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Changes in Left Anterior Descending Coronary Artery Wall Thickness Detected by High Resolution Transthoracic Echocardiography
Changes in Left Anterior Descending Coronary Artery Wall Thickness Detected by High Resolution Transthoracic Echocardiography Rebecca Perry, BSc, DMU (Cardiac)*, Carmine G. De Pasquale, BMBS, PhD, Derek P. Chew, MBBS, MPH, Lynn Brown, RN, Philip E. Aylward, BM, PhD, and Majo X. Joseph, MBBS Recently, it has been demonstrated that high-resolution transthoracic echocardiography (HRTTE) is able to detect differences in the wall thickness of the left anterior descending coronary artery (LAD) between patients with coronary artery disease (CAD) and normal volunteers. The aim of this study was to further validate this technique. One hundred ten volunteers, 58 patients with angiographically proved CAD and 52 control subjects, underwent assessments of their LADs using HRTTE. Anterior and posterior wall thicknesses differed between subjects in the CAD group and controls (1.9 ⴞ 0.6 vs 1.2 ⴞ 0.3 mm, p <0.001, and 1.8 ⴞ 0.5 vs 1.2 ⴞ 0.3 mm, p <0.001, respectively). External LAD diameter was also greater in subjects in the CAD group compared with controls (5.2 ⴞ 1.9 vs 4.4 ⴞ 0.9 mm, respectively, p ⴝ 0.01). However, there was no difference in luminal diameter between subjects in the CAD group and the controls (1.9 ⴞ 0.9 vs 2.1 ⴞ 0.8 mm, respectively, p ⴝ 0.3). In conclusion, HRTTE demonstrated that LAD wall thicknesses and external diameters in patients with CAD were significantly larger than in normal volunteers. Luminal diameter, however, was maintained in the 2 groups, indicating that subjects in the CAD group had undergone positive remodeling at the site measured. This objectively visualized evidence of coronary atherosclerosis with HRTTE would likely be undetected during coronary angiography. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:937–940) Intravascular ultrasound and epicardial echocardiographic studies have demonstrated that coronary atherosclerosis is a diffuse disease process and rarely spares the proximal coronary arteries, especially the proximal left anterior descending coronary artery (LAD).1–7 In fact, it has been shown that before clinical coronary artery disease (CAD) is evident, ⱖ90% of the coronary artery tree is atherosclerotic.5,8 Accurate baseline measurements of the LAD luminal and external diameters and wall thickness have been shown to be achievable using a recently described technique of highresolution transthoracic echocardiography (HRTTE).9,10 We sought to use this technique to demonstrate differences in coronary atherosclerosis between patients with CAD and controls. Methods and Results This study was approved by the Flinders Research Ethics Committee, and all subjects gave written informed consent to participate in the study. Healthy volunteers (n ⫽ 52) without histories of or risk factors for CAD (control group; no clinical hypertension, no hypercholesterolemia, nonsmoking, nondiabetic, and no history of periph-
Cardiac Services, Flinders Medical Centre/Flinders University, Bedford Park, South Australia, Australia. Manuscript received September 7, 2007; revised manuscript received and accepted November 13, 2007 Dr. Joseph is supported by a Cardiovascular Lipid Grant from Pfizer Australia, Sydney, Australia. *Corresponding author: Tel: 61-882046075; fax: 61-882044907. E-mail address: [email protected] (R. Perry). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.11.053
eral or cerebral vascular disease) and consecutive hospital inpatients with angiographically proved CAD (defined as a coronary artery stenosis ⬎50% in any coronary artery branch other than the LAD; n ⫽58) underwent ultrasound scans to measure luminal and external artery caliber and anterior and posterior LAD wall thicknesses. The patients with CAD were prospectively identified while in the hospital. Subject characteristics for the CAD group are listed in Table 1. Examinations were obtained using a commercially available ultrasound system (iE33; Philips Medical Systems, Bothell, Washington) with a high-frequency transducer (S8-3). The LAD was recorded using a parasternal long-axis examination, with a slight inferior tilt to obtain long-axis images of the LAD as it runs along the interventricular septum. In our hands, the inter- and intraoperator variability of this method is r ⫽ 0.86 (p ⬍0.001) and r ⫽ 0.86 (p ⬍0.001), respectively. Readers were blinded to any clinical data. The presence of 2 linear echoes anterior to the interventricular septum in ⱖ3 consecutive frames was used to identify the LAD. Segments with the largest luminal diameters were selected to ensure that the measured cross section of the artery was through the center and thus the results were not confounded by off-axis images. Where multiple linear echoes were noted anterior to the interventricular septum, the thicker walled vascular structure was measured to avoid potential confusion with the great cardiac vein. Pulsed-wave spectral and color Doppler (Figure 1) was used to further delineate the LAD from the great cardiac vein if required. For all measurements, the diswww.AJConline.org
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The American Journal of Cardiology (www.AJConline.org)
Table 1 Subject characteristics of coronary artery disease group in total cohort and subgroup analysis Variable Age (yrs) Men Total cholesterol Triglyceride Low-density lipoprotein High-density lipoprotein C-reactive protein (mg/L) Right coronary disease Left circumflex disease Previous statin therapy Previous angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy Previous aspirin therapy Hypertension Diabetes mellitus Smokers
CAD Group (Total CAD Cohort, n ⫽ 50)
CAD Subgroup (CAD Subjects Aged ⬍55 Years, n ⫽ 22)
p Value
51 ⫾ 7 42 (84%) 4.9 ⫾ 1.7 mmol/L (190 ⫾ 65 mg/dl) 2.0 ⫾ 1.3 mmol/L (77 ⫾ 50 mg/dl) 3.0 ⫾ 1.6 mmol/L (117 ⫾ 62 mg/dl) 1.4 ⫾ 1.2 mmol/L (54 ⫾ 46 mg/dl) 8.0 ⫾ 9.4 37 (74%) 30 (60%) 21 (42%) 9 (18%)
44 ⫾ 2 17 (77%) 4.9 ⫾ 1.6 mmol/L (190 ⫾ 62 mg/dl) 1.9 ⫾ 0.9 mmol/L (78 ⫾ 35 mg/dl) 3.1 ⫾ 1.5 mmol/L (52 ⫾ 59 mg/dl) 1.2 ⫾ 0.3 mmol/L (46 ⫾ 12 mg/dl) 8.4 ⫾ 10.7 16 (73%) 14 (63%) 9 (41%) 4 (18%)
0.01 0.22 0.57 0.44 0.92 0.15 0.45 0.55 0.43 0.2 0.54
18 (36%) 13 (26%) 3 (6%) 17 (34%)
7 (31%) 6 (27%) 1 (5%) 11 (50%)
0.43 0.55 0.53 0.07
Continuous data are expressed as mean ⫾ SD and discrete variables as number (percentage).
Figure 1. A modified parasternal long-axis view to demonstrate color flow in the LAD as it runs along the interventricular septum (IVS). Some color flow in the right ventricular inflow tract (RVIT) can also be detected. LV ⫽ left ventricular cavity.
tance between the inner edges of the lines representing vascular walls was used. Continuous variables are expressed as mean ⫾ SD. A paired Student’s t test was used to determine if there was any significant difference in each measurement between the 2 groups. Discrete variables were compared using chi-square analysis and are expressed as numbers and
percentages. A p value ⬍0.05 was considered statistically significant. Adequate imaging of the LAD was possible in 50 of the 52 subjects (96%) in the control group (42 men) and in 50 of the 58 subjects (86%) in the CAD group (32 men). The 10 subjects without adequate imaging were excluded from the analysis. The subjects in the CAD group were significantly older than
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respectively, p ⫽ 0.03). However, as seen in the total cohort, there was no difference in luminal diameter between the age-matched CAD group and the controls (2.0 ⫾ 1.1 vs 2.4 ⫾ 0.7 mm, respectively, p ⫽ 0.5) (Figure 3). Discussion
Figure 2. Graph demonstrating the differences in LAD wall thickness, luminal diameter, and external artery diameter between normal subjects and patients with angiographically proved CAD ⬎50% in any part of the coronary tree other than the proximal or mid LAD.
Figure 3. Graph demonstrating the differences in LAD wall thickness, luminal diameter, and external artery diameter between age-matched normal subjects and patients with angiographically proved CAD.
those in the control group (51 ⫾ 6 vs 35 ⫾ 9 years, p ⬍0.001) and had higher body mass indexes (29 ⫾ 4 vs 25 ⫾ 4 kg/m2, p ⫽ 0.02). Anterior and posterior wall thicknesses differed significantly between subjects in the CAD group and controls (1.9 ⫾ 0.6 vs 1.2 ⫾ 0.3 mm, p ⬍0.001, and 1.8 ⫾ 0.5 vs 1.2 ⫾ 0.3 mm, p ⬍0.001, respectively). External LAD diameter was also increased in subjects in the CAD group compared with controls (5.2 ⫾ 1.9 vs 4.4 ⫾ 0.9 mm, respectively, p ⫽ 0.01). However, there was no difference in luminal diameter between subjects in the CAD group and controls (1.9 ⫾ 0.9 vs 2.1 ⫾ 0.8 mm, respectively, p ⫽ 0.3) (Figure 2). To determine if this difference in wall thickness and external diameter was due to the effects of age, a subgroup analysis was performed using control subjects aged ⬎35 years and subjects with CAD aged ⬍55 years. In this subgroup analysis, there were 23 control subjects (13 men) and 22 patients with CAD (17 men). The subgroup subject characteristics in the CAD group did not significantly differ from those of the total cohort, except that they were significantly younger (Table 1). There was no difference in age between the 2 subgroups (control group 42 ⫾ 5 years vs CAD group 44 ⫾ 2 years, p ⫽ 0.3). The anterior and posterior wall thickness significantly differed between the age-matched CAD group and controls (1.7 ⫾ 0.5 vs 1.2 ⫾ 0.3 mm, p ⫽ 0.001, and 1.8 ⫾ 0.5 vs 1.3 ⫾ 0.4 mm, p ⫽ 0.001, respectively). The external LAD diameter was again also increased in the age-matched CAD group compared with controls (5.2 ⫾ 1.9 vs 4.5 ⫾ 0.8 mm,
This study confirms that HRTTE can detect structural differences in proximal LAD morphology suggestive of atherosclerosis-induced positive remodeling in patients with confirmed significant luminal CAD in other coronary vascular territories. We found the LAD wall thicknesses and external diameters of subjects with CAD to be significantly larger than those of normal volunteers, indicating atherosclerotic buildup (Figure 4). Luminal diameters, however, were the same in the 2 groups, indicating the well-recognized phenomenon of positive remodeling at the measured site in subjects in the CAD group. Because of the preservation of luminal diameter in this group, this atherosclerotic thickening was not detected during angiography. Subjects in the CAD group were older, thereby introducing a bias that could potentially account for the differences in wall thickness and external artery diameter, a limitation also observed by the pioneering work of Gradus-Pizlo et al.9 To counter this, we performed a subgroup analysis using the older control subjects (⬎35 years) and the younger subjects with CAD (⬍55 years). The comparative difference in visualized proximal LAD existed between the groups after this analysis, thereby confirming that the differences were not solely age related. The increased wall thickening seen in subjects in the CAD group despite the benign angiographic appearance of the proximal and mid LAD region indicates that this method of HRTTE may be more sensitive than angiography for the detection of subclinical atherosclerosis. This may have future clinical relevance in an era when high-risk subgroup-targeted primary prevention therapeutic intervention exists, such as statin and aspirin therapy. In the study by Gradus-Pizlo et al,9 the average wall thickness, luminal diameter, and external diameter in the CAD group were 1.9 ⫾ 0.4, 2.2 ⫾ 0.5, and 6.0 ⫾ 1.1 mm, respectively, and in the control group, these values were 0.9 ⫾ 0.1, 2.1 ⫾ 0.6, and 3.9 ⫾ 0.7 mm, respectively. The corresponding values in this study closely agree with these values, supporting robust interobserver variability for this novel technique. There is a potential risk for confusion of the LAD for the great cardiac vein because in most cases, the 2 vessels run parallel to each other along the anterior surface of the heart. This risk was minimized, however, by measurement of the thicker walled vascular structure visualized and by using pulsed-wave Doppler analysis to define the arterial from the venous blood flow in a subset of patients. There were a number of subjects (10%) in whom the LAD could not be imaged well enough to make accurate measurements of the wall thickness. Echocardiography, particularly at a high frequency, is limited in imaging subjects with poor intercostal spaces, significant lung
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The American Journal of Cardiology (www.AJConline.org)
Figure 4. HRTTE of the LAD of subjects in the control group (A) and in the CAD group (B). Arrows demonstrate anterior LAD wall thickness.
