Immune-checkpoint myocarditis phenotype when using systematic troponin surveillance in cancer patients.
Authors: Cribari F , Hamdi I , Henriquez S , Joulia M L , Charles P , Colle R , Amabile N , Loirat D , Girard N , Lillo Le Louet M A , Caussin C , Mirabel M 
Published: October 2024

Abstract

Background
ICI myocarditis, often described as potentially fulminant in registries from specialized centers, lacks sufficient data on its subclinical forms. ESC 2022 guidelines advocate systematic troponin measurements for early detection, resulting in numerous suspected cases of ICI myocarditis. Additionally, many patients receive other potentially cardiotoxic cancer drugs (e.g.,anthracyclines), adding complexity to the management.

Purpose
To identify factors associated with ICI-myocarditis diagnosis in a single-center unselected cohort referred for suspicion of CV immune-related adverse events(irAEs). Patients underwent standardized evaluation, including serum testing, ECG, echocardiogram, cardiac MRI(CMRi) and multidisciplinary team assessment including cardiology and internal medicine specialists. Coronary imaging and myocardial biopsy (EMB) were performed as needed. ICI-myocarditis diagnosis was adjudicated by expert panel (FC, MM, SH) based on Dallas, ESC, and IC-OS criteria.

Results
We enrolled 175 consecutive patients from March 2022 to October 2023; 40 (22.89%) were male, with a median age of 61 (IQR 48.0-72.0) years. 92(52.57%) were referred for lone asymptomatic troponin raise, 101 (57.7%) had breast cancer; 142 (81.11%) received other cardiotoxic drugs. We identified 95 (61.71%) patients with CV irAEs at referral (8 had &gt;=2 CV irAEs) with a total of 108 CV irAEs after follow up, including 72 (41.14%) with ICI-myocarditis at referall. No CV deaths occurred within 30 days from referall. Characteristics and univariate analysis are depicted in the Table1. Reasons for referral in the ICI-myocarditis population are depicted in the Figure1. On multivariate regression analysis, prior CV disease history (OR 6.232 [CI 1.204-32.260], p=0.029), EMB (OR 24.969 [5.139-121.32], p=&lt;.0001), IC-OS criteria fulfilled (OR 43.108 [9.222-201.510], p=&lt;.0001), and positive Lake Louise criteria on CMRi (OR 6.583[1.416-30.610], p=0.0163) were associated with myocarditis. In a sub-analysis group of breast cancer patients (largely receiving anthracyclines), ICI-myocarditis was associated on multivariate regression with abnormal ECG (OR 14.227 [CI 1.632-124.040], p=&lt; 0.0163) and EMB (OR 8.508 [CI 2.718-26.638], p=0.0002). The same characteristics were significantly associated with other CV irAEs in the group of breast cancer patients. In the group of patients with cancers other than breast, factors significantly associated with ICI myocarditis diagnosis were: EMB (OR 70.656 [CI 5.970-836.161], 0.0007), and no arterial hypertension (OR 9.554 [CI 1.792-50.940], p= 0.0082).

Conclusions
The FAST TRACK study highlights the high proportion of patients fulfilling ICI-myocarditis criteria despite no or mild symptoms, mainly referred for troponin elevation. However, subclinical ICI-myocarditis appears to bear good prognosis. Endomyocardial biopsy is key to increase the diagnosis rate of ICI-myocarditis across different cancer populations when mildly symptomatic.Table 1Figure 1