Skip to main content
SpringerLink
Log in

Quantitative Coronary Physiology for Clinical Management: the Imaging Standard

  • Nuclear Cardiology (V Dilsizian, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Pressure derived FFR and coronary flow capacity by PET define a physiologic severity-risk-benefit continuum wherein probability of benefit from revascularization over risk of the procedure and risk of residual global diffuse disease guides personalized, informed, evidenced based, interventional decisions. For the many variations in PET or MRI protocols for quantifying myocardial perfusion to define physiologic severity, the simple standard performance test combining measurement accuracy and clinical coronary pathophysiology to assure correct clinical decisions is the capacity to measure (i) rest perfusion of 0.2 cm3/min/gm in transmural scar in at least five patients to test low perfusion accuracy (ii) regional and global CFR of 4.0 or stress perfusion of 2.9 cm3/min/gm on two sequential rest-stress PET perfusion studies in the same subject with ±15 % variability for at least 15 young healthy volunteers with no risk factors, no smoking, no obesity, and no measureable blood caffeine levels.

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.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CAD:

Coronary artery disease

PET:

Positron emission tomography

CFR:

Absolute coronary flow reserve

relCFR:

Relative coronary flow reserve

FFR:

Fractional flow reserve

PCI:

Percutaneous coronary intervention

SPECT:

Single photon emission computed tomography

MI:

Myocardial infarction

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Johnson NP, Tóth GG, Lai D, Zhu H, Açar G, Agostoni P, et al. Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes. J Am Coll Cardiol. 2014;64:1641–54. From a large database establishes statistically the severity-risk-benefit continuum of CAD having profound implications for the imaging standard of quantifying severity and personalized management.

    Article  PubMed  Google Scholar 

  2. Taqueti VR, Hachamovitch R, Murthy VL, Naya M, Foster CR, Hainer J, et al. Global coronary flow reserve associates with adverse cardiovascular events independently of luminal angiographic severity, and modifies. The effect of early revascularization. Circulation. 2015;131:19–27. Documents CFR thresholds for high, intermediate and low risk global diffuse CAD.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gould KL, Johnson NP, Kaul S, Kirkeeide RL, Mintz GS, Rentrop KP, et al. Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics. Circ Cardiovasc Imaging. 2015;8, e003099. doi:10.1161/CIRCIMAGING.114.003099. Establishes basic concepts and clinical implications of the severity-risk-benefit continuum to explain failure of randomized intervention trials to reduce risk of MI or mortality and criteria for patient selection clinically and for future trials to demonstrate improved event free survival.

    Article  PubMed  Google Scholar 

  4. Johnson NP, Gould KL. Physiologic basis for angina and ST change: PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve. J Am Coll Cardiol Img. 2011;4:990–8.

    Article  Google Scholar 

  5. Johnson NP, Gould KL. Integrating noninvasive absolute flow, coronary flow reserve, and ischemic thresholds into a comprehensive map of physiologic severity. J Am Coll Cardiol Img. 2012;5:430–40. Reports the concept of Coronary Flow Capacity to define physiologic severity of CAD that incorporates stress flow in cc/min/gm and CFR thereby accounting for the great heterogeneity of continuous values into a simple color coded evidences based schema for interventional and management decisions.

    Article  Google Scholar 

  6. Gould KL, Johnson NP, Bateman TM, Beanlands RS, Bengel FM, Bober R, et al. Anatomic versus physiologic assessment of coronary artery disease: role of CFR, FFR, and PET imaging in revascularization decision-making. J Am Coll Cardiol. 2013;62:1639–53. Overview of physiologic severity of focal and global diffuse CAD with review of the world’s literature on quantitative myocardial perfusion.

    Article  PubMed  Google Scholar 

  7. Goff SL, Mazor KM, Ting HHT, Kleppel R, Rothberg MB. How cardiologists present the benefits of percutaneous coronary interventions to patients with stable angina—a qualitative analysis. JAMA Intern Med. 2014;174:1614–21.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Rothberg MB, Scherer L, Kashef MA, Coylewright M, Ting HHT, Hu B, et al. The effect of information presentation on beliefs about the benefits of elective percutaneous coronary intervention. JAMA Intern Med. 2014;174:1623–9. Documents common invalid informed consent for PCI “to prevent heart attack or death” based on absence of improved event free survival after PCI in randomized trials.

    Article  PubMed  Google Scholar 

  9. Hachamovitch R, Nutter B, Hlatky MA, et al. Patient management after noninvasive cardiac imaging results from SPARC (study of myocardial perfusion and coronary anatomy imaging rolesin coronary artery disease). J Am Coll Cardiol. 2012;59:462–74.

    Article  PubMed  Google Scholar 

  10. Hermann LK, Newman DH, Pleasant WA, et al. Yield of routine provocative cardiac testing among patients in an emergency department-based chest pain unit. JAMA Intern Med. 2013;173:1128–33.

    Article  PubMed  Google Scholar 

  11. Young LH, Wackers FJ, Chyun DA, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301:1547–55.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Patel MR, Dai D, Hernandez AF, et al. Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J. 2014;167:846–52.e2.

    Article  PubMed  Google Scholar 

  13. 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;87:1354–67.

    Article  PubMed  CAS  Google Scholar 

  14. Pijls NH, van Schaardenburgh P, Manoharan G, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER study. J Am Coll Cardiol. 2007;49:2105–11.

    Article  PubMed  Google Scholar 

  15. Pijls NH, Fearon WF, Tonino PA, et al. 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;56:177–84.

    Article  PubMed  Google Scholar 

  16. De Bruyne B, Fearon WF, Pijls NH, Barbato E, Tonino P, Piroth Z, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014;371:1208–17. FAME 2 results showing no reduced MI or death after PCI compared to medical treatment for visually significant angiogram stenosis with FFR of 0.8 or less.

    Article  PubMed  Google Scholar 

  17. Curzen N, Rana O, Nicholas Z, Golledge P, Zaman A, Oldroyd K, et al. Does routine pressure wire assessment influence management strategy at coronary angiography for diagnosis of chest pain? The RIPCORD study. Circ Cardiovasc Interv. 2014;7:248–55.

    Article  PubMed  Google Scholar 

  18. Van Belle E, Rioufol G, Pouillot C, Cuisset T, Bougrini K, Teiger E, et al. Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry. Circulation. 2014;129:173–85. Documents frequent discordant between low FFR and absence of significant angiogram stenosis.

    Article  PubMed  Google Scholar 

  19. Toth G, Hamilos M, Pyxaras S, Mangiacapra F, Nelis O, De Vroey F, et al. Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenosis. Eur Heart J. 2014;35:2831–8. Documents frequent discordant between low FFR and absence of significant angiogram stenosis.

    Article  PubMed  Google Scholar 

  20. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574–651. Also 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. J Am Coll Cardiol. 2011;58(24):e44-e122. doi: 10.1016/j.jacc.2011.08.007.

  21. Wijeysundera HC, Nallamothu BK, Krumholz HM, Tu JV, Ko DT. Meta-analysis: effects of percutaneous coronary intervention versus medical therapy on angina relief. Ann Intern Med. 2010;152:370–9.

    Article  PubMed  Google Scholar 

  22. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356:1503–16.

    Article  PubMed  CAS  Google Scholar 

  23. Inducible Myocardial Ischemia and Outcomes in Patients With Coronary Artery Disease and Left Ventricular Dysfunction—Substudy of STICH With Reversible Ischemia by SPECT. J Am Coll Cardiol. 2013;61:1860–1870.

  24. Johnson NP, Kirkeeide RL, Gould KL. Is discordance of coronary flow reserve (CFR) and fractional flow reserve (FFR) due to methodology or clinically relevant coronary pathophysiology? J Am Coll Cardiol Img. 2012;5:193–202.

    Article  Google Scholar 

  25. Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, et al. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. 2011;124:2215–24.

    Article  PubMed  PubMed Central  Google Scholar 

  26. De Bruyne B, Baudhuin T, Melin JA, Pijls NH, Sys SU, Bol A, et al. Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography. Circulation. 1994;89:1013–22.

