Intravascular imaging of serial changes of disease in saphenous vein grafts after coronary artery bypass grafting

Intravascular imaging of serial changes of disease in saphenous vein grafts after coronary artery bypass grafting N o b u y u k i K o m i y a m a , MD, Shigemoto Nakanishi, MD, Shinichiro Nishiyama, MD, a n d Akira Seki, MD

Tokyo, Japan

To clarify the structural changes of saphenous vein grafts after coronary artery bypass grafting, intravascular ultrasound and angioscopic images were obtained from 23 grafts in vivo and 5 grafts and 3 new veins in vitro; the images were compared with histologic findings. Intravascular ultrasound demonstrated a single-layered appearance at new veins and all of the angiographically normal grafts within 6 months after surgery. A triple-layered appearance that might be related to the remarkably proliferative and degenerated intima was revealed histologically at 73.3% of the normal sites of grafts between 5 and 10 years after operation, in 83.3% of the stenoses at several years after operation, angioscopy showed yellow atheromatous plaques, often with a friable surface; a heterogeneous, lucent echo pattern was revealed on intravascular ultrasound. Thus intravascular ultrasound and angioscopy may be used to identify the morphologic changes of grafts at different points after implantation more precisely than conventional angiography. (Am Heart J 1996;132:30-40.)

dalities h a v e become available for clinical use a n d investigation. I n t r a v a s c u l a r u l t r a s o u n d (IVUS) can be used to visualize a cross-section of the vessel, m a k i n g it possible to e v a l u a t e t h e s t r u c t u r e of the v a s c u l a r wall. 1°, 11 Angioscopy m a y be u s e d to obtain information about the surface characteristics of the vessel wall. 12, 13 The a p p e a r a n c e of the intimal surface a n d the presence of small t h r o m b i m a y be assessed with angioscopy. These t e c h n i q u e s can provide a p l e t h o r a of i n f o r m a t i o n about graft disease t h a t c a n n o t be revealed b y conventional angiography. T h e purpose of this s t u d y was to clarify the s t r u c t u r a l changes in SVGs after C A B G by in vivo techniques of IVUS and angioscopy a n d to correlate these observations with histologic findings.

C o r o n a r y a r t e r y bypass grafting (CABG) has b e e n one of the most i m p o r t a n t developments in the t r e a t m e n t of coronary a r t e r y disease. The s a p h e n o u s vein g r a f t (SVG), which is the graft m o s t commonly u s e d for CABG, m a y become occluded or stenosed several y e a r s a f t e r CABG. 1"5 The morphologic changes in the SVG t h a t h a v e been delineated with in vitro techniques are likely associated w i t h the connection of the venous conduit to the high-pressure arterial system. 6-9 Knowledge of the precise pathologic changes in the SVG after CABG m a y be useful in developing a t r e a t m e n t s t r a t e g y for diseased conduits. Recently two in vivo i n t r a v a s c u l a r imaging mo-

in 22 patients were examined in vivo with IVUS and angioscopy in the catheterization laboratory. The patient profile with clinical manifestation is shown in Table I. The subjects were divided into three groups. Group E consisted of six men aged 62.2 +_ 6.5 years in whom six SVGs were examined within 6 months of surgery (mean 1.5 _+ 1.1 months). These SVGs were anastomosed to the left anterior descending artery (LAD; n = 1), left circUmflex artery (LCX; n = 3), right coronary artery (RCA; n = 1) or the first diagonal branch of the LAD (n = 1). In this group, five patients had no symptoms and underwent follow-up angiography. One patient had recurrent effort angina 4 months after operation caused by a stenosis in the LCX just below the distal anastomotic site to an SVG. He underwent percutaneous transluminal coronary angioplasty (PTCA) to the stenosis. In group E, angioscopy and IVUS were performed after angiography or PTCA. Group M consisted of three men aged 60.7 +_ 3.2 years in whom three SVGs were anastomosed to the right coronary arteries. These grafts were examined between 1 and 2 years after surgery (mean 19.7 _+ 6.7 months). All three patients had recurrent effort angina. Two of the patients underwent PTCA or directional coronary atherectomy to newly appeared stenotic lesions in the graft bodies. In another patient with an an-

From the Division of Cardiology, Cardiovascular Center Toranomon Hospital. Received for publication July 6, 1995; accepted Nov. 21, 1995. Repnnt requests: Nobuyuki Komiyama, MD, Division of Cardiology, Cardiovascular Center, Toranomon Hospital, 2-2-2 Toranomon Minate-ku Tokyo 105, Japan. Copyright © 1996 by Mosby-Year Book, Inc. 0002-8703/96/$5.00 + 0 411/71981

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METHODS Patients and SVGs studied in vivo. ~venty-three SYGs

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1

;i:

D

Fig. 1. IVUS and angioscopic images of SVG in group E. At two sites (1, 2) on angiography (A), singlelayered appearance on IVUS {B, C) and whitish smooth-vessel wall on angioscopy (D, E) are demonstrated.

Table I. P a t i e n t profile with clinical manifestation

No. of patients Male Age (yr) Duration aider CABG Reason for examination Recurrent effort angina Rest angina Positive exercise test results Follow-up examination (no sign and no symptom) No. of examined SVGs Anglography Total body segments Normal ->50% narrowing No. of treated SVGs PTCA DCA

giographically 50% long narrowing i n the SVG, PTCA was performed only to the 90% stenosis in the posterior descending artery below the anastomotic site to the SVG. Group L consisted o f l 2 m e n a n d 1 w o m a n aged 60.5 -+ 8.3 years i n whom 14 SVGs were examined between 5 and 10 years after surgery (mean 6.5 - 1.8 years). These SVGs

Group E

Group M

Group L

6 6 62.2 _+6.5 1.5 _+ 1.1 mo

3 3 60.7 _+3.2 19.7 _+6.7 mo

13 12 60.5 -+ 1.8 6.5 + 1.8 yr

1 0 0 5 6

3 0 0 0 3

5 1 5 2 14

18 18

9 6 3 2 1 1

42 30 12 12 11 1

were anastomosed to the LAD (n = 7), the LCX (n = 4), the RCA (n = 2), or the first d i a g o n a l b r a n c h of the LAD (n = 1). I n this group two patients without newly appeared signs a n d symptoms of myocardial ischemia u n d e r w e n t follow-up angiography. Five patients had recurrent effort angina, 1 had rest angina, 5 had a positive exercise test. All

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32 K o m i y a m a et al.

~

,

A

Fig. 2. A and B, IVUS and angioscopic images of newly harvested saphenous vein. Single-layered appearance on IVUS (A) and whitish-blue smooth surface by angioscopy (B) are demonstrated. C and D, Corresponding histologic section. Note absence of intimal (I) hyperplasia. Vessel wall (W) mainly consists of smooth-muscle cells and collagen fibers (elastica van Gieson stain, original magnification ×5).

Table II. Characteristics of 12 stenotic lesions in group L Angiography Characteristic

Angioscopy

Intravascular ultrasound

No.

Characteristic

No.

Filling defect

7 3

7 6 1 1

Heterogeneous echolucent plaque

Broad base

Diaphragmatic Ulceration

1 1

Yellow,polyp-like protrusion With a friable surface Yellowplaque with a friable surface Yellow plaque with a friable surface and whitish plaque Whitish plaque Yellowplaque Ulceration with a red thrombus

1 1 1

Homogeneousplaque Heterogeneous echolucent plaque Not examined

of the patients with newly appeared myocardial ischemia had significant discrete narrowings on their SVGs revealed by angiography and underwent PTCA or directional coronary atherectomy. No patients in this group had diffusely degenerated SVGs shown by angiography. This study had been approved by the Committee on Human Research of Toranomon Hospital, and informed consent was obtained from all patients. Angiography. The angiogram of an SVG was evaluated with a Digital Cardiac Imaging system (DCI, Philips, Best, The Netherlands). The body of each SVG was divided into three portions of equal length on angiography: the proximal, middle, and distal segments. Two anastomotic sites of an SVG to aorta and a native coronary artery were excluded in this study. At a stenotic lesion, lesion length

Characteristic

No.

Heterogeneous echolucent plaque Heterogeneous, partly echogenicplaque

and percentage of stenosis were calculated. Of 69 segments, 54 were normal and 15 had >-50% narrowings on angiography. In this study, the following morphologic features ofSVG stenoses were demonstrated: filling defect, an eccentric stenosis with its length of-<5 mm; broad base, an eccentric stenosis with its length of >5 mm and a tapered vessel lumen; diaphragmatic, an eccentric stenosis with a slitlike appearance; ulceration, an eccentric stenosis with a contrast medium remaining inside a plaque. A n g i o s c o p y . Angioscopy was performed by a doubleguide catheter method with a videofiberscope (VFS-1300, Nihon Kohden, Tokyo, Japan), a 0.7 mm-diameter angiofiberscopic catheter with an image guide of 3000 pixels made of doped silica glass, a PTCA guiding catheter (8F), an inner guide catheter (5F), and a PTCA guide wire (0.010

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et al.

ii, L

Fig. 3. IVUS and angioscopic images of angiographically normal SVG in group L. At two sites (1, 2) on angiography (A), triple-layered appearance is shown on IVUS (B, C) and whitish, smooth surface structure is shown on angioscopy (D, E).

Fig. 4. IVUS and angioscopic images of SVG with filling-defect-type stenosis on angiography in group L. At normal site on angiography (A, 1), triple-layered appearance is revealed on IVUS (B) and whitish, smooth surface is shown on angioscopy (D). At site of stenosis on angiography (A, 2), echolucent eccentric plaque is shown on IVUS (C), and yellowish atheromatous plaque is demonstrated on angioscopy

(E).

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Fig. 5. Angioscopic images of diseased grafts in group L. At site of broad-base-type stenosis on angiography (A, 1 and 2), relatively whitish smooth plaques (B, arrows) and yellowish atheromatous plaque with friable surface (G, arrows) are demonstrated on angioscopy. At site of ulceration-type lesion on angiography (D, arrowhead), ulceration with red thrombus (E and F, arrows) is revealed on angioscopy. to 0.014 inches). In patients in all three groups who underwent only follow-up angiography or PTCA to the lesions on native coronary arteries, angioscopy was performed just after those procedures. In candidates for PTCA or directional coronary atherectomy to their SVG lesions, angioscopy was performed only before the interventions. Before angioscopy, heparin was administered intravenously to every patient to elongate activated clotting time

AmericanHeartJournal

to ->300 seconds. During angioscopy, the distal vessel was flushed with Ringer lactate solution that was heated up to 37 ° C and injected manually through an inner guide catheter. Angioscopy images were obtained totally in 45 (83.3%) of the 54 normal segments and in all of the 15 narrowed segments; the position of the fiber-catheter tip was verified by fluoroscopy and cineangiography. The images were observed on a monitor screen in real time, recorded into U-matic videotapes, and analyzed to determine colors and surface structures of angiographically normal vessel walls and lesions. Two patients in group L had anginal pain with elevation of ST segments in electrocardiograms during the angioscopy procedure. Other serious complications from this procedure did not occur in every patient. Intravascular ultrasound. The IVUS system consisted of an ultrasound system (INSIGHT, CVIS, Sunnyvale, Calif.) with a 4.3F or 2.9F imaging catheter inserted through a 7F or 8F PTCA guiding catheter. IVUS was performed after the angioscopy procedure in 19 patients. Three patients with tight stenotic lesions in the SVGs underwent IVUS only after interventional treatment by a 4.3F catheter because a 2.9F catheter was not available at that time. Of the 15 narrowed segments of the SVGs, 12 were examined before interventions and 3 were studied after interventions. IVUS images were obtained in all 69 segments as the transducer catheter was pulled back from the distal coronary artery; the position of the transducer was verified by fluoroscopy and cineangiography. These images were observed on a monitor screen in real time and recorded into super VHS videotapes for later analysis. No complications occurred during the IVUS procedures. The mean wall thickness of SVGs in groups E and L was measured with off-line IVUS images at the angi0graphicaUy normal sites without an obvious plaque finding on IVUS. Three distinct locations separated by ->1 cm and which had been observed on angioscopy were selected in each SVG. The lumen-vessel interface and the external border of the outer echogenic layer, which might represent adventitia, were traced by planimetry at end-diastole (the onset of the QRS complex), and mean wall thickness was calculated. The average of values measured at those three sites was defined as a representative value of each SVG. These data were compared by using Student's t test between two groups. In vitro study. Four men aged 63.5 -+ 2.7 years had five SVGs that removed at reoperation 6 to 8 years after grafting. On angiography just before the reoperation, 2 SVGs were normal, 2 were diffusely degenerated, and 1 had a discrete stenosis. These grafts were studied in vitro along with three newly harvested saphenous veins by using angioscopy and IVUS. Each vessel was examined while a constant intraluminal pressure of 100 mm Hg was maintained, simulating the in vivo condition. The sites imaged by angloscopy and IVUS were marked with needles and sutured at the end of observation, verifying the location of the needles in angioscopy and IVUS images. Each vein segment was subsequently distended and fixed with 10% buffered formalin at the same pressure used during angioscopy and IVUS. Trans-

