Abstract
Introduction: Myocarditis is a rare but highly morbid complication of immune-checkpoint inhibitors (ICI) use. Improved methods for detection and risk stratification are needed. Cytotoxic chemotherapy associates with reduced global circumferential strain (GCS) but no data is available on the utility of GCS in ICI myocarditis. Hypothesis: We hypothesized that GCS by echocardiography would be reduced in ICI myocarditis and the magnitude of reduction would have prognostic implications. Methods: In this retrospective cohort, GCS from 75 patients with ICI myocarditis (cases) and 49 ICI treated patients without myocarditis (controls) was compared. Pre-ICI GCS values were available for 10 cases and 39 controls. Measurements were performed by a reader blinded to group and time (TomTec, Germany). Major adverse cardiac event was defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. Results: Cases and controls had similar age (66±15 vs. 63±12 years; p=0.19), sex (male: 55% vs. 66%; p=0.22) and cancer type (p=0.08). Pre-ICI GCS values were lower in cases (n=10) than in controls (n=39) (-21.7±2.0 vs. -23.5±2.9, p=0.04), but within normal range. Overall, 56% (n=42) of cases had left ventricular ejection fraction (LVEF) >50% at presentation. The GCS was lower in cases than in controls (-17.5±4.2 vs. -23.5±3.0, p<0.001) in the entire cohort and in both preserved (-19.7±3.8 vs. -23.6±3.0, p<0.001) and reduced EF (-14.6±2.7 vs. -20.9±2.3, p<0.001) strata. Over a median follow-up of 30 days, 28 events occurred. An absolute GCS value < the median (17.1%) was associated with an increased rate of events (HR: 4.9, 95% CI: 1.6-15.0, p=0.005, Figure), adjusted for age and LVEF. The association was also noted when GCS is treated as continuous (HR: 1.18, 95% CI: 1.03-1.35, p=0.02). Conclusions: Global circumferential strain is lower in patients with ICI-myocarditis and the magnitude of the reduction in GCS has prognostic significance.
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