Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor–Associated Myocarditis
Bibliographic record
Abstract
Introduction: myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose and timing. Methods: from an international registry of patients with ICI myocarditis diagnosed between 2013 and 2019, data on the type, dose (in methylprednisolone equivalent dose) and timing of steroids were extracted. Major cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically-significant complete heart block. Results: in total, 143 ICI myocarditis patients (67±13 years old, 29% women) were included. Among them, 125 received corticosteroids (87%), with the initial agent being either methylprednisolone (95, 76%), prednisone (25, 20%), hydrocortisone (2, 1.6%) or dexamethasone (3, 2.4%). The rates of overall MACE (by admission time tertile 1: 45.8%, tertile 2: 43.8%, tertile 3: 38.3%, P=0.746) and individual elements of MACE were unchanged from 2013 to 2019. The initial corticosteroid dose was categorized as low (<60mg), intermediate (≥60mg and ≤500mg) and high (>500mg). There was an inverse relationship between the occurrence of MACE and initial dose of corticosteroid, where MACE declined with increasing doses (low 61.9%, intermediate 54.6%, high 20.4%, P<0.001). The median time from admission to the first corticosteroids was 45 (15.5, 89) hours. Patients receiving corticosteroids within 24 hours had significantly lower MACE (7.0%) compared to those between 24-72 hours (34.3%) and those >72 hours (85.7%, P<0.001). The dose interacted with timing of initiation whereby high dose corticosteroids within 24 hours achieved the best outcome and low corticosteroids after 72 hours had the worst outcome (Fig 1). Conclusions: ICI myocarditis is associated with high rate of MACE. Higher initial dose and earlier initiation of corticosteroids were associated with improved outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".