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Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Research Foundation Flanders (FWO grant number 1211620N) &amp; TTW-Dutch Heart Foundation partnership program "Early recognition of cardiovascular diseases" (project number 14740) Background Acoustic radiation force-based shear wave elastography (SWE) is a promising technique to non-invasively assess mechanical properties of the heart based on the propagation speed of acoustically induced shear waves. However, the interpretation of cardiac SWE measurements remains complex, and it is unclear how other factors such as loading affect shear wave propagation speed (SWS) measurements in diastole and systole. Purpose We applied transthoracic SWE in a pig model to investigate the dependencies of diastolic and systolic SWS on pressure-volume (PV) loop derived indices of loading, myocardial stiffness and contractility. Methods In 7 pigs, loading conditions were altered (increasing or decreasing preload; increasing afterload) and myocardial stiffness was changed (LAD occlusion for 60-100 minutes followed by 40 minutes of reperfusion). For each intervention, transthoracic SWE measurements were performed in a parasternal long-axis view with a high frame rate ultrasound system (&amp;gt; 6.2 kHz). Recordings of 28 ms were repeated at 34 Hz during 1.5 s to track shear waves throughout the cardiac cycle. To determine systolic and diastolic SWS in a robust manner, a piecewise linear model was fitted to the SWS data of each intervention representing multiple acquisitions, heartbeats and M-lines (fig. 1a). PV loops were recorded simultaneously with SWE measurements to estimate end-diastolic pressure (EDP), end-systolic pressure (ESP), end-diastolic pressure volume relation (EDPVR with exponential coefficient β in fig. 1b) and preload-recruitable stroke work (PRSW). Passive chamber stiffness was evaluated as the local slope of the EDPVR, i.e. β·EDP. Linear regressions and Pearson’s correlation coefficients were calculated. Results   Diastolic SWS was significantly correlated to EDP when altering loading (blue in fig. 2a: R = 0.55; p &amp;lt; 0.01) and stiffness (orange in fig. 2a: R = 0.66; p &amp;lt; 0.01). A similar correlation is found between SWS and passive chamber stiffness β·EDP (fig. 2b). Diastolic SWS is more sensitive to changes in stiffness than in loading, as reflected by the larger slope of the regression line (0.79 vs. 0.28 in fig. 2b). Furthermore, systolic SWS significantly correlated with measures of contractility during loading alterations: ESP in fig. 2c (R = 0.69; p &amp;lt; 0.001) and PRSW in fig. 2d (R = 0.63; p = 0.02). However, no significant correlation was found between systolic SWS and contractility during infarct/reperfusion. Conclusion This study shows that diastolic SWS reflects the instantaneous stiffness of the myocardium, but is not a load-independent measure of the intrinsic passive mechanical properties of the heart. Instantaneous stiffness, and thus diastolic SWS, might be altered by loading (due to material non-linearity) or intrinsic mechanical changes. Furthermore, loading experiments suggest that systolic SWS is related to contractility. The relation between SWS and contractility in the presence of myocardial infarct deserves further study. Abstract Figure. Fig. 1: SWS and PV analysis.  Abstract Figure. Fig. 2: SWS vs. PV-derived indices.

On the interplay of loading, myocardial stiffness and contractility in transthoracic acoustic radiation force-induced shear wave measurements in pigs