title: Use of cardiac magnetic resonance imaging to evaluate cardiac structure, function and fibrosis in children with infantile Pompe disease on enzyme replacement therapy.
abstract: BACKGROUND
  Pompe disease (acid α-glucosidase deficiency) is one of several lysosomal storage diseases amenable to treatment with enzyme replacement therapy (ERT). While echocardiography (echo) has been the standard method to evaluate the cardiac response to ERT, cardiac magnetic resonance imaging (CMR) has the advantage of a better tissue definition and characterization of myocardial fibrosis. However, CMR for Pompe disease is not frequently performed due to a high risk of sedation. We report the first use of CMR in a feasible protocol to quantify left ventricular (LV) mass, function, and the presence of myocardial fibrosis in the Pompe population.
  
  
  METHODS
  Children with Pompe disease on ERT were assessed with transthoracic echo and CMR over a 3 year period at a single institution. Echocardiography was performed using standard techniques without sedation. CMR was performed using retrospectively gated and real-time imaging, with and without sedation. LV mass indexed to body surface area (LVMI) and ejection fraction (EF) were measured by both echo and CMR, and evaluated for change over time. Myocardial fibrosis was assessed by CMR with delayed enhancement imaging 5-10 min after gadolinium contrast using single shot inversion recovery sequences with inversion time set to null the signal from normal myocardium.
  
  
  RESULTS
  Seventeen CMR scans were successfully performed in 10 subjects with Pompe disease (median age at first CMR is 9 months, range 1-38 months, 80% male), with sedation only performed in 4 studies. There was a median interval of 5 months (range 0-34 months) from the start of ERT to first CMR (baseline). At baseline, the median indexed LVMI by CMR (140.0 g/m(2), range 43.8-334.0) tended to be lower than that assessed by echo (median 204.0 g/m(2), range 52.0-385.0), but did not reach statistical significance. At baseline, CMR EF was similar to that assessed by echo (55% vs. 55%). Overall, there was no significant decrease in CMR measured LVMI over time (CMR median LVMI at baseline 94 g/m(2) (range 43.8-334) vs. CMR median at most recent study 44.5 g/m(2) (range 34-303), p=0.44). In 5 patients with serial CMR scans over time, LVMI decreased in 2, was similar in 2, and increased in 1 patient with high sustained antibodies to exogenous enzyme. Delayed enhancement was noted in only l separate patient who also had high sustained antibodies to exogenous enzyme.
  
  
  CONCLUSIONS
  CMR is an imaging tool that is feasible to use to serially follow LVMI and EF in children with Pompe disease on ERT. Real-time imaging is adequate for quantification purposes in these patients and minimizes the need for sedation. Quantitative CMR LVMI is generally lower than echo derived LVMI. Delayed enhancement appears to be a rare finding by CMR in Pompe disease. A further follow-up is necessary to better understand the long term effects of ERT in infantile Pompe survivors, especially those with high sustained antibody titers or advanced cardiac disease at treatment outset.
authors.affiliation: Division of Pediatric Cardiology, Duke University Medical Center, Durham, NC 27710, USA. piers.barker@duke.edu
authors.forename: Piers C A
authors.initials: PC
authors.lastname: Barker
authors.forename: Sara K
authors.initials: SK
authors.lastname: Pasquali
authors.forename: Stephen
authors.initials: S
authors.lastname: Darty
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Ing
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Li
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Kim
authors.forename: Stephanie
authors.initials: S
authors.lastname: DeArmey
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Campbell
mesh_terms: D009202:Cardiomyopathies; D002675:Child, Preschool; D004452:Echocardiography; D056947:Enzyme Replacement Therapy; D005260:Female; D005355:Fibrosis; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009206:Myocardium / Q000473:pathology*; D000520:alpha-Glucosidases / Q000627:therapeutic use
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases