This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van den Heuvel, A. F. M. Articles by Crijns, H. J. G. M. Search for Related Content PubMed PubMed Citation Articles by van den Heuvel, A. F. M. Articles by Crijns, H. J. G. M.

CLINICAL STUDIES

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy

Ad F. M. van den Heuvel, MD^a, Dirk J. van Veldhuisen, MD, PhD, FACC^a, Ernst E. van der Wall, MD, PhD, FACC^*, Paul K. Blanksma, MD, PhD^a, Hans-Marc J. Siebelink, MD^a, Willem M. Vaalburg, PhD, Wiek H. van Gilst, PhD^a and Harry J. G. M. Crijns, MD, Phd^a

^a Department of Cardiology, University Hospital Groningen, Groningen, The Netherlands
^* Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
National Positron Emission Tomography Center, University Hospital Groningen, Groningen, The Netherlands

Manuscript received March 19, 1999; revised manuscript received July 27, 1999, accepted September 14, 1999.

Reprint requests and correspondence: Dr. D. J. van Veldhuisen, Department of Cardiology/Thoraxcenter, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
d.j.van.veldhuisen{at}thorax.azg.nl

OBJECTIVES

We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC).

BACKGROUND

Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur.

METHODS

We studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (¹⁸FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (k_mono) were assessed at rest and during submaximal dobutamine infusion (20 µg/kg body weight per min).

RESULTS

Global MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 ± 0.21 vs. 2.7 ± 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = –0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased ¹⁸FDG uptake) was observed in 17 ± 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 ± 0.13 vs. 1.90 ± 0.18, p < 0.05). During dobutamine infusion k_mono was higher in the mismatch regions than in the normal regions (0.104 ± 0.017 vs. 0.087 ± 0.016 min^–1, p < 0.05). In the mismatch regions ¹⁸FDG uptake correlated negatively with rest k_mono (r = –0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism.

CONCLUSIONS

Patients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CHF = congestive heart failure   CI = confidence interval   18FDG = fluorine-18 deoxyglucose   IDC = idiopathic dilated cardiomyopathy   LV = left ventricular   LVEF = left ventricular ejection fraction   MBF = myocardial blood flow   NYHA = New York Heart Association   PET = positron emission tomography   O2max = peak oxygen consumption

This article has been cited by other articles:

				C. Whee Park, H. Wook Kim, J. Hee Lim, K. Dong Yoo, S. Chung, S. Joon Shin, H. Wha Chung, S. Ju Lee, C.-B. Chae, Y.-S. Kim, et al. Vascular Endothelial Growth Factor Inhibition by dRK6 Causes Endothelial Apoptosis, Fibrosis, and Inflammation in the Heart via the Akt/eNOS Axis in db/db Mice Diabetes, November 1, 2009; 58(11): 2666 - 2676. [Abstract] [Full Text] [PDF]

				R. A. Tio, A. Dabeshlim, H.-M. J. Siebelink, J. de Sutter, H. L. Hillege, C. J. Zeebregts, R. A.J.O. Dierckx, D. J. van Veldhuisen, F. Zijlstra, and R. H.J.A. Slart Comparison Between the Prognostic Value of Left Ventricular Function and Myocardial Perfusion Reserve in Patients with Ischemic Heart Disease J. Nucl. Med., February 1, 2009; 50(2): 214 - 219. [Abstract] [Full Text] [PDF]

				D. Neglia and A. L'Abbate Myocardial Perfusion Reserve in Ischemic Heart Disease J. Nucl. Med., February 1, 2009; 50(2): 175 - 177. [Full Text] [PDF]

				E. P. Tsagalou, M. Anastasiou-Nana, E. Agapitos, A. Gika, S. G. Drakos, J. V. Terrovitis, A. Ntalianis, and J. N. Nanas Depressed Coronary Flow Reserve Is Associated With Decreased Myocardial Capillary Density in Patients With Heart Failure Due to Idiopathic Dilated Cardiomyopathy J. Am. Coll. Cardiol., October 21, 2008; 52(17): 1391 - 1398. [Abstract] [Full Text] [PDF]

				N. Beohar, A. K. Erdogan, D. C. Lee, H. N. Sabbah, M. J. Kern, J. Teerlink, R. O. Bonow, and M. Gheorghiade Acute heart failure syndromes and coronary perfusion. J. Am. Coll. Cardiol., July 1, 2008; 52(1): 13 - 16. [Abstract] [Full Text] [PDF]

				L. De Luca, A. Mebazaa, G. Filippatos, J. T. Parissis, M. Bohm, A. A. Voors, M. Nieminen, F. Zannad, A. Rhodes, A. El-Banayosy, et al. Overview of emerging pharmacologic agents for acute heart failure syndromes Eur J Heart Fail, February 1, 2008; 10(2): 201 - 213. [Abstract] [Full Text] [PDF]

				D. Neglia, A. De Caterina, P. Marraccini, A. Natali, M. Ciardetti, C. Vecoli, A. Gastaldelli, D. Ciociaro, P. Pellegrini, R. Testa, et al. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3270 - H3278. [Abstract] [Full Text] [PDF]

				D. Neglia, R. De Maria, S. Masi, M. Gallopin, P. Pisani, S. Pardini, A. Gavazzi, A. L'Abbate, and O. Parodi Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy Heart, July 1, 2007; 93(7): 808 - 813. [Abstract] [Full Text] [PDF]

				L. J Blows and S. R Redwood The pressure wire in practice Heart, April 1, 2007; 93(4): 419 - 422. [Abstract] [Full Text] [PDF]

				D. Erdogan, H. Gullu, M. Caliskan, O. Ciftci, S. Baycan, A. Yildirir, and H. Muderrisoglu Nebivolol improves coronary flow reserve in patients with idiopathic dilated cardiomyopathy Heart, March 1, 2007; 93(3): 319 - 324. [Abstract] [Full Text] [PDF]

				E. M. deGoma, R. H. Vagelos, M. B. Fowler, and E. A. Ashley Emerging Therapies for the Management of Decompensated Heart Failure: From Bench to Bedside J. Am. Coll. Cardiol., December 19, 2006; 48(12): 2397 - 2409. [Abstract] [Full Text] [PDF]

				M. J.W. Gotte, T. Germans, I. K. Russel, J. J.M. Zwanenburg, J. T. Marcus, A. C. van Rossum, and D. J. van Veldhuisen Myocardial Strain and Torsion Quantified by Cardiovascular Magnetic Resonance Tissue Tagging: Studies in Normal and Impaired Left Ventricular Function J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2002 - 2011. [Abstract] [Full Text] [PDF]

				P. Knaapen, M. J. W. Gotte, W. J. Paulus, J. J. M. Zwanenburg, P. A. Dijkmans, R. Boellaard, J. T. Marcus, J. W. R. Twisk, C. A. Visser, A. C. van Rossum, et al. Does Myocardial Fibrosis Hinder Contractile Function and Perfusion in Idiopathic Dilated Cardiomyopathy? PET and MR Imaging Study. Radiology, August 1, 2006; 240(2): 380 - 388. [Abstract] [Full Text] [PDF]

				Y. Izumiya, I. Shiojima, K. Sato, D. B. Sawyer, W. S. Colucci, and K. Walsh Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload Hypertension, May 1, 2006; 47(5): 887 - 893. [Abstract] [Full Text] [PDF]

				P. Boekstegers, P. Raake, R. Hinkel, T. Pohl, C. Kupatt, A. Knez, F. Christ, S. Eifert, G. Steinbeck, B. Reichart, et al. Hemodynamic and Vascular Effects of Ventricular Sourcing by Stent-Based Ventricle to Coronary Artery Bypass in Patients With Multivessel Disease Undergoing Coronary Artery Bypass Surgery Circulation, August 30, 2005; 112(9_suppl): I-304 - I-310. [Abstract] [Full Text] [PDF]

				R. Scognamiglio, C. Negut, S. V. De Kreutzenberg, A. Tiengo, and A. Avogaro Postprandial Myocardial Perfusion in Healthy Subjects and in Type 2 Diabetic Patients Circulation, July 12, 2005; 112(2): 179 - 184. [Abstract] [Full Text] [PDF]

				P. Knaapen, A. A. Lammertsma, and F. C. Visser Enhancement of perfusion reserve by cardiac resynchronization therapy Eur. Heart J., July 2, 2005; 26(14): 1447 - 1448. [Full Text] [PDF]

				E. Bramanti, C. Vecoli, D. Neglia, M. P. Pellegrini, G. Raspi, and R. Barsacchi Speciation and Quantification of Thiols by Reversed-Phase Chromatography Coupled with On-Line Chemical Vapor Generation and Atomic Fluorescence Spectrometric Detection: Method Validation and Preliminary Application for Glutathione Measurements in Human Whole Blood Clin. Chem., June 1, 2005; 51(6): 1007 - 1013. [Abstract] [Full Text] [PDF]

