대한내과학회지 : 제 73 권제 3 호 2007 관상동맥우회로술후이식편협착및폐쇄를유발하는위험인자의분석 아주대학교의과대학흉부외과학교실 홍준화 임홍석 최진욱 박인덕 이철주 =Abstract= Risk factors affecting graft stenosis and occlusion after coronary artery bypass graft surgery Joon Hwa Hong, M.D., Hong Seok Lim, M.D., Jin Wook Choi, M.D., In Duk Park, R.N. and Cheol Joo Lee, M.D. Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon, Korea Background : Coronary artery bypass graft (CABG) surgery has been a main treatment modality of ischemic heart disease since Sabiston reported the first CABG operation using a saphenous vein graft in 1963. However, graft stenosis that happens after CABG surgery is one of the main limitations of the procedure. We investigated risk factors that are related to graft stenosis and occlusion in patients that needed a coronary angiogram after CABG surgery. Methods : From May 1995 to April 2004, we performed 348 CABG surgeries. Among them, we performed follow up coronary angiogram for 45 patients because of clinical indications, corresponding to 146 graft vessels. According to the angiography findings, patients with 27 graft vessels that showed stenosis or occlusion were defined as group S and patients with 119 graft vessels that showed no stenosis or occlusion were defined as group P. Results : The mean patient age of group S is 59.44 (±8.549) years and the mean patient age of group P is 57.99 (± 8.676) years. Group P patients had more stenotic native coronary arteries than group S patients, which is statistically significant (80.0±7.2% vs. 68.0±11.9%, p=0.005). Group S patients had a statistically significant lower postoperative HDL level than the level of the group P patients (40.4±15.9 mg/dl vs. 50.5±4.4 mg/dl, p=0.002). Conclusions : When performing CABG surgery and postoperative patient management, the severity of native coronary artery stenosis and the postoperative HDL level should be considered for better patient outcome.(korean J Med 73:293-298, 2007) Key Words : Coronary artery bypass surgery, Graft occlusion, vascular, HDL cholesterol 서론관상동맥협착증의치료에는여러방법이쓰여왔으며이중관상동맥우회로조성술은 1963년 Sabiston 1) 이보고한이래주된치료방법으로사용되어왔다. 