European Heart Journal Advance Access originally published online on November 15, 2007
European Heart Journal 2007 28(24):2957-2959; doi:10.1093/eurheartj/ehm512
Use of the electrocardiogram in optimizing reperfusion for ST-elevation myocardial infarction: a new role for an old tool?
1 Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA
2 VA Health Services Research & Development Center of Excellence, Ann Arbor VA Medical Center, Ann Arbor, MI, USA
* Corresponding author. Tel: +1 734 936 8214; fax: +1 734 615 3326.E-mail address: ckasapis{at}med.umich.edu
This editorial refers to ‘The electrocardiographic window of opportunity to treat vs. the different evolving stages of ST-elevation myocardial infarction: correlation with therapeutic approach, coronary anatomy and outcome in the DANAMI-2 trial’ by M.J. Eskola et al., on page 2985
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. 
Rapidly obtaining an electrocardiogram (ECG) is the critical first step in the evaluation of patients with chest pain. For >25 years, the ECG has been used to detect those patients with ST-elevation myocardial infarction (STEMI) who are eligible for reperfusion therapy with either fibrinolytic therapy or primary percutaneous coronary intervention (PCI).1,2 The ECG also has been instrumental in identifying those patients at highest risk for complications following STEMI and who may gain the most benefit from reperfusion therapy, based on features such as infarct location, the sum of ST-elevations, and the presence of reciprocal ST-depression or arrhythmias.3
Once patients with STEMI are identified, the decision to administer reperfusion therapy should be made as rapidly as possible and, ideally, it should be delivered within 12 h from symptom onset. Primary PCI is generally recognized as superior to fibrinolytic therapy due to its higher TIMI 3 (Thrombolysis In Myocardial Infarction) flow rates and lower rates of reinfarction, intracerebral haemorrhage, and mortality.4 However, primary PCI is not immediately available at many hospitals, and time delays in performing it may negate its advantages over fibrinolytic therapy.5 In fact, fibrinolytic therapy may actually be preferred when patients present very early after symptom onset and face potentially long delays to primary PCI.6
With these challenges in mind, risk stratification in STEMI has become increasingly important in selecting the optimal type of reperfusion therapy. The intent is to identify those patients who might benefit the most from primary PCI or, conversely, those who may be safely treated with fibrinolytic therapy. Using data from the landmark DANAMI-2 trial,7 for example, Thune et al. found that differences in mortality between primary PCI and fibrinolytic therapy were primarily driven by a high-risk subgroup of patients with TIMI risk scores of 
5.8 Importantly, only 25% of the study population was considered high risk using these clinical criteria, indicating that the benefits of urgent transfer for primary PCI are attained for a minority of patients.
Moving a step further, a large observational study by Pinto and colleagues evaluated the potential for risk stratification in the context of the ‘real-world’ challenges of providing primary PCI in a timely manner.9 After stratifying patients based on three clinical factors—age (<65, 65 years old), infarct location (anterior, non-anterior), and time from symptom onset to presentation (
2, >2 h)—the investigators compared in-hospital mortality between primary PCI and fibrinolytic therapy across different time intervals of PCI-related delay (i.e. median door-to-balloon time minus median door-to-needle time). In patients with high mortality risk, early presentation, and low bleeding risk, equipoise between primary PCI and fibrinolytic therapy was reached after only short PCI-related time delays (e.g. as short as 40 min). In contrast, equipoise was reached much later in patients with low mortality risk, later presentation, and high bleeding risk (e.g. as long as 179 min), suggesting that PCI-related time delays were less critical in these individuals.
Successful examples of regional systems of care for primary PCI have implemented these approaches in risk stratification in STEMI.10 However, it is important to recognize potential limitations to this approach. Patients often do not recall the precise time of symptom onset, especially when symptoms are intermittent or atypical, and this type of data is a key criterion for many transfer protocols. In addition, it is unlikely that the presence of a handful of clinical factors entirely accounts for the large variation in outcomes noted between primary PCI and fibrinolytic therapy. Practical application of these strategies, therefore, leaves room for improvement, especially when the decision about reperfusion therapy is applied to an individual patient and not populations.
The study by Eskola and colleagues adds new information to this ongoing debate by proposing an expanded role for the ECG in risk stratification in STEMI.11 In a post hoc analysis of 1300 patients from the DANAMI-2 trial, these investigators evaluated the prognostic significance of two distinct and easily recognizable ECG patterns in STEMI—the pre-infarction syndrome (PIS) (Figure 2A in Eskola et al.) and the evolving myocardial infarction (EMI) pattern (Figure 2B–D)—and their potential impact on the choice between primary PCI and fibrinolytic therapy. Possible advantages of this approach include its immediate availability and overall simplicity, since it does not require complex quantitative assessments like prior approaches.12–15
In this study, the PIS pattern (n = 952) was specifically defined as the presence of anterior or inferior STEMI (given patients with lateral STEMIs and left bundle branch blocks were excluded), without evidence of pathological Q-waves or inverted T-waves in the leads with an injury current. The EMI pattern (n = 348) was specifically defined as the presence of myocardial necrosis (i.e. the presence of pathological Q-waves) with or without signs of reperfusion (i.e. negative or biphasic T waves). The PIS pattern was more common than the EMI pattern in patients with both anterior STEMI (59 vs. 41%, respectively) and inferior STEMI (86 vs. 14%). EMI patients also had a >1 h longer median time delay from symptom onset to randomization, consistent with the presence of greater myocardial necrosis at presentation.
The first noteworthy finding from this study was a higher rate of the composite end-point of death, reinfarction, and disabling stroke in EMI vs. PIS patients at a median follow-up of 2.7 years (11.4 vs. 6.9% per 100 person-years, respectively; P < 0.001). This is not entirely unexpected, since anterior STEMI and longer time delays to presentation were more common in EMI patients. However, the more remarkable finding was that PIS patients treated with primary PCI had a 40% relative risk reduction of the composite end-point compared with PIS patients treated with fibrinolytic therapy. In contrast, there were no significant differences between reperfusion therapies in EMI patients, with the exception of 139 patients with anterior infarcts and no evidence of reperfusion (i.e. absence of negative or biphasic T-waves) who also demonstrated benefit with primary PCI.
These results conflict somewhat with earlier reports. For example, the PIS pattern was linked to improved outcomes with primary PCI despite its association with a lower rate of the composite end-point. This is counterintuitive to the findings of the study by Thune et al., which found that the benefits of primary PCI were strongest in high-risk patients within the same study population.8 A potential explanation is that these two ECG patterns are limited in their ability to identify high-risk patients when used in isolation from clinical factors. This possibility is supported by the finding of benefit with primary PCI in EMI patients with anterior STEMI and no ECG evidence of reperfusion, a high-risk subgroup.
Another concern is the small overall number of patients identified by the EMI pattern in this study, which resulted in limited statistical power to detect significant differences between reperfusion therapies in these patients. The close resemblance of survival curves for patients treated with fibrinolytic therapy and primary PCI in the PIS and EMI patterns (Figure 3A and B in Eskola et al.) actually suggests that the benefit of primary PCI may have been comparable between both groups. Furthermore, these results imply that the discerning ability of these ECG patterns is limited when used in isolation from clinical factors. Only 209 of 1300 patients in the study population could be safely deferred to fibrinolytic therapy based on these results. In comparison, Thune et al. used clinical factors to identify 1134 patients from the same study population with no mortality differences between primary PCI and fibrinolytic therapy. Understanding how these ECG patterns incrementally enhance prior risk stratification in STEMI therefore will be critical.
It was also interesting to note that improved outcomes with primary PCI in PIS patients were linked to earlier presentations after symptom onset. Pinto et al., in contrast, demonstrated that patients with earlier presentations required primary PCI to be performed very rapidly in order for its mortality advantage over fibrinolytic therapy to be maintained.9 We believe this discrepancy is largely explained by two reasons. First, and most importantly, the study populations were quite different. The DANAMI-2 trial included highly selected patients in a clinical trial setting who were treated rapidly and within an integrated healthcare system.7 The study by Pinto and colleagues examined a more diverse study population within an observational registry of hospitals across the USA where times to treatment were often prolonged. Secondly, Pinto and colleagues focused on in-hospital mortality, whereas a lower rate of the composite end-point with primary PCI in the Eskola et al. study was driven primarily by lower reinfarction rates.
Notwithstanding these limitations, we believe that the concepts introduced by Eskola et al. are highly provocative with potentially important implications for regional systems of care for STEMI. Simple ECG patterns, such as the PIS and EMI, or even more complex patterns that can be incorporated into automated interpretation software, may have the ability to augment clinical factors that are currently being used with success. Although this approach undoubtedly requires further investigation, these early data appear promising for a diagnostic tool with such a deep-rooted history in STEMI.
Acknowledgments
We are grateful to Drs Eric R. Bates and Henry H. Ting for their insightful comments on an earlier draft of this manuscript.
Conflict of interest: none declared.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
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