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

Division of Cardiology, University of Ottawa Heart Institute, Ontario, Canada.

OBJECTIVES: The aim of this study was to evaluate patients with coronary artery disease to 1) determine the relation between flow reserve measured by nitrogen-13 (N-13) ammonia kinetic modeling and stenosis severity assessed by quantitative angiography, and 2) examine whether flow reserve is impaired in regions supplied by vessels without significant angiographic disease. BACKGROUND: With the advent of new therapeutic approaches for coronary disease, an accurate noninvasive approach for absolute quantification of flow and flow reserve is needed to evaluate functional severity and extent of atherosclerosis. Nitrogen-13 ammonia kinetic modeling may permit such evaluation. METHODS: Twenty-seven subjects were classified into three groups: group 1 = 5 young volunteers: group 2 = 7 middle-aged volunteers; and group 3 = 15 patients with coronary artery disease. Dynamic N-13 ammonia positron emission tomographic imaging was performed at rest and during adenosine infusion. A three-compartment model was fit to regional N-13 ammonia kinetic data to determine myocardial flow. Group 3 patients underwent quantitative coronary angiography. RESULTS: The regional blood flow results in patients with coronary disease were classified into four subgroups: no significant detectable disease and mild (50% to 69.9% area stenosis), moderate (70% to 94.9% area stenosis) or severe (95% to 100% area stenosis) coronary disease. Flow reserve was 2.95 +/- 0.65; 2.09 +/- 0.47; 2.02 +/- 0.51; 1.3 +/- 0.32, respectively (p < or = 0.01 except mild vs. moderate). Flow reserve was correlated with percent area stenosis (r = -0.56) and minimal lumen diameter (r = 0.75). In volunteers (groups 1 and 2), flow reserves were greater than in segments without detectable disease in group 3 patients (4.10 +/- 0.71 and 3.79 +/- 0.42, respectively, vs. 2.88 +/- 0.56, p < or = 0.02). CONCLUSIONS: The functional severity of coronary disease measured by N-13 ammonia positron emission tomography varied for a given stenosis but was significantly related to angiographic severity. Among patients with coronary disease, myocardial regions without significant angiographic stenoses displayed reduced flow reserve than did regions in control subjects, indicating that vascular reactivity was more diffusely impaired in group 3 than was suggested by angiography. Noninvasive quantification of myocardial flow reserve using dynamic N-13 ammonia positron emission tomography yields important functional data that permit definition of the extent of disease even when disease is not apparent by angiography.

This article has been cited by other articles:

				M. F. Di Carli and V. L. Murthy Cardiac PET/CT for the Evaluation of Known or Suspected Coronary Artery Disease RadioGraphics, September 1, 2011; 31(5): 1239 - 1254. [Abstract] [Full Text] [PDF]

				J. R. Ghadri, A. P. Pazhenkottil, R. N. Nkoulou, R. Goetti, R. R. Buechel, L. Husmann, B. A. Herzog, M. Wolfrum, C. A. Wyss, C. Templin, et al. Very high coronary calcium score unmasks obstructive coronary artery disease in patients with normal SPECT MPI Heart, June 15, 2011; 97(12): 998 - 1003. [Abstract] [Full Text] [PDF]

				K.-T. Ho, K.-C. Chua, E. Klotz, and C. Panknin Stress and Rest Dynamic Myocardial Perfusion Imaging by Evaluation of Complete Time-Attenuation Curves With Dual-Source CT J. Am. Coll. Cardiol. Img., August 1, 2010; 3(8): 811 - 820. [Abstract] [Full Text] [PDF]

				V. Vaccarino, J. Votaw, T. Faber, E. Veledar, N. V. Murrah, L. R. Jones, J. Zhao, S. Su, J. Goldberg, J. P. Raggi, et al. Major Depression and Coronary Flow Reserve Detected by Positron Emission Tomography Arch Intern Med, October 12, 2009; 169(18): 1668 - 1676. [Abstract] [Full Text] [PDF]

