The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer; however, at the potential cost of serious adverse events including cardiac injury. OBJECTIVE: To assess the baseline and longitudinal changes in high sensitivity-Troponin (hs-Tn) in patients treated with pembrolizumab as a potential predictor for the development of major adverse cardiac events (MACE) and survival. METHODS: We performed a retrospective analysis of cancer patients treated with pembrolizumab at our center. All participants had baseline measurements of hs-TnI prior to initiation of pembrolizumab (T1), with half of the patients performing follow-up measurements at their second encounter for therapy introduction (T2). We first evaluated the prevalence of abnormally elevated serum hs-TnI (> 50 nanogram per liter) at T1 and T2. We then evaluated the predictive value of abnormal levels at T1 or T2 in relation to the development of MACE (composite outcomes of myocarditis, acute coronary syndrome, heart failure, venous thromboembolism, cardiovascular hospitalization and cardiovascular mortality) and all-cause mortality. RESULTS: Among 135 patients, the mean age was 72 years, predominantly male (61%). Abnormally elevated hs-TnI at T1 was observed in 7 (5%) patients and emerged as a significant independent predictor for MACE (HR 8.1, 95% CI 1.67-37.4, p = 0.009) and all-cause mortality (HR 5.37, 95% CI 2.1-13.57, p < 0.001). Abnormally elevated hs-TnI at T2 was observed in 8 (11%) patients and emerged as a significant independent predictor for MACE (HR 10.49, 95% CI 1.68-65.5, p = 0.009), but not for mortality (p = 0.200). CONCLUSIONS: Abnormally elevated baseline and follow-up hs-TnI served as significant independent predictors for MACE, with an increased risk of development being 8-tenfold. Furthermore, elevated baseline hs-TnI showed a predictive value for all-cause mortality. Central illustration: Novel immune checkpoint inhibitor (ICIs) therapy has been found to revolutionize cancer therapy through increased activation of host immune systems to target and reduce tumor burden, but may come at the cost of serious adverse cardiac events. Identification of early biomarkers for the prediction and detection of these events is necessary.

Immune Checkpoint Inhibitor-Induced Myocarditis vs. COVID-19 Vaccine-Induced Myocarditis-Same or Different?

Immune checkpoint inhibitor (ICI) and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis possibly share common mechanisms secondary to overactivation of the immune system. We aimed to compare the presenting characteristics of ICIs and COVID-19 vaccine-induced myocarditis. We performed a retrospective analysis of characteristics of patients diagnosed with either ICIs or COVID-19 vaccine-induced myocarditis and compared the results to a control group of patients diagnosed with acute viral myocarditis. Eighteen patients diagnosed with ICIs (ICI group) or COVID-19 vaccine (COVID-19 vaccine group)-induced myocarditis, and 20 patients with acute viral myocarditis (Viral group) were included. The ICI group presented mainly with dyspnea vs. chest pain and fever among the COVID-19 vaccine and Viral groups. Peak median high sensitivity Troponin I was markedly lower in the ICI group (median 619 vs. 15,527 and 7388 ng/L, p = 0.004). While the median left ventricular (LV) ejection fraction was 60% among all groups, the ICI group had a lower absolute mean LV global longitudinal strain (13%) and left atrial conduit strain (17%), compared to the COVID-19 vaccine (17% and 30%) and Viral groups (18% and 37%), p = 0.016 and p = 0.001, respectively. Despite a probable similar mechanism, ICI-induced myocarditis's presenting characteristics differed from COVID-19 vaccine-induced myocarditis.