NATIONAL HEALTH LABORATORY SERVICE

CARDIOMYOPATHY

UNIVERSITY OF KWAZULU-NATAL

Instructor

  • Dr. O. Maphanyane
  • Department of Anatomical Pathology
  • Date: 11 March 2026

Learning Outcomes

  • Definition of cardiomyopathy
  • Causes of cardiomyopathy
  • Classification of cardiomyopathy
  • Clinical features of cardiomyopathy
  • Gross pathology
  • Histopathology

Definition of Cardiomyopathy

  • Cardiomyopathy literally means heart muscle disease.
  • It refers to heart disease resulting from an abnormality in the myocardium.

Causes of Cardiomyopathy

Primary vs. Secondary

  • Primary Cardiomyopathy:
    • Heart muscle disease that occurs due to an unknown cause.
    • The disease is predominantly confined to the heart muscle.
  • Secondary Cardiomyopathy:
    • Characterized by myocardial involvement as part of a systemic or multi-organ disorder.

General Causes

  • Most causes of cardiac failure can be attributed to:
    • Ischaemic heart disease
    • Valvular disorders
    • Congenital heart disorders
    • Hypertension

Specific Causes of Secondary Cardiomyopathy

Multisystem Diseases
  • Sarcoidosis
  • Rheumatic disease
  • Amyloidosis
  • Acromegaly
  • Thyrotoxicosis
  • Myxoedema
Other Secondary Causes
  1. Alcoholism
  2. Peripartum cardiomyopathy
  3. Iatrogenic disease (doctor-induced)
    • Cytotoxic drugs and radiotherapy used, particularly in the treatment of mediastinal tumors.

Classification of Cardiomyopathy

  1. Dilated Cardiomyopathy (DCM)
  2. Hypertrophic Cardiomyopathy (HCM)
  3. Restrictive Cardiomyopathy (RCM)

Dilated Cardiomyopathy (DCM)

Overview

  • DCM is characterized by:
    • Left ventricular systolic dysfunction with an increased left ventricular cavity diameter.
    • Increased chamber volumes and ventricular wall thickening.
    • It can be referred to as congestive cardiomyopathy with causes being primary or secondary.

Causes of DCM

Genetic Influences
  • Inheritance Patterns:
    • Autosomal dominant
    • Autosomal recessive
    • X-linked
    • Mitochondrial
  • Involves mutations in genes that code for cytoskeletal and sarcomere proteins.
Environmental and Other Causes
  • Alcohol exposure, other toxins:
    • Alcohol is strongly associated with DCM due to ethanol toxicity/nutritional disturbance.
    • Alcohol and its metabolites have a direct toxic effect on the myocardium.
    • Chemotherapy agents like Doxorubicin.
  • Myocarditis induced by viral infections (Coxsackieviruses A and B, CMV, HIV).
  • Peripartum cardiomyopathy has a multifactorial mechanism involving:
    • Pregnancy induced hypertension (PIH)
    • Volume overload
    • Nutritional deficiency
    • Metabolic derangement
  • Iron overload conditions (haemochromatosis, multiple transfusions)
  • Supraphysiological stress (persistent tachycardia, hyperthyroidism, excess catecholamines).
  • Idiopathic DCM is diagnosed when no known etiology can be identified.

Clinical Features of DCM

  • Affects individuals aged 20 to 50 years.
  • Symptoms may progress to congestive heart failure (CHF).
  • Signs of secondary mitral regurgitation may occur.
  • Potential development of arrhythmias.
  • Risk of death due to:
    • Progressive cardiac failure
    • Arrhythmia
    • Embolism
  • At the end stage of DCM, ejection fraction (EF) may fall below 25% (normal range is 50% - 65%).

Gross Pathology of DCM

  • The heart is typically enlarged and heavy (2 to 3 times normal weight with an average of 280-350g, varying by gender).
  • The heart appears dilated and flabby, exhibiting a globular appearance.
  • There is four-chamber dilation, particularly of the left ventricle.
  • Left ventricular wall thickening:
    • Wall thickness ≥15 mm,
    • Septal/posterior wall thickness ratio >1.3 in normotensive patients.
  • Potential formation of mural thrombi, posing a risk for embolization.
  • Mitral regurgitation can develop due to left ventricular dilatation.

Histopathology of DCM

  • Abnormalities observed are typically non-specific and may include:
    • Myocyte hypertrophy (± atrophy)
    • Enlarged nuclei (nuclear variation includes being elongated, stretched, or irregular)
    • Loss of myofibrillary structure
    • Interstitial and endocardial fibrosis
    • Small subendocardial scars.
  • The microscopic findings may show dilated chambers with mural thrombi and patent coronary arteries; myocyte cellular changes involving both hypertrophy and atrophy can be noted, along with interstitial fibrosis likely related to hypoperfusion.

Hypertrophic Cardiomyopathy (HCM)

Overview

  • HCM is characterized by myocardial hypertrophy, which results in a poorly compliant left ventricular myocardium.
  • This leads to abnormal diastolic filling.
  • In about one-third of cases, there may be intermittent ventricular outflow obstruction.

Pathogenesis of HCM

  • HCM has a genetic basis predominantly influenced by autosomal dominant inheritance with variable penetrance.
  • Mutations in genes encoding sarcomeric proteins are implicated, with over 400 known mutations across nine different genes including:
    • β-myosin heavy chain (β-MHC)
    • cardiac troponin T (cTnT)
    • α-tropomyosin
    • myosin-binding protein C (MYBP-C).

Clinical Features of HCM

  • Impaired diastolic filling leads to a reduced stroke volume, contributing to:
    • Compromised cardiac output
    • Pulmonary venous pressure increase
    • Exertional dyspnea is common as a result of reduced chamber size and decreased compliance in the hypertrophied left ventricle.
  • Additional symptoms include:
    • Angina
    • Atrial fibrillation leading to mural thrombus formation, possible embolization, and cardiac failure
    • Ventricular arrhythmias and sudden death are potential outcomes, especially in young athletes.
  • A characteristic harsh systolic ejection murmur is noted due to outflow obstruction.

Gross Pathology of HCM

  • Key features include:
    • Left ventricular hypertrophy without ventricular dilation.
    • Asymmetric septal hypertrophy, with the septum thickening more than the left ventricle free wall (a ratio greater than 3:1).
    • Possible endocardial thickening or mural plaque formation, especially in the left ventricular outflow tract.
    • Longitudinal sectioning may reveal a "banana-like" configuration of the left ventricle due to the bulging ventricular septum.
    • The left ventricular outflow tract may feature associated fibrous endocardial plaques, particularly impacting the anterior mitral leaflet due to its contact with the septum during systole.

Histopathology of HCM

  • Extensive myocyte hypertrophy is commonly observed.
  • Myofiber disarray is a hallmark of HCM, showing several myocytes bundled in a disorganized fashion rather than the normal parallel organization.
  • Increased interstitial fibrous tissue is noted, detectable using specific staining techniques.

Restrictive Cardiomyopathy (RCM)

Overview

  • RCM is characterized by a primary decrease in ventricular compliance, which leads to impaired filling of the ventricles during diastole.
  • Contractile (systolic) function of the left ventricle is generally maintained.
  • RCM can be classified as:
    • Idiopathic
    • Associated with distinct diseases or conditions that affect the myocardium, such as:
    • Radiation-induced fibrosis
    • Amyloidosis
    • Sarcoidosis
    • Metastatic tumors
    • Metabolite deposition due to inborn errors of metabolism.

Clinical Features of RCM

  • Clinical manifestations depend on the underlying cause.
  • RCM can often mimic constrictive pericarditis or hypertrophic cardiomyopathy because the contractile function of the left ventricle remains typically unaffected.

Gross Pathology of RCM

  • The ventricles may be normal size or slightly enlarged, with the cavities typically not dilated.
  • The myocardium appears firm and non-compliant.
  • There's a pronounced biatrial dilation.

Histopathology of RCM

  • Observed abnormalities are often non-specific, including:
    • Myocyte hypertrophy
    • Patchy or diffuse interstitial fibrosis
    • Myofiber disarray

Cardiac Amyloidosis

  • An important cause of secondary restrictive cardiomyopathy, characterized by the infiltration of the myocardium by amyloid.
  • The presence of amyloid is confirmed by staining techniques; for instance, Lugol's iodine imparts a mahogany brown coloration to amyloid deposits.
  • Amyloid features as an extracellular pink-hyaline amorphous deposit consisting of fibrillar material.

Staining Techniques for Amyloid

  • Different stains can be employed to identify and interpret amyloid deposits histologically; further details may be referenced from pathology textbooks or specialized resources.

References

  • Robbins & Cotran. Pathological Basis of Disease. 9th ed. Authors: Vinay Kumar, Abul K. Abbas, Jon C. Aster.
  • Underwood’s pathology