2. Pathology
2.1. Role of Acute Plaque Change
Slowly accruing high-grade stenoses of epicardial coronary arteries
may progress to complete occlusion but do not usually precipitate
STEMI, probably because of the development over time of a rich collateral
network. However, during the natural evolution of atherosclerotic
plaques, especially those that are lipid laden, an abrupt and catastrophic
transition may occur, characterized by plaque disruption by rupture
of the fibrous cap or erosion of the surface of the fibrous cap
(Figure 2) (8-10).
Plaques that are prone to disruption are usually nonobstructive,
are characterized by abundant macrophages and other inflammatory
cells, and are often located at branch points or bends in the arterial
tree (11-15).
They are referred to as vulnerable or high-risk plaques. After plaque
disruption, there is exposure of substances that promote platelet
activation, adhesion, and aggregation, thrombin generation, and
ultimately thrombus formation (16,17).
The resultant thrombus can completely occlude the epicardial infarct
artery. If there is an insufficient collateral supply, a wave front
of myocardial necrosis begins within 15 minutes and spreads from
the endocardium toward the epicardium (18).
This may be modulated by the extent of collateral flow and determinants
of myocardial oxygen consumption, affording opportunity for significant
myocardial salvage (19). Of note,
intravascular ultrasound studies suggest that in addition to the
disruptured plaque, several other vulnerable or high-risk plaques
may coexist throughout the coronary vasculature.
2.2. Acute Coronary Syndromes
Disruption of vulnerable or high-risk plaques is the common pathophysiological
substrate of the acute coronary syndromes that comprise a spectrum
of myocardial ischemia. Patients with an acute coronary syndrome
include those whose clinical presentations cover the following range
of diagnoses: unstable angina, MI without ST elevation (NSTEMI),
and MI with ST elevation (STEMI) (Figure
2) (8-10).
Patients with STEMI have a high likelihood of a coronary thrombus
occluding the infarct artery (20,21).
Angiographic evidence of coronary thrombus formation may be seen
in more than 90% of patients with STEMI but in only 1% of patients
with stable angina and about 35% to 75% of patients with unstable
angina or NSTEMI (20-24).
However, not every STEMI evolves into a Q-wave MI; likewise, a patient
with NSTEMI may develop Q waves. The acute coronary syndrome spectrum
concept is a useful framework for developing therapeutic strategies.
Antithrombin therapy and antiplatelet therapy should be administered
to all patients with an acute coronary syndrome regardless of the
presence or absence of ST-segment elevation. Patients presenting
with persistent ST-segment elevation are candidates for reperfusion
therapy (either pharmacological or catheter-based) to restore flow
promptly in the occluded epicardial infarct-related artery and are
the subject of this guideline (Figure
3) (24-40).
Patients presenting without ST-segment elevation are not candidates
for immediate pharmacological reperfusion but should receive anti-ischemic
therapy and catheter-based therapy where applicable as discussed
in the ACC/AHA Guidelines for Management of Patients with UA/NSTEMI
(4).
2.3. Pathophysiology
A key concept in the pathophysiology of STEMI is ventricular remodeling,
a term that refers to changes in size, shape, and thickness of the
left ventricle involving both the infarcted and noninfarcted segments
of the ventricle (41,42).
Acute dilatation and thinning of the area of infarction that is
not due to additional myocardial necrosis is referred to as infarct
expansion (43). An extra load is
placed on the residual functioning myocardium, which results in
compensatory hypertrophy. Inhibition of the renin-angiotensin-aldosterone
sys-tem is a key therapeutic maneuver in patients with STEMI (44).
Additional important pathophysiological concepts in patients with
STEMI that form the basis for recommendations in this guideline
include cardiac arrhythmias such as those that result from electrical
instability, pump failure/excessive sympathetic stimulation, and
conduction disturbances. Mechanical problems that result from dysfunction
or disruption of critical myocardial structures (e.g., mitral regurgitation
[MR], rupture of the interventricular septum, ventricular aneurysm
formation, and free wall rupture) may require a combination of pharmacological,
catheterbased, and surgical treatments.
2.4. Epidemiology
STEMI continues to be a significant public health problem in industrialized
countries and is becoming an increasingly significant problem in
developing countries (45). Although
the exact incidence is difficult to ascertain, using first-listed
and secondary hospital discharge data, there were 1 680 000 unique
discharges for ACS in 2001 (46).
Applying the conservative estimate of 30% of the ACS patients who
have STEMI from the National Registry of Myocardial Infarction [NRMI-4]
(46a), we estimate 500,000 STEMI
events per year in the U.S. However, there has been a steady decline
in the mortality rate from STEMI over the last several decades.
This appears to be due to a combination of a fall in the incidence
of MI (replaced in part by an increase in the incidence of unstable
angina) and a reduction in the case fatality rate once an MI has
occurred (47-49).
There has been a progressive increase in the proportion of patients
who present with NSTEMI compared with STEMI.
The committee strongly endorses several public health campaigns
that are likely to contribute to a reduction in the incidence of
and fatality from STEMI in the future. These include the following:
1) recognition of diabetes mellitus and chronic kidney disease as
“risk equivalents” to coronary heart disease (CHD) and
therefore recommendation for more aggressive attempts at control
of other risk factors (50,51);
2) recognition of the importance of dyslipidemia as a major risk
factor for CHD and recommendation for aggressive attempts at cholesterol
reduction and treatment of the metabolic syndrome (50);
3) aggressive primary prevention efforts at smoking cessation as
emphasized by the World Health Organization; 4) patient education
campaigns regarding the signs and symptoms of MI and the appropriate
courses of action to be taken (52,53);
and 5) implementation at a professional level of quality assurance
projects such as the ACC’s “Guidelines Applied in Practice”
(54) and the AHA’s “Get
with the Guidelines” (55)
to improve compliance with established treatment strategies when
caring for patients with MI. A proposal that holds great promise
for reducing the morbidity and mortality associated with STEMI is
the regionalization of care for patients with acute coronary syndromes
using centers of excellence (56-58).
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