Early Initiation of Enzyme Replacement Therapy in Infantile Onset Pompe Disease Improves Cardiac Outcomes: A...

The objective of this study is to evaluate whether early enzyme replacement therapy (ERT) initiation is associated with a lower incidence of echocardiogram abnormalities and cardiac conduction abnormalities compared to later ERT initiation. We identified a cohort of patients treated with ERT for infantile onset Pompe disease (IOPD) and evaluated their cardiac outcomes by comparing clinically collected longitudinal functional echocardiogram and electrocardiogram (EKG) data. Longitudinal mixed-effects analysis was used to compare cardiac outcomes among the cohort based on timing of ERT initiation as a continuous variable (months of age) and accounted for repeated measures in an individual patient. Time-to-event analysis and Cox regression were performed to evaluate the time to achievement of normal left ventricular mass index (LVMI) based on ERT initiation as a dichotomous variable (≤ 1 month versus > 1 month of age). Early treatment was associated with significant improvements in cardiac remodeling as demonstrated by multiple cardiac parameters with better outcomes based on earlier treatment such as interventricular septum thickness in diastole and systole, left ventricular posterior wall thickness in diastole and systole, and biventricular hypertrophy. The early-treated cohort (those started on ERT ≤ 1 month of age) achieved a normal LVMI faster compared to late-treated patients. Early treatment with ERT in patients with IOPD leads to improved cardiac chamber dimension parameters. Treatment initiation ≤ 1 month of age can shorten the time to achieve a normal LVMI. Our findings were limited by the nature of the data collection, which was retrospective and clinically driven; the results presented in this study, however, support the clinical importance of early therapeutic intervention in IOPD. Early initiation with ERT in patients with IOPD can shorten the time to achieve a normal LVMI and can improve cardiac chamber dimension parameters.