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Fig. 6. A and B, IVUS and angioscopic images of old SVG examined in vitro. Triple-layered appearance on IVUS (A) and whitish smooth surface on angioscopy (B) are demonstrated. C and D, Corresponding histologic section. Concentric circumferential fibrointimal proliferation (I) with faintly stained, degenerated fibers and proliferation of darkly stained elastins and other fibers in media (M) and adventitia (Ad) are evident (elastica van Gieson stain; original magnification: C, ×5, D, ×25).

verse sections were obtained from the vessels at the specific marked sites where angioscopy and IVUS images had been recorded. Histologic sections were stained with hematoxylineosin, elastica van Gieson, and azan-Mallory stains. RESULTS New veins and SVGs soon after CABG (group E and in vitro study). In all 18 observed segments in group E,

in vivo IVUS demonstrated an echogenic, single-layered SVG wall, and angioscopy showed a smooth, whitish intimal surface (Fig. 1). The newly harvested veins without fibrointimal proliferation had similar characteristics on in vitro examination (Fig. 2). SVGs in the late stages after CABG (group L and in vitro study). In 22 (73.3%) of the 30 normal segments

shown on angiography in group L, IVUS revealed a triple-layered wall without a plaque structure. This wall consisted of inner and outer echogenic layers and a medial echolucent layer, mimicking the IVUS images of native coronary arteries with normal or mildly thickened intima. Angioscopy showed a relatively smooth, whitish intimal surface at the same sites (Fig. 3). In six segments of two SVGs, IVUS did not demonstrate the triple-layered appearance.

Seven (58.3%) of the 12 stenotic lesions in group L corresponded to the filling defect type on angiography. One patient with an ulceration type stenosis had rest angina, a n d the other 11 patients had recurrent effort angina or positive exercise test

results. The relation among the findings on angiography, angioscopy, and IVUS is shown in Table II. Angioscopy revealed yellow atheromatous plaques at 10 (83.3%) of the 12 narrowings (Fig. 4), and a friable surface of the plaque was demonstrated at 8 (66.7%) of them (Fig. 5, C). At the same sites, IVUS showed eccentric atheromatous plaques that were heterogeneous and relatively echolucent and that did not have the triple-layered appearance of the graft wall (Fig. 4). At the whitish plaques revealed by angioscopy in two lesions, IVUS demonstrated relatively echogenic and homogenous plaques. At the ulceration of the SVG shown on angiography in one patient with rest angina, angioscopy revealed an ulceration with a red and nonmobile thrombns (Fig. 5, E). In the resected SVGs, histologic examination at the sites where there was a triple-layered appearance without a plaque formation on IVUS revealed severe fibrointimal proliferation that consisted of degenerated fibers faintly stained with elastica van Gieson and azan-Mallory stains. The proliferation of elastins and collagen fibers was demonstrated in the adventitia and media. At these sites, the intima was thicker than the media (Fig. 6). In an SVG that was normal on angiography before resection, the triplelayered appearance was not shown on IVUS. The intimal proliferation was not so remarkable in this SVG. At the sites where yellow plaque was demonstrated by angioscopy, lipid-rich atheroma with a

36

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Komiyama et al.

