Early Identification of ImpairedMyocardial Reperfusion With Serial

Assessment of ST Segments AfterPercutaneous Transluminal Coronary

Angioplasty During AcuteMyocardial Infarction

Junko Watanabe, MD, Seishi Nakamura, MD, Tetsuro Sugiura, MD,Kazuya Takehana, MD, Shinichi Hamada, MD, Hironori Miyoshi, MD, Daiki Saito, MD,

Kengo Hatada, MD, Hirohiko Kurihara, MD, Masato Baden, MD, andToshiji Iwasaka, MD

To evaluate the relation between ST-segment analysisand microvascular reperfusion in patients with acutemyocardial infarction (AMI), we studied 51 patients withfirst AMI who were successfully treated by percutaneoustransluminal coronary angioplasty (PTCA). The leadshowing the greatest ST-segment elevation on the 12-lead electrocardiogram (ECG) was serially investigateduntil 24 hours after PTCA. Successful reperfusion wasdetermined by technetium-99m tetrofosmin single-pho-ton emission computed tomography. Impaired reperfu-sion (group 1: <4 change in the sum of the defect scorefrom before to immediately after PTCA) was observed in24 patients, and successful reperfusion (group 2) wasobserved in 27 patients. Although ST-segment elevationwas reduced significantly at 30 minutes after PTCA in

group 2 (2.2 � 1.4 to 1.7 � 1.3 mm, p � 0.01), therewas no significant change in group 1 (1.9 � 1.9 to 2.4� 1.7 mm). Ten of 14 patients (71%) with persistentST-segment elevation (�ST >0 mm change in ST seg-ment from before to 30 minutes after PTCA >0) were ingroup 1, whereas 23 of 37 patients (62%) with ST-segment resolution (�ST <0) were in group 2. The sen-sitivity and specificity of persistent ST-segment elevationfor predicting impaired microvascular reperfusion were42% and 85%, respectively. Thus, persistent ST-segmentelevation 30 minutes after primary PTCA was a highlyspecific electrocardiographic marker of impaired reper-fusion in patients with AMI. �2001 by Excerpta Med-ica, Inc.

(Am J Cardiol 2001;88:956–959)

Recent studies have shown that ST-segmentchanges on the electrocardiogram (ECG) after

reperfusion therapy provide information about pa-tency of the infarct-related artery and late functionaloutcome in patients with acute myocardial infarction(AMI). 1–3 Although persistent ST-segment elevationafter successful percutaneous transluminal coronaryangioplasty (PTCA) may indicate the absence of ad-equate reperfusion,4–10 the relation between ST-seg-ment analysis and microvascular condition of thereperfused myocardium has not yet been examined.The aim of this study was to evaluate the relationbetween ST-segment change and scintigraphic estima-tion of impaired myocardial reperfusion immediatelyafter successful PTCA.

METHODSPatients: We studied 70 consecutive patients with

first Q-wave AMI who were admitted to our hospitalbetween January 1996 and September 1999, and whounderwent primary PTCA. The criteria for enrollmentin this study were: (1)�30 minutes of chest pain, (2)ST-segment elevation (�0.1 mV from TP segment) in�2 contiguous leads in the same vascular territory, (3)a �2-fold increase in creatine kinase serum levels,and (4) successful PTCA, defined as restoration ofThrombolysis in Myocardial Infarction (TIMI) grade3 flow and �50% diameter stenosis of the infarct-related artery after PTCA. Nine patients with unsuc-cessful PTCA (TIMI flow grade�2 after PTCA) and11 patients (6 patients with cardiogenic shock andpulmonary edema, 2 patients with complete atrioven-tricular block, 1 patient with implanted pacemaker,and 2 patients with atrial fibrillation) with lack ofnuclear imaging or electrocardiographic analysis wereexcluded. The remaining 51 patients formed the studygroup (40 men and 11 women; mean age 64� 13years). The infarct location was anterior in 27 andinferior in 24 patients.

