Non-ischemic Primary and Secondary Cardiomyopathy

1356229 - Pilot study of serial cardiovascular magnetic resonance imaging in patients with Anderson Fabry disease receiving enzyme replacement therapy

Thursday, January 26, 2023

1:00 PM – 2:00 PM

Location: Pacific Jewel

Presenting Author(s)

DG

Dakshin Gangadharamurthy, MD

Advanced Cardiac Imaging Fellow
The Ohio State University
Columbus, Ohio, United States

Primary Author(s)

DG

Dakshin Gangadharamurthy, MD

Advanced Cardiac Imaging Fellow
The Ohio State University
Columbus, Ohio, United States

Co-Author(s)

AL

Ann Lowery Black

Medical Student
The Ohio State University, United States
SS

Suzanne Smart, BSc, CCRP

Research Associate
The Ohio State University, United States
JM

Jan Mazur

Medical Student
University of Cincinnati Medical Center, United States
KM

Katarzyna Mikrut, MD

Assistant Professor
Advocate Lutheran General Hospital, Illinois, United States
Karolina M. Zareba, MD

Associate Professor
The Ohio State University
Columbus, Ohio, United States

Disclosure(s):

Karolina M. Zareba, MD: No financial relationships to disclose

Background: Anderson-Fabry disease (AFD) is an X-linked inherited disorder causing alpha galactosidase A deficiency and resulting in the accumulation of glycosphingolipids in multiple organs including the heart. Enzyme replacement therapy (ERT) has changed the course of AFD, particularly when initiated early. Cardiovascular magnetic resonance (CMR) remains an important tool in diagnosing AFD given its robust myocardial tissue characterization (1-3). Limited data exist on utilizing CMR as a monitoring tool to determine response to therapy in patients with AFD.

Methods: We retrospectively evaluated patients with confirmed AFD who had undergone serial CMR imaging at 1.5T while receiving ERT. Confirmed AFD was defined according to guidelines (positive genetic testing in females; positive genetic testing or negative enzymatic function in males). The electronic medical record was utilized to obtain clinical characteristics. CMR evaluation consisted of biventricular size and function analysis, T1 mapping (MOLLI) including extracellular volume fraction (ECV), and late gadolinium enhancement (LGE) analyses. Mean T1 values were obtained utilizing the whole mid short axis slice with careful attention to avoid partial volume effects. LGE was evaluated by segmental analysis. CMR parameters were compared between baseline and repeat imaging using the paired t-test.

Results: A total of 6 patients with confirmed AFD were included in the analysis (4 females, 2 males, mean age 43±13 years). All patients were treated with enzyme replacement therapy and repeat CMR imaging was performed at a mean 1212 ± 735 days following the baseline scan. Accounting for the small sample size, there were no significant differences between ventricular size and function, maximum left ventricular (LV) wall thickness or LV mass index when comparing baseline and follow up CMR indices while on ERT (Table 1). However, there was a trend towards significance in native myocardial T1 mapping with a mean increase of 52 ± 53 ms (p=0.059) from baseline to follow up CMR (Figure 1). A total of 4 patients exhibited non-ischemic midwall LGE at baseline and on follow up imaging with no change in number of American Heart Association segments over time (2.3±0.6 segments). Two patients remained free of fibrosis.

Conclusion: Cardiovascular magnetic resonance is an established diagnostic tool in patients with Anderson Fabry disease but may also be useful in monitoring response to therapy. Patients receiving enzyme replacement therapy showed a near-significant improvement in native myocardial T1 signal in this pilot study, while no change was noted in ventricular size, function, and wall thickness. Larger studies are needed to evaluate the utility of CMR in the surveillance and long-term monitoring of ERT in patients with AFD.