Medical & Biological Engineering & Computing

, Volume 46, Issue 11, pp 1059–1068 | Cite as

Cardiovascular disease management: the need for better diagnostics

  • John J. RicottaEmail author
  • Jose Pagan
  • Michalis Xenos
  • Yared Alemu
  • Shmuel Einav
  • Danny Bluestein
Special Issue - Review


Current diagnostic testing for cardiovascular pathology usually rests on either physiological or anatomic measurement. Multiple tests must then be combined to arrive at a conclusion regarding treatment of a specific pathology. Much of the diagnostic decisions currently made are based on rough estimates of outcomes, often derived from gross anatomic observations or extrapolation of physical laws. Thus, intervention for carotid and coronary disease is based on estimates of diameter stenosis, despite data to suggest that plaque character and lesion anatomy are important determinants of outcome. Similarly, abdominal aortic aneurysm (AAA) intervention is based on maximal aneurysm diameter without regard for arterial wall composition or individual aneurysm geometry. In other words, our current diagnostic tests do not reflect the sophistication of our current knowledge of vascular disease. Using a multimodal approach, computer modeling has the potential to predict clinical outcomes based on a variety of factors including arterial wall composition, surface anatomy and hemodynamic forces. We term this more sophisticated approach “patient specific diagnostics”, in which the computer models are reconstructed from patient specific clinical visualizing modalities, and material properties are extracted from experimental measurements of specimens and incorporated into the modeling using advanced material models (including nonlinear anisotropic models) and performed as dynamic simulations using the FSI (fluid structure interaction) approach. Such an approach is sorely needed to improve the effectiveness of interventions. This article will review ongoing work in “patient specific diagnostics” in the areas of carotid, coronary and aneurismal disease. We will also suggest how this approach may be applicable to management of aortic dissection. New diagnostic methods should allow better patient selection, targeted intervention and modeling of the results of different therapies.


Cardiovascular diagnostic testing Fluid structure interactions 


  1. 1.
    Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis (1991) North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 325:445–453Google Scholar
  2. 2.
    Bettermann K, Toole JF (2005) Diagnostic evaluation and medical management of patients with ischemic cerebrovascular disease. In: Rutherford RB (ed) Vascular surgery. Elsevier, Philadelphia 1904–1905Google Scholar
  3. 3.
    Bluestein D, Yared A, Avrahami I, Dumont K, Gharib M, Ricotta J, Einav S (2008) Influence of microcalcifications on vulnerable plaque mechanics using FSI modeling. J Biomech 41:1111–1118. doi: 10.1016/j.jbiomech.2007.11.029 CrossRefGoogle Scholar
  4. 4.
    Bluestein D, Dumont K, De Beule M, Ricotta J, Impellizzeri P, Verhegghe B, Verdonck P (2008) Intraluminal thrombus and risk of rupture in patient specific abdominal aortic aneurysm—FSI modeling. Comput Methods Biomech Biomed Engin 27:1–9. doi: 10.1080/10255840802176396 Google Scholar
  5. 5.
    Eggebrecht H, Nienaber CA, Neuhauser M, Baumgart D, Kische S, Schmermund A, Herold U, Rehders TC, Jakob HG, Erbel R (2006) Endovascular stent-graft placement in aortic dissection: a meta-analysis. Eur Heart J 27:489–498. doi: 10.1093/eurheartj/ehi493 CrossRefGoogle Scholar
  6. 6.
    Endarterectomy for asymptomatic carotid stenosis (1995) Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 273:1421–1428. doi: 10.1001/jama.273.18.1421 Google Scholar
  7. 7.
    Fillinger M (2006) The long-term relationship of wall stress to the natural history of abdominal aortic aneurysm (finite element analysis and other methods). Ann NY Acad Sci 1085:22–28. doi: 10.1196/annals.1383.037 CrossRefGoogle Scholar
  8. 8.
    Finet G, Ohayon J, Rioufol G (2004) Biomechanical interactions between cap thickness, lipid core composition and blood pressure in vulnerable coronary plaque: impact on stability or instability. Coron Artery Dis 15:13–20. doi: 10.1097/00019501-200402000-00003 CrossRefGoogle Scholar
  9. 9.
    Fukumoto Y, Hiro T, Fujii T et al (2008) Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution. J Am Coll Cardiol 51:645–650. doi: 10.1016/j.jacc.2007.10.030 CrossRefGoogle Scholar
  10. 10.
    Grogan JK, Skaalan WE, Cheng H et al (2005) B-mode ultrasonographic characterization of carotid atherosclerotic plaques in symptomatic and asymptomatic patients. J Vasc Surg 42:435–441. doi: 10.1016/j.jvs.2005.05.033 CrossRefGoogle Scholar
  11. 11.
    Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, Evangelista A, Fattori R, Suzuki T, Oh JK, Moore AG, Malouf JF, Pape LA, Gaca C, Sechtem U, Lenferink S, Deutsch HJ, Diedrichs H, Marcos y Robles J, Llovet A, Gilon D, Das SK, Armstrong WF, Deeb GM, Eagle KA (2000) The International Registry of Acute Aortic Dissection (IRAD): new Insights into an old disease. JAMA 283:897–903. doi: 10.1001/jama.283.7.897 CrossRefGoogle Scholar
  12. 12.
    Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, Thomas D (2004) Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomized controlled trial. Lancet 363:1491–1502. doi: 10.1016/S0140-6736(04)16146-1 CrossRefGoogle Scholar
  13. 13.
    Hennerici MG (2004) The unstable plaque. Cerebrovasc Dis 17(Suppl 3):17–22. doi: 10.1159/000075300 CrossRefGoogle Scholar
  14. 14.
    Hua J, Mower WR (2001) Simple geometric characteristics fail to reliably predict abdominal aneurysm wall stresses. J Vasc Surg 34:308–315. doi: 10.1067/mva.2001.114815 CrossRefGoogle Scholar
  15. 15.
    Imoto k, Hiro T, Fujii T et al (2005) Longitudinal structural determinants of atherosclerotic plaque vulnerability: a computational analysis of stress distribution using vessel models and three dimensional ultrasound imaging. J Am Coll Cardiol 46:1507–1515CrossRefGoogle Scholar
  16. 16.
    Kakkos SK, Stevens JM, Nicolaides AN, Kyriacou E, Pattichis CS, Geroulakos G, Thomas D (2007) Texture analysis of ultrasonic images of symptomatic carotid plaques can identify those plaques associated with ipsilateral embolic brain infarction. Eur J Vasc Endovasc Surg 33:422–429. doi: 10.1016/j.ejvs.2006.10.018 CrossRefGoogle Scholar
  17. 17.
    Kern MJ, Lerman A, Bech JW, De Bruyne B, Eeckhout E, Fearon WF, Higano ST, Lim MJ, Meuwissen M, Piek JJ, Pijls NH, Siebes M, Spaan JA (2006) Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: scientific statement from the American Heart Association Committee on Diagnostic and Interventional cardiac Catheterization, Council on Clinical Cardiology. Circulation 114:1321–1341. doi: 10.1161/CIRCULATIONAHA.106.177276 CrossRefGoogle Scholar
  18. 18.
    Lederle FA, Wilson SE, Johnson GR, Reinke DB, Littooy FN, Acher CW, Ballard DJ, Messina LM, Gordon IL, Chute EP, Krupski WC, Busuttil SJ, Barone GW, Sparks S, Graham LM, Rapp JH, Makaroun MS, Moneta GL, Cambria RA, Makhoul RG, Eton D, Ansel HJ, Freischlag JA, Bandyk D, Aneurysm Detection Management Veterans Affairs Cooperative Study Group (2002) Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 346:1437–1444. doi: 10.1056/NEJMoa012573 CrossRefGoogle Scholar
  19. 19.
    Li ZY, Howarth SPS, Tang T, Gillard J (2006) How critical is fibrous cap thickness to carotid plaque stability? A flow plaque interaction model. Stroke 37:1195–1199. doi: 10.1161/01.STR.0000217331.61083.3b CrossRefGoogle Scholar
  20. 20.
    Makamura T, Obata JE, Kitta Y et al (2008) Rapid stabilization of vulnerable carotid plaque within one month of treatment in patients with acute coronary syndrome. J Cardiovasc Pharmacol 51:365–371. doi: 10.1097/FJC.0b013e318165dcad CrossRefGoogle Scholar
