Cardiomyopathy

Overview

Cardiomyopathy = “heart muscle disease,” originally meant UNKNOWN-cause myocardial disease (WHO definition still excludes known-cause disease). Loosely used otherwise too. Resolved by splitting: A) Primary (unknown cause), B) Secondary (known cause/association).

A. Primary cardiomyopathy — 3 pathophysiologic categories

Each = a different pump failure mode: contraction failure / outflow obstruction+arrhythmia / filling failure.

1. Dilated (congestive)

Progressive failure + dilatation of ALL 4 chambers. Adults, survival <5yr from onset.

Etiology (unknown, associations): viral myocarditis (coxsackie B — viral nucleic acid in myocardium), toxins (cobalt, doxorubicin/anthracyclines), inherited sarcomere protein mutations (troponin-T/I, myosin, actin — direct contractile dysfunction) + dystrophin gene mutation (links to muscular dystrophy), chronic alcoholism (via thiamine deficiency/beri-beri; moderate alcohol is actually cardioprotective — only heavy use toxic; “beer drinkers’ myocardiosis” = cobalt additive toxicity), peripartum (poorly-nourished women, ±1 month of delivery).

Morphology:

• Gross: enlarged/heavy heart (up to 1000g), GLOBULAR shape from all-4-chamber dilatation (wall thickening masked by dilation), thickened endocardium, mural thrombi common, valves NORMAL (myocardial not valvular disease)
• Micro: non-specific/variable — some fibre hypertrophy+some atrophy, interstitial fibrosis, occasional focal mononuclear infiltrate. Non-specificity itself matters — diagnosis by gross/functional pattern + exclusion, not histology alone.

2. Hypertrophic

AKA asymmetrical hypertrophy/hypertrophic subaortic stenosis/Teare’s disease. Age 25-50. Often asymptomatic — heavy exertion → dyspnoea/angina/CHF/SUDDEN DEATH.

Etiology: AD inheritance (~half cases). Sarcomere gene mutations — MORE common than in dilated CM (β-myosin, troponin-I/T). Contributory: myocardial ischaemia (intramyocardial artery fibrosis → compensatory hypertrophy — self-reinforcing cycle), ↑catecholamines.

Morphology:

• Gross: enlarged/heavy heart but NORMAL/SMALL cavities (contrast dilated CM) — added mass is muscle not chamber. ASYMMETRIC hypertrophy, septum > free walls. Non-obstructive (apical septum only) vs obstructive (extends to mitral valve level → subaortic stenosis/LVOT obstruction)
• Micro: myocardial cell DISORGANISATION in septum — haphazard fibre bundles (not parallel), interstitial fibrous bands, hypertrophied cells with large nuclei. This disarray (not just mass) = substrate for sudden-death arrhythmias.

3. Restrictive (obliterative/infiltrative)

Restricted filling from ↓ventricular volume. Shared defect: abnormal DIASTOLIC function. 5 entities:

Cardiac amyloidosis — any systemic amyloidosis or isolated senile cardiac amyloid, subendocardial deposits.

Endocardial fibroelastosis — infants/children <2yr (infantile: sudden breathlessness/cyanosis/failure/death) or adults (longer course). Etiology (multiple theories): congenital intrauterine anoxia / acquired anoxia (anomalous coronaries) / pressure overload (septal defects, coarctation) / genetic (familial) / connective tissue disorder / myocardial injury trigger (thiamine deficiency, prior myocarditis) / lymphatic obstruction. Morphology: diffuse/patchy pearly-white RIGID endocardial thickening, LV>LA>RV>RA, valves often affected, mural thrombi, heart enlarged (LVH) but chamber VOLUME ↓. Micro: collagen+elastic tissue proliferation (fibroelastosis), endocardium-confined (spares myocardium), NO inflammation.

Endomyocardial fibrosis — TROPICAL disease (Africa esp. Uganda/Nigeria; also South India, Sri Lanka, Malaysia, tropical S.America). Children/young adults, CHF of unknown cause. Etiology: obscure — malnutrition, viral infection, heavy banana consumption (serotonin-rich) implicated by geography. Morphology: fibrous scarring, endocardium → INNER THIRD of myocardium. AV valves affected, semilunar SPARED. Heart normal/hypertrophied, chamber volume ↓. Micro: destruction+fibrous replacement, MONONUCLEAR infiltrate, NO elastic tissue (opposite of fibroelastosis) — superficial hyalinisation/calcification possible.

