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1 대한내과학회지 : 제 79 권제 5 호 2010 관상동맥 CT 혈관조영술상정상이었으나심혈관계사건이발생한 2예 연세대학교의과대학내과학교실 이찬주 김광준 오창명 유희태 장지용 최동훈 장혁재 Normal coronary CT angiography with subsequent adverse cardiac events Chan Joo Lee, M.D., Kwang Joon Kim, M.D., Chang Myung Oh, M.D., Hee Tae Yu, M.D., Ji Yong Jang, M.D., Donghoon Choi, M.D., and Hyuk-Jae Chang, M.D. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Multi-detector row coronary computed tomography (CT) angiography is an emerging noninvasive diagnostic tool for coronary artery disease. Because of the high negative predictive value of the test, coronary CT angiography is useful for ruling out significant coronary artery stenosis in patients with chest pain. Between 2003 and 2009, 2,148 (50%) of 4,337 patients who underwent coronary CT angiography had a normal coronary artery. Of the 2,148 patients, only two (0.09%) experienced cardiovascular events within three months of their index visit. One patient underwent invasive coronary angiography based on a positive exercise test result, while the second underwent invasive coronary angiography due to an episode of chest pain. Coronary angiographic examination of these two patients revealed significant luminal narrowing of the proximal left anterior descending artery; both patients underwent revascularization at the discretion of their physician. (Korean J Med 79: , 2010) Key Words: Coronary artery stenosis; Coronary angiography; Computed tomography 서론관상동맥질환은우리나라에서도사망률수위를차지하는주요질환군이며이로인한사회, 경제적비용또한심각한수준이다. 과거침습적 X-선관상동맥조영술이관상동맥질환의진단에있어표준진단방법으로간주되어왔으나, 최근다검출나선형컴퓨터단층촬영장치 (multi-detector row CT, 이하 MDCT) 가임상에도입되면서비침습적으로관상동맥질환을진단하기위한검사로써관상동맥 CT 혈관조영 술의사용이급격히증가하고있다. 관상동맥질환이의심되는환자들에서 CT 혈관조영술을침습적인 X-선관상동맥조영술과비교하여 CT 혈관조영술의관상동맥질환진단의정확도를분석한연구들에따르면, 민감도와특이도는각각 90% 이상으로매우높아임상적으로관상동맥질환이의심되는경우 CT 혈관조영술은관상동맥의유의한협착을여부를진단하는데매우유용하게사용될수있음이알려져있다 1). 또한응급실에서급성흉통을주소로내원한환자들을대상으로 CT를시행하는경우진단 Received: Revised: Accepted: Correspondence to Hyuk-Jae Chang, M.D., Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul , Korea hjchang@yuhs.ac

- The Korean Journal of Medicine: Vol. 79, No. 5, 2010 - 에소요되는시간을단축하고불필요한입원을줄여주는역할을한다고알려져있으며 2), 이외에도관상동맥스텐트의개통도를평가하거나관상동맥이식편 (bypass graft) 의개통도를평가하는데에도사용하고있다 3,4).

2 - The Korean Journal of Medicine: Vol. 79, No. 5, 에소요되는시간을단축하고불필요한입원을줄여주는역할을한다고알려져있으며 2), 이외에도관상동맥스텐트의개통도를평가하거나관상동맥이식편 (bypass graft) 의개통도를평가하는데에도사용하고있다 3,4). 이러한다양한임상적적응증에있어공통적으로기반하고있는관상동맥 CT 혈관조영술의기술적강점은높은음성예측도이다. 즉, CT에서관상동맥의협착이발견되지않는경우유의한관상동맥질환을배제할수있으며특히 CT 혈관조영술에서정상소견을보인환자들의경우예후추적연구에서도그예후가매우양호하다는사실이알려진바있다 5). 그러나관상동맥 CT 혈관조영술이음성예측도가 95~99% 로과거에사용되었던여러비침습적검사방법에비해현저히우수하다하더라도비침습적검사의속성상위음성의가능성은상존하고있으며이는 CT 검사시의영상획득관련지표와판독자의숙련도등여러요소에의해좌우될수있다 6). 저자등은본원에서 2003년 3월부터 2009년 4월까지관상동맥질환의심하에관상동맥 CT 혈관조영술을시행한환자 4,337명중 2,148명 (50%) 에서 CT 혈관조영술상정상관상동맥소견을보였으며이들환자들은 3개월간의단기추적기간에매우양호한예후를보였으나일부환자에서추적기간중유의한심근허혈이증명되었거나또는심장혈관계사건이발생하여재관류술을필요로하였던증례를경험하였기에이를문헌고찰과함께보고하는바이다. 증례증례 1 환자 : 김 자, 여자, 54세주소 : 가슴부위의찌르는듯한통증현병력 : 내원 7개월전부터불규칙적인좌측가슴부위의통증을주소로외래내원하였다. 과거력 : 특이병력없음. 흡연력, 음주력없음. 가족력 : 언니가협심증으로치료중임. 이학적소견 : 내원시생체징후는혈압 115/68 mmhg, 맥박수 70회 / 분, 호흡수 15회 / 분, 체온은 36.5 였다. 심음은규칙적이었고, 심잡음은청진되지않았으며, 호흡음은정상소견이었다. 체질량지수는 25.8 kg/m 2 였다. 혈액검사소견 : 혈청생화학검사상혈당 84 mg/dl, 총콜레스테롤 229 mg/dl, 고밀도지단백콜레스테롤 77 mg/dl, 저밀도지단백콜레스테롤 132 mg/dl, 중성지방 155 mg/dl 였다. 단순흉부 X-선촬영 : 심비대, 폐문부울혈이나종격동의확장소견은보이지않았다. 표면심전도검사 : 정상동율동이었으며 ST 분절의변화나다른심전도상의변화는관찰되지않았다. 관상동맥 CT 혈관조영술 (Sensation 64, Siemens Medical Systems, Forchheim, Germany; scan parameters: 330- millisecond gantry rotation time, 120 kv, 800 mas, 0.6 mm A B C Figure 1. Case 1 involved a 54-year-old patient with atypical chest pain (BMI=25.8 kg/m 2 ). (A) and (B) Volume-rendered and curved multiplanar reconstruction images (thickness=0.75 mm; heart rate=69 bpm) showing a motion artifact (arrow) in the left anterior descending artery (LAD). (C) Conventional X-ray angiograph showing severe stenosis (arrowhead) of the mid LAD

3 - Chan Joo Lee, et al. Normal coronary CT angiography with subsequent adverse cardiac events - slice collimation, 1 mm slice width, and 3.3 mm table feed/rotation; 심박수 69회 ): 관상동맥질환의심소견이관찰되지않았다 ( 관상동맥석회화수치 : 0). 운동부하심전도검사 : Bruce protocol 4단계에서 II, III, avf, V4-6 의 ST 분절하강 (1 mm) 이관찰되었다. 임상경과 : 입원후시행한 X-선관상동맥조영술상좌전하행지중간부위의 80% 협착소견이보여 sirolimus 용출성스텐트 (Cypher ) 를삽입하였으며이후증상없이외래통원치료중이다. 증례증례 2 환자 : 정 섭, 남자, 73세주소 : 가슴부위의터질듯한통증현병력 : 내원 8개월전부터걸으면심해지는통증있어외래내원하여운동부하검사및관상동맥 CT를시행받고이상소견없어경과관찰하였으나증상악화되어응급실내원하였다. 개인력 : 내원 8개월전고혈압진단받고투약중임. 