				Y.-s. Yoon, S. Uchida, O. Masuo, M. Cejna, J.-S. Park, H.-c. Gwon, R. Kirchmair, F. Bahlman, D. Walter, C. Curry, et al. Progressive Attenuation of Myocardial Vascular Endothelial Growth Factor Expression Is a Seminal Event in Diabetic Cardiomyopathy: Restoration of Microvascular Homeostasis and Recovery of Cardiac Function in Diabetic Cardiomyopathy After Replenishment of Local Vascular Endothelial Growth Factor Circulation, April 26, 2005; 111(16): 2073 - 2085. [Abstract] [Full Text] [PDF]

				O. Lindner, J. Vogt, D. Baller, A. Kammeier, P. Wielepp, J. Holzinger, B. Lamp, D. Horstkotte, and W. Burchert Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block Eur J Heart Fail, March 2, 2005; 7(2): 225 - 230. [Abstract] [Full Text] [PDF]

				T. Y. Wong, W. Rosamond, P. P. Chang, D. J. Couper, A. R. Sharrett, L. D. Hubbard, A. R. Folsom, and R. Klein Retinopathy and Risk of Congestive Heart Failure JAMA, January 5, 2005; 293(1): 63 - 69. [Abstract] [Full Text] [PDF]

				M. Vanderheyden, J. Bartunek, S. Verstreken, L. Mortier, M. Goethals, and B. de Bruyne Non-invasive assessment of coronary flow reserve in idiopathic dilated cardiomyopathy: hemodynamic correlations Eur J Echocardiogr, January 1, 2005; 6(1): 47 - 53. [Abstract] [Full Text] [PDF]

				W. Okumura, T. Iwasaki, T. Toyama, T. Iso, M. Arai, N. Oriuchi, K. Endo, T. Yokoyama, T. Suzuki, and M. Kurabayashi Usefulness of Fasting 18F-FDG PET in Identification of Cardiac Sarcoidosis J. Nucl. Med., December 1, 2004; 45(12): 1989 - 1998. [Abstract] [Full Text] [PDF]

				E. I. Skalidis, F. I. Parthenakis, A. P. Patrianakos, M. I. Hamilos, and P. E. Vardas Regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2027 - 2032. [Abstract] [Full Text] [PDF]

				R. A. Tio, E. S. Tan, G. A.J. Jessurun, N. Veeger, P. L. Jager, R. H.J.A. Slart, R. M. de Jong, J. Pruim, G. A.P. Hospers, A. T.M. Willemsen, et al. PET for Evaluation of Differential Myocardial Perfusion Dynamics After VEGF Gene Therapy and Laser Therapy in End-Stage Coronary Artery Disease J. Nucl. Med., September 1, 2004; 45(9): 1437 - 1443. [Abstract] [Full Text] [PDF]

				P. Knaapen, L. M.C. van Campen, C. C. de Cock, M. J.W. Gotte, C. A. Visser, A. A. Lammertsma, and F. C. Visser Effects of Cardiac Resynchronization Therapy on Myocardial Perfusion Reserve Circulation, August 10, 2004; 110(6): 646 - 651. [Abstract] [Full Text] [PDF]

				L. Ye, H. K Haider, S.-J. Jiang, and E. K. Sim Therapeutic Angiogenesis Using Vascular Endothelial Growth Factor Asian Cardiovasc Thorac Ann, June 1, 2004; 12(2): 173 - 181. [Abstract] [Full Text] [PDF]

				L. A. Nikolaidis, D. Trumble, T. Hentosz, A. Doverspike, R. Huerbin, M. A. Mathier, Y.-T. Shen, and R. P. Shannon Catecholamines restore myocardial contractility in dilated cardiomyopathy at the expense of increased coronary blood flow and myocardial oxygen consumption (MvO2 cost of catecholamines in heart failure) Eur J Heart Fail, June 1, 2004; 6(4): 409 - 419. [Abstract] [Full Text] [PDF]

				P. van der Harst, A. A. Voors, D. J. van Veldhuisen, J. K. Liao, K. Node, M. Fujita, M. Hori, and M. Kitakaze Short-Term Statin Therapy and Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy * Response Circulation, February 10, 2004; 109 (5): e34 - e34. [Full Text] [PDF]

				M. van Bilsen, P. J.H Smeets, A. J Gilde, and G. J van der Vusse Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc Res, February 1, 2004; 61(2): 218 - 226. [Abstract] [Full Text] [PDF]

				S. Hasegawa, H. Kusuoka, K. Maruyama, T. Nishimura, M. Hori, and J. Hatazawa Myocardial positron emission computed tomographic images obtained with fluorine-18 fluoro-2-deoxyglucose predict the response of idiopathic dilated cardiomyopathy patients to beta-blockers J. Am. Coll. Cardiol., January 21, 2004; 43(2): 224 - 233. [Abstract] [Full Text] [PDF]

