1Division of Cardiology, Sahlgrenska University Hospital/Östra, SE-41685 Göteborg, Sweden
2Duke University Medical Center, Durham, NC, USA
3University of Alberta, Edmonton, Canada
4Canadian Heart Research Center, and Terrence Donnelly Heart Centre, St Michael's Hospital, University of Toronto, Canada
5Thoraxcenter, Akademiska Hospital, Uppsala, Sweden
Received 10 December 2003; revised 9 February 2005; accepted 17 February 2005; online publish-ahead-of-print 11 April 2005.
* Corresponding author. Tel: +46 31 343 4000; fax: +46 31 25 9254. E-mail address: pj{at}hjl.gu.se
This paper was guest edited by Prof. Bernard J. Gersh, Mayo Clinic, Rochester, USA
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods and results We collected 234 patients with ST-elevation MI, without signs of previous MI, bundle branch block, or hypertrophy. MI size was determined by the Selvester score and was forecasted at: admission with patients stratified by delay time and an ECG acuteness score into three groups (EARLY, DISCORDANT, and LATE); 90 min after Rx by 70% ST-recovery or not and occurrence of "reperfusion peaks"; 4 h after Rx by ST re-elevations. EARLY patients had smaller final infarct sizes than LATE (9.4 vs. 20%, P=0.01). EARLY patients with
70% ST-recovery without a reperfusion peak had smaller infarct sizes than those with (3.1 vs. 12.5%, P=0.001). EARLY patients without ST re-elevations had smaller infarct sizes (1.5%) than those with some (9%) or many re-elevations (12%), P<0.001.
Conclusion Final infarct size can be forecasted using delay time and serial ECGs. Serially updated forecasts seem especially important when both clock-time and initial ECG- signs indicate earliness.
Key Words: Myocardial infarction ECG Infarct size Fibrinolysis
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Serial forecasts of salvagability and final infarct size before, during, and after reperfusion treatment of STEMI would allow the identification of (i) high-risk patients with a predicted major loss of viable myocardium at a stage when treatment may still be modified and (ii) low-risk patients with predictions of small infarcts and good outcome after primary reperfusion therapy. This paper examines a model for such serial forecasting, using evolving time and ECG-analyses to stratify patients with STEMI.
The amount of myocardium at risk for infarction can be assessed by ST-segment analyses from the admission ECG.1,2 This first ECG can also be used to estimate the acuteness of the infarction process3 complementary to information from symptom delay.4 Treatment efficacy, i.e. speed and quality of restoration of epicardial flow57 and myocardial perfusion8,9 can be assessed by ST-segment recovery analyses. Rapid, high-grade, and stable ST-recovery has consistently been associated with better clinical outcome.1013 This association is likely secondary to the fact that faster restoration of myocardial perfusion results in greater myocardial salvage and smaller infarct size.14 Recent studies have shown that early and complete ST-recovery is indicative of smaller infarct size.15,16
We hypothesized that combinations of clock-time and previously evaluated ECG variables could be useful for serially updated forecasts of final infarct size and that these forecasts would change with ECG signs of successful/unsuccessful reperfusion treatment.
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
For inclusion in the present substudy, availability of an admission ECG, either a discharge ECG or, if missing, a 2436 h ECG, and continuous ST-monitoring data were required. Out of the 374 patients from the vectorcardiographic (VCG) ST-monitoring substudy of the ASSENT 2,12 303 fulfilled these criteria.
Quantitative analyses of serial ECGs
Serial ECGs were read by readers at the ECG Core Laboratories (Canadian VIGOUR Centre, University of Alberta, Edmonton and Canadian Heart Research Centre, Toronto) without knowledge of outcomes.
Admission ECG
The amount of ST-segment deviation (from the reference level in the PR segment) was measured manually using a hand-held calliper at J+20 ms. On the basis of the lead with the maximal ST-deviation, patients were divided into anterior or inferior infarct location. Patients with maximal ST-elevation in leads V1V3 were classified as anterior, whereas those with maximal ST-elevation in II, aVF, or III (or ST-depression in V1V3) as inferior location. ST-deviation in the admission ECG was summated according to the Aldrich ST-score to estimate the area jeopardized for infarction.1
The AndersonWilkins (AW) acuteness score3 was also calculated from the admission ECG. This score ranges from 1.0 (least acute) to 4.0 (most acute) and takes QRS-, ST-, and T-measurements into consideration for judgment of how early during the infarct process the ECG was recorded.
Pre-discharge ECG
Final infarct size was defined by the Selvester QRS score either from the pre-discharge ECG or, if such an ECG was not available, from the 2436 h ECG. Selvester scoring of the QRS-complex has previously been detailed.18 Briefly, this QRS score is based on the consideration of 50 criteria, producing a maximum of 31 points, each of which representing 3% infarction of the left ventricle.
ST-monitoring
Patients were monitored for 24 h after admission with high-fidelity digital continuous ST-monitoring, using the MIDA system for continuous VCG (Ortivus Medical AB, Täby, Sweden).12 By this system, ST-vectormagnitude (ST-VM) is calculated from the orthogonal leads X, Y, and Z, according to the formula: ST-VM=(Xi2+Yi2+Zi2) and represents the total, spatial ST-segment deviation from the baseline. Xi, Yi, and Zi are the magnitudes of ST-deviation in the three leads. ST-VM is presented online on a computer screen as a trend curve (Figure 1). ST-segment changes were measured 20 ms after the J-point.
|
As in previous VCG-studies on recurrent ST-elevations,12,19,20 during the first 4 h, an increase in ST-VM from 1 min to the other exceeding 25 µV for 2 min was counted as an ST-event. During such events, the total area under the ischemia curve (AUC) was summated (µVxmin).
Exacerbation of ST-segment elevation at the time of reperfusion is proposed as a sign of poor outcome, indicating a reperfusion syndrome.21 We prospectively defined the occurrence of a marked (>80 µV) and rapidly evolving (<5 min) exacerbation of ST-VM,22 if it occurred prior to 50% ST-recovery and within 90 min from onset of therapy, as a reperfusion peak.23
All analyses were made by two blinded and independent observers at the Ischemia Core Lab, Sahlgrenska University Hospital/Östra, Göteborg.
Modelling of the serial forecast method
Three serial forecasts were done at admission, 90 min, and 4 h after treatment (Figure 2).
|
Model development
Three models were developed sequentially in our study (Table 3), incorporating information collected on admission, at 90 min, and 4 h. The following variables were included in each of the predicting infarct size models (i) on admission: baseline patient demographics data (Table 1), presenting characteristics, Aldrich score and acuteness score. (ii) At 90 min: in addition to the baseline demographics data, presenting characteristics, Aldrich score and acuteness score, the variables complete ST-recovery at 90 min, and occurrence of a reperfusion peak were added into the model. (iii) At 4 h: occurrence of ST re-elevation by 4 h was added into the model in addition to the variables included in the 90 min model. Multiple logistic regression procedures based on the stepwise, backward variable selection method were used to develop these models. The models were evaluated on the basis of the discriminatory capacity (i.e. c-statistic) and the linearity assumption was tested using the Box-Tidwell test.
|
|
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Patient delay was assessed by historical time and AW acuteness score. One-hundred and seventeen patients (50%) had a delay time 2 h and 163 (70%) had an AW-score
3, indicating high acuteness i.e. a short delay. Eighty-two patients (35%) were concordantly early by both measurements (EARLY) and 36 (15%) were concordantly late by both (LATE); in 116 (50%) patients, these measurements were discordant (DISCORDANT). Demographics for these patient groups are also shown in Table 1.
Final infarct size
Table 2 illustrates the individual time and electrocardiographic variables that were investigated and how they were distributed over four groups of infarct size, when dividing this endpoint by quartiles.
|
|
However, in the EARLY group, occurrence of a reperfusion peak prior to ST-recovery, i.e. a marked and rapidly evolving worsening of ST-elevation after onset of treatment, was associated with significantly larger infarcts (12.5 vs. 3.1% of the left ventricle, P=0.001) among patients with 70% ST-recovery (Figure 4). In the DISCORDANT and LATE groups, the admission forecasts of medium and large final median infarct size, respectively, were not changed significantly by either presence of a reperfusion peak or ST-recovery at 90 min. Again, the area of initially jeopardized myocardium (Aldrich score) did not vary significantly between the groups (Figure 4).
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
First forecasting of infarct size
We have demonstrated that a combined analysis of ECG and time variables clinically available at first contact might be of use for identifying patients who are more likely to benefit from fibrinolytic reperfusion therapy and possibly those who will benefit less from such therapy. In patients with one or both of these variables indicating earliness, final infarct size was significantly smaller, and <50% of the final infarct size that was found in patients with both variables indicating lateness. These observations are consistent with previous findings. Historical timing of the acuteness of an AMI, i.e. the patient's description time-delay from symptom onset to hospital presentation and initiation of therapy, has shown that early reperfusion therapy resulted in smaller final infarct size, irrespective of how much myocardium that was initially jeopardized.24 The model for using the AW acuteness score from the admission ECG together with historical timing, has been explored and shown to refine the estimation of acuteness of an AMI.4 In the current population, however, median delay times did not differ significantly over the quartiles of infarct size (Table 2). Furthermore, our findings in the DISCORDANT group indicate that when delay time and the acuteness score point in different directions, the acuteness score probably gives a better estimate of the earliness of an AMI.
Second forecasting of infarct size
Rapid and high-grade ST-segment resolution following an acute MI has been associated with better left ventricular function,10,25,26 smaller final infarct size as measured by enzymes,10,15 and Selvester QRS-scoring of the pre-discharge ECG,15 and with greater myocardial salvage, measured by nuclear imaging.16 Rapid and high-grade ST-segment resolution has consistently been shown to be useful for early identification of patients at low- or high risk for subsequent morbidity and mortality.10,13,27
We expected that patients who were early by both historical time and AW-score and had a high-grade early ST-recovery would have small final infarct sizes. Contrary to these expectations, complete ST-recovery within 90 min as opposed to non-complete ST-recovery, was not by itself associated with smaller final infarct sizes in any of the three groups. Similarly, smaller infarct size was not preceded by shorter median times to 50 or 70% ST-recovery. This potential inconsistency might, however, be explained by the fashion, in which ST-segment resolution is calculated during continuous ST-monitoring: the reference value is continuously updated, using the preceding peak value for the calculations of ST-resolution at a certain time. When considering the occurrence of a significant worsening of ST-elevation, preceding ST resolution, here defined as a reperfusion peak,22,23 a group of patients with very small final infarct sizes could be identified. Absence of such a reperfusion peak was significantly associated with very small final infarct sizes among the EARLY patients with complete ST-recovery.
