Introduction and Definitions
Acute coronary syndrome is the term used to refer to a group of disorders that are characterised by their symptomatic presentation. These share an aetiology of thrombus formation on an atherosclerotic plaque, and are all associated with an increased risk of myonecrosis and cardiac death. There are approximately 120,000 new ACS cases in England & Wales per year, and incidence for any suspected ACS is increasing.
There are three distinct syndromes that make up the acute coronary syndromes, sharing similar pathogenesis and clinical presentation. These are:
Myocardial infarction is defined as myocyte necrosis occurring as a result of prolonged ischaemia. A standardised diagnostic definition was developed in 2000, which has evolved into the current Universal Definition of Myocardial Infarction.
This is an extensive definition, but the key points are listed in the box to the right. It can be summarised as:
Over 90% of acute coronary syndromes result from atherosclerotic plaque disruption with intracoronary thrombus formation to form an atherothrombus that occludes the lumen of a coronary artery. Many other causes occur more rarely and are listed to the right.
This process begins with the formation of fatty streaks – raised, non-obstructive yellow dots 1-2mm across that form early in life. The process begins with lipids entering the arterial intima as intact LDL, which is then modified. A brief overview of the process of atherogenesis is shown in the diagram below:
Fatty streaks are non-obstructive lesions and are clinically silent. Once fatty streaks have formed, they may either regress, remain as fatty streaks or progress to a fibrolipid plaque. Progression occurs in multiple stages and is driven by many processes. One such process is the migration and transformation of smooth muscle cells, a cell with high plasticity key to atherogenesis.
So there is a balance of synthesis (collagen and elastin) and degradation (MMPs) of the fibrous cap of the plaque occurring continuously. Smooth muscle and foam cells gradually die off over the years, due to inflammatory stimulation or apoptosis activation. This causes the cellular contents to be released into the plaque - contributing more lipids and cellular debris into the lipid core, and increasing the level of luminal narrowing. It also importantly reduces the SMC content of the plaque, resulting in less collagen/elastin production à thinner fibrous cap and higher plaque vulnerability
Atherosclerotic plaques are broadly divided into two types, dependant on their integrity.
Unstable plaques are more likely to rupture than their stable counterparts, and rupture can cause a thrombotic event superimposed onto the already narrowed lumen. This may result in complete occlusion of the artery distal to the thrombus, causing ischaemia of the tissue supplied by the artery – or even infarct. Rupture results in:
The pathophysiology of the acute coronary syndromes shares the common element of thrombus formation on an atherosclerotic plaque causing total or near-total occlusion of a coronary artery and subsequent disruption of anterograde blood flow. However, the process is different for each coronary syndrome, and they are all in turn discussed below:
Unstable Angina – Thrombus formation on a ruptured atherosclerotic plaque causes brief total or subtotal coronary artery occlusion, resulting in ischaemia at rest that shows up on the ECG as ST depression. As there is no infarct of the tissues and hence no myocyte necrosis, troponin levels are normal. The pain in UA typically lasts <20 minutes
NSTEMI – Thrombus formation on a ruptured atherosclerotic plaque causes subtotal occlusion of the coronary artery, resulting in ischaemia of the area supplied by the artery. This thrombus then embolizes into the distal microcirculation, which produces small areas of myocyte necrosis known as microinfarcts. There is associated myocyte necrosis and hence biomarker release (particularly troponin), hence why this is defined as a myocardial infarction. The pain in myocardial infarction typically lasts >20 minutes.
STEMI - Thrombus formation on a ruptured atherosclerotic plaque occurs and the thrombus is stabilised by a mesh of cross-linked fibrin strands and trapped RBCs. This results in complete, protracted occlusion of a coronary artery resulting in cessation of anterograde blood flow leading to a large area of infarct and massive release of biomarkers.
It is important to remember that any elevation of either troponins or CK-MB is taken to be evidence of myocardial necrosis and therefore if either of these are positive then the patient has a myocardial infarction – i.e. it is not UA.
Risk factors for ACS are similar to those for coronary heart disease and can be subdivided into modifiable and non-modifiable risk factors.
90% of myocardial infarctions are explained by the 5 most important risk factors:
Pain – Chest pain is the cardinal symptom of ACS. It is usually described as a substernal or left-sided, crushing and severe in nature, although not always (particularly in the elderly). Pressure or heaviness on the chest may be reported. Referred pain to the arm (particularly left), neck, jaw or abdomen may accompany the chest pain or may be the only pain present. Acute MI should be suspected if the pain lasts for >20 minutes.
Nausea & Vomiting – this is commonly seen and occurs as a result of increased vagal tone
Diaphoresis – Very profuse sweating may occur in ACS patients as a result of autonomic activation
Dyspnoea – sudden onset breathlessness unrelated to any existing condition is commonly seen and indicative of ACS
Light-headedness & Syncope – these are more commonly seen in elderly patients.
Cardiac syndrome X
Though ECG findings can be very variable, there are certain patterns of ECG changes seen much more commonly in ACS. Patterns of 'typical' ECG changes exist for the different types of acute coronary syndrome experienced, and are described below.
ST Depression and T-wave inversion T-wave Inversion
Above are examples of the ECG changes seen in NSTEMI/UA patients. On the left is ST-segment depression with T-wave inversion seen in V5, and on the right is isolated T-wave inversion in V3.
The characteristic changes seen in STEMI are indicative of more severe, often transmural, injury. The most common are ST-segment elevation and new onset left bundle branch block, but a posterior infarct (dominant R wave and ST depression in leads V1 + V2) is also diagnostic of a STEMI.
ST-Segment Elevation in V3 New LBBB in V1
The typical changes in NSTEMI/UA are ST-depression and T-wave inversion. These are the most common changes of ischaemia, and the changes in NSTEMI are identical to those of UA, despite the differences in pathophysiology.
Above are examples of ECG changes seen in STEMI - on the left is ST-segment elevation with T-wave inversion in V3, and on the right is new onset left bundle branch block (LBBB) seen in V1.
Because the different leads of the ECG measure current at different vectors, it is possible to use the pattern of ECG changes to narrow down the location of the infarct in the heart. One easy way of doing this is by looking at what leads show ST-elevation - this has been shown to correspond to particular areas of infarcting myocardium and their supplying arteries.
Anterior Infarcts show ST elevation in praecordial leads V1-V6. These are associated with left anterior descending (LAD) artery occlusion. - Septal infarcts occur in the ventricular septum, which is also supplied by the LAD, and these show ST elevation in leads V1-V4.
Lateral Infarcts show ST elevation in limb leads I, aVR, aVL, and praecordial leads V5-V6. These are associated with circumflex artery (Cx) occlusion.
Inferior Infarcts show ST elevation in limb leads II, III and aVF. These are most commonly associated with right coronary artery (RCA) occlusion.
Below is a labelled diagram of an ECG showing the areas of ST-elevation for different infarcts:
Various invasive and non-invasive imaging techniques exist to visualise the structures of the heart and the coronary arteries. These are useful in establishing the diagnosis when it is ambiguous, assessing the level of damage and functional impairment, and in locating the occlusive thrombus.
These two techniques are the most commonly performed imaging methods in patients with ACS. More recently, newer non-invasive techniques have been developed and are becoming more widespread in their use. These include cardiac magnetic resonance imaging (CMR), which can visualise the myocardium, assess it's function, and assess myocardial perfusion simultaneously. It is also very good at visualising the scar tissue associated with infarct, but is currently only available in some centres.
Other techniques, such as technetium myocardial perfusion scanning and CT angiograhy are also useful - technetium scanning is particularly helpful at distinguishing ischaemic areas from infarcted areas. Again, these are often limited by availability of equiptment and trained staff.
The initial management of any suspected ACS is the same.
Do not wait for blood results (i.e. troponins) to come back in a patient with suspected STEMI. In a patient identified as having STE ACS, the following should be rapidly performed and administered:
In a patient with STE ACS, reperfusion is the ultimate goal of therapy as the length of time that coronary circulation is compromised is proportional to the degree of myocardial necrosis, infarct size and adverse events – this important principle is known as TIME=MUSCLE. All patients who present within 12 hours of symptom onset should receive reperfusion therapy. Reperfusion is regarded to have happened if there is a >50% fall in ST-segment elevation or new idioventricular rhythm.
This means that transfer to a PCI centre should be arranged if such facilities are in-hospital or if they are available within 60 minutes. If this cannot be done, thrombolysis should be performed as soon as possible unless contraindicated – absolute contraindications are listed to the right.
Thrombolysis involves the IV administration of an agent such as tenecteplase, a recombinant tissue plasminogen activator, in order to disrupt the clot and restore anterograde blood flow. This can be performed in the hospital, and increasingly paramedics are being trained to administer it en-route to the hospital. In keeping with the TIME=MUSCLE principle, the longer thrombolysis is delayed the more likely an adverse event is to occur and survival rates are lower. All patients who receive thrombolysis should be transferred to the nearest PCI centre. If reperfusion does not occur within 12 hours following thrombolysis, ‘rescue PCI’ should be performed, as this has shown better results than conservative management or repeat fibrinolysis.
PCI avoids these complications and is associated with higher reperfusion rates, better survival and lower complication rates, hence why it is the preferred treatment modality in STEMI. All patients undergoing PCI for this should receive a GP IIb/IIIa inhibitor such as abciximab intravenously before undergoing the procedure.
Although patients with NSTE ACS are rarely life-threateningly unwell at presentation, they are at very high risk of death or further MI and need to be rapidly managed and continually monitored with serial ECGs.
IV access obtained
Antianginal therapy –
Anticoagulant therapy –
Antiplatelet therapy -
The further management for these two conditions is very similar and based primarily on risk stratification as calculated using a risk predictor tool. Many different tools exist but the NICE recommended tool is the GRACE risk calculator.
This calculator is based on a number of parameters, such as age, Killip class, cardiac biomarkers and blood pressure, to derive a value for the predicted in-hospital and 6-month mortality risk expressed as a percentage. Guidelines recommend using the 6-month mortality score to classify a patients risk as lowest-highest, a table for which (from SIGN guidelines) is to the right. However, each patient is an individual and these are only intended for use as guidance.
It is also important to get an idea of the patient’s risk of bleeding. Again there are many tools available, but the CRUSADE score is a commonly-used tool that can be used to assess this.
Generally speaking, more aggressive treatments are used for patients at higher risk. This is reflected in that patients with moderate-high risk need to undergo coronary angiography +/- revascularisation within 5 days of presentation, while patients in lower risk groups generally require more
conservative management with a focus on secondary prevention, and angiography in these patients may be done without urgency or may be unnecessary. The treatment algorithm is shown in the following diagram.
Arrhythmia – occurs in the majority of MI patients. Common arrhythmias include AF, Mobitz type II heart block, third degree heart block, VT and VF. SA node dysfunction may occur, particularly after right coronary artery occlusion
Myocardial rupture – although infrequent, this is a significant cause of mortality. Interventricular rupture is less common producing a loud systolic murmur at the left sternal border. Free wall rupture shows signs of tamponade and is almost always fatal.
Pericarditis – develops in first 3 days as a friction rub in a third of patients. Rarely progresses to tamponade
Dressler’s Syndrome (Post-MI Syndrome) – appears occasionally in the weeks following MI. Pericarditis, pericardial/pleural effusions, pyrexia, joint and pleuritic pain are part of this syndrome. Treatment is with NSAIDS but the condition may recur
Good implementation of secondary prevention measures have been shown as able to reduce the risk of hospital readmission by 60% and the end-outcomes of MI, stroke or death by half. This consists of various measures implementable by both the physician and the patient, divisible into lifestyle and drug measures. These are listed in the table below.
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