Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis

• Authors: Magid Awadalla, Massachusetts General Hospital; Syed S. Mahmood, New York Presbyterian Hospital; John D. Groarke, Brigham & Women's Hospital; Malek Z.O. Hassan, Massachusetts General Hospital; Anju Nohria, Brigham & Women's Hospital; Adam Rokicki, Massachusetts General Hospital; Sean P. Murphy, Massachusetts General Hospital; Nathaniel D. Mercaldo, Massachusetts General Hospital; Lili Zhang, Massachusetts General Hospital; Daniel A. Zlotoff, Massachusetts General Hospital; Kerry L. Reynolds, Massachusetts General Hospital; Raza M. Alvi, Massachusetts General Hospital; Dahlia Banerji, Massachusetts General Hospital; Shiying Liu, Massachusetts General Hospital; Lucie M. Heinzerling, Friedrich-Alexander-University Erlangen-Nurnberg; Maeve Jones-O'Connor, Massachusetts General Hospital; Rula B. Bakar, Massachusetts General Hospital; Justine V. Cohen, Massachusetts General Hospital; Michael C. Kirchberger, Friedrich-Alexander-University Erlangen-Nurnberg; Ryan J. Sullivan, Massachusetts General Hospital; Dipti Gupta, Memorial Sloan Kettering Cancer Center; Connor P. Mulligan, Massachusetts General Hospital; Sachin P. Shah, Lahey Hospital & Medical Center; Sarju Ganatra, Lahey Hospital & Medical Center; Muhammad A. Rizvi, Lehigh Valley Hospital; Gagan Sahni, The Mt. Sinai Hospital; Carlo G. Tocchetti, Federico II University; Donald P. Lawrence, Massachusetts General Hospital; Michael Mahmoudi, University of Southampton; Richard B. Devereux, New York Presbyterian Hospital; Brian J. Forrestal, MedStar Washington Hospital Center; Anant Mandawat, Emory University; Alexander Lyon, Royal Brompton Hospital and Imperial College; Carol L. Chen, Memorial Sloan Kettering Cancer Center; Ana Barac, MedStar Washington Hospital Cente; Judy Hung, Massachusetts General Hospital; Paaladinesh Thavendiranathan, University of Toronto; Michael H. Picard, Massachusetts General Hospital; Franck Thuny, Aix-Marseille Universite; Stephane Ederhy, Hopitaux Universitaires est Paris; Michael G. Fradley, H. Lee Moffitt Cancer Center & Research Institute; Thomas G. Neilan, Massachusetts General Hospital
• Journal Title: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
• Volume: Volume 75, Number 5
• Publisher: ELSEVIER SCIENCE INC | 2020-02-11, Pages 467-478
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.jacc.2019.11.049
• Subjects: Health Sciences, Immunology; Health Sciences, Oncology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; global longitudinal strain; immune checkpoint inhibitors; major adverse cardiac events; myocarditis; VENTRICULAR EJECTION FRACTION; SPECKLE-TRACKING ECHOCARDIOGRAPHY; ALL-CAUSE MORTALITY; RISK PREDICTION; CANCER; CARDIOTOXICITY; DIAGNOSIS; CARDIOMYOPATHY; INFARCTION; CONSENSUS

Abstract

Background: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. Objectives: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. Methods: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. Results: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). Conclusions: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.