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Published in: Pediatric Cardiology 4/2017

01-04-2017 | Original Article

Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients

Authors: Elizabeth S. Makil, Xinyu Tang, Elizabeth A. Frazier, R. Thomas Collins II

Published in: Pediatric Cardiology | Issue 4/2017

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Abstract

Myocardial dysfunction and heart failure are common in pediatric patients with congenital and acquired heart disease. Alkaline phosphatase (AP) has been suggested as a biomarker for myocardial dysfunction after Fontan operation. We hypothesized that pediatric patients with myocardial dysfunction requiring orthotopic heart transplant (OHT) have diminished AP compared to normal. A retrospective review was performed in all patients who underwent OHT at Arkansas Children’s Hospital between January 2007 and October 2012. Anatomic diagnoses, therapeutic interventions, and ventricular ejection fraction (EF) were recorded. Z scores for AP levels in the study group were determined by comparing the observed AP levels to age- and gender-matched normative values. T tests were performed to compare the mean AP Z score prior to and after OHT. p values <0.05 were considered statistically significant. During the study period, 124 OHTs were performed. Complete study data were available and analyzed from 71/124 patients (mean age at OHT 3.9 years; 51% female). The mean AP Z score was significantly lower in the study group prior to OHT compared to normal (p < 0.0001). The initiation of ACE inhibitor therapy prior to OHT was associated with a significant increase in AP and the ventricular EF (p < 0.001 for both). Treatment with milrinone was associated with an increase in EF. AP is significantly lower in pediatric patients with myocardial dysfunction prior to OHT compared to normal. AP increases significantly after the initiation of therapies to improve myocardial function. Diminished AP is an indicator of myocardial dysfunction in pediatric patients.
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Literature
1.
go back to reference Van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenburg JJ et al (2011) Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 58:2241–2247CrossRefPubMed Van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenburg JJ et al (2011) Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 58:2241–2247CrossRefPubMed
2.
go back to reference Thygesen K, Mair J, Mueller C, Huber K, Weber M, Plebani M et al (2012) Recommendations for the use of natriuretic peptides in acute cardiac care: a position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. Eur Heart J 33(16):2001–2006CrossRefPubMed Thygesen K, Mair J, Mueller C, Huber K, Weber M, Plebani M et al (2012) Recommendations for the use of natriuretic peptides in acute cardiac care: a position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. Eur Heart J 33(16):2001–2006CrossRefPubMed
3.
go back to reference Cantinotti M, Law Y, Vittorini S, Crocetti M, Marco M, Murzi B et al (2014) The potential and limitations of plasma BNP measurement in the diagnosis, prognosis, and management of children with heart failure due to congenital cardiac disease: an update. Heart Fail Rev 19:727–742CrossRefPubMed Cantinotti M, Law Y, Vittorini S, Crocetti M, Marco M, Murzi B et al (2014) The potential and limitations of plasma BNP measurement in the diagnosis, prognosis, and management of children with heart failure due to congenital cardiac disease: an update. Heart Fail Rev 19:727–742CrossRefPubMed
4.
go back to reference Chin AJ, Stephens AJ, Goldmuntz E, Leonard MB (2009) Serum alkaline phosphatase reflects post-Fontan hemodynamics in children. Pediatr Cardiol 30:138–145CrossRefPubMed Chin AJ, Stephens AJ, Goldmuntz E, Leonard MB (2009) Serum alkaline phosphatase reflects post-Fontan hemodynamics in children. Pediatr Cardiol 30:138–145CrossRefPubMed
5.
go back to reference Van Hoof VO, De Broe ME (1994) Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit Rev Clin Lab Sci 31:197–293CrossRefPubMed Van Hoof VO, De Broe ME (1994) Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit Rev Clin Lab Sci 31:197–293CrossRefPubMed
6.
