Skip to main content
Log in

Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. 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 58:2241–2247

    Article  PubMed  Google Scholar 

  2. 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):2001–2006

    Article  CAS  PubMed  Google Scholar 

  3. 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 19:727–742

    Article  PubMed  Google Scholar 

  4. Chin AJ, Stephens AJ, Goldmuntz E, Leonard MB (2009) Serum alkaline phosphatase reflects post-Fontan hemodynamics in children. Pediatr Cardiol 30:138–145

    Article  PubMed  Google Scholar 

  5. Van Hoof VO, De Broe ME (1994) Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit Rev Clin Lab Sci 31:197–293

    Article  PubMed  Google Scholar 

  6. 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 36:875–878

    PubMed  Google Scholar 

  7. Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294

    Article  CAS  PubMed  Google Scholar 

  8. 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 82:2056–2061

    CAS  PubMed  Google Scholar 

  9. 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 39:314–319

    Article  CAS  PubMed  Google Scholar 

  10. Williams LR, Leggett RW (1989) Reference values for resting blood flow to organs of man. Clin Phys Physiol Meas 10:187–217

    Article  CAS  PubMed  Google Scholar 

  11. Gross PM, Heistad DD, Marcus ML (1979) Neurohumoral regulation of blood flow to bones and marrow. Am J Physiol 237(4):H440–H448

    CAS  PubMed  Google Scholar 

  12. 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 69:57–64

    Article  CAS  PubMed  Google Scholar 

  13. 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 117:564–572

    Article  Google Scholar 

  14. 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 10:447–457

    Article  CAS  PubMed  Google Scholar 

  15. Day RW, Denton DM, Jackson WD (2000) Growth of children with a functionally single ventricle following palliation at moderately increased altitude. Cardiol Young 10:193–200

    Article  CAS  PubMed  Google Scholar 

  16. 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 50:1876–1883

    Article  PubMed  Google Scholar 

  17. Mehrizi A, Drash A (1962) Growth disturbance in congenital heart disease. J Pediatr 61:418–429

    Article  CAS  PubMed  Google Scholar 

  18. Daymont C, Neal A, Prosnitz A, Cohen MS (2013) Growth in children with congenital heart disease. J Pediatr 131:e236–e242.

    Article  Google Scholar 

  19. 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 165:168–174

    Article  PubMed  Google Scholar 

  20. 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):816–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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 33:888–909

    Article  PubMed  Google Scholar 

  22. 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 35:569–582

    Article  CAS  PubMed  Google Scholar 

  23. Morrow DA, De Lemos JA (2007) Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation 115:949–952

    Article  PubMed  Google Scholar 

  24. 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 114:1063–1069

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. 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 32:11–14

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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 62:1203–1212

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Thomas Collins II.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to report, whether real or perceived, regarding this work.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Because the study was a retrospective review of previously obtained clinical data, the need for informed consent was waived by the University Institutional Review Board.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 780 KB)

Supplementary material 2 (DOCX 11 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Makil, E.S., Tang, X., Frazier, E.A. et al. Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients. Pediatr Cardiol 38, 762–769 (2017). https://doi.org/10.1007/s00246-017-1577-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-017-1577-x

Keywords

Navigation