Restrictive Cardiomyopathy

Slide 1 · Restrictive Cardiomyopathy

Pathogenesis · morphology · clinicopathologic correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Define ventricular restriction as a diastolic filling abnormality.

Relate myocardial or endocardial lesions to chamber morphology.

Distinguish amyloid, endomyocardial fibrosis and eosinophilic disease.

Recognize major mimics and the limits of morphology alone.

Slide 3 · Cardiomyopathy: Primary myocardial dysfunction

Cardiomyopathies arise from intrinsic myocardial dysfunction.

Primary forms predominantly involve the myocardium.

Secondary forms reflect systemic disease affecting cardiac muscle.

Coronary, hypertensive, valvular and congenital causes require separate consideration.

Slide 4 · Three major functional cardiomyopathy patterns

Phenotype

Dominant physiological problem

Typical morphological emphasis

Dilated

Systolic failure

Dilation of cardiac chambers

Hypertrophic

Diastolic impairment

Increased ventricular wall mass

Restrictive

Diastolic impairment

Stiff ventricles; atrial enlargement

Slide 5 · Restrictive cardiomyopathy: Defining abnormality

The primary defect is reduced ventricular compliance.

Impaired relaxation-phase filling is the functional consequence.

The defining problem is diastolic rather than principally systolic.

Slide 6 · Compliance links pressure to volume

Lower ventricular compliance

Greater filling pressure for a given volume

Impaired diastolic filling

Upstream atrial pressure load

A physiological sequence, not a measured relationship

Slide 7 · A stiff ventricle has an altered filling relation

Ventricular filling volume →

Filling pressure ↑

Conceptual normal relation

Restrictive / stiff ventricle

Qualitative schematic; Not patient data or a measured curve

Slide 8 · The functional lesion is not necessarily poor contraction

Left-ventricular contractile function is usually relatively unaffected.

Normal or near-normal contraction does not imply normal filling.

Restrictive disease can therefore be confused with other diastolic disorders.

Slide 9 · Why the atria enlarge

Impaired ventricular filling

Sustained atrial pressure load

Atrial remodeling

Biatrial dilation

Slide 10 · Chamber configuration in restriction

Reference configuration

RA

LA

RV

LV

Restrictive pattern

RA

LA

RV

LV

Atrial enlargement with relatively nondilated ventricles · schematic

Slide 11 · What gross examination can—and cannot—show

Biatrial enlargement is common.

Ventricular size is near normal or only slightly increased.

Ventricular cavities usually lack overt dilation.

The remaining myocardium may look largely unremarkable.

Slide 12 · Nonspecific interstitial fibrosis

Simplified tissue schematic — not a histology image

Collagen between myocytes

Fibrous tissue increases passive stiffness

Distribution may be patchy or diffuse

Amount of fibrosis varies by cause

Slide 13 · Fibrosis is not a universal diagnostic signature

Microscopic fibrosis ranges from minimal to extensive.

Lesion distribution may be patchy or diffuse.

A nondiagnostic biopsy does not itself exclude restriction.

Slide 14 · Etiologies: Idiopathic and secondary forms

Idiopathic

No cause identified

Functional phenotype defined

Secondary

Distinct myocardial disorder

Specific pathologic substrate

A restrictive phenotype does not specify its cause.

Slide 15 · Conditions associated with a restrictive phenotype

Pathobiologic setting

Examples directly named in Robbins

Protein deposition

Amyloidosis

Granulomatous / infiltrative

Sarcoidosis; metastatic tumors

Fibrotic injury

Radiation-induced fibrosis

Metabolite accumulation

Inborn errors of metabolism

Endocardial disease

Endomyocardial fibrosis; Loeffler disease; fibroelastosis

Slide 16 · A shared physiology can reflect distinct lesions

Amyloid, fibrosis, infiltrates or storage

Altered myocardial / endocardial properties

Loss of compliance

Restricted filling

Slide 17 · Infiltration versus fibrosis: Distinct substrates

Infiltrative disease

Fibrotic disease

Extracellular deposits or cellular infiltrates

Myocardium stiffens despite limited chamber dilation

Examples: Amyloid, sarcoid, metastatic disease

Interstitial or endocardial scarring

Scarring mechanically impairs distensibility

Examples: Radiation injury, tropical EMF

Both mechanisms can produce a similar hemodynamic phenotype.

Slide 18 · Cardiac amyloidosis as a restrictive cause

Extracellular protein fibril accumulation

Expansion of myocardial interstitium

Less compliant ventricular wall

Restrictive filling physiology

Slide 19 · Why amyloid deposits persist

Amyloid comprises extracellular protein fibrils.

Fibrils adopt insoluble β-pleated-sheet architecture.

Accumulation may involve myocardium and multiple cardiac structures.

