Send letter to journal:
Re: Elevation of BNP in Newborns with Hypertrophic Cardiomyopathy due to Pompe disease

Dear Editor,

Kaski et al. (1) recently reported that in children with hypertrophic cardiomyopathy (HC) the B-type natriuretic peptide (BNP) level correlated with maximal left ventricular (LV) wall thickness and could be a useful tool in assessing disease severity. In adult patients with HC, circulating plasma BNP has been related to the magnitude of heart failure and can be used to detect HC in patients when symptom evaluation is difficult (2). Here we further demonstrate the role of BNP in newborn babies affected by Pompe disease.

We detect Pompe disease (acid alpha-glucosidase deficiency) in newborns though large-scale newborn screening (manuscript in press). We totally identified five patients at a median age of 0.75 months (range: 0.25-1 month) and none of them showed symptoms like feeding difficulty, dyspnea, or muscle weakness at the time of diagnosis. However, their median left ventricular mass index (LVMI) was 120.3 g/m2 (range: 108.9-186 g/m2; normal levels, 47.4 +/-6.2 g/m (3)), and mean BNP level was as high as 556.97 pg/mL (range: 420.37-1300 pg/mL, normal babies less than one month of age: median 28.61 pg/mL, 97.5th percentile 169.10 pg/mL, n=23). After receiving two infusions biweekly of human recombinant acid alpha- glucosiase (Myozyme, Genzyme), their median BNP level dropped to 16.35 pg/mL (range 0-77 pg/mL). We observed a positive correlation between BNP and LVMI (correlation coefficient=0.63) in the five babies detected by screening. We also examined BNP and LVMI in four older infants with Pompe disease who were diagnosed by clinical symptoms. In comparison with the newborn cases, those patients were discovered at a later age (median: 3.1 months, range: 1.8-4 months, p=0.016), tended to have higher LVMI (median: 189.1 g/m2, range: 151.6-307.5 g/m2, p=0.19), but lower median BNP level (412.6 pg/mL, range: 132.8-5190.5 pg/mL, p=0.556). However, the correlation between BNP and LVMI was very high (correlation coefficient=0.92). After 2 doses of Myozyme, their median BNP level dropped to 70.86 pg/mL (range: 12.45- 724.09 pg/mL), slightly higher than the babies detected by screening (p=0.016).

Our observation suggests that in Newborns with Hypertrophic Cardiomyopathy due to Pompe disease, BNP is not only a good marker to monitor the treatment for HC, but also a very useful tool to make early diagnosis of Pompe disease, before the appearance of skeletal muscle weakness. Our current experience in treating early-diagnosed Pompe patients suggests that treatment initiated before the age of one month would be most fruitful (manuscript in preparation). Therefore, BNP will be indispensable in diagnosing HC among newborn babies affected by Pompe disease, probably as well as among babies affected by other congenital cardiomyopathies.

Interestingly, the BNP levels in the Pompe newborns seem to be higher than the levels in the clinically-diagnosed cases that had more advanced disease and higher LVMI. BNP is synthesized and released by ventricular myocardial cells in response to myocyte stretch (4). It is possible that the hemodynamic abnormalities in newborn babies with Pompe disease are different from the older patients, which leads to the less correlation between BNP and LVMI. The higher pulmonary resistance in newborns may also exaggerate the ventricular wall stress in Pompe newborns. Further researches will be necessary to increase our knowledge about BNP and its applications.

References

1. Kaski JP, Tome-Esteban MT, Mead-Regan SJ, Pantazis A, Marek J, Deanfield JE, McKenna WJ, Elliott PM
B-Type Natriuretic Peptide Predicts Disease Severity in Children With Hypertrophic Cardiomyopathy
Heart 2007.

2. Binder J, Ommen SR, Chen HH, Ackerman MJ, Tajik AJ, Jaffe AS
Usefulness of brain natriuretic peptide levels in the clinical evaluation of patients with hypertrophic cardiomyopathy
Am J Cardiol 2007; 100:712- 714.

3. Joyce JJ, Dickson PI, Qi N, Noble JE, Raj JU, Baylen BG
Normal right and left ventricular mass development during early infancy
Am J Cardiol 2004; 93:797-801.