    Article  PubMed  Google Scholar 

  27. Johnson NP, Johnson DT, Kirkeeide RL, Berry C, De Bruyne B, Fearon WF, et al. Repeatability of fractional flow reserve (FFR) despite variations I systemic and coronary hemodynamics. J m Coll Cardiol: Cardiovascular Interventions. 2015 (In Press).

  28. Tauchert M. Coronary reserve capacity and maximum oxygen consumption of the human heart. Basic Res Cardiol. 1973;68(2):183–223.

    Article  PubMed  CAS  Google Scholar 

  29. Marcus M, Wright C, Doty D, Eastham C, Laughlin D, Krumm P, et al. Measurements of coronary velocity and reactive hyperemia in the coronary circulation of humans. Circ Res. 1981;49(4):877–91.

    Article  PubMed  CAS  Google Scholar 

  30. White CW, Wright CB, Doty DB, Hiratza LF, Eastham CL, Harrison DG, et al. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med. 1984;310(13):819–24.

    Article  PubMed  CAS  Google Scholar 

  31. Wilson RF, Laughlin DE, Ackell PH, Chilian WM, Holida MD, Hartley CJ, et al. Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man. Circulation. 1985;72(1):82–92.

    Article  PubMed  CAS  Google Scholar 

  32. Marcus ML, Wilson RF, White CW. Methods of measurement of myocardial blood flow in patients: a critical review. Circulation. 1987;76(2):245–53.

    Article  PubMed  CAS  Google Scholar 

  33. Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation. 1990;82(5):1595–606.

    Article  PubMed  CAS  Google Scholar 

  34. Wang L, Jerosch-Herold M, Jacobs DR, Shahar E, Detrano R, Folsom AR. Coronary calcification and myocardial perfusion in asymptomatic adults. J Am Coll Cardiol. 2006;48:1018–26.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Wang L, Jerosch-Herold M, Jacobs DR, Shahar E, Detrano R, Folsom AR. Coronary risk factors and myocardial perfusion in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol. 2006;47:565–72.

    Article  PubMed  Google Scholar 

  36. Sdringola S, Johnson NP, Kirkeeide RL, Cid E, Gould KL. Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers. J Am Coll Cardiol Img. 2011;4:402–12.

    Article  Google Scholar 

  37. Murdock RH, Cobb FR. Effects of infarcted myocardium on regional blood flow measurements to ischemic regions in canine heart. Circ Res. 1980;47:701–9.

    Article  PubMed  Google Scholar 

  38. Rivas F, Cobb FR, Bache RJ, Greenfield JC. Relationship of blood flow toischemic regions and extent of myocardial infarction—serial measurement of blood flow to ischemic regions in dogs. Circ Res. 1976;38:439–47.

    Article  PubMed  CAS  Google Scholar 

  39. Zhang WZ, Zha DG, Cheng GX, Yang SQ, Huang XB, Qin JX, et al. Assessment of regional myocardial blood flow with myocardial contrast echocardiography: an experimental study. Echocardiography. 2004;21:409–16.

    Article  PubMed  CAS  Google Scholar 

  40. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis. Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol. 1974;33:87–94.

    Article  PubMed  CAS  Google Scholar 

  41. Johnson NP, Gould KL. Regadenoson versus dipyridamole hyperemia for cardiac PET imaging. J Am Coll Cardiol Img. 2015;8:438–47.

    Article  Google Scholar 

  42. Johnson NP, Gould KL. Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by Markovian analysis of P.E.T. identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects. J Nucl Med. 2005;46:1427–37.

    PubMed  Google Scholar 

  43. Loghin C, Sdringola S, Gould KL. Does coronary vasodilation after adenosine override endothelin-1 induced coronary vasoconstriction? Experimental validation of a new concept in myocardial perfusion imaging: resting perfusion defects that improve after adenosine are markers of coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2007;292:496–502.

    Article  Google Scholar 

  44. Johnson NP, Gould KL. Physiology of endothelin in producing myocardial perfusion heterogeneity: a mechanistic study using darusentan and positron emission tomography. J Nucl Cardiol. 2013;20:835–44.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gould KL, Kirkeeide R, Johnson NP. Coronary branch steal—experimental validation and clinical implications of interacting stenosis in branching coronary arteries. Circ Cardiovasc Imaging. 2010;3:701–9.

