PHATOPHYSIOLOGI ACUTE MYOCARD INFARCTION

It is generally accepted that a prolonged imbalance between myocardial oxygen supply and demand leads to the death of myocardial tissue. Coronary atherosclerosis is an essential part of the process in most patients. Ischemic heart disease seems to progress through a process of plaque rupture that transiently increases the amount of luminal impingement by the stenotic lesion. Infarction may occur when the plaque ruptures and leads to thrombosis, erosion of the plaque causes thrombosis, or when cardiac work exceeds the ability of the narrowed coronary artery to supply nutritive perfusion. Recent work suggests that inflammation may play a pivotal role in the genesis of plaque rupture.
Greater numbers of acute infarctions occur during the early morning hours (from 6:00 AM to 12:00 noon) than any other time of the day, suggesting that perhaps the increased catecholamine secretion associated with awakening or circadian changes in coagulation common in the early morning (eg, increases in type-1 plasminogen activator inhibitor [PAI-1]) may induce platelet aggregation and lead to thrombus formation. Beta-blockers reduce this propensity and psychiatric depression shifts this pattern back 6 h—as it does with other circadian patterns. In keeping with this pattern, most infarctions do not appear to be induced by exertion. When severe exertion or severe emotional distress does occur, it appears to induce a window of vulnerability for roughly an hour or two after the acute event in susceptible individuals.
In general, patients with acute infarction tend to be males in their 50s and 60s, although infarction in elderly women in their 70s and older is now equally common. Indeed, acute infarction is now equal in incidence between women and men. Most often, those individuals have risk factors for the development of coronary artery disease, such as an increased cholesterol, diabetes, hypertension, cigarette smoking, a sedentary life-style, or a family history of early coronary artery disease. These risks are not present in all patients, however, and the absence of risk factors does not eliminate the possibility of infarction. This is especially true with the increasing prevalence of drug abuse. In patients who have AMI without apparent risk factors, an evaluation for the presence of novel risk factors, such as homocysteine, lipoprotein(a), small dense low-density lipoprotein (LDL), and markers of inflammation such as C-reactive protein and phospholipase A2 is warranted.
A. TOTAL THROMBOTIC OCCLUSION

In many patients (roughly 50%), total thrombotic occlusion is superimposed on the atherosclerotic plaque. The occlusion is thought to develop in response to plaque rupture when the luminal diameter of the coronary artery is sufficiently reduced to initiate clot formation or if erosion of the plaque causes exposure of procoagulant factors. Procoagulant factors (such as tissue factor) reside within the plaque itself and the absence of counterbalancing antithrombotic factors (eg, heparin, tissue-factor-inhibitor) and fibrinolytic activities (tissue plasminogen activator [t-PA] and single-chain urokinase-type plasminogen activator) within the endothelial cells of the coronary artery can cause thrombosis. Total thrombotic occlusion occurs most commonly in proximal coronary arteries; its presence has been documented during the first 4 h after infarction in more than 85% of patients who present with ST segment elevation (Figure 5–1). Most patients who present in this manner subsequently develop Q waves. A similar type of myocardial insult occurs occasionally despite angiographically normal coronary arteries and is caused by emboli (eg, in patients with prosthetic valves or those with endocarditis), dissection of the coronary artery (most commonly in pregnant women), or on rare occasions, coronary vasospasm. It can also be caused by thrombosis in situ, the probable mechanism by which patients who have variant angina or who abuse cocaine can suffer acute infarction. In these cases, vasoconstriction secondary to endothelial dysfunction and a propensity to thrombosis is of sufficient magnitude and duration to cause thrombus formation. Oxygen consumption and possibly direct myocyte toxicity also increase with cocaine use. In addition, thrombosis in situ can apparently cause infarction among women who take estrogens (especially if they smoke).

Figure 5–1. Incidence of total occlusion in patients with acute myocardial infarction. Reproduced, with permission, from DeWood MA, Spores J, Notske R et al: Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980;303:897.

B. NON-Q WAVE INFARCTION

The remainder of infarctions occur generally in the absence of total thrombotic occlusion. The term non-Q wave infarction is used because the infarction is not associated with the development of new Q waves on the electrocardiogram. (This term is preferred to nontransmural infarction because no correlation has been found between Q waves and the presence of infarction through all levels of the ventricle). The frequency of this type of infarction is increasing because of the use of newer more sensitive and specific markers such as the troponins to detect small events.
Although, overall, the coronary anatomy of patients with non-Q wave infarctions is virtually identical to that of patients with Q wave infarctions, the incidence of documented total thrombotic occlusion during the initial 24 h after presentation with non-Q wave infarctions is only 29%.
Some clinicians believe that non-Q wave infarction is caused by small clots that dissolve prior to investigation, leaving only an open artery to be detected. Evidence for this includes an early rise in both the total and the MB isoenzyme of creatine kinase (CK2) and the finding of contraction-band necrosis (a sign of calcium overload commonly seen after reperfusion). The rapidity of the rise and fall of marker proteins and the presence of contraction bands are related to coronary blood flow, however, and continued antegrade flow could also be responsible. Because smaller infarctions also tend to have earlier times to peak CK concentrations, early enzyme peaking could represent a small infarction or the presence of antegrade coronary flow rather than spontaneous coronary recanalization.
Nonetheless, abundant data confirm that thrombosis is common in such patients if diagnosed by an elevated troponin level, especially if concomitant ST depression is present. There are other pathophysiologic possibilities for non-Q wave infarctions. An imbalance of myocardial oxygen supply and demand could be the result of a prolonged increase in myocardial work and oxygen consumption in the distribution of a coronary artery unable to increase its blood flow because of atherosclerosis or endothelial dysfunction. The coronary artery could also constrict abnormally and cause a similar imbalance. Small amounts of vasoconstriction can cause major changes in the cross-sectional area of a vessel since A = pr2.
Patients with non-Q wave infarction and partial coronary occlusion are at increased risk for subsequent total occlusion and recurrent infarction during the hospital course and in the weeks and months following the event. After the first few days, although these infarctions are smaller, mortality rates increase more rapidly than in patients with Q wave infarctions because of the greater number of recurrent events. By 6 months, mortality rates are similar to those for patients with Q wave infarctions. However, it is now clear that invasive interventions such as stenting with the assistance of potent anticoagulant modalities such as IIB/IIIA antiplatelet agents and low-molecular-weight heparins (LMWH) can reduce these subsequent events.
Non-Q wave infarction is often seen when other medical illnesses coexist with ischemic heart disease. Pulmonary embolism, septic shock, severe anemia, or even great emotional distress can increase myocardial oxygen demand, reduce coronary perfusion pressure, or evoke paradoxical coronary artery responses and lead to non-Q wave infarction.
Regardless of the cause, the process of myocyte death occurs as a wavefront. It is clear that by 20 min after occlusion (in animal models and likely in humans) some myocytes have died. Then the infarction spreads, usually from the subendocardium toward the epicardium. In experimental animals, infarction is complete in 3–4 h, and it is difficult to save myocardium after that time. In human patients, the time window for myocardial salvage is less clear because the time of onset is more difficult to delineate. Some antegrade flow may occur in many coronary arteries from subtotal occlusion or transient constriction and relaxation of the affected vessel, or myocyte viability may be sustained by collateral perfusion from other vessels. There appears to be some time (in general, perhaps as long as 12 h, and in some patients possibly even longer) during which it may be possible to modify the extent of the myocardial injury by increasing blood flow to the infarct area.