Chronic coronary syndrome is a long-term clinical condition characterized by stable atherosclerotic plaque and/or vasomotor dysfunction in the coronary arteries, causing episodic or persistent myocardial ischemia typically manifesting as exertional angina.

Chronic Coronary Syndrome (CCS)

Chronic Coronary Syndrome (CCS) — formerly and still commonly called Stable Ischaemic Heart Disease (SIHD) or Stable Angina — is the clinical entity that arises when there is a chronic mismatch between myocardial oxygen supply and demand, most commonly due to a fixed atherosclerotic stenosis of one or more epicardial coronary arteries ^[1]^[2].

Let's break down the name:

"Chronic" = a long-standing, stable process (as opposed to the acute plaque rupture/thrombosis of ACS)
"Coronary" = relating to the coronary arteries (from Latin corona = crown, because these arteries encircle the heart like a crown)
"Syndrome" = a collection of signs and symptoms that cluster together

The 2019 ESC Guidelines deliberately renamed "Stable CAD" to "Chronic Coronary Syndromes" (plural) to reflect the fact that this is not a single, static disease but rather a dynamic continuum of clinical scenarios that share the common pathophysiology of coronary atherosclerosis but differ in their risk profile and presentation ^[1].

The hallmark is angina pectoris provoked by exertion or emotional stress and relieved by rest or sublingual nitrate, implying that ischaemia only occurs when myocardial oxygen demand increases beyond what the fixed stenosis can supply. ^[1]^[2]

Key Conceptual Distinction

Think of it this way: in CCS, the plaque is stable with a thick fibrous cap → the lumen is narrowed but the plaque doesn't rupture → symptoms only appear when demand rises (exercise). In ACS, the plaque ruptures or erodes → thrombus forms → supply drops acutely even at rest. Both sit on the same atherosclerotic spectrum.

The Six Clinical Scenarios of CCS (ESC 2019)

The ESC 2019 guidelines define six clinical scenarios that fall under CCS ^[1]:

Patients with suspected CAD and stable anginal symptoms and/or dyspnoea — the "classic" presentation
Patients with new onset of heart failure or LV dysfunction suspected to be due to CAD
Patients with stabilised symptoms < 1 year after an ACS or recent revascularisation
Patients > 1 year after initial diagnosis or revascularisation
Patients with angina and suspected vasospastic or microvascular disease
Asymptomatic individuals in whom CAD is detected at screening

This is a paradigm shift from the old binary "stable vs unstable" model: a patient who had a STEMI 2 years ago and is now stable on optimal medical therapy is still classified under CCS scenario 4.

2. Epidemiology

Parameter	Detail
Prevalence of stable angina	~3–4% of the adult population in developed countries; higher in older age groups
Male : Female ratio	~2:1 before age 65; approaches 1:1 after age 75
Annual mortality of stable angina	1–3% per year (depends on anatomy and LV function)
Prognosis after diagnosis	Much better than ACS if optimally managed; 5-year survival > 90% in low-risk patients

3. Risk Factors

Risk factors for CCS are essentially risk factors for atherosclerosis — because coronary atherosclerosis is the underlying pathology in > 95% of cases.

Factor	Mechanism / Explanation
Advanced age	Cumulative vascular endothelial injury and oxidative stress over decades; longer exposure to risk factors ^[2]
Male sex	Oestrogen is vasoprotective (promotes NO release, ↓LDL oxidation, anti-inflammatory); males lack this protection. Post-menopausal females lose this advantage
Family history of premature CVD (1st-degree male relative < 55y, female < 65y)	Genetic predisposition to endothelial dysfunction, lipid metabolism disorders (e.g., familial hypercholesterolaemia), prothrombotic states ^[2]^[3]

Factor	Mechanism / Explanation
Cigarette smoking	Endothelial injury by free radicals, ↑LDL oxidation, ↓HDL, ↑platelet reactivity, ↑fibrinogen → accelerated atherosclerosis. Strong dose-response relationship. Risk drops significantly within 2–5 years of quitting ^[2]^[3]^[4]
Hypertension	↑Shear stress on arterial endothelium → endothelial dysfunction → promotes entry of lipoproteins into intima → accelerates atheroma formation. Also promotes left ventricular hypertrophy (LVH) → ↑myocardial O₂ demand ^[2]^[3]
Dyslipidaemia (↑LDL-C, ↓HDL-C, ↑TG)	LDL particles penetrate damaged endothelium → oxidised → taken up by macrophages → foam cells → fatty streak → atheroma. HDL is protective (reverse cholesterol transport). Target LDL-C < 1.4 mmol/L in very high-risk patients (ESC 2019) ^[3]^[4]
Diabetes mellitus	Hyperglycaemia → advanced glycation end-products (AGEs) → endothelial dysfunction, ↑oxidative stress, ↑inflammation. Also a/w dyslipidaemia (↑TG, ↓HDL, small dense LDL particles), prothrombotic state. DM doubles the risk of CAD and is a CHD risk equivalent ^[2]^[3]^[4]
Abdominal obesity / metabolic syndrome	Central adiposity → release of free fatty acids + pro-inflammatory adipokines (TNF-α, IL-6) → insulin resistance → dyslipidaemia, HTN, hyperglycaemia. The metabolic syndrome is a clustering of these risk factors ^[3]
Physical inactivity	↓AMPK activation → ↓glucose uptake, ↓fatty acid oxidation → contributes to obesity, insulin resistance, dyslipidaemia ^[3]
Chronic kidney disease (CKD)	Independent risk factor: ↑inflammatory state, uraemic toxins → endothelial dysfunction; ↑Ca × PO₄ product → medial vascular calcification; ↑prevalence of traditional risk factors ^[5]

INTERHEART Study Mnemonic

The 9 modifiable risk factors for MI (from the landmark INTERHEART study) can be remembered as: "SHAD FACED" — Smoking, Hypertension, Abdominal obesity, Diabetes, Fruit/veg intake (lack of), Alcohol excess, Cholesterol (ApoB/A ratio), Exercise (lack of), Depression/psychosocial factors. These account for > 90% of the population-attributable risk of MI globally.

Risk factors for CCS: modifiable — abdominal obesity, BP, cholesterol, cigarette smoking, diet, DM, lack of exercise. Non-modifiable — family Hx of CVD, male gender, advanced age. ^[2]

4. Anatomy and Function of the Coronary Arteries

Understanding coronary anatomy is essential because the location of the stenosis determines which territory is ischaemic and therefore which symptoms and ECG changes you will see.

The heart is supplied by two main coronary arteries arising from the aortic root (specifically the sinuses of Valsalva):

Artery	Major Branches	Territory Supplied
Left Main Stem (LMS)	Divides into LAD and LCx	Supplies ~75–80% of LV in left-dominant systems
Left Anterior Descending (LAD)	Diagonal branches, septal perforators	Anterior wall, anterior septum, apex of LV
Left Circumflex (LCx)	Obtuse marginal branches	Lateral wall, posterior wall (if left-dominant)
Right Coronary Artery (RCA)	Posterior descending artery (PDA), AV nodal branch	Inferior wall, posterior septum, RV, SA node (60%), AV node (80–90%)

5. Aetiology (with Hong Kong Focus) and Pathophysiology

5.1 Atherosclerosis — The Dominant Aetiology (> 95% of CCS)

The overwhelmingly dominant cause of CCS is coronary atherosclerosis ^[1]^[2]^[3].

The pathogenesis follows a well-characterised sequence from fatty streak → fibrous plaque → complicated plaque ^[6]:

Step 1: Endothelial Injury/Dysfunction

Risk factors (smoking, HTN, hyperglycaemia, shear stress, oxidised LDL) damage the vascular endothelium
Dysfunctional endothelium: ↓NO production, ↑adhesion molecule expression (VCAM-1, ICAM-1), ↑permeability to lipoproteins

Step 2: Lipid Accumulation and Oxidation

LDL particles enter the intima through the permeable endothelium
LDL is oxidised (oxLDL) in the subendothelial space → highly pro-inflammatory
OxLDL is chemotactic for monocytes and toxic to endothelium → perpetuates the cycle

Step 3: Inflammatory Cell Recruitment — Foam Cell Formation (Fatty Streak)

Monocytes adhere to endothelium → migrate into intima → differentiate into macrophages
Macrophages engulf oxLDL via scavenger receptors (no negative feedback, unlike LDL receptors) → become foam cells
Collection of foam cells = fatty streak (the earliest visible lesion, found even in teenagers)

Fatty streak → foam cell (intracellular cholesterol) → free (extracellular) cholesterol → months-years of progression → fibrous cap → plaque formation ^[6]

Step 4: Smooth Muscle Cell Migration and Fibrous Cap Formation

Growth factors (PDGF, TGF-β) from macrophages and endothelium stimulate smooth muscle cell (SMC) migration from media to intima
SMCs proliferate and produce extracellular matrix (collagen, elastin) → forms the fibrous cap over the lipid core
The mature plaque consists of: lipid/necrotic core + fibrous cap

Step 5: Stable Plaque vs Vulnerable Plaque

This is the critical fork in the road:

Feature	Stable Plaque (→ CCS)	Vulnerable Plaque (→ ACS)
Fibrous cap	Thick, collagen-rich	Thin, inflammation-rich
Lipid core	Small	Large
Inflammation	Less	Abundant macrophages (degrade cap via MMPs)
Lumen	Progressive fixed stenosis	May have minimal stenosis until rupture
Clinical result	Effort angina (supply-demand mismatch)	Plaque rupture → thrombus → ACS

In CCS, the stable plaque causes a fixed stenosis. Ischaemia only occurs when demand increases because at rest, compensatory mechanisms (collateral circulation, coronary vasodilation) maintain adequate flow. ^[2]

Step 6: Compensatory Remodelling (Glagov Phenomenon)

In early atherosclerosis, the artery undergoes outward (positive) remodelling — the vessel wall expands to accommodate the plaque so that the lumen size is preserved
Symptoms don't appear until the stenosis reaches approximately ≥ 70% luminal diameter (or ≥ 50% for LMS) — at this point, compensatory vasodilation is exhausted and flow becomes limited during stress

While atherosclerosis dominates, always consider:

Cause	Mechanism	Comment
Coronary vasospasm (Prinzmetal/variant angina)	Focal spasm of an epicardial coronary artery → transient severe stenosis/occlusion	Often at rest (classically early morning); a/w smoking; ST elevation during spasm
Coronary microvascular disease (Syndrome X)	Dysfunction of small coronary arteries (< 500 μm) → impaired microvascular vasodilation	More common in women; angina with ischaemic changes on stress testing but normal epicardial arteries on angiography
Aortic stenosis (AS)	↑LV pressure → ↑wall stress → ↑O₂ demand; also ↓coronary perfusion pressure gradient	Angina is one of the cardinal symptoms of severe AS, even without coronary disease
Hypertrophic cardiomyopathy (HCM/HOCM)	↑LV mass → ↑O₂ demand; ↑intramural pressure → ↓subendocardial perfusion; possible dynamic LVOT obstruction	Important cause of exertional chest pain in young patients
Severe anaemia	↓O₂ carrying capacity → ↓myocardial O₂ supply	May unmask underlying subclinical CAD
Thyrotoxicosis	↑HR + ↑contractility → ↑O₂ demand	May precipitate angina in patients with borderline coronary stenosis

Conditions that may exacerbate angina: anaemia, thyrotoxicosis ^[2]

6. Classification

The Canadian Cardiovascular Society (CCS) Functional Classification is used to grade the severity of stable angina:

CCS Grade	Activity Triggering Angina	Example
Class I	Ordinary physical activity does NOT cause angina; angina only with strenuous, rapid, or prolonged exertion	Running, heavy lifting
Class II	Slight limitation of ordinary activity; angina with walking > 2 blocks or climbing > 1 flight of stairs at normal pace	Walking uphill, after meals, in cold, emotional stress
Class III	Marked limitation of ordinary activity; angina with walking 1–2 blocks or climbing 1 flight of stairs	Flat ground walking at normal pace
Class IV	Unable to carry on any physical activity without angina; angina may be present at rest	Minimal activity or rest

CCS Class III or IV = clinically severe angina → indication for invasive coronary angiography for risk stratification ^[2]

CCS vs NYHA

CCS grades angina severity. NYHA grades heart failure severity. Don't confuse them. CCS is about chest pain, NYHA is about dyspnoea/fatigue. However, both broadly indicate functional limitation.

Type	Mechanism	Example
Fixed epicardial stenosis	Atherosclerotic plaque → demand-related ischaemia	Classic CCS
Dynamic epicardial stenosis	Coronary vasospasm ± atherosclerosis	Vasospastic angina (Prinzmetal)
Microvascular dysfunction	Impaired vasodilation of small coronary vessels	Microvascular angina (Syndrome X)
Non-coronary supply-demand mismatch	↑Demand (AS, HOCM, HTN) or ↓Supply (anaemia, hypoxia)	Secondary angina

7. Clinical Features

7.1 Symptoms

Angina pectoris: symptom complex arising from myocardial ischaemia ^[2]

The ESC defines typical angina as meeting all three criteria:

Substernal chest discomfort of characteristic quality and duration
Provoked by exertion or emotional stress
Relieved by rest and/or sublingual nitrate within 5 minutes

Atypical angina = 2 of 3 criteria
Non-anginal chest pain = ≤ 1 of 3 criteria

Let's unpack each feature using OPQRST:

Feature	Typical Angina	Pathophysiological Basis
Onset / Provocation	Builds up gradually in proportion to intensity of exertion; also provoked by emotional stress, cold exposure, heavy meals	Exertion → ↑HR, ↑BP, ↑contractility → ↑O₂ demand → demand exceeds supply at the fixed stenosis. Cold → sympathetic activation → coronary vasoconstriction + ↑afterload. Meals → ↑splanchnic blood flow → coronary steal
Quality	Typically dull, constricting, choking, 'heavy'. Described as squeezing, crushing, burning, aching or even as breathlessness. Patients often emphasise it is a discomfort not a pain. Levine's sign: characteristic gesture of a clenched fist on chest	Visceral pain from the heart is poorly localised and often described in vague terms; it is not sharp or stabbing (which would suggest somatic/parietal pain)
Region / Radiation	Retrosternal chest discomfort ± radiation to arms (especially left), shoulder, jaw, neck, epigastrium	Referred pain via cardiac sympathetic afferents entering spinal cord at T1–T5 (convergence-projection theory)
Severity	Variable, but consistently reproducible at a similar workload (the "angina threshold")	The stenosis is fixed → the workload at which demand exceeds supply is predictable
Timing / Duration	< 30 minutes (typically 2–10 minutes)	Stopping exertion → demand drops → supply catches up → ischaemia resolves → pain resolves. If > 30 min, think ACS
Termination	Relieved by rest or sublingual nitrate ≤ 5 minutes	Rest → ↓demand. GTN → coronary vasodilation + venodilation (↓preload) → ↓demand + ↑supply

Important

Angina that is recent-onset, rapidly worsening (crescendo), or occurring at rest = UNSTABLE ANGINA → ACS until proven otherwise! Do not classify this as CCS. A change in pattern is an alarm sign that a previously stable plaque has become complicated.

7.2 Signs

Physical examination in CCS is frequently unremarkable — and that itself is a teaching point. The stable plaque causes no detectable physical signs unless there is underlying structural heart disease, LV dysfunction, or generalised atherosclerosis ^[2].

However, a systematic examination may reveal:

Sign	What It Tells You	Mechanism
Xanthelasma (yellowish plaques around eyes)	Dyslipidaemia (but may be non-specific in older patients)	Lipid deposition in skin
Corneal arcus (grey-white ring at corneal periphery)	Dyslipidaemia (especially if < 50 years)	Lipid deposition in corneal stroma
Tendon xanthomas (Achilles, extensor tendons of hands)	Familial hypercholesterolaemia	Cholesterol deposition in tendons — pathognomonic for FH
Eruptive xanthomas	Severe hypertriglyceridaemia	TG-rich lipoproteins deposited in skin
Acanthosis nigricans	Insulin resistance / metabolic syndrome	Insulin/IGF-1 stimulation of keratinocyte proliferation
↑BMI / central obesity	Metabolic syndrome	Adiposity → insulin resistance
Nicotine staining of fingers	Active smoking	Direct evidence

Sign	What It Tells You	Mechanism
Cardiac murmurs	May be due to valvular heart disease or HOCM — conditions that cause secondary angina ^[2]	AS murmur (ejection systolic) → ↑afterload → ↑O₂ demand; AR murmur → ↓diastolic BP → ↓coronary perfusion
Dyskinetic apex beat	LV dysfunction — suggests previous MI with LV remodelling ^[2]	Scarred/thinned myocardium → paradoxical outward movement during systole
Gallop rhythm (S3 or S4)	LV dysfunction or impaired compliance ^[2]	S3 = rapid ventricular filling into dilated LV (systolic dysfunction). S4 = atrial contraction against stiff, non-compliant LV (diastolic dysfunction, LVH)
Displaced apex beat	LV dilatation from chronic ischaemic cardiomyopathy	Chronic ischaemia → myocardial fibrosis → LV remodelling/dilatation

Sign	What It Tells You	Mechanism
Carotid bruit	Carotid artery stenosis — indicates generalised atherosclerosis ^[2]	Turbulent flow through narrowed carotid → audible bruit. These patients have a high likelihood of concomitant CAD
Signs of peripheral vascular disease (PVD)	Generalised atherosclerosis ^[2]	Absent or diminished peripheral pulses, skin changes (hair loss, shiny skin, ulceration), intermittent claudication on history
Abdominal aortic aneurysm (pulsatile expansile mass)	Atherosclerotic aortic disease	Atherosclerosis weakens aortic wall → aneurysmal dilatation

"Presence of all peripheral pulses" should be documented ^[2] — this is both a positive finding (reassuring) and a reminder to check.

Sign	Condition	Why It Worsens Angina
Pallor, tachycardia, flow murmur	Anaemia ^[2]	↓O₂ carrying capacity → ↓myocardial O₂ supply
Tremor, tachycardia, goitre, lid lag	Thyrotoxicosis ^[2]	↑metabolic rate → ↑HR → ↑contractility → ↑O₂ demand
Hypertension (↑BP on measurement)	HTN	↑Afterload → ↑wall stress → ↑O₂ demand

Clinical Pearl

Always check for precipitating/exacerbating factors in a patient with angina. If you find and treat severe anaemia or thyrotoxicosis, the angina may resolve without any coronary intervention. This is an easy win that examiners love to test.

The ESC 2019 guidelines use a clinical likelihood model (updated from the old Diamond-Forrester model which overestimated PTP) to estimate the probability of obstructive CAD based on: ^[1]

Factors that DECREASE clinical likelihood:

Normal exercise ECG
Absence of coronary calcium (Agatston score = 0)

Factors that INCREASE clinical likelihood:

Risk factors for CVD (dyslipidaemia, diabetes, hypertension, smoking, family history)
Changes on resting ECG (Q-waves, ST-segment/T-wave changes)
LV dysfunction suggestive of CAD
Abnormal exercise ECG
Coronary calcium on CT

In addition to the classic Diamond and Forrester classes, patients with dyspnoea only or dyspnoea as the primary symptom are included. ^[1]

Pre-Test Probability	Interpretation	Next Step
< 5% (very low)	CAD can generally be excluded	No further testing needed
5–15% (low)	Consider testing only if clinical features suggest CAD	Consider CT coronary angiography or functional testing
15–85% (intermediate)	Offer diagnostic testing	CTCA or functional ischaemia testing
> 85% (very high)	CAD can be assumed	May proceed directly to invasive coronary angiography

8. Important Pathophysiological Concepts — Synthesis

Glyceryl trinitrate (GTN, sublingual nitrate):

Venodilation (dominant effect at low doses) → ↓preload → ↓LVEDV → ↓wall stress → ↓O₂ demand
Coronary vasodilation → ↑supply (especially to ischaemic zones via collateral recruitment)
Arteriolar dilation (at higher doses) → ↓afterload → ↓O₂ demand
Net effect: relief of ischaemia within 1–3 minutes

High Yield Summary

Definition: CCS (formerly stable angina/SIHD) = chronic supply-demand mismatch, most commonly due to fixed coronary atherosclerotic stenosis. ESC 2019 recognises 6 clinical scenarios.

