Cardiomyopathies

Slide 1 · Cardiomyopathies

Definitions • etiologic framework • functional patterns

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Define intrinsic myocardial dysfunction and distinguish primary from secondary disease.

Classify cardiomyopathies by morphology and dominant functional defect.

Associate etiologic categories with characteristic phenotypes and key mimics.

Apply a cause-oriented framework to ambiguous cardiac presentations.

Slide 3 · Cardiomyopathy: The defining lesion

A disease of heart muscle resulting from intrinsic myocardial dysfunction.

The affected myocardium may show abnormal contractility, compliance, or both.

Cardiomyopathy is an etiologic diagnosis—not merely an enlarged or poorly functioning heart.

The same phenotype may arise through multiple biological mechanisms.

Slide 4 · Intrinsic disease versus secondary remodeling

Intrinsic myocardial disorder

Heart muscle disease is the primary or systemic disease-related source of dysfunction.

Example: Genetic or toxic myocardial injury.

Remodeling from another lesion

Myocardial change follows an extrinsic load or structural cardiac abnormality.

Example: Pressure overload from valve disease.

Slide 5 · Diagnostic boundary: Four major exclusions

Coronary artery disease can cause myocardial dysfunction without constituting primary cardiomyopathy.

Hypertension can lead to compensatory hypertrophy and subsequent failure.

Valvular disease can impose chronic pressure or volume overload.

Congenital structural heart disease may produce secondary ventricular dysfunction.

Slide 6 · Phenotype is not the same as cause

Genetic, acquired,

Or systemic insult

→

Myocyte dysfunction

Or altered structure

→

Dilated, thick-walled,

Or restrictive pattern

Identical morphologic appearances may have distinct causal pathways.

Slide 7 · Primary and secondary cardiomyopathy

Primary

Principally confined to the heart muscle. Genetic disorders affecting myocardial proteins are representative examples.

Secondary

Cardiac manifestation of a systemic disorder. Examples include sarcoidosis, iron overload, and muscular dystrophy.

Slide 8 · Primary does not necessarily mean inherited

“Primary” describes where the disorder principally manifests.

Genetic factors are prominent, but the classification is not simply genetic versus environmental.

A clinically restricted heart-muscle phenotype does not establish one molecular etiology.

Family and systemic evaluation help refine an initially descriptive label.

Slide 9 · Secondary cardiomyopathy: Systemic context

The myocardial phenotype can reflect a broader metabolic, inflammatory, infiltrative, or neuromuscular illness.

Cardiac involvement may dominate presentation even when the cause is extracardiac.

Recognition of extracardiac clues can convert a nonspecific phenotype into a cause-specific diagnosis.

Examples: Hemochromatosis, sarcoidosis, muscular dystrophy, storage disorders.

Slide 10 · “Idiopathic” is a status of knowledge

Idiopathic cardiomyopathy means no cause has yet been established.

It does not imply that no underlying mechanism exists.

The source emphasizes that many previously unexplained cases now have identifiable genetic bases.

Etiologic attribution can evolve with family evaluation and molecular investigation.

Slide 11 · Different classification axes answer different questions

Cause

Genetic, toxic, inflammatory…

→

Anatomy

Dilated, hypertrophic, restrictive

→

Physiology

Systolic or diastolic dysfunction

A complete diagnosis should integrate cause, morphology, and function rather than select only one axis.

Slide 12 · The three major pathologic patterns

Dilated

Enlarged ventricular chamber; Contractile impairment dominates.

Hypertrophic

Excessive myocardial thickening; Impaired ventricular filling predominates.

Restrictive

Reduced compliance without major chamber dilation; Impaired filling predominates.

Slide 13 · Cardiomyopathy geometry: Three schematics

Dilated

Large cavity

Reduced contraction

Hypertrophic

Thick wall

Reduced filling

Restrictive

Near-normal chamber

Stiff myocardium

Schematic LV short-axis cavity–wall relationships; Not a specimen or quantitative anatomy.

Slide 14 · Systolic and diastolic defects

Systolic dysfunction

Ineffective ventricular contraction reduces emptying.

Best exemplified by the dilated pattern.

Diastolic dysfunction

Reduced chamber compliance or cavity size impairs filling.