				R. W. Bauer, C. Thilo, S. A. Chiaramida, T. J. Vogl, P. Costello, and U. J. Schoepf Noncalcified Atherosclerotic Plaque Burden at Coronary CT Angiography: A Better Predictor of Ischemia at Stress Myocardial Perfusion Imaging Than Calcium Score and Stenosis Severity Am. J. Roentgenol., August 1, 2009; 193(2): 410 - 418. [Abstract] [Full Text] [PDF]

				M. Ruel, R. S. Beanlands, M. Lortie, V. Chan, N. Camack, R. A. deKemp, E. J. Suuronen, F. D. Rubens, J. N. DaSilva, F. W. Sellke, et al. Concomitant treatment with oral L-arginine improves the efficacy of surgical angiogenesis in patients with severe diffuse coronary artery disease: The Endothelial Modulation in Angiogenic Therapy randomized controlled trial. J. Thorac. Cardiovasc. Surg., April 1, 2008; 135(4): 762 - 770.e1. [Abstract] [Full Text] [PDF]

				G. P. Chen, K. R. Branch, A. M. Alessio, P. Pham, R. Tabibiazar, P. Kinahan, and J. H. Caldwell Effect of Reconstruction Algorithms on Myocardial Blood Flow Measurement with 13N-Ammonia PET J. Nucl. Med., August 1, 2007; 48(8): 1259 - 1265. [Abstract] [Full Text] [PDF]

				M. F. Di Carli, S. Dorbala, J. Meserve, G. El Fakhri, A. Sitek, and S. C. Moore Clinical Myocardial Perfusion PET/CT J. Nucl. Med., May 1, 2007; 48(5): 783 - 793. [Abstract] [Full Text] [PDF]

				A. M. Alessio, S. Kohlmyer, K. Branch, G. Chen, J. Caldwell, and P. Kinahan Cine CT for Attenuation Correction in Cardiac PET/CT J. Nucl. Med., May 1, 2007; 48(5): 794 - 801. [Abstract] [Full Text] [PDF]

				M. F. Di Carli and R. Hachamovitch New Technology for Noninvasive Evaluation of Coronary Artery Disease Circulation, March 20, 2007; 115(11): 1464 - 1480. [Full Text] [PDF]

				S. Dorbala, D. Vangala, U. Sampson, A. Limaye, R. Kwong, and M. F. Di Carli Value of Vasodilator Left Ventricular Ejection Fraction Reserve in Evaluating the Magnitude of Myocardium at Risk and the Extent of Angiographic Coronary Artery Disease: A 82Rb PET/CT Study J. Nucl. Med., March 1, 2007; 48(3): 349 - 358. [Abstract] [Full Text] [PDF]

				M. Schwaiger, S. Ziegler, and S. G. Nekolla PET/CT: Challenge for Nuclear Cardiology J. Nucl. Med., October 1, 2005; 46(10): 1664 - 1678. [Abstract] [Full Text] [PDF]

				P. Koepfli, C. A. Wyss, M. Namdar, M. Klainguti, G. K. von Schulthess, T. F. Luscher, and P. A. Kaufmann {beta}-Adrenergic Blockade and Myocardial Perfusion in Coronary Artery Disease: Differential Effects in Stenotic Versus Remote Myocardial Segments J. Nucl. Med., October 1, 2004; 45(10): 1626 - 1631. [Abstract] [Full Text] [PDF]

				T H Schindler, E Nitzsche, N Magosaki, I Brink, M Mix, M Olschewski, U Solzbach, and H Just Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation Heart, May 1, 2003; 89(5): 517 - 526. [Abstract] [Full Text] [PDF]

				A. Kjaer, C. Meyer, F. S. Nielsen, H.-H. Parving, and B. Hesse Dipyridamole, Cold Pressor Test, and Demonstration of Endothelial Dysfunction: A PET Study of Myocardial Perfusion in Diabetes J. Nucl. Med., January 1, 2003; 44(1): 19 - 23. [Abstract] [Full Text] [PDF]