disease, and obesity. Finally, although it is also possible that variations in coronary anatomy made it difficult to visualize the LAD in some subjects who may have had an adequate parasternal window, the proximal LAD is a very rare site of congenital anatomic abnormality. 1. McPherson DD, Sirna SJ, Hiratzka LF, Thorpe L, Armstrong ML, Marcus ML, Kerber RE. Coronary arterial remodelling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis. J Am Coll Cardiol 1991;17:79 – 86. 2. Tuzcu EM, Hobbs RE, Rincon G, Bott-Silvermann C, De Franco AC, Robinson K, McCarthy PM, Stewart RW, Guyer S, Nissen SE. Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation: insights from intravascular ultrasound. Circulation 1995;91:1706 –1713. 3. Abizaid A, Mintz GS, Pichard AD, Kent KM, Satler LF, Popma JJ, Leon MB. Is intravascular ultrasound clinically useful or is it just a research tool? Heart 1997;78:27–30. 4. Topol EJ, Nissen SE. Our preoccupation with coronary luminology: the dissocation between clinical and angiographic findings in ischemic heart disease. Circulation 1995;92:2333–2342. 5. McPherson DD, Hiratzka LF, Lamberth WC, Brandt B, Hunt M, Kieso RA, Marcus ML, Kerber RE. Delineation of the extent of coronary
6.
7.
8.
9.
10.
atherosclerosis by high-frequency epicardial echocardiography. N Engl J Med 1987;316:304 –309. Hausmann D, Johnson JA, Sudhir K, Mullen WL, Friedrich G, Fitzgerald PJ, Chou TM, Ports TA, Kane JP, Malloy MJ, Yock PG. Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins. J Am Coll Cardiol 1996;27:1562–1570. Hermiller JB, Tenaglia AN, Kisslo KB, Phillips HR, Bashore TM, Stack RS, Davidson CJ. In vivo validation of compensatory enlargement of atherosclerotic coronary arteries. Am J Cardiol 1993;71:665– 668. Nakamura Y, Takemori H, Shiraishi K, Inoki I, Sakagami M, Shimakura A, Usuda K, Kubota K, Takata S, Kobayashi K. Compensatory enlargement of angiographically normal coronary segments in patients with coronary artery disease. In vivo documentation using intravascular ultrasound. Angiology 1996;47:775–781. Gradus-Pizlo I, Sawada SG, Wright D, Segar DS, Feigenbaum H. Detection of subclinical coronary atherosclerosis using two- dimensional, high-resolution transthoracic echocardiography. J Am Coll Cardiol 2001;37:1422–1429. Perry R, Joseph MX, De Pasquale CG, Chew DP, Yiu D, Aylward PE, Mangoni AA. High resolution transthoracic echocardiography of the left anterior descending coronary artery: a novel non-invasive assessment of coronary vasoreactivity. J Am Soc Echocardiography. In press.
