Sudden Cardiac Death

Slide 1 · Sudden Cardiac Death

Mechanisms, structural substrates, inherited arrhythmias and clinicopathologic correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Define sudden cardiac death and distinguish an electrical terminal event from a myocardial lesion.

Explain how ischemia, fibrosis and re-entry lead to lethal ventricular rhythms.

Classify major ischemic, structural and inherited nonatherosclerotic substrates.

Interpret the morphology, clinical clues and prevention principles.

Clinicopathologic emphasis: The heart may not show a new infarct.

Slide 3 · Sudden death is a clinical event, not a single lesion

The term describes an unexpected fatal cardiac event within a defined time window.

Multiple diseases can converge on a final lethal cardiac rhythm.

Therefore, clinical circumstances and underlying cardiac pathology must be interpreted together.

CONCEPTUAL PATHWAY — SCHEMATIC

Underlying cardiac disease

Electrical or hemodynamic failure

Sudden death

Slide 4 · The operational definition uses two time windows

Death occurs within 1 hour after the onset of symptoms, when observed.

Alternatively, the person was last known to be well within the preceding 24 hours.

These are operational timing criteria; They do not identify the mechanism in an individual case.

SIDE-BY-SIDE DISTINCTION

Observed event

≤ 1 hour after symptoms

Unwitnessed event

Last seen well ≤ 24 hours

Slide 5 · A major global burden

Approximately 325,000 cases annually in the United States.

The corresponding worldwide estimate is 4–5 million per year.

These are estimates reported in the supplied 11th-edition text, not newly validated surveillance data.

ANNUAL CASE ESTIMATES

325,000

United States / year

4–5 million

Worldwide / year

Slide 6 · A lethal arrhythmia is the dominant final mechanism

Ventricular fibrillation is the prototypical fatal rhythm.

Asystole is another recognized electrical endpoint.

The shared consequence is abrupt loss of effective cardiac output.

CONCEPTUAL PATHWAY — SCHEMATIC

Electrical instability

VF or asystole

Loss of effective output

Slide 7 · Ventricular fibrillation and asystole are not equivalent

In ventricular fibrillation, depolarization becomes chaotic with no effective ventricular contraction.

In asystole, electrical activity is absent.

Both can lead rapidly to collapse, but they differ in electrical behavior.

SIDE-BY-SIDE DISTINCTION

Ventricular fibrillation

Chaotic electrical activity

Ineffective contraction

Asystole

No electrical activity

No effective cardiac output

Slide 8 · The clinical spectrum of rhythm disturbances

A rhythm disturbance may be intermittent or sustained.

Palpitations or a perceived racing heart can precede major events.

Sustained loss of cardiac output causes presyncope, syncope or sudden death.

CONCEPTUAL PATHWAY — SCHEMATIC

Palpitations

Near syncope / syncope

Potential fatal collapse

Slide 9 · An arrhythmia may arise at many cardiac levels

The sinoatrial node, atrioventricular pathways and ventricular myocardium can all initiate abnormal rhythms.

Arrhythmias are commonly grouped as supraventricular or ventricular in origin.

The anatomical site of abnormal firing does not by itself predict lethality.

CONCEPTUAL PATHWAY — SCHEMATIC

Nodal / atrial activity

Conducted rhythm disturbances

Ventricular myocardial activity

Slide 10 · Most fatal instability is not confined to the nodes

Conduction-system injury can produce a serious rhythm disturbance.

Electrically irritable myocardium away from major conducting structures.

The ventricular muscle can therefore generate fatal activity without focal nodal destruction.

SIDE-BY-SIDE DISTINCTION

Major conduction system

Can be injured directly

Working ventricular myocardium

Frequent source of electrical irritability

Slide 11 · Three broad substrates alter cardiac electrical stability

Ischemia changes myocyte excitability.

Structural remodeling, including hypertrophy and fibrosis, disrupts orderly conduction.

Channel defects alter depolarization or repolarization without necessarily changing gross anatomy.

RELATED SUBSTRATES / COMPONENTS

Ischemia

Fibrosis / hypertrophy

Ion channel dysfunction

Slide 12 · Gap junctions coordinate ventricular depolarization

Neighboring cardiomyocytes transmit electrical current through gap junctions.

Normal intercellular coupling permits an ordered wave of activation.

Abnormal distribution or structure of junctions can destabilize conduction.

CONCEPTUAL PATHWAY — SCHEMATIC

Myocyte

Gap junction coupling

Adjacent myocyte

Slide 13 · Ischemia increases myocyte electrical irritability

Ischemic myocardium may fire aberrantly without undergoing lethal necrosis.

Spontaneous depolarization can recruit interconnected neighboring cells.

These events may initiate abnormal paths of ventricular activation.

CONCEPTUAL PATHWAY — SCHEMATIC

Myocardial ischemia

Increased excitability

Aberrant impulses

Slide 14 · Fibrosis creates nonuniform pathways of conduction

Fibrotic foci interrupt direct myocyte-to-myocyte signaling.

Current must propagate through surviving pathways with altered geometry.

The resulting heterogeneity provides a setting for re-entry circuits.

CONCEPTUAL PATHWAY — SCHEMATIC

Local fibrosis

Altered signal propagation

Re-entry susceptibility

Slide 15 · Re-entry sustains inappropriate ventricular activation

An excitation wave can circulate through a pathway and reactivate myocardium.

Scar, inflammation and electrical heterogeneity facilitate abnormal circuits.

This mechanism links structural substrate to sustained ventricular tachyarrhythmia.

RE-ENTRY: CONCEPTUAL SEQUENCE

Abnormal propagation

Reactivation

Sustained circuit

A circulating impulse may repeatedly re-excite myocardium.

Slide 16 · Ventricular tachycardia can precede fibrillation

A re-entry circuit may initiate ventricular tachycardia.

Multiple or disorganized circuits can evolve into ventricular fibrillation.

This provides a mechanistic sequence from myocardial remodeling to sudden death.

CONCEPTUAL PATHWAY — SCHEMATIC

Re-entry circuit

Ventricular tachycardia

Ventricular fibrillation

Slide 17 · Fibrillation terminates effective pump activity

During fibrillation, ventricular contraction loses coordinated timing.

Chaotic depolarization does not generate functional forward output.

The electrical disorder is sufficient to explain rapid collapse.

CONCEPTUAL PATHWAY — SCHEMATIC

Chaotic depolarization

Disorganized contraction

Hemodynamic collapse

Slide 18 · The substrate–trigger–endpoint model integrates SCD

Substrate: Obstructive coronary disease, healed injury or inherited channelopathy.

Trigger: Spontaneous aberrant depolarization or another disturbance of electrical activity.

Endpoint: Sustained ventricular rhythm disturbance, often fibrillation.

RELATED SUBSTRATES / COMPONENTS

Substrate

Electrical trigger

Lethal rhythm

Slide 19 · Coronary atherosclerotic disease is the leading cause

Coronary artery disease accounts for most sudden cardiac deaths.

Its importance reflects both acute ischemic effects and established structural injury.

Absence of an acute infarct does not remove coronary disease from the differential.

CONCEPTUAL PATHWAY — SCHEMATIC

Coronary disease

Ischemic electrical instability

Sudden death

Slide 20 · Sudden death may be the first manifestation of IHD

A patient may have no previously recognized ischemic heart disease.

Severe coronary pathology can remain clinically silent until a lethal electrical event.

This disconnect between symptoms and disease burden is central to the pathology of SCD.

No previous angina or infarct is required for SCD to reveal severe CAD.

Slide 21 · Fixed critical coronary stenosis is a typical substrate

Severe chronic coronary atherosclerosis with fixed critical narrowing.

Reduced flow reserve predisposes the myocardium to ischemic instability.

A new occlusive thrombus is not necessary in the typical SCD case.

CORONARY ARTERY CROSS-SECTION — SCHEMATIC

Plaque / narrowed lumen

Slide 22 · Acute plaque disruption is a minority finding

The reported frequency of acute plaque disruption in SCD is 10–20%.

Most patients therefore lack this particular acute plaque event.

Atherosclerosis may still be extensive despite the absence of rupture.

ANNUAL CASE ESTIMATES

10–20%

Acute plaque disruption

Most cases

No identified acute plaque disruption

Slide 23 · Sudden electrical death does not require new necrosis

Myocardial irritability may arise from nonlethal ischemia.

The patient may die before histologic infarction becomes apparent.

Clinical and pathological findings must not be forced into an acute-MI-only model.

SIDE-BY-SIDE DISTINCTION

Ischemia

May disturb electrophysiology

Can remain nonlethal to cells

Infarction

Requires myocardial cell death

Morphology evolves over time

Slide 24 · Resuscitated SCD often lacks evidence of infarction

That 80–90% of successfully resuscitated patients show no enzymatic or ECG evidence of myocardial necrosis.

This statistic applies to the stated resuscitated population, not every sudden death.

It reinforces the separation between fatal arrhythmia and acute myocardial necrosis.

ANNUAL CASE ESTIMATES

80–90%

No enzyme/ECG evidence of necrosis among successfully resuscitated patients

Slide 25 · Healed remote infarction leaves an arrhythmic substrate

Healed myocardial infarctions are reported in approximately 40% of SCD cases.

Residual fibrosis can fragment normal electrical propagation.

A remote healed injury may be clinically more informative than the absence of fresh necrosis.

CONCEPTUAL PATHWAY — SCHEMATIC

Old infarction

Healed scar / fibrosis

Re-entry-prone myocardium

Slide 26 · Subendocardial vacuolization signals chronic ischemia

Vacuolization of subendocardial myocytes as a common finding.

This morphologic change is interpreted in the text as evidence of severe chronic ischemia.

It is distinct from diagnosing a fresh transmural myocardial infarct.

Morphology: Subendocardial myocyte vacuolization → chronic ischemic stress.

Slide 27 · Three pathological observations can coexist in SCD

Severe fixed coronary stenoses provide chronic ischemic substrate.

Healed infarct scars establish prior myocyte injury and fibrosis.

Chronic subendocardial change may be present without a fresh infarction.

RELATED SUBSTRATES / COMPONENTS

Fixed coronary stenosis

Old myocardial scar

Subendocardial vacuoles

Slide 28 · IHD produces several clinical syndromes

Angina reflects ischemia insufficient to cause infarction.

Myocardial infarction requires ischemia-associated necrosis.

Chronic IHD may produce heart failure; SCD may occur across this spectrum.

CATEGORIZED FEATURES

Angina

Acute infarction

Chronic IHD

Sudden cardiac death

Slide 29 · Acute infarction can provoke fatal rhythm disturbances

Myocardial infarction increases irritability and disrupts conduction.

MI-associated arrhythmias include ventricular tachycardia, fibrillation and block.

The Robbins discussion places maximal serious arrhythmia risk early after infarction.

CONCEPTUAL PATHWAY — SCHEMATIC

Acute myocardial injury

Electrical disturbance

Serious arrhythmia

Slide 30 · Hypertrophic fibrotic hearts form a second major pattern

Increasing SCD in hypertrophic, fibrotic hearts without IHD in high-resource countries.

Hypertension, obesity and cocaine exposure are given as associated contexts.

The shared substrate is remodeled myocardium capable of unstable electrical conduction.

CONCEPTUAL PATHWAY — SCHEMATIC

Hypertrophy and fibrosis

Electrical heterogeneity

Potential fatal rhythm

Slide 31 · Hypertension, obesity and cocaine provide distinct contexts

Hypertension is linked in the source to hypertrophic and fibrotic cardiac remodeling.

Obesity is listed among contexts associated with this non-IHD pattern.

Cocaine is additionally included among non-prescription drug contributors to SCD.

RELATED SUBSTRATES / COMPONENTS

Hypertension

Obesity

Cocaine exposure

Slide 32 · Ischemic and nonischemic substrates can converge

Coronary stenosis favors ischemic electrical instability.

Hypertrophy and interstitial fibrosis favor disturbed myocardial conduction.

Both pathways may end in the same fatal ventricular rhythm.

SIDE-BY-SIDE DISTINCTION

Ischemic substrate

Severe coronary stenosis

Chronic ischemic injury

Nonischemic remodeling

Myocardial hypertrophy

Fibrosis without CAD

Slide 33 · Age changes the etiologic differential

Coronary atherosclerosis dominates the overall population burden.

Younger individuals are more likely to have nonatherosclerotic causes.

Age directs attention to cardiomyopathy, congenital lesions, myocarditis and inherited electrical disease.

SIDE-BY-SIDE DISTINCTION

Overall population

CAD most frequent

Younger patients

Nonatherosclerotic causes relatively more common

Slide 34 · Nonatherosclerotic SCD has a broad structural differential

Dilated or hypertrophic cardiomyopathy can be associated with sudden death.

Congenital coronary arterial abnormalities and myocarditis are recognized alternatives.

Mitral valve prolapse and pulmonary hypertension also appear in the Robbins list.

CATEGORIZED FEATURES

Cardiomyopathy

Coronary anomalies

Myocarditis

MVP / pulmonary hypertension

Slide 35 · Cardiomyopathy can create an arrhythmogenic myocardium

Dilated cardiomyopathy is an example of a disease with abnormal myocardial coupling.

Hypertrophic cardiomyopathy is a recognized structural cause of SCD.

Both illustrate how altered myocardium can be electrically hazardous.

SIDE-BY-SIDE DISTINCTION

Dilated phenotype

Abnormal intercellular coupling

Hypertrophic phenotype

Myocardial structural remodeling

Slide 36 · Congenital coronary anomalies belong in younger patients

Congenital coronary arterial abnormalities are listed causes of SCD.

They should remain in consideration when conventional atherosclerotic disease is absent.

The SCD source does not specify individual anatomical variants or their frequencies.

Coronary pathology is not synonymous with atherosclerosis.

Slide 37 · Myocarditis couples inflammation to electrical instability

Inflammatory injury is one of the stated promoters of spontaneous myocyte depolarization.

Myocarditis is also explicitly listed among nonatherosclerotic causes of SCD.

Inflammation can therefore provide the electrical substrate even without coronary obstruction.

CONCEPTUAL PATHWAY — SCHEMATIC

Myocardial inflammation

Irritability / ectopic firing

Potential ventricular arrhythmia

Slide 38 · Valvular and pulmonary vascular disease also appear

Mitral valve prolapse is a listed nonatherosclerotic association.

Pulmonary hypertension is separately included among potential etiologies.

Robbins does not give a syndrome-specific risk estimate within this SCD passage.

SIDE-BY-SIDE DISTINCTION

Mitral valve prolapse

Listed structural association

Pulmonary hypertension

Listed vascular/hemodynamic association

Slide 39 · Catastrophic hemodynamic conditions require separate thought

Pericardial tamponade and pulmonary embolism are specifically named in the differential.

Systemic metabolic or hemodynamic alterations also appear among miscellaneous causes.

Not every rapidly fatal cardiac-related event must share the same antecedent myocardial lesion.

RELATED SUBSTRATES / COMPONENTS

Pericardial tamponade

Pulmonary embolism

Systemic disturbance

Slide 40 · Adrenergic agents and stimulants are relevant exposures

Catecholamines are listed among potential contributors to SCD.

Cocaine and methamphetamine use.

An exposure history may be essential when severe coronary atherosclerosis is not demonstrated.

RELATED SUBSTRATES / COMPONENTS

Catecholamines

Cocaine

Methamphetamine

Slide 41 · Structural disease and primary electrical disease differ

Structural diseases produce recognizable myocardial, coronary or valve abnormalities.

Primary electrical syndromes can cause fatal arrhythmias in the absence of visible structural pathology.

This distinction determines what clinical history and inherited disease evidence may add.

SIDE-BY-SIDE DISTINCTION

Structural substrate

Coronary disease / scar / remodeling

Primary electrical substrate

Channel defect; Structure may appear normal

Slide 42 · Inherited cardiac causes merit focused recognition

Inherited arrhythmogenic conditions can occur with or without structural abnormality.

Recognition matters because intervention can prevent some sudden deaths.

A positive family history or unexplained nonlethal arrhythmia should raise concern.

CONCEPTUAL PATHWAY — SCHEMATIC

Family history / unexplained event

Consider inherited syndrome

Potential preventive intervention

Slide 43 · Channelopathies disturb cardiac ion currents

Mutations affect channel components or proteins required for their function.

Sodium, potassium and calcium handling are represented Table 12.6.

Abnormal depolarization or repolarization may predispose to dangerous ventricular rhythms.

RELATED SUBSTRATES / COMPONENTS

Na⁺ current

K⁺ current

Ca²⁺ handling

Slide 44 · Different channels contribute to distinct electrical phases

Channel currents are necessary for the electrical activity that organizes contraction.

Repolarization changes are exemplified by long- and short-QT syndromes.

Abnormal intracellular calcium handling is represented by CPVT-associated genes.

RELATED SUBSTRATES / COMPONENTS

Depolarization

Repolarization

Calcium release

Slide 45 · QT syndromes illustrate opposite repolarization phenotypes

Long QT syndrome is characterized by excessive prolongation of repolarization.

Short QT syndrome is associated with abbreviated repolarization.

Either phenotype can confer susceptibility to serious ventricular arrhythmia.

SIDE-BY-SIDE DISTINCTION

Long QT

Prolonged repolarization

Short QT

Abbreviated repolarization

Slide 46 · Long QT syndrome: Clinical phenotype

QT prolongation may accompany life-threatening ventricular arrhythmias.

Patients can present with stress-induced syncope or SCD.

An association with swimming for some forms.

CONCEPTUAL PATHWAY — SCHEMATIC

Repolarization prolonged

Stress-associated event

Syncope or SCD

Slide 47 · Long QT: Potassium-channel loss of function

KCNQ1 loss of function appears Table 12.6.

KCNH2 loss of function is another listed cause.

Both are examples of impaired potassium-channel function associated with prolonged QT.

SIDE-BY-SIDE DISTINCTION

KCNQ1

K⁺ channel; Loss of function

KCNH2

K⁺ channel; Loss of function

Slide 48 · Long QT: Increased sodium-current mechanisms

SCN5A gain of function is listed as a long-QT mechanism.

CAV3 is included in the table as affecting caveolin and sodium current.

Different molecular changes can converge on the same clinical repolarization phenotype.

SIDE-BY-SIDE DISTINCTION

SCN5A

Na⁺ current; Gain of function

CAV3

Caveolin / Na⁺ current; Gain of function

Slide 49 · Short QT syndrome: Abbreviated repolarization

The source describes an abnormally short repolarization interval.

Presentations may include palpitations, syncope or sudden death.

A shortened QT phenotype is not benign simply because repolarization is faster.

CONCEPTUAL PATHWAY — SCHEMATIC

Abbreviated repolarization

Arrhythmia susceptibility

Syncope / SCD

Slide 50 · Short QT: Potassium-channel gain of function

The table lists KCNQ1 gain-of-function mutations.

KCNH2 gain of function is also listed.

The opposite functional direction in these genes contrasts with long-QT disease.

SIDE-BY-SIDE DISTINCTION

KCNQ1

K⁺ channel; Gain of function

KCNH2

K⁺ channel; Gain of function

Slide 51 · Brugada syndrome: Recognizable ECG phenotype

ST-segment elevation and a right bundle-branch-block pattern.

Structural heart disease may be absent.

Syncope or SCD classically occurs during rest, sleep or after a large meal.

CONCEPTUAL PATHWAY — SCHEMATIC

Characteristic ECG changes

Often no structural lesion

Rest / sleep events

Slide 52 · Brugada: Source-listed loss-of-function genes

Gene / syndrome

Channel / trigger

Feature / functional change

SCN5A

Na⁺

Loss of function

CACNB2b

Ca²⁺

Loss of function

SCN1b

Na⁺

Loss of function

SCN1b is listed for sodium-channel loss of function.

Slide 53 · CPVT: Adrenergically triggered ventricular arrhythmia

Catecholaminergic polymorphic ventricular tachycardia often presents in childhood.

Life-threatening arrhythmias are associated with adrenergic stimulation or stress.

CPVT lacks characteristic resting ECG changes.

CONCEPTUAL PATHWAY — SCHEMATIC

Adrenergic stimulation

Calcium-handling abnormality

Serious ventricular arrhythmia

Slide 54 · CPVT: Altered diastolic calcium release

RYR2 gain of function affects diastolic calcium release.

CASQ2 loss of function is another source-listed cause.

Both appear under the CPVT phenotype despite differing molecular direction.

SIDE-BY-SIDE DISTINCTION

RYR2

Diastolic Ca²⁺ release

Gain of function

CASQ2

Diastolic Ca²⁺ release

Loss of function

Slide 55 · Trigger patterns discriminate inherited syndromes

Gene / syndrome

Channel / trigger

Feature / functional change

Long QT

Stress; Swimming in some forms

QT prolonged

Short QT

No trigger specified in text

QT abbreviated

Brugada

Rest / sleep / large meals

Characteristic ECG

CPVT

Adrenergic stress

No characteristic ECG change

CPVT is linked to childhood arrhythmias with adrenergic stress.

Slide 56 · Gain versus loss of function is phenotype-specific

The same gene can be associated with different electrical syndromes.

For KCNQ1 and KCNH2, loss of function appears with long QT and gain of function with short QT.

A gene name alone does not establish mutation-level function or a patient phenotype.

SIDE-BY-SIDE DISTINCTION

Loss of K⁺ function

KCNQ1 / KCNH2

Long-QT association

Gain of K⁺ function

KCNQ1 / KCNH2

Short-QT association

Slide 57 · Family history and unexplained arrhythmia change evaluation

Some inherited electrical diseases are not evident by gross structural inspection.

Genetic testing with a positive family history or unexplained nonlethal arrhythmia.

