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Current Cardiovascular Imaging Reports
Published in: Current Cardiovascular Imaging Reports 2/2015

01-02-2015 | Cardiac Nuclear Imaging (A Cuocolo, Section Editor)

From Physiology of the Coronary Circulation to Myocardial Perfusion Imaging

Author: Henry Gewirtz

Published in: Current Cardiovascular Imaging Reports | Issue 2/2015

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Abstract

The present paper reviews important recent publications concerning the application of principles of coronary physiology to quantitative PET myocardial perfusion imaging. Invasive measurements as well as coronary computed tomography angiography are also considered. The review focuses on physiological concepts relevant to the understanding of the effects of coronary atherosclerosis on myocardial blood flow (MBF) responses to stress. It also highlights the increasing shift from an anatomical paradigm of stenosis severity assessment to a physiological one, emphasizing the importance of absolute measurements of MBF. Key concepts and supporting literature reviewed in the present paper include quantitative PET measurements of absolute rest and stress MBF, the use of stress MBF alone for physiological assessment of stenosis functional severity, the utility of ratios such as fractional flow reserve (FFR) and coronary flow reserve (CFR) in assessing stenosis severity, and most importantly, the absolute level of MBF required to sustain vigorous physical exercise (9–10 metabolic equivalents (METs)) in healthy adults.
Literature
1.
Sones Jr FM. Diagnosis of septal defects by the combined use of heart catheterization and selective cinecardioangiography. Am J Cardiol. 1958;2(6):724–31.PubMedCrossRef
2.
Sones Jr FM, Shirey EK. Cine coronary arteriography. Mod Concepts Cardiovasc Dis. 1962;31:735–8.PubMed
3.
Proudfit WL, Shirey EK, Sones Jr FM. Selective cine coronary arteriography. Correlation with clinical findings in 1,000 patients. Circulation. 1966;33(6):901–10.PubMedCrossRef
4.
Gould KL, Hamilton GW, Lipscomb K, Ritchie JL, Kennedy JW. Method for assessing stress-induced regional malperfusion during coronary arteriography. Experimental validation and clinical application. Am J Cardiol. 1974;34:557–64.PubMedCrossRef
5.
Gould KL, Lipscomb K, Calvert C. Compensatory changes of the distal coronary vascular bed during progressive coronary constriction. Circulation. 1975;51:1085–94.PubMedCrossRef
6.
Gould KL. Pressure-flow characteristics of coronary stenoses in unsedated dogs at rest and during coronary vasodilation. Circ Res. 1978;43:242–53.PubMedCrossRef
7.
Gould KL. Non-invasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacological coronary vasodilation. I. Physiological basis and experimental validation. Am J Cardiol. 1978;41:267–78.PubMedCrossRef
8.
9.
Gould KL. Percent coronary stenosis: battered gold standard, pernicious relic or clinical practicality. J Am Coll Cardiol. 1988;11:886–8.PubMedCrossRef
10.
Zir LM, Miller SW, Dinsmore RE, Gilbert JP, Harthorne JW. Interobserver variability in coronary angiography. Circulation. 1976;53(4):627–32.PubMedCrossRef
11.
White CW, Wright CB, Doty DB, Hiratzka LF, Eastham CL, Harrison DG, et al. Does visual interpretation of the coronary arteriogram predict the physiological importance of a coronary stenosis. N Engl J Med. 1984;310:819–24.PubMedCrossRef
12.
Wilson RF, Marcus ML, White CW. Prediction of the physiological significance of coronary artery lesions by quantitative lesion geometry in patients with limited coronary artery disease. Circulation. 1987;75:723–32.PubMedCrossRef
13.
Nakazato R, Tamarappoo BK, Kang X, Wolak A, Kite F, Hayes SW, et al. Quantitative upright-supine high-speed SPECT myocardial perfusion imaging for detection of coronary artery disease: correlation with invasive coronary angiography. J Nucl Med. 2010;51(11):1724–31.PubMedCentralPubMedCrossRef
14.
Tamarappoo BK, Dey D, Nakazato R, Shmilovich H, Smith T, Cheng VY, et al. Comparison of the extent and severity of myocardial perfusion defects measured by CT coronary angiography and SPECT myocardial perfusion imaging. JACC Cardiovasc Imaging. 2010;3(10):1010–9.PubMedCrossRef
15.••
Berman DS, Shaw LJ, Min JK, Hachamovitch R, Abidov A, Germano G, et al. SPECT/PET myocardial perfusion imaging versus coronary CT angiography in patients with known or suspected CAD. Q J Nucl Med Mol Imaging. 2010;54(2):177–200. Excellent review of SPECT/PET myocardial perfusion imaging and concordance or lack thereof with coronary anatomy as defined by CCTA.PubMed
16.
Tamarappoo BK, Gutstein A, Cheng VY, Nakazato R, Gransar H, Dey D, et al. Assessment of the relationship between stenosis severity and distribution of coronary artery stenoses on multislice computed tomographic angiography and myocardial ischemia detected by single photon emission computed tomography. J Nucl Cardiol. 2010;17(5):791–802.PubMedCentralPubMedCrossRef
17.
Berman DS, Shaw LJ, Hachamovitch R, Friedman JD, Polk DM, Hayes SW, et al. Comparative use of radionuclide stress testing, coronary artery calcium scanning, and noninvasive coronary angiography for diagnostic and prognostic cardiac assessment. Semin Nucl Med. 2007;37(1):2–16.PubMedCrossRef
18.
Demer LL, Gould KL, Goldstein RA, Kirkeeide RL, Mullani NA, Smalling RW, et al. Assessment of coronary artery disease severity by positron emission tomography: comparison with quantitative coronary arteriography in 193 patients. Circulation. 1989;79:825–35.PubMedCrossRef
19.••
Gould KL, Johnson NP, Bateman TM, Beanlands RS, Bengel FM, Bober R, et al. Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making. J Am Coll Cardiol. 2013;62(18):1639–53. Key reference which provides essential data and analysis for understanding the role of PET quantitative measurement of absolute MBF in clinical decision making regarding coronary revascularization.PubMedCrossRef
20.
Hajjiri MM, Leavitt MB, Zheng H, Spooner AE, Fischman AJ, Gewirtz H. Comparison of positron emission tomography measurement of adenosine-stimulated absolute myocardial blood flow versus relative myocardial tracer content for physiological assessment of coronary artery stenosis severity and location. JACC Cardiovasc Imaging. 2009;2(6):751–8.PubMedCrossRef
21.
Gould KL. Coronary flow reserve and pharmacologic stress perfusion imaging: beginnings and evolution. JACC Cardiovasc Imaging. 2009;2(5):664–9.PubMedCrossRef
22.
Dean LS. Adjunctive diagnostic instruments for PCI. J Invasive Cardiol. 2008;20(3):E88–9.PubMed
23.
24.
Topol EJ, Nissen SE. Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease. Circulation. 1995;92(8):2333–42.PubMedCrossRef
25.
26.••
Johnson NP, Kirkeeide RL, Gould KL. Coronary anatomy to predict physiology: fundamental limits. Circ Cardiovasc Imaging. 2013;6(5):817–32. Superb review of the limits of anatomical coronary stenosis severity for predicting the functional effects of the lesion on the coronary circulation. The measurement of absolute MBF is essential for clinical decision making regarding coronary revascularization.PubMedCrossRef
27.
Pijls NH, Fearon WF, Tonino PA, Siebert U, Ikeno F, Bornschein B, 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(3):177–84.PubMedCrossRef
28.••
De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991–1001. Report of FAME 2 trial.PubMedCrossRef
29.
Meuwissen M, Siebes M, Chamuleau SA, van Eck-Smit BL, Koch KT, de Winter RJ, et al. Hyperemic stenosis resistance index for evaluation of functional coronary lesion severity. Circulation. 2002;106(4):441–6.PubMedCrossRef
30.
Petraco R, van de Hoef TP, Nijjer S, Sen S, van Lavieren MA, Foale RA, et al. 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;7:492–502.PubMedCrossRef
31.
Jeremias A, Maehara A, Genereux P, Asrress KN, Berry C, De Bruyne B, et al. 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. 2013;63(13):1253–61.PubMedCrossRef
