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Noninvasive quantification of coronary endothelial function by SPECT imaging in children with a history of Kawasaki disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The feasibility of coronary function estimation by single photon emission computed tomography (SPECT) has been recently demonstrated. The aim of this study was to apply SPECT imaging in patients with previous Kawasaki disease (KD) to assess the coronary functional status at long-term follow-up of the acute phase of the disease.

Methods

Sixteen children with a history of KD underwent 99mTc-sestamibi imaging at rest and during the cold pressor test (CPT). Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Coronary endothelial function was expressed as the ratio of the CPT to rest MBF.

Results

Six KD patients without coronary artery lesions served as controls and ten with coronary artery aneurysms during the acute phase of the disease were separated into two groups: group 1 (n = 4) with regressed and group 2 (n = 6) with persistent aneurysm at follow-up. The estimated coronary endothelial function was higher in controls compared to patients with coronary artery aneurysms (2.5 ± 0.3 vs 1.7 ± 0.7, p < 0.05). A significant difference in coronary endothelial function among groups was found (F = 5.21, p < 0.02). Coronary endothelial function was higher in patients of group 1 than in those of group 2 (1.9 ± 0.6 vs 1.4 ± 0.7, p < 0.02).

Conclusion

SPECT may be applied as a noninvasive method for assessing coronary vascular function in children with a history of KD, demonstrating an impaired response to the CPT, an endothelial-dependent vasodilator stimulus. These findings reinforce the concept that coronary endothelial dysfunction may represent a long-term sequela of KD.

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References

  1. Burns JC, Shike H, Gordon JB, Malhotra A, Schoenwetter M, Kawasaki T. Sequelae of Kawasaki disease in adolescents and young adults. J Am Coll Cardiol 1996;28:253–7.

    Article  CAS  PubMed  Google Scholar 

  2. Burns JC, Glodé MP. Kawasaki syndrome. Lancet 2004;364:533–44.

    Article  PubMed  Google Scholar 

  3. Kato H, Sugimura T, Akagi T, Sato N, Hashino K, Maeno Y, et al. Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation 1996;94:1379–85.

    CAS  PubMed  Google Scholar 

  4. Ishiwata S, Fuse K, Nishiyama S, Nakanishi S, Watanabe Y, Seki A. Adult coronary artery disease secondary to Kawasaki disease in childhood. Am J Cardiol 1992;69:692–4.

    Article  CAS  PubMed  Google Scholar 

  5. Kato H, Inoue O, Kawasaki T, Fujiwara H, Watanabe T, Toshima H. Adult coronary artery disease probably due to childhood Kawasaki disease. Lancet 1992;340:1127–9.

    Article  CAS  PubMed  Google Scholar 

  6. Sugimura T, Kato H, Inoue O, Takagi J, Fukuda T, Sato N. Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate. J Pediatr 1992;121:684–8.

    Article  CAS  PubMed  Google Scholar 

  7. Mitani Y, Okuda Y, Shimpo H, Uchida F, Hamanaka K, Aoki K, et al. Impaired endothelial function in epicardial coronary arteries after Kawasaki disease. Circulation 1997;96:454–61.

    CAS  PubMed  Google Scholar 

  8. Yamakawa R, Ishii M, Sugimura T, Akagi T, Eto G, Iemura M, et al. Coronary endothelial dysfunction after Kawasaki disease: evaluation by intracoronary injection of acetylcholine. J Am Coll Cardiol 1998;31:1074–80.

    Article  CAS  PubMed  Google Scholar 

  9. Iemura M, Ishii M, Sugimura T, Akagi T, Kato H. Long term consequences of regressed coronary aneurysms after Kawasaki disease: vascular wall morphology and function. Heart 2000;83:307–11.

    Article  CAS  PubMed  Google Scholar 

  10. Furuyama H, Odagawa Y, Katoh C, Iwado Y, Yoshinaga K, Ito Y, et al. Assessment of coronary function in children with a history of Kawasaki disease using (15)O-water positron emission tomography. Circulation 2002;105:2878–84.

    Article  PubMed  Google Scholar 

  11. Furuyama H, Odagawa Y, Katoh C, Iwado Y, Ito Y, Noriyasu K, et al. Altered myocardial flow reserve and endothelial function late after Kawasaki disease. J Pediatr 2003;142:149–54.

    Article  PubMed  Google Scholar 

  12. Cicala S, Galderisi M, Grieco M, Lamberti A, Cosimi R, Pellegrini F, et al. Transthoracic echo-Doppler assessment of coronary microvascular function late after Kawasaki disease. Pediatr Cardiol 2008;29:321–7.

    Article  CAS  PubMed  Google Scholar 

  13. Taki J, Fujino S, Nakajima K, Matsunari I, Okazaki H, Saga T, et al. (99m)Tc-sestamibi retention characteristics during pharmacologic hyperemia in human myocardium: comparison with coronary flow reserve measured by Doppler flowire. J Nucl Med 2001;42:1457–63.

    CAS  PubMed  Google Scholar 

  14. Sugihara H, Yonekura Y, Kataoka K, Fukai D, Kitamura N, Taniguchi Y. Estimation of coronary flow reserve with the use of dynamic planar and SPECT images of Tc-99m tetrofosmin. J Nucl Cardiol 2001;8:575–9.

    Article  CAS  PubMed  Google Scholar 

  15. Ito Y, Katoh C, Noriyasu K, Kuge Y, Furuyama H, Morita K, et al. Estimation of myocardial blood flow and myocardial flow reserve by 99mTc-sestamibi imaging: comparison with the results of [15O]H2O PET. Eur J Nucl Med Mol Imaging 2003;30:281–7.

    Article  CAS  PubMed  Google Scholar 

  16. Petretta M, Soricelli A, Storto G, Cuocolo A. Assessment of coronary flow reserve using single photon emission computed tomography with technetium 99m-labeled tracers. J Nucl Cardiol 2008;15:456–65.

    Article  PubMed  Google Scholar 

  17. Storto G, Soricelli A, Pellegrino T, Petretta M, Cuocolo A. Assessment of the arterial input function for estimation of coronary flow reserve by single photon emission computed tomography: comparison of two different approaches. Eur J Nucl Med Mol Imaging 2009;36:2034–41.

    Article  Google Scholar 

  18. de Zorzi A, Colan SD, Gauvreau K, Baker AL, Sundel RP, Newburger JW. Coronary artery dimensions may be misclassified as normal in Kawasaki disease. J Pediatr 1998;133:254–8.

    Article  PubMed  Google Scholar 

  19. Kurotobi S, Nagai T, Kawakami N, Sano T. Coronary diameter in normal infants, children and patients with Kawasaki disease. Pediatr Int 2002;44:1–4.

    Article  PubMed  Google Scholar 

  20. Japanese Circulation Society Joint Research Group. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease. Pediatr Int 2005;47:711–32.

    Article  Google Scholar 

  21. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. 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. Pediatrics 2004;114:1708–33.

    Article  PubMed  Google Scholar 

  22. Iida H, Kanno I, Takahashi A, Miura S, Murakami M, Takahashi K, et al. Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect. Circulation 1988;78:104–15.

    CAS  PubMed  Google Scholar 

  23. Bergmann SR, Herrero P, Markham J, Weinheimer CJ, Walsh MN. Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. J Am Coll Cardiol 1989;14:639–52.

    Article  CAS  PubMed  Google Scholar 

  24. Araujo LI, Lammertsma AA, Rhodes CG, McFalls EO, Iida H, Rechavia E, et al. Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. Circulation 1991;83:875–85.

    CAS  PubMed  Google Scholar 

  25. Noto N, Karasawa K, Kanamaru H, Ayusawa M, Sumitomo N, Okada T, et al. Non-invasive measurement of coronary flow reserve in children with Kawasaki disease. Heart 2002;87:559–65.

    Article  CAS  PubMed  Google Scholar 

  26. Storto G, Cirillo P, Vicario ML, Pellegrino T, Sorrentino AR, Petretta M, et al. Estimation of coronary flow reserve by Tc-99m sestamibi imaging in patients with coronary artery disease: comparison with the results of intracoronary Doppler technique. J Nucl Cardiol 2004;11:682–8.

    Article  PubMed  Google Scholar 

  27. Marini C, Bezante G, Gandolfo P, Modonesi E, Morbelli SD, Depascale A, et al. Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes. Eur J Nucl Med Mol Imaging 2010;37:357–67.

