Unstable Angina
Unstable angina is an acute coronary syndrome characterized by new-onset, worsening, or rest angina due to coronary plaque disruption and thrombosis without myocardial necrosis.
Unstable angina (UA) is a clinical syndrome within the acute coronary syndrome (ACS) spectrum, defined as anginal pain with at least one of the following features: (1) is of new onset and severe; (2) occurs at rest or with minimal exertion; (3) pain is worsening in severity and length of each episode (i.e. occurring in a crescendo pattern) [1]. Crucially, UA is distinguished from NSTEMI by the absence of elevated cardiac biomarkers (i.e. no evidence of myocardial necrosis) and from STEMI by the absence of persistent ST-segment elevation on ECG.
Let's break the name down:
- "Unstable" — the clinical situation is not fixed or predictable; there is a dynamic, evolving obstruction that may progress to complete occlusion and infarction at any moment.
- "Angina" — from Latin angere = "to strangle/choke"; chest pain or discomfort due to myocardial ischaemia.
So the name literally tells you: this is a strangling chest pain that is unpredictable and potentially worsening — a medical emergency because it sits on the knife-edge between stable coronary disease and full myocardial infarction.
Key Concept
UA, NSTEMI and STEMI form a continuum of the same underlying pathology — atherosclerotic plaque disruption with superimposed thrombosis. The difference lies in the degree and duration of coronary occlusion and whether myocardial necrosis has occurred. UA = ischaemia without necrosis; NSTEMI = partial occlusion with some necrosis; STEMI = complete occlusion with transmural necrosis [2][3].
Unstable angina and NSTEMI are classified together as NSTE-ACS because they are clinically indistinguishable at presentation — the only differentiator is the subsequent troponin result [2].
Epidemiology
- Ischaemic heart disease (IHD) remains the number one cause of death in men and women (27% of deaths) [4].
- Angina is most common in middle-aged and elderly men. Among persons 60–79 years of age, approximately 25% of men and 16% of women have coronary heart disease, rising to 37% and 23% among men and women > 80 years of age, respectively [4].
- The incidence of coronary heart disease and angina in women after menopause is similar to that of men [4] — this is because oestrogen is cardioprotective (promotes NO-mediated vasodilation, favourable lipid profile with ↑HDL); loss of oestrogen post-menopause removes this protection.
- The initial manifestation of IHD is angina pectoris in 50%, and about 50% of patients presenting to hospital with ACS have preceding angina [4].
- Within 12 months of initial diagnosis, 10–20% of patients with stable angina progress to MI or unstable angina [4].
- In Hong Kong, IHD is among the top 3 causes of death. The prevalence of coronary artery disease is rising due to an ageing population and increasing prevalence of metabolic risk factors (diabetes, obesity, hypertension). Hong Kong Chinese patients tend to present with more diffuse, small-vessel disease and have a higher prevalence of diabetes mellitus as a risk factor compared with Western populations.
An important modern note: with the advent of high-sensitivity cardiac troponin (hs-cTn) assays, many cases previously classified as UA are now reclassified as NSTEMI because even tiny amounts of myocardial necrosis are detected. This means the proportion of "true UA" (completely normal troponin) is shrinking in contemporary practice. However, UA remains a clinically important entity because it represents ischaemia at imminent risk of progression.
Risk Factors
These are essentially the risk factors for atherosclerotic cardiovascular disease (ASCVD), since the underlying pathology is coronary atherosclerosis with plaque instability.
| Risk Factor | Explanation |
|---|---|
| Advanced age | Cumulative endothelial damage and plaque burden over time |
| Male sex | Oestrogen in premenopausal women is protective (↑HDL, ↑NO, anti-inflammatory); men lack this advantage |
| Family history of premature CVD (male 1° relative < 55y, female 1° relative < 65y) | Genetic susceptibility to endothelial dysfunction, dyslipidaemia, thrombotic tendency |
| Previous vascular event (prior MI, stroke, PVD) | Indicates established atherosclerotic burden [2][5] |
| Risk Factor | Mechanism |
|---|---|
| Cigarette smoking | Endothelial injury → ↑oxidative stress → ↑LDL oxidation → accelerated atherogenesis; also ↑platelet aggregation and ↑fibrinogen → pro-thrombotic |
| Hypertension | Haemodynamic shear stress → endothelial damage → accelerated atherosclerosis; also promotes LV hypertrophy → ↑O₂ demand |
| Diabetes mellitus | Hyperglycaemia → advanced glycation end-products (AGEs) → endothelial dysfunction; also promotes dyslipidaemia (↑TG, ↓HDL, small dense LDL) and pro-thrombotic state |
| Dyslipidaemia (esp. ↑LDL-C, ↓HDL-C) | LDL penetrates damaged endothelium → oxidised → engulfed by macrophages → foam cells → fatty streak → plaque [6] |
| Abdominal obesity / metabolic syndrome | Central adiposity → insulin resistance → chronic inflammation, dyslipidaemia, pro-thrombotic state |
| Physical inactivity | Lack of exercise → ↓HDL, ↑insulin resistance, ↑BP, ↑weight |
| Diet (high saturated fat, low fruit/vegetable) | Directly contributes to dyslipidaemia and oxidative stress |
Predisposing factors for the acute transition from stable plaque to unstable plaque rupture and ACS include [7]:
- Unusual heavy exercise
- Emotional stress
- Progression from unstable angina
- Surgical procedures
- Infection e.g. pneumonia
- Circadian periodicity — peak incidence between 0600–1200 [7]
The circadian pattern is explained by the morning catecholamine surge (↑sympathetic tone on waking) → ↑heart rate, ↑blood pressure, ↑platelet aggregability, and ↑coronary vasomotor tone — all combining to increase the likelihood of plaque rupture and thrombosis.
Hong Kong-Specific Considerations
In Hong Kong, particular attention should be paid to:
- Very high prevalence of DM (>10% of the population), often as the predominant risk factor
- Smoking remains common especially in males
- Increasing obesity in younger populations
- Lower rates of familial hypercholesterolaemia awareness compared with Western populations [6]
Anatomy and Function: The Coronary Arterial System
Understanding UA requires understanding the coronary anatomy, because the location of the culprit lesion determines both the clinical presentation and risk.
The heart is supplied by two main coronary arteries arising from the aortic root (sinuses of Valsalva):
| Artery | Territory Supplied | Clinical Significance if Occluded |
|---|---|---|
| Left main coronary artery (LMCA) | Bifurcates into LAD and LCx | Occlusion = "widow maker" — supplies ~75–80% of LV; often fatal |
| Left anterior descending (LAD) | Anterior wall of LV, anterior 2/3 of interventricular septum, apex | Most commonly involved in ACS; anterior STEMI |
| Left circumflex (LCx) | Lateral wall of LV, +/- posterior wall (if left-dominant) | Lateral MI |
| Right coronary artery (RCA) | Inferior wall of LV, RV, SA node (60%), AV node (80–85%) | Inferior MI; may cause bradycardia/heart block due to SA/AV node ischaemia |
- Right-dominant (~85%): RCA gives rise to the posterior descending artery (PDA)
- Left-dominant (~8%): LCx gives rise to PDA
- Co-dominant (~7%): both contribute
- Coronary arteries are end-arteries (limited collateral circulation in most people) — so even partial occlusion can cause ischaemia
- They fill during diastole (the myocardium compresses intramural vessels during systole) — this is why tachycardia (↓diastolic time) worsens ischaemia
- They are subject to high pulsatile flow and bifurcation turbulence — predisposing to endothelial injury and atherosclerosis at branch points
Aetiology and Pathophysiology
The fundamental concept: UA is caused by an acute reduction in coronary blood flow that is not severe or prolonged enough to cause myocardial necrosis (that would be MI), but is severe enough to cause ischaemia at rest or with minimal exertion.
The cause is dynamic obstruction rather than the fixed stenosis of stable angina [2].
Mechanisms of Unstable Angina (listed in order of frequency)
This is the dominant mechanism and the reason UA exists:
Stable atherosclerotic plaque
↓
Plaque becomes "vulnerable" (thin fibrous cap, large lipid core,
inflammatory infiltrate with activated macrophages)
↓
Plaque rupture or endothelial erosion
↓
Exposure of subendothelial collagen and lipid core to blood
↓
Platelet adhesion → activation → aggregation
↓
Coagulation cascade activation → thrombin generation → fibrin deposition
↓
NON-OCCLUSIVE thrombus ("white thrombus", platelet-rich)
↓
Acute ↓ in coronary lumen → ↓ myocardial O₂ supply
↓
Ischaemia WITHOUT necrosis = UNSTABLE ANGINAWhy does the thrombus not occlude completely? In UA (as opposed to STEMI), the thrombus is typically:
- Platelet-rich ("white thrombus") rather than fibrin-rich ("red thrombus")
- Non-occlusive — it significantly narrows but does not completely block flow
- Dynamic — it may partially lyse and re-form, causing intermittent ischaemia
- Microemboli from the thrombus may travel distally, causing small areas of downstream ischaemia
Vulnerable Plaque – Why Some Plaques Rupture
Not all plaques are equal. The plaques most likely to rupture ("vulnerable plaques") have:
- Thin fibrous cap ( < 65 μm)
- Large lipid-rich necrotic core (> 40% of plaque volume)
- Abundant inflammatory cells (macrophages releasing matrix metalloproteinases [MMPs] that degrade collagen in the cap)
- Few smooth muscle cells (SMCs produce collagen to stabilise the cap; inflammation inhibits SMC function)
- Neovascularisation (fragile new vessels within the plaque → intraplaque haemorrhage)
Paradoxically, these vulnerable plaques often cause only mild-to-moderate stenosis (< 70%) on angiography — which is why patients with "insignificant" stenoses can still present with ACS. The degree of stenosis does NOT predict the risk of plaque rupture.
- Intense focal spasm of an epicardial coronary artery → transient complete or near-complete occlusion
- Can occur in arteries with or without significant underlying atherosclerosis
- Mechanism: endothelial dysfunction → ↓NO production → unopposed smooth muscle contraction; also involves ↑endothelin-1, ↑thromboxane A₂
- Classically occurs at rest, often early morning (correlating with circadian ↑vascular tone)
- Triggers: smoking, cocaine, cold exposure, hyperventilation, alkalosis
- ECG may show transient ST-elevation during vasospasm (not true STEMI because it reverses)
- Important in the Hong Kong/Asian population: coronary vasospasm is more prevalent in East Asian populations compared to Caucasians
- Gradual progression of atherosclerotic plaque (without acute rupture) to critical stenosis
- Or in-stent restenosis after previous PCI
- Does not involve acute thrombotic event — rather, the plaque slowly encroaches until ischaemia occurs at rest
- Angina precipitated by conditions that increase myocardial oxygen demand or decrease supply in the setting of pre-existing coronary stenosis
- Demand-side: fever, tachycardia, thyrotoxicosis, severe hypertension, aortic stenosis
- Supply-side: anaemia, hypoxaemia, hypotension
- Important to identify because treating the secondary cause may resolve the UA
- Systemic inflammation (e.g. during pneumonia, sepsis) can destabilise plaques through:
- ↑circulating cytokines (IL-6, TNF-α) → activate macrophages within plaque
- ↑acute phase reactants (CRP, fibrinogen) → pro-thrombotic state
- Endothelial activation → ↑tissue factor expression → thrombosis
At its core, angina (including UA) occurs when myocardial O₂ demand > supply [2][3]:
Myocardial O₂ Demand is determined by:
- Heart rate (most important — ↑HR = ↑demand)
- Contractility (↑inotropy = ↑demand)
- Wall tension/stress (= pressure × radius / wall thickness, by Laplace's law)
- ↑Afterload (HTN, AS) → ↑wall stress → ↑demand
- ↑Preload (volume overload) → ↑LV radius → ↑demand
Myocardial O₂ Supply is determined by:
- Coronary blood flow (affected by stenosis, vasospasm, diastolic time)
- Arterial O₂ content (affected by Hb level, SaO₂)
- O₂ extraction (myocardium already extracts ~75% of delivered O₂ at rest — very little reserve, so the only way to increase supply is to increase flow)
Why can't the heart just extract more oxygen? Unlike skeletal muscle, the myocardium has near-maximal O₂ extraction at baseline (~75% vs ~25% in skeletal muscle). Therefore, the myocardium is almost entirely dependent on increasing coronary blood flow to meet increased demand. This is why coronary stenosis is so dangerous.
Myocardial ischaemia → metabolite accumulation → stimulation of cardiac sympathetic nerves → pain [2][3]
The "ischaemic cascade" occurs in this order:
This is important because:
- ECG changes precede symptoms — a patient may have "silent ischaemia" with ST changes but no pain (common in diabetics due to autonomic neuropathy)
- Diastolic dysfunction is the earliest sign — this is why S4 gallop may be heard during ischaemia (stiff, non-compliant LV)
Classification
| Unstable Angina | NSTEMI | STEMI | |
|---|---|---|---|
| Pathology | Severe ischaemia at rest without infarction [2] | Partial occlusion of coronary arteries (usually due to critical narrowing) → some myocardial necrosis but not transmural [2] | Complete occlusion of coronary arteries (usually due to acute plaque disruption leading to complete thrombosis) → transmural myocardial necrosis [2] |
| Troponin | Normal | Elevated | Elevated |
| ECG | ST depression, T-wave inversion, or normal | ST depression, T-wave inversion, or normal | ST elevation or new LBBB |
| Thrombus type | Non-occlusive, platelet-rich ("white") | Non-occlusive or transiently occlusive | Occlusive, fibrin-rich ("red") |
2. Braunwald Classification of Unstable Angina
This is a classic and high-yield classification for risk stratification [1]:
| Class | Description |
|---|---|
| Class I | New-onset or progressive CCS Class III or IV angina in the past 2 weeks — but no rest pain [1] |
| Class II | Prolonged ( > 20 min) rest angina, now resolved, with moderate or high likelihood of CAD — rest angina in prior month but not in past 48 hours [1] |
| Class III | Prolonged ongoing ( > 20 min) rest pain — rest angina within past 48 hours [1] |
| Circumstance | Description |
|---|---|
| A — Secondary | Precipitated by an extracardiac condition (e.g. anaemia, fever, thyrotoxicosis, hypotension) |
| B — Primary | Develops in the absence of an extracardiac precipitant |
| C — Post-infarction | Develops within 2 weeks of documented MI (highest risk) |
| Description | |
|---|---|
| 1 | Absence of treatment or minimal treatment |
| 2 | Occurring despite standard anti-anginal therapy |
| 3 | Occurring despite maximal anti-anginal therapy (including IV nitroglycerin) |
| Feature | High Risk | Intermediate Risk | Low Risk |
|---|---|---|---|
| History | Accelerating tempo of ischaemic symptoms in preceding 48 hrs | Prior MI, peripheral or cerebrovascular disease, CABG, or prior aspirin use | |
| Character of Pain | Prolonged ongoing ( > 20 min) rest pain | Prolonged ( > 20 min) rest angina, now resolved, with moderate or high likelihood of CAD | New-onset or progressive CCS Class III or IV angina the past 2 weeks |
| Clinical Findings | Pulmonary oedema; new or worsening MR murmur; S3 or new/worsening rales; hypotension, bradycardia, tachycardia; age > 75 years | Age > 70 years | |
| ECG | Angina at rest with transient ST-segment changes > 0.05 mV; new or presumed new BBB; sustained ventricular tachycardia | T-wave inversions > 0.2 mV; pathological Q waves | Normal or unchanged ECG during an episode of chest discomfort |
| Cardiac Markers | Elevated (TnT or TnI > 0.1 ng/mL) | Slightly elevated (TnT > 0.01 but < 0.1 ng/mL) | Normal |
Exam Pearl
Note that by modern definition, if troponin is elevated (even slightly), the patient has NSTEMI — not UA. The Braunwald classification was developed before hs-cTn assays. In practice, the risk stratification framework remains clinically useful, but strictly speaking, "UA with elevated troponin" is now NSTEMI by the 4th Universal Definition of MI (2018).