Slide 20 · Systemic versus predominantly cardiac amyloid

Systemic involvement

Predominantly cardiac involvement

Cardiac disease as part of systemic amyloidosis

May accompany plasma-cell neoplasms or inflammation-associated amyloid

Look beyond the heart for the underlying disorder

Amyloid may be largely confined to the heart

Recognized particularly in older individuals

Wild-type transthyretin is prominent in this form

Both can alter ventricular compliance.

Slide 21 · ATTRwt: Transthyretin deposition in older adults

Wild-type transthyretin (ATTRwt) is a normal circulating protein.

It is produced by the liver.

It transports thyroxine and retinol-binding protein.

Cardiac deposition is particularly recognized in older adults.

Slide 22 · Hereditary transthyretin can accelerate deposition

Transthyretin variants may increase amyloidogenic propensity.

Hereditary transthyretin amyloidosis can involve the heart.

Genetic variation should be distinguished from acquired wild-type deposition.

Slide 23 · Cardiac territories that amyloid may involve

Interstitium

Myocyte separation

Reduced compliance

Conduction system

Electrical involvement

Rhythm abnormalities

Vasculature

Small-vessel narrowing

Potential ischemia

Valves / serosa

Valves, endocardium

Pericardium

Distribution helps explain heterogeneity of presentation.

Slide 24 · Amyloidosis can have several cardiac phenotypes

Restrictive dysfunction is the most frequent presentation.

Cardiac deposition may also be asymptomatic.

Dilation, arrhythmias or ischemic/valvular mimics can occur.

The location of deposition influences the clinical picture.

Slide 25 · Gross appearance of an amyloid heart

Consistency can range from normal to firm and rubbery.

Chambers are often normal sized but may be dilated.

Ventricular walls may be thickened.

Atrial endocardium may show wax-like, semitranslucent nodules.

Slide 26 · Interstitial amyloid: Histologic concept

Simplified tissue schematic — not a histology image

Deposits between myocardial fibers

Extracellular material expands interstitium

Myocytes become separated by deposits

Specific deposition requires appropriate stain

Slide 27 · Histologic amyloid is extracellular and hyaline

Routine sections can show amorphous eosinophilic deposits.

Deposits may involve interstitium and vascular walls.

Conduction tissue and valves may also be affected.

Appearance alone does not establish amyloid protein type.

Slide 28 · Congo red establishes amyloid deposition

Suspicious extracellular deposits

Apply Congo red stain

Examine under polarized light

Classic apple-green birefringence

Slide 29 · Vascular amyloid and myocardial ischemia

Intramural arterial amyloid deposition

Narrowed small-vessel lumen

Reduced myocardial perfusion

Small-vessel ischemic injury

Slide 30 · Specific etiology matters beyond the label “RCM”

The same physiological restriction has several causal substrates.

Tissue findings may suggest an underlying systemic disease.

An etiologic label can be more informative than morphology alone.

Slide 31 · Endomyocardial restriction: A separate lesion family

Entity

Main pathologic emphasis

Clinical context in Robbins

Endomyocardial fibrosis

Apical endocardial/subendocardial scarring

Young people; tropical regions

Loeffler endomyocarditis

Eosinophilic injury, mural thrombi, fibrosis

Often peripheral/systemic eosinophilia

Endocardial fibroelastosis

Fibroelastic LV endocardial thickening

Predominantly infants

Slide 32 · Endomyocardial fibrosis: Geographical setting

Principally affects children and young adults.

Described in Africa and other tropical areas.

A major restrictive disorder worldwide.

Morphology is dominated by ventricular endocardial scarring.

Slide 33 · Endomyocardial fibrosis advances from the apex

Ventricular apical region

Endocardial and subendocardial scarring

Progressive extension upward

Possible atrioventricular valve involvement

Slide 34 · Endomyocardial fibrosis alters the wall surface

Ventricular wall with endocardial/subendocardial fibrosis

Fibrotic endocardium / subendocardium

Underlying myocardium (schematic)

Layer thicknesses are exaggerated for explanation; Not histologic measurements

Slide 35 · Why an endocardial plaque restricts filling

Extensive endocardial/subendocardial fibrosis

Reduced effective chamber volume

Reduced chamber compliance

Diastolic restriction

Slide 36 · Valve involvement changes the anatomy

Fibrosis can spread from the apex toward the atrioventricular valves.

The tricuspid and mitral valves may eventually be involved.

The precise gross distribution is important in anatomical assessment.

Slide 37 · Mural thrombi and organized fibrosis

Ventricular mural thrombus formation

Thrombus organization

Contribution to endocardial fibrosis

Further loss of compliant chamber surface

Slide 38 · Proposed associations of tropical EMF

Nutritional context

Nutritional deficiencies

Association—not proof of cause

Inflammatory context

Parasitic infections

Possible eosinophilia

These as linked factors, not a single established mechanism.

