Ischemic Heart Disease

Slide 1 · Ischemic Heart Disease

Coronary supply–demand imbalance, myocardial injury, and clinicopathologic consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · What this lecture explains

Define myocardial ischemia and relate oxygen supply to cardiac workload.

Explain how fixed coronary obstruction and acute plaque change generate different clinical syndromes.

Trace the myocardial response to ischemia, infarction, and reperfusion.

Interpret infarct morphology, major complications, chronic IHD, and sudden cardiac death.

Slide 3 · Ischemia is a supply–demand mismatch

Reduced coronary supply

Atherosclerosis, thrombosis, spasm

Oxygen and substrate deficit

ATP depletion; Metabolite retention

Myocardial dysfunction

Angina, contractile failure, arrhythmia

Prolonged severe injury

Myocyte death and infarction

Schematic

Slide 4 · Why coronary perfusion matters

Oxygen and nutrients

Metabolic clearance

Myocytes depend on oxidative ATP generation

Perfusion also removes metabolic by-products

Ischemia rapidly reduces energy production

Accumulated metabolites participate in injury and pain

Contractile dysfunction arises before necrosis

Decreasing flow compromises waste removal

Reperfusion restores substrate delivery

Reperfusion also helps clear metabolites

Slide 5 · The major clinical expressions of IHD

Transient ischemia

Angina or silent ischemia

Acute plaque–thrombus event

Unstable angina or infarction

Accumulated ischemic damage

Chronic ischemic heart failure

Electrical instability

Sudden cardiac death

Schematic

Slide 6 · Coronary atherosclerosis dominates IHD

Atherosclerosis involving epicardial coronary arteries is the principal substrate.

Fixed stenosis restricts flow reserve, especially under stress.

Plaque disruption, thrombosis, and superimposed spasm produce abrupt reductions in flow.

Less common causes include coronary spasm, embolism, vasculitis, and systemic perfusion deficits.

Slide 7 · Population burden reflects preventable vascular disease

Robbins characterizes IHD as the leading single cause of death globally.

Tobacco exposure, dyslipidemia, hypertension, and diabetes contribute to coronary disease burden.

Earlier diagnosis and treatment have reduced IHD mortality in many high-resource settings.

Population-level prevention and emergency access influence disease outcomes.

Slide 8 · Risk modification acts before plaque rupture

Risk-factor intervention

Clinical purpose

Smoking cessation

Limit vascular injury and thrombosis risk

Cholesterol reduction

Slow atherosclerotic progression; Favor plaque stability

Blood-pressure control

Reduce vascular stress and cardiac oxygen demand

Exercise, weight, glycemic control

Reduce metabolic and cardiovascular risk

Slide 9 · Coronary territories connect lesion to infarct

Artery

Typical major myocardial territory

Left anterior descending (LAD)

Anterior LV, apex, anterior two-thirds of septum

Right coronary artery (RCA)

Inferior/posterior LV and posterior septum in right dominance; RV involvement possible

Left circumflex (LCX)

Lateral LV free wall (typical right-dominant circulation)

Slide 10 · Coronary dominance refers to septal supply

Dominance is assigned by the artery supplying the posterior third of the interventricular septum.

In right-dominant hearts, the RCA perfuses this posterior septal territory.

An RCA occlusion may therefore cause LV as well as right-sided injury.

Anatomic variation means the injured territory must be interpreted using actual coronary distribution.

Slide 11 · Fixed stenosis consumes coronary flow reserve

Unobstructed epicardial lumen

Atherosclerotic lumen with reduced reserve

Exercise raises demand; Maximal vasodilation cannot fully compensate for fixed obstruction.

Schematic

Slide 12 · Critical stenosis is a functional threshold

>70% reduction in luminal cross-sectional area as a conventional threshold for exertional ischemia.

Very severe obstruction (~90% of area) can impair flow even at rest.

Extent of stenosis alone does not fully predict symptoms or events.

These refer to cross-sectional area—not interchangeable diameter measurements.

Slide 13 · Coronary flow reserve is more than anatomy

Proximal narrowing

Pressure drop across stenosis

Distal arteriolar dilation

Compensates at baseline

Additional workload

Demand rises

Exhausted flow reserve

Transient myocardial ischemia

Schematic

Slide 14 · Collateral channels modify ischemic injury

Slowly progressive narrowing

Distal perfusion pressure decreases

Collateral enlargement

Alternate coronary connections conduct flow

Perfusion support

Potentially smaller ischemic territory

Abrupt occlusion without collateralization

Greater area at risk

Schematic

Slide 15 · Single- and multivessel disease coexist

LAD, LCX, and RCA may be affected singly or in combination.

Major stenoses tend to occur in proximal portions of epicardial arteries.

Intramyocardial penetrating arteries are less commonly the primary site of atherosclerotic plaque.

Lesion distribution, collateralization, and physiological reserve jointly determine risk.

Slide 16 · Stable plaque and vulnerable plaque differ

Fibrous-cap–rich lesion

Thin-cap, lipid-rich lesion

Rupture propensity depends on cap strength, inflammation, plaque structure, and mechanical stress.

Schematic

Slide 17 · Plaque stability depends on matrix turnover

Smooth muscle cells

Synthesize cap collagen

Macrophage-rich inflammation

Promotes matrix proteolysis

Collagen balance

Determines mechanical cap strength

Cap failure under stress

Plaque fissure or rupture

Schematic

Slide 18 · Acute coronary syndrome starts at the plaque

Plaque rupture or erosion

Thrombogenic material exposed

Platelet adhesion and activation

Local aggregate and mediators

Coagulation activation

Fibrin-rich evolving thrombus

Reduction of coronary flow

Unstable angina or MI

Schematic

Slide 19 · Erosion and rupture expose different surfaces

Plaque rupture

Plaque erosion

Structural failure of fibrous cap

Loss/dysfunction of surface endothelial cells

Exposes thrombogenic atheromatous contents

Exposes prothrombotic subendothelial matrix

Often associated with large lipid core, thin cap, inflammation

Can occur without overt cap rupture

Both may provoke an acute coronary thrombosis

Both may provoke an acute coronary thrombosis

Slide 20 · The platelet–coagulation amplification loop

Exposed collagen / tissue factor

Thrombogenic trigger

Platelet adhesion and activation

ADP, thromboxane A₂, serotonin

Coagulation / fibrin deposition

Thrombus stabilizes and grows

Possible complete occlusion

Profound ischemia and necrosis

Schematic

Slide 21 · Occlusive and nonocclusive thrombi diverge

Nonocclusive or transient thrombus

Persistent occlusive thrombus

Residual flow may be sufficient to delay transmural necrosis

Severely compromises supplied myocardium

Unstable angina, microembolism, or limited MI

Often produces extensive acute MI

Clinical outcome depends on duration and flow

Myocyte loss expands without reperfusion

Not reliably predicted from previous angina severity

May arise from a previously noncritical plaque

Slide 22 · The culprit lesion may not be critically stenotic

Most infarct-related disruptions do not occur at a lesion previously causing severe fixed flow limitation.

Vulnerability and thrombotic response matter, not only plaque bulk.

Clinically silent plaque injury and healing can enlarge stenoses over time.

A history without exertional angina does not exclude an abrupt coronary event.

Slide 23 · Why plaque change can cause sudden death

Coronary plaque event

Thrombosis ± vasospasm

Acute myocardial ischemia

ATP loss and ionic disturbance

Electrical instability

Ventricular tachyarrhythmia / fibrillation

Collapse

Sudden cardiac death before necrosis is demonstrable

Schematic

Slide 24 · Angina is reversible ischemia without myocyte necrosis

Transient myocardial ischemia may provoke substernal or precordial discomfort.

Ischemic metabolites stimulate visceral afferent pathways.

A typical attack resolves when coronary supply–demand balance improves.

Angina and acute MI differ fundamentally by the presence of irreversible cardiomyocyte death.

Slide 25 · Stable angina: Demand exceeds fixed supply

Chronic coronary narrowing

Restricted ability to augment flow

Exercise or emotional stress

Heart rate and contractility rise

Transient ischemia

Squeezing / pressure-like discomfort

Rest or vasodilator

Demand falls or flow improves

Schematic

Slide 26 · Vasospastic angina: Transient dynamic obstruction

Coronary arterial spasm can produce ischemia without increased physical demand.

Episodes may occur at rest and may coexist with coronary atherosclerosis.

Attacks generally respond to vasodilator treatment.

Distinguish the dynamic vascular lesion from a fixed exertional stenosis.

Slide 27 · Unstable angina signals acute plaque pathology

Episodes become more frequent, longer, more severe, or occur with less exertion and at rest.

Plaque disruption with thrombosis, distal embolization, and/or spasm underlies the syndrome.

Necrosis is absent by definition; Evolving myocardial injury may instead establish MI.

Unstable symptoms represent an urgent risk of complete coronary occlusion.

Slide 28 · Silent ischemia is clinically consequential

Not all ischemic episodes produce recognizable chest pain.

Older adults and patients with diabetic neuropathy may report atypical or absent pain.

Dyspnea, diaphoresis, fatigue, palpitations, and gastrointestinal symptoms can predominate.

Absence of pain must not be equated with absence of myocardial ischemia.

Slide 29 · Anginal phenotypes at a glance

Pattern

Dominant mechanism

Usual setting

Stable

Fixed atherosclerotic flow limitation

Predictable demand-related episodes

Vasospastic

Dynamic coronary vasoconstriction

Often at rest; Responds to vasodilators

Unstable

Plaque disruption ± thrombus / spasm

Crescendo or rest symptoms; Risk of MI

Silent

Ischemia without recognized anginal pain

Older age or autonomic neuropathy

Slide 30 · Case: Recurrent exertional pressure

Clinical vignette

A person experiences reproducible substernal pressure during uphill walking. Symptoms disappear soon after resting. There is no evidence of myocardial necrosis.

What coronary pathophysiology best explains this pattern?

Slide 31 · Myocardial infarction is ischemic myocyte death

MI is necrosis of cardiac myocytes caused by sufficiently severe or prolonged ischemia.

Atherosclerotic plaque change and thrombosis are the usual proximate events.

The extent of infarction depends on time, perfusion territory, collateral flow, and myocardial demand.

Nonatherothrombotic mechanisms must be considered when no culprit plaque thrombus is found.

Slide 32 · An acute infarct usually follows four linked events

Plaque disruption

Cap erosion or rupture

Thrombosis

Platelets + tissue factor pathway

Coronary occlusion

Abrupt fall in local myocardial blood flow

Sustained ischemia

Irreversible myocyte necrosis

Schematic

Slide 33 · Not every infarct is caused by plaque thrombosis

Alternative mechanism

Illustrative setting

Coronary vasospasm

Spasm with/without atherosclerosis; Stimulant exposure

Coronary embolus

Atrial mural thrombus; Endocarditis vegetation

Small-vessel disease

Vasculitis or vascular amyloid

Reduced systemic oxygen delivery

Shock, hypotension, or hematologic abnormalities

Other vascular injury

Coronary dissection; Selected postoperative settings

Slide 34 · ATP falls before tissue necrosis appears

Seconds

Aerobic metabolism declines

<2 min

Contractility lost

20–40 min

Irreversible injury emerges

Hours

Necrosis expands through at-risk tissue

Schematic

Slide 35 · Contractile failure precedes cell death

Oxidative phosphorylation falls within seconds of major perfusion loss.

ATP depletion and metabolite accumulation impair excitation–contraction coupling.

Severe ischemia can abolish mechanical contraction within approximately 1–2 minutes.

Early contractile dysfunction may be reversible even when function is severely reduced.

Slide 36 · The myocardial injury threshold is time-dependent

Very severe ischemia sustained for roughly 20–40 minutes produces irreversible injury.

Cell death spreads through the area at risk as perfusion deprivation continues.

An infarct may become near-complete within approximately 6–12 hours without intervention.

Restoring flow rapidly provides the greatest potential to salvage viable myocardium.

Slide 37 · Subendocardium is the earliest vulnerable zone

Endocardial surface lies at bottom

The subendocardium receives blood last and experiences greater intramural compressive pressure.

Epicardial side

Endocardial side

Schematic

Slide 38 · Necrosis advances as a wavefront

Early subendocardial zone

Later near-transmural zone

Early: Inner-wall injury

Prolonged severe ischemia: Necrosis extends toward epicardium within the supplied territory.

Epicardial side

Endocardial side

Schematic

Slide 39 · Area at risk is not identical to final infarct size

Arterial territory

Defines myocardium at risk

Occlusion severity + duration

Determines sustained flow deficit

Collaterals / reperfusion

Preserve threatened viable tissue

Final necrotic mass

Dictates many structural consequences

Schematic

Slide 40 · Location, time, and flow determine infarct size

Coronary anatomy establishes the perfusion zone and size of myocardium at risk.

Obstruction site and severity modify residual tissue flow.

Collateral channels and reperfusion can reduce completed necrosis.

Heart rate, oxygenation, spasm, and metabolic demand further modify injury.

Slide 41 · Transmural and subendocardial infarcts differ

Transmural necrosis

Subendocardial necrosis

Persistent epicardial occlusion may cause nearly full-thickness infarction.

Partial/transient occlusion or global hypoperfusion may leave necrosis limited to the inner wall.

Epicardial side

Endocardial side

Schematic

Slide 42 · Subendocardial infarction can be circumferential

Transient thrombotic occlusion may injure the inner portion of one coronary territory.

Global hypotension superimposed on stenosis may produce a circumferential subendocardial pattern.

Reperfusion before completion can limit the depth of necrosis.

Thus, transmural extent and coronary territory do not always correspond one-to-one.

Slide 43 · Small intramural vessel injury produces microinfarcts

Microemboli, vasculitis, and vasospasm can obstruct small intramyocardial vessels.

Injury is patchy and may not form a single large epicardial-territory infarct.

Adrenergic stimulation can combine coronary constriction with increased oxygen demand.

Interpret microinfarcts in the context of vascular pathology and systemic illness.

Slide 44 · Regional infarcts reflect arterial supply

Occluded artery

Common myocardial pattern

Potential additional injury

LAD

Anterior left ventricular wall, apex, anterior septum

Extensive anteroapical injury

RCA (right dominance)

Inferior/posterior LV, posterior septum

Right ventricular involvement; Conduction disturbance

LCX

Lateral left ventricular wall

Posterolateral injury varies with dominance

Slide 45 · The earliest infarct is grossly inconspicuous

MI generally cannot be diagnosed from gross appearance in the first several hours.

Triphenyl tetrazolium chloride staining can reveal loss of dehydrogenase activity after early necrosis.

Viable myocardium stains red; Infarcted nonviable regions remain pale.

Apparent absence of a gross infarct does not exclude fatal early ischemic injury.

Slide 46 · Coagulative necrosis evolves over hours

0–4 h

Grossly unapparent; Subtle early changes

4–12 h

Early coagulative necrosis and edema

12–24 h

Hypereosinophilia; Early neutrophils

1–3 d

Prominent neutrophils; Necrotic fibers

Schematic

Slide 47 · Wavy fibers mark early mechanical injury

Noncontractile necrotic fibers are stretched by adjacent viable contracting myocardium.

At the infarct margin, fibers may appear narrowed and wavy.

Edema separates injured myocardial fibers.

The finding must be interpreted against postmortem interval and adjacent morphology.

Slide 48 · Neutrophils dominate the early infarct

Coagulative myocyte necrosis triggers an acute inflammatory response.

Neutrophilic infiltration becomes prominent during the first several days.

Inflammation clears injured tissue but contributes to transient tissue fragility.

The cellular composition changes predictably as healing advances.

Slide 49 · Macrophage clearance creates a vulnerable wall

1–3 d

Necrotic fibers and neutrophils

3–7 d

Macrophages digest dead fibers

7–10 d

Granulation tissue at margins

Weeks

Collagen replaces dead myocardium

Schematic

Slide 50 · Gross healing changes from mottling to scar

12–24 h

Dark mottling

3–7 d

Yellow-tan softening; Hyperemic rim

10–14 d

Depressed red-gray margins

>2 mo

Dense pale fibrous scar

Schematic

Slide 51 · Granulation tissue replaces cleared necrosis

Capillary ingrowth and fibroblast activity begin at the margins of necrotic tissue.

Vascular granulation tissue forms a matrix for subsequent collagen deposition.

Large infarcts heal from border toward center and may take longer to scar.

Adult cardiomyocytes do not replace the lost contractile cell population by meaningful regeneration.

Slide 52 · Old infarcts become mechanically distinct scar

Mature infarcts contain dense collagen replacing dead myocytes.

Scar lacks normal force-generating properties and disrupts local conduction.

Adjacent viable cardiomyocytes can become hypertrophic.

The microscopic age of a fully healed scar cannot be determined reliably from appearance alone.

Slide 53 · Morphologic dating is approximate

Time after infarction

Dominant expected finding

0.5–4 hours

Often minimal LM change; Possible wavy fibers

4–24 hours

Evolving coagulative necrosis and early neutrophils

1–3 days

Neutrophilic infiltrate

3–7 days

Macrophage removal; Tissue softening

7–14 days

Granulation tissue and beginning collagen

Weeks to months

Progressive fibrous scarring

Slide 54 · Reperfusion salvages viable at-risk myocardium

Early arterial reopening

Thrombolysis or catheter intervention

Perfusion restored

Oxygen / substrate delivery resume

Viable threatened myocardium

Necrosis prevented

Residual dysfunction

May recover over days

Schematic

Slide 55 · Successful reperfusion can alter morphology

Reperfused infarcts are often hemorrhagic because previously injured microvessels leak.

Myocytes already irreversibly injured may develop contraction band necrosis.

Additional injury may involve reactive oxygen species, Ca²⁺ overload, and microvascular dysfunction.

Clinical significance of reperfusion injury is an area of continuing investigation.

Slide 56 · Reperfusion injury has several interacting causes

Mitochondrial injury

Permeability changes and cell-death signals

Calcium overload

Myocyte hypercontraction

Oxidants + leukocytes

Membrane and microvascular damage

Platelets / complement

Additional endothelial injury

Schematic

Slide 57 · No-reflow is a microvascular problem

Epicardial obstruction relieved

Macrovascular inflow re-established

Microvascular injury

Endothelial swelling / leukocyte plugging

Local perfusion remains impaired

No-reflow despite an open artery

Residual ischemic damage

Limited tissue-level recovery

Schematic

Slide 58 · Stunning and hibernation are viable dysfunction

Stunned myocardium

Hibernating myocardium

Prolonged transient dysfunction after short ischemia/reperfusion

Chronic downregulation under persistent sublethal ischemia

Viable cells with delayed contractile recovery

Viable but persistently low-function cells

Typically improves after a recovery period

Often improves after revascularization

Not equivalent to infarct scar

Not equivalent to infarct scar

Slide 59 · Reversible dysfunction must be separated from scar

Ischemia without death

Stunning / hibernation

Prolonged severe ischemia

Cardiomyocyte necrosis

Necrotic tissue removed

Inflammation and granulation tissue

Noncontractile scar

Permanent replacement fibrosis

Schematic

Slide 60 · Acute MI diagnosis integrates different evidence

Clinical presentation

Chest discomfort, dyspnea, autonomic symptoms

Electrocardiogram

Signs of regional ischemia or injury

Serial cardiac troponin

Detect acute myocardial injury

Clinical interpretation

Determine whether ischemia caused injury

Schematic

Slide 61 · Myocardial injury may occur without classic pain

Crushing or pressure-like prolonged chest discomfort is typical but not universal.

Diaphoresis, nausea, vomiting, dyspnea, and weakness may accompany acute MI.

Some patients have clinically silent or atypical presentations.

Symptoms alone cannot establish the presence, extent, or mechanism of myocyte necrosis.

Slide 62 · STEMI and NSTEMI are clinical ECG categories

ST-elevation and non–ST-elevation MI describe electrocardiographic presentation.

The ECG pattern reflects ischemic injury distribution and electrical manifestations.

Many transmural infarcts with STEMI and many subendocardial infarcts with NSTEMI.

Anatomical transmurality and ECG labels are not perfectly interchangeable in individual patients.

Slide 63 · Troponin release requires membrane injury

Cardiomyocyte necrosis

Sarcolemmal permeability / integrity lost

Intracellular proteins escape

Cardiac troponin T / I enters interstitium

Circulation and lymphatics

Protein becomes detectable in blood

Serial laboratory analysis

Supports diagnosis of acute myocardial injury

Schematic

Slide 64 · Troponin is a marker of injury, not etiology

Cardiac troponins T and I are sensitive indicators of myocardial injury.

An acute rising/falling pattern is interpreted with symptoms, ECG, and clinical context.

Myocarditis and myocardial trauma can cause substantial troponin release.

Heart failure, pulmonary embolism, sepsis, and renal disease may also show elevated troponin.

Slide 65 · Case: Elevated troponin with systemic illness

Clinical vignette

A critically ill patient with sepsis has elevated cardiac troponin but no clear acute coronary symptoms or regional ECG changes.

What should be concluded from the troponin result alone?

Slide 66 · Postinfarction outcomes track injury extent

Infarct size, location, and wall thickness predict complication patterns.

Large transmural infarcts carry substantial risk of pump failure, arrhythmia, and structural complications.

Residual LV function is an important determinant of prognosis.

Stenoses supplying remaining viable myocardium influence long-term outcome.

Slide 67 · Loss of contractile mass can cause shock

Large myocardial infarct

Loss of viable contractile tissue

LV pump dysfunction

Cardiac output declines

Hypotension + pulmonary congestion

End-organ and lung hypoperfusion

Cardiogenic shock

Severe systemic circulatory failure

Schematic

Slide 68 · Rupture targets three distinct structures

Site of rupture

Immediate result

Clinical consequence

LV free wall

Blood enters pericardial space

Hemopericardium and tamponade

Ventricular septum

New interventricular communication

Acute left-to-right shunt

Papillary muscle

Acute loss of valve support

Severe mitral regurgitation

Slide 69 · Days 3–7 are a major rupture-risk interval

Coagulative necrosis

Dead cardiac muscle

Inflammatory clearance

Macrophages digest structural material

Transiently soft tissue

Weak mechanical resistance

Rupture risk

Before mature scar formation

Schematic

Slide 70 · Ischemic papillary muscle dysfunction causes MR

Ischemia or infarction can impair papillary muscle contraction without anatomic rupture.

Complete rupture causes abrupt severe regurgitation.

Later ventricular dilation or papillary scarring also alters mitral geometry.

Clinical severity depends on the mechanism and timing of valve incompetence.

Slide 71 · Arrhythmia may be the earliest fatal event

Acute ischemia and infarction create heterogeneous electrical conduction and irritability.

Potential disturbances include conduction block, ectopy, ventricular tachycardia, and fibrillation.

Risk of malignant rhythm disturbance is particularly high soon after symptom onset.

Electrical death can precede grossly or biochemically apparent infarction.

Slide 72 · Infarction can inflame the overlying pericardium

Transmural injury may induce fibrinous or fibrinohemorrhagic pericarditis.

Early post-MI pericarditis may develop within a few days.

Later immune-mediated postinfarction pericarditis is described as Dressler syndrome.

These phenomena differ from free-wall rupture with hemopericardium and tamponade.

