Point-of-care cardiac elastography with external vibration for quantification of diastolic myocardial stiffness

Background Heart failure is an increasing health problem in Western societies. Approximately 50% of patients with heart failure have preserved ejection fraction (HFpEF) and concomitant diastolic dysfunction (DD), in part caused by increased myocardial stiffness not detectable by standard echocardiography. While elastography can map tissue stiffness, cardiac applications are currently limited, especially in patients with a higher body mass index (BMI). Therefore, we developed point-of-care cardiac elastography to detect abnormal diastolic myocardial stiffness associated with DD. Methods Cardiac time-harmonic elastography (THE) using standard medical ultrasound and continuous external vibration was developed and applied to healthy controls and participants with DD due to wild-type transthyretin amyloidosis (ATTR) in this prospective single-center study between June 2020 and December 2022. A subgroup of participants with ATTR was on tafamidis treatment. Diastolic shear wave speed (SWS) was determined as surrogate marker of myocardial stiffness in different cardiac regions including the septum, posterior wall and automatically detected global left ventricular wall. Results A total of 130 participants were screened and 44 participants with ATTR (4 women, mean age: 80±7 years, BMI range: 20-37) and 54 healthy controls (26 women, mean age: 47±16 years, BMI range: 15-32) were included. In all analyzed regions, SWS was higher in patients than in controls providing area-under-the-curve (AUC) values (septum: 1.8±0.3m/s versus 2.9±0.6m/s, AUC=0.996; posterior wall: 1.9±0.3m/s versus 2.7±0.5m/s, AUC=0.938; global left ventricular wall: 2.0±0.3m/s versus 2.6±0.4m/s, AUC=0.912). Furthermore, SWS was reduced in participants treated with tafamidis (septum: 2.6±0.4 m/s; posterior wall: 2.4±0.3m/s; global left ventricular wall: 2.3±0.3m/s, all p<.005) suggesting the use of THE for therapy monitoring and patient management. Conclusions Cardiac THE detects abnormal myocardial stiffness in patients with DD, independent of BMI and ROI selection. Because it uses standard ultrasound components, THE can be cost-effectively implemented as a point-of-care device for widespread clinical use. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement German Research Foundation (DFG, SFB1340 Matrix in Vision, GRK2260 BIOQIC) and Pfizer (WP2487656) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB or Charité - University Medicine Berlin approved this study I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes SWS data generated or analyzed during the study are available from the corresponding author upon reasonable request