospectively after being referred to our cardiology department with suspected ICImyocarditis in 2022-2024. Baseline characteristics and follow-up are shown in Table 1. Diagnostic tests included Tn in 94%, ECG in 91%, cMRI in 88% and EMB in 41% of cases. To grade disease severity, we applied the 2018 American Society of Clinical Oncology Clinical Practice Guideline. Statistical analysis used Fisher’s exact or unpaired t-test; after Bonferroni correction, p<0.05 was considered significant.
Results
24 patients met IC-OS criteria (confirmed cases). Thereof, 3 patients each could be diagnosed via conclusive EMB or cMRI. The remaining 18 cases required multimodal assessment. ICImyocarditis was mild to moderate in 18 cases, 4 were asymptomatic and 2 were severe. At baseline, patients meeting the IC-OS criteria tended to be older, more often male, have fewer cardiovascular risk factors and comorbidities but a higher rate of distant metastases and higher Tn levels. Mean follow-up was 13.4 ± 9.1 months. We recorded a total of 13 deaths, 3 were tumor-associated, 2 infectious, 2 strokes, only 1 cardiac (a patient with severe ICImyocarditis) and 5 of unknown cause. 66.7% of confirmed cases were treated in one oncology centre which initiated 464 patients on ICI in 2022-2024. This cohort showed an ICImyocarditis incidence of 3.4%.
Conclusion
Only 25% of confirmed cases were diagnosed by conclusive EMB or cMRI. Multimodal assessment and attention to minor criteria is therefore essential and patients with suspected ICImyocarditis should be referred to specialised cardio-oncology centres. The higher incidence of ICImyocarditis in our case series and the high rate of non-severe ICI myocarditis (91.7%) suggests that close clinical monitoring has revealed previously underreported cases. After including all deaths of unknown cause, the possibly attributable mortality reached only 18.7%, which is lower than previously reported. We hypothesize that early and close clinical monitoring might prevent the development of severe ICImyocarditis. Close interdisciplinary cooperation as recommended in the 2022 ESC Guidelines on cardio-oncology may further improve outcomes.