- Email: [email protected]
Effect of the transmural extent of myocardial scar on left ventricular systolic wall thickening during intravenous dobutamine administration
Effect of the Transmural Extent of Myocardial Scar on Left Ventricular Systolic Wall Thickening During Intravenous Dobutamine Administration Pairoj Rerkpattanapipat, MD, William C. Little, MD, Hollins P. Clark, MD, Craig A. Hamilton, PhD, Kerry M. Link, MD, and W. Gregory Hundley, MD Using magnetic resonance imaging, the extent of scar tissue due to chronic infarction and quantification of dobutamine systolic wall thickening (SWT) can be measured simultaneously in human subjects. To determine whether the transmural extent of scar tissue determines dobutamine SWT in chronic ischemic heart disease, we assessed the transmural extent of hyperenhancement and dobutamine SWT with magnetic resonance imaging in 16 patients. The transmural extent of hyperenhancement correlated inversely with dobutamine SWT (r ⴝ ⴚ0.7, p <0.001). All segments with dobutamine SWT >2 mm showed a transmural extent of hyperenhancement of <50%. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:495– 498)
obutamine systolic wall thickening (SWT) and wall thickness have been used to predict myocardial D viability. In chronic ischemic heart disease, dysfunctional myocardial segments often result from scar tissue from previous myocardial infarction that extends variably from the subendocardium toward the epicardium.1 Previous histopathologic studies from explanted human hearts have suggested that the amount of fibrosis and necrosis in myocardial segments is associated with dobutamine SWT2– 4; however, limitations in these in vitro studies have included an anatomic misalignment and a variable interval between assessment of dobutamine SWT and explantation of the heart during heart transplantation surgery. Using contrast-enhanced magnetic resonance imaging (MRI), the transmural extent of myocardial scar associated with previous infarction in patients who have chronic ischemic heart disease can be quantified noninvasively.5,6 We hypothesized that impaired dobutamine SWT in dysfunctional myocardial segments in patients who have chronic ischemic heart disease was due to extensive transmural scarring and related to wall thickness at rest. To test this hypothesis, we measured wall thickness and SWT before and during intravenous dobutamine administration and the extent of myocardial scar tissue during a cardiac MRI examination. From the Departments of Internal Medicine (Cardiology Section), Radiology, and Biomedical Engineering, Wake Forest University School of Medicine, Winston-Salem, North Carolina. This research was supported in part by the NIA Claude Pepper Older Americans Independence Centers, Wake Forest University (grant 1P30AG021332-01), Winston-Salem, North Carolina. Dr. Rerkpattanapipat’s address is: Bangkok Heart Institute, 2 Soi Soonvijai 7, New Petchaburi Road, Bangkapi, Huay-Kwuay, Bangkok 10320, Thailand. E-mail: [email protected]. Manuscript received June 17, 2004; revised manuscript received and accepted October 15, 2004. ©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 February 15, 2005
•••
The institutional review board of the Wake Forest University School of Medicine (Winston-Salem, North Carolina) approved the study, and all participants gave written informed consent. We prospectively studied 16 patients who had stable coronary artery disease with regional wall motion abnormalities at rest (mean ⫾ SD left ventricular ejection fraction 41 ⫾ 9%). Patients who had myocardial infarction ⬍6 months, unstable angina, New York Heart Association class III or IV congestive heart failure, or contraindications to MRI or dobutamine administration were excluded. Patients’ characteristics are listed in Table 1. All images were acquired on a CV/i 1.5-T wholebody MRI system (General Electric Medical Systems, Waukesha, Wisconsin) with patients in the supine position and a phased-array receiver coil placed on the chest. Acquisition parameters for acquiring white blood images of left ventricular contraction included a 10- to 14-ms repetition time, a 5-ms echo time, a 30° flip angle, a 32- to 