Fig. 7. IVUS and angioscopic images of old, diseased SVG examined in vitro. At site of stenosis on angiography (A), eccentric plaque with heterogeneous echo pattern that has no layer structure is demonstrated on IVUS (B) and yellow plaque is revealed by angioscopy (C). Corresponding histologic section (D) shows lipid-rich eccentric atheroma with necrosed tissue (elastica van Gieson stain; original magnification ×5).

necrosed tissue were revealed histologically. On IVUS, there was a heterogeneous echo pattern without an obvious layer structure (Fig. 7). Comparison of mean wail thickness between groups E and L. The mean wall thickness of SVGs in group L, measured at the sites without a plaque structure on IVUS images, was greater t h a n t h a t in group E (1.1 +_ 0.1 m m vs. 0.7 +_ 0.1 ram; p < 0.001; Fig. 8). SVGs in the middle stage after CABG (group M). In the SVG 24 months after CABG, IVUS revealed the triple-layered appearance of the vessel wall at the angiographically normal segments (Fig. 9). In the other two SVGs, IVUS showed a single-layered appearance at the normal segments (Fig. 10). In a long stenosis of the SVG 12 months after CABG, IVUS demonstrated a thick internal layer with a homogeneous and relatively dense echo pattern, possibly

representing excessive intimal thickening. This layer differed from the sites with the triple-layered appearance in group L (Fig. 10). At the two narrowed sites, angioscopy showed tapered lumens with a whitish intimal surface. At a slitlike stenosis on demonstrated on angiography, angioscopy also demonstrated a projecting fold of the vessel wall (Fig. 9, G). Histologic examination of a specimen resected from a stenosed lesion treated by directional coronary atherectomy revealed thickening of the intima, which contained elastic fibers (Fig. 9, H). DISCUSSION

Many histologic studies have been performed on SVG specimens obtained at reoperation or during postmortem examinations. 6-9 One of the characteristic structural changes t h a t occur in SVGs within 12

Volume 132, Number 1, Part 1 American Heart Journal

months of CABG surgery is fibrointimal proliferation, which results in intimal thickening as a result of the formation of vascular, highly cellular connective tissue that comprises proliferating smooth-muscle cells in a loose matrix of acid mucopolysaccharide and collagen. 7, s After 1 year, the characteristic morphologic changes include atherosclerosis with varying degrees of lipid deposition or foam cell infiltration of the entire vessel wall, including the intima. Some of these SVGs exhibit only fibrointimal thickening without atherosclerotic changes. The thickened intima contains fewer cellular components than are seen within 12 months of grafting. 7, s The pattern at 1 year is more pronounced after 5 or 6 years. In this sense, the SVG is a model of in vivo progressive arteriosclerosis. IVUS and angioscopy could be used to delineate the serial structural changes in the SVGs. The triple-layered appearance without a plaque structure visualized with IVUS has been reported in normal muscular arteries or coronary arteries with mild to moderate intimal thickening. 1416 The inner echogenic, middle echolucent, and outer echogenic layers are thought to represent the complex ofintima and the internal elastic membrane, medial smoothmuscle layer, and complex of external elastic membrane and adventitia, respectively. The smoothmuscle layer with little collagen and elastin is thought to have lower acoustic impedance than the surrounding layers. The medial smooth-muscle layer is the thickest component of the normal coronary arterial wall, as demonstrated histologically. Thus the medial echolucent layer by IVUS may also be shown to be the thickest layer. On the other hand, the triple-layer structure shown on IVUS at the sites with no angiographic evidence of narrowing in SVGs several years after CABG may have a different pathologic and acoustic significance than the layer structure of the normal muscular artery. To prove the cause of the layered appearance on an IVUS image, it is necessary to measure the acoustic impedance of each histological layer component with an acoustic microscope or other techniques. However, the histologically demonstrated smooth-muscle layer of the SVG would have higher acoustic impedance than the smoothmuscle layer in normal muscular arteries because it consisted of proliferated elastins and collagen fibers and smooth-muscle cells (Fig. 6). Furthermore, as the histologic examination revealed, the layer was thinner than the intima and adventitia. Accordingly, the outer echogenic layer in the SVGs seen on IVUS may correspond with the complex of the internal elastic lamina, smooth-muscle layer with prolifer-

Komiyama et al.

I

E1.2

p < 0.001

37

I

CCOCCO

ogoo

1

0

0.8f,,)

0.6m u

0.40.2-

0.7+0.1

1.1+0.1

0

Group E Group L Fig. 8. Comparison of mean wall thickness between groups E and L. ated fibers, external elastic lamina, and adventitia. The middle echolucent layer on IVUS may represent the proliferated and degenerated intima or the attenuation of ultrasonic signals caused b y strong reflection at the lumen-intimal interface and the intima. In any case, the proliferated intima may participate in the cause of the triple-layered appearance without a plaque structure on IVUS. In two SVGs of group L, the triple-layered appearance was not demonstrated on IVUS at angiographically normal segments because the difference in acoustic impedance of the vessel wall might not be enough to Show the layer structure on an IVUS image. Within 1 to 2 years after CABG, most SVG stenoses are thought to be caused by excessive fibrous intimal proliferation. 7, s A specimen resected from a stenotic SVG lesion in group M had a fibroproliferative intima with many elastic fibers (Fig. 9, H). The internal dense echo layer revealed by IVUS in another SVG of group M might be caused by the fibrous proliferation of intima. Several years after CABG, the stenotic lesions in the SVG are usually caused by atherosclerosis. 69 In such lesions, angioscopy principally demonstrated yellow, atheromatous plaques with a friable surface, and IVUS mostly revealed heterogeneous echolucencies. Several investigators have already reported on

July 1996 38

[~oTn,iyaTna 8t at.

American Heart Journal

=

Fig. 9. Angioscopic and IVUS images of angiographically narrowed SVG (A, arrow) in group M; SVG treated by directional coronary atherectomy (B). G, Angioscopy performed before directional coronary atherectomy shows tapered lumina and white, projecting fold of vessel wall. D, E, and F, IVUS performed after directional coronary atherectomy demonstrates triple-layered appearance at angiographically normal sites (C, 1, 3) and residual eccentric plaque with homogeneous and dense echo pattern at lesion (C, 2). H, Histologic view ofresected specimen shows thickening ofintima, which contains elastic fibers (elastica van Gieson stain, original magnification x25). IVUS or angioscopic imaging of SVGs. Although Coy et al. 14 and WiUard et 31.17 als0 reported that the triple-layered structure in IVUS images appear in SVGs several years after CABG, t h e y did not describe the histologic cause of the finding as finely as we have. Concerning the increase of thickening in SVGs after CABG and the superiority of IVUS to conventional angiography in detecting minimal lesions of SVGs, Jain et al. is and Nase-Hueppmeier et

al. 19 reported the same results as we found. White et al. 2° described the efficacy of angioscopy for detecting complex lesion morphologic changes in SVGs. The difference between our study and the previous reports is t h a t we applied both INCUSand angioscopy to in vivo and in vitro evaluation of serial changes in the structure of SVGs after CABG. We suggest t h a t IVUS and angioscopy can show differences in SVG lesion morphologic characteristics at different points