Löeffler’s endocarditis (“fibroplastic parietal endocarditis with peripheral eosinophilia”) — variant of endomyocardial fibrosis but: peripheral blood EOSINOPHILIA, EOSINOPHIL-rich infiltrate (not mononuclear), WORSE prognosis.

Other causes: haemochromatosis (transfusion/haemoglobinopathy iron overload), myocardial sarcoidosis, carcinoid syndrome, scleroderma, neoplastic infiltration.

B. Secondary cardiomyopathy

Known cause/association — EXCLUDES ischaemic/hypertensive/valvular/pericardial/congenital/inflammatory heart disease (covered elsewhere). Categories: nutritional (alcoholism, thiamine deficiency), toxic chemicals (cobalt, arsenic, lithium, hydrocarbons), drugs (cyclophosphamide, adriamycin, catecholamines), metabolic (amyloidosis, haemochromatosis, glycogen storage disease, thyroid/K+ disorders), neuromuscular (Friedreich’s ataxia, muscular dystrophies), infiltration (leukaemia, carcinoma), connective tissue disease (RA, systemic sclerosis, dermatomyositis, SLE).

Comparison table

Clinical relevance

3 primary types map onto 3 ways a ventricle fails as a pump — losing contractile force / losing outflow patency+rhythm stability / losing compliance+fill volume — frame it functionally, not as 3 separate memorised lists. Hypertrophic CM’s DISARRAY (not just mass) = substrate for sudden death — naive “hypertrophy” reading would only predict obstruction; disorganised architecture is what predisposes to fatal arrhythmia even in young asymptomatic patients during exertion. Fibroelastosis vs endomyocardial fibrosis — easily confused (both restrictive/fibrosing/young patients) — discriminate by geography (tropical vs not), depth (inner-third myocardial extension vs endocardium-only), histology (mononuclear+no elastic tissue vs no infiltrate+prominent elastic tissue). Löeffler’s vs endomyocardial fibrosis — distinguished by ONE specific feature: peripheral eosinophilia + eosinophil-rich infiltrate.

Overview

Cardiomyopathy literally means “disease of the heart muscle,” but was originally coined to mean myocardial disease of unknown cause — the WHO definition still excludes heart muscle disease of known etiology. In practice the term is used loosely (alcoholic cardiomyopathy, amyloid cardiomyopathy, ischaemic cardiomyopathy), so the field resolves this by splitting cardiomyopathy into two groups:

• A. Primary cardiomyopathy — myocardial disease of unknown cause.
• B. Secondary cardiomyopathy — myocardial disease of known cause or clinical association.

This note follows that split, since it is where nearly all the mechanistic depth of the topic actually lives — the pathophysiology and morphology of the three primary subtypes are the load-bearing content here.

A. Primary Cardiomyopathy — Three Pathophysiologic Categories

Idiopathic (unknown-cause) myocardial disease divides into three categories that are functionally, not just morphologically, distinct — each represents a different failure mode of the pumping cycle (failure of contraction, failure of relaxation from excess muscle, or failure of filling from a stiff chamber).

1. Idiopathic Dilated (Congestive) Cardiomyopathy

Definition/course: gradually progressive cardiac failure with dilatation of all four chambers. More common in adults; average survival from onset to death is under 5 years.

Etiology (genuinely unknown, but several associations proposed):

• Viral myocarditis — particularly coxsackievirus B; viral nucleic acids have been demonstrated in affected myocardium, suggesting a prior infective insult that then progresses independently of ongoing infection.
• Toxic damage — cobalt, and chemotherapy agents (doxorubicin and other anthracyclines).
• Inherited mutations — familial clustering implicates mutations in sarcomere proteins (cardiac troponin-T and I, β- and α-myosin, α-cardiac actin), which cause contractile dysfunction directly; also a mutation in the cytoskeletal protein dystrophin (X-linked) links this cardiomyopathy to muscular dystrophy.
• Chronic alcoholism (“alcoholic cardiomyopathy”) — possibly via thiamine deficiency inducing beri-beri heart disease; notably, moderate alcohol consumption is cardioprotective against IHD (raises HDL), so the toxic effect is specifically a heavy-consumption phenomenon — “beer drinkers’ myocardiosis” describes a distinct variant attributed to cobalt (once added to beer to improve foam) causing direct toxic myocardial injury.
• Peripartum association — poorly-nourished women may develop this cardiomyopathy within a month before or after delivery.

Morphology:

• Gross: heart enlarged and heavy (up to 1000 g); the hallmark finding is dilatation of all four chambers, giving a characteristic globular shape. Any ventricular wall thickening present is masked by the dilatation. Endocardium thickened; mural thrombi common in ventricles and atria. Valves are usually normal (a useful negative finding — this is myocardial disease, not valvular disease).
• Microscopy: non-specific and variable — hypertrophy of some fibres alongside atrophy of others, degenerative change, small areas of interstitial fibrosis, occasional focal mononuclear inflammatory infiltrate. The non-specificity itself is diagnostically important: histology alone cannot confirm dilated cardiomyopathy; it is a diagnosis of gross/functional pattern plus exclusion.

2. Idiopathic Hypertrophic Cardiomyopathy

Also known as asymmetrical hypertrophy, hypertrophic subaortic stenosis, or Teare’s disease. Peak occurrence age 25–50. Often asymptomatic, but heavy physical activity can precipitate dyspnoea, angina, congestive failure, or sudden death — a clinically important contrast with dilated cardiomyopathy’s more gradual course.

Etiology:

• Autosomal dominant inheritance in about half of cases.
• Sarcomere protein gene mutations — reported in a much larger proportion of hypertrophic cardiomyopathy cases than in dilated cardiomyopathy, particularly heavy/light chains of cardiac β-myosin, troponin-I, and troponin-T.
• Contributory: myocardial ischaemia (from intramyocardial artery fibrosis, itself provoking compensatory hypertrophy), raised circulating catecholamines, and ischaemia from the thickened myocardial vasculature itself — a degree of self-reinforcing pathophysiology (hypertrophy → vascular compromise → ischaemia → further hypertrophic stimulus).

Morphology:

• Gross: cardiac enlargement and increased weight, but with normal or small ventricular cavities (in direct contrast to dilated cardiomyopathy’s enlarged cavities) — the added mass is muscle, not chamber volume. Hypertrophy is characteristically asymmetrical, preferentially affecting the interventricular septum over the free walls. Two morphologic subtypes: non-obstructive (asymmetric septal hypertrophy confined to the apical septum) and obstructive (hypertrophy extends to the mitral valve level, causing subaortic stenosis and left ventricular outflow obstruction).
• Microscopy: the classic finding is myocardial cell disorganisation in the ventricular septum — muscle fibre bundles are irregularly, haphazardly arranged rather than the normal parallel pattern, separated by bands of interstitial fibrous tissue; individual muscle cells show hypertrophy with large, prominent nuclei. This disorganised architecture (not just increased muscle mass) is what predisposes to the arrhythmias responsible for sudden death in this condition.

3. Idiopathic Restrictive (Obliterative/Infiltrative) Cardiomyopathy

Characterised by restricted ventricular filling from reduced ventricular volume — the shared functional abnormality across this heterogeneous group is abnormal diastolic function (a failure of filling, distinct from dilated cardiomyopathy’s failure of contraction and hypertrophic cardiomyopathy’s outflow obstruction). Five recognised entities:

I) Cardiac amyloidosis — occurs in any systemic amyloidosis, or as isolated age-related (senile) cardiac amyloid, producing subendocardial deposits.

II) Endocardial fibroelastosis — uncommon, mainly infants/children under 2 (infantile form: sudden breathlessness, cyanosis, failure, death; adult form: longer-lasting symptoms).

• Etiology (multiple proposed mechanisms): congenital intrauterine endocardial anoxia (infantile form) or acquired anoxic lesions (anomalous coronary arteries, metabolic derangement) in adults; haemodynamic pressure overload (congenital septal defects, coarctation); genetic factors (familial clustering, association with other congenital malformations); a proposed connective tissue disorder mechanism; myocardial injury (thiamine deficiency, prior idiopathic myocarditis) triggering the endocardial process; and a proposed lymphatic obstruction mechanism.
• Morphology: diffuse/patchy, rigid, pearly-white thickening of the mural endocardium, predominantly left ventricle > left atrium > right ventricle > right atrium; valves (especially left heart) often affected; mural thrombi in some cases; heart enlarged (mainly from LV hypertrophy) but chamber volume decreased. Microscopically: proliferation of collagen and elastic tissue (fibroelastosis) confined to the endocardium, generally sparing the underlying myocardium, with no inflammatory infiltrate.