40-cm field of view, an 8-mm thickness, and an 8- to 12-second breath-hold.7 Dobutamine was administered intravenously at a starting dose of 5 g/kg/min for 3 minutes and then increased to 10 g/kg/min for 3 minutes. Gadoteridol (ProHance, Bracco Diagnostics Inc., Princeton, New Jersey) was given intravenously (0.2 mmol/kg body weight) right after acquisition of cine magnetic resonance images of the left ventricle at the end of the dobutamine infusion protocol. Twenty minutes after contrast administration, contrast-enhanced images of the left ventricle were acquired with a gated fastgradient echo sequence with inversion recovery in 3 short-axis planes acquired to assess left ventricular wall thickening. Image parameters included a 7.2-ms repetition time, a 3.1-ms echo time, a 200- to 350-ms inversion time (adjusted to achieve a null myocardial signal), a 256 ⫻ 192 matrix, a 34- ⫻ 34-cm field of view, a 20° flip angle, an 8-mm slice thickness, and 24 views per segment. Cine images of the left ventricle at baseline and during administration of 10 g/kg/min of dobutamine and contrast-enhanced images were analyzed for 16 myocardial segments (6 basal, 6 middle, and 4 apical).8 Wall thickness in each segment was measured at end-diastole and end-systole at rest and during smalldose dobutamine administration. SWT was calculated from the difference between end-systolic and enddiastolic wall thicknesses according to previously published techniques.9 Dobutamine SWT ⬍2 mm in severely hypokinetic, akinetic, or dyskinetic segments was identified as a lack of viability or contractile reserve.9 Transmural extent of hyperenhancement was 0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.10.019
495
TABLE 1 Patients’ Characteristics Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Age (yrs)/ Sex 53 57 57 59 60 62 65 65 66 69 70 71 72 72 75 75
M M M M M M M M F M M M M M M M
Diabetes
Hypertension
Current Smoker
⫹ ⫺ ⫺ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺
⫹ ⫹ ⫹ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹ ⫺
⫺ ⫺ ⫹ ⫺ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
Hypercholesterolemia
Previous Myocardial Infarction
Previous Coronary Revascularization
⫹ ⫹ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺
⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
FIGURE 1. Contractile response to dobutamine infusion and transmural extent of hyperenhancement (EH). Cine magnetic resonance images show the left ventricle at the mid–short-axis level at end-systole (ES) at rest (left column) and during low-dose dobutamine administration (middle column). Contrast-enhanced magnetic resonance images show the left ventricle at the same level as cine images (right column). Segments (anteroseptal, septal, inferior, and posterior walls) with subendocardial infarction and <50% EH showed improvement in contractility with dobutamine infusion (top row). In contrast, systolic thickening of segments (anteroseptal, septal, and anterior walls) with >50% EH did not improve with dobutamine infusion (bottom row).
determined for each segment by calculating the percentage of the ratio of the hyperenhanced area to the total area of that myocardial segment.6 Two-sided Student’s t tests were used to compare continuous variables, which were expressed as mean ⫾ SD. The association among transmural extent of hyperenhancement, dobutamine SWT, and end-diastolic wall thickness at baseline was analyzed by lin496 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 95
ear regression analysis. Statistical significance was set at a p value ⬍0.05. All p values were based on a 2-sided test of significance. Of the 256 myocardial segments displayed in the collected images, 48 were severely hypokinetic, akinetic, or dyskinetic at rest; these segments were included in the analysis. Transmural extent of hyperenhancement correlated inversely with dobutamine SWT FEBRUARY 15, 2005
FIGURE 2. Relation between dobutamine-induced SWT (y axis) and transmural extent of hyperenhancement (x axis).
FIGURE 3. Relation between dobutamine-induced SWT (DobSWT) and segmental extent of hyperenhancement (EH) in segments with end-diastolic wall thickness (EDWT) <6 or > 6 mm.
(r ⫽ ⫺0.73, p ⬍0.001; Figures 1 and 2). Segments with dobutamine SWT ⱖ2 mm differed from those with ⬍2 mm with respect to end-diastolic wall thickness (12.1 ⫾ 3.6 vs 7.7 ⫾ 3.5 mm, p ⬍0.001) and transmural extent of hyperenhancement (11 ⫾ 16% vs 77 ⫾ 22%, p ⬍0.001). All myocardial segments with an end-diastolic wall thickness ⬍6 mm showed a dobutamine SWT ⬍2 mm and a transmural extent of hyperenhancement ⱖ50%. End-diastolic wall thickness correlated inversely with transmural extent of hyperenhancement (r ⫽ ⫺0.70, p ⬍0.001). Values for transmural extent of hyperenhancement were 92 ⫾ 12% versus 38 ⫾ 14% (p ⬍0.001) and those for dobutamine SWT were 0.3 ⫾ 0.4 versus 2.7 ⫾ 2.7 mm (p ⬍0.001) in segments that had end-diastolic wall thicknesses of ⬍6 and ⱖ6 mm, respectively. The relation among end-diastolic wall thickness, dobutamine SWT, and transmural extent of hyperenhancement is shown in Figure 3. •••
There are 2 important findings in this study. First, myocardial thinning with an end-diastolic wall thickness ⬍6 mm and dobutamine SWT ⬍2 mm is an indicator of chronic transmural scarring from infarction. Second, dobutamine SWT in patients who have chronic ischemic
heart disease is influenced by the transmural extent of scar. Dysfunctional segments with ⬍50% transmural extent of scar tissue are likely to exhibit a contractile response to inotropic stimulation. Previous studies have associated myocardial thinning with the absence of dobutamine SWT after coronary arterial revascularization.9,10 An autopsy study10 associated transmural scarring with myocardial thinning, which is usually ⬍6 mm. In our study, all segments with end-diastolic wall thickness ⬍6 mm had dobutamine SWT ⬍2 mm and ⱖ50% transmural extent of hyperenhancement. Our results indicate that a large percentage of myocardial infarcted tissue may be responsible for inappropriate dobutamine-induced SWT in these thinned myocardial segments. Our results suggest that the amount of transmural scar tissue is an important factor for determining the response to inotropic stimulation in patients who have chronic ischemic heart disease. All segments with dobutamine SWT ⱖ2 mm had ⬍50% transmural extent of hyperenhancement. These data are consistent with those reported by Kim et al,6 in which myocardial segments with ⬍50% transmural extent of hyperenhancement were likely to improve regional function after coronary arterial revascularization. They are also consistent with positron emission tomographic or nuclear scintigraphic data in which a glucose or thallium uptake ⬎50% was associated with improved regional function after revascularization.11,12 Because our analytic method used only short-axis views, we missed the 17th segment or apical cap, which is usually examined from the long axis of the left ventricle. Ischemia at the apical segments during magnetic resonance image stress testing had important prognostic implications as noted by Hundley et al.13
Acknowledgment: Contrast material (Prohance) administered in this study was kindly supplied by Bracco Diagnostics, Inc., Princeton, New Jersey.
1. Antman EM, Braunwald E. Acute myocardial infarction. In: Braunwald E, Zipes
DP, Libby P, eds. Heart Disease. Philadelphia: W.B. Saunders Co., 2001:1111–1231. 2. Baumgartner H, Porenta G, Lau YK, Wutte M, Klaar U, Mehrabi M, Siegel RJ,
Czernin J, Laufer G, Sochor H, et al. Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts. J Am Coll Cardiol 1998;32: 1701–1708. 3. Zamorano J, Delgado J, Almeria C, Moreno R, Gomez SM, Rodrigo J, Fernandez C, Ferreiros J, Rufilanchas J, Sanchez-Harguindey L. Reason for discrepancies in identifying myocardial viability by thallium-201 redistribution, magnetic resonance imaging, and dobutamine echocardiography. Am J Cardiol 2002;90:455– 459. 4. Gunning MG, Kaprielian RR, Pepper J, Pennell DJ, Sheppard MN, Severs NJ, Fox KM, Underwood SR. The histology of viable and hibernating myocardium in relation to imaging characteristics. J Am Coll Cardiol 2002;39:428 – 435. 5. Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999;100:1992–2002. 6. Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000;343:1445–1453.
BRIEF REPORTS
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7. Hundley WG, Hamilton CA, Thomas MS, Herrington DM, Salido TB,
Kitzman DW, Little WC, Link KM. Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography. Circulation 1999; 100:1697–1702. 8. Armstrong WF, Pellikka PA, Ryan T, Crouse L, Zoghbi WA. Stress echocardiography: recommendations for performance and interpretation of stress echocardiography. Stress Echocardiography Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 1998;11:97–104. 9. Baer FM, Theissen P, Schneider CA, Voth E, Sechtem U, Schicha H, Erdmann E. Dobutamine magnetic resonance imaging predicts contractile recovery of chronically dysfunctional myocardium after successful revascularization. J Am Coll Cardiol 1998;31:1040 –1048. 10. Cwajg JM, Cwajg E, Nagueh SF, He ZX, Qureshi U, Olmos LI, Quinones MA, Verani MS, Winters WL, Zoghbi WA. End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-
redistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol 2000;35:1152–1161. 11. Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, O’Gara PT, Carabello BA, Russell RO Jr, Cerqueira MD, et al. ACC/AHA/ ASNC guidelines for the clinical use of cardiac radionuclide imaging— executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC committee to revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 2003;108:1404 –1418. 12. Bax JJ, Polderman D, Schinkel AF, Boersma AF, Elhendy A, Maat A, Valkema R, Krenning EP, Roelandt JR. Perfusion and contractile reserve in chronic dysfunctional myocardium: relation to functional outcome after surgical revascularization. Circulation 2004;106:I14 –I18. 13. Hundley WG, Rerkpattanapipat P, Little WC, Link KM, Morgan TM. Relation of cardiac prognosis to segment location with apical left ventricular ischemia. Am J Cardiol 2003;92:1206 –1208.
Intravascular Ultrasound Assessment of Lesions With Target Vessel Failure After Sirolimus-Eluting Stent Implantation Hideo Takebayashi, MD, Yoshio Kobayashi, MD, Gary S. Mintz, MD, Stéphane G. Carlier, MD, PhD, Kenichi Fujii, MD, Takenori Yasuda, MD, Issam Moussa, MD, Roxana Mehran, MD, George D. Dangas, MD, PhD, Michael B. Collins, MD, Edward Kreps, MD, Alexandra J. Lansky, MD, Gregg W. Stone, MD, Martin B. Leon, MD, and Jeffrey W. Moses, MD Intravascular ultrasound (IVUS) evaluation was performed in 33 lesions with sirolimus-eluting stent (SES) failure: 4 thromboses, 26 in-stent restenoses (including 6 edge stenoses), 4 new stenoses >5 mm proximal to the stent, and 1 patient with no evidence of the implanted SES (presumably because of embolization). A minimum stent area <5.0 mm2 (stent underexpansion) was observed in 67% of all SES failures (in particular, 67% of intrastent restenosis); negative remodeling was observed in 4 of 6 stent edge restenoses, and new lesions were secondary to an increase in plaque area. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:498 –502)
o patient in the original cohort of 45 patients treated with sirolimus-eluting stents (SESs) in N the First In Man study had a clinical event within the first 12 months.1 Patients treated with SES in the Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions study had a 1-year event-free survival of 94.1%.2 In the Sirolimus-eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial, the rate of target vessel failure (TVF) was 8.6%.3 Intravascular ultrasound (IVUS) is useful in assessing causes of TVF after stent implantation.4 Therefore, we report on a group of patients studied with IVUS who presented From the Cardiovascular Research Foundation, New York, New York. Dr. Moses’ address is: Columbia University Medical Center, 161 Fort Washington Avenue, 5th Floor, New York, New York 10032. E-mail: [email protected]. Manuscript received August 5, 2004; revised manuscript received and accepted October 7, 2004
498
©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 February 15, 2005
TABLE 1 Clinical, Angiographic, Procedural, and Intravascular Ultrasound (IVUS) Finding in the Overall Cohort of 33 Patients With Target Vessel Failure (TVF) After Sirolimus-eluting Stent (SES) Implantation Characteristics
Values
Age (yrs) Men Diabetes mellitus Unstable angina pectoris Chronic total occlusion Bifurcation Kissing stents Ostial No. of SESs Total SES length (mm) Final balloon (mm) Maximum inflation pressure (atm) Postdilatation Use of glycoprotein IIb/IIIa inhibitors Angiography Lesion length (mm) Reference (mm) Preintervention MLD (mm) Postintervention MLD (mm) TVF classification Stent thrombosis SES restenosis Intrastent (multiple) Stent edge (both edges) Intrastent ⫹ stent edge Stent embolization Intrastent ⫹ new lesion Stent edge ⫹ new lesion New lesion only IVUS Minimum stent CSA (mm2) Minimum stent CSA ⬍5.0 Minimum stent CSA ⬍4.0 Minimum stent CSA ⬍3.0 Gap between stents
63 ⫾ 10 22 (67%) 17 (52%) 7 (21%) 2 (6%) 9 (27%) 7 (21%) 5 (15%) 1.8 ⫾ 0.8 35 ⫾ 18 3.1 ⫾ 0.4 16 ⫾ 3 21 (64%) 8 (24%) 19.0 2.77 0.79 2.64
⫾ ⫾ ⫾ ⫾
13.2 0.54 0.35 0.61
4 27 20 (1) 3 (1) 1 1 1 1 2 4.6 ⫾ 1.7 22 (67%) 13 (39%) 8 (24%) 0
MLD ⫽ minimum lumen diameter.
0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.10.020
obutamine systolic wall thickening (SWT) and wall thickness have been used to predict myocardial D viability. In chronic ischemic heart disease, dysfunctional myocardial segments often result from scar tissue from previous myocardial infarction that extends variably from the subendocardium toward the epicardium.1 Previous histopathologic studies from explanted human hearts have suggested that the amount of fibrosis and necrosis in myocardial segments is associated with dobutamine SWT2– 4; however, limitations in these in vitro studies have included an anatomic misalignment and a variable interval between assessment of dobutamine SWT and explantation of the heart during heart transplantation surgery. Using contrast-enhanced magnetic resonance imaging (MRI), the transmural extent of myocardial scar associated with previous infarction in patients who have chronic ischemic heart disease can be quantified noninvasively.5,6 We hypothesized that impaired dobutamine SWT in dysfunctional myocardial segments in patients who have chronic ischemic heart disease was due to extensive transmural scarring and related to wall thickness at rest. To test this hypothesis, we measured wall thickness and SWT before and during intravenous dobutamine administration and the extent of myocardial scar tissue during a cardiac MRI examination. From the Departments of Internal Medicine (Cardiology Section), Radiology, and Biomedical Engineering, Wake Forest University School of Medicine, Winston-Salem, North Carolina. This research was supported in part by the NIA Claude Pepper Older Americans Independence Centers, Wake Forest University (grant 1P30AG021332-01), Winston-Salem, North Carolina. Dr. Rerkpattanapipat’s address is: Bangkok Heart Institute, 2 Soi Soonvijai 7, New Petchaburi Road, Bangkapi, Huay-Kwuay, Bangkok 10320, Thailand. E-mail: [email protected]. Manuscript received June 17, 2004; revised manuscript received and accepted October 15, 2004. ©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 February 15, 2005
•••
The institutional review board of the Wake Forest University School of Medicine (Winston-Salem, North Carolina) approved the study, and all participants gave written informed consent. We prospectively studied 16 patients who had stable coronary artery disease with regional wall motion abnormalities at rest (mean ⫾ SD left ventricular ejection fraction 41 ⫾ 9%). Patients who had myocardial infarction ⬍6 months, unstable angina, New York Heart Association class III or IV congestive heart failure, or contraindications to MRI or dobutamine administration were excluded. Patients’ characteristics are listed in Table 1. All images were acquired on a CV/i 1.5-T wholebody MRI system (General Electric Medical Systems, Waukesha, Wisconsin) with patients in the supine position and a phased-array receiver coil placed on the chest. Acquisition parameters for acquiring white blood images of left ventricular contraction included a 10- to 14-ms repetition time, a 5-ms echo time, a 30° flip angle, a 32- to 40-cm field of view, an 8-mm thickness, and an 8- to 12-second breath-hold.7 Dobutamine was administered intravenously at a starting dose of 5 g/kg/min for 3 minutes and then increased to 10 g/kg/min for 3 minutes. Gadoteridol (ProHance, Bracco Diagnostics Inc., Princeton, New Jersey) was given intravenously (0.2 mmol/kg body weight) right after acquisition of cine magnetic resonance images of the left ventricle at the end of the dobutamine infusion protocol. Twenty minutes after contrast administration, contrast-enhanced images of the left ventricle were acquired with a gated fastgradient echo sequence with inversion recovery in 3 short-axis planes acquired to assess left ventricular wall thickening. Image parameters included a 7.2-ms repetition time, a 3.1-ms echo time, a 200- to 350-ms inversion time (adjusted to achieve a null myocardial signal), a 256 ⫻ 192 matrix, a 34- ⫻ 34-cm field of view, a 20° flip angle, an 8-mm slice thickness, and 24 views per segment. Cine images of the left ventricle at baseline and during administration of 10 g/kg/min of dobutamine and contrast-enhanced images were analyzed for 16 myocardial segments (6 basal, 6 middle, and 4 apical).8 Wall thickness in each segment was measured at end-diastole and end-systole at rest and during smalldose dobutamine administration. SWT was calculated from the difference between end-systolic and enddiastolic wall thicknesses according to previously published techniques.9 Dobutamine SWT ⬍2 mm in severely hypokinetic, akinetic, or dyskinetic segments was identified as a lack of viability or contractile reserve.9 Transmural extent of hyperenhancement was 0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.10.019
495
TABLE 1 Patients’ Characteristics Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Age (yrs)/ Sex 53 57 57 59 60 62 65 65 66 69 70 71 72 72 75 75
M M M M M M M M F M M M M M M M
Diabetes
Hypertension
Current Smoker
⫹ ⫺ ⫺ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺
⫹ ⫹ ⫹ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹ ⫺
⫺ ⫺ ⫹ ⫺ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
Hypercholesterolemia
Previous Myocardial Infarction
Previous Coronary Revascularization
⫹ ⫹ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺
⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
FIGURE 1. Contractile response to dobutamine infusion and transmural extent of hyperenhancement (EH). Cine magnetic resonance images show the left ventricle at the mid–short-axis level at end-systole (ES) at rest (left column) and during low-dose dobutamine administration (middle column). Contrast-enhanced magnetic resonance images show the left ventricle at the same level as cine images (right column). Segments (anteroseptal, septal, inferior, and posterior walls) with subendocardial infarction and <50% EH showed improvement in contractility with dobutamine infusion (top row). In contrast, systolic thickening of segments (anteroseptal, septal, and anterior walls) with >50% EH did not improve with dobutamine infusion (bottom row).
determined for each segment by calculating the percentage of the ratio of the hyperenhanced area to the total area of that myocardial segment.6 Two-sided Student’s t tests were used to compare continuous variables, which were expressed as mean ⫾ SD. The association among transmural extent of hyperenhancement, dobutamine SWT, and end-diastolic wall thickness at baseline was analyzed by lin496 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 95
ear regression analysis. Statistical significance was set at a p value ⬍0.05. All p values were based on a 2-sided test of significance. Of the 256 myocardial segments displayed in the collected images, 48 were severely hypokinetic, akinetic, or dyskinetic at rest; these segments were included in the analysis. Transmural extent of hyperenhancement correlated inversely with dobutamine SWT FEBRUARY 15, 2005
FIGURE 2. Relation between dobutamine-induced SWT (y axis) and transmural extent of hyperenhancement (x axis).
