@article{1a4ee3355852495ab9ba7e86227dd0ca,
title = "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 This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left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.",
keywords = "Alglucosidase alfa, Pompe disease, cardiomyopathy, dysrhythmia, enzyme replacement therapy, left ventricular mass",
author = "{Pompe ADVANCE Study Consortium} and Byrne, {Barry J.} and Colan, {Steven D.} and Kishnani, {Priya S.} and Foster, {Meredith C.} and Sparks, {Susan E.} and Gibson, {James B.} and {An Haack}, Kristina and Stockton, {David W.} and Pe{\~n}a, {Loren D.M.} and Hahn, {Si Houn} and Judith Johnson and Tanpaiboon, {Pranoot X.} and Leslie, {Nancy D.} and David Kronn and Hillman, {Richard E.} and Wang, {Raymond Y.}",
note = "Funding Information: This study was supported by Sanofi Genzyme. The ADVANCE study and writing assistance for this manuscript were supported by Sanofi Genzyme. B.J.B. reports receiving personal fees from Sanofi Genzyme for membership in the Pompe Registry Advisory Board. S.D.C. has nothing to disclose. P.S.K. reports grants from Amicus Therapeutics, Sanofi Genzyme, and Valerion Therapeutics; consulting fees and honoraria from Amicus Therapeutics, Asklepios BioPharmaceuticals (AskBio), and Sanofi Genzyme; membership of the Pompe and Gaucher Disease Registry Advisory Boards for Amicus Therapeutics, Baebies, and Sanofi Genzyme; and equity with Asklepios BioPharmaceuticals (AskBio). J.B.G. discloses study sponsorship and professional writing assistance from Sanofi Genzyme during the conduct of the study and advisory board membership for Mallinckrodt Pharmaceuticals outside the submitted work. D.W.S. is a member of the Sanofi Genzyme Pompe Registry Advisory Board outside the submitted work and discloses grant support from Sanofi Genzyme during the conduct of the study. L.D.M.P. discloses grant support and advisory board membership for Avexis, Inc., Retrophin, Orphazyme, and Ultragenyx, grant support from Biogen, Ionis, and Sanofi Genzyme, advisory board membership for Roche/Genentech, and research support from Roivant, Inc. and Takeda Shire. S.H.H. reports personal fees from Alexion and Seattle Children's Hospital, and personal fees and grants from Sanofi Genzyme outside the submitted work. P.T. discloses current employment by Quest Diagnostics. N.D.L. reports personal fees (honoraria for advisory board activities) and non-financial support (professional writing support) from Sanofi Genzyme during the conduct of the study and outside the submitted work. D.K. reports research funding from Sanofi Genzyme and New York Medical College during the conduct of the study and is on the Sanofi Genzyme speakers' bureau for Pompe disease. K.A.H., M.C.F., J.J., and S.S. disclose being employees of Sanofi Genzyme (K.A.H.'s spouse is also an employee of Sanofi Genzyme). R.H. and R.Y.W. declare that they have nothing to disclose. Funding Information: Financial support. This study was supported by Sanofi Genzyme. Funding Information: Conflicts of interest. The ADVANCE study and writing assistance for this manuscript were supported by Sanofi Genzyme. B.J.B. reports receiving personal fees from Sanofi Genzyme for membership in the Pompe Registry Advisory Board. S.D.C. has nothing to disclose. P.S.K. reports grants from Amicus Therapeutics, Sanofi Genzyme, and Valerion Therapeutics; consulting fees and honoraria from Amicus Therapeutics, Asklepios BioPharmaceuticals (AskBio), and Sanofi Genzyme; membership of the Pompe and Gaucher Disease Registry Advisory Boards for Amicus Therapeutics, Baebies, and Sanofi Genzyme; and equity with Asklepios BioPharmaceuticals (AskBio). J.B.G. discloses study sponsorship and professional writing assistance from Sanofi Genzyme during the conduct of the study and advisory board membership for Mallinckrodt Pharmaceuticals outside the submitted work. D.W.S. is a member of the Sanofi Genzyme Pompe Registry Advisory Board outside the submitted work and discloses grant support from Sanofi Genzyme during the conduct of the study. L.D.M.P. discloses grant support and advisory board membership for Avexis, Inc., Retrophin, Orphazyme, and Ultragenyx, grant support from Biogen, Ionis, and Sanofi Genzyme, advisory board membership for Roche/Genentech, and research support from Roivant, Inc. and Takeda Shire. S.H.H. reports personal fees from Alexion and Seattle Children{\textquoteright}s Hospital, and personal fees and grants from Sanofi Genzyme outside the submitted work. P.T. discloses current employment by Quest Diagnostics. N.D.L. reports personal fees (honoraria for advisory board activities) and non-financial support (professional writing support) from Sanofi Genzyme during the conduct of the study and outside the submitted work. D.K. reports research funding from Sanofi Genzyme and New York Medical College during the conduct of the study and is on the Sanofi Genzyme speakers{\textquoteright} bureau for Pompe disease. K.A.H., M.C.F., J.J., and S.S. disclose being employees of Sanofi Genzyme (K.A.H.{\textquoteright}s spouse is also an employee of Sanofi Genzyme). R.H. and R.Y.W. declare that they have nothing to disclose. Publisher Copyright: {\textcopyright} 2022 Cambridge University Press. All rights reserved.",
year = "2022",
month = mar,
day = "23",
doi = "10.1017/S1047951121002079",
language = "English",
volume = "32",
pages = "364--373",
journal = "Cardiology in the Young",
issn = "1047-9511",
number = "3",
}