Early cardiac involvement in females carrying α-galactosidase A mutation: role of hybrid PET-MR imaging and speckle tracking echocardiography

Background: Hybrid ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography and magnetic resonance (PET-MR) imaging may differentiate mature fibrosis or scar from fibrosis associated to active inflammation in patients with Anderson-Fabry disease (AFD), even in non-hypertrophic stage. Aim: This study was designed to compare the results of PET-MR cardiac imaging with those of speckle tracking echocardiography in heterozygous AFD females.

Methods: Twenty-four heterozygous females carrying α-galactosidase A (α-Gal A) mutation and without left ventricular (LV) hypertrophy underwent cardiac PET-MR using ¹⁸F-FDG for glucose uptake and two-dimensional strain echocardiography. ¹⁸F-FDG myocardial uptake was quantified by measuring the coefficient of variation (COV) of the standardized uptake value using a 17-segment model.

Results: Focal ¹⁸F-FDG uptake with COV >0.17 was detected in 13 patients, including 2 patients with late gadolinium enhancement at MR. COV was 0.30±0.14 in patients with focal ¹⁸F-FDG uptake and 0.12±0.03 in those without (P<0.001). Strain echocardiography revealed worse global longitudinal systolic strain in patients with COV >0.17 compared to those with COV &#8804;0.17 (-18.5±2.7% vs. -22.2±1.8 %, P<0.05). According to receiver operating characteristic analysis, global longitudinal strain and the sum of segments with longitudinal strain >-15% were associated with COV >0.17, with area under the curves of 0.86 and 0.98, respectively (both P<0.0001). Conclusion: In females carrying α-Gal A mutation, focal ¹⁸F-FDG uptake represents an early sign of disease-related myocardial damage and is associated with impaired LV longitudinal function. These findings support the hypothesis that inflammation plays an important role in glycosphingolipids storage disorders.