Synopsis of Clinical Coronary Physiology

  • Tim P. van de HoefEmail author


After decades of angiography-guided coronary intervention, the value of coronary physiology tools to improve patient selection for coronary intervention is nowadays undisputed. The fractional flow reserve represents the cornerstone of clinical coronary physiology tools, and has proved to be of substantial diagnostic and prognostic value in daily clinical practice. Nonetheless, it remains only one of several physiological tools available to the practicing clinician. The large armamentarium of physiology tools ranges from conventional coronary pressure–derived indices for stenosis severity assessment to more complex comprehensive physiology tools based on combined assessment of coronary pressure and flow (velocity), which allow selective identification of epicardial and microvascular contributions to myocardial perfusion impairment. With increasing understanding and acknowledgment of a complex multilevel involvement of the coronary circulation in ischemic heart disease, a combination of physiology tools that allow evaluation of the coronary circulation beyond the epicardial stenosis becomes increasingly relevant. This chapter describes the currently available tools to assess coronary physiology and their clinical application in individual patients.


  1. 1.
    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, PA MC, Fearon WF. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–24.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Johnson NP, Toth GG, Lai D, Zhu H, Acar G, Agostoni P, Appelman Y, Arslan F, Barbato E, Chen SL, Di Serafino L, Dominguez-Franco AJ, Dupouy P, Esen AM, Esen OB, Hamilos M, Iwasaki K, Jensen LO, Jimenez-Navarro MF, Katritsis DG, Kocaman SA, Koo BK, Lopez-Palop R, Lorin JD, Miller LH, Muller O, Nam CW, Oud N, Puymirat E, Rieber J, Rioufol G, Rodes-Cabau J, Sedlis SP, Takeishi Y, Tonino PA, Van Belle E, Verna E, Werner GS, Fearon WF, Pijls NH, De Bruyne B, Gould KL. Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes. J Am Coll Cardiol. 2014;64(16):1641–54.CrossRefPubMedGoogle Scholar
  3. 3.
    Chilian WM, Eastham CL, Marcus ML. Microvascular distribution of coronary vascular resistance in beating left ventricle. Am J Phys. 1986;251(4 Pt 2):H779–88.Google Scholar
  4. 4.
    Pries AR, Badimon L, Bugiardini R, Camici PG, Dorobantu M, Duncker DJ, Escaned J, Koller A, Piek JJ, de Wit C. Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the Working Group on Coronary Pathophysiology and Microcirculation. Eur Heart J. 2015;36(45):3134–46.CrossRefPubMedGoogle Scholar
  5. 5.
    Camici PG, d'Amati G, Rimoldi O. Coronary microvascular dysfunction: mechanisms and functional assessment. Nat Rev Cardiol. 2015;12(1):48–62.CrossRefPubMedGoogle Scholar
  6. 6.
    Tune JD, Gorman MW, Feigl EO. Matching coronary blood flow to myocardial oxygen consumption. J Appl Physiol. 2004;97(1):404–15.CrossRefPubMedGoogle Scholar
  7. 7.
    Heusch G. Adenosine and maximum coronary vasodilation in humans: myth and misconceptions in the assessment of coronary reserve. Basic Res Cardiol. 2010;105(1):1–5.CrossRefPubMedGoogle Scholar
  8. 8.
    van de Hoef TP, Meuwissen M, Escaned J, Davies JE, Siebes M, Spaan JA, Piek JJ. Fractional flow reserve as a surrogate for inducible myocardial ischaemia. Nat Rev Cardiol. 2013;10(8):439–52.CrossRefPubMedGoogle Scholar
  9. 9.
    Barbato E, Bartunek J, Aarnoudse W, Vanderheyden M, Staelens F, Wijns W, Heyndrickx GR, Pijls NH, De Bruyne B. Alpha-adrenergic receptor blockade and hyperaemic response in patients with intermediate coronary stenoses. Eur Heart J. 2004;25(22):2034–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Adjedj J, Toth GG, Johnson NP, Pellicano M, Ferrara A, Floré V, Di Gioia G, Barbato E, Muller O, De Bruyne B. Intracoronary adenosine: dose–response relationship with hyperemia. J Am Coll Cardiol Intv. 2015;8(11):1422–30.CrossRefGoogle Scholar
  11. 11.
    Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. 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. 1993;87(4):1354–67.CrossRefPubMedGoogle Scholar
  12. 12.
    van de Hoef TP, Siebes M, Spaan JA, Piek JJ. Fundamentals in clinical coronary physiology: why coronary flow is more important than coronary pressure. Eur Heart J. 2015;36:3312–9a.CrossRefPubMedGoogle Scholar
  13. 13.
    Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS guidelines on myocardial revascularization. EuroIntervention. 2015;10(9):1024–94.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pijls NH, Tanaka N, Fearon WF. Functional assessment of coronary stenoses: can we live without it? Eur Heart J. 2012;34(18):1335–44.CrossRefPubMedGoogle Scholar
  15. 15.
    van Nunen LX, Zimmermann FM, Tonino PA, Barbato E, Baumbach A, Engstrom T, Klauss V, MacCarthy PA, Manoharan G, Oldroyd KG, Ver Lee PN, Van't Veer M, Fearon WF, De Bruyne B, Pijls NH, Investigators FS. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. 2015;386(10006):1853–60.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Mobius-Winckler S, Rioufol G, Witt N, Kala P, Maccarthy P, Engstrom T, Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Juni P, Fearon WF. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367:991.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    De Bruyne B, Fearon WF, Pijls NH, Barbato E, Tonino P, Piroth Z, Jagic N, Mobius-Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T, Oldroyd K, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Limacher A, Nuesch E, Juni P, Investigators FT. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014;371(13):1208–17.CrossRefPubMedGoogle Scholar
  18. 18.
    Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, van't Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, De Bruyne B. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol. 2010;56(3):177–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Fearon WF, Shilane D, Pijls NH, Boothroyd DB, Tonino PA, Barbato E, Juni P, De Bruyne B, Hlatky MA. Fractional flow reserve versus angiography for multivessel evaluation I. Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve. Circulation. 2013;128(12):1335–40.CrossRefPubMedGoogle Scholar
  20. 20.
    Sen S, Escaned J, Malik IS, Mikhail GW, Foale RA, Mila R, Tarkin J, Petraco R, Broyd C, Jabbour R, Sethi A, Baker CS, Bellamy M, Al-Bustami M, Hackett D, Khan M, Lefroy D, Parker KH, Hughes AD, Francis DP, Di Mario C, Mayet J, Davies JE. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (Adenosine Vasodilator Independent Stenosis Evaluation) study. J Am Coll Cardiol. 2012;59(15):1392–402.CrossRefPubMedGoogle Scholar
  21. 21.
    Petraco R, Al-Lamee R, Gotberg M, Sharp A, Hellig F, Nijjer SS, Echavarria-Pinto M, van de Hoef TP, Sen S, Tanaka N, Van Belle E, Bojara W, Sakoda K, Mates M, Indolfi C, De Rosa S, Vrints CJ, Haine S, Yokoi H, Ribichini FL, Meuwissen M, Matsuo H, Janssens L, Katsumi U, Di Mario C, Escaned J, Piek J, Davies JE. Real-time use of instantaneous wave-free ratio: results of the ADVISE in-practice: an international, multicenter evaluation of instantaneous wave-free ratio in clinical practice. Am Heart J. 2014;168(5):739–48.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Jeremias A, Maehara A, Genereux P, Asrress KN, Berry C, De Bruyne B, Davies JE, Escaned J, Fearon WF, Gould KL, Johnson NP, Kirtane AJ, Koo BK, Marques KM, Nijjer S, Oldroyd KG, Petraco R, Piek JJ, Pijls NH, Redwood S, Siebes M, Spaan JA, van’t Veer M, Mintz GS, Stone GW. Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study. J Am Coll Cardiol. 2014;63(13):1253–61.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    van de Hoef TP, Meuwissen M, Escaned J, Sen S, Petraco R, van Lavieren MA, Echavarria-Pinto M, Nolte F, Nijjer S, Chamuleau SA, Voskuil M, van Eck-Smit BL, Verberne HJ, Henriques JP, Koch KT, de Winter RJ, Spaan JA, Siebes M, Tijssen JG, Davies JE, Piek JJ. Head-to-head comparison of basal stenosis resistance index, instantaneous wave-free ratio, and fractional flow reserve: diagnostic accuracy for stenosis-specific myocardial ischaemia. EuroIntervention. 2015;11(8):914–25.CrossRefPubMedGoogle Scholar
  24. 24.
