Global circumferential and radial strain among patients with immune checkpoint inhibitor myocarditis

• Type of Material: Article
• Authors: Thiago Quinaglia, Massachusetts General Hospital; Carlos Gongora, Massachusetts General Hospital; Magid Awadalla, Massachusetts General Hospital; Malek Z.O. Hassan, Massachusetts General Hospital; Amna Zafar, Massachusetts General Hospital; Zsofia D. Drobni, Massachusetts General Hospital; Syed S. Mahmood, Weill Cornell Medicine; Lili Zhang, Albert Einstein College of Medicine; Otavio R. Coelho-Filho, State University of Campinas; Giselle A. Suero-Abreu, Rutgers New Jersey Medical School; Anant Mandawat, Emory University; Eduardo Zatarain-Nicolás, Hospital General Universitario Gregorio Marañón; Michael Mahmoudi, University of Southampton; Ryan Sullivan, Massachusetts General Hospital; Sarju Ganatra, Lahey Hospital and Medical Center; Lucie M. Heinzerling, University Hospital Erlangen; Franck Thuny, Aix-Marseille University; Stephane Ederhy, Hopitaux Universitaires Est Parisien; Hannah K. Gilman, Massachusetts General Hospital; Supraja Sama, Massachusetts General Hospital; Sofia Nikolaidou, Massachusetts General Hospital; Ana González Mansilla, Hospital General Universitario Gregorio Marañón; Antonio Calles, Hospital General Universitario Gregorio Marañón; Marcella Cabral, McGill University; Francisco Fernández-Avilés, Hospital General Universitario Gregorio Marañón; Juan José Gavira, Clínica Universidad de Navarra; Nahikari Salterain González, Clínica Universidad de Navarra; Manuel García de Yébenes Castro, Clínica Universidad de Navarra; Ana Barac, MedStar Heart and Vascular Institute; Jonathan Afilalo, McGill University; Daniel A. Zlotoff, Massachusetts General Hospital; Leyre Zubiri, Massachusetts General Hospital; Kerry L. Reynolds, Massachusetts General Hospital; Richard Devereux, Weill Cornell Medical Center; Judy Hung, Harvard University; Michael H. Picard, Harvard University; Eric H. Yang, University of California, Los Angeles; Dipti Gupta, Weill Cornell Medicine; Caroline Michel, McGill University; Alexander R. Lyon, Imperial College London; Carol L. Chen, Weill Cornell Medicine; Anju Nohria, Brigham and Women's Hospital; Michael G. Fradley, University of Pennsylvania; Paaladinesh Thavendiranathan, University of Toronto; Tomas G. Neilan, Massachusetts General Hospital
• Language: English
• Date: 2022-09-14
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 the American College of Cardiology Foundation. Published by Elsevier.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.jcmg.2022.06.014
• Title of Journal or Parent Work: JACC: Cardiovascular Imaging
• Volume: 15
• Issue: 11
• Start Page: 1883
• End Page: 1896
• Grant/Funding Information: 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. Dr. Neilan is also supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute grants (R01HL130539, R01HL137562, K24HL150238); Dr. Zubiri is supported by SEOM (Sociedad Española de Oncología Médica) grant. This work was supported by the National Institutes of Health (P30CA008748 to DG and CLC; R01HL137562, R01HL130539; and T32HL007208-39 to DAZ). Dr. Nohria receives support from the Catherine Geoff Fitch fund and Gelb Master Clinician Fund. Dr. Eric Yang receives research funding from CSL Behring.
• Keywords: Strain modalities; immune checkpoint inhibitors; cardiovascular risk stratification; myocarditis; survival analysis
• Research Categories: Health Sciences, Immunology; Health Sciences, Epidemiology

Abstract

Background: GCS and GRS are reduced with cytotoxic chemotherapy. There are limited data on the effect of ICI myocarditis on GCS and GRS. Objectives: To detail the role of global circumferential (GCS) and radial strain (GRS) in immune checkpoint inhibitor (ICI) myocarditis. Methods: In this retrospective study, GCS and GRS from 75 ICI myocarditis patients (cases) 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 (MACE) 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 vs. 63±12 years; p=0.2), sex (male: 73% vs. 61%; p=0.2) 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 myocarditis cases presented with preserved LVEF. GCS and GRS were lower in myocarditis compared to 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 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 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.