Epidemiology: Leading cause of death globally and in HK. More common in males, incidence rises with age.

Risk Factors: Non-modifiable (age, male sex, family Hx). Modifiable (smoking, HTN, DM, dyslipidaemia, obesity, physical inactivity). Remember INTERHEART "SHAD FACED."

Pathophysiology: Atherosclerosis → stable plaque with thick fibrous cap → fixed stenosis → ischaemia on exertion. Haemodynamically significant = ≥50% diameter stenosis. Symptomatic typically at ≥70%.

Ischaemic cascade: Subendocardial ischaemia → diastolic dysfunction → RWMA → ST changes → anginal pain (pain is the LAST thing to appear).

Angina pectoris: Retrosternal, dull/constricting, < 30 min, provoked by exertion/emotion, relieved by rest/GTN within 5 min. Radiation to arms/jaw/neck. Levine's sign.

Examination: Often normal! Look for: risk factor signs (xanthomas, arcus, obesity), cardiac disease (murmurs, gallop, displaced apex), generalised atherosclerosis (carotid bruit, PVD), and exacerbating conditions (anaemia, thyrotoxicosis).

Clinical likelihood (ESC 2019): Updated PTP model incorporating risk factors, resting ECG changes, coronary calcium, exercise ECG → guides whether testing is needed and which test to choose.

Active Recall - Chronic Coronary Syndrome (Definition to Clinical Features)

Differential Diagnosis of Chronic Coronary Syndrome

The main differentials for stable chest pain are divided into potentially severe and benign ^[2]^[8]:

Potentially Severe	Relatively Benign
Stable ischaemic heart disease	GERD and other oesophageal pathologies
Subacute/chronic pulmonary embolism	Musculoskeletal pain
Malignancy with pleural/chest wall involvement	Psychogenic chest pain
Pulmonary hypertension	Herpes zoster

Now let's expand this comprehensively, system by system, and explain why each condition can mimic CCS and how to distinguish it.

A. Cardiac Causes (Non-CCS) That Mimic Exertional Chest Pain

The single most important distinction you must make is CCS versus ACS. ^[2]

Feature	CCS (Stable Angina)	ACS (Unstable Angina / MI)
Pattern	Predictable, at a reproducible workload	New-onset, crescendo, or at rest ^[9]
Duration	< 2–10 min ^[2]	> 20–30 min, not relieved by rest ^[2]
Response to GTN	Relieved ≤ 5 min ^[2]	Often NOT relieved
Troponin	Normal	Elevated in NSTEMI/STEMI
ECG	May be normal or have chronic changes	Dynamic ST changes, new T-wave inversion, ST elevation
Autonomic features	Usually absent	Diaphoresis, N/V may occur ^[2]

Why ACS can be confused with CCS: A patient with known stable angina who develops a change in pattern (lower threshold, rest pain, prolonged episodes) is transitioning from CCS to ACS — the plaque has become unstable. This is "accelerating angina" and is a medical emergency ^[9].

Features suggesting onset of ACS over usual stable angina: (1) Angina at rest — prolonged > 20 min, (2) New-onset angina — at least CCS II, (3) Increasing angina — previous angina with ↑frequency, ↑duration, or ↓threshold to ≥ CCS III severity, (4) Post-infarct angina — recurrent angina after recent MI ^[9]

B. Vascular Causes

C. Gastrointestinal Causes

Gastrointestinal causes account for up to 42% of chest pain presentations in some series ^[6].

D. Musculoskeletal Causes

E. Respiratory Causes

F. Psychiatric / Other

Diagnosis	Character of Pain	Provocation	Duration	Key Distinguishing Feature
CCS (stable angina)	Dull, constricting	Exertion, emotion	2–10 min, relieved by rest/GTN	Predictable threshold, ECG ischaemia on stress test
ACS	Crushing, severe	Rest or minimal exertion	> 20 min, NOT relieved	↑Troponin, dynamic ECG changes
Aortic stenosis	Exertional angina-like	Exertion	Variable	Ejection systolic murmur, slow-rising pulse
HCM	Exertional angina-like	Exertion, Valsalva	Variable	Young patient, FHx sudden death, murmur ↑ with Valsalva
Vasospastic angina	Angina-like	Rest (early AM)	Minutes	Transient ST elevation, normal coronaries
Microvascular angina	Angina-like	Exertion	May be prolonged	Normal angiogram, ↓CFR
Aortic dissection	Tearing, severe	Sudden onset at rest	Persistent	Max at onset, BP asymmetry, widened mediastinum
PE	Pleuritic or crushing	Sudden onset	Persistent	Pleuritic, dyspnoea, DVT signs, D-dimer, CTPA
Pulmonary HTN	Exertional discomfort	Exertion	Variable	Loud P2, RV heave, signs of RHF
GERD	Burning	Lying down, meals	Minutes–hours	Relieved by antacids/PPI, no ECG changes
Oesophageal spasm	Crushing	Swallowing	Minutes	May respond to GTN (pitfall!), manometry diagnostic
Costochondritis	Sharp, localised	Palpation, movement	Variable	Reproducible on palpation
Panic disorder	Atypical, diffuse	Stress, not exertion	Minutes–hours	Hyperventilation, paraesthesias, diagnosis of exclusion
Takotsubo	Angina-like	Emotional/physical stress	Prolonged	Post-menopausal women, apical ballooning, no CAD

Always re-evaluate if a patient labelled with "stable angina" develops any of the following:

Red Flag	Think...
Pain at rest, > 20 min, not relieved by GTN	ACS (plaque rupture/erosion)
Sudden onset, maximal severity immediately	Aortic dissection, PE, pneumothorax
Associated with syncope/presyncope	ACS with arrhythmia, massive PE, severe AS, HOCM with LVOTO
Haemodynamic instability (↓BP, ↑HR, cool peripheries)	Massive PE, ACS with cardiogenic shock
New murmur	VSD (post-MI complication), acute AR (dissection), rupture of papillary muscle
Unilateral leg swelling + chest pain	PE from DVT

If you suspect ACS: admit CCU, bed rest, continuous ECG monitoring, 12-lead ECG stat, serial troponins, and initiate anti-ischaemic + antithrombotic therapy while awaiting results. ^[8]

High Yield Summary — DDx of CCS

The most important distinction is CCS vs ACS — change in pattern (rest pain, crescendo, prolonged > 20 min) = ACS until proven otherwise.
Cardiac non-CCS mimics: AS, HOCM (exertional angina from ↑O₂ demand), vasospastic angina (rest pain, ST elevation), microvascular angina (normal angiogram), myopericarditis (pleuritic, diffuse ST changes), Takotsubo (emotional trigger, apical ballooning).
Vascular mimics: Aortic dissection (tearing, sudden max onset, back), chronic PE (pleuritic + dyspnoea + VTE risk factors), pulmonary HTN (exertional dyspnoea + RHF signs).
GI mimics (commonest non-cardiac cause — 42%): GERD (burning, postural, antacid-responsive), oesophageal spasm (may respond to GTN — exam pitfall!), PUD, cholecystitis.
MSK (28%): Costochondritis — reproducible on palpation, not truly exertional.
Psychiatric: Panic disorder — diagnosis of exclusion, pain often atypical and after (not during) exertion.
Don't forget precipitants: Anaemia and thyrotoxicosis can unmask subclinical CAD or cause demand ischaemia → always check CBC and TFT.

Active Recall - Differential Diagnosis of CCS

References

^[2] Senior notes: Ryan Ho Cardiology.pdf (p54–58: Angina pectoris, OPQRST, Other causes of chest pain, Clinical approach to stable and acute chest pain) ^[6] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p16–17: Differential diagnosis of ACS table, frequency of chest pain aetiologies) ^[8] Senior notes: Ryan Ho Fundamentals.pdf (p199–203: Chest pain approach, DDx tables for stable and acute chest pain) ^[9] Senior notes: Ryan Ho Cardiology.pdf (p128: Clinical features of ACS — distinguishing from stable angina) ^[10] Senior notes: felixlai.md (Aortic dissection: CXR findings, CT angiography) ^[11] Senior notes: Ryan Ho Haemtology.pdf (p131: VTE clinical features, DVT/PE DDx) ^[12] Senior notes: Ryan Ho Respiratory.pdf (p138–139: Pulmonary hypertension classification, clinical features) ^[13] Senior notes: Ryan Ho Respiratory.pdf (p98, p111: Asthma DDx, COPD DDx)

Diagnostic Criteria, Diagnostic Algorithm, and Investigation Modalities for Chronic Coronary Syndrome

STEP 1: Clinical Assessment — Establishing Clinical Likelihood of CAD

Diagnosis based on history alone may be difficult → generally divided into ^[2]^[8]:

Category	Definition	Criteria met
Typical angina	Substernal discomfort of characteristic quality + provoked by exertion/emotion + relieved by rest or GTN ≤ 5 min	3 of 3
Atypical angina	Meets two of the three criteria above	2 of 3
Non-anginal chest pain	Meets one or none of the three criteria	≤ 1 of 3

The ESC 2019 updated PTP table replaces the old Diamond-Forrester model (which overestimated CAD prevalence). PTP is estimated from age, sex, and nature of symptoms (typical, atypical, non-anginal, dyspnoea only) ^[1]:

In addition to the classic Diamond and Forrester classes, patients with dyspnoea only or dyspnoea as the primary symptom are included. ^[1]

Age	Typical angina (M/F)	Atypical angina (M/F)	Non-anginal (M/F)	Dyspnoea only (M/F)
30–39	3% / 5%	4% / 3%	1% / 1%	0% / 3%
40–49	22% / 10%	10% / 6%	3% / 2%	12% / 3%
50–59	32% / 13%	17% / 6%	11% / 3%	20% / 7%
60–69	44% / 16%	26% / 11%	22% / 6%	27% / 14%
70+	52% / 27%	34% / 19%	24% / 10%	32% / 12%

Shaded cells with PTP < 5% → CAD can generally be excluded without further testing. PTP 5–15% → testing may be considered if clinical features favour CAD. PTP > 15% → offer diagnostic testing. PTP > 85% → CAD can be assumed; proceed to risk stratification/management.

STEP 2: Baseline Investigations

These are done for every patient with suspected CCS, regardless of PTP. Their purpose is threefold: (a) detect evidence of ischaemia/prior MI, (b) assess risk factors and comorbidities, (c) evaluate LV function ^[2]^[8].

Test	Purpose	Key Findings
CBC	Detect anaemia (↓Hb → ↓O₂ supply → exacerbates angina)	Hb < 10 g/dL may cause demand ischaemia even in mild stenosis
HbA1c	Screen for/monitor DM — a major risk factor and affects prognosis	≥ 6.5% = DM; target < 7% in established CAD
Fasting lipid profile	Assess dyslipidaemia — drives treatment target	LDL-C is the key target: < 1.4 mmol/L for very high-risk patients (ESC 2019)
TFT	Detect thyrotoxicosis (↑O₂ demand) or hypothyroidism (2° dyslipidaemia)	TSH is the screening test
Renal function (Cr, eGFR)	CKD is an independent CVD risk factor; also impacts contrast/drug dosing	eGFR < 60 → ↑CVD risk, caution with contrast/metformin
Fasting glucose	Screen for DM/pre-diabetes

Basic blood tests: CBC, HbA1c, lipid profile, TFT ^[2]^[8]

The baseline ECG is mandatory in every patient with suspected CCS. It may be normal in up to 50% of patients with CCS, but abnormalities carry diagnostic and prognostic significance ^[2]^[8]:

Finding	Significance	Mechanism
Pathological Q waves	Evidence of previous MI — implies established CAD	Transmural necrosis → loss of electrical vectors → Q waves in leads facing the infarct
LBBB	May indicate prior extensive anterior MI (LAD territory) or cardiomyopathy; masks ischaemic ST changes	Disruption of the left bundle conduction → altered depolarisation sequence
ST-segment/T-wave changes	Evidence of ischaemia — ST depression/T inversion at rest suggests significant CAD	Ongoing subendocardial ischaemia at rest implies severe stenosis or microvascular disease
LVH	Suggests long-standing HTN → ↑O₂ demand; also reduces specificity of stress testing (false positive ST changes from repolarisation abnormality)	Increased LV mass → altered repolarisation
Pre-excitation (WPW)	May cause chest pain mimicking angina (SVT episodes); also invalidates stress ECG interpretation	Accessory pathway conducts abnormally → altered baseline ST/T
Arrhythmias, AF	AF → ↑HR → ↑demand; also a source of cardioembolism

Baseline 12-lead ECG: evidence of ischaemia or previous MI (pathological Q, LBBB, ST/T changes); other evidence of cardiac disease (LVH, pre-excitation, arrhythmias, AF) ^[2]^[8]

This is where understanding the principles of diagnostic testing is critical. There are two broad categories of tests:

Category	What It Detects	Examples	Advantage	Limitation
Anatomical tests	Physical narrowing of coronary arteries	CT coronary angiography (CTCA), invasive coronary angiography (ICA)	Directly visualises stenosis; excellent NPV (CTCA)	May detect anatomically significant but haemodynamically insignificant stenosis (50–70% range)
Functional tests	Haemodynamic consequence of stenosis (ischaemia)	ETT, stress echo, stress CMR, SPECT-MPI, PET	Detects physiologically significant disease; better correlation with symptoms	May miss non-obstructive disease; lower spatial resolution

Choice of the test based on clinical likelihood, patient characteristics and preference, availability, as well as local expertise ^[1]

The ESC 2019 Diagnostic Approach

The ESC 2019 algorithm can be summarised in six steps ^[1]:

Step 1–2: Clinical assessment → Assess symptoms and risk factors Step 3: Estimate clinical likelihood of obstructive CAD using PTP table + modifiers Step 4: If very low ( < 5%) → generally no further testing needed; if very high ( > 85%) → assume CAD, consider ICA directly Step 5: Offer diagnostic testing →

Coronary CTA (preferred first-line in most patients)
Testing for ischaemia (imaging testing preferred) — stress echo, stress CMR, SPECT, PET

Step 6: Choose appropriate therapy based on symptoms and event risk ^[1]

High clinical likelihood and symptoms inadequately responding to medical treatment, high event risk based on clinical evaluation (such as ST-segment depression, combined with symptoms at a low workload or systolic dysfunction indicating CAD), or uncertain diagnosis on non-invasive testing → invasive coronary angiography ^[1]

Functional imaging for myocardial ischaemia if coronary CTA has shown CAD of uncertain grade or is non-diagnostic ^[1]

Consider also angina without obstructive disease in the epicardial coronary arteries (vasospastic or microvascular angina) ^[1]

STEP 3 (Detailed): Investigation Modalities

What it is: Patient exercises on a treadmill or bicycle ergometer following a standardised protocol (e.g. Bruce protocol) while continuous 12-lead ECG, BP, and symptoms are monitored ^[2].

Principle: Exercise → ↑HR, ↑BP, ↑contractility → ↑myocardial O₂ demand → if fixed stenosis exists, supply cannot match demand → subendocardial ischaemia → ST depression on ECG.

Positive test defined as horizontal or downsloping ST depression of ≥ 0.1 mV (1 mm) 80 ms after J point during exercise ^[2]

Aspect	Detail
Best for	Low-intermediate PTP (15–65%); normal baseline ECG; not on anti-ischaemic drugs ^[2]
NOT suitable for	Abnormal baseline ECG (LBBB, paced rhythm, WPW, AF, LVH, digoxin); limited exercise tolerance (unable to reach 85% max predicted HR) due to non-cardiac disease ^[2]
Sensitivity	~68% (modest)
Specificity	~77% (modest)
Advantages	Cheap, widely available, provides functional capacity data, prognostic information
Limitations	Cannot localise ischaemia to a territory; cannot be used if baseline ECG is abnormal; lower diagnostic accuracy than imaging tests

Why 85% max HR matters: If the patient doesn't reach an adequate heart rate, the test is "non-diagnostic" (submaximal) — you haven't stressed the heart enough to unmask ischaemia. Max predicted HR ≈ 220 − age.

Additional prognostic parameters from ETT:

Exercise capacity (in METs) — the strongest prognostic variable from ETT; poor exercise capacity ( < 5 METs) predicts poor outcome
BP response — failure of BP to rise or a fall in BP during exercise suggests severe CAD (failing LV cannot augment CO)
Chronotropic incompetence — failure to reach 85% max HR
Duke Treadmill Score = exercise time (min) − (5 × max ST deviation in mm) − (4 × angina index). Score ≤ −11 = high risk; ≥ +5 = low risk

Why Can't You Use ETT with LBBB?

In LBBB, the septum depolarises abnormally (right→left instead of left→right). This produces baseline ST-T changes that mimic ischaemia, making it impossible to interpret exercise-induced ST changes. The same applies to paced rhythms, WPW, and LVH with repolarisation abnormality. These patients need imaging-based stress testing instead.

What it is: ECG-gated contrast-enhanced CT providing high-resolution 3D images of the coronary arteries ^[2]^[7]^[14].

Principle: Iodinated contrast opacifies the coronary lumen → CT detects anatomical stenosis, plaque morphology, and calcification.

Aspect	Detail
Best for	Low-intermediate PTP (15–50%); adequate breath-holding; HR ≤ 65 bpm; Agatston calcium score < 400; younger individuals; LVH (where stress testing specificity is reduced) ^[2]
NOT suitable for	Severe obesity (poor image quality); CKD (contrast nephropathy risk); prior CABG (metallic clips degrade image); prior stenting (metal artefact); asymptomatic screening ^[2]
Significant stenosis	≥ 70% stenosis (or ≥ 50% for LMS) ^[2]
Sensitivity	95–99%
Specificity	64–83% (lower in heavily calcified vessels)
Key strength	Excellent negative predictive value (NPV) of 99–100% → especially suitable for those with low-intermediate PTP ^[2] — if CTCA is normal, you can essentially rule out obstructive CAD
Key limitation	Overestimates stenosis severity in calcified vessels; cannot tell you if a 60% stenosis is haemodynamically significant

CT Calcium Scoring (Agatston Score):

CT calcification (Agatston) score: no need for contrast. Coronary calcium content is exclusively due to coronary atherosclerosis except in renal failure patients (a/w medial calcification). Quantification: > 130 HU pixels regarded as calcium, Agatston score > 100 generally correlated with significant risk of CAD. Caveat: poor correlation with degree of luminal stenosis → zero calcium score cannot be used to rule out coronary artery stenoses in symptomatic individuals. Role: ↑Ca score a/w ↓specificity of CTA → NOT interpret CTA with Agatston > 400 ^[2]

Agatston score = 0 → decreases clinical likelihood of CAD ^[1] (it's a modifier, not a standalone diagnostic tool)
Agatston > 400 → CTCA becomes unreliable (calcification artefacts) → consider functional testing or ICA instead

C. Stress Imaging Tests

When the patient cannot exercise, has an abnormal baseline ECG, or when you need to localise ischaemia to a specific territory, stress imaging is preferred. All stress imaging modalities share the same principle: compare myocardial perfusion or function at rest vs stress to detect ischaemia.

Once CAD is confirmed, the next question is: "How dangerous is this?" This determines whether the patient needs revascularisation (PCI/CABG) in addition to medical therapy, or whether optimal medical therapy (OMT) alone is sufficient.