go back to reference Van Hoof VO, Hoylaerts MF, Geryl H, Van Mullem M, Lepourte LG, De Broe ME (1990) Age and sex distribution of alkaline phosphatase isoenzymes by agarose electrophoresis. Clin Chem 36:875–878PubMed Van Hoof VO, Hoylaerts MF, Geryl H, Van Mullem M, Lepourte LG, De Broe ME (1990) Age and sex distribution of alkaline phosphatase isoenzymes by agarose electrophoresis. Clin Chem 36:875–878PubMed
7.
go back to reference Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294CrossRefPubMed Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294CrossRefPubMed
8.
go back to reference Tobiume H, Kanzaki S, Hida S, Ono T, Moriwake T, Yamauchi S et al (1997) Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy. J Clin Endocrinol Metab 82:2056–2061PubMed Tobiume H, Kanzaki S, Hida S, Ono T, Moriwake T, Yamauchi S et al (1997) Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy. J Clin Endocrinol Metab 82:2056–2061PubMed
9.
go back to reference Adachi H, Strauss W, Ochi H, Wagner HN Jr (1976) The effect of hypoxia on the regional distribution of cardiac output in the dog. Circ Res 39:314–319CrossRefPubMed Adachi H, Strauss W, Ochi H, Wagner HN Jr (1976) The effect of hypoxia on the regional distribution of cardiac output in the dog. Circ Res 39:314–319CrossRefPubMed
10.
go back to reference Williams LR, Leggett RW (1989) Reference values for resting blood flow to organs of man. Clin Phys Physiol Meas 10:187–217CrossRefPubMed Williams LR, Leggett RW (1989) Reference values for resting blood flow to organs of man. Clin Phys Physiol Meas 10:187–217CrossRefPubMed
11.
go back to reference Gross PM, Heistad DD, Marcus ML (1979) Neurohumoral regulation of blood flow to bones and marrow. Am J Physiol 237(4):H440–H448PubMed Gross PM, Heistad DD, Marcus ML (1979) Neurohumoral regulation of blood flow to bones and marrow. Am J Physiol 237(4):H440–H448PubMed
12.
go back to reference Leithe ME, Margorien RD, Hermiller JB, Unverferth DV, Leier CV (1984) Relationship between central hemodynamics and regional blood flow in normal subjects and in patients with congestive heart failure. Circulation 69:57–64CrossRefPubMed Leithe ME, Margorien RD, Hermiller JB, Unverferth DV, Leier CV (1984) Relationship between central hemodynamics and regional blood flow in normal subjects and in patients with congestive heart failure. Circulation 69:57–64CrossRefPubMed
13.
go back to reference Bayer LM, Robinson SJ (1960) Growth history of children with congenital heart defects. Size according to sex, age decade, surgical status, and diagnostic category. Am J Dis Child 117:564–572CrossRef Bayer LM, Robinson SJ (1960) Growth history of children with congenital heart defects. Size according to sex, age decade, surgical status, and diagnostic category. Am J Dis Child 117:564–572CrossRef
14.
go back to reference Cohen MI, Bush DM, Ferry RJ Jr, Spray TL, Moshang T Jr, Wernovsky G et al (2000) Somatic growth failure after the Fontan operation. Cardiol Young 10:447–457CrossRefPubMed Cohen MI, Bush DM, Ferry RJ Jr, Spray TL, Moshang T Jr, Wernovsky G et al (2000) Somatic growth failure after the Fontan operation. Cardiol Young 10:447–457CrossRefPubMed
15.
go back to reference Day RW, Denton DM, Jackson WD (2000) Growth of children with a functionally single ventricle following palliation at moderately increased altitude. Cardiol Young 10:193–200CrossRefPubMed Day RW, Denton DM, Jackson WD (2000) Growth of children with a functionally single ventricle following palliation at moderately increased altitude. Cardiol Young 10:193–200CrossRefPubMed
16.
go back to reference Vogt KN, Manlhiot C, Van Arsdell G, Russell JL, Mital S, McCrindle BW (2007) Somatic growth in children with single ventricle physiology: impact of physiologic state. J Am Coll Cardiol 50:1876–1883CrossRefPubMed Vogt KN, Manlhiot C, Van Arsdell G, Russell JL, Mital S, McCrindle BW (2007) Somatic growth in children with single ventricle physiology: impact of physiologic state. J Am Coll Cardiol 50:1876–1883CrossRefPubMed
17.
18.
go back to reference Daymont C, Neal A, Prosnitz A, Cohen MS (2013) Growth in children with congenital heart disease. J Pediatr 131:e236–e242.CrossRef Daymont C, Neal A, Prosnitz A, Cohen MS (2013) Growth in children with congenital heart disease. J Pediatr 131:e236–e242.CrossRef
19.
