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Europen Journl of Crdio-thorcic Surgery 21 (2002) 181 186 www.elsevier.com/locte/ejcts Stged crotid nd coronry surgery for concomitnt crotid nd coronry rtery disese Pedro E. Antunes, Gbriel Ancleto, J.M. Ferrão de Oliveir, Luís Eugénio, Mnuel J. Antunes* Crdiothorcic Surgery, University Hospitl, 3049 Coimbr, Portugl Received 13 July 2001; received in revised form 18 October 2001; ccepted 15 November 2001 Abstrct Objective: To demonstrte tht stged, consecutive, crotid endrterectomy (CEA) nd coronry rtery bypss grfting (CABG) re sfe, perhps preferble, lterntive for the tretment of ptients with severe crotid nd coronry rtery disese. Methods: During n 8-yer period ending December 1999, 77 (2.1%) of 3633 consecutive ptients who were referred for isolted coronry surgery were found to hve significnt crotid disese nd underwent CEA, nd subsequently, CABG. The men ge ws 65:2 ^ 5:9 yers nd 66 (85.7%) were mles. The mjority (84.4%) hd triple vessel nd 19.4% hd left min disese. Crotid disese ws unilterl in 71 ptients (92.2%) nd bilterl in six (7.8%), nd 57 (74.0%) were neurologiclly symptomtic. Only obstructions.70% were considered for endrterectomy. Results: Eighty-three isolted CEAs were performed with direct clmping of the rtery (men 20:1 ^ 5:9 min) in ll but one. There were no deths. There were two strokes (2.4%) nd three (3.6%) myocrdil infrctions (MI). The men dmission time ws 6:0 ^ 3:5 dys. The stging intervl ws 32.4 dys. During coronry surgery, men of 2.9 coronry grfts/ptient ws performed nd ll but one ptient received t lest one IMA grft. One ptient (1.3%) died. There were two cses (2.6%) of MI nd three ptients (3.9%) hd stroke. Hence, the overll rtes of periopertive mortlity, MI nd stroke were 1.3, 6.3 nd 6.3%, respectively. The men dmission time ws 8:3 ^ 6:0 dys. Conclusions: Stging of crotid nd coronry opertions resulted in low globl periopertive mortlity nd morbidity rtes in these high-risk ptients nd is good lterntive therpeutic option. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Crotid rtery stenosis; Coronry rtery disese; Crotid endrterectomy; Coronry rtery bypss; Stged pproch 1. Introduction Although significnt mount of informtion is currently vilble with regrd to the dilemm of myocrdil revsculristion in the presence of crotid rteril disese, the choice of tretment for ptients who present with severe crotid rtery stenosis tht is incidentlly found during preprtion for coronry rtery bypss grfting (CABG) is still mtter of debte. The options vry from simultneous (sme nesthetic) to stged procedure, whereby crotid endrterectomy (CEA) is performed severl dys prior to (stged pproch) or fter (reversed stged pproch) coronry revsculristion. To dte, no welldesigned prospective rndomised tril hs clrified this problem. Ech of these methods hs its dvntges nd disdvntges, which cn be mesured, essentilly, by the globl mortlity nd incidence of MI nd of stroke. Since 1992, it hs been our philosophy to mnge these * Corresponding uthor. Tel.: 1351-239-400418; fx: 1351-239- 829674. E-mil ddress: ntunes.cct.huc@mil.telepc.pt (M.J. Antunes). ptients by the stged pproch. This decision resulted, essentilly, from the fct tht in our country crdic surgery nd vsculr surgery re two different specilties, mking it more difficult to coordinte two surgicl tems to perform both procedures during the sme nesthetic session. The purpose of this work ws to evlute our erly results in 77 consecutive ptients who underwent such surgery. 2. Mterils nd methods During n 8-yer period ending December 1999, 77 (2.1%) of 3633 consecutive ptients who hd isolted coronry rtery bypss grfting (CABG) underwent crotid, nd subsequently, coronry surgery for severe concomitnt rteril disese. To void the introduction of potentilly conflicting fctors, ptients who hd ssocited procedures, such s vlvulr surgery, nd those who hd undergone unrelted crotid surgery in the pst, were not included in this series. 1010-7940/02/$ - see front mtter q 2002 Elsevier Science B.V. All rights reserved. PII: S1010-7940(01)01097-1

182 P.E. Antunes et l. / Europen Journl of Crdio-thorcic Surgery 21 (2002) 181 186 2.1. Dignosis nd generl mngement protocol All ptients were originlly dmitted to our hospitl for CABG nd the dignosis of internl crotid rtery disese ws mde during the preopertive clinicl workup. They underwent crotid rtery evlution on selective bsis, minly dependent on the usculttion of bruit in the neck nd/or history of neurologicl symptoms consistent with cerebrovsculr disese. Although most of these ptients hd duplex studies, the dignosis nd severity of the crotid disese ws finlly estblished in ll cses by crotid ngiogrphy. Selection criteri for crotid surgery were constnt throughout nd well defined, i.e. ptients underwent CEA if they hd hemodynmiclly significnt lesion (luminl dimeter.70%, using the dimeter of the distl internl crotid rtery s reference) of either or both crotid rteries, independent of the symptomtic neurologicl sttus. During the period covered by this study, ll ptients were treted using the stged pproch, i.e. CEA ws performed first, followed by CABG t second opertion. In ptients with bilterl disese, surgery to ech of the two crotid rteries ws performed in different nesthetic times. In the mjority of cses (66 ptients; 85.7%) CEA ws performed in our Deprtment of Vsculr Surgery. Immeditely fter surgery, they were dmitted to the Coronry Cre Unit, where they usully styed until the next morning nd then returned to the Vsculr Deprtment wrd. During the period mediting between hospitl dischrge from CEA nd re-dmission for CABG, crdiologist of our own Deprtment closely monitored these ptients. As rule, the CABG ws performed within minimum time intervl of 2 weeks from the crotid surgery, during different period of hospitlistion, unless the crdic condition dictted erlier surgery (two cses). This intervl ws dictted by the protocol in use in the Deprtment of Vsculr Surgery, which clls for minimum period of 1 week of nti-pltelet ggregtion followed by 1 week of suspension prior to CABG. 2.2. Preopertive ptients dt The clinicl dt of the 77 ptients is detiled in Tble 1. The men ge ws 65:2 ^ 5:9 yers (rnge 49 81 yers) nd 66 (85.7%) were mles. Nineteen (24.7%) ptients were dibetic, nd 51 (66.2%) hd dislipidemi. Thirty-four (44.2%) nd 43 (55.8%) ptients were, respectively, in clss I/II nd III/IV of the Cndin Crdiovsculr Society. A history of previous MI ws recorded in 43 ptients (55.8%). Five (6.5%) ptients, otherwise stble on the dy of crotid rtery surgery, hd been on intrvenous nti-nginl mediction in the previous 2 dys. Twenty-three ptients (29.9%) hd peripherl vsculr disese. Sixty-five ptients Tble 1 Preopertive clinicl, ngiogrphic nd opertive crdic dt of ptients who hd the stged procedure versus ptients who hd isolted CABG during the sme period Vrible Stged opertion (%) Isolted CABG (%) P vlue Ptients (n) 77 3556 Men ge (yers) 65.2 ^ 5.9 60.1 ^ 9.3, 0.001 Femle sex (14.2) (11.4) NS Fmily history of CAD (22.1) (22.4) NS Smoking (51.9) (55.5) NS Dibetes mellitus (24.7) (21.5) NS Dislipidemi (66.2) (54.5) NS Hypertension (72.7) (56.8) 0.005 History of MI (55.8) (59.1) NS Peripherl vsculr disese (29.9) (9.5), 0.0001 History of stroke or TIA (26.0) (4.5), 0.0001 One vessel disese (2.6) (5.1) NS Two vessels disese (13.0) (18.3) NS Three vessels disese (84.4) (76.6) NS Left min disese (19.4) (15.8) NS Left ventriculr function Norml (49.3) (51.6) NS Mild dysfunction (39.0) (32.5) NS Moderte dysfunction (9.1) (11.1) NS Severe dysfunction (2.6) (3.4) NS Men no. of coronry grfts 2.9 2.9 NS Arteril conduit Left IMA (98.7) (99.1) NS Bilterl IMA (9.1) (25.2), 0.0001 Coronry endrterectomy (19.5) (7.1), 0.0001 TIA, trnsient ischemic ttck; MI, myocrdil infrction; CAD, coronry rtery disese; NS, not significnt.

P.E. Antunes et l. / Europen Journl of Crdio-thorcic Surgery 21 (2002) 181 186 183 (84.4%) hd triple vessel coronry disese nd 15 (19.4%) hd left min disese. Moderte or severe left ventriculr dysfunction (ejection frction,40%) ws present in nine cses (11.7%). There were no cses of redo-cabg mong these ptients. For comprison, dt on 3556 ptients without known crotid disese subjected to isolted CABG during the sme period of time is lso presented in Tble 1. The stged opertion group ws significntly older (65.2 yers versus 60.1 yers, P, 0:001), hd more ptients with cerebrl (26.0 versus 4.5%, P, 0:0001) nd peripherl vsculr (29.9 versus 9.5%, P, 0:0001) disese, nd with hypertension (72.2 versus 56.8%, P ¼ 0:005). This group lso presented significntly higher incidence of ptients who hd coronry endrterectomy nd lower incidence of use of bilterl IMA. The preopertive neurologicl symptoms nd ntomy of the crotid disese re shown in Tble 2. Twenty ptients (26.0%) hd neurologicl symptoms, including 11 ptients with permnent stroke nd nine with trnsient symptoms (five with trnsient ischemic ttcks nd four with murosis fugx). Crotid disese ws unilterl in 71 ptients (92.2 %) nd bilterl in six (7.8%), with no cses of contrlterl occlusion. 2.3. Opertive techniques crotid nd coronry surgery In ll but two cses (2.4%) the CEA ws performed under generl nesthesi. Invsive rteril blood pressure nd crdic rhythm were continuously monitored. Direct clmping of the rtery (men 20 ^ 6 min) ws used in ll ptients but one who hd temporry shunt inserted. The technique for coronry revsculristion involved ortic nd right tril cnnultion nd mild systemic hypothermic crdiopulmonry bypss (30 328C). A left ventriculr vent ws routinely introduced through the right superior pulmonry vein. We hve dopted the method of ventriculr fibrilltion for construction of the distl nstomosis. Proximl nstomosis of vein grfts were Tble 2 Neurologicl nd crotid ngiogrphic dt in ptients submitted to the stged opertion N % Neurologicl symptoms Asymptomtic 57 74.0 Symptomtic Stroke 11 14.3 TIA 5 6.5 Amurosis fugx 4 5.2 Crotid ngiogrphy Stenosis 70 90% 68 88.3. 90% 9 11.7 Bilterl disese 6 7.8 TIA, trnsient ischemic ttck. constructed during single period of ortic side-clmping. Internl mmmry rtery (AMI) grfts were used in ll but one ptient (98.7%), including seven (9.1%) in whom both AMIs were used. An verge of 2.9 coronry rtery brnches were bypssed per ptient. Coronry endrterectomies, mostly of the right, were performed in 15 ptients (19.4%). Crdiopulmonry bypss time ws 64 ^ 18 min. 2.4. Dt nlysis Periopertive events included those occurring within 30 dys of surgery or during the sme hospitlistion. Stndrd sttisticl tests (Student t nd x 2 ) were used for comprison of dt, nd sttisticl significnce ws inferred for P, 0:05. 3. Results 3.1. Crotid surgery nd stging intervl There were 83 isolted CEAs performed in the 77 ptients, with no mortlity. There were two cses (2.4%) of permnent ipsilterl stroke. Cerebrl computed tomogrphy (CT) showed n re of infrct in both cses nd non-invsive crotid rtery evlution reveled ptency of the CEA site. These two ptients underwent CABG subsequently with stging intervl of 55 nd 40 dys, respectively. Additionlly, two ptients (2.4%) hd trnsient ischemic ttcks (TIA), with negtive CT scns nd permeble crotids. There were no cses of contrlterl centrl neurologicl ccidents. Four ptients developed minor peripherl neurologicl deficits, of which two did not resolve during the postopertive follow-up: one hd left vocl chordl plsy nd the other hd isolted hypoglossl nerve plsy. There were three (3.6%) cses of MI, ll occurring in the erly (hospitl) period nd evolving with hemodynmic stbility. Four ptients developed unstble ngin nd two of them, who did not respond to intrvenous mediction, required urgent CABG. One ptient hd n episode of ventriculr fibrilltion during the crotid surgery, without clinicl consequences. Three ptients were re-explored for revision of hemostsis nd one hd wound infection treted by debridement nd ntibiotics. All ptients returned home in stble crdic sitution. The time of hospitl sty ws 6:2 ^ 3:4 dys. After hospitl dischrge nd through to the time of coronry surgery, there ws no mortlity or new cses of neurologicl complictions or MI. Nevertheless, two ptients (2.4%) developed unstble ngin nd required hospitlistion with successful medicl control. The men stging intervl ws 32.4 dys. 3.2. Coronry surgery There ws one deth (1.3 %) due to stroke. Seven ptients (9.1%) required inotropic support in the immedite postopertive period. There were electrocrdiogrm (ECG)

184 P.E. Antunes et l. / Europen Journl of Crdio-thorcic Surgery 21 (2002) 181 186 criteri of periopertive MI in two ptients (2.6%). Twentythree ptients (29.9%) developed tril rrhythmis (fibrilltion nd/or flutter) tht required tretment nd two ptients (2.6%) hd n episode of ventriculr fibrilltion without clinicl consequences. Two ptients (2.6%) were re-operted for bleeding nd one for sternl dehiscence. Five ptients (6.5%) developed trnsient cute renl insufficiency (cretinine $2.5 mg/dl), not requiring dilysis. There were three cses (3.9%) of stroke, ll ipsilterl to the CEA. The one, which ws the cuse of the single inhospitl deth in this study, occurred in ptient with history of permnent stroke in the pst nd who ws submitted to bilterl CEA (the lst performed 28 dys before CABG). This ptient did not wke up from nesthesi nd died on postopertive dy 10. The necropsy study showed mjor infrction of the right cerebrl hemisphere nd extensive right crotid thrombosis. The second ptient, who lso hd history of permnent stroke in the pst, ws submitted to urgent CABG 6 dys fter left CEA, becuse of untretble unstble ngin. In the immedite postopertive period, he developed severe nd prolonged period of hypotension s result of mjor bleeding from the ortic cnnultion site, nd right hemiplegi ws noted when he woke up. The third ptient sustined n ipsilterl stroke on postopertive dy 2, probbly embolic from the CEA left site (performed 27 dys before), which ws ptent s ssessed by non-invsive mens. Both ptients were mbultory, lbeit with sequele, t dischrge. There were no cses of trnsient ischemic ttcks or reversible ischemic neurologicl deficit. The hospitl sty ws 8:3 ^ 6:0 dys. 4. Discussion The incidence of mjor neurologicl complictions occurring during the performnce of coronry rtery surgery vries widely, depending on the definition nd ccurcy of dignosis, nd hs been reported between 1 nd 6% [1]. Although the role of crotid disese in the genesis of periopertive stroke in ptients undergoing isolted myocrdil revsculristion remins incompletely defined, becuse of the multifctoril etiology, severl reports indicte tht significnt crotid rtery stenosis is n importnt, nd for some the strongest, incrementl risk fctor [2 4]. Nevertheless, D Agostino et l., estimted periopertive risk t,2% in ptients with crotid stenosis,50%, 10% with stenosis 50 80%, nd 11 19% with stenosis.80% [5]. Routine crotid evlution before CABG hs yielded significnt internl crotid stenosis (.70%) in 3 12% of ptients [1,6]. In our experience, the dignosis of severe crotid disese ws secondrily mde in 2.1% of the ptients who hd been dmitted for isolted CABG. However, this could obviously be n underestimtion of the rel incidence of crotid disese becuse routine preopertive evlution of ll CABG ptients, other thn usculttion of bruits, ws not crried out. Mny surgicl groups perform crotid duplex studies routinely in ptients who re to undergo CABG, but this hs not proven to led to better outcome. On the other hnd, controversy still exists in the literture s to whether or not CEA is protective ginst stroke. However, some rndomised trils hve now unequivoclly demonstrted significnt benefit of CEA over continued medicl tretment for ptients with symptomtic, nd more recently, with symptomtic severe crotid rtery stenosis. The North Americn Symptomtic Crotid Endrterectomy Tril (NASCET) study [7] showed tht in symptomtic ptients with 70 99% crotid stenosis, CEA decresed the 2-yer rte of ipsilterl stroke from 26% (in mediclly treted ptients) to 9%. The Asymptomtic Crotid Atherosclerosis Study (ACAS) study [8] demonstrted reduction in totl ipsilterl neurologicl events in ptients with.60% crotid stenosis from 18 to 7%, over 5 yers. These dt my, perhps, be extrpolted to ptients requiring CABG nd rgue for n ggressive surgicl pproch in this popultion. We believe tht the rtionl pproch for virtully ll ptients who present with severe combined rteril disese is to submit them to crotid surgery before myocrdil revsculristion. In this context, the surgicl options re then either simultneous procedure (sme nesthetic) or stged pproch with CEA performed severl dys prior to CABG. Proponents of both types of pproches hve published series procliming the sfety of ech technique. However, no well-designed prospective rndomised tril hs, until now, clrified this problem. Consequently, the optiml strtegy for mngement remins undefined nd ech centre must select nd nlyse its own tretment policy nd compre the results with those described in other published reports. In 1992, we dopted the stged pproch Tble 3 Studies reporting results with the stged pproch Series No. of ptients MI Stroke Deth Stroke 1 deth Bernhrd et l. [12] 16 3 (18.8%) 2 (12.5%) 5 (31.3%) 7 (43.5%) Reul et l. [13] 164? 4 (2.4%) 8 (4.9%) 12 (7.3%) Hertzer et l. [14] 24 1 (4.2%) 1 (4.2%) 1 (4.2%) 2 (8.4%) Fgioly et l. [15] 17? 0 0 0 Crrel et l. [16] 45 4 (8.8%) 0 2 (2.2%) 2 (4.4%) Coyle et l. [17] 45? 2 (4.4%) 1 (2.2%) 3 (6.6%) Tkch et l. [18] 257 12 (4.7%) 5 (1.9%) 4 (1.6%) 9 (3.5%) Totl 568 20 (5.8%) 14 (3.7%) 21 (3.7%) 35 (6.2%)

P.E. Antunes et l. / Europen Journl of Crdio-thorcic Surgery 21 (2002) 181 186 185 Tble 4 Prcel nd globl results: mortlity, MI nd stroke Vrible CEA1SI N ¼ 83 b CABG N ¼ 77 CEA1CABG Mortlity 0 1 (1.3%) 1 (1.3%) c MI 3 (3.6%) 2 (2.6%) 5 (6.3%) Stroke 2 (2.4%) 3 (3.9%) 5 (6.3%) Totl stroke nd mortlity 5 (6.3%) b c SI indictes stging intervl. Totl number of crotid endrterectomies performed on the 77 ptients. The ptient who died is one of five who hd stroke. to tret ll ptients who present with concomitnt rteril crotid nd coronry disese. Our decision ws mde minly becuse two different surgicl tems (crdic nd vsculr) re involved, mking simultneous procedure difficult to coordinte. Most unstble ptients cn now be stbilised mediclly in the coronry cre unit. This ws successfully done in ll (five) of our ptients. If stbilistion cnnot be chieved or the coronry lesions re of extreme severity, CABG should be performed first. As fr s we cn recll, this ws necessry in three of our cses. Although the results with the simultneous pproch hve been well documented, fewer studies report results with the stged pproch (Tble 3). The overll risk of mortlity ws 3.7%, tht for MI ws 5.8% nd tht for stroke ws 2.5%, with composite rte of deth nd stroke of 6.2%. In generl, these studies lso reported incresed composite rtes of deth nd stroke in the simultneous compred with the stged group, lthough there ws often bis in ssigning higher risk ptients to the simultneous pproch. The sme conclusion, suggesting tht combined CABG nd CEA my be ssocited with higher risk of stroke or deth thn in stged procedures, ws recently reported in metnlysis by Borger et l. [11]. To the best of our knowledge, this is the first report of the results of the stged opertion used s the routine method to tret ll ptients with identified concomitnt crotid nd coronry rteril disese, nd this my be one of its weknesses, s we do not hve control group with which to compre our results. In fct, ll series deling with the results of the stged opertion (Tble 3) cme from institutions tht lso use other tretment options, including the combined pproch. In the beginning of this experience, we were nturlly concerned bout the eventul consequences of this method of tretment, with regrds to the eventul occurrence of MI during CEA nd in the stging intervl. In the pst, some influentil studies hd ssocited CEA in ptients with severe uncorrected coronry rtery disese with prohibitive rtes of periopertive mortlity nd of MI [9,10]. We gree tht this group of ptients my be t higher risk of periopertive coronry ischemic events, but our results, reported herein, with no mortlity nd n incidence of MI of 3.6%, pper to demonstrte the reltive sfety of this pproch. Becuse ptient selection is one criticl fctor in this clinicl evlution, we intended to compre our series (Tble 4) only with others, which nlyse the simultneous pproch s method to tret ll ptients. Even considering tht our series is reltively smll by comprison with some included, our globl mortlity (1.3%) nd composite deth nd stroke (6.3%) rtes compre fvourbly with those reported in the literture since 1992 for ptients mnged using simultneous pproch (Tble 5). However, s it probbly might hve been expected, our incidence of MI ws higher. On the other hnd, we did not expect the reltively high incidence of stroke fter CABG (three ptients; 3.9%), nd lso the fct tht ll were ipsilterl to the CEA site. This result underscores the multifctoril etiology of stroke fter CABG, prticulrly in these high-risk ptients, but is insufficient to question the vlue of prophylctic CEA in reducing the incidence of stroke. We believe tht the rte of cerebrovsculr ccidents in our ptients would hve been even higher if they hd not undergone the CEA before the CABG. However, the occurrence of three strokes, resulting from cerebrl dmge ipsilterl to the CEA, rises the question of residul crotid disese. Perhps routine duplex scnning or ngiogrphy, which we hve not used until now, should be considered in these cses. In conclusion, stroke fter CABG is dredful compliction. Crotid disese is significntly ssocited with this neurologicl outcome. Hence, we believe tht the rtionl pproch for the tretment of ptients with severe combined Tble 5 Series reporting results of concomitnt crotid nd coronry opertions since 1992 Series No. of ptients MI Stroke Deth Stroke 1 deth Vermeulen et l. [19] 230 4 (1.8%) 7 (3.0%) 8 (3.5%) 15 (6.5%) Akins et l. [21] 200 5 (2.5%) 6 (3.0%) 7 (3.5%) 13 (6.5%) Dily et l. [23] 100 1 (1.0%) 0 4 (4.0%) 4 (4.0%) Trchiotis et l. [24] 88 0 4 (4.5%) 3 (3.4%) 7 (7.9%) Drling et l. [20] 420? 5 (1%) 10 (2.4%) 15 (3.4%) Plestis et l. [25] 213 5 (2.3%) 11 (5.1%) 12 (5.6%) 23 (10.7%) Evgelopoulos et l. [22] 313 10 (2.2%) 7 (2.2%) 28 (8.9%) 35 (11.1%) Khitn et l. [26] 121? 7 (5.8%) 7 (5.8%) 14 (11.6%) Totl 1685 25 (2.2%) 47 (2.8%) 79 (4.7%) 126 (7.5%) Reversible or permnent stroke.

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