Risk stratification for all-cause mortality in all diagnosed CAD patients → guide need of revascularization ^[2]:

Risk Category	Annual Mortality	Management
High risk	≥ 3%/year	OMT + invasive coronary angiography ± revascularization
Intermediate risk	≥ 1% but < 3%/year	OMT + consider ICA based on comorbidities and patient preferences
Low risk	< 1%/year	Trial of OMT only

Prognostic factors ^[2]:

Factor	Detail
Clinical evaluation	S/S of HF, pattern and severity of angina. Poor prognosis in recent onset or unstable, poor exercise tolerance. Clinical risk factors: CKD, PVD, prior MI, current smoking, background HTN. Baseline investigations: old infarct on ECG, diabetes, ↑total cholesterol
LVEF	Strongest predictor of long-term survival. LVEF < 50% a/w ↑↑ event risk regardless of severity of ischaemia. Baseline echocardiography recommended for all patients
Stress testing	Exercise ECG: exercise capacity, BP response, exercise-induced ischaemia, Duke score. Stress imaging: High risk = area of ischaemia > 10%; Intermediate = 1–10%; Low = no ischaemia
Coronary anatomy	Number of vessels: mortality 1VD < 2VD < 3VD < LMS disease

Modality	Type	Sensitivity	Specificity	NPV	Best For	Contraindications/Limitations
ETT	Functional	~68%	~77%	~85%	Low-intermediate PTP, normal ECG, able to exercise	Abnormal baseline ECG, cannot exercise
CTCA	Anatomical	95–99%	64–83%	99–100%	Low-intermediate PTP, rule-out	Heavy calcification, CKD, prior stents/CABG
Stress Echo	Functional	80–85%	80–88%	~90%	Cannot exercise or abnormal ECG; available bedside	Poor acoustic windows, operator-dependent
SPECT-MPI	Functional	82–88%	70–88%	~90%	Intermediate-high PTP, risk stratification, viability	Radiation, attenuation artefacts, balanced ischaemia may give false negative
Stress CMR	Functional	86–91%	81–91%	~92%	High diagnostic accuracy, scar assessment	Expensive, limited access, metallic implants
PET	Functional	90–95%	85–90%	~95%	Highest accuracy, quantitative flow	Very expensive, limited tracer availability
ICA	Anatomical (gold standard)	Reference	Reference	–	High risk, failed non-invasive, pre-revascularisation	Invasive, risks (access site, stroke, MI)
ICA + FFR/iFR	Anatomical + Functional	–	–	–	Uncertain lesion significance (50–70%)	Additional cost, adenosine may cause AV block

The Key Teaching Point on Test Selection

CTCA is best when you want to RULE OUT CAD (excellent NPV in low-intermediate PTP). Functional imaging is best when you want to CONFIRM ISCHAEMIA (especially to guide revascularisation decisions — an anatomical stenosis without functional significance does not benefit from stenting). ICA is reserved for when non-invasive testing is inconclusive, the patient is high-risk, or you are planning revascularisation.

Special Scenarios in Diagnosis

Definition: evidence of MI with normal or near-normal coronary findings (≤ 50% stenosis on angiography) ^[2]
Workup: echo, cardiac MRI, coronary angiography with provocative testing, endomyocardial biopsy, thrombophilia screen ^[2]
Cardiac MRI is particularly valuable: LGE pattern distinguishes ischaemic (subendocardial) from non-ischaemic (mid-wall/epicardial) causes such as myocarditis

High Yield Summary — Diagnostic Approach to CCS

Step 1: Clinical assessment — classify angina as typical/atypical/non-anginal; estimate PTP using age, sex, symptoms.

Step 2: Baseline investigations for ALL patients — blood tests (CBC, HbA1c, lipids, TFT, RFT), resting ECG, resting echo (LVEF is strongest prognostic predictor), ± CXR.

Step 3: Choose diagnostic test based on PTP:

Very low PTP ( < 5%) → no testing, consider alternative Dx
Low-intermediate PTP → CTCA (excellent rule-out, NPV 99–100%) or functional testing
Intermediate-high PTP → Functional imaging (stress echo, SPECT, CMR, PET) preferred
Very high PTP or high risk → ICA ± FFR

Step 4: Risk stratify — high risk (≥ 3%/yr) → OMT + revasc; intermediate → OMT ± ICA; low ( < 1%/yr) → OMT alone.

Key prognostic factors: LVEF (strongest), stress test result (area of ischaemia > 10% = high risk), coronary anatomy (1VD < 2VD < 3VD < LMS), clinical features (HF, CKD, PVD, prior MI).

ETT: Only if normal baseline ECG + can exercise. Positive = ≥ 1 mm ST depression. Cannot localise ischaemia.

CTCA: Excellent NPV. Not for calcified vessels (Agatston > 400), stents, or CABG.

MPI (SPECT/PET): Based on coronary steal. Reversible defect = ischaemia; fixed defect = infarct.

ICA: Gold standard. Reserved for high-risk, failed non-invasive, or pre-revascularisation. FFR < 0.80 = significant.

Active Recall - Diagnosis of CCS

References

^[1] Lecture slides: GC 032. Chest pain on exertion_ischaemic heart disease; angina pectoris.pdf (ESC 2019 PTP table, clinical likelihood modifiers, diagnostic approach steps 1–6) ^[2] Senior notes: Ryan Ho Cardiology.pdf (p54–58, p115–120: Roadmap to stable IHD, baseline ECG, CTCA, ETT, stress imaging interpretation, prognostic factors, risk stratification, ICA indications) ^[7] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p43, p57: CT angiography, MPI principle, coronary steal, radiopharmaceuticals, interpretation) ^[8] Senior notes: Ryan Ho Fundamentals.pdf (p199–203: Clinical approach to chest pain, baseline investigations) ^[14] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p43: Cardiac CT, calcium scoring, coronary CTA)

Management of Chronic Coronary Syndrome

PILLAR 1: Lifestyle Modification and Risk Factor Control

This is the unglamorous but most impactful part of management. Every patient with CCS must receive this, and you should be able to explain why each recommendation matters.

General measures: lifestyle — stop smoking, regular exercise (but not beyond point of discomfort). Treat precipitating factors: thyrotoxicosis, anaemia. Manage risk factors. ^[2]

Lipids: ↓LDL to < 1.8 mmol/L with lifestyle and drug ^[2]

Statins are recommended in all patients. The aim is to reduce LDL-C by ≥ 50% from baseline and to achieve LDL-C < 1.4 mmol/L (< 55 mg/dL) for very high-risk patients ^[1]^[15]

If the LDL-C goal is not achieved after 4–6 weeks with the maximally tolerated statin dose, combination with ezetimibe is recommended ^[15]

If the LDL-C goal is not achieved after 4–6 weeks despite maximally tolerated statin therapy and ezetimibe, the addition of a PCSK9 inhibitor is recommended ^[15]

The lipid-lowering escalation ladder:

High-intensity statin (1st line): atorvastatin 40–80 mg or rosuvastatin 20–40 mg ^[3]
Ezetimibe (2nd line): if LDL-C target not met → add ezetimibe 10 mg daily
PCSK9 inhibitor (3rd line): evolocumab or alirocumab SC injection if still not at target

Statin	High Intensity (≥ 50% ↓LDL)	Moderate Intensity (30-49% ↓LDL)	Low Intensity ( < 30% ↓LDL)
Simvastatin	(80 mg — rarely used due to myopathy risk)	20–80 mg	10 mg
Atorvastatin	40 mg	10–40 mg	—
Rosuvastatin	40 mg	10–40 mg	—

PILLAR 2: Pharmacological Therapy

Part A: Prognostic Drugs (Reduce MI and Death)

These are prescribed to all patients with confirmed CCS regardless of symptoms.

Aspirin is recommended for all patients without contraindications at a dose of 75–100 mg daily ^[2]^[15]^[16]

Drug	Mechanism	Dose	Indications	Contraindications
Aspirin	Irreversibly inhibits COX-1 → ↓TXA₂ → ↓platelet aggregation	75–100 mg daily (low dose)	All patients with CAD indefinitely ^[2]	Active GI bleeding, aspirin allergy, severe asthma (aspirin-exacerbated respiratory disease)
Clopidogrel (Plavix)	Irreversibly blocks P2Y₁₂ ADP receptor → ↓platelet activation	75 mg daily	Equally/more effective; used as alternative to aspirin if intolerant ^[2]	Active bleeding, severe hepatic impairment

Clopidogrel 75 mg daily when aspirin is not tolerated because of hypersensitivity or GI intolerance ^[15]^[16]

Why not dual antiplatelet therapy (DAPT) in stable CCS? Combination therapy: standard of care post-ACS/PCI, but not associated with benefit in stable CAD ^[2] — in stable disease, the risk of bleeding from DAPT outweighs the benefit of additional platelet inhibition because the plaque is stable and not actively thrombosing.

Exception — Extended antithrombotic strategies: Consider rivaroxaban 2.5 mg BID ^[1] in addition to aspirin in selected high-risk patients with polyvascular disease (COMPASS trial) — this "vascular dose" of rivaroxaban ↓MACE at the cost of modest ↑ bleeding.

Consider extended treatment with P2Y₁₂ inhibitor ^[1] in patients who are beyond 12 months post-ACS if they remain at high ischaemic risk and low bleeding risk.

Statins: recommended in all patients ^[2]

Mechanism of statins ("statin" from static = to stop [cholesterol synthesis]):

Primary: Inhibit HMG-CoA reductase → ↓intracellular cholesterol synthesis in hepatocytes → compensatory ↑LDL receptor expression on hepatocyte surface → ↑clearance of LDL-C from blood → ↓plasma LDL-C ^[3]
Pleiotropic effects: plaque stabilisation, ↓inflammation, reversal of endothelial dysfunction, ↓thrombogenicity ^[3] — these effects are at least as important as the cholesterol-lowering in CCS

Agent	Mechanism	Key Points
Statin	HMG-CoA reductase inhibitor	1st line; high-intensity preferred; monitor LFTs, CK if myopathy symptoms
Ezetimibe	Blocks NPC1L1 cholesterol transporter in intestinal brush border → ↓cholesterol absorption	2nd line add-on; 10 mg daily; well-tolerated
PCSK9 inhibitor (evolocumab, alirocumab)	Monoclonal antibody against PCSK9 → prevents degradation of LDL receptors → ↑LDL-C clearance	3rd line; SC injection Q2–4 weeks; expensive; ↓LDL-C by additional ~60%
Icosapent ethyl	Consider icosapent ethyl ^[1] — purified EPA → ↓TG and anti-inflammatory; REDUCE-IT trial showed ↓MACE in patients on statin with persistent ↑TG ≥ 1.5 mmol/L	Add-on for residual hypertriglyceridaemia
Fibrate	PPARα agonist → ↑lipoprotein lipase → ↓TG, modest ↑HDL	Consider when TG > 5.7 mmol/L (pancreatitis prevention) ^[3]

Statin side effects:

Myopathy: ranges from myalgia, myopathy, myositis to rhabdomyolysis ^[3]
Risk factors: lipophilic statins (e.g. simvastatin), hypothyroidism, CYP3A4 inhibitors ^[3]
Diagnosis: clinical + biochemical (↑CK) evidence of muscle injury with compatible temporal pattern ^[3]
Management: stop statin if severe; switch to pravastatin, fluvastatin, or pitavastatin if mild ^[3]
Hepatotoxicity: transient ↑ALT (usually < 3× ULN and clinically insignificant); monitor LFTs
New-onset DM: modest ↑ risk, but cardiovascular benefit far outweighs this

Statin Intolerance — Common Exam Scenario

True statin intolerance (rhabdomyolysis, severe myositis with CK > 10× ULN) is rare ( < 1%). Many patients report subjective myalgia (nocebo effect). Approach: (1) Re-challenge with the same or different statin, (2) Try alternate-day dosing of long half-life statins (rosuvastatin, atorvastatin), (3) If truly intolerant → ezetimibe monotherapy → add PCSK9 inhibitor if needed. Never simply stop all lipid-lowering therapy.

ACEI/ARB: evidence unclear in stable CAD alone without comorbidities ^[2]

Indications: when comorbidities are present, e.g. DM, HTN, LV HF where otherwise indicated ^[2]

Drug Class	Mechanism	Indications in CCS	Key Points
ACEI (ramipril, perindopril)	Inhibits ACE → ↓Ang II → ↓vasoconstriction, ↓aldosterone → ↓preload/afterload; also ↑bradykinin → vasodilation + anti-remodelling	HTN, DM, LVEF < 40%, CKD, post-MI	First choice; proven mortality benefit in high-risk CAD (HOPE, EUROPA trials)
ARB (valsartan, losartan)	Blocks AT1 receptor → similar haemodynamic effects to ACEI	Alternative if ACEI-intolerant (cough, angioedema)	Use: either one is used (combination a/w ↑adverse events without ↑benefits) ^[2]

Why ACEI/ARB in CCS with comorbidities?

↓Afterload → ↓LV wall stress → ↓O₂ demand
Prevent adverse LV remodelling post-MI (↓fibrosis, ↓hypertrophy)
Anti-atherosclerotic effects: ↓endothelial dysfunction, ↓oxidative stress
Renoprotection in DM/CKD (↓intraglomerular pressure)

Contraindications: Bilateral renal artery stenosis, hyperkalaemia (K⁺ > 5.5), pregnancy, history of angioedema (for ACEI)

Part B: Anti-Anginal Drugs (Relieve Symptoms)

The goal of anti-anginal therapy is to restore the supply-demand balance by either:

↓O₂ demand (↓HR, ↓contractility, ↓preload, ↓afterload), or
↑O₂ supply (coronary vasodilation, redistribution of flow)

Step 1: First-Line Anti-Anginal Agents

Mechanism: Block β₁-adrenoreceptors on the heart → ↓HR + ↓contractility + ↓BP → all three determinants of O₂ demand are reduced. The ↓HR also prolongs diastole → ↑coronary filling time → ↑supply. This is why BB is uniquely effective in CCS — it attacks the problem from both sides.

Beta-blockers unless contraindicated ^[16]

Drug	Cardioselectivity	Key Features
Metoprolol	β₁-selective	Most commonly used; can titrate to HR 55–60 bpm
Bisoprolol	β₁-selective	Long-acting, once daily, excellent tolerability
Atenolol	β₁-selective	Not atenolol (per AHA/ACC slide) ^[1] — due to inferior outcomes vs other BBs in trials
Carvedilol	Non-selective (β₁ + β₂ + α₁)	Preferred in HFrEF; additional vasodilation from α₁-blockade
Nebivolol	β₁-selective + NO-mediated vasodilation	Third-generation; additional vasodilatory effect

Target: Resting HR 55–60 bpm (this is where the anti-anginal effect is maximised without excessive bradycardia)

Contraindications:

Absolute: Severe bradycardia (HR < 50), 2nd/3rd degree AV block (without pacemaker), decompensated acute HF, severe hypotension
Relative: Asthma (risk of bronchospasm — β₂ blockade; can cautiously use β₁-selective agents in mild asthma/COPD), Prinzmetal angina (unopposed α-mediated coronary vasoconstriction), peripheral vascular disease with critical ischaemia

There are two main classes, and understanding the difference is essential:

Subclass	Examples	Mechanism	Main Effect	Heart Rate
Rate-limiting (non-DHP)	Diltiazem, Verapamil	Block L-type Ca²⁺ channels in cardiac myocytes and SA/AV nodes	↓HR, ↓contractility, ↓conduction, mild vasodilation	↓
Dihydropyridine (DHP)	Amlodipine, Nifedipine, Felodipine	Block L-type Ca²⁺ channels in vascular smooth muscle	Potent arterial vasodilation → ↓afterload + coronary vasodilation	↑ (reflex tachycardia)

Calcium antagonists (diltiazem or verapamil) if contraindications to beta-blockers and no heart failure ^[16]

When to use which CCB:

Rate-limiting CCBs (diltiazem/verapamil): alternative first-line when BB is contraindicated (e.g. asthma). Do NOT combine with BB — additive negative chronotropy/inotropy → risk of severe bradycardia, AV block, or HF.
DHP CCBs (amlodipine): CAN be combined with BB — the reflex tachycardia from DHP is counteracted by BB's negative chronotropy, producing excellent anti-anginal synergy.

Consider amlodipine if additional blood pressure therapy needed ^[1]

Contraindications:

Verapamil/Diltiazem: Severe LV systolic dysfunction (HFrEF), severe bradycardia, 2nd/3rd degree AV block, concurrent BB (risk of complete heart block)
DHP (short-acting nifedipine): Avoid in unstable angina/ACS — reflex tachycardia can worsen ischaemia (long-acting formulations are safe)

The BB + CCB Combination Rule

BB + DHP-CCB (e.g. bisoprolol + amlodipine) = SAFE and SYNERGISTIC — excellent combination for refractory angina. BB + non-DHP CCB (e.g. bisoprolol + verapamil) = DANGEROUS — both slow the heart → risk of severe bradycardia, heart block, cardiogenic shock. This is a classic exam pitfall.

Clinical Scenario	Preferred 1st Line	Why
CCS, no contraindication	BB (metoprolol/bisoprolol)	↓HR, ↓contractility, ↓BP; post-MI mortality benefit
CCS + asthma	Rate-limiting CCB (diltiazem) or DHP-CCB (amlodipine)	BB contraindicated (bronchospasm risk)
CCS + Prinzmetal angina	DHP-CCB (amlodipine)	Need coronary vasodilation; BB may worsen vasospasm
CCS + HFrEF	BB (bisoprolol/carvedilol/metoprolol succinate)	Mortality benefit in HFrEF; avoid verapamil/diltiazem
CCS + severe bradycardia	DHP-CCB (amlodipine)	No negative chronotropic effect

If monotherapy (BB or CCB alone) is insufficient:

BB + DHP-CCB (e.g. bisoprolol + amlodipine) — the most common and effective combination
BB or CCB + long-acting nitrate

C. Nitrates

Nitrates (long-acting or short-acting as prn) in the presence of angina ^[16]

Mechanism: Arteriovenous dilatation by release of NO → ↑supply by (1) dilating coronary arteries (2) redistributing perfusion from epicardial to endocardial sites → ↓demand by (1) venodilation (major) → ↓preload (2) arteriodilation (modest) → ↓afterload ^[2]

Formulation	Use	Dose	Key Points
Sublingual GTN	For ALL patients with symptomatic stable CAD — acute relief ^[2]	0.3–0.6 mg Q5min, max 1.2 mg within 15 min ^[2]	Should rest sitting while taking (standing → syncope; supine → ↑VR → ↑preload) ^[2]
GTN spray	Acute relief (acts quicker than SL tab)	Up to 3 sprays in 15 min ^[2]	More convenient, longer shelf-life than SL tablets
SL isosorbide dinitrate	Acute or pre-exertional prophylaxis	5 mg → slower onset (3–4 min) but effect lasts ~1h ^[2]	Useful before planned exertion
Oral ISDN/ISMN	Long-acting angina prophylaxis via regular use ^[2]	ISMN 20–60 mg BD or SR 60–120 mg OD	Usually 2nd line if BB/CCB ineffective (risk of worsening endothelial dysfunction with long-term use) ^[2]
Transdermal GTN patches	Prophylaxis	Applied 12h on / 12h off	Convenient but tolerance develops quickly

Critical concept — Nitrate Tolerance: Long-acting nitrates must be used with a nitrate-free or nitrate-low interval of 8–10 hours ^[2]. Continuous nitrate exposure → depletion of intracellular sulfhydryl groups needed for NO generation → ↓effect. The overnight nitrate-free window prevents this.

Contraindications: Concurrent phosphodiesterase-5 inhibitors (sildenafil, tadalafil) → both ↑cGMP → profound hypotension/syncope/death. Also: severe aortic stenosis (preload-dependent), HOCM (↓preload worsens obstruction), hypotension, ↑ICP.

If dual therapy (BB + CCB or BB + nitrate) fails, consider adding:

Drug	Mechanism	Indication	Contraindications
Ivabradine	Selective If ("funny") channel blocker in SA node → ↓HR without ↓contractility or ↓BP	CCS with resting HR > 70 bpm despite maximally tolerated BB (or if BB contraindicated); also indicated in HFrEF	Severe bradycardia, SSS, SA block, AF (ineffective — If channel not the primary pacemaker in AF), concurrent verapamil/diltiazem
Nicorandil	K⁺-ATP channel opener + nitrate-like effect → coronary vasodilation + venodilation	Add-on for refractory angina	Hypotension; rare but serious: GI/mucocutaneous ulceration (stop immediately if ulcers develop)
Ranolazine	Inhibits late Na⁺ current (INa,late) → ↓intracellular Ca²⁺ overload → ↓diastolic wall tension → ↓O₂ demand; NO effect on HR or BP	Add-on for refractory angina; particularly useful in DM (also ↓HbA1c)	QT prolongation (avoid with other QT-prolonging drugs), severe hepatic/renal impairment
Trimetazidine	Shifts myocardial metabolism from fatty acid to glucose oxidation → ↑ATP yield per O₂ molecule consumed (glucose oxidation is more oxygen-efficient)	Add-on; popular in some Asian and European centres	Parkinsonism (can worsen or induce movement disorders — must ask about tremor), severe renal impairment

PILLAR 3: Revascularisation (PCI vs CABG)

Revascularisation is indicated for two reasons:

Prognostic benefit — to reduce mortality/MI (high-risk anatomy)
Symptomatic benefit — persistent symptoms despite adequate trial of GDMT → consider revascularisation to improve symptoms ^[1]

Risk stratification determines the need for revascularisation after institution of OMT ^[2]:

Risk	Annual Mortality	Approach
High risk ≥ 3%/yr	3VD, LMS, proximal LAD, LVEF < 35% + large ischaemia	OMT + invasive coronary angiography ± revascularisation
Intermediate 1–3%/yr	1-2VD with moderate ischaemia	OMT + consider ICA based on comorbidities and patient preferences
Low risk < 1%/yr	Minimal/no ischaemia	Trial of OMT only

PCI vs CABG — How to Choose

Potential revascularisation procedure warranted on the basis of assessment of coexisting cardiac and non-cardiac factors and patient preferences → Heart team concludes that anatomy and clinical factors indicate revascularisation may improve symptoms → Heart team determines optimal method of revascularisation on the basis of patient preferences, anatomy, other clinical factors, and local resources and expertise ^[1]

The decision is made by a Heart Team (interventional cardiologist + cardiac surgeon + referring physician):

Factor	Favours PCI	Favours CABG
Anatomy	Simple vascular anatomy (1VD, 2VD); no proximal disease ^[2]	Complex anatomy: 3VD, LMS disease ^[2]; diffuse disease; bifurcation lesions
Diabetes	Less preferred in DM with multi-vessel disease	Preferred in DM + multi-vessel disease (FREEDOM trial: CABG superior for DM + MVD)
LV function	LVEF > 40%	LVEF < 40% (CABG gives more complete revascularisation → better long-term outcomes)
Surgical risk	High surgical risk ^[2] — PCI preferred	Low surgical risk
Complexity scores	Low SYNTAX score ( < 22)	High SYNTAX score ( > 32)
Prior surgery	Prior CABG with graft failure → redo PCI preferred	First presentation
Acuity	ACS with single culprit → PCI	Stable + complex anatomy → CABG electively

Category	Drug	Mechanism (Brief)	Indication	Key C/I
Antiplatelet	Aspirin 75–100 mg	COX-1 inhibition → ↓TXA₂	All CCS patients	Active bleeding, aspirin allergy
	Clopidogrel 75 mg	P2Y₁₂ inhibition	If aspirin-intolerant	Active bleeding
Lipid-lowering	High-intensity statin	HMG-CoA reductase inhibition	All CCS patients	Active liver disease, pregnancy, myopathy
	Ezetimibe 10 mg	NPC1L1 blockade	Add-on if LDL not at target	— (very well tolerated)
	PCSK9 inhibitor	↓LDL-receptor degradation	3rd line if still not at target	Cost
RAAS	ACEI/ARB	↓Ang II / AT1 blockade	HTN, DM, HF, CKD, post-MI	Bilateral RAS, pregnancy, hyperkalaemia
Anti-anginal 1st line	BB	β₁ blockade → ↓HR, contractility	1st line; especially post-MI	Severe bradycardia, asthma, decompensated HF
	Non-DHP CCB	L-type Ca²⁺ channel block (cardiac)	BB-intolerant, no HF	HFrEF, concurrent BB
	DHP-CCB	L-type Ca²⁺ channel block (vascular)	Combine with BB; vasospasm	Unstable angina (short-acting nifedipine)
Anti-anginal 2nd line	Long-acting nitrate	NO release → vasodilation	Refractory angina	PDE5 inhibitors, severe AS, HOCM
Anti-anginal 3rd line	Ivabradine	If channel block → ↓HR	HR > 70 despite BB; HFrEF	AF, severe bradycardia
	Nicorandil	K-ATP opener + NO donor	Add-on	Hypotension, GI ulceration
	Ranolazine	Late INa block → ↓Ca²⁺ overload	Add-on; useful in DM	QT prolongation
	Trimetazidine	Metabolic shift (FA → glucose)	Add-on	Parkinsonism

High Yield Summary — Management of CCS

Pillar 1: Lifestyle + Risk Factor Modification — Smoking cessation (most impactful single intervention), exercise, weight management, BP < 130/80, LDL < 1.4 mmol/L (very high risk) or < 1.8 mmol/L, HbA1c < 7% (prefer SGLT2i/GLP-1a in established ASCVD).

Pillar 2: Pharmacotherapy —

Prognostic: Aspirin (all patients), statin (all patients, high-intensity, escalate to ezetimibe → PCSK9i), ACEI/ARB (if HTN/DM/HF/CKD).
Anti-anginal: Step 1 = BB or rate-limiting CCB. Step 2 = BB + DHP-CCB or add long-acting nitrate. Step 3 = ivabradine, nicorandil, ranolazine, trimetazidine.
SL GTN for ALL symptomatic patients for acute episodes. Long-acting nitrates need a nitrate-free interval of 8–10h.
NEVER combine BB + verapamil/diltiazem (risk of severe bradycardia/heart block).

Pillar 3: Revascularisation — Only after adequate trial of OMT (or high-risk anatomy). PCI for simple anatomy, high surgical risk. CABG for 3VD, LMS, DM + MVD, low LVEF. Heart Team decision. Post-PCI: DAPT ≥ 6 months. Post-CABG: lifelong aspirin + statin.

Active Recall - Management of CCS

References

^[1] Lecture slides: GC 032. Chest pain on exertion_ischaemic heart disease; angina pectoris.pdf (ESC 2019 CCS management algorithm, GDMT for stable IHD, revascularisation decision pathway, Katz D et al. Annals Int Med 2019) ^[2] Senior notes: Ryan Ho Cardiology.pdf (p120–126: Risk stratification, general measures, prognostic and anti-anginal treatment, nitrates, revascularisation PCI vs CABG) ^[3] Senior notes: Ryan Ho Endocrine.pdf (p85, p97, p128–131: DM management with SGLT2i/GLP-1a, statin dosing, side effects, lipid-lowering escalation, dyslipidaemia management targets HK 2016) ^[15] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p55: ESC 2020 pharmacological long-term management recommendations — statin, ezetimibe, PCSK9i targets) ^[16] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p54–55: Antiplatelet therapy — aspirin, clopidogrel, ticagrelor; anti-ischaemic therapy — BB, CCB, nitrates; secondary prevention)

Complications of Chronic Coronary Syndrome

1. Progression to Acute Coronary Syndrome (ACS)

This is the single most important complication of CCS. The transition from stable to unstable represents the moment a previously stable plaque becomes complicated.

Most common aetiology of acute coronary syndrome is the slow development of atherosclerotic coronary artery plaque, which presents acutely by thrombus formation on fissured plaque ^[6]

Patient may note abrupt change in pattern and severity of symptoms, often symptomatic at rest ^[6]

The clinical spectrum of ACS ranges from oligo/asymptomatic → increasing chest pain/symptoms → persistent chest pain/symptoms → cardiogenic shock/acute heart failure → cardiac arrest ^[17]

Entity	Pathology	ECG	Troponin	Mechanism
Unstable angina (UA)	Severe ischaemia at rest without infarction ^[2]	ST depression or T-wave inversion or normal	Normal	Partial/transient thrombus → critical stenosis without necrosis
NSTEMI	Partial occlusion → some myocardial necrosis but not transmural ^[2]	ST-segment depression ^[17]	Rise and fall ^[17]	Partial/non-occlusive thrombus → subendocardial necrosis
STEMI	Complete occlusion → transmural myocardial necrosis ^[2]	ST-segment elevation ^[17]	Rise and fall (higher peak) ^[17]	Complete thrombotic occlusion → transmural infarction

Acute myocardial infarction: myocardial cell death due to prolonged myocardial ischaemia. Mortality: 40% overall in 4 weeks (half ≤ 2h due to VF), 6–7% in 30 days for those surviving to hospital ^[2]

The Key Teaching Point

CCS and ACS are on a continuum. Every patient with CCS is at risk of ACS. This is why prognostic therapy (aspirin, statin, ACEI/ARB) is prescribed to ALL CCS patients — the goal is to prevent plaque destabilisation and thrombosis, not just to relieve angina symptoms.

2. Ischaemic Cardiomyopathy and Heart Failure

3. Arrhythmias

Arrhythmias in CCS arise from two distinct mechanisms:

These are dramatic, life-threatening complications that occur when transmural infarction weakens the myocardial wall. While they classically follow acute MI, they represent the worst-case endpoint of the CCS → ACS continuum.

AMI complications: heart failure, arrhythmias, VSD (anterior MI), mitral regurgitation complicating papillary muscle dysfunction (inferior MI), pericarditis ^[15]

Complication	Timing Post-MI	Mechanism	Clinical Features
Free wall rupture	Days 3–7 (peak)	Transmural necrosis weakens wall → ↑intracavity pressure → rupture → haemopericardium → cardiac tamponade → PEA arrest	Sudden haemodynamic collapse, PEA, Beck's triad (hypotension, muffled heart sounds, ↑JVP). Almost universally fatal without immediate surgery
Ventricular septal defect (VSD)	Days 3–7	Necrosis of interventricular septum → rupture → L→R shunt. VSD complicates anterior MI (LAD territory involves septum) ^[15]	New harsh pansystolic murmur at LLSB, acute biventricular failure, step-up in O₂ saturation from RA to RV on Swan-Ganz
Papillary muscle rupture/dysfunction	Days 2–7 (rupture); acute or chronic (dysfunction)	Ischaemia/necrosis of papillary muscle (posteromedial > anterolateral because single blood supply from PDA). Mitral regurgitation complicating papillary muscle dysfunction (inferior MI) ^[15]	Acute severe MR: new pansystolic murmur at apex radiating to axilla, flash pulmonary oedema, cardiogenic shock

Ventricular aneurysm: occurs in 8–15% with STEMI, especially for those with persistent occlusion ^[2]:

70–85% located at anterior or apical walls → due to LAD total occlusion without collateral ^[2]
Consequences: acute decompensated HF with angina (wasted mechanical energy to enlarge aneurysm), ventricular arrhythmia due to myocardial irritation, systemic embolisation — mural thrombus occurs in > 50% ^[2]
Diagnosis: paradoxical impulse on chest wall, ECG showing persistent ST elevation and Q despite reperfusion, CXR showing unusual bulge from cardiac silhouette, echo is diagnostic ^[2]
Management: oral anticoagulation if documented mural thrombus; aneurysmectomy + CABG if intractable ventricular arrhythmias or heart failure refractory to medical therapy ^[2]

CCS is a local manifestation of a systemic disease — atherosclerosis. Therefore, patients with CCS are at high risk of atherosclerotic complications in other vascular beds:

Vascular Bed	Complication	Clinical Significance
Carotid arteries	Carotid stenosis → ischaemic stroke/TIA	Carotid bruits on examination suggest coexistent disease ^[6]
Cerebral arteries	Ischaemic stroke	2nd/3rd leading cause of death in HK; shares risk factors with CCS
Peripheral arteries	Peripheral arterial disease (PAD) — intermittent claudication, critical limb ischaemia	Peripheral pulses, peripheral skin discolouration or hair loss ^[6]; ankle-brachial index (ABI) < 0.9 confirms diagnosis
Aorta	Aortic aneurysm (AAA), aortic dissection	Shared atherosclerotic pathology; AAA screening recommended in elderly male smokers
Renal arteries	Renal artery stenosis → renovascular hypertension, ischaemic nephropathy	May worsen CKD; unilateral = HTN, bilateral = renal failure

> 15 mm Hg arm blood pressure disparity = increased risk for peripheral arterial disease (PAD) and cardiovascular death ^[6]

CCS is a Systemic Disease

Always remember: a patient with coronary atherosclerosis very likely has atherosclerosis elsewhere. Screen for carotid disease (bruits, duplex ultrasound), PAD (peripheral pulses, ABI), and AAA (ultrasound in at-risk populations). Managing one vascular bed without addressing the systemic disease is incomplete care.

8. Complications of Treatment

PCI complications (mortality < 0.5%) ^[2]:

Category	Detail
Coronary artery-related	ALL can lead to myocardial ischaemia or infarction. Dissection and abrupt closure (rare now due to routine stenting). Intramural haematoma (6.7%) and perforation (0.2–0.6%). Side branch occlusion (up to 19%) ^[2]
Stent-related	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 ^[2]. In-stent restenosis (ISR): chronic event, usually presents with recurrent stable angina. Due to intimal proliferation at ≥ 6–9 months. Prevention: DES ^[2]
Others	Access-related: bleeding, infection, atheroembolism. Systemic: AKI (contrast, haemodynamic instability, atheroembolism), stroke, bacteraemia ^[2]

CABG complications ^[2]:

Cardiac	Non-Cardiac
Perioperative MI (< 1–2%)	Bleeding
Graft occlusion (5–10% in 30 days, ~1–2%/yr for first 6 years then ~5%/yr)	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

Drug	Key Complication	Mechanism
Aspirin	GI bleeding, haemorrhagic stroke	COX-1 inhibition → ↓gastric mucosal protection; ↓platelet function
Statin	Myopathy/rhabdomyolysis, hepatotoxicity, new-onset DM	Myopathy: unclear, possibly mitochondrial dysfunction; DM: ↓insulin secretion
BB	Bradycardia, fatigue, bronchospasm, masking of hypoglycaemia	β₁ blockade → ↓HR/conduction; β₂ blockade → bronchoconstriction; ↓sympathetic hypoglycaemia awareness
ACEI	Dry cough (10–15%), hyperkalaemia, AKI, angioedema	Cough: ↑bradykinin accumulation; hyperkalaemia: ↓aldosterone; AKI: ↓efferent arteriolar tone in CKD
Nitrates	Headache, hypotension, tolerance	Vasodilation → ↓BP/↑cerebral venous pressure → headache; tolerance from sulfhydryl group depletion

High Yield Summary — Complications of CCS

1. ACS — the most feared complication. Plaque rupture/erosion → thrombus → UA/NSTEMI/STEMI. Mortality 40% at 4 weeks for AMI. Prevention: aspirin, statin, risk factor control.

2. Ischaemic cardiomyopathy/HF — chronic ischaemia → myocyte loss → fibrosis → LV remodelling → HFrEF. LVEF is the strongest prognostic predictor. Hibernating myocardium is viable and may recover with revascularisation.

3. Arrhythmias — Ischaemia-induced (VF/VT → sudden cardiac death, accounts for 85% of cardiac arrests). Scar-related (monomorphic VT → ICD). AF from atrial remodelling.

4. Mechanical complications (post-MI) — Free wall rupture (tamponade), VSD (anterior MI, LAD), papillary muscle rupture → acute MR (inferior MI, PDA territory), ventricular aneurysm (anterior/apical, persistent ST elevation, mural thrombus in > 50%).

5. Pericardial — PIP (day 2–3, pericardial rub), Dressler syndrome (weeks later, autoimmune, fever + pericarditis + pleurisy).

6. Pump failure — ↓systolic + ↓diastolic function → vicious cycle of ischaemia; cardiogenic shock if ≥ 40% LV damage.

7. Systemic atherosclerosis — CCS = coronary manifestation of systemic disease. Screen for carotid disease, PAD, AAA.

8. Treatment complications — PCI: stent thrombosis (DAPT prevents), in-stent restenosis (DES prevents). CABG: graft failure, AF (30%), stroke, mediastinitis. Drugs: statin myopathy, aspirin GI bleed, ACEI cough/AKI, BB bradycardia.

Active Recall - Complications of CCS

References

^[2] Senior notes: Ryan Ho Cardiology.pdf (p124–126: PCI complications, CABG complications, stent thrombosis, in-stent restenosis; p139–142: Post-MI arrhythmias, pump failure, pericardial complications, mechanical complications, ventricular aneurysm) ^[6] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p10: Atherosclerosis to ACS progression, plaque rupture, thrombus formation; p19: Physical examination assessing complications — CHF signs, arrhythmias, PAD) ^[7] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p57: MPI for viability assessment — hibernating myocardium) ^[15] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p56: AMI complications — HF, arrhythmias, VSD, MR, pericarditis) ^[17] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (p11: Clinical spectrum of ACS — ESC Guideline 2023; p45: Aims of treatment; p55: Anti-ischaemic therapy) ^[18] Senior notes: Ryan Ho Critical Care.pdf (p28: Cardiac arrest causes — CAD 85%, structural 10%, others 5%)

Chronic Coronary Syndrome

1. Definition

2. Epidemiology

Global and Hong Kong Context

Key Epidemiological Points

3. Risk Factors

Non-Modifiable Risk Factors

Modifiable Risk Factors

4. Anatomy and Function of the Coronary Arteries

Coronary Arterial Supply

Coronary Dominance

Why LMS Disease is So Dangerous

Coronary Physiology — The Supply-Demand Equation

5. Aetiology (with Hong Kong Focus) and Pathophysiology

5.1 Atherosclerosis — The Dominant Aetiology (> 95% of CCS)

Pathogenesis of Atherosclerosis: Step-by-Step

Haemodynamic Significance of Stenosis

5.2 Non-Atherosclerotic Causes of CCS

5.3 Pathophysiology of Myocardial Ischaemia in CCS

5.4 Coronary Steal Phenomenon (Relevant to Stress Testing)

6. Classification

6.1 Classification of Angina (CCS Grading System)

6.2 Classification by Underlying Mechanism

6.3 ESC 2019 Clinical Scenarios of CCS (Reiterated)

7. Clinical Features

7.1 Symptoms

A. Angina Pectoris — The Cardinal Symptom

B. Angina Equivalents

C. What Angina is NOT

7.2 Signs

A. Signs of Cardiovascular Risk Factors

B. Signs of Underlying Heart Disease

C. Signs of Generalised Atherosclerotic Disease

D. Signs of Conditions That May Exacerbate Angina

7.3 ECG Findings in CCS

7.4 Pre-Test Probability of CAD — The Clinical Likelihood Model (ESC 2019)

8. Important Pathophysiological Concepts — Synthesis

The "Stable Plaque" Model

Why Angina is Predictable in CCS

Why Rest Relieves Angina

Why GTN Relieves Angina

Active Recall - Chronic Coronary Syndrome (Definition to Clinical Features)

References

Conceptual Framework — Why Differential Diagnosis Matters in CCS

DDx Organised by System

A. Cardiac Causes (Non-CCS) That Mimic Exertional Chest Pain

1. Acute Coronary Syndrome (ACS) — The Most Critical DDx

2. Aortic Valve Stenosis (AS)

3. Hypertrophic Cardiomyopathy (HCM/HOCM)

4. Coronary Vasospasm (Prinzmetal / Variant Angina)

5. Cardiac Syndrome X / Microvascular Angina

6. Myopericarditis

7. Takotsubo Syndrome (Stress Cardiomyopathy)

8. Tachyarrhythmias

B. Vascular Causes

9. Aortic Dissection

10. Chronic/Subacute Pulmonary Embolism (PE)

11. Pulmonary Hypertension

C. Gastrointestinal Causes

12. Gastro-Oesophageal Reflux Disease (GERD)

13. Oesophageal Spasm / Motility Disorders

14. Peptic Ulcer Disease / Gastritis

15. Biliary Disease (Cholecystitis)

16. Pancreatitis

D. Musculoskeletal Causes

17. Costochondritis (Tietze Syndrome)

18. Cervical/Thoracic Spine Pathology

E. Respiratory Causes

19. Asthma / COPD

20. Pleurisy / Pneumonia

F. Psychiatric / Other

21. Panic Disorder / Anxiety

22. Herpes Zoster

23. Anaemia

Systematic DDx Diagram

Master DDx Table — "How to Tell Them Apart"

Relative Frequency of Chest Pain Aetiologies

Red Flags — When Stable Chest Pain Is Actually Something Dangerous

Active Recall - Differential Diagnosis of CCS

Conceptual Framework — How Do We "Diagnose" CCS?