Volume 132, Number 1, Part 1 American Heart Journal

after CABG, differences that are not apparent on conventional angiography. Although PTCA has become a primary method of intervention for vein graft stenosis after CABG, a high incidence of restenosis and complications such as distal embolization have been reported. 21 Angloscopy could be used to reveal the friability of the atheromatous plaques and to demonstrate the existence of thrombi. This information could be used to modify the approach to PTCA, which might include the use of an intraaortic balloon pump to provide distal embolization or thrombolytic agents to eliminate the thrombi. The incidence ofrestenosis after PTCA of the SVG is higher than the incidence after PTCA of the native coronary arteries. 21 Recently metallic stents have been used to lower the incidence of restenosis, u2 However, we and other investigators have reported that the incidence of restenosis after PTCA of a lipid-rich atheroma in an SVG is lower than the incidence after PTCA of a fiber-rich plaque. 23, 24 Thus the evaluation of SVG lesions with angioscopy and IVUS before PTCA may be useful for the prediction ofrestenosis. Further study should be performed to confirm that these two modalities could then be used to direct or modify the therapeutic approach to the graft disease. Study limitations. A couple of limitations in this study have to be taken into account. First, the s a m e SVG was not serially examined at three different points after CABG. Concerning the comparison of the mean wall thickness between groups E and L, the lack of data within 6 months after implantation in group L precludes determination as to whether the mean wall thickness in this group had increased over the years after CABG. This question needs to be addressed through a prospective study design in which the same SVG is examined at different points after implantation. Nevertheless, the result of the comparison of mean wall thickness between the two groups might be compatible with the serial changes of histopathologic structures of SVGs revealed by other investigators and in this study. Second, we recognize the relative small sample size of ou r study population. However, these pilot data might provide important information on understanding the structural changes of SVGs after CABG and more usefulness of IVUS and angioscopy than conventional angiography. Conclusion. The complementary use of IVUS and angioscopy revealed further information about the structural changes of SVGs after CABG. In particular, IVUS may contribute to clarification of the structural changes of SVGs at angiographically and

Komiyama et al. 39

Fig. 10. AngiogTaphic (left) and IVUS (right) images of SVG with long stenosis in group M. Single-layered appearance is shown at angiographically normal site (1). At site of stenosis, IVUS demonstrates thick internal layer with homogeneous, relatively dense echo pattern (2).

angioscopically normal sites, changes which have previously been revealed only by in vitro investigation, Angioscopy may be used to clarify fine structure of lesions such as friability and the existence of thrombi in SVGs that may be difficult to identify by angiography and IVUS. Thus the in vivo application of IVUS and angioscopy m a y be used to identify more precisely the morphologic features of SVGs at different points after CABG than conventional angiography. REFERENCES

1. Campeau L, Lesperance J, Corbara F, Hermann J, Grondin CM, Bourassa MG. Aortocoronary saphenous vein bypass grafL changes 5 to 7 years after surgery. Circulation 1978;58(suppl I):170-5. 2. Campeau L, Enjalbelt M, Lesperance J, Vaislic C, Grondin CM, Bourassa MG. Atherosclerosis and late closure ofaortocoronary saphenous vein grafts: sequential angiographic studies at 2 weeks, 1 year, 5 to 7 years, and 10 to 12 years after surgery. Circulation 1983;68(suppl II):1-7. 3. Lytle BW, Loop FD, Cosgrove DM, Ratliff NB, Easley K, Taylor PC. Long-term (5 to 12 years) serial studies of internal mammary artery and saphenous vein coronary bypass grafts. J Thorac Cardiovasc Surg 1985;89:248-58, 4. Fitzgibbon GM, Leach AJ, Kafka liP, Keen WJ. Coronary bypass graft fate: long-term angiographic study. J Am Coll Cardio11991;17:1075-80. 5. Grondin CM, Campeau L, Lesperance J, Solymoss C, Vouhe P, Castondguay YR, Meere C, Bourassa MG. Atherosclerotic changes in coronary vein grafts six years after operation: angiographic aspect in 110 patients. J Thorac Cardiovasc Surg 1979;77:24-31. 6. Atkinson JB, Forman MB, Perry JM, Virmani R. Correlation efsaphenous vein bypass graft angiograms with histologic changes at necropsy. Am J Cardio] 1985;55:952-5. 7. Virmani R, Atkinson JB, Forman MB. Aortocoronary saphenous vein

40

8.

9.

10.

11. 12.

13.

14. 15.

16.