Cardiac Services, Flinders Medical Centre/Flinders University, Bedford Park, South Australia, Australia. Manuscript received September 7, 2007; revised manuscript received and accepted November 13, 2007 Dr. Joseph is supported by a Cardiovascular Lipid Grant from Pfizer Australia, Sydney, Australia. *Corresponding author: Tel: 61-882046075; fax: 61-882044907. E-mail address: [email protected] (R. Perry). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.11.053
eral or cerebral vascular disease) and consecutive hospital inpatients with angiographically proved CAD (defined as a coronary artery stenosis ⬎50% in any coronary artery branch other than the LAD; n ⫽58) underwent ultrasound scans to measure luminal and external artery caliber and anterior and posterior LAD wall thicknesses. The patients with CAD were prospectively identified while in the hospital. Subject characteristics for the CAD group are listed in Table 1. Examinations were obtained using a commercially available ultrasound system (iE33; Philips Medical Systems, Bothell, Washington) with a high-frequency transducer (S8-3). The LAD was recorded using a parasternal long-axis examination, with a slight inferior tilt to obtain long-axis images of the LAD as it runs along the interventricular septum. In our hands, the inter- and intraoperator variability of this method is r ⫽ 0.86 (p ⬍0.001) and r ⫽ 0.86 (p ⬍0.001), respectively. Readers were blinded to any clinical data. The presence of 2 linear echoes anterior to the interventricular septum in ⱖ3 consecutive frames was used to identify the LAD. Segments with the largest luminal diameters were selected to ensure that the measured cross section of the artery was through the center and thus the results were not confounded by off-axis images. Where multiple linear echoes were noted anterior to the interventricular septum, the thicker walled vascular structure was measured to avoid potential confusion with the great cardiac vein. Pulsed-wave spectral and color Doppler (Figure 1) was used to further delineate the LAD from the great cardiac vein if required. For all measurements, the diswww.AJConline.org
938
The American Journal of Cardiology (www.AJConline.org)
Table 1 Subject characteristics of coronary artery disease group in total cohort and subgroup analysis Variable Age (yrs) Men Total cholesterol Triglyceride Low-density lipoprotein High-density lipoprotein C-reactive protein (mg/L) Right coronary disease Left circumflex disease Previous statin therapy Previous angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy Previous aspirin therapy Hypertension Diabetes mellitus Smokers
CAD Group (Total CAD Cohort, n ⫽ 50)
CAD Subgroup (CAD Subjects Aged ⬍55 Years, n ⫽ 22)
p Value
51 ⫾ 7 42 (84%) 4.9 ⫾ 1.7 mmol/L (190 ⫾ 65 mg/dl) 2.0 ⫾ 1.3 mmol/L (77 ⫾ 50 mg/dl) 3.0 ⫾ 1.6 mmol/L (117 ⫾ 62 mg/dl) 1.4 ⫾ 1.2 mmol/L (54 ⫾ 46 mg/dl) 8.0 ⫾ 9.4 37 (74%) 30 (60%) 21 (42%) 9 (18%)
44 ⫾ 2 17 (77%) 4.9 ⫾ 1.6 mmol/L (190 ⫾ 62 mg/dl) 1.9 ⫾ 0.9 mmol/L (78 ⫾ 35 mg/dl) 3.1 ⫾ 1.5 mmol/L (52 ⫾ 59 mg/dl) 1.2 ⫾ 0.3 mmol/L (46 ⫾ 12 mg/dl) 8.4 ⫾ 10.7 16 (73%) 14 (63%) 9 (41%) 4 (18%)
0.01 0.22 0.57 0.44 0.92 0.15 0.45 0.55 0.43 0.2 0.54
18 (36%) 13 (26%) 3 (6%) 17 (34%)
7 (31%) 6 (27%) 1 (5%) 11 (50%)
0.43 0.55 0.53 0.07
Continuous data are expressed as mean ⫾ SD and discrete variables as number (percentage).
Figure 1. A modified parasternal long-axis view to demonstrate color flow in the LAD as it runs along the interventricular septum (IVS). Some color flow in the right ventricular inflow tract (RVIT) can also be detected. LV ⫽ left ventricular cavity.
tance between the inner edges of the lines representing vascular walls was used. Continuous variables are expressed as mean ⫾ SD. A paired Student’s t test was used to determine if there was any significant difference in each measurement between the 2 groups. Discrete variables were compared using chi-square analysis and are expressed as numbers and
percentages. A p value ⬍0.05 was considered statistically significant. Adequate imaging of the LAD was possible in 50 of the 52 subjects (96%) in the control group (42 men) and in 50 of the 58 subjects (86%) in the CAD group (32 men). The 10 subjects without adequate imaging were excluded from the analysis. The subjects in the CAD group were significantly older than
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respectively, p ⫽ 0.03). However, as seen in the total cohort, there was no difference in luminal diameter between the age-matched CAD group and the controls (2.0 ⫾ 1.1 vs 2.4 ⫾ 0.7 mm, respectively, p ⫽ 0.5) (Figure 3). Discussion
Figure 2. Graph demonstrating the differences in LAD wall thickness, luminal diameter, and external artery diameter between normal subjects and patients with angiographically proved CAD ⬎50% in any part of the coronary tree other than the proximal or mid LAD.
