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

Magid Awadalla, Syed S. Mahmood, John D. Groarke, Malek Z.O. Hassan, Anju Nohria, Adam Rokicki, Sean P. Murphy, Nathaniel D. Mercaldo, Lili Zhang, Daniel A. Zlotoff, Kerry L. Reynolds, Raza M. Alvi, Dahlia Banerji, Shiying Liu, Lucie M. Heinzerling, Maeve Jones-O'Connor, Rula B. Bakar, Justine V. Cohen, Michael C. Kirchberger, Ryan J. SullivanDipti Gupta, Connor P. Mulligan, Sachin P. Shah, Sarju Ganatra, Muhammad A. Rizvi, Gagan Sahni, Carlo G. Tocchetti, Donald P. Lawrence, Michael Mahmoudi, Richard B. Devereux, Brian J. Forrestal, Anant Mandawat, Alexander R. Lyon, Carol L. Chen, Ana Barac, Judy Hung, Paaladinesh Thavendiranathan, Michael H. Picard, Franck Thuny, Stephane Ederhy, Michael G. Fradley, Tomas G. Neilan

Research output: Contribution to journalArticlepeer-review

176 Scopus citations


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.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalJournal of the American College of Cardiology
Issue number5
StatePublished - 11 Feb 2020


  • global longitudinal strain
  • immune checkpoint inhibitors
  • major adverse cardiac events
  • myocarditis


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