Prognostic value of ST-segment resolution—when and what to measure

Per Johansona,*, Tomas Jernbergb, Gunnar Gunnarssona, Bertil Lindahlb, Lars Wallentinb and Mikael Dellborga

a Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, SE-41685 Göteborg, Sweden
b Department of Cardiology, University Hospital Uppsala, Uppsala, Sweden

Received August 21, 2002; accepted October 9, 2002 * Corresponding author. Tel: +46-31-343-4000; fax: +46-31-191416
pj{at}hjl.gu.se


    Abstract
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Aims Analyses of ST-segment resolution during acute myocardial infarction has, during recent years, challenged coronary angiography as gold-standard for predictingmyocardial reflow and future risk. We have previously reported that continuous ST-monitoring can be done accurately in the clinical setting. We now set out to compare the prognostic value of previously suggested cut-offs for ST-segmentresolution, and determine the times to measure these.

Methods and results We analysed 752 patients with ST-elevation infarction, from the second Assessment of Safety and Efficacy of a New Thrombolytic (ASSENT 2) and ASSENT-PLUS studies, either with vectorcardiography or continuous 12-lead ST-monitoring. All analyses were made blindly by two independent observers. Times to 20, 30, 50 and 70% ST-segment resolution were examined in relation to 30-day mortality.

The optimal cut-off for ST-segment resolution analyses was found to be 50%, measured at 60min. We could hereby identify a large low-risk group, 40% of the population, with only 1.4% 30-day mortality. Furthermore, 88% of deaths were correctly predicted within 1h of observation and treatment.

Conclusion Continuous ST-monitoring of patients with acute myocardial infarction yields important prognostic information after 60min of observation and should be used for very early-risk stratification in these patients.

Key Words: Acute myocardial infarction • Prognosis • Electrocardiography


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
The role of ST-segment resolution during an ST-elevation infarction has, over the years, grown into not only an alternative way of approximating risk and chances of reperfusion in the absence of a coronary angiogram, but also a method challenging the traditional ‘gold-standard’ for predicting risk and reperfusion at the myocardial level.1 ST-segment resolution has been shown to be better than thrombolysis in myocardial infarction-(TIMI-)flow in predicting the outcome following a successful primary angioplasty.2 The angiographic snapshot has already been discussed 10 years ago as not giving the same physiological information on reperfusion as the ST-monitoring does.3 In 1993, angiographic findings were proposed to represent an illusion of reperfusion4 and attention was called to more physiological methods, such as evaluations of ST-segment resolution and contrast-echocardiography,5 to analyse myocardial reflow. Furthermore, early ST-segment resolution has been used for validating angiographic signs of myocardial reperfusion.6

Several reports have shown that a rapid and high-grade resolution of ST-segment elevationduring treatment of acute myocardial infarctionis associated with better prognosis1,7–10 and witha higher extent of normalised epicardial perfusion.11–15 Different cut-offs for ST-resolution and times to ST-analysis have been suggested and used in these reports, but have not been explored and compared with each other. Thus, there are still questions demanding answers: how rapid, and to what extent, is the optimal ST-resolution foridentification of patients at very low or high risk? We have previously reported that continuous ST-monitoring can be done as accurate in the clinical setting as in a core-laboratory.16 An accurate risk-validation during the very early phase of a myocardial infarction would give us means to tailor early pharmacological and/or invasive strategies.

In our aim to investigate as to which extent of ST-segment resolution should be analysed for optimal-risk stratification by prospectively testing previously suggested cut-offs, we used continuous vectorcardiography (VCG) and 12-lead monitoring, shown to identify the same-risk groups amongpatients with unstable angina or non-q-waveinfarction.17


    2. Methods
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
The present study was conducted as a substudy of the second Assessment of Safety and Efficacy of a New Thrombolytic (ASSENT 2) trial18 and the ASSENT-PLUS trial.19 Briefly, the ASSENT 2 trial was a worldwide, multicentre study, comparing a new single-bolus thrombolytic, TNK with standard, front-loaded alteplase. The study was designed to show equivalence and patients were recruited during 1997 and 1998. The ASSENT-PLUS trial on the other hand, conducted in Scandinavia and USA from 1998 to 1999, was designed to examine efficacy and safety of dalteparin as conjunctive anti-coagulant therapy together with alteplase, compared toroutine heparin therapy.

