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. Sullivan; Dipti 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

doi:10.1016/j.jacc.2019.11.049

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 journal › Article › peer-review

171 Scopus citations

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.

Original language	English (US)
Pages (from-to)	467-478
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	75
Issue number	5
DOIs	https://doi.org/10.1016/j.jacc.2019.11.049
State	Published - Feb 11 2020
Externally published	Yes

Keywords

global longitudinal strain
immune checkpoint inhibitors
major adverse cardiac events
myocarditis

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jacc.2019.11.049

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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., ... 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

Awadalla, M, Mahmood, SS, Groarke, JD, Hassan, MZO, Nohria, A, Rokicki, A, Murphy, SP, Mercaldo, ND, Zhang, L, Zlotoff, DA, Reynolds, KL, Alvi, RM, Banerji, D, Liu, S, Heinzerling, LM, Jones-O'Connor, M, Bakar, RB, Cohen, JV, Kirchberger, MC, 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, 'Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis', Journal of the American College of Cardiology, vol. 75, no. 5, pp. 467-478. https://doi.org/10.1016/j.jacc.2019.11.049

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title = "Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis",

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.",

keywords = "global longitudinal strain, immune checkpoint inhibitors, major adverse cardiac events, myocarditis",

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

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = feb,

day = "11",

doi = "10.1016/j.jacc.2019.11.049",

language = "English (US)",

volume = "75",

pages = "467--478",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

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TY - JOUR

T1 - Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis

AU - Awadalla, Magid

AU - Mahmood, Syed S.

AU - Groarke, John D.

AU - Hassan, Malek Z.O.

AU - Nohria, Anju

AU - Rokicki, Adam

AU - Murphy, Sean P.

AU - Mercaldo, Nathaniel D.

AU - Zhang, Lili

AU - Zlotoff, Daniel A.

AU - Reynolds, Kerry L.

AU - Alvi, Raza M.

AU - Banerji, Dahlia

AU - Liu, Shiying

AU - Heinzerling, Lucie M.

AU - Jones-O'Connor, Maeve

AU - Bakar, Rula B.

AU - Cohen, Justine V.

AU - Kirchberger, Michael C.

AU - Sullivan, Ryan J.

AU - Gupta, Dipti

AU - Mulligan, Connor P.

AU - Shah, Sachin P.

AU - Ganatra, Sarju

AU - Rizvi, Muhammad A.

AU - Sahni, Gagan

AU - Tocchetti, Carlo G.

AU - Lawrence, Donald P.

AU - Mahmoudi, Michael

AU - Devereux, Richard B.

AU - Forrestal, Brian J.

AU - Mandawat, Anant

AU - Lyon, Alexander R.

AU - Chen, Carol L.

AU - Barac, Ana

AU - Hung, Judy

AU - Thavendiranathan, Paaladinesh

AU - Picard, Michael H.

AU - Thuny, Franck

AU - Ederhy, Stephane

AU - Fradley, Michael G.

AU - Neilan, Tomas G.

PY - 2020/2/11

Y1 - 2020/2/11

N2 - 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.

AB - 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.

KW - global longitudinal strain

KW - immune checkpoint inhibitors

KW - major adverse cardiac events

KW - myocarditis

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JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

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ER -

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

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Keywords

ASJC Scopus subject areas

UN SDGs

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