Ischaemic Heart Disease & MI Pathology

Ischaemic heart disease (IHD) is the umbrella term for a group of syndromes caused by an imbalance between myocardial oxygen supply and demand, almost always due to coronary atherosclerosis. For NEET PG, the single most rewarding theme is the temporal sequence of morphological changes after myocardial infarction (MI) — gross and microscopic — alongside biomarkers and mechanical complications.

Definition & classification

IHD (also called coronary artery disease, CAD) results from reduced coronary blood flow relative to myocardial demand. More than 90% of cases are due to coronary atherosclerosis, with the remainder from vasospasm, emboli, vasculitis, or coronary anomalies.

The classic clinical-pathological spectrum:

Syndrome	Mechanism	Pathology
Stable (typical) angina	Fixed ≥70% stenosis; demand ischaemia	No myocyte death; reversible ischaemia
Prinzmetal (variant) angina	Coronary vasospasm	Transient, at rest, ST elevation
Unstable angina	Disrupted plaque + non-occlusive thrombus	No/minimal necrosis; normal troponin
NSTEMI	Partial/intermittent occlusion	Subendocardial necrosis; troponin rises
STEMI	Complete occlusion by thrombus	Transmural necrosis; troponin rises
Sudden cardiac death	Lethal arrhythmia (often VF)	May have acute plaque change ± old scar
Chronic IHD (ischaemic cardiomyopathy)	Progressive ischaemic damage	Diffuse fibrosis, heart failure

High-yield: Unstable angina, NSTEMI and STEMI together form the acute coronary syndromes (ACS). They lie on a continuum determined by the degree and duration of luminal occlusion.

The two morphological patterns of infarct:

• Transmural infarct — full-thickness necrosis; due to complete occlusion of an epicardial artery; correlates with STEMI; classic regional pattern in a single artery's territory.
• Subendocardial infarct — inner one-third to one-half of the wall; the least perfused, most vulnerable zone; due to global hypoperfusion (shock), transient occlusion with lysis, or severe diffuse CAD; correlates with NSTEMI; often circumferential, not limited to one artery.

Etiology & pathophysiology

The dominant substrate is the atherosclerotic plaque. Stable angina arises from a fixed stenosis limiting flow under exertion. Acute coronary syndromes arise from acute plaque change:

Plaque disruption (rupture/fissure/erosion) → exposure of subendothelial collagen & lipid core → platelet adhesion and activation → thrombin generation and fibrin → partial or complete occlusive thrombus → downstream myocardial ischaemia → necrosis if occlusion persists.

The most rupture-prone ("vulnerable") plaques have a thin fibrous cap, a large lipid core, and dense inflammation (macrophages secreting metalloproteinases that degrade the cap). Importantly, vulnerable plaques are frequently not the most stenotic — many MIs arise from lesions that were <50% stenotic before rupture.

Coronary artery frequency of involvement (high-yield ranking):

Artery	Approx. frequency	Region infarcted
LAD (left anterior descending)	~40–50%	Anterior wall LV, anterior 2/3 septum, apex
RCA (right coronary)	~30–40%	Inferior/posterior LV, posterior septum, RV
LCX (left circumflex)	~15–20%	Lateral wall LV

High-yield: LAD is the most commonly occluded coronary artery overall. The RCA supplies the AV node in ~90% (right-dominant circulation), so inferior wall MI (RCA) is classically associated with bradyarrhythmias and AV block.

Irreversible myocyte injury begins after 20–40 minutes of severe ischaemia. The infarct evolves as a wavefront from subendocardium toward epicardium; early reperfusion (thrombolysis/PCI) can salvage the outer wall. Total necrosis of the at-risk territory is typically complete by 6 hours (longer with collaterals or intermittent flow).

Timeline of MI morphology — the marquee topic

This temporal table is the single most tested item from this chapter. Memorise both gross and microscopic columns.

Time after MI	Gross appearance	Microscopic features
0–4 h (≤½ day)	None (or none visible)	None / waviness of fibres at border
4–12 h	Dark mottling (occasionally)	Early coagulative necrosis, oedema, haemorrhage; contraction bands
12–24 h	Dark mottling / pallor	Ongoing coagulative necrosis, pyknosis of nuclei; early neutrophils; contraction bands
1–3 days	Mottling with yellow-tan infarct centre	Coagulative necrosis; brisk neutrophilic infiltrate, loss of nuclei & striations
3–7 days	Hyperaemic border; central yellow-tan softening	Macrophages begin; disintegration of dead myofibres; early phagocytosis at margins
7–10 days	Maximally yellow-tan & soft, depressed; red-tan margins	Well-developed phagocytosis; early granulation tissue at margins
10–14 days	Red-grey depressed infarct borders	Granulation tissue with new vessels & collagen deposition
2–8 weeks	Grey-white scar progressing from border to core	Increased collagen, decreasing cellularity
>2 months	Completed dense fibrous (collagenous) scar	Dense collagen scar; no cellular infiltrate

A condensed memory frame:

12 h → pallor begins · 24 h → neutrophils · 3–4 days → maximal neutrophils · 5–7 days → macrophages · 1–2 weeks → granulation tissue · 8 weeks → scar.

High-yield: Contraction band necrosis (hypereosinophilic transverse bands) is characteristic of reperfusion injury and is seen early. Wavy fibres at the infarct border reflect stretching of non-contractile dead fibres by adjacent viable myocardium.

High-yield: The infarct is softest and most prone to rupture around days 3–7 (up to ~day 10) when neutrophil-mediated lysis and macrophage clearance have removed dead myocytes but collagen has not yet been laid down.

Mnemonic for the inflammatory-to-healing sequence: "Neutrophils Make Granulation Scar" → Neutrophils (1–3 d) → Macrophages (3–7 d) → Granulation tissue (1–2 wk) → Scar (≥6–8 wk).

High-yield: Earliest ultrastructural change of reversible injury is within minutes; the earliest light-microscopic reliable change is coagulative necrosis at ~4–12 h. Special stains (TTC — triphenyl tetrazolium chloride) detect infarcts grossly from ~2–3 h by loss of red staining where dehydrogenase enzymes have leaked out (pale unstained = infarcted).

Clinical features

Classic MI presents with severe, crushing retrosternal chest pain >20–30 minutes, radiating to the left arm, jaw or epigastrium, with diaphoresis, dyspnoea, nausea and a sense of impending doom. The pain is not relieved by rest or nitrates (unlike stable angina).

• Silent / atypical MI is common in diabetics, elderly, and women (autonomic neuropathy / altered perception).
• Inferior MI may present with vagally mediated bradycardia, hypotension and vomiting.
• Examination may reveal an S4 gallop, new mitral regurgitation murmur (papillary muscle dysfunction), or signs of failure.

Diagnosis & investigation of choice

Three pillars: clinical history + ECG + cardiac biomarkers (the "troponin is king" rule).

ECG:

• STEMI → ST-segment elevation, evolving Q waves; localises the territory (anterior = V1–V4, inferior = II/III/aVF, lateral = I/aVL/V5–V6).
• NSTEMI / unstable angina → ST depression and/or T-wave inversion without persistent ST elevation.

Cardiac biomarkers — timing is heavily tested:

Marker	Rises	Peaks	Returns to normal	Notes
Troponin T/I	3–4 h (high-sensitivity ~1–3 h)	~24–48 h	7–10 days	Most sensitive & specific; investigation of choice
CK-MB	3–6 h	~24 h	2–3 days	Best marker to detect re-infarction
Myoglobin	1–2 h	~6–9 h	~24 h	Earliest to rise but non-specific
LDH / LDH-1	~10 h	2–3 days	~7 days	Historical; "flipped LDH-1 > LDH-2"
AST (SGOT)	~12 h	~2 days	~3–4 days	Non-specific, obsolete

High-yield: Cardiac troponin (cTnI / cTnT) is the biomarker of choice — most sensitive and specific. Because it stays elevated 7–10 days, CK-MB is preferred to diagnose re-infarction (it normalises faster, so a fresh rise signals a new event).

High-yield: Troponin can also be elevated in renal failure, sepsis, PE, myocarditis and heart failure — interpret with the clinical picture and a rise-and-fall pattern (delta) supports acute MI.

Management / drug of choice (concise, exam-oriented)

Reperfusion is the priority in STEMI:

Recognise STEMI → MONA-B initial therapy → emergent reperfusion (primary PCI preferred; fibrinolysis if PCI unavailable within target time) → dual antiplatelet + anticoagulation → secondary prevention.

• MONA-B: Morphine, Oxygen (only if hypoxic), Nitrates, Aspirin (chewed, loading dose), Beta-blocker.
• Primary PCI is the reperfusion strategy of choice if achievable within ~90–120 minutes; otherwise fibrinolysis (tenecteplase/alteplase) within 12 h of symptom onset.
• Dual antiplatelet therapy: aspirin + a P2Y12 inhibitor (ticagrelor/clopidogrel).
• Long term: statin (high-intensity), beta-blocker, ACE inhibitor, and lifestyle modification.

High-yield: In right ventricular / inferior MI, nitrates and diuretics are dangerous — these patients are preload-dependent; give IV fluids, avoid nitrates. Suspect RV infarct with inferior STEMI + hypotension + raised JVP + clear lungs; confirm with right-sided leads (ST elevation in V4R).

Complications

Complications track the morphological timeline — another favourite linkage:

Complication	Typical timing	Mechanism
Arrhythmias (VF, AV block)	Minutes–first 24 h	Electrical instability; #1 cause of pre-hospital death
Cardiogenic shock	Early; large infarct (>40% LV)	Pump failure
Acute LV failure / pulmonary oedema	First days	Loss of contractile mass
Cardiac (free wall) rupture	3–7 days (peak ~day 4–7)	Macrophage softening → haemopericardium & tamponade
Ventricular septal rupture (VSR)	3–7 days	Acute left-to-right shunt, new harsh murmur
Papillary muscle rupture	3–7 days	Acute severe mitral regurgitation (esp. posteromedial muscle, single RCA blood supply)
Fibrinous pericarditis	2–4 days	Transmural inflammation reaching epicardium
Mural thrombus / systemic embolism	~1 week+	Stasis over akinetic endocardium
True ventricular aneurysm	Weeks–months	Thinned fibrous scar bulges; persistent ST elevation
Dressler syndrome	Weeks (2–10 wk)	Autoimmune pericarditis, fever, effusion

High-yield: Cardiac free-wall rupture classically occurs 3–7 days post-MI (weakest, most softened wall) and presents with sudden cardiac tamponade, pulseless electrical activity and death. Rupture risk is higher in first MI, elderly, hypertensive, female, and with late/no reperfusion.

High-yield: A true aneurysm has a wall composed of scarred myocardium and rarely ruptures; a pseudoaneurysm (false aneurysm) is a contained rupture walled off by pericardium/thrombus and has a high rupture risk. ECG hallmark of a true aneurysm: persistent ST-segment elevation weeks after MI.

Differentiate the two post-MI pericarditides:

Feature	Early (peri-infarction) pericarditis	Dressler syndrome
Timing	2–4 days	2–10 weeks
Mechanism	Direct transmural inflammation	Immune/autoimmune
Antibodies	Absent	Anti-myocardial antibodies
Recurrence	Uncommon	Can recur

Key differentials

Chest pain mimics that must be distinguished from MI:

• Unstable angina — same presentation but normal troponin (no necrosis).
• Aortic dissection — tearing pain radiating to back, BP differential between arms, widened mediastinum; thrombolysis contraindicated.
• Acute pericarditis — pleuritic, positional pain relieved by leaning forward, diffuse saddle-shaped ST elevation with PR depression, friction rub.
• Pulmonary embolism — pleuritic pain, dyspnoea, hypoxia, S1Q3T3; troponin may be mildly raised.
• Takotsubo (stress) cardiomyopathy — apical ballooning post-emotional stress, mimics anterior MI but non-obstructed coronaries.
• GORD / oesophageal spasm, musculoskeletal pain, pneumothorax — non-cardiac causes.

High-yield: Reperfusion injury paradoxically worsens myocyte damage on restoring flow (oxygen free radicals, calcium overload, mitochondrial permeability transition). Histological signatures: contraction band necrosis and haemorrhage within the infarct. Myocardial stunning = reversible contractile dysfunction after brief ischaemia; hibernating myocardium = chronic low-flow downregulation that recovers with revascularisation.

Recently asked / exam angle

• "Neutrophilic infiltrate is maximal" at MI → answer: 1–3 days (peak day 2–4).
• "Granulation tissue is seen at" → 1–2 weeks (7–14 days).
• "Dense collagenous scar forms by" → ~6–8 weeks (≥2 months).
• "Cardiac rupture is most common" → 3–7 days post-MI.
• "Most sensitive & specific biomarker" → troponin; "marker to detect re-infarction" → CK-MB.
• "Earliest biomarker to rise" → myoglobin.
• "Most commonly occluded coronary artery" → LAD.
• "Contraction band necrosis indicates" → reperfusion injury.
• "Subendocardium is" → most vulnerable to ischaemia (last perfused).
• "Persistent ST elevation weeks after MI" → ventricular aneurysm.
• Image-based: H&E slides showing wavy fibres (early), dense neutrophils (1–3 d), macrophage-rich tissue (week 1), granulation tissue (1–2 wk), or pink acellular collagen scar (months).
• "New holosystolic murmur day 3–5 post-MI" → think VSR or papillary muscle rupture.

Rapid revision

1. LAD is the most commonly occluded coronary artery; supplies anterior wall, anterior septum and apex.
2. Irreversible myocyte injury starts at ~20–40 min of severe ischaemia; necrosis spreads subendocardium → epicardium (wavefront).
3. Subendocardium is the most vulnerable zone — earliest to die, last to be perfused.
4. Pallor/dark mottling grossly by ~12–24 h; gross infarct unreliable before ~12 h (use TTC stain from ~2–3 h).
5. Neutrophils infiltrate at 1–3 days (peak day 2–4); macrophages at 3–7 days.
6. Granulation tissue at 1–2 weeks; dense fibrous scar by ~6–8 weeks.
7. Infarct is softest and most rupture-prone at 3–7 days (up to day 10).
8. Contraction band necrosis = reperfusion injury; wavy fibres = early border change.
9. Troponin is most sensitive/specific (rises 3–4 h, persists 7–10 d); CK-MB best for re-infarction; myoglobin rises earliest.
10. Mechanical complications (free-wall rupture, VSR, papillary muscle rupture) cluster at 3–7 days; Dressler syndrome at 2–10 weeks.
11. RV/inferior MI is preload-dependent → give fluids, avoid nitrates; RCA supplies AV node → bradyarrhythmias/AV block.
12. Primary PCI is the reperfusion strategy of choice in STEMI; persistent ST elevation weeks later suggests ventricular aneurysm.