JACC Vol. 26, No. 3 675 ST Segment Trackng for Rapd Determnaton of Patency of the nfarct-related Artery n Acute Myocardal nfarcton ALAND R. FERNANDEZ, MD, RAFAEL F. SEQUERA, MD, FRCP, FACC, SMON CHAKKO, MD, FACC, LUS F. CORREA, MD, EDUARDO J. DE MARCHENA, MD, FACC, ROBERT A. CHAHNE, MD, FACC, DENSE A. FRANCEOUR, RN, ROBERT J. MYERBURG, MD, FACC Mam, Florda Objectves. Ths study was desgned to test the hypothess that montorng the ST segment on a sngle electrocardographc (ECG) lead reflectng actvty n the nfarct zone provdes senstve and specfc recognton of reperfuson wthn 60 ran of ntaton of therapy n acute myocardal nfarcton. Background. nfarct-related arteres that fal to recanalze early may beneft from mmedate rescue angoplasty. Hence, detecton of reperfuson has mportant practcal clncal mplcatons. Methods. Of 41 patents wth acute myocardal nfarcton who had ambulatory ECG (Holter) montors placed, 38 had adequate ST segment montorng for 3 h; 35 of the 38 were treated wth thrombolytc agents and 3 wth prmary angoplasty. All patents underwent early coronary angography and were classfed nto two groups: Group P (22 patents) had angographc patency (Thrombolyss n Myocardal nfarcton [TM] grade 2 or 3 flow), and Group O (16 patents) had persstent occluson (TM grade 0 or 1 flow) of the nfarct-related vessel at 60 mn from ntaton of therapy. The ntal ST segment level was defned as the frst ST segment level recorded; thepeak ST segment level was defned as the hghest ST segment level measured durng the 1st 60 mn. To assess the optmal ST segment recovery crtera for reperfuson, the presence or absence of a >75%, >50% and >25% decrement from ntal and peak ST segment levels, sampled and analyzed at 2.5-, 5-, 10-, 15- and 20-mn ntervals, was correlated wth patency of the nfarctrelated artery at 60 ran. Results. ST segment recovery of >50% reducton from peak ST segment levels wth samplng rates at < 10-mn ntervals provded the optmal crteron for recognzng coronary artery patency at 60 mn (senstvty 96%, 95% confdence nterval [C] 77% to 99%; specfcty 94%, 95% C 69% to 99%, p < 0.00001). The subgroup of 13 patents n Group P wth TM grade 3 reperfuson flow all met ths crteron (senstvty 100%, 95% C 75% to 100%). The use of the ntal ST segment level as the baselne for determnng the presence of a >50% reducton n ST segment levels wthn 60 mn was less senstve. Predcton of coronary reperfuson wthn 60 ran of therapy on the bass of a >75% decrement from peak ST segment levels was less senstve, and the use of a >25% decrement was less specfc. Conclusons. ST segment montorng of a sngle lead reflectng the nfarct zone provdes a relable method for assessng reperfuson wthn 60 ran of acute myocardal nfarcton. Optmal crtera for ECG reperfuson nclude a >50% decrease from peak ST segment levels, wth ST segment measurements recorded contnuously or at least every 10 mn. (J Am CoU Cardol 1995;26:675-83) The prompt restoraton of coronary artery patency n acute myocardal nfarcton has been lnked to a marked mprovement n survval (1-4). However, n 15% to 25% of patents treated wth thrombolytc agents, the nfarct-related artery fals to recanalze, and further nterventons such as mmedate rescue angoplasty may be of beneft (5-7). Unfortunately, the methods avalable for rapd and accurate detecton of faled thrombolyss are lmted. Assessment of clncal varables can be used but s mperfect. Early coronary angography s accurate but costly, s unavalable n many hosptals and may lead to From the Dvson of Cardology, Department of Medcne, Unversty of Mam School of Medcne, Mam, Florda. Manuscrpt receved July 14, 1994; revsed manuscrpt receved March 13, 1995, accepted Aprl 7, 1995. Address for correspondence: Dr. Rafael F. Sequera, Unversty of Mam School of Medcne, Jackson Memoral Hosptal, Cardovascular Laboratory., 161l NW 12th Avenue, Mam, Florda 33136. complcatons. n addton, t does not provde contnuous assessment of the dynamc changes n perfuson that occur after thrombolyss (8). Hence, there s a need for smple, nonnvasve markers that promptly dentfy faled reperfuson and contnuously montor the patency of the nfarct-related vessel. The role of the electrocardogram (ECG) n the recognton of successful thrombolyss n acute myocardal nfarcton s controversal. Prevous studes (9-21) have reported conflctng data on the value of ST segment montorng n predctng coronary artery patency. Possble explanatons for these dvergng results nclude the use of the ntal ST segment level as the baselne for measurng changes reflectng reperfuson, a lack of unform ECG crtera of reperfuson, varable samplng rates for ST segment level measurements and lack of angographc correlaton at the tme of ECG analyss. The am of the present study was to defne the optmal methodology, verfed by coronary angography, for the accurate dentfcaton of (~)1995 by the Amercan College of Cardology (/735-1097/95/$9.50 0735-1097(95)0(120S-L
