Skip to main content
SpringerLink
Log in

Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Kawasaki disease (KD) is the leading cause of acquired heart disease in children and can result in life-threatening coronary artery aneurysms in up to 25 % of patients. These aneurysms put patients at risk of thrombus formation, myocardial infarction, and sudden death. Clinicians must therefore decide which patients should be treated with anticoagulant medication, and/or surgical or percutaneous intervention. Current recommendations regarding initiation of anticoagulant therapy are based on anatomy alone with historical data suggesting that patients with aneurysms \(\ge \)8 mm are at greatest risk of thrombosis. Given the multitude of variables that influence thrombus formation, we postulated that hemodynamic data derived from patient-specific simulations would more accurately predict risk of thrombosis than maximum diameter alone. Patient-specific blood flow simulations were performed on five KD patients with aneurysms and one KD patient with normal coronary arteries. Key hemodynamic and geometric parameters, including wall shear stress, particle residence time, and shape indices, were extracted from the models and simulations and compared with clinical outcomes. Preliminary fluid structure interaction simulations with radial expansion were performed, revealing modest differences in wall shear stress compared to the rigid wall case. Simulations provide compelling evidence that hemodynamic parameters may be a more accurate predictor of thrombotic risk than aneurysm diameter alone and motivate the need for follow-up studies with a larger cohort. These results suggest that a clinical index incorporating hemodynamic information be used in the future to select patients for anticoagulant therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Bazilevs Y, Hsu M, Benson D, Sankaran S, Marsden A (2009) Computational fluid-structure interaction: methods and application to a total cavopulmonary connection. Comput Mech 45(1):77–89

    Google Scholar 

  • Biasetti J, Hussain F, Gasser TC (2011) Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intraluminal thrombus formation. J R Soc Interface 8(63):1449–1461

    Article  Google Scholar 

  • Burattini R, Sipkema P, Vanhuis GA, Westerhof N (1985) Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model. Ann Biomed Eng 13(5):385–404

    Article  Google Scholar 

  • Cebral JR, Castro MA, Burgess JE, Pergolizzi RS, Sheridan MJ, Putman CM (2005) Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models. Am J Neuroradiol 26(10):2550–2559

    Google Scholar 

  • Earls JP, Berman EL, Urban BA et al (2008) Prospectively gated transverse coronary CT angiography versus retrospectively gated helical technique: improved image quality and reduced radiation dose. Radiology 246(3):742–753

    Article  Google Scholar 

  • Esmaily-Moghadam M, Hsia T-Y, Marsden AL (2013) A non-discrete method for computation of residence time in fluid mechanics simulations. Phys Fluids 25:110802

    Article  Google Scholar 

  • Figueroa CA, Vignon-Clementel IE, Jansen KE, Hughes TJR, Taylor CA (2006) A coupled momentum method for modeling blood flow in three-dimensional deformable arteries. Comput Methods Appl Mech Eng 195(41–43):5685–5706

    Google Scholar 

  • Fraser KH, Zhang T, Taskin ME, Griffith BP, Wu ZJ (2012) A quantitative comparison of mechanical blood damage parameters in rotary ventricular assist devices: shear stress, exposure time and hemolysis index. J Biomech Eng Trans Asme 134(8):11

    Article  Google Scholar 

  • Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LB (2010) Hospitalizations for Kawasaki syndrome among children in the United States, 1997–2007. Pediatr Infect Dis J 29(6):483–488

    Google Scholar 

  • Holzapfel GA, Sommer G, Gasser CT, Regitnig P (2005) Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling. Am J Physiol-Heart Circul Physiol 289(5):H2048–H2058

    Article  Google Scholar 

  • Hundley WG, Lange RA, Clarke GD et al (1996) Assessment of coronary arterial flow and flow reserve in humans with magnetic resonance imaging. Circulation 93(8):1502–1508

    Google Scholar 

  • Hwang J, Ing MH, Salazar A et al (2003) Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression—implication for native LDL oxidation. Circ Res 93(12):1225–1232

    Article  Google Scholar 

  • Johnson KR, Patel SJ, Whigham A, Hakim A, Pettigrew RI, Oshinski JN (2004) Three-dimensional, time-resolved motion of the coronary arteries. J Cardiovasc Magn Reson 6(3):663–673

    Article  Google Scholar 

  • Johnson K, Sharma P, Oshinski J (2008) Coronary artery flow measurement using navigator echo gated phase contrast magnetic resonance velocity mapping at 3.0 T. J Biomech 41(3):595–602

    Article  Google Scholar 

  • Kato H, Sugimura T, Akagi T et al (1996) Long-term consequences of Kawasaki disease—A 10- to 21-year follow-up study of 594 patients. Circulation. 94(6):1379–1385

    Article  Google Scholar 

  • Kim HJ, Vignon-Clementel IE, Figueroa CA et al (2009) On coupling a lumped parameter heart model and a three-dimensional finite element Aorta model. Ann Biomed Eng 37(11):2153–2169

    Article  Google Scholar 

  • Kim HJ, Vignon-Clementel IE, Coogan JS, Figueroa CA, Jansen KE, Taylor CA (2010) Patient-specific modeling of blood flow and pressure in human coronary arteries. Ann Biomed Eng 38(10):3195–3209

    Google Scholar 

  • Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL (1996) Platelets and shear stress. Blood 88(5):1525–1541

    Google Scholar 

  • Ku DN, Giddens DP, Zarins CK, Glagov S (1985) Pulsatile flow and atherosclerosis in the human carotid bifurcation—positive correlation between plaque location and low and oscillating shear-stress. Arteriosclerosis 5(3):293–302

    Article  Google Scholar 

  • Kung E, Les A, Figueroa CA et al (2011) In vitro validation of finite element analysis of blood flow in deformable models. Ann Biomed Eng 39(7):1947–1960

    Article  Google Scholar 

  • Lagana K, Dubini G, Migliavacca F et al (2002) Multiscale modelling as a tool to prescribe realistic boundary conditions for the study of surgical procedures. Biorheology 39(3–4):359–364

    Google Scholar 

  • Lei M, Archie JP, Kleinstreuer C (1997) Computational design of a bypass graft that minimizes wall shear stress gradients in the region of the distal anastomosis. J Vasc Surg 25(4):637–646

    Google Scholar 

  • Les AS, Shadden SC, Figueroa CA et al (2010) Quantification of hemodynamics in abdominal aortic aneurysms during rest and exercise using magnetic resonance imaging and computational fluid dynamics. Ann Biomed Eng 38(4):1288–1313

    Article  Google Scholar 

  • Long CC, Hsu MC, Bazilevs Y, Feinstein JA, Marsden AL (2012) Fluid-structure interaction simulations of the Fontan procedure using variable wall properties. Int J Numer Methods Biomed Eng 28(5): 513–527

    Google Scholar 

  • Lu X, Pandit A, Kassab G (2004) Biaxial incremental homeostatic elastic moduli of coronary artery: two-layer model. Am J Physiol Heart Circ Physiol 287(4):H1663–H1669

    Google Scholar 

  • Marcus JT, Smeenk HG, Kuijer JPA (1999) Flow profiles in the left anterior descending and the right coronary artery assessed by MR velocity quantification: effects of through-plane and in-plane motion of the heart. J Comput Assist Tomogr 23(4):567–576

    Article  Google Scholar 

  • Marsden AL, Reddy VM, Shadden SC, Chan FP, Taylor CA, Feinstein JA (2010) A new multiparameter approach to computational simulation for fontan assessment and redesign. Congenit Heart Dis 5(2):104–117

    Article  Google Scholar 

  • Min J, Berman D, Shaw L et al (2012) Fractional flow reserved derived from computed tomographic angiography (FFRCT) for Intermediate Severity Coronary Lesions: Results from the DeFACTO Trial (Determination of Fractional Flow Reserve by Anatomic Computed TOmographic Angiography). J Am coll Cardiol 60(17):B6–B6

    Article  Google Scholar 

  • Moghadam ME, Bazilevs Y, Hsia T-Y, Vignon-Clementel IE, Marsden AL (2011) Modeling Congenital Hearts A. A comparison of outlet boundary treatments for prevention of backflow divergence with relevance to blood flow simulations. Comput Mech 48(3): 277–291

    Google Scholar 

  • Nakamura Y, Yashiro M, Uehara R et al (2012) Epidemiologic features of Kawasaki disease in Japan: results of the 2009–2010 nationwide survey. J Epidemiol 22(3):216–221

    Article  Google Scholar 

  • Newburger JW, Takahashi M, Beiser AS et al (1991) A single intravenous-infusion of gamma-globulin as compared with 4 infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324(23):1633–1639

    Article  Google Scholar 

  • Newburger JW, Takahashi M, Gerber MA et al (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(17):2747–2771

    Article  Google Scholar 

  • Ohkubo T, Fukazawa R, Ikegami E, Ogawa S (2007) Reduced shear stress and disturbed flow may lead to coronary aneurysm and thrombus formations. Pediatr Int 49(1):1–7

    Article  Google Scholar 

  • Passerini AG, Polacek DC, Shi CZ et al (2004) Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta. Proc Natl Acad Sci USA 101(8):2482–2487

    Article  Google Scholar 

  • Sahni O, Muller J, Jansen KE, Shephard MS, Taylor CA (2006) Efficient anisotropic adaptive discretization of the cardiovascular system. Comput Methods Appl Mech Eng 195(41–43):5634–5655

    Article  MathSciNet  MATH  Google Scholar 

  • Sankaran S, Marsden A (2010) The impact of uncertainty on shape optimization of idealized bypass graft models in unsteady flow. Phys Fluids 22(12):121902. doi:10.1063/1.3529444

    Google Scholar 

  • Sankaran S, Marsden A (2011) A Stochastic Collocation Method for Uncertainty Quantification and Propagation in Cardiovascular Simulations. J Biomech Eng 133(3):031001. doi:10.1115/1.4003259

    Google Scholar 

  • Sankaran S, Moghadam ME, Kahn AM, Tseng EE, Guccione JM, Marsden AL (2012) Patient-Specific Multiscale Modeling of Blood Flow for Coronary Artery Bypass Graft Surgery. Ann Biomed Eng 40(10):2228–2242

    Google Scholar 

  • Sengupta D, Kahn AM, Burns JC, Sankaran S, Shadden SC, Marsden AL (2012) Image-based modeling of hemodynamics in coronary artery aneurysms caused by Kawasaki disease. Biomech Model Mechanobiol 11(6):915–932

    Google Scholar 

  • Shadden SC, Taylor CA (2008) Characterization of coherent structures in the cardiovascular system. Ann Biomed Eng 36(7):1152–1162

    Article  Google Scholar 

  • Siogkas PK, Sakellarios AI, Exarchos TP et al (2011) Blood flow in arterial segments: rigid vs. deformable walls simulations. J Serb Soc Comput Mech 5(1):69–77

    Google Scholar 

  • Sriramarao P, Languino LR, Altieri DC (1996) Fibrinogen mediates leukocyte-endothelium bridging in vivo at low shear forces. Blood 88(9):3416–3423

    Google Scholar 

  • Suda K, Iemura M, Nishiono H et al (2011) Long-term prognosis of patients with Kawasaki disease complicated by giant coronary aneurysms: a single-institution experience. Circulation 123(17):1836–1842

    Article  Google Scholar 

  • Sugahara Y, Ishii M, Muta H, Iemura M, Matsuishi T, Kato H (2008) Warfarin therapy for giant aneurysm prevents myocardial infarction in Kawasaki disease. Pediatr Cardiol 29(2):398–401