Radionuclide study: All patients were given a chew-able baby aspirin tablet (81 mg) and 3,000 U of

From The Cardiovascular Center, Kansai Medical University, Osaka;Department of Clinical Laboratory Medicine, Kochi Medical School,Kochi; and Division of Cardiology, Takarazuka Hospital, Takarazuka,Japan. Manuscript received February 13, 2001; revised manuscriptreceived and accepted June 13, 2001.

Address for reprints: Seishi Nakamura, MD, Cardiovascular Cen-ter, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi,Osaka, 570-8507, Japan. E-mail: nakamurs@takii.kmu.ac.jp.

956 ©2001 by Excerpta Medica, Inc. All rights reserved. 0002-9149/01/$–see front matterThe American Journal of Cardiology Vol. 88 November 1, 2001 PII S0002-9149(01)01969-5

intravenous heparin, and transported promptly to thenuclear laboratory. The initial study was performedduring preparation for catheterization in the nuclearlaboratory located next to the catheterization labora-tory. Single-photon emission computed tomographicimages were obtained 15 minutes after the injection oftechnetium-99m tetrofosmin. Images were acquiredand processed using a previously described tech-nique.11 An activity ratio of 1:2 with a time interval of2 hours between the 2 images was used in the 1-daystress-rest protocol.12,13 The study protocol was ap-proved by the local ethical committee on human re-search. Written informed consent was obtained fromall patients.

Angiographic study: PTCA was performed by con-ventional techniques after administration of 7,000 Uof intravenous heparin. Coronary flow of the infarct-related artery before and after PTCA was graded vi-sually according to the TIMI study group flow classi-fication.14 Adequate collateral flow was consideredpresent when it was graded 2 or 3.15 Time fromadmission to PTCA was calculated as the time be-tween admission and first balloon inflation.

Electrocardiographic analysis: The study protocol isshown in Figure 1. Electrocardiographic tracings wereobtained before PTCA, and at 30 minutes, 1 hour, and24 hours after PTCA. Serial ST-segment analysis wasperformed by 2 independent observers who were un-aware of angiographic findings, and the clinical andradionuclide data. ST-segment elevation was mea-sured 0.08 second after the J-point with hand-heldcalipers. The lead showing the greatest magnitude ofST-segment elevation (millimeters) in the 12-leadECG before PTCA was serially investigated. Persis-tent ST-segment elevation was defined as �ST(change in ST segment from before to 30 minutes afterPTCA) �0 mm.

Analysis of radionuclide image: The single-photonemission computed tomographic image was dividedinto 13 segments; the short-axis images were obtainedat middle and lower ventricular levels and were di-vided into 6 segments (anteroseptal, anterior, lateral,

posterior, inferior, and inferoseptal). The apex of theleft ventricle was obtained from the vertical long-axisimage. Technetium-99m tetrofosmin uptake in each ofthe 13 segments was graded as: 3 � complete defect;2 � severely reduced; 1 � mildly reduced; and 0 �normal perfusion. Defect score was calculated as thesum of the perfusion defect. The tomograms werevisually interpreted by 2 independent observers whowere unaware of the clinical and angiographic data. Asuccessful myocardial reperfusion was determined byquantitative tetrofosmin perfusion scintigraphy anddefined as a change (from before to after PTCA) of�4 in the total defect score. Because mean absoluteinterobserver variability in the defect score was 2.0 �0.8, an absolute change of �4 (mean � 2 SD) wasconsidered to be a significant difference between the 2measurements using the cut-off value of score 4.11

Statistical analysis: Results are expressed as mean� SD. A change in the ST-segment elevation wasestimated by 2-way repeated measures analysis ofvariance. Comparison between the 2 groups was per-formed with Student’s t test for continuous variablesand Fisher’s exact probability test for discrete vari-ables. A p value of �0.05 was considered significant.

RESULTSClinical course: Time from the onset of AMI to

revascularization was 9.9 � 9.1 hours (range 2.5 to24) and the time from admission to therapy was 71 �6 minutes (range 39 to 90). Technetium-99m tetrofos-min was intravenously administered 15 � 9 minutes(range 10 to 25) after admission to the hospital (firststudy) and 65 � 21 minutes (range 48 to 156) afterprimary PTCA (second study).