Inclusion criteria in both studies were: (1) symptoms of acute myocardial infarction within 6h of onset; (2) ST-elevation ≥0.1mV in two or more limb-leads, or ≥0.2mV in two or more contiguous precordial leads, or left bundle branch block;and (3) age ≥18 years. In the ASSENT-PLUS trial, patients also had to be eligible for angiography. Exclusion criteria, described in detail in the report of the main study,18 were similar to the onesgenerally used clinically when refraining from thrombolysis. Furthermore, patients who had any known history of stroke or transient ischemic attack and those who received any GP2b/3a antagonists within the preceding 12h were also excluded.

2.1. ST-monitoring
We prospectively decided not to include patients with bundle branch block . A total of 864 patients from 30 hospitals were included in the ST-monitoring substudy, 617 from the ASSENT 2 trial and 247 from the ASSENT-PLUS trial. Patients were monitored for 24h after admission usingthe MIDA-system for VCG or continuous 12-lead ST-monitoring .

2.1.1. Quality criteria for ST-monitoring
Patients with >30min delay between thrombolysis and the start of monitoring were excluded. Bad quality and short recordings, if analysable material was less than: 70min of the first 90min; 3h of the first 4h and 20h of the first 24h, were alsoexcluded. By these criteria, even recordings shorter than 24h with high initial quality could be included in an ‘intention to monitor’ manner.

2.1.2. Continuous VCG
Continuous VCG was performed with the MIDA 1000 or Coronet systems (Ortivus Medical AB, Täby,Sweden), or with the HP-MIDA system (Hewlett Packard, Andover, MA, USA). VCG has previously been described in detail.20 Concisely, eight electrodes are placed according to Frank,21 resulting in three orthogonal leads X, Y and Z, which arecontinuously monitored and analysed. After the operator (MIDA 1000 and Coronet systems), or the computer (HP-MIDA), accepts a template QRS-complex for that patient, the computer automatically discards all QRS-complexes with grossly altered configuration and, thereby, hinders e.g. ventricular extrasystolies and sequences of rapid intraventricular rhythm from disturbing theanalysis. Beats were averaged over 1min.

ST-vectormagnitude (ST-VM) was calculated from the orthogonal leads according to the formula: , representing thetotal, spatial ST-segment shift from the baseline. , and are the magnitudes of ST-deviation in leads X, Y and Z, respectively. ST-VM is presented on-line on a computer screen as a trend-curve(Fig. 1). ST-segment changes were measured 60ms after the J-point.



View larger version (6K):
[in this window]
[in a new window]
 
Fig. 1 ST-VM trend-curve of a patient with acute ST-elevation infarction.

 
2.1.3. Continuous 12-lead ECG
Continuous 12-lead ECG was performed using the ST-Guard system (GE Medical Systems, Information Technologies, Milwaukee, USA). Data from all the 12 leads are continuously collected and, every minute averaged over the last 10s of each minute. From these averages, a ST-trend for each lead is constructed, stored and displayed on-line. ST-analyses were made on the worst lead, defined as the lead showing the highest initial ST-elevation.

ST-segment changes were measured at , corresponding to at a heart rate of 62.5 beats per minute.

2.1.4. Trend-curve analysis
Times to 20, 30, 50 and 70% ST-segment resolution from maximal ST-elevation were analysed from start of recording. ST-segment resolution at 90min, as well as the initial and maximal ST-elevations were registered.

All analyses were made by two blinded andindependent observers at either the IschemiaCore-laboratory, Sahlgrenska University Hospital/Östra, Göteborg, Sweden (VCG), or UppsalaUniversity Hospital, Uppsala, Sweden (continuous 12-lead monitoring). Disagreements were solved by consensus-agreement between the two observers and a third experienced person.

2.2. Statistical analysis
Statistics were calculated with the SPSS 6.1 (SPSS Inc. Chicago, Ill, USA) for Macintosh. t-Tests were used for normally distributed continuous variables. The Mann–Whitney U-test was used tonon-parametrically compare median times to 20, 30, 50 and 70% ST-resolution since patients never reaching the actual degree of ST-resolution were assigned the maximal recorded value and datawere not normally distributed. Categorical data were compared with the {chi}2test.

Survival analyses were examined with Kaplan– Meier plots and the prognostic value of ST-variables in comparison to traditional risk factors was evaluated in a Cox-regression (backward conditional). The value was considered to be significant.


