Original Articles Korean Circulation J 2000;30 7 : 정맥내미세기포투여를이용한 Pulse Inversion Harmonic 심근조영심초음파검사의관상동맥협착증진단 : Tc-99m Sestamibi SPECT 와비교연구 권

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1 Original Articles Korean Circulation J 2000;307: 정맥내미세기포투여를이용한 Pulse Inversion Harmonic 심근조영심초음파검사의관상동맥협착증진단 : Tc-99m Sestamibi SPECT 와비교연구 권기환 1 정남식 1 하종원 1 임세중 1 김현주 1 장길진 1 이병권 1 편욱범 1 김인제 1 김대경 1 최동훈 1 장양수 1 이종두 2 조승연 1 김성순 1 Assessments of Myocardial Perfusion in Human Using Stress Intravenous PESDA Myocardial Contrast Echocardiography and Pulse Inversion Harmonic Imaging A Comparison Study with Tc-99m Sestamibi SPECT Kihwan Kwon, MD 1, Namsik Chung, MD 1, Jong-Won Ha, MD 1, Se-Joong Rim, MD 1, Hyun-Joo Kim, RN 1, Kil-Jin Chang, MD 1, Byoung-Kwon Lee, MD 1, Wook-Bum Pyun, MD 1, In-Jee Kim, MD 1, Dea-Kyung Kim, MD 1, Donghoon Choi, MD 1, Yangsoo Jang, MD 1, Jong-Doo Lee, MD 2, Seung-Yun Cho, MD 1 and Sung-Soon Kim, MD 1 1 Cardiology Division, Yonsei Cardiovascular Center, Yonsei Cardiovascular Resesarch Institute, 2 Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, Korea ABSTRACT ObjectiveThe object of this study was to assess the accuracy of dipyridamole stress intravenous IV myocardial contrast echocardiography MCE using pulse inversion harmonic imaging and PESDA in the detection of perfusion defect in the patients with coronary artery disease in comparison with dipyridamole stress Tc- 99m sestamibi SPECT. MethodsTotal 46 patients 29 males, mean age 64 years old were consecutively enrolled. Patients with prior myocardial infarction were excluded. MCE and Tc-99m sestamibi SPECT were performed at the same day during rest and after 0.56 or 0.84mg/Kg dipyridamole infusion. Continuous IV infusion of PESDA 25 ml/min was administered while obtaining triggered 11end-systolic apical 2, 4 chamber and long axis views. Tc-99m sestamibi was injected 3 minutes after dipyridamole. Tc-99m sestamibi SPECT images were obtained one hour later. Coronary angiography was followed within two days in all patients. Tc-99m sestamibi SPECT images were matched to the sixteen segments of left ventricle according to American Society of Echocardiography for segmental comparison. Both images were analyzed visually. ResultsUsing coronary angiography as the standard, MCE showed overall sensitivity of 70.7%, specificity of 95.8%, positive predictive value PPV of 87.8% and negative predictive value NPVof 88.5% in the detection of coronary atherosclerosis 70% stenosis. Tc-99m sestamibi SPECT showed sensitivity of 75.6%, specificity of 98.9%, PPV of 96.8% and NPV of 90.6%. The overall concordance rate between MCE and Tc- 99m sestamibi SPECT for the detection of perfusion defects was 86.9% Cohen s kappa value 0.63 according 793

2 to the coronary territory and 86.8% Cohen s kappa value 0.55 according to segmental analysis. Conclusion Dipyridamole stress IV MCE using pulse inversion harmonic imaging and PESDA is feasible and comparable to Tc-99m sestamibi SPECT in identifying significant coronary stenosis and inducible myocardial perfusion defects in the patients with coronary artery disease. MCE using pulse inversion harmonic imaging seems to be a promising modality for assessing myocardial perfusion in the patients with suspected coronary artery disease. Korean Circulation J 2000;307: KEY WORDSCoronary artery disease Myocardial contrast echocardiography PESDA Tc-99m sesta- MIBI SPECT Pulse inversion harmonic imaging. 서론 재료및방법 대상 794 Korean Circulation J 2000;307:

3 PESDA 제조 심근조영심초음파와 Tc-99m sestamibi SPECT 영상의획득 Fig. 1. A single-day protocol of MCE and Tc-99m sestamibi SPECT. 795

4 관상동맥조영술 영상자료분석 796 결과분석및통계처리 결과 대상환자의임상적특성 Table 1. Baseline characteristics of enrolled patients Age year 648 Male 29 63% Stable angina 13 28% Unstable angina 15 33% Vasospastic angina 8 17 Atypical chest pain 7 15 Left ventricular ejection fraction % 6220 Risk factors Diabetes 18 38% Hypertension 23 50% Smoking 26 56% Coronary angiography 1 VD % 2 VD % 3 VD % Near normal/minimal disease % Korean Circulation J 2000;307:

5 Table 2. Overall accuracy of myocardial contrast echocardiography and Tc-99m sestamibi SPECT in the diagnosis of coronary artery stenosis Sensitivity Specificity PPV NPV MCE 29/ % 93/ % 29/ % 93/ % SPECT 31/ % 96/ % 31/ % 96/ % MCEmyocardial echocardiography SPECTTc-99m sestamibi single photon emission tomography PPVpositive predictive value NPVnegative predictive value Table 3. Sensitivity and specificity of MCE in the diagnosis of coronary artery stenosis according to the vascular territory LAD LCA RCA Sensitivity 15/ % 7/ % 7/ % Specificity 23/ % 35/ % 35/ % LADleft anterior descending artery LCAleft circumflex artery RCAright coronary artery Table 4. Sensitivity and specificity of Tc-99m sestamibi SPECT in the diagnosis of coronary artery stenosis according to the vascular territory Sensitivity 16/2080.0% LAD LCA RCA 7/1070.0% 8/1172.7% Specificity 26/26100% 24/24100% 33/3594.2% LADleft anterior descending artery LCAleft circumflex artery RCAright coronary artery 관상동맥영역별분석 Fig. 2. Observed agreement on the detection of perfusion defects between two modalities according to the vascular territory.the index of choice for measurement of observed agreement in nominal or existential scale which corrects for agreement expected by chance. 심근분절별분석 797

Fig. 3. An example of normal perfusion before and after dipyridamole stress.

현기증이 12예(26%) 모두 정상소견이었던 환자가 22명으로 두 검사법의 진 로 가장 많았으며, 심전도 변화를 동반하지 않은 일시 단 일치율은 82.6%(κ 0.64)였다(Fig. 6).

두통 전반적인 정확도 관상동맥 내경 협착이 70% 이상인 경우를 의미 있 과 흉통 등 dipyridamole에 의한 부작용과 투여된 dipyridamole의 용량은 상관관계가 없었다.

6%, 특이도는 98.9%, 양성예측도는 96.8%, 음성예측도는 90.6%였다(Fig. 7).

6 Fig. 3. An example of normal perfusion before and after dipyridamole stress. 환자별 분석 검사에 따른 부작용 심근조영 심초음파검사와 Tc-99m sestamibi SPECT PESDA에 의한 부작용은 관찰되지 않았으며, dipy- 두 검사에서 모두 관류결손을 보인 환자는 16명, 두 검사 ridamole 투여 후 경한 두통 및 현기증이 12예(26%) 모두 정상소견이었던 환자가 22명으로 두 검사법의 진 로 가장 많았으며, 심전도 변화를 동반하지 않은 일시 단 일치율은 82.6%(κ 0.64)였다(Fig. 6). 적인 흉통 4예, 그리고 복통을 호소한 경우가 1예 있었 으나 검사를 중단할 정도로 심한 경우는 없었다. 두통 전반적인 정확도 관상동맥 내경 협착이 70% 이상인 경우를 의미 있 과 흉통 등 dipyridamole에 의한 부작용과 투여된 dipyridamole의 용량은 상관관계가 없었다. 는 관상동맥 협착증으로 정의하였을 때 이를 발견할 수 있는 심근조영 심초음파검사의 민감도는 70.7%, 특이도 고 찰 는 95.8%, 양성예측도는 87.8%, 음성예측도는 88.5% 였으며, Tc-99m sestamibi SPECT의 민감도는 75.6%, 특이도는 98.9%, 양성예측도는 96.8%, 음성예측도는 90.6%였다(Fig. 7). 심근조영 심초음파검사와 Tc-99m sestamibi SPECT 심근관류를 평가하는 방법에서 심근조영 심초음파검 사와 방사성 동위원소를 이용한 Tc-99m sestamibi SPECT는 그 기전에 있어 몇 가지 다른점이 있다. 먼 관찰자간 진단 일치률(interobserver agreement) 저 이들은 심근에서 분포 위치가 다르다. 심근조영 초 심근조영 심초음파검사의 관류결손 진단에 있어 진 음파검사에 사용되는 PESDA와 같은 미세기포는 미세 단 일치률은 관상동맥 영역별 분석에서 97.8%, 심근 혈관 내에만 분포하며 세포간질이나 심근세포 내부로 분절별 분석에서 97.6%, 그리고 각 환자별 분석에서 이동하지 않는다.14) 따라서 PESDA는 미세혈관 내에 92.6%였다. 서 적혈구와 동일하게 행동하며 미세혈관기능의 온전 798 Korean Circulation J 2000;30(7):

