Abstract
Myocardial perfusion imaging remains a powerful tool for evaluating the entire spectrum of severity in the natural history of coronary atherosclerosis. Although measures of ischemic burden (ie, perfusion defects) remain the primary endpoint of interest in the noninvasive evaluation of obstructive CAD, measures of MBF and coronary vasodilator reserve may be better suited for delineating populations at risk in preclinical stages of atherosclerosis. The data presented above demonstrate the value of measures of coronary vasodilator function for early detection of patients at risk for CAD and for monitoring the effects of therapeutic interventions. Detection of patients at risk may offer an opportunity for early medical intervention aimed at halting the progression of atherogenesis and ultimately lead to a reduction in cardiovascular events.
References
Smits P, Williams SB, Lipson DE, et al. Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans [published erratum appears in Circulation 1996;93:1942]. Circulation 1995;92:2135–41.
Buus NH, Bottcher M, Hermansen F, et al. Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia. Circulation 2001;104:2305–10.
Czernin J, Barnard RJ, Sun KT, et al. Effect of short-term cardiovascular conditioning and low-fat diet on myocardial blood flow and flow reserve. Circulation 1995;92:197–204.
Guethlin M, Kasel AM, Coppenrath K, et al. Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin. Circulation 1999;99:475–81.
Yokoyama I, Momomura S, Ohtake T, et al. Improvement of impaired myocardial vasodilatation due to diffuse coronary atherosclerosis in hypercholesterolemics after lipid-lowering therapy. Circulation 1999;100:117–22.
Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP. Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test. Circulation 1988;77:43–52.
Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium [see comments]. J Am Coll Cardiol 1989;14:1181–90.
Zeiher AM, Drexler H, Wollschlager H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991;84:1984–92.
Kichuk MR, Seyedi N, Zhang X, et al. Regulation of nitric oxide production in human coronary microvessels and the contribution of local kinin formation. Circulation 1996;94:44–51.
Nitenberg A, Valensi P, Sachs R, et al. Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function. Diabetes 1993;42:1017–25.
Ronderos RE, Boskis M, Chung N, et al. Correlation between myocardial perfusion abnormalities detected with intermittent imaging using intravenous perfluorocarbon microbubbles and radioisotope imaging during high-dose dipyridamole stress echo. Clin Cardiol 2002;25:103–11.
Ibrahim T, Nekolla SG, Schreiber K, et al. Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography. J Am Coll Cardiol 2002;39:864–70.
Kuhle WG, Porenta G, Huang SC, et al. Quantification of regional myocardial blood flow using 13N-ammonia and reoriented dynamic positron emission tomographic imaging. Circulation 1992;86: 1004–17.
Muzik O, Beanlands RS, Hutchins GD, et al. Validation of nitrogen-13-ammonia tracer kinetic model for quantification of myocardial blood flow using PET. J Nucl Med 1993;34:83–91.
Nitzsche EU, Choi Y, Czernin J, et al. Noninvasive quantification of myocardial blood flow in humans. A direct comparison of the [13N]ammonia and the [15O]water techniques. Circulation 1996; 93:2000–6.
Rodriguez-Porcel M, Lerman LO, Herrmann J, et al. Hypercholesterolemia and hypertension have synergistic deleterious effects on coronary endothelial function. Arterioscler Thromb Vasc Biol 2003;23:885–91.
Di Carli MF, Janisse J, Grunberger G, Ager J. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 2003;41:1387–93.
Di Carli MF, Dorbala S, Hassan A, et al. Relation of coronary vasodilator reserve to features of the metabolic syndrome in patients with documented or at risk for coronary artery disease. Circulation. 2003;108(Suppl):IV-404.
Campisi R, Nathan L, Pampaloni MH, et al. Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration. Circulation 2002;105:425–30.
Peterson LR, Eyster D, Davila-Roman VG, et al. Short-term oral estrogen replacement therapy does not augment endotheliumindependent myocardial perfusion in postmenopausal women. Am Heart J 2001;142:641–7.
Duvernoy CS, Rattenhuber J, Seifert-Klauss V, et al. Myocardial blood flow and flow reserve in response to short-term cyclical hormone replacement therapy in postmenopausal women. J Gend Specif Med 2001;4:21–7, 47.
Cicinelli E, Ignarro LJ, Matteo MG, et al. Effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women. Am J Obstet Gynecol 1999;180:334–9.
Czernin J, Sun K, Brunken R, et al. Effect of acute and long-term smoking on myocardial blood flow and flow reserve. Circulation 1995;91:2891–7.
Kaufmann PA, Gnecchi-Ruscone T, di Terlizzi M, et al. Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation 2000;102:1233–8.
Campisi R, Czernin J, Schoder H, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation 1998;98:119–25.
Campisi R, Czernin J, Schoder H, Sayre JW, Schelbert HR. L-arginine normalizes coronary vasomotion in long-term smokers. Circulation 1999;99:491–7.
Hamasaki S, Al Suwaidi J, Higano ST, et al. Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy. J Am Coll Cardiol 2000;35:1654- 60.
Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990;323:22–7.
Treasure CB, Klein JL, Vita JA, et al. Hypertension and left ventricular hypertrophy are associated with impaired endotheliummediated relaxation in human coronary resistance vessels. Circulation 1993;87:86–93.
Houghton JL, Frank MJ, Carr AA, von Dohlen TW, Prisant LM. Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease. J Am Coll Cardiol 1990;15:43–51.
Akinboboye OO, Chou RL, Bergmann SR. Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: a comparison of lisinopril and losartan. J Am Coll Cardiol 2002;40:703–9.
Laine H, Raitakari OT, Niinikoski H, et al. Early impairment of coronary flow reserve in young men with borderline hypertension. J Am Coll Cardiol 1998;32:147–53.
Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129–33.
Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289–98.
Kane JP, Malloy MJ, Ports TA, et al. Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA 1990;264:3007–12.
Gould KL, Ornish D, Scherwitz L, et al. Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification. JAMA 1995;274:894- 901.
Watts GF, Lewis B, Brunt JN, et al. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas’ Atherosclerosis Regression Study (STARS). Lancet 1992;339:563–9.
Schwartz RG, Pearson TA, Kalaria VG, et al. Prospective serial evaluation of myocardial perfusion and lipids during the first six months of pravastatin therapy: coronary artery disease regression single photon emission computed tomography monitoring trial. J Am Coll Cardiol 2003;42:600–10.
Green A, Bain C. Epidemiological overview of oestrogen replacement and cardiovascular disease. Baillieres Clin Endocrinol Metab 1993;7:95–112.
Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605–13.
Kirkeeide RL, Gould KL, Parsel L. Assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VII. Validation of coronary flow reserve as a single integrated functional measure of stenosis severity reflecting all its geometric dimensions. J Am Coll Cardiol 1986;7:103- 13.
Gould KL, Goldstein RA, Mullani NA, et al. Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generatorproduced rubidium-82. J Am Coll Cardiol 1986;7:775–89.
Wilson RF, Marcus ML, White CW. Prediction of the physiologic significance of coronary arterial lesions by quantitative lesion geometry in patients with limited coronary artery disease. Circulation 1987;75:723–32.
Van Train KF, Garcia EV, Maddahi J, et al. Multicenter trial validation for quantitative analysis of same-day rest-stress technetium- 99m-sestamibi myocardial tomograms. J Nucl Med 1994;35: 609–18.
Di Carli M, Czernin J, Hoh CK, et al. Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease. Circulation 1995;91:1944–51.
Uren NG, Melin JA, De Bruyne B, et al. Relation between myocardial blood flow and the severity of coronary-artery stenosis. N Engl J Med 1994;330:1782–8.
Beanlands RS, Muzik O, Melon P, et al. Noninvasive quantification of regional myocardial flow reserve in patients with coronary atherosclerosis using nitrogen-13 ammonia positron emission tomography. Determination of extent of altered vascular reactivity. J Am Coll Cardiol 1995;26:1465–75.
Uren NG, Crake T, Lefroy DC, et al. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction [see comments]. N Engl J Med 1994;331:222–7.
Yoshinaga K, Katoh C, Noriyasu K, et al. Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15-labeled water PET. J Nucl Cardiol 2003;10:275–83.
Al Suwaidi J, Reddan DN, Williams K, et al. Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes. Circulation 2002;106:974–80.
Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899–906.
Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation 2002;106: 653–8.
Schindler TH, Hornig B, Buser PT, et al. Prognostic value of abnormal vasoreactivity of epicardial coronary arteries to sympathetic stimulation in patients with normal coronary angiograms. Arterioscler Thromb Vasc Biol 2003;23:495–501.
Dayanikli F, Grambow D, Muzik O, et al. Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation 1994;90:808–17.
Pitkanen OP, Raitakari OT, Niinikoski H, et al. Coronary flow reserve is impaired in young men with familial hypercholesterolemia. J Am Coll Cardiol 1996;28:1705–11.
Yokoyama I, Murakami T, Ohtake T, et al. Reduced coronary flow reserve in familial hypercholesterolemia. J Nucl Med 1996;37: 1937–42.
Yokoyama I, Ohtake T, Momomura S, et al. Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis. Circulation 1996;94:3232–8.
Yokoyama I, Ohtake T, Momomura S, et al. Altered myocardial vasodilatation in patients with hypertriglyceridemia in anatomically normal coronary arteries. Arterioscler Thromb Vasc Biol 1998;18:294–9.
Meyer C, Schwaiger M. Myocardial blood flow and glucose metabolism in diabetes mellitus. Am J Cardiol 1997;80:94A-101A.
Yokoyama I, Momomura S, Ohtake T, et al. Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1997;30:1472–7.
Pitkanen OP, Nuutila P, Raitakari OT, et al. Coronary flow reserve is reduced in young men with IDDM. Diabetes 1998;47:248–54.
Di Carli MF, Bianco-Batlles D, Landa ME, et al. Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus. Circulation 1999;100:813–9.
Di Carli MF, Afonso L, Campisi R, et al. Coronary vascular dysfunction in premenopausal women with diabetes mellitus. Am Heart J 2002;144:711–8.
Baller D, Notohamiprodjo G, Gleichmann U, et al. Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis. Circulation 1999;99: 2871–5.
Janatuinen T, Laaksonen R, Vesalainen R, et al. Effect of lipidlowering therapy with pravastatin on myocardial blood flow in young mildly hypercholesterolemic adults. J Cardiovasc Pharmacol 2001;38:561–8.
Huggins GS, Pasternak RC, Alpert NM, Fischman AJ, Gewirtz H. Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse. Circulation 1998;98:1291–6.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Campisi, R., Di Carli, M.F. Assessment of coronary flow reserve and microcirculation: A clinical perspective. J Nucl Cardiol 11, 3–11 (2004). https://doi.org/10.1016/j.nuclcard.2003.11.003
Issue Date:
DOI: https://doi.org/10.1016/j.nuclcard.2003.11.003