III) Endomyocardial fibrosis — a tropical condition (Africa — especially Uganda and Nigeria; also South India, Sri Lanka, Malaysia, tropical South America), affecting children and young adults, presenting as congestive failure of unknown cause.

• Etiology: obscure, but geographic distribution implicates malnutrition, viral infection, and heavy banana consumption (rich in serotonin) as contributory factors.
• Morphology: fibrous scarring of ventricular endocardium extending into the inner third of the myocardium; AV valve leaflets often affected, semilunar valves spared; mural thrombi may occur; heart normal-sized or hypertrophied but affected chamber volume diminished. Microscopically: destruction and fibrous replacement of endocardium and inner myocardium, distinguished from endocardial fibroelastosis by having a mononuclear inflammatory infiltrate and lacking elastic tissue; superficial layer may show dense hyalinised tissue, even calcification.

IV) Löeffler’s endocarditis (“fibroplastic parietal endocarditis with peripheral blood eosinophilia”) — regarded by some as a variant of endomyocardial fibrosis, but distinguished by: peripheral blood eosinophilia, an inflammatory infiltrate that is chiefly eosinophilic (rather than mononuclear), and a worse prognosis than endomyocardial fibrosis proper.

V) Other causes of restrictive cardiomyopathy: haemochromatosis (iron overload from multiple transfusions or haemoglobinopathies), myocardial sarcoidosis, carcinoid syndrome, scleroderma, neoplastic infiltration of the heart.

B. Secondary Cardiomyopathy

Myocardial disease of known etiology or clinical association — this deliberately excludes the well-defined entities covered elsewhere (ischaemic, hypertensive, valvular, pericardial, congenital, and inflammatory heart disease). Recognised categories:

1. Nutritional — chronic alcoholism, thiamine deficiency (beri-beri heart disease).
2. Toxic chemicals — cobalt, arsenic, lithium, hydrocarbons.
3. Drugs — cyclophosphamide, adriamycin, catecholamines.
4. Metabolic disease — amyloidosis, haemochromatosis, glycogen storage disease, hypo-/hyperthyroidism, hypo-/hyperkalaemia.
5. Neuromuscular disease — Friedreich’s ataxia, muscular dystrophies.
6. Infiltration — leukaemia, carcinoma.
7. Connective tissue disease — rheumatoid arthritis, systemic sclerosis, dermatomyositis, lupus erythematosus.

Summary Comparison of the Three Primary Types

Clinical Relevance

• The three primary cardiomyopathies map cleanly onto the three ways a ventricle can fail to act as an effective pump — losing contractile force (dilated), losing outflow patency and rhythm stability (hypertrophic), or losing compliance and fill volume (restrictive) — and holding this functional framework in mind makes the morphology of each type predictable rather than three lists to memorise independently.
• Hypertrophic cardiomyopathy’s myocardial disarray (not simply increased muscle mass) being the substrate for its characteristic sudden death risk is a critical distinction — a naive reading of “hypertrophy” alone would predict only outflow obstruction, but the disorganised fibre architecture is what actually predisposes to fatal arrhythmia, including in young, otherwise asymptomatic patients during exertion.
• Endocardial fibroelastosis and endomyocardial fibrosis are frequently confused since both are restrictive, fibrosing endocardial diseases in young patients — the reliable discriminators are geography (tropical distribution for endomyocardial fibrosis vs no such pattern for fibroelastosis), depth of involvement (inner-third myocardial extension in endomyocardial fibrosis vs endocardium-confined in fibroelastosis), and histology (mononuclear infiltrate, no elastic tissue in endomyocardial fibrosis vs no infiltrate, prominent elastic tissue in fibroelastosis).
• Löeffler’s endocarditis being distinguished from endomyocardial fibrosis specifically by peripheral eosinophilia and an eosinophil-rich (not mononuclear) infiltrate is a useful reminder that closely related restrictive entities can still be told apart by a single, specific laboratory/histologic feature rather than by overall clinical picture alone.

• Three primary cardiomyopathies as three pump-failure modes: contraction vs outflow vs filling failure, with matched chamber/morphology changes
• Endocardial fibroelastosis vs endomyocardial fibrosis vs Löeffler’s endocarditis: a discriminating comparison (geography, depth of involvement, infiltrate type)