Abstract 11170: Cardiac Hypertrophy in Pompe disease is Significantly Reduced During Enzyme Replacement Therapy. A United Kingdom Cohort
Introduction: Progressive severe cardiac hypertrophy has historically been the major cause of mortality in infantile onset Pompe disease (alpha-glucosidase deficiency). The advent of enzyme replacement therapy (ERT) has, in some patients, resulted in a dramatic improvement of the phenotype. We report results of a retrospective analysis of the cardiac response of infantile onset Pompe patients treated with ERT. We examined the effects of ERT on left ventricular structure and function by echocardiography for patients treated in the UK.
Methods: Patients treated between 2006 and 2012 were included. Pompe disease was confirmed via measurement of enzyme activity. All patients were treated with Myozyme® at 20mg/kg iv at weekly/biweekly intervals. Serial echocardiography was performed at baseline and throughout treatment with measurement of left ventricular mass index (LVMI) and standard measurements of ventricular geometry and function..
Results: 22 patients (13 girls) were included. Median age at diagnosis 2.7 (0.25 to 31 months). ERT was started at median 4 (0.5 - 31) months. Survival was 64% (14/22) with survivors receiving treatment for median 16 months (6-89 months) and non-survivors dying median 9.5 (6 to 60) months. 5/14 survivors required long term ventilation. Cardiorespiratory arrest was the main cause of death.
Baseline LVMI was significantly increased median 241 mg/m2 (IQR 110). Lower LVMI at presentation was associated with survival. (229 mg/m2 (IQR125) vs 300 mg/m2 (IQR 69.5) p=0.046). LVMI increased with age at presentation (Spearman r= 0.546, p=0.023).
LVMI was normal in 11/14 survivors 13 months (IQR 9 ½ months) after the start of treatment. None of the 8 non-survivors normalised their LVMI prior to death Left ventricular dilatation was present in 10/22 patients at baseline. 60% with an increased LVED z score died with progressive ventricular dilatation prior to death.
Conclusions: The natural history for untreated Pompe disease is death from cardiorespiratory failure within the first year of life. ERT improves the cardiac phenotype with significant reduction in LVMI and improved survival for more than 50% of treated patients. Those who fail to respond or have left ventricular dilatation at presentation have a worse outcome.
- © 2013 by American Heart Association, Inc.