    Sen S, Asrress K, Nijjer S, Petraco R, Malik I, Foale R, Mikhail G, Foin N, Broyd C, Hadjiloizou N, Sethi A, Al-Bustami M, Hackett D, Khan M, Khawaja M, Baker C, Bellamy M, Parker K, Hughes A, Francis D, Mayet J, Di Mario C, Escaned J, Redwood S, Davies J. Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (the Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study). J Am Coll Cardiol. 2013;61(13):1409–20.CrossRefPubMedGoogle Scholar
  25. 25.
    Petraco R, van de Hoef TP, Nijjer S, Sen S, van Lavieren MA, Foale RA, Meuwissen M, Broyd C, Echavarria-Pinto M, Foin N, Malik IS, Mikhail GW, Hughes AD, Francis DP, Mayet J, Di Mario C, Escaned J, Piek JJ, Davies JE. Baseline instantaneous wave-free ratio as a pressure-only estimation of underlying coronary flow reserve: results of the JUSTIFY-CFR study (Joined Coronary Pressure and Flow Analysis to Determine Diagnostic Characteristics of Basal and Hyperemic Indices of Functional Lesion Severity–Coronary Flow Reserve). Circ Cardiovasc Interv. 2014;7(4):492–502.CrossRefPubMedGoogle Scholar
  26. 26.
    Escaned J, Echavarria-Pinto M, Garcia-Garcia HM, van de Hoef TP, de Vries T, Kaul P, Raveendran G, Altman JD, Kurz HI, Brechtken J, Tulli M, Von Birgelen C, Schneider JE, Khashaba AA, Jeremias A, Baucum J, Moreno R, Meuwissen M, Mishkel G, van Geuns RJ, Levite H, Lopez-Palop R, Mayhew M, Serruys PW, Samady H, Piek JJ, Lerman A, Group AIS. Prospective assessment of the diagnostic accuracy of instantaneous wave-free ratio to assess coronary stenosis relevance: results of ADVISE II international, multicenter study (Adenosine Vasodilator Independent Stenosis Evaluation II). JACC Cardiovasc Interv. 2015;8(6):824–33.CrossRefPubMedGoogle Scholar
  27. 27.
    Nijjer SS, Sen S, Petraco R, Escaned J, Echavarria-Pinto M, Broyd C, Al-Lamee R, Foin N, Foale RA, Malik IS, Mikhail GW, Sethi AS, Al-Bustami M, Kaprielian RR, Khan MA, Baker CS, Bellamy MF, Hughes AD, Mayet J, Francis DP, Di Mario C, Davies JE. Pre-angioplasty instantaneous wave-free ratio pullback provides virtual intervention and predicts hemodynamic outcome for serial lesions and diffuse coronary artery disease. JACC Cardiovasc Interv. 2014;7(12):1386–96.CrossRefPubMedGoogle Scholar
  28. 28.
    Davies JE, Sen S, Dehbi H-M, Al-Lamee R, Petraco R, Nijjer SS, Bhindi R, Lehman SJ, Walters D, Sapontis J, Janssens L, Vrints CJ, Khashaba A, Laine M, Van Belle E, Krackhardt F, Bojara W, Going O, Härle T, Indolfi C, Niccoli G, Ribichini F, Tanaka N, Yokoi H, Takashima H, Kikuta Y, Erglis A, Vinhas H, Canas Silva P, Baptista SB, Alghamdi A, Hellig F, Koo B-K, Nam C-W, Shin E-S, Doh J-H, Brugaletta S, Alegria-Barrero E, Meuwissen M, Piek JJ, van Royen N, Sezer M, Di Mario C, Gerber RT, Malik IS, ASP S, Talwar S, Tang K, Samady H, Altman J, Seto AH, Singh J, Jeremias A, Matsuo H, Kharbanda RK, Patel MR, Serruys P, Escaned J. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI. N Engl J Med. 2017;376:1824–34.CrossRefPubMedGoogle Scholar
  29. 29.
    Götberg M, Christiansen EH, Gudmundsdottir IJ, Sandhall L, Danielewicz M, Jakobsen L, Olsson S-E, Öhagen P, Olsson H, Omerovic E, Calais F, Lindroos P, Maeng M, Tödt T, Venetsanos D, James SK, Kåregren A, Nilsson M, Carlsson J, Hauer D, Jensen J, Karlsson A-C, Panayi G, Erlinge D, Fröbert O. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI. N Engl J Med. 2017;376:1813–23.CrossRefPubMedGoogle Scholar
  30. 30.
    Echavarria-Pinto M, van de Hoef TP, Garcia-Garcia HM, de Vries T, Serruys PW, Samady H, Piek JJ, Lerman A, Escaned J, Group AIS. Diagnostic accuracy of baseline distal-to-aortic pressure ratio to assess coronary stenosis severity: a post-hoc analysis of the ADVISE II study. JACC Cardiovasc Interv. 2015;8(6):834–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Johnson NP, Jeremias A, Zimmermann FM, Adjedj J, Witt N, Hennigan B, Koo BK, Maehara A, Matsumura M, Barbato E, Esposito G, Trimarco B, Rioufol G, Park SJ, Yang HM, Baptista SB, Chrysant GS, Leone AM, Berry C, De Bruyne B, Gould KL, Kirkeeide RL, Oldroyd KG, Pijls NH, Fearon WF. Continuum of vasodilator stress from rest to contrast medium to adenosine hyperemia for fractional flow reserve assessment. JACC Cardiovasc Interv. 2016;9(8):757–67.CrossRefPubMedGoogle Scholar
  32. 32.
    Seiler C, Kirkeeide RL, Gould KL. Measurement from arteriograms of regional myocardial bed size distal to any point in the coronary vascular tree for assessing anatomic area at risk. J Am Coll Cardiol. 1993;21(3):783–97.CrossRefPubMedGoogle Scholar
  33. 33.
    Seiler C, Kirkeeide RL, Gould KL. Basic structure–function relations of the epicardial coronary vascular tree. Basis of quantitative coronary arteriography for diffuse coronary artery disease. Circulation. 1992;85(6):1987–2003.CrossRefPubMedGoogle Scholar
  34. 34.
    Pijls NHJ, De Bruyne B, Smith L, Aarnoudse W, Barbato E, Bartunek J, Bech GJW, van de Vosse F. Coronary thermodilution to assess flow reserve validation in humans. Circulation. 2002;105:2482–6.CrossRefPubMedGoogle Scholar
  35. 35.
    De Bruyne B, Pijls NHJ, Smith L, Wievegg M, Heyndrickx GR. Coronary thermodilution to assess flow reserve: experimental validation. Circulation. 2001;104(17):2003–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Emanuelsson H, Holmberg S, Selin K, Wallin J. Factors that modify the flow response to intracoronary injections. Circulation. 1985;72(2):287–91.CrossRefPubMedGoogle Scholar
  37. 37.
    van't Veer M, Geven MC, Rutten MC, van der Horst A, Aarnoudse WH, Pijls NH, van de Vosse FN. Continuous infusion thermodilution for assessment of coronary flow: theoretical background and in vitro validation. Med Eng Phys. 2009;31(6):688–94.CrossRefPubMedGoogle Scholar
  38. 38.
    Aarnoudse W, Van't Veer M, Pijls NH, Ter Woorst J, Vercauteren S, Tonino P, Geven M, Rutten M, van Hagen E, de Bruyne B, van de Vosse F. Direct volumetric blood flow measurement in coronary arteries by thermodilution. J Am Coll Cardiol. 2007;50(24):2294–304.CrossRefPubMedGoogle Scholar
  39. 39.
