Differential diagnosis of hypertrophic cardiomyopathy, fabry cardiomyopathy and transthyretin cardiac amyloidosis: insights from right ventricular strain imaging echocardiography
Authors: Mata E , Tinoco M , Pereira T , Castro M , Pinheiro L , Lage Garcia B , Cordeiro F , Fernandes M , Azevedo O , Lourenco A 
Published: January 2025

Introduction

Timely differential diagnosis between hypertrophic cardiomyopathy (HCM), Fabry cardiomyopathy (FC) and wild-type transthyretin cardiac amyloidosis (ATTR-CA) is crucial for appropriate treatment and family screening. Right ventricle (RV) involvement is common in these diseases, making the systematic RV assessment essential. Two-dimensional speckle-tracking echocardiography (2D-STE) offers potential for precise RV myocardial mechanics evaluation, however its utility in distinguishing these conditions remains uncertain.

Methods

This study retrospectively compared matched controls (n=30) with three patient cohorts of nonobstructive HCM (n=30), ATTR-CA (n=30) and FC (n=30) referred to cardiomyopathy consultation between 2014 and 2021. Two blinded researchers independently performed morfofunctional echocardiographic evaluation of RV and 2D-STE analysis of RV myocardial strain. Receiver operating characteristic (ROC) analysis assessed the diagnostic performance of these parameters. Inter- and intra-observer reproducibility used Bland-Altman analysis and intraclass correlation coefficients.

Results

Male gender predominated in all groups (ATTR-CA 50%; FC 63%; HCM 63%). ATTR-CA patients were older when compared to FC and HCM (Median [IQR]: 84 [5] vs. 64.5 [18.75] vs. 57 [18.25] years, p&lt;0.001) and had higher NT-proBNP (Median [IQR]: 5841 [11742] vs. 467 [1203] vs. 812 [857] pg/ml, p&lt;0.001). ATTR-CA patients had the highest RV wall thickness (RVWT) in comparison to FC (9.0 vs. 7.4 mm, p=0.001) and HCM (9.0 vs. 5.5 mm, p&lt;0.001). Patients with ATTR-CA had lower TAPSE (p=0.001), RV S’ (p=0.001), and RV-FAC values (p=0.003) compared to FC, with no significant differences compared to HCM. RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS) were significantly reduced in ATTR-CA (11.6% ± 4.7 and 15.5% ± 7.6) comparing to FC (19.3% ± 3.2 and 24.7% ± 3.9) and HCM (18.9% ± 3.1 and 25.6% ± 5.2) (p&lt;0.001). RV systolic dysfunction according to RV strain analysis (RV-FWS &lt;23%) led to substantial reclassification and increased prevalence in all groups (ATTR-CA: 37% to 87%; FA 0% to 20%; HCM: 3% to 27%). In ROC analysis, RV-GLS emerged as the most effective parameter for distinguishing ATTR-CA from FC (AUC 0.91; 95% CI 0.81-0.97, p&lt;0.001) with an optimal cut-off of 15.0% yielding 83% sensitivity and 93% specificity. RVWT was the best discriminative parameter for distinguishing ATTR-CA from HCM (AUC 0.98; 95% CI 0.90-0.99, p&lt;0.001; optimal cut-off of 6.5mm; 97% sensitivity, 90% specificity) and FC from HCM (AUC 0.91, 95% CI 0.81-0.97, p&lt;0.001; optimal cut-off of 6.5mm; 83% sensitivity, 90% specificity). RVWT and strain parameters analyses were consistent Intra- and inter-observer with excellent agreement.

Conclusion

This study underscores the importance of RV thickness and RV-GLS for the differential diagnosis of HCM from phenocopies.