This is used for grading the functional severity of angina and is referenced in the Braunwald classification:
| CCS Class | Description |
|---|---|
| I | Angina only with strenuous/rapid/prolonged exertion |
| II | Slight limitation of ordinary activity (e.g. walking > 2 blocks, climbing > 1 flight) |
| III | Marked limitation of ordinary activity (e.g. walking 1–2 blocks, climbing 1 flight) |
| IV | Inability to carry out any physical activity without angina; angina may be present at rest |
Clinical Features
Symptoms
The cardinal symptom of UA is chest pain/discomfort with features suggesting myocardial ischaemia, but with a pattern that is new, more severe, or occurring at rest.
- Typically dull, constricting, choking, 'heavy' [2][3]
- Described as squeezing, crushing, burning, aching or even as breathlessness [2][3]
- Patients often emphasise it is a discomfort, not a pain [2][3]
- Levine's sign: characteristic gesture of a clenched fist on chest when describing angina [2][3]
Pathophysiological basis: Myocardial ischaemia → accumulation of metabolites (adenosine, lactate, bradykinin, H⁺) → stimulation of cardiac sympathetic afferent nerve endings (unmyelinated C-fibres) → travel via cardiac sympathetic nerves → converge on the same dorsal horn neurons as somatic afferents from the chest wall, arm, and jaw → visceral-somatic convergence in the spinal cord → the brain "misinterprets" the visceral signal as coming from the somatic territory → this explains the dull, poorly localised, diffuse nature of cardiac pain (visceral pain is inherently poorly localised because the visceral nervous system has fewer afferent fibres and larger receptive fields).
ACS: typically takes minutes to develop, may occur at rest or with exertion [2][3]
The unstable pattern distinguishes UA from stable angina:
| Feature | Stable Angina | Unstable Angina |
|---|---|---|
| Onset | Predictable, with exertion | At rest, or with less exertion than before, or new-onset severe |
| Duration | < 5–10 min, relieved by rest/GTN | > 10–20 min, may not fully resolve with rest/GTN |
| Pattern | Reproducible, unchanging | Crescendo pattern — worsening in severity and length of each episode [1] |
| Frequency | Stable over weeks-months | Accelerating tempo of symptoms [1] |
Pathophysiological basis: In stable angina, there is a fixed stenosis — ischaemia only occurs when demand increases (exertion). In UA, the dynamic thrombus on a ruptured plaque causes variable degrees of obstruction — even at rest, blood flow may be insufficient. The crescendo pattern reflects progressive plaque instability or growing thrombus burden.
- Arms (especially left), shoulder, jaw, neck, back, epigastrium [2][3]
- Left arm radiation is "classic" but right arm, both arms, or jaw radiation can occur
Pathophysiological basis: Cardiac sympathetic afferents enter the spinal cord at T1–T5 levels. These segments also receive somatic afferents from the upper limbs (via brachial plexus — C5–T1), jaw (trigeminal nucleus connections), and shoulder. The convergence of cardiac visceral and somatic afferents at these spinal levels causes referred pain to these regions.
| Symptom | Pathophysiological Basis |
|---|---|
| Dyspnoea | Ischaemia → transient LV diastolic dysfunction (stiff, non-compliant LV) → ↑LV end-diastolic pressure → ↑pulmonary venous pressure → pulmonary congestion → breathlessness. May be an "angina equivalent" especially in elderly and diabetics |
| Diaphoresis (sweating) | Sympathetic nervous system activation in response to pain and haemodynamic stress → ↑catecholamines → generalised sympathetic discharge including activation of eccrine sweat glands |
| Nausea/vomiting | Vagal stimulation from inferior wall ischaemia (the inferior surface of the heart is richly supplied by vagal afferents); also a response to severe pain |
| Palpitations | Ischaemia-induced arrhythmias (ectopic beats, tachycardia) or sympathetic activation |
| Light-headedness / pre-syncope | ↓Cardiac output from ischaemia-induced LV dysfunction → ↓cerebral perfusion |
| Sense of impending doom | Massive sympatho-adrenal activation; also visceral afferent stimulation |
Some patients, particularly elderly, female, and diabetic patients, may present with "atypical" symptoms rather than classic chest pain:
- Exertional dyspnoea alone (most common equivalent)
- Epigastric pain (mimicking GERD or peptic ulcer disease)
- Fatigue or exercise intolerance
- Syncope or near-syncope
Why diabetics have atypical presentations: Diabetic autonomic neuropathy → damage to cardiac afferent nerves → impaired pain perception → "silent ischaemia." These patients may have ST changes on ECG without any pain.
Must-Know: Features That DIFFERENTIATE UA from Other Chest Pains
Anginal chest pain:
- Dull, constricting, "heavy" (not sharp/stabbing)
- Retrosternal with typical radiation
- Lasts minutes, not seconds (fleeting pain is rarely cardiac) and not hours (unrelenting pain > 20–30 min → think MI or non-cardiac)
- Provoked by exertion/emotion in stable angina; occurs at rest/crescendo in UA
- Relieved by rest and/or sublingual GTN within 5 minutes in stable angina; in UA, may not be fully relieved by GTN [2]
NOT anginal:
- Sharp, stabbing, knife-like → pleuritic (PE, pneumothorax, pericarditis)
- Tearing pain radiating to back → aortic dissection
- Retrosternal burning worse with meals/lying down → GERD
- Reproducible with palpation → musculoskeletal
- Fleeting (seconds) → usually non-cardiac
Signs (Physical Examination)
Physical examination may be normal in many UA patients — this is a key teaching point. A normal exam does NOT exclude UA [2][3].
However, examination is critical to:
- Identify haemodynamic compromise (suggesting extensive ischaemia)
- Identify precipitating/exacerbating conditions
- Look for evidence of underlying cardiovascular disease
- Exclude non-cardiac causes of chest pain
| Sign | Pathophysiological Basis |
|---|---|
| S4 gallop (atrial gallop) | Ischaemia → impaired LV relaxation (diastolic dysfunction) → atrium contracting against a stiff ventricle → audible S4. This is the most common auscultatory finding during active ischaemia |
| S3 or new/worsening rales [1] | Ischaemia → LV systolic dysfunction → ↑LV end-diastolic pressure → ↑pulmonary capillary wedge pressure → transudative fluid in alveoli → rales/crackles. S3 = rapid ventricular filling against a volume-overloaded ventricle. Indicates significant LV impairment — high risk |
| New or worsening MR murmur [1] | Ischaemia of papillary muscle (esp. posteromedial papillary muscle — single blood supply from PDA) → transient papillary muscle dysfunction → mitral leaflet fails to coapt → functional mitral regurgitation → pansystolic murmur at apex radiating to axilla. High risk sign |
| Hypotension [1] | Extensive ischaemia → ↓LV contractility → ↓cardiac output → ↓BP. Indicates cardiogenic shock physiology. High risk |
| Tachycardia [1] | Compensatory sympathetic activation due to ↓stroke volume; also a direct effect of catecholamine release from pain/anxiety. Worsens ischaemia by ↑O₂ demand and ↓diastolic filling time |
| Bradycardia [1] | Inferior wall ischaemia → enhanced vagal tone (Bezold-Jarisch reflex); or ischaemia of SA/AV node (supplied by RCA in 60%/85%). High risk |
| Pulmonary oedema [1] | Severe LV dysfunction from extensive ischaemia → flash pulmonary oedema. High risk — indicates large territory at jeopardy |
| Diaphoresis, pallor | Sympathetic activation → peripheral vasoconstriction (pallor) + eccrine sweating (diaphoresis) |
| Transient paradoxical splitting of S2 | Ischaemia → delayed LV ejection → delayed aortic valve closure → A2 falls after P2 |
| Sign | Significance |
|---|---|
| Evidence of VHD, especially AS, AR, HOCM [2] | These conditions themselves can cause angina by ↑O₂ demand (LVH in AS/HOCM) or ↓coronary perfusion pressure (↓diastolic BP in AR) |
| Risk factors: HTN, DM [2] | Hypertensive retinopathy, acanthosis nigricans (insulin resistance) |
| LV dysfunction: cardiomegaly, gallop rhythm [2] | Displaced apex beat (LV dilatation), S3/S4 |
| Other arterial diseases: carotid bruit, signs of PVD (presence of all peripheral pulses) [2] | Atherosclerosis is a systemic disease — presence of PVD or carotid disease significantly increases the pre-test probability of CAD |
| Conditions that may exacerbate angina: anaemia, thyrotoxicosis [2] | Pallor, tachycardia (anaemia); tremor, lid lag, goitre (thyrotoxicosis) — these are secondary causes of "demand ischaemia" |
| Xanthelasma, tendon xanthomata, arcus senilis (if < 50y) | Suggest familial hypercholesterolaemia → premature ASCVD [6] |
Clinical Pearl: The 'Silent' Examination
A completely normal physical examination in a patient with typical anginal chest pain does NOT reassure you — it is actually the norm. The diagnosis of UA is primarily clinical (history-driven) and confirmed with ECG and serial troponins. The examination is more about risk stratification (finding high-risk features like pulmonary oedema, new MR murmur, or hypotension) and excluding alternatives.
High Yield Summary
- Unstable angina (UA) = anginal chest pain that is new-onset and severe, occurs at rest, or is crescendo in pattern — WITHOUT troponin elevation (no myocardial necrosis)
- UA sits on the ACS spectrum between stable angina and NSTEMI/STEMI — same underlying pathology of atherosclerotic plaque disruption with non-occlusive thrombosis
- The key pathological difference: UA has a non-occlusive, platelet-rich "white" thrombus → ischaemia but no infarction
- Risk factors: modifiable (smoking, HTN, DM, dyslipidaemia, obesity, inactivity) and non-modifiable (age, male sex, family Hx, prior CVD)
- Precipitants: heavy exercise, emotional stress, surgery, infection, circadian peak 0600–1200
- Clinical features: dull/constricting retrosternal chest discomfort ± radiation to arms/jaw/neck, occurring at rest or with ↓threshold; associated dyspnoea, diaphoresis, nausea
- Examination may be normal — look for: S4 (diastolic dysfunction), S3/rales (systolic dysfunction), new MR murmur (papillary muscle ischaemia), hypotension, tachycardia → all indicate high risk
- Braunwald classification stratifies by severity (I–III), clinical context (A–C), and treatment context (1–3)
- With hs-cTn assays, many former "UA" cases are now reclassified as NSTEMI
- In Hong Kong: high prevalence of DM as major risk factor; coronary vasospasm more common in East Asians
Active Recall - Unstable Angina: Definition, Epidemiology, Pathophysiology and Clinical Features
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p15, p32) [2] Senior notes: Ryan Ho Cardiology.pdf (p54, p57, p58, p115, p126) [3] Senior notes: Ryan Ho Fundamentals.pdf (p199, p203) [4] Lecture slides: GC 032. Chest pain on exertion_ischaemic heart disease; angina pectoris.pdf (p9) [5] Senior notes: Ryan Ho Neurology.pdf (p75) — risk factors for atherosclerotic vascular disease [6] Senior notes: Ryan Ho Endocrine.pdf (p125, p131); Ryan Ho Chemical Path.pdf (p46, p48) — dyslipidaemia and FH [7] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p10)
Differential Diagnosis of Unstable Angina
When a patient presents with acute chest pain suspicious for UA, you are really asking: "Is this ACS, and if not, what life-threatening mimic must I not miss?" The clinical features of UA (rest pain, crescendo pattern, retrosternal discomfort) overlap substantially with many cardiac and non-cardiac conditions. A structured approach is essential because the consequences of missing a true ACS — or misdiagnosing aortic dissection as ACS and giving anticoagulation — can be fatal.
Diagnosis based on history alone may be difficult → generally divided into: typical (chest pain typical of a cardiac origin), atypical (cannot be attributed to a certain cause), and non-cardiac (typical of a non-cardiac cause) [2][3].
Before discussing the full differential, every clinician must first exclude these five emergencies that can present similarly to UA but require completely different management:
Main differentials of acute chest pain [2][3]:
| Potentially severe or life-threatening | Relatively benign causes |
|---|---|
| Acute coronary syndrome (ACS) | Episode of stable angina |
| Acute decompensated heart failure | GERD |
| Aortic dissection | Small pneumothorax |
| Acute pulmonary embolism | Musculoskeletal pain |
| Tension or massive pneumothorax | Panic attack |
| Pneumonia | |
| Myopericarditis ± cardiac tamponade |
The lecture slides provide an excellent framework organised by organ system [1]:
Differential diagnoses of acute coronary syndromes in the setting of acute chest pain [1]:
| Cardiac | Pulmonary | Vascular | Gastrointestinal | Orthopaedic | Other |
|---|---|---|---|---|---|
| Myopericarditis | Pulmonary embolism | Aortic dissection | Oesophagitis, reflux, or spasm | Musculoskeletal disorders | Anxiety disorders |
| Cardiomyopathies | (Tension)-pneumothorax | Symptomatic aortic aneurysm | Peptic ulcer, gastritis | Chest trauma | Herpes zoster |
| Tachyarrhythmias | Bronchitis, pneumonia | Stroke | Pancreatitis | Muscle injury/inflammation | Anaemia |
| Acute heart failure | Pleuritis | Cholecystitis | Costochondritis | ||
| Hypertensive emergencies | Cervical spine pathologies | ||||
| Aortic valve stenosis | |||||
| Takotsubo syndrome |
The lecture slides also show the frequency of diagnoses in patients presenting with acute chest pain [1]:
- Gastrointestinal 42%
- Ischaemic heart disease 31%
- Chest wall syndrome 28%
- Pericarditis 4%
- Pleuritis 2%
- Pulmonary embolism 2%
- Lung cancer 1.5%
- Aortic aneurysm 1%
- Aortic stenosis 1%
- Herpes zoster 1%
This is clinically important — GI causes are actually the most common cause of chest pain overall, though IHD is the most common serious cause. In exams, always think broadly.
Detailed Differential Diagnosis with Distinguishing Features
Let me walk through each differential systematically, explaining why each can mimic UA and how to distinguish them. This is essentially how you think on a ward round.
A. Cardiac Differentials
- Why it mimics UA: Identical clinical presentation. NSTEMI is characterised by clinical features of unstable angina in addition to elevated cardiac markers. Cardiac markers are elevated as a result of myocardial necrosis [1][5].
- How to distinguish: You cannot distinguish UA from NSTEMI at the bedside — the only differentiator is troponin. This is why serial troponins are mandatory.
- Key point: UA and NSTEMI are managed identically at presentation (both are NSTE-ACS). The distinction matters for risk stratification and prognosis (NSTEMI has higher short-term event rates).
- Why it mimics UA: Same pathophysiology (plaque rupture + thrombosis), but with complete coronary occlusion.
- How to distinguish: STEMI is characterised by clinical features of myocardial infarction in addition to ST-segment elevation on a 12-lead ECG [1][5]. Pain is usually more severe, prolonged ( > 30 min), unrelieved by GTN, with more prominent autonomic features. ECG shows persistent ST elevation (or new LBBB).
- Critical distinction: STEMI requires emergent reperfusion (primary PCI or thrombolysis); UA/NSTEMI does not require immediate reperfusion.
- Why it mimics UA: Central chest pain, may have ST changes on ECG.
- How to distinguish: Aggravated by respiratory movement, sharp, knife-like; radiates to the trapezius ridge (characteristic site of pericardial pain) [7]. Pain is typically positional (worse lying flat, better sitting forward). ECG shows diffuse concave ST elevation (not localised to a coronary territory), PR depression (pathognomonic), and no reciprocal ST depression (unlike STEMI). Troponin may be mildly elevated if myocarditis is present.
- Pathophysiology: Inflammation of pericardium → irritation of phrenic nerve (C3-5, which also supplies the trapezius ridge via the supraclavicular nerve) → explains the characteristic shoulder/trapezius pain.
Exam Trap
Pericarditis can cause troponin elevation (when there is associated myocarditis), and its ST elevation can mimic STEMI. Key distinguishing ECG features: pericarditis has diffuse concave-up ST elevation, PR depression, and no reciprocal changes. STEMI has localised convex-up ST elevation WITH reciprocal depression and often pathological Q waves.
- Why it mimics UA: Same quality of pain (dull, constricting, retrosternal).
- How to distinguish: Stable angina occurs only at exertion and is relieved by rest or nitrates within ≤5 min; lasts < 5–10 min [2][3]. The pattern is predictable and reproducible. UA by definition has new/changing/rest features.
- Clinical significance: An episode of stable angina is a relatively benign presentation that does not require emergency management, whereas UA is a medical emergency.
- Why it mimics UA: Severe AS causes angina due to increased myocardial O₂ demand (LVH) with relatively decreased subendocardial perfusion.
- How to distinguish: Angina in AS is typically exertional and accompanied by the classical triad of angina, syncope, and dyspnoea. On examination: ejection systolic murmur radiating to carotids, slow-rising pulse (pulsus parvus et tardus), narrow pulse pressure.
- Why it mimics UA: Presents with chest pain, ST elevation (can mimic STEMI), and troponin rise — triggered by emotional or physical stress.
- How to distinguish: Angiography shows no obstructive coronary disease; ventriculography/echo shows apical ballooning (the "tako-tsubo" = octopus pot shape). Predominantly affects post-menopausal women with preceding emotional stress. Mechanism: catecholamine surge → direct myocyte toxicity + microvascular spasm.
- These can all cause demand-type ischaemia in patients with underlying coronary stenosis (i.e. "Type 2 MI" or secondary UA). The key is identifying the primary precipitant — treating the arrhythmia, heart failure, or hypertension will resolve the ischaemia.
B. Vascular Differentials
- Why it mimics UA: Severe central chest pain; can cause coronary ostial occlusion → true STEMI.
- How to distinguish: Radiation to back, ripping or tearing sensation [7][8]. Pain is classically sudden onset, maximal at onset (unlike ACS which builds over minutes), severe ("worst pain of life"), and may radiate to the interscapular region. Look for: blood pressure differential between arms ( > 20 mmHg), aortic regurgitation murmur (proximal dissection tears aortic valve annulus), pulse deficit, widened mediastinum on CXR [8].
- Critical safety point: CXR can differentiate aortic dissection from pneumothorax; ECG can differentiate aortic dissection from AMI [8]. If you suspect dissection, do NOT give anticoagulation or thrombolysis — these will be catastrophic (worsening haemorrhage through the false lumen). CT angiography is the definitive investigation.
DANGER: Aortic Dissection Masquerading as ACS
Type A aortic dissection can occlude the right coronary ostium → inferior STEMI with ST elevation in II, III, aVF. If you treat this as a primary ACS and give antiplatelets + anticoagulation + PCI, the patient may die from uncontrolled haemorrhage. Always consider dissection in any patient with acute chest pain, especially if the pain is sudden-onset, tearing, radiating to the back, or associated with a pulse/BP differential.
- Why it mimics UA: Central chest pain, dyspnoea, haemodynamic compromise, ECG changes (ST/T changes can look like NSTE-ACS).
- How to distinguish: Hemoptysis [7]; pleuritic chest pain (sharp, worse with inspiration) — unlike angina which is dull and not respiratory-phase-dependent. Risk factors for VTE (immobilisation, recent surgery, DVT, OCP use, malignancy). ECG: sinus tachycardia, S1Q3T3, right heart strain pattern [9]. CXR may show wedge-shaped opacity (Hampton's hump), oligaemia (Westermark sign). D-dimer elevated. CT pulmonary angiography (CTPA) is diagnostic.
- Pathophysiology of chest pain in PE: (a) Pleuritic pain from pulmonary infarction irritating pleura; (b) RV strain → RV ischaemia → central crushing pain (in massive PE, mimicking ACS).
ECG Pitfall
PE is a cause of false-positive ST elevation on ECG [10]. The right heart strain pattern (T-wave inversions V1-V4, S1Q3T3, new RBBB) can be confused with anterior ischaemia. Clinical context and risk factor assessment are key.
C. Pulmonary Differentials
- Why it mimics UA: Acute chest pain, dyspnoea.
- How to distinguish: Sudden onset, maximal at onset (unlike ACS which builds gradually) [2][3]. Pain is pleuritic (sharp, worse with breathing). Examination: absent breath sounds, hyperresonant percussion on affected side, tracheal deviation (away from affected side in tension PTX). CXR is diagnostic. Tension PTX is a clinical diagnosis requiring immediate needle decompression.
- Why it mimics UA: Chest pain (pleuritic), dyspnoea.
- How to distinguish: Fever, productive cough, crackles on auscultation. Pain is pleuritic (sharp, breathing-related) — completely different quality from anginal pain. CXR shows consolidation.
D. Gastrointestinal Differentials
- Why it mimics UA: This is one of the most common mimics. Gastrointestinal causes account for 42% of acute chest pain presentations [1]. Oesophageal pain can be retrosternal, burning or constricting, and may even respond to nitrates (because GTN also relaxes oesophageal smooth muscle!).
- How to distinguish: Pain related to meals (postprandial, worse lying down), associated with dysphagia, acid taste, waterbrash. Relieved by antacids/PPIs. Not provoked by exertion. ECG normal.
- Pathophysiology of overlap: The oesophagus and heart share the same visceral afferent innervation (vagus nerve + T1-T5 sympathetic) → referred pain to the same region → indistinguishable by location alone.
Clinical Pearl
"Response to GTN" does NOT confirm cardiac origin — GTN is a smooth muscle relaxant that also relieves oesophageal spasm. Similarly, "response to antacids" does not conclusively exclude ACS (both can coexist). The ECG and troponin are the arbiters.
- Epigastric pain can radiate to the chest. Pancreatitis can cause severe epigastric pain radiating to the back. Cholecystitis can cause referred pain to the right shoulder (phrenic nerve → C3-5).
- Distinguished by abdominal tenderness, raised amylase/lipase, abnormal LFTs, and abdominal imaging.
E. Musculoskeletal Differentials
- Why it mimics UA: Chest wall pain, retrosternal location.
- How to distinguish: Pain is reproducible with palpation (press on the costochondral junction → exact same pain reproduced). Typically sharp, positional, related to movement. Not associated with exertion per se (though may occur after physical activity involving the chest wall). ECG normal, troponin normal.
- Chest wall syndrome accounts for 28% of chest pain presentations [1].
- Radiculopathy from C5-T1 can mimic arm/shoulder radiation of angina. Distinguished by dermatome distribution, provocation by neck movement, and Spurling's test.
F. Other Differentials
- Why it mimics UA: Chest pain, palpitations, dyspnoea, diaphoresis, sense of doom — virtually identical to ACS symptomatically. Panic disorder has been historically known as "irritable heart" and "Da Costa's syndrome" [11] — highlighting how closely it mimics cardiac disease.
- How to distinguish: Symptoms peak within minutes and resolve. Associated with paraesthesias (hyperventilation → respiratory alkalosis → ↓ionised Ca²⁺), derealization, fear of dying. ECG and troponin are normal. Importantly, panic disorder is a diagnosis of exclusion in the acute setting — always rule out ACS first in patients with cardiac risk factors.
- Thoracic dermatomal pain before the rash appears can mimic cardiac pain. Once the vesicular rash appears in a dermatomal distribution, diagnosis is straightforward.
- Severe anaemia can precipitate "secondary" or "demand" UA in patients with pre-existing coronary stenosis. The reduced O₂-carrying capacity (↓Hb → ↓CaO₂) shifts the supply-demand balance toward ischaemia. Identifying and treating the anaemia is the priority.
Key teaching point: The algorithm emphasises that ECG should be performed within 10 minutes of first medical contact — this is the single most important first step. It immediately separates STEMI (which needs emergent reperfusion) from everything else.
The lecture slides present the diagnostic pathway clearly [6]:
Working suspicion of ACS on admission → ECG → Biochemistry → Risk stratification → Diagnosis [6]:
| Finding | Persistent ST elevation | ST/T abnormalities | Normal/undetermined ECG |
|---|---|---|---|
| Troponin | Positive | Positive | 2× Negative |
| Risk | — | High risk | Low risk |
| Diagnosis | STEMI | NSTEMI | Unstable Angina |
This is highly examinable. The lecture slides explicitly list conditions that cause false positive and false negative ST changes:
False positives (conditions that mimic STEMI on ECG) [10]:
- Benign early repolarisation
- LBBB
- Pre-excitation (WPW)
- Brugada syndrome
- Peri-/myocarditis
- Pulmonary embolism
- Subarachnoid haemorrhage
- Metabolic disturbances such as hyperkalaemia
- Failure to recognise normal limits for J-point displacement
- Lead transposition or use of modified leads configuration
- Cholecystitis
False negatives (conditions where MI is present but ECG may miss it) [10]:
- Prior Q waves and/or persistent ST-elevation
- Paced rhythm
- LBBB
Why LBBB appears on both lists
LBBB causes abnormal depolarisation of the LV → secondary ST-T changes that mimic ischaemia (false positive). But new LBBB in the context of ACS may itself indicate acute MI. Furthermore, pre-existing LBBB makes it impossible to detect new ischaemic changes (false negative). This is why new LBBB is treated as STEMI-equivalent until proven otherwise. The Sgarbossa criteria help distinguish true MI from LBBB-related changes [4].
| Condition | Quality of Pain | Onset | Duration | Radiation | Key Distinguishing Feature |
|---|---|---|---|---|---|
| UA / NSTEMI | Dull, constricting, heavy | Minutes, at rest or crescendo | > 20 min, may wax/wane | Arms, jaw, neck | ECG ± ST depression/T inversion; troponin differentiates UA vs NSTEMI |
| STEMI | Crushing, severe | Minutes, often at rest | > 30 min, unrelenting | Arms, jaw, neck | Persistent ST elevation; elevated troponin |
| Aortic dissection | Tearing, ripping [7] | Sudden, maximal at onset | Hours | Back, interscapular [7] | BP differential, pulse deficit, widened mediastinum |
| PE | Pleuritic or crushing (massive) | Sudden | Variable | — | Hemoptysis [7], pleuritic, VTE risk factors, S1Q3T3 |
| Pericarditis | Sharp, knife-like [7] | Hours | Hours-days | Trapezius ridge [7] | Positional (better sitting forward), pericardial rub, diffuse ST elevation |
| Pneumothorax | Sharp, pleuritic | Sudden | Persistent | Ipsilateral shoulder | Absent breath sounds, hyperresonance |
| GERD / oesophageal spasm | Burning / constricting | Postprandial | Minutes-hours | — | Meal-related, relieved by antacids, dysphagia |
| Musculoskeletal | Sharp, localised | Variable | Variable | — | Reproducible with palpation |
| Panic attack | Variable | Sudden peaks in minutes | 10-30 min | — | Hyperventilation, paraesthesias, derealization |
High Yield Summary
- The differential of UA is essentially the differential of acute chest pain — think systematically across cardiac, vascular, pulmonary, GI, musculoskeletal, and psychiatric causes.
- Five life-threatening mimics not to miss: STEMI, aortic dissection, PE, tension pneumothorax, cardiac tamponade.
- UA vs NSTEMI: clinically indistinguishable — only troponin differentiates them.
- Aortic dissection is the most dangerous mimic — sudden-onset, tearing, radiating to back, BP differential. NEVER anticoagulate before excluding it.
- GERD is the most common overall cause of chest pain (42%); it can even respond to GTN — do not assume GTN response = cardiac.
- ECG pitfalls: Know the causes of false-positive ST elevation (early repolarisation, LBBB, pericarditis, PE, SAH, hyperkalaemia, Brugada) and false negatives (paced rhythm, LBBB, prior Q waves).
- Panic disorder closely mimics ACS — but is always a diagnosis of exclusion in the acute setting.
Active Recall - Differential Diagnosis of Unstable Angina
References
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p15, p16, p17) [2] Senior notes: Ryan Ho Cardiology.pdf (p54, p55, p57, p58) [3] Senior notes: Ryan Ho Fundamentals.pdf (p199, p200, p202, p203) [4] Senior notes: Ryan Ho Cardiology.pdf (p128, p129) [5] Senior notes: Ryan Ho Cardiology.pdf (p115, p126) [6] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p57) [7] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p13) [8] Senior notes: felixlai.md (p1328) [9] Senior notes: Ryan Ho Respiratory.pdf (p135); Ryan Ho Haemtology.pdf (p131) [10] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p30) [11] Senior notes: Ryan Ho Psychiatry.pdf (p178)
Diagnostic Criteria for Unstable Angina
Unlike NSTEMI or STEMI, unstable angina has no single definitive biomarker or imaging finding that confirms it. Instead, the diagnosis is reached by demonstrating:
- A clinical presentation consistent with ACS (typical anginal symptoms with unstable features)
- No persistent ST elevation on ECG (which would make it STEMI)
- No elevation of cardiac troponin on serial sampling (which would make it NSTEMI)
In other words, UA is what remains after you have excluded STEMI (by ECG) and NSTEMI (by troponin). Think of it as ACS with ischaemia but without necrosis.
Formal Diagnostic Criteria
Unstable angina is defined as anginal pain with at least one of the following features [1]:
- Is of new onset and severe
- Occurs at rest or with minimal exertion
- Pain is worsening in the severity and length of each episode (i.e. occurring in a crescendo pattern) [1]
More specifically, the ACS clinical presentation includes [4]:
- Angina at rest: prolonged > 20 min angina at rest
- New-onset angina: at least CCS Class II
- Increasing angina: previous angina with ↑frequency, ↑duration, or ↓threshold to ≥CCS III severity
- Post-infarct angina: recurrent angina after recent MI
NSTE-ACS ECG features [4]:
- ST depression
- T wave changes
- ± some loss of R waves (if infarcted)
For UA specifically, the ECG may show any of the above or may be entirely normal. The ECG distinguishes UA from STEMI (persistent ST elevation or new LBBB = STEMI) but cannot distinguish UA from NSTEMI on its own.
Cardiac markers: Normal in UA [1][12].
This is the single defining laboratory feature. The 4th Universal Definition of Myocardial Infarction (2018) requires a rise and/or fall of cardiac troponin (cTn) with at least one value above the 99th percentile of the upper reference limit (URL) to diagnose MI [13]. If troponin remains normal on serial testing, the patient has UA rather than NSTEMI.
On the diagnostic pathway: working suspicion of ACS → ECG → Biochemistry (troponin) → Risk stratification → Diagnosis [12]:
- Persistent ST elevation → STEMI
- ST/T abnormalities + Troponin positive → NSTEMI
- Normal or undetermined ECG + Troponin 2× negative → Unstable Angina [12]
The Shrinking Diagnosis
With high-sensitivity cardiac troponin (hs-cTn) assays now standard, very small amounts of myocardial necrosis are detectable. Many patients formerly classified as "UA" are now reclassified as NSTEMI because their hs-cTn crosses the 99th percentile URL. The ESC 2023 NSTE-ACS guidelines now emphasise that true UA (genuinely negative hs-cTn on serial testing) has become uncommon. However, it still exists and remains a valid diagnosis — particularly relevant for patients with very brief episodes of ischaemia that self-terminate before necrosis occurs.
Understanding the MI definition helps you understand precisely where UA sits:
| Type | Description | Criteria |
|---|---|---|
| Type 1 | Spontaneous MI due to primary coronary event, e.g. plaque erosion/rupture | Detection of ↑/↓ cardiac biomarker values (preferably cTn) with ≥1 value above 99th URL; plus ≥1 of: (1) Symptoms of ischaemia; (2) New or presumed new significant ST-T changes or new LBBB; (3) Development of pathological Q waves; (4) Imaging evidence of new loss of viable myocardium or new RWMA; (5) Identification of intracoronary thrombus by angiography or post-mortem [13] |
| Type 2 | MI secondary to ischaemia due to imbalance between O₂ demand and supply, e.g. coronary spasm, anaemia, hypotension | Same biomarker criteria as Type 1 [13] |
| Type 3 | Sudden cardiac death | Symptoms of ischaemia + new ischaemic ECG changes or LBBB; but death before biomarkers obtained [13] |
| Type 4a | MI associated with PCI | ↑cTn > 5× 99th URL [13] |
| Type 4b | MI associated with stent thrombosis | Verified stent thrombosis + biomarker rise [13] |
| Type 5 | MI associated with CABG | ↑cTn > 10× 99th URL [13] |
UA is essentially "Type 1 MI pathophysiology WITHOUT meeting the biomarker threshold." The plaque has ruptured, the thrombus has formed, ischaemia has occurred — but it was transient enough that myocardial cell death did not reach the detection threshold of troponin assays.
Overview of the Pathway
The clinical spectrum of ACS ranges from oligo/asymptomatic → increasing chest pain/symptoms → persistent chest pain/symptoms → cardiogenic shock/acute heart failure → cardiac arrest [14]. The diagnostic workup follows a structured sequence:
Investigation Modalities — Detailed
1. Electrocardiography (12-Lead ECG)
The single most important first-line investigation. Must be performed within 10 minutes of first medical contact (ESC 2023 recommendation).
- It is fast, cheap, universally available, non-invasive
- It immediately separates STEMI (needs emergent reperfusion) from NSTE-ACS (different pathway)
- Serial ECGs detect dynamic changes that evolving ischaemia/infarction produce
| Finding | Description | Pathophysiological Basis |
|---|---|---|
| ST depression | Horizontal or downsloping ST depression ≥0.5 mm in ≥2 contiguous leads | Subendocardial ischaemia: the subendocardium is the most vulnerable zone (furthest from epicardial coronary supply, highest wall stress). Ischaemia causes delayed repolarisation of this region → net vector of repolarisation directed away from the electrode → ST depression |
| T-wave inversion | Symmetrical T-wave inversion ≥1 mm in ≥2 contiguous leads | Altered repolarisation sequence due to ischaemia — normally repolarisation proceeds from epicardium to endocardium; ischaemia reverses this → inverted T wave |
| T-wave inversions > 0.2 mV; pathological Q waves [1] | Deep T-wave inversion or Q waves | Intermediate risk in Braunwald classification [1] — suggests significant ischaemia or prior infarction |
| Angina at rest with transient ST-segment changes > 0.05 mV; new or presumed new BBB; sustained ventricular tachycardia [1] | Dynamic ST changes, new BBB, sustained VT | High risk in Braunwald classification [1] |
| Normal or unchanged ECG during an episode of chest discomfort [1] | No ischaemic changes during pain | Low risk in Braunwald classification [1] — but does NOT exclude UA |
Wellens syndrome: deeply inverted or biphasic T waves in V2-3 → highly specific for critical LAD stenosis → extremely high risk for extensive anterior wall MI in subsequent days/weeks [4]. This is a pattern you may see in UA patients between episodes — the ECG looks deceptively "non-urgent" but represents a ticking time bomb.
ST elevation in aVR with diffuse ST depression: usually indicates left main stem occlusion [4]. This is the highest-risk pattern in NSTE-ACS and demands urgent invasive strategy.
Pseudonormalization of T wave: transient normalization of T wave from an inverted form → indicates transient recanalization of coronary artery [4]. If you see previously inverted T waves suddenly become upright during chest pain, this paradoxically indicates active ischaemia — the coronary artery has briefly opened then re-occluded.
12-lead ECG stat and repeat at least daily ×3d (more frequently in severe cases) [2][3]. The rationale for serial ECGs is that ischaemia is dynamic in UA — the first ECG may be normal, but subsequent ECGs during recurrent symptoms may capture diagnostic changes.
Must-Know: Normal ECG Does NOT Exclude UA
A single normal ECG has a sensitivity of only ~50% for ACS. Up to 6% of patients with a normal initial ECG will have NSTEMI/UA. This is why serial ECGs and serial troponins are mandatory. If the clinical suspicion is high, a normal ECG simply means "not STEMI right now" — it does NOT mean "not ACS."
2. Cardiac Biomarkers
This is the gold standard biomarker for differentiating UA from NSTEMI.
What is troponin? Troponin is a regulatory protein complex in cardiac muscle involved in calcium-mediated contraction. It has three subunits:
- Troponin C (TnC) — binds calcium
- Troponin I (TnI) — inhibits actin-myosin interaction
- Troponin T (TnT) — anchors complex to tropomyosin
Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) have cardiac-specific isoforms not found in skeletal muscle. When cardiomyocytes undergo necrosis (irreversible cell death), the cell membrane loses integrity → intracellular troponin leaks into the bloodstream → detectable by assay.
Why "high-sensitivity"? Modern hs-cTn assays can detect concentrations ~10–100× lower than conventional assays. This means:
- Earlier detection (troponin rises within 1–3 hours of necrosis onset with hs-cTn vs 4–6 hours with conventional assays)
- Detection of very small amounts of necrosis (reclassifying many former "UA" as NSTEMI)
The rapid rule-in/rule-out algorithm is now standard:
| Timing | Interpretation |
|---|---|
| 0h sample | Baseline hs-cTn at presentation |
| 1h sample (preferred) or 2h sample | Look for absolute change (delta) from baseline |
| Rule-out | Very low 0h value AND no significant rise at 1h → ACS very unlikely (NPV > 99%) |
| Rule-in | High 0h value OR significant rise at 1h → NSTEMI confirmed |
| Observe zone | Neither rule-in nor rule-out → repeat at 3h, continue clinical observation |
For UA: Both 0h and serial troponins remain below the 99th percentile URL with no significant delta. Cardiac markers: Normal [1].
Cardiac enzymes daily ×3d (repeat troponin 6–12h later if 1st Tn is normal) [2][3]. While the 0h/1h algorithm is now preferred for rapid triage, the principle of serial testing remains — you must demonstrate the absence of a rise-and-fall pattern before confidently labelling a patient as UA.
| Biomarker | Rise Time | Peak | Duration | Notes |
|---|---|---|---|---|
| hs-cTnT / hs-cTnI | 1–3h | 12–24h | 7–14 days | Gold standard; most sensitive and specific |
| CK-MB | 3–6h | 12–24h | 2–3 days | Used to detect re-infarction (short half-life allows detection of new rise) |
| Myoglobin | 1–2h | 6–8h | 12–24h | Very early but non-specific (also rises with skeletal muscle injury). Largely obsolete now |
| BNP / NT-proBNP | — | — | — | Not for diagnosis of MI; elevated in heart failure. Used for prognosis in ACS — ↑BNP correlates with ↑LV filling pressure and ↑mortality |
Cardiac enzymes: cTnT, cTnI, CK-MB [8].
Key Principle
In UA, all troponin values remain below the 99th percentile URL. If even a single value crosses this threshold with a rise-and-fall pattern, the diagnosis is reclassified to NSTEMI. The troponin is the diagnostic arbiter.
Basic bloods: CBC, L/RFT, lipid profile (≤24h), aPTT/INR (as baseline for heparin) [2][3].
| Test | Rationale | Key Findings |
|---|---|---|
| CBC | Identify anaemia (secondary cause of demand ischaemia); leukocytosis (infection/inflammation as precipitant); thrombocytopenia (affects antiplatelet/anticoagulant choices) | ↓Hb → demand ischaemia; ↑WCC → infection trigger |
| Renal function (U/Cr, eGFR) | Baseline for contrast use in angiography; renal impairment affects drug dosing (especially LMWH, P2Y12 inhibitors); CKD is an independent adverse prognostic factor | ↑Cr → dose-adjust renally cleared drugs |
| Liver function | Baseline for statin therapy; hepatic congestion (↑ALT/AST) may indicate right heart failure | ↑Transaminases → consider hepatic congestion or shock liver |
| Fasting glucose / HbA1c | Screen for DM (major risk factor); hyperglycaemia at presentation is an independent adverse prognostic marker even in non-diabetics | ↑Glucose → worse prognosis in ACS |
| Fasting lipid profile | Identify dyslipidaemia as modifiable risk factor; guide statin intensity. Best measured within 24h (lipids fall acutely after MI due to acute phase response) | ↑LDL-C → aggressive lipid-lowering target |
| aPTT / INR | Baseline before initiating anticoagulation (heparin); identify pre-existing coagulopathy | Abnormal → adjust anticoagulant dosing |
| TFT | Thyrotoxicosis as precipitant of demand ischaemia | ↓TSH → treat thyrotoxicosis |
CXR: usually non-diagnostic in ACS, look for other causes (e.g. aortic dissection, PE, pneumonia or pneumothorax) [2][3].
| Finding | Significance |
|---|---|
| Normal | Does NOT exclude ACS; expected in most UA cases |
| Pulmonary oedema (bilateral alveolar infiltrates, upper lobe diversion, Kerley B lines, peribronchial cuffing) | Suggests significant LV dysfunction from extensive ischaemia → high risk |
| Cardiomegaly (CTR > 0.5) | Pre-existing cardiomyopathy or chronic heart failure |
| Widened mediastinum | Raises suspicion for aortic dissection — STOP anticoagulation, arrange urgent CT aortography [8] |
| Pneumothorax | Alternative diagnosis |
| Consolidation | Pneumonia — may be a precipitant of secondary UA |
Routine baseline echocardiography is recommended by ESC to evaluate for (1) regional wall motion abnormalities (2) LVEF → important prognostic parameter (3) other structural cardiac conditions [5][3].
| Finding | Interpretation |
|---|---|
| Regional wall motion abnormality (RWMA) | Hypokinesis/akinesis in a coronary territory → evidence of ischaemia or prior infarction; helps localise the culprit lesion. Important caveat: RWMA may be absent between ischaemic episodes in UA |
| LVEF | Strongest predictor of long-term survival; LVEF < 50% associated with ↑↑ event risk regardless of severity of ischaemia [5]. Guides need for ACEI/ARB, beta-blocker, and consideration for ICD |
| Valvular disease | May identify AS, MR (new ischaemic MR from papillary dysfunction), or HOCM as the cause of angina |
| Pericardial effusion | Raises suspicion for pericarditis (alternative dx) or aortic dissection with haemopericardium |
| RV dilatation / dysfunction | Consider PE or RV infarction |
Timing: Bedside echocardiography should be performed urgently in haemodynamically unstable patients to identify mechanical complications or alternative diagnoses (e.g. tamponade, massive PE, aortic dissection). In stable UA patients, it can be performed within the admission.
