Ruptured Atheromatous Plaques in Saphenous Vein

Coronary Artery Bypass Grafts: A Mechanismof Acute, Thrombotic, Late Graft Occlusion

ANN E. WALTS, M.D., MICHAEL C. FISHBEIN, M.D., HECTOR SUSTAITA, M.D.,

AND JACK M. MATLOFF, M.D.

SUMMARY Although early occlusion of saphenous vein coronary artery bypass grafts is usually throm-botic, late occlusion is most often a result of progressive intimal fibromuscular proliferation or atheroma for-mation in the implanted vein. We describe another mechanism of late graft occlusion: atheromatous plaquerupture with superimposed occlusive thrombosis. Four men, ages 48-67 years underwent repeat bypass sur-

gery for recurrent angina. Six of eight vein grafts excised 5-8 years after original bypass showed completeluminal occlusion by recent thrombus superimposed on ruptured atheromatous plaques. Similar findings were

present at autopsy in two of three vein grafts from a 66-year-old man who died 7 years after bypass. Theselesions are indistinguishable from those that occur in native coronary arteries of many patients with acute myo-cardial infarction. Unlike previously described graft occlusions, the present lesion represents a mechanism ofacute, thrombotic, late graft occlusion. If recognized early, it may be amenable to nonsurgical intervention byangioplasty or thrombolysis.

SAPHENOUS VEIN aortocoronary artery bypassgrafts may undergo a variety of morphologic changesthat lead to graft occlusion.'1 Early graft occlusion isusually caused by technical factors6"9 or compromisedanatomic runoff0 12 and is almost always throm-botic."1 In contrast, late graft occlusion is usually aresult of structural changes within the graft itself andis not usually associated with occlusive thrombo-sis.10- 4 Progressive fibrous or fibromuscular intimalproliferation'0 11, 14-16 and, less frequently, athero-matous plaque formation 10,1l-18 are the most com-mon pathologic changes found in grafts that becomeoccluded late after coronary artery bypass surgery.Recurrent symptoms of myocardial ischemia some-times necessitate revascularization. 9-21

Excision of occluded grafts at reoperation hasenabled us to study the pathologic changes responsiblefor acute late graft occlusion. In this communicationwe describe a lesion that has not been previouslyemphasized in saphenous vein grafts, although it iswell recognized in native coronary arteries: athero-matous plaque rupture with superimposed occlusivethrombosis. This lesion, which we observed in five pa-tients, represents a mechanism of graft occlusion thatappears to occur as an acute event late after coronaryartery bypass grafting. This lesion may be amenableto nonsurgical correction by percutaneous, intra-vascular, thrombolytic22' 23 or angioplastic tech-

24niques.

From the Divisions of Anatomic Pathology and CardiovascularSurgery, Cedars-Sinai Medical Center, Los Angeles, California.

Supported in part by grant HL-17651-06, SCOR in IschemicHeart Disease, NIH.Address for correspondence: Ann E. Walts, M.D., Division of

Anatomic Pathology, Cedars-Sinai Medical Center, 8700 BeverlyBoulevard, Los Angeles, California 90048.

Received January 27, 1981; revision accepted April 23, 1981.Circulation 65, No. 1, 1982.

PatientsPatient 1RW, a 53-year-old, obese, hypertensive male, pre-

sented with recurrent angina pectoris 5 years aftersaphenous vein coronary artery bypass. Angiographyshowed occlusion of grafts to the left anterior descend-ing and the circumflex coronary arteries. At reopera-tion, new vein grafts were placed. The occluded graftswere excised and submitted for pathologic examina-tion.

Histologic sections of the vein graft to the left cir-cumflex coronary artery showed complete luminalocclusion by recent thrombus superimposed on a rup-tured atheromatous plaque (fig. 1). Thrombotic andatheromatous material were mixed. Although theplaque was composed primarily of fibrous tissue,numerous lipid-laden cells, cholesterol clefts, chronicinflammatory cells and focal calcifications were pres-ent. The media was focally fibrotic and thinned. Thesefindings are indistinguishable from atheroscleroticplaques that occur in native arteries. In some areas,the atheromatous material extended from intima toadventitia. Some regions showed a marked inflamma-tory reaction to the lipid, including foreign body giantcells. Adventitial fibrosis was also present.

Histologic examination of the graft to the leftanterior descending coronary artery also showedmarked luminal occlusion. In this vessel, however, asmall focal thrombus was superimposed on amarkedly fibrotic, thickened intima. Atheroma withlipid-laden cells and calcification was present in only asmall region of the graft. Medial and adventitialfibrosis was marked.

