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Echocardiographic Parameters During and Beyond Onset of Kawasaki Disease Correlate with Onset Serum N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP)

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Abstract

The N-terminal proBNP (NT-proBNP), produced by cardiomyocytes, has several reported utilities and associations in acute Kawasaki disease (KD). The objective of this study is to examine the relationship between serum values of NT-proBNP at time of KD diagnosis with cardiac systolic, diastolic function and electrocardiographic changes, at onset of the disease and during the first year of follow-up. KD was diagnosed in 127 children between March 2007 and July 2014, mean diagnostic age 3.5 ± 2.9 years. Coronary artery maximum z score was 2.6 ± 2.8 (range − 0.6 to + 18.9), with giant aneurysm in 5/122 (4.1%). Age-adjusted NT-proBNP was 2.6 ± 1.6 z score, 78/122 (63.9%) > 2.0. There was a crescendo correlation between onset NT-proBNP z score and C-Reactive protein (CRP) serum levels (slope + 0.49, p < 0.001). There was a crescendo correlation between NT-proBNP z score and indexed left ventricular (LV) mass (slope + 1.86, p = 0.02), LV diastolic function parameter E/e′ ratio (slope + 0.31, p = 0.04) and a decrescendo correlation with age-adjusted LV shortening fraction (SF) (− 0.63, p = 0.02). Lower SF z score, higher left ventricular mass index and E/e′ ratio were associated with higher NT-proBNP z score, but without correlation with CRP levels. Within 2–3 months from the onset of the disease, there was a resolution of the systolic dysfunction. Electrocardiographic parameter changes were associated with decreased LV shortening fraction but not with NT-proBNP. KD patients with elevated NT-proBNP at onset have sub-clinical myocardial involvement and might benefit from follow-up and continued evaluation, even in the absence of coronary artery involvement.

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References

  1. Burns JC, Glode MP (2004) Kawasaki syndrome. Lancet 364(9433):533–544. https://doi.org/10.1016/S0140-6736(04)16814-1

    Article  PubMed  Google Scholar 

  2. Taubert KA, Rowley AH, Shulman ST (1991) Nationwide survey of Kawasaki disease and acute rheumatic fever. J Pediatr 119(2):279–282

    Article  CAS  Google Scholar 

  3. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E, American Heart Association Rheumatic Fever E, Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Y, Council on C, Stroke N, Council on Cardiovascular S, Anesthesia, Council on E, Prevention (2017) Diagnosis, treatment, and long-term management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation 135(17):e927–e999. https://doi.org/10.1161/CIR.0000000000000484

    Article  Google Scholar 

  4. Lin KH, Chang SS, Yu CW, Lin SC, Liu SC, Chao HY, Lee MT, Wu JY, Lee CC (2015) Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis. BMJ Open 5(4):e006703. https://doi.org/10.1136/bmjopen-2014-006703

    Article  PubMed  PubMed Central  Google Scholar 

  5. Shiraishi M, Fuse S, Mori T, Doyama A, Honjyo S, Hoshino Y, Hoshino E, Kawaguchi A, Kuroiwa Y, Hotsubo T (2013) N-terminal pro-brain natriuretic Peptide as a useful diagnostic marker of acute Kawasaki disease in children. Circ J 77(8):2097–2101

    Article  CAS  Google Scholar 

  6. McNeal-Davidson A, Fournier A, Spigelblatt L, Saint-Cyr C, Mir TS, Nir A, Dallaire F, Cousineau J, Delvin E, Dahdah N (2012) Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease. Pediatr Int 54(5):627–633. https://doi.org/10.1111/j.1442-200X.2012.03609.x

    Article  CAS  PubMed  Google Scholar 

  7. Adjagba PM, Desjardins L, Fournier A, Spigelblatt L, Montigny M, Dahdah N (2015) N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement. Cardiol Young 25(7):1311–1318. https://doi.org/10.1017/S1047951114002431

    Article  PubMed  Google Scholar 

  8. Burns JC, Shike H, Gordon JB, Malhotra A, Schoenwetter M, Kawasaki T (1996) Sequelae of Kawasaki disease in adolescents and young adults. J Am Coll Cardiol 28(1):253–257

    Article  CAS  Google Scholar 

  9. Amoozgar H, Ahmadipour M, Amirhakimi A (2013) QT dispersion and T wave peak-to-end interval dispersion in children with Kawasaki disease. Int Cardiovasc Res J 7(3):99–103

    PubMed  PubMed Central  Google Scholar 

  10. Postema PG, De Jong JS, Van der Bilt IA, Wilde AA (2008) Accurate electrocardiographic assessment of the QT interval: teach the tangent. Heart Rhythm 5(7):1015–1018. https://doi.org/10.1016/j.hrthm.2008.03.037

    Article  PubMed  Google Scholar 

  11. Kampmann C, Wiethoff CM, Wenzel A, Stolz G, Betancor M, Wippermann CF, Huth RG, Habermehl P, Knuf M, Emschermann T, Stopfkuchen H (2000) Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart 83(6):667–672. https://doi.org/10.1136/heart.83.6.667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brown H, Prescott R (2015) Applied mixed models in medicine

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

    CAS  PubMed  Google Scholar 

  14. Yutani C, Okano K, Kamiya T, Oguchi K, Kozuka T, Ota M, Onishi S (1980) Histopathological study on right endomyocardial biopsy of Kawasaki disease. Br Heart J 43(5):589–592

    Article  CAS  Google Scholar 

  15. Liu AM, Ghazizadeh M, Onouchi Z, Asano G (1999) Ultrastructural characteristics of myocardial and coronary microvascular lesions in Kawasaki disease. Microvasc Res 58(1):10–27. https://doi.org/10.1006/mvre.1999.2155

    Article  CAS  PubMed  Google Scholar 

  16. Takahashi K, Oharaseki T, Yokouchi Y (2018) Histopathological aspects of cardiovascular lesions in Kawasaki disease. Int J Rheum Dis 21(1):31–35. https://doi.org/10.1111/1756-185X.13207

    Article  CAS  PubMed  Google Scholar 

  17. Frank B, Davidson J, Tong S, Martin B, Heizer H, Anderson MS, Glode MP, Dominguez SR, Jone PN (2016) Myocardial strain and strain rate in Kawasaki disease: range, recovery, and relationship to systemic inflammation/coronary artery dilation. J Clin Exp Cardiol 7(4):432. https://doi.org/10.4172/2155-9880.1000432

    Article  Google Scholar 

  18. Mavrogeni S, Papadopoulos G, Hussain T, Chiribiri A, Botnar R, Greil GF (2013) The emerging role of cardiovascular magnetic resonance in the evaluation of Kawasaki disease. Int J Cardiovasc Imaging 29(8):1787–1798. https://doi.org/10.1007/s10554-013-0276-9

    Article  PubMed  Google Scholar 

  19. Mavrogeni S, Papadopoulos G, Karanasios E, Cokkinos DV (2009) Cardiovascular magnetic resonance imaging reveals myocardial inflammation and coronary artery ectasia during the acute phase of Kawasaki disease. Int J Cardiol 136(3):e51–53. https://doi.org/10.1016/j.ijcard.2008.05.005

    Article  CAS  PubMed  Google Scholar 

  20. Printz BF, Sleeper LA, Newburger JW, Minich LL, Bradley T, Cohen MS, Frank D, Li JS, Margossian R, Shirali G, Takahashi M, Colan SD, Pediatric Heart Network I (2011) Noncoronary cardiac abnormalities are associated with coronary artery dilation and with laboratory inflammatory markers in acute Kawasaki disease. J Am Coll Cardiol 57(1):86–92. https://doi.org/10.1016/j.jacc.2010.08.619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hsu HB, Fu YC, Tsai SC, Yen RF, Hwang B (2003) Usefulness of Tc-99m HMPAO-labeled WBC heart scan to predict impaired ventricular function and coronary artery dilation in children with Kawasaki disease. Int J Cardiol 92(1):65–69

    Article  Google Scholar 

  22. Anderson TM, Meyer RA, Kaplan S (1985) Long-term echocardiographic evaluation of cardiac size and function in patients with Kawasaki disease. Am Heart J 110(1 Pt 1):107–115

    Article  CAS  Google Scholar 

  23. Newburger JW, Sanders SP, Burns JC, Parness IA, Beiser AS, Colan SD (1989) Left ventricular contractility and function in Kawasaki syndrome. Effect Intraven Gamma Globul Circ 79(6):1237–1246

    CAS  Google Scholar 

  24. 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(2 Pt 1):217–223

    CAS  PubMed  Google Scholar 

  25. Bratis K, Hachmann P, Child N, Krasemann T, Hussain T, Mavrogeni S, Botnar R, Razavi R, Greil G (2017) Cardiac magnetic resonance feature tracking in Kawasaki disease convalescence. Ann Pediatr Cardiol 10(1):18–25. https://doi.org/10.4103/0974-2069.197046

    Article  PubMed  PubMed Central  Google Scholar 

  26. Xu QQ, Ding YY, Lv HT, Zhou WP, Sun L, Huang J, Yan WH (2014) Evaluation of left ventricular systolic strain in children with Kawasaki disease. Pediatr Cardiol 35(7):1191–1197. https://doi.org/10.1007/s00246-014-0915-5

    Article  PubMed  Google Scholar 

  27. Yu JJ, Kwak BO, Jeon YH, Park YM, Lee R, Chung S, Bae SH, Pyun BY (2009) Elevation of the index of left ventricular mass during the acute and subacute phase of Kawasaki disease, and its association with indexes of diastolic function. Cardiol Young 19(1):64–69. https://doi.org/10.1017/S1047951108003405

    Article  PubMed  Google Scholar 

  28. Azak E, Cetin II, Gursu HA, Kibar AE, Surucu M, Orgun A, Pamuk U (2018) Recovery of myocardial mechanics in Kawasaki disease demonstrated by speckle tracking and tissue Doppler methods. Echocardiography 35(3):380–387. https://doi.org/10.1111/echo.13773

    Article  PubMed  Google Scholar 

  29. Selamet Tierney ES, Newburger JW, Graham D, Baker A, Fulton DR, Colan SD (2011) Diastolic function in children with Kawasaki disease. Int J Cardiol 148(3):309–312. https://doi.org/10.1016/j.ijcard.2009.11.014

    Article  PubMed  Google Scholar 

  30. Kurotobi S, Kawakami N, Shimizu K, Aoki H, Nasuno S, Takahashi K, Kogaki S, Ozono K (2005) Brain natriuretic peptide as a hormonal marker of ventricular diastolic dysfunction in children with Kawasaki disease. Pediatr Cardiol 26(4):425–430. https://doi.org/10.1007/s00246-004-0812-4

    Article  CAS  PubMed  Google Scholar 

  31. Sornsin S (1987) First degree atrioventricular block. J Emerg Med 5(1):29–34. https://doi.org/10.1016/0736-4679(87)90007-2

    Article  CAS  PubMed  Google Scholar 

  32. Dahdah NS, Jaeggi E, Fournier A (2002) Electrocardiographic depolarization and repolarization: long-term after Kawasaki disease. Pediatr Cardiol 23(5):513–517. https://doi.org/10.1007/s00246-001-0072-5

    Article  CAS  PubMed  Google Scholar 

  33. Sumitomo N, Karasawa K, Taniguchi K, Ichikawa R, Fukuhara J, Abe O, Miyashita M, Kanamaru H, Ayusawa M, Harada K (2008) Association of sinus node dysfunction, atrioventricular node conduction abnormality and ventricular arrhythmia in patients with Kawasaki disease and coronary involvement. Circ J 72(2):274–280

    Article  Google Scholar 

  34. Ichida F, Fatica NS, O'Loughlin JE, Snyder MS, Ehlers KH, Engle MA (1988) Correlation of electrocardiographic and echocardiographic changes in Kawasaki syndrome. Am Heart J 116(3):812–819

    Article  CAS  Google Scholar 

  35. Chung KJ, Fulton DR, Lapp R, Spector S, Sahn DJ (1988) One-year follow-up of cardiac and coronary artery disease in infants and children with Kawasaki disease. Am Heart J 115(6):1263–1267

