Natural shear waves after mitral valve closure and how their timing influences their relationship with left ventricular hemodynamics

Background: Shear wave (SW) elastography based on natural SWs after mitral valve closure (MVC) has been used to assess left ventricular (LV) diastolic function properties, i.e. intrinsic myocardial stiffness and LV filling pressures. However, these SWs occur by definition after end-diastole (ED), i.e. in the isovolumic contraction period when the myocardium starts to stiffen. Therefore, this study aimed to investigate how the timing of SWs affects measures derived from pressure-volume (PV) loop analysis in a pig model.

Methods: 6 pigs underwent sequential interventions to alter their loading  and intrinsic myocardial properties (Figure 1, upper panel): (1) baseline, (2) preload decrease, (3) afterload increase, (4) preload increase, (5) coronary artery occlusion, (6) ischemia/reperfusion (I/R) injury and (7) preload decrease after I/R. PV loops were recorded at all conditions (Figure 1A). In parallel, high frame rate (HFR) imaging was performed in a parasternal long axis view with a research ultrasound scanner (~1304 Hz). An M-mode line was drawn in the mid-wall of the LV septum and tissue acceleration (TA) maps were created, so as to visualize SWs after MVC. Their speed was then semi-automatically calculated by measuring the spatiotemporal slope of the peak TA using a cross-correlation algorithm. (Figure 1B and 1C-upper panel). The PV and HFR data were temporally aligned by cross-correlating their respective ECGs. (Figure 1C). The same M-mode was used to manually indicate the start and end time of the SW, giving access to the time delay with respect to ED and the instantaneous pressures (P₁, P₂). The average of P₁ and P₂ represented the mean pressure (P_m) during SW propagation (Figure 1A). Pearson’s correlation and regression analysis was performed.

Results: The SW after MVC occurred on average 40±6 ms after ED; P_m was 34.2±11 mmHg. There was no difference in timing among the conditions, except baseline and preload decrease after I/R. The SW speed correlated with end-diastolic pressure EDP for the different loading conditions (1 to 4; r = 0.42, p = 0.026) and after ischemia induction (1, 5 to 7; r = 0.55, p = 0.028) (Figure D). It also correlated with the Pm, but only for the different ischemia conditions (1, 5 to 7; r = 0.53, p = 0.035) (Figure E), whereas there was no correlation with the systolic indices dP/dt or end-systolic pressure (ESP). In a multilinear regression model that included EDP, β stiffness constant, ESP, Pm and dP/dt, only EDP (β coefficient= 0.56, p <0.001), followed by β (β coefficient=0.32, p=0.01) independently predicted SW speed.

Conclusion: Our results show that the timing of SW after MVC depends neither on loading conditions nor tissue properties, except in the extreme case where both have been altered. SW speed after MVC is influenced by myocardial stiffness as well as LV filling pressures, and even though the SW after MVC occurs at early contraction and its speed correlates with P_m, it even more strongly correlates with EDP, the gold standard for LV filling pressure.