Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Area of Science:

• Cardiology
• Oncology
• Immunology

Background:

• Immune-checkpoint inhibitors (ICI) can cause life-threatening myocarditis, often accompanied by myositis and respiratory failure.
• Milder presentations of ICI-myocarditis are increasingly recognized, but prognostic factors remain unclear.
• The autoimmune process underlying ICI-myocarditis can affect multiple organ systems, termed 'cardiomyotoxicity'.

Purpose of the Study:

• To identify prognostic factors for severe outcomes in patients with ICI-associated cardiomyotoxicity.
• To develop and validate a risk score for predicting severe adverse events.
• To guide clinical management strategies for ICI-induced cardiomyotoxicity.

Main Methods:

• A retrospective multicenter registry study involving 748 patients from 17 countries (2014-2023).
• Multivariable Cox regression analysis was used to determine risk factors for a composite outcome of severe arrhythmia, heart failure, respiratory muscle failure, and/or death.
• A prognostic risk score was derived from identified parameters and externally validated in independent cohorts.

Main Results:

• The 30-day incidence of the composite outcome was 33%, with a 13% incidence of cardiomyotoxicity-related death.
• Key predictors for the composite outcome included active thymoma, cardio-muscular symptoms, low QRS voltage, LVEF <50%, and elevated troponin levels.
• The derived risk score demonstrated good performance, with 30-day outcome incidence increasing from 3.9% to 81.3% based on risk score values.

Conclusions:

• ICI-myocarditis carries significant morbidity and mortality, influenced by troponin levels, thymoma, low QRS voltage, LVEF, and symptoms.
• A validated risk score incorporating these factors effectively predicts severe ICI-cardiomyotoxicity.
• The risk score can identify low-risk patients who may not require immunosuppression, preventing adverse events.