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Natriuretic Peptide as an Adjunctive Diagnostic Test in the Acute Phase of Kawasaki Disease

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Abstract

Coronary arteritis rather than myocardial involvement is typically emphasized in Kawasaki disease (KD). Moreover, the criteria and the usual biological markers oversee the importance of cardiac-specific markers in diagnosing this disease. We sought to study the clinical usefulness of measuring B-type natriuretic peptide (BNP) and its N-terminal moiety (NT-proBNP) at the onset of KD. Our objective was to evaluate blood concentrations of BNP and NT-proBNP during the acute and subacute phases of KD. We conducted a prospective study comparing newly diagnosed KD patients to non-KD febrile controls. Blood specimens were collected at presentation, 6–12 h after intravenous immunoglobulin (IVIG) therapy, 1–2 weeks later, and 2–3 months later, or only upon reenrollment for controls. Forty-there KD and 19 control patients were enrolled consecutively. The mean age was 47.1 ± 34.3 and 62.2 ± 44.9 months, respectively (p = NS). Pre-IVIG NT-proBNP levels were significantly higher in KD patients than in controls (923.6 ± 1361.7 vs. 186.2 ± 198.0 ng/L; p < 0.001), with no statistical difference for BNP (141.9 ± 227.5 vs. 59.9 ± 72.4 ng/L; p = 0.112). In conclusion, our data indicate that NT-proBNP is a better marker of myocardial involvement in acute KD than BNP, particularly in cases with incomplete diagnostic criteria, and suggest that it may be a valid adjunctive diagnostic method to support the diagnosis of KD.

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References

  1. Albers S, Mir TS, Haddad M, Läer S (2006) N-terminal pro brain natriuretic peptide: evaluation of pediatric reference values including method comparison and interlaboratory variability. Clin Chem Lab Med 44:80–85

    Article  PubMed  CAS  Google Scholar 

  2. Anderson T, Meyer RA, Kaplan S (1985) Long-term echocardiographic evaluation of cardiac size and function in patients with Kawasaki disease. Am Heart J 110:107–115

    Article  PubMed  CAS  Google Scholar 

  3. Ayusawa M, Kanamaru H, Karasawa K, Noto N, Sumitomo N, Yamaguchi H, Izumi H, Okada T, Harada K (2002) Estimation of “selective” intravenous gamma globulin treatment indicated by Harada score. Pediatr Res 53(1):181 (abstr)

    Google Scholar 

  4. Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, Ishii M, Harada K (2005) Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 47:232–234

    Article  PubMed  Google Scholar 

  5. Belay ED, Maddox RA, Holman RC, Curns AT, Ballah K, Schonberger LB (2006) Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994–2003. Pediatr Infect Dis J 25:245–249

    Article  PubMed  Google Scholar 

  6. Burns JC, Mason WH, Glode MP, Shulman ST, Melish ME, Meissner C, Bastian J, Beiser AS, Meyerson HM, Newburger JW (1991) Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. United States Multicenter Kawasaki Disease Study Group. J Pediatr 118(5):680–686

    Article  PubMed  CAS  Google Scholar 

  7. Checchia PA, Borensztajn J, Shulman ST (2001) Circulating cardiac troponin I levels in Kawasaki disease. Pediatr Cardiol 22:102–106

    Article  PubMed  CAS  Google Scholar 

  8. Costello-Boerrigter LC, Boerrigter G, Redfield MM, Rodeheffer RJ, Urban LH, Mahoney DW, Jacobsen SJ, Heublein DM, Burnett JC (2006) Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J Am Coll Cardiol 47:345–353

    Article  PubMed  CAS  Google Scholar 

  9. Dahdah NS, Jaeggi E, Fournier A (2002) Electrocardiographic depolarization and repolarization: long-term after Kawasaki disease. Pediatr Cardiol 23(5):513–517