FIGURE 3. Relation between dobutamine-induced SWT (DobSWT) and segmental extent of hyperenhancement (EH) in segments with end-diastolic wall thickness (EDWT) <6 or > 6 mm.
(r ⫽ ⫺0.73, p ⬍0.001; Figures 1 and 2). Segments with dobutamine SWT ⱖ2 mm differed from those with ⬍2 mm with respect to end-diastolic wall thickness (12.1 ⫾ 3.6 vs 7.7 ⫾ 3.5 mm, p ⬍0.001) and transmural extent of hyperenhancement (11 ⫾ 16% vs 77 ⫾ 22%, p ⬍0.001). All myocardial segments with an end-diastolic wall thickness ⬍6 mm showed a dobutamine SWT ⬍2 mm and a transmural extent of hyperenhancement ⱖ50%. End-diastolic wall thickness correlated inversely with transmural extent of hyperenhancement (r ⫽ ⫺0.70, p ⬍0.001). Values for transmural extent of hyperenhancement were 92 ⫾ 12% versus 38 ⫾ 14% (p ⬍0.001) and those for dobutamine SWT were 0.3 ⫾ 0.4 versus 2.7 ⫾ 2.7 mm (p ⬍0.001) in segments that had end-diastolic wall thicknesses of ⬍6 and ⱖ6 mm, respectively. The relation among end-diastolic wall thickness, dobutamine SWT, and transmural extent of hyperenhancement is shown in Figure 3. •••
There are 2 important findings in this study. First, myocardial thinning with an end-diastolic wall thickness ⬍6 mm and dobutamine SWT ⬍2 mm is an indicator of chronic transmural scarring from infarction. Second, dobutamine SWT in patients who have chronic ischemic
heart disease is influenced by the transmural extent of scar. Dysfunctional segments with ⬍50% transmural extent of scar tissue are likely to exhibit a contractile response to inotropic stimulation. Previous studies have associated myocardial thinning with the absence of dobutamine SWT after coronary arterial revascularization.9,10 An autopsy study10 associated transmural scarring with myocardial thinning, which is usually ⬍6 mm. In our study, all segments with end-diastolic wall thickness ⬍6 mm had dobutamine SWT ⬍2 mm and ⱖ50% transmural extent of hyperenhancement. Our results indicate that a large percentage of myocardial infarcted tissue may be responsible for inappropriate dobutamine-induced SWT in these thinned myocardial segments. Our results suggest that the amount of transmural scar tissue is an important factor for determining the response to inotropic stimulation in patients who have chronic ischemic heart disease. All segments with dobutamine SWT ⱖ2 mm had ⬍50% transmural extent of hyperenhancement. These data are consistent with those reported by Kim et al,6 in which myocardial segments with ⬍50% transmural extent of hyperenhancement were likely to improve regional function after coronary arterial revascularization. They are also consistent with positron emission tomographic or nuclear scintigraphic data in which a glucose or thallium uptake ⬎50% was associated with improved regional function after revascularization.11,12 Because our analytic method used only short-axis views, we missed the 17th segment or apical cap, which is usually examined from the long axis of the left ventricle. Ischemia at the apical segments during magnetic resonance image stress testing had important prognostic implications as noted by Hundley et al.13
Acknowledgment: Contrast material (Prohance) administered in this study was kindly supplied by Bracco Diagnostics, Inc., Princeton, New Jersey.
