Acute Coronary Syndrome (ACS)
Acute coronary syndrome (ACS) describes the spectrum of conditions caused by sudden reduction in coronary blood flow, including unstable angina, non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI). It is a medical emergency requiring rapid diagnosis and treatment to reduce myocardial damage and improve survival.
Background Information
Definition
Acute coronary syndrome (ACS) is an umbrella term that describes the spectrum of conditions caused by sudden reduction in coronary blood flow, including unstable angina, NSTEMI, and STEMI. [Ref]
| Unstable angina | NSTEMI (Non-ST elevation myocardial infarction) | STEMI (ST elevation myocardial infarction) | |
|---|---|---|---|
| Pathophysiology | Partial vessel occlusion → ischaemia WITHOUT infarction | Partial vessel occlusion → partial thickness (subendocardial) infarction | Complete vessel occlusion → full thickness (transmural) infarction |
| ECG changes |
No ST elevation Possible ECG changes include ST depression and/or T wave inversion ECG may be normal |
ST elevation in at least 2 contiguous leads | |
| Cardiac troponin | <99th centile of URL | Rise and/or fall + >99th centile of URL | |
Risk Factors
Major risk factors: [Ref]
- Age (>65 y/o)
- Male
- Cardiovascular risk factors
- Family history of premature coronary artery disease
- Presence of other cardiovascular diseases
- Established coronary artery disease (e.g. previous MI, coronary revascularisation)
Other risk factors: [Ref]
- CKD
- Chronic inflammatory conditions (e.g. rheumatoid arthritis, SLE)
- Premature menopause
- Pregnancy-related complications (e.g. pre-eclampsia, gestational diabetes)
Complications
Complications of MI can be organised by the time frame after the event: [Ref1, Ref2]
| Timeframe | Complication | Presentation |
|---|---|---|
| Early (0-24 hours) | Arrhythmia | Common life-threatening arrhythmias:
|
| Acute heart failure / cardiogenic shock | ||
| Intermediate (0-1 week) | Papillary muscle rupture | Presents as acute mitral regurgitation
|
| Ventricular septal rupture | Presents as left-to-right shunting:
|
|
| Ventricular free wall rupture | Presents as cardiac tamponade (Beck’s triad):
|
|
| Late (>1-2 weeks) | Congestive heart failure | Causes HFrEF |
| Left ventricular aneurysm | Presents as:
|
|
| Dressler syndrome | Autoimmune pericarditis:
Typical pericarditis ECG features – widespread concave ST elevation + PR depression |
|
Diagnosis
Clinical Features
Chest pain / discomfort is the main presenting feature of ACS, and can be mapped to the SOCRATES framework: [Ref]
- Site: central or retrosternal (typically non-specific)
- Onset: sudden onset, usually at rest
- Character: heavy / crushing / tightness
- Radiation: either arm, neck, jaw, shoulders and epigastrium
- Associated symptoms: dyspnoea, nausea, vomiting, diaphoresis
- Timing: builds to a crescendo over minutes, may wax and wane, and often lasts >15 min and does not resolve spontaneously
- Exacerbating factors: often precipitated by exertion or emotional stress but may occur at rest (unlike stable angina, ACS symptoms characteristically do not fully resolve by rest and/or nitrates)
- Severity: can be severe
Typical ACS features: [NICE CG95]
- Chest pain / discomfort lasting >15 min
- Chest pain associated with dyspnoea, nausea, vomiting, and diaphoresis (particularly a combination of these)
- Chest pain associated with haemodynamic instability
- Abrupt deterioration in previously stable angina, with recurrent chest pain occurring frequently and with little or no exertion
Atypical features of ACS include epigastric pain or the absence of chest pain with accompanying N&V, dyspnoea, and diaphoresis. They are usually seen in:
- Inferior MI (esp. if epigastric pain)
- Female
- Diabetes (due to autonomic neuropathy)
Reproducible chest pain on palpation makes ACS less likely, it is more suggestive of musculoskeletal causes of chest pain.
Other clues of musculoskeletal chest pain:
- Pain on movement
- Pain in a very specific location (cardiac chest pain is typically non-specific)
Referral and Initial Assessment
Referral Criteria
This mainly applies to those who present to a non-hospital setting (e.g. GP, health centre)
There are 2 main referral scenarios: [NICE CG95]
| Scenario | Recommended action |
|---|---|
|
Emergency referral to hospital (usually via ambulance) |
|
Urgent same-day referral to hospital |
Initial Assessment
Apart from a detailed clinical history and examination, perform the following in suspected ACS cases: [NICE CG95]
- 12-lead ECG – most immediate test to perform (followed by serial ECGs)
- High-sensitivity cardiac troponin T/I (followed by serial samples)
- Other tests
- Routine bloods (e.g. FBC, U&Es, glucose)
- Chest X-ray – to rule out chest pathologies (e.g. pneumothorax, pneumonia) and ACS complications
Diagnostic Criteria
Diagnostic criteria of ACS: [Ref]
| ACS spectrum | Diagnostic criteria |
|---|---|
| STEMI |
|
| NSTEMI | |
| Unstable angina |
|
Troponin Interpretation
Rise and/or fall of cardiac troponin is indicative of myocardial infarction (which could be STEMI or NSTEMI) (but not unstable angina) [Ref]
- Troponin is a marker of myocardial injury, not specific to MI
- Necrosis in STEMI and NSTEMI causes a dynamic release of troponin, thus the rise and/or fall pattern
- A persistently raised troponin level is NOT indicative of ACS
Choice of cardiac biomarkers in re-infarction (myocardial infarction occurring within 28 days from the initial event) (NB if it occurs >28 days, it is termed a recurrent infarction)
- Creatine kinase-MB was historically used to diagnose re-infarction due to its shorter half-life (compared to troponin), which allows the detection of a new rise after the initial peak
- However, the latest guidelines recommend cardiac troponin as the preferred biomarker in re-infarction [Ref1][Ref2]
- If a re-infarction is suspected, a cardiac troponin measurement should be obtained immediately, followed by a second sample at 3-6 hours after
- Re-infarction can be diagnosed if there is a ≥20% increase in the second cardiac troponin value (provided this value also exceeds the 99th percentile upper reference limit)
Important non-ACS causes of elevated troponin: [Ref]
| Category | Important causes |
|---|---|
| Cardiovascular causes |
|
| Non-cardiac causes |
|
ECG Interpretation
STEMI
Dynamic ECG changes seen in STEMI: [Ref]
- ST elevation in ≥2 contiguous leads
- Reciprocal ST depression in opposite territory (strengthens diagnosis of STEMI as opposed to other causes of ST elevation)
- Hyperacute T waves, T wave inversion, pathological Q wave
Dynamic changes in ECG (and troponin levels) are characteristic of ACS.
ECG changes over time in STEMI:
- Hyperacute T waves
- ST elevation
- T wave inversion
- Q wave (pathological) formation – may persist indefinitely
ECG changes in various myocardial territories: [Ref]
| Territory | Coronary artery involved | Leads with ST elevation | Leads with reciprocal ST depression | Other notes |
|---|---|---|---|---|
| Anterior | Left anterior descending (LAD) | V1-V4 | Inferior leads (II, III, aVF) | Poor R wave progression is common |
| Lateral | Left circumflex (LCx) | V5-V6, I, aVL | Often occurs with anterior MI (→ anterolateral MI) | |
| Inferior | Right coronary artery (RCA) | II, III, aVF | Lateral leads (I, aVL +/- V5-V6) | AV block is common in inferior MI |
| Posterior | Posterior descending artery (PDA) | V7-V9 | Anterior leads (V1-V4) | Often occurs with inferior MI |
Other important causes of ST elevation:
| Cause | Features |
|---|---|
| Pericarditis | Widespread ‘global’ changes (not specific to myocardial territory):
No reciprocal ST depression, apart from in V1 and aVR Clinical features are important in distinguishing from STEMI:
|
| Myocarditis | Non-specific ECG changes, often widespread:
Clinical features are important in distinguishing from STEMI:
Note that myocarditis commonly causes an elevated cardiac troponin |
| Left bundle branch block | ECG changes:
|
| Brugada syndrome | ECG changes seen in V1-V3
|
| Prinzmetal (vasospastic) angina | Transient ST elevation during angina episodes
Classically caused by cocaine induced coronary vasospasm |
| Early repolarisation | Seen in young, healthy adults
In contrast, STEMI typically produces convex ST elevation and is dynamic |
NSTEMI and Unstable Angina
Main changes include: [Ref]
- ST depression (horizontal / down-sloping)
- T wave inversion
NSTEMI and unstable angina can have a completely normal ECG
Management
Immediate Management
Once ACS is suspected clinically, the following should be started ASAP (often given pre-hospital): [NICE CG95]
- Aspirin 300mg
- Pain relief
- GTN (sublingual /buccal) – but should be avoided in suspected right ventricular infarction (e.g. inferior MI)
- IV morphine (esp. if MI is suspected)
- Oxygen therapy (only indicated if SpO2 <94%, or <88% in those who are at risk of type 2 respiratory failure)
MONA is a common acronym:
- M – Morphine
- O – Oxygen
- N – Nitrate
- A – Aspirin 300mg
Treatment for ACS should be initiated immediately upon clinical suspicion (based on clinical features + ECG changes), without waiting for confirmation with troponin results.
Definitive Management
Approach: there are 2 definitive management pathways:
- STEMI pathway
- Reperfusion therapy (PCI / fibrinolysis), OR
- Medical management
- NSTEMI / unstable angina pathway (depending on risk stratification)
- PCI, OR
- Medical management
STEMI criteria as per ESC guidelines require new ST elevation in at least 2 contiguous leads:
- ST elevation in V2-V3
- Men <40 y/o: ≥2.5 mm
- Men ≥40 y/o: ≥2.0 mm
- Women of any age: ≥1.5 mm
AND/OR
- Other leads: ≥1 mm in the absence of LVH / LBBB
STEMI Pathway
Ensure aspirin 300 mg has been given (if not already given as part of immediate management) [NICE NG185]
Definitive management depends on eligibility for reperfusion therapy, which is determined by time from symptom onset (cut-off is 12 hours) [NICE NG185]
Onset <12 hours → Reperfusion Therapy
There are 2 options for reperfusion therapy: [NICE NG185]
- Angiography +/- primary percutaneous coronary intervention (PCI), or
- Fibrinolysis (also known as thrombolysis)
The choice depends on whether there is access to PCI (i.e. a cath lab) within 120 min (2 hours) [NICE NG185]
Primary PCI vs non-primary PCI:
- Primary PCI: PCI used as the initial reperfusion treatment for an acute STEMI, performed urgently instead of fibrinolysis
- Non-primary PCI: PCI performed in any other context (e.g. rescue PCI after failed fibrinolysis)
Access Within 120 min → Angiography +/- Primary PCI
Coronary angiography identifies the culprit coronary artery and defines the coronary anatomy. PCI is performed if a suitable obstructive lesion is found and can be treated interventionally
PCI involves angioplasty +/- stent placement
- Drug-eluting stent preferred over bare metal stent (if stenting is indicated) [NICE NG185]
- Radial access is preferred over femoral access [NICE NG185]
Adjuvant drug therapy: [NICE NG185]
| Dual antiplatelet therapy (DAPT) | DAPT should be given once primary PCI is planned:
Aspirin would already have been given as part of the initial management. Here, DAPT means adding a second antiplatelet agent, not giving another dose of aspirin. |
| Anti-thrombotic therapy during PCI | Routine IV anti-thrombotic therapy:
Bailout GpIIb/IIIa inhibitor |
No Access Within 120 min → Fibrinolysis
Offer all the following:
- Fibrinolytic agent: tissue plasminogen activator (e.g. alteplase, streptokinase)
- Antithrombin (e.g. enoxaparin, UFH)
- Dual antiplatelet therapy (DAPT)
- 1st line: aspirin + ticagrelor
- High bleeding risk: aspirin + clopidogrel OR aspirin monotherapy
Perform an ECG 60-90 minutes after fibrinolysis:
- If ST elevation still present on ECG → seek specialist advice for angiography +/- PCI
- Do not repeat fibrinolytic therapy
Onset >12 hours → Medical Management (Usually NOT for Reperfusion)
Offer medical management with dual antiplatelet therapy (DAPT):
- 1st line: aspirin + ticagrelor
- High bleeding risk: aspirin + clopidogrel OR aspirin monotherapy
Exception: consider PCI if onset >12 hours with evidence of MI or develops cardiogenic shock [NICE NG185]
Tests Before Discharge
ALL STEMI patients require an echocardiogram to assess left ventricular function before discharge [NICE NG185]
Left ventricular function determines ongoing secondary prevention management (see below).
NSTEMI / Unstable Angina Pathway
Initial management (offer both): [NICE NG185]
- Aspirin 300 mg (if not already given as part of immediate management)
- Antithrombin therapy
- 1st line: fondaparinux
- If high bleeding risk or renal impairment or immediate angiography planned: UFH
Definitive management depends on risk stratification with GRACE score (which predicts 6-month mortality).
If the patient is clinically unstable (e.g. hypotension, shock) → offer immediate PCI without taking GRACE score into account. [NICE NG185]
GRACE >3.0% (Intermediate / High / Highest Risk)
Offer ALL of the following: [NICE NG185]
- Angiography +/- PCI within 72 hours
- UFH, even if fondaparinux has been given
- Dual antiplatelet therapy (DAPT)
- 1st line: aspirin + prasugrel / ticagrelor
- Already taking oral anticoagulant: aspirin + clopidogrel
Recommendations regarding angiography +/- PCI (same as STEMI): [NICE NG185]
- Drug-eluting stent, if stenting indicated
- Radial access, preferred over femoral access
GRACE ≤3.0% (Low / Lowest)
Offer medical management with dual antiplatelet therapy (DAPT): [NICE NG185]
- 1st line: aspirin + ticagrelor
- High bleeding risk: aspirin + clopidogrel OR aspirin monotherapy
Only consider angiography +/- PCI if ischaemia testing (e.g. stress echo, myocardial perfusion imaging) is positive
Tests Before Discharge
Offer echocardiogram to assess left ventricular function [NICE NG185]
- Offer in all NSTEMIs; consider in unstable angina
- Left ventricular function determines ongoing secondary prevention management (see below).
Consider ischaemia testing in those who have been medically managed without coronary angiography
Overview – Choice of Dual Antiplatelet Therapy in ACS
This section aims to summarise the recommendations of dual antiplatelet therapy in various ACS scenarios. [NICE NG185]
| Scenario | Choice of DAPT |
|---|---|
| PCI is not intended (applies to STEMI, NSTEMI, unstable angina) |
|
| PCI intended for STEMI |
|
| PCI intended for NSTEMI / unstable angina |
|
The above recommendations are based on outcomes from various trials. Key points to be aware of regarding the choice of P2Y12 inhibitors:
- Clopidogrel has the lowest bleeding risk (but moderate efficacy at reducing thrombotic events)
- Prasugrel and ticagrelor have greater efficacy at reducing thrombotic events, but at the cost of a higher bleeding risk
- Prasugrel is by far the most potent agent
Myocardial Infarction Secondary Prevention
Conservative Management
Offer ALL the following: [NICE NG185]
- Cardiac rehabilitation program
- Lifestyle advice
- Mediterranean-style diet
- Regular physical activity
- Smoking cessation
- Advice on alcohol consumption
- Weight management
- Sexual activity can be resumed 4 weeks after
NICE recommendations on use of supplements: [NICE NG185]
| Omega-3 fatty acid | Do not recommend
But if the person chooses to, there is no evidence of harm |
| Beta-carotene | Advise against |
| Vitamin E/C/B9 (folic acid) | Do not recommend |
Pharmacological Management
4 cornerstone therapies for post-MI secondary prevention: [NICE NG185]
| Dual antiplatelet therapy (DAPT) (aspirin + a P2Y12 inhibitor) | Continue the previously started DAPT for 12 months
After 12 months, stop the P2Y12 inhibitor and continue aspirin for life In patients who are allergic to aspirin, consider clopidogrel monotherapy |
| High-intensity statin | Continue for life
Most common: atorvastatin 80mg (also see the Lipid Lowering Therapy and Cardiovascular Risk Reduction article) |
| ACE inhibitor | Initiate once haemodynamically stable
Continue for life Also optimise hypertension management in line with those outlined in the Hypertension (Primary) article |
| Beta blocker | Initiate once haemodynamically stable
Treatment duration depends on LVEF:
|
Other therapy: [NICE NG185]
- Aldosterone antagonist (e.g. spironolactone)
- Indicated in those who had an acute MI + clinical features of heart failure + ↓ LVEF
- Initiate within 3-14 days of the MI, preferably after starting ACE inhibitor
- Also see the Chronic Heart Failure article
- GLP-1 agonist (semaglutide)
- Indicated in those with BMI ≥27 kg/m2 after an MI (or any other CVD, e.g. stroke, symptomatic peripheral arterial disease)
Do not offer nicorandil (a potassium channel activator) to reduce cardiovascular risk after a myocardial infarction.
Do not routinely offer calcium channel blockers to reduce cardiovascular risk after a myocardial infarction. Unless it is used to treat hypertension and/or angina.
Antiplatelet therapy in patients with ongoing separate indication for anticoagulation (e.g. anticoagulation in atrial fibrillation): [NICE NG185]
- Patients who had PCI → continue anticoagulation + clopidogrel for up to 12 months
- Patients who did NOT have PCI → continue anticoagulation + aspirin for up to 12 months (unless there is a high risk of bleeding)
Do not routinely offer prasugrel or ticagrelor in combination with an anticoagulant