NYMC Faculty Publications

Cardiac Responses in Paediatric Pompe Disease in the ADVANCE Patient Cohort


Barry J. Byrne, Department of Pediatrics, College of Medicine, Powell Gene Therapy Center, University of Florida, Gainesville, FL, USA.
Steven D. Colan, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Priya S. Kishnani, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Meredith C. Foster, Biostatistics, Rare Diseases, Sanofi Genzyme, Cambridge, MA, USA.
Susan E. Sparks, Biostatistics, Rare Diseases, Sanofi Genzyme, Cambridge, MA, USA.
James B. Gibson, Department of Clinical and Metabolic Genetics, Clinical and Metabolic Genetics, Dell Children's Medical Group, Austin, TX, USA.
Kristina An Haack, Rare Diseases, Sanofi Genzyme, Shanghai, China.
David W. Stockton, Department of Pediatrics, Division of Genetic, Genomic, and Metabolic Disorders, Central Michigan University, Children's Hospital of Michigan, Detroit, MI, USA.
Loren D. Peña, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Si Houn Hahn, Departments of Pediatrics and Medicine, Biochemical Genetics Program, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
Judith Johnson, Biostatistics, Rare Diseases, Sanofi Genzyme, Cambridge, MA, USA.
Pranoot X. Tanpaiboon, Department of Genetics, Children's National Hospital, Washington, DC, USA.
Nancy D. Leslie, Department of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
David Kronn, Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY, USA.
Richard E. Hillman, Department of Pediatrics, University of Missouri Child Health, Columbia, MO, USA.
Raymond Y. Wang, Department of Pediatrics, Foundation of Caring Multidisciplinary Lysosomal Storage Disease Program, Children's Hospital of Orange County, Orange, CA, USA.

Author Type(s)


Journal Title

Cardiology in the Young

First Page


Last Page


Document Type


Publication Date





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 This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left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.