Typical of hypertrophic and restrictive patterns.

Slide 15 · Ejection fraction is a functional descriptor

Left ventricular ejection fraction describes the fraction of end-diastolic volume ejected per beat.

A reduced value supports depressed systolic performance.

A preserved or increased value does not demonstrate normal relaxation or adequate filling.

Interpret ejection fraction with the structural phenotype and clinical context.

Slide 16 · Functional patterns and textbook EF ranges

Pattern

LV ejection fraction

Dominant defect

Dilated

<40%

Reduced contractility

Hypertrophic

50%–80%

Reduced compliance

Restrictive

35%–55%

Reduced compliance

Slide 17 · Do not treat EF bands as diagnostic cutoffs

The textbook gives approximate, phenotype-associated EF ranges—not exclusive diagnostic criteria.

Hypertrophic and restrictive phenotypes may retain substantial systolic function.

Clinical and morphologic patterns overlap; Ejection fraction alone cannot establish causation.

The same patient may exhibit both filling and contraction abnormalities.

Slide 18 · Dilated cardiomyopathy dominates the group

The dilated pattern as the most frequent major cardiomyopathy category.

It accounts for approximately 90% of cases classification.

The dilated phenotype encompasses both genetic and acquired forms.

This epidemiologic figure is textbook-specific and not a substitute for population-based contemporary estimates.

Slide 19 · Dilated pattern: Morphology and mechanical deficit

Chamber enlargement

→

Inadequate contractile

Emptying

→

Systolic heart failure

Phenotype

The phenotype is the endpoint; Identifying an underlying injury or inherited mechanism remains essential.

Slide 20 · Hypertrophic pattern: Structure and filling

Marked increase in

Ventricular wall thickness

→

Smaller or less

Compliant chamber

→

Impaired diastolic

Filling

A thick wall is not by itself evidence of genetic hypertrophic cardiomyopathy: Pressure overload is a mimic.

Slide 21 · Restrictive pattern: Compliance is central

Abnormal myocardial

Material or fibrosis

→

Reduced ventricular

Compliance

→

Restricted filling;

Atrial pressure burden

Systolic contraction can be relatively maintained despite substantial clinical disease.

Slide 22 · Why chamber size and function can diverge

Large chamber, weak contraction

A dilated ventricle can have a large end-diastolic volume but still empty inefficiently.

Contractile dysfunction dominates.

Non-dilated chamber, poor filling

A thick or stiff ventricle may eject a relatively preserved fraction of a limited filled volume.

Diastolic dysfunction dominates.

Slide 23 · A first-pass differential begins with chamber geometry

Dilated

Large cavity

Reduced contraction

Hypertrophic

Thick wall

Reduced filling

Restrictive

Near-normal chamber

Stiff myocardium

Schematic LV short-axis cavity–wall relationships; Not a specimen or quantitative anatomy.

Slide 24 · Atrial dilation can reveal impaired filling

Restricted ventricular filling increases atrial pressure burden.

The restrictive schematic highlights atrial dilation despite near-normal ventricular size.

The hypertrophic pattern may also show left atrial enlargement.

Atrial size complements ventricular wall and cavity observations.

Slide 25 · Overlap is an expected biological reality

Clinical overlap among cardiomyopathy groups.

Contractile impairment may coexist with abnormal relaxation or reduced compliance.

The final phenotype need not reveal its initiating insult.

Avoid interpreting the three-pattern schema as three mutually exclusive molecular diseases.

Slide 26 · Disease severity varies within each pattern

The same morphologic category includes a spectrum of functional impairment.

Structural change and clinical presentation are not necessarily proportional.

Symptoms and risk may reflect cardiac rhythm as well as mechanical dysfunction.

Classification organizes investigation; It does not replace individual assessment.

Slide 27 · Etiologic map: Seven broad categories

Injury / exposures

Infection, toxins, drug effects, irradiation, inflammatory or immune injury.

Systemic disorders

Metabolic disease, iron accumulation, infiltrative deposition, storage disorders.

Inherited disease

Sarcomeric or structural-protein defects; Neuromuscular syndromes with cardiac involvement.

Slide 28 · Genetic causes: Beyond a single gene

Genetic disorders may selectively disrupt myocardial fibers.

The causal proteins and mechanisms differ between cardiomyopathy patterns.

A familial phenotype does not necessarily predict one cardiac morphology.

The expanding genetic basis is an important reason to revisit “idiopathic” cases.

Slide 29 · Cardiac-limited versus multisystem inheritance

Predominantly cardiac

A heritable disorder can be expressed mainly as heart-muscle dysfunction.

The cardiac phenotype may drive family evaluation.

Multisystem

Inherited skeletal muscle, metabolic, and storage disorders can include cardiomyopathy.

Extracardiac findings may identify the cause.

Slide 30 · Family history refines the etiologic hypothesis

Multiple relatives with cardiomyopathy supports an inherited contribution.

Family reports of unexplained sudden death or rhythm disease may be relevant.

Variable expression can complicate simple affected/unaffected pedigree labels.

Family information supplements—not substitutes for—clinical and structural assessment.

Slide 31 · Infectious mechanisms can injure myocardium

Table 12.11 lists viruses, bacteria, fungi, protozoa, chlamydiae, and rickettsiae.

Infectious myocarditis is a disease of the myocardium, not simply an extracardiac infection.

Inflammatory injury may produce subsequent contractile dysfunction.

Pathogen identification and inflammatory evidence require separate evaluation.

Slide 32 · Immune-mediated and inflammatory categories

Myocarditis may be associated with several inflammatory mechanisms.

Sarcoidosis can cause myocardial dysfunction within a multisystem disease.

Posttransplant rejection is listed among immunologic cardiac muscle disorders.

Myocardial inflammation should be interpreted in its cause and systemic context.

Slide 33 · Iron overload bridges metabolic and myocardial injury

Hemochromatosis appears among metabolic causes of cardiomyopathy.

Cardiac iron excess may be hereditary or related to repeated red-cell transfusion.

Oxidative injury and interference with metal-dependent enzymes.

Iron overload may generate a dilated functional phenotype.

Slide 34 · Storage and deposition diseases

Table 12.11 includes glycogen storage disease, Fabry disease, and Hunter–Hurler syndrome.

Amyloidosis is an important extracellular deposition disorder affecting myocardium.

Different deposited or accumulated materials need not produce the same cardiac geometry.

Systemic features may distinguish a deposition-related phenotype from primary myocardial disease.

Slide 35 · Infiltrative disease and myocardial stiffness

Sarcoidosis and carcinomatosis are listed among infiltrative etiologies.

Radiation-related fibrosis can alter myocardial compliance.

The resulting phenotype may be restrictive, but the mechanism is not uniform across causes.

Etiologic diagnosis therefore requires more than documenting impaired filling.

Slide 36 · Toxins: A mechanistically diverse group

Alcohol, cobalt, catecholamines, carbon monoxide, lithium, hydrocarbons, and arsenic.

Several cytotoxic medications are also listed as myocardial toxins.

Toxic exposures may produce myocardial dysfunction without a distinctive gross pattern.

Exposure history can be decisive when the structural phenotype is nonspecific.

Slide 37 · Antineoplastic therapy belongs in the history

The table includes doxorubicin, daunorubicin, and cyclophosphamide.

Therapy-related myocardial dysfunction must be considered in the appropriate exposure context.

A phenotype alone does not attribute damage to a specific chemotherapy agent.

Do not infer drug-specific risk or dose thresholds from the introductory textbook table.

Slide 38 · Nutritional and metabolic contributors

Table 12.11 lists protein deficiency, thiamine deficiency, and other avitaminoses.

Nutrient-related myocardial dysfunction can accompany systemic illness or substance misuse.

The etiologic task is to establish the relevant nutritional disturbance.

An apparent idiopathic phenotype may become explainable after targeted history and testing.

Slide 39 · Endocrine and electrolyte disturbances

Hyperthyroidism and hypothyroidism are listed metabolic conditions.

Both hyperkalemia and hypokalemia are included among possible myocardial disorders.

Their influence on cardiac function is context-dependent and does not establish a single fixed phenotype.

Consider reversible systemic disturbances before applying an unexplained label.

Slide 40 · Neuromuscular disease points beyond the heart

Muscular dystrophy is an explicit systemic cause of cardiomyopathy.

