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

Awadalla, M.; Mahmood, S. S.; Groarke, J. D.; Hassan, M. Z. O.; Nohria, A.; Rokicki, A.; Murphy, S. P.; Mercaldo, N. D.; Zhang, L.; Zlotoff, D. A.; Reynolds, K. L.; Alvi, R. M.; Banerji, D.; Liu, S.; Heinzerling, L. M.; Jones-O'Connor, M.; Bakar, R. B.; Cohen, J. V.; Kirchberger, M. C.; Sullivan, R. J.; Gupta, D.; Mulligan, C. P.; Shah, S. P.; Ganatra, S.; Rizvi, M. A.; Sahni, G.; Tocchetti, C; Lawrence, D. P.; Mahmoudi, M.; Devereux, R. B.; Forrestal, B. J.; Mandawat, A.; Lyon, A. R.; Chen, C. L.; Barac, A.; Hung, J.; Thavendiranathan, P.; Picard, M. H.; Thuny, F.; Ederhy, S.; Fradley, M. G.; Neilan, T. G.

doi:10.1016/j.jacc.2019.11.049

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.

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis / Awadalla, M.; Mahmood, S. S.; Groarke, J. D.; Hassan, M. Z. O.; Nohria, A.; Rokicki, A.; Murphy, S. P.; Mercaldo, N. D.; Zhang, L.; Zlotoff, D. A.; Reynolds, K. L.; Alvi, R. M.; Banerji, D.; Liu, S.; Heinzerling, L. M.; Jones-O'Connor, M.; Bakar, R. B.; Cohen, J. V.; Kirchberger, M. C.; Sullivan, R. J.; Gupta, D.; Mulligan, C. P.; Shah, S. P.; Ganatra, S.; Rizvi, M. A.; Sahni, G.; Tocchetti, C; Lawrence, D. P.; Mahmoudi, M.; Devereux, R. B.; Forrestal, B. J.; Mandawat, A.; Lyon, A. R.; Chen, C. L.; Barac, A.; Hung, J.; Thavendiranathan, P.; Picard, M. H.; Thuny, F.; Ederhy, S.; Fradley, M. G.; Neilan, T. G.. - In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - ISSN 0735-1097. - 75:5(2020), pp. 467-478. [10.1016/j.jacc.2019.11.049]