    3. Results
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
3.1. Patients
Out of the 864 patients included for study, 112 cases (with 9.8% 30-day mortality) were lost dueto diskette-and/or computer problems orexcluded according to the quality criteria described under , . Analyses of ST-parameters were made on the remaining 752 patients, 571 were monitored by VCG and 181 by 12-lead monitoring.

Baseline characteristics are presented inTable 1. Mortality at 30-day follow-up was 4.2% (32 of 752). When the patients were divided according to method of monitoring, there were 28 deaths (4.9%) in the VCG-group and four (2.2%) in the continuous 12-lead group, .


View this table:
[in this window]
[in a new window]
 
Table 1 Baseline characteristics

 
During the follow-up time, 14% of the patients underwent angioplasty. The frequency of angioplasties was equally distributed between the patients showing early signs of reperfusion on the ST-monitor and those showing no such signs.

3.2. ST-monitoring
A comparison of times to 20, 30, 50 and 70% ST-segment resolution is presented in Table 2, which shows significantly shorter times to all but the 20% cut-off, for those alive as compared to those dead at 30 days.


View this table:
[in this window]
[in a new window]
 
Table 2 Median time to ST-segment resolution

 
Relative risk for 30-day mortality at four ST-resolution cut-offs, at 60, 90 and 180min is presented in Fig. 2. Achieving 50% ST-resolution at any of these time-points significantly reduced risk for mortality. Patients reaching 50% ST-resolution within 60min had a relative risk of 0.2 (95%confidence interval: 0.07–0.6) compared to those not reaching 50%. Mortality in the two groups was 1.4% (4 patients) and 6.1% (28 patients), respectively, (Fig. 3). The deaths correctlypredicted were 88% compared to only 66%,while analysing 50% ST-resolution at 90min.The 30-day mortality-rates for patients who reached 50% ST-resolution at 90min and those who did not were 2.6 and 6.4%, respectively,.



View larger version (15K):
[in this window]
[in a new window]
 
Fig. 2 Relative risk, with 95% confidence intervals, for 30-day mortality at four different cut-offs of ST-segment resolution analysed at three different times. Number of patients reaching each ST-resolution at each time is presented.

 


View larger version (8K):
[in this window]
[in a new window]
 
Fig. 3 Kaplan–Meier plot of cumulative mortality in patients with and without 50% ST-segment resolution at 60min.

 
Time to 50% ST-segment resolution was compared with traditional risk factors (see subsequently) in a Cox-regression, and found to be the only factor, together with age, contributing toinformation about 30-day mortality. Each minute of extra time to 50% ST-resolution yielded a 1.0023 relative risk (95% confidence interval: 1.001–1.003 at ) for 30-day mortality, resulting in an estimated 7.5% risk elevation for each half an hour of not reaching 50% resolution during the first hours. Each year of age yielded a relative riskof 1.17 (95% confidence interval: 1.1–1.25 at). Hypertension, previous myocardialinfarction, time to treatment, diabetes and sex did not contribute to information on mortality in this multivariate comparison.

Median ST-resolution at 90min was 50%. When ST-resolution at 90min was divided into three groups, <30; 30–69 and ≥70%, the mortality rates at 30 days were 8.4% (14 patients), 3.9% (14 patients) and 1.8% (4 patients), respectively (Fig. 4). A summation of ST-resolution at 60 and 90min and their relationship to 30-day mortality is shown in Fig. 5.



View larger version (10K):
[in this window]
[in a new window]
 
Fig. 4 Kaplan–Meier plot of cumulative mortality in patients reaching less than 30, 30–60, and 70% or more ST-segment resolution at 90min.

 


View larger version (19K):
[in this window]
[in a new window]
 
Fig. 5 Summation of ST-segment resolution at 60 and 90min and mortality at 30 days.

 
When the patients were divided according to method of monitoring, 30-day mortality rates inthe <30% resolution-group were 8.1 vs. 10.5%; in the 30–69% resolution group, 4.8 vs. 1.1%; in the70% resolution group, 2.0 vs. 1.7%, VCG andcontinuous 12-lead monitoring, respectively. At 60min, using the 50% cut-off, mortality rates in the <50% resolution group were 6.7 vs. 3.4% and inthe ≥50% group, 1.5 vs. 1.1%, VCG and continuous 12-lead, respectively.