이식편 으로는주로내흉동맥, 복재정맥등이사용되어우수한장기개존율을보이고있는데 2) 복재정맥은약 40% 내지 50% 의 10년개존율을보이는것으로보고되고있으며내흉동맥의개존율은그보다우세하여 7년에서 10년사이에는 85% 에서 95% 가유의한협착을보이지않는 Received : 2006. 7. 25 Accepted : 2006. 12. 12 Correspondence to : Cheol Joo Lee, Department of Thoracic and Cardiovascular Surgeru, Ajou University School of Medicine, San 5, Wonchondong, Yeongtonggu, Suwon 442-721, Korea E-mail : cjlee@ajou.ac.kr - 293 -
-The Korean Journal of Medicine : Vol. 73, No. 3, 2007 - 것으로보고되고있다 4-9). 복재정맥은장기추적에서동맥경화성변화에의한협착이발생하여이식편의협착이진행되는것으로보고되고있으며 5) 내흉동맥은그보다는적은경우에있어동맥경화성협착이발생하나관상동맥과의경쟁적혈류등다양한기전에의해협착이진행될수있는것으로보고되고있다 6, 9, 12-14). 뿐만아니라관상동맥자체역시동맥경화성병변의진행을보인다 5). 이러한이식편의협착이나폐쇄에는다양한기전및요소들이관련되어있을것으로생각되며이에본연구의저자들은관상동맥우회로조성술을시행받은후다양한이유로관상동맥조영술을다시시행받았던환자군을대상으로이식편협착증의위험인자를분석해보고자하였다. 대상및방법 1. 환자군 1995년 5월부터 2004년 4월까지본원흉부외과에서관상동맥우회로조성술을시행받은 348명의환자를대상으로연구를하였다. 이중 45명의환자가수술후의흉통, 호흡곤란, 심전도이상, 심근효소치상승등의임상적적응증에의해추적관상동맥조영술을시행받았다. 이들환자군중최소침습관상동맥우회로조성술 (MIDCAB) 을시행받은한명을제외한대부분의환자는정중흉골절개후심폐바이패스하에전향적, 후향적심정지액을사용하여심정지를유발한상태에서수술을시행받았다. 또, 위망동맥이우측후하행지에문합된 2명의환자를제외한대부분의환자에서좌측내흉동맥과복재정맥이이식편으로사용되었다. 대상환자군중 Y형이식편이시행된환자는 3명있었으며순차적문합 (sequential anastomosis) 를시행받은환자는 7명이있었다. 이 45 명의환자중하나또는그이상의이식편협착이나폐쇄가발견되어중재시술을받은환자는 24명이었으며모든이식편의개존을보인환자는 21명이었다. 이식이시행된총 146개의이식편중참고혈관이식편 (reference vessel graft) 을기준으로 50 % 이상의내경협착및폐쇄를보인 27개의이식편을협착군 (Group S) 으로정의하였으며개존을보인 119개의이식편을개존군 (Group P) 으로정의하였다. 이상의환자군을대상으로하여위험인자로추정할수있는생활습관, 혈압, 혈액검사소견, 수술전시행한심장초음파, 관상동맥조영술소견등 을대상으로그영향을비교분석하고자하였다. 2. 정보수집대상이된각환자의의무기록을검토하였으며일부위험인자의수술전후의변화를측정하였다. 또한, 수술전과후의심초음파검사와관상동맥조영술을비교, 검토하여좌심실구출율, 운동장애, 변병의위치, 협착정도, 문합부위의관상동맥크기를측정하였다. 3. 통계및분석단일변수검사 (univariate test) 로양군간의임상적요소, 관상동맥조영술소견, 수술적요소의차이를비교하였다. 카이스퀘어검사를사용하여구분된변수들을분석했으며연속변수는 Student t-test 또는 U test를사용하여분석하였다. 모든검사에있어 p value 가 0.05 미만인경우를통계적으로유의한것으로간주하였다. 결과 1. 임상적특징이식편을대상으로했을때남녀비는 92:54, 평균연령은약 58.2±68.7세, 평균체중은약 63.4±8.1 kg, 키는 161.0±6.9 cm이었다. 환자를대상으로했을때 45명의환자중남자는 28명, 여자는 17명이었으며평균연령은 58.7±8.6 세였다. 평균체중은 64.6±7.6 kg, 신장은 162.2 ±7.0 cm였다. 총추적기간은 5일에서약 65개월로평균추적기간은 20개월에해당되었다. 두군의나머지임상적특징은표 1과같다. 두군간에통계학적으로유의한차이를보인인자는체중, 신장, 수술후 HDL 콜레스테롤수치등이었으나이중체중과신장은체질량지수 (BMI) 로변환하였을경우의미가없는것으로나타나수술후 HDL 콜레스테롤수치가높을수록이식편의협착및폐쇄가더적게오는것으로나타났다. 2. 수술전조영술및심초음파소견표 2에는수술전시행한두군의관상동맥조영술소견과시행된수술방법을연관지어나타내었다. 이표에서는문합이시행된관상동맥의협착정도만을나타냈으며분지에문합이시행된경우에는분지자체에협착이없는경우라도본가지의근위부에협착이있으면 ( 예 : - 294 -