Figure 3. Graph demonstrating the differences in LAD wall thickness, luminal diameter, and external artery diameter between age-matched normal subjects and patients with angiographically proved CAD.
those in the control group (51 ⫾ 6 vs 35 ⫾ 9 years, p ⬍0.001) and had higher body mass indexes (29 ⫾ 4 vs 25 ⫾ 4 kg/m2, p ⫽ 0.02). Anterior and posterior wall thicknesses differed significantly between subjects in the CAD group and controls (1.9 ⫾ 0.6 vs 1.2 ⫾ 0.3 mm, p ⬍0.001, and 1.8 ⫾ 0.5 vs 1.2 ⫾ 0.3 mm, p ⬍0.001, respectively). External LAD diameter was also increased in subjects in the CAD group compared with controls (5.2 ⫾ 1.9 vs 4.4 ⫾ 0.9 mm, respectively, p ⫽ 0.01). However, there was no difference in luminal diameter between subjects in the CAD group and controls (1.9 ⫾ 0.9 vs 2.1 ⫾ 0.8 mm, respectively, p ⫽ 0.3) (Figure 2). To determine if this difference in wall thickness and external diameter was due to the effects of age, a subgroup analysis was performed using control subjects aged ⬎35 years and subjects with CAD aged ⬍55 years. In this subgroup analysis, there were 23 control subjects (13 men) and 22 patients with CAD (17 men). The subgroup subject characteristics in the CAD group did not significantly differ from those of the total cohort, except that they were significantly younger (Table 1). There was no difference in age between the 2 subgroups (control group 42 ⫾ 5 years vs CAD group 44 ⫾ 2 years, p ⫽ 0.3). The anterior and posterior wall thickness significantly differed between the age-matched CAD group and controls (1.7 ⫾ 0.5 vs 1.2 ⫾ 0.3 mm, p ⫽ 0.001, and 1.8 ⫾ 0.5 vs 1.3 ⫾ 0.4 mm, p ⫽ 0.001, respectively). The external LAD diameter was again also increased in the age-matched CAD group compared with controls (5.2 ⫾ 1.9 vs 4.5 ⫾ 0.8 mm,
This study confirms that HRTTE can detect structural differences in proximal LAD morphology suggestive of atherosclerosis-induced positive remodeling in patients with confirmed significant luminal CAD in other coronary vascular territories. We found the LAD wall thicknesses and external diameters of subjects with CAD to be significantly larger than those of normal volunteers, indicating atherosclerotic buildup (Figure 4). Luminal diameters, however, were the same in the 2 groups, indicating the well-recognized phenomenon of positive remodeling at the measured site in subjects in the CAD group. Because of the preservation of luminal diameter in this group, this atherosclerotic thickening was not detected during angiography. Subjects in the CAD group were older, thereby introducing a bias that could potentially account for the differences in wall thickness and external artery diameter, a limitation also observed by the pioneering work of Gradus-Pizlo et al.9 To counter this, we performed a subgroup analysis using the older control subjects (⬎35 years) and the younger subjects with CAD (⬍55 years). The comparative difference in visualized proximal LAD existed between the groups after this analysis, thereby confirming that the differences were not solely age related. The increased wall thickening seen in subjects in the CAD group despite the benign angiographic appearance of the proximal and mid LAD region indicates that this method of HRTTE may be more sensitive than angiography for the detection of subclinical atherosclerosis. This may have future clinical relevance in an era when high-risk subgroup-targeted primary prevention therapeutic intervention exists, such as statin and aspirin therapy. In the study by Gradus-Pizlo et al,9 the average wall thickness, luminal diameter, and external diameter in the CAD group were 1.9 ⫾ 0.4, 2.2 ⫾ 0.5, and 6.0 ⫾ 1.1 