Patient 2JL, a 67-year-old, obese, hypertensive male with a

history of heavy smoking, presented for evaluation ofrecurrent refractory angina pectoris 8 years afterbypass surgery. Angiography showed occlusion of the

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showed increased collagen and decreased smooth mus-cle content. Thus, this lesion was morphologicallyidentical to atherosclerosis that occurs in nativearteries. Previous rupture of the vein graft (fig. 2Cthrough a discontinuity in the media had resulted inextravasation of atheromatous material into the peni-vascular soft tissue. A marked granulomatous andchronic inflammatory response was localized to the2~~~~~~~~~E' i0i

FIGURE 1. Saphenous vein graft to left circumflex coro-nary artery from patient 1. Histologic section shows disrup-tion offibrous cap (fc) of the atherom'a (A) with spillage ofatheromatous material into vein lumen (L) that containsthrombus (darker-staining material). A theroma has alsopenetrated through media of vein graft into surroundingadventitia (arrow). Masson trichrome stain; original 'magnification X 1. 7

saphenous vein graft to the left anterior descendingcoronary artery. At reoperation a 3.5-cm segment Afrom the proximal portion of the occluded graft wasexcised. The patent graft to the right coronary arterywas not disturbed, but an additional saphenous veingraft to the left circumflex coronary artery was placed.

Histologic examination of the excised saphenousvein graft showed complete luminal occlusion bythrombus, which was mixed with material from an un-derlying circumferential atheromatous plaque (fig. 2Aand B). The plaque was composed of collagen, elastictissue, clacium deposits, lipid-laden and inflamma-tory cells and cholesterol clefts. The thinned media

FIGURE 2. Saphenous vein graft to left anterior descend-ing coronary artery from patient 2. (A) Histologic sectionfrom occluded segment of graft shows hemorrhage into .atheroma (A), disruption offibrous cap (between asterisks),and thrombotic occlusion of residual lumen (L).A theromatous material (lighter staining) and hemorrhage(darker staining) are present deep in the vessel wall (arrows).Masson trichome stain; original magnification X 3. Insetshows admixture of atheromatous (lighter) and thrombotic(darker) material evident on cut section of the graft. (B) . 4Higher magnification shows disruption of plaque (between 't .asterisks). Cholesterol clefts are present in the atheroma andin the defect. Atheromatous plaque (A) contains a mixtureof darker-staining blood and ligher-staining atheromatous - -material. Some atheromatous material has entered thelumen (L), which also contains thrombus. Masson trichomestain; original magnification X 16. (C) Histologic sectionshowing rupture of atheromatous material through vesselwall (between asterisks) with confinement only by a thinlayer of adventitial collagen (A). Masson trichrome stain;original magnification X 16. -;-A

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rupture site. There was diffuse adventitial fibrosis; thisfibrosis may have prevented severe hemorrhage.

Patient 3MR, a 48-year-old, hypertriglyceridemic, hyper-

cholesterolemic male with a 50-pack-year history ofcigarette smoking, was admitted for evaluation of restangina 5 years after saphenous vein grafts had beenplaced to the left circumflex-marginal and right cor-onary arteries. Angiography showed complete occlu-sion of both grafts. He underwent reoperation forplacement of new grafts and excision of the occludedgrafts.

Pathologic examination of the resected graft to theright coronary artery showed complete luminal occlu-sion by relatively dense collagenous tissue. Multiplerecanalized channels were present. No lipid or calciumdeposits were present. The findings suggested recanali-zation and organization of an old thrombus.The graft to the circumflex system was occluded by

thrombotic material superimposed on and mixed withatheromatous material from an underlying rupturedatheromatous plaque that contained collagen, calciumdeposits, chronic inflammatory cells, lipid-laden cellsand cholesterol clefts (fig. 3). There was marked focalthinning, fibrosis and chronic inflammation of themedia as well as adventitial fibrosis.

Patient 4LM, a 65-year-old male with a history of heavy

smoking and myocardial infarction, presented withsevere angina 7 years after coronary artery bypass sur-gery. Angiography showed complete occlusion ofsaphenous vein grafts to the right, left circumflex, anda diagonal branch of the left anterior descending cor-onary arteries. At reoperation, segments of the graftswere excised for pathologic study.

All three grafts showed similar histologic findings.There was complete luminal occlusion by thrombussuperimposed on ruptured atheromatous plaques (fig.

FIGURE 3. Saphenous vein graft to left circumflex cor-

onary artery from patient 3. Histologic section of graftshows disruption offibrous cap (between asterisks) of theatheroma (A), with complete occlusion of the lumen (L) bythrombus. Masson trichrome stain; original magnificationX 16.

FIGURE 4. Saphenous vein graft to left circumflex cor-onary artery from patient 4. Histologic section shows site ofplaque rupture (between asterisks), hemorrhage into theatheromatous plaque (A), and thrombotic material withinthe lumen (L). Masson trichrome stain; original magnifica-tion X 16.

4). Atheromatous material was mixed with throm-botic material. The atheromatous plaques containedcollagen, elastic tissue, foam cells, cholesterol cleftsand a chronic inflammatory cell infiltrate. The latterwas presumably a reaction to the lipids released fromthe plaque. Each vessel showed focal disruption of thethinned and fibrotic media with spillage of athero-matous material into the adventitial tissues. A foreignbody giant cell granulomatous reaction surroundedthe lipid material, which had extravasated outside thevessel. There was also diffuse adventitial fibrosis.

Patient 5

BL, a 66-year-old, obese, hypertensive, diabeticsmoker, was admitted with sudden onset of severeangina and myocardial infarction 7 years after three-vessel saphenous vein coronary artery bypass surgery.He died 1 week after admission. At autopsy, rupturedatheromatous plaques with thrombosis identical tothose described in the other four patients were presentin the occluded grafts to the left anterior descendingand left circumflex coronary arteries (fig. 5).

DiscussionIn 1906, Carrell and Guthrie25 described the inti-

mal changes that lead to luminal narrowing in veinsimplanted within the arterial system. Subsequent lightand electron microscopic studies have demonstratedthat the usual intimal proliferation noted consists ofcollagen fibers, elastic fibers and ground substancesynthesized by smooth muscle cells that have migratedfrom the media.26 28 These substances are present invarying amounts, depending on several factors, in-cluding the duration of implantation.'0 '" Fibrindeposition, inflammatory cell infiltration and pro-liferation of small vessels have also been observed.26The intimal lesions in some grafts are indistinguish-able from the atheromatous plaques of arterialatherosclerosis."`'l Although the factors that lead toprogressive intimal proliferation with or without

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FIGURE 5. Saphenous vein graft to left circumflex coro-

nary artery from patient 5. Lumen (L) of vein is occluded bythrombus mixed with atheromatous material that containscholesterol clefts. In this section, the atheroma is partiallydisrupted (arrow) with continuity between plaque contentsand the luminal thrombus. Masson trichrome stain; originalmagnification X 1.

atheroma formation are unclear, the same factors thatinfluence naturally occurring atherogenesis are

probably important in saphenous vein grafts as well(e.g., age, hypertension, hyperlipidemia,29 anddiabetes).

Eight of 11 grafts in the patients of this study were

occluded by thrombus superimposed on rupturedatheromatous plaques. These lesions are histologicallyidentical to those described in coronary arteries as theprecipitating event in acute transmural infarc-tion.30' 31 The thrombosis is thought to result whenplaque disruption (endothelial injury) leads to therelease of thrombogenic substances from the plaque.32As with rupture of native coronary artery plaques, thecause of rupture of saphenous vein bypass graftplaques is uncertain. In three of five patients, ruptureof plaques with thrombosis occurred synchronously intwo or more vessels, suggesting that the process was

not due only to local factors within the graft, but tosome unknown predisposing factor common to all thevein grafts in these patients. In six of the 11 grafts, theatheromatous plaques had destroyed the media andextended into the adventitia, focally eliciting an in-flammatory response that included foreign body giantcell formation and fibrosis. Preexistent adventitialfibrosis, common to all implanted vein grafts,' mayhave prevented hemorrhage and exsanguinationthrough such a rupture.

This striking morphologic alteration has not beenemphasized previously, although many implantedsaphenous veins have been studied at necrop-Sy5,. 14, 16, 33 Most of these grafts were probablystudied long after acute thrombosis had occurred. Fewvein grafts are excised by surgeons and examined bypathologists at revascularization procedures, and

probably even fewer are excised soon after a suddendeterioration in a patient's condition.

Even if this lesion occurs infrequently, it is of prac-tical importance because it represents a mechanism ofacute, late, cardiovascular deterioration after a long,sometimes symptom-free, postoperative period.Prompt intervention may prevent myocardial injury.The recognition of late thrombotic atheroscleroticgraft occlusion may allow appropriate nonsurgical in-tervention to reopen the acutely occluded vessel bythrombolytic therapy, or increase luminal patency byangioplastic therapy. Intravascular thrombolytictherapy22' 23 and transluminal angioplasty24 have beenused to treat coronary arterial narrowing and, in a fewcases, early thrombotic vein graft occlusion.22

AddendumSince recognition of this lesion and submission of the manuscript,

surgeons at our institution have more regularly excised occludedcoronary grafts. As a result, we have studied seven additional aorto-coronary saphenous vein bypass grafts that showed similar lesions.Six such grafts were excised from men 45-74 years old and onewas excised from a 71-year-old woman. The occlusions occurred5-9 years after bypass. In addition, Kern and associates34 recentlyprovided additional documentation of this lesion.

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A E Walts, M C Fishbein, H Sustaita and J M Matloffmechanism of acute, thrombotic, late graft occlusion.

Ruptured atheromatous plaques in saphenous vein coronary artery bypass grafts: a

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1982 American Heart Association, Inc. All rights reserved.

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