These findings are supported by previous reports. Additional ST-elevation at the time for the restitution of coronary flow in an infarct related artery has been shown in 2750% of cases,21,22 and has, in most previous studies, been associated with unfavourable outcome such as reduced microcirculation, large infarct size, or impaired left ventricular function.21,28,29 In our study, angiographic measurements of coronary flow to correlate with the timing of the occurrence of a reperfusion peak were not available. However, the definition used has previously been found to correlate very well with angiographic reflow in patients with STEMI treated by either fibrinolytics or angioplasty.22
Third forecasting of infarct size
ST-segment re-elevations either during the first hours of fibrinolytic treatment of an STEMI12,19,20,30,31 or later during the first 24 h32 have consistently been associated with worse outcome measured as morbidity and mortality. Two previous studies address the possible relationship between ST re-elevations and infarct size.26,30 In these reports, patients with ST re-elevations had larger infarct sizes as measured by enzyme levels. When compared with the predictive information from mere ST-segment resolution at a certain time-point, ST-dynamics beyond this have been shown to yield further predictive information. In a previous study, we found that early ST-segment resolution did not contribute to the information on TIMI flow or persistence of thrombi in the culprit coronary artery 47 days after the acute event, whereas ST re-elevations during the first 24 h did.20
Our expectations of smaller final infarct sizes in patients without ST re-elevations were confirmed, at least in the EARLY group. Patients with some and more re-elevations had a six- and eight-fold increase in final infarct size, respectively, when compared with those with no re-elevation.
Clinical implications
Our findings suggest that the impact of thrombolytic therapy on final infarct size in patients with STEMI may be non-invasively forecasted and, at least in the EARLY patients, serially updated following the first ECG. The model could, therefore, be clinically valuable especially for patients who are early by both the ECG acuteness score and the delay time. In the present study, these patients had smaller final infarct sizes but were also the only ones who had significant changes in the subsequent forecasts on the basis of ECG dynamics. Their initial forecast of a small infarct size, changed to either very small in the subgroups with ECG signs indicating efficient reperfusion therapy or medium in the subgroups without such signs. As for the LATE patients in this small study, it might actually be questioned whether fibrinolytic treatment resulted in any gain at all, even if the groups are too small to conduct any meaningful mortality comparisons. The amount of initially jeopardized myocardium equalled the amount of finally infarcted myocardium in all subgroups of these patients, irrespective of subsequent ECG dynamics. Their initial forecast of a large infarct size thus remained unchanged.
Combinations of bioelectrical markers such as the ones used in our model and biochemical markers could also be of further value.3335 However, our methods, used both for assessing information from the admission ECG and for continuous assessments of ECG dynamics thereafter, are not routinely employed in clinical practice. Indeed, both the different scoring systems of static ECGs and the information from continuous ST-monitoring are generally employed in a research setting. Nevertheless, in an era of evolving digitized ECG analysis methods, automated systems for such scoring will be available in the near future. Furthermore, ischemia monitoring by continuous ST-monitoring is gaining favour both in research applications and as real time bedside monitors.36,37
We believe this report provides novel information based on monitoring tools which can be routinely employed in the treatment of STEMI patients and may be combined for increased predictive value and for clinical decision making. However, these first findings require additional verification before recommending general use in STEMI risk stratification.
Limitations
Although the Selvester QRS score is well validated for the estimations of infarct size, the sole use of the ECG for infarct size definition is a limitation of this study. Moreover, this score probably yields a relatively wide variation in its correlation to anatomical infarct size and should, therefore, be considered as an estimate, not an absolute measurement of infarct size. As in many substudies, questions on representability of our population should be raised. The data loss due to lack of follow-up ECGs and the extensive exclusion criteria used for enabling the calculations of Selvester and AW acuteness scores have resulted in a study population with very low 30 day mortality when compared with the mortality in the main trial. The extensive exclusion criteria have also resulted in comparisons between rather small groups. It would, for instance, at the 4 h forecast, have been desirable to include the subdivider used at 90 min (complete vs. non-complete ST-recovery), but the patient groups would then have become far too small.
Finally, the consideration of reperfusion peaks in this particular analysis was a post hoc decision even if this variable actually was prospectively defined when first deciding which variables to collect when designing the original ST-monitoring substudy.
![]() |
Acknowledgements |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Appendix 1 |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Acuteness score calculation
The Acuteness Score (AS) is calculated by dividing the sum of points by the number of leads involved (aVR not included)
![]() |
![]() |
Appendix 2 |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|