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 advanced 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.

Territories

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.

Left anterior descending (LAD) infarcts (40-50%) involve the anterior left ventricle near the apex, the anterior septum, and the apex circumferentially. These anterior MI's have a significant impact on cardiac output due to loss of contractility, leading to hypotension, tachycardia, and heart failure.

Left circumflex (LCX)/ramus circumflexus (RCX) infarcts (15-20%) involve the lateral wall of the left ventricle, except the apex.

Right cerebral artery (RCA) infarcts (30-40%) involve:

• the inferior/posterior wall of the left ventricle
• the posterior septum
• right ventricle
• SA and AV node, posterial left bundle branch

As the right ventricle is dependent on preload for cardiac output, hypotension is common, and should be treated with IV fluid boluses. Nitroglycerin should be used with extreme caution, given the risk of preload reduction.

Disruption to the vasculature can also have a significant impact on heart rhythms, as described at right.

History

Symptoms of ACS vary considerably. Typically, the character of chest discomfort, timing of onset, radiation of pain/pressure, duration of pain/pressure and alleviating and exacerbating factors must be explored.

However, this may often be described in a variety of ways not typical of "pain": squeezing, heaviness, pressure, or tightening. Radiation of discomfort to the left arm or shoulder, shoulder blades or neck are suggestive of ACS. If the discomfort is anginal, increasing symptoms with exertion are often present. However, angina can also occur at rest in which it usually lasts approximately 2 to 5 minutes (to a maximum of 20 minutes). Again, interpreting these historical description of symptoms within the context of each patient is essential. Dyspnea, nausea, vomiting, diaphoresis, weakness, dizziness, excessive fatigue or anxiety may also be present.

Atypical presentations are common, especially in females. Complaints of unusual indigestion or heartburn (in a patient without gastroesophageal reflux disease) may occur and should prompt inclusion of ACS on a differential diagnosis. Also, changes in the character of reflux symptoms in a patient with known gastroesophageal reflux disease should raise suspicion.

• 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.

Clinical characteristics that raise the likelihood of cardiac chest pain include:

• dull, pressure-like retrosternal chest discomfort
• duration approximately 2 to 5 minutes
• gradual onset
• reproducible/exacerbated with exertion
• pain not reproducible with palpation

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.

Particular attention should be paid to risk factors for cardiovascular disease:

• male gender
• increasing age
• smoking history
• hypertension
• diabetes mellitus
• hypercholesterolemia
• family history of cardiovascular disease (first degree relatives, male < 55 y & female < 65 y)
• substance abuse (particularly cocaine abuse)

Physical Exam

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

The physical exam should focus on cardiovascular, respiratory, abdominal and neurological findings. The goal is to explore for other factors that may contribute to the patients symptoms and increase or decrease the likelihood of a diagnosis of ACS. A useful way to remember factors that reduce the likelihood of chest pain being cardiac in origin is the "three P's": pleuritic, positional and reproducible by palpation.

Signs of right ventricular infarction are as follows:

• jugular vein distension
• hypotension
• lung fields free

Lab Investigations

Serum markers of myocardial injury are also an important component of the ACS work-up. In an emergency department setting, these are most useful in patients with a non-diagnostic ECG yet the clinician retains a strong clinical suspicion for myocardial injury.

Fatally injured myocytes leak proteins into the blood. These include myoglobin, troponins, 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.

For appropriate interpretation, serial measurements are usually obtained every 6 - 8 hours until levels have peaked.

troponin-T -I, and -C

• much more sensitive
• begins to rise 3-4 hours, peaking at 12-36 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

An electrocardiogram (ECG) is an essential component of the patient work up, and should be performed within 10 minutes of medical contact. Typical ECG findings of ACS include:

• T wave morphology changes (hyperacute and inversion)
• ST segment depressions (more likely ischemia) or elevations (more likely infarction)
• left bundle branch block
• QRS complex changes (new bundle branch block; evidence of Q waves - suggestive of old infarct)
• rhythm disturbances

If available, comparison with an old ECG is particularly helpful. It is important to note that ECG changes are dynamic and thus, change over time. Therefore, in a patient in which ACS is highly suspected, serial ECGs are often appropriate.

The location of a myocardial infarct can be determined from the pattern of morphological changes on the ECG.

A list of select examples is provided:

• anterior infarcts: pre-cordial leads (V1 - V4)
• septal infarcts: V1 and V2
• anteriolateral infarcts: V1 - V6 and I and aVL
• infarction involving the left anterior descending artery typically demonstrate ST segment elevation in leads V2 - V3 along with ST segment depression in lead II and III and/or aVF 
• lateral infarcts: (I, aVL, V5 - V6)
• inferior infarctions: (II, III and aVF)
• isolated posterior infarctions are rare but can be demonstrated in accessory leads (V7 - V9)

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

Chest radiography should also be ordered - largely for the purpose of determining the appropriateness of certain therapies (e.g. fibrinolytic therapy). A chest X Ray is also valuable in determining if pulmonary congestion is evident.

Echocardiography is a useful test for the evaluation of patients with ACS. In particular, regional wall motion abnormalities contribute to the evidence supporting a diagnosis of acute MI. However, echocardiography usually takes some time to obtain and is somewhat dependent on operator technical skill and thus, less valuable in the acute setting. It is quite useful for an assessment of the extent of myocardial injury once the patient is stable.

Other diagnostic imaging modalities that may be used include myocardial scintigraphy and computed tomography.

Once the clinician suspects acute coronary syndrome, a number of treatments (barring contraindications) should be initiated - beginning with an assessment of the patients airway, breathing and circulation.

Bedrest and telemetry

Acute treatment for suspected ACS include (pneumonic MONA)

• oxygen
• nitroglycerin (not if a right-sided MI is suspected, as cardiac output becomes very dependent on preload)
• aspirin
• morphine

Beta-blocker

Treatment with the following drugs should also be considered (with regard to vital signs, co-morbidities, etc.):

• antiplatelet agents - both ASA and clopidogrel
• anticoagulants - low molecular weight heparin, or heparin
• beta-blockers - if/once hemodynamically stable.
• nitrates - sublingually or IV
• angiotensin-converting enzyme inhibitors

Fibrinolytics

Fibrinolytics may be given within 12 hours of onset of symptoms, though aim for a door to needle time below 30 minutes

Approximately half the risk of death with ULMWH.

enoxaparin is better

fondaparinux

• factor X inhibitor (i thnk)
• fixed dose, once daily sc administration
• chepaer than enoxaparin
• OASIS-5 showed much decreased risk of bleeding
• now preferred drug for anti-thrombin
• does not provent thrmbosis on lines, wires, etc

bivalirudin

• direct thrombin inhibitor
• short half life minimizes bleeding
• expensive

throbolytic therapy contraindicated in UA and NSTEMI

thrombolytics only work 45-50% of time

metaanalyisis shows field treatment with thrombolytics has a small benefit

Stroke predictors include old age, female, low predictors etc

Catheterization

Catheterization should be considered in patients with STEMI, or NSTEMI and:

• recurrent angina, despite therapy
• CHF or LV dysfunction
• hemodynamic isntability
• high TIMI score
• recurrent or sustained ventricular tachycardia
• dynamic ECG changes
• high-risk findings
• PCI within last 6 months
• repeated episodes of acute coronary syndrome

Pre-treat with anti-platelet therapy

Contraindications include:

• people beyond 12 hours
• severe peripheral vascular disease (difficult catheterization)
• chronic renal insufficiency (relative contraindication)

Chronic

Once stable, patients should be treated with:

• ASA
• ACE inhibitors
• clopidogrel
• lipid-lowering agents
• beta-blockers