anterior descending artery after dipyridamole stress (middle) compared to

The simultaneous Tc-99m sestamibi SPECT showed apical and septal perfusion

Tc-99m sestamibi SPECT의 경우 공간해상도(spatial resolution) 가 낮아 좌심실 벽의 두께가 얇아지거나

16) 실제로 좌심실 벽운동이상이 있으면서 심근조영 초음파검사에서 관류결손을 보인 경우에 SPECT와 진 단일치율이 높게 보고된 예가

있다. 동위원소 스캔은 주로 인접한 연부 조직때문에 발생하는 약화현상(attenuation)에 의한 위양성이지만,18) 심근조영

영 상야에 일정하게 전달되지 못하는 물리적인 특성, 미세기 포의 파괴 등에 의해 발생한다.

7 Fig. 4. Note the newly developed perfusion defects atthe territory of the left anterior descending artery after dipyridamole stress (middle) compared to the rest image (left). The simultaneous Tc-99m sestamibi SPECT showed apical and septal perfusion defects that were identical with those of MCE. 다른점은 두 검사법의 영상특성에 있다. Tc-99m sestamibi SPECT의 경우 공간해상도(spatial resolution) 가 낮아 좌심실 벽의 두께가 얇아지거나 수축기에 좌심 실 벽 운동장애가 있을 경우 관류결손이 과장되게 나타 난다.16) 실제로 좌심실 벽운동이상이 있으면서 심근조영 초음파검사에서 관류결손을 보인 경우에 SPECT와 진 단일치율이 높게 보고된 예가 있다.17) 두 검사법 모두 여 러 가지 원인에 의한 위양성(false defect)이 있을 수 있 는데 그 원인에 있어서는 차이가 있다. 동위원소 스캔은 주로 인접한 연부 조직때문에 발생하는 약화현상(attenuation)에 의한 위양성이지만,18) 심근조영 심초음파검사는 부적절한 초음파신호의 획득(gain), 초음파의 약화현상 (attenuation), 탐촉자에서 송신하는 초음파의 강도가 영 상야에 일정하게 전달되지 못하는 물리적인 특성, 미세기 포의 파괴 등에 의해 발생한다.19) 따라서 이러한 두 검사 법 사이의 근본적인 기전의 차이에 의해서 서로 다른 결과 를 보일 수 있어 그 결과가 일치하지 않을 수 있다. 성을 반영하는 반면,6) Tc-99m sestamibi는 미세혈관 외부로 확산되며 심근의 관류량에 비례하여 심근세포의 심근조영 심초음파검사와 Tc-99m sestamibi SPECT의 세포막을 통과한 후 세포내의 미토콘드리아에 축적되므 일치율 로15) 심근세포막의 온전성과 대사기능을 반영한다. 또 정맥 내 미세기포 주사후 시행한 심근조영초음파검 799

8 Fig. 5. Observed agreement on the detection of perfusion defects between two modalities according to the myocardial segment. Fig. 6. Observed agreement on the detection of perfusion defects between two modalities according to the patient. Fig. 7. Overall sensitivity, specificity, positive and negative values of two modalities are depicted. 800 Pulse Inversion Harmonic Imaging을이용한심근조영심초음파검사의가능성과진단정확도 Korean Circulation J 2000;307:

9 본연구의제한점 연구목적 : 요약 방법 : 결과 : 결론 : 중심단어 REFERENCES 1) Kaul S, Newell JB, Chesler DA, Pohost GM, Okada RD, Guiney TE, et al. Value of computer analysis of exercise thallium images in the noninvasive detection of coronary artery disease. JAMA 1996;225: ) Kaul S, Finkelstein DM, Homma S, Leavitt M, Okada RD, Boucher CA. Superiority of exercise thallium-201 variables in determining long-term prognosis in ambulatory patients with chest pain a comparison with cardiac catheterization. J Am Coll Cardiol 1988;12: ) Kaul S. Contrast echocardiography and myocardial perfusion. Clin Cardiol 1991;14:V ) Wei K, Sky a DM, Firchke C, Lindner JR, Jayaweera 801

