Author: Jason M Kendall / Editor: Elizabeth Kate Florey / Codes: CAP7, HAP8 / Published: 25/01/2019 Review Date: 25/01/2022
Acute coronary syndromes (ACS) encompass a range of presentations including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI).
Myocardial infarction (MI) is defined pathologically as myocardial cell death following prolonged ischaemia . In the context of cardiac marker rise, ST segment changes on the ECG will define either STEMI or NSTEMI. At the time of presentation, however, cardiac marker status is unknown and classification of patients presenting with ischaemic chest pain is based largely on the ECG. Most patients with ST elevation progress to STEMI and their management is the subject of this session. Patients with chest pain and other ECG changes or with a normal ECG are the subjects of other Learning Zone sessions.
Patients suffering from acute myocardial infarction (AMI) usually present with severe chest pain, anxiety and variable degrees of breathlessness. The pain is due to an imbalance between demand and supply of oxygen to the myocardium; demand is increased when the heart works harder and supply is reduced by occlusion of the coronary arteries (see image).
Simple measures that increase supply and reduce demand should be instituted without delay. They should be considered alongside specific reperfusion therapies and will include delivery of supplemental oxygen (if oxygen saturations are reduced), Glyceryl Trinitrate (GTN), relief of pain and anxiety and the reduction of sympathetic over-activity.
Relief of Pain and Anxiety
Pain and anxiety contribute to sympathetic over-activity that, in turn, causes vasoconstriction and increases workload of the heart. Therefore, relief of these symptoms, as well as a primary goal of the emergency physician for humane reasons, is physiologically beneficial in the setting of AMI.
Intravenous opiates (diamorphine or morphine) are the drugs of choice. Beta-blockers are also beneficial in this context and have been shown to reduce mortality . Atenolol is commonly used and is given orally in a dose of 12.525mgs or intravenously (if the patient is vomiting or rapid blood pressure control is required to facilitate thrombolysis) in a dose of up to 5mgs in repeated 1mg aliquots. Bisoprolol (at a dose of 2.5-10mgs orally) is an alternative beta blocker. Anti-emetics may be co-administered with opiates in the setting of AMI, particularly since patients often suffer with nausea and vomiting as part of the presenting complaint.
Dont forget cardiac first aid for patients with ischaemic cardiac pain: aspirin, opiates, oxygen (if oxygen saturation is reduced), GTN and beta-blockers.
Primary Percutaneous Coronary Intervention (PPCI) is defined as angioplasty or stenting without prior or concomitant thrombolytic therapy.
PPCI is effective in achieving and maintaining coronary artery patency without exposing the patient to the increased bleeding risks of thrombolysis.
In the UK, PPCI has become the favoured option and systems are evolving to develop an exclusively PPCI-based approach to reperfusion for STEMI.
There is robust evidence for the superiority of PPCI over in-hospital thrombolysis , with better short-term mortality, reduced re-infarction rates and a lower incidence of stroke. However, there is no robust evidence of superiority of PPCI over PHT .
The benefits of PPCI over thrombolysis are unequivocal in patients presenting later during the course of their event (symptom onset greater than 3 hours)  but are unproven early in the course of STEMI, and especially within the first two hours after symptom onset. In relation to the delay to PPCI when compared to thrombolysis (the balloon time minus the needle time), any potential benefit from PPCI may become harm when a period of somewhere between one and two hours is exceeded , irrespective of the time of onset of symptoms. The nature of UK geography and the way that ambulance services are organised means that the vast majority of patients (approximately 95%) are suitable for PPCI based on these time criteria. There may still be some remote areas within the UK where thrombolysis (or, more specifically, pre-hospital thrombolysis) is the only reperfusion strategy which can be delivered in a timely manner.
PPCI is the preferred option in patients presenting with cardiogenic shock, irrespective of time of onset of symptoms , and in those patients with a contra-indication to thrombolysis. Recommendations for reperfusion have been summarised in guidelines published by the American Heart Association/American College of Cardiology  and The European Society of Cardiology .
PPCI offers definitive reperfusion, but delay to therapy may be harmful in some patients.
|Summary Guidance from the AHA/ACC and the ESC [7,8]|
|Thrombolysis is generally preferred:
|PPCI is generally preferred:
Guidance on the management of STEMI specific to the UK will be published by the National Institute of Health and Clinical Excellence (NICE) in 2013.
The priority of early therapy is to establish reperfusion in the affected myocardium. Current alternatives to achieve this goal are pharmacological (thrombolysis) or mechanical (primary percutaneous coronary intervention (PPCI)).
There is a non-linear relationship between time delay and outcome following thrombolysis, with much greater benefit in patients with short symptom onset to treatment
times . Up to 60 deaths per thousand treated are prevented if thrombolysis is delivered within one hour of onset of symptoms. The clear relationship between delay to treatment and reduced benefit has been the rationale for the implementation of pre-hospital thrombolysis (PHT).
The evidence comparing in-hospital thrombolysis with PHT demonstrates clear superiority of PHT in reducing mortality ; widespread implementation of PHT has led to significantly improved performance against National Service Framework standards (call-to-needle and door-to-needle times). Bolus agents (reteplase or tenecteplase) are most suitable for the pre-hospital environment and are being administered promptly by paramedics in many parts of the UK.
The main hazard of thrombolysis is haemorrhage and, in particular, intracranial haemorrhage. There is an excess of 3.9 cerebral events per 1000 patients treated , the risk being maximal during the 24 hours immediately following thrombolysis. Specific risk factors for intracranial haemorrhage include female gender, advanced age, low body weight and elevated blood pressure at presentation.
Table 1 lists the conventional contra-indications to thrombolysis. Advanced age is not, in itself, a contra-indication to thrombolysis. Whilst there is an increased risk of intracranial haemorrhage associated with thrombolysis in the elderly, overall mortality is significantly reduced by thrombolytic therapy in patients over the age of 75 years who present within 12 hours of onset of symptoms .
Advanced age, in itself, is not a contra-indication to thrombolysis.
The main limitation of thrombolysis is failure to reperfuse (defined by lack of resolution by >50% of ST segment elevation 90 minutes after thrombolytic administration). This is estimated to occur in up to 30% of patients. These patients should be referred for Rescue PCI (PCI performed on a coronary artery that has remained occluded despite thrombolysis) .
Thrombolysis, even if successful at achieving early reperfusion, should not be considered the definitive treatment: pre-discharge angiography (within 6-24 hours of thrombolysis) results in improved outcome and is recommended by the European Society of Cardiology: Lyse now, stent later .
This should not be confused with Facilitated PCI which is when PCI is performed immediately after thrombolytic therapy; there is no robust evidence to support this strategy in routine clinical practice .
Up to one third of patients will fail to reperfuse following thrombolysis Rescue PCI should be performed in these patients.
Should we thrombolyse a patient on warfarin?
This is a difficult question to which there is no evidence-based answer. By the very nature of the pathophysiology of ACS, it is unusual for patients who are on warfarin therapy to have an occlusive coronary event.
Clearly, the concern is that, following thrombolysis, these patients will be at increased risk of bleeding and, in particular, of intracranial haemorrhage. One could argue, however, that, in presenting with a STEMI, they need anti-thrombotic/ thrombolytic treatment even more because they have broken through their anticoagulation.
How should we deal with this situation?
This situation will, as always, need to be dealt with on an individual patient basis balancing risks and benefits. However, in these cases, an urgent INR will help to inform the decision within a reasonable time frame (i.e. within 20 minutes).
A sub-therapeutic International Normalized Ratio (INR) (e.g. <2.0) would tend to favour administration of thrombolysis, particularly where the potential for benefit is great (e.g. anterior STEMI with an early presentation).
Cases where the INR is above the therapeutic range (e.g. >3.0) would contraindicate thrombolysis irrespective of the potential benefit because the risk of intracranial haemorrhage is likely to be much higher.
Where the INR is therapeutic (e.g. 2.0 3.0) the decision will have to be made based on likely benefit (territory of infarct, timing of presentation) balanced against risk of haemorrhage (advanced age, female gender, low body mass index).
What other approaches to treatment are there?
Other approaches to treatment to be considered: antiplatelet treatment should be given (i.e. aspirin) and, if it is available, PPCI will be a better alternative to thrombolysis in these patients.
The various types of adjunctive anti-thrombotic therapies are as listed below:
Aspirin irreversibly acetylates platelet cyclooxygenase and therefore inhibits platelet aggregation; it is also an indirect antithrombotic agent. Aspirin is the most cost-effective treatment available for patients with AMI (indeed, with any ACS) and should be administered early in all patients with ischaemic cardiac chest pain who do not have a known allergy or active gastro-intestinal bleeding. Aspirin should be given in a dose between 150 and 325mg, and continued indefinitely at a daily dose of between 75 and 150mg.
Aspirin is the most cost-effective treatment for AMI, and is associated with a survival benefit similar to thrombolysis.
Clopidogrel is also an anti-platelet agent; it promotes formation of platelet c-AMP, lowering platelet calcium and reducing platelet aggregation. It also prevents the transformation of the glycoprotein IIB/IIIA receptor into its high affinity state, further reducing platelet aggregation. Two recent trials have reported the beneficial effects of clopidogrel in patients with STEMI: patients receiving clopidogrel, in addition to thrombolysis, aspirin and heparin, had a significantly reduced incidence of adverse events at 30 days [15-16].
Prasugrel is, like clopidogrel, an oral anti-platelet agent and acts in a similar way to clopidogrel but with a faster onset of action. It has recently undergone a NICE Technology Appraisal which has recommended its use alongside aspirin as an alternative to clopidogrel in patients with STEMI undergoing PPCI .
Prasugrel has become the preferred option over clopidogrel in patients receiving PPCI for STEMI.
Ticagrelor is another novel oral anti-platelet agent which is an antagonist to the P2Y12 ADP receptor and, co-administered with aspirin, is indicated in the management of patients with acute coronary syndromes. It has also recently undergone a NICE Technology Appraisal which has recommended its use in combination with aspirin as an alternative to clopidogrel in patients with STEMI undergoing PPCI . Ticagrelor is being increasingly adopted instead of clopidogrel in STEMI patients undergoing PPCI who are unsuitable for prasugrel.
Unfractionated heparin (UH) inhibits clot formation by preventing the conversion of fibrinogen to fibrin. Low Molecular Weight Heparins (LMWH) inhibit the coagulation system in a similar way and also bind to Factor Xa which is resistant to inactivation by UH. LMWH also has a longer half-life, less individual variability of the anticoagulant response, more predictable kinetics and less platelet activation than UH. These agents do not enhance immediate clot lysis, but prevent re-occlusion following thrombolysis.
A recent direct comparison of UH and the LMWH enoxaparin in patients with STEMI receiving in-hospital thrombolysis reported improved outcome at 30 days in the enoxaparin group . Indeed, one of the lowest 30 day mortality rates of recent trials (5.4%) was reported using the combination of thrombolysis and enoxaparin . However, there have been concerns of increased intracranial haemorrhage in the elderly with this regime used in the pre-hospital setting.
With the increased use of PPCI and the emergence of the newer anti-thrombotic agents discussed above, heparins are used much less frequently as anti-thrombotic agents in the initial management of STEMI.
Fondaparinux is a selective Factor Xa Inhibitor that has recently been evaluated in the setting of STEMI: it was found to be associated with reduced mortality and reduced re-infarction when compared to UH or placebo . It is indicated in patients who are managed initially with thrombolytics or who have no specific reperfusion therapy. It is not indicated in patients undergoing PPCI. It has a long half-life and is given once daily.
Glycoprotein IIB/IIIA inhibitors
Clinical studies have not reported improved outcome with GpIIB/IIIA Inhibitors agents as adjuvant therapy with thrombolysis in the setting of STEMI and there is, therefore, no role for GpIIB/IIIA Inhibitors in this context in routine clinical practice .
Left ventricular failure associated with pulmonary oedema presents with increasing breathlessness, reduced arterial oxygen saturations, tachycardia, a third heart sound and pulmonary crepitations. Clinical examination should be directed to exclude other complications as causes of heart failure (arrythmias and valvular abnormalities). Chest x-ray will confirm pulmonary congestion, and echocardiography may quantify mechanical left ventricular function (ventricular wall akinesis, reduced ejection fraction, etc.).
Treatment consists of measures to treat the underlying STEMI (i.e. reperfusion) and specific therapies for left ventricular failure and pulmonary oedema: diuretics, intravenous nitrates, non-invasive ventilatory support, ACE inhibitors and, where appropriate, tracheal intubation.
Pulmonary oedema, like many of the early complications of STEMI, is treated by effective reperfusion.
Cardiogenic Shock Left Ventricular Dysfunction
Cardiogenic shock, as a consequence of left ventricular dysfunction, is an ominous complication of STEMI and indicates significant myocardial damage.
How does it usually occur?
It usually occurs as a consequence of anterior AMI, or in the presence of Left bundle branch block (LBBB).
It is characterised by systemic hypoperfusion (tachycardia, reduced systolic blood pressure, cool peripheries and reduced renal output), associated with adequate central venous filling pressures. Clinical assessment should aim to exclude other causes of hypotension (hypovolaemia, arrythmias, drug related side effects, right ventricular infarction and mechanical complications of STEMI).
What is the most effective treatment?
The most effective treatment for cardiogenic shock is early and effective myocardial reperfusion: for these patients PPCI, if available, is superior to thrombolysis . In addition to reperfusion, specific measures to treat hypotension may be required (eg. the use of inotropes and/or an intra-aortic balloon pump), particularly where there is evidence of poor cerebral or renal perfusion.
Right Ventricular Dysfunction
Infarction of the right ventricle is normally associated with inferior infarction, but may occur in isolation. Patients present with hypotension and distended neck veins, but without signs of pulmonary oedema. This clinical picture in the setting of inferior infarction should prompt the recording of a right sided chest lead (V4R) which may confirm ST elevation.
What will echocardiography demonstrate at this stage?
Echocardiography demonstrates varying degrees of right ventricular myocardial wall dysfunction and/or functional tricuspid incompetence due to ventricular dilatation.
It is important to recognise hypotension due to right ventricular infarction because its management is significantly different to that for cardiogenic shock resulting from left ventricular dysfunction. In particular, it is vital to maintain right ventricular preload: the use of drugs that reduce preload (such as nitrates and opiates) can cause significant reductions in blood pressure. A fluid challenge is effective in maintaining venous return, and should be administered alongside careful haemodynamic monitoring. Rapid reperfusion is also necessary in order to improve the haemodynamic state.
It is important to recognise right ventricular infarction because it has implications for management, e.g. Avoidance of nitrates, may require fluid challenge.
The mechanical complications of STEMI are:
Mitral regurgitation is the commonest mechanical complication of STEMI. Patients develop signs of acute cardiac failure (associated with both pulmonary oedema and hypotension). The underlying pathological causes of acute mitral regurgitation in this setting are chordal rupture, papillary muscle infarction and rupture, or functional regurgitation due to dilatation of the mitral valve ring associated with left ventricular dilatation. Clinical signs of sudden haemodynamic deterioration associated with a new murmur are suggestive of mitral regurgitation. Echocardiography confirms the diagnosis and distinguishes mitral regurgitation from ventricular septal rupture. Definitive treatment of this complication requires urgent surgery and reperfusion of the infarct related coronary artery. In the meantime, treatment is aimed at controlling pulmonary oedema and supporting the circulation.
Ventricular septal rupture
Ventricular septal rupture is a complication that occurs most commonly with anterior or posterior AMI. The clinical presentation is similar to mitral regurgitation with haemodynamic compromise and a pan-systolic murmur. Echocardiography is required to distinguish between these two conditions. Definitive treatment requires urgent surgery to repair the defect, with interim measures to support the circulation, and reperfusion of the infarct related coronary artery.
Cardiac rupture and tamponade
Echocardiagram demonstrating large pericardial blood collection (LV = left ventricle, RV = right ventricle, LA = left atrium, RA = right atrium, * = blood in pericardium).
Acute cardiac wall rupture is a cause of sudden death following AMI, and is more common in the elderly. In subacute cardiac rupture the pericardium contains the blood loss from myocardial rupture and a tamponade develops. There is sudden haemodynamic deterioration with signs of a cardiac tamponade: hypotension, distended neck veins and muffled heart sounds.
Diagnosis is confirmed by echocardiography and, whilst pericardiocentesis may temporarily improve the haemodynamic state, definitive management requires urgent surgery.
Clinical assessment of an arrythmia should attempt to identify and correct reversible underlying causes (e.g. hypoxia, continuing ischaemia, acidosis, hypothermia, electrolyte disturbance), as well as quantify the haemodynamic consequences of the arrhythmia. The urgency of treatment depends upon the haemodynamic state of the patient.
Ventricular fibrillation accounts for the majority of pre-hospital sudden deaths in patients suffering AMI. Treatment for ventricular fibrillation or pulseless ventricular tachycardia requires immediate defibrillation in accordance with current resuscitation guidelines. Ventricular tachycardia without significant haemodynamic compromise may require treatment with amiodarone or lignocaine or, if haemodynamic compromise is significant, synchronised electrical cardioversion.
An accelerated idioventricular rhythm, which may resemble ventricular tachycardia, is an innocent finding that occurs during reperfusion: it does not cause haemodynamic compromise, is spontaneously self-limiting and requires no intervention.
Ventricular extrasystoles are common following AMI and usually require no specific treatment.
Atrial fibrillation is the most common supraventricular tachycardia to complicate AMI. It is often recurrent and ultimately self-limiting. Treatment with beta-blockers, amiodarone or digoxin may be indicated or, if there is significant haemodynamic compromise, synchronised DC cardioversion. Patients with atrial fibrillation should also receive anti-thrombotic treatment, although this is already likely to have occurred in the setting of AMI.
Various conduction defects and degrees of heart block can occur following AMI.
First-degree heart block is benign and requires no intervention.
Type one second-degree heart block (Wenckebach), in association with an inferior infarct, is rarely associated with haemodynamic compromise and is usually self-limiting. However, in the setting of anterior infarction, Wenckebach has a worse prognosis and may require pacing. Atropine should be used as an initial measure.
Type two second-degree and third-degree (complete) heart block are indications for transvenous pacing, which is more likely to be permanent in the presence of anterior infarction. Axis deviation should be identified in patients with right bundle branch block, since this indicates bifascicular block that may progress to complete heart block.
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