676 FERNANDEZ ET AL. JACC Vol. 26, No. 3 ST SEGMENT MONTORNG N ACUTE MYOCARDAl_ NFAR('TON reperfuson wthn 60 mn of ntaton of treatment n acute myocardal nfarcton. The study was desgned to test the hypothess that contnuous ST segment montorng of a sngle selected lead and a specfc ECG crteron for reperfuson-- namely, a ->50% reducton from the peak ST segment level-- provdes a senstve and specfc marker of the tme of reperfuson. The ratonale for trackng ST segment devatons from the peak ST segment level s based on the observaton that ST segment fluctuatons are unstable durng the evoluton of acute myocardal nfarcton and, therefore, the ntal ST level s an unrelable baselne (8). The feasblty of the study derved from our partcpaton n the Thrombolyss n Myocardal nfarcton (TM)-4 thrombolytc tral (22), whch provded the justfcaton for acute angographc assessment of the perfuson status of the nfarct-related artery. The data demonstrate the valdty of the method tested, as well as some lmtatons, based on the ECG response to schema and reperfuson. Methods Patent selecton. Forty-one consecutve patents admtted to the Unversty of Mam/Jackson Memoral Hosptal were prospectvely enrolled n a study of contnuous ST segment montorng durng treatment of acute myocardal nfarcton. Thrty-eght patents were enrolled n the TM-4 thrombolytc tral (22) and 3 patents were treated wth prmary angoplasty because of contrandcatons to thrombolytc therapy. Patents were ncluded f they had symptoms of myocardal schema lastng ->30 ran and -<6 h, and ST segment elevaton ->1 mm n at least two contguous EGG leads. Excluson crtera ncluded age >79 years and the presence of left bundle branch block on the admsson ECG. The study was approved by the nsttutonal Revew Board of the Unversty of Mam School of Medcne and all patents gave wrtten nformed consent. Thrombolytc protocol. Patents elgble for thrombolytc therapy were randomzed n the TM-4 protocol to one of the followng regmens: 1) accelerated alteplase (Actvase), n a bolus dose of 15 mg followed by 0.75 mg/kg body weght over a 30-ran perod, not to exceed 50 rag, and 0.5 mg/kg, up to 35 rag, over the next 60 ran; 2) anstreplase (Emnase), 30 U over 2 to 5 ran; or 3) the combnaton of Emnase, 20 U bolus over 2 to 5 mn, and Actvase, 15 mg bolus followed by 0.75 mg/kg up to 50 mg over 3( ran. All patents were gven oral asprn, 325 rag, and ntravenous heparn. ntravenous metoprolol (15 mg dvded over three doses) was admnstered unless ts use was contrandcated. nvasve protocol. All patents underwent early cardac catheterzaton. The tme of ntaton of therapy was defned as the tme of admnstraton of thrombolytc therapy or 60 ran before balloon nflaton n those undergong prmary angoplasty. All tmes were measured from the tme of ntaton of therapy. Coronary,' angography was performed wthn 60 ran n all patents, and seral angograms of the nfarct-related vessel were obtaned at 15-ran ntervals thereafter to a maxmum of 120 ran. The TM crtera (23) were used for gradng the perfuson of the nfarct-related artery. Patency was defned as TM grade 2 or 3 flow. nfarct-related arteres wth TM grade 0 or 1 flow were consdered occluded. nfarct-related vessels wth angographc occluson >90 mn from the onset of thrombolytc therapy were consdered for rescue angoplasty. Patents wth contrandcatons to thrombolytc therapy underwent prmary, angoplasty mmedately after coronary angography. Coronary angograms were revewed at separate research stes (Beth srael Hosptal, Boston, Massachusetts and Unversty of Mam, Mam, Florda) by ndependent observers who had no knowledge of the ECG data, to control for nterobserver varablty n the assessment of nfarct-vessel perfuson. Duraton of chest pan. All patents were asked at 10- to 15-ran ntervals, by a research nurse who had no knowledge of the ECG data, to report the presence or absence of chest pan. The tme from ntaton of therapy to resoluton of chest pan was correlated wth the angographc patency of the nfarctrelated vessel at 60 ran. ST segment montorng. Ambulatory ECG (Holter) montors wth three channels were placed on all patents wthn _+ 10 mn of ntaton of therapy, and contnuous ST segment montorng was performed. The bpolar leads were postoned to montor the anteror, nferor or lateral wall accordng to the nfarct ste as determned from the 12-lead ECG, and the lead exhbtng the maxmal ST segment elevaton was chosen for ST segment measurements. All recordngs were calbrated and analyzed on a dgtzed, computer system (Zymed 1610). The frequency response of the recordng system for ST segment measurements met the recommendatons of the Amercan Heart Assocaton (24). The soelectrc pont was set as the precedng PR segment. Computer-derved and manuallyverfed ST segment measurements were obtaned 80 ms after the J pont every 2.5 ran for 3 h and the mean ST segment level of fve complexes was recorded. Ventrcular ectopc beats were excluded from analyss. The ntal ST segment level was defned as the frst ST segment level (ram) recorded; the peak ST segment level was defned as the hghest ST segment clevaton (mm) measured n the 1st 60 ran. To assess the optmal crtera for dagnosng reperfuson, a ->75%, ->50% and ->25% decrement from ntal and peak ST segment levels wthn 60 ran of ntaton of therapy, ST recovery was correlated wth patency of the nfarct-related artery at 60 ran. The tme to ST recovery was defned as the tme at whch the percent ST change crteron was met wth the qualfcaton that the ST segment levels dd not ncrease by >10% n the ensung l0 ran. ST level samplng rates (2.5-, 5-, 10-, 15- and 20-ran ntervals) were analyzed to determne the mnmal frequency of ST segment samplng requred for prompt recognton of coronary reperfuson. Statstcal analyss. Data are expressed as mean value _+ SD. Statstcal analyss was performed wth commercally avalable software (Graphpad-nstat). Dfferences between groups were examned by Student unpared t test. The 95% confdence ntervals (C) for proportons were calculated by standard methods. nter- and ntraobserver varabltes were analyzed by pared Student t test. The Fsher exact test was used to test
