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.