Meta-analysis reveals CMR and biomarkers key in ICI myocarditis
This meta-analysis, encompassing 3568 patients from multiple studies, provides a comprehensive evaluation of diagnostic and prognostic parameters for immune checkpoint inhibitor-related myocarditis (ICI-M). The findings underscore the heterogeneity of ICI-M presentation and the necessity of a multimodal diagnostic approach.
Cardiac magnetic resonance imaging (CMR) abnormalities were prevalent, with abnormal CMR present in 63.4% of patients. Late gadolinium enhancement (LGE) was the most common finding, observed in 65.3% of cases, and was significantly associated with ICI-M (OR 5.32, 95% CI 1.61-17.50, p=0.006). The most frequent LGE pattern was mid-myocardial (43%), suggesting a non-ischemic etiology. Myo- or pericardial oedema on CMR was less common (16.4%) and showed a non-significant trend toward association (OR 4.79, 95% CI 0.96-23.92, p=0.06).
Echocardiographic assessment revealed decreased left ventricular ejection fraction (LVEF) in 35.9% of patients, which was strongly associated with ICI-M (OR 5.22, 95% CI 2.02-8.42, p=0.001). Importantly, reduced LVEF also predicted major adverse cardiovascular events (MACE) (OR 5.11, 95% CI 2.53-7.68, p<0.001), highlighting its prognostic value.
Cardiac biomarkers were also significantly elevated in ICI-M. Cardiac troponins (cTn) showed a standardized mean difference (SMD) of 0.79 (95% CI 0.14-1.44, p=0.02), while brain natriuretic peptides (BNP/NT-proBNP) had an SMD of 0.92 (95% CI 0.30-1.54, p=0.003). Troponin I elevation further predicted MACE (SMD 2.27, 95% CI 0.33-4.22, p=0.02), though this analysis was limited by small sample size (n=76).
The study's strengths include a large pooled sample and systematic evaluation of multiple diagnostic modalities. However, as a meta-analysis of observational data, results are pooled estimates and subject to heterogeneity across included studies. The analysis did not report specific limitations or funding sources, which should be considered when interpreting the findings.
Clinically, these results emphasize that no single parameter is diagnostic for ICI-M. Instead, a combination of CMR findings (especially LGE), echocardiographic LVEF, and cardiac biomarkers should be used to support the diagnosis and risk stratify patients. The strong association of reduced LVEF and troponin elevation with MACE underscores their prognostic importance. Given the increasing use of immune checkpoint inhibitors, early recognition and management of ICI-M are critical. This meta-analysis provides valuable aggregate data to guide clinicians in selecting appropriate diagnostic tests and identifying patients at highest risk for adverse outcomes.