Slide 39 · Loeffler endomyocarditis: Similar endpoint

Produces endomyocardial fibrosis, often with large mural thrombi.

Overall cardiac morphology resembles tropical endomyocardial fibrosis.

A prominent eosinophilic systemic context distinguishes the syndrome.

Slide 40 · The eosinophilic component

Peripheral eosinophilia is often present.

Eosinophilic infiltration may involve myocardium and other organs.

Eosinophil products are implicated in endomyocardial injury.

Slide 41 · Major basic protein as a proposed mediator

Eosinophil infiltration / activation

Release of toxic granule products

Endomyocardial necrosis

Subsequent scarring

Slide 42 · Loeffler lesion: An injury-to-scar sequence

Endomyocardial necrosis

Mural thrombus deposition

Thrombus organization

Fibrotic restriction

Slide 43 · Why the thrombus may be prominent

The damaged endocardial surface becomes layered by thrombus.

Large mural thrombi are characteristic in many cases.

Organized thrombus can contribute to fibrotic thickening.

Slide 44 · A hematologic clue to a cardiac lesion

A subset of patients has a myeloid neoplasm with eosinophilia.

Acquired rearrangements may involve tyrosine kinase genes.

An eosinophilic cardiac lesion therefore warrants etiologic evaluation.

Slide 45 · Why identifying a kinase-driven disorder matters

Myeloid neoplasm with eosinophilia

Tyrosine kinase gene rearrangement

Tyrosine kinase inhibitor therapy

Reported hematologic and endocardial improvement

Slide 46 · Tropical EMF versus Loeffler disease

Feature

Tropical endomyocardial fibrosis

Loeffler endomyocarditis

Clinical setting

Young people in tropical areas

Often peripheral eosinophilia

Dominant pathology

Apical endocardial fibrosis

Fibrosis and often large mural thrombi

Proposed association

Nutritional/inflammatory factors

Eosinophil granule toxicity

Additional concern

Valve extension

Possible kinase-driven myeloid neoplasm

Slide 47 · Endocardial fibroelastosis: Characteristic lesion

An uncommon cause of endocardial thickening.

Fibroelastic tissue accumulates along the endocardium.

Left ventricular endocardium is typically involved.

Slide 48 · The disease is principally pediatric

Most often encountered in the first two years of life.

Some cases accompany aortic valve obstruction.

Other congenital cardiac abnormalities may coexist.

Slide 49 · Endocardial fibroelastosis: Layer schematic

Left-ventricular endocardial fibroelastic thickening

Thickened fibroelastic endocardial layer

Underlying myocardium (schematic)

Layer thicknesses are exaggerated for explanation; Not histologic measurements

Slide 50 · Potential etiologic pathways in fibroelastosis

Infectious insult

Proposed prenatal viral injury

Example: Intrauterine mumps

Genetic insult

Tafazzin mutations

Mitochondrial inner membrane

Fibroelastosis may be a shared morphologic endpoint of different injuries.

Slide 51 · Tafazzin connects a gene to mitochondria

Tafazzin protein

Mitochondrial inner-membrane integrity

Potential mitochondrial dysfunction

Fibroelastosis association

Slide 52 · Diffuse fibroelastosis can be clinically severe

Diffuse endocardial involvement can compromise ventricular function.

Some affected infants develop rapid cardiac decompensation.

Severity relates to extent and underlying associated disease.

Slide 53 · Where each restrictive lesion predominantly lives

Lesion

Principal tissue compartment

Morphological clue

Idiopathic/secondary RCM

Myocardium

Variable interstitial fibrosis

Amyloidosis

Interstitial / vascular / conduction

Extracellular protein deposition

Endomyocardial fibrosis

Endocardium and subendocardium

Apical-to-basal scarring

Loeffler disease

Endomyocardial surface

Thrombus plus eosinophilic injury

Fibroelastosis

Left ventricular endocardium

Fibroelastic thickening

Slide 54 · Gross morphology provides clues, not a full diagnosis

Pattern

Expected structural finding

Interpretive limitation

General restriction

Biatrial dilation; nondilated ventricles

Nonspecific phenotype

Cardiac amyloid

Variable firmness, wall thickness

May resemble other processes

Endomyocardial fibrosis

Apical endocardial thickening

Cause may remain uncertain

Loeffler disease

Thrombus and fibrosis

Requires systemic context

Fibroelastosis

Endocardial thickening in infant

Multiple possible insults

Slide 55 · Microscopic findings are etiologic clues

Observation

Interpretation

Additional clarification

Interstitial collagen

Fibrosing myocardial disease

Nonspecific by itself

Hyaline extracellular deposits

Consider amyloid

Congo red confirmation

Fibrous endocardial tissue

Endomyocardial scarring

Assess extent/site

Eosinophils with injury

Eosinophilic cardiac process

Consider hematologic context

Fibroelastic endocardium

Fibroelastosis

Assess pediatric associations

Slide 56 · Cardiac imaging is useful for tissue characterization

Imaging can assess ventricular and atrial configuration.

Increasingly, imaging can characterize suspected myocardial infiltrates.

An abnormal imaging pattern is not automatically an etiologic diagnosis.

Slide 57 · What endomyocardial biopsy may contribute

Sampling may occasionally suggest a specific etiology.

A positive amyloid stain supports tissue deposition.

Patchy fibrosis can limit representativeness of small samples.

Interpret biopsy with cardiac imaging and clinical context.

Slide 58 · Restrictive myocardial disease vs pericardial constriction

Restrictive cardiomyopathy

Constrictive pericarditis

Primary abnormality in ventricular myocardial compliance

Variable myocardial infiltration or fibrosis

Heart muscle is the principal site of disease

External mechanical limitation from pericardium

May yield a similar diastolic filling syndrome

Pericardial lesion is the principal anatomic process

This clinically important diagnostic confusion.

Slide 59 · Restrictive disease versus hypertrophic cardiomyopathy

Restrictive

Hypertrophic

Low compliance due to diverse infiltration or fibrosing lesions

Ventricles are usually not greatly enlarged

Biatrial dilation may be prominent

Primary myocardial hypertrophy, often asymmetric

Poor compliance with thickened ventricular wall

Myocyte disarray is a histologic hallmark

Both may present with diastolic dysfunction; Morphology and cause differ.

Slide 60 · Restrictive versus dilated cardiomyopathy

Restrictive

Dilated

Impaired ventricular filling predominates

Cavities remain nondilated in typical morphology

Systolic function may be relatively retained

Ineffective contraction predominates

Four-chamber dilation is characteristic

Impaired ejection underlies the phenotype

Cardiomyopathy categories are patterns, not etiologic diagnoses.

Slide 61 · Integrating phenotype and cause

Confirm a restrictive filling phenotype

Evaluate myocardium vs pericardium

Identify structural / tissue clue

Correlate with systemic cause

Slide 62 · Clinicopathologic case: Older adult

An older adult has a stiff ventricle, enlarged atria and a firm, mildly thickened myocardium. A sample shows amorphous extracellular deposits.

Discussion

Which etiologic category becomes likely?

Which special stain would help confirm the deposits?

Why might small vessels also matter?

Slide 63 · Clinicopathologic case: Tropical endocardial disease

A young person from a tropical region has restrictive filling and fibrous thickening concentrated near a ventricular apex, extending toward an atrioventricular valve.

Discussion

What restrictive entity does this distribution suggest?

Why may the effective cavity volume be reduced?

How might organized mural thrombus contribute?

Slide 64 · Clinicopathologic case: Eosinophilia and thrombus

A patient with marked peripheral eosinophilia develops large ventricular mural thrombi and endomyocardial scarring.

Discussion

What named disease process is suggested?

What putative toxin mediates myocardial damage?

Which accompanying hematologic process deserves consideration?

Slide 65 · Clinicopathologic case: Early infancy

An infant with rapid cardiac deterioration shows diffuse thickening of the left ventricular endocardial surface containing fibroelastic tissue.

Discussion

Which restrictive-associated condition is most consistent?

What congenital lesion may coexist?

What mitochondrial membrane-associated protein is mentioned?

Slide 66 · Common interpretive errors

Equating preserved contraction with absence of cardiac disease.

Treating atrial enlargement alone as proof of myocardial restriction.

Calling any interstitial fibrosis diagnostic of a specific etiology.

Conflating endomyocardial fibrosis, Loeffler disease and fibroelastosis.

Slide 67 · Five anatomical clues worth retaining

Myocardium

Reduced compliance

Variable fibrosis

Atria

Common dilation

Pressure load

Amyloid

Interstitial deposits

Congo red

Endocardium

Apical / LV fibrosis

Disease-specific pattern

Locate the lesion before naming the disease.

Slide 68 · Restrictive cardiomyopathy: Integrated summary

The primary lesion is reduced ventricular compliance and impaired filling.

Typical chambers show enlarged atria without major ventricular dilation.

Myocardial deposition, fibrosis and endocardial disease are major substrates.

Specific diagnosis depends on lesion distribution and associated disease.

Slide 69 · Reference and source boundaries

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

Chapter 12: The Heart — Cardiomyopathies; Restrictive Cardiomyopathy.

Related source subsection: Amyloidosis, pp. 522–523.

Schematics are original and editable; no textbook figure or synthetic specimen reproduced.