    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
These results show, in no controversy to previous reports, that patients with a low-grade ST-segment resolution, as well as the older patients, are at higher risk when experiencing an acuteST-elevation infarction.

We analysed times to 20, 30, 50 and 70% ST-segment resolution and all but the most low-grade, which previously has been proposed to be the best cut-off for predicting patency,13 were found to be significantly connected to 30-day mortality. The cut-off 50% ST-resolution is the most frequently used cut-off in previous reports, evaluated atdifferent points of time: 120–180min;22,23; 4h;8 continuously, but focused on 90min;9 continuously, but focused on time for angiography(90–180min).1,15 In the present study, time to50% ST-resolution turned out to have the closest association to prognosis, both when analysing time to 50%, and when this cut-off was analysed at different time-points. The lowest relative risk, 0.2, for dying within 30 days was found if 50% was reached at the earliest time-point analysed, 60min. At this time-point, it was possible toidentify a large low-risk group, 40% of the population, with slightly more than 1% 30-day mortality. No mortality at all was seen during the first 5 days in this group of 293 patients. Our finding might indicate that this is not the population to focuson for immediate adjunctive pharmacological or invasive therapy. On the other hand, the population not reaching 50% ST-resolution during the first hour comprises 88% of all deaths and this seems to be the group we should focus our very early efforts on. Early angiographic prediction of risk, using TIMI 3 flow, is also recently validated. TIMI 3 flow at 60min appeared to be a valid alternative to 90-min analyses.24

The importance of time, estimated from the relative risk for each minute of time to 50% ST-resolution, is even emphasised by the fact that 34% of all deaths are placed in the ‘reperfused’ or ‘low-risk’ group if we wait until 90min to see whether 50% is achieved or not. When the population is divided according to Schroder,10 the cut-offs 30 and 70% at 90min also seemed to provide useful information as shown in Fig. 4. A stepwise evaluation of risk would be plausible and Fig. 5 shows that even though we readily can identify the low-risk group already at 60min, the high-risk group can be further stratified at 90min into intermediate and high risks.

Using specific grades of ST-segment resolution at specific times for the risk-stratification, makes it possible to record single ECG-s at these times and use the cut-offs mentioned previously to identify patients at low or at high risk. In that case, we would, however, have less knowledge of thetrue peak ST-elevation and be totally unaware of the dynamics of the ST-segment between therecordings. Spontaneously recurrent ST-elevations, described for the first time by Thygesen et al.,25 have been demonstrated during thrombolytictreatment and shown to correlate to intermittent closures in the infarct related artery.26 Recurrent ST-elevations have also been shown to predict subsequent reocclusion.27 From the GUSTO-1 population, it has been shown that electrocardiographic signs of reocclusion, i.e. ST-reelevation, 6–24h after thrombolysis, predict worse outcome.28Furthermore, we have previously shown that even very small variations of the ST-segment during the first 4h of observation have a negative effect on 30-day29 and 1-year30 outcome, and that we can sharpen the risk-prediction by combining ST-segment resolution with ST-variability data.29 We have also recently reported that continuous ST-monitoring can be done as accurate bed-side, in the clinical setting as in a core-laboratory, and it yields truly on-line information on prognosis.16

A rational way to use this information in the clinical setting would be to continuously monitor ST-trends and, thereby, continuously risk-stratify the patient. Our data suggest that a first evaluation of treatment can be done, and support for clinical decision-making may already be available at 60min: has the patient reached 50% ST-segment resolution? If so, myocardial flow is most probably restored and the patient belongs to the 40% at very low risk. If not, it may be time to prepare further invasive or pharmacological treatment, albeit such measures yet need to be documented in randomised trials. By then, using the well-documented Schroder-criteria10 30min later, here modified by including further knowledge on the true peak ST-elevation, decisions taken can be reconsidered or consolidated. ST-monitoring should probably thereafter proceed at least for 24h, since late electrocardiographic signs of reocclusion previously have been shown to predict worse outcome.28

4.1. Limitations
This study was conducted using two conceptually different ST-monitoring devices, where the major part of the population was collected by continuous VCG and a smaller part by continuous 12-leadmonitoring. This latter part of 181 patients showed a remarkably low 30-day mortality of only 2.2%(4 patients), which however was not statistically different from the mortality in the VCG-group and could not be explained by differences in baseline characteristics.