32.
Sen S, Asrress KN, Nijjer S, Petraco R, Malik IS, Foale RA, et al. Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study). J Am Coll Cardiol. 2013;61(13):1409–20.PubMedCrossRef
33.
De Bruyne B, Bartunek J, Sys SU, Heyndrickx GR. Relation between myocardial fractional flow reserve calculated from coronary pressure measurements and exercise-induced myocardial ischemia. Circulation. 1995;92(1):39–46.PubMedCrossRef
34.
Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’t Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–24.PubMedCrossRef
35.
Petraco R, Sen S, Nijjer S, Echavarria-Pinto M, Escaned J, Francis DP, et al. Fractional flow reserve-guided revascularization: practical implications of a diagnostic gray zone and measurement variability on clinical decisions. JACC Cardiovasc Interv. 2013;6(3):222–5.PubMedCrossRef
36.
Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van’t Veer M, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Cardiol. 2007;49(21):2105–11.PubMedCrossRef
37.
Meuwissen M, Siebes M, Spaan JA, Piek JJ. Rationale of combined intracoronary pressure and flow velocity measurements. Z Kardiol. 2002;91 Suppl 3:108–12.PubMedCrossRef
38.••
van de Hoef TP, van Lavieren MA, Damman P, Delewi R, Piek MA, Chamuleau SA, et al. 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. Important clinical description of the frequency with which FFR and CFR differ; normal versus abnormal.PubMedCrossRef
39.••
Johnson NP, Kirkeeide RL, Gould KL. Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology? JACC Cardiovasc Imaging. 2012;5(2):193–202. Important review of the physiology underlying why FFR and CFR may differ; normal versus abnormal.PubMedCrossRef
40.
Siebes M, Chamuleau SA, Meuwissen M, Piek JJ, Spaan JA. Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model. Am J Physiol Heart Circ Physiol. 2002;283(4):H1462–70.PubMed
41.
Gewirtz H. Fractional flow reserve. Circulation. 1996;94(9):2306–7.PubMed
42.
Sen S, Nijjer S, Petraco R, Malik IS, Francis DP, Davies J. Instantaneous wave-free ratio: numerically different, but diagnostically superior to FFR? Is lower always better? J Am Coll Cardiol. 2013;62(6):566.PubMedCrossRef
43.
Sen S, Escaned J, Malik IS, Mikhail GW, Foale RA, Mila R, et al. 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.PubMedCrossRef
44.
Berry C, Van’t Veer M, Witt N, Kala P, Bocek O, Pyxaras SA, et al. VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice): a multicenter study in consecutive patients. J Am Coll Cardiol. 2013;61(13):1421–7.PubMedCrossRef
45.
Blankstein R, Shturman LD, Rogers IS, Rocha-Filho JA, Okada DR, Sarwar A, et al. Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography. J Am Coll Cardiol. 2009;54(12):1072–84.PubMedCrossRef
46.••
Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012;308(12):1237–45. First report of CCTA and computational fluid dynamics for noninvasive measurement of FFR.PubMedCentralPubMedCrossRef
47.
Nakazato R, Park HB, Berman DS, Gransar H, Koo BK, Erglis A, et al. Noninvasive fractional flow reserve derived from computed tomography angiography for coronary lesions of intermediate stenosis severity: results from the DeFACTO study. Circ Cardiovasc Imaging. 2013;6(6):881–9.PubMedCrossRef
48.••
Nieman K, de Feijter PJ. Aerodynamics in cardiac CT. Circ Cardiovasc Imaging. 2013;6(6):853–4. Important review of assumptions, methods, and limitations underlying CCTA-based FFR measurements.PubMedCrossRef
49.••
Gewirtz H. PET measurement of adenosine stimulated absolute myocardial blood flow for physiological assessment of the coronary circulation. J Nucl Cardiol. 2012;19(2):347–54. Important review of PET measurements of absolute, maximal MBF for assessment of the coronary circulation and recognition of functionally significant CAD.PubMedCrossRef
50.