- Joon Hwa Hong, et al : Risk factor analysis of CAB graft stenosis - Table 1. Characteristics of group S and group P patients Male:Female Year, Age Kg, Weight Cm, Height Kg/m 2, BMI Days after CABG DM (%) Family history (%) Previous history (%) Preop. Group S Group P p 18 : 9 59.4±8.5 66.5±6.7 164.0±7.1 24.7±2.3 627.0±867.2 10(37.0%) 2(7.4%) 3(11.1%) Postop. Preop. 74 : 45 58.0±8.7 62.7±8.4 160.3±6.9 24.4±3.3 554.9±644.8 20(16.8%) 5(4.2%) 25(21.0%) Postop. Preop. Smoking (%) Hypertension (%) mg/dl, LDL-C mg/dl, HDL-C mg/dl, TC mg/dl, TG 13(48.1%) 14(51.9%) 131.5±34.6 39.9±7.9 215±65.5 220±70.9 10(37.5%) 7(25.9%) 108.6±28.6 40.4±15.9 185.6±68.7 185±90.8 17(14.3%) 91(76.5%) 125.6±32.8 42.7±9.9 212.6±72.2 225.7±89.1 13(10.9%) 55(46.2%) 101.5±34.5 50.5±4.4 185.5±54.3 170.5±97.8 0.334 0.454 0.436 0.161 0.265 0.337 0.335 0.630 0.397 0.002 0.397 0.193 BMI, body mass index; LDL-C, LDL cholesterol level; HDL-C, HDL cholesterol level; TC, total cholesterol level; TG, triglyceride 0.5 0.449 0.016 0.021 0.564 0.636 0.073 0.768 0.269 Postop. diagonal artery 에협착이없는경우라도 proximal left anterior descending artery에협착이있는경우 ) 본가지의협착정도를분지의협착으로계산하였다. 순차적문합 (sequential anastomosis) 이시행된경우에는모두이식편근위부에협착이왔으므로근위부에문합이시행된관상동맥 ( 예 : 이식편이 aorta to diagonal artery to obtuse marginal artery에순차적으로문합된경우 diagonal artery) 의협착정도를계산하였다. 수술전시행한조영술상나타난관상동맥의협착정도와수술후시행한조영술상나타난이식편의협착및폐쇄를분석한결과 group P에서통계학적으로유의하게더심한관상동맥의협착소견을보여관상동맥의협착이심할수록이식편의협착및폐쇄가덜오는것으로나타났다 (p=0.005). 또, 수술전심초음파검사로관찰한두환자군의좌심실구출율등의운동성지표는표 3에나타내었다. Group S와 group P의좌심실구출율은각각 51.26± 19.83%, 57.87±15.91% 로유의한차이가없었으며좌심실구출율외의다른이상운동성도두군간에유의한차이를보이지는않았다. 3. 이식편의종류와이식편의협착및폐쇄수술에사용된이식편의종류는 group S에서좌내흉 동맥 5개 (18.5%), 복재정맥 22개 (81.5%) 이고, group P에서는좌내흉동맥 30개 (25.2%), 복재정맥 87개 (73.1%), 위망동맥 2개 (1.7%) 로두군간에통계학적으로유의한차이는없었다 (p=0.306). 고찰본연구는관상동맥우회로조성술후이식편의협착을야기할수있는위험인자를분석하기위한연구이다. 본연구는복재정맥이식편, 내흉동맥이식편에서모두문합이시행된관상동맥의문합근위부협착이심하지않을경우이식편의협착이진행되는결과를나타냈다. 또, 이식에사용된혈관의종류와는상관없이수술후낮은 HLD 콜레스테롤수치가협착의유의한위험인자로작용하는것으로나타났다. 키와몸무게또한수술후이식편의협착이나폐쇄를일으키는위험인자로나타났으나체질량지수로보정한후에는그의미가없는것으로나타났다. 본연구는수술중이식편의개통정도를혈류측정기 (flow meter) 등으로측정한자료가없어수술후이식편의협착및폐쇄가수술중에발생했던기술적문제 (technical problem) 와연관이있는가를규명하지못한문제가있다. 또, 다른연구들에비해추적기간이평균 - 295 -
- 대한내과학회지 : 제 73 권제 3 호통권제 565 호 2007 - Table 2. Preoperative stenosis of native coronary arteries Anastomosis method & site LIMA-proxima LAD LIMA-mid LAD LIMA-distal LAD Aorta-Dx Aorta-OM Aorta-RCA Aorta-PDA Aorta-OM-Dx Aorta-1 Dx, 2 Dx Aorta-RCA-PDA Aorta-LAD LIMA-Dx Aorta-Ramus intermedius LIMA-OM GEA-PDA Total Group S 58.0 67.5 72.6 65.1 59.3 86.7 77.5 50.0 83.3 60.0 68.0±11.9 % stenosis Group P 79.8 80.1 86.5 83.1 78.1 69.3 79.7 83.5 80.5 100 80.0±7.2 LIMA, left internal mammarian artery; LAD, left anterior descending artery; Dx, diagonal artery; OM, obtuse marginal artery; RCA, right coronary artery; PDA, posterior descending artery; GEA, gastroepiploic artery Table 3. Preoperative cardiac functions LVEDF (%) No RWMA Hypokinesia Akinesia Group S Group P p 51.26±19.83 78 (66%) 9 (7%) 32 (27%) 57.87±15.91 16 (59%) 2 (8%) 9 (33%) LVEDF, left ventricular ejection fraction; RWMA, regional wall motion abnormality 0.111 0.615 약 20개월로짧아주된위험인자로나타난관상동맥의협착정도와 HDL수치가실제로본연구의대상들에게얼마나영향을미쳤는지도의문이다. 다른연구에비해비교적짧은기간에이식편에협착이온것으로보이는것은수술후관상동맥조영술을시행해야하는여러임상적적응증에해당되는환자들만이본연구에포함되었기때문으로생각된다. 위에언급된제한점들에대한정확한규명을위해서는향후대조군과의장기비교추적관찰이필요하리라생각된다. 동맥이식편이정맥이식편보다더좋은장기개존율을보이는것은이미여러연구에서보고된바있어 4, 7), 최근에는가능한한양쪽내흉동맥이나위망동맥, 요골동맥등을사용하는추세이다. 동맥이식편이정맥이식편보다좋은장기개존율을보이는이유는두혈관의서로다른성격때문이다. 동맥이식편은정맥이식편에 비해 vasoactive substance에더잘반응하며혈관내피세포에의해 nitric oxide와같은혈관을이완시키는물질을보다많이생산한다 10). 또, 동맥이식편이관상동맥우회로조성술후의높은압력과혈류에보다잘적응한다. 이러한해부생리학적차이가수술후이식편의장기개존율을보이는요인일것으로생각된다. 관상동맥자체에도수술후에점차동맥경화성변화가진행되는것으로알려져있다 5). 어떤연구는복재정맥이식편의협착및폐쇄는원관상동맥의협착정도에반비례함을보고하였다 11). 즉, 본래의관상동맥의협착이심하지않을경우그원위부에문합된이식편의퇴화및폐쇄가빨리진행된다는것이다. 본연구의결과에의하면이와같은현상은복재정맥이식편뿐만아니라동맥이색편의경우에도적용될수있는것으로나타났으며이는 Pagni 등 12) 이진행한연구에도나타나있다. 이들은정상좌전하행지에문 - 296 -
- 홍준화외 4 인 : 관상동맥우회로술후이식편협착위험인자분석 - 합한내흉동맥의 70% 협착을보고하였다. 또, Shimizu 등 13) 의연구와 Nasu 등 14) 의연구역시이와같은현상을뒷받침해준다. 이에반대되는연구들도있다. Spence 등 15) 은 canine 실험모델을이용하여협착이없는정상좌전하행지에내흉동맥을문합한후에도내흉동맥의혈류는잘유지됨을보고함으로써, 내흉동맥혈류의감소가폐쇄의원인이아니라고주장하였다. Lust 등 16) 은동일한실험모델을이용한연구에서내흉동맥과본래의관상동맥사이에 8주간의경쟁적혈류를조성한후에도내흉동맥혈류가감소하지않음을보고한바있다. Kawasuji 등 17) 도경쟁적혈류에의한이식편폐쇄는발생하지않았다고보고한바있다. 이들연구외에도경쟁적혈류에의한이식편의폐쇄에대해서는아직도논란이있다. HDL 콜레스테롤수치와관상동맥질환과의역상관관계는이미여러연구자에의해보고된바있다 18). 