Original Artices Korean Circulation J 2002;329:756-765 급성심근경색증에서중재시술후관동맥혈류예비력과 예후와의관계 윤명호 탁승제 최소연 염철훈 최태영장혁재 황교승 신준한 김한수 최병일 Coronary Flow Reserve as a Predictor of Long-Term Clinical Outcome after Acute Myocardial Infarction Myeong-Ho Yoon, MD, Seung-Jea Tahk, MD, So-Yeon Choi, MD, Zhe-Xun Lian, MD, Tae-Young Choi, MD, Hyuk-Jae Jang, MD, Gyo-Seung Hwang, MD, Joon-Han Shin, MD, Han-Soo Kim, MD and Byung-Il W. Choi, MD Department of Cardiology, College of Medicine, Ajou University, Suwon, Korea ABSTRACT Background and ObjectivesIt has been shown that the coronary flow reserve CFR of an infarct related artery can predict left ventricular functional recovery following acute myocardial infarction AMI. However, the prognostic value of CFR on the long-term clinical outcome of patients with an AMI has not been studied. Subjects and MethodsUsing a Doppler guide wire, we measured the CFR in 130 patients with an AMI following successful intervention 63 days after onset of the AMI. Two-year follow-up was conducted with regard to end points, includingcardiac death, non-fatal AMI, and severe congestive heart failure CHF NYHA III. ResultsDuring the follow-ups, occurred in 17 patients 5 deaths, 3 non-fatal AMIs and 9 severe CHFs. After analysis of the receiver operating characteristic curves, the best cut-off value for CFR in predicting was 1.4 sensitivity 76.5%, specificity 73.5%, accuracy 82.0%. With as an end point, a 2-year Kaplan-Meier event survival analysis revealed that the patients with a CFR1.4 had a worse prognosis than those with a CFR1.4 Event free survival rates were 69.8% vs. 95.4%, respectively, p0.001). Using Cox proportional hazard analyses, as an independent predictor, age, heart rate, CFR and left ventricular end systolic volume index, were also found to be significantly associated with cardiac events hazard ratios 1.1224, 1.0404, 0.1887, and 1.0588, respectively. ConclusionThe coronary flow reserve, of infarct related arteries, measured during the early recovery phase can be used as an independent predictor for the prognosis of patients with an acute myocardial infarction following successful intervention. Korean Circulation J 2002;329:756-765 KEY WORDSCoronary circulationmyocardial infarction. 756
서론 - - - 대상및방법 대상환자 방법 - 757
- - - 결과 대상환자의임상적특성 추적기간중심장관련주요사건의발생 심장관련주요사건발생의예측인자 - 758 Korean Circulation J 2002;329:756-765
Table 1. Comparison of patients characteristics between group with major and group without major Group without major n113 Group with major cardiac events n17 Age year 53.510.6 66.110.6 0.001 Gender MF 9320 125 0.319 Heart rate beatmin 00760013 00910015 0.001 Risk factor Hypertension, n % 38 33.6 07 41.2 0.589 DM, n % 26 23.0 08 47.1 0.071 Dyslipidemia, n % 38 33.6 09 52.9 0.175 Smoking, n % 77 70.6 13 76.5 0.583 Lipid profile T.Chol mgdl 02070050 02230049 0.221 TG mgdl 01870155 02240164 0.414 LDL mgdl 01290043 01360030 0.632 HDL mgdl 00420014 00410007 0.823 CK IUL 36042952 35232127 0.937 CK-MB ngml 02520276 03530228 0.300 Killip class, n % I 93 82.3 11 64.7 II 07 14.2 04 23.5 III 04 03.5 02 11.8 IV 0 012.2 00 0 00 TPA, n % 62 54.9 10 58.8 0.800 -blocker, n % 56 49.6 05 29.4 0.192 Calcium blockers, n % 31 27.4 05 29.4 1.000 ACE inhibitors, n % 69 61.1 12 70.6 0.594 DMdiabetes mellitus, T.Choltotal cholesterol, TGtriglyceride, LDLlow density lipoprotein cholesterol, HDL high density lipoprotein cholesterol, CKcreatine kinase, CK-MBcreatine kinase-myocardial band, tpatissue type plasminogen inhibitor, ACEangiotensin converting enzyme p - 관동맥혈류예비력과심장관련주요사건의발생과의관계 - 759
