Characterization of Cardiovascular Events and Prognosis in Immune Checkpoint Inhibitor–Related Myocarditis
Milagros Pereyra, Juan Farina, Isabel G. Scalia, Michael C. Roarke, Ahmed Mahmoud, Rajeev Masson, Beman Wasef, Cecilia Tagle‐Cornell, Courtney Kenyon, Mohammed Tiseer Abbas, Nima Baba Ali, Kamal Awad, Moaz Kamel, Ebram F Said, Michael O’Shea, Timothy Barry, Hema Narayanasamy, Jordan Ray, Hicham El Masry, Carolyn Larsen, Joerg Herrmann, Reza Arsanjani, Chadi Ayoub
Abstract
OBJECTIVE: To evaluate the incidence, timing, and characteristics of immune checkpoint inhibitor-related myocarditis (ICIrM) and associated cardiovascular events at 3-year follow-up. METHODS: All patients treated with immune checkpoint inhibitors (ICIs) at a multicenter institution from 2011 to 2022 were retrospectively reviewed for ICIrM. A propensity score-matched control group was identified from patients treated with ICIs without development of myocarditis (ratio of 1:4). Baseline characteristics, cardiovascular events, and mortality outcomes were manually curated during extended 3-year follow-up. Major adverse cardiovascular events (MACE) were defined as transient ischemic attack/stroke, heart failure, and myocardial infarction. RESULTS: Of 5423 patients treated with ICIs, ICIrM occurred in 59 (1.1%), and 236 propensity score-matched patients who received ICIs without myocarditis were identified as controls. Mean age was 68.5 ± 12.3 years; 65.4% were male. Median time to development of ICIrM was 44 days (interquartile range, 28 to 102 days), with median troponin value of 364 ng/L (interquartile range, 115 to 1224 ng/L). Patients with ICIrM had increased risk of cardiac death (hazard ratio [HR], 34.0; 95% CI, 7.8 to 148.0; P<.001), MACE (HR, 5.0; 95% CI, 3.1 to 8.1; P<.001), ventricular tachycardia (HR, 12.3; 95% CI, 1.3 to 118.4; P=.03), and complete heart block (HR, 2.3; 95% CI, 1.0 to 5.1; P=.046); these occurred predominantly within 120 days after diagnosis of ICIrM. Triple-M syndrome (myocarditis, myasthenia, and myositis) occurred in 12 (20.3%), with increased risk for all-cause mortality (HR, 2.1; 95% CI, 1.0 to 4.1; P=.04) but not for cardiac death or MACE. CONCLUSION: Immune checkpoint inhibitor-related myocarditis is associated with increased cardiovascular events that are further characterized on extended follow-up, with most occurring in the first 4 months after diagnosis.