6. Risk Stratification Scores
Risk stratification is integral to the diagnostic workup because it determines the urgency and strategy of further investigation and treatment.
The ESC-recommended tool for risk assessment. Variables include [15]:
| Variable | Points Basis |
|---|---|
| Age | Increasing points with age |
| Resting heart rate | Higher HR = more points |
| Systolic blood pressure | Lower BP = more points |
| Initial serum creatinine | Higher creatinine = more points |
| Killip class (degree of heart failure) | Higher class = more points |
| Cardiac arrest at presentation | Yes = high points |
| ST-segment deviation | Yes = more points |
| Elevated cardiac biomarkers | Yes = more points |
| History of CHF | Yes = more points |
| History of MI | Yes = more points |
| No in-hospital PCI | Yes = more points |
The GRACE score predicts 6-month post-discharge all-cause mortality and guides the invasive strategy [15]:
| GRACE Score | Risk | Strategy |
|---|---|---|
| > 140 | High risk | Early/inpatient invasive strategy [15] |
| 109–140 | Intermediate risk | Invasive strategy within 72h |
| < 109 | Low risk | Non-invasive testing or selective invasive |
Already covered in the previous section — stratifies UA into high, intermediate, and low risk based on history, character of pain, clinical findings, ECG, and cardiac markers [1].
Immediate transfer/invasive strategy ( < 2h) — "Very high risk":
- Haemodynamic instability or cardiogenic shock
- Acute heart failure presumed secondary to ongoing myocardial ischaemia
- Life-threatening arrhythmias or cardiac arrest after presentation
- Mechanical complications
- Recurrent dynamic ECG changes suggestive of ischaemia
Early/inpatient invasive strategy ( < 24h) — "High risk" [15]:
- Elevated cardiac biomarkers
- Confirmed diagnosis of NSTEMI based on ESC algorithms
- GRACE risk score > 140
- Transient ST-segment elevation
- Dynamic ST-segment or T wave changes
Low risk — "In patients without very-high or high-risk features and a low index of suspicion for unstable angina" [15]: non-invasive assessment first.
This is the definitive anatomical test that visualises the coronary arteries and identifies the culprit lesion.
Principle: A catheter is advanced (usually via radial or femoral artery) to the coronary ostia, and radiopaque contrast is injected while fluoroscopic X-ray images are captured → real-time visualisation of coronary lumen.
| When to Perform | Rationale |
|---|---|
| Very high risk NSTE-ACS | Immediate ( < 2h) — to identify and treat culprit lesion emergently |
| High risk NSTE-ACS | Early ( < 24h) |
| Intermediate risk | Within 72h |
| UA with low risk features | May not need angiography acutely; can undergo non-invasive testing first and proceed to ICA if positive |
Key Findings:
- Culprit lesion — ruptured plaque with thrombus, typically appearing as a "hazy" filling defect or eccentric stenosis
- Degree of stenosis — significant = ≥70% (≥50% for left main)
- Number of vessels — mortality of 1VD < 2VD < 3VD < LMS disease [5]
Coronary angiography findings may include ambiguous/hazy lesion, calcification, tortuosity/eccentricity — in such cases, intravascular imaging (IVUS or OCT) is used for further characterisation [16]:
- IVUS or OCT imaging findings can distinguish erosion, nodule, and rupture [16] — this is important because the underlying plaque pathology may influence management.
8. Non-Invasive Testing (For Stable / Low-Risk Patients After Acute Phase)
For patients diagnosed with UA who are stabilised and at low-to-intermediate risk, non-invasive functional or anatomical testing may be used to evaluate the extent of ischaemia and guide further management:
Positive test defined as horizontal or downsloping ST depression of ≥0.1 mV (1 mm) 80 ms after J point during exercise [5].
| Useful For | Not Useful For |
|---|---|
| Low-intermediate PTP (15–65%); normal baseline ECG; not on anti-ischaemic drugs [5] | Abnormal baseline ECG (LBBB, paced rhythm, WPW, AF, LVH, digoxin); limited exercise tolerance due to non-cardiac disease [5] |
Why these limitations? Pre-existing ST-T changes (from LBBB, LVH, digoxin) will obscure exercise-induced ischaemic changes → uninterpretable results. If the patient cannot reach 85% of maximum predicted heart rate (220 − age), the test is inadequate (insufficient stress to provoke ischaemia).
Myocardial perfusion imaging (MPI) uses the coronary steal phenomenon [17]:
- At rest, partial coronary stenosis limits blood flow but remains substantial due to collaterals and ischaemia-induced vasodilation
- With stress, vessels supplying normal myocardium also dilate → blood siphoned to normal myocardium ('steal') → ↓↓ perfusion of affected myocardium → appears as 'cold spots' [17]
Interpretation [17]:
- Normal → homogenous perfusion
- Ischaemia → cold spots when under stress (but normal at rest)
- Infarct → cold spots when at rest + under stress
| Modality | Advantages | Limitations |
|---|---|---|
| Stress echocardiography | No radiation; evaluates wall motion + valves; relatively inexpensive | Operator-dependent; limited by body habitus |
| SPECT MPI | High sensitivity; well-validated | Radiation; attenuation artefacts; limited spatial resolution |
| Cardiac MRI | Excellent spatial resolution; no radiation; can assess viability | Contraindicated with certain implants; expensive; longer acquisition |
| PET | Best for viability assessment; less attenuation artefact than SPECT | Expensive; limited availability |
High risk on stress imaging = area of ischaemia > 10% [5].
Useful for low-intermediate PTP (15–50%); excellent NPV (99–100%) [5].
Significant stenosis = ≥70% stenosis on CTCA [5].
Agaston calcium score > 100 generally correlated with significant risk of CAD [5]; ↑Ca score associated with ↓specificity of CTA → NOT interpret CTA with Agaston > 400 [5].
For UA patients: CTCA may be used in the low-risk group after the acute phase to rule out significant CAD non-invasively. If negative (no significant stenosis), the patient can be safely discharged with outpatient follow-up.
| Phase | Investigation | Purpose | Key Finding in UA |
|---|---|---|---|
| Immediate (< 10 min) | 12-lead ECG | Exclude STEMI; detect ischaemic changes | ST depression, T-wave inversion, or normal |
| Immediate | Bloods: hs-cTn (0h), CBC, RFT, glucose, lipids, coagulation | Exclude NSTEMI; identify precipitants; baseline for treatment | Troponin normal at 0h |
| 1–3h | Serial hs-cTn (1h or 2h recheck) | Confirm absence of troponin rise | Troponin remains normal, no delta |
| Within admission | CXR | Exclude other causes; assess for pulmonary oedema | Usually normal in UA |
| Within admission | Echocardiography | LVEF (prognosis); RWMA; structural disease | May be normal or show transient RWMA during ischaemia |
| Risk-dependent | GRACE score / Braunwald classification | Determine timing of invasive strategy | Guides urgency |
| If high risk | Invasive coronary angiography | Identify culprit lesion; plan revascularisation | Culprit plaque with non-occlusive thrombus; degree and number of vessels |
| If low risk / post-stabilisation | Non-invasive stress test or CTCA | Assess extent of ischaemia / anatomy | Inducible ischaemia or significant stenosis → proceed to ICA |
High Yield Summary
- UA is a clinical diagnosis = typical ACS presentation + no persistent ST elevation + serial troponins normal
- ECG within 10 minutes of presentation → separates STEMI from NSTE-ACS
- Serial hs-cTn (0h and 1h or 0h and 2h) → separates NSTEMI from UA. Rule-out requires low baseline AND no significant delta
- The 4th Universal Definition of MI requires troponin above 99th percentile URL with rise/fall pattern → UA does not meet this threshold
- GRACE score is the ESC-recommended tool for risk stratification → determines timing of invasive strategy
- Very high risk features (shock, acute HF, life-threatening arrhythmias, mechanical complications, recurrent dynamic ECG changes) → immediate invasive strategy < 2h
- Know Wellens syndrome (critical LAD stenosis with biphasic/deeply inverted T in V2-3) and aVR ST elevation (LMS occlusion) — both are high-risk ECG patterns
- Non-invasive testing (ETT, stress imaging, CTCA) is for low-risk stabilised patients to guide further management
- Echocardiography for all patients: LVEF is the strongest predictor of long-term survival
- CXR is mainly to exclude alternatives (dissection, pneumothorax, pneumonia) and detect complications (pulmonary oedema)
Active Recall - Diagnosis of Unstable Angina
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p15, p32) [2] Senior notes: Ryan Ho Cardiology.pdf (p54, p55, p58) [3] Senior notes: Ryan Ho Fundamentals.pdf (p199, p200, p202, p203) [4] Senior notes: Ryan Ho Cardiology.pdf (p128, p129) [5] Senior notes: Ryan Ho Cardiology.pdf (p115, p116, p117, p120) [8] Senior notes: felixlai.md (p1328) [12] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p57) [13] Senior notes: Ryan Ho Cardiology.pdf (p127) [14] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p11) [15] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p33) [16] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p50) [17] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p57)
Management of Unstable Angina
The management of UA (and NSTE-ACS broadly) flows logically from the pathophysiology:
- The plaque has ruptured and a non-occlusive thrombus is present → you need to prevent thrombus propagation (anticoagulants) and prevent further platelet aggregation (antiplatelets)
- Myocardial O₂ supply-demand mismatch exists → you need to reduce demand (beta-blockers, nitrates) and increase supply (nitrates, revascularisation)
- The patient is at risk of progression to MI → you need to risk-stratify and decide whether to pursue an invasive strategy (angiography ± revascularisation) or a conservative/ischaemia-guided strategy
- Long-term: the atherosclerotic process is ongoing → you need secondary prevention to stabilise remaining plaques and reduce future events
Phase 1: Acute Management ( < 24 Hours)
Admit CCU if high-risk (ongoing chest pain, ↓BP, APO, ventricular arrhythmia…) [2][3].
| Measure | Detail | Rationale |
|---|---|---|
| Bed rest with continuous ECG monitoring [2][3][18] | Cardiac monitor, telemetry | Detect arrhythmias early — ischaemic myocardium is electrically unstable (re-entry circuits, triggered activity) |
| Inform on-call cardiologist [18] | Early specialist involvement | Access to catheterisation lab and expert risk assessment |
| O₂ supplementation | Keep SpO₂ > 90%, PaO₂ > 60 mmHg [18] | Only if hypoxaemic — routine O₂ in normoxaemic patients may cause coronary vasoconstriction (hyperoxia → ↑ROS) |
| Correct precipitating factors [18] | Anaemia, hypoxia, tachyarrhythmia, thyrotoxicosis, fever | These are "demand" triggers that worsen ischaemia — correcting them may resolve secondary UA |
| Nil by mouth or soft diet + stool softener [18] | Ileus common post-MI; Valsalva manoeuvre during straining increases vagal tone | Avoid bearing down → avoid vagal bradycardia or haemodynamic compromise |
| Explain disease to patient [18] | Allay anxiety | Anxiety → ↑catecholamines → ↑HR, ↑BP → ↑O₂ demand → worsening ischaemia |
Consider IV morphine if nitrates do not relieve pain completely [2][3].
| Drug | Dose | Mechanism | Rationale |
|---|---|---|---|
| IV morphine | 2–5 mg IV boluses, titrate | μ-opioid receptor agonist → analgesia + anxiolysis + venodilation (↓preload) | ↓distress, ↓adrenergic drive → ↓SVR, BP, risk of ventricular arrhythmias [18]. Only use if nitrates insufficient — morphine may ↓absorption of oral P2Y12 inhibitors (delayed gastric emptying) |
| IV metoclopramide | 5–10 mg [18] | Dopamine D₂ antagonist → antiemetic + prokinetic | Counteract morphine-induced nausea/vomiting and gastroparesis |
Modern Caveat on Morphine
The ESC 2023 guidelines now advise cautious use of morphine in NSTE-ACS. Morphine delays gastric absorption of oral P2Y12 inhibitors (ticagrelor, clopidogrel), potentially blunting their antiplatelet effect during the critical first hours. If morphine is needed, consider IV cangrelor (parenteral P2Y12 inhibitor) as a bridge, or use IV paracetamol for milder pain.
C. Anti-Ischaemic Therapy
The goal is to restore the O₂ supply-demand balance:
Nitrates (long-acting or short acting as prn) in the presence of angina [20].
| Formulation | Route / Dose | Use |
|---|---|---|
| Sublingual GTN | 0.3–0.6 mg Q5min up to 3 doses [5] | Acute symptom relief |
| GTN spray | 1–2 sprays sublingually (acts faster than tablet) | Acute relief — quicker onset |
| IV GTN infusion | Start 5–10 μg/min, titrate by 5–10 μg/min Q5–10 min | Ongoing/refractory pain; titrate to pain relief and BP (aim sBP > 90 mmHg) |
| Oral ISDN/ISMN | ISDN 10–40 mg TDS or ISMN 20–60 mg BD | Longer-term angina prophylaxis after stabilisation |
Mechanism: Arteriovenous dilatation by release of NO → (1) ↑supply by dilating coronary arteries and redistributing perfusion from epicardial to endocardial sites; (2) ↓demand by venodilation (major → ↓preload) and arteriodilation (modest → ↓afterload) [5].
Why predominantly venodilation? At therapeutic doses, NO preferentially relaxes venous capacitance vessels (larger cross-section, more smooth muscle) → ↓venous return → ↓LV end-diastolic volume → ↓wall stress (by Laplace's law) → ↓O₂ demand. At higher doses, arterial dilation occurs → ↓afterload.
Contraindications:
- Hypotension (sBP < 90 mmHg) — will worsen shock
- Recent PDE-5 inhibitor use (sildenafil within 24h, tadalafil within 48h) — PDE-5 inhibitors prevent breakdown of cGMP → synergistic vasodilation → profound hypotension
- Severe aortic stenosis or HOCM — preload-dependent conditions; ↓preload → ↓CO → syncope/death
- Right ventricular infarction — RV is preload-dependent; nitrates ↓preload → ↓RV output → ↓↓CO
Note: should rest sitting while taking nitrates (standing → syncope; supine → ↑VR → ↑preload) [5].
Side effects: Headache (meningeal vasodilation), flushing, hypotension, reflex tachycardia. Tolerance develops with continuous use → need a nitrate-free interval of 8–10 hours daily [5].
Beta blockers unless contraindicated [20].
| Drug | Dose | Selectivity |
|---|---|---|
| Metoprolol (Betaloc) | 25–100 mg BD [5][18] | β₁-selective |
| Bisoprolol (Zebeta) | 1.25–10 mg OD | β₁-selective |
| Carvedilol | 3.125–25 mg BD | α₁β-non-selective |
Mechanism: Blocks β receptors → ↓HR, ↓contractility, ↓AVN conduction, ↓ectopic activity [5].
Why is this the first-line anti-anginal? Let's think from first principles:
- ↓HR is the most effective way to reduce myocardial O₂ demand (HR is the single largest determinant). It also increases diastolic time → ↑coronary filling time → ↑O₂ supply.
- ↓Contractility → ↓work → ↓O₂ demand
- ↓Ectopic activity → antiarrhythmic → ↓risk of VF/VT (the main cause of sudden death in ACS)
Role: potential prognostic effect renders BB as the 1st line anti-anginal therapy in patients without contraindications [5]:
- Anti-anginal: clearly effective in ↓exercise-induced angina, ↑exercise tolerance, limit ischaemic episodes
- Prognostic: definitely prognostic in post-MI
Contraindications: Bradycardia, AVB, ↓BP, asthma [18].
- NOT contraindicated in: HF (once stabilised), COPD, peripheral vascular disease [18]. This is a common exam mistake.
- Why not asthma? β₂-blockade → bronchospasm → potentially fatal bronchospasm. Even "β₁-selective" agents are not 100% selective at higher doses.
Side effects: Precipitates ADHF, bronchospasm, exacerbates PAD, fatigue, sexual dysfunction, hypoglycaemia (masks warning signs), hyperkalaemia [5].
Calcium antagonists (diltiazem or verapamil) if contraindications to beta-blockers and no heart failure [20].
± DHP CCB if persistent discomfort after nitrates + BB [18].
| Class | Examples | Main Effects | Use in UA |
|---|---|---|---|
| Non-DHP | Diltiazem, Verapamil | Cardiac + vascular: ↓HR, ↓contractility, vasodilation | Alternative to BB when BB contraindicated; NEVER combine with BB (risk of 3° heart block, severe bradycardia) [5] |
| DHP | Amlodipine, Nifedipine | Mainly vascular: vasodilation with little cardiac effect | Add-on to BB if persistent symptoms; safe to combine with BB [5]; C/I in severe AS, HOCM [5] |
Mechanism: Block Ca²⁺ channel → ↓inward current during phase 2 of action potential [5]. In vascular smooth muscle → vasodilation → ↓afterload + coronary dilation. In cardiac tissue (SAN/AVN) → ↓HR, ↓conduction.
Critical Rule
NEVER combine non-DHP CCB (verapamil/diltiazem) with beta-blocker — both depress SA node automaticity and AV node conduction → risk of severe bradycardia, heart block, or asystole. DHP CCBs (amlodipine, nifedipine) are safe to combine with BB because they have minimal cardiac conduction effects.
D. Antithrombotic Therapy
This is the cornerstone of acute UA management — you are fighting the non-occlusive thrombus.
1. Antiplatelet Therapy
Aspirin is recommended for all patients without contraindications at a dose of 75–100 mg daily [19][20].
| Timing | Dose |
|---|---|
| Loading dose | 150–300 mg chewed (for rapid buccal absorption) at first suspicion of ACS |
| Maintenance | 75–100 mg daily, indefinitely [20] |
Mechanism: Irreversibly acetylates cyclooxygenase-1 (COX-1) in platelets → inhibits thromboxane A₂ (TXA₂) synthesis → TXA₂ is a potent platelet aggregator and vasoconstrictor → its inhibition ↓platelet aggregation. Because platelets are anucleate (no new protein synthesis), the inhibition lasts the lifetime of the platelet (~7–10 days).
Contraindications: Active GI bleeding, known aspirin allergy/hypersensitivity, severe bleeding diathesis. Side effects: GI bleeding (mucosal COX-1 inhibition → ↓protective prostaglandins), aspirin-exacerbated respiratory disease (in susceptible individuals: COX-1 inhibition shunts arachidonic acid to leukotriene pathway → bronchoconstriction).
A P2Y12 receptor inhibitor is recommended in addition to aspirin, and maintained over 12 months unless there are contraindications or an excessive risk of bleeding [20]:
- Ticagrelor 90 mg b.i.d.
- Clopidogrel 75 mg/d [20]
Clopidogrel 75 mg QD when aspirin is not tolerated because of hypersensitivity or GI intolerance [20].
| Drug | Mechanism | Onset | Reversibility | Key Points |
|---|---|---|---|---|
| Ticagrelor | Direct, reversible P2Y12 antagonist (active drug, no prodrug activation needed) | Rapid (30 min) | Reversible (offset ~3–5 days) | Preferred over clopidogrel (ESC 2023); superior efficacy in PLATO trial. S/E: dyspnoea (↑adenosine levels — ticagrelor inhibits adenosine reuptake), bradycardia |
| Clopidogrel | Irreversible P2Y12 antagonist (prodrug — requires hepatic CYP2C19 activation) | Slower (2–6h) | Irreversible (offset ~5–7 days) | If ticagrelor not available or contraindicated [19][20]. Caveat: clopidogrel interacts with PPI → inhibits CYP2C19/3A4 activation of clopidogrel prodrug → treatment failure [18]. Also ~30% of Asians are CYP2C19 poor metabolisers → clopidogrel resistance |
| Prasugrel | Irreversible P2Y12 antagonist (prodrug — faster/more reliable activation than clopidogrel) | Rapid (30 min) | Irreversible (offset ~7 days) | After defining coronary anatomy (at PCI) [19]. C/I: prior stroke/TIA, age ≥ 75, body weight < 60 kg (↑bleeding risk) |
Mechanism of P2Y12 inhibition: ADP released from injured vessel walls and activated platelets binds to the P2Y12 receptor on platelet surface → amplifies platelet activation and aggregation via the GPIIb/IIIa pathway. Blocking P2Y12 prevents this amplification loop → ↓platelet aggregation.
Dual antiplatelet therapy (DAPT) = aspirin + P2Y12 inhibitor — this combination attacks two different pathways of platelet activation simultaneously (COX-1/TXA₂ pathway + ADP/P2Y12 pathway), providing synergistic antiplatelet effect.
The antiplatelet algorithm for NSTE-ACS [19]:
| Phase | Recommendation |
|---|---|
| First medical contact (pretreatment) | Ticagrelor (preferred) or Clopidogrel (if ticagrelor not available or contraindicated) [19] |
| If PCI performed | Continue ticagrelor or prasugrel. Prasugrel: after defining coronary anatomy [19]. Consider cangrelor in patients not pretreated (IV P2Y12 inhibitor — rapid onset/offset) [19] |
| If CABG needed | Withdraw ticagrelor for 5 days and prasugrel for 7 days [19] (to reduce surgical bleeding). Clopidogrel: withdraw 5 days pre-CABG |
| If no revascularisation | Continue medical management with DAPT |
| Discharge | Continue prasugrel or ticagrelor for 12 months. If CABG performed: resume ticagrelor as soon as possible [19] |
GPIIb/IIIa inhibitor for selected patients only [18].
Mechanism: GPIIb/IIIa is the final common pathway of platelet aggregation — it's the surface receptor that binds fibrinogen to cross-link platelets. Blocking this receptor is the most potent antiplatelet strategy available.
Indication in NSTE-ACS: Now very limited — primarily considered:
- During PCI if large thrombus burden or no-reflow
- In very high-risk patients with ongoing ischaemia
- As a bailout during procedural complications
Not used routinely — increased bleeding risk with modern potent P2Y12 inhibitors (ticagrelor/prasugrel) has made upfront GPIIb/IIIa inhibitors obsolete in most scenarios.
Heparin/LMWH at diagnosis [18][2][3].
| Drug | Dose | Mechanism | Key Points |
|---|---|---|---|
| Enoxaparin (LMWH) | 1 mg/kg SC BD | Binds antithrombin III → preferentially inhibits Factor Xa (and to lesser extent thrombin/IIa) | Preferred over UFH in NSTE-ACS (more predictable pharmacokinetics, no need for aPTT monitoring, superior efficacy in SYNERGY/ExTRACT trials). Dose-adjust in renal impairment (CrCl < 30: 1 mg/kg OD) |
| Unfractionated heparin (UFH) | 60 U/kg bolus (max 4000 U) then 12 U/kg/h infusion, titrate to aPTT 1.5–2.5× control | Binds antithrombin III → inhibits thrombin (IIa) and Factor Xa equally | Preferred when PCI planned imminently (easier to monitor/reverse with protamine) or in severe renal failure |
| Fondaparinux | 2.5 mg SC OD | Selective Factor Xa inhibitor via antithrombin III | Lowest bleeding risk; preferred if conservative strategy planned. Need supplemental UFH bolus if patient goes to PCI (risk of catheter thrombosis) |
Why anticoagulation in addition to antiplatelets? The thrombus in ACS has both a platelet component (white thrombus) and a fibrin component (coagulation cascade). Antiplatelets attack the platelet component; anticoagulants attack the coagulation cascade component. Together they provide comprehensive antithrombotic coverage.
Duration: Anticoagulation is maintained during the acute hospitalisation phase and discontinued after revascularisation or discharge (unless otherwise indicated, e.g. AF requiring long-term anticoagulation).
E. Other Acute Medications
High-intensity statin always (≤24h) [18].
| Drug | Dose |
|---|---|
| Atorvastatin | 80 mg daily |
| Rosuvastatin | 20–40 mg daily |
Mechanism: HMG-CoA reductase inhibitor → ↓hepatic cholesterol synthesis → ↑hepatic LDL receptor expression → ↑LDL clearance from blood → ↓LDL-C.
Why start immediately, regardless of cholesterol levels? Beyond lipid-lowering, statins have pleiotropic effects that are critical in ACS:
- Plaque stabilisation: ↓inflammation within plaque, ↓macrophage activity, ↑fibrous cap thickness
- Anti-inflammatory: ↓CRP, ↓cytokines
- Endothelial function: ↑NO bioavailability → vasodilation
- Antithrombotic: ↓tissue factor expression, ↓platelet reactivity
- These effects occur within hours and are independent of LDL reduction
Aim at LDL < 1.8 mmol/L and/or > 50% reduction [5].
ACEI for patients with CHF, LV dysfunction (EF < 40%), hypertension, or diabetes [20].
| Drug | Example Dose |
|---|---|
| Ramipril | 2.5–10 mg OD |
| Perindopril | 2–8 mg OD |
| Valsartan (ARB) | 80–320 mg OD (if ACEI-intolerant) |
Mechanism: ACEI inhibits angiotensin-converting enzyme → ↓angiotensin II (potent vasoconstrictor + promotes aldosterone release + promotes cardiac remodelling) and ↑bradykinin (vasodilator). Net effects: ↓afterload, ↓preload, ↓cardiac remodelling, ↓fibrosis.
Why in ACS? Post-MI, angiotensin II drives adverse LV remodelling (dilatation, fibrosis, hypertrophy) → heart failure. ACEI/ARB prevent this. Particular benefit when LVEF < 40% or clinical heart failure.
β-blockers, ACEI/ARB always (≤24h) [18].
MRA if LVEF ≤40% + HF/DM [18].
| Drug | Dose |
|---|---|
| Eplerenone | 25–50 mg OD |
| Spironolactone | 25–50 mg OD |
Mechanism: Blocks aldosterone receptor → ↓Na⁺/H₂O retention, ↓K⁺ loss, and critically → ↓cardiac fibrosis (aldosterone promotes myocardial collagen deposition). EPHESUS/RALES trials showed mortality benefit in post-MI heart failure.
This is where UA management diverges from STEMI:
No benefit if done routinely in NSTE-ACS. Thrombolysis may even be harmful (not thrombotic occlusion → no benefit at all) [18].
CRITICAL: No Thrombolysis in UA/NSTEMI
Unlike STEMI where the artery is completely occluded by a fibrin-rich "red" thrombus (amenable to fibrinolysis), UA/NSTEMI has a platelet-rich "white" thrombus that is non-occlusive. Thrombolysis is ineffective against platelet-rich thrombi and may paradoxically worsen the situation by:
- Activating platelets (thrombin released during fibrinolysis is a potent platelet activator)
- Causing bleeding without therapeutic benefit
NEVER give thrombolysis for UA or NSTEMI.
Invasive vs Ischaemia-Guided Strategy
Two main strategies (AHA/ACC) [18]:
- Invasive strategy: invasive coronary angiography in ≤2h (immediate), ≤24h (early), 25–72h (delayed)
- Ischaemia-driven strategy: invasive coronary angiography only if refractory angina at risk of failing medical therapy; objective evidence of ischaemia on non-invasive stress test; clinical indicators of very high prognostic risk score [18]
The choice depends on risk stratification [1][15][18]:
| Risk Level | Criteria | Timing | Strategy |
|---|---|---|---|
| Very high risk | Haemodynamic instability/cardiogenic shock; acute HF from ongoing ischaemia; life-threatening arrhythmias/cardiac arrest; mechanical complications; recurrent dynamic ECG changes [15] | Immediate ( < 2h) | Invasive |
| High risk | Elevated biomarkers; GRACE > 140; transient ST elevation; dynamic ST/T changes [15] | Early ( < 24h) | Invasive |
| Intermediate risk | GRACE 109–140; diabetes; renal insufficiency; LVEF < 40% | < 72h | Invasive |
| Low risk | No high/very-high risk features; low clinical suspicion | Selective | Non-invasive stress testing for low/intermediate risk patients free of ischaemia [18]; proceed to angiography only if positive |
For true UA (troponin-negative, no dynamic ECG changes, low GRACE score):
- Often falls into the low-risk category
- Ischaemia-guided strategy is appropriate
- Can undergo non-invasive stress testing pre-discharge
- Angiography only if stress test positive
When angiography is performed, the choice between PCI and CABG depends on coronary anatomy:
| Anatomy | Preferred Strategy | Rationale |
|---|---|---|
| Simple vascular anatomy (1VD, 2VD), no proximal disease, high surgical risk | PCI [5] | Less invasive; faster recovery; suitable for focal lesions |
| 3VD / LMS disease / complex anatomy | CABG | Survival benefit in 3VD and LMS disease (SYNTAX trial); complete revascularisation more achievable with CABG |
| Multivessel disease with diabetes | CABG preferred | FREEDOM trial showed mortality benefit of CABG over PCI in diabetics with multivessel disease |
| No significant stenosis | Medical management ± MINOCA workup | Consider coronary vasospasm, microvascular dysfunction, Takotsubo |
PCI only for selected high-risk individuals in NSTE-ACS [18]. The decision should involve a Heart Team approach (cardiologist + cardiac surgeon).
Coronary angiography findings may require intravascular imaging (IVUS or OCT) for ambiguous lesions [16].