mm, respectively, and in the control group, these values were 0.9 ⫾ 0.1, 2.1 ⫾ 0.6, and 3.9 ⫾ 0.7 mm, respectively. The corresponding values in this study closely agree with these values, supporting robust interobserver variability for this novel technique. There is a potential risk for confusion of the LAD for the great cardiac vein because in most cases, the 2 vessels run parallel to each other along the anterior surface of the heart. This risk was minimized, however, by measurement of the thicker walled vascular structure visualized and by using pulsed-wave Doppler analysis to define the arterial from the venous blood flow in a subset of patients. There were a number of subjects (10%) in whom the LAD could not be imaged well enough to make accurate measurements of the wall thickness. Echocardiography, particularly at a high frequency, is limited in imaging subjects with poor intercostal spaces, significant lung
940
The American Journal of Cardiology (www.AJConline.org)
Figure 4. HRTTE of the LAD of subjects in the control group (A) and in the CAD group (B). Arrows demonstrate anterior LAD wall thickness.
disease, and obesity. Finally, although it is also possible that variations in coronary anatomy made it difficult to visualize the LAD in some subjects who may have had an adequate parasternal window, the proximal LAD is a very rare site of congenital anatomic abnormality. 1. McPherson DD, Sirna SJ, Hiratzka LF, Thorpe L, Armstrong ML, Marcus ML, Kerber RE. Coronary arterial remodelling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis. J Am Coll Cardiol 1991;17:79 – 86. 2. Tuzcu EM, Hobbs RE, Rincon G, Bott-Silvermann C, De Franco AC, Robinson K, McCarthy PM, Stewart RW, Guyer S, Nissen SE. Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation: insights from intravascular ultrasound. Circulation 1995;91:1706 –1713. 3. Abizaid A, Mintz GS, Pichard AD, Kent KM, Satler LF, Popma JJ, Leon MB. Is intravascular ultrasound clinically useful or is it just a research tool? Heart 1997;78:27–30. 4. Topol EJ, Nissen SE. Our preoccupation with coronary luminology: the dissocation between clinical and angiographic findings in ischemic heart disease. Circulation 1995;92:2333–2342. 5. McPherson DD, Hiratzka LF, Lamberth WC, Brandt B, Hunt M, Kieso RA, Marcus ML, Kerber RE. Delineation of the extent of coronary
6.
7.
8.
9.
10.
atherosclerosis by high-frequency epicardial echocardiography. N Engl J Med 1987;316:304 –309. Hausmann D, Johnson JA, Sudhir K, Mullen WL, Friedrich G, Fitzgerald PJ, Chou TM, Ports TA, Kane JP, Malloy MJ, Yock PG. Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins. J Am Coll Cardiol 1996;27:1562–1570. Hermiller JB, Tenaglia AN, Kisslo KB, Phillips HR, Bashore TM, Stack RS, Davidson CJ. In vivo validation of compensatory enlargement of atherosclerotic coronary arteries. Am J Cardiol 1993;71:665– 668. Nakamura Y, Takemori H, Shiraishi K, Inoki I, Sakagami M, Shimakura A, Usuda K, Kubota K, Takata S, Kobayashi K. Compensatory enlargement of angiographically normal coronary segments in patients with coronary artery disease. In vivo documentation using intravascular ultrasound. Angiology 1996;47:775–781. Gradus-Pizlo I, Sawada SG, Wright D, Segar DS, Feigenbaum H. Detection of subclinical coronary atherosclerosis using two- dimensional, high-resolution transthoracic echocardiography. J Am Coll Cardiol 2001;37:1422–1429. Perry R, Joseph MX, De Pasquale CG, Chew DP, Yiu D, Aylward PE, Mangoni AA. High resolution transthoracic echocardiography of the left anterior descending coronary artery: a novel non-invasive assessment of coronary vasoreactivity. J Am Soc Echocardiography. In press.