    Meuwissen M, Siebes M, Chamuleau SAJ, Verhoeff B, Henriques JPS, Spaan JAE, Piek JJ. Role of fractional and coronary flow reserve in clinical decision making in intermediate coronary lesions. Interv Cardiol. 2009;1(2):237–55.CrossRefGoogle Scholar
  40. 40.
    van de Hoef TP, Echavarria-Pinto M, van Lavieren MA, Meuwissen M, Serruys PW, Tijssen JG, Pocock SJ, Escaned J, Piek JJ. Diagnostic and prognostic implications of coronary flow capacity: a comprehensive cross-modality physiological concept in ischemic heart disease. JACC Cardiovasc Interv. 2015;8(13):1670–80.CrossRefPubMedGoogle Scholar
  41. 41.
    Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation. 1990;82(5):1595–606.CrossRefPubMedGoogle Scholar
  42. 42.
    Kern MJ, Bach RG, Mechem CJ, Caracciolo EA, Aguirre FV, Miller LW, Donohue TJ. Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation and coronary artery disease. J Am Coll Cardiol. 1996;28(5):1154–60.CrossRefPubMedGoogle Scholar
  43. 43.
    van de Hoef TP, Bax M, Meuwissen M, Damman P, Delewi R, de Winter RJ, Koch KT, Schotborgh C, Henriques JP, Tijssen JG, Piek JJ. Impact of coronary microvascular function on long-term cardiac mortality in patients with acute ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2013;6(3):207–15.CrossRefPubMedGoogle Scholar
  44. 44.
    van de Hoef TP, Bax M, Damman P, Delewi R, Hassell ME, Piek MA, Chamuleau SA, Voskuil M, van Eck-Smit BL, Verberne HJ, Henriques JP, Koch KT, de Winter RJ, Tijssen JG, Piek JJ, Meuwissen M. Impaired coronary autoregulation is associated with long-term fatal events in patients with stable coronary artery disease. Circ Cardiovasc Interv. 2013;6(4):329–35.CrossRefPubMedGoogle Scholar
  45. 45.
    Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010;55(25):2825–32.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Britten MB, Zeiher AM, Schachinger V. Microvascular dysfunction in angiographically normal or mildly diseased coronary arteries predicts adverse cardiovascular long-term outcome. Coron Artery Dis. 2004;15(5):259–64.CrossRefPubMedGoogle Scholar
  47. 47.
    Hoffman JI. Problems of coronary flow reserve. Ann Biomed Eng. 2000;28(8):884–96.CrossRefPubMedGoogle Scholar
  48. 48.
    Cortigiani L, Rigo F, Galderisi M, Gherardi S, Bovenzi F, Picano E, Sicari R. Diagnostic and prognostic value of Doppler echocardiographic coronary flow reserve in the left anterior descending artery in hypertensive and normotensive patients [corrected]. Heart. 2011;97(21):1758–65.CrossRefPubMedGoogle Scholar
  49. 49.
    Cortigiani L, Rigo F, Gherardi S, Bovenzi F, Molinaro S, Picano E, Sicari R. Coronary flow reserve during dipyridamole stress echocardiography predicts mortality. J Am Coll Cardiol Img. 2012;5(11):1079–85.CrossRefGoogle Scholar
  50. 50.
    Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, Blankstein R, Dorbala S, Sitek A, Pencina MJ, Di Carli MF. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. 2011;124(20):2215–24.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Naya M, Murthy VL, Taqueti VR, Foster CR, Klein J, Garber M, Dorbala S, Hainer J, Blankstein R, Resnic F, Di Carli MF. Preserved coronary flow reserve effectively excludes high-risk coronary artery disease on angiography. J Nucl Med. 2014;55(2):248–55.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Taqueti VR, Hachamovitch R, Murthy VL, Naya M, Foster CR, Hainer J, Dorbala S, Blankstein R, Di Carli MF. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation. 2015;131(1):19–27.CrossRefPubMedGoogle Scholar
  53. 53.
    Iwakura K, Ito H, Takiuchi S, Taniyama Y, Nakatsuchi Y, Negoro S, Higashino Y, Okamura A, Masuyama T, Hori M, Fujii K, Minamino T. Alternation in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction. Circulation. 1996;94(6):1269–75.CrossRefPubMedGoogle Scholar
  54. 54.
