Myocardial stiffness - not just a matter of wall thickness

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Abstract Background/Introduction Heart failure, including HFpEF, is a growing global health problem. Diastolic dysfunction (DD) is a critical component of HFpEF and is mainly caused by increased myocardial stiffness(1). Current cardiac elastography methods allow the noninvasive quantification of myocardial stiffness(2, 3). Time harmonic elastography (THE) combines conventional ultrasound with continuous external vibrations(4) to generate full field-of-view stiffness maps. Novel, cost-effective cardiac THE (cTHE) with full coverage of the left ventricle (LV) in parasternal long axis view (PLAX) has recently been shown to be sensitive to increased myocardial stiffness in patients with wild-type amyloidosis (wtATTR)(5). Numerous heart diseases are linked to both myocardial stiffening and LV hypertrophy. However, they differ in the underlying pathophysiology such as reactive fibrosis due to pressure overload (hypertension (HT) or aortic stenosis (AS)) or storage disease (ATTR or Fabry disease (FD)). Purpose We aim to investigate the diagnostic value of myocardial stiffness as a quantitative parameter for the characterization of cardiac function independent of wall thickness. Methods 62 participants were enrolled in our study, including 11 healthy controls (age range 27-88 years), 19 patients with HT (age range 44-79 years), 13 patients with AS (age range 61-89 years), 11 patients with wtATTR (age range 64-86 years), 3 patients with HCM (age range 36-70 years) and 5 patients with FD (age range 50-60 years). All subjects underwent a standard echo examination before cTHE (figure 1). Multifrequency vibrations (60,70,80Hz) were induced using a custom portable vibration pillow (Elastance Imaging, Columbus, Ohio, US) underneath the subject’s thorax. A customized ultrasound scanner (GAMPT, Merseburg, Germany) was used for image acquisitions in PLAX with 15cm depth. Images were acquired in breath-hold over 4s with 100Hz frame rate. Measurements were repeated five times. Time-resolved shear wave speed maps (SWS) were generated using k-MDEV inversion(6). Diastolic frames were averaged to obtain a map of diastolic myocardial stiffness. Regions of interest for averaging were manually drawn for the septum and posterior wall. Results Using cTHE, we observed an increase in myocardial stiffness in all groups (Controls: 1.5±0.2ms/s, HT: 1.8±0.4ms/s, AS: 2.0±0.2ms/s, HCM: 2.0±x0.4ms/s, Fabry: 1.9±0.3ms/s, wtATTR: 2.1±0.3ms/s, all p<0.05). SWS correlated with wall thickness only in a pooled analysis (R=0.47, p<0.01), but not within individual groups (figure 2). Conclusions cTHE detects increased myocardial stiffness in a variety of cardiac diseases. Myocardial stiffness is known to be associated with increased wall thickness(7), however our analysis within individual groups showed independence of both parameters. Quantitative assessment of myocardial stiffness could add important diagnostic information to the detection and treatment monitoring of myocardial disease. Figure 1: Setup of cTHE Figure 2: Stiffness Maps/Correlations