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PA26.6 | Ischaemic Heart Disease & Acute Coronary Syndromes — SDL Guide

Learning Objectives

Define IHD and describe the epidemiology and risk factors underlying coronary atherosclerosis
Explain the pathophysiology of stable angina versus acute plaque change leading to the ACS spectrum
Distinguish STEMI, NSTEMI, and unstable angina by mechanism, coronary occlusion pattern, and biomarker profile
Describe the gross and microscopic evolution of myocardial infarction across its full timeline from 0 hours to 8 weeks
Interpret cardiac biomarker kinetics (troponin I/T, CK-MB, myoglobin) in the clinical context of ACS
List the major complications of myocardial infarction and their clinicopathological basis
Identify key ECG changes and describe reperfusion injury including contraction band necrosis

INSTRUCTIONS

Cardiovascular disease kills more people worldwide than any other cause — and IHD is its dominant driver. For a Year-2 student, this module bridges the vascular pathology you studied in Cluster CV-1 (atherosclerosis) with the clinical emergency you will encounter in every hospital posting. Understanding the evolution of a myocardial infarct — hour by hour, cell by cell — is foundational for interpreting ECGs, interpreting troponin trends, and understanding why MI complications occur when they do. Work through each section sequentially; the micro_quiz blocks are placed immediately after high-yield concepts to reinforce retention.

References

Robbins & Cotran Pathologic Basis of Disease, 10th ed., Ch 12 (Heart) (textbook)
Harsh Mohan Textbook of Pathology, 8th ed., Ch 16 (Cardiovascular System) (textbook)
2023 ESC Guidelines for the management of ACS (guideline)

Version 2.0 | NMC CBUC 2024

CLINICAL SCENARIO

A 55-year-old male construction worker collapses at a worksite. His colleagues describe crushing chest pain radiating to the left arm for 40 minutes before he lost consciousness. In the emergency room his troponin I is 18 ng/mL (reference < 0.04), ECG shows ST elevation in leads II, III, and aVF, and his BP is 80/50. The cardiologist calls a 'Code STEMI'.

Every minute of delay costs 1.9 million myocardial cells. By the time you finish this module, you will understand exactly what is happening at the molecular, cellular, and tissue level inside this patient's heart — and why each minute matters.

WHY THIS MATTERS

Ischaemic heart disease (IHD) is the single leading cause of death in India and globally, accounting for approximately 17% of all deaths. It is the pathological culmination of coronary atherosclerosis — a process that begins in the second decade of life and accelerates through adult risk factor exposure.

For your clinical postings, IHD is unavoidable: every ICU, every casualty, and every general medicine ward will present you with ACS, MI complications, and troponin trends. The NMC CBUC competency PA26.6 specifically requires you to interpret cardiac function tests in ACS — an examined competency in both theory papers and OSCE.

RECALL

Before proceeding, recall from Cluster CV-1:

What is the sequence of events in atherosclerotic plaque formation (endothelial injury → foam cells → fibrous cap)?
What are the major modifiable risk factors for atherosclerosis?
What is the difference between stable and unstable plaque morphology?
Recall the coronary arterial supply: which artery supplies the anterior wall? The inferior wall?

If any of these are uncertain, spend 5 minutes reviewing your CV-1 SDL before proceeding — this module builds directly on that foundation.

Definition and Epidemiology of IHD

Three-panel infographic explaining ischaemic heart disease as coronary atherosclerosis causing myocardial oxygen supply-demand mismatch, with epidemiology figures and classified risk factors. — **Panel A:** Anterior heart, right coronary artery, left main coronary artery, left anterior descending artery, atherosclerotic narrowing, reduced myocardial oxygen supply, myocardial oxygen demand, supply-demand mismatch, coronary atherosclerosis.. **Panel B:** Global burden of IHD, India burden of IHD, earlier age of onset in India, higher case-fatality rate, estimated 60 million Indians living with IHD, 1 in 3 deaths in men aged 35-64 attributable to IHD.. **Panel C:** Coronary artery plaque cross-section, non-modifiable risk factors, modifiable risk factors, emerging risk factors, dyslipidaemia, hypertension, diabetes mellitus, smoking, obesity, physical inactivity, psychosocial stress, metabolic syndrome, elevated Lp(a), homocysteine, high-sensitivity CRP, sleep apnoea..

Ischaemic heart disease is a broad term for conditions in which the myocardial oxygen supply is inadequate relative to demand, almost always due to coronary artery disease (CAD) from atherosclerosis.

Epidemiology — key figures to remember:
• Leading cause of death globally (WHO 2023) and in India (GBD 2022)
• 1 in 3 deaths in men aged 35–64 are attributable to IHD
• India bears a disproportionate burden — earlier age of onset (~10 years younger than Western populations) and higher case-fatality rate
• Estimated 60 million Indians currently living with IHD

Risk factors (identical to atherosclerosis risk — this is not coincidental; IHD is atherosclerosis applied to coronaries):

Non-modifiable: age (men >45, women >55), male sex, family history (first-degree relative with premature CAD)

Modifiable: dyslipidaemia (↑LDL, ↓HDL), hypertension, diabetes mellitus, smoking, obesity, physical inactivity, psychosocial stress, metabolic syndrome

Emerging risk factors: elevated Lp(a), homocysteine, high-sensitivity CRP, sleep apnoea.

Pathophysiology: From Stable Plaque to ACS

Diagram comparing stable coronary plaque causing demand ischaemia with plaque rupture or erosion causing thrombus formation and acute coronary syndrome subtypes. — **Panel A:** Stable atherosclerotic plaque, thick fibrous cap, smaller lipid core, intact endothelium, fixed coronary stenosis, narrowed lumen, no thrombus, exertion/increased oxygen demand, stable angina.. **Panel B:** Vulnerable plaque, thin fibrous cap rupture, large lipid core, macrophages, exposed subendothelial collagen, platelet aggregation, fibrin strands, coronary thrombus.. **Panel C:** Plaque erosion, endothelial cell loss, exposed subendothelial matrix, platelet adhesion, fibrin formation, coronary thrombus without frank plaque rupture.. **Classification strip:** Unstable angina with partial/transient occlusion and no necrosis, NSTEMI with partial/sustained occlusion and subendocardial necrosis, STEMI with complete occlusion and transmural necrosis..

Understanding IHD pathophysiology requires distinguishing two fundamentally different mechanisms:

1. Fixed stenosis → Demand ischaemia (Stable Angina)
A stable atherosclerotic plaque with a thick fibrous cap progressively narrows the coronary lumen. When stenosis exceeds ~70% diameter, the fixed obstruction limits blood flow during exertion or stress. The result is stable angina — predictable, effort-induced chest pain that resolves with rest or nitrates. There is no thrombosis; the plaque is structurally intact.

2. Acute plaque change → Supply ischaemia (ACS)
Acute plaque change is the pivotal event that converts chronic stable disease into a life-threatening emergency. It has two main forms:
- Plaque rupture: A vulnerable plaque (thin fibrous cap, large lipid core, abundant macrophages) ruptures, exposing the thrombogenic subendothelial collagen and lipid core to flowing blood
- Plaque erosion: Endothelial cells overlying a plaque are lost without frank rupture; subendothelial matrix is exposed

Both mechanisms trigger the coagulation cascade and platelet aggregation → coronary thrombus.

The extent of thrombus determines the ACS subtype:

ACS Type	Occlusion	Myocardial Injury
Unstable Angina	Partial, transient	None (no necrosis)
NSTEMI	Partial, sustained	Subendocardial necrosis
STEMI	Complete, sustained	Transmural necrosis

Vasospasm (Prinzmetal/variant angina) is a separate mechanism — transient severe spasm of a coronary artery, often at the site of a plaque, causing complete but reversible occlusion.

Three-panel diagram showing stable coronary plaque, partially occlusive thrombus causing NSTEMI, and complete occlusive thrombus causing STEMI with labelled plaque components and blood-flow arrows. — **Panel A:** Stable coronary plaque with intact endothelium, fibrous cap, lipid core, calcification, narrowed lumen, and preserved residual flow.. **Panel B:** Ruptured plaque with exposed lipid core, partially occlusive platelet-rich thrombus, reduced residual flow, and subendocardial myocardial injury representing NSTEMI.. **Panel C:** Ruptured plaque with complete occlusive thrombus, absent forward coronary flow, and transmural myocardial injury representing STEMI..

