Global longitudinal strain predicts CV risk in immune checkpoint inhibitor-related myocarditis
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Patients with myocarditis related to immune checkpoint inhibitors and either a preserved or reduced ejection fraction had a reduced global longitudinal strain, according to a study published in the Journal of the American College of Cardiology.
The study also found that decreased global longitudinal strain (GLS) in patients with myocarditis related to immune checkpoint inhibitors was linked to major adverse cardiac events.
“We see the most utility whereby there’s a concern that this patient may have checkpoint inhibitor-associated myocarditis but the initial testing was indeterminate and the ejection fraction is preserved,” Tomas G. Neilan, MD, MPH, director of the cardio-oncology program and co-director of the cardiovascular imaging research center at Massachusetts General Hospital, told Healio. “That’s where its real usefulness is in clinical practice. The second area where the usefulness will be in clinical practice — although we have to prove this — is guiding us as to what to do with the patient once the diagnosis is made.”
Patients with myocarditis
Magid Awadalla, MD, research fellow in cardiology and radiology at Massachusetts General Hospital, and colleagues analyzed data from 101 patients (mean age, 66 years; 73% men; 60% preserved EF) who presented with immune checkpoint inhibitor-related myocarditis from November 2013 to January 2019. Controls (n = 92; mean age, 64 years; 64% men) who started immune checkpoint inhibitor therapy and did not develop myocarditis were also included. Several covariates were obtained from medical records including CV risk factors, demographics, cardiac biomarker levels, medications and cancer-specific factors.
The outcome of interest was major adverse cardiac events, which were defined as a composite of cardiac arrest, CV death, hemodynamically significant complete heart block and cardiogenic shock.
Global longitudinal strain before immune checkpoint inhibitor therapy was similar in the patients with myocarditis compared with the control group (20.3% vs. 20.6%, respectively; P = .6).
For control patients, global longitudinal strain did not change before and while on immune checkpoint inhibitor therapy (20.6% vs. 20.5%, respectively; P = .41). Patients who developed myocarditis had a decrease in global longitudinal strain to 14.1% (P < .001).
Once patients presented with myocarditis, global longitudinal strain was lower in those with preserved (15.3%) or reduced EF (12.3%; P < .001).
Major adverse cardiac events occurred in 51% of patients during a median follow-up of 162 days. The lowest incidence of major adverse cardiac events was observed in patients with a global longitudinal strain greater than 16%, and the highest was seen in those with levels less than 14%.
After adjusting for EF, each percent reduction in global longitudinal strain was linked to a 4.4-fold increase in major adverse cardiac events in patients with a preserved EF (HR = 4.4; 95% CI, 2.4-7.8) and a 1.5-fold increase in those with a reduced EF (HR = 1.5; 95% CI, 1.2-1.8).
Further research
“The next study is a prospective, observational study whereby all patients who are at high risk for immune checkpoint inhibitor myocarditis undergo an echocardiogram with measurement of global longitudinal strain,” Neilan said in an interview. “One of the major limitations in our study was that people did not have standardized measurements of global longitudinal strain.”
Neilan also spoke about the importance of increased awareness of immune checkpoint inhibitor-associated myocarditis among cardiologists. He said, “It's important to recognize that immunotherapy represents an option for patients with cancer who previously did not have options. Harnessing the power of the immune system is a major area of investigation. I anticipate that more and more patients will get immunotherapy for treatment of their cancer, so I anticipate that cardiologists will see more suspected cases of immune checkpoint inhibitor-associated myocarditis, that the number of cases is going to go up.” – by Darlene Dobkowski
For more information:
Tomas G. Neilan, MD, MPH, can be reached at tneilan@mgh.harvard.edu.
Disclosures: Neilan reports he received advisory fees from Aprea Therapeutics, Bristol-Myers Squibb, H3 Biomedicine, Intrinsic Imaging and Paraxel. Awadalla reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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