기타특이병력없음, 흡연력, 음주력없음. 가족력 : 없음. 이학적소견 : 내원시생체징후는혈압 119/63 mmhg, 맥박수 66회 / 분, 호흡수 15회 / 분, 체온은 36.5 였다. 심음은규칙적이었고, 심잡음은청진되지않았으며, 호흡음은정상소견이었다. 체질량지수는 24.4 kg/m 2 였다. 혈액검사소견 : 혈청생화학검사상혈당 109 mg/dl, 총콜레스테롤 107 mg/dl, 고밀도지단백콜레스테롤 46 mg/dl, 저밀도지단백콜레스테롤 62 mg/dl, 중성지방 67 mg/dl였다. 단순흉부 X-선촬영 : 심비대, 폐문부울혈이나종격동의확장소견은보이지않았다. 표면심전도검사 : 정상동율동이었으며 ST 분절의변화나다른심전도상의변화는보이지않았다. 관상동맥 CT 혈관조영술 (Sensation 64, Siemens Medical Systems, Forchheim, Germany; scan parameters: 330 millisecond gantry rotation time, 120 kv, 800 mas, 0.6 mm slice collimation, 1 mm slice width, and 3.3 mm table feed/rotation; 심박수 62회 ): 관상동맥의협착소견은보이지않았다 ( 관상동맥석회화수치 : 0). 운동부하심전도검사 : Bruce protocol 3단계에서 V5-6의 ST 분절의불분명한 (equivocal) 변화가관찰되었으나저명한 ST 분절하강소견은관찰되지않았고, 운동중흉통발생없었다. 임상경과 : 기준방문 (index visit) 1주후급격한흉통을호소하며응급실에내원하여불안정형협심증진단하에시행 A B C Figure 2. Case 2 involved a 73-year-old patient with unstable angina (BMI=24.4 kg/m 2 ). (A) and (B) High-quality volume-rendered and curved multiplanar reconstruction images (thickness=0.75 mm; heart rate=62 bpm) showing stenosis (arrowhead) of the proximal left anterior descending artery; however, the official reading was no evidence of coronary artery disease. (C) Conventional X-ray angiograph showing significant luminal narrowing (arrow) of the proximal LAD

4 - 대한내과학회지 : 제 79 권제 5 호통권제 603 호 한 X-선관상동맥조영술상좌전하행지근위부의 90% 협착소견이보여 zotarolimus 용출스텐트 (Endeavor ) 를삽입하였다. 이후증상없이외래통원치료중이다. 고찰 1990년대후반 MDCT 기술이처음개발된이후 4절편에서 16절편그리고 64절편다검출기 (MDCT) 를이용한관상동맥 CT 혈관조영술기법이임상에적용되면서 MDCT 를이용한관상동맥질환의비침습적진단의정확성은획기적으로향상되었다. 16절편다검출기 CT와 64절편다검출기 CT를비교한연구에따르면특이도 69% vs. 90%, 양성예측률은 79% vs. 93% 로 64절편다검출기 CT가 16절편다검출기 CT 에비해특이도와양성예측률이의미있게향상된결과를보여주었다 7). 이와같은결과는기본적으로검출기절편두께 (slice thickness) 감소, 갠트리 (gantry) 회전속도증가, 새로운영상재조합기술개발등장비의하드웨어혹은소프트웨어상의기술개발을통한공간해상도와시간해상도의향상에따른것이며이를바탕으로임상에서관상동맥 CT 혈관조영술의사용이급격히증가하고있다. 현재가장널리임상에서사용되는 64절편 MDCT 를이용한 CT 혈관조영술의관상동맥질환진단의정확도를분석한연구들에따르면, X-선관상동맥조영술과비교하였을때 64 절편다검출기 CT 혈관조영술의민감도는 86~96%, 특이도는 92~98%, 양성예측률 56~97%, 음성예측률 92~99% 로나타났다. 특히, 여러연구에서공통적으로지적하는바는음성예측률이매우높다는것이며이는흉통을호소하는환자에서선별검사로서 CT 혈관조영술의강점을시사하는것이라할수있다 1). 즉, CT에서관상동맥의유의한협착이발견되지않는경우, 특히정상관상동맥소견을보이는경우관상동맥질환을배제할수있다. 최근미국심장학회등은관상동맥 CT 혈관조영술시행에있어적합성의기준을발표한바있으며이에따르면 CT 혈관조영술은흉통등의관상동맥질환을의심할만한증상이있으나, 위험인자들을고려할때관상동맥질환의가능성이낮거나중간이하로생각되는사람에게서가장유용하게사용될수있다고하였다 8). 이는검사의민감도가높기는하지만관상동맥질환의특성과기존의임상적치료과정을고려할때관상동맥질환이강력히의심되는환자에서이를확인하는용도보다 CT의높은음성예측도를이용한관상동맥질환을배제하는데사용하는것이더효과적이기때문이다. 그러나 CT 혈관조영술은다른여러비침습적검사와같이여러요인이검사의정확도에영향을줄수있기때문에검사결과를비판없이받아들이기전에다음의여러요인들에대한고려가필요하다. 첫째로, 적정한범위의심박수에서얻은영상으로부터도출된결과인가? Raff 등이발표한논문에따르면심박수가 70회 / 분이하에서는민감도 97%, 특이도 95%, 양성예측률 97%, 음성예측률 95% 이나 70회 / 분보다높을때는민감도 88%, 특이도 71%, 양성예측률 78%, 음성예측률 83% 로 CT의정확성이크게떨어졌다 9). 또한 Pugliese 등의연구에서도 CT 혈관조영술의영상의질이떨어지는이유를분석한결과, 50% 가움직임에의한것이었고, 특히이는우관상동맥의영상판독결과에많이영향을주는것으로나타났다 10). 따라서적절한영상을얻기위해서는장비에따라적정한범위로환자의심박수를조절하는것이필수적이다. 관상동맥의석회화도영상의질에영향을줄수있다. 관상동맥의석회화는심혈관계질환의위험인자중하나로생각되고있으며, 관상동맥석회화점수 (coronary artery calcium score) 가높을수록관상동맥질환의중증도 (burden) 가매우높음을시사하는소견이다 11,12). 심한관상동맥석회화가동반된경우 CT 혈관조영술의민감도, 특이도, 양성예측률, 음성예측률모두감소하며, 석회화가위양성과위음성결과의주원인이된다고알려져있다 13,14). 또한환자의비만도가영상의화질과관련이있다는보고도있으며, Raff 등의연구에서체질량지수 (body mass index; BMI) 가정상 (<25 kg/m 2 ) 인경우 CT 혈관조영술의민감도, 특이도, 양성예측률, 음성예측률모두 100% 였으나비만 (BMI>30 kg/m 2 ) 인경우 90%, 86%, 91%, 86% 로현저히감소하는결과를보였다 9). 따라서임상적으로허혈성심질환이의심되는환자에서 CT상에서음성이나온경우라도이상과같은요소는영상의질에영향을미쳐위음성을증가시킬수있기때문에관상동맥질환을배제하기전에이를반드시고려하여야한다. CT 혈관조영술을판독하는의사의경험또한중요한요소로최근에 Pugliese 등이발표한논문에서는피험자들이 1 년동안 1주일에 12개이상의 CT 혈관조영술을판독하게한후 4주, 8주, 6개월, 1년후판독의진단정확도 (diagnostic odd ratio) 를분석하였고, 적어도 1년이상의경험이 CT 혈관조영술의판독능력을향상시켜준다고주장하였다 15). 미국심장학회에서는관상동맥 CT 혈관조영술의판독을하는의사들의판독능력향상을위한훈련지침과기준을만들어숙련된

5 - 이찬주외 6 인. 위음성결과의관상동맥 CT 혈관조영술 - 판독을위해서는적어도 300개이상의판독을시행할것을권장하고있다 16). 또한, 위음성과위양성을줄이기위해서판독방법에대한지침을제시한바있다 17). 따라서상기원인으로 CT 검사가부적절하거나단독으로적절한진단이불가능할경우다른영상학적검사를함께이용하는것도도움이된다. 최근 Sato 등은 130명의환자를대상으로 CT 혈관조영술과 SPECT (single photon emission computed tomography) 를이용한심근관류영상을촬영한후에 CT 혈관조영술만의정확도와 CT와심근관류영상을함께이용하였을때의정확도를비교하였는데, 두가지영상검사를함께이용하는것이 CT 혈관조영술만을이용하였을때보다특이도는 70% 에서 87% 로증가하였고, 양성예측률도 82% 에서 91% 로증가한결과를보여 CT와심근관류영상을함께사용하는것이진단에도움이될수있음을보고한바있다 18). 증례 1의경우는흉통의양상은비전형적이었으며나이나성별, 콜레스테롤수치등을종합할때전통적인고위험군은아니었다. 관상동맥 CT상에서관상동맥질환이없다고판독되었으나, 외래추적관찰시에다시시행한문진상환자가지속적이고 isosorbide dinitrate (Isoket ) 분무제에호전되는흉통을호소하였기에시행한운동부하검사상에서심근허혈이확실히의심되었기때문에 X-선관상동맥조영술을시행하여좌전하행지에협착을발견하였다. 이환자의경우관상동맥촬영시심박수가 69회 / 분으로빨라영상의질이좋지않았기때문에검사의신뢰도가떨어졌던경우로, 적절한영상을얻기위해서는환자의심박수를적정한범위로유지하는것이중요함을보여준다고할수있다. 또한, 관상동맥협착을완전히배제할수없는경우운동부하검사같이심근허혈을기능적으로검사할수있는검사방법이부가적인도움을줄수있음을볼수있는사례라할수있다. 증례 2는임상적으로안정형협심증이의심되었으나운동부하검사상에서애매한 (equivocal) 결과를보였으며관상동맥 CT상에서석회화및관상동맥질환소견이없어외래에서경과관찰하던중에급격히악화된흉통으로응급실로내원한경우였다. 그러나 X-선관상동맥조영술상에서좌전하행지의협착소견이보여불안정형협심증진단하에중재시술을받았다. 추후해당부위에대한영상분석시관상동맥의동맥경화가의심되고 CT 혈관조영술의영상의질을저하시킬다른요인도확인되지않아판독오류에의한위음성일가능성을고려해볼수있었다. 결론적으로, CT 혈관조영술의음성예측도가높다고는하나판독결과가음성이라할지라도영상판독에영향을미치는 여러요인을이해하고환자의증상과위험인자를주의깊게문진하는것이필요하며또한필요한경우관상동맥질환진단의정확성을향상시키기위해심근관류영상같은심근허혈을기능적으로확인할수있는검사가함께이루어진다면위음성과위양성을줄일수있을것이다. 요 저자들은관상동맥 CT 혈관조영술상정상소견이었으나단기추적중심혈관계사건이발생한증례를경험하였기에문헌고찰과함께보고하는바이다. 중심단어 : 관상동맥협착, 관상동맥조영술, 컴퓨터단층촬영 약 REFERENCES 1) Bastarrika G, Lee YS, Ruzsics B, Schoepf UJ. Coronary CT angiography: applications. Radiol Clin North Am 47:91-107, ) Bastarrika G, Thilo C, Headden GF, Zwerner PL, Costello P, Schoepf UJ. Cardiac CT in the assessment of acute chest pain in the emergency department. AJR Am J Roentgenol 193: , ) Gaspar T, Halon DA, Lewis BS, Adawi S, Schliamser JE, Rubinshtein R, Flugelman MY, Peled N. Diagnosis of coronary in-stent restenosis with multidetector row spiral computed tomography. J Am Coll Cardiol 46: , ) Malagutti P, Nieman K, Meijboom WB, van Mieghem CA, Pugliese F, Cademartiri F, Mollet NR, Boersma E, de Jaegere PP, de Feyter PJ. Use of 64-slice CT in symptomatic patients after coronary bypass surgery: evaluation of grafts and coronary arteries. Eur Heart J 28: , ) Lesser JR, Flygenring B, Knickelbine T, Hara H, Henry J, Kalil A, Pelak K, Lindberg J, Pelzel J, Schwartz RS. Clinical utility of coronary CT angiography: coronary stenosis detection and prognosis in ambulatory patients. Catheter Cardiovasc Interv 69:64-72, ) Jacobs JE, Boxt LM, Desjardins B, Fishman EK, Larson PA, Schoepf J. ACR practice guideline for the performance and interpretation of cardiac computed tomography (CT). J Am Coll Radiol 3: , ) Hamon M, Morello R, Riddell JW. Coronary arteries: diagnostic performance of 16- versus 64-section spiral CT compared with invasive coronary angiography: meta-analysis. Radiology 245: , ) Hendel RC, Patel MR, Kramer CM, Poon M, Carr JC, Gerstad NA, Gillam LD, Hodgson JM, Kim RJ, Lesser JR, Martin ET, Messer JV, Redberg RF, Rubin GD, Rumsfeld JS, Taylor AJ,

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