Cardiac responses in paediatric Pompe disease in the ADVANCE patient cohort.

ABSTRACT

Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and "fraction of life" (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks' treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change -0.8 ± 1.83; 95% confidence interval -1.3 to -0.2; all patients, change -0.5 ± 1.71; 95% confidence interval -1.0 to -0.1). Patients with "fraction of life" <0.79 had left ventricular mass z score decreasing (enrolment +0.1 ± 3.0; Week 52 -1.1 ± 2.0); those with "fraction of life" ≥0.79 remained stable (enrolment -0.9 ± 1.5; Week 52 -0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff-Parkinson-White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.Trial registry ClinicalTrials.gov Identifier NCT01526785 https//clinicaltrials.gov/ct2/show/NCT01526785.Social Media Statement Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.