				M. P. Czubryt and E. N. Olson Balancing Contractility and Energy Production: The Role of Myocyte Enhancer Factor 2 (MEF2) in Cardiac Hypertrophy Recent Prog. Horm. Res., January 1, 2004; 59(1): 105 - 124. [Abstract] [Full Text]

				M. R. Mehrabi, P. Haslmayer, S. Humpeler, G. Strauss-Blasche, W. Marktl, F. Tamaddon, N. Serbecic, G. Wieselthaler, T. Thalhammer, H. D. Glogar, et al. Quantitative analysis of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) expression in arteries and hearts of patients with ischaemic or dilated cardiomyopathy Eur J Heart Fail, December 1, 2003; 5(6): 733 - 739. [Abstract] [Full Text] [PDF]

				H. Yamagishi, N. Shirai, M. Takagi, M. Yoshiyama, K. Akioka, K. Takeuchi, and J. Yoshikawa Identification of Cardiac Sarcoidosis with 13N-NH3/18F-FDG PET J. Nucl. Med., July 1, 2003; 44(7): 1030 - 1036. [Abstract] [Full Text] [PDF]

				R. Maestri, A. F. Milia, M. B. Salis, G. Graiani, C. Lagrasta, M. Monica, D. Corradi, C. Emanueli, and P. Madeddu Cardiac Hypertrophy and Microvascular Deficit in Kinin B2 Receptor Knockout Mice Hypertension, May 1, 2003; 41(5): 1151 - 1155. [Abstract] [Full Text] [PDF]

				R A De Boer, R H Henning, R A Tio, Y M Pinto, R M H J Brouwer, R J Ploeg, M Bohm, W H Van Gilst, and D J Van Veldhuisen Identification of a specific pattern of downregulation in expression of isoforms of vascular endothelial growth factor in dilated cardiomyopathy Heart, October 1, 2002; 88(4): 412 - 414. [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]

				L. A. Nikolaidis, A. Doverspike, R. Huerbin, T. Hentosz, and R. P. Shannon Angiotensin-Converting Enzyme Inhibitors Improve Coronary Flow Reserve in Dilated Cardiomyopathy by a Bradykinin-Mediated, Nitric Oxide-Dependent Mechanism Circulation, June 11, 2002; 105(23): 2785 - 2790. [Abstract] [Full Text] [PDF]

				D. Neglia, C. Michelassi, M. G. Trivieri, G. Sambuceti, A. Giorgetti, L. Pratali, M. Gallopin, P. Salvadori, O. Sorace, C. Carpeggiani, et al. Prognostic Role of Myocardial Blood Flow Impairment in Idiopathic Left Ventricular Dysfunction Circulation, January 15, 2002; 105(2): 186 - 193. [Abstract] [Full Text] [PDF]

				T. Saito, K. Maehara, K. Tamagawa, Y. Oikawa, T. Niitsuma, S.-I. Saitoh, and Y. Maruyama Alterations of endothelium-dependent and -independent regulation of coronary blood flow during heart failure Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H80 - H86. [Abstract] [Full Text] [PDF]

				F. Frouin, P. Merlet, Y. Bouchareb, V. Frouin, J.-L. Dubois-Rande, A. De Cesare, A. Herment, A. Syrota, and A. Todd-Pokropek Validation of Myocardial Perfusion Reserve Measurements Using Regularized Factor Images of H215O Dynamic PET Scans J. Nucl. Med., December 1, 2001; 42(12): 1737 - 1746. [Abstract] [Full Text] [PDF]

				R. Nakamura, K. Egashira, K. Arimura, Y. Machida, T. Ide, H. Tsutsui, H. Shimokawa, and A. Takeshita Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2619 - H2625. [Abstract] [Full Text] [PDF]

				R. M. de Jong, J. H. Cornel, H. J.G.M. Crijns, and D. J. van Veldhuisen Abnormal contractile responses during dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy Eur J Heart Fail, August 1, 2001; 3(4): 429 - 436. [Abstract] [Full Text] [PDF]

				R. A. de Boer, H.-M. J. Siebelink, R. A. Tio, F. Boomsma, and D. J. van Veldhuisen Carvedilol increases plasma vascular endothelial growth factor (VEGF) in patients with chronic heart failure Eur J Heart Fail, June 1, 2001; 3(3): 331 - 333. [Full Text] [PDF]

				A. A. Young, S. Dokos, K. A. Powell, B. Sturm, A. D. McCulloch, R. C. Starling, P. M. McCarthy, and R. D. White Regional heterogeneity of function in nonischemic dilated cardiomyopathy Cardiovasc Res, February 1, 2001; 49(2): 308 - 318. [Abstract] [Full Text] [PDF]