    Hirsch A, Nijveldt R, Haeck JD, Beek AM, Koch KT, Henriques JP, van der Schaaf RJ, Vis MM, Baan J Jr, de Winter RJ, Tijssen JG, van Rossum AC, Piek JJ. Relation between the assessment of microvascular injury by cardiovascular magnetic resonance and coronary Doppler flow velocity measurements in patients with acute anterior wall myocardial infarction. J Am Coll Cardiol. 2008;51(23):2230–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Bax M, de Winter RJ, Schotborgh CE, Koch KT, Meuwissen M, Voskuil M, Adams R, Mulder KJJ, Tijssen JGP, Piek JJ. Short- and long-term recovery of left ventricular function predicted at the time of primary percutaneous coronary intervention in anterior myocardial infarction. J Am Coll Cardiol. 2004;43(4):534–41.CrossRefPubMedGoogle Scholar
  56. 56.
    van de Hoef TP, van Lavieren MA, Damman P, Delewi R, Piek MA, Chamuleau SA, Voskuil M, Henriques JP, Koch KT, de Winter RJ, Spaan JA, Siebes M, Tijssen JG, Meuwissen M, Piek JJ. Physiological basis and long-term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity. Circ Cardiovasc Interv. 2014;7(3):301–11.CrossRefPubMedGoogle Scholar
  57. 57.
    Johnson NP, Kirkeeide RL, Gould KL. Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology? J Am Coll Cardiol Img. 2012;5(2):193–202.CrossRefGoogle Scholar
  58. 58.
    Lee JM, Jung JH, Hwang D, Park J, Fan Y, Na SH, Doh JH, Nam CW, Shin ES, Koo BK. Coronary flow reserve and microcirculatory resistance in patients with intermediate coronary stenosis. J Am Coll Cardiol. 2016;67(10):1158–69.CrossRefPubMedGoogle Scholar
  59. 59.
    Echavarria-Pinto M, Escaned J, Macias E, Medina M, Gonzalo N, Petraco R, Sen S, Jimenez-Quevedo P, Hernandez R, Mila R, Ibanez B, Nunez-Gil IJ, Fernandez C, Alfonso F, Banuelos C, Garcia E, Davies J, Fernandez-Ortiz A, Macaya C. Disturbed coronary hemodynamics in vessels with intermediate stenoses evaluated with fractional flow reserve: a combined analysis of epicardial and microcirculatory involvement in ischemic heart disease. Circulation. 2013;128(24):2557–66.CrossRefPubMedGoogle Scholar
  60. 60.
    Smalling RW, Kelley K, Kirkeeide RL, Fisher DJ. Regional myocardial function is not affected by severe coronary depressurization provided coronary blood flow is maintained. J Am Coll Cardiol. 1985;5(4):948–55.CrossRefPubMedGoogle Scholar
  61. 61.
    van de Hoef TP, Nolte F, Rolandi MC, Piek JJ, van den Wijngaard JP, Spaan JA, Siebes M. Coronary pressure–flow relations as basis for the understanding of coronary physiology. J Mol Cell Cardiol. 2012;52(4):786–93.CrossRefPubMedGoogle Scholar
  62. 62.
    van Lavieren MA, van de Hoef TP, Sjauw KD, Piek JJ, Ferrara A, De Bruyne B, Gould KL. How should I treat a patient with refractory angina and a single stenosis with normal FFR but abnormal CFR? EuroIntervention. 2015;11(1):125–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Meuwissen M, Siebes M, Chamuleau SA, van Eck-Smit BL, Koch KT, de Winter RJ, Tijssen JG, Spaan JA, Piek JJ. Hyperemic stenosis resistance index for evaluation of functional coronary lesion severity. Circulation. 2002;106(4):441–6.CrossRefPubMedGoogle Scholar
  64. 64.
    Meuwissen M, Chamuleau SA, Siebes M, de Winter RJ, Koch KT, Dijksman LM, van den Berg AJ, Tijssen JG, Spaan JA, Piek JJ. The prognostic value of combined intracoronary pressure and blood flow velocity measurements after deferral of percutaneous coronary intervention. Catheter Cardiovasc Interv. 2008;71(3):291–7.CrossRefPubMedGoogle Scholar
  65. 65.
    van de Hoef TP, Nolte F, Damman P, Delewi R, Bax M, Chamuleau SA, Voskuil M, Siebes M, Tijssen JG, Spaan JA, Piek JJ, Meuwissen M. Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity. Circ Cardiovasc Interv. 2012;5(4):508–14.CrossRefPubMedGoogle Scholar
  66. 66.
    van de Hoef TP, Petraco R, van Lavieren MA, Nijjer S, Nolte F, Sen S, Echavarria-Pinto M, Henriques JP, Koch KT, Baan J Jr, de Winter RJ, Siebes M, Spaan JA, Tijssen JG, Meuwissen M, Escaned J, Davies JE, Piek JJ. Basal stenosis resistance index derived from simultaneous pressure and flow velocity measurements. EuroIntervention. 2016;12(2):e199–207.CrossRefPubMedGoogle Scholar
  67. 67.
    van de Hoef TP, Meuwissen M, Sen S, Nolte F, Voskuil M, Chamuleau SAJ, Siebes M, Tijssen JGP, Spaan JAE, Davies JE, Piek JJ. Basal stenosis resistance index and instantaneous wave-free ratio have the same diagnostic performance as fractional flow reserve to detect myocardial ischemia using myocardial perfusion imaging. J Am Coll Cardiol. 2013;61(10 Suppl):E1756.CrossRefGoogle Scholar
  68. 68.
    Nolte F, van de Hoef TP, de Klerk W, Baan J Jr, Lockie TP, Spaan JA, Piek JJ, Siebes M. Functional coronary stenosis severity assessed from the mean pressure gradient–velocity relationship obtained by contrast medium–induced submaximal hyperaemia. EuroIntervention. 2014;10(3):320–8.CrossRefPubMedGoogle Scholar
  69. 69.
    Meuwissen M, Chamuleau SAJ, Siebes M, Schotborgh CE, Koch KT, de Winter RJ, Bax M, de Jong A, Spaan JAE, Piek JJ. Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions. Circulation. 2001;103(2):184–7.CrossRefPubMedGoogle Scholar
  70. 70.
    Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, Ho MY, Kim HS, Loh JP, Oldroyd KG. Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention. Circulation. 2013;127(24):2436–41.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Patel N, Petraco R, Dall'Armellina E, Kassimis G, De Maria GL, Dawkins S, Lee R, Prendergast BD, Choudhury RP, Forfar JC, Channon KM, Davies J, Banning AP, Kharbanda RK. Zero-flow pressure measured immediately after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction provides the best invasive index for predicting the extent of myocardial infarction at 6 months: an OxAMI study (Oxford Acute Myocardial Infarction). JACC Cardiovasc Interv. 2015;8(11):1410–21.CrossRefPubMedGoogle Scholar
  72. 72.
    Teunissen PF, de Waard GA, Hollander MR, Robbers LF, Danad I, Biesbroek PS, Amier RP, Echavarria-Pinto M, Quiros A, Broyd C, Heymans MW, Nijveldt R, Lammertsma AA, Raijmakers PG, Allaart CP, Lemkes JS, Appelman YE, Marques KM, Bronzwaer JG, Horrevoets AJ, van Rossum AC, Escaned J, Beek AM, Knaapen P, van Royen N. Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention. Circ Cardiovasc Interv. 2015;8(3):e001786.CrossRefPubMedGoogle Scholar
  73. 73.
    Carrick D, Haig C, Ahmed N, Carberry J, Teng Yue May V, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous Abouzaid A, Mordi I, Ford I, Radjenovic A, Oldroyd KG, Berry C. Comparative prognostic utility of indices of microvascular function alone or in combination in patients with an acute ST-segment elevation myocardial infarction. Circulation. 2016;134:1833.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Aarnoudse W, Fearon WF, Manoharan G, Geven M, van de Vosse F, Rutten M, De Bruyne B, Pijls NH. Epicardial stenosis severity does not affect minimal microcirculatory resistance. Circulation. 2004;110(15):2137–42.CrossRefPubMedGoogle Scholar
  75. 75.