    Article  PubMed  CAS  Google Scholar 

  10. Dahdah N, Ibrahim R, Cannon L (2007) First recanalization of a coronary artery chronic total obstruction in an 11-year-old child with Kawasaki disease sequelae using the CROSSER catheter. Pediatr Cardiol 28(5):389–393

    Article  PubMed  CAS  Google Scholar 

  11. de Lemos JA, McGuire DK, Drazner MH (2003) B-type natriuretic peptide in cardiovascular disease. Lancet 362(9380):316–322

    Article  PubMed  CAS  Google Scholar 

  12. Fujiwara H, Hamashima Y (1978) Pathology of the heart in Kawasaki disease. Pediatrics 61(1):100–107

    PubMed  CAS  Google Scholar 

  13. Hobbs FD, Davis RC, Roalfe AK, Hare R, Davies MK, Kenkre JE (2004) Reliability of N-terminal proBNP assay in diagnosis of left ventricular dysfunction within representative and high risk population. Heart 90:866–870

    Article  PubMed  CAS  Google Scholar 

  14. Honkanen VEA, McCrindle BW, Laxer RM, Feldman BM, Schneider R, Silverman ED (2003) Clinical relevance of the risk factors for coronary artery inflammation in Kawasaki disease. Pediatr Cardiol 24:122–126

    Article  PubMed  CAS  Google Scholar 

  15. Ishii M, Ueno T, Ikeda H, Iemura M, Sugimura T, Furui J, Sugahara Y, Muta H, Akagi T, Nomura Y, Homma T, Yokoi H, Nobuyoshi M, Matsuishi T, Kato H (2000) Sequential follow-up results of catheter intervention for coronary artery lesions after Kawasaki disease: quantitative coronary artery angiography and intravascular ultrasound imaging study. Circulation 105:3004–3010

    Article  Google Scholar 

  16. Kao C, Hsieh K, Wang Y, Chen CW, Liao SQ, Wang SJ, Yeh SH (1992) Tc-99 m HMPAO labeled WBC scan for the detection of myocarditis in different phases of Kawasaki disease. Clin Nucl Med 17:185–190

    Article  PubMed  CAS  Google Scholar 

  17. Kao CH, Hsieh KS, Chen CW, Wang YL, Wang SJ, Yeh SH (1995) Labeled WBC cardiac imaging and two-dimensional echocardiography to evaluate high-dose gamma globulin treatment in Kawasaki disease. Clin Nucl Med 20:813–816

    PubMed  CAS  Google Scholar 

  18. Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, Parekh RS, Steinburger J (2006) Cardiovascular risk reduction in high-risk pediatric patients. A scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research. Circulation 114:2710–2738

    Article  PubMed  Google Scholar 

  19. Kawamura T, Wago M (2002) Brain natriuretic peptide can be a useful biochemical marker for myocarditis in patients with Kawasaki disease. Cardiol Young 12:153–158

    Article  PubMed  Google Scholar 

  20. Kawamura T, Wago M, Kawagushi H, Tahara M, Yuge M (2000) Plasma brain natriuretic peptide concentrations in patients with Kawasaki disease. Pediatr Int 42:241–248

    Article  PubMed  CAS  Google Scholar 

  21. Kawasaki T (1967) Acute febrile mucocutaneous syndrome. Jpn J Allergy 16:178–222

    CAS  Google Scholar 

  22. Kim M, Kim K (1998) Changes in cardiac troponin I in Kawasaki disease before and after treatment with intravenous gammaglobulin. Jpn Circ J 62:479–482

    Article  PubMed  CAS  Google Scholar 

  23. Kim M, Kim K (1999) Elevation of cardiac troponin I in the acute stage of Kawasaki disease. Pediatr Cardiol 20:184–188

    Article  PubMed  CAS  Google Scholar 

  24. Kurotobi S, Kawakami N, Shimizu K, Aoki H, Nasuno S, Takahashi H, Kogaki S, Ozono K (2005) Brain natriuretic peptide as a hormonal marker of ventricular diastolic dysfunction in children with Kawasaki disease. Pediatr Cardiol 26:425–430

    Article  PubMed  CAS  Google Scholar 

  25. Liu AM, Ghazizadeh M, Onouchi Z, Asano G (1999) Ultrastructural characteristics of myocardial and coronary microvascular lesions in Kawasaki disease. Microvasc Res 58:10–27

    Article  PubMed  CAS  Google Scholar 

  26. McCrindle BW, Li JS, Minich LL, Colan SD, Atz AM, Takahashi M, Vetter VL, Gersony WM, Mitchell PD, Newburger JW, for the Pediatric Heart Network Investigators (2007) Coronary artery involvement in children with Kawasaki disease risk factors from analysis of serial normalized measurements. Circulation 116:174–179

    Article  PubMed  Google Scholar 

  27. Moran AM, Newburger JW, Sanders SP, Parness IA, Spevak PJ, Burns JC, Colan SD (2000) Abnormal myocardial mechanics in Kawasaki disease: rapid response to gamma-globulin. Am Heart J 139:217–223

    PubMed  CAS  Google Scholar 

  28. Moreno N, Méndez-Echevarría A, de Inocencio J, del Castillo F, Baquero-Artiago F, García-Miguel MJ, de José MI, Aracil J (2008) Coronary involvement in infants with Kawasaki disease treated with intravenous G-globulin. Pediatr Cardiol 29(1):31–35

    Article  PubMed  Google Scholar 

  29. Mueller T, Gegenhuber A, Poelz W, Haltmayer M (2003) Comparison of the Biomedica NT-proBNP enzyme immunoassay and the Roche chemiluminescence immunoassay: implications for the prediction of symptomatic and asymptomatic structural heart disease. Clin Chem 49:976–979

    Article  PubMed  Google Scholar 

  30. Nakamura Y, Yanagawa H, Harada K, Kato H, Kawasaki T (2002) Mortality among persons with a history of Kawasaki disease in Japan: the fifth look. Arch Pediatr Adolesc Med 156(2):162–165

    PubMed  Google Scholar 

  31. Nakamura Y, Yashiro M, Uehara R, Watanabe M, Tajimi M, Oki I, Ojima T, Sonobe T, Yanagawa H (2004) Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease. Pediatr Int 46:33–38

    Article  PubMed  Google Scholar 

  32. Nakano H, Saito A, Ueda K, Nojima K (1986) Clinical and characteristics of myocardial infarction following Kawasaki disease: report of 11 cases. J Pediatr 108:198–203

    Article  PubMed  CAS  Google Scholar 

  33. Nakao K, Ogawa Y, Suga S-I, Imura H (1992) Molecular biology and biochemistry of the natriuretic peptide system. II: Natriuretic peptide receptors. J Hypertens 10:1111–1114

    Article  PubMed  CAS  Google Scholar 

  34. Newburger JW, Sanders S, Burns JC, Parness IA, Beiser AS, Colan SD (1989) Left ventricular contractility and function in Kawasaki syndrome. Effect of intravenous gammaglobulin. Circulation 79:1237–1246

    PubMed  CAS  Google Scholar 

  35. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA (2004) Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 110:2747–2771

    Article  PubMed  Google Scholar 

  36. Nir A, Bar-Oz B, Perles Z, Brooks R, Korach A, Rein A (2004) N-terminal pro-B-type natriuretic peptide: reference plasma levels from birth to adolescence: elevated levels at birth and in heart diseases. Acta Paediatr 93:603–607

    Article  PubMed  CAS  Google Scholar 

  37. Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwanchtgen L, Koch A, Falkenberg J, Mir TS (2009) NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol 30:3–8

    Article  PubMed  Google Scholar 

  38. Sonobe T, Kiyosawa N, Tsuchia K, Aso S, Imada Y, Imai Y, Yashiro M, Nakamura Y, Yanagawa H (2007) Prevalence of coronary artery abnormality in incomplete Kawasaki disease. Pediatr Int 49:421–426

    Article  PubMed  Google Scholar 

  39. Takahashi M (1989) Myocarditis in Kawasaki syndrome: a minor villain? Circulation 79:1398–1400

    PubMed  CAS  Google Scholar 

  40. Takeuchi M, Matsushita T, Kurotobi S, Sano T, Kogaki S, Ozono K (2006) Application of signal-averaged electrocardiogram to myocardial damage in the late stage of Kawasaki disease. Circ J 70(11):1443–1445

    Article  PubMed  Google Scholar 

  41. Takeuchi D, Saji T, Takatsuki S, Fujiwara M (2007) Abnormal tissue Doppler images are associated with elevated plasma brain natriuretic peptide and increased oxidative stress in acute Kawasaki disease. Circ J 71:357–362

    Article  PubMed  CAS  Google Scholar 

  42. Tseng CF, FU YC, Fu LS, Betau H, Chi CS (2001) Clinical spectrum of Kawasaki disease in infants. Zhonghua Yi Xue Za Zhi (Taipei) 64:168–173

    CAS  Google Scholar 

  43. Tsuda E, Kitamura S, Kimura K, Kobayashi J, Miyazaki S, Echigo S, Yagihara T (2002) Long-term patency of internal thoracic artery graft of coronary artery stensosis due to Kawasaki disease: comparison of early with recent results in small children. Am Heart J 153(6):995–1000

    Article  Google Scholar 

  44. Tsuda E, Kamiya T, Ono Y, Kimura K, Kurosaki K, Echigo S (2005) Incidence of stenotic lesions predicted by acute phase changes in coronary arterial diameter during Kawasaki disease. Pediatr Cardiol 26:73–79

    Article  PubMed  CAS  Google Scholar 

  45. Vanderheyden M, Bartunek J, Goethals M (2004) Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail 6(3):261–268

    Article  PubMed  CAS  Google Scholar 

  46. Wilson Tang WH (2007) B-type natriuretic peptide: a critical review. CHF 13:48–52

    Google Scholar 

  47. Yonesaka S, Takahashi T, Matubara T, Nakada T, Furukawa H, Tomimoto K, Oura H (1991) Histopathological study on Kawasaki disease with special reference to the relation between the myocardial sequellae and regional wall motion abnormalities of the left ventricle. Jpn Circ C 56:352–358

    Google Scholar 

  48. Yutani C, Go S, Kamiya T, Hirose O, Misawa H, Maeda H, Kozuka T, Onishi S (1981) Cardiac biopsy of Kawasaki disease. Arch Pathol Lab Med 105:470–473

    PubMed  CAS  Google Scholar 

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Acknowledgments

Costs of natriuretic peptide measurements were provided by Roche-Diagnostics Canada and Abbott Canada.

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Authors and Affiliations

  1. Division of Pediatric Cardiology, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, 3175 Côte Sainte-Catherine, Montréal, QC, H3T 1C5, Canada

    Nagib Dahdah, Ana Siles & Anne Fournier

  2. Department of Clinical Biochemistry, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC, Canada

    Jocelyne Cousineau & Edgard Delvin

  3. Division of Rheumatology and Immunology, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC, Canada

    Claire Saint-Cyr

  4. Department of Pediatrics, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, QC, Canada

    Linda Spiegelblatt & Yvette Bonny

  5. Hôpital de la Cité-de-la-Santé, Laval, QC, Canada

    Michèle Vartian & Martine Montigny

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  1. Nagib Dahdah
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  2. Ana Siles
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Correspondence to Nagib Dahdah.

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Dahdah, N., Siles, A., Fournier, A. et al. Natriuretic Peptide as an Adjunctive Diagnostic Test in the Acute Phase of Kawasaki Disease. Pediatr Cardiol 30, 810–817 (2009). https://doi.org/10.1007/s00246-009-9441-2

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