Natural shear wave measurements detect changes in operational stiffness induced by mechanical ventilation in sheep

Abstract Shear wave elastography (SWE) has the potential to non-invasively measure myocardial stiffness, based on the propagation speed of shear waves traveling through the myocardium after valve closure. However, shear wave propagation speed (SWS) is related to the operational stiffness of the heart, which is defined by the slope of the end-diastolic stress-strain relationship at the operating volume/pressure. Therefore, operational stiffness can be altered by both changes in intrinsic myocardial stiffness and myocardial loading conditions. We aimed to investigate whether SWE can detect differences in operational stiffness induced by loading changes during mechanical ventilation, and whether SWE combined with respiratory hold manoeuvres could detect an evolution in stiffness during the course of ischemic cardiomyopathy (ICM). We assessed SWS in 8 sedated and mechanically ventilated sheep: 1 healthy control, 3 within 8 weeks, and 4 after at least 16 weeks following left coronary artery ligation (early vs. late ICM). Left ventricular parasternal long-axis views were acquired with a state-of-the-art ultrasound scanner with high frame rate technology (> 1100 Hz). Shear waves after mitral valve closure were considered during an inspiratory hold at 30 cmH2O and 15 cmH2O and expiratory hold at 0 cmH2O (atmospheric pressure). We used linear regression to assess the trend of the SWS during ventilation manoeuvres per animal and a two-tailed Student’s T-test to assess changes between ICM stages and their respective response to ventilation manoeuvres. In all but one sheep, SWS declined with higher inspiratory pressures (see fig. 1), possibly due to a reduction in preload at higher inspiratory pressures resulting in a shift towards a reduced slope on the myocardial stress-strain relation. The sheep with a positive slope was excluded from further analyses. SWS during expiratory hold at atmospheric pressure was 3.4 m/s in the healthy control and was significantly lower in early vs. late ICM (mean±SD 4.0±0.6 vs. 9.0±1.7 m/s; p=0.007). Furthermore, the change in SWS was larger in late vs. early ICM (slope of regression line -0.16 vs. -0.05 m/s/cmH2O; p=0.03). These observations suggest loading on a steeper part of the end-diastolic stress strain relationship in late ICM. In conclusion, our results suggest that SWE is able to detect differences in operational stiffness induced by mechanical ventilation. Secondly, SWE appears to distinguish between different time points in the course of ICM based on the magnitude of the SWS during expiratory hold at atmospheric pressure, but also on the magnitude of the SWS change during loading alterations induced by mechanical ventilation. Further work should assess whether SWE combined with respiratory hold manoeuvres could contribute to differentiate intrinsic from hemodynamic stiffening, and to exploit its full potential as a non-invasive bedside method for the assessment of operational stiffness.