Elevated myocardial stiffness in asymptomatic ATTRv carriers as possible early sign of cardiac affection

Abstract Background/Introduction In amyloidosis, a misfolding of proteins is followed by extracellular deposition of fibrils, with the consequence of organ dysfunction. Cardiac deposition results in a restrictive cardiomyopathy with increased myocardial stiffness. Transthyretin amyloidosis (ATTR) can either be age-related (ATTR wild-type; ATTRwt), or genetically determined (ATTR variant; ATTRv) (Merlini and Westermark 2004), which is inherited in an autosomal dominant manner. Detecting symptom onset in ATTRv carriers is crucial to initiate appropriate treatment. Novel ultrasound-based cardiac elastography allows for non-invasive quantification of myocardial stiffness. Time Harmonic Ultrasound elastography (THE) based on portable vibration pillows and conventional ultrasound, recently showed the capacity to detect increased myocardial stiffness in cardiac ATTRwt Amyloidosis (Meyer, Wellge et altera 2025). Purpose We examined asymptomatic ATTRv carriers using THE to investigate the potential of early, stiffness-based detection of cardiac dysfunction. Methods 19 healthy volunteers (10 women, age range 19-88 years) and 14 ATTRv carriers (8 woman, age range 33-79years) were examined with standard echocardiography and measured with THE. In the ATTRv group a bone scintigraphy and biomarker testing was added according to ESC recommendations (Garcia-Pavia, Rapezzi et altera 2021). For THE, harmonic multifrequency vibrations (60,70, 80 Hz) were induced by a custom-built vibration pillow (Elastance Imaging, Columbus, Ohio, US) placed underneath the thorax (see Figure 1). Data were acquired in parasternal long axis view in breath hold (15 cm penetration depth, 4s acquisition time) with a THE device (GAMPT Merseburg, Germany). Diastolic shear wave speed maps (SWS) were generated using k-MDEV gradient inversion. Manually drawn regions of interest were placed in the septum and the posterior wall. Results All ATTRv carriers showed normal echocardiography data and negative bone scintigraphy (Perugini Grade 0). NTproBNP and Troponin T were in a normal range( NTproBNP mean 57.9ng/l; Troponin T mean 5.8ng/l). SWS was increased in ATTRv patients (septum: 2.0 1.7-2.5 m/s; posterior wall: 2.2 1.7-2.5 m/s) compared to healthy controls (septum: 1.6 1.3-2.5 m/s; posterior wall: 1.9 1.6-2.3; both p0.05) with an area under the curve of 0.9 and 0.75 for the separation of the groups based on septal and posterior wall stiffness respectively. Conclusion We found elevated myocardial stiffness in asymptomatic ATTRv carriers suggesting ATTR Amyloidosis related organ dysfunction prior to subjective symptoms or objective signs measured with standard tools. These results highlight the potential of early stiffness-based detection of myocardial dysfunction and may initiate a re-evaluation of the current amyloidosis work-up and the time to start a specific therapy.THE Setup Comparison ATTRv versus healthy controls