    Verhoeff BJ, van de Hoef TP, Spaan JA, Piek JJ, Siebes M. Minimal effect of collateral flow on coronary microvascular resistance in the presence of intermediate and noncritical coronary stenoses. Am J Physiol Heart Circ Physiol. 2012;303(4):H422–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Verhoeff BJ, Siebes M, Meuwissen M, Atasever B, Voskuil M, de Winter RJ, Koch KT, Tijssen JG, Spaan JA, Piek JJ. Influence of percutaneous coronary intervention on coronary microvascular resistance index. Circulation. 2005;111(1):76–82.CrossRefPubMedGoogle Scholar
  77. 77.
    van Lavieren MA, van de Hoef TP, Piek JJ. Coronary wedge pressure and collateral flow contribution: not a dichotomy! EuroIntervention. 2014;9(12):1485–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Yong AS, Layland J, Fearon WF, Ho M, Shah MG, Daniels D, Whitbourn R, Macisaac A, Kritharides L, Wilson A, Ng MK. Calculation of the index of microcirculatory resistance without coronary wedge pressure measurement in the presence of epicardial stenosis. JACC Cardiovasc Interv. 2013;6(1):53–8.CrossRefPubMedGoogle Scholar
  79. 79.
    Chamuleau SA, Siebes M, Meuwissen M, Koch KT, Spaan JA, Piek JJ. Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease. Am J Physiol Heart Circ Physiol. 2003;285(5):H2194–200.CrossRefPubMedGoogle Scholar
  80. 80.
    Layland J, Carrick D, McEntegart M, Ahmed N, Payne A, McClure J, Sood A, McGeoch R, MacIsaac A, Whitbourn R, Wilson A, Oldroyd K, Berry C. Vasodilatory capacity of the coronary microcirculation is preserved in selected patients with non-ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2013;6(3):231–6.CrossRefPubMedGoogle Scholar
  81. 81.
    Di Mario C, Krams R, Gil R, Serruys PW. Slope of the instantaneous hyperemic diastolic coronary flow velocity–pressure relation. A new index for assessment of the physiological significance of coronary stenosis in humans. Circulation. 1994;90(3):1215–24.CrossRefPubMedGoogle Scholar
  82. 82.
    Mancini GB, Cleary RM, DeBoe SF, Moore NB, Gallagher KP. Instantaneous hyperemic flow-versus-pressure slope index. Microsphere validation of an alternative to measures of coronary reserve. Circulation. 1991;84(2):862–70.CrossRefPubMedGoogle Scholar
  83. 83.
    Escaned J, Flores A, Garcia-Pavia P, Segovia J, Jimenez J, Aragoncillo P, Salas C, Alfonso F, Hernandez R, Angiolillo DJ, Jimenez-Quevedo P, Banuelos C, Alonso-Pulpon L, Macaya C. Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts. Circulation. 2009;120(16):1561–8.CrossRefPubMedGoogle Scholar
  84. 84.
    van der Hoeven N, Quiros A, de Waard G, Broyd C, Nijjer S, van de Hoef T, Petraco R, Driessen R, Mejia-Renteria H, van Lavieren M, Meuwissen M, Danad I, Knaapen P, Piek J, Davies J, van Royen N, Escaned J. TCT-523 instantaneous hyperemic diastolic velocity pressure slope for comprehensive physiological evaluation of epicardial and microvascular status. J Am Coll Cardiol. 2016;68(18S):B211.CrossRefGoogle Scholar
  85. 85.
    Shimada K, Sakanoue Y, Kobayashi Y, Ehara S, Hirose M, Nakamura Y, Fukuda D, Yamagishi H, Yoshiyama M, Takeuchi K, Yoshikawa J. Assessment of myocardial viability using coronary zero flow pressure after successful angioplasty in patients with acute anterior myocardial infarction. Heart. 2003;89(1):71–6.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Dattilo PB, Prasad A, Honeycutt E, Wang TY, Messenger JC. Contemporary patterns of fractional flow reserve and intravascular ultrasound use among patients undergoing percutaneous coronary intervention in the United States: insights from the National Cardiovascular Data Registry. J Am Coll Cardiol. 2012;60(22):2337–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.AMC Heartcentre, Academic Medical Center – University of AmsterdamAmsterdamThe Netherlands

Personalised recommendations