Acute Ischemic Heart Disease
A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty Xander H.T. Wehrens, MSc, Pieter A. Doevendans, MD, PhD, Ton J. Oude Ophuis, MD, PhD, and Hein J.J. Wellens, MD, PhD, FACC Maastricht, The Netherlands
Background Dff I erent electrocardiographic changes have been described during thrombolytic therapy for acute myocar- dial infarction to indicate successful reperfusion. The occluded coronary artery also can be reopened by percutaneous translumi-
nal coronary angioplasty (PTCA). This study was performed to compare electrocardiographic changes during primary or rescue
PTCA and thrombolytic therapy. The electrocardiographic changes were studied directly at the moment of reperfusion during PTCA.
Methods and Results c on muous t 12-lead electrocardiographic monitoring was performed in 1 10 patients with acute myocardial infarction undergoing a reperfusion intervention (thrombolytic therapy or primary or rescue PTCA) to
assess electrocardiographic changes during reperfusion. Patency and Thrombolysis In Myocardial Infarction flow in the
infarct-related artery were assessed by coronary angiography. During reperfusion of the infarct-related coronary artery,
early signs of reperfusion were an increase of ST-segment deviation (30%), ST-segment normalization (70%), and terminal T-
wave inversion (60%); only 1 1% of patients showed no ST-segment changes. Thrombolytic therapy was significantly more
often accompanied by a transient increase in ST-segment deviation compared with primary PTCA. Accelerated idioventricu-
lar rhythm was documented in 5 1%, an increase in the number of ventricular premature complexes in 42%, nonsustained
ventricular tachycardia in 7%, and bradycardia in 18% of all patients.
Conclusions This study confirms the occurrence of specific electrocardiographic changes at the time of reperfusion. The pattern of ST-segment change upon reperfusion relates to the type of treatment. Awareness of electrocardiographic
changes at the moment of reperfusion will help to select patients for rescue PTCA and can be used to assess the effect of
future pharmacologic interventions to limit reperfusion damage (Am Heart J 2000; 139:430-6.)
See related Editorial on page 390.
Previous studies described the clinical and electrocar- diographic signs of reperfusion during thrombolytic therapy for an acute myocardial infarction. Decrease or disappearance of chest pain was an important indicator of reperfusion. 1 The most important electrocardiographic signs of reperfusion were rapid normalization of ST-seg- ment deviation, development of terminal T-wave inver- sion,- an increase in the number of ventricular premature beats,,3 and the occurrence of accelerated idioventricular rhythm (AIVR).* The temporal relation between these
From the Deportment of Cordlology, Unwersky Hospttol Maortrtchi, Cordtovosculor
Submttted June I, 1999; accepted August I, 1999
Reprinl requests- Pefer A. Doevendans, MD, PhD, Deportment of Cordrology, Unl-
verrdy Hosp~tol Moostncht, PO Box 5800, 6202 Ai! Moosrnchr, The Nerherlonds E-mall. email@example.com
Copyright 0 2000 by Mosby, fnc
0002.8703/2000/$12.00+ 0 4/I/103222
electrocardiographic changes and the exact moment of reperfusion, however, has never been documented. New pharmacologic approaches to reduce myocardial infarct size and to limit reperfusion damage are being evaluated in clinical trials (free radical scavengers, Na+/H+Txchanger blockers).5 The electrocardiographic changes during reopening of the infarct-related artery may provide an excellent tool to evaluate the effects of these drugs in individual patients. We documented the incidence, magnitude, and time course of the electro- cardiographic changes in relation to reperfusion during primary percutaneous transluminal coronary angioplasty (PTCA) or after thrombolytic therapy. Reperfusion was documented by coronary angiography in all patients. This study provides a baseline to evaluate protective measures against reperfusion damage in future studies.
Most recent studies on reperfusion-associated ST-seg- ment changes and arrhythmias have been performed in the setting of thrombolytic therapy to define electrocar- diographic criteria to predict reopening of the occluded
A,,,er,con Hem Journo~ volume 139, Number 3 Wehrens et al 431
coronary artery noninvasively. However, the incidence and patterns of electrocardiographic changes occurring in patients treated with a primary FTCA, a rescue FTCA, or thrombolytic therapy have never been compared before. These differences might provide additional insight into the relation between the mode of vessel reopening and reperfusion injury.
In total, 110 consecutive patients with acute myocardial infarction (symptoms lasting 45 minutes, together with ST-segment elevation >O. 1 mV in at least 2 extremity leads or >0.2 mV in at least 2 precordial leads. Two patients were excluded because of continuous atrial fibrillation (n = 2). Conventional antianginal treatment was used as needed.