JACC Vol. 26, No. 3 FERNANDEZ ET AL. 677 ST SEGMENT MONTORNG N ACUTE MYOCARDAL NFARCTON Table 1. Baselne Clncal Features of Patents Wth Patent (Group P) and Occluded (Group O) nfarct-related Arteres at 60 Mnutes From ntaton of Therapy Group P Group O p (n 22) (n 16) Value* Age (yr) 58 -+ 13 57 _+ 10 0.7788 Prevous M 14% 19% 0.9999 Anteror M 50% 62% 0.5204 Sngle-vessel dsease 64% 38% 0.1881 *p < 0.05 consdered sgnfcant. Data are expressed as mean value _+ SD or percent of group. M = myocardal nfarcton. the correlaton between ST segment change and coronary artery patency; p values (two-taled) -<0.05 were consdered sgnfcant. Results Clncal data. Forty-one consecutve patents wth acute myocardal nfarcton were evaluated. Adequate ECG analyss was acheved n 38 patents (93%); 3 patents were excluded because of techncal falure of the recorder, ncorrect placement of leads or frequent ventrcular ectopc mpulses. Tmes to ST recovery were measured n all patents by two ndependent revewers; there were no sgnfcant nter- or ntraobserver dfferences. All patents underwent cardac catheterzaton mmedately after ntaton of therapy; angography of the nfarct-related vessel was acheved at -<40 ran n 13 patents, at 45 to 55 mn n 7 and at 60 ran n 18. The nfarct-related artery was the left anteror descendng coronary artery n 21 patents (55%), the rght coronary artery n 12 (32%) and the left crcumflex coronary artery n 5 (13%). Patents were classfed nto two groups: Group P conssted of 22 patents wth anglo- graphc patency of the nfarct-related artery at 60 ran; 13 of these had TM 3 grade flow and 9 had TM 2 grade flow. Group O ncluded 16 patents wth an occluded artery (TM grade 0 or 1 flow) at 60 mn. Baselne characterstcs were comparable n the two groups (Table 1). There were no sgnfcant nter- or ntraobserver dfferences n the assessment of angographc patency. Resoluton of chest pan. The duraton of chest pan before the ntaton of therapy (Table 2) was smlar n both groups (144 +_ 71 ran n Group P, 168 +_ 85 ran n Group O, p = 0.544). Overall, the tme from ntaton of therapy to resoluton of symptoms was shorter n Group P (44 2 24 ran) than n Group O (85 2 30 ran, p = 0.0002). Predcton of angographc patency (TM grade 2 or 3 flow) of the nfarct-related vessel, based on the presence or absence of chest pan at 60 ran (Table 3), had only lmted power (senstvty 77% [95% C 54% to 92%], specfcty 60% [95% C 38% to 83%], p = 0.038). ST segment data. No sgnfcant dfferences were found between Groups P and O n mean ntal and mean peak ST segment levels (Table 2). The mean peak ST segment level for all patents studed was sgnfcantly hgher (5.4 _+ 2.5 ram) than the mean ntal ST level (3.7 _+ 1.8 ram, p - 0.0015). Among 16 patents (42%) who had ntal ST segment levels -<3 mm (mean 2,0 + 0.7 ram), all had further ncrements n ST segment levels durng the 1st 60 ran (mean peak ST = 3.6 _+ 1.3 ram, p = 0.0001). Mean ST segment levels at 60 ran were sgnfcantly lower n Group P (1.4 _+ 1.6 ram) than n Group O (4.0 _+ 2.1 ram, p = 0.0001). Moreover, wthn Group P there was a hghly sgnfcant dfference between those wth TM grade 3 versus TM grade 2 flow (0.96 _+ 0.67 mm vs. 3.1 _+ 2.1 ram, p = 0.0008). The mean ST segment at 60 ran n patents wth TM grade 2 flow was not sgnfcantly dfferent Table 2. Salent Features of Patents Wth Patent (Group P) and Occluded (Group O) nfarct-related Arteres at 60 Mnutes From ntaton of Therapy Group P TM1 2 or 3 TM 3 TM 2 p (n = 22) (n 13) (n - 9) Group O Value* ST segment levels (mm) ntal 3.2 _+ 1.7 2.8 + 1,3 4.0 + 1.9 4.3 + 1.9 0.092 Peak 5.5 _+ 2.6 4.8 _+ 2.8 6.2 _+ 2.4 5.3 + 2.3 1.000 At 60 mn 1.4 + 1.6 0.96 _+ 0,67 3.1 _+ 2.1? 4.0 + 2.1 0.0004 At 180 mn 0.98 _+ 1.1 (.98_+ 1,2 1.2 + 0.68 2.0 _+ 1.3 0.0118 Tme (mn) From symptom onset to start of therapy 144 + 7l 136 + 65 156 _+ 81 168 + 85 0.544 From start of therapy To resoluton of symptoms 44 _+ 24 42 + 22 47 + 28 85 + 30 0.0002 To peak ST segment levels 21 + 14 19 _+ 13 25 _+ 15 30 + 22 0.1321 To ->50% decrease from ntal ST segment levels 65 + 39 39 _+ 19 94 + 39t 143 _+ 39 < 0.0001 To ->50% decrease from peak ST segment levels 40 _+ 20 30 + 15 55 +_ 15t 127 _+ 47 < 0.0001 From peak ST segment level to ts 50% level 21 _+ 16 13 + 7.7 35 +_ 15t 96 + 38 < 0.0001 Rate of declne from peak ST segment level to ts -0.21 + 0.11-0.28 +_ 0.14t 0.12 + 0.06t 0.04 + 0.01 < 0.0001 50% level (ram/ran) *p value comparng Groups P and O. [p < 0.05 comparng patents wth Thrombolyss n Myocardal nfarcton (TM) flow grades 2 and 3 at 60 ran from ntaton of therapy n Group P. Data are expressed as mean value + SD. ntal ST segment level - level of the frst ST segment recorded; Peak ST segment level - the hghest ST segment level measured n the 1st 60 mn.