Myocardial perfusion: Defect score decreased sig-nificantly after PTCA (14 � 5 to 10 � 4, p �0.001).Of 663 segments, 373 segments had abnormal perfu-sion (defect grade �1 before PTCA). Such segmentswere more frequently observed in the area reperfusedby PTCA (187 of 231 segments, 83%) compared withthe surrounding area not directly supplied by the ves-sel undergoing PTCA (186 of 432 segments, 39%, p�0.001). Mean defect grade in the segments withabnormal perfusion was significantly higher in thereperfused area (2.2 � 0.8) than in the surroundingarea (1.8 � 0.8, p �0.001). One hundred ninety-fourof 373 segments showed improvement in perfusion(change in defect grade �1) after PTCA. There wasno significant difference in the number of segmentswith improvement in perfusion after PTCA betweenthe reperfused area (99 of 187 segments, 53%) and thesurrounding area (95 of 186 segments, 51%).

Patients were divided into 2 groups according tothe change in defect score after PTCA; 24 patientswith impaired myocardial reperfusion (group 1) and27 patients with successful reperfusion (group 2). The2 groups did not differ significantly in age, gender,infarct location, recanalizaion time, collateral gradebefore PTCA, and the number of diseased vessels(Table 1). None of the patients received glycoproteinIIb/IIIa blockers and thrombolysis was not performedin all patients. Nine patients received stents (18%), but

FIGURE 1. Study protocol. First imaging study was performedbefore PTCA. Images were obtained 15 minutes after injection oftechnetium-99m (99mTc) tetrofosmin (370 MBq). Twice the initialdosage of technetium-99m tetrofosmin (740 MBq) was adminis-tered at the end of the angiographic procedure, and a secondimaging study was performed. A conventional 12-lead ECG wasobtained before PTCA, 30 minutes after, 1 hour after, and 24hours after PTCA. The lead showing the greatest ST-segment ele-vation on the 12-lead ECG before PTCA was serially investi-gated.

CORONARY ARTERY DISEASE/ST-SEGMENT ANALYSIS AND IMPAIRED MICROVASCULAR REPERFUSION 957

there was no significant difference in the frequency ofstent usage between the 2 groups. Serum creatinekinase levels were significantly higher in group 1 thanin group 2.

Quantitative serial ST-segment analysis (Figures 2and 3) : The time course of the change in ST-segmentelevation is shown in Figure 2. There was no signifi-cant difference in the magnitude of ST-segment ele-vation before PTCA between the 2 groups. AlthoughST-segment elevation decreased significantly at 30minutes after PTCA in group 2 (2.2 � 1.4 to 1.7 � 1.3mm, p � 0.01), patients in group 1 showed no signif-icant change in the ST-segment elevation (1.9 � 1.9 to

2.4 � 1.7 mm). There was no significant difference inthe magnitude of ST-segment elevation between the 2groups thereafter (Figure 3). �ST was significantlylarger in group 2 compared with group 1 (group 1:�0.5 � 1.6 mm vs group 2: 0.5 � 0.8 mm, p � 0.01).When the patients were divided into 2 groups (25patients revascularized �6 hours after the onset ofAMI and 26 patients revascularized after �6 hours),there was no significant difference in the ST segmentbefore PTCA (1.7 � 0.9 vs 2.4 � 2.1 mm), 30minutes after PTCA (1.8 � 1.5 vs 2.3 � 1.6 mm), andin the incidence of persistent ST-segment elevation 30minutes after PTCA (32% vs 23%).

Qualitative ST-segment analysis (Table 2): Patientswith persistent ST-segment elevation had a signifi-cantly higher incidence of impaired myocardial reper-fusion compared with those with successful myocar-dial perfusion. The sensitivity, specificity, and accu-racy of persistent ST-segment elevation in predictingimpaired myocardial reperfusion were 42%, 85%, and65%, respectively.