In total, 44 patients were treated with prourokinase intra- venously (Satuplase. GrunenthaI, Aachen, Germany), with reperfusion status confirmed by subsequent coronary angiogra- phy (group A). Prourokinase was given as a bolus injection of 20 mg followed by infusion of 60 mg in the subsequent hour. In addition, patients studied were referred to the catheteriza- tion laboratory for either primary PTCA (group B; n = 42) or rescue PTCA (group C; n = 22). A rescue PTCA was performed if thrombolytic therapy did not lead to reperfusion (Throm- bolysis In MyocardiaI Infarction [TlMI] flow grade 0 or 1).
Electrocardiographic evaluation All patients were connected to a Marquette CASE 12 electro-
cardiograph (Marquette Electronics, Milwaukee, Wis) before administration of prourokinase or transfer to the catheterization laboratory, allowing continuous 12-lead electrocardiographic monitoring. During catheterization the patients were connected to a Siemens electrocardiograph, and the leads selected were dependent on the infarct localization. In the setting of an ante- rior waII myocardial infarction, leads I, V,, Vs, and aVR were used and in inferior myocardial infarction, leads I, II, III, and aVF were recorded continuously. The leads were adapted in case the maximal ST-segment deviation before angiography was observed in any of the remaining leads. The tracings were ana- lyzed by 2 blinded, experienced investigators.
ST segment In patients of group A, ST segments were measured every 5
minutes throughout the entire monitoring period, starting 15 minutes before administration of prourokinase. ST segments were measured 60 ms after the J-point.6 and this score was used for determining the changes in the ST segment that occurred. Compared with baseline ST-segment deviation, a change of 25% in 1 lead was considered significant and scored as either a decrease or increase of ST-segment deviation. Ter- minal T-wave inversion was considered present if the terminal part of the T wave changed direction from positive to nega- tive or vice versa. In patients undergoing a PTCA (groups B and C), the electrocardiogram was continuously monitored, starting approximately 10 minutes before and up to 10 min- utes after angiographically documented reperfusion. The ST-
segment changes and arrhythmias registered directly after contrast injection were excluded, resulting in a blanking period of 60 seconds after each contrast injection.
Arrhythmia monitoring In group A, the number of ventricular premature beats was
counted during every 5mInute interval. The number of ven- tricular premature beats during 15 minutes before thrombolytic therapy divided by 3 was used as a baseline count. A 2-fold increase during a 5minute interval was considered as a posi- tive result. In groups B and C, the number of ventricular pre- mature complexes was counted during a lOminute period before and after documented reperfusion. When after reperfu- sion the number of ventricuIar premature complexes increased 2-fold or more per minute, this was considered a positive result. When the baseline count was II per minute, an increase to t2 per minute was considered a positive score.
For arrhythmias, the following criteria were used. Acceler- ated idioventricular rhythm was defined as a run of >3 con- secutive ventricular beats, with a rate between 60 and 120 beats/n-tin; nonsustained ventricular tachycardia, ventricular rhythm > 120 beats/min lasting ~30 seconds; and bradycardia, rate 150 beats/mIn.
Coronary angiography Patency and flow in the infarct-related coronary artery were
assessed by 2 interventional cardiologists who did not partici- pate in the procedure and were not informed about the elec- trocardiographic changes that occurred during the procedure. For the classification of the coronary flow, the TIM1 trial trite- ria were used.7 In group A, coronary angiography was per- formed between 60 and 90 minutes after the start of throm- bolytic therapy in ail patients Irrespective of the clinical findIngs to assess infarct-related coronary artery patency. In patients undergoing a PTCA (groups B and C), the moment of reperht- sion was defined by the fmt visualization of TIM1 flow grade 2 or 3. Flow could be restored during the coronary angiography, after passage of a guide wire, or after PTCA. Only when TIMI 2 or 3 flow was obtained, 20 minutes of the electrocardio graphic tracings were analyzed starting 10 minutes before the moment of angiographicaIly documented reperfusion.
Statistical analysis Results are expressed as mean value f SD. Data were analyzed
with the use of the Statistical Package for the Social Sciences program for Windows, version 7.5. The Student f test was used to compare groups with continuous variables with a nor- mal distribution, the Mann-Whitney U test for those with a non- normal distribution, and the cl-&square test for groups with dis Crete variables. A value of P < .05 was considered significant.