    Article  PubMed  Google Scholar 

  28. Iwado Y, Yoshinaga K, Furuyama H, Ito Y, Noriyasu K, Katoh C, et al. Decreased endothelium-dependent coronary vasomotion in healthy young smokers. Eur J Nucl Med Mol Imaging 2002;29:984–90.

    Article  CAS  PubMed  Google Scholar 

  29. Zeiher AM, Drexler H, Wollschläger H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991;84:1984–92.

    CAS  PubMed  Google Scholar 

  30. Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol 1989;14:1181–90.

    Article  CAS  PubMed  Google Scholar 

  31. Hamaoka K, Onouchi Z, Kamiya Y, Sakata K. Evaluation of coronary flow velocity dynamics and flow reserve in patients with Kawasaki disease by means of a Doppler guide wire. J Am Coll Cardiol 1998;31:833–40.

    Article  CAS  PubMed  Google Scholar 

  32. Hauser M, Bengel F, Kuehn A, Nekolla S, Kaemmerer H, Schwaiger M, et al. Myocardial blood flow and coronary flow reserve in children with “normal” epicardial coronary arteries after the onset of Kawasaki disease assessed by positron emission tomography. Pediatr Cardiol 2004;25:108–12.

    Article  CAS  PubMed  Google Scholar 

  33. Suzuki A, Miyagawa-Tomita S, Komatsu K, Nishikawa T, Sakomura Y, Horie T, et al. Active remodeling of the coronary arterial lesions in the late phase of Kawasaki disease: immunohistochemical study. Circulation 2000;101:2935–41.

    CAS  PubMed  Google Scholar 

  34. Suzuki A, Miyagawa-Tomita S, Komatsu K, Nakazawa M, Fukaya T, Baba K, et al. Immunohistochemical study of apparently intact coronary artery in a child after Kawasaki disease. Pediatr Int 2004;46:590–6.

    Article  PubMed  Google Scholar 

  35. Fujiwara T, Fujiwara H, Nakano H. Pathological features of coronary arteries in children with Kawasaki disease in which coronary arterial aneurysm was absent at autopsy. Quantitative analysis. Circulation 1988;78:345–50.

    CAS  PubMed  Google Scholar 

  36. Masuda H, Kanda M, Naoe S, Tanaka N. Coronary artery lesions after Kawasaki disease: assessment of the intramural coronary vessels. Clin Immunol 1982;14:441–50.

    Google Scholar 

  37. Suzuki A, Yamagishi M, Kimura K, Sugiyama H, Arakaki Y, Kamiya T, et al. Functional behavior and morphology of the coronary artery wall in patients with Kawasaki disease assessed by intravascular ultrasound. J Am Coll Cardiol 1996;27:291–6.

    Article  CAS  PubMed  Google Scholar 

  38. Schindler TH, Zhang XL, Prior JO, Cadenas J, Dahlbom M, Sayre J, et al. Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with (13)N-ammonia and PET. Eur J Nucl Med Mol Imaging 2007;34:1178–88.

    Article  PubMed  Google Scholar 

  39. Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al. Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET. J Nucl Med 2006;47:1420–6.

    PubMed  Google Scholar 

  40. Jacobs F, Thierens H, Piepsz A, Bacher K, Van de Wiele C, Ham H, et al. Optimized tracer-dependent dosage cards to obtain weight-independent effective doses. Eur J Nucl Med Mol Imaging 2005;32:581–8.

    Article  CAS  PubMed  Google Scholar 

  41. Capannari TE, Daniels SR, Meyer RA, Schwartz DC, Kaplan S. Sensitivity, specificity and predictive value of two-dimensional echocardiography in detecting coronary artery aneurysms in patients with Kawasaki disease. J Am Coll Cardiol 1986;7:355–60.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Alberto Cuocolo.

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Cicala, S., Pellegrino, T., Storto, G. et al. Noninvasive quantification of coronary endothelial function by SPECT imaging in children with a history of Kawasaki disease. Eur J Nucl Med Mol Imaging 37, 2249–2255 (2010). https://doi.org/10.1007/s00259-010-1575-1

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  • DOI: https://doi.org/10.1007/s00259-010-1575-1

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