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Global longitudinal strain and cardiac events in patients with immune checkpoint inhibitor-related myocarditis

Global longitudinal strain and cardiac events in patients with immune checkpoint inhibitor-related myocarditis
Global longitudinal strain and cardiac events in patients with immune checkpoint inhibitor-related myocarditis
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, immune checkpoint inhibitors, major adverse cardiac events, myocarditis
0735-1097
467-478
Awadalla, Magid
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Groarke, John
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Hassan, Malek
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Murphy, Sean
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Mercaldo, Nathaniel
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Zhang, Lili
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Zlotoff, Daniel
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Reynolds, Kerry
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Alvi, Raza
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Banerji, Dahlia
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liu, Shiying
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Neilan, Tomas
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Awadalla, Magid, Mahmood, Syed S., Groarke, John, Hassan, Malek, Nohria, Anju, Rokicki, Adam, Murphy, Sean, Mercaldo, Nathaniel, Zhang, Lili, Zlotoff, Daniel, Reynolds, Kerry, Alvi, Raza, Banerji, Dahlia, liu, Shiying, Heinzerling, Lucie, Jones-O'Connor, Maev, Bakar, Rula, Cohen, Justine, Kirchberger, Michael, Sullivan, Ryan, Gupta, Dipti, Mulligan, Connor, Shah, Sachin, Ganatra, Sarju, Rizvi, Muhammad, Sahni, Gagan, Tocchetti, Carlo, Lawrence, Donald, Mahmoudi, Michael, Devereux, Richard, Forrestal, Brian, Mandawat, Anant, Lyon, Alexander, Chen, Carol, Barac, Ana, Hung, Judy, Thavendiranathan, Paaladinesh, Picard, Michael, Thuny, Franck, Ederhy, Stephane, Fradley, Michael and Neilan, Tomas (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. (doi:10.1016/j.jacc.2019.11.049).

Record type: Article

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.

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Figure 1- Consort Flow Diagram - Accepted Manuscript
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Figure 2- GLS among Cases and Controls - Accepted Manuscript
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Figure 3- KM curve updated - Accepted Manuscript
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Figure 4- Central Illustration - Accepted Manuscript
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ICI GLS Supplementary Tables
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Accepted/In Press date: 22 November 2019
e-pub ahead of print date: February 2020
Published date: February 2020
Keywords: global longitudinal strain, immune checkpoint inhibitors, major adverse cardiac events, myocarditis

Identifiers

Local EPrints ID: 437373
URI: http://eprints.soton.ac.uk/id/eprint/437373
ISSN: 0735-1097
PURE UUID: 6608704d-d0e0-462a-8e19-70cc70879b96
ORCID for Michael Mahmoudi: ORCID iD orcid.org/0000-0003-1293-8461

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Date deposited: 29 Jan 2020 17:30
Last modified: 28 Apr 2022 06:30

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Contributors

Author: Magid Awadalla
Author: Syed S. Mahmood
Author: John Groarke
Author: Malek Hassan
Author: Anju Nohria
Author: Adam Rokicki
Author: Sean Murphy
Author: Nathaniel Mercaldo
Author: Lili Zhang
Author: Daniel Zlotoff
Author: Kerry Reynolds
Author: Raza Alvi
Author: Dahlia Banerji
Author: Shiying liu
Author: Lucie Heinzerling
Author: Maev Jones-O'Connor
Author: Rula Bakar
Author: Justine Cohen
Author: Michael Kirchberger
Author: Ryan Sullivan
Author: Dipti Gupta
Author: Connor Mulligan
Author: Sachin Shah
Author: Sarju Ganatra
Author: Muhammad Rizvi
Author: Gagan Sahni
Author: Carlo Tocchetti
Author: Donald Lawrence
Author: Richard Devereux
Author: Brian Forrestal
Author: Anant Mandawat
Author: Alexander Lyon
Author: Carol Chen
Author: Ana Barac
Author: Judy Hung
Author: Paaladinesh Thavendiranathan
Author: Michael Picard
Author: Franck Thuny
Author: Stephane Ederhy
Author: Michael Fradley
Author: Tomas Neilan

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