또, 일부연구는여러지단백질중 HDL 콜레스테롤이관상동맥질환과가장밀접한역상관관계를가지고있다고보고한바있다 19). 이는관상동맥자체의질환뿐아니라관상동맥우회로조성술이후의환자에있어서도이식편의협착및폐쇄와수술을시행받은환자의장기생존율에영향을미치는것으로보고되고있다 20). 본연구의대상환자중추적관상동맥조영술을시행받는시점에항이상지혈증 (anti-dyslipidemic) 약물을투약받고있던환자는소수에불과해두군간에통계학적으로의미있는차이를보이지는않았으나이또한앞으로연구해야할과제라생각된다. 최근관상동맥우회로술후환자의추적조사에있어다절편전산화단층촬영 (MDCT) 의유용성이보고되고있으나 21) 본연구와같이이식편의협착이나폐쇄를배제하기어려운증상및임상양상이있는경우에는중재술의가능성을고려할때 MDCT 보다는혈관조영술이더적합한검사라고생각된다. 요약목적 : 허혈성심장병의주된치료로알려진관상동맥우회로술은 1963년 Sabiston에의해 wjdaorbus 을이용한최초의수술이처음보고된이후로널리시행되고있다. 하지만이식편으로동맥을사용하든정맥을사용하든재협착에의한다양한합병증들이문제가되어수술의큰제한점으로대두하고있다. 따라서저자들은관상 동맥우회로술후에이식편의재협착에영향을미치는인자들을수술후의관상동맥조영술을분석하여찾아보고자하였다. 방법 : 1995년부터 2004년사이에관상동맥우회로술을시행하였던 348명의환자군중허혈성심장병의증세를보여관상동맥조영술을시행하였던 45명의환자에서전체 146개의이식편을대상으로분석하였다. 협착을보였던 27개 (S group) 과완전한개존을보인 119개 (P group) 에서위험인자들을분석하였다. 결과 : S군의평균연령은 59.44 (±8.549) 세이고, P군은 57.99 (±8.676) 세였다. P군의본래의관상동맥협착의정도가 S군에비해통계적으로유의하게심했다.(80.0±7.2% vs. 68.0±11.9%, p=0.005). S군에서수술후의 HDL 수치가유의하게낮은것으로분석되었다 (40.4±15.9 mg/dl vs. 50.5±4.4 mg/dl, p=0.002). 결론 : 관상동맥우회로술을결정할때는수술전의환자자신의관상동맥협착정도와수술후혈중 HDL을높게유지하는것이이식편의장기개통율에영향을미 치는것으로판단된다. 중심단어 : 관상동맥우회로술, 이식편협착, 혈관, 고밀도지방, 혈중콜레스테롤 REFERENCES 1) Sabiston DC Jr. Direct surgical management of congenital and acquired lesion of the coronary circulation. Prog Cardiovasc Dis 6:299-316, 1963 2) Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, Davis K, Killip T, Passamani E, Norris R. Effect of coronary bypass graft surgery on survival: overview of 10 year results from randomized trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 344:563-570, 1994 3) Campeau L, Enjalbert M, Lesperance J, Vaislic C, Grondin CM, Bourassa MG. Atherosclerosis and late closure of aortocoronary saphenous vein grafts: sequential angiographic studies at 2 weeks, 1 year, 5 to 7 years, and 10 to 12 years after surgery. Circulation 68(Suppl II):II1-II7, 1983 4) Barner HB, Barnett MG. Fifteen to twenty oneyear angiographic assessment of internal thoracic artery as a bypass conduit. Ann Thorac Surg 57:1526-1528, 1994 5) Bourassa MG, Enjalbert M, Campeau L, Lesperance J. Progression of atherosclerosis in coronary arteries - 297 -
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