Natural shear wave elastography reveals hidden cardiac dysfunction in adult survivors of childhood cancer during cardiopulmonary stress testing
Authors: Youssef A , Verschueren S , Vanrusselt D , Van Ermengem N , Uyttebroeck A , Wouters L , Hornikx M , Pleysier S , Cools B , Dhooge J , Voigt J U 
Published: January 2025

Abstract

Background
Hidden cardiotoxicity in adult survivors of childhood cancer may carry significant prognostic implications. Many of these survivors are asymptomatic at rest but show impaired cardiorespiratory fitness during exercise. Stress echocardiography combined with cardiopulmonary exercise testing (CPET) can reveal hidden diastolic dysfunction, although it presents major challenges. High frame rate (HFR) natural shear wave (SW) imaging is emerging as an innovative method for assessing myocardial stiffness, a key determinant of diastolic function.

Purpose
We investigated the relationship between natural SW measured at rest as a marker of myocardial stiffness and patient performance during CPET as markers of cardiorespiratory fitness.

Methods
A total of 115 subjects; 72 cancer survivors (mean age 20 ±4 years) and 43 matched healthy volunteers (HV) were recruited. We acquired both conventional as well as high frame rate echocardiographic images (ca. 1200 frames/second) at rest. During an incremental, symptom-limited cardiopulmonary exercise test on a treadmill, both peak and efficiency of oxygen consumption (VO2 peak and VO2/work slope) were recorded. All HFR data were analysed offline by drawing an anatomical M-mode along the ventricular septum in the parasternal long axis view, colour coded for tissue acceleration. SW after mitral valve closure (MVC) appeared as green bands and their velocities were measured by estimating the slope semi-automatically.

Results
In our survivors’ cohort, the prevalence of cardiac dysfunction based on reduced global longitudinal strain was 9.7%. In a univariate regression model, predictors of peak VO2 were age, body mass index (BMI), systolic blood pressure (SBP), left ventricular end-diastolic diameter (LVEDD), left atrial volume indexed (LAVi), mitral inflow to mitral relaxation velocity ratio (E/e’) and SW velocities after MVC. In the multivariate model, SW velocities remained as the strongest predictor for peak VO2, followed by LVEDD, BMI and SBP (Figure 1). Moreover, natural SWs correlate significantly with both peak VO2 and VO2/work slope (r= -0.65; p &lt;0.001, and r=-0.31; p =0.002 respectively) (Figure 2A&B). Interestingly, SW velocities were on average significantly higher in survivors with reduced peak VO2 (non-fit survivors) compared to both survivors with normal peak VO2 (fit survivors) and HV (4.2 ±0.6 m/s vs 3.5 ±0.5 m/s & 3.2 ±0.3 m/s respectively; p &lt;0.001) (Figure 2C).

Conclusions
Our preliminary data indicate that natural SW velocities measured at rest are related to cardiorespiratory fitness and can identify hidden cardiac dysfunction among childhood cancer survivors. Natural SW elastography appears as promising and innovative echocardiographic parameter for early detection of cardiac dysfunction in follow-up of adult survivors of childhood cancer.
Figure 1
Figure 2