go back to reference Witzel C, Sreeram N, Coburger S, Schickendantz S, Brockmeier K, Schoenau E (2006) Outcome of muscle and bone development in congenital heart disease. Eur J Pediatr 165:168–174CrossRefPubMed Witzel C, Sreeram N, Coburger S, Schickendantz S, Brockmeier K, Schoenau E (2006) Outcome of muscle and bone development in congenital heart disease. Eur J Pediatr 165:168–174CrossRefPubMed
20.
go back to reference Avitabile CM, Leonard MB, Bodsky JL, Whitehead KK, Ravishankar C, Cohen MS et al (2015) Usefulness of insulinlike growth factor 1 as a marker of heart failure in children and young adults after the fontan palliation procedure. Am J Cardiol 115(6):816–820CrossRefPubMedPubMedCentral Avitabile CM, Leonard MB, Bodsky JL, Whitehead KK, Ravishankar C, Cohen MS et al (2015) Usefulness of insulinlike growth factor 1 as a marker of heart failure in children and young adults after the fontan palliation procedure. Am J Cardiol 115(6):816–820CrossRefPubMedPubMedCentral
21.
go back to reference Kirk R, Kipchand AI, Rosenthal DN, Addonizio L, Burch M, Chrisant M et al (2014) The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. J Heart Lung Transplant 33:888–909CrossRefPubMed Kirk R, Kipchand AI, Rosenthal DN, Addonizio L, Burch M, Chrisant M et al (2014) The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. J Heart Lung Transplant 33:888–909CrossRefPubMed
22.
go back to reference Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 35:569–582CrossRefPubMed Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 35:569–582CrossRefPubMed
23.
go back to reference Morrow DA, De Lemos JA (2007) Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation 115:949–952CrossRefPubMed Morrow DA, De Lemos JA (2007) Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation 115:949–952CrossRefPubMed
24.
go back to reference Price JF, Thomas AK, Grenier M, Eidem BW, O’Brian Smith E, Denfield SW et al (2006) B-type natriuretic peptide predicts adverse cardiovascular events in pediatric outpatients with chronic left ventricular systolic dysfunction. Circulation 114:1063–1069CrossRefPubMed Price JF, Thomas AK, Grenier M, Eidem BW, O’Brian Smith E, Denfield SW et al (2006) B-type natriuretic peptide predicts adverse cardiovascular events in pediatric outpatients with chronic left ventricular systolic dysfunction. Circulation 114:1063–1069CrossRefPubMed
25.
go back to reference Atz AM, Zak V, Breitbart RE, Colan SD, Pasquali SK, Hsu DT et al (2011) Factors associated with serum brain natriuretic peptide levels after the fontan procedure. Cong Heart Dis 6:313–321.CrossRef Atz AM, Zak V, Breitbart RE, Colan SD, Pasquali SK, Hsu DT et al (2011) Factors associated with serum brain natriuretic peptide levels after the fontan procedure. Cong Heart Dis 6:313–321.CrossRef
26.
go back to reference Kantor PF, Rusconi P, Lipshultz S, Mital S, Wilkinson JD, Burch M (2011) Current applications and future needs for biomarkers in pediatric cardiomyopathy and heart failure: summary from the second international conference on pediatric cardiomyopathy. Prog Pediatr Cardiol 32:11–14CrossRefPubMedPubMedCentral Kantor PF, Rusconi P, Lipshultz S, Mital S, Wilkinson JD, Burch M (2011) Current applications and future needs for biomarkers in pediatric cardiomyopathy and heart failure: summary from the second international conference on pediatric cardiomyopathy. Prog Pediatr Cardiol 32:11–14CrossRefPubMedPubMedCentral
27.
go back to reference Eindhoven JA, Van den Bosch AE, Ruys TP, Opic P, Cuypers JA, McGhie JS et al (2013) N-terminal pro-B-type natriuretic peptide and its relationship with cardiac function in adults with congenital heart disease. J Am Coll Cardiol 62:1203–1212CrossRefPubMed Eindhoven JA, Van den Bosch AE, Ruys TP, Opic P, Cuypers JA, McGhie JS et al (2013) N-terminal pro-B-type natriuretic peptide and its relationship with cardiac function in adults with congenital heart disease. J Am Coll Cardiol 62:1203–1212CrossRefPubMed
Metadata
Title
Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients
Authors
Elizabeth S. Makil
Xinyu Tang
Elizabeth A. Frazier
R. Thomas Collins II
Publication date
01-04-2017
Publisher
Springer US
Published in
Pediatric Cardiology / Issue 4/2017
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-017-1577-x

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