678 FERNANDEZ ET AL. JACC Vol. 26, No. 3 ST SEGMENT MONTORNG N ACUTE MYOCARDAL NFARCTON Table 3. Correlaton Between Electrocardographc Markers of Reperfuson and Angographc Patency (Group P) and Occluson (Group O) of the nfarct-related Artery at 60 Mnutes From ntaton of Therapy Group P Predctve Value "M 2 or 3 TM 3 Group O Senstvty Specfcty Postve Negatve p (n 22) (n- 13) (n- 16) (%) (%) (%) (%) Value Resoluton of chest pan TM 2 or 3 17 -- 6 77 (54-92) 60 (38-83) 74 (51-89) 66 (38-88) 0.0379 TM1 3 -- 11 6 85 (54-98) 60 (32-83) 65 (38-85) 82 (48-97) 0.0237 From ntal ST segment level ->50% decrease n ST segment level TM 2 or 3 14 -- 0 64 (40-82) 100 (79-100) 100 (76-100) 67 (44-84) 0.00008 TM 3 -- 12 92 (63-99) 100 (79-100) 100 (73-100) 94 (71-99) < 0.00001 From peak ST segment level TM 2 or 3 21 -- 1 96 (77-99) 94 (69-99) 96 (77-99) 94 (69-99) < 0.00001 TM 3 -- 13 1 100 (75-100) 94(69-99) 93 (66-99) 100 (78-100) < 0.00001 >-75% decrease n ST segment level From ntal ST segment level 9 -- 0 41 (20-63) 100 (79-100) 100 (66-100) 55 (35-73) 0.00486 From peak ST segment level 12 -- 0 54 (32-75) 100 (79-100) 100 (73-100) 61 (40-79) 0.00028 >-25% decrease n ST segment level From ntal ST segment level 19 -- 6 86 (65 97) 62 (35-84) 76 (54-90) 77 (46-94) 0.00256 From peak ST segment level 22 -- 9 100 (84-100) 44 (19-70) 71 (51-85) 100 (59-100) 0.00091 For selected markers, data for patents who acheved TM1 grade 2 or 3 flow and TM grade 3 flow are compared wth data n Group O. The 95% confdence ntervals are n parentheses. Unless otherwse ndcated, data are expressed as number of patents. Abbrevatons as n Table 2. from that n patents wth TM grade 0 or 1 flow, p = 0.5253. Tmes from ntaton of therapy to peak ST segment elevaton were not sgnfcantly dfferent between Groups P and O (21 _+ 14 vs. 30 -+ 22 ran, p = 0.132). ST segment recovery measured from ntal and peak ST segment levels. Predcton of coronary artery patency wthn 60 mn of ntaton of therapy, based on the presence of ST recovery, vared wth the ST level measured (ntal vs. peak), frequency of ST segment samplng and the grade of TM reperfuson (Fg. 1 to 5). The tme requred to reach ST segment recovery crtera for reperfuson n patents wth angographcally documented coronary artery patency at 60 ran (Group P) dffered between measurements obtaned from the ntal versus the peak ST segment level (Fg. A). A 50% decrease n ST segment levels occurred an average of 25 mn earler when measured from the peak ST segment level (mean 40 _+ 20 mn) than when measured from the ntal ST level (mean 65 +_ 39 mn, p = 0.02) (Table 2), largely because of the rapd declne from the peak ST segment elevaton. The rapd fall from peak ST segment elevaton n patents n Group P (tme from peak ST to 50% decrease from the peak 21 _+ 16 ran) permtted accurate detecton of coronary reperfuson wthn 60 mn of ntaton of therapy (Fg. 5). Twentyone of the 22 patents n Group P (Fg. 2) acheved a >-50% declne n peak ST segment levels by 60 ran (96% senstvty [95% C 77% to 99%]). n contrast, only 14 of the 22 patents n ths group developed a >-50% decrement from the ntal ST segment level wthn 60 mn of the start of therapy (senstvty 64% [95% C 40% to 82%]) (Table 3). The recognton of persstent occluson of the nfarct-related artery at 60 mn (Group O) (Fg. 1B) was hghly specfc based on the absence of a >-50% reducton n ether the ntal or the peak ST level at 60 mn (specfcty 94% to 100%) (Table 2). Grade of TM reperfuson and rate of ST segment decrease. Comparson of varous ndexes of ST segment resoluton n those wth TM grade 3 versus TM grade 2 flow showed marked dfferences (Table 2). The tme elapsed from peak ST to a 50% decrement of ths level was much brefer n those wth TM grade 3 flow at 60 ran (mean tme 13 z 7.7 mn) than n those wth TM grade 2 flow (mean tme 35 _+ 15 ran, p = 0.001). Furthermore, the rate of ST segment declne from peak ST to ts 50% level was sgnfcantly steeper for those wth TM grade 3 than for those wth TM grade 2 reperfuson (-0.28-0.14 ram/ran vs. -0.12 +_ 0.06 mm/mn, respectvely, p -- 0.004). Ths brsk declne n ST segment elevaton n patents wth TM grade 3 reperfuson (Fg. 3) allowed accurate recognton of nfarct-related vessel patency at 60 mn n ths group when a >-50% reducton from ether peak ST segment levels (senstvty 100%) or ntal ST levels (senstvty 92%) was used. Percent decrease n ST segment levels. Defnng ST recovery as a >-50% reducton n peak ST segment levels led to optmal senstvty and specfcty of the test (Table 3). n contrast, predcton of patency of the nfarct-related artery at 60 ran based on a >-75 % reducton n peak ST levels wthn 60 ran of ntaton of therapy was less senstve (54% [95% C 32% to 75%]); ST segment analyss based on a ->25% reducton of peak ST levels wthn 60 ran had a lower specfcty of 44%. Frequency of ST segment montorng. The frequency of ST level samplng was an mportant determnant of the predctve power of ST segment montorng for determnng patency of the nfarct-related artery (Fg. 4). However, ST segment montorng relably predcted nfarct vessel occluson at 60 mn, regardless of the frequency of ST segment level measurements (specfcty 87% to 100%).
JACC Vol. 26, No. 3 FERNANDEZ ET AL. 679 ST SEGMENT MONTORNG N ACUTE MYOCARDAL NFARCTON from ntal ST level +100% +50%, Fgure 1. Mean percent ST devaton wth 95% confdence ntervals (vertcal bars) from ntal and peak ST segment levels versus tme from ntaton of therapy. A, Patents wth angographc coronary artery patency at 60 ran (Group P). B, Patents wth angographc coronary artery occluson at 60 mn (Group O). n patents n Group P a 50% reducton n ST segment levels occurs 25 mn earler when values are measured from peak rather than ntal ST segment levels. Ambulatory electrocardographc (Holter) montors were placed wthn 210 mn of ntaton of therapy; therefore, ST devaton at 0 mn s not precsely zero n all cases. % O, $ T -50% d e -100%, Y from peak ST level o o n -50% A -100% +100% *50%. % 0. S T -5C% d e -100*~ v o a t O n -50% 0 60 120 180 Tme from ntaton of therapy (mn) from ntal ST level from peak ST level [ ' B -100% 60 120 180 Tme from ntaton of therapy (ran) Evaluaton of ST recovery at 60 versus 90 mn. Among the 38 patents, 16 (Group O) had angographc occluson of the nfarct-related artery at 60 ran; excludng 1 patent who underwent prmary angoplasty, only 4 others (27%) had reperfuson wthout mechancal nterventon between 60 and 90 mn. Thus, 73% of ths group had faled reperfuson by 120 p P l P pp ll #, P P pp Fgure 2. Plot of tme (n mnutes) to reach a ->50% reducton from peak ST segment levels (Tme to ST g- Recovery) versus tme (n mnutes) to the frst ango-._~ gram that showed patency of the nfarct-related vessel - ~n (Ango Reperfuson Tme). NR = fve patents who dd not have reperfuson demonstrated by electrocardog- " raphy wthn 180 mn of ntaton of therapy; p =._o o successful rescue angoplasty; pp = prmary angoplasty. r- = Groups as defned n Fgure 1. < 60 PP.~- *P PP p pp Y( Group P Group O 0... 60 120 180 NR Tme to ST Recovery
680 FERNANDEZ ET A.. JACC Vol. 26, No. 3 ST SEGMENT MONTORN(; N A.CUTE MYOCARDAL NFARCTON % S T d -50% a t o n 0-100% from peak 8T level TM 3 TM 0-1 0 60 120 180 Tme from ntaton of therapy (mn) Fgure 3. Mean percent ST segment devaton from peak ST segment levels (hghest ST segment level measurement n the 1st 60 ran of therapy) versus tme from ntaton of therapy for patents wth Thrombolyss n Myocardal nfarcton (TM) grade 3, 2 or 0 to perfuson at 60 ran. Note that patents wth TM grade 3 perfus(m acheve a 50% decrement n peak ST segment levels a mean of 25 ran earler than patents wth TM group 2 perfuson. 90 ran. Comparson of ST recove~ crtera for angographc reperfuson among all patents at 60 and 90 mn showed mportant dfferences. f the dagnoss s made at 90 ran usng 50% declne from peak ST, the senstvty would be lowered to 85% (95% C 65% to 95%). Coronary patency was eventually acheved n all patents by ether spontaneous reperfuson or coronary angoplasty (Fg. 2). Fgure 6 llustrates the potental beneft of ST montorng for the detecton not only of reperfuson, but also of rcoccluson after thrombolyss, whch n some cases may be slent (25). Dscusson Although t s generally beleved that ST segment montorng may be a vald method to detect coronary reperfuson n acute myocardal nfarcton, varous nvestgators (9-21) have reported nconsstent results. The present study provdes explanatons for these conflctng results and descrbes a method that provdes optmal dagnostc accuracy. ST segment montorng does not appear to correlate wth late arteral patency. However, we report that early ST montorng does appear to correlate very well wth early patency. Furthermore, the evaluaton of ST segment montorng appears to be enhanced by quanttatve computer-asssted measurement. Prevous studes (9,10) that tmed reperfuson n relaton to vsual qualtatve "mprovement" n ST segment levels may have led some to conclude that ECG dagnoss of reperfuson was not accurate. Angographc assessment of coronary patency must be documented early durng thrombolytc therapy, because late angograms, performed hours after thrombolyss, wll not relably reflect the dynamcs of coronary flow at the tme of ST segment analyss (20-22,25-27). Among the recent studes of ST segment montorng desgned to correlate quanttatve ST segment data wth early coronary angography (15-19,26), there were major dfferences n the ECG crtera of reperfuson and the reported accuracy of the test. Furthermore, the ECG recognton of reperfuson 2 to 3 h after ntaton of therapy, as proposed n these studes, delays the performance of further nterventons, whch may lmt ther mpact on nfarct sze. Our data demonstrate the feasblty of ECG recognton of corona n' reperfuson wthn 60 ran of ntaton of therapy and, hence, valdate