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Comparison Between Currently Recommended Long-Term Medical Management of Coronary Artery Aneurysms After Kawasaki Disease and Actual Reported Management in the Last Two Decades

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Abstract

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was “indicated.” Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2–25% for RL 5, and 0–5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

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References

  1. Kato H, Sugimura T, Akagi T, Sato N, Hashino K, Maeno Y, Kazue T, Eto G, Yamakawa R (1996) Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation 94:1379–1385

    Article  CAS  Google Scholar 

  2. McCrindle BW (2009) Kawasaki disease: a childhood disease with important consequences into adulthood. Circulation 120:6–8

    Article  Google Scholar 

  3. 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 28:253–257

    Article  CAS  Google Scholar 

  4. 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 (2017) Diagnosis, treatment, and long-term management of kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation 135:e927–e999

    Article  Google Scholar 

  5. 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  Google Scholar 

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

    Article  Google Scholar 

  7. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42:377–381

    Article  Google Scholar 

  8. Takahashi M, Mason W (1986) Kawasaki syndrome, Reye syndrome, and aspirin. Pediatrics 77:616–617

    CAS  PubMed  Google Scholar 

  9. Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL, Diaz R, Commerford PJ, Valentin V, Yusuf S, Clopidogrel in Unstable angina to prevent Recurrent Events Trial I (2003) Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 108:1682–1687

    Article  CAS  Google Scholar 

  10. Suda K, Kudo Y, Higaki T, Nomura Y, Miura M, Matsumura M, Ayusawa M, Ogawa S, Matsuishi T (2009) Multicenter and retrospective case study of warfarin and aspirin combination therapy in patients with giant coronary aneurysms caused by Kawasaki disease. Circ J 73:1319–1323

    Article  CAS  Google Scholar 

  11. Suda K, Tahara N, Honda A, Yoshimoto H, Kishimoto S, Kudo Y, Kaida H, Abe T, Ueno T, Fukumoto Y (2015) Statin reduces persistent coronary arterial inflammation evaluated by serial (1)(8)fluorodeoxyglucose positron emission tomography imaging long after Kawasaki disease. Int J Cardiol 179:61–62

    Article  Google Scholar 

  12. Bekki M, Tahara N, Tahara A, Honda A, Igata S, Sugiyama Y, Nakamura T, Sun J, Kurata S, Fujimoto K, Abe T, Tanaka H, Suda K, Fukumoto Y (2018) Anti-inflammatory effect of statin in coronary aneurysms late after Kawasaki disease. J Nucl Cardiol 26:671

    Article  Google Scholar 

  13. Hamaoka A, Hamaoka K, Yahata T, Fujii M, Ozawa S, Toiyama K, Nishida M, Itoi T (2010) Effects of HMG-CoA reductase inhibitors on continuous post-inflammatory vascular remodeling late after Kawasaki disease. J Cardiol 56:245–253

    Article  Google Scholar 

  14. Huang SM, Weng KP, Chang JS, Lee WY, Huang SH, Hsieh KS (2008) Effects of statin therapy in children complicated with coronary arterial abnormality late after Kawasaki disease: a pilot study. Circ J 72:1583–1587

    Article  CAS  Google Scholar 

  15. Duan C, Du ZD, Wang Y, Jia LQ (2014) Effect of pravastatin on endothelial dysfunction in children with medium to giant coronary aneurysms due to Kawasaki disease. World J Pediatr 10:232–237

    Article  CAS  Google Scholar 

  16. Niedra E, Chahal N, Manlhiot C, Yeung RS, McCrindle BW (2014) Atorvastatin safety in Kawasaki disease patients with coronary artery aneurysms. Pediatr Cardiol 35:89–92

    Article  Google Scholar 

  17. He M, Chen Z, Martin M, Zhang J, Sangwung P, Woo B, Tremoulet AH, Shimizu C, Jain MK, Burns JC, Shyy JY (2017) miR-483 targeting of CTGF suppresses endothelial-to-mesenchymal transition: therapeutic implications in kawasaki disease. Circ Res 120:354–365

    Article  CAS  Google Scholar 

  18. Manlhiot C, Brandao LR, Somji Z, Chesney AL, MacDonald C, Gurofsky RC, Sabharwal T, Chahal N, McCrindle BW (2010) Long-term anticoagulation in Kawasaki disease: Initial use of low molecular weight heparin is a viable option for patients with severe coronary artery abnormalities. Pediatr Cardiol 31:834–842