    Article  Google Scholar 

  • Tsuda E, Hirata T, Matsuo O, Abe T, Sugiyama H, Yamada O (2011) The 30-year outcome for patients after myocardial infarction due to coronary artery lesions caused by Kawasaki disease. Pediatr Cardiol 32(2):176–182

    Google Scholar 

  • Vignon-Clementel IE, Figueroa CA, Jansen KE, Taylor CA (2006) Outflow boundary conditions for three-dimensional finite element modeling of blood flow and pressure in arteries. Comput Methods Appl Mech Eng 195(29–32):3776–3796

    Google Scholar 

  • Vignon-Clementel IE, Figueroa CA, Jansen KE, Taylor CA (2010) Outflow boundary conditions for 3D simulations of non-periodic blood flow and pressure fields in deformable arteries. Comput Methods Biomech Biomed Eng 13(5):625–640

    Google Scholar 

  • Whiting CH, Jansen KE (2001) A stabilized finite element method for the incompressible Navier–Stokes equations using a hierarchical basis. Int J Numer Methods Fluids 35(1):93–116

    Article  MATH  Google Scholar 

  • Wilder MS, Palinkas LA, Kao AS, Bastian JF, Turner CL, Burns JC (2007) Delayed diagnosis by physicians contributes to the development of coronary artery aneurysms in children with Kawasaki syndrome. Pediatr Infect Dis J 26(3):256–260

    Google Scholar 

  • Xu ZL, Chen N, Shadden SC et al (2009) Study of blood flow impact on growth of thrombi using a multiscale model. Soft Matter 5(4):769–779

    Article  Google Scholar 

  • Yang WG, Feinstein JA, Marsden AL (2010) Constrained optimization of an idealized Y-shaped baffle for the Fontan surgery at rest and exercise. Comput Methods Appl Mech Eng 199(33–36):2135–2149

    Article  MATH  Google Scholar 

  • Zeng D, Boutsianis E, Ammann M, Boomsma K, Wildermuth S, Poulikakos D (2008) A study on the compliance of a right coronary artery and its impact on wall shear stress. J Biomech Eng 130(4):041014. doi:10.1115/1.2937744

    Google Scholar 

  • Zhou J, Fung YC (1997) The degree of nonlinearity and anisotropy of blood vessel elasticity. Proc Natl Acad Sci USA 94(26):14255–14260

    Article  Google Scholar 

Download references

Acknowledgments

Support for this project was provided by NIH NHLBI Grant RHL102596A to A.M., A.K., J.C.B., a Burroughs Wellcome Fund Career Award at the Scientific Interface to AM, and a Macklin Foundation grant to J.C.B. and A.K. The authors acknowledge the contributions of Susan Fernandez, Shawn Shadden, Katerina Neskorodova, and Nina V. Gagarina

Author information

Authors and Affiliations

  1. Department of Mechanical and Aerospace Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA , 92037, USA

    Dibyendu Sengupta, Ethan Kung, Mahdi Esmaily Moghadam & Alison L. Marsden

  2. Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Andrew M. Kahn

  3. Sechenov First Moscow State University, Moscow, Russia

    Olga Shirinsky & Galina A. Lyskina

  4. Department of Pediatrics, University of California San Diego, La Jolla, CA, USA

    Jane C. Burns

Authors
  1. Dibyendu Sengupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew M. Kahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ethan Kung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahdi Esmaily Moghadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olga Shirinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Galina A. Lyskina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jane C. Burns
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alison L. Marsden
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alison L. Marsden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sengupta, D., Kahn, A.M., Kung, E. et al. Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease. Biomech Model Mechanobiol 13, 1261–1276 (2014). https://doi.org/10.1007/s10237-014-0570-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-014-0570-z

Keywords

Search

Navigation