Phase 3: Long-Term Management / Secondary Prevention
| Measure | Detail | Evidence |
|---|---|---|
| Smoking cessation | Drastic ↓MI risk after just 1 year; smoking doubles 5-year mortality [18] | Single most effective lifestyle intervention |
| Regular exercise | Cardiac rehabilitation; 150 min/week moderate-intensity aerobic exercise | Stop smoking, regular exercise (but not beyond point of discomfort) [5] |
| Diet | Mediterranean diet; ↓saturated fat, ↑fruits/vegetables, ↑omega-3 | PREDIMED trial: 30% ↓cardiovascular events |
| Weight management | BMI target < 25 kg/m² | |
| HTN control | Aim < 140/90, use BB if indicated [5] | |
| DM control | Aim HbA1c < 7%, consider SGLT2i or GLP-1a [5] | SGLT2i/GLP-1a have CV mortality benefit independent of glucose control |
| Lipid control | ↓LDL to < 1.8 mmol/L with lifestyle and drug [5] | High-intensity statin ± ezetimibe ± PCSK9 inhibitor |
B. Long-Term Drug Therapy
| Drug | Duration | Dose |
|---|---|---|
| Aspirin | Indefinitely [18] | 81–325 mg daily or Cartia 100 mg daily [18] |
| P2Y12 inhibitor | ≥12 months if any stent used (mandatory); 1–12 months even if no PCI done [18] | Clopidogrel 75 mg QD, prasugrel 10 mg QD, or ticagrelor 90 mg BD [18] |
After 12 months, DAPT can be de-escalated to aspirin monotherapy in most patients. In selected high-risk patients (e.g. DM, recurrent events, complex PCI), extended DAPT ( > 12 months) or low-dose rivaroxaban (COMPASS trial) may be considered.
High dose statins for aggressive ↓lipid (regardless of serum cholesterol level) → ↓mortality [18].
- If LDL target not achieved with maximally tolerated statin → add ezetimibe → if still not at target → add PCSK9 inhibitor (evolocumab, alirocumab)
MRA if LVEF ≤40% + HF/DM [18]
Takes 4–6 weeks to replace necrotic tissue by fibrotic tissues → restrict physical activities until then, offer cardiovascular rehabilitation. Usually: mobilize in 2 days, discharge in 3–5 days, resume work in 4–6 weeks [18].
For true UA (no necrosis), mobilisation and discharge are often earlier.
The classic mnemonic MONA (Morphine, Oxygen, Nitrates, Aspirin) is a useful memory aid but outdated as a rigid protocol. The modern approach adds Beta-blockers, P2Y12 inhibitors, anticoagulation, and statin:
| Component | Agent | When |
|---|---|---|
| M — Morphine | IV morphine ± metoclopramide | If nitrates insufficient; use cautiously |
| O — Oxygen | Supplemental O₂ | Only if SpO₂ < 90% |
| N — Nitrates | SL GTN → IV GTN if ongoing | Immediate; first-line symptom relief |
| A — Aspirin | 150–300 mg chewed → 75–100 mg OD | At first suspicion; indefinitely |
| B — Beta-blocker | Metoprolol/bisoprolol | Within 24h if no C/I; indefinitely |
| + P2Y12 inhibitor | Ticagrelor (preferred) or clopidogrel | At diagnosis; 12 months |
| + Anticoagulant | Enoxaparin or UFH or fondaparinux | At diagnosis; during hospitalisation |
| + Statin | Atorvastatin 80 mg or rosuvastatin 40 mg | Within 24h; indefinitely |
| + ACEI/ARB | Ramipril/perindopril | Within 24h if LVEF < 40%/HF/HTN/DM |
High Yield Summary
- No thrombolysis in UA/NSTEMI — platelet-rich thrombus is not amenable to fibrinolysis; may worsen outcome
- Acute management = Anti-ischaemic + Antithrombotic + Adjunctive
- Anti-ischaemic: Nitrates (↓preload, coronary dilation) + Beta-blocker (↓HR, ↓contractility) ± CCB
- Antithrombotic: DAPT (aspirin + ticagrelor/clopidogrel) + anticoagulant (enoxaparin/UFH/fondaparinux)
- Adjunctive: high-intensity statin + ACEI/ARB (if EF < 40%/HF/HTN/DM)
- Risk stratification (GRACE score) determines invasive strategy timing: very high risk < 2h; high risk < 24h; intermediate < 72h; low risk = ischaemia-guided
- Ticagrelor preferred over clopidogrel in NSTE-ACS; prasugrel after defining coronary anatomy at PCI
- Never combine non-DHP CCB with beta-blocker (risk of heart block)
- Clopidogrel + PPI interaction → inhibits CYP2C19 activation → treatment failure; use pantoprazole (least interaction) if PPI needed
- Long-term secondary prevention: aspirin indefinitely, P2Y12 for 12 months, beta-blocker, ACEI/ARB, high-intensity statin, risk factor modification, cardiac rehabilitation
- PCI for simple anatomy (1-2VD); CABG for 3VD/LMS/complex disease
Active Recall - Management of Unstable Angina
References
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p32) [2] Senior notes: Ryan Ho Cardiology.pdf (p58) [3] Senior notes: Ryan Ho Fundamentals.pdf (p203) [5] Senior notes: Ryan Ho Cardiology.pdf (p115, p120, p122, p123, p126) [15] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p33) [16] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p50) [18] Senior notes: Ryan Ho Cardiology.pdf (p132, p136, p138, p139, p144) [19] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p40) [20] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p54, p55)
Complications of Unstable Angina
Before diving in, understand a critical distinction: unstable angina by definition involves ischaemia without myocardial necrosis (troponin-negative). Therefore, the mechanical complications classically associated with myocardial infarction (free wall rupture, VSD, papillary muscle rupture) are complications of MI, not of UA per se. However, UA is part of the ACS continuum, and its complications arise from two main mechanisms:
- Progression of UA to myocardial infarction — this is the primary danger and the reason UA is a medical emergency. Once MI occurs, all MI complications become relevant.
- Consequences of ongoing ischaemia itself — even without necrosis, ischaemia causes electrical instability, transient pump dysfunction, and haemodynamic compromise.
Think of it this way: UA sits on a tightrope. The most important "complication" is falling off that tightrope into MI or sudden death. The management of UA is essentially about preventing that fall.
Atherothrombosis is a generalised and progressive process — from stable angina → unstable angina → MI → ischaemic stroke/TIA → critical leg ischaemia [21][22]. The complications we discuss reflect this progressive nature.
The clinical spectrum of ACS ranges from oligo/asymptomatic → increasing chest pain/symptoms → persistent chest pain/symptoms → cardiogenic shock/acute heart failure → cardiac arrest [14].
Aims of treatment for NSTE-ACS: relieve symptoms (anti-ischaemic therapy); prevention of progression and complications (anti-thrombotic Rx, revascularisation) [23]. Every complication below is what we are trying to prevent.
This is the most feared and most common complication of UA.
Pathophysiology: The non-occlusive platelet-rich thrombus on a ruptured plaque can propagate. If:
- The thrombus grows and becomes occlusive → STEMI (complete occlusion → transmural necrosis)
- The thrombus embolises distally or causes prolonged near-total obstruction → NSTEMI (partial/subendocardial necrosis)
Unstable angina (UA): severe ischaemia at rest without infarction. NSTEMI: partial occlusion → some myocardial necrosis but not transmural. STEMI: complete occlusion → transmural myocardial necrosis [5].
AMI: mortality 40% overall in 4 weeks (half ≤2h due to VF), 6–7% in 30 days for those surviving to hospital [5].
Clinical recognition: Worsening or unrelenting chest pain, new persistent ST elevation, rising troponin. This is why serial ECG and cardiac enzymes are mandatory [2][3].
Prevention: This is the entire rationale for DAPT + anticoagulation + anti-ischaemic therapy + risk-based invasive strategy.
II. Arrhythmias
Arrhythmias are the most common cause of death in the first hours of ACS. Even in UA (without frank necrosis), ischaemia renders the myocardium electrically unstable.
Cardiac arrest: causes include coronary artery disease (85%), including myocardial ischaemia, AMI, and prior MI with myocardial scarring [24].
Ischaemic myocardium undergoes rapid biochemical changes:
- ↓ATP → failure of Na⁺/K⁺-ATPase → intracellular K⁺ leaks out → ↑extracellular K⁺ → partial depolarisation of resting membrane potential → ↓conduction velocity
- Intracellular Ca²⁺ overload → triggered activity (delayed afterdepolarisations)
- Heterogeneous ischaemia creates zones of different conduction velocities and refractory periods → re-entry circuits (the substrate for VT and VF)
- ↑Catecholamines (sympathetic response to pain/stress) → ↑automaticity → ectopic foci
These mechanisms create the perfect storm for lethal arrhythmias even before any myocardial necrosis has occurred.
| Type | Details | Management |
|---|---|---|
| VF | Totally uncoordinated contraction of ventricles [24]. Most common cause of sudden death in first hour of ACS. 80% reversed by defibrillation but 10% ↓survival per minute delay [24] | Prompt defibrillation per ACLS algorithm [18] |
| VT (sustained) | LV rate too fast to pump blood effectively [24]. In ACS setting, treat as VT until proven otherwise in wide complex tachycardia [18] | Stable sustained monomorphic VT: amiodarone 150 mg IV over 10 min; sustained polymorphic VT: unsynchronized cardioversion 200 J [18] |
| AF/Atrial flutter | Common and frequently transient, can be a sign of impending or overt LVF [18]. Mechanism: atrial stretch from ↑LVEDP; atrial ischaemia; ↑catecholamines | Digoxin, diltiazem, or amiodarone for rate/rhythm control [18] |
| AV block | Inferior MI → AV nodal ischaemia (AV node supplied by RCA in 85%). Conservative if 1° or Mobitz I; pacing if Mobitz II or complete HB [18] | Atropine first; temporary pacing if unresponsive |
| Sinus bradycardia | Inferior wall ischaemia → enhanced vagal tone (Bezold-Jarisch reflex) | Atropine 0.3–0.6 mg IV bolus; pacing if unresponsive [18] |
| Sinus tachycardia | Compensatory response to ↓CO, pain, anxiety. Worsens ischaemia (↑O₂ demand, ↓diastolic filling time) | Treat underlying cause; beta-blocker if appropriate |
Pump failure mechanism: downward spiral exacerbating myocardial ischaemia — ↓systolic function → ↓coronary perfusion → ↓supply → ischaemia; ↓diastolic function → ↑pulmonary congestion → hypoxaemia → ischaemia [18].
Indicates extensive myocardial damage → poor prognosis (↑likelihood of other complications) [18].
A. Killip Classification
This is used to stratify the severity of haemodynamic compromise in ACS:
| Killip Class | Signs | Implications |
|---|---|---|
| I | No rales or S3 | No clinical signs of HF |
| II | Rales < 50% lung field or S3, ↑JVP | Pulmonary congestion |
| III | Rales > 50% lung field | Pulmonary oedema |
| IV | SBP < 90 mmHg + peripheral vasoconstriction | Cardiogenic shock |
Pathophysiology of the vicious cycle:
In UA specifically, pump failure occurs when a large territory of myocardium is ischaemic (not yet infarcted):
- Ischaemic myocardium becomes hypokinetic (stunned) → ↓stroke volume → ↓CO
- ↓CO → ↓coronary perfusion pressure → worsens ischaemia → more myocardium becomes dysfunctional
- Simultaneously, ↓CO → ↑sympathetic activation → ↑HR, ↑SVR → ↑afterload → ↑O₂ demand → further ischaemia
- ↑LVEDP → pulmonary congestion → hypoxaemia → further ischaemia
This creates a self-perpetuating downward spiral — the "ischaemia begets ischaemia" cycle. Breaking this cycle (with nitrates, beta-blockers, urgent revascularisation, ± inotropes/IABP in cardiogenic shock) is the goal.
In the Braunwald classification, the following are high-risk features indicating pump failure complicating UA [1]:
- Pulmonary oedema
- New or worsening MR murmur
- S3 or new/worsening rales
- Hypotension, bradycardia, tachycardia
Cardiogenic shock / acute heart failure represents the extreme end of the ACS clinical spectrum [14].
This is Killip Class IV and carries extremely high mortality ( > 50%).
Mechanism: Massive ischaemia involving ≥40% of LV myocardium → severe ↓CO → multi-organ hypoperfusion.
Clinical features [24]:
- Forward failure: pallor, peripheral cyanosis, cold extremities, delayed capillary refill, oliguria, altered consciousness
- Backward failure: dyspnoea, wheeze, cough with pink frothy sputum, basal crackles, displaced apex, gallop
Management: Urgent revascularisation is the only definitive treatment. Supportive measures include inotropes (dobutamine), vasopressors (noradrenaline), intra-aortic balloon pump (IABP), or ECMO as a bridge.
Watch out for other causes: mechanical complications, arrhythmia, excessive use of anti-hypertensives [18].
Post-ACS ischaemia is indicated by symptoms/ECG changes + new rise in cTn > 20% or to > 5× ULN (if normal baseline) [18].
This means the patient has re-infarcted or has ongoing ischaemia despite treatment. In UA patients, this manifests as:
- Recurrent chest pain despite optimal medical therapy
- New or worsening ECG changes
- Troponin that was initially negative now becomes positive (i.e., the UA has "converted" to NSTEMI)
High risk → prompt coronary angiography/PCI + IV GPIIb/IIIa inhibitor (if dynamic ECG changes) [18].
Why does this happen?
- The culprit thrombus is dynamic — it may partially lyse then re-form
- Distal microembolisation from the unstable plaque
- Residual stenosis after incomplete revascularisation
- New plaque rupture at a different site
These are complications of established MI rather than UA itself, but they are included here because UA can progress to MI, and understanding them is essential for the ACS continuum.
AMI complications: heart failure, arrhythmias, VSD (anterior MI), mitral regurgitation complicating papillary muscle dysfunction (inferior MI), pericarditis [25].
| Complication | Timing | Mechanism | Presentation | Management |
|---|---|---|---|---|
| VSD (ventricular septal rupture) | Usually ~24h but up to 2 weeks [18] | Usually complicates anterior MI (LAD); rupture occurs at margin of necrotic and non-necrotic myocardium [18] | Sudden haemodynamic deterioration + new onset pansystolic murmur (at RLSB) → L-to-R shunting → usually develops RV failure [18] | Observe with delayed surgery if stable; emergency cardiac catheterisation and repair if unstable [18] |
| Acute mitral regurgitation | Days 2–7 | Ischaemia/necrosis of papillary muscle (posteromedial PM most vulnerable — single blood supply from PDA) → partial or complete rupture → severe MR | Sudden acute pulmonary oedema + new loud pansystolic murmur at apex ± thrill. D/dx from VSD: MR → LLSB/apex + APO; VSD → RLSB + RV failure [18] | Emergency surgical repair/replacement; IABP as bridge |
| LV free wall rupture | < 1%, 50% occurs ≤5 days, > 90% ≤2 weeks [18] | Transmural infarction weakens wall → rupture through necrotic tissue | Complete: cardiac tamponade → sudden profound RHF + shock → PEA and death. Incomplete: sealed by pericardium → persistent/recurrent pleuritic chest pain [18] | Emergency percutaneous pericardiocentesis → surgical repair if blood aspirated [18] |
| Post-MI pericarditis | Days 1–3 (early) or 2–10 weeks (Dressler's syndrome) | Early: direct inflammation of pericardium overlying infarct. Dressler's: autoimmune reaction to myocardial antigens exposed by necrosis | Pleuritic chest pain, pericardial friction rub, diffuse ST elevation | NSAIDs/colchicine for early; corticosteroids for Dressler's. Avoid anticoagulation if haemorrhagic pericarditis suspected |
Ventricular Aneurysm
Occurs in 8–15% with STEMI, especially for those with persistent occlusion [18]:
- 70–85% located at anterior or apical walls → due to LAD total occlusion without collateral
- Consequences: acute decompensated HF with angina; ventricular arrhythmia; systemic embolisation (mural thrombus occurs in > 50%)
- Dx: paradoxical impulse on chest wall; ECG — persistent ↑ST and Q despite reperfusion; CXR — unusual bulge; echo — diagnostic
- Mx: oral anticoagulation if mural thrombus documented; aneurysmectomy + CABG if intractable arrhythmias or refractory HF [18]
Most common in (1) anterior STEMI (2) LAD infarct (3) large infarct with EF < 30% [18].
| Source | Mechanism | Consequence |
|---|---|---|
| LV mural thrombus | Wall motion abnormality/aneurysm → stasis → thrombus formation. Risk of embolisation in non-anticoagulated documented LV thrombus is 10–15% [18] | Stroke, mesenteric ischaemia, limb ischaemia — classically occurring 1–3 weeks after MI [18] |
| Atrial thrombus | AF (common arrhythmia post-MI) → atrial stasis → thrombus | Stroke, systemic embolism |
Prevention: Anticoagulation indicated when LV thrombus documented or high-risk features present (large anterior MI, apical akinesis, EF < 30%, AF).
In UA specifically, embolism risk is lower (no large wall motion abnormality or aneurysm formation since there is no necrosis). However, microembolisation from the unstable plaque can occur — small platelet-fibrin aggregates break off from the culprit thrombus and lodge in downstream microvasculature → patchy myocardial necrosis or troponin leak.
This is a long-term complication if UA progresses to MI:
Mechanism: After MI, the infarcted territory is replaced by fibrous scar tissue (takes 4–6 weeks). The remaining viable myocardium undergoes compensatory hypertrophy and chamber dilatation to maintain cardiac output. Over time, this maladaptive remodelling leads to:
- Progressive LV dilatation
- ↓LVEF
- Neurohormonal activation (RAAS, sympathetic) → fluid retention, further remodelling
- → Chronic heart failure
LVEF is the strongest predictor of long-term survival; LVEF < 50% associated with ↑↑event risk [5].
Prevention: ACEI/ARB + beta-blocker + MRA (if EF ≤ 40%) — all proven to ↓remodelling and ↓mortality. Early revascularisation to salvage ischaemic but viable myocardium also prevents remodelling.
IX. Complications of Treatment
These are iatrogenic complications that must be considered:
PCI complications (mortality < 0.5%) [5]:
| Category | Details |
|---|---|
| Coronary artery related | Dissection and abrupt closure; intramural haematoma (6.7%); perforation (0.2–0.6%); side branch occlusion (up to 19%) — all can lead to myocardial ischaemia or infarction [5] |
| Stent thrombosis (1–2%) | Acute event, usually presents with severe STEMI or cardiac death. Due to thrombus formation at exposed stent surface before endothelialisation. Majority occurs < 30 days. Prevention: DAPT [5] |
| In-stent restenosis (ISR) | Chronic event, usually presents with recurrent stable angina. Due to intimal proliferation. Usually ≥6–9 months after stenting. Prevention: drug-eluting stent (DES) [5] |
| Others | Access-related (bleeding, infection, atheroembolism); AKI (contrast, haemodynamic instability); stroke; bacteraemia [5] |
CABG complications [5]:
| Cardiac | Non-cardiac |
|---|---|
| Perioperative MI ( < 1–2%) | Bleeding |
| Graft occlusion (5–10% in 30 days) | Neurological: stroke, cognitive impairment — classically from aortic thrombus |
| Low cardiac output from ventricular dysfunction | Infection: wound infection with mediastinitis |
| Arrhythmia (30% AF in 1st week) | AKI |
| Pericarditis, effusion, tamponade |
Dual antiplatelet + anticoagulant therapy significantly increases bleeding risk:
- GI bleeding — aspirin inhibits protective mucosal prostaglandins; managed with PPI cover (use pantoprazole if on clopidogrel to avoid CYP2C19 interaction)
- Intracranial haemorrhage — rare but devastating; higher risk with ticagrelor/prasugrel than clopidogrel
- Access site bleeding — post-PCI; radial access has lower bleeding risk than femoral
- Heparin-induced thrombocytopenia (HIT) — immune-mediated complication of heparin; paradoxically causes thrombosis rather than bleeding
Often overlooked but clinically significant:
- Anxiety and depression — very common after ACS; up to 20–30% of ACS patients develop major depression within 12 months
- Mechanism: multifactorial — existential fear of death, loss of perceived health, autonomic dysregulation, neuroinflammation
- Impact: depression post-ACS is an independent predictor of mortality (↑sympathetic tone, ↓medication adherence, ↑inflammation)
- Management: screening, cognitive-behavioural therapy, SSRIs (sertraline is safest post-ACS)
| Timing | Complications |
|---|---|
| Immediate (minutes-hours) | VF, VT, cardiac arrest, cardiogenic shock, progression to MI |
| Early (hours-days) | Ongoing ischaemia, arrhythmias (AF, AV block), acute heart failure, acute MR |
| Subacute (days-2 weeks) | VSD, free wall rupture, ventricular aneurysm, pericarditis, systemic embolism, stent thrombosis |
| Late (weeks-months) | Chronic heart failure, ventricular remodelling, in-stent restenosis, Dressler's syndrome, depression |
| Iatrogenic (any time) | Bleeding (from DAPT/anticoagulation), contrast nephropathy, PCI/CABG complications |
High Yield Summary
- The primary complication of UA is progression to MI — this is why UA is a medical emergency requiring immediate treatment
- Arrhythmias are the most common cause of death in first hours of ACS — especially VF (80% reversible if defibrillated promptly, 10% ↓survival per minute delay) — hence the need for continuous ECG monitoring
- Pump failure creates a vicious cycle: ↓systolic function → ↓coronary perfusion → ischaemia → further ↓function. Classified by Killip class (I–IV)
- Mechanical complications (VSD, acute MR, free wall rupture) occur if UA progresses to MI — timing is typically days 1–14 post-MI
- VSD: new PSM at RLSB + RV failure; Acute MR: new PSM at apex + APO — the clinical differentiation is important
- Free wall rupture: presents with sudden tamponade → PEA → death; incomplete rupture → pleuritic pain
- Ventricular aneurysm: persistent ST elevation + Q waves despite reperfusion; risk of mural thrombus → embolism
- Embolism: LV thrombus (wall motion abnormality/aneurysm) → stroke/limb ischaemia at 1–3 weeks; prevented by anticoagulation
- Treatment complications: stent thrombosis (acute, STEMI-like, prevented by DAPT), in-stent restenosis (chronic, stable angina-like, prevented by DES), bleeding from antithrombotic therapy
- Depression post-ACS is an independent mortality predictor — screen and treat
Active Recall - Complications of Unstable Angina
References
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p32) [2] Senior notes: Ryan Ho Cardiology.pdf (p58) [3] Senior notes: Ryan Ho Fundamentals.pdf (p203) [5] Senior notes: Ryan Ho Cardiology.pdf (p120, p124, p126) [14] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p11) [18] Senior notes: Ryan Ho Cardiology.pdf (p132, p139, p141, p142, p144) [21] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p7) [22] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p4) [23] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p45) [24] Senior notes: Ryan Ho Critical Care.pdf (p28) [25] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p56)
High Yield Summary
- Unstable angina (UA) = anginal chest pain that is new-onset and severe, occurs at rest, or is crescendo in pattern — WITHOUT troponin elevation (no myocardial necrosis)
- UA sits on the ACS spectrum between stable angina and NSTEMI/STEMI — same underlying pathology of atherosclerotic plaque disruption with non-occlusive thrombosis
- The key pathological difference: UA has a non-occlusive, platelet-rich "white" thrombus → ischaemia but no infarction
- Risk factors: modifiable (smoking, HTN, DM, dyslipidaemia, obesity, inactivity) and non-modifiable (age, male sex, family Hx, prior CVD)
- Precipitants: heavy exercise, emotional stress, surgery, infection, circadian peak 0600–1200
- Clinical features: dull/constricting retrosternal chest discomfort ± radiation to arms/jaw/neck, occurring at rest or with ↓threshold; associated dyspnoea, diaphoresis, nausea
- Examination may be normal — look for: S4 (diastolic dysfunction), S3/rales (systolic dysfunction), new MR murmur (papillary muscle ischaemia), hypotension, tachycardia → all indicate high risk
- Braunwald classification stratifies by severity (I–III), clinical context (A–C), and treatment context (1–3)
- With hs-cTn assays, many former "UA" cases are now reclassified as NSTEMI
- In Hong Kong: high prevalence of DM as major risk factor; coronary vasospasm more common in East Asians
High Yield Summary
- The differential of UA is essentially the differential of acute chest pain — think systematically across cardiac, vascular, pulmonary, GI, musculoskeletal, and psychiatric causes.
- Five life-threatening mimics not to miss: STEMI, aortic dissection, PE, tension pneumothorax, cardiac tamponade.
- UA vs NSTEMI: clinically indistinguishable — only troponin differentiates them.
- Aortic dissection is the most dangerous mimic — sudden-onset, tearing, radiating to back, BP differential. NEVER anticoagulate before excluding it.
- GERD is the most common overall cause of chest pain (42%); it can even respond to GTN — do not assume GTN response = cardiac.
- ECG pitfalls: Know the causes of false-positive ST elevation (early repolarisation, LBBB, pericarditis, PE, SAH, hyperkalaemia, Brugada) and false negatives (paced rhythm, LBBB, prior Q waves).
- Panic disorder closely mimics ACS — but is always a diagnosis of exclusion in the acute setting.
High Yield Summary
- UA is a clinical diagnosis = typical ACS presentation + no persistent ST elevation + serial troponins normal
- ECG within 10 minutes of presentation → separates STEMI from NSTE-ACS
- Serial hs-cTn (0h and 1h or 0h and 2h) → separates NSTEMI from UA. Rule-out requires low baseline AND no significant delta
- The 4th Universal Definition of MI requires troponin above 99th percentile URL with rise/fall pattern → UA does not meet this threshold
- GRACE score is the ESC-recommended tool for risk stratification → determines timing of invasive strategy
- Very high risk features (shock, acute HF, life-threatening arrhythmias, mechanical complications, recurrent dynamic ECG changes) → immediate invasive strategy < 2h
- Know Wellens syndrome (critical LAD stenosis with biphasic/deeply inverted T in V2-3) and aVR ST elevation (LMS occlusion) — both are high-risk ECG patterns
- Non-invasive testing (ETT, stress imaging, CTCA) is for low-risk stabilised patients to guide further management
- Echocardiography for all patients: LVEF is the strongest predictor of long-term survival
- CXR is mainly to exclude alternatives (dissection, pneumothorax, pneumonia) and detect complications (pulmonary oedema)
High Yield Summary
- No thrombolysis in UA/NSTEMI — platelet-rich thrombus is not amenable to fibrinolysis; may worsen outcome
- Acute management = Anti-ischaemic + Antithrombotic + Adjunctive
- Anti-ischaemic: Nitrates (↓preload, coronary dilation) + Beta-blocker (↓HR, ↓contractility) ± CCB
- Antithrombotic: DAPT (aspirin + ticagrelor/clopidogrel) + anticoagulant (enoxaparin/UFH/fondaparinux)
- Adjunctive: high-intensity statin + ACEI/ARB (if EF < 40%/HF/HTN/DM)
- Risk stratification (GRACE score) determines invasive strategy timing: very high risk < 2h; high risk < 24h; intermediate < 72h; low risk = ischaemia-guided
- Ticagrelor preferred over clopidogrel in NSTE-ACS; prasugrel after defining coronary anatomy at PCI
- Never combine non-DHP CCB with beta-blocker (risk of heart block)
- Clopidogrel + PPI interaction → inhibits CYP2C19 activation → treatment failure; use pantoprazole (least interaction) if PPI needed
- Long-term secondary prevention: aspirin indefinitely, P2Y12 for 12 months, beta-blocker, ACEI/ARB, high-intensity statin, risk factor modification, cardiac rehabilitation
- PCI for simple anatomy (1-2VD); CABG for 3VD/LMS/complex disease
High Yield Summary
- The primary complication of UA is progression to MI — this is why UA is a medical emergency requiring immediate treatment
- Arrhythmias are the most common cause of death in first hours of ACS — especially VF (80% reversible if defibrillated promptly, 10% ↓survival per minute delay) — hence the need for continuous ECG monitoring
- Pump failure creates a vicious cycle: ↓systolic function → ↓coronary perfusion → ischaemia → further ↓function. Classified by Killip class (I–IV)
- Mechanical complications (VSD, acute MR, free wall rupture) occur if UA progresses to MI — timing is typically days 1–14 post-MI
- VSD: new PSM at RLSB + RV failure; Acute MR: new PSM at apex + APO — the clinical differentiation is important
- Free wall rupture: presents with sudden tamponade → PEA → death; incomplete rupture → pleuritic pain
- Ventricular aneurysm: persistent ST elevation + Q waves despite reperfusion; risk of mural thrombus → embolism
- Embolism: LV thrombus (wall motion abnormality/aneurysm) → stroke/limb ischaemia at 1–3 weeks; prevented by anticoagulation
- Treatment complications: stent thrombosis (acute, STEMI-like, prevented by DAPT), in-stent restenosis (chronic, stable angina-like, prevented by DES), bleeding from antithrombotic therapy
- Depression post-ACS is an independent mortality predictor — screen and treat