Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis.

Background: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.
Objectives: This study aimed to detail the role of GCS and GRS in ICI myocarditis.
Methods: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.
Results: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).
Conclusions: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.
Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health (P30CA008748 to DG and CLC; R01HL137562, R01HL130539; and T32HL007208-39 to DAZ). Dr Mahmood has received consultancy fees from Health and Wellness Partners, OMR Globus, Alpha Detail, and Opinion Research Team. Dr Zhang is consultant for MERCK. Dr Sullivan has served as a consultant for Merck and Novartis. Dr Heinzerling has received consultancy, advisory board, and speaker fees from Merck Sharp & Dohme, BMS, Roche, Novartis, Amgen, Sun Pharma, Pierre Fabre, and CureVac. Dr Gavira has received research support from Amgen. Dr Zubiri has served as a consultant to Merck and is supported by a SEOM (Sociedad Española de Oncología Médica) grant. Dr Yang has received research funding from CSL Behring. Dr Nohria has received research support from Amgen and has been a consultant for Takeda Oncology, Boehringer Ingelheim, and AstraZeneca; and he has received support from the Catherine Geoff Fitch fund and Gelb Master Clinician Fund. Dr Fradley has received consulting fees from AstraZeneca and Abbott and has received a research grant from Medtronic. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award; has received advisory fees from AbbVie, Amgen, C4 Therapeutics, H3-Biomedicine, Genentech, Roche, BMS, and Intrinsic Imaging; has received grant funding from AstraZeneca; and he is also supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL130539, R01HL137562, K24HL150238). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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