Early detection of immune checkpoint inhibitor-related subclinical cardiotoxicity: A pilot study by using speckle tracking imaging and three-dimensional echocardiography

Abstract

Background: Early detection of subclinical cardiotoxicity of immune checkpoint inhibitor (ICI) therapy can be challenging.

Objective: To evaluate subclinical cardiac dysfunction using two-dimensional speckle tracking imaging (2D-STI) and three-dimensional echocardiography in Chinese patients.

Methods: Fifty-five consecutive patients with malignant tumors treated by immunotherapy were included. They were examined by echocardiography before immunotherapy and after immunotherapy. Left ventricular ejection fraction (LVEF) was calculated in three-dimensional imaging. Moreover, left ventricular global longitudinal peak systolic strain (LVGLS), left ventricular global circumferential peak systolic strain (LVGCS), right ventricular global longitudinal systolic strain (RVGLS), right ventricular free wall longitudinal peak systolic strain (RVFWLS), and tricuspid annular plane systolic excursion (TAPSE) were evaluated. Clinical and laboratory parameters were recorded. Cardiac toxicity events were defined as the presence of heart failure symptoms, LVEF reduction, and increase in troponin. Subclinical cardiac toxicity was defined as cardiac dysfunction associated with ICI treatment, with absent or delayed ICI-associated cardiotoxicity clinical symptoms.

Results: Compared with baseline, the LVGLS, TAPSE, and RVGLS significantly deteriorated after ICI treatment [(-18.63 ± 2.53)% vs. (-17.35 ± 2.58)%, P = 0.000; 18.29 ± 6.23 vs. 14.57 ± 3.81, P = 0.0001; and (-18.45 ± 4.65)% vs. (-14.98 ± 3.85)%, P = 0.0001, respectively]. LVGLS (-17.35 ± 2.58, P = 0.000), TAPSE (14.57 ± 3.81, P = 0.0001), and RVGLS [(-14.98 ± 3.85)%, P = 0.0001] were decreased after ICI immunotherapy. Kaplan-Meier curve analysis showed that LVGLS was more sensitive than the cardiac toxicity events to assess ICI-related subclinical cardiac dysfunction (log-rank P = 0.205). The ROC curve showed that the cutoff value of ΔLVGLS was -13%.

Conclusion: Subclinical cardiac dysfunction can be detected using two-dimensional speckle-tracking imaging. LVGLS, RVGLS, and TAPSE are more sensitive indices for detection.

Clinical trial registration: [https://www.chictr.org.cn/showprojen.aspx?proj=27498], identifier [ChiCTR1800016216].

Keywords: ICIs; TAPSE; echocardiography; strain; subclinical cardiotoxicity.

FIGURE 1

Changes in left ventricular ejection fraction (LVEF), left ventricular global longitudinal peak systolic strain (LVGLS), left ventricular global circumferential peak systolic strain (LVGCS), tricuspid annular plane systolic excursion (TAPSE), right ventricular global longitudinal systolic strain (RVGLS), and right ventricular free-wall longitudinal peak systolic strain (RVFWLS) before and after immune checkpoint inhibitors (ICIs) treatment; (A): LVEF; (B): LVGLS; (C): LVGCS; (D): TAPSE; (E): RVGLS; (F): RVFWLS; *P < 0.05.

FIGURE 2

Kaplan–Meier curve showing the cumulative survival rate according to decreased or preserved left ventricular global longitudinal peak systolic strain (LVGLS), left ventricular ejection fraction (LVEF), right ventricular global longitudinal systolic strain (RVGLS), and tricuspid annular plane systolic excursion (TAPSE); (A): LVGLS; (B): LVEF; (C): RVGLS; (D): TAPSE. (E): Kaplan–Meier curve showing the immune checkpoint inhibitor (ICI)-related cardiotoxicity survival time through LVGLS reduced by more than 15% (blue curve), and events (red curve) including heart failure symptoms, troponin increased exceeding the normal range, and LVEF reduced by more than 10% and less than 53%.

FIGURE 3

Receiver operator characteristic curve for analyzing left ventricular global longitudinal peak systolic strain (LVGLS). The area under the receiver operator characteristic (ROC) curve was 0.693. The cutoff value of ΔLVGLS was –13%.