Differences in ST-resolution have been found between different types of monitors. In the GUSTO-1 study, for instance, continuous VCG and 12-lead monitoring were used in addition to continuous Holter.15 A difference in ST-resolutionbetween VCG and 12-lead-monitoring, on one hand, and Holter, on the other, was reported. Although information on myocardial reperfusion theoretically might be lost by analysing only the single worst lead in the 12-lead population as compared to analysing summarised spatial ST-changes in the VCG-population, we know as previously discussed, that both these systems are equally good in identifying a high-risk population among patients with non-ST-elevation infarctions17 and that the similarities really are greater than the differences. Furthermore, in this study-population, the two methods seem to equally well-classify the patients as being high or low risk at the 60- or 90-min analyses despite the very low event-rate in the 12-lead group. Thus, despite the methodological difference in data-collection, we found pooling of the two groups as being justified.


    5. Conclusions
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Continuous ST-monitoring of patients with acute myocardial infarction yields important prognostic information after only 1h of observation and treatment. This can be used for very early-risk stratification, and possibly supports a future basis for individualised treatment of these patients.


    Acknowledgments
 
Invaluable support was given by Monika Eriksson, Gerd Källström, Jenny Rössberg, Gunilla Norman, Ann-Marie Svensson, Helena Svensson, all research nurses at the Ischemia Core-lab, SahlgrenskaUniversity Hospital/Östra, Göteborg, and also by Jörgen Cronblad, research nurse at Department of Cardiology, Uppsala. The study was supportedby grants from the Swedish Heart and LungFoundation; Ortivus AB, Täby, Sweden; University of Göteborg; Boehringer Ingelheim, Skärholmen, Sweden and GE Medical Systems, InformationTechnologies, Milwaukee, USA.


