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Primary Cardiomyopathies

Cardiomyopathia

For medical students2 min readUpdated 2026-10-10

Primary cardiomyopathies are a heterogeneous group of non-coronary heart muscle diseases characterized by intrinsic myocardial dysfunction. While their exact etiology is not fully elucidated, they inevitably lead to severe arrhythmias and heart failure.

Main TargetMyocardium (primary dystrophy without coronary artery disease or primary valvular disease)

Dangerous OutcomeHeart failure and sudden cardiac death

Right Ventricular FormThe only type with a definitively proven genetic etiology

TransplantationDilated cardiomyopathy is a leading indication for heart transplantation

General Characteristics and Clinical Manifestations

Idiopathic cardiomyopathies comprise disorders primarily affecting the heart muscle, while excluding inflammatory, congenital, rheumatic, or ischemic (coronary) etiologies.

Despite different pathogenetic mechanisms, all forms share a similar clinical picture:

Dyspnea on exertion or worsening shortness of breath.
Various arrhythmias and tachycardia.
Tendency toward dizziness and sudden fainting (syncope).
Terminal-stage development of severe heart failure.

Dilated Cardiomyopathy (DCM)

DCM is the most common form, accounting for approximately 60% of all idiopathic myocardial disorders. It predominantly affects males aged 10 to 30 years.

Etiology and Pathogenesis Exact causes remain unclear, but the leading hypothesis links DCM to a preceding latent viral myocarditis. The process begins with atrophy and death of cardiomyocytes. Interstitial fibrosis develops in their place, while surviving muscle fibers undergo compensatory hypertrophy.

Morphological Findings

Macroscopic: The heart adopts a characteristic globular shape with a blunted apex (transverse dimension equals or exceeds longitudinal). Organ weight increases to 600–800 g (sometimes up to 1200 g). Marked dilation of all chambers is observed. The left ventricular wall thickness is typically 2–2.5 cm, which is disproportionately thin for the massive heart weight. The valve apparatus and coronary arteries remain intact.
Microscopic: Findings are non-specific, showing a mixture of hypertrophied and atrophied fibers, areas of myocytolysis, contraction band necrosis, focal interstitial fibrosis, and proliferation of intermyofibrillar adipose tissue. Cellular inflammatory infiltrate is typically minimal.
Ultrastructural: Separation of intercalated discs between cardiomyocytes occurs, which is the primary cause of myocardial electrical instability.

Clinically, DCM presents with fatigue, cough, hemoptysis, chest pain, pallor, and acrocyanosis.

Hypertrophic and Restrictive Forms

Hypertrophic cardiomyopathy (synonym: hypertrophic obstructive cardiomyopathy) is characterized by marked thickening of the myocardium, most commonly affecting the left ventricle. Ventricular cavities are significantly reduced. The primary functional impairment is impaired diastolic relaxation with preserved or even enhanced systolic function.

Restrictive cardiomyopathy is characterized by rigid ventricular walls and extensive endocardial fibrosis.

Pathophysiology: Rigid walls impede normal diastolic filling of the chambers, and atrioventricular valve function is impaired. Pulmonary hypertension develops, leading to cor pulmonale.
Etiology: This pathology is extremely rare. A suspected cause is Löffler endocarditis (eosinophilic endomyocardial disease). A geographic hypothesis also exists: in certain African populations, endomyocardial fibrosis may develop due to cerium excess combined with magnesium deficiency.
Morphogenesis: Gross endocardial fibrosis (typically of the left ventricle), hyalinosis, and calcification are observed. The ventricular cavity is reduced, and sclerosis often extends to the posterior leaflet of the mitral valve. Microscopy reveals cardiomyocyte death and compensatory hypertrophy of remaining cells.
Complications and Outcome: Decreased contractility leads to mural thrombus formation and thromboembolism. The prognosis is extremely poor, with approximately 70% of patients dying within the first 5 years.

Arrhythmogenic Right Ventricular Cardiomyopathy

Synonym: arrhythmogenic right ventricular dysplasia (ARVD). This is a rare form with a definitively proven genetic basis.

It is of paramount clinical importance as a leading cause of sudden cardiac death in infants, children, adolescents, and athletes.

Morphogenesis: Characterized by thinning of the right ventricular wall due to progressive confluent areas of myocyte loss. The destroyed myocardium is replaced by fibrofatty tissue, creating a so-called "parchment heart."

Clinical Presentation and Complications: Patients suffer from severe arrhythmias (ventricular tachycardia, premature ventricular contractions, sinoatrial block). In rare cases, the thinned right ventricular wall may rupture, leading to fatal cardiac tamponade.

Mnemonic

To quickly remember the main forms, use the mnemonic DGRA: Dilated (Dilated, globular heart), Gressive/Hypertrophic (Giant walls), Restrictive (Rigid endocardium), Arrhythmogenic dysplasia (Atrophy of the right ventricle).

Frequently asked questions

What macroscopic and microscopic features characterize hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy features marked myocardial hypertrophