Acute Coronary Syndrome

Plaque disruption

Most often, ACS results from abrupt disruption of a previously only partially stenosed plaque, which undergoes any of the following:

• rupture/fissuring, exposing highly thrombogenic plaque constituents
• erosion or ulceration, exposing thrombogenic basement membrane
• hemorrhage into the plaque, expanding its volume

Those that undergo abrupt disruption often are only mildly to moderately stenosed. A rather large number of asymptomatic adults therefore are at risk of ACS.

The triggering events are complex and poorly understood, but include plaque characteristics, blood pressure, and platelet reactivity. Adrenergic increases in blood pressure or local vasospasm can be lethal. Awakening and arising leads to the peak incidence of MI occurring between 6am-noon. Emotional stress can also contribute to plaque disruption, illustrated by the increase in sudden death following disasters.

It is increasingly clear that plaque disruption and thrombosis can occur in silent repetitive waves.

Inflammation is also very important throughout atherosclerosis. T cells produce TNF, IL-6, and IFN-gamma, stimulating endothelial cells and activating macrophages. Macrophage secretion of metalloproteinases weaken the fibrous cap and can lead to rupture.

Markers of inflammation such as C-reactive protein may be useful in estimating risk.

Vasoconstriction can be mediated by adrenergic factors, platelet activation, and possible inflammatory mediators.

Frequently, within minutes, the lumen is completely blocked.

Tissue Infarction

Within seconds, aerobic glycolysis stops and lactic acid begins to breakdown. A striking loss of contractility occurs within 60 seconds of ischemia onset, which can precipitate heart failure long before infarction. Only severe ischemia lasting 20-40 minutes leads to cell death in the form of coagulation necrosis.

Most MIs are transmural, in which necrosis extends through the ventricular wall. A wavefront of cell death moves through the wall, and necrosis appears largely complete within 6 hours. Hearts with developed coronary arterial collaterals may take up to 12 hours to fully necrose.

The subendocardium is most susceptible to damage, and some MIs are limited to the inner half of the wall. Subendocardial infarctions can result from a thrombus which is lysed early after forming, but can also follow prolonged shock superimposed on nonruptured coronary stenosis.

Scarring is well advance after 6 weeks.

In unstable angina and NSTEMI, the vessel is usually not completely blocked, resulting in no or little necrosis. If the vessel is blocked, however, severe ischemia results in the significant necrosis accompanying STEMI.

Areas of Tissue Infarction

Nearly all transmural infarcts involve at least a portion of the left ventricle, including the septum. About 15-30% of those affecting the posterior wall extend into the right atrium. Atrial tissue can sometimes become infarcted with large posterior wall infarcts.

LAD infarcts (40-50%) involve the anterior left ventricle near the apex, the anterior septum, and the apex circumferentially

RCA infarcts (30-40%) involve the inferior/posterior wall of the left ventricle, the posterior septum, and the right ventricular free wall

LCA infarcts (15-20%) involve the lateral wall of the left ventricle, except the apex.

• Gross image of LV post-MI (new window)
• Cross section of recent transmural MI (new window)

History

• at least 15 minutes of ischemic chest pain at rest
• worsening of previously stable effort angina, ie frequency, severity, or duration
• history of recent (2 mo) onset of CCS class III or IV angina

Dyspnea can result from pulmonary congestion and edema.

In 10-15% of people, particuarly the elderly and those with diabetes, silent MIs are only discovered later by ECG changes, usually new Q waves.

Physical Exam

People can have a rapid, weak pulse and are often sweating profusely.

Lab Investigations

Fatally injured myocytes leak proteins into the blood. These include myoglobin, troponins T and I, creatine kinase-MB, lactate dehydrogenase, and others. The preferred biomarkers are cardiac-specific, particularly the troponins. An absence of change in CK within 2 days essentially excludes MI. Reperfusion acceletates biopmarker presence due to enzyme washout.

troponin-T and I

• much more sensitive
• begins to rise 3-4 hours, peaking at 18-36 hours
• remain elevated 7-10 days after event

creatine kinase-MB

• former gold standard
• begins to rise with 2-4 hours ,peaks at 24 hours
• returns to normal within 72 hours, much shorter than the troponins

myoglobin

• cleared quickly by kidneys

cholesterol

BUN (kidneys)

Reperfusion

Before reperfusion: protrombin time (PT) and partial thromboplastin time (PTT) to ensure extrinsic and intrinsic clotting pathways are ok

Diagnostic Imaging

Perform ECG within 10 minutes of medical contact

• ST elevation or new LBBB

ST depression

• troponin -ve - UA (45%)
• troponin +ve - NSTEMI (35%)

ST elevation

• STEMI (20%)

MI: biomarker evidence of necrosis (over 99th centile of upper reference limit) plus ischemic symptoms, new ischemic ECG changes, new pathological Qs, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality