An angiographic technique for coronary fractional flow reserve measurement: in vivo validation

Original Paper

Abstract

Fractional flow reserve (FFR) is an important prognostic determinant in a clinical setting. However, its measurement currently requires the use of invasive pressure wire, while an angiographic technique based on first-pass distribution analysis and scaling laws can be used to measure FFR using only image data. Eight anesthetized swine were instrumented with flow probe on the proximal segment of the left anterior descending (LAD) coronary arteries. Volumetric blood flow from the flow probe (Qp), coronary pressure (Pa) and right atrium pressure (Pv) were continuously recorded. Flow probe-based FFR (FFRq) was measured from the ratio of flow with and without stenosis. To determine the angiography-based FFR (FFRa), the ratio of blood flow in the presence of a stenosis (QS) to theoretically normal blood flow (QN) was calculated. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. QS was measured using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. QN was estimated from the total coronary arterial volume using scaling laws. Pressure-wire measurements of FFR (FFRp), which was calculated from the ratio of distal coronary pressure (Pd) divided by proximal pressure (Pa), were continuously obtained during the study. A total of 54 measurements of FFRa, FFRp, and FFRq were taken. FFRa showed a good correlation with FFRq (FFRa = 0.97 FFRq +0.06, r2 = 0.80, p < 0.001), although FFRp overestimated the FFRq (FFRp = 0.657 FFRq + 0.313, r2 = 0.710, p < 0.0001). Additionally, the Bland–Altman analysis showed a close agreement between FFRa and FFRq. This angiographic technique to measure FFR can potentially be used to evaluate both anatomical and physiological assessments of a coronary stenosis during routine diagnostic cardiac catheterization that requires no pressure wires.

Keywords

Coronary blood flow Fractional flow reserve Coronary angiography Catheterization 

Notes

Acknowledgments

The authors would like to thank Drs. Jerry Wong and Charles Dang for their technical support. We would like to acknowledge the funding for Zhang Zhang from the China National Natural Science Foundation grant 30870698, and Tianjin application basis and leading edge research program 10JCYBJC11000. This work was supported by the National Heart, Lung and Blood Institute and the Department of Health and Human Services [R01 HL89941].

Conflict of interest

None.

References

  1. 1.
    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: a scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Circulation 114(12):1321–1341. doi: 10.1161/CIRCULATIONAHA.106.177276 PubMedCrossRefGoogle Scholar
  2. 2.
    van Liebergen RA, Piek JJ, Koch KT, de Winter RJ, Schotborgh CE, Lie KI (1999) Quantification of collateral flow in humans: a comparison of angiographic, electrocardiographic and hemodynamic variables. J Am Coll Cardiol 33(3):670–677. doi: 10.1016/S0735-1097(98)00640-8 PubMedCrossRefGoogle Scholar
  3. 3.
    White CW, Wright CB, Doty DB, Hiratza LF, Eastham CL, Harrison DG, Marcus ML (1984) Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 310(13):819–824. doi: 10.1056/NEJM198403293101304 PubMedCrossRefGoogle Scholar
  4. 4.
    Folland ED, Vogel RA, Hartigan P, Bates ER, Beauman GJ, Fortin T, Boucher C, Parisi AF (1994) Relation between coronary artery stenosis assessed by visual, caliper, and computer methods and exercise capacity in patients with single-vessel coronary artery disease. The Veterans Affairs ACME Investigators. Circulation 89(5):2005–2014PubMedCrossRefGoogle Scholar
  5. 5.
    De Bruyne B, Baudhuin T, Melin JA, Pijls NH, Sys SU, Bol A, Paulus WJ, Heyndrickx GR, Wijns W (1994) Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography. Circulation 89(3):1013–1022PubMedCrossRefGoogle Scholar
  6. 6.
    Pijls NH, De Bruyne B, Peels K, Van Der Voort PH, Bonnier HJ, Bartunek JKJJ, Koolen JJ (1996) Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 334(26):1703–1708. doi: 10.1056/NEJM199606273342604 PubMedCrossRefGoogle Scholar
  7. 7.
    Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF (2009) Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 360(3):213–224. doi: 10.1056/NEJMoa0807611 PubMedCrossRefGoogle Scholar
  8. 8.
    Baumgart D, Haude M, Goerge G, Ge J, Vetter S, Dagres N, Heusch G, Erbel R (1998) Improved assessment of coronary stenosis severity using the relative flow velocity reserve. Circulation 98(1):40–46PubMedCrossRefGoogle Scholar
  9. 9.
    Bassenge E, Heusch G (1990) Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 116:77–165PubMedGoogle Scholar
  10. 10.
    Knaapen P, Camici PG, Marques KM, Nijveldt R, Bax JJ, Westerhof N, Gotte MJ, Jerosch-Herold M, Schelbert HR, Lammertsma AA, van Rossum AC (2009) Coronary microvascular resistance: methods for its quantification in humans. Basic Res Cardiol 104(5):485–498. doi: 10.1007/s00395-009-0037-z PubMedCrossRefGoogle Scholar
  11. 11.
    Liu Y, Gutterman DD (2009) Vascular control in humans: focus on the coronary microcirculation. Basic Res Cardiol 104(3):211–227. doi: 10.1007/s00395-009-0775-y PubMedCrossRefGoogle Scholar
  12. 12.
    Spaan JA, Piek JJ, Hoffman JI, Siebes M (2006) Physiological basis of clinically used coronary hemodynamic indices. Circulation 113(3):446–455. doi: 10.1161/CIRCULATIONAHA.105.587196 PubMedCrossRefGoogle Scholar
  13. 13.
    Heusch G (2010) Adenosine and maximum coronary vasodilation in humans: myth and misconceptions in the assessment of coronary reserve. Basic Res Cardiol 105(1):1–5. doi: 10.1007/s00395-009-0074-7 PubMedCrossRefGoogle Scholar
  14. 14.
    Molloi S, Ersahin A, Tang J, Hicks J, Leung CY (1996) Quantification of volumetric coronary blood flow with dual-energy digital subtraction angiography. Circulation 93(10):1919–1927PubMedCrossRefGoogle Scholar
  15. 15.
    Molloi S, Kassab GS, Zhou Y (2001) Quantification of coronary artery lumen volume by digital angiography: in vivo validation. Circulation 104(19):2351–2357. doi: 10.1161/hc4401.098435 PubMedCrossRefGoogle Scholar
  16. 16.
    Khoo NS, Smallhorn JF, Kaneko S, Myers K, Kutty S, Tham EB (2011) Novel insights into RV adaptation and function in hypoplastic left heart syndrome between the first 2 stages of surgical palliation. JACC Cardiovasc Imaging 4(2):128–137. doi: 10.1016/j.jcmg.2010.09.022 PubMedCrossRefGoogle Scholar
  17. 17.
    Zhang Z, Takarada S, Molloi S (2011) Quantification of coronary microvascular resistance using angiographic images for volumetric blood flow measurement: in vivo validation. Am J Physiol Heart Circ Physiol 300(6):H2096–H2104. doi: 10.1152/ajpheart.01123.2010 PubMedCrossRefGoogle Scholar
  18. 18.
    Molloi S, Bednarz G, Tang J, Zhou Y, Mathur T (1998) Absolute volumetric coronary blood flow measurement with digital subtraction angiography. Int J Card Imaging 14(3):137–145PubMedCrossRefGoogle Scholar
  19. 19.
    Wong J, Xu T, Husain A, Le H, Molloi S (2004) Effect of area x-ray beam equalization on image quality and dose in digital mammography. Phys Med Biol 49(16):3539–3557PubMedCrossRefGoogle Scholar
  20. 20.
    West GB, Brown JH, Enquist BJ (1997) A general model for the origin of allometric scaling laws in biology. Science 276(5309):122–126PubMedCrossRefGoogle Scholar
  21. 21.
    Kassab GS (2006) Scaling laws of vascular trees: of form and function. Am J Physiol Heart Circ Physiol 290(2):H894–H903. doi: 10.1152/ajpheart.00579.2005 PubMedCrossRefGoogle Scholar
  22. 22.
    Molloi S, Wong JT (2007) Regional blood flow analysis and its relationship with arterial branch lengths and lumen volume in the coronary arterial tree. Phys Med Biol 52(5):1495–1503. doi: 10.1088/0031-9155/52/5/018 PubMedCrossRefGoogle Scholar
  23. 23.
    Choy JS, Kassab GS (2008) Scaling of myocardial mass to flow and morphometry of coronary arteries. J Appl Physiol 104(5):1281–1286. doi: 10.1152/japplphysiol.01261.2007 PubMedCrossRefGoogle Scholar
  24. 24.
    Wong JT, Molloi S (2008) Determination of fractional flow reserve (FFR) based on scaling laws: a simulation study. Phys Med Biol 53(14):3995–4011. doi: 10.1088/0031-9155/53/14/017 PubMedCrossRefGoogle Scholar
  25. 25.
    Molloi S, Chalyan D, Le H, Wong JT (2011) Estimation of coronary artery hyperemic blood flow based on arterial lumen volume using angiographic images. Int J Cardiovasc Imaging. doi: 10.1007/s10554-010-9766-1 Google Scholar
  26. 26.
    Waters SL, Alastruey J, Beard DA, Bovendeerd PH, Davies PF, Jayaraman G, Jensen OE, Lee J, Parker KH, Popel AS, Secomb TW, Siebes M, Sherwin SJ, Shipley RJ, Smith NP, van de Vosse FN (2011) Theoretical models for coronary vascular biomechanics: progress & challenges. Prog Biophys Mol Biol 104(1–3):49–76. doi: 10.1016/j.pbiomolbio.2010.10.001 PubMedCrossRefGoogle Scholar
  27. 27.
    Wong JT, Le H, Suh WM, Chalyan DA, Mehraien T, Kern MJ, Kassab GS, Molloi S (2011) Quantification of fractional flow reserve based on angiographic image data. Int J Cardiovasc Imaging. doi: 10.1007/s10554-010-9767-0 Google Scholar
  28. 28.
    Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL (1993) Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation 87(4):1354–1367PubMedCrossRefGoogle Scholar
  29. 29.
    Pijls NH, Uijen GJ, Hoevelaken A, Arts T, Aengevaeren WR, Bos HS, Fast JH, van Leeuwen KL, van der Werf T (1990) Mean transit time for the assessment of myocardial perfusion by videodensitometry. Circulation 81(4):1331–1340PubMedCrossRefGoogle Scholar
  30. 30.
    Siebes M, Chamuleau SA, Meuwissen M, Piek JJ, Spaan JA (2002) Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model. Am J Physiol Heart Circ Physiol 283(4):H1462–H1470. doi: 10.1152/ajpheart.00165.2002 PubMedGoogle Scholar
  31. 31.
    Pantely GA, Ladley HD, Bristow JD (1984) Low zero-flow pressure and minimal capacitance effect on diastolic coronary arterial pressure-flow relationships during maximum vasodilation in swine. Circulation 70(3):485–494PubMedCrossRefGoogle Scholar
  32. 32.
    Siebes M, Verhoeff BJ, Meuwissen M, de Winter RJ, Spaan JA, Piek JJ (2004) Single-wire pressure and flow velocity measurement to quantify coronary stenosis hemodynamics and effects of percutaneous interventions. Circulation 109(6):756–762. doi: 10.1161/01.CIR.0000112571.06979.B2 PubMedCrossRefGoogle Scholar
  33. 33.
    Zhang Z, Takarada S, Molloi S (2011) Assessment of coronary microcirculation in a swine animal model. Am J Physiol Heart Circ Physiol 301(2):H402–H408. doi: 10.1152/ajpheart.00213.2011 PubMedCrossRefGoogle Scholar
  34. 34.
    Verhoeff BJ, Siebes M, Meuwissen M, Atasever B, Voskuil M, de Winter RJ, Koch KT, Tijssen JG, Spaan JA, Piek JJ (2005) Influence of percutaneous coronary intervention on coronary microvascular resistance index. Circulation 111(1):76–82. doi: 10.1161/01.CIR.0000151610.98409.2F PubMedCrossRefGoogle Scholar
  35. 35.
    de Marchi SF, Gloekler S, Rimoldi SF, Rolli P, Steck H, Seiler C (2011) Microvascular response to metabolic and pressure challenge in the human coronary circulation. Am J Physiol Heart Circ Physiol 301(2):H434–H441. doi: 10.1152/ajpheart.01283.2010 PubMedCrossRefGoogle Scholar
  36. 36.
    Sambuceti G, Marzilli M, Fedele S, Marini C, L’Abbate A (2001) Paradoxical increase in microvascular resistance during tachycardia downstream from a severe stenosis in patients with coronary artery disease: reversal by angioplasty. Circulation 103(19):2352–2360PubMedCrossRefGoogle Scholar
  37. 37.
    Chamuleau SA, Siebes M, Meuwissen M, Koch KT, Spaan JA, Piek JJ (2003) Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease. Am J Physiol Heart Circ Physiol 285(5):H2194–H2200. doi: 10.1152/ajpheart.01021.2002 PubMedGoogle Scholar
  38. 38.
    Marzilli M, Sambuceti G, Fedele S, L’Abbate A (2000) Coronary microcirculatory vasoconstriction during ischemia in patients with unstable angina. J Am Coll Cardiol 35(2):327–334. doi: 10.1016/S0735-1097(99)00554-9 PubMedCrossRefGoogle Scholar
  39. 39.
    Aarnoudse W, Fearon WF, Manoharan G, Geven M, van de Vosse F, Rutten M, De Bruyne B, Pijls NH (2004) Epicardial stenosis severity does not affect minimal microcirculatory resistance. Circulation 110(15):2137–2142. doi: 10.1161/01.CIR.0000143893.18451.0E PubMedCrossRefGoogle Scholar
  40. 40.
    Fearon WF, Aarnoudse W, Pijls NH, De Bruyne B, Balsam LB, Cooke DT, Robbins RC, Fitzgerald PJ, Yeung AC, Yock PG (2004) Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: experimental validation. Circulation 109(19):2269–2272. doi: 10.1161/01.CIR.0000128669.99355.CB PubMedCrossRefGoogle Scholar
  41. 41.
    de Groot D, Grundmann S, Timmers L, Pasterkamp G, Hoefer IE (2011) Assessment of collateral artery function and growth in a pig model of stepwise coronary occlusion. Am J Physiol Heart Circ Physiol 300(1):H408–H414. doi: 10.1152/ajpheart.00070.2010 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, B.V. 2012

Authors and Affiliations

  1. 1.Department of Radiological Sciences, Medical Sciences, B-140University of CaliforniaIrvineUSA
  2. 2.Department of RadiologyTianjin Medical University General HospitalTianjinChina

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