Ischemia-induced ST-segment elevation: classification, prognosis, and therapy

Abstract

The standard 12-lead electrocardiogram (ECG) remains the most useful tool for the diagnosis, early risk stratification, triage, and guidance of therapy in patients with acute coronary syndromes. However, the initial and the terminal part of the QRS complex, the ST segments, and the T waves are influenced by anatomical and metabolic factors such as the “myocardium at risk” and “severity” and “duration” of ischemia. Moreover, there are complex interactions between all these factors. The ECG can identify potential candidates for reperfusion therapy as well as the completeness and success of reperfusion, whereas it can also identify those patients who will have no benefit from reperfusion because of either late arrival or nonischemic etiologies of ECG changes. These patients may have a “pseudo” ST-elevation acute myocardial infarction (STEAMI) or “pseudo-pseudo” STEAMI. The presence of Q waves and additional ST-segment depression and T-wave inversion on the admission ECG in patients with STEAMI may provide us information regarding the potential myocardial reserves, and various ECG scoring systems are in current use for that purpose. The pattern and timing of changes in Q waves, ST segment, and T waves may all be markers of the patency status of the infarct-related artery. We review and discuss each of the dynamic ECG variables during ischemia and reperfusion: the initial QRS (Q and R waves), the terminal QRS (Sclarovsky-Birnbaum score), the ST segment, and the T waves.

Introduction

Despite major advances in cardiac imaging techniques, the standard 12-lead electrocardiogram (ECG) remains the most used tool for the diagnosis, early risk stratification, triage, and guidance of therapy in patients with acute coronary syndromes, including acute myocardial infarction (AMI). In general, patients with either ST elevation or presumably new left bundle branch block are referred for urgent reperfusion therapy (thrombolysis or percutaneous mechanical interventions) [1], whereas those with ST depression, T-wave inversion without ST elevation, or no acute ST-T changes are treated more conservatively, at least initially [2]. However, this simplified classification, although practical for generalized guidelines, may underestimate the complexity of reality. There are many patients with chest pain and baseline nonischemic ST elevation, either related to early repolarization, secondary to left ventricular hypertrophy, or cardiomyopathy. Some of these patients may have subsequently increase in cardiac markers without any further ECG changes (No ST resolution, no new Q-wave development, and no T-wave inversion) (Fig. 1). These patients may have non–ST-elevation acute myocardial infarction (STEAMI) with baseline ST elevation, or “pseudo” STEAMI. On the other hand, many patients with transient ST elevation have ST resolution without an increase in the cardiac markers. Although some of them may have acute pericarditis, vasospastic angina, or “aborted myocardial infarction” [3], many have simply transient “early repolarization” or “pseudo-pseudo” STEAMI (Fig. 2). This entity has not been well characterized. The clinician encountering a patient with suggestive symptoms and ST elevation has to make therapeutic decisions concerning urgent revascularization rapidly, in many times before the increase in cardiac markers occurs. It means that we are treating “suspected” STEAMI and not proven STEAMI. It is unclear how many patients with pseudo or pseudo-pseudo STEAMI have been included in randomized trials of STEAMI. Increasing the “threshold” for ST elevation (ie, 2 mm in the precordial leads) may decrease the occurrence of “false-positive” cases but may result in reduced sensitivity and underutilization of reperfusion therapy. Availability of previous ECG recordings and selective use of echocardiograms may enable the clinician to improve the accuracy of the diagnosis of true STEAMI that may benefit from urgent reperfusion therapy.

The immediate and long-term prognoses after AMI correlate with the amount of remaining viable and functioning myocardium, that is, the myocardial reserve. This is determined not only by the extent of acutely ischemic/infarcted zone, but also by the presence of old infarcts, “stunned” myocardium that recovers its function after reperfusion, the amount of remote and chronically ischemic (“hibernating”) myocardium, and the remote myocardium that is acutely ischemic either because collateral vessels to that area have occluded or because compensatory demands to that area have increased. Whereas the myocardial reserve of patients with single-vessel disease and first AMI is in general inversely correlated with the size of the ischemic area at risk, in those with multivessel disease and/or previous myocardial injury, a relatively small AMI can cause significant decompensation. For example, occlusion of the distal posterior descending artery would by itself cause a small inferior AMI, but the outcome could be much worse if the artery was also providing collaterals to remote viable myocardial segments (ie, anterior and septal walls in a patient with severely narrowed left anterior descending coronary artery).

