Cardiovascular abnormalities in late-onset Pompe disease and response to enzyme replacement therapy
Daniel Forsha, Jennifer S Li, P Brian Smith, Ans T van der Ploeg, Priya Kishnani, Sara K Pasquali, Late-Onset Treatment Study Investigators, Paula Clemens, Diana M Escolar, Robert T Leshner, Pascal Laforêt, Alan Pestronk, Melissa Wasserstein, Ans van der Ploeg, Barry Rosenbloom, Edward Culper, Eugen Mengel, Robert Hopkin, Robin Casey, Joel Charrow, David Sillence, Bernard Lemieux, Katherine Sims, C Ronald Scott, Isablle Durieu, Alain Furby, Fabien Zagnoli, Richard Barohn, Sharon Nations, Reed Pyeritz, Terence Edgar, Bruce Barship, Mark Olsen, James Tita, G Bradley Schaefer, Kirk Aleck, Daniel Forsha, Jennifer S Li, P Brian Smith, Ans T van der Ploeg, Priya Kishnani, Sara K Pasquali, Late-Onset Treatment Study Investigators, Paula Clemens, Diana M Escolar, Robert T Leshner, Pascal Laforêt, Alan Pestronk, Melissa Wasserstein, Ans van der Ploeg, Barry Rosenbloom, Edward Culper, Eugen Mengel, Robert Hopkin, Robin Casey, Joel Charrow, David Sillence, Bernard Lemieux, Katherine Sims, C Ronald Scott, Isablle Durieu, Alain Furby, Fabien Zagnoli, Richard Barohn, Sharon Nations, Reed Pyeritz, Terence Edgar, Bruce Barship, Mark Olsen, James Tita, G Bradley Schaefer, Kirk Aleck
Abstract
Purpose: We evaluated the prevalence of cardiovascular abnormalities and the efficacy and safety of enzyme replacement therapy in patients with late-onset Pompe disease.
Methods: Ninety patients were randomized 2:1 to enzyme replacement therapy or placebo in a double-blinded protocol. Electrocardiograms and echocardiograms were obtained at baseline and scheduled intervals during the 78-week study period. Baseline cardiovascular abnormalities, and efficacy and safety of enzyme replacement therapy were described. Three pediatric patients were excluded.
Results: Eighty-seven patients were included. Median age was 44 years; 51% were men. At baseline, a short PR interval was present in 10%, 7% had decreased left ventricular systolic function, and 5% had elevated left ventricular mass on echocardiogram (all in mild range). There was no change in cardiovascular status associated with enzyme replacement therapy. No significant safety concerns related to enzyme replacement therapy were identified.
Conclusions: Although some patients with late-onset Pompe disease had abnormalities on baseline electrocardiogram or echocardiogram, those classically seen in infantile Pompe disease, such as significant ventricular hypertrophy, were not noted. Cardiovascular parameters were not impacted by enzyme replacement therapy, and there were no cardiovascular safety concerns. The cardiovascular abnormalities identified may be related to Pompe disease or other comorbid conditions.
Trial registration: ClinicalTrials.gov NCT00158600.
Source: PubMed