    Article  CAS  Google Scholar 

  36. Higham PD, Furniss SS, Campbell RW (1995) QT dispersion and components of the QT interval in ischaemia and infarction. Br Heart J 73(1):32–36

    Article  CAS  Google Scholar 

  37. Osada M, Tanaka Y, Komai T, Maeda Y, Kitano M, Komori S, Tamura K, Sugiyama H, Yanai J, Nakazawa S (1999) Coronary arterial involvement and QT dispersion in Kawasaki disease. Am J Cardiol 84(4):466–468

    Article  CAS  Google Scholar 

  38. Reddy S, Rai M, Singh Chouhan RR, Rao S, Kamath N (2018) Electrocardiographic analysis of repolarization changes in South Indian children with Kawasaki disease after the acute phase of illness. Int J Pediatr 2018:1062154. https://doi.org/10.1155/2018/1062154

    Article  PubMed  PubMed Central  Google Scholar 

  39. Orenstein JM, Shulman ST, Fox LM, Baker SC, Takahashi M, Bhatti TR, Russo PA, Mierau GW, de Chadarevian JP, Perlman EJ, Trevenen C, Rotta AT, Kalelkar MB, Rowley AH (2012) Three linked vasculopathic processes characterize Kawasaki disease: a light and transmission electron microscopic study. PLoS ONE 7(6):e38998. https://doi.org/10.1371/journal.pone.0038998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dionne A, Dahdah N (2018) Myocarditis and Kawasaki disease. Int J Rheum Dis 21(1):45–49. https://doi.org/10.1111/1756-185X.13219

    Article  PubMed  Google Scholar 

  41. Weber MA, Ashworth MT, Risdon RA, Malone M, Burch M, Sebire NJ (2008) Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series. Arch Dis Child 93(7):594–598. https://doi.org/10.1136/adc.2007.128686

    Article  CAS  PubMed  Google Scholar 

  42. Kitulwatte ID, Kim PJ, Pollanen MS (2010) Sudden death related myocarditis: a study of 56 cases. Forensic Sci Med Pathol 6(1):13–19. https://doi.org/10.1007/s12024-009-9125-5

    Article  PubMed  Google Scholar 

  43. Phillips M, Robinowitz M, Higgins JR, Boran KJ, Reed T, Virmani R (1986) Sudden cardiac death in Air Force recruits. A 20-year review. JAMA 256(19):2696–2699

    Article  CAS  Google Scholar 

  44. Grun S, Schumm J, Greulich S, Wagner A, Schneider S, Bruder O, Kispert EM, Hill S, Ong P, Klingel K, Kandolf R, Sechtem U, Mahrholdt H (2012) Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery. J Am Coll Cardiol 59(18):1604–1615. https://doi.org/10.1016/j.jacc.2012.01.007

    Article  PubMed  Google Scholar 

  45. Maron BJ, Udelson JE, Bonow RO, Nishimura RA, Ackerman MJ, Estes NA 3rd, Cooper LT Jr., Link MS, Maron MS, American Heart Association E, Arrhythmias Committee of Council on Clinical Cardiology CoCDiYCoC, Stroke Nursing CoFG, Translational B, American College of C (2015) Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology. Circulation 132(22):e273–280. https://doi.org/10.1161/CIR.0000000000000239

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Cardiology, CHU Mère-Enfant Ste-Justine, Université de Montréal, 3175, Côte Sainte-Catherine, Montréal, QC, H3T 1C5, Canada

    Laurent Desjardins, Audrey Dionne, Léamarie Meloche-Dumas, Anne Fournier & Nagib Dahdah

  2. Division of Pediatric Cardiology, IWK Health Centre, Dalhousie University, Halifax, NS, Canada

    Laurent Desjardins

  3. Division of Pediatric Cardiology, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Audrey Dionne

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Desjardins, L., Dionne, A., Meloche-Dumas, L. et al. Echocardiographic Parameters During and Beyond Onset of Kawasaki Disease Correlate with Onset Serum N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP). Pediatr Cardiol 41, 947–954 (2020). https://doi.org/10.1007/s00246-020-02340-z

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