The presenting ECG of patients with STEAMI may provide us information about the potential myocardial reserves. For example, the presence of QS waves in the precordial leads in a patient with inferior STEAMI indicates old anterior AMI with lower myocardial reserves. This combination may be associated with a greater risk than anterior STEAMI with Q waves in the inferior leads [4]. The presence of ST depression in the lateral leads, especially V₄ through V₆, in patients with inferior STEAMI is associated with concomitant left anterior descending coronary artery disease and/or 3-vessel disease [5], [6], [7].

Final infarct size is determined by the amount of myocardium perfused by the occluded artery (the ischemic “myocardium at risk”), the “duration of the ischemia,” and the “severity of ischemia” (or “rate of progression of necrosis”). Theoretically, knowing the following variables “myocardial reserves, the amount of myocardium at risk, the duration of ischemia, the amount of this area that had already infracted, the severity of ischemia” in addition to the expected time to reperfusion and the expected success rate of reperfusion may enable the clinician not only to make the diagnosis, but also to predict prognosis and to choose the appropriate therapeutic modality (ie, thrombolytic therapy, transfer for percutaneous intervention, etc). For example, one could predict that acute reperfusion would be most beneficial in patients with a large ischemic zone but a small amount of necrosis, as opposed to those with a small ischemic zone that has almost completely infarcted. Reperfusion might improve remodeling and/or prevent an arrhythmia in the latter group, but it would not preserve myocardial function.

The duration of ischemia is a major determinant of final infarct size. However, most patients do not recall the exact time when pain started. Moreover, in many patients, at least initially, there are cyclic episodes of occlusion and reperfusion that may cause fluctuations in the severity of symptoms. It is unclear if we should measure the time from first onset of symptoms or from the point of maximal continued pain. Moreover, episodes of spontaneous reperfusion [8] may alter the correlation between ischemic time and necrosis. Furthermore, there is a lag period between the time that one makes the decision to proceed with reperfusion therapy and the time reperfusion actually occurs (usually 45-90 minutes with thrombolytic therapy; 1-2 hours with primary percutaneous intervention). Thus, total ischemic time may be more important than the time from onset of symptoms to presentation.

The severity of ischemia or the rate of necrosis varies considerably. It is determined by the amount of residual myocardial perfusion (either by anterograde flow through the culprit vessel [incomplete occlusion] or perfusion by collaterals) and by metabolic factors (mismatch between supply and demand [heart rate, afterload], presence of protective mechanisms such as “ischemic preconditioning,” and the effect of various drugs). Currently, we can measure residual myocardial perfusion with imaging techniques (contrast echocardiogram, radionuclide imaging, or magnetic resonance imaging). However, we currently do not have a method for estimating the effects of the “metabolic factors.”

Many studies have investigated the ability of the 12-lead ECG to estimate the size of the ischemic myocardial zone at risk, the severity of ischemia, the amount of myocardium that has already infarcted, and the presence and quality of reperfusion. Arnold and Simoons [9] have integrated all these variables to define the “expected myocardial infarct size without reperfusion therapy.” However, nowadays, we would also like to know the “expected myocardial infarct size if thrombolysis is administered” and the “expected myocardial infarct size with primary percutaneous interventions.”

The ECG variables that evolve during ischemia and reperfusion are (1) the initial QRS (Q and R waves), (2) the terminal QRS (Sclarovsky-Birnbaum score) [10], [11], (3) the ST segment, and (4) the T waves. Investigators have examined each variable alone and several variables using analysis of covariance or logistic regression and have also incorporated changes in 2 or more variables to define clinically meaningful patterns, templates, or scores.