Komiyama et al. bypass grains. In: Waller BF, ed. Contemporary issues in cardiovascular pathology. Philadelphia: F.A. Davis, 1988:41-62. Solymoss BC, Leung TK, Pelletier LC, Campeau L. Pathologic changes in coronary artery vein grafts and related etiologic factors. In: Waters DD, Bourassa MG, eds. Care of the patients with previous coronary bypass surgery. Philadelphia: F.A. Davis, 1991:45-65. Qiao JH, Walts AE, Fishbein MC. The severity of the atherosclerosis at sites of plaque rupture with occlusive thrombosis in saphenous vein coronary artery bypass grafts. Am Heart J 1991;122:955-8. Tobis JM, Mallery J, Mahon D, Lel{mann K, Zalesky P, Griffith J, Gessert J, Moriuchi'M, McRae M, Dwyer ML, Greep N, Henry WL. Intravascular ultrasound imaging of h u m a n coronary arteries in vivo. Circulation 1991;83:913-26. Tobis JM, Yock PG. Intravascular ultrasound imaging. New York: Churchill Livingstone, 1992. Sherman CT, Litvack F, Grundfest W, Lee M, Hickey A, Chaux A, Kass R, Blanche C, MatloffJ, Morgenstern L, Ganz W, Swan HJC, Forrester J. Coronary angioscopy in patients with unstable angina. N Engl J Med 1986;315:912-9. Ramee SR, White CJ, Collins TJ, Mesa JE, Murgo JP. Percntaneous angioscopy during percutaneous coronary angioplasty using a steerable microangioscope. J Am Coll Cardiol 1991;17:100-5. Coy KM, Maurer G and Siegel RJ. Intravascular ultrasound imaging: a current perspective. J Am Coll Cardiol 1991;18:1811-23. Moriuchi M, Gordon I, Honye J, Yen R, Tobis JM. Validation ofintravascular ultrasound imaging. In: Tobis JM, Yock PG, eds. Intravascular ultrasound imaging. New York: Churchill Livingstone, 1992;5%70. Fitzgerald PJ, St. Goar FGS, Connolly AJ, Pinto F J, Billingham ME, Popp RL, Yock PG. Intravascalar ultrasound imaging of coronary arteries. Circulation 1992;86:154-8.

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17. Willard JE, Netto D, Demian SE, Haagen DR, Brickner ME, Eichhorn E J, Grayburn PA. Intravascular ultrasound imaging of saphenous vein grafts in vitro: comparison with histologic and quantitative anglographic findings. J Am Coll Cardiol 1992;19:759-64. 18. Jain SP, Roubin GS, Nanda NC, Dean LS, Agrawal SK, Pinheiro L. Intravascular ultrasound imaging of saphenons vein graft stenosis. Am J Cardiol 1992;69:133-6. t9. Nase-Hueppmeier S, Uebis R, Doerr R, Hanrath P. Intravascular ultrasound to assess aortocoronary venous bypass grafts in vivo. Am J Cardiol 1992;70:455-8. 20. White CJ, Ramee SR, Collins TJ, Mesa JE, Jain A. Percutaneous angioscopy of saphenous vein coronary bypass grafts. J Am Coll Cardiol 1993;21:1181-5. 21. de Feyter PM, van Suylen RJ, de Jaegere PIT, Topol EJ, Serruys PW. Balloon angioplasty for the treatment of lesions in saphenous vein bypass grafts. J Am Coll Cardiol 1993;21:1539-49. 22. Piana RN, Moscucci M, Cohen DJ, Kugelmass AD, Senerchia C, Kuntz RE, Bairn DS; Carrozza JP Jr. Palmatz-Schatz stenting for treatment of focal vein graft stenosis: immediate results and long-term outcome. J Am Coll Cardiol 1994;23:1296-304. 23. Komiyama N, Nakanishi S, Nishiyama S, Fuse K, Akira S. Angioscopic evaluation of saphenous vein grafts long-term after coronary artery bypass grafting (abstract). J Am Coll Cardiol 1992;19:319A. 24. Mintz GS, Pichard AD, Kobach JA, Kent KM, Satler LF, Javier SP, Pompa JJ, Leon MB. Impact of preintervention intravascular ultrasound imaging on transcatheter treatment strategies in coronary artery disease. Am J Cardiol 1994;73:423-30.