  21. 21.
    Meuwissen M, Chanuleau SA, Siebes M, de Winter RJ, Koch KT, DIjskman LM, van den Berg AJ, Tijssen JG, Spaan JA, Piek JJ (2008) The prognostic value of combined intracoronary pressure and blood flow velocity measurements after deferral of percutaneous coronary intervention. Catheter Cardiovasc Interv 71:291–297. doi: 10.1002/ccd.21331 CrossRefGoogle Scholar
  22. 22.
    Moore WS, Hall AD (1968) Ulcerated atheroma of the carotid artery: a cause of transient cerebral ischemia. Am J Surg 116:237–242. doi: 10.1016/0002-9610(68)90499-6 CrossRefGoogle Scholar
  23. 23.
    (1998) Mortality results for randomized controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysm. The UK Small Aneurysm Trial Participants. Lancet 352:1649–1655. doi: 10.1016/S0140-6736(98)10137-X
  24. 24.
    National Institutes of Health (1994) National Heart, Lung, and Blood Institute report of the task force on research in epidemiology and prevention of cardiovascular diseases. In: Public Health ServiceGoogle Scholar
  25. 25.
    Nicolaides AN, Kakkos S, Griffin M, Geroulakos G, Ioannidou E (2005) Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study. Eur J Vasc Endovasc Surg 30:275–284. doi: 10.1016/j.ejvs.2005.04.031 CrossRefGoogle Scholar
  26. 26.
    Nienaber CA, Zannetti S, Barbieri B, Kische S, Schareck W, Rehders TC, INSTEAD study collaborators (2005) INvestigation of STEnt grafts in patients with type B Aortic Dissection: design of the INSTEAD trial—a prospective, multicenter, European randomized trial. Am Heart J 147:592–599. doi: 10.1016/j.ahj.2004.05.060 CrossRefGoogle Scholar
  27. 27.
    O’Holleran LW, Kennelly MM, McClurken M, Johnson JM (1987) Natural history of asymptomatic carotid plaque. Five year follow-up study. Am J Surg 154:659–662. doi: 10.1016/0002-9610(87)90238-8 CrossRefGoogle Scholar
  28. 28.
    Ohayon J, Finet G, Gharib AM et al (2008) Necrotic core thickness and possible arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol 295:H717–H727. doi: 10.1152/ajpheart.00005.2008 CrossRefGoogle Scholar
  29. 29.
    Rissland P, Alemu Y, Einav S, Ricotta J, Bluestein D (2008) Abdominal aortic aneurysm risk of rupture: patient-specific FSI simulations using anisotropic model. J Biomech Eng (in press)Google Scholar
  30. 30.
    Roederer GO, Langlois YE, Jager KA, Primozich JF, Beach KW, Phillips DJ, Strandness DE Jr (1984) The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. Stroke 15:605–613Google Scholar
  31. 31.
    Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y, American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2007) Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115:e69–e171. doi: 10.1161/CIRCULATIONAHA.106.179918 CrossRefGoogle Scholar
  32. 32.
    Rothwell PM, Eliasziw M, Gutnikov SA, Fox AJ, Taylor DW, Mayberg MR, Warlow CP, Barnett HJ, Carotid Endarterectomy Trialists’ Collaboration (2003) Analysis of pooled data from the randomized controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 361:107–116. doi: 10.1016/S0140-6736(03)12228-3 CrossRefGoogle Scholar
  33. 33.
    Schermerhorn M, Zwolak R, Velazquez O, Makaroun M, Fairman R, Cronenwett J (2008) Ultrasound screening for abdominal aortic aneurysm in medicare beneficiaries. Ann Vasc Surg 22:16–24. doi: 10.1016/j.avsg.2007.07.026 CrossRefGoogle Scholar
  34. 34.
    Slager CJ, Wentzel JJ, Gijsen FJ, Thury A, van der Wal AC, Schaar JA, Serruys PW (2005) The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications. Nat Clin Pract Cardiovasc Med 2:456–464. doi: 10.1038/ncpcardio0298 CrossRefGoogle Scholar
  35. 35.
    Spaan JA, Piek JJ, Hoffman JI, Siebes M (2006) Physiological basis of clinically used coronary hemodynamic indices. Circulation 113:446–455. doi: 10.1161/CIRCULATIONAHA.105.587196 CrossRefGoogle Scholar
  36. 36.
    Truijers M, Pol JA, Schultzekool LJ, van Sterkenburg SM, Fillinger MF, Blankensteijn JD (2007) Wall stress analysis in small asymptomatic, symptomatic and ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 33:401–407. doi: 10.1016/j.ejvs.2006.10.009 CrossRefGoogle Scholar
  37. 37.
    van den Wijngaard JP, Kolyva C, Siebes M, Dankelman J, van Gemert MJ, Piek JJ, Spaan JA (2008) Model prediction of subendocardial perfusion of the coronary circulation in the presence of an epicardial coronary artery stenosis. Med Biol Eng Comput 46(5):421–432CrossRefGoogle Scholar
  38. 38.
    Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, Davis K, Killip T, Passamani E, Norris R et al (1994) Effect of coronary artery bypass graft surgery on survival: overview of ten-year results from randomized trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 344:563–570. doi: 10.1016/S0140-6736(94)91963-1 CrossRefGoogle Scholar
  39. 39.
    Zankl AR, Schumacher H, Krumsdorf U, Katus HA, Jahn L, Tiefenbacher CP (2007) Pathology, natural history and treatment of abdominal aortic aneurysms. Clin Res Cardiol 96:140–151. doi: 10.1007/s00392-007-0472-5 CrossRefGoogle Scholar

Copyright information

© International Federation for Medical and Biological Engineering 2008

Authors and Affiliations

  • John J. Ricotta
    • 1
    Email author
  • Jose Pagan
    • 1
  • Michalis Xenos
    • 2
  • Yared Alemu
    • 2
  • Shmuel Einav
    • 2
  • Danny Bluestein
    • 2
  1. 1.Division of Vascular Surgery, Department of SurgeryHealth Sciences Center T-19, Stony Brook University Medical CenterStony BrookUSA
  2. 2.Department of Biomedical EngineeringStony Brook University Medical CenterStony BrookUSA

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