Slide 73 · Mural thrombus arises from stasis and injury

Infarcted segment weakens

Reduced regional contraction

Chamber geometry changes

Dilation and local stasis

Endocardial injury

Thrombogenic luminal surface

Mural thrombus

Risk of systemic embolization

Schematic

Slide 74 · Infarct expansion and ventricular aneurysm

Early infarct expansion

Late true ventricular aneurysm

Stretching and thinning of necrotic wall

Outpouching formed by scarred ventricular wall

May worsen wall stress and dilation

Associated with mural thrombus, arrhythmia, and failure

Occurs before stable collagen scar

Usually follows a large transmural infarct

Structural weakness raises concern for rupture

Scarred true aneurysm typically does not rupture

Slide 75 · Mechanical complications depend on infarct depth

More often with transmural injury

Less characteristic of limited subendocardial injury

Pericardial inflammation

Epicardial surface usually spared

Free-wall or septal rupture

Wall retains more full-thickness myocardium

Scarred ventricular aneurysm

Less extensive full-wall scar substrate

Marked chamber dysfunction

May still occur if ischemic burden is large

Slide 76 · Ventricular remodeling links MI to chronic failure

Infarcted myocardium

Loss of contractile cells

Residual muscle hypertrophy

Initial functional compensation

Wall dilation and altered geometry

Increased stress and oxygen demand

Progressive dysfunction

Chronic ischemic heart disease

Schematic

Slide 77 · Chronic IHD reflects accumulated injury

Chronic ischemic heart disease denotes progressive cardiac failure from prior infarction and/or ongoing inadequate perfusion.

Decompensation of hypertrophied viable myocardium compounds earlier ischemic loss.

Some patients develop heart failure with severe CAD but without a recognized prior MI.

Coronary obstruction and ventricular remodeling act together.

Slide 78 · Chronic IHD has a characteristic pathology

Gross morphology

Microscopic morphology

Cardiomegaly; LV hypertrophy and dilation

Hypertrophied remaining cardiomyocytes

Stenotic epicardial atherosclerosis

Interstitial and replacement fibrosis

Discrete healed infarct scars

Subendocardial myocyte vacuolization

Endocardial fibrous thickening ± mural thrombi

Mixed chronic ischemic and remodeling changes

Slide 79 · Chronic ischemia is also an electrical substrate

Scar and interstitial fibrosis

Discontinuous electrical propagation

Surviving myocyte strands

Conduction heterogeneity

Reentry susceptibility

Ventricular tachyarrhythmias

Electrical instability

Risk of sudden cardiac death

Schematic

Slide 80 · Sudden cardiac death is usually arrhythmic

SCD as unexpected cardiac death soon after symptom onset or after being last seen well.

Ventricular fibrillation and other fatal rhythm disturbances are the common mechanism.

Coronary artery disease is the leading underlying cause.

SCD may be the first clinical manifestation of IHD.

Slide 81 · Sudden death need not follow a completed MI

Severe fixed CAD can trigger fatal ischemic arrhythmia without a new thrombosis.

An acute plaque disruption is not demonstrable in every coronary-related sudden death.

Old infarct scars can provide reentrant electrical pathways.

At autopsy, absence of an acute infarct does not exclude ischemic arrhythmic death.

Slide 82 · Consider other causes of sudden death in younger patients

Category

Examples listed by Robbins

Electrical disease

Inherited / acquired conduction disease and channelopathies

Structural myocardial disease

Hypertrophic or dilated cardiomyopathy; Myocarditis

Congenital abnormality

Anomalous coronary origins / courses

Other cardiac and systemic processes

Mitral valve prolapse, pulmonary hypertension, embolism, stimulant use

Slide 83 · An integrated causal map of IHD

Epicardial coronary atherosclerosis

Fixed narrowing or plaque disruption

Reduced myocardial perfusion

Transient or prolonged ischemia

Syndrome

Angina / MI / electrical instability

Longer-term consequence

Scar + remodeling → heart failure; Sudden death possible

Schematic

Slide 84 · Case: Collapse after brief chest discomfort

Clinical vignette

A patient with advanced coronary atherosclerosis collapses unexpectedly after brief chest discomfort. No established acute myocardial necrosis is found.

Which mechanism must remain high on the differential?

Slide 85 · Five pathology principles to retain

Coronary oxygen supply must be evaluated relative to myocardial demand.

Fixed stenosis predicts exertional ischemia; Acute plaque thrombosis predicts abrupt coronary syndromes.

Early severe ischemia causes rapid dysfunction; Irreversible necrosis requires sustained flow deprivation.

Myocyte necrosis is followed by inflammation, granulation tissue, and permanent collagen scar.

Infarct complications and chronic sequelae follow from lost muscle, mechanical fragility, fibrosis, and electrical instability.

Slide 86 · Primary reference and scope

Primary course source

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 12: The Heart, pp. 492–504.

Primary project transcript: robbins.md, chapter section “Ischemic Heart Disease” and adjacent subsections.

This lecture includes the parent disease section and directly related manifestations through sudden cardiac death.