Background: Left ventricular (LV) wall thickness is a common finding in echocardiographic examinations and present in several cardiomyopathies, including cardiac amyloidosis (CA) and Fabry disease (FD). Various echocardiographic characteristics have been described to differentiate these cardiomyopathies, such as a sparkling myocardium in CA and hypertrophic papillary muscles (PM) in FD. Nevertheless, diagnosis and subsequent specific treatment are still often delayed. Therefore, we evaluate new diagnostic indices, including the mitral valve thickness and the ratio of PM to LV area (PM/LV-ratio), to distinguish CA and FD. 

Methods: The present retrospective study was a single-center trial enrolling patients with CA and FD from 2013 to 2021. Echocardiographic analysis was performed offline with EchoPAC PC (GE Vingmed, Horton, Norway). Measurements comprised the mitral valve leaflet thickness in mid-diastole in the parasternal long axis view and PM/LV-ratio at end-diastole in the parasternal short axis view according to Nieman et al. (Ultrasound Med Biol., 2011) in transthoracic echocardiography (Vivid E9 or E95, GE Vingmed, Horton, Norway, M5S[c] 1.5–4.5MHz transducer). Receiver operating characteristic (ROC) curve analysis were calculated to determine the diagnostic accuracy of measurements.

Results: Of the 129 patients examined, 49 patients had genetically confirmed FD and 80 patients diagnosed CA. Assessment of the mitral valve demonstrated significantly thicker leaflets in CA compared to FD patients (4±1 mm in CA vs. 3±1 mm in FD, p<0.001). Moreover, a larger area of PM and LV was observed in CA patients in comparison to FD, resulting in a comparable PM/LV-ratio between the two groups (0.23 [0.20-0.26] in CA vs. 0.21 [0.14 0.28] in FD, p=0.223). In detail, the posteromedial PM and the LV area were significantly larger in CA patients, while the increase in anterolateral PM area did not reach significance. The best diagnostic accuracy of the analysed parameters was achieved by the mitral valve thickness corresponding to an area under the curve (AUC) of 0.75 (95% confidence interval [CI] 0.65-0.85) to discriminate CA from FD. Reproducibility of leaflet measurement showed a good to excellent agreement and was calculated by intra-class correlation coefficient for intra-observer (0.92 [95% CI 0.79-0.97]) and inter-observer agreement (0.85 [95% CI 0.64-0.94]).

Conclusion: In contrast to previous studies, papillary muscle hypertrophy and PM/LV-ratio did not indicate FD in our cohort. However, as mitral valve leaflets were significantly thicker in CA versus FD patients, the measurement may be implemented in routine clinical practice.