Mitral valve thickness: A promising echocardiographic parameter for distinguishing between cardiac amyloidosis and Fabry disease

Abstract

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): The study was financially supported by Alnylam Pharmaceuticals (Cambridge, MA, USA). Background Left ventricular (LV) "hypertrophy" is present in various cardiomyopathies, such as cardiac amyloidosis (CA) and Fabry disease (FD). To differentiate both, multiple echocardiographic characteristics have been evaluated, but diagnosis and treatment are still often delayed. Purpose We evaluated new diagnostic indices, including the thickness of the mitral valve leaflets (ML) and the ratio of PM to LV area (PM/LV ratio), to distinguish between CA and FD. Methods We retrospectively enrolled patients with diagnosed CA and genetically confirmed FD and measured (i) the thickness of the ML in mid-diastole in the parasternal long axis view and (ii) the PM/LV ratio at end-diastole in the parasternal short axis view, as described by Nieman et al. in an offline analysis (EchoPAC PC, GE Vingmed, Horton, Norway; Vivid E9 or E95, GE Vingmed, Horton, Norway, M5S[c] 1.5–4.5MHz transducer). Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of the measurements. The reproducibility of leaflet measurement was calculated using the intra-class correlation coefficient for intra-observer agreement and inter-observer agreement. Results A total of 129 patients with FD (n=49) and CA (n=80) were analyzed. The ML were significantly thicker, and the area of PM and LV were significantly larger in CA compared to FD patients (ML: 4±1 mm in CA vs. 3±1 mm in FD, p<0.001). This resulted 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). Specifically, the posteromedial PM and the LV area were significantly larger in CA patients, while the increase in anterolateral PM area did not reach statistical significance. The thickness of the ML showed the best diagnostic accuracy (area under the curve [AUC]: 0.75, 95% confidence interval [CI]: 0.65–0.85) for discriminating between CA and FD. The reproducibility of leaflet measurement had a good to excellent agreement (intra-class correlation coefficient for intra-observer agreement: 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, the PM/LV ratio did not differ between FD and CA. Nevertheless, the measurement of ML may be useful in routine clinical practice to differentiate between the two cardiomyopathies.