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Global Longitudinal Strain and Cardiac Events in ICI Myocarditis
Study Questions:
Is echocardiographic global longitudinal strain (GLS) associated with worse outcomes in patients with immune-checkpoint inhibitor (ICI) myocarditis?
Methods:
The authors retrospectively analyzed echocardiography-derived GLS data from 101 cases of ICI-related myocarditis (27% on combination ICI) and 92 randomly selected controls who received ICI (6% on combination ICI) but were not diagnosed with ICI-related myocarditis. The GLS data were obtained from echocardiograms performed at the time of diagnosis of myocarditis in cases. The timing of echocardiograms for controls varied (42 pre-ICI, 50 on-ICI). A subset of patients (30 in cases and 14 in controls) had a paired pre-ICI echocardiogram. The primary outcome was a composite of cardiovascular death, cardiac arrest, cardiogenic shock, and hemodynamically significant complete heart block (major adverse cardiac events [MACE]).
Results:
The mean age of cases was 66, with 73% men and the median time to onset of myocarditis from starting ICI was 57 days. The predominant underlying malignancies being treated with ICI were melanoma and lung cancer in both groups. Overall, GLS at the time of myocarditis was significantly lower in cases compared to controls (14.1% vs. 20.5%, p < 0.0), regardless as to whether they presented with preserved (n = 61) or reduced ejection fraction (EF) (n = 40). Amongst the 30 cases with pre-ICI GLS, there was a significant decrease in GLS with the development of myocarditis (20.3% vs. 14.1%), while no change in GLS was noted in the 14 controls (20.6% vs. 20.5%). Across groups, 51 (51%) had a MACE (n = 19 for heart block, n = 14 for cardiogenic shock, n = 12 for cardiac arrest, and n = 6 for cardiac deaths). GLS was associated with MACE in both cases and controls, independently of EF.
Conclusions:
GLS is reduced in patients with ICI myocarditis and associated with outcomes independently of EF.
Perspective:
This study represents the largest case-control study reporting on GLS in ICI-related myocarditis. The findings are unsurprising, and consistent with GLS as a prognostic marker, arguably more sensitive than EF. Whether GLS is associated with in-hospital outcomes is not reported and could have been informative with regards to guiding ICI-related myocarditis therapy. Interestingly, GLS was unchanged post-ICI in the 14 patients with pre- and post-ICI echocardiography, suggesting exposure to ICI is not in itself associated with subclinical injury, and likely requires additional factors. There are major limitations to this study to keep in mind, as echocardiograms were not performed systematically, subgroups were inconsistent between cases and controls, and the lack of adjustment for multiple comparisons. The study also does not examine GLS in the risk-stratification of candidates for ICI. A role for GLS in the management of ICI-related cardiotoxicity remains to be defined.
Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound
Keywords: Carcinoma, Bronchogenic, Cardiotoxicity, Death, Sudden, Cardiac, Diagnostic Imaging, Echocardiography, Heart Arrest, Heart Block, Heart Failure, Lung Neoplasms, Melanoma, Myocarditis, Risk Assessment, Shock, Cardiogenic, Stroke Volume, Ventricular Dysfunction, Left
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