Genetic findings must be interpreted in relation to syndrome and mutation effect.

CONCEPTUAL PATHWAY — SCHEMATIC

Suspicious clinical or family history

Genetic investigation

Syndrome-level interpretation

Slide 58 · A structurally normal heart does not exclude arrhythmic SCD

Primary electrical syndromes can produce lethal arrhythmias with no recognizable structural disease.

Brugada is explicitly described as potentially lacking structural heart disease.

The absence of a gross lesion cannot independently rule out an inherited channelopathy.

Anatomically normal ≠ electrically normal.

Slide 59 · Prevention targets patients at risk of lethal rhythms

Pharmacological interventions improve prognosis in vulnerable patients.

Implantable automatic cardioverter-defibrillators are another preventive strategy.

The supplied source does not provide drug selection, device eligibility criteria or guideline thresholds.

CONCEPTUAL PATHWAY — SCHEMATIC

Recognize vulnerability

Medical / device intervention

Reduce fatal arrhythmic events

Slide 60 · An implantable defibrillator senses and terminates VF

An implanted device can detect episodes of ventricular fibrillation.

It responds electrically to counteract the arrhythmia.

Its purpose is to interrupt a lethal rhythm, not reverse coronary atherosclerosis or myocardial scar.

CONCEPTUAL PATHWAY — SCHEMATIC

Sensing

Rhythm recognition

Electrical therapy

Slide 61 · Case: Death without documented acute infarction

A person collapses unexpectedly and is successfully resuscitated.

Evaluation shows severe chronic coronary stenoses but no enzyme or ECG evidence of myocardial necrosis.

Question: Does the absence of infarction evidence make an arrhythmic coronary mechanism unlikely?

Interpret the coronary substrate separately from evidence of new necrosis.

Slide 62 · Case interpretation: Electrical instability can precede necrosis

No: Chronic CAD is the leading substrate for SCD in the Robbins discussion.

Nonlethal ischemia and healed myocardial injury can still trigger dangerous ventricular rhythms.

This pattern matches the textbook observation that many resuscitated patients lack infarction evidence.

CONCEPTUAL PATHWAY — SCHEMATIC

Chronic CAD

Ischemic irritability

Lethal rhythm despite no new MI

Slide 63 · Case: A young person with stress-related syncope

A child experiences recurrent syncope associated with adrenergic stress.

A characteristic resting ECG signature is absent; Structural assessment is unrevealing.

Question: Which source-listed inherited syndrome strongly fits the trigger pattern?

Use trigger context and electrical phenotype; Do not invent ECG criteria.

Slide 64 · Case interpretation: Consider CPVT

CPVT is associated with life-threatening stress-triggered arrhythmias, often presenting in childhood.

The lack of a characteristic resting ECG change.

The table links CPVT to RYR2 and CASQ2 abnormalities of diastolic calcium release.

CONCEPTUAL PATHWAY — SCHEMATIC

Childhood + stress-triggered events

CPVT pattern

RYR2 / CASQ2 examples

Slide 65 · Clinicopathologic recognition: Five useful distinctions

An acute plaque rupture is not necessary to establish coronary-associated SCD.

Healed infarction and chronic ischemic change can be clues even without fresh necrosis.

In younger patients, congenital, myocardial and inherited electrical causes become more important.

A structurally normal heart may still harbor a serious channelopathy.

CATEGORIZED FEATURES

Fixed stenosis ≠ rupture

Fibrosis ≠ fresh MI

Younger ≠ usual CAD pattern

Normal anatomy ≠ normal currents

Slide 66 · Core concepts: The substrate matters more than a single lesion

SCD is an unexpected terminal event; Ventricular fibrillation is the characteristic electrical mechanism.

Coronary atherosclerosis, often without acute plaque rupture or necrosis, is the leading substrate.

Myocyte irritability, disturbed cell-to-cell coupling and re-entry connect pathology to fatal rhythm.

Structural nonatherosclerotic disease and inherited channelopathies broaden the differential.

Identify the substrate, explain the rhythm and interpret the morphology.

Slide 67 · Primary references

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026). Chapter 12, The Heart; Sudden Cardiac Death, p. 504.

Supporting adjacent text: Arrhythmias, pp. 503–504; ischemic heart disease / myocardial infarction, pp. 492–503.

Inherited arrhythmogenic gene associations: Robbins Table 12.6 (modified there from Cerrone M, Priori SG. Eur Heart J. 2011;32:2109–2118).