				R. S. B. Beanlands, T. D. Ruddy, R. A. deKemp, R. M. Iwanochko, G. Coates, M. Freeman, C. Nahmias, P. Hendry, R. J. Burns, A. Lamy, et al. Positron emission tomography and recovery following revascularization (PARR-1): the importance of scar and the development of a prediction rule for the degree of recovery of left ventricular function J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1735 - 1743. [Abstract] [Full Text] [PDF]

				A. F.M van den Heuvel, J. J Bax, P. K Blanksma, W. Vaalburg, H. J.G.M Crijns, and D. J van Veldhuisen Abnormalities in myocardial contractility, metabolism and perfusion reserve in non-stenotic coronary segments in heart failure patients Cardiovasc Res, July 1, 2002; 55(1): 97 - 103. [Abstract] [Full Text] [PDF]

				T. Ibrahim, S. G. Nekolla, K. Schreiber, K. Odaka, S. Volz, J. Mehilli, M. Guthlin, W. Delius, and M. Schwaiger Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography J. Am. Coll. Cardiol., March 6, 2002; 39(5): 864 - 870. [Abstract] [Full Text] [PDF]

				G. Sambuceti, M. Marzilli, S. Fedele, C. Marini, and A. L'Abbate Paradoxical Increase in Microvascular Resistance During Tachycardia Downstream From a Severe Stenosis in Patients With Coronary Artery Disease : Reversal by Angioplasty Circulation, May 15, 2001; 103(19): 2352 - 2360. [Abstract] [Full Text] [PDF]

				P. A. Kaufmann, T. Gnecchi-Ruscone, M. di Terlizzi, K. P. Schafers, T. F. Luscher, and P. G. Camici Coronary Heart Disease in Smokers : Vitamin C Restores Coronary Microcirculatory Function Circulation, September 12, 2000; 102(11): 1233 - 1238. [Abstract] [Full Text] [PDF]

				K. L. Gould, Y. Nakagawa, K. Nakagawa, S. Sdringola, M. J. Hess, M. Haynie, N. Parker, N. Mullani, and R. Kirkeeide Frequency and Clinical Implications of Fluid Dynamically Significant Diffuse Coronary Artery Disease Manifest as Graded, Longitudinal, Base-to-Apex Myocardial Perfusion Abnormalities by Noninvasive Positron Emission Tomography Circulation, April 25, 2000; 101(16): 1931 - 1939. [Abstract] [Full Text] [PDF]

				I. Kosa, R. Blasini, J. Schneider-Eicke, T. Dickfeld, F. J. Neumann, S. Ziegler, I. Matsunari, J. Neverve, A. Schomig, and M. Schwaiger Early recovery of coronary flow reserve after stent implantation as assessed by positron emission tomography J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1036 - 1041. [Abstract] [Full Text] [PDF]

				M. Guethlin, A. M. Kasel, K. Coppenrath, S. Ziegler, W. Delius, and M. Schwaiger Delayed Response of Myocardial Flow Reserve to Lipid-Lowering Therapy With Fluvastatin Circulation, February 2, 1999; 99(4): 475 - 481. [Abstract] [Full Text] [PDF]

				K. Bhagat Endothelial function and myocardial infarction Cardiovasc Res, August 1, 1998; 39(2): 312 - 317. [Full Text] [PDF]

				D. Baumgart, M. Haude, G. Goerge, J. Ge, S. Vetter, N. Dagres, G. Heusch, and R. Erbel Improved Assessment of Coronary Stenosis Severity Using the Relative Flow Velocity Reserve Circulation, July 7, 1998; 98(1): 40 - 46. [Abstract] [Full Text] [PDF]

				M. Schwaiger and I. Kosa Cardiovascular Positron Emission Tomography: A Possible Tool for Assessment of New Pharmaceuticals Drug Information Journal, July 1, 1997; 31(3): 1029 - 1034. [Abstract] [PDF]