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

Awadalla M, Mahmood SS, Groarke JD, Hassan MZ, Nohria A, Rokicki A, Murphy SP, Mercaldo ND, Zhang L, Zlotoff DA, Reynolds KL, Alvi RM, Banerji D, Liu S, Heinzerling L, Jones-O'Connor M, Bakar RB, Cohen JV, Kirchberger M, Sullivan RJ, Gupta D, Mulligan CP, Shah SP, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Lawrence DP, Mahmoudi M, Devereux RB, Forrestal BJ, Mandawat A, Lyon AR, Chen CL, Barac A, Hung J, Thavendiranathan P, Picard MH, Thuny F, Ederhy S, Fradley MG, Neilan TG (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 75

Pages Range: 467-478

Journal Issue: 5

DOI: 10.1016/j.jacc.2019.11.049

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.

Authors with CRIS profile

Involved external institutions

Massachusetts General Hospital United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) MedStar Washington Hospital Center United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Mount Sinai Hospital United States (USA) (US) Weill Cornell Medicine United States (USA) (US) Lehigh Valley Health Network United States (USA) (US) Aix-Marseille University / Aix-Marseille Université France (FR) University of Toronto Canada (CA) Università degli Studi di Napoli Federico II Italy (IT) Hôpital Saint-Antoine France (FR) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) Lahey Hospital & Medical Center United States (USA) (US) University of Southampton United Kingdom (GB) Royal Brompton Hospital United Kingdom (GB) Emory University United States (USA) (US)

How to cite

APA:

Awadalla, M., Mahmood, S.S., Groarke, J.D., Hassan, M.Z., Nohria, A., Rokicki, A.,... Neilan, T.G. (2020). Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis. Journal of the American College of Cardiology, 75(5), 467-478. https://doi.org/10.1016/j.jacc.2019.11.049

MLA:

Awadalla, Magid, et al. "Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis." Journal of the American College of Cardiology 75.5 (2020): 467-478.

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