    Article  Google Scholar 

  19. Manlhiot C, Newburger JW, Low T, Dahdah N, Mackie AS, Raghuveer G, Giglia TM, Dallaire F, Mathew M, Runeckles K, Pahl E, Harahsheh AS, Norozi K, de Ferranti SD, Friedman K, Yetman AT, Kutty S, Mondal T, McCrindle BW et al (2020) Low-molecular-weight heparin vs warfarin for thromboprophylaxis in children with coronary artery aneurysms after Kawasaki disease: a pragmatic registry trial. Can J Cardiol 36:1598

    Article  Google Scholar 

  20. Teitel DF, Newburger JW, Sutton N, Tani LY, Harahsheh AS, Jone PN, Mensch DJ, Cotts T, Davidson A, Dahdah N, Johnson WH Jr, Portman MA (2020) Development and utility of quality metrics for ambulatory pediatric cardiology in Kawasaki disease. Clin Pediatr 59:245–251

    Article  Google Scholar 

  21. Harahsheh AS, Hom LA, Clauss SB, Cross RR, Curtis AR, Steury RD, Mitchell SJ, Martin GR (2016) The impact of a designated cardiology team involving telemedicine home monitoring on the care of children with single-ventricle physiology after norwood palliation. Pediatr Cardiol 37:899–912

    Article  Google Scholar 

Download references

Acknowledgements

The International Kawasaki Disease Registry (IKDR) is grateful for the hard work of the multiple research coordinators, research nurses, and students who collected the data for this registry across all participating centers. The IKDR specifically wishes to thanks: Annette L. Baker (Boston Children’s Hospital), Tanveer Collins (The Hospital for Sick Children, Toronto), Amy Cooper (Nationwide Children’s Hospital), Sarah D. De Ferranti (Boston Children’s Hospital), Catherine Dimes (Nationwide Children’s Hospital), Anne Fournier (CHU Ste-Justine, Montreal), Kevin G. Friedman (Boston Children’s Hospital), Patrick Gould (Boston Children’s Hospital), Michelle M. Grcic (Nationwide Children’s Hospital), Sunita O’Shea (The Hospital for Sick Children, Toronto), Craig A. Sable (Children’s National Medical Centre, Washington), Sam Sabouni (Children’s National Medical Centre, Washington), and Devin D. Tinker (Cincinnati Children’s Hospital Medical Centre).

International Kawasaki Disease Registry Carolyn A. Altman MD18, Brett R. Anderson MD19, Carolyn E. Boychuk BSc6, Elizabeth Braunlin MD PhD20, Michael R. Carr MD21, Jessica H. Colyer MD9, Adam Dempsey PhD11, Laurent Desjardins MD7, Anna Ferris MBBS19, Michael Gewitz MD13, Steven C. Greenway MD22, Kevin C. Harris MD MHSc23, Kevin D. Hill MD24, Pei-Ni Jone MD25, Thomas R. Kimball MD26, Shelby Kutty MD PhD8, Lillian Lai MHA MD27, Sean M. Lang MD26, Simon Lee MD28, Jennifer S. Li MD MHS24, Ming-Tai Lin MD PhD29, William T. Mahle MD30, Kimberly E. McHugh MD31, Kimberly Myers MD22, Elfriede Pahl MD21, Claudia Renaud MD32, S. Kristen Sexson Tejitel MD PhD MPH18, Karen M. Texter MD28, Deepika Thacker MD33, Elif Seda Selamet Tierney MD34, Adriana H. Tremoulet MD MAS12, Sharon Wagner-Lees RN-BC BSN MBA16, Kenny K. Wong MD35, Mei-Hwan Wu MD PhD29. 18Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA. 19Columbia University - College of Physicians and Surgeons, New York, New York, USA. 20University of Minnesota, Minneapolis, Minnesota, USA. 21Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA. 22Alberta Children's Hospital, Calgary, Alberta, Canada. 23Children's Heart Centre, University of British Columbia, Vancouver, British Columbia, Canada. 24Duke University Medical Center, Durham, North Carolina, USA. 25Pediatric Cardiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA. 26Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA. 27Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada. 28The Heart Center at Nationwide Children's Hospital, Columbus, Ohio, USA. 29National Taiwan University, Taipei, Taiwan. 30Children's Healthcare of Atlanta, Atlanta, Georgia, USA. 31Medical University of South Carolina, Charleston, South Carolina, USA. 32Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada. 33Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital For Children, New Castle County, Delaware, USA. 34Department of Pediatrics, Division of Pediatric Cardiology, Stanford University, School of Medicine, Palo Alto, California, USA. 35IWK Health Centre, Halifax, Nova Scotia, Canada.

