Echocardiographic myocardial stiffness for the diagnosis and tissue characterization of cardiac amyloidosis

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation Philips Healthcare. Introduction Intrinsic cardiac elastography in echocardiography estimates myocardial stiffness by measuring the propagation of the myocardial stretch generated by atrial contraction. The aims of the present study were (A) to assess its value in differentiating cardiac amyloidosis (CA) from hypertrophic cardiomyopathy (HCM) and healthy volunteers (controls), and B) to correlate it with an established marker of cardiac amyloid burden and fibrosis. Methods This prospective study evaluated myocardial stiffness in 52 participants with CA (n=27), HCM (n=9) and controls (n=16) by ultra-high-frame rate (above 250 frames/sec) ultrasound imaging using diverging beam mode. The slope of the isovelocity wave front was measured as the intrinsic velocity propagation of myocardial stretch (iVP, in m/s). Additionally, participants with CA and HCM underwent comprehensive transthoracic echocardiography including quantification of global longitudinal strain (GLS) by speckle-tracking imaging. The relative apical sparing (RELAPS) ratio was calculated as the average GLS of apical segments / average GLS of midventricular and basal segments. Extracellular volume (ECV) by native and post-contrast T1 mapping from cardiac magnetic resonance (CMR) was quantified in 12 participants with CA and 4 with HCM. Results iVP was significantly higher in CA (i.e., 2.6 m/s [1.7–3.8]) than in HCM (1.2 m/s [1.0–1.8], p = 0.001) and controls (1.4 m/s [1.3–1.5], p = 0.004) but did not differ between HCM and controls (p = 0.928; Panel A). The diagnostic accuracy of iVP to identify CA was 82% and similar to the RELAPS ratio (i.e., 84%). iVP > 2.0 m/s has a sensitivity, specificity, positive predictive value and negative predictive value of 59%, 100%, 100%, and 69% to diagnose CA among the 52 participants. There was a strong correlation of iVP with ECV (rho=0.747, p = 0.001; Panel B). In contrast, iVP correlated weakly to moderately with GLS (rho=0.514, p = 0.001), RELAPS ratio (rho=0.433, p = 0.008), E/e’ (rho=0.413, p = 0.014) and NT-proBNP (rho=0.476, p = 0.006). Conclusions Echocardiographic myocardial stiffness is highly specific to diagnose cardiac amyloidosis and provides unique insights into myocardial tissue composition.