Chronic Coronary Syndrome (Previously Stable Angina)

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

Exam domain	One-glance essentials
Definition / diagnosis	Chronic coronary syndrome = dynamic, chronic CAD with stable phases; fixed stenosis causes demand ischaemia ^[1] Typical angina has all 3: constricting discomfort, exertional/emotional trigger, relief with rest or GTN ^[3]
Epidemiology / risks	Major modifiable risks: smoking, hypertension, diabetes and dyslipidaemia ^[3] Premature family history: first-degree male < 55 years or female < 65 years ^[3]
Core mechanism	Endothelial injury → LDL oxidation → foam cells → fibroatheroma → fixed flow limitation ^[3] Exertion raises demand beyond coronary flow reserve → subendocardial ischaemia → ST depression and angina ^[3]
Clinical picture	Predictable retrosternal pressure with exertion, relieved by rest/GTN within minutes ^[3] Dyspnoea or fatigue may be an anginal equivalent, especially in diabetes and older adults ^[3]
Investigations	*Can exercise + interpretable resting ECG → exercise treadmill ECG; otherwise use stress imaging* ^[1] CTCA is a strong rule-out test; invasive angiography is used for high-risk or unclear results ^[1] FFR ≤ 0.80 supports haemodynamically significant disease ^[3]
Management	*First-line symptom control: beta-blocker or calcium-channel blocker; carry short-acting GTN* ^[1] *Aspirin, high-intensity statin and ACEI/ARB when HTN, DM, CKD or LVEF ≤ 40%* ^[1]^[2] Revascularise refractory symptoms or high-risk anatomy; CABG favoured for left main/complex multivessel disease ^[3]
Complications	Plaque destabilisation → unstable angina, NSTEMI or STEMI ^[3] Recurrent ischaemia/infarction → ischaemic cardiomyopathy, VT/VF and sudden death ^[3]
Prevention / follow-up	Stop smoking, exercise, optimise weight, BP, diabetes and lipids ^[3] Continue antiplatelet/statin therapy and reassess new or worsening symptoms promptly ^[2]
Exam traps	Normal resting ECG and troponin do not exclude CCS; ischaemia may only appear under stress ^[1] Rest pain, crescendo symptoms or pain > 20 minutes → treat as ACS until excluded ^[3] GTN response is not diagnostic: oesophageal spasm may also improve ^[3]

References

^[1] Lecture slides: GC 032. Chest pain on exertion_ischaemic heart disease; angina pectoris.pdf ^[2] Lecture slides: Handbook of Internal Medicine 2024.pdf ^[3] Senior notes: Block A - WCS32 Chest pain on exertion_ ischaemic heart disease; angina pectoris.pdf

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

The 2019 ESC guidelines formally replaced the old term "stable coronary artery disease" with "Chronic Coronary Syndromes" to emphasise that coronary artery disease (CAD) is a dynamic continuum — patients can cycle between stable and unstable phases throughout their lifetime. The plural "syndromes" captures the fact that CCS is not a single snapshot but includes several clinical scenarios ^[3]:

Patients with suspected CAD and stable anginal symptoms ± dyspnoea
Patients with new-onset heart failure or LV dysfunction suspected to be due to CAD
Asymptomatic or symptomatic patients < 1 year after an ACS or recent revascularisation
Asymptomatic or symptomatic patients > 1 year after initial diagnosis or revascularisation
Patients with angina and suspected vasospastic or microvascular disease
Asymptomatic individuals in whom CAD is detected on screening

The key conceptual shift: CAD is not "stable vs. unstable" as a binary. A patient can sit in a chronic stable phase for years, then destabilise into ACS, then return to CCS. The underlying atherosclerotic process is always present and always evolving ^[1]^[2]^[3].

High Yield – Nomenclature

The term "Chronic Coronary Syndromes" (CCS) supersedes "stable angina" and "stable CAD" per ESC 2019 (reaffirmed 2024). However, many HKUMed lecture slides still use "stable angina" or "IHD." Understand that these are the same entity. In exams, use whichever term the question uses, but know the modern framing.

Epidemiology

Cardiovascular disease is the number 1 killer globally in the 21st century ^[1].
CAD alone accounts for ~1/3 of all deaths in people > 35 years of age worldwide.
Prevalence of angina in Western populations: ~3–4% (age 45–64), rising to ~10–15% in those > 65.

Coronary heart disease is the 3rd leading cause of death in Hong Kong (after cancer and pneumonia), accounting for ~6,000 deaths/year (CHP data 2023–2024).
Hong Kong's ageing population + rising prevalence of obesity, T2DM, and metabolic syndrome are driving an increasing burden of CCS.
Unique local factors: relatively lower smoking rates compared to mainland China; high prevalence of T2DM (> 10% of adults); substantial hypertension prevalence (~27% of adults ≥15 y).
Prevalence of CAD in Chinese populations is somewhat lower than Western cohorts of similar age, partly due to historically lower LDL-C levels and dietary differences, but this gap is narrowing rapidly with Westernisation of diet.

Males are more commonly affected than females (roughly 2:1 for symptomatic CCS) ^[1].
Females present ~10 years later (oestrogen-mediated vascular protection pre-menopause).
Females are more likely to have microvascular angina and vasospastic angina than obstructive epicardial CAD.
In diabetic women, the sex-based protective effect is largely abolished.

For stable angina without treatment, 10–20% progress to MI or unstable angina ^[1].
For those who are treated, this risk drops to ~0.8% — highlighting the enormous benefit of medical therapy ^[1].

Risk Factors

Understanding risk factors is essential because CCS is fundamentally a disease of atherosclerosis, and atherosclerosis is driven by endothelial injury + lipid accumulation + chronic inflammation.

Factor	Explanation
Age	Male ≥ 45 y, Female ≥ 55 y. Atherosclerosis is a time-dependent process — longer exposure to risk factors = more plaque.
Male sex	Oestrogen is cardioprotective (↑NO, ↑HDL, antioxidant). Males lack this until females reach menopause.
Family history of premature CHD	Male first-degree relative < 55 y, Female first-degree relative < 65 y ^[1]^[4]. Reflects shared genetic susceptibility (polygenic) + shared environment.
Ethnicity	South Asians have higher CAD rates even after adjusting for traditional risk factors (possibly related to insulin resistance, Lp(a), smaller coronary arteries).

Factor	Mechanism of Atherogenicity
Hypercholesterolaemia	LDL penetrates and accumulates in arterial intima → oxidised LDL → macrophage uptake → foam cells → fatty streaks → atheromatous plaque ^[1]^[5].
Hypertension	Mechanical shear stress damages endothelium → ↑permeability to LDL, ↑smooth muscle cell proliferation, ↑arterial wall stiffness.
Diabetes mellitus	Hyperglycaemia → advanced glycation end-products (AGEs) → endothelial dysfunction + ↑oxidative stress + prothrombotic state + dyslipidaemia (↑TG, ↓HDL, small dense LDL).
Smoking	Most lethal of abused substances. 50% of coronary deaths in women are due to smoking ^[1]. Nicotine → sympathetic activation → ↑HR, ↑BP. Carbon monoxide → endothelial hypoxia. Oxidative chemicals → direct endothelial damage + ↑LDL oxidation + ↓HDL + prothrombotic (↑fibrinogen, ↑platelet aggregation).
Obesity / Metabolic syndrome	Central obesity → adipocytes release FFA + pro-inflammatory adipokines (TNF-α, IL-6, leptin) → insulin resistance → hyperinsulinaemia → ↑hepatic VLDL production → atherogenic dyslipidaemia ^[6].
Physical inactivity	↓AMPK activation → ↓glucose uptake + ↓FFA oxidation → insulin resistance. Also ↓endothelial NO production.
Poor nutrition	High saturated fat, trans fat, excess sodium, low fruit/vegetable intake → ↑LDL, ↑BP, ↑oxidative stress.

Factor	Note
Alcohol	J-shaped curve: mild intake → ↓risk of CAD (↑HDL, mild anticoagulant effect), but higher intake → ↑risk (direct myocardial cytotoxicity, AF, DCM, HT) ^[1].
Cocaine	Direct myocardial cytotoxicity, coronary vasoconstriction, procoagulant, ↑BP — more relevant in Western practice but occasionally seen in HK ^[1].
Chronic kidney disease	Accelerated atherosclerosis + vascular calcification + dyslipidaemia + chronic inflammation.
Chronic inflammatory diseases	RA, SLE, psoriasis — systemic inflammation accelerates atherogenesis.
Obstructive sleep apnoea	Intermittent hypoxia → sympathetic surge → ↑BP, endothelial dysfunction, oxidative stress.
Hyperhomocysteinaemia	Endothelial toxicity + prothrombotic. Can cause both arterial and venous thrombosis ^[7].
Elevated Lp(a)	Genetically determined; competes with plasminogen → prothrombotic; carries oxidised phospholipids → pro-inflammatory.

Arterial vs. Venous Thrombosis Risk Factors

Hypercholesterolaemia, DM, HT, CKD, male gender are risk factors ONLY for arterial thrombosis (not venous) ^[7]. Inherited thrombophilias (Protein C/S deficiency, Factor V Leiden, etc.) are risk factors for VTE but NOT arterial thrombosis. Antiphospholipid syndrome and hyperhomocysteinaemia can cause both ^[7].

A cluster of metabolic disorders linked by insulin resistance and associated with accelerated atherosclerosis ^[6]. Diagnosis requires ≥3 of:

Central obesity (waist circumference: ≥90 cm male, ≥80 cm female for Asians)
Raised triglycerides (≥1.7 mmol/L)
Low HDL-C ( < 1.03 mmol/L male, < 1.29 mmol/L female)
Raised BP (≥130/85 mmHg or on treatment)
Raised fasting glucose (≥5.6 mmol/L or T2DM)

Anatomy and Function of the Coronary Arteries

Understanding coronary anatomy is critical — it tells you which territory is ischaemic based on symptoms, ECG changes, and imaging findings.

The heart receives its blood supply from two coronary arteries arising from the aortic sinuses of Valsalva just above the aortic valve:

Artery	Territory Supplied	Clinical Significance
LAD	Anterior wall of LV, anterior 2/3 of interventricular septum, apex	"The Widow-Maker" — proximal LAD occlusion → large anterior MI → high mortality. Septal perforators supply the bundle of His → LBBB/conduction block.
LCx	Lateral wall and posterior wall of LV (in left-dominant systems)	Lateral MI; may be clinically "silent" on standard 12-lead ECG.
RCA	Right ventricle, inferior wall of LV, posterior 1/3 of septum, SA node (55%), AV node (80–90%)	Inferior MI → bradycardia/heart block (AV node supply), RV infarction.
PDA	Inferior interventricular septum, inferior LV wall	In ~85% of people, PDA arises from RCA ("right-dominant"). In ~8% from LCx ("left-dominant"). In ~7% co-dominant.

Right-dominant (85%): PDA from RCA
Left-dominant (8%): PDA from LCx
Co-dominant (7%): PDA from both

The subendocardium (inner layer of myocardium) is the first to suffer in ischaemia because:

It is the furthest from the epicardial coronary arteries (oxygen must diffuse through the full wall thickness).
It is subject to the highest intraventricular pressure during systole → compression of subendocardial vessels → reduced perfusion during systole.
Coronary flow occurs predominantly in diastole (when ventricular wall relaxes); any condition that shortens diastole (tachycardia) or raises diastolic pressure preferentially harms the subendocardium.

This is why early ischaemia shows ST depression (subendocardial ischaemia) on ECG, while transmural ischaemia (full-thickness, as in STEMI) shows ST elevation.

Etiology (Hong Kong Focus)

Two main classifications of the etiologies of IHD: primary cardiac causes and primary non-cardiac causes ^[1].

A. Primary Cardiac Causes

This is the cause in > 95% of CCS cases. The pathophysiology is detailed below.

Cause	Mechanism	Notes
Coronary artery spasm (Prinzmetal's / variant angina)	Focal or diffuse spasm of epicardial coronary artery → transient transmural ischaemia. Triggered by smoking, cocaine, cold exposure, hyperventilation, or idiopathic. ST elevation during spasm (resolves after).	More common in East Asian populations (Japanese, Chinese, Korean) — important for HK! Often occurs at rest, especially early morning.
Coronary artery dissection	Spontaneous or secondary to aortic dissection (Type A with retrograde extension). Intimal tear → blood tracks in media → false lumen compresses true lumen.	Spontaneous coronary artery dissection (SCAD) — most common cause of MI in young women, especially peripartum.
Coronary embolism	Embolus from AF, atrial myxoma, prosthetic valve, or paradoxical embolism via PFO.	Rare cause; suspect in young patient with ACS + known AF/structural heart disease.
Coronary arteritis (vasculitis)	Inflammation of coronary vessel wall → luminal narrowing/occlusion/aneurysm.	Takayasu (large-vessel), PAN (medium-vessel), Kawasaki (medium-vessel), EGPA (small-vessel) ^[2]. Kawasaki disease is the leading cause of acquired heart disease in children — coronary aneurysms.
Coronary artery abnormalities	Congenital anomalous origin, myocardial bridging (LAD tunnels through myocardium → systolic compression).	Myocardial bridging is common (autopsy prevalence ~25%) but rarely clinically significant.

Normal epicardial coronary arteries on angiography but abnormal coronary microvascular function.
Cause: endothelial dysfunction, smooth muscle dysfunction, or structural remodelling of arterioles.
More common in women, patients with DM and HT.
Now formally recognised by ESC as an important entity under CCS.

These cause ischaemia by increasing myocardial oxygen demand or decreasing oxygen-carrying capacity, even in the absence of significant coronary stenosis:

Cause	Mechanism
Anaemia	↓O₂-carrying capacity → myocardium cannot meet demand even at rest or mild exertion
Thyrotoxicosis	↑metabolic rate + ↑HR → ↑myocardial O₂ demand
Aortic stenosis	↑afterload → ↑LV wall stress → ↑O₂ demand + LVH compresses subendocardial vessels
Hypertensive crisis	Acute ↑afterload + ↑wall stress
Tachyarrhythmias	↑HR → ↑O₂ demand + ↓diastolic filling time (coronary perfusion occurs in diastole)
Hypertrophic cardiomyopathy	↑muscle mass → ↑O₂ demand + ↓capillary density per unit muscle + dynamic LVOT obstruction

Vasospastic Angina in East Asia

Coronary vasospasm is significantly more prevalent in East Asian populations compared to Caucasians (~40–50% of angina with non-obstructive coronaries in Japanese/Korean studies). This is highly relevant for Hong Kong practice. Suspect it in patients with typical angina at rest (especially nocturnal/early morning), normal coronary angiography, and ST elevation during episodes.

Pathophysiology

A. Atherosclerosis — The Fundamental Process

Atherosclerosis is a chronic inflammatory disease of the arterial intima driven by lipid accumulation and immune response. Understanding this step-by-step is essential:

Risk factors (HT, smoking, DM, dyslipidaemia, oxidative stress) damage the endothelial lining of coronary arteries.
Damaged endothelium becomes permeable to circulating LDL and expresses adhesion molecules (VCAM-1, ICAM-1) that recruit monocytes.

LDL accumulates in the arterial intima and becomes oxidised (ox-LDL) — a critical step ^[2].
Oxidised LDL is highly pro-inflammatory and cytotoxic.

Monocytes migrate into the intima and differentiate into macrophages.
Macrophages engulf ox-LDL via scavenger receptors (SR-A, CD36) — these are NOT regulated by intracellular cholesterol (unlike LDL receptors), so macrophages become engorged → foam cells ^[2].
Collections of foam cells = fatty streaks — slightly raised yellow deposits visible even in childhood/adolescence ^[2].