DISCUSSIONImpaired myocardial reperfusion after successful

PTCA implicates ongoing structural and/or functionalproblems of distal microcirculation.16–20 Myocardialperfusion imaging with technetium-99m compoundsis one of the standard methods used to estimate mi-crovascular perfusion.21,22 We have previously dem-onstrated that angiographically successful reflow doesnot necessarily indicate adequate scintigraphic myo-cardial reperfusion in patients with AMI and thatpatients with poor improvement in myocardial perfu-sion immediately after PTCA had a significantlylarger final infarct size compared with those withsuccessful reperfusion.11 In our study, time betweenadmission to therapy was 71 � 6 minutes, which isnearly identical to previous reports at a 24-hour cov-erage interventional cardiology department.23,24

Several studies have demonstrated that completeST-segment resolution after reperfusion therapy pre-dicts smaller infarct size, fewer complications, andlower mortality.1,2 In contrast, persistent ST-segmentelevation has been observed despite TIMI 3 flow afterrevascularization therapy.7,10,25 However, there havebeen few studies that have evaluated the relation be-tween serial ST-segment analysis and the microvas-cular condition of the reperfused myocardium. Toderive a simple and inexpensive tool for early identi-fication of impaired myocardial reperfusion, we chose

TABLE 1 Clinical Characteristics

Impaired Myocardial Perfusion

� O(n � 24) (n � 27)

Age (yrs) 66 � 14 60 � 12Men/women 20/4 20/7Infarct location

(anterior/inferior)12/12 15/12

Recanalization time (h) 11 � 11 9 � 7Collateral 38% 59%Single-/multivessel disease 13/11 18/9Stent usage 21% 15%Peak creatine kinase (U/L)* 3,349 � 1,229 2,389 � 1,172

*p �0.01.

FIGURE 2. Time course of the change in ST-segment elevation.

FIGURE 3. Comparison of the change in ST-segment between the2 groups. White circles, patients with impaired myocardialreperfusion (group 1). Black circles, patients without impairedmyocardial reperfusion (group 2).

TABLE 2 Impaired Myocardial Reperfusion and Persistent ST-segment Elevation

Impaired Myocardial Perfusion

� O(n � 24) (n � 27)

Persistent ST-segment elevation* 10 (71%) 4 (29%)ST-segment resolution 14 (38%) 23 (62%)

*Chi square 4.7; p � 0.03.

958 THE AMERICAN JOURNAL OF CARDIOLOGY� VOL. 88 NOVEMBER 1, 2001

a ST-segment analysis using single-lead monitoringand assessed ST-segment changes until 24 hours afterPTCA. As a result, we found that the magnitude ofST-segment elevation 30 minutes after PTCA wassignificantly greater in patients with impaired myocar-dial reperfusion compared with those with successfulreperfusion. Persistent ST-segment elevation aftersuccessful reperfusion was observed in approximately20% to 50% of patients.1,3–6,8,10 Previous studies havesuggested that persistent ST-segment elevation is in-duced by accelerated microvascular injury after reper-fusion (reperfusion injury) because patients with per-sistent ST-segment elevation had unfavorable out-come while convalescent.1,10,25 The cause of impairedmyocardial reperfusion after PTCA was not fully ex-amined, but our data indicated that revascularizationtime was not the major determinant of persistent ST-segment elevation after PTCA.

Although segments with abnormal perfusion weremore frequently observed in the reperfused area com-pared with the surrounding area, there was no signif-icant difference in the incidence of improvement inperfusion after PTCA between the 2 areas. Thus,opening the vessel of the infarct-related artery resultsin improving myocardial perfusion not only in thereperfused area but also in the surrounding area theinfarcted region. This may, in a part, cause the dis-cordance between ST-segment analysis and scinti-graphic estimation of myocardial reperfusion. How-ever, persistent ST-segment elevation was a highly.specific marker for predicting impaired myocardialreperfusion and using single-lead ST-segment analysiswas beneficial of identifying patients with impairedmyocardial reperfusion.

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