SELF-CHECK

A 62-year-old woman develops chest pain on climbing stairs that resolves within 5 minutes of rest. Coronary angiography shows 75% stenosis of the LAD with a smooth, calcified plaque and intact endothelium. No biomarker elevation. Which mechanism best explains her symptoms?

A. Plaque rupture with partial coronary thrombosis

B. Fixed stenosis causing demand ischaemia during exertion

C. Coronary vasospasm at the site of the plaque

D. Complete coronary occlusion with collateral supply

Reveal Answer

Answer: B. Fixed stenosis causing demand ischaemia during exertion

This is classic stable angina: a fixed high-grade stenosis limits flow only when myocardial oxygen demand increases (exertion), and symptoms resolve with rest when demand falls. Plaque rupture would produce ACS with biomarker elevation. Vasospasm is typically nocturnal and unpredictable. Complete occlusion without collaterals would cause infarction.

Coronary Territory Map and MI Localisation

A three-panel medical diagram maps LAD, RCA, and LCx coronary territories to ECG infarct localisation and compares transmural with subendocardial myocardial infarction. — **Panel A:** Anterior heart with LAD, RCA, LCx, anterior LV wall, lateral wall, inferior/posterior wall inset, apex, anterior two-thirds septum, posterior one-third septum, AV node, SA node, anterolateral papillary muscle, posteromedial papillary muscle, bundle branches.. **Panel B:** 12-lead ECG territory map showing LAD anterior MI leads I, aVL, V1-V6; RCA inferior MI leads II, III, aVF; LCx lateral MI leads I, aVL, V5-V6; note LCx may be electrically silent on standard ECG.. **Panel C:** Ventricular wall cross-sections showing epicardium, myocardium, endocardium, full-thickness transmural necrosis, subendocardial necrosis limited to inner one-third to one-half, STEMI/ST elevation/Q waves, NSTEMI pattern with ST depression or T-wave inversion..

Knowing which coronary artery supplies which territory is essential for localising infarcts clinically:

Left Anterior Descending (LAD): Supplies the anterior wall and apex of the left ventricle, anterior two-thirds of the interventricular septum, anterolateral papillary muscle, and bundle branches. LAD occlusion produces anterior MI (ST elevation in leads I, aVL, V1–V6). LAD infarcts are typically the largest and carry the highest mortality.

Right Coronary Artery (RCA): Supplies the inferior wall and posterior wall (dominant in 80% of people), the posterior one-third of the septum, AV node (SA node in 60%), and the posteromedial papillary muscle. RCA occlusion produces inferior MI (ST elevation in II, III, aVF). RCA infarcts may present with AV conduction blocks and right ventricular infarction.

Left Circumflex (LCx): Supplies the lateral wall and, when dominant, the posterior wall. LCx occlusion produces lateral MI (ST elevation in I, aVL, V5–V6). LCx infarcts are often 'electrically silent' on standard ECG as leads for the lateral wall have lower sensitivity.

Transmural vs. Subendocardial MI:
- Transmural MI: Full-thickness necrosis across the ventricular wall; typically from complete coronary occlusion (STEMI). Associated with ST elevation and Q wave formation on ECG.
- Subendocardial MI: Necrosis confined to the inner one-third to one-half of the wall (the subendocardium is most vulnerable as it is furthest from epicardial coronaries and bears the highest wall tension). Associated with NSTEMI; no Q waves.

Anterior and inferior heart diagrams show LAD territory in blue, RCA territory in green, and LCx territory in orange with corresponding ECG lead localisation. — **Panel A:** Anterior heart view showing LAD artery, diagonal branches, anterior wall, interventricular septum, LCx lateral territory, septal leads V1-V2, anterior leads V3-V4, and lateral leads I, aVL, V5-V6.. **Panel B:** Inferior heart view showing right coronary artery, posterior descending artery, RCA inferior/posterior territory, LCx posterolateral territory, inferior leads II, III, aVF, posterior leads V7-V9, and lateral leads I, aVL, V5-V6.. **Panel C:** ECG localisation key linking LAD with V1-V4, RCA with II, III, aVF and posterior V7-V9, and LCx with I, aVL, V5-V6 plus possible posterior V7-V9 in left dominance..