1. Antman EM, Braunwald E. Acute myocardial infarction. In: Braunwald E, Zipes
DP, Libby P, eds. Heart Disease. Philadelphia: W.B. Saunders Co., 2001:1111–1231. 2. Baumgartner H, Porenta G, Lau YK, Wutte M, Klaar U, Mehrabi M, Siegel RJ,
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Intravascular Ultrasound Assessment of Lesions With Target Vessel Failure After Sirolimus-Eluting Stent Implantation Hideo Takebayashi, MD, Yoshio Kobayashi, MD, Gary S. Mintz, MD, Stéphane G. Carlier, MD, PhD, Kenichi Fujii, MD, Takenori Yasuda, MD, Issam Moussa, MD, Roxana Mehran, MD, George D. Dangas, MD, PhD, Michael B. Collins, MD, Edward Kreps, MD, Alexandra J. Lansky, MD, Gregg W. Stone, MD, Martin B. Leon, MD, and Jeffrey W. Moses, MD Intravascular ultrasound (IVUS) evaluation was performed in 33 lesions with sirolimus-eluting stent (SES) failure: 4 thromboses, 26 in-stent restenoses (including 6 edge stenoses), 4 new stenoses >5 mm proximal to the stent, and 1 patient with no evidence of the implanted SES (presumably because of embolization). A minimum stent area <5.0 mm2 (stent underexpansion) was observed in 67% of all SES failures (in particular, 67% of intrastent restenosis); negative remodeling was observed in 4 of 6 stent edge restenoses, and new lesions were secondary to an increase in plaque area. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:498 –502)
o patient in the original cohort of 45 patients treated with sirolimus-eluting stents (SESs) in N the First In Man study had a clinical event within the first 12 months.1 Patients treated with SES in the Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions study had a 1-year event-free survival of 94.1%.2 In the Sirolimus-eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial, the rate of target vessel failure (TVF) was 8.6%.3 Intravascular ultrasound (IVUS) is useful in assessing causes of TVF after stent implantation.4 Therefore, we report on a group of patients studied with IVUS who presented From the Cardiovascular Research Foundation, New York, New York. Dr. Moses’ address is: Columbia University Medical Center, 161 Fort Washington Avenue, 5th Floor, New York, New York 10032. E-mail: [email protected]. Manuscript received August 5, 2004; revised manuscript received and accepted October 7, 2004
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©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 February 15, 2005
TABLE 1 Clinical, Angiographic, Procedural, and Intravascular Ultrasound (IVUS) Finding in the Overall Cohort of 33 Patients With Target Vessel Failure (TVF) After Sirolimus-eluting Stent (SES) Implantation Characteristics
Values
Age (yrs) Men Diabetes mellitus Unstable angina pectoris Chronic total occlusion Bifurcation Kissing stents Ostial No. of SESs Total SES length (mm) Final balloon (mm) Maximum inflation pressure (atm) Postdilatation Use of glycoprotein IIb/IIIa inhibitors Angiography Lesion length (mm) Reference (mm) Preintervention MLD (mm) Postintervention MLD (mm) TVF classification Stent thrombosis SES restenosis Intrastent (multiple) Stent edge (both edges) Intrastent ⫹ stent edge Stent embolization Intrastent ⫹ new lesion Stent edge ⫹ new lesion New lesion only IVUS Minimum stent CSA (mm2) Minimum stent CSA ⬍5.0 Minimum stent CSA ⬍4.0 Minimum stent CSA ⬍3.0 Gap between stents
63 ⫾ 10 22 (67%) 17 (52%) 7 (21%) 2 (6%) 9 (27%) 7 (21%) 5 (15%) 1.8 ⫾ 0.8 35 ⫾ 18 3.1 ⫾ 0.4 16 ⫾ 3 21 (64%) 8 (24%) 19.0 2.77 0.79 2.64
⫾ ⫾ ⫾ ⫾
13.2 0.54 0.35 0.61
4 27 20 (1) 3 (1) 1 1 1 1 2 4.6 ⫾ 1.7 22 (67%) 13 (39%) 8 (24%) 0
MLD ⫽ minimum lumen diameter.
0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.10.020