Echocardiographic and Cardiac MRI Comparison of Longitudinal Strain and Strain Rate in Cancer Patients Treated with Immune Checkpoint Inhibitors

Abstract

Background: Immune checkpoint inhibitor (ICI)-induced cardiac side effects in cancer patients are increasingly being recognized and can be fatal. There is no standardized cardiac imaging test to examine the effects of ICIs in myocardial morphology and function. Objective: To study the utility of echocardiography and cardiac MRI in examining regional and global changes arising from ICI-induced myocarditis and cardiomyopathy in high-risk subjects suspected to have developed ICI cardiomyopathy. Methods: We studied eight consecutive patients referred for cardiac MRI (CMR) from a comprehensive cancer center for suspected ICI-induced myocarditis and compared the data with sixteen age-matched controls. Using newly developed strain analysis algorithms, we measured myocardial strain and strain rates using echocardiography and CMR. Then, we compared the mean longitudinal strain and strain rates derived from echocardiography and CMR in the same ICI-treated cohort of patients (n = 8). They underwent both of these imaging studies with images taken 24−48 h apart and followed up prospectively within the same hospital course. Results: All our cases had preserved ejection fraction (EF) > 50%. Echocardiogram showed reduced mean systolic longitudinal strain (LS, %) (ICI: −12.381 ± 4.161; control: −19.761 ± 1.925; p < 0.001), peak systolic strain rate (SRS, s−1) (ICI: −0.597 ± 0.218; control: −0.947 ± 0.135; p = 0.002) and early diastolic strain rate (SRE, s−1) (ICI: 0.562 ± 0.295; control: 1.073 ± 0.228; p = 0.002) in ICI-treated cases. Direct comparison between the echocardiogram vs. CMR obtained within the same hospital course demonstrated strong a correlation of LS scores (r = 0.83, p = 0.012) and SRS scores (r = 0.71, p = 0.048). The Bland−Altman plots showed that 95% of the data points fitted within the ±1.96 SD of the mean difference, suggesting an agreement among these two imaging modalities. Conclusion: In this feasibility cohort study, both echocardiography- and CMR-based strain indices illustrate changes in myocardial contractility and relaxation suggestive of ICI-induced cardiomyopathy. Our data, after validation in a larger cohort, can form the basis of myocardial imaging in cancer patients treated with ICIs.

Keywords: cardiac MRI; cardiotoxicity; checkpoint inhibitors; echocardiography; immunotherapy; strain imaging.

Figure 1

Left ventricular (LV) longitudinal strain imaging of immune checkpoint inhibitor (ICI)-induced cardiomyopathy using speckle tracking echocardiography. The midventricular and apical segments are relatively hypokinetic.

Figure 2

Strain curves illustrating changes in left ventricular (LV) longitudinal strain and strain rate over the course of one cardiac cycle. Strain curves were generated by averaging individual strain curves calculated at each time point. n = 8 normal and immune checkpoint inhibitor (ICI)-treated patients. A. LV, longitudinal strain curves; B. LV, longitudinal strain rate curves. SR_S = peak systolic strain rate; SR_E = early diastolic strain rate.

Figure 3

Left ventricular (LV) longitudinal strain imaging of immune checkpoint inhibitor (ICI)-induced cardiomyopathy using cardiac MRI (CMR) under 4 chamber view (4CH). (A) Representative 4CH-CMR image of a control; (B) Representative 4CH-CMR image of an ICI-treated patient. (C) Scatter plots showing the correlation between the mean longitudinal strain and strain rates derived from echocardiography versus CMR. (D) Bland–Altman agreement plots for ICI-induced cardiomyopathy detected on echocardiography compared with CMR for mean longitudinal strain and strain rates. Bland–Altman plots display the difference between values measured by echocardiography and CMR against the mean of these 2 values. The upper and lower dashed lines represent the 95% confidence intervals.

Figure 3

Left ventricular (LV) longitudinal strain imaging of immune checkpoint inhibitor (ICI)-induced cardiomyopathy using cardiac MRI (CMR) under 4 chamber view (4CH). (A) Representative 4CH-CMR image of a control; (B) Representative 4CH-CMR image of an ICI-treated patient. (C) Scatter plots showing the correlation between the mean longitudinal strain and strain rates derived from echocardiography versus CMR. (D) Bland–Altman agreement plots for ICI-induced cardiomyopathy detected on echocardiography compared with CMR for mean longitudinal strain and strain rates. Bland–Altman plots display the difference between values measured by echocardiography and CMR against the mean of these 2 values. The upper and lower dashed lines represent the 95% confidence intervals.