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Dobutamine-Induced Contractile Reserve in Stunned, Hibernating, and Scarred Myocardium in Patients with Ischemic Cardiomyopathy

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Dobutamine-Induced Contractile Reserve in Stunned, Hibernating, and Scarred Myocardium in Patients with Ischemic Cardiomyopathy CLINICAL INVESTIGATIONS Dobutamine-Induced Contractile Reserve in Stunned, Hibernating, and Scarred Myocardium in Patients with Ischemic Cardiomyopathy Arend F.L. Schinkel, MD, PhD1; Jeroen J. Bax, MD, PhD2; Ron van Domburg, PhD1; Abdou Elhendy, MD, PhD1; Roelf Valkema, MD, PhD3; Eleni C. Vourvouri, MD, PhD1; Fabiola B. Sozzi, MD, PhD1; Jos R.T.C. Roelandt, MD, PhD1; and Don Poldermans, MD, PhD1 1Thoraxcenter, Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands; 2Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; and 3Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Because of damage to cardiomyocytes and the contractile appa- In patients with ischemic cardiomyopathy, distinguishing ratus, contractile reserve may be observed less frequently in hi- between hibernating, stunned, and scarred myocardium may bernating than in stunned myocardium. The aim of this study was have important implications for clinical management and to assess the presence of contractile reserve in response to do- butamine infusion in a large group of patients with stunned and outcome. If hibernating or stunned myocardium is present, hibernating myocardium. Methods: A total of 198 consecutive coronary revascularization may not only reverse regional patients with ischemic cardiomyopathy (left ventricular ejection wall motion abnormalities but also improve global function, fraction Յ 40%) underwent resting 2-dimensional echocardiogra- heart failure symptoms, and survival (1–3). Hibernating phy to assess regional contractile dysfunction. On the basis of myocardium has been defined as a chronic state of contrac- assessment of perfusion (with 99mTc-tetrofosmin SPECT) and glu- tile dysfunction with reduced blood flow at rest (4,5). Fre- 18 cose use (with F-FDG SPECT), dysfunctional segments were quently, however, regional perfusion in chronic dysfunc- grouped. Dysfunctional segments with normal perfusion were classified as stunned. Dysfunctional segments with a perfusion tional myocardium has been normal or nearly normal and defect were classified as hibernating when a perfusion–18F-FDG has been referred to as stunning or repetitive stunning (6). mismatch was present. Dysfunctional segments with a perfusion Instead of 2 different entities, it is likely that stunning and defect were classified as scar tissue when a perfusion–18F-FDG hibernation form a continuum and that a gradual reduction match was present; these segments were subdivided into non- of flow is accompanied by more ultrastructural damage on transmural and transmural scars. Contractile reserve was evalu- the myocyte level (7,8). Because of damage to the myocytes ated by dobutamine stress echocardiography. Results: Dobu- and the contractile apparatus, contractile reserve may be tamine-induced contractile reserve was more frequently found in stunned than in hibernating myocardium (61% vs. 51%, respec- observed less frequently in hibernating myocardium than in tively; P Ͻ 0.01). Only 14% of the scarred segments improved in stunned myocardium. However, the presence or absence of wall motion during dobutamine infusion, significantly less than contractile reserve in these different entities has not been stunned or hibernating myocardium (P Ͻ 0.001). Nontransmural studied extensively. Therefore, the aim of this study was to scars exhibited contractile reserve more frequently than did trans- assess the presence or absence of contractile reserve in mural scars. Conclusion: The progressive reduction of contractile response to dobutamine infusion in a large group of patients reserve in stunned, hibernating, and scarred myocardium supports with stunned or hibernating myocardium. the hypothesis that stunning, hibernation, and scarring are not circumscript pathophysiologic entities but represent gradual ultra- structural damage on the myocyte level. MATERIALS AND METHODS Key Words: contractile reserve; myocardial viability; 18F-FDG SPECT; heart failure Study Population A total of 198 consecutive patients with a clinically stable heart, J Nucl Med 2003; 44:127–133 angiographically proven chronic coronary artery disease, a left ventricular ejection fraction (LVEF) Յ 40%, and heart failure symptoms were studied at least 6 mo after myocardial infarction. Patients with primary cardiomyopathy, significant valvular heart Received May 2, 2002; revision accepted Sep. 17, 2002. disease, or an inadequate acoustic window were not included in the For correspondence or reprints contact: Don Poldermans, MD, PhD, De- study protocol. partment of Cardiology, Erasmus Medical Center, Thoraxcenter Room Ba 300, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. The study protocol was as follows. First, LVEF was assessed by E-mail: [email protected] radionuclide ventriculography. Next, dysfunctional myocardium CONTRACTILE RESERVE IN MYOCARDIUM • Schinkel et al. 127 was identified by resting 2-dimensional echocardiography; the to enhance myocardial 18F-FDG uptake. The plasma glucose level dysfunctional myocardium was then evaluated for the presence of was measured again, and additional insulin was given if necessary. stunning or hibernation by assessment of perfusion and glucose With this regimen, the image quality was good in all patients metabolism using SPECT. Finally, the presence of contractile studied. A triple-head gamma camera (Prism 3000XP; Picker, reserve was evaluated by dobutamine stress echocardiography. All Cleveland, OH) was used. The camera was equipped with com- patients gave their informed consent; the local Ethics Committee mercially available high-energy 511-keV collimators (13). The approved the study protocol. energies were centered on the 140-keV photon peak of 99mTc- tetrofosmin with a 15% window and on the 511-keV photon peak Radionuclide Ventriculographic Assessment of LVEF of 18F-FDG with a 15% window. Data were acquired over 360° 99m After injection of Tc (740 MBq), radionuclide ventriculog- (120 sectors of 3°), with the patient supine. Total imaging time was raphy was performed at rest with the patient supine. A small-field- 32 min. Data were stored in a 64 ϫ 64, 16-bit matrix. The image of-view gamma camera (Orbiter; Siemens, Erlangen, Germany) data were reconstructed by filtered backprojection using a Butter- was used, oriented in a 45° left anterior oblique position with a worth filter (cutoff frequency, 0.17 cycles per pixel); 6-mm-thick 5°–10° caudal tilt. The LVEF was calculated by standard methods (1 pixel) transaxial slices were obtained. Subsequently, standard (3). short- and long-axis projections perpendicular to the heart axis Two-Dimensional Echocardiographic Assessment of were reconstructed. Regional Dysfunction and Contractile Reserve The left ventricle was divided into 16 segments identical to the 99m A commercially available imaging system (Sonos 5500; echocardiographic segmentation (10). Both Tc-tetrofosmin and 18 Hewlett Packard, Andover, MA) and a 1.8-MHz transducer using F-FDG studies were analyzed quantitatively (segments normal- second harmonic imaging to optimize endocardial border visual- ized to maximum tracer uptake). Dysfunctional segments (identi- ization were used (9). Two-dimensional imaging was performed fied by resting echocardiography) were evaluated for viability with the patient in the left lateral position; standard views were (14–16). Dysfunctional segments with normal perfusion (accord- 99m Ͼ recorded onto an optical disk (cine loops). ing to a normalized Tc-tetrofosmin uptake of 80%) were For the assessment of contractile reserve in dysfunctional myo- classified as stunned. Dysfunctional segments with a perfusion 99m Ͻ cardium, dobutamine stress echocardiography was performed as defect (normalized Tc-tetrofosmin uptake 80%) were classi- 18 described previously (9). ␤-Blocker therapy was not routinely fied as hibernating when a perfusion– F-FDG mismatch was 18 Ն discontinued during dobutamine stress echocardiography. Two present (increase in F-FDG uptake 10%, compared with 99m patients were in atrial fibrillation. After the resting echocardio- Tc-tetrofosmin uptake). Dysfunctional segments with a perfu- 18 graphic study, dobutamine was administered intravenously, start- sion defect were classified as scar tissue when a perfusion– F- Ͻ ing at a dose of 5 ␮g per kilogram of body weight per minute for FDG match was present ( 10% difference in tracer activities); 5 min, followed by a 10 ␮g/kg/min dose for 5 min (low dose). these segments were subdivided into nontransmural and transmu- 99m 18 Ն Incremental doses of 10 ␮g/kg/min were given at 3-min intervals ral scars. Segments with Tc tetrofosmin and F-FDG uptake up to a dose of 40 ␮g/kg/min (high dose), and atropine was added 50% but without mismatch were classified as nontransmural scars, Ͻ if necessary. whereas segments with tracer activities 50% were classified as Two experienced observers, unaware of the clinical data or the transmural scars (14–16). SPECT results, scored the digitized echocardiograms offline. In Statistical Analysis cases of disagreement, a majority decision was reached by a third Values are expressed as mean Ϯ SD, and percentages are observer. The left ventricle was divided into 16 segments accord- rounded when appropriate. Continuous variables were compared ing to the method of the American Society of Echocardiography using the Student t test for unpaired samples. Differences between (10). Regional wall motion and systolic wall thickening were proportions were compared using the ␹2 test. A value of P Ͻ 0.05
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