Friedreich ataxia and congenital atrophies are also listed.

Neurologic or skeletal-muscle signs can redirect the etiologic workup.

Cardiac and extracardiac phenotypes should be interpreted together.

Slide 41 · One phenotype can arise from multiple causes

Dilated pattern

Hypertrophic pattern

Restrictive pattern

Genetic disorders

Genetic disorders

Amyloidosis

Alcohol / myocarditis

Storage disorders

Radiation fibrosis

Anthracyclines

Friedreich ataxia

Idiopathic

Iron overload

Infant of diabetic mother

—

Slide 42 · Cause-to-pattern mapping is many-to-many

A cause such as a systemic metabolic disorder can produce more than one expression of disease.

A morphologic pattern often has multiple unrelated etiologies.

A population category cannot be applied as a certain individual-level diagnosis.

Keep the cause and observed phenotype as distinct statements in the final diagnosis.

Slide 43 · Cardiomyopathy mimics: Recognize the competitor

Pressure overload

Hypertension or aortic stenosis may produce substantial hypertrophy.

Volume overload

Valve defects and congenital abnormalities can produce chamber enlargement.

Ischemic injury

Coronary disease may produce regional injury, remodeling, and reduced systolic function.

Slide 44 · A dilated ventricle is not automatically DCM

Dilated cardiomyopathy phenotype

Intrinsic heart-muscle dysfunction can cause progressive ventricular dilation and poor contraction.

Secondary dilation

Ischemic, hypertensive, valvular, or congenital disease may produce an enlarged dysfunctional heart.

Slide 45 · A thick ventricle is not automatically HCM

Hypertrophic cardiomyopathy

Primary myocardial disease with pronounced hypertrophy and impaired filling.

Pressure-overload hypertrophy

Longstanding hypertension or aortic stenosis may also yield increased wall thickness.

Slide 46 · Restricted filling is not always restrictive CM

Myocardial restriction

A stiff myocardium reduces ventricular compliance and limits filling.

Constrictive pericarditis

A pericardial mechanical constraint may mimic restriction without an intrinsic myocardial cause.

Slide 47 · Reason through the phenotype before the label

Describe chambers,

Walls and filling

→

Exclude dominant CAD,

Valve, BP or congenital cause

→

Investigate myocardial

And systemic etiologies

A defensible diagnosis distinguishes what the heart looks like from why it became abnormal.

Slide 48 · Heart failure is a consequence, not the etiology

Impaired contractility can lead to reduced forward ejection.

Impaired compliance can raise filling pressures despite relatively preserved ejection fraction.

Both physiologic routes may produce clinical heart-failure syndromes.

Describing heart failure alone does not identify the causative cardiomyopathy.

Slide 49 · Electrical and mechanical disease intersect

Arrhythmogenic cardiomyopathy within the dilated-pattern discussion.

Myocardial and conduction abnormalities may overlap.

Rhythm disturbance does not itself define the same mechanism as impaired contraction.

An electrical presentation can warrant evaluation for structural myocardial disease.

Slide 50 · Why morphology alone has limits

An enlarged ventricle describes a structural endpoint shared by multiple causes.

Fibrosis or myocyte hypertrophy may represent nonspecific responses to myocardial injury.

A deposition or inflammatory lesion may be more etiologically informative when present.

Combine morphology with exposure, systemic, functional, and family information.

Slide 51 · An integrated assessment uses three evidence streams

Phenotype

Ventricular size, thickness, contraction, compliance and atrial geometry.

Etiology

Genetics, inflammatory / systemic disease, toxin or treatment exposures.

Competing causes

Coronary disease, hypertension, valve disease, congenital abnormality; Pericardial constriction where relevant.

Slide 52 · A cause-oriented history changes the differential

Family cardiac disease or sudden death suggests possible inherited susceptibility.

Medication, alcohol, occupational, or environmental exposures may implicate toxicity.

Neuromuscular, inflammatory, infiltrative, and metabolic histories support secondary forms.

A negative initial history does not establish idiopathic disease conclusively.

Slide 53 · Structural assessment must answer focused questions

Is the ventricle dilated, thick-walled, or approximately normal in size?

Is impaired contraction or impaired filling the dominant defect?

Are the atria enlarged in a pattern compatible with filling pressure elevation?

Could an extrinsic pressure, volume, ischemic, or pericardial problem explain the findings?

Slide 54 · An etiologic diagnosis can remain provisional

A patient may satisfy a recognizable cardiomyopathy phenotype before its cause is known.

“Idiopathic” should be qualified by the evaluation undertaken and available evidence.

Some inherited and acquired mechanisms yield indistinguishable late morphologies.

Diagnostic revision is appropriate when new evidence emerges.

Slide 55 · Case 1: Marked dilation and poor contraction

A patient has a globally enlarged ventricular chamber and markedly reduced contractile function. No cause has yet been established.

Which functional pattern is most compatible?

What competing disease categories must be assessed?

Slide 56 · Case 1: Identify phenotype, then exclude mimics

The dominant pattern is dilated with systolic dysfunction.

Assess ischemic, hypertensive, valvular, and congenital explanations before labeling primary DCM.

Then consider genetic disease, myocardial inflammation, iron excess, alcohol or medication toxicity.

Unknown cause after evaluation may justify a provisional idiopathic designation.

Slide 57 · Case 2: Thick ventricle with impaired relaxation

Imaging shows increased left ventricular wall thickness and reduced diastolic filling without major ventricular cavity dilation.

Which cardiomyopathy pattern is suggested?

Why must blood pressure and valve history be reviewed?

Slide 58 · Case 2: Hypertrophy has competing explanations

The appearance is compatible with a hypertrophic functional pattern.

Hypertensive heart disease and aortic stenosis can mimic this geometry.

An intrinsic cardiomyopathy requires evidence beyond increased wall thickness alone.

An etiologic label should integrate clinical and familial information.

Slide 59 · Case 3: Stiff chambers and atrial enlargement

The ventricles are not substantially dilated, but filling is restricted and both atria are enlarged. A systemic disorder is suspected.

Which functional pattern is plausible?

What two broad etiologic and mimicking categories are relevant?

Slide 60 · Case 3: Separate myocardial from pericardial causes

The dominant physiology suggests restrictive cardiomyopathy.

Infiltrative / deposition disorders, including amyloidosis, are important etiologic possibilities.

Pericardial constriction can mimic a restrictive functional presentation.

Structural myocardial evidence and clinical context are needed for attribution.

Slide 61 · Case 4: Systolic failure after drug exposure

A patient has newly recognized global myocardial dysfunction and a history of treatment with a potentially cardiotoxic antineoplastic drug.

Which etiologic category is raised?

Does that exposure prove drug-induced cardiomyopathy?

Slide 62 · Case 4: Exposure is a clue, not proof

Medication-associated toxicity is a plausible acquired cause.

Anthracyclines and cyclophosphamide among potential myocardial toxins.

Temporal association and phenotype require interpretation alongside alternative causes.

The introductory source does not provide agent-specific causal thresholds.

Slide 63 · Three-pattern rapid differential

Question

Dilated

Hypertrophic

Restrictive

Chamber cavity

Increased

Usually not dilated

Usually not dilated

Wall change

Variable hypertrophy

Marked hypertrophy

Often subtle

Main defect

Systolic

Diastolic

Diastolic

Key mimic

CAD / valves

Hypertension / stenosis

Constrictive pericarditis

Slide 64 · Four errors that lead to misclassification

Equating reduced ejection fraction with every cardiomyopathy.

Calling any thick-walled heart genetic hypertrophic cardiomyopathy.

Calling ventricular enlargement primary dilated cardiomyopathy before excluding competitors.

Ignoring systemic etiologies when the heart is the dominant presenting organ.

Slide 65 · Integrative conclusions

Cardiomyopathy denotes intrinsic myocardial dysfunction and requires etiologic context.

The three major patterns organize dominant geometry and contractile/filling physiology.

Most patterns have multiple possible causes; Primary and systemic disorders can converge phenotypically.

Exclude common nonmyopathic mimics before labeling an unexplained phenotype idiopathic.

Slide 66 · Primary textbook reference

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026).

Chapter 12, The Heart: “Cardiomyopathies” introductory section.

Classification and causes interpreted from Tables 12.10 and 12.11.

Morphologic pattern comparisons based on the discussion accompanying Figure 12.28.