    Article  PubMed  Google Scholar 

  46. Loghin C, Sdringola S, Gould KL. Common artifacts in PET myocardial perfusion images due to attenuation-emission misregistration: clinical significance, causes and solutions in 1177 patients. J Nucl Med. 2004;45:1029–39.

    PubMed  Google Scholar 

  47. Gould KL, Pan T, Loghin C, Johnson N, Guha A, Sdringola S. Frequent diagnostic errors in cardiac PET-CT due to misregistration of CT attenuation and emission PET images: a definitive analysis of causes, consequences and corrections. J Nucl Med. 2007;48:1112–21.

    Article  PubMed  Google Scholar 

  48. Johnson NP, Pan T, Gould KL. Shifted helical CT to optimize cardiac PET-CT co-registration: quantitative improvement and limitations. J Mol Imaging. 2010;9:256–67.

    Google Scholar 

  49. Klein R, Beanlands RSB, deKemp RA. Quantification of myocardial blood flow and flow reserve: technical aspects. J Nucl Cardiol. 2010;17:555–70.

    Article  PubMed  Google Scholar 

  50. deKemp RA, Yoshinaga KY, Beanlands RSB. Will 30dimensional PET-CT enable the routine quantification of myocardial blood flow. J Nucl Cardiol. 2007;14:380–97.

    Article  PubMed  Google Scholar 

  51. Gould KL, Pan T, Loghin C, Johnson NP, Sdringola. Reducing radiation dose in rest stress cardiac PET-CT by single post stress cine CT for attenuation correction—quantitative validation. J Nucl Med. 2008;49:738–45.

    Article  PubMed  Google Scholar 

  52. Kaster TS, Dwivedi G, Susser L, Renaud JM, Beanlands RS, Chow BJ, et al. Single low-dose CT scan optimized for rest-stress PET attenuation correction and quantification of coronary artery calcium. J Nucl Cardiol. 2015;22:419–28.

    Article  PubMed  Google Scholar 

  53. Vasquez AF, Johnson NP, Gould KL. Variation in quantitative myocardial perfusion due to arterial input selection. J Am Coll Cardiol Img. 2013;6:559–68.

    Article  Google Scholar 

  54. Yoshida K, Mullani N, Gould KL. Coronary flow and flow reserve by positron emission tomography simplified for clinical application using Rb-82 or N-13 ammonia. J Nucl Med. 1996;37:1701–12.

    PubMed  CAS  Google Scholar 

  55. Renaud JM, DaSilva JN, Beanlands RSB, deKemp RA. Characterizing the normal range of myocardial blood flow with rubidium-82 and N-13 ammonia PET imaging. J Nucl Cardiol. 2013;20:578–91.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Weatherhead PET Center For Preventing and Reversing Atherosclerosis, Division of Cardiology, Department of Medicine, University of Texas Medical School and Memorial Hermann Hospital, Houston, TX, USA

    K. Lance Gould & Nils P. Johnson

  2. Weatherhead PET Center, University of Texas Medical School at Houston, 6431 Fannin St., Room MSB 4.256, Houston, TX, 77030, USA

    K. Lance Gould

Authors
  1. K. Lance Gould
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nils P. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Lance Gould.

Ethics declarations

Conflict of Interest

K. Lance Gould and Nils P. Johnson declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Financial Support and Relationships with Industry

KLG received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis and is the 510(k) applicant for CFR Quant (K113754) and HeartSee (K143664), software packages for cardiac positron emission tomography image processing and analysis, including absolute flow quantification. All royalties will go to a University of Texas scholarship fund.

NPJ received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis and has received significant institutional research support from St. Jude Medical (for NCT02184117) and Volcano/Philips Corporation (for NCT02328820), makers of intracoronary pressure and flow sensors.

Additional information

This article is part of the Topical Collection on Nuclear Cardiology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gould, K.L., Johnson, N.P. Quantitative Coronary Physiology for Clinical Management: the Imaging Standard. Curr Cardiol Rep 18, 9 (2016). https://doi.org/10.1007/s11886-015-0684-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-015-0684-7

Keywords

Search

Navigation