Prognostic Significance of a Standard 12-lead ECG
after Myocardial Infarction

Wojciech Zareba

the Heart Research Follow-up Program, Cardiology Unit, University of Rochester, Rochester, USA

Correspondence: Heart Research Follow-up Program, Cardiology Unit, University of Rochester, Box 653, 601 Elmwood Ave.
Rochester, NY, 14642, USA. E-mail: wojciech_zareba@urmc.rochester.edu, phone: 585-2755391, fax: 585-2735283

1.  Introduction

Identification of postinfarction patients at risk for cardiac death and sudden cardiac death may lead to optimization of medical therapy and implantation of cardioverter-defibrillators. In the current era of technological developments in cardiology, there are a number of methods that could be utilized for the risk stratification purposes. Historically, left ventricular ejection fraction was the first widely accepted risk stratifier in postinfarction patients. Subsequently interest in Holter recorded ventricular arrhythmias, late potentials on signal-averaged ECG, and heart rate variability substantiated prognostic value of these parameters in patients with prior myocardial infarction. New approaches including heart rate turbulence, T wave alternans, QT variability, and baroreflex sensitivity are being exercised for risk stratification purposes. Simultaneously, invasive electrophysiology testing with induction of ventricular tachycardia or fibrillation has been utilized for risk stratification purposes, however, its usefulness is at least questionable in light of results from recent trials. All the above methods are worth exploring and there are some advantages and limitations of these methods. There is a limited general access to the technology and methodology needed to implement some of these more sophisticated techniques as well as there are no standardizations of several of these methods. A standard 12-lead ECG is broadly available and it should not be neglected as a powerful tool when considering risk stratification in postinfarction patients. The aim of this summary is to emphasize the prognostic significance of ECG parameters derived from a standard 12-lead ECG.

2.  Heart Rate

The prognostic significance of heart rate was first established in epidemiological cohort studies and in studies of hypertensive patients [Kannel WB. Et al 1987; Palatini P 1999]. Subsequently, heart rate was also shown to be predictive in postinfarction patients including experience from large database of the GUSTO study [Hathaway et al. 1998]. In a recent study Berton et al [2002] showed that heart rate >80 bpm was associated with a 3-fold increased risk of mortality in patients with acute myocardial infarction. Data from the GESICA trial demonstrate that elevated heart rate in CHF population is predictive, but also might identify patients who benefit from amiodarone therapy [Nul et al. 1997]. Our observations from postinfarction studies in over 4000 patients show that heart rate is predictive for cardiac death both in patients off and on beta-blockers although heart rate cutoff for predicting death is different in these two groups: >64 bpm in patients off beta blockers and >80 bpm in those on beta-blockers [unpublished data].

3.  P Wave Morphology and Atrial Fibrillation

P wave morphology is rarely considered as a marker of the mortality risk in postinfarction patients. Abnormal P wave is usually considered as an ECG marker of substantial myocardial damage with subsequent atrial enlargement and hypertrophy. We studied the prognostic significance of atrial abnormality, defined as terminal deflection of the P wave ³0.1 mV deep and ³40 ms in duration in lead V1, in 1034 postinfarction patients with ECG recorded 5-7 days after myocardial infarction (Perkiomaki et al. 2002). Such an abnormality was found in 13% of the patients. Multivariate Cox analysis showed that atrial abnormality was a significant and independent predictor of cardiac death during a mean 2-year follow-up (hazard ratio = 2.46; p = 0.009). This strong association indicates that P wave abnormality is worth paying attention to in current era of aggressive treatment of acute myocardial infarction patients.

The prognostic significance of atrial fibrillation after myocardial infarction has been studied extensively and all studies indicate that atrial fibrillation even in thrombolytic era is an important risk factor for future cardiac events including cardiac death, but also stroke [Pizzetti et al 2001; Wong et al. 2002]. In the GISSI-3 trial [Pizzetti et al 2001] the incidence of in-hospital atrial fibrillation or flutter in patients with acute myocardial infarction was 7.8%. Atrial fibrillation was associated with indicators of a worse prognosis (age > 70 years, female sex, higher Killip class, previous myocardial infarction, treated hypertension, high systolic blood pressure at entry, insulin dependent diabetes, signs or symptoms of heart failure). After adjustment for other prognostic factors, atrial fibrillation remained an independent predictor of increased in-hospital mortality: 12.6% v 5%, adjusted relative risk (RR) 1.98, 95% confidence interval (CI) 1.67 to 2.34. Data on long term mortality (four years after acute myocardial infarction) confirmed the persistent negative influence of atrial fibrillation (RR 1.78, 95% CI 1.60 to 1.99). Similar data were reported from GUSTO III trial [Wong et al. 2002] where atrial fibrillation or flutter was associated with odds ratio of 1.49 (95% CI, 1.17-1.89) for 1-year mortality after myocardial infarction. In another study, Aronov et al [2001] also showed that chronic atrial fibrillation after myocardial infarction is associated with about 50% increased risk of mortality (Hazard ratio =1.5).

