Acute coronary syndrome without ST segment elevation: unstable angina pectoris, myocardial infarction without ST segment elevation

At a glance

1. Non-ST-elevation acute coronary syndrome (NSTE-ACS) is an acute coronary syndrome without persistent ST elevation on the ECG: a non-ST-elevation myocardial infarction (NSTEMI) when troponin rises, or unstable angina when it does not.
2. It is usually caused by a plaque that ruptures or erodes and grows a thrombus that does not fully block the artery, or that is blocked with collaterals feeding the muscle beyond.
3. Rest pain, new severe angina or worsening angina are typical. The ECG may show ST depression or T-wave inversion, or be normal.
4. High-sensitivity troponin at presentation and 1 or 2 hours later rules infarction in or out in most patients. A raised troponin needs a clinical context: myocardial injury is not always infarction.
5. Very high-risk patients (shock, refractory pain, arrhythmias, heart failure) need immediate angiography, as in STEMI, high-risk patients within 24 hours, and the rest a selective approach.
6. Aspirin, a second antiplatelet drug, an anticoagulant and revascularisation follow, then the same long-term prevention as after STEMI.

01Definition and overview

The acute coronary syndromes are a spectrum, classed at first by the ECG because it decides the urgency. Patients with acute chest pain and persistent ST elevation (or an equivalent) have the working diagnosis of STEMI. The rest have a working diagnosis of NSTE-ACS, which divides, once the troponin is known, into:

• non-ST-elevation myocardial infarction (NSTEMI): myocardial ischaemia with a rise or fall of cardiac troponin, at least one value above the 99th percentile;
• unstable angina: myocardial ischaemia at rest or on minimal effort without myocyte death, with no rise or fall in troponin.

Unstable angina takes four forms: angina at rest, usually lasting more than 20 minutes; new-onset angina that is severe; crescendo angina, which comes more often, lasts longer or appears with less effort; and angina in the days after an infarction. High-sensitivity troponin assays find a small infarction in many patients who would once have had unstable angina, which has become less common, and its outlook is better.

The current universal definition of infarction separates myocardial injury (a troponin above the 99th percentile, using sex-specific limits), which is acute when the values rise or fall and chronic when they are stable, from myocardial infarction, which is acute injury with evidence of ischaemia. Infarction is then classed as primary (an acute coronary event), secondary (an imbalance of supply and demand in another illness) or procedure-related; the details are in STEMI.

02Etiology and pathophysiology

Causes

• Rupture or erosion of an atherosclerotic plaque with a thrombus, the commonest cause. The thrombus, rich in platelets, narrows the artery or blocks it intermittently, and fragments embolise downstream and cause small infarcts. In about a quarter of patients with NSTEMI the artery is in fact blocked, often the circumflex artery, whose territory is poorly seen on the standard ECG.
• Other acute coronary causes: spontaneous coronary artery dissection, spasm and coronary embolism.
• Secondary infarction: an imbalance of supply and demand caused by another acute illness (anaemia, a tachyarrhythmia, hypotension, severe hypertension or sepsis), without an acute coronary lesion; it is confirmed by obstructive coronary disease or by a new wall-motion abnormality on imaging.

Myocardial injury with non-obstructive coronary arteries

About 1 in 20 patients with an apparent infarction have no significant narrowing at angiography. The current definition renamed this myocardial injury with non-obstructive coronary arteries (MINOCA), a working diagnosis that needs a cause. Cardiac MRI finds one in most: an infarct from a plaque disruption, spasm or embolism that has cleared, or myocarditis, takotsubo syndrome or a cardiomyopathy. It is commoner in women.

Why the ECG differs from STEMI

In STEMI the artery is blocked and the infarct spreads through the wall, which shows as ST elevation over the injured region. In NSTE-ACS the ischaemia is usually confined to the subendocardium, which shows as ST depression or T-wave inversion that does not point to the artery involved, or as no change at all.

03Clinical features

• Chest pain like angina but at rest or on minimal effort, lasting more than 20 minutes, or a change in the pattern of known angina. It may ease with glyceryl trinitrate, which does not exclude an acute coronary syndrome.
• Breathlessness, sweating, nausea or syncope, or only breathlessness, fatigue or epigastric pain, more often in women, older people and people with diabetes or kidney disease.

The examination is often normal. It looks for heart failure, a new murmur (mitral regurgitation), signs of the other causes of chest pain (aortic dissection, pulmonary embolism, pneumothorax, pericarditis) and for triggers such as anaemia, infection, thyrotoxicosis or a fast arrhythmia.

04Diagnosis and management

The ECG

An ECG within 10 minutes of the first medical contact, and repeated with each recurrence of pain and whenever the diagnosis is uncertain:

• ST depression, horizontal or downsloping, of 0.5 mm or more in two contiguous leads, the most specific finding;
• transient ST elevation;
• T-wave inversion, especially deep and symmetrical, or biphasic T waves in V2 and V3 (Wellens pattern), a sign of a critical narrowing of the left anterior descending artery;
• a normal ECG, in more than a third.

ST depression in V1 to V3 may be a posterior STEMI, and posterior leads (V7 to V9) are then recorded. ST depression of 1 mm or more in six or more leads with ST elevation in aVR or V1 suggests left main or multivessel disease, especially with haemodynamic compromise.

Troponin

High-sensitivity cardiac troponin (T or I) is measured at presentation and repeated after 1 hour (or 2 hours) with a validated algorithm:

The cut-offs are specific to each assay; for one widely used troponin T assay, for example, below 5 ng/L at presentation rules out, and 52 ng/L or more, or a rise of 5 ng/L or more at 1 hour, rules in. The algorithms rule out with a negative predictive value above 99 per cent.

Other tests

• Echocardiography for wall motion, the ejection fraction and other diagnoses.
• CT coronary angiography in patients with a low or intermediate likelihood, normal or borderline troponin and a normal ECG, to rule out coronary disease.
• Full blood count, creatinine, glucose, lipids.

Risk

The GRACE score estimates the risk of death in hospital and at 6 months from age, heart rate, systolic pressure, creatinine, Killip class, cardiac arrest at admission, ST deviation and raised troponin. The risk of bleeding is weighed too: older age, kidney disease, anaemia, low body weight, previous bleeding and anticoagulants raise it, and they shape the choice of drugs and access.

Timing of angiography

In a large trial, angiography within about 12 hours, compared with 2 to 3 days, did not improve outcomes overall, but it did in patients with a GRACE score above 140. After an out-of-hospital cardiac arrest without ST elevation, a stable patient does not need immediate angiography.

Drugs

• Aspirin 150 to 300 mg by mouth at once, then 75 to 100 mg daily.
• A P2Y12 inhibitor: prasugrel is preferred to ticagrelor in patients who go on to PCI, after a head-to-head trial in which it reduced death, infarction or stroke from 9.3 to 6.9 per cent without more major bleeding. Ticagrelor suits patients managed without PCI, and clopidogrel is used when the others cannot be (with an oral anticoagulant, or a high bleeding risk). When angiography will be done within 24 hours, the P2Y12 inhibitor is usually started once the anatomy is known, not routinely before. 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. Glycoprotein IIb/IIIa inhibitors are kept for a heavy thrombus or poor flow during PCI.
• A parenteral anticoagulant at diagnosis: unfractionated heparin (or enoxaparin) when angiography is early; fondaparinux when it is not, with heparin added during PCI. It is usually stopped straight after PCI.
• Nitrates (sublingual, then intravenous) for ongoing pain, hypertension or heart failure, and early beta-blockers for ongoing ischaemia if there is no heart failure or shock.
• A high-intensity statin, started at once.

Revascularisation

Angiography shows the culprit and the extent of disease. The culprit is usually treated with a drug-eluting stent through the radial artery. With multivessel disease, complete revascularisation is considered, by PCI or by bypass surgery when there is left main or complex three-vessel disease, especially with diabetes. Patients with no culprit lesion are investigated for the causes of MINOCA.

After the admission

Long-term treatment is the same as after STEMI: dual antiplatelet treatment for 12 months by default, shorter or de-escalated in patients at high risk of bleeding, then usually aspirin alone; a high-intensity statin to an LDL cholesterol below 1.4 mmol/L and a fall of at least 50 per cent; ACE inhibitors, beta-blockers and mineralocorticoid antagonists according to the ejection fraction and other diseases; cardiac rehabilitation; stopping smoking. Patients who need an oral anticoagulant, usually for atrial fibrillation, take it with clopidogrel, with aspirin added for no more than about a week (up to a month when the ischaemic risk is high), to limit bleeding; a direct oral anticoagulant is preferred to warfarin.

05Epidemiology

NSTEMI is now commoner than STEMI, and its share is growing, as the population ages and more sensitive troponin tests find smaller infarcts. The annual incidence of NSTE-ACS in Europe has been estimated at about 3 per 1000 people, varying between countries. Patients are older than those with STEMI, more often women, and have more diabetes, kidney disease, heart failure and previous coronary disease. Unstable angina has become uncommon with high-sensitivity troponin. Women and older patients are less often offered angiography and full treatment, and they do worse.

06Prognosis

Death in hospital is lower than after STEMI, a few per cent, but the gap closes in the following months, and over the following years it can be higher, because the patients are older and sicker. Mortality at 6 months has fallen from about 1 in 6 in the 1990s to about 1 in 16 today. The risk is greater with age, a higher GRACE score, ST depression, a high troponin, heart failure, kidney disease and diabetes. Unstable angina with a normal high-sensitivity troponin carries a much lower risk. Many later events arise from other plaques, often ones that looked mild at angiography, which is why long-term prevention matters as much as the first treatment.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1A woman has had 30 minutes of chest pain at rest, with ST depression on her ECG. What separates a non-ST-elevation myocardial infarction from unstable angina?

The length of the painThe depth of the ST depressionA rise or fall of cardiac troponin with at least one value above the 99th percentileThe response to glyceryl trinitrate

2Which patient with a non-ST-elevation acute coronary syndrome needs immediate coronary angiography?

A stable patient with a raised troponin and a GRACE score of 120A patient with ongoing pain despite treatment, a systolic pressure of 80 mmHg and pulmonary oedemaA patient whose pain has settled, with a normal troponin at 0 and 1 hourA patient with diabetes and a raised troponin who is pain-free

3A 60-year-old man has had an hour of central chest pain that is now settling. His first ECG is normal. What is the right next step?

Discharge him, because a normal ECG excludes an acute coronary syndromeAn exercise ECG the same dayImmediate coronary angiographyRepeat ECGs and high-sensitivity troponin at presentation and 1 or 2 hours later

4A patient with a non-ST-elevation myocardial infarction is to have coronary angiography within 24 hours. When should the P2Y12 inhibitor be started?

Usually once the coronary anatomy is known, not routinely beforehandIn the ambulance, at the highest dose, in every patientNever, because aspirin alone is enoughOnly after discharge

5A patient on haemodialysis has a high-sensitivity troponin that is above the 99th percentile but the same at 0 and 3 hours, with no symptoms of ischaemia. How is this best described?

Acute myocardial infarctionChronic myocardial injuryUnstable anginaA false-positive test that can be ignored