Two Faces of the Right Ventricle in Fabry Cardiomyopathy: Septal-Coupled and Atrial-Coupled Strain Patterns and Their Differential Associations with Enzyme Replacement Therapy

Right ventricular global longitudinal strain (RVGLS) and right ventricular free-wall longitudinal strain (RVFWLS) are both used to assess right ventricular involvement, but they include different myocardial components. We examined their cross-sectional correlates and longitudinal changes associated with enzyme replacement therapy (ERT) in 100 patients with genetically confirmed Fabry disease, including 69 with serial echocardiography. RVGLS was independently associated with left ventricular global longitudinal strain (LVGLS; standardized β = 0.466, p < 0.001) and interventricular septal thickness (standardized β = 0.257, p = 0.027), whereas RVFWLS was independently associated with right atrial reservoir strain (standardized β = −0.542, p < 0.001). RVGLS and RVFWLS were not significantly correlated (r = 0.053, p = 0.654). In the paired RV strain subgroup, longitudinal RVGLS change differed between untreated and ERT-treated patients (+2.06 ± 3.94% vs. −1.28 ± 3.64%, p = 0.017), whereas RVFWLS change did not (p = 0.838). In a sensitivity model adjusted for age, sex, genotype, and baseline RVGLS, ERT remained associated with ΔRVGLS (β = −3.28 percentage points, 95% CI −5.25 to −1.32; p = 0.001). These findings identify different correlates of septal-inclusive and free-wall RV strain and require prospective validation.