    References
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

  1. Shah A, Wagner GS, Granger CB, et al. Prognostic implications of TIMI flow grade in the infarct related artery compared with continuous 12-lead ST-segment resolution analysis. Reexamining the ‘gold standard’ formyocardial reperfusion assessment. J Am Coll Cardiol. 2000;35(3):666–672[CrossRef][ISI][Medline]
  2. van 't Hof AW, Liem A, de Boer MJ, et al. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Zwolle Myocardial Infarction Study Group. Lancet. 1997;350(9078):615–619[CrossRef][Medline]
  3. Dellborg M, Topol EJ, Swedberg K. Dynamic QRS complexand ST segment vectorcardiographic monitoring canidentify vessel patency in patients with acute myocardial infarction treated with reperfusion therapy. Am Heart J. 1991;122(4 Pt 1):943–948[CrossRef][Medline]
  4. Lincoff AM, Topol EJ. Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation. 1993;88(3):1361–1374[Abstract]
  5. Ito H, Tomooka T, Sakai N, 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(5):1699–1705[Abstract]
  6. van 't Hof AW, Liem A, Suryapranata H, et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation. 1998;97(23):2302–2306[Abstract/Free Full Text]
  7. Barbash GI, Roth A, Hod H, et al. Rapid resolution of ST elevation and prediction of clinical outcome in patients undergoing thrombolysis with alteplase (recombinant tissue-type plasminogen activator): results of the Israeli Study of Early Intervention in Myocardial Infarction. Br Heart J. 1990;64(4):241–247[Abstract]
  8. Mauri F, Maggioni AP, Franzosi MG, et al. A simple electrocardiographic predictor of the outcome of patients with acute myocardial infarction treated with a thrombolytic agent. A Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2)-Derived Analysis. J Am Coll Cardiol. 1994;24(3):600–607[Medline]
  9. Lundin P, Eriksson SV, Strandberg LE, et al. Prognostic information from on-line vectorcardiography in acute myocardial infarction. Am J Cardiol. 1994;74(11):1103–1108[CrossRef][Medline]
  10. Schroder R, Wegscheider K, Schroder K, et al. Extent of early ST segment elevation resolution: a strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimens.A substudy of the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial. J Am Coll Cardiol. 1995;26(7):1657–1664[CrossRef][ISI][Medline]
  11. Krucoff MW, Green CE, Satler LF, et al. Noninvasive detection of coronary artery patency using continuous ST-segment monitoring. Am J Cardiol. 1986;57(11):916–922[ISI][Medline]
  12. Saran RK, Been M, Furniss SS, et al. Reduction in ST segment elevation after thrombolysis predicts either coronary reperfusion or preservation of left ventricular function. Br Heart J. 1990;64(2):113–117[Abstract]
  13. Clemmensen P, Ohman EM, Sevilla DC, et al. Changes in standard electrocardiographic ST-segment elevation predictive of successful reperfusion in acute myocardial infarction. Am J Cardiol. 1990;66(20):1407–1411[Medline]
  14. Dellborg M, Steg PG, Simoons M, et al. Vectorcardiographic monitoring to assess early vessel patency after reperfusion therapy for acute myocardial infarction. Eur Heart J. 1995;16(1):21–29[Abstract]
  15. Klootwijk P, Langer A, Meij S, et al. Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial. Eur Heart J. 1996;17(5):689–698[Abstract]
  16. Johanson P, Rossberg J, Dellborg M. Continuous ST monitoring: a bedside instrument? A report from the Assessment of the Safety of a New Thrombolytic (ASSENT 2) ST monitoring substudy. Am Heart J. 2001;142(1):58–62[CrossRef][Medline]
  17. Jernberg T, Abrahamsson P, Lindahl B, et al. Comparisonof continuous vectorcardiography and continuous 12-lead electrocardiography of patients with unstable coronaryartery disease: do they identify the same population? Coron Artery Dis. 2001;12(3):187–195[CrossRef][Medline]
  18. The ASSENT-2 Investigators. Single-bolus tenecteplasecompared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Assessment of the Safety and Efficacy of a New Thrombolytic Investigators. Lancet. 1999;354(9180):716–722[CrossRef][ISI][Medline]
  19. Wallentin L, Dellborg DM, Lindahl B, et al. The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study. Clin Cardiol. 2001;24(Suppl 3):I12–I14[ISI][Medline]
  20. Dellborg M, Riha M, Swedberg K. Dynamic QRS and ST-segment changes in myocardial infarction monitored by continuous on-line vectorcardiography. J Electrocardiol. 1990;23(Suppl):11–19[CrossRef][Medline]
  21. Frank E. Accurate, clinically practical system for spatial vectorcardiography. Circulation. 1956;13:737–744[ISI]
  22. Hogg KJ, Hornung RS, Howie CA, et al. Electrocardiographic prediction of coronary artery patency after thrombolytic treatment in acute myocardial infarction: useof the ST segment as a non-invasive marker. Br Heart J. 1988;60(4):275–280[Abstract]
  23. Bossaert L, Conraads V, Pintens H. ST-segment analysis: a useful marker for reperfusion after thrombolysis withAPSAC? The Belgian EMS Study Group. Eur Heart J. 1991;12(3):357–362[Abstract]
  24. Gibson CM, Murphy SA, Marble SJ, et al. Can we replace the 90-min thrombolysis in myocardial infarction (TIMI) flow grades with those at 60 min as a primary end pointin thrombolytic trials? TIMI Study Group. Am J Cardiol. 2001;87(4):450–453[CrossRef][Medline]
  25. Thygesen K, Horder M, Nielsen BL, et al. The variability of ST segment in the early phase of acute myocardial infarction. Acta Med Scand Suppl. 1978;623:61–70[Medline]
  26. Hackett D, Davies G, Chierchia S, et al. Intermittent coronary occlusion in acute myocardial infarction. Value of combined thrombolytic and vasodilator therapy. N Engl J Med. 1987;317(17):1055–1059[Abstract]
  27. Kwon K, Freedman SB, Wilcox I, et al. The unstable ST segment early after thrombolysis for acute infarction and its usefulness as a marker of recurrent coronary occlusion. Am J Cardiol. 1991;67(2):109–115[Medline]
  28. Langer A, Krucoff MW, Klootwijk P, et al. Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST SegmentMonitoring Substudy. J Am Coll Cardiol. 1998;31(4):783–789[CrossRef][Medline]
  29. Johanson P, Svensson AM, Dellborg M. Clinical implications of early ST-segment variability. A report from the ASSENT 2 ST-monitoring sub-study. Coron Artery Dis. 2001;12(4):277–283[CrossRef][Medline]
  30. Johanson P, Swedberg K, Dellborg M. ST variability during the first 4 hours of acute myocardial infarction predicts 1-year mortality. Ann Noninvasive Electrocardiol. 2001;6(3):198–202[Medline]