DIANNOSTIC ACUTE MYOCARD IINFARCTION

Clinical Findings
The clinical presentations of patients with AMI vary. Although most patients have had chest discomfort prior to the onset of infarction, 20% or more have infarction as a first manifestation of ischemic heart disease; in 20–30% of patients, infarction may go unrecognized. Nonetheless, symptoms are generally present.
A. SYMPTOMS AND SIGNS

The most common and best symptom on which to base a consideration of MI is chest discomfort, usually described as “pressure,” “dull,” “squeezing,” “aching,” or “oppressive,” although it may be described differently because of individual variability, differences in articulation or verbal abilities, or concomitant disease processes. The discomfort is usually in the center of the chest and may radiate to the left arm or the neck. In general, patients with ischemic chest pain tend to be still, but patients with infarction can be restless as well. The nature of the pain may lead patients to place a hand over the sternum (Levine’s sign). These clinical signs and symptoms were originally defined in groups of males. It is now clear that women often have more disease symptoms or more atypical symptoms.
Patients with diabetes or hypertension also may have atypical presentations; a classic presentation in a diabetic is with abdominal pain that mimics the discomfort commonly associated with gallstones. Elderly patients often present with heart failure: by age 85, only 40% of patients will present with chest discomfort. Patients who present with symptoms compatible with ischemia, (paroxysms of dyspnea, for example) or atypical chest discomfort should have the diagnosis of MI considered. Patients can also present with discomfort that is sharper or that radiates to the back. These patients can have pericarditis alone, pericarditis induced by infarction, or a dissecting aortic aneurysm—with or without concomitant infarction.
Much has been made of the presence of associated symptoms and findings such as dyspnea, diaphoresis, nausea and vomiting, and the response of chest discomfort to antianginal agents. Although positive findings should evoke increased consideration of a diagnosis of ischemic heart disease, their absence is not definitive.
B. PHYSICAL EXAMINATION

The physical examination may vary tremendously, from markedly abnormal, with signs of severe congestive heart failure (CHF), to totally normal. In general, an S4 sound is heard in patients with ischemic heart disease. Dyskinesis can be palpated in patients with larger infarctions. Signs of heart failure, such as neck vein distention, S3 sounds, and rales, should be looked for specifically.
C. DIAGNOSTIC STUDIES

The diagnosis of infarction in patients with suspected acute ischemic heart disease requires evidence of myocardial necrosis. This finding usually depends on elevated molecular markers of cardiac injury.
1. Troponins are the markers of choice— They are significantly more sensitive than CK2, and now with second- and third-generation assays, they have nearly absolute cardiac specificity. Absent analytic false-positives, one can be sure that the release of troponin is indicative of cardiac injury. However, because they are so sensitive, they detect cardiac insults that are nonischemic in nature (Table 5–1). Thus, the diagnosis of AMI requires clinical, electrocardiographic (ECG), or other (eg, coronary angiographic) evidence of acute ischemia (see Table 5–1). Troponin is elevated between 4 and 6 h after onset of an AMI and remains elevated for 8–12 days. Thus, the late or retrospective diagnosis of AMI can be made with this marker, making the use of lactate dehydrogenase isoenzymes superfluous. Troponin elevations in patients with ST elevation at the time of admission presage a lower rate of recanalization regardless of reperfusion modality used and a worse prognosis. This may be, at least in part, because patients with elevations present later than those without elevations. Patients who present with ST depression also have a worse prognosis if troponin is elevated to any extent. Even minor elevations are of significance (Figure 5–2). This group also has a unique beneficial response to LMWH and IIb/IIIa agents. Patients at low risk for ischemic heart disease who present with chest pain have a high frequency of coronary artery disease if troponin is elevated. Because increases in troponin persist for up to 2 weeks after an acute event, if the initial troponin value is elevated, it may be of value to define a shorter-lived marker (eg, CK2) if the cardiac injury is acute or has occurred in the days or weeks prior to presentation.

Table 5–1. ESC/ACC definition of myocardial infarction.

Figure 5–2. Prognosis in patients with acute coronary syndrome (ACS), elevated troponin, and no elevation of CK2 (isoenzyme of creatinine kinase), Peto odds ratio (OR), and 95% confidence interval (fixed). Adapted, with permission, from Am Heart J 2000;140:917.

Coronary recanalization, whether spontaneous or induced pharmacologically or mechanically, alters the timing of all markers’ appearance in the circulation. Because it increases the rapidity with which the marker is washed out from the heart, leading to rapid increases in plasma, the diagnosis of infarction can be made much earlier—generally within 2 h of coronary recanalization. Although patency can be approximated from the marker rise, distinguishing between thrombolysis in myocardial infarction (TIMI) II and TIMI III flow is not highly accurate. It should also be understood that peak elevations are accentuated, which must be taken into account if one wants to use peak values as a surrogate for infarct size.
2. Other molecular markers— The diagnosis of infarction requires increases in molecular markers of myocardial injury. Myoglobin release from injured myocardium occurs quite early and is very sensitive for detecting infarction. Unfortunately, it is not very specific because minor skeletal muscle trauma also releases myoglobin. Myoglobin is cleared renally, so even minor decreases in glomerular filtration rate lead to elevation. The other early marker advocated by some are isoforms of CK2. This marker has comparable early sensitivity to myoglobin, but because it uses such sensitive criteria, it also has nearly similar specificity as well. The marker of choice in past years was the MB isoenzyme of creatine kinase (CK2). A typical rising-and-falling pattern of CK2 alone (in the proper clinical setting) was sufficient for the diagnosis of acute infarction. In the typical pattern of CK2 release after infarction, the enzyme marker level exceeds the upper bound of the reference range within 6–12 h after the onset of infarction. Peak levels occur by 18–24 h and generally return to baseline within no more than 48 h. However, elevations can occur due to release of the enzyme from skeletal muscle. The lack of a rising-and-falling pattern should raise the suspicion that the release is from skeletal muscle, which is usually due to a chronic skeletal muscle myopathy. Elevations of CK2 in patients with hypothyroidism (where clearance CK2 is retarded) and those with renal failure (where clearance is normal because CK2 is not cleared renally) have elevations caused, in part, by myopathy. The percentage of CK2 with respect to total CK2 is an unreliable criterion for the diagnosis of infarction.
3. Electrocardiography— Only a few ECG patterns have high specificity for infarction (Figure 5-3). In general, an upwardly concave elevation of the ST segment is considered diagnostic of acute myocardial injury, with a high degree of specificity. Patients with inferior infarction should all be evaluated with right-sided chest leads to determine if right ventricular (RV) infarction is present by detecting ST elevation in V3R or V4R. Patients with ST segment depression in V1 and V2 may have total circumflex occlusions, which can be unmasked by the findings of ST segment elevation in the so-called posterior leads (V7–V9). The Q waves that tend to develop mark these patients as potential candidates for strategies designed to reduce the extent of infarction (discussed in the section on Implementation Reperfusion Strategies). Reperfusion accelerates the appearance of the Q waves often associated with this type of infarction. The electrocardiogram may not show typical changes, however, because of concomitant conduction disturbances (eg, left bundle branch block [LBBB]) that may mask the findings or because only ST depression, which is considered more nonspecific, is present. Without acute ST segment elevation or the development of new Q waves, no other ECG changes can be considered highly specific—and even these findings are not 100% specific. The ECG can even be totally normal. In the absence of an old ECG for comparison, any changes present should be presumed to be new. Although persistent or fixed changes are more characteristic of infarction, labile changes have a greater predictive value for the presence of ischemia for patients with elevated biomarkers thought to have non-Q wave MI, the presence of ST depression is a negative prognostic sign.

Figure 5–3. Typical evolution of the electrocardiographic changes of acute myocardial infarction. A: Anterior infarction. B: Inferior infarction. Reproduced, with permission, from Lipman BS, Dunn MI, Massie E: Clinical Electrocardiography. St. Louis: Mosby, 1984.

4. Imaging— Imaging can also be used to confirm the presence or absence of acute infarction, but it is rarely used in modern practice. Infarct-avid imaging with technetium 99m pyrophosphate indium-111-labeled myosin or 99m sestamibi can be used. These techniques detect large AMIs well. With smaller infarctions, however, sensitivity is lost. In addition, with larger infarctions, a significant number (20–30%) of images will remain persistently positive for at least 6 months.
Echocardiography also may be helpful in detecting an AMI. Some researchers argue that the absence of regional abnormalities on the ECG is strong evidence against the presence of acute infarction. The sensitivity of echocardiography, however, is critically dependent on the quality of the views obtained; the absence of an abnormal ECG should not of itself be used to exclude the presence of ischemic heart disease. Furthermore, echocardiography cannot distinguish acute infarction from a persistent defect caused by an old myocardial injury. At present, therefore, it is diagnostically useful for AMI when the ECG and clinical history are equivocal. It is valuable in defining the presence of the complications of AMI.