the role of ST segment montorng n the early management of acute myocardal nfarcton. Resoluton of symptoms. Prevous studes (9,10,26) have concluded that the relef of schemc symptoms after thrombolytc therapy s an unrelable predctor of coronary artery Senstvty 100-96 -- 91 91 90 -- -- 8o ] 70 64 6O ~. SO 4O 3O 20, 10 0, 2.5 5 10 Specfcty lo0 68 68 15 20 2.5 5 10 15 20 Fgure 4. Senstvty and specfcty of ST recovery, defned as the presence of a ->50% reducton n ether ntal or peak ST segment levels, for recognzng coronary artery patency wthn 60 mn of ntaton of therapy. Results of analyzng the electrocardographc data at varous ST segment samplng ntervals are shown. Sold bars = from ntal ST segment level (the frst ST segment level recorded); open bars = from peak ST segment level (the hghest ST segment level measurement durng the frst 60 ran). ST segment samplng nterval (mn)
JACC Vol. 26, No. 3 FERNANDEZ ET AL. 681 ST SEGMENT MONTORNG N ACUTE MYOCARDAL NFARCTON 8T segment level (ram) 12. Fgure 5. Plots of ST segment levels versus tme from therapy n two selected patents wth patency of the nfarct-related vessel at 60 mn (Group P). Note that a 50% decrease n ST segment levels wthn 60 ran occurred only when measurements were made from the peak ST segment level (hghest ST segment level measurement wthn the 1st 60 ran). 0. 0 60 120 Tme from thrombolyte therapy (ran) 180 patency. The clncal value of resoluton of chest pan as a marker of reperfuson s lmted by ts subjectve assessment n patents often treated wth sedatves and narcotc drugs. n addton, as cardac myonecross progresses, symptoms wll abate regardless of the patency of the nfarct-related vessel. Our data concur wth results of prevous studes: The accurate recognton of coronary reperfuson at 60 ran based on the presence or absence of chest pan had only modest sgnfcance for symptoms. Baselne ST segment level. Prevous nvestgators (9-21) have used the ntal ST segment level as the baselne for ECG analyss. The recent recognton (26,28) of broad shfts n ST segment levels suggests that the magntude of the ntal ST level wll vary dependng on the tmng of ts measurement, and hence does not provde a stable fducal pont for ST segment analyss. The mechansm of the dynamc ST segment shfts durng acute myocardal nfarcton has not been elucdated, but Hackett et al. (8) mpled a correlaton wth a changng coronary vasomotor tone. Other postulates nclude the presence of njury currents that vary wth tme and amount of myonecross, and fluctuatons n blood supply to the nfarct zone. The present study reveals sgnfcant dfferences n the predctve power of ST segment montorng dependng on whether ntal or peak ST segment levels are used as the baselne, largely as a result of these ST segment shfts. The rate of declne of ST segment levels among patents wth coronary patency at 60 ran was faster and a >-50% reducton was reached a mean of 25 mn earler when values were measured from the peak rather than the ntal ST level. The rapd reducton n peak ST segment levels n these patents explans the hgh senstvty (96%) of the method tested n predctng coronary reperfuson wthn 60 mn of ntaton 10 ST segment level (ram) A P TCA t Fgure 6. Plots of ST segment levels versus tme from ntaton of therapy n two selected patents wth angographc reoccluson. Patent A showed wde ST segment shfts n the 1st 40 mn, angographc and electrocardographc reperfuson at 90 mn and reoccluson at 120 mn that requred coronary angoplasty (PTCA). Patent B had successful thrombolyss wthn 60 mn of t o.. ntaton of therapy; at 16 h, schema recurred and coronary angoplasty was performed. ~ ~ ~ ~PTC~ + 6- O" 0 60 120 180 16hr 18hr Tme from thrombolytc therapy (mn)
682 FERNANDEZ ET AL. JACC Vol, 26, No. 3 ST SEGMENT MONTORNG N ACUTE MYOCARDAl. NFARCTON of therapy. The longer tme requred to reach a ->50% decrement from ntal ST segment levels led to consderable delays n the recognton of patency of the nfarct-related artery at 60 mn. Resoluton of ST segment elevaton. Prevous studes have used several dfferent crtera for ECG evdence of reperfuson. Rchardson et al. (27) defned a >-2-ram decrease or normalzaton of ST segment levels as evdence for reperfuson and reported a senstvty of 26% and specfcty of 67%. Other nvestgators (16-20) have doubted the sgnfcance of absolute changes n ST segment levels and have examned nstead fractonal changes. Most reports (16,18,19,26) have suggested that a 50% decrease n ST segment levels s a smple and optmal crteron for dagnosng reperfuson, and have correlated lower fractonal ST changes wth poor specfcty. Analyss of our data usng the crteron of a >-25% decrease n ether ntal or peak ST segment level yelded a specfcty of only 44%, and the crteron of a >75c~ decrease led to a low senstvty (41% to 54%). Krucoff et al. (15) consdered the achevement of ST steady state wthn 100 mn of thrombolytc therapy as a crteron