Table 2. Comparison of angiographic findings between group with major and group without major Group without major Group with major Intervention, n % 0.888 Stent 68 60% 10 59% Balloom 28 28% 5 29% No need intervention 17 15% 2 12% Infarct related artery, n % 0.440 LAD 74 65.5 12 70.6 LCx 10 08.8 00 0 00 RCA 29 25.7 05 29.4 Vessel disease severity, n % 0.443 Nomal-minimal 16 14.2 02 11.8 1VD 75 66.4 10 58.8 2VD 17 15.0 05 29.4 3VD 05 04.4 00 0 00 Major side branch, n % 09 8 0.. 03 17.6 0.193 Lesion length mm 13.8006.00 14.2008.70 0.820 Diffuse 20mm, n % 99 87.6 15 88.2 1.000 Pre-intervention MLD mm 00.7600.56 00.4600.46 0.068 DS % 76.6015.60 85.7014.20 0.053 Post-intervention MLD mm 02.9000.66 02.8000.85 0.626 DS % 10.7112.80 12.8020.00 0.640 RVD mm 03.2500.51 03.1800.46 0.626 LADleft anterior descending artery, LCxleft circumflex artery, RCAright coronary artery, VDvessel disease, MLDminimal lumen diameter, DSdiameter stenosis, RVDreference vessel diameter p Table 3. Comparison of echocardiographic findings between group without major and group with major Group without major Group with major P LVEDVImLm 2 43.7015.00 53.4017.20 0.016 LVESVImLm 2 21.00 9.90 31.3012.90 0.001 EF% 51.80 9.40 43.00 8.70 0.001 WMSI 01.5200.30 01.6400.25 0.110 LVEDVIleft ventricular end diastolic volume index, LVESVIleft ventricular end systolic volume index, EFejection fraction, WMSIwall motion score index 고찰 760 Korean Circulation J 2002;329:756-765
Table 4. Comparison of coronary flow velocity index in group without major and group with major Baseline Group without Group with major Major cardiac cardiacevents events APVcm/sec 21.0010.00 22.3009.70 0.621 DSVR 02.6002.80 02.2002.10 0.631 Hyperemic APVcm/sec 39.3018.70 29.7013.80 0.044 DSVR 02.0002.00 01.8000.90 0.636 CFR 01.9500.61 01.3300.34 0.001 APVaveraged peak velocity, DSVRdiastolic systolic velocity ratio, CFRcoronary flow reserve p Fig. 1. Comparison of coronary flow reserve between group without major and group with major. Fig. 2. Receiver operating characteristic curve analysis of CFR for major. CFRcoronary flow reserve, AUCarea under the curve. Table 5. Comparison of predictors of major cardiac event between group without major and group with major Group without major Group with major Univariate Cox proportional hazard analysis p Hazard ratio P Age 5311 6611 0.001 1.1217 0.0002 HR 7613 9115 0.001 1.0408 0.0348 HAPV cmsec 39.3018.70 29.7013.80 >0.044 NS CFR 01.9500.61 01.3300.34 0.001 0.1858 0.0314 LVEDVImLm 2 43.7015.00 53.4017.20 >0.016 NS LVESVImLm 2 21.0009.90 43.0008.70 0.001 1.0599 0.0028 EF % 51.8009.40 43.0008.70 0.001 NS WMSI 01.5200.30 01.6400.25 >0.110 NS DM 26113 817 >0.071 NS HRheart rate, hapvhyperemic average peak velocity, CFRcoronary flow reserve, LVEDVIleft ventricular end diastolic volume index, LVESVIleft ventricular end diastolic volume index, EFejection fraction, WMSIwall motion score index, DMdiabetes mellitus 761
Fig. 3. Kaplan-Meier survival curve of major cardiac events between CFR1.4 group and CFR1.4 group p0.0001. CFRcoronary flow reserve. Table 6. Comparison of major between CFR1.4 group and CFR1.4 group 762 CFR1.4 n43 CFR1.4 n87 Total major event,n % 13030.2% 404.6% 0.001 Death, n % 04009.3% 101.1% 0.041 Re-MI, n % 02004.7% 101.1% 0.254 CHF, n % 07016.3% 202.3% 0.006 Angina, n % 06014.0% 809.2% 0.548 CFRcoronary flow reserve, Re-MIrecurred non fatal myocardial infarction, CHFcongestive heart failure p Korean Circulation J 2002;329:756-765
요약 배경및목적 : - 방법 : - 결과 : 결론 : 중심단어 REFERENCES 1) Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction and improved survival: should the paradigm be expanded? Circulation 1989; 763
79:441-4. 2) Linderer T, Guhl B, Spielberg C, Wunderlich W, Schnitzer L, Schroder R. Effect on global and regional left ventricular function by percutaneous transluminal coronary angioplasty in the chronic stage after myocardial infarction. Am J Cardiol 1992;69:997-1002. 3) Kim CB, Braunwald E. Potential benefits of late reperfusion of infarcted myocardium: the open artery hypothesis. Circulation 1993;88:2426-36. 4) Krug A, de Rochemont WM, Korb G. Blood supply of the myocardium after temporary coronary occlusion. Circ Res 1966; 19:57-62. 5) Kloner RA, Ganote CE, Jennings RB. The no reflow phenomenon after temporary coronary occlusion in dog. J Clin Invest 1974;54:1496-508. 6) Willerson JT, Watson JT, Hutton I, Templeton GH, Fixler DE. Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog. Circ Res 1975;36:771-81. 7) Ito H, Tomooka T, Sakai N, Yu H, Higashino Y, Fujii K, Masuyama T, Kitabatake A, Minamino T. Lack of myocardial perfusion immediately after successful thrombolysis: a predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation 1992;85:1699-705. 8) Ito H, Maruyama A, Iwakura K, Takiuchi S, Masuyama T, Hori M, Higashino Y, Fujii K, Minamino T. Clinical implication of no reflow phenomenon: a predictor of complication and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 1996;93:223-8. 9) Ragosta M, Camarano G, Kaul S, Powers ER, Sarembock IJ, Gimple LW. Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction: new insights using myocardial contrast echocardiography. Circulation 1994;89:2562-9. 10) Przyklenk K, Kloner RA. Reperfusion injury by oxygenderived free radicals?: effect of superoxide dismutase plus catalase, given at the time of reperfusion, on myocardial infarct size, contractile function, coronary microvasculature, and regional myocardial blood flow. Circ Res 1989; 64:86-96. 11) Claeys MJ, Bosmans J, Veenstra L, Jorens P, de Raedt H, Vrints CJ. Determinants and prognostic implications of persistent ST-segment elevation after angioplasty for acute myocardial infarction: importance of microvascular reperfusion injury on clinical outcome. Circulation 1999;99:1972-7. 12) Iliceto S, Galiuto L, Marchese A, Colonna P, Oliva S, Rizzon P. Functional role of microvascular integrity in patients with infarct-related artery patency after acute myocardial infarction. Eur Heart J 1997;18:618-24. 13) Pierard LA, de Landsheere CM, Berthe C, Rigo P, Kulbertus HE. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coll Cardiol 1990;15: 1021-31. 14) Barilla F, Gheorghiade M, Alam M, Khaja F, Goldstein S. Low-dose dobutamine in patients with acute myocardial infarction identifies viable but not contractile myocardium and predicts the magnitude of improvement in wall motion abnormalities in response to coronary revascularization. Am Heart J 1991;122:1522-31. 15) Lepper W, Hoffmann R, Kamp O, Franke A, de Cock CC, Kuhl HP, Sieswerda GT, Dahl J, Janssens U, Voci P, Visser CA, Hanrath P. Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary transluminal coronary angiography in patients with acute myocardial infarction Circulation 2000;101:2368-74. 16) Sakuma T, Hayashi Y, Sumii K, Imazu M, Yamakido M. Prediction of short-and intermediate- term prognosis of patients with acute myocardial infarction using myocardial contrast echocardiography one day after recanalization. J Am Coll Cardiol 1998;32:890-7. 17) Ahn JC, Lim DS, Oh YJ, Lee HJ, Shin SH, Lee EM, Hwang GS, Song WH, Park CG, Kim YH, Seo HS, Shim WJ, Oh DJ, Ro YM. Relation between coronary flow reserve and myocardial perfusion state and changes of coronary flow reserve in acute myocardial infarction. Korean Circ J 1999; 29:1289-96. 18) Teiger E, Garot J, Aptecar E, Bosio P, Woscoboinik J, Pernes JM, Gueret P, Kern M, Dubois-Rande JL, Dupouy P. Coronary blood flow reserve and wall motion recovery in patients undergoing angioplasty for myocardial infarction. Eur Heart J 1999;20:285-92. 19) Tahk SJ, Yoon MH, Shin JH, Lian ZX, Choi SY, Chang HJ, Kim HS, Choi BI. Coronary flow velocity reserve as a predictor of left ventricular volume and functional change after acute myocardial infarction Abstr. J Am Coll Cardiol 2001; 37Number 2 Suppl A 357A. 20) The Global Use of Strategies to Open Occluded Coronary Arteries GUSTO IIIInvestigators. A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med 1997;337:1118-23. 21) Assessment of the Safety and Efficacy of a New Thrombolytic ASSENT-2 Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomized trial. Lancet 1999;354:716-22. 22) Stack RS, Phillips HR 3rd, Grierson DS, Behar VS, Kong Y, Peter RH, Swain JL, Greenfield JC Jr. Functional improvement of jeopardized myocardium following intracoronary streptokinase infusion in acute myocardial infarction. J Clin Invest 1983;72:84-95. 23) Erlebacher JA, Weiss JL, Weisfeldt ML, Bulkley BH. Early dilatation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute ventricular enlargement. J Am Coll Cardiol 1984;4:201-8. 24) Gaudron P, Eillis C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction: potential mechanisms and early predictors. Circulation 1993;87:755-63. 25) Hochman JS, Choo H. Limitation of myocardial infarct expansion by reperfusion independent of myocardial salvage. Circulation 1987;75:299-306. 26) Reimer KA, Tanaka M, Murry CE, Richard VJ, Jennings RB. Evaluation of free radical injury in myocardium. Toxicol Pathol 1990;18:470-80. 27) Kloner R, Rude R, Carlson N, Maroko P, DeBoer LW, Braunwald E. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation 1980;62:945-52. 764 Korean Circulation J 2002;329:756-765
28) Kloner RA, Giacomelli F, Alker KJ, Hale SL, Matthews R, Bellows S. Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion. Circulation 1991;84:1758-72. 29) Iwakura K, Ito H, Taniyama Y, Takiuchi Y, Nakatsuchi Y, Negro S, Higashino Y, Okamura A, Masuyama T, Hori M, Fujii K, Minamino T. Alteration in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction. Circulation 1996;94:1269-75. 30) Mazur W, Bitar JN, Lechin M, Grinstead WC, Khalil AA, Khan MM, Sekili S, Zoghbi WA, Reizner AE, Kleiman NS. Coroanry flow reserve may predict myocardial recovery after myocardial infarction in patients with TIMI grade 3 flow. Am Heart J 1998;136:335-44. 765