10 AR, Kaul S. Interaction between microbubbles and ultrasound: in vitro and in vivo observations. J Am Coll Cardiol 1997;29: ) Vernon S, Kaul S, Powere ER, Camarano Gustavo, Lawrence WG. Myocardial viability in patients with chronic artery disease and previous myocardial infarction: Comparison of myocardial contrast echocardiography and perfusion scintigraphy. Am Heart J 1997;134: ) Kaul S, Force T. Assessment of myocardial perfusion with contrast two-dimensional echocardiography In: Weyman AE, ed. Principles and practice of Echocardiography. 2nd ed. Pennsylvania Lea & Febiger1993. p ) Ito H, Tomooka T, Sakai N, Yu H, Higashino Y, Fujii K, et al. Lack of myocardial perfusion immediately after successful thrombolysis: a predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation 1992;85: ) Villanueva FS, Spotnitz WD, Jayaweera AR, Gimple LW, Dent J, Kaul S. On-line intraoperative quantitation of regional myocardial perfusion during coronary artery bypass graft operations with myocardial contrast twodimensional echocardiography. J Thorac Cardiovasc Surg 1992;104: ) Skyba DM, Camarano G, Goodman NC, Price RJ, Skalak TC, Kaul S. Hemodynamic characteristics, myocardial kinetics, and microvascular rheology of FS-069, a second generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection. J Am Coll Cardiol 1996;28: ) Porter TR, Xie F. Transient myocardial contrast after initial exposure to diagnostic ultrasound pressures with minute doses of intravenously injected microbubbles: demonstration and potential mechanisms. Circulation 1995;92: ) Vannan MA, Burns PN, Simpson DH, Averkiou M. Pulse inversion detection, an improved method for myocardial contrast echocardiography: experimental studies and preliminary clinical experience. Circulation 1998;98suppl 1: ) Porter TR, Xie F, Kricsfeld D, Armbruster RW. Improved myocardial contrast with second harmonic transient ultrasound contrast response imaging in humans using intravenous perfluorocarbon-exposed sonicated dextrose albumin. J Am Coll Cardiol 1996;27: ) Kramer MS, Feinstein AR. Clinical biostatistics: the biostatistics of concordance. Clin Pharmacol Ther 1981; 29: ) Keller MW, Segal SS, Kaul S, Duling B. The behavior of sonicated albumin microbubbles within the microcirculation: a basis for their use during myocardial contrast echocardiography. Circ Res 1989;65: ) Dahlberg ST, Leppo JV. Physiologic properties of myocardial perfusion tracers. Cardiol Clin 1994;12: ) Parodi P, Schelbert HR, Schwaiger M. Cardiac emission computed tomography: underestimation of regional tracer concentrations due to wall motion abnormalities. J Comput Assist Tomogr 1984;8: ) Marwick TH, Brunken R, Meland N, Brochet E, Baker FM, Binder T, et al. Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice. Comparison with wall motion and Tc-99m sestamibi SPECT, J Am Coll Cardiol 1998;32: ) DePeuy EG, Garcia EV. Optimal specificity of thallium- 201 SPECT through recognition of imaging artifacts. J Nucl Med 1989;30: ) Bach DS, Muller DW, Cheirif J, Armstrong WF. Regional heterogeneity in myocardial contrast echocardiography without severe obstructive coronary artery disease. Am J Cardiol 1995;75: ) Meza MF, Mobarek S, Sonnemaker R, Shuler S, Ramee SR, Collins TJ, et al. Myocardial contrast echocardiography in human beings: Correlation of resting perfusion defects to sestamibi single photon emission computed tomography. Am Heart J 1996;132: ) Kaul S, Roxy SR, Dittrich H, Raval U, Khattar Raj, Lahiri A. Detection of coronary artery disease with myocardial contrast echocardiography: Comparison with Tc- 99m sestamibi single-photon emission computed tomography. Circulation 1997;92: ) Nagueh SF, Vaduganathan P, Ali N, Blaustein A, Verani MS, et al. Identification of hibernating myocardium: Comparative accuracy of myocardial contrast echocardiography, rest-redistribution thallium-201 tomography and dobutamine echocardiography. J Am Coll Cardiol 1997; 29: ) Sharir T, Rabinowitz b, Livschitz S, Moalem I, Baron J, Kaplinsky E, et al. Underestimation of extent and severity of coronary artery disease by dipyridamole stress thallium- 201 singlephoton emission computed tomographic myocardial perfusion imaging in patients taking antianginal drugs. J Am Coll Cardiol 1998;31: ) Becher H, Tiemann K, Schlief R, Nanda NC. Harmonic power Doppler contrast echocardiography: Preliminary clinical results. Echocardiography 1997;14: ) Heinle SK, Noblin J, Goree-Best P, Mello A, Ravad G, Mull S, et al. Assessment of myocardial perfusion by harmonic power Doppler imaging at rest and during adenosine stress. Comparison with 99mTc-Sestamibi SPECT imaging. Circulation 2000;102: Korean Circulation J 2000;307:

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