for reperfuson and reported hgh predctve values. However, the detecton of ST steady state n ther study requred contnuous montorng for >30 ran after the resoluton of ST elevaton and may have resulted n unwarranted delays n the dagnoss of faled reperfuson. n the present study, ST segment montorng was hghly accurate n predctng the perfuson status of the nfarct-related artery.' at 60 ran, based on the presence or absence of a ->50% decrement from peak ST segment levels wthn 60 ran of ntaton of therapy. Tmng of ECG analyss. Recent nvestgators (15-18) have delayed the ECG dagnoss of reperfuson to 2 to 3 h from the admnstraton of thrombolytc therapy. n our opnon, an earler dagnoss of faled reperfuson s essental for ths test to have a clncal mpact on the treatment of acute myocardal nfarcton. Hohnloser et al. (19) reported ECG data at 90 ran but revealed dsappontng results (60% senstvty). The present study s the frst to report accurate assessment of coronary artery patency (TM grade 2 or 3 flow) wthn 60 ran of ntaton of treatment n acute myocardal nfarcton. n patents wth TM grade 3 flow at 60 ran, the declne from peak ST segment elevaton was faster, and the ECG crteron of reperfuson was met wthn 3( + 15 mn of ntaton of therapy. The present study also demonstrates a lower senstvty for detectng reperfuson n patents wth later reperfuson (.e., >60 mn). n these patents, the slower declne of the ST segment could reflect ether reperfuson wth vablty, and hence mprovement of njury current, or persstent occluson wth completon of the myocardal nfarcton process. Others (16,27) have also found a decreased senstvty and specfcty when the perod of ST montorng for the detecton of repotfuson was extended over hours. Hence, assessng reperfuson by ST segment montorng >60 ran after thrombolytc therapy may be less accurate and may result n unnecessary delays to further nterventon. Frequency of ST segment montorng. Earler studes (12-14,17,18) on ST segment montorng n acute myocardal nfarcton compared statc ECGs obtaned at fxed tme ntervals. Wth the frequent shfts n ST segment levels, t became clear that frequent montorng s essental to adequately record the dynamc nature of ST segment trends. Our data renforce ths concept and show sgnfcant reductons n the senstvty of the test as the frequency of ST montorng decreases. ST segment samplng ntervals of -<10 mn led to an accurate correlaton between coronary artery patency and the presence of a 50% decrement n peak ST segment levels at 60 ran. n contrast, decreasng the frequency of ST segment montorng to 15 to 20 ran resulted n a lower senstvty of the test and n mssng of the actual peak ST segment level--and therefore n an attenuaton n ts observed heght and full extent of ts rate of declne--thus delayng the tme to reach the 50% crteron and the dagnoss of reperfuson. Lmtatons of the study. Some mportant lmtatons of our study mert emphass. The patent group studed s relatvely small. Nevertheless, sgnfcant dfferences were seen n the ST varables of reperfuson between those wth and wthout angographc reperfuson, and clear separaton was also shown between those wth TM grade 2 and grade 3 flow. Karagouns et al. (29) have suggested that TM grade 3 perfuson alone may best measure the reperfuson success of thrombolytc therapy, whereas TM grade 2 perfuson s generally nsuffcent to optmze myocardal salvage. The prmary drawback of ST segment trackng as a nonnvasve marker of reperfuson s the need for computer-derved ST segment montorng at the bedsde. Our data were obtaned from Holter recordngs that were analyzed at a later tme; nonetheless, the practcal aspects of ths method of montorng coronary, perfuson may be enhanced by the recent avalablty of real-tme, computerzed ST segment recorders (30,31) that allow ST montorng at the bedsde. Determnng the tme of ECG reperfuson on the bass of a >-50% reducton n ST segment levels can be dtfcult because of wde fluctuatons n ST segment levels around the 50% cutoff end pont. We found that sgnfcant ST segment shfts before the tme of reperfuson usually remaned above the 50% level; seven patents dd exhbt transent reductons n ST segment levels below the 50% level, but these lasted for -<10 ran. n our experence, the achevement of a 50% reducton n ST segment levels that lasted for > 10 mn correlated wth a contnung declne n ST levels toward steady state. Prevous nvestgators (12,13,18), ctng potental lmtatons of the ECG n patents wth low ST voltages, summated the ST segment levels n all affected leads. We have shown that the use of a selected sngle nfarct-related lead s an adequate montor of reperfuson. Although 42% of our patents had -<3-ram ntal ST segment elevaton n a sngle lead, the ST levels subsequently ncreased n all and reperfuson was accurately predcted. n the present study, no comparson was made between sngle-lead and 12-lead ST segment montorng for the purpose of determnng patency of the nfarct-related artery. A recent publcaton (31) reported that contnuous 12-lead montorng
