Acute coronary syndrome: Acute myocardial infarction with ST segment elevation

01Definition and overview

Myocardial infarction is death of heart muscle caused by ischaemia. The current universal definition separates two things:

• myocardial injury: a cardiac troponin above the 99th percentile of a healthy population, using sex-specific limits; it is acute when the values rise or fall;
• myocardial infarction: acute myocardial injury with evidence of ischaemia, from the symptoms, new ischaemic ECG changes or Q waves, a new regional wall-motion abnormality or loss of viable myocardium on imaging, or an acute coronary lesion (thrombus, dissection, embolism or spasm) on angiography.

It then classifies infarction by its setting:

The acute coronary syndromes are a spectrum, classed at first by the ECG because it decides the urgency. STEMI is the working diagnosis when the ECG shows persistent ST elevation, or an equivalent, with symptoms: it signals an artery blocked completely, which needs opening at once.

02Etiology and pathophysiology

Causes

• Rupture of a lipid-rich plaque with a thin fibrous cap, the commonest cause, or erosion of the endothelium over a plaque. Both expose collagen and tissue factor and set off a thrombus.
• Less often: spontaneous coronary artery dissection (mostly in women, including around pregnancy), coronary embolism (from atrial fibrillation, endocarditis or a prosthetic valve), spasm (including from cocaine), and aortic dissection extending into a coronary artery.

The triggers include heavy exertion, emotional stress, infection, cold, and the early morning hours. The risk factors are those of coronary atherosclerosis, discussed in stable angina.

How the infarct forms

1. 1

   The plaque breaks

   The cap ruptures or the endothelium erodes, and platelets adhere, activate and release thromboxane A2 and ADP, which recruit more platelets and constrict the artery.
2. 2

   The artery closes

   Thrombin turns fibrinogen into fibrin, and a red, fibrin-rich thrombus blocks the lumen completely.
3. 3

   The wavefront spreads

   Myocytes begin to die after 20 to 30 minutes, first in the subendocardium. Over the next 3 to 6 hours the necrosis spreads outward through the wall, becoming transmural. This is why time is muscle, and why reperfusion helps most in the first hours.
4. 4

   Reperfusion salvages

   Opening the artery saves the myocardium that is still alive at its edge and limits the size of the infarct, the main predictor of later heart failure and death.
5. 5

   The scar forms

   Neutrophils enter in the first days, and macrophages then clear the dead muscle, at about days 3 to 7, when the wall is weakest and can rupture. Granulation tissue follows, and a collagen scar forms over 6 to 8 weeks. The rest of the ventricle may dilate and remodel.

Where the infarct is

The right coronary artery usually supplies the sinus and atrioventricular nodes, so inferior infarction often causes bradycardia and heart block, usually transient.

03Clinical features

• Central chest pain, heavy or crushing, lasting more than 20 minutes, not relieved by glyceryl trinitrate, often spreading to the arms, neck or jaw.
• Sweating, nausea and vomiting, breathlessness, a sense of doom.
• Presentations without chest pain, or dominated by other symptoms, are more common in older people, women and people with diabetes: breathlessness, fatigue, epigastric pain, confusion, syncope. Most of these patients still have some chest discomfort. Some infarcts are silent and are found later.
• Sudden death: many deaths happen before the patient reaches hospital, mostly from ventricular fibrillation in the first hour.

The examination may be normal, or show a pale, clammy, anxious patient, a tachycardia or bradycardia, hypotension, a fourth heart sound, and signs of complications: crackles and a third heart sound in heart failure, a new murmur in mitral regurgitation or septal rupture, a rub in pericarditis.

In right ventricular infarction the patient is hypotensive with a raised jugular venous pressure and clear lungs.

04Diagnosis and management

The ECG

STEMI on the ECG is new ST elevation at the J point in at least two contiguous leads:

The ECG evolves: tall, peaked hyperacute T waves in the first minutes, then ST elevation, then Q waves and T-wave inversion over hours to days, with the ST segment settling. Persistent ST elevation weeks later suggests a ventricular aneurysm.

Some patients with a blocked artery or critical ischaemia do not show classic ST elevation, and they go straight to angiography as in STEMI:

• left or right bundle branch block, or a paced rhythm, with symptoms that strongly suggest ongoing ischaemia;
• a posterior infarction, with ST depression in V1 to V3 and elevation in the posterior leads V7 to V9;
• ST depression of 1 mm or more in six or more leads with ST elevation in aVR or V1, especially with haemodynamic compromise, which suggests left main or multivessel disease and calls for immediate angiography; fibrinolysis does not help ST depression other than a posterior infarction.

Right-sided leads (V3R, V4R) are recorded in every inferior infarction. A normal first ECG is repeated every 15 to 30 minutes while the pain continues.

Other tests

• Troponin confirms the infarction and its size, but reperfusion is never delayed for the result.
• Echocardiography, when the diagnosis is uncertain, and in every patient with shock or a new murmur: it shows the wall motion, the ejection fraction, the mechanical complications and other diagnoses (aortic dissection, pericardial effusion, pulmonary embolism, takotsubo).
• Full blood count, creatinine and electrolytes, glucose, lipids.

The first minutes

• Continuous ECG monitoring with a defibrillator at hand.
• Aspirin 150 to 300 mg chewed (or intravenously).
• Oxygen only if the saturation is below 90 per cent; in patients who are not hypoxaemic it does not help.
• Intravenous morphine for severe pain, with an antiemetic; it slows the absorption of oral antiplatelet drugs.
• Nitrates for ongoing pain if the blood pressure allows, but not in right ventricular infarction, hypotension, or after sildenafil or tadalafil.

Reperfusion

Every patient with STEMI and symptoms for less than 12 hours needs the artery opened.

• Primary PCI, the preferred treatment, if it can be done within 120 minutes of the diagnosis; hospitals aim to cross the artery with the wire within 60 minutes of the diagnosis when it is made at a PCI centre, and within 90 minutes when it is made in the ambulance or at a hospital without a catheter laboratory. It is done through the radial artery with a drug-eluting stent, under unfractionated heparin (enoxaparin or bivalirudin are alternatives), with a potent P2Y12 inhibitor, prasugrel or ticagrelor, added to aspirin.
• Fibrinolysis if primary PCI cannot be done within 120 minutes, given within 10 minutes of diagnosis, ideally before hospital. A fibrin-specific drug (tenecteplase, at half dose over the age of 75) is given with aspirin, clopidogrel and enoxaparin. It saves about 30 lives for every 1000 patients treated within 6 hours. The patient is then transferred to a PCI centre: rescue PCI if the ST elevation has not fallen by at least half within 60 to 90 minutes, or if pain or instability persist, and otherwise angiography within 2 to 24 hours.
• Beyond 12 hours, primary PCI is still done if symptoms, heart failure, shock or arrhythmias persist, and is reasonable up to 48 hours. An artery found blocked after 48 hours in a stable patient is not routinely opened, because a large trial showed no benefit.

Many patients have narrowing of other arteries too. They are opened as well, during the first procedure or within 45 days, which reduces further infarction. In cardiogenic shock only the culprit artery is treated at first, because opening the others at once increased death or kidney failure in a trial; an intra-aortic balloon pump is not used routinely. After a resuscitated cardiac arrest, primary PCI follows if the ECG shows persistent ST elevation, while a stable patient without ST elevation does not need immediate angiography.

Complications

The mechanical complications have become rare, below 1 per cent of infarctions, with early reperfusion, but they remain highly lethal.

Before discharge and after

• Echocardiography for the ejection fraction. If it is 40 per cent or less, it is measured again 6 to 12 weeks after revascularisation and full treatment, and a defibrillator is considered if it stays at 35 per cent or less. A defibrillator for primary prevention is not implanted in the first 40 days, whereas ventricular tachycardia or fibrillation after the first 48 hours is assessed for one at once.
• Dual antiplatelet treatment, aspirin with prasugrel or ticagrelor, for 12 months, shorter in patients at high risk of bleeding, with a proton pump inhibitor in those at high risk of gastrointestinal bleeding; then usually aspirin alone for life. Prasugrel is not given after a previous stroke or transient ischaemic attack, and a lower dose is used at 75 or over or under 60 kg.
• A high-intensity statin, started at once, to an LDL cholesterol below 1.4 mmol/L and a fall of at least 50 per cent, adding ezetimibe and then a PCSK9 inhibitor as needed.
• Beta-blockers for an ejection fraction of 40 per cent or less, where they reduce death and reinfarction, and probably also at 40 to 49 per cent. With a normal ejection fraction, recent trials found little or no benefit, so their routine use is being reconsidered.
• An ACE inhibitor (or ARB) for a reduced ejection fraction, heart failure, hypertension, diabetes or kidney disease, and a mineralocorticoid receptor antagonist when the ejection fraction is 40 per cent or less with heart failure or diabetes.
• Patients who need an anticoagulant, for atrial fibrillation for example, take it with clopidogrel, and aspirin for at most a week.
• Cardiac rehabilitation: exercise training, education, stopping smoking, diet and weight, blood pressure and diabetes control, psychological support, and annual influenza vaccination. It reduces deaths and readmissions.

05Epidemiology

Ischaemic heart disease is the commonest cause of death in Europe: across Europe and its neighbouring countries there are about 5.8 million new cases each year, and it causes about 44 per cent of cardiovascular deaths in men and 38 per cent in women. STEMI is becoming less common while non-ST-elevation infarction becomes more common, a shift that reflects prevention, an older population and more sensitive troponin tests. Its incidence in European countries ranges from about 40 to 140 per 100,000 people a year. STEMI is commoner in men and in younger patients than non-ST-elevation infarction; women are on average several years older when it happens, more often have symptoms other than chest pain, and are reperfused later.

06Prognosis

Before modern treatment, about a third of patients died in the first month, many before reaching hospital. With reperfusion, in-hospital mortality in Europe is about 4 to 12 per cent, and about 1 in 10 patients dies within a year. The outlook is worse with older age, a long delay to reperfusion, an anterior or large infarction, a higher Killip class, a low ejection fraction, diabetes and kidney disease; risk scores such as GRACE combine these. Cardiogenic shock still kills about 4 to 5 in 10 patients.

The ejection fraction after the infarction is the strongest predictor of the long-term outlook. Survivors remain at high risk of another event, especially in the first year, and the drugs, lifestyle changes and rehabilitation started after the infarction reduce it substantially.