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Procollagen type III amino-terminal propeptide: a serum biomarker of left ventricular remodelling in paediatric dilated cardiomyopathy

Published online by Cambridge University Press:  06 November 2013

Beth D. Kaufman ,
Nancy Videon ,
Xuemei Zhang ,
Matthew A. Harris ,
Robert E. Shaddy  and
Elizabeth Goldmuntz
Beth D. Kaufman*
Affiliation:
Department of Pediatrics, Division of Cardiology, Lucille Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, United States of America
Nancy Videon
Affiliation:
Clinical Trials Office, Children’s Hospital of Philadelphia, Philadelphia, United States of America
Xuemei Zhang
Affiliation:
Department of Biostatistics and Data Management, Children’s Hospital of Philadelphia, Westat, Philadelphia, United States of America
Matthew A. Harris
Affiliation:
Department of Pediatrics, Division of Cardiology, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Robert E. Shaddy
Affiliation:
Department of Pediatrics, Division of Cardiology, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
Elizabeth Goldmuntz
Affiliation:
Department of Pediatrics, Division of Cardiology, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
*
Correspondence to: Dr B. D. Kaufman, MD, Department of Pediatrics, Division of Pediatric Cardiology, Lucille Packard Children’s Hospital, 750 Welch Road, Suite 325, Palo Alto, California 94304, United States of America. Tel: 650-736-7419; Fax: 650-725-8343; E-mail: bethkaufman@stanford.edu
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Abstract

Background

Procollagen type III amino-terminal propeptide is a collagen III cleavage product released in blood. The serum levels of this propeptide in adults with dilated cardiomyopathy are associated with cardiac remodelling and prognosis. The utility of procollagen type III amino-terminal propeptide as a biomarker in paediatric dilated cardiomyopathy is unknown.

Methods

This was a prospective, longitudinal study of children with dilated cardiomyopathy and changes in procollagen type III amino-terminal propeptide. The serum level of propeptide was measured serially, compared with paediatric normal values, and correlated with clinical status and left ventricular size and function on echocardiograms and cardiac magnetic resonance imaging.

Results

Procollagen type III amino-terminal propeptide was measured serially in 149 samples from 39 patients, age 9.0±6.4 years, followed up for 16.8±16.3 months. Procollagen type III amino-terminal propeptide in dilated cardiomyopathy was higher than in normal children. On multivariate analyses, procollagen type III amino-terminal propeptide had a positive correlation with left ventricular dilation, left ventricular end-diastolic diameter index (p<0.0001), and left ventricular end-diastolic diameter Z-score (p=0.0003), and a negative correlation with shortening fraction changes over time (p=0.001). Patients with myocarditis (n=12) had higher procollagen type III amino-terminal propeptide values than those with idiopathic dilated cardiomyopathy (n=20).

Conclusions

Procollagen type III amino-terminal propeptide increases with left ventricular dilation and decreases with improvement in systolic function in paediatric dilated cardiomyopathy, indicating a role as a biomarker of cardiac remodelling in children. The diagnostic utility of procollagen type III amino-terminal propeptide to differentiate myocarditis from idiopathic dilated cardiomyopathy warrants further investigation.

Keywords

Biomarkercardiomyopathycardiac remodellingcollagen IIImyocarditis
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Issue 2 , February 2015 , pp. 228 - 236
Copyright
Copyright &#x00A9; Cambridge University Press 2013 

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References

1. Lipshultz, SE, Sleeper, LA, Towbin, JA, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 2003; 348: 1647–1655.Google Scholar
2. Nugent, AW, Daubeney, PE, Chondros, P, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 2003; 348: 1639–1646.Google Scholar
3. Holmgren, D, Wahlander, H, Eriksson, BO, Oldfors, A, Holme, E, Tulinius, M. Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J 2003; 24: 280–288.Google Scholar
4. Wilkinson, JD, Landy, DC, Colan, SD, et al. The pediatric cardiomyopathy registry and heart failure: key results from the first 15 years. Heart Failure Clinics 2010; 6: 401–413.Google Scholar
5. Xie, SB, Yao, JL, Zheng, SS, Yao, CL, Zheng, RQ. The levels of serum fibrosis marks and morphometric quantitative measurement of hepatic fibrosis. Hepatobiliary Pancreat Dis Int 2002; 1: 202–206.Google Scholar
6. Lijnen, PJ, Petrov, VV. Role of intracardiac renin-angiotensin-aldosterone system in extracellular matrix remodeling. Methods Find Exp Clin Pharmacol 2003; 25: 541–564.Google Scholar
7. Berry, C, Murphy, N, De Vito, G, et al. Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker. Eur J Heart Fail 2007; 9: 429–434.Google Scholar
8. Mak, GJ, Ledwidge, MT, Watson, CJ, et al. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. J Am Coll Cardiol 2009; 54: 1674–1682.Google Scholar
9. Radauceanu, A, Ducki, C, Virion, J-M, et al. Extracellular matrix turnover and inflammatory markers independently predict functional status and outcome in chronic heart failure. J Card Fail 2008; 14: 467–474.Google Scholar
10. Barasch, E, Gottdiener, JS, Aurigemma, G, et al. The relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly/clinical perspective. Circ Heart Fail 2011; 4: 733–739.Google Scholar
11. Zannad, F, Dousset, B, Alla, F. Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship. Hypertension 2001; 38: 1227–1232.Google Scholar
12. Zannad, F, Alla, F, Dousset, B, Perez, A, Pitt, B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales investigators. Circulation 2000; 102: 2700–2706.Google Scholar
13. Rutschow, S, Li, J, Schultheiss, HP, Pauschinger, M. Myocardial proteases and matrix remodeling in inflammatory heart disease. Cardiovasc Res 2006; 69: 646–656.Google Scholar
14. Klappacher, G, Franzen, P, Haab, D, et al. Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol 1995; 75: 913–918.CrossRefGoogle ScholarPubMed
15. Struthers, AD. The clinical implications of aldosterone escape in congestive heart failure. Eur J Heart Fail 2004; 6: 539–545.Google Scholar
16. Lin, YH, Lin, C, Lo, MT, et al. The relationship between aminoterminal propeptide of type III procollagen and heart rate variability parameters in heart failure patients: a potential serum marker to evaluate cardiac autonomic control and sudden cardiac death. Clin Chem Lab Med 2010; 48: 1821–1827.Google Scholar
17. Crofton, PM, Ahmed, SF, Wade, JC, et al. Bone turnover and growth during and after continuing chemotherapy in children with acute lymphoblastic leukemia. Pediatr Res 2000; 48: 490–496.Google Scholar
18. Crofton, PM, Ahmed, SF, Wade, JC, et al. Effects of intensive chemotherapy on bone and collagen turnover and the growth hormone axis in children with acute lymphoblastic leukemia. J Clin Endocrinol Metab 1998; 83: 3121–3129.Google Scholar
19. Crofton, PM, Wade, JC, Taylor, MR, Holland, CV. Serum concentrations of carboxyl-terminal propeptide of type I procollagen, amino-terminal propeptide of type III procollagen, cross-linked carboxyl-terminal telopeptide of type I collagen, and their interrelationships in schoolchildren. Clin Chem 1997; 43: 1577–1581.Google Scholar
20. Doherty, CP, Crofton, PM, Sarkar, MA, et al. Malnutrition, zinc supplementation and catch-up growth: changes in insulin-like growth factor I, its binding proteins, bone formation and collagen turnover. Clin Endocrinol 2002; 57: 391–399.Google Scholar
21. Trivedi, P, Hindmarsh, P, Ristell, J, Ristell, L, Mowat, AP, Brook, CGD. Growth velocity, growth hormone therapy, and serum concentrations of the amino-terminal propeptide of type III procollagen. J Pediatr 1989; 114: 225–230.Google Scholar
22. Spagnoli, A, Branca, F, Spadoni, GL, et al. Urinary pyridinium collagen cross-links predict growth performance in children with idiopathic short stature and with growth hormone (GH) deficiency treated with GH. Skeletal metabolism during GH treatment. J Clin Endocrinol Metab 1996; 81: 3589–3593.Google Scholar
23. Grenier, MA, Osganian, SK, Cox, GF, et al. Design and implementation of the North American Pediatric Cardiomyopathy Registry. Am Heart J 2000; 139 (Pt 3): S86–S95.Google Scholar
24. Orion Corporation. Orion Diagnostica. UniQ PIIINP N-Terminal Propeptide of Type III Procollagen Radioimmunoassay Kit Catalogue No. 06098. Orion Corporation, Espoo, Finland, 2003.Google Scholar
25. Cicoira, M, Rossi, A, Bonapace, S, et al. Independent and additional prognostic value of aminoterminal propeptide of type III procollagen circulating levels in patients with chronic heart failure. J Card Fail 2004; 10: 403–411.Google Scholar
26. Hayashi, M, Tsutamoto, T, Wada, A, et al. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003; 107: 2559–2565.Google Scholar
27. Rossi, A, Cicoira, M, Golia, G, et al. Amino-terminal propeptide of type III procollagen is associated with restrictive mitral filling pattern in patients with dilated cardiomyopathy: a possible link between diastolic dysfunction and prognosis. Heart 2004; 90: 650–654.Google Scholar
28. Poulsen, SH, Host, NB, Jensen, SE, Egstrup, K. Relationship between serum amino-terminal propeptide of type III procollagen and changes of left ventricular function after acute myocardial infarction. Circulation 2000; 101: 1527–1532.Google Scholar
29. Zile, MR, Desantis, SM, Baicu, CF, et al. Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure. Circ Heart Fail 2011; 4: 246–256.Google Scholar
30. Hayashi, M, Tsutamoto, T, Wada, A, et al. Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 2001; 38: 1375–1382.Google Scholar
31. Hsia, T-Y, Ringewald, JM, Stroud, RE, et al. Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy. Cardiol Young 2011; 21: 52–61.Google Scholar
32. Foerster, SR, Canter, CE, Cinar, A, et al. Ventricular remodeling and survival are more favorable for myocarditis than for idiopathic dilated cardiomyopathy in childhood: an outcomes study from the Pediatric Cardiomyopathy Registry. Circ Heart Fail 2010; 6: 689–697.Google Scholar