Johnson NP, Gould KL. Physiological basis for angina and ST-segment change PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve. JACC Cardiovasc Imaging. 2011;4(9):990–8.PubMedCrossRef
51.••
Johnson NP, Gould KL. Integrating noninvasive absolute flow, coronary flow reserve, and ischemic thresholds into a comprehensive map of physiological severity. JACC Cardiovasc Imaging. 2012;5(4):430–40. Important review of PET measurements of absolute MBF and CFR for assessment of the coronary circulation and recognition of functionally significant CAD.PubMedCrossRef
52.••
Kajander SA, Joutsiniemi E, Saraste M, Pietila M, Ukkonen H, Saraste A, et al. Clinical value of absolute quantification of myocardial perfusion with 15O-water in coronary artery disease. Circ Cardiovasc Imaging. 2011;4(6):678–84. Important report of PET measurements of absolute, maximal MBF for detection of functionally significant (FFR < 0.80) CAD.PubMedCrossRef
53.
Danad I, Raijmakers PG, Appelman YE, Harms HJ, de Haan S, van den Oever ML, et al. Hybrid imaging using quantitative H215O PET and CT-based coronary angiography for the detection of coronary artery disease. J Nucl Med. 2013;54(1):55–63.PubMedCrossRef
54.
Laaksonen MS, Kalliokoski KK, Luotolahti M, Kemppainen J, Teras M, Kyrolainen H, et al. Myocardial perfusion during exercise in endurance-trained and untrained humans. Am J Physiol Regul Integr Comp Physiol. 2007;293(2):R837–43.PubMedCrossRef
55.
Ball RM, Bache RJ, Cobb FR, Greenfield Jr JC. Regional myocardial blood flow during graded treadmill exercise in the dog. J Clin Invest. 1975;55(1):43–9.PubMedCentralPubMedCrossRef
56.
Berman M, Fischman AJ, Southern J, Carter E, Mirecki F, Strauss HW, et al. Myocardial adaptation during and after sustained, demand-induced ischemia. Observations in closed-chest, domestic swine. Circulation. 1996;94(4):755–62.PubMedCrossRef
57.
Skopicki HA, Abraham SA, Picard MH, Alpert NM, Fischman AJ, Gewirtz H. Effects of dobutamine at maximally tolerated dose on myocardial blood flow in humans with ischemic heart disease. Circulation. 1997;96(10):3346–52.PubMedCrossRef
58.
Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev. 2008;88(3):1009–86.PubMedCrossRef
59.
Tawakol A, Forgione MA, Stuehlinger M, Alpert NM, Cooke JP, Loscalzo J, et al. Homocysteine impairs coronary microvascular dilator function in humans. J Am Coll Cardiol. 2002;40(6):1051–8.PubMedCrossRef
60.
Bourque JM, Holland BH, Watson DD, Beller GA. Achieving an exercise workload of > or = 10 metabolic equivalents predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? J Am Coll Cardiol. 2009;54(6):538–45.PubMedCentralPubMedCrossRef
61.
Gregory SA, MacRae CA, Aziz K, Sims KB, Schmahmann JD, Kardan A, et al. Myocardial blood flow and oxygen consumption in patients with Friedreich’s ataxia prior to the onset of cardiomyopathy. Coron Artery Dis. 2007;18(1):15–22.PubMedCrossRef
62.
Taegtmeyer H. Cardiac metabolism as a target for the treatment of heart failure. Circulation. 2004;110(8):894–6.PubMedCrossRef
63.
Taegtmeyer H. Glucose for the heart: too much of a good thing? J Am Coll Cardiol. 2005;46(1):49–50.PubMedCrossRef
64.
65.
Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: part I: general concepts. Circulation. 2002;105(14):1727–33.PubMedCrossRef
66.
Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: part II: potential mechanisms. Circulation. 2002;105(15):1861–70.PubMedCrossRef
67.
Gewirtz H, Fischman AJ, Abraham SA, Gilson M, Strauss HW, Alpert NM. Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction. J Am Coll Cardiol. 1994;23:851–9.PubMedCrossRef
Metadata
Title
From Physiology of the Coronary Circulation to Myocardial Perfusion Imaging
Author
Henry Gewirtz
Publication date
01-02-2015
Publisher
Springer US
Published in
Current Cardiovascular Imaging Reports / Issue 2/2015
Print ISSN: 1941-9066
Electronic ISSN: 1941-9074
DOI
https://doi.org/10.1007/s12410-014-9313-x

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