Funding

There was no Grant funding for this study. Funding for the data coordinating center was partially provided by the CIBC Childrens Foundation Chair in Child Health Research (Brian McCrindle) and the Labatt Family Heart Centre at SickKids Hospital (Brian McCrindle). Additional local funding for participation in the International Kawasaki Disease Registry (IKDR) was provided by les Fonds BoBeau Coeur of the Ste-Justine Hospital Foundation (Nagib Dahdah), the McCance Family Foundation (Jane Newburger), and the Vella Fund (Jane Newburger).

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Authors and Affiliations

  1. Division of Cardiology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Jonathon Osborne, Kyle Runeckles, Tisiana Low, Mathew Mathew & Brian W. McCrindle

  2. Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Kevin Friedman & Jane W. Newburger

  3. Children’s Hospital at Montefiore, New York, NY, USA

    Nadine F. Choueiter

  4. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Therese M. Giglia

  5. Centre de Recherche du Centre Hospitalier, Universitaire de Sherbrooke, Sherbrooke, QC, Canada

    Frederic Dallaire

  6. Stollery Children’s Hospital, Edmonton, AB, Canada

    Andrew S. Mackie

  7. Division of Pediatric Cardiology, Centre Hospitalier Universitaire Ste-Justine, University of Montreal, Montreal, QC, Canada

    Nagib Dahdah

  8. Children’s Hospital & Medical Center of Omaha, Omaha, NE, USA

    Anji T. Yetman

  9. Pediatrics - Cardiology, Children’s National Hospital/George Washington University School of Medicine, Washington, DC, USA

    Ashraf S. Harahsheh

  10. Children’s Mercy Hospital, Kansas City, MO, USA

    Geetha Raghuveer

  11. Department of Paediatrics, Western University, London, ON, Canada

    Kambiz Norozi

  12. Department of Pediatrics, University of California San Diego, Rady Children’s Hospital-San Diego, San Diego, CA, USA

    Jane C. Burns

  13. Maria Fareri Children’s Hospital at Westchester Medical Center (WMC) Health, New York Medical College, Valhalla, NY, USA

    Supriya Jain

  14. McMaster Children’s Hospital, Hamilton, ON, Canada

    Tapas Mondal

  15. Seattle Children’s Research Institute, Seattle, WA, USA

    Michael A. Portman

  16. Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    Jacqueline R. Szmuszkovicz

  17. Toronto General Hospital, Toronto, ON, Canada

    Andrew Crean

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  1. Jonathon Osborne
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  22. Brian W. McCrindle
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Consortia

for the International Kawasaki Disease Registry

  • Carolyn A. Altman
  • , Brett R. Anderson
  • , Carolyn E. Boychuk
  • , Elizabeth Braunlin
  • , Michael R. Carr
  • , Jessica H. Colyer
  • , Adam Dempsey
  • , Laurent Desjardins
  • , Anna Ferris
  • , Michael Gewitz
  • , Steven C. Greenway
  • , Kevin C. Harris
  • , Kevin D. Hill
  • , Pei-Ni Jone
  • , Thomas R. Kimball
  • , Shelby Kutty
  • , Lillian Lai
  • , Sean M. Lang
  • , Simon Lee
  • , Ming-Tai Lin
  • , William T. Mahle
  • , Kimberly E. McHugh
  • , Kimberly Myers
  • , Elfriede Pahl
  • , Claudia Renaud
  • , Karen M. Texter
  • , Deepika Thacker
  • , Elif Seda Selamet Tierney
  • , Adriana H. Tremoulet
  • , Sharon Wagner-Lees
  • , Kenny K. Wong
  •  & Mei-Hwan Wu

Corresponding author

Correspondence to Brian W. McCrindle.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All sites obtained local Research Ethics Board approval for the study, and all data were collected under a waiver of consent for retrospective research as approved by each site’s Research Ethics Board. All procedures performed 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.

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Members of the study group International Kawasaki Disease Registry are listed in Acknowledgements section.

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Osborne, J., Friedman, K., Runeckles, K. et al. Comparison Between Currently Recommended Long-Term Medical Management of Coronary Artery Aneurysms After Kawasaki Disease and Actual Reported Management in the Last Two Decades. Pediatr Cardiol 42, 676–684 (2021). https://doi.org/10.1007/s00246-020-02529-2

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  • DOI: https://doi.org/10.1007/s00246-020-02529-2

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