4.  QRS Complex

Current aggressive treatment of myocardial infarction contributes to an increased incidence of non-Q wave myocardial infarctions and to a smaller damage caused by ischemic injury. In prethrombolytic era, stable postinfarction patients after myocardial infarction had a similar long-term prognosis regardless of presence or absence of Q waves. In our analysis of 549 patients with first myocardial infarction [Zareba 1994], we found that 1/3 of them had non-Q wave MI and their two-year risk of cardiac events (defined as unstable angina, nonfatal reinfarction or cardiac death) was 17%, comparable to 16% observed in Q wave MI patients. Recent data from studies evaluating the significance of Q waves in thrombolytic era indicate that patients with non-Q wave MI have better prognosis than patients with Q-wave MI. Goodman et al. [2002] reported observations from combined 5 large clinical trials and they found that among patients receiving thrombolysis, those who developed a non-Q wave MI experienced significantly lower inhospital (absolute differences -3.8%) and 1-year mortality (absolute difference -6.4%) when compared with those who had a Q-wave MI.

QRS duration remains a very powerful predictor of future cardiac events in postinfarction patients [Hathaway et al. 1998; Pudil et al. 2001; Brilakis et al 2002]. QRS duration reflects well the magnitude of left ventricular dysfunction and therefore not surprisingly is a powerful predictor of mortality in postinfarction patients [Murkofsky et al. 1998]. Despite this strong association between QRS duration and ejection fraction, QRS duration measured on a standard ECG remains a powerful predictor of mortality after adjustment for ejection fraction and other clinical covariates. Our data in a large population of postinfarction patients indicate that QRS³0.12 sec is associated with hazard ratio of 1.7; p=0.001 [Fadl et al 2003].

5.  ST Segment

Persistent ST segment depression in patients after myocardial infarction is associated with adverse outcome. In MSSMI study conducted mostly in pre-thrombolytic era, Moss et al. [1993] demonstrated that in stable postinfarction patients (2 months after MI) persistent ST depression >1 mm on a standard 12-lead ECG is predictive for cardiac events. Recently, we evaluated the prognostic significance of ST segment in over 1,000 postinfarction patients enrolled in the THROMBO study [Perkiomaki et al 2002] and we found that lateral ST-segment depression predicted death (hazard ratio = 4.76; p <0.0001) as well as predicted a combined end point of cardiac death/nonfatal AMI/unstable angina (hazard ratio = 1.49; p = 0.003). Persistent ST depression in postinfarction patients likely reflects myocardial remodeling with involvement of left ventricle hypertrophy and should not be considered as a sign of ischemia.

6.  QT Interval Duration and Dispersion

In numerous electrophysiological studies, dispersion of repolarization has been proven to play a critical role in arrhythmogenesis. Over the last several years, QT duration and QT dispersion (measured in surface ECG recordings) has been explored as a potential noninvasive measure of nonuniform recovery of ventricular excitability in myocardium [Davey 2000; Zareba 2001]. There are convincing data demonstrating that QT dispersion is an imperfect measure of T wave morphology, affected by projection phenomena of T loop morphology and possibly by local repolarization changes. These conceptual limitations of QT dispersion analysis are further worsened by methodological problems including poor reproducibility and lack of standardization. Despite the above limitations, several studies have reported a significant association between QT dispersion and cardiac events in postinfarction patients although some other studies have not confirmed such an association. All these findings indicate that there is a need to develop novel methods quantifying repolarization morphology directly (for example using principal component analysis), not just through QT dispersion analysis. Therefore, QT dispersion measured manually is not recommended as routine clinical tool for risk stratification.

7.  Conclusive Remarks

As discussed above, a standard 12-lead ECG serves as an extremely useful tool in the risk stratification after myocardial infarction. Careful analysis of ECG provides comprehensive information about pathology of the heart, which could lead to cardiac events including reinfarction, progression of heart failure, and death. Heart rate is a reflection of the influence of the autonomic nervous system on the heart, whereas P wave abnormalities, QRS prolongation, chronic ST depression illustrate the magnitude of changes in myocardial substrate. QT prolongation and increased QT dispersion or T wave abnormalities could be considered as another measure of substrate or could reflect vulnerability of the myocardium to arrhythmias. Therefore, 12-lead ECG informs about important mechanistic pathways leading to cardiac events in postinfarction patients.

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