Key result
Each 1% reduction in GLS linked to ~93% higher MACE risk in ICI myocarditis.
Why the study?
Improved methods for detection and risk stratification of immune checkpoint inhibitor-associated myocarditis are needed, but data on the use of GLS in ICI-myocarditis were lacking.
Does lower global longitudinal strain predict major adverse cardiac events in patients with immune checkpoint inhibitor-related myocarditis?
Observational (n=193)
Single-blind
Yes
Does lower global longitudinal strain predict major adverse cardiac events in patients with immune checkpoint inhibitor-related myocarditis?
Hazard Ratio: 1.93 (95% CI 1.56–2.39)
p-value: p=<0.001
Global longitudinal strain is a sensitive marker that decreases during ICI-myocarditis and strongly predicts major adverse cardiac events, even in patients with preserved ejection fraction.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Additional work is needed to test if the GLS decrease occurs prior to the development of clinical myocarditis, can provide an early method of detection, and whether tailoring immunosuppressive therapy based on the measurement of GLS at presentation with myocarditis may be of value.”
“unclear if GLS assessment has incremental value to such readily available biomarkers”
GLS may refine MACE risk stratification in ICI-myocarditis with preserved EF; leaves open incremental value over biomarkers and need for prospective validation.
Background: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICI’s). 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. Methods: We retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI-myocarditis (cases, n=101) and patients receiving ICI without myocarditis (controls, n=92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) was defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. Results: Cases and controls were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal EF. Pre-ICI, GLS was similar between cases and controls (20.3±2.6 vs. 20.6±2.0 %, p=0.60). There was no change in GLS among controls 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 (HR 1.5, CI 1.2–1.8) and a 4.4-fold increase with a preserved EF (HR 4.4, CI 2.4–7.8). Conclusion: GLS decreases with ICI-myocarditis and, compared to controls, 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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Awadalla et al. (2020) conducted an observational in Immune checkpoint inhibitor-related myocarditis (n=193). Lower global longitudinal strain (GLS) vs. Higher global longitudinal strain (GLS) was evaluated on Major adverse cardiac events (composite of cardiogenic shock, arrest, complete heart block, and cardiac death) (HR 1.93, 95% CI 1.56-2.39, p=<0.001). Each 1% reduction in global longitudinal strain was associated with a 1.93-fold increased risk of major adverse cardiac events in patients with immune checkpoint inhibitor-related myocarditis.
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