Results Clinical data
In total, 108 patients with a mean age of 59 years admitted for an acute myocardial infarction were included in this study. All patients are characterized by documented successful reperfusion therapy of the infarct-related coronary artery, achieved by throm-
432 Wehrens et al Americans Heart Journal
Table I. Characteristics of patients with documentedreperfusion (n = 108) ft a er th rombolytic therapy, primory PTCA, ond rescue PTCA
Thrombolytic therapy Primary PTCA Rescue PTCA (group A) (group W (group Cl
No. of patients Men Mean (y) age History of angina pectoris >l mo
Prior myocordial infarction Infarct localization
Mean duration of pain before reperfusion Enzyme release
Maximal serum glutamic oxaloacetic transominase (U/l) Time to peak level (h)
1 -Vessel disease 2-Vessel disease J-Vessel diseose left main stem
Coronary artery flow
TIMI 2 TIMI 3
44 42 22 37 (84) 32 (73) 16 (73) 60+ 10 59f 12 58f 11
9 120) 12 (27) 4 (18) 4 (91 7 (16) 4 (18)
24 (55) 21 (50) 8 (361 14 (32) 18 (41) 12 (55)
4 (9) 3 (7) 2 19) 2 (5) 0 PI 0 (01
2.0 * 1 .o* 3.8f 1.5 4.3 f 1.4
325&220 305+220 270f 148 13?6t 17f6 16+8
22 (50) 16 (36) 7 (32) 14 (32) 14 (32) 6 127)
5 (111 9 (20) 8 (36) 3 (7) 3 (7) 1 (5)
10 (23) 8 1191 6 (27) 34 (77) 34 (81) 16 (73)
Values are expressed 01 number (%.) or meon + SD PC ,001, A VI B and A vs C. ~P
American Heart Journal Volume 139, Number 3
Wehrens et cd 433
A, Typical electrocardiographic changes indicating reperfusion during thrombolytic therapy. Alteration intervals (time from start therapy)
show acute anterior myocardial infarction, increase of ST-segment deviation, terminal negative T waves, AIVR, and electrocardiogram dur-
ing coronary angiography. 6, Reperfusion in inferior wall myocardial infarction induced by contrast injection. Note development of AIVR
ST-segment normalization and terminal negative T waves. C, Reperfusion during rescue PTCA. Note ST-segment normalization, terminal T-
wave inversion, and appearance of ventricular premature complexes.
434 Wehrens et al American Heart Journal
Table II. Electrocardiographic changes after reperftiion of the infarct-related artery after thrombolytic therapy, primary PTCA, and rescue PTCAPTCA
Thrombolytic therapy (group Al
Primary PTCA (group B)
Rescue PTCA (group Cl
No. of patients ST segment
Temporarily increased deviation Decreased deviation Terminal T-wave inversion
No changes Arrhythmia
Increased No. of ventricular premature complexes AIVR Nonsustained ventricular tachycardia
Atriai fibrillation Bradycardio Ventricular fibrillation No arrhythmias
Values are expressed OS No. (%) l P < .05, A VI B. ~Pc.Ol,AvsC.
AA A2 22
26 (59)'t 5 (121 1 (5) 37(84) 25 (61) 1 A (64) 25 (57) 27(64) 13 (60)
5 (111 5 (12) 2 (9)
24(55) 22 (52) 9(411 20(45) 1 A(33) 11 (50)
A (9) 2 15) 2 (91 1 PI 4 (101 1 (5) 9 (20) 7(17) 3 (141 0 (01 1 PI 2 (91 2 I51 10 (24) 2 (9)
observed in 55% (A), 52% (B), and 41% (C) of patients (Table 11). In addition, AIVR developed in 45 (42%) patients and nonsustained ventricular tachycardia developed in 8 (7%). Atria1 (6%) and ventricular (3%) fibrillation occurred less frequently. Transient slow heart rate was observed in 19 (18%) patients; sinus bradycardia was seen most often (n = 15). In 14 patients, no arrhythmias occurred after reperfusion. In a comparison of patients with TIM1 grades 2 and 3 flow through the infarct-related artery after reperfu- sion, no differences were observed in the occurrence of arrhythmias (Table III). In patients in whom reper- fusion arrhythmias developed, serum creatine kinase (CK) levels were significantly higher compared with patients without arrhythmias (3145 f 2032 vs 2090 f 1138 U/L; P < .05). This difference in serum CK levels could not be explained by preexisting differences in ST-segment deviations before reperfusion.
Influence of infarct location The ST-segment changes and arrhythmias were not
dependent on the location of myocardial infarction, with bradycardia being the only exception. Transient slow heart rates occurred significantly more often in the setting of an inferoposterior (31%) than in anterior (4%) myocardial infarction (P < .Ol).
Discussion Although some of the bedside markers of reperfusion,
such as rapid relief of chest pain, early peak of serum CK levels,* rapid decrease in ST-segment elevation,*,9 early inversion of T waves, 1 33 and reperfusion arrhyth- mias* have been shown to predict reperfusion after thrombolytic therapy, the reliability of these markers is
still controversial. We sought to relate the temporal relation of electrocardiographic changes and angiograph- ically documented reperfusion. The main finding was that in a group of patients with docum...