Smooth muscle cells migrate from the media to the intima, proliferate, and produce extracellular matrix (collagen, elastin) → forms a fibrous cap over the lipid-rich necrotic core.
Atheromatous plaque = fibrous cap + necrotic centre (lipid, cholesterol crystals, cellular debris, calcification) ^[2].
Plaque grows concentrically or eccentrically, progressively narrowing the lumen.

Feature	Stable Plaque (→ CCS)	Unstable/Vulnerable Plaque (→ ACS)
Fibrous cap	Thick, intact	Thin fibrous cap ^[2]
Lipid core	Small	Large, growing necrotic core ^[2]
Inflammation	Low	High (many macrophages at cap shoulders)
Smooth muscle cells	Abundant in cap	Few in cap
Collagen content	High	Low (MMPs degrade collagen)
Clinical presentation	Stable angina on exertion	ACS (plaque rupture/erosion → thrombus)

Stable plaque → gradually narrows the lumen → produces demand ischaemia on exertion → CCS.
Unstable plaque → plaque rupture → thrombus formation → occlusion ^[2] → ACS.

The key insight: CCS is not just about the degree of stenosis. A 50% stenosis with a thin-cap fibroatheroma can be more dangerous than a 90% stenosis with a thick, stable cap.

Initially, the artery remodels outward (Glagov remodelling) to accommodate plaque growth → no luminal narrowing → no symptoms.
Once ~40% of the vessel cross-section is occupied by plaque, outward remodelling is exhausted → lumen begins to narrow.
Significant CAD is usually defined as stenosis ≥50% on invasive coronary angiography ^[2].
Stenosis < 70% is typically not flow-limiting and rarely causes angina or ischaemia at rest ^[2].
PCI is indicated for stable CAD (SIHD) when occlusion ≥70% (or ≥50% for left main) ^[2].

Why referred pain? Cardiac afferent nerves converge on the same spinal cord segments (T1–T5) as somatic afferents from the chest wall, left arm, jaw, and epigastrium → the brain misinterprets the source → referred pain to these areas.

Why relieved by rest? Stopping exertion → ↓HR, ↓BP, ↓contractility → ↓myocardial O₂ demand → supply catches up → ischaemia resolves → pain subsides (usually within 1–5 minutes).

Why relieved by GTN? Glyceryl trinitrate (GTN) → releases NO → venodilation (↓preload, most important) + coronary artery dilation + some arteriolar dilation (↓afterload) → ↓myocardial O₂ demand + ↑coronary flow → relief within 1–3 minutes.

When myocardial ischaemia develops, events occur in a specific sequence:

Perfusion abnormality (detected by myocardial perfusion imaging)
Diastolic dysfunction (impaired relaxation → ↑filling pressures)
Regional wall motion abnormality (systolic dysfunction — detected by stress echo)
ECG changes (ST depression = subendocardial ischaemia)
Angina (symptom — LAST to appear)

This means that by the time a patient feels angina, there has already been significant metabolic and functional derangement. Conversely, ischaemia can be "silent" (no angina) — especially in diabetics with autonomic neuropathy.

Classification

As outlined in the definition above, the ESC recognises 6 clinical scenarios. For examination purposes, the most commonly tested is Scenario 1 (suspected CAD with stable angina).

This is the standard functional classification for stable angina severity:

CCS Class	Description	Example
I	Angina only with strenuous, rapid, or prolonged exertion	Running, heavy lifting
II	Slight limitation of ordinary activity	Walking > 2 blocks on the level, climbing > 1 flight of stairs at normal pace
III	Marked limitation of ordinary physical activity	Walking 1–2 blocks on the level, climbing 1 flight of stairs
IV	Inability to carry out any physical activity without discomfort; angina may be present at rest	Any physical activity causes angina

Note: CCS Class IV at rest starts to overlap with unstable angina (ACS). The distinction is that in CCS, the symptoms are predictable and reproducible, while in ACS they are new, accelerating, or occurring at rest without a predictable pattern.

Three characteristic features of angina:

Constricting discomfort in the chest, neck, jaw, shoulder, or arm
Provoked by physical exertion or emotional stress
Relieved by rest or GTN within ~5 minutes

Category	Features Present
Typical angina	All 3 features
Atypical angina	2 of 3 features
Non-anginal chest pain	≤1 feature

The updated ESC 2019 PTP tables use age, sex, and nature of symptoms (typical/atypical/non-anginal/dyspnoea) to estimate the likelihood of obstructive CAD. This guides investigation strategy:

PTP < 5%: CAD unlikely → usually no further testing needed
PTP 5–15%: Low probability → consider testing only if clinical features suggest CAD
PTP > 15%: Non-invasive testing recommended

The old Diamond-Forrester model (1979) significantly overestimated PTP. The ESC 2019 model uses contemporary data showing lower prevalence of obstructive CAD in modern populations.

Clinical Likelihood vs. PTP

ESC 2019 introduced the concept of "clinical likelihood" which goes beyond PTP: it incorporates PTP + risk factors (DM, HT, smoking, dyslipidaemia, family Hx) + resting ECG changes + coronary artery calcium score + LV dysfunction. This modifies the testing strategy even further.

Factors that increase risk of adverse events despite medical treatment (i.e., "high-risk CAD") ^[1]:

Heart function: If baseline LV function already compromised (↓EF) → indicates pre-existing myocardial damage → higher risk ^[1].
Number and degree of vessels affected: Greater the number and severity of stenosis → lower the 5-year survival ^[1].
- 1-vessel disease: ~93% 5-year survival (may be managed medically)
- 3-vessel disease + ≥95% blockage in proximal LAD → should consider revascularisation
Left main stem disease: Always high-risk — it supplies ~75% of the LV (via LAD + LCx).
Diabetes mellitus: Associated with more diffuse, multivessel disease and worse outcomes.
Proximal LAD involvement: Jeopardises a large myocardial territory.

Clinical Features

A. Symptoms

Angina pectoris literally means "choking of the chest" (Latin: angere = to choke/strangle; pectus = chest).

Feature	Description	Pathophysiological Basis
Quality	Dull, constricting, choking, 'heavy', squeezing, crushing, burning, aching. Patients often emphasise it is a discomfort, not a pain. Levine's sign: characteristic gesture of a clenched fist held over the sternum when describing the discomfort ^[4].	Ischaemia → metabolite accumulation (adenosine, lactate, K⁺, bradykinin) → stimulation of unmyelinated C-fibres in the myocardium → visceral pain (poorly localised, deep, heavy quality — unlike somatic pain which is sharp and well-localised).
Location	Retrosternal / central chest. Can be diffuse (patient uses open hand, not a finger, to indicate location).	Cardiac afferent nerves converge on dorsal horn neurons at T1–T5 → brain perceives pain as arising from these dermatomes → central chest.
Radiation	Left arm (medial aspect), jaw, neck, shoulders, epigastrium, interscapular region. Can radiate to right arm (less common).	Same convergence mechanism: T1–T2 (medial arm/ulnar nerve), C3–C4 (jaw/neck via phrenic and cervical nerves), T5–T6 (epigastrium).
Onset & provocation	Builds up gradually with exertion (walking uphill, climbing stairs, carrying heavy loads) or emotional stress. Predictable and reproducible at a similar level of exertion.	Exertion → ↑HR × ↑BP (rate-pressure product) → ↑myocardial O₂ demand → exceeds capacity of stenosed coronary arteries to ↑flow → ischaemia.
Duration	Typically 1–5 minutes after cessation of activity. Rarely > 15 minutes (if > 20 min, suspect ACS).	Stopping exertion → demand ↓ → supply catches up → metabolites washed out → pain resolves.
Relieving factors	Relieved by rest (within 1–5 min) or sublingual GTN (within 1–3 min) ^[2].	Rest → ↓demand. GTN → venodilation (↓preload → ↓wall stress → ↓O₂ demand) + coronary vasodilation (↑supply).
Aggravating factors	Cold weather (↑sympathetic tone → vasoconstriction + ↑HR/BP), heavy meals (↑splanchnic blood flow → coronary steal), emotional stress (↑catecholamines).	All increase myocardial O₂ demand or decrease supply.

Stable vs. Unstable Angina

Stable angina: chest pain with exertion, predictable, relieved by rest/GTN → implies fixed stenosis with adequate resting flow ^[2]. Unstable angina: ↑frequency, ↑severity, ↑duration, onset at rest, not fully relieved by rest/GTN → implies acute plaque instability → treat as ACS ^[1]. The 30-minute rule: if angina lasts > 20–30 minutes, it is almost certainly ACS (UA or MI), not stable angina.

Some patients, particularly elderly, diabetics, and women, may not experience classic chest pain. Instead, they present with:

Equivalent	Pathophysiological Basis
Exertional dyspnoea (most common equivalent)	Ischaemia → ↓LV compliance → ↑LVEDP → ↑pulmonary venous pressure → pulmonary congestion → dyspnoea.
Exertional fatigue / exercise intolerance	↓Cardiac output due to ischaemic LV dysfunction → inadequate peripheral perfusion → fatigue.
Epigastric discomfort / "indigestion"	Inferior wall ischaemia → referred pain via T5–T6 → misinterpreted as GI symptoms.
Nausea, diaphoresis	Ischaemia → vagal activation (especially inferior MI) → nausea. Sympathetic activation → diaphoresis.

Causes of painless MI / "silent ischaemia": DM (autonomic neuropathy destroys afferent pain fibres), complete infarct (> 6 hours — nerves already dead), elderly (altered pain perception) ^[2].

Dyspnoea: if there is coexistent LV dysfunction or transient ischaemic mitral regurgitation.
Palpitations: may reflect arrhythmias triggered by ischaemia.
Presyncope/syncope: rare in CCS; if present, suggests severe disease (left main, critical 3-vessel) or arrhythmia.

B. Signs

Physical examination in CCS is often entirely normal. However, examination serves three important purposes: (1) identify risk factors, (2) detect signs suggesting CAD or its complications, (3) identify alternative diagnoses or exacerbating conditions.

Sign	Significance
Xanthelasma (yellowish plaques around eyelids)	Hyperlipidaemia — lipid deposition in skin.
Corneal arcus (arcus senilis) — especially if age < 50	Lipid deposition in the corneal periphery → suggests hyperlipidaemia.
Tendon xanthomas (Achilles, extensor tendons of hands, knees, elbows)	Pathognomonic of familial hypercholesterolaemia ^[5]. Achilles and hand/wrist tendons are the most common sites.
Eruptive xanthomas	Associated with severe hypertriglyceridaemia (Type I or V).
Nicotine staining of fingers/teeth	Smoking.
Central obesity (↑waist circumference)	Metabolic syndrome.
Absent/weak peripheral pulses, reduced ABPI	Peripheral arterial disease → suggests diffuse atherosclerosis (as in the interactive tutorial case: absent R dorsalis pedis pulse, weak L dorsalis pedis and posterior tibial pulses) ^[8].
Carotid bruit	Carotid atherosclerosis → generalised atherosclerotic burden. (Case: soft L carotid bruit) ^[8].

Sign	Pathophysiological Basis
Dyskinetic apex beat	Regional wall motion abnormality from previous MI → paradoxical outward movement during systole.
S4 gallop	Forceful atrial contraction into a stiff, non-compliant LV (diastolic dysfunction from ischaemia or LVH) → audible 4th heart sound.
S3 gallop	Rapid ventricular filling into a dilated, failing LV (systolic dysfunction) → suggests reduced EF.
Functional mitral regurgitation murmur	Papillary muscle dysfunction or LV dilatation → mitral leaflet malcoaptation → MR.
Ejection systolic murmur over aortic area	May indicate aortic sclerosis/stenosis (co-existing pathology) OR increased flow in atherosclerotic aorta. (Case: 2/6 ESM over aortic area) ^[8].
Signs of LV failure	Elevated JVP, bibasal crepitations, peripheral oedema → indicate ischaemic cardiomyopathy with reduced EF.

Sign	Condition
Pallor, koilonychia, glossitis	Anaemia → ↓O₂-carrying capacity.
Tremor, tachycardia, exophthalmos, lid lag	Thyrotoxicosis → ↑O₂ demand.
Slow-rising pulse, narrow pulse pressure, ejection click	Aortic stenosis → ↑afterload → ↑O₂ demand.
Irregularly irregular pulse	AF → tachycardia → ↓diastolic filling time + ↑demand.

Stage	What Happens	Detection Method
1. Perfusion defect	Reduced blood flow to affected territory	Myocardial perfusion imaging (SPECT/PET)
2. Diastolic dysfunction	Impaired relaxation → ↑LVEDP	Doppler echocardiography (E/A ratio changes)
3. Systolic dysfunction	Regional wall motion abnormality	Stress echocardiography
4. ECG changes	ST depression (subendocardial) or ST elevation (transmural)	Exercise ECG / continuous monitoring
5. Angina	Pain / discomfort	Patient history

High Yield Summary

CCS = Chronic Coronary Syndromes (ESC 2019) — replaces "stable angina/stable CAD." CAD is a dynamic continuum, not a binary stable/unstable state.
Atherosclerosis is the cause in > 95% of cases — a chronic inflammatory process: endothelial injury → LDL accumulation → foam cells → fibroatheroma → stable plaque (thick cap, small core) → fixed stenosis → demand ischaemia on exertion.
Non-atherosclerotic causes to remember: vasospasm (Prinzmetal — common in East Asians!), dissection (SCAD — young women), embolism (AF), vasculitis (Kawasaki, Takayasu, PAN, EGPA).
Risk factors: Smoking (most lethal), HT, DM, hyperlipidaemia, obesity, family Hx, physical inactivity. Metabolic syndrome = ≥3 of: central obesity, ↑TG, ↓HDL, ↑BP, ↑glucose.
Angina features: retrosternal constricting discomfort, provoked by exertion, relieved by rest/GTN within 1–5 min. Typical = 3/3 features, atypical = 2/3, non-anginal = ≤1.
CCS classification: Grade I (strenuous exertion only) → IV (any activity / rest).
Significant stenosis = ≥50% on coronary angiography; flow-limiting = ≥70% (or ≥50% left main). PCI for stable CCS when ≥70%.
Examination is often normal but look for: xanthomata (hyperlipidaemia), absent peripheral pulses/bruits (diffuse atherosclerosis), S4 (diastolic dysfunction), S3 (systolic dysfunction), signs of conditions exacerbating angina (anaemia, thyrotoxicosis, AS).
Angina equivalents (dyspnoea, fatigue, nausea): common in elderly, DM, women. Silent ischaemia: DM (autonomic neuropathy), complete infarct (> 6h), elderly.
Untreated stable angina: 10–20% progress to MI/UA. Treated: ~0.8%.

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

^[1] Senior notes: Block A - WCS32 Chest pain on exertion: ischaemic heart disease; angina pectoris (Epidemiology, Etiologies, Risk Factors, High-Risk CAD sections) ^[2] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai) (pp. 384–395, Coronary artery disease / Stable CAD / ACS sections) ^[3] ESC 2019 Guidelines for the diagnosis and management of chronic coronary syndromes (current guideline framing) ^[4] Senior notes: Ryan Ho Fundamentals (pp. 199–203, Approach to Chest Pain / Angina Pectoris) ^[5] Senior notes: Ryan Ho Endocrine (pp. 125–131, Lipid disorders / FH) ^[6] Senior notes: Ryan Ho Endocrine (p. 77, Metabolic syndrome / T2DM pathogenesis) ^[7] Senior notes: Block A - Leg swelling and chest pain: DVT; PE; Thrombophilia (Arterial vs venous risk factors) ^[8] Senior notes: Block A - Cardiology Interactive Tutorial (pp. 4–5, Case 2 — 61-year-old woman with chest pain)

Differential Diagnosis of Chronic Coronary Syndrome

When a patient presents with recurrent, exertional chest discomfort, CCS (stable angina) sits at the top of your differential. However, the chest is a crowded anatomical neighbourhood — the heart, great vessels, lungs, pleura, oesophagus, musculoskeletal structures, and nerves all live within centimetres of each other and can all produce "chest pain." Your job is to systematically consider and exclude mimics, because:

Some mimics are life-threatening and require immediate intervention (e.g., ACS that is masquerading as "just another episode of stable angina").
Some mimics are common and benign but cause unnecessary anxiety (e.g., GERD, musculoskeletal pain).
CCS itself may coexist with another condition that is worsening angina (e.g., anaemia, thyrotoxicosis superimposed on fixed coronary stenosis).

Formulate the list of differential diagnoses of chest pain based on anatomy and pathophysiology ^[8]^[10].

The approach below is organised by anatomical origin, with the pathophysiological reasoning for why each condition can mimic CCS, and the key discriminating features that help you tell them apart.

A. Cardiac Causes

This is by far the most critical differential to distinguish from CCS. Both arise from coronary atherosclerosis, but the mechanism and urgency differ entirely.

Feature	CCS (Stable Angina)	ACS (UA / NSTEMI / STEMI)
Mechanism	Fixed stenosis → demand ischaemia	Acute plaque rupture/erosion → thrombus → supply ischaemia ^[2]^[9]
Onset	Builds up gradually in proportion to intensity of exertion ^[4]	Typically takes minutes to develop, may occur at rest or with exertion ^[4]
Duration	1–5 minutes, rarely > 15 min	> 20 minutes, often > 30 min
Pattern	Predictable, reproducible at similar exertion level	↑Frequency, ↑severity, ↑duration; onset at rest ^[2]
Response to rest/GTN	Relieved within 1–5 minutes ^[2]	Chest pain might not go away ^[2]
ECG	Often normal (or old changes)	ST elevation (STEMI), ST depression / T-wave inversion (NSTEMI), or normal (UA) ^[9]
Troponin	Normal	Elevated in NSTEMI/STEMI; normal in UA

When Does Stable Become Unstable?

When is angina considered unstable? Anginal pain with at least one of: is of new onset and severe; occurs at rest or with minimal exertion; pain is worsening in the severity and length of each episode ^[9]. If your "stable" patient reports any of these changes, treat as ACS until proven otherwise. Not all patients have the classical playing tennis then collapse story — they can be oligo/asymptomatic, have increasing chest pain, persistent chest pain, cardiogenic shock/acute heart failure, or cardiac arrest ^[9].

Why this matters: A patient with known CCS may present with what seems like "just another episode." The key discriminator is change from baseline — any crescendo pattern, rest pain, or prolonged pain (> 20 min) should trigger ACS workup (ECG + troponin).

Feature	Discriminating from CCS
Mechanism	Focal transient vasospasm of epicardial coronary artery ± superimposed CAD ^[1]
Timing	Occurs at rest, common after cold exposure, cyclical in nature ^[1] — typically early morning (circadian cortisol rise)
Patient	Middle-aged female ^[1]; more common in East Asian populations
ECG during attack	Episodic ST-segment elevations (transmural ischaemia from complete transient occlusion) — resolves when spasm abates ^[1]
Coronary angiogram	Normal or mild CAD; deliver acetylcholine → provocation of spasm, reversed with nitroglycerin ^[1]
Key distinction	CCS pain is exertional and predictable; Prinzmetal pain is at rest, unpredictable, and associated with transient ST elevation

Normal epicardial coronary arteries on angiography.
Angina is exertional (like CCS) but coronary angiogram is clean → problem is at the arteriolar/microvascular level.
More common in women with risk factors (DM, HT).
Diagnosis: abnormal coronary flow reserve on invasive testing (acetylcholine/adenosine provocation) or cardiac MRI stress perfusion.
Important to recognise because these patients still have ↑CV event risk and benefit from anti-anginal therapy.

Acute pericarditis is different to AMI / CCS because ^[11]:

Aggravated by respiratory movement, sharp, knife-like (pleuritic pain)
Radiates to the trapezius ridge (characteristic — phrenic nerve runs along pericardium → referred pain to C3–C5 dermatomes including trapezius)
Sitting up or leaning forward may ease pain (MI pain is not positional) ^[11]
ECG: widespread upward-concave ST elevation (diffuse, not following a single coronary territory — unlike MI which is territorial) ^[14]
Pericardial rub on auscultation

Myocarditis ^[15]:

History: recent flu-like syndrome accompanied by fever, arthralgia, malaise
Elevated cardiac enzymes, ECG may mimic AMI or pericarditis
CT coronary angiogram / cardiac catheterization: to R/O clinically significant CAD ^[15]

The key question: "Is the chest pain pleuritic (worse with breathing, positional) or anginal (worse with exertion, relieved by rest)?"

Both can cause exertional chest pain that closely mimics stable angina:

Condition	Why It Mimics CCS	Key Differentiators
Aortic stenosis	↑Afterload → ↑LV wall stress → ↑O₂ demand; LVH → ↓subendocardial perfusion; concurrent coronary atherosclerosis is common in elderly patients	Ejection systolic murmur radiating to carotids, slow-rising pulse, narrow pulse pressure, syncope triad (angina + syncope + dyspnoea)
HOCM	Massive septal hypertrophy → ↑O₂ demand + ↓capillary density + dynamic LVOT obstruction → ↓coronary perfusion pressure	Cardiac murmurs may be due to valvular heart disease or HOCM ^[4]; murmur ↑ with Valsalva (↓preload → worsens obstruction); young patient, family Hx of sudden death

Tachyarrhythmias (e.g., paroxysmal SVT, AF with rapid ventricular rate) can cause chest discomfort by:

↑O₂ demand (↑HR)
↓Diastolic filling time (coronary perfusion predominantly in diastole)
May unmask underlying subclinical CAD

Key differentiator: patient reports palpitations as the primary symptom, with chest discomfort being secondary.

B. Vascular Causes

Feature	Discriminating from CCS
Onset	Very sudden onset, maximal at onset ^[4]^[12] — unlike CCS which builds up gradually
Quality	Tearing or ripping sensation ^[11]^[12]
Radiation	Radiates to back (between scapulae for Type A; lower back for Type B) ^[11]^[12]
Associated findings	BP asymmetry between arms, new aortic regurgitation murmur, pulse deficits, widened mediastinum on CXR
Why it can mimic CCS	If dissection flap occludes coronary ostium → true MI (coronary malperfusion) with ST elevation ^[14]

Feature	Discriminating from CCS
Quality	Pleuritic pain, worse on deep inspiration / coughing ^[11]
Associated symptoms	Haemoptysis, acute dyspnoea, tachycardia ^[11]
Risk factors	Recent immobilisation, DVT, malignancy, OCP — completely different risk profile from CCS
ECG	Sinus tachycardia; classically S₁Q₃T₃ (right heart strain); NOT typical ischaemic changes
Why it can mimic CCS	Massive PE → ↓cardiac output → central crushing chest pain, ↓BP, collapse

Substernal chest pressure, worsened by exertion ^[12] — very similar to stable angina
Mechanism: ↑RV afterload → RV ischaemia (↑wall stress + ↓coronary perfusion of RV)
Key differentiators: prominent dyspnoea out of proportion to chest pain; loud P₂; RV heave; signs of right heart failure (raised JVP, peripheral oedema, hepatomegaly)

Condition	Key Features	Why It Differs from CCS
Pneumonia	Pleuritic pain, fever, SOB, cough, sputum ^[12]	Pain is pleuritic (sharp, worse on inspiration), not exertional. Systemic inflammatory features.
Pneumothorax — CANNOT miss!!! ^[12]	Sudden onset, SOB, hyperresonance on percussion, ↓breath sounds	Sudden, maximal at onset. Unilateral findings on examination.
Pleural effusion / Mesothelioma	Mesothelioma: severe and constant pain ^[12]; pleural effusion: dull ache, stony dull percussion	Pain is constant (not exertional-relievable), often progressive. Asbestos exposure history for mesothelioma.

D. Gastrointestinal Causes — The Classic "Trap"

These are the most common benign mimics of CCS and often coexist with CAD (especially in the elderly population).

Feature	GERD / Oesophageal Spasm	CCS
Quality	Retrosternal burning ^[4]; can be constricting (oesophageal spasm)	Constricting, heavy
Provocation	Unrelated to exertion; worsen when lies down ^[12]; worse after meals, spicy food, alcohol	Provoked by exertion
Relief	Relieved by swallowing (warm water) ^[12], antacids, PPI	Relieved by rest, GTN
Tricky overlap	GTN can also relieve oesophageal spasm (smooth muscle relaxation) — so GTN response alone does NOT confirm cardiac origin!

Angina pectoris is a differential diagnosis of GERD ^[16]. And vice versa. For a chief complaint of epigastric pain, the most sinister non-GI causes that you must exclude immediately include: myocardial infarction, pulmonary embolism, DKA, ruptured AAA ^[17].

GTN Response Is NOT Diagnostic

A common exam trap: "Pain relieved by GTN = cardiac." This is wrong. GTN is a smooth muscle relaxant that also relaxes oesophageal smooth muscle. Both oesophageal spasm and angina can respond to GTN. The time course helps: anginal relief is typically within 1–3 minutes; oesophageal spasm relief can be slower and less consistent.

Epigastric pain, may radiate to chest; worse with meals (gastric ulcer) or relieved by meals (duodenal ulcer).
Epigastric tenderness on examination ^[10].
Distinguished by: burning quality, relationship to food, absence of exertional pattern.
NSAIDs/aspirin use (which CCS patients are often on!) can cause peptic ulcers → coexistence is common.

Right upper quadrant or epigastric pain, may refer to right shoulder (biliary) or back (pancreatitis).
Usually constant (biliary colic is actually constant, not colicky — misnomer), lasting hours.
Distinguished by: association with fatty meals, localisation to RUQ, raised amylase/lipase.

Condition	Key Features	Why It Differs from CCS
Muscle strains	Worsen with movement ^[12]; point tenderness; reproducible with palpation	CCS is not reproducible by pressing on the chest wall. Musculoskeletal pain often occurs after exertion, not during.
Costochondritis (Tietze syndrome)	Localised tenderness at costochondral junctions; ↑with palpation	Not exertional. Reproducible with palpation.
Rib fracture / Rib tumour	Localised tenderness ^[12]; history of trauma or known malignancy

Pain that is sharp, stabbing, pricking, knife-like, or worsened by inspiration is more likely pleuritic or musculoskeletal than anginal ^[4]. Pain that occurs after exertion (not during) is more suggestive of musculoskeletal or psychogenic origin ^[4].

Condition	Key Features
Thoracic herpes zoster	Thoracic nerve root distribution; precedes typical vesicular rash of herpes zoster ^[12]. Burning, lancinating pain in a dermatomal band. Pain may precede rash by days → initially confused with angina.
Cervical/thoracic radiculopathy	Radiating pain following nerve root distribution; ↑with neck/spine movement; numbness/tingling.

Condition	Key Features	Why It Differs from CCS
Panic attacks ^[4]^[12]	Sudden onset of chest tightness, palpitations, diaphoresis, hyperventilation, tingling in extremities, sense of doom	Onset is not clearly exertional; associated hyperventilation and anxiety symptoms; ECG normal; negative troponin. Young patient with no risk factors.
Psychogenic chest pain	Vague, poorly localised, variable quality; not reproducibly exertional; may last hours/days	Inconsistent pattern; no ECG/biomarker abnormalities. Diagnosis of exclusion.

These are not alternative diagnoses per se — they are comorbidities that unmask or worsen existing CCS by shifting the supply–demand balance:

Condition	Mechanism
Anaemia	↓O₂-carrying capacity → ischaemia at lower exertion thresholds
Thyrotoxicosis	↑HR, ↑contractility, ↑metabolic rate → ↑O₂ demand
Aortic stenosis	↑Afterload → ↑wall stress → ↑O₂ demand
Tachyarrhythmias	↑HR → ↑demand + ↓diastolic coronary filling time
Hypertensive crisis	Acute ↑afterload
Fever / Infection	↑metabolic rate → ↑O₂ demand

Other conditions that may exacerbate angina should be looked for on physical examination: anaemia, thyrotoxicosis ^[4]. Always check for these in a patient whose previously stable angina is worsening — the coronary disease may not have changed, but the haemodynamic stress has.

System	Condition	Key Discriminating Feature
Cardiac	ACS (UA/NSTEMI/STEMI)	Crescendo pattern, rest pain, duration > 20 min, ↑troponin, ECG changes
	Vasospastic angina	Rest pain (nocturnal), ST elevation during attack, normal angiogram
	Microvascular angina	Exertional pain but normal coronary angiogram; abnormal CFR
	Pericarditis	Pleuritic, positional (better leaning forward), trapezius radiation, diffuse ST elevation
	Myocarditis	Recent viral illness, ↑troponin, ECG mimics MI but normal coronaries
	Aortic stenosis / HOCM	Murmur, syncope, young (HOCM) or elderly calcific (AS)
Vascular	Aortic dissection	Sudden tearing pain radiating to back, BP asymmetry, widened mediastinum
	Pulmonary embolism	Pleuritic, haemoptysis, DVT risk factors, tachycardia, S₁Q₃T₃
	Pulmonary hypertension	Exertional substernal pressure, loud P₂, RV signs
Pulmonary	Pneumonia	Pleuritic, fever, productive cough
	Pneumothorax	Sudden onset, unilateral ↓breath sounds, hyperresonance
GI	GERD / Oesophageal spasm	Burning, postprandial, worse lying down, relieved by antacids
	Peptic ulcer	Epigastric, food-related, NSAID use
MSK	Costochondritis / Strain	Reproducible with palpation/movement, not exertional
Neuro	Herpes zoster	Dermatomal, precedes vesicular rash
Psych	Panic attack	Hyperventilation, tingling, young, no risk factors, normal workup

A 61-year-old woman with 9-month history of intermittent substernal pain. Sometimes on exertion (mopping the floor, walking uphill), lasting > 5 min after cessation. At other times onset at rest, notably after dinner, persisting up to 30 minutes.

The senior note commentary is instructive: "The case is deliberately very ambiguous. 30 minutes is the cutoff time between stable and unstable angina. Even though they mentioned rest pain, they make it confusing by saying it notably occurs after dinner → so not sure. Could either be stable or unstable angina" ^[8].

Key differential points for this case:

CCS (stable angina): Exertional pain, reproducible. The post-dinner "rest" pain could be demand ischaemia from ↑splanchnic blood flow (postprandial coronary steal).
Unstable angina: The rest pain and 30-minute duration raise concern.
GERD / Oesophageal pathology: Post-dinner onset, substernal location — classic for reflux.
Aortic stenosis: 2/6 ejection systolic murmur over aortic area on examination ^[8].
Peripheral arterial disease: Absent R dorsalis pedis pulse, weak L dorsalis pedis and posterior tibial pulses, soft L carotid bruit ^[8] → diffuse atherosclerosis → CCS highly likely.

High Yield Summary – Differential Diagnosis

Approach: Anatomy-based (cardiac → vascular → pulmonary → GI → MSK → neuro → psych).

"Cannot miss" diagnoses ^[10]^[12]:

ACS (crescendo, rest pain, > 20 min, ↑troponin)
Aortic dissection (sudden tearing to back, BP asymmetry)
Pulmonary embolism (pleuritic, haemoptysis, DVT risk)
Pneumothorax (sudden, unilateral ↓BS, hyperresonance)

Most common benign mimics: GERD/oesophageal spasm, musculoskeletal pain, psychogenic.

Key discriminators for CCS:

Pain is exertional, reproducible, and predictable.
Duration 1–5 min, relieved by rest/GTN within minutes.
Not pleuritic, positional, reproducible by palpation, or associated with rash/fever.

Always check for demand-ischaemia triggers (anaemia, thyrotoxicosis, tachyarrhythmia, AS, fever) when stable angina worsens — the problem may be the haemodynamic context, not new coronary disease.

Active Recall - DDx of Chronic Coronary Syndrome

References

^[1] Senior notes: Block A - WCS32 Chest pain on exertion: ischaemic heart disease; angina pectoris (Prinzmetal variant, congenital anomalies sections) ^[2] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai) (pp. 384, 399 — Stable CAD overview, DDx table) ^[4] Senior notes: Ryan Ho Fundamentals (pp. 199–203, Approach to Chest Pain, OPQRST table) ^[8] Senior notes: Block A - Cardiology Interactive Tutorial (pp. 4–5, Case 2) ^[9] Senior notes: Block A - Accelerating chest pain: Acute Coronary Syndromes (pp. 7–8, ACS spectrum, diagnosis) ^[10] Senior notes: Block A - Chest Pain - Department of Medicine (p. 1, DDx and physical examination approach) ^[11] Senior notes: Block A - Sudden severe chest pain: AMI; aortic dissection (p. 6, Differentials) ^[12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai) (p. 399, DDx table of chest pain by type) ^[14] Senior notes: Block A - Introduction to CVS investigations including ECG (pp. 8–9, ECG patterns) ^[15] Lecture slides: Three Cases SOB 20211.pdf (p. 32, Myocarditis diagnosis) ^[16] Senior notes: Block A - Indigestion and heartburn: nausea and vomiting; gastric motility problems; benign esophageal lesions (p. 5, DDx of GERD) ^[17] Senior notes: Block A - Upper abdominal pain: peptic ulcer; pancreatitis and gallstone (p. 3, Non-GI causes of epigastric pain)

Diagnostic Criteria

In Chronic Coronary Syndrome (CCS), the diagnostic question is fundamentally different from ACS. In ACS, you are confirming acute myocardial injury (troponin rise). In CCS, you are trying to confirm:

The presence of obstructive coronary artery disease (anatomical question)
The presence of inducible myocardial ischaemia (functional question)
The severity and extent of disease (prognostic question)

There is no single "diagnostic criterion" for CCS the way there is for MI. Instead, the diagnosis is built from a clinical probability assessment followed by stepwise non-invasive and/or invasive testing guided by pre-test probability (PTP).

Significant CAD is usually defined as stenosis ≥50% on invasive coronary angiography ^[2]. However, the clinical relevance depends on whether the stenosis is flow-limiting:

Stenosis Severity	Haemodynamic Significance	Clinical Implication
< 50%	Not significant	Unlikely to cause angina; medical therapy for risk factor control
50–69%	May or may not be flow-limiting	Requires functional assessment (stress test, FFR) to determine if ischaemia is provoked
≥70%	Typically flow-limiting	Likely cause of angina; PCI indicated for stable CAD when occlusion ≥70% ^[2]
≥50% left main	Always significant	High-risk; revascularisation (usually CABG) recommended

Why this distinction matters: a plaque that narrows the lumen by 60% may cause zero ischaemia at rest (compensatory vasodilation of downstream arterioles maintains adequate flow) and may even tolerate mild exertion. It is only when the stenosis exceeds ~70% that the vasodilatory reserve is exhausted and exertional ischaemia becomes manifest ^[18].

Compensatory vasodilation in response to hypoxaemia means that significant ischaemia will not set in with < 50% stenosis despite presence of structural lesions detected in anatomical imaging. This gives an advantage to functional testing over anatomical tests ^[18].

As established in the previous section, the clinical diagnosis of angina rests on three characteristic features:

Constricting discomfort in the chest, neck, jaw, shoulder, or arm
Provoked by physical exertion or emotional stress
Relieved by rest or GTN within ~5 minutes

Category	Features Present	Interpretation
Typical angina	All 3	High clinical likelihood of obstructive CAD
Atypical angina	2 of 3	Intermediate clinical likelihood
Non-anginal chest pain	≤1	Low clinical likelihood (consider non-cardiac causes)

GC Lecture High Yield – Decision Algorithm

The GC 032 lecture slide presents a detailed non-invasive investigation decision algorithm ^[19] that is the foundation of the diagnostic approach. Know this flowchart inside out — it is very commonly tested in HKUMed in-house exams.

The ESC 2019 updated PTP model uses age, sex, and symptom type (typical angina / atypical angina / non-anginal pain / dyspnoea only) to estimate the probability of obstructive CAD. The clinical likelihood is then further modified by:

Risk factors: DM, HT, smoking, dyslipidaemia, family history
Resting ECG: ST-T changes, Q waves, LBBB
LV dysfunction on echocardiography
Coronary artery calcium (CAC) score if available
Exercise ECG if performed

PTP Category	Estimated PTP	Action
Very low	< 5%	No further testing needed; consider other causes
Low	5–15%	Consider testing only if clinical features strongly suggest CAD (modifiers present)
Intermediate-high	> 15%	Non-invasive diagnostic testing recommended

Diagnostic Algorithm

Node 1: Contraindication for stress test?

Physical inability to exercise (musculoskeletal, neurological)
Severe aortic stenosis (relative CI)
Uncontrolled HF, severe arrhythmia, acute illness
If yes → skip directly to coronary imaging

Node 2: Symptoms/clinical findings warranting direct coronary imaging?

The patient did not have a contraindication for stress test, BUT they had quite severe symptoms or clinical findings warranting coronary imaging → so skip the stress test, go directly for coronary imaging ^[1]
Examples: very high PTP, rest angina features, significant LV dysfunction, signs of extensive vascular disease

Node 3: Resting ECG interpretable?

The exercise ECG relies on detecting new ST changes during exertion
If baseline ECG already has ST-T abnormalities (e.g., LVH with strain, LBBB, digitalis effect, pre-excitation), new ischaemic changes cannot be reliably identified → need imaging-based stress test instead
Also if previous revascularisation (PCI/CABG) → ETT alone is insufficient; need imaging

Node 4: Able to exercise?

If yes → exercise stress (physiological, better prognostic data)
If no → pharmacological stress agent

Investigation Modalities

Level 1: Baseline Investigations (Every Patient)

Following history and physical examination for a patient with suspected CAD but no active symptoms (i.e., stable angina), three classes of blood tests should be performed ^[1]:

Class	Tests	Rationale
Lipid levels	LDL, HDL, total cholesterol, TG, Lp(a) ^[1]	Assess and quantify dyslipidaemia; guide statin therapy targets; Lp(a) is an independent genetic risk factor
Metabolic evaluation	Fasting plasma glucose, HbA1c, serum creatinine/eGFR, TFT ^[1]	Identify DM (accelerates atherosclerosis), CKD (affects drug dosing + ↑CV risk), hypothyroidism (secondary dyslipidaemia), thyrotoxicosis (demand ischaemia)
Markers for cardiac function	hs-CRP, BNP/NT-proBNP ^[1]	hs-CRP: since inflammation plays a big role in CAD, can help predict risk ^[1]. BNP: screen for LV dysfunction / HF.

High-sensitivity troponin is ordered for patients with active cardiac chest pain (to differentiate NSTEMI from UA), but has less of a role in stable patients ^[1]. In CCS, troponin should be normal. If elevated → suspect acute event (→ treat as ACS) or chronic conditions (HF, CKD, myocarditis).

Key laboratory findings from the Interactive Tutorial case ^[8]:

Fasting glucose 9.1 mmol/L, HbA1c 10.2 → poorly controlled T2DM (HbA1c target generally < 7%)
Total cholesterol 5.2, TG 2.8, LDL 3.1, HDL 0.72 mmol/L → atherogenic dyslipidaemia (↑TG, ↓HDL, moderately ↑LDL)
These findings confirm multiple CV risk factors → high clinical likelihood of CAD

Baseline 12-lead ECG should be performed in all patients ^[4]. Key findings and their interpretation:

Finding	Significance
Normal resting ECG	Does NOT exclude CAD — ischaemia is only provoked during demand (exertion). A normal ECG at rest is common in CCS.
ST-segment depression	Suggests ischaemia (if dynamic) or LVH strain pattern (if persistent). Lower threshold for V2-V3 than other leads ^[20].
T-wave inversion	Non-specific; can be ischaemic, LVH strain, or normal variant. T wave inversion in V3 — quite non-specific, could be the juvenile pattern ^[10].
Pathological Q waves	Suggest prior MI → already established CAD. Any Q wave in V2-V3 would be abnormal (should see septal R wave). Other leads: ≥1 small square wide ^[20].
Left bundle branch block (LBBB)	Makes ST-segment analysis uninterpretable → stress imaging required, NOT exercise ECG alone. New LBBB should be managed as STEMI ^[20].
LVH criteria	Suggests longstanding HT → ↑demand ischaemia risk; strain pattern confounds ischaemia assessment.
Pre-excitation (delta wave)	WPW — confounds ST analysis; also a cause of palpitations/arrhythmia.
AF	Irregularly irregular; ↑demand ischaemia + source of coronary embolism.

Key ECG Principle

Q waves indicate potential previous MI. NEW LBBB — have to be careful for patients with chest pain → should be managed as the same as patients with ST elevation ^[20]. In a stable CCS patient, finding Q waves on resting ECG tells you they have already had a prior infarction, which affects prognosis and management.

Routine baseline echocardiogram is recommended by ESC to evaluate for ^[4]:

Regional wall motion abnormalities — indicate ischaemia or prior MI (e.g., anterior wall hypokinesis = LAD territory)
LVEF → important prognostic parameter — lower the ejection fraction, higher the risk ^[1]
Other structural cardiac conditions — valvular disease (AS, MR), cardiomyopathy (HOCM, DCM), pericardial disease

Usually non-diagnostic in CCS specifically.
Useful to: exclude non-cardiac causes (pneumonia, pneumothorax, pleural effusion), assess for pulmonary congestion (HF), identify widened mediastinum (aortic dissection).
Cardiomegaly on CXR suggests LV dilatation (ischaemic cardiomyopathy) or pericardial effusion.

Level 2: Non-Invasive Functional Testing (Stress Tests)

The fundamental principle: at rest, coronary flow may be adequate despite a significant stenosis (due to compensatory vasodilation). A stress test unmasks ischaemia by increasing myocardial demand (exercise or pharmacological) and looking for evidence of supply–demand mismatch via ECG, echo, or nuclear imaging.

The exercise treadmill ECG is the first-line non-invasive test when the resting ECG is interpretable, the patient has not been previously revascularised, and the patient is able to exercise ^[19].

Protocol: Bruce protocol (7-stage test with treadmill increasing speed and grade) ^[21].

How it works:

Patient exercises until one of: target HR reached (HR = (220 − age) × 0.8), symptomatic, or ST-T changes appear ^[21].
Stop antihypertensive on the day of test ^[21] — β-blockers blunt HR response and may mask ischaemia.

What you are looking for:

Finding	Interpretation
≥1 mm horizontal/downsloping ST depression	Positive for inducible ischaemia (subendocardial)
ST elevation	Transmural ischaemia or coronary spasm (rare on ETT)
Angina during exercise	Symptom confirmation
Failure to reach target HR	Chronotropic incompetence (may be drug-related or intrinsic) → non-diagnostic
Hypotension with exercise	Suggests severe CAD (LV unable to augment output) → high risk
Ventricular arrhythmias	Ischaemia-triggered → high risk

Duke Treadmill Score: a validated composite score based on exercise time, presence of angina, and maximum net ST segment changes ^[21] → stratifies into low / intermediate / high risk.

Interactive Tutorial case finding: Exercise ECG test: 7 METS achieved. Stopped for dyspnoea. 2 mm ST depression over leads II, III, aVF, and V4-6 ^[8] → positive test indicating ischaemia in inferior (RCA territory) and anterolateral (LAD/LCx territory) → multi-vessel disease.

Interpreting the Case ETT Result

2 mm ST depression in II, III, aVF AND V4-6 — this is ischaemia in two separate coronary territories (inferior + anterolateral). Multi-territorial ischaemia on stress testing is a high-risk feature that should prompt coronary imaging (CT coronary angiogram or invasive angiography) rather than continued medical therapy alone ^[1]^[19].

Limitations of ETT:

Cannot be used if baseline ECG is uninterpretable (LBBB, LVH with strain, pre-excitation, digitalis)
Lower sensitivity (~68%) and specificity (~77%) compared to imaging-based tests
Cannot localise ischaemia as precisely as imaging

B. Stress Imaging Tests — When ETT Is Insufficient or Uninterpretable

These add imaging to the stress component, providing both ischaemia detection AND localisation.

Exercise stress echo ^[19]: Patient exercises (or receives dobutamine if unable) → echo performed immediately before and after stress.

Finding	Interpretation
New regional wall motion abnormality (RWMA) during stress	Ischaemia in that coronary territory — the ischaemic segment fails to contract normally
No change from baseline	Negative for ischaemia
Fixed RWMA (present at rest and stress)	Scar tissue from prior MI — no viable/ischaemic tissue

Advantages: no radiation, widely available, also assesses valvular function and LV geometry.
Limitations: operator-dependent, limited acoustic windows (obesity, emphysema).
Pharmacological alternative: Dobutamine stress echo — dobutamine is a β₁-agonist that ↑HR and contractility, simulating exercise. C/I: recent MI ^[21].

Indication: screening and diagnosis of coronary artery disease ^[18]. Invasive tests (e.g., cardiac catheterization) usually reserved for high-risk patients ^[18].

Principle — the coronary steal phenomenon ^[18]:

At rest: partial coronary stenosis limits blood flow, but blood flow remains substantial due to collaterals and ischaemia-induced vasodilation ^[18].
With stress: vessels supplying normal myocardium also dilated → blood siphoned to normal myocardium ("steal") → ↓↓perfusion of affected myocardium → appears as "cold spots" in perfusion scan ^[18].

Radiopharmaceuticals used: Thallium-201 (²⁰¹Tl) and ⁹⁹ᵐTc-sestamibi ^[18]^[21].

Interpretation ^[18]:

Pattern	Rest	Stress	Meaning
Normal	Homogeneous	Homogeneous	No ischaemia, no scar
Ischaemia (reversible defect)	Normal	Cold spot	Viable but ischaemic tissue — will benefit from revascularisation
Infarct (fixed defect)	Cold spot	Cold spot	Non-viable scar tissue — unlikely to benefit from revascularisation
Hibernating myocardium	Cold spot	Cold spot BUT viable on redistribution/rest reinjection	Chronically ischaemic but viable → may benefit from revascularisation

Stress agents: exercise, vasodilators (adenosine, dipyridamole), or inotropes (dobutamine + atropine) ^[18].

Adenosine: C/I in asthma (causes bronchoconstriction via A₁ receptors) ^[21].
Dobutamine: C/I in recent MI ^[21].

After doing pharmacological stress test, you can either do cardiac MRI or SPECT ^[8].

Main uses of MPI ^[18]:

Determine adequacy of blood flow ± stress (functional — detect haemodynamically significant stenosis defined by ≥50% diameter stenosis)
Determine viability of myocardium (→ decide whether to perform PCI or CABG)

The advantage of MPI over anatomical tests is that it detects functional significance — a 60% stenosis that is not causing ischaemia on MPI does not need revascularisation.

Uses gadolinium contrast to assess perfusion (first-pass perfusion imaging) and viability (late gadolinium enhancement, LGE).
Very high spatial resolution; no radiation.
Limitations: expensive, time-consuming, claustrophobia, CI in patients with certain metallic implants/pacemakers (though newer MRI-conditional devices exist).
With increasing expensive tests, greater sensitivity and specificity ^[1].

Gold standard for myocardial viability assessment and quantitative coronary flow reserve measurement.
Less widely available and more expensive.

Level 3: Non-Invasive Anatomical Testing

Direct visualization of the anatomy → see the blood vessels/blockage, can see nice coronary artery lumen ^[1].

Technology: Newer CT scanners have much higher scans per second (320 slices), can visualize coronary artery anatomy much better → very high resolution ^[1]. Older scanners (16-slice) were inadequate for coronary imaging.

Aspect	Detail
What it shows	Coronary artery lumen, plaque (calcified and non-calcified), degree of stenosis
Sensitivity	Very high (~95–99%) for ruling out significant CAD — High sensitivity for stenosis detection, so a normal CTA can reliably rule out disease ^[9]
Specificity	Low specificity → many false positives especially when there is calcium ^[1] — calcified plaques cause blooming artefact → overestimates stenosis
NPV	NPV is high so a good rule-out test ^[1]
Radiation	Radiation, especially for young patients, but reduced with ECG-gating, low-dose protocols ^[9]. Interestingly, radiation dose is actually lower (1/4) than that of the thallium SPECT scintigraphy scan ^[1]
Contrast	Requires IV iodinated contrast — CT with contrast eGFR cutoff → 30 mL/min ^[22]

"Triple rule-out": the CTCA can help you rule out the three big cannot-miss diagnoses: myocardial infarction, pulmonary embolism, aortic dissection ^[9].

When to use CTCA (per ESC 2019):

First-line anatomical test when non-invasive testing is preferred
Especially useful in patients with low-intermediate PTP where high NPV can confidently exclude CAD
As an alternative to functional testing when local expertise/availability favours it

Non-contrast CT used to assess degree of calcification of coronary arteries ^[23].

Score	Interpretation
0	Very low likelihood of obstructive CAD; excellent prognosis (< 1% 10-year CV event rate)
1–99	Mild calcification; may have non-obstructive CAD
100–399	Moderate calcification; ↑risk
≥400	Severe calcification; high risk of obstructive CAD

Useful as a "gatekeeper" — a CAC of 0 in a low-risk patient essentially rules out significant atherosclerosis.
Useful as an early marker: heterozygous FH patients develop coronary artery calcification early (< 23 y) — useful screening marker.
Limitation: does not detect non-calcified (soft) plaque — can underestimate disease in younger patients with lipid-rich plaques.

Just one invasive investigation exists for CAD confirmation: the coronary angiogram ^[1] — this is the fluoroscopy-guided procedure where they inject contrast directly into coronary ostia.

Indications for invasive coronary angiogram ^[1]^[19]:

Unacceptable angina despite medical therapy (for consideration of revascularisation)
Non-invasive testing results with high-risk features
Angina or risk factors for CAD in the setting of depressed LVEF
For diagnostic purposes, in the individual in whom the results of non-invasive testing are unclear

What it provides:

Gold standard for anatomical assessment of coronary stenosis (severity, number of vessels, location)
Can be combined with fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) — functional assessment of haemodynamic significance of borderline lesions (50–70% stenosis)
- FFR: adenosine-induced hyperaemia; ratio of distal to proximal coronary pressure. FFR ≤0.80 = haemodynamically significant → revascularise. FFR > 0.80 = not significant → medical therapy.
- iFR: resting measurement (no adenosine needed); iFR ≤0.89 = significant.
Can proceed directly to PCI in the same session (diagnostic + therapeutic)

Risks: vascular access complications (haematoma, pseudoaneurysm), contrast nephropathy, stroke (~0.1%), coronary dissection, MI, death (~0.05%).

Condition	Investigation	Key Finding
Vasospastic (Prinzmetal) angina	Coronary angiogram with provocation testing: deliver acetylcholine → mimic the spasm episode to create vasoconstriction, reversed with nitroglycerin ^[1]	Focal/diffuse coronary artery spasm with transient ST elevation
	Ambulatory ECG (Holter)	Transient ST changes (usually elevation) during symptoms with subsequent resolution ^[24]
Microvascular angina	Invasive coronary angiogram (normal epicardial arteries) + coronary flow reserve (CFR) measurement with adenosine	CFR < 2.0 = abnormal microvascular function
	Cardiac MRI stress perfusion	Subendocardial perfusion defects despite normal epicardial arteries

Tests available to detect an old MI ^[25]:

ECG: Development of new pathological Q waves — Any Q wave in V2-V3 ≥0.02 seconds, or QS complex in V2-V3. Q wave ≥0.03 seconds and ≥0.1 mV deep, or QS complex in any two contiguous leads of I, aVL, V6, V4-V6, II, III, aVF ^[25].
Nuclear imaging: Fixed perfusion defect (cold spot at rest and stress)
Cardiac MRI: Late gadolinium enhancement (LGE) in a coronary artery territory pattern (subendocardial or transmural) — highly sensitive and specific
Echocardiography: Fixed regional wall motion abnormality (akinesis/dyskinesis) with wall thinning

Investigation	What It Assesses	Sensitivity	Specificity	Radiation	Key Limitation
ETT	Functional (ischaemia)	~68%	~77%	None	Needs interpretable ECG; cannot localise precisely
Stress Echo	Functional (ischaemia + RWMA)	~80–85%	~85–90%	None	Operator-dependent; acoustic windows
MPI (SPECT)	Functional (perfusion)	~85–90%	~70–75%	High	Lower specificity; attenuation artefacts
Stress CMR	Functional (perfusion + viability)	~90%	~80%	None	Cost, availability, claustrophobia
PET	Functional (perfusion + viability + flow quantification)	~92%	~85%	Low	Cost, availability
CTCA	Anatomical (stenosis)	~95–99%	~65–83%	Low–moderate	False positives with calcium; does not assess function
CAC score	Anatomical (calcification)	N/A	N/A	Very low	Misses non-calcified plaque
Invasive angiography	Anatomical (gold standard) + functional (with FFR/iFR)	Gold standard	Gold standard	Moderate	Invasive; procedural risks

Cardiac troponin is the gold standard biomarker for myocardial ischaemia/injury ^[21]. However, its role differs:

Context	Troponin Role
ACS	Detection of rise and/or fall of cardiac biomarker values, preferably cardiac troponin, with at least one value above the 99th percentile URL → diagnostic of MI ^[2]^[21]
CCS	Should be normal. If elevated → suspect ongoing ischaemia (ACS), HF, CKD, myocarditis. hs-troponin ordered for patients with active cardiac chest pain, less of a role in stable patients ^[1]

CK-MB utility: shorter half-life than troponin → CK-MB is better at detecting reinfarction (if troponin already elevated from index event) and helps with timeline (if presenting late, 48 hours after onset of AMI, then only +ve troponin with -ve CK-MB → helps with the timeline) ^[9].

Universal Definition of MI – Types

While CCS itself does not involve MI, understanding the MI classification helps you understand when a CCS patient transitions to ACS ^[21]^[24]:

Type 1: Spontaneous MI due to plaque rupture/erosion → thrombotic occlusion
Type 2: MI secondary to supply-demand mismatch (e.g., anaemia, hypotension, tachyarrhythmia on background of CCS) — check CBC for anaemia, PR for GI bleed ^[21]
Type 3: Sudden cardiac death before biomarkers obtained
Type 4a/4b: PCI-associated / stent thrombosis
Type 5: CABG-associated

High Yield Summary – Diagnosis of CCS

No single "diagnostic criterion" for CCS — diagnosis is built from clinical assessment + stepwise testing.
Significant CAD = ≥50% on angiography. Flow-limiting = ≥70% (or ≥50% LM). PCI for stable CCS when ≥70%.
Baseline workup for all patients: bloods (lipids, glucose/HbA1c, creatinine/eGFR, TFT, hs-CRP, BNP), resting ECG, echocardiogram, CXR.
GC 032 Lecture Slide Decision Algorithm ^[19]:
- Can exercise + interpretable ECG → ETT (first-line)
- Cannot exercise OR uninterpretable ECG → stress imaging (echo, MPI, CMR)
- Contraindication to stress testing OR high-risk features → coronary imaging (CTCA or invasive)
Stress test interpretation: ETT: ≥1 mm ST depression = positive. MPI: cold spot on stress only = ischaemia; cold spot at rest + stress = infarct/scar. Stress echo: new RWMA = ischaemia.
CTCA: very high sensitivity/NPV → good rule-out test. Low specificity with calcium. "Triple rule-out" for MI/PE/aortic dissection.
Invasive coronary angiography indications: unacceptable angina despite medical therapy, high-risk non-invasive results, depressed LVEF, unclear non-invasive results.
FFR ≤0.80 (or iFR ≤0.89) on invasive angiography = haemodynamically significant lesion → revascularise.
Troponin should be NORMAL in CCS — if elevated, suspect ACS or other causes (HF, CKD, myocarditis).

Active Recall - Diagnosis of Chronic Coronary Syndrome

^[1] Senior notes: Block A - WCS32 Chest pain on exertion: ischaemic heart disease; angina pectoris (pp. 21, 28–31 — Blood tests, CT coronary angiogram, decision algorithm, high-risk CAD, invasive investigations) ^[2] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai) (pp. 384, 395, 400 — Stable CAD overview, diagnostic criteria) ^[4] Senior notes: Ryan Ho Fundamentals (pp. 199–203) / Ryan Ho Cardiology (p. 57 — Approach to Stable Chest Pain) ^[8] Senior notes: Block A - Cardiology Interactive Tutorial (pp. 4–5, Case 2 — exercise ECG findings, investigation discussion) ^[9] Senior notes: Block A - Accelerating chest pain: Acute Coronary Syndromes (pp. 8, 22 — biomarkers, CTCA triple rule-out) ^[10] Senior notes: Block A - Chest Pain - Department of Medicine (p. 1 — ECG interpretation, T-wave inversion) ^[18] Senior notes: Ryan Ho Diagnostic Radiology (p. 57 — Myocardial Perfusion Imaging) ^[19] Lecture slides: GC 032. Chest pain on exertion: ischaemic heart disease; angina pectoris (pp. 38, 43, 44, 48 — Non-invasive investigation algorithm, CT coronary angiogram, stress echo, invasive investigations) ^[20] Senior notes: Block A - Cardiology Data Interpretation (p. 7 — Q waves, ST depression thresholds) ^[21] Senior notes: Maksim Medicine Notes (pp. 7, 9 — Stress testing, biomarkers, AMI types) ^[22] Senior notes: Block A - Chest Pain - Department of Radiology (p. 1 — CT contrast eGFR cutoff, alternative imaging) ^[23] Senior notes: Ryan Ho Diagnostic Radiology (p. 43 — Cardiac CT, calcium scoring, CT angiography) ^[24] Senior notes: Ryan Ho Cardiology (pp. 127, 142 — Universal definition of MI, vasospastic angina, MINOCA) ^[25] Senior notes: Block A - Sudden severe chest pain: AMI; aortic dissection (p. 17 — Old MI detection, ECG criteria)

Overarching Philosophy

The management of CCS has two parallel goals running simultaneously ^[1]:

Reduce angina symptoms and exercise-induced ischaemia — improve quality of life
Prevent cardiovascular events (MI, stroke, cardiovascular death) — improve survival

An optimal treatment is one that satisfactorily controls symptoms and prevents cardiac events, enabling maximum patient adherence with minimal side effects ^[1].

No universal definition of which drug or combination is "optimal" exists. Anti-ischaemic drug therapies must be adapted to each patient's characteristics and preferences ^[1].

The management framework can be broken into:

A. General measures (lifestyle, risk factor control)
B. Pharmacological therapy (anti-anginal + secondary prevention)
C. Revascularisation (PCI, CABG)

For every patient with CAD, 5 general principles of management ^[1]:

Principle	Details	Rationale
1. Rule out and control aggravating conditions	Associated non-cardiac diseases (anaemia, thyrotoxicosis, fever), associated cardiac diseases (arrhythmias, valvular disease), use of drugs aggravating angina (stimulants, vasoconstrictors) ^[1]	These shift supply–demand balance; correcting them may eliminate symptoms without changing coronary anatomy
2. Smoking cessation	Most impactful single lifestyle intervention; reduces CV mortality by ~36%	Eliminates ongoing endothelial damage, ↓LDL oxidation, ↓prothrombotic state
3. Dietary counselling for body weight and lipid control	Mediterranean diet pattern; ↓saturated fat, ↑omega-3; caloric restriction if overweight	Directly reduces atherogenic lipid burden and inflammation
4. Exercise prescription	Regular exercise but not beyond point of discomfort ^[26]; supervised exercise rehabilitation	Improves endothelial function, ↑coronary collateral formation, ↑insulin sensitivity, ↓BP
5. Treat to targets	Hypertension, blood lipids, diabetes ^[1]; antiplatelet therapy	See specific targets below

Specific Risk Factor Targets (ESC 2019 / local practice)

Risk Factor	Target	Key Drug
Blood pressure	< 130/80 mmHg (if tolerated); < 140/90 as minimum	ACEI/ARB preferred in CCS (see below)
LDL cholesterol	↓LDL to < 1.8 mmol/L AND ≥50% reduction from baseline (very high-risk patients; ESC 2019) ^[26]	Statin first-line; add ezetimibe/PCSK9i if not at target
HbA1c	< 7% (individualised) ^[26]	Metformin first-line; consider SGLT2i or GLP-1RA especially if established CVD ^[27]
Smoking	Complete cessation	Pharmacotherapy (varenicline, NRT) + counselling

GC Lecture High Yield – T2DM + CVD

Per ADA/ESC guidelines and GC 028 lecture slides ^[28]: for T2DM patients with established CVD or CKD, SGLT2i (especially if heart failure) or GLP-1RA should be used as add-on (or even first-line alongside metformin) ^[27]. These agents have proven cardiovascular outcome benefits beyond glucose lowering — SGLT2i reduces HF hospitalisation, GLP-1RA reduces MACE.

B. Pharmacological Therapy

Part 1: Anti-Anginal Drugs (Symptom Relief)

These drugs work by restoring the supply–demand balance — either by decreasing myocardial oxygen demand (↓HR, ↓contractility, ↓preload, ↓afterload) or by increasing coronary blood supply (coronary vasodilation).

First-Line Agents

The cornerstone of anti-anginal therapy ^[28].

Aspect	Details
Mechanism	Block β₁-adrenoceptors on the heart → ↓HR (negative chronotropy) + ↓contractility (negative inotropy) + ↓BP → ↓myocardial O₂ demand. Also ↑diastolic filling time → ↑coronary perfusion time.
Indications	First-line monotherapy or in combination with CCB or nitrates, used to prevent or reduce the frequency of angina in patients with CAD. For patients with systolic LV failure (EF < 40%), heart failure, and prior MI. Ventricular rate control in AF ^[19].
Preferred agents	Cardioselective: metoprolol (25 mg BD, titrate), atenolol, bisoprolol. If reduced EF: bisoprolol, carvedilol, metoprolol succinate ^[21].
Target	Titrate to HR < 70 bpm ^[21]^[29]
Side effects	Bradycardia, syncope, hypotension, bronchial spasm, impaired glucose tolerance ^[19]
Contraindications	AV block, sinus node dysfunction; bronchial asthma; vasospastic angina; PAD; Raynaud phenomenon; depression ^[19]

Why first-line? β-blockers are the only anti-anginal agents with proven mortality benefit post-MI and in HFrEF. They reduce both symptoms AND future events.

Beta-Blockers and Vasospastic Angina

Beta-blockers are CONTRAINDICATED in vasospastic (Prinzmetal) angina ^[19]. Why? By blocking β₂-mediated coronary vasodilation, they leave α-adrenergic vasoconstriction unopposed → can paradoxically worsen coronary spasm. Use CCBs instead.

Three subtypes with different pharmacological profiles:

Subtype	Example	Primary Action	Cardiac Effects
Phenylalkylamine	Verapamil	Cardiac > vascular	Strong negative chronotropy + inotropy + dromotropy
Benzothiazepine	Diltiazem	Cardiac ≈ vascular	Moderate negative chronotropy + inotropy
Dihydropyridine (DHP)	Nifedipine, Amlodipine	Vascular >> cardiac	Potent arteriolar vasodilation; minimal cardiac depression; reflex tachycardia (esp. short-acting nifedipine)

Aspect	Details
Mechanism	Block L-type Ca²⁺ channels → ↓Ca²⁺ entry into myocytes and vascular smooth muscle → vasodilation (↓afterload + coronary dilation) ± ↓HR/contractility (non-DHP)
Indications	As monotherapy (β-blockers contraindicated or intolerant) or in combination with β-blockers or nitrates, used to prevent or reduce the frequency of angina. Vasospastic angina. Ventricular rate control in AF ^[19].
Side effects	Bradycardia (non-DHP CCBs), syncope, hypotension, peripheral oedema, headache, dizziness, constipation ^[19]
Contraindications	AV block, sinus node dysfunction, and HF (non-DHP CCBs) ^[19]

Why not combine non-DHP CCB + β-blocker? Both cause ↓HR and ↓contractility → risk of severe bradycardia, AV block, or HF. If you combine a CCB with a β-blocker, use a DHP (e.g., amlodipine) — its vasodilatory reflex tachycardia is counteracted by the β-blocker.

The drug used for vasospastic angina is CCB (verapamil or diltiazem; DHP also effective) — NOT β-blocker ^[19].

For patients where β-blockers are contraindicated ^[28]:

Calcium-channel blockers (diltiazem, verapamil) → if there are contraindications to beta-blockers and no heart failure

Second-Line Agents

Aspect	Details
Mechanism	Release NO → activates guanylyl cyclase → ↑cGMP → smooth muscle relaxation. Venodilatation (↓preload → ↓wall stress → ↓O₂ demand) + coronary vasodilatation (↑supply) ^[19]. Some arteriolar dilation (↓afterload).
Short-acting nitrates (SL GTN)	To relieve acute anginal pain; use prophylactically to improve exercise tolerance and prevent exercise-induced ischaemia ^[19]. Patient carries SL GTN spray and uses before/during angina. Onset 1–3 minutes.
Long-acting nitrates (ISDN, ISMN)	As monotherapy or in combination with β-blockers or CCBs, used to prevent or reduce the frequency of angina ^[19]. ISDN (Isordil) 10–30 mg TDS; ISMN (Elantan) 20–40 mg BD or (Imdur) 60–120 mg daily ^[29].
Nitrate tolerance	Continuous nitrate exposure → ↓responsiveness. Prevent by ensuring a nitrate-free interval (≥8–12 hours/day, usually overnight). This is why Imdur is given once daily (morning) rather than continuous infusion for chronic use.
Side effects	Hypotension, syncope, tachycardia (reflex), headache, facial flushing. Less common: methaemoglobinaemia ^[19]
Contraindications	HOCM (↓preload worsens LVOT obstruction); concomitant PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) — same-day use causes severe life-threatening hypotension; SBP < 90 mmHg ^[19]

Nitrates + Sildenafil = Danger

Nitrates are contraindicated with PDE-5 inhibitors ^[19]. Both increase cGMP → synergistic vasodilation → profound hypotension → shock. Must ask about erectile dysfunction medication use before prescribing nitrates!

Agent	Mechanism	Notes
Ivabradine	Selective If channel inhibitor ("funny current") in SA node → ↓HR without affecting contractility or BP	Used when β-blockers are contraindicated or HR remains > 70 despite β-blocker. Only works in sinus rhythm.
Ranolazine	Inhibits late Na⁺ current → ↓intracellular Ca²⁺ overload → ↓diastolic tension → ↓O₂ demand; does NOT affect HR or BP	Add-on when first-line agents insufficient. Also ↓HbA1c slightly.
Nicorandil	K⁺-ATP channel opener + nitrate-like action → arteriolar + venous dilation + coronary vasodilation	Can cause oral/GI ulceration (rare but characteristic side effect).
Trimetazidine	Metabolic modulator: shifts myocardial metabolism from fatty acid oxidation to glucose oxidation → more O₂-efficient ATP production	Does not affect haemodynamics. Useful add-on especially in diabetics.

Part 2: Secondary Prevention Drugs (Event Prevention / Prognostic Benefit)

These are the drugs that save lives — reducing future MI, stroke, and cardiovascular death.

Aspect	Details
Rationale	Atherosclerotic plaques are thrombogenic; platelets adhere to damaged endothelium and can trigger thrombotic occlusion. Antiplatelet agents reduce this risk.
Drug of choice	Aspirin 75–100 mg daily, recommended for all patients without contraindications ^[28]
Mechanism of aspirin	Irreversibly acetylates cyclooxygenase-1 (COX-1) → blocks thromboxane A₂ (TXA₂) synthesis → ↓platelet aggregation. Effect lasts the lifetime of the platelet (~7–10 days).
If aspirin-intolerant	Clopidogrel 75 mg daily — P2Y₁₂ receptor antagonist. Blocks ADP-mediated platelet activation.
After PCI	DAPT required (see revascularisation section below)

For stable CCS without recent ACS or PCI: single antiplatelet therapy (aspirin alone) is standard. DAPT is NOT routinely needed.

DAPT Duration After PCI in Stable CCS vs. ACS

For patients with stable CAD who underwent PCI → 6 months of DAPT (can still do 12, but 6 also OK) ^[30]. For patients with acute MI who underwent PCI → 12 months of DAPT still required ^[30]. The difference reflects the higher re-thrombosis risk in ACS (inflamed, disrupted plaque) vs. stable CCS (stable plaque, elective stenting).

Aspect	Details
Rationale	LDL is the causal driver of atherosclerosis. Statins reduce LDL, stabilise plaques (↑fibrous cap thickness, ↓inflammation), and ↓CV events by ~25–35%.
Mechanism	"Statin" = HMG-CoA reductase inhibitor. HMG-CoA reductase is the rate-limiting enzyme in hepatic cholesterol synthesis. Inhibition → ↓intrahepatic cholesterol → ↑LDL receptor expression on hepatocyte surface → ↑LDL clearance from blood → ↓serum LDL.
Indication	Should be given regardless of baseline LDL-C level in the absence of contraindications ^[29] — even if LDL appears "normal," statins reduce residual CV risk through pleiotropic anti-inflammatory and plaque-stabilising effects.
Choice	High-intensity statins preferred: atorvastatin (40–80 mg) or rosuvastatin (20–40 mg). These achieve ≥50% LDL reduction.
Target	LDL < 1.8 mmol/L AND ≥50% reduction from baseline (ESC 2019 for very high-risk) ^[26]. For extremely high-risk (recurrent events on statin), target LDL < 1.4 mmol/L.
If not at target on max statin	Add ezetimibe (blocks intestinal cholesterol absorption via NPC1L1 transporter) → most commonly used second-line therapy ^[31]
If still not at target	Add PCSK9 inhibitor (evolocumab, alirocumab) — monoclonal antibodies that ↓PCSK9 → ↑LDL receptor recycling → ↓LDL by additional ~60%. Or inclisiran (siRNA against PCSK9 mRNA) — given every 6 months SC ^[31].
Side effects	Myalgia (most common complaint), rhabdomyolysis (rare), ↑transaminases (usually transient), new-onset DM (small ↑risk with high-intensity statins — but CV benefit far outweighs risk)

Aspect	Details
Mechanism	ACEI: blocks ACE → ↓angiotensin II → ↓vasoconstriction (↓afterload) + ↓aldosterone (↓Na⁺/water retention, ↓preload) + ↓cardiac remodelling. Also ↑bradykinin → vasodilation (but causes cough). ARB: blocks AT₁ receptor directly (no ↑bradykinin → no cough).
Indications in CCS	ACE inhibitors should be prescribed in all patients with stable ischaemic heart disease who also have hypertension, diabetes mellitus, LVEF ≤40%, or CKD, unless contraindicated ^[19]. ARBs are recommended for patients with SIHD who have hypertension, DM, LV systolic dysfunction, or CKD and have indications for, but are intolerant of, ACE inhibitors ^[19].
Side effects	Cough (ACEI), syncope, hypotension, angioedema, hyperkalaemia ^[19]
Contraindications	High-grade bilateral renal artery stenosis ^[19] (both kidneys dependent on angiotensin II to maintain GFR via efferent arteriolar constriction; blocking this → acute renal failure); pregnancy (teratogenic); hyperkalaemia (K⁺ > 5.5); anaphylaxis to prior dose

GC 032 Lecture Slide High Yield – ACEI/ARB Indications

The GC 032 slide explicitly states: ACEI for patients with SIHD who also have HT, DM, EF ≤40%, or CKD. ARB if ACEI-intolerant (cough, angioedema) ^[19]. This is a very commonly examined point — know the specific indications, not just "give ACEI to everyone."

Agent	Indication	Notes
Proton pump inhibitor (PPI)	For patients at high risk of GI bleeding (esp. on DAPT, aspirin + anticoagulant, or elderly) ^[29]	Aspirin inhibits COX-1 → ↓prostaglandin-mediated gastroprotection → ↑GI ulcer/bleeding risk. PPI (e.g., omeprazole, pantoprazole) co-prescription is protective.
Influenza vaccination	Annual — recommended for all CAD patients	↓risk of ACS triggered by acute infection/inflammation

Decision trees are dependent on patient profile — using blood pressure and heart rate as deciders ^[1]. Essentially:

Patient Profile	Preferred First-Line	Add-On
HR > 70, BP normal/high	β-blocker (↓HR is the primary goal)	Add DHP CCB or long-acting nitrate
HR < 70, BP high	DHP CCB (amlodipine — ↓BP, no HR effect) or ACEI/ARB	Add long-acting nitrate
HR < 70, BP normal/low	Long-acting nitrate (minimal haemodynamic compromise)	Consider nicorandil, ranolazine
Vasospastic angina	CCB (verapamil, diltiazem, or DHP); NO β-blockers ^[19]	Add long-acting nitrate
Post-MI with LV dysfunction	β-blocker + ACEI/ARB (both have mortality benefit)	Add nitrate if symptomatic
HFrEF	β-blocker (bisoprolol/carvedilol/metoprolol succinate) + ACEI/ARB/ARNI + MRA + SGLT2i ^[26]	Quadruple therapy for HFrEF

C. Revascularisation (Non-Pharmacological Treatment)

Two non-pharmacological treatments for chronic angina ^[1]:

Percutaneous coronary intervention (PCI)
Coronary artery bypass graft (CABG)

Revascularization methods are only for those who do not respond well to treatment ^[1] — i.e., they are reserved for:

Unacceptable angina despite optimal medical therapy (OMT)
High-risk anatomy on angiography (regardless of symptoms)

Aspect	Details
Technique	Balloon to reopen lumen, then stent to keep it open ^[1]
Stent types	Drug-eluting stents (DES) are now standard — have drug-releasing properties that reduce hyperplasia of the coronary arteries + restenosis ^[1]. Bare-metal stents (BMS) still occasionally used but rarely.
Indication in CCS	Stenosis ≥70% (or ≥50% LM) on angiography with corresponding ischaemia OR symptoms refractory to OMT. FFR ≤0.80 / iFR ≤0.89 for borderline lesions.
DAPT post-DES	Drug-eluting stent: need antiplatelet for a year ^[1] (in stable CCS, can shorten to 6 months if low bleeding risk ^[30]). Bare-metal stent: only need antiplatelet therapy for 4 weeks ^[1].
Advantage over CABG	Less invasive, shorter recovery, lower periprocedural risk
Disadvantage	Higher restenosis/re-intervention rate compared to CABG for multi-vessel disease; not suitable for complex anatomy (diffuse disease, LM bifurcation)

Aspect	Details
Technique	Surgical conduit (internal mammary artery preferred; saphenous vein graft alternative) bypasses the stenosed coronary segment
Preferred over PCI when	3-vessel disease; left main disease; proximal LAD disease; diabetic patients with multi-vessel disease ^[1] — these are the high-risk anatomies where CABG provides superior long-term survival
Graft patency	Internal mammary artery (IMA): ~90–95% patency at 10 years (gold standard). Saphenous vein graft (SVG): ~50–60% patency at 10 years (accelerated atherosclerosis in vein grafts).
Why IMA is better	Arterial grafts produce endothelium-derived NO → less prone to atherosclerosis and spasm. Vein grafts lack this endothelial phenotype and are exposed to arterial pressures they were not designed for → intimal hyperplasia.

Anatomy	PCI	CABG
1-vessel disease (non-LM, non-proximal LAD)	✅ Preferred	Not typically needed
2-vessel disease without proximal LAD	✅ Preferred	Consider if complex lesions
2-vessel disease with proximal LAD	Consider	✅ Preferred
3-vessel disease	Consider if low SYNTAX score	✅ Preferred (mortality benefit)
Left main disease	Consider if low SYNTAX score and isolated LM	✅ Preferred
DM + multi-vessel disease	Inferior long-term outcomes	✅ Preferred (FREEDOM trial)

1 vessel disease, 93% 5 year survival, can be good with just treating medically vs. 3 vessel disease + > 95% blockage in proximal LAD, should think of alternate means ^[1].

After the acute phase, treatment modalities in secondary prevention ^[28]:

Category	Drug	Duration / Detail
Antiplatelet therapy	Aspirin 75–100 mg daily (lifelong) + P2Y₁₂ inhibitor (ticagrelor 90 mg BID or clopidogrel 75 mg daily)	Maintained over 12 months post-ACS unless contraindicated or excessive bleeding risk; try to maintain at least 3–6 months ^[28]. After stable PCI: 6 months DAPT ^[30].
Anti-ischaemic therapy	Beta-blockers unless contraindicated (cornerstone)	Lifelong if post-MI or EF < 40%
	ACEI → for patients with CHF, LV dysfunction (EF < 40%), hypertension, diabetes ^[28]	Lifelong
	CCB (diltiazem, verapamil) → if contraindications to beta-blockers and no heart failure ^[28]
	Nitrates (long-acting or short-acting PRN) → in the presence of angina ^[28]
Lipid-lowering	Statin (high-intensity, regardless of baseline LDL) ^[29]	Lifelong; add ezetimibe/PCSK9i if not at target

For AF with MI → triple therapy (aspirin + clopidogrel + DOAC) → not recommended long term since bleeding risk is unacceptable → no more than 30 days ^[30]. Add PPI when using 2 or more antithrombotics ^[30].

Special Situations

Severe aortic stenosis has specific drug contraindications ^[32]:

Beta-blockers → negative inotropes (may cause decompensation in fixed-output state)
Non-DHP CCBs → negative inotropes
Nitrates → compromise preload (in AS, cardiac output is preload-dependent due to fixed obstruction)

The definitive treatment is aortic valve replacement (surgical or TAVI) rather than anti-anginal drugs.

After diagnosing a congenital coronary anomaly ^[1]:

Avoid competitive sport
Consider surgical intervention if positive for myocardial ischaemia

Drug	↓HR	↓BP	↓Preload	↓Afterload	Coronary Dilation	Mortality Benefit
β-blocker	✅✅✅	✅	–	✅	–	✅ (post-MI, HFrEF)
Non-DHP CCB	✅✅	✅✅	–	✅✅	✅	–
DHP CCB	– (reflex ↑HR)	✅✅✅	–	✅✅✅	✅✅	–
Nitrate	– (reflex ↑HR)	✅	✅✅✅	✅	✅✅	–
Ivabradine	✅✅	–	–	–	–	–
Ranolazine	–	–	–	–	–	–

High Yield Summary – Management of CCS

General Measures (ALL patients): 1. Rule out/treat aggravating conditions. 2. Smoking cessation. 3. Dietary counselling/weight control. 4. Exercise. 5. Treat to targets (HT, lipids, DM).

Anti-anginal drugs (symptom control):

First-line: β-blocker OR CCB. β-blocker preferred if post-MI or HFrEF.
CCB if β-blocker contraindicated. Non-DHP (verapamil/diltiazem) for vasospastic angina. DHP (amlodipine) if combining with β-blocker.
Second-line: long-acting nitrates, ivabradine, ranolazine, nicorandil, trimetazidine.
Nitrates: CONTRAINDICATED with PDE-5 inhibitors (sildenafil) and in HOCM.

Secondary prevention (event reduction):

Aspirin 75–100 mg daily (lifelong) ± P2Y₁₂ inhibitor (duration depends on context).
High-intensity statin (regardless of baseline LDL); target LDL < 1.8 mmol/L + ≥50% reduction.
ACEI/ARB if HT, DM, EF ≤40%, or CKD.
PPI if on DAPT or high GI bleeding risk.

Revascularisation: only if refractory to OMT or high-risk anatomy.

PCI for 1–2 vessel disease, non-LM, non-proximal LAD.
CABG for 3-vessel disease, LM, proximal LAD, DM + multi-vessel.
Post-DES DAPT: 12 months (ACS), 6 months (stable CCS).

Active Recall - Management of Chronic Coronary Syndrome

^[1] Senior notes: Block A - WCS32 Chest pain on exertion: ischaemic heart disease; angina pectoris (pp. 30, 32–33, 47, 56 — Management principles, general measures, anti-ischaemic agents, PCI/CABG, Prinzmetal, congenital anomalies) ^[19] Lecture slides: GC 032. Chest pain on exertion: ischaemic heart disease; angina pectoris (pp. 60, 62, 63, 65 — ACEI/ARB, β-blockers, CCBs, nitrates indications/CI/SE) ^[21] Senior notes: Maksim Medicine Notes (pp. 7, 9, 11 — Stress testing, biomarkers, β-blocker dosing, STEMI management) ^[26] Senior notes: Ryan Ho Cardiology (p. 120 — Risk stratification, general measures, LDL targets) ^[27] Senior notes: Block A - Deterioration of eyesight in a diabetic patient: diabetic complications (p. 26 — SGLT2i/GLP-1RA in CVD/CKD) ^[28] Lecture slides: GC 028. Accelerating chest pain: Acute coronary syndromes (p. 55 — Secondary prevention anti-ischaemic therapy) ^[29] Lecture slides: Handbook of Internal Medicine 2024 (p. 25 — Nitrate dosing, statin regardless of LDL, ACEI within 24h, PPI) ^[30] Senior notes: Block A - Clinical pharmacology of antiplatelets and anticoagulation (p. 6 — DAPT duration, triple therapy, PPI with multiple antithrombotics) ^[31] Senior notes: Block A - Three cases of lipid disorders (p. 3 — Ezetimibe, PCSK9 inhibitors, inclisiran) ^[32] Senior notes: Block A - Clinical Pharmacology of anti-HT and anti-HF medications (p. 5 — Severe AS drug contraindications)

Complications of Chronic Coronary Syndrome

CCS is not a benign, static condition. The underlying atherosclerotic process is always present and always evolving. Complications arise from three fundamental mechanisms:

Plaque destabilisation — the stable plaque ruptures or erodes → ACS (the most feared complication)
Progressive myocardial damage — chronic ischaemia → myocardial hibernation, stunning, or infarction → LV dysfunction → heart failure
Treatment-related complications — from medications (bleeding, drug side effects) and revascularisation procedures (PCI/CABG)

Additionally, since CCS is a manifestation of systemic atherosclerosis, complications frequently involve vascular beds beyond the coronary arteries.

This is the most important and most feared complication of CCS. It occurs when a previously stable plaque becomes unstable.

Mechanism	Pathophysiology	Clinical Outcome
Plaque rupture	Thin-cap fibroatheroma → macrophage metalloproteinase (MMP) digestion of collagen in fibrous cap → rupture → exposure of thrombogenic necrotic core to blood → platelet aggregation + coagulation cascade → thrombus formation ^[2]	Subtotal occlusion → unstable angina / NSTEMI; Complete occlusion → STEMI
Plaque erosion	Endothelial denudation without rupture → subendothelial collagen exposure → thrombus. More common in women and younger patients.	Usually NSTEMI (non-occlusive thrombus)
Calcified nodule	Calcified plaque protrudes through fibrous cap into lumen → thrombosis. Uncommon.	STEMI or NSTEMI

For stable angina without treatment, 10–20% progress to MI or unstable angina per year. For those treated, this risk drops to ~0.8% ^[1] — this dramatically illustrates why secondary prevention is so critical.

How can a patient with ACS present? Not all patients have the classical playing tennis then collapse story — they can be oligo/asymptomatic, have increasing chest pain, persistent chest pain, cardiogenic shock/acute heart failure, or cardiac arrest ^[9].

When Stable Becomes Unstable

Any CCS patient who reports a change from baseline — ↑frequency, ↑severity, ↑duration of angina, new rest angina, or angina unresponsive to usual GTN dose — must be treated as possible ACS until proven otherwise. Even an "asymptomatic" patient can present with sudden MI or cardiac arrest as the first sign of plaque rupture.

B. Heart Failure (Ischaemic Cardiomyopathy)

Chronic ischaemia and recurrent/unrecognised MI lead to progressive loss of functioning myocardium. This is the most common cause of heart failure in the developed world.

Term	Definition	Clinical Relevance
Myocardial stunning	Transient contractile dysfunction after a brief ischaemic episode, despite restoration of flow. Myocardium is viable but "stunned."	Recovery expected over hours–days if no further ischaemia.
Myocardial hibernation	Chronic reduction in contractile function in response to chronic ↓flow. Myocardium is viable but "sleeping" — downregulates its metabolic activity to match reduced supply.	Can be detected by viability testing (PET, MRI). Determines whether to perform PCI or CABG ^[18] — revascularisation can restore function in hibernating myocardium.
Myocardial necrosis/scar	Irreversible cell death → replaced by fibrotic scar tissue.	Non-viable. Will not benefit from revascularisation. Substrate for arrhythmias.

The final common path of all cardiac diseases is heart failure ^[33]. Heart failure is not a diagnosis — it is secondary to many cardiac pathologies ^[33]. In CCS, HF is due to ischaemic cardiomyopathy (loss of contractile myocardium from cumulative ischaemic injury).

Signs to assess for on physical examination ^[19]^[34]:

Congestive heart failure: JVD, S₃, S₄, displaced point of maximal impulse, hepatomegaly, pulmonary/peripheral oedema ^[19]^[34]
Ischaemic mitral regurgitation (papillary muscle dysfunction from ischaemia → MR → volume overload → worsens HF)
Low-output cardiac failure (↓CO → fatigue, ↓exercise tolerance, hypotension)

CABG for ischaemic cardiomyopathy ^[33] — if there is viable (hibernating) myocardium, revascularisation can improve LV function.
ICD: primary prevention in patients with low LVEF, CAD ± inducible VT ^[33] — because scarred myocardium is arrhythmogenic.
Prophylactic ICD placement should be considered in patients with NYHA II–III (LVEF < 30%) ^[33], following 3 months of optimal medical therapy in patients with PMHx of MI.
CRT (biventricular pacing) should be considered if NYHA III despite optimal medical therapy, sinus rhythm, QRS > 120 ms (LBBB), LVEF < 35% and LVD > 5.5 cm ^[33].
Pharmacological therapy: HFrEF quadruple therapy (ACEI/ARB/ARNI + β-blocker + MRA + SGLT2i + loop diuretic for congestion).

Ischaemic myocardium is electrically unstable. Both acute ischaemia and chronic scarring create substrates for arrhythmias.

Arrhythmia	Mechanism	Clinical Significance
Ventricular premature beats (VPBs)	Irritable ischaemic myocardium → abnormal automaticity or re-entry	Common; usually benign in isolation but warn of electrical instability
Ventricular tachycardia (VT)	Re-entrant circuits around scar tissue borders (scar acts as anatomical block with slow conduction around it)	Can degenerate into VF → cardiac arrest. Sustained monomorphic VT in patient with prior MI = classic ischaemic arrhythmia.
Ventricular fibrillation (VF)	Chaotic electrical activity → no coordinated contraction → no cardiac output	Prompt defibrillation required (ACLS algorithm) ^[35].
Atrial fibrillation (AF)	LA dilatation from ↑LVEDP → structural remodelling of atria → re-entry circuits	Ectopy, atrial fibrillation are recognised complications of CAD ^[19]^[34]. AF ↑stroke risk (→ need anticoagulation), worsens ischaemia (loss of atrial kick + tachycardia).
Bradyarrhythmias / Heart block	Ischaemia of conduction system (RCA supplies AV node in 80–90%; LAD supplies bundle of His via septal perforators)	Inferior MI → AV block (often transient, Mobitz I/complete HB with narrow escape). Anterior MI → bundle branch block, bifascicular block → higher risk of asystole.

Sudden Cardiac Death (SCD)

Cardiac arrest — causes: coronary artery disease (85%): myocardial ischaemia, AMI, prior MI with myocardial scarring ^[35].

SCD is the most catastrophic complication of CAD. In CCS patients:

Risk increases as LVEF decreases (scarred, dilated ventricle = more arrhythmogenic substrate)
As the ejection fraction goes down lower, the indication for prophylactic ICD becomes stronger → since the chance of lethal ventricular arrhythmias increases with reducing LVEF ^[33]
80% of VF/pulseless VT can be reversed by defibrillation, but 10% ↓survival per minute delay ^[35] — hence the critical importance of early defibrillation

These are complications of acute MI — but since ACS is itself the most common complication of CCS, understanding them is essential. They typically occur 3–7 days post-MI when infarcted tissue is at its weakest (necrotic tissue before fibrotic repair is complete).

Complication	Mechanism	Presentation	Management
Ventricular septal rupture (VSR) ^[21]	Necrosis of interventricular septum → perforation	New pansystolic murmur + acute HF + haemodynamic deterioration	Emergency cardiac catheterisation and repair if unstable; observe if stable (repair later) ^[29]
LV free wall rupture ^[21]	Transmural necrosis → myocardial wall gives way	Sudden haemodynamic collapse → cardiac tamponade → PEA arrest	Emergency surgery (usually fatal without)
Papillary muscle rupture → acute severe MR ^[21]	Necrosis of papillary muscle (usually posteromedial — single blood supply from PDA) → flail mitral leaflet	Acute pulmonary oedema + new pansystolic murmur at apex with radiation to axilla	Emergency mitral valve surgery; stabilise with vasodilator (↓afterload → ↓regurgitant fraction) and IABP
LV aneurysm	Non-contractile, thin-walled scar → paradoxical bulging during systole → acts as a "waste chamber"	Persistent ST elevation and Q waves on ECG; HF, mural thrombus (→ systemic embolisation), ventricular arrhythmias	Oral anticoagulation if mural thrombus; aneurysmectomy + CABG if intractable VAs or refractory HF ^[26]

Pump failure mechanism: downward spiral exacerbating myocardial ischaemia — ↓systolic function → ↓coronary perfusion → ↓supply → ischaemia; ↓diastolic function → ↑pulmonary congestion → hypoxaemia → ischaemia ^[26].

Type	Timing	Mechanism	Management
Peri-infarct pericarditis	Days 1–3 post-MI	Transmural necrosis → inflammation of overlying pericardium	Aspirin (high-dose) — NOT NSAIDs or steroids (may impair infarct healing); paracetamol as adjunct
Post-cardiac injury syndrome (Dressler syndrome)	2–10 weeks post-MI	Autoimmune reaction to exposed cardiac antigens (pericardial/myocardial proteins released during necrosis trigger immune response)	High-dose aspirin with colchicine or NSAID with colchicine for post-cardiac injury syndrome (but not peri-infarct pericarditis) ^[29]; Colchicine 0.5 mg daily PO (< 70 kg) or 0.5 mg BD PO (> 70 kg) ^[29]

Need to differentiate post-cardiac injury syndrome (Dressler syndrome) from peri-infarct pericarditis ^[29]. Dressler syndrome occurs later, is immune-mediated, and responds to anti-inflammatory therapy. Peri-infarct pericarditis is early and directly related to tissue necrosis.

Patients with CCS are at risk of thromboembolic events from multiple sources:

Source	Mechanism	Clinical Event
LV mural thrombus	Akinetic or dyskinetic LV segment (from prior MI) → blood stasis → thrombus formation on damaged endocardium	Systemic embolism: stroke, renal infarction, limb ischaemia, mesenteric ischaemia
Atrial fibrillation	LA stasis (especially in LA appendage) → thrombus → embolism	Ischaemic stroke (most common; accounts for ~15–20% of all strokes)
Atherothrombosis	Plaque erosion/rupture in non-coronary arteries (carotid, cerebral, mesenteric, renal, peripheral)	Stroke, TIA, peripheral arterial ischaemia

CCS is not an isolated coronary disease — it is a marker of generalised atherosclerosis. Patients with CCS have a significantly higher prevalence of:

Vascular Bed	Clinical Manifestation	Connection
Carotid arteries	Carotid bruits; TIA; ischaemic stroke ^[19]^[34]	Same atherosclerotic process affecting carotid bifurcation
Peripheral arteries (lower limbs)	Peripheral pulses ↓/absent; peripheral skin discolouration or hair loss; intermittent claudication; critical limb ischaemia ^[19]^[34]	PAD shares identical risk factors with CAD; often coexist
Renal arteries	Renovascular hypertension; ischaemic nephropathy	Bilateral RAS → accelerated CKD
Abdominal aorta	AAA	Infrarenal aorta is a common site for atherosclerotic aneurysm
Aortic arch	Atheroembolism (cholesterol crystal emboli)	Shower of emboli from friable aortic plaques → blue toe syndrome, livedo reticularis, renal failure

H. Complications of Treatment

Complications of PCI (overall mortality < 0.5%, may require emergency CABG if unstable) ^[21]^[26]^[36]:

Category	Complication	Detail
Access site	Bleeding, haematoma, pseudoaneurysm, AV fistula, retroperitoneal bleeding	Retroperitoneal bleeding: femoral access with artery puncture; diagnosed with haemodynamic compromise (↑HR, ↓BP) ^[36]
Coronary artery	Dissection and acute closure	Dissections found up to 50% after PTCA immediately due to guidewire passage or controlled injury; routine stenting reduces risk of acute closure ^[36]
	Coronary artery perforation	Requires inflation of perfusion balloon at site to stop blood flow into pericardium → pericardiocentesis → covered stent ^[36]
Stent-related	In-stent restenosis (ISR, ~15% with BMS, < 5% with DES)	Due to combination of elastic recoil and neointimal hyperplasia ^[36]. Chronic event presenting as recurrent stable angina, usually ≥6–9 months after stenting ^[26].
	Stent thrombosis (1–2%)	Acute event presenting with severe STEMI or cardiac death. Associated with cessation of DAPT ^[26]^[36]. Most occurs < 30 days ^[26].
	Stent infection	Associated with formation of mycotic aneurysm and spontaneous coronary artery perforation ^[36]. Very rare.
Systemic	Contrast-induced AKI	Manifests within 48 hours and peaks at Day 3–5 ^[36]. Risk factors: pre-existing CKD, DM, volume depletion, large contrast volume. Prevention: hydration.
	Stroke	Ischaemic stroke from dislodgement of thrombus, calcific material, or atherosclerotic plaques during catheter manipulation; haemorrhagic stroke from antiplatelet regimens ^[36]

Complications of CABG ^[21]^[26]:

Complication	Incidence	Detail
Mortality	1–2%
Post-op AF	30% in first week	Most common arrhythmia post-CABG; usually self-limiting
Perioperative stroke	2.5%	Microembolisation of gaseous and particulate matter ^[21]; minimised by "no-touch" aortic technique
Perioperative MI	< 1–2%	Graft failure, incomplete revascularisation
Post-op low cardiac output syndrome (LCOS)	Variable	Due to ventricular dysfunction ^[21]
Graft occlusion	5–10% in 30 days; ~1–2%/year for first 6 years, then ~5%/year thereafter	Vein grafts > arterial grafts. Management: PCI to graft or re-CABG if failed ^[26].
Wound infection / Mediastinitis	~1–2%	Serious complication; higher risk in DM, obesity, bilateral IMA harvest
AKI	Variable	Cardiopulmonary bypass → non-pulsatile flow + haemodilution → renal hypoperfusion
Pericarditis / Effusion / Tamponade		Post-operative inflammation

Drug	Complication	Mechanism
Aspirin	GI bleeding, peptic ulceration	COX-1 inhibition → ↓prostaglandin-mediated gastric mucosal protection
Clopidogrel / Ticagrelor	Bleeding (any site); ticagrelor: dyspnoea (adenosine-mediated)	P2Y₁₂ inhibition → impaired platelet aggregation
Statins	Myalgia, rhabdomyolysis (rare), ↑transaminases, new-onset DM	Unclear mechanism for myopathy; possibly mitochondrial dysfunction
ACEI	Cough (ACEI-specific), hyperkalaemia, AKI (esp bilateral RAS), angioedema	Cough: ↑bradykinin accumulation in lungs. Hyperkalaemia: ↓aldosterone → ↓K⁺ excretion.
β-blockers	Bradycardia, bronchospasm, masking of hypoglycaemia (in DM), fatigue, depression	Bradycardia: ↓SA node automaticity. Bronchospasm: β₂ blockade (esp non-selective). Masked hypo: ↓sympathetic awareness.
Nitrates	Headache (most common), hypotension, reflex tachycardia, tolerance with continuous use	Headache: vasodilation of meningeal vessels. Tolerance: ↓NO bioavailability with continuous exposure.

CKD and CCS have a bidirectional relationship:

CKD accelerates atherosclerosis (vascular calcification, dyslipidaemia, chronic inflammation, uraemia-mediated endothelial dysfunction)
CCS treatment can worsen CKD (contrast nephropathy from angiography, ACEI/ARB-induced haemodynamic changes)
Coronary artery calcifications increase with increasing years of dialysis ^[37] — dramatically accelerating CV risk in ESRD patients

Often underappreciated but highly impactful:

Complication	Prevalence	Impact
Depression	15–25% of CCS patients	↑non-adherence to medications, ↓physical activity, ↑cortisol/catecholamines → ↑ischaemic events
Anxiety	Common; can mimic angina	Chest pain/palpitations from panic attacks → frequent ED visits → unnecessary investigations
Reduced quality of life	Universal to varying degrees	Avoidance of physical activity, social withdrawal, occupational disability

High Yield Summary – Complications of CCS

A. Progression to ACS — the #1 complication. Untreated: 10–20% per year progress to MI/UA; treated: ~0.8% ^[1]. Mechanism: plaque rupture/erosion → thrombus.

B. Heart failure (ischaemic cardiomyopathy) — chronic ischaemia → stunning, hibernation, necrosis → ↓LVEF → HFrEF. Hibernating myocardium is viable and may recover with revascularisation ^[18].

C. Arrhythmias — ischaemic myocardium is electrically unstable. VT/VF → SCD. CAD accounts for 85% of cardiac arrests ^[35]. ICD for primary prevention if LVEF < 30% after ≥3 months OMT post-MI ^[33].

D. Mechanical complications (post-MI): VSR, free wall rupture, papillary muscle rupture, LV aneurysm — occur 3–7 days post-MI.

E. Pericarditis: peri-infarct (early, days 1–3) vs. Dressler syndrome (late, 2–10 weeks, autoimmune, treat with aspirin + colchicine) ^[29].

F. Systemic thromboembolism: LV mural thrombus, AF → stroke.

G. Systemic atherosclerosis: carotid disease (stroke), PAD, RAS, AAA — CCS is a marker of generalised vascular disease.

H. Treatment complications: PCI (stent thrombosis, ISR, contrast-AKI, dissection); CABG (AF 30%, stroke 2.5%, graft occlusion); medications (bleeding, GI ulcer, myopathy, cough, hyperkalaemia).

Active Recall - Complications of Chronic Coronary Syndrome

References

^[1] Senior notes: Block A - WCS32 Chest pain on exertion: ischaemic heart disease; angina pectoris (pp. 30, 33, 55 — Progression rates, management principles, emerging approaches) ^[2] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai) (p. 384 — Pathology of atherosclerosis, stable vs unstable plaque) ^[9] Senior notes: Block A - Accelerating chest pain: Acute Coronary Syndromes (pp. 7–8, 32 — Clinical spectrum of ACS, anti-ischaemic measures) ^[18] Senior notes: Ryan Ho Diagnostic Radiology (p. 57 — MPI: determine viability of myocardium, functional assessment) ^[19] Lecture slides: GC 032. Chest pain on exertion: ischaemic heart disease; angina pectoris (p. 30 — Physical examination: assessing for complications) ^[21] Senior notes: Maksim Medicine Notes (pp. 13–14 — PCI complications, CABG complications, graft types) ^[26] Senior notes: Ryan Ho Cardiology (pp. 120, 124, 126, 139, 142 — Risk stratification, PCI complications table, CABG complications, pump failure, LV aneurysm) ^[29] Lecture slides: Handbook of Internal Medicine 2024 (pp. 24, 30 — Pericarditis management, mechanical complications, pump failure) ^[33] Senior notes: Block A - Shortness of breath on exertion: heart failure (p. 38 — ICD, CRT indications, CABG for ischaemic cardiomyopathy, final common path) ^[34] Lecture slides: GC 028. Accelerating chest pain: Acute coronary syndromes (p. 19 — Physical examination: assessing for complications including CHF, arrhythmias, PAD) ^[35] Senior notes: Ryan Ho Critical Care (p. 28 — Cardiac arrest: 85% CAD, defibrillation, ACLS) ^[36] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai) (p. 412 — PCI complications table: access, coronary, stent, systemic) ^[37] Senior notes: Block A - Chronic Kidney Disease and its Complications (p. 33 — Coronary artery calcification in dialysis patients)

High Yield Summary

CCS = Chronic Coronary Syndromes (ESC 2019) — replaces "stable angina/stable CAD." CAD is a dynamic continuum, not a binary stable/unstable state.
Atherosclerosis is the cause in > 95% of cases — a chronic inflammatory process: endothelial injury → LDL accumulation → foam cells → fibroatheroma → stable plaque (thick cap, small core) → fixed stenosis → demand ischaemia on exertion.
Non-atherosclerotic causes to remember: vasospasm (Prinzmetal — common in East Asians!), dissection (SCAD — young women), embolism (AF), vasculitis (Kawasaki, Takayasu, PAN, EGPA).
Risk factors: Smoking (most lethal), HT, DM, hyperlipidaemia, obesity, family Hx, physical inactivity. Metabolic syndrome = ≥3 of: central obesity, ↑TG, ↓HDL, ↑BP, ↑glucose.
Angina features: retrosternal constricting discomfort, provoked by exertion, relieved by rest/GTN within 1–5 min. Typical = 3/3 features, atypical = 2/3, non-anginal = ≤1.
CCS classification: Grade I (strenuous exertion only) → IV (any activity / rest).
Significant stenosis = ≥50% on coronary angiography; flow-limiting = ≥70% (or ≥50% left main). PCI for stable CCS when ≥70%.
Examination is often normal but look for: xanthomata (hyperlipidaemia), absent peripheral pulses/bruits (diffuse atherosclerosis), S4 (diastolic dysfunction), S3 (systolic dysfunction), signs of conditions exacerbating angina (anaemia, thyrotoxicosis, AS).
Angina equivalents (dyspnoea, fatigue, nausea): common in elderly, DM, women. Silent ischaemia: DM (autonomic neuropathy), complete infarct (> 6h), elderly.
Untreated stable angina: 10–20% progress to MI/UA. Treated: ~0.8%.

High Yield Summary – Differential Diagnosis

Approach: Anatomy-based (cardiac → vascular → pulmonary → GI → MSK → neuro → psych).

"Cannot miss" diagnoses ^[10]^[12]:

ACS (crescendo, rest pain, > 20 min, ↑troponin)
Aortic dissection (sudden tearing to back, BP asymmetry)
Pulmonary embolism (pleuritic, haemoptysis, DVT risk)
Pneumothorax (sudden, unilateral ↓BS, hyperresonance)

Most common benign mimics: GERD/oesophageal spasm, musculoskeletal pain, psychogenic.

Key discriminators for CCS:

Pain is exertional, reproducible, and predictable.
Duration 1–5 min, relieved by rest/GTN within minutes.
Not pleuritic, positional, reproducible by palpation, or associated with rash/fever.

High Yield Summary – Diagnosis of CCS

No single "diagnostic criterion" for CCS — diagnosis is built from clinical assessment + stepwise testing.
Significant CAD = ≥50% on angiography. Flow-limiting = ≥70% (or ≥50% LM). PCI for stable CCS when ≥70%.
Baseline workup for all patients: bloods (lipids, glucose/HbA1c, creatinine/eGFR, TFT, hs-CRP, BNP), resting ECG, echocardiogram, CXR.
GC 032 Lecture Slide Decision Algorithm ^[19]:
- Can exercise + interpretable ECG → ETT (first-line)
- Cannot exercise OR uninterpretable ECG → stress imaging (echo, MPI, CMR)
- Contraindication to stress testing OR high-risk features → coronary imaging (CTCA or invasive)
Stress test interpretation: ETT: ≥1 mm ST depression = positive. MPI: cold spot on stress only = ischaemia; cold spot at rest + stress = infarct/scar. Stress echo: new RWMA = ischaemia.
CTCA: very high sensitivity/NPV → good rule-out test. Low specificity with calcium. "Triple rule-out" for MI/PE/aortic dissection.
Invasive coronary angiography indications: unacceptable angina despite medical therapy, high-risk non-invasive results, depressed LVEF, unclear non-invasive results.
FFR ≤0.80 (or iFR ≤0.89) on invasive angiography = haemodynamically significant lesion → revascularise.
Troponin should be NORMAL in CCS — if elevated, suspect ACS or other causes (HF, CKD, myocarditis).

High Yield Summary – Management of CCS

General Measures (ALL patients): 1. Rule out/treat aggravating conditions. 2. Smoking cessation. 3. Dietary counselling/weight control. 4. Exercise. 5. Treat to targets (HT, lipids, DM).

Anti-anginal drugs (symptom control):

First-line: β-blocker OR CCB. β-blocker preferred if post-MI or HFrEF.
CCB if β-blocker contraindicated. Non-DHP (verapamil/diltiazem) for vasospastic angina. DHP (amlodipine) if combining with β-blocker.
Second-line: long-acting nitrates, ivabradine, ranolazine, nicorandil, trimetazidine.
Nitrates: CONTRAINDICATED with PDE-5 inhibitors (sildenafil) and in HOCM.

Secondary prevention (event reduction):

Aspirin 75–100 mg daily (lifelong) ± P2Y₁₂ inhibitor (duration depends on context).
High-intensity statin (regardless of baseline LDL); target LDL < 1.8 mmol/L + ≥50% reduction.
ACEI/ARB if HT, DM, EF ≤40%, or CKD.
PPI if on DAPT or high GI bleeding risk.

Revascularisation: only if refractory to OMT or high-risk anatomy.

PCI for 1–2 vessel disease, non-LM, non-proximal LAD.
CABG for 3-vessel disease, LM, proximal LAD, DM + multi-vessel.
Post-DES DAPT: 12 months (ACS), 6 months (stable CCS).

High Yield Summary – Complications of CCS

A. Progression to ACS — the #1 complication. Untreated: 10–20% per year progress to MI/UA; treated: ~0.8% ^[1]. Mechanism: plaque rupture/erosion → thrombus.

D. Mechanical complications (post-MI): VSR, free wall rupture, papillary muscle rupture, LV aneurysm — occur 3–7 days post-MI.

E. Pericarditis: peri-infarct (early, days 1–3) vs. Dressler syndrome (late, 2–10 weeks, autoimmune, treat with aspirin + colchicine) ^[29].

F. Systemic thromboembolism: LV mural thrombus, AF → stroke.

G. Systemic atherosclerosis: carotid disease (stroke), PAD, RAS, AAA — CCS is a marker of generalised vascular disease.

H. Treatment complications: PCI (stent thrombosis, ISR, contrast-AKI, dissection); CABG (AF 30%, stroke 2.5%, graft occlusion); medications (bleeding, GI ulcer, myopathy, cough, hyperkalaemia).

Chronic Coronary Syndrome (Previously Stable Angina)

References

Definition

Epidemiology

Global Perspective

Hong Kong Context

Sex Differences

Natural History (untreated)

Risk Factors

Non-Modifiable Risk Factors

Major Modifiable Risk Factors

Other Risk Factors & Associations

Metabolic Syndrome

Anatomy and Function of the Coronary Arteries

Coronary Arterial Supply

Coronary Dominance

Why Is the Subendocardium Most Vulnerable?

Etiology (Hong Kong Focus)

Primary Classification

A. Primary Cardiac Causes

1. Atherosclerosis of Coronary Arteries (by far the most common) [1][2]

2. Non-Atherosclerotic Coronary Artery Disease [1][2]

3. Microvascular Angina (Cardiac Syndrome X — older term)

B. Primary Non-Cardiac Causes (Demand Ischaemia)

Pathophysiology

A. Atherosclerosis — The Fundamental Process

Step 1: Endothelial Injury / Dysfunction

Step 2: Lipid Accumulation and Oxidation

Step 3: Foam Cell Formation (Fatty Streak)

Step 4: Fibroatheroma (Advanced Plaque)

Step 5: Stable vs. Unstable Plaque — The Critical Distinction

Step 6: Remodelling

B. Mechanism of Angina in CCS

C. Ischaemic Cascade

Classification

A. Clinical Scenarios of CCS (ESC 2019)

B. Canadian Cardiovascular Society (CCS) Grading of Angina

C. Definition of Angina by Number of Typical Features (ESC)

D. Pre-Test Probability (PTP) of Obstructive CAD

E. High-Risk CAD

Clinical Features

A. Symptoms

1. Angina Pectoris — The Cardinal Symptom

2. Angina Equivalents

3. Associated Symptoms

B. Signs

1. Signs of Cardiovascular Risk Factors

2. Cardiac Signs

3. Signs of Conditions That Exacerbate Angina

Summary of the Ischaemic Cascade and Its Clinical Correlates

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

References

Differential Diagnosis of Chronic Coronary Syndrome

Conceptual Framework: Why Differential Diagnosis Matters Here

Mermaid Diagram: Anatomical Approach to DDx of Chest Pain in Suspected CCS

A. Cardiac Causes

1. Acute Coronary Syndrome (ACS) — THE "Cannot Miss" Differential

2. Vasospastic (Prinzmetal Variant) Angina

3. Microvascular Angina (formerly Cardiac Syndrome X)

4. Pericarditis / Myocarditis

5. Valvular Heart Disease — Aortic Stenosis (AS) and HOCM

6. Arrhythmias

B. Vascular Causes

1. Aortic Dissection — CANNOT miss!!! [12]

2. Pulmonary Embolism — CANNOT miss!!! [12]

3. Pulmonary Hypertension

C. Pulmonary / Pleural Causes

D. Gastrointestinal Causes — The Classic "Trap"

1. GERD and Oesophageal Spasm

2. Peptic Ulcer Disease

3. Biliary Colic / Pancreatitis

E. Musculoskeletal / Chest Wall

F. Neurological / Dermatological

G. Psychiatric / Functional

H. Conditions That Exacerbate True CCS (Demand Ischaemia Triggers)

Structured Differential Diagnosis Table: Putting It All Together

The Interactive Tutorial Case Revisited [8]

Active Recall - DDx of Chronic Coronary Syndrome

References

Diagnostic Criteria