JACC Vol. 26, No. 3 FERNANDEZ ET AL. 683 ST SEGMENT MONTORNG N ACUTE MYOCARDAL NFARCTON n ths settng was a useful marker of faled reperfuson. However, 12-lead montorng s less practcal for clncal use. Our method of sngle-lead montorng s both smple and effectve and resulted n mpressve senstvty and specfcty. Fnally, the value of ST segment montorng as a marker of reperfuson may be lmted by the presence of bundle branch block, recurrent ventrcular arrhythma and old transmural nfarcton. Conclusons. Our data suggest that ST segment montorng of a sngle selected lead s useful n the management of acute myocardal nfarcton. The presence or absence of a ---50% decrease n peak ST segment levels wthn 60 mn of the treatment of acute myocardal nfarcton shows promse as a nonnvasve marker of the perfuson status of the nfarctrelated artery. To acheve optmal dagnostc accuracy, ST segment levels should be measured contnuously or at least every 10 mn. We thank the Angographc Core laboratory at Beth srael Hosptal, Boston, Massachusetts for readng the coronary angograms. We apprecate the contrbutons of nurses and techncans n the cardac catheterzaton laboratores, coronary care unts and heart staton of Jackson Memoral Hosptal, Mam, Florda. References 1. SS-2 (Second nternatonal Study of nfarct Survval) Collaboratve Group. Randomzed tral of ntravenous strcptoknase, oral asprn, both or nether among 17,187 cases of suspected acute myocardal nfarcton. Lancet 1988; 2:349-60. 2. AMS Tral Study Group. Effect of ntravenous APSAC on mortalty after acute myocardal nfarcton: prelmnary report of a placebo-controlled clncal tral. Lancet 1988;1:545-9. 3. Wlcox RG, Von der Lppe G, Olson CG, Jenscn G, Skene AM, Hamptom JR. Tral of tssue plasmnogen actvator for mortalty reducton n acute myocardal nfarcton: the Anglo-Scandnavan Study of Early Thrombolyss (ASSET). Lancet 1988;2:525-30. 4. Braunwald E. Myocardal reperfuson, lmtaton of nfarct sze, reducton of left ventrcular dysfuncton and mproved survval. Should the paradgm be expanded? Crculaton 1989;79:441-4. 5. Abbonsmth CW, Topo E J, George BS, et al. Fate of patents wth acute myocardal nfarcton wth patency of the nfarct-related vessel acheved wth successful thrombolyss versus rescue angoplasty. J Am Col Cardol 1990; 16:770-8. 6. Ells SG, da Slva ER, Hendrck G. Randomzed comparson of rescue angoplasty wth conservatve management of patents wth early falure of thrombolyss for acute myocardal nfarcton. Crculaton 1994;90:2280-4. 7. Calff RM, Topo E J, Stock RS, et al. Evaluaton of thrombolytc therapy and tmng of cardac catheterzaton n acute myocardal nfarcton. Results of Thrombolyss and Angoplasty n Myocardal nfarcton--phase 5 randomzed tral. Crculaton 1991;83:1543-56. 8. Hackett D, Daves G, Chcrcha S, Maser A. ntermttent coronary occluson n acute myocardal nfarcton: value of combned thrombolytc and vasodlator therapy. 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The TM Study Group: The thrombolyss n myocardal nfarcton (T1M) tral: Phase fndngs. N Engl J Med 1985;312:932-6. 24. Sheffeld LT, Berson A, Bragg-Remschel D, et al. Recommendatons for standards of nstrumentaton and practce n the use of ambulatory electrocardography. Crculaton 1985;71:626A-36A. 25. Kwon K-k, Freedman B, Wlcox, et al. The unstable ST segment early after thrombolyss for acute nfarcton and ts usefulness as a marker of recurrent coronary occluson. Am J Cardol 1991;67:109-15. 26. Shecter M, Rabnowtz B, Beker B, et al. Addtonal ST segment elevaton durng the frst hour of thrombolytc therapy: an electrocardographc sgn predctng a favorable clncal outcome. J Am Col Cardol 1992;20:1460-4. 27. Rchardson SG, Morton P, Murtagh JG, Scott ME, O'Keefe DB. Relaton of coronary arteral patency and left ventrcular functon to electrocardographc changes after strcptoknase treatment durng acute myocardal nfarcton. Am J Cardol 1988;61:961-5. 28. Shah PK, Cercek B, Lew A, Ganz W. Angographc valdaton of bedsde markers of reperfuson. J Am Coll Cardol 1993;21:55-61. 29. Karagouns L, Sorensen SG, Menlove RL, Moreno F, Andersen JL. Does Thrombolyss n Myocardal nfarcton (TM) perfuson grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatc and electrocardographc evdence from the TEAM-2 study. J Am Coll Cardol 1992;19: 1-10. 30. Krucoff MW, Wagner NB, Pope JE, et al. The portable programmable mcroprocessor-drven real-tme 12-lead electrocardographc montor: a prelmnary report of a new devce for the non-nvasve detecton of successful reperfuson or slent coronary reoccluson. Am J Cardol 1990;65: 143-8. 31. Krucoff MW, Croll MA, Pope JE, et al. Contnuous 2-1ead ST-segment recovery analyss n the TAM 7 study: Performance of a non-nvasve method for real-tme detecton of faled myocardal reperfuson. Crculaton 1993;88:437-46.