Intrinsic Differences in Immune Checkpoint Inhibitor-Induced Myocarditis: A Retrospective Analysis of Real World Data

Abstract

Immune-related myocarditis is a severe and even life-threatening immune-related adverse event (irAE) which may also be underestimated due to the challenge in diagnosis. The inherent difference between individuals with immune-associated myocarditis has received little attention. Our study aimed to identify which baseline characteristics could contribute to distinguishing mild from severe ICI myocarditis. A retrospective analysis was conducted between March 2019 and June 2020 in West China Hospital, and 18 patients with immune-related myocarditis were studied. Patients were classified as having mild (n = 12) or severe myocarditis (n = 6), according to the clinical manifestations and hemodynamic complications. Factors associated with severe myocarditis were identified by comparing covariates derived from medical records in various groups. In this retrospective analysis, the median age of the 18 patients was 60 years old. Most myocarditis cases occur early and approximately after the first or second ICI infusion. The severity of myocarditis may be correlated with lactate dehydrogenase (LDH) (p = 0.04) and troponin levels (p = 0.0057). The relationship between troponin and myocarditis was further confirmed in another cohort, which included 30 patients. In addition, patients are more likely to develop multi-irAEs, and myositis was the most common second irAE. Those who experience multi-irAEs usually had significantly higher LDH (p = 0.02) and myoglobin levels (p = 0.02) than those who did not experience them. All patients were treated with steroids timely, and the mortality rate was 5.6% in our study. In this study, we explored risk factors for severe myocarditis and emphasized the importance of a multidisciplinary team in assisting diagnosis and treatment options. It is critical to initiate corticosteroid therapy, regardless of the severity of the myocarditis.

Identification of features and differences in PD-1 inhibitor-associated myocarditis and acute myocardial infarction using proteomic analysis

“…The basic clinical data of ve patients with ICIs-related myocarditis and the ve matched patients with AMI are listed as shown in Table 1. In the myocarditis group, 80% of patients were male, which is consistent with previous studies [6,23]. Cardiac troponin I is currently the most sensitive blood biomarker for diagnosing ICIs-related myocarditis, but it is also increased in the MI group.…”

The Heart of the Matter: Immune Checkpoint Inhibitors and Immune-Related Adverse Events on the Cardiovascular System

“…Acquisition of an electrocardiogram (ECG) is the first step in most cardiovascular evaluations. In multiple assessments of ICI-induced myocarditis, the most common cardiotoxicity identified as an irAE with ICI therapy, 94.4% of confirmed myocarditis cases showed irregular ECG markings, including abnormal T waves, ST segment, conduction defects, and sinus tachycardia [48]. Another study recorded an immense array of ICIinduced ECG changes, such as prolonged QRS and QTc, decreased QRS voltage, and various conduction blocks [49].…”

“…Troponin levels have been noted in patients lacking clinically apparent symptoms of cardiac irAEs, which begs the question of smoldering myocarditis or subclinical cardiotoxicity in patients treated with ICIs [40]. Brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) are very sensitive markers of early myocardial damage [53] An increase in cardiac LDH levels may indicate ICI-induced myocarditis [48]. However, LDH may not distinguish correctly between cases of mild myocarditis versus severe myocarditis [48].…”

“…Brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) are very sensitive markers of early myocardial damage [53] An increase in cardiac LDH levels may indicate ICI-induced myocarditis [48]. However, LDH may not distinguish correctly between cases of mild myocarditis versus severe myocarditis [48].…”

“…This grading system provides a guide on properly treating the patient based on the severity of their condition instead of a scale to determine the likelihood an irAE might occur. Grade 1 is defined as close monitoring during treatment in an asymptomatic patient with aberrant cardiac biomarkers and irregular ECG tracings, grade 2 involves minor symptoms, grade 3 is severe symptoms with steroid treatment required, and grade 4 is moderate to severe decompensation of life-threatening situations that demand IV injections of medication or intervention [48]. Utilizing this scale, a grade 1 or 2 is considered mild, whereas a grade 3 or 4 is considered severe [48].…”