Real-time 3D shear wave elastography discriminates ATTR cardiac amyloidosis in patients with left ventricular hypertrophy

Background ATTR Cardiac amyloidosis (ATTR-CA) results from myocardial amyloid fibril deposition, leading to increased myocardial stiffness (MS) and diastolic dysfunction. We developed a novel ultrasound based technique, transthoracic 3D shear wave elastography (SWE), to generate and track shear wave propagation with 3D ultrafast imaging using a custom matrix probe (Fig. A), enabling quantitative assessment of MS through shear wave velocity (SWV). This study aims to evaluate the value of cardiac 3D-SWE for ATTR-CA screening in patients with left ventricular hypertrophy (LVH) referred for suspected CA. Methods A total of 107 patients with Left ventricular Hypertrophy (>12mm) and referred for suspected CA underwent comprehensive clinical evaluation, including echocardiography, bone scintigraphy, tissue biopsy, blood testing, and 3D-SWE. For each target myocardial segment, ten 3D-SWE measurements were obtained: the right ventricular (RV) anterior free wall, the basal anteroseptal (AS) wall in the parasternal long-axis view, and the apex in the apical four-chamber view. SWV was assessed during diastasis using ECG synchronization within a myocardial volume of 10x16x16 mm³ in all segments. Results Based on gold-standard reference evaluation, the cohort of 107 patients was classified into: 49 with ATTR-CA (79±8 years); 53 non-ATTR patients, comprising 27 with AL-CA (64±9 years) and 26 non-amyloid patients (63±14 years); 4 with non-typable CA (87±8 years); and 1 with suspected CA (70 years). Standard echocardiographic parameters, including LV thickness, remodeling indices, and strain, failed to reliably discriminate ATTR-CA patients from the rest of the cohort. Conversely, SWV was significantly higher in ATTR-CA patients compared to non-ATTR patients in both the AS wall (p<0.001) and RV free wall (p<0.001), though not at the apex. A multiparametric diagnostic algorithm combining patient age, NT-proBNP levels, and median SWV in the AS and RV walls was able to classify ATTR-CA patients with a sensitivity of 98% and a specificity of 100% within this cohort. Conclusion Real-time 3D-SWE measurements identified ATTR-CA in patients with LVH referred for suspected CA with excellent accuracy. Standard echocardiography could not reliably descriminate ATTR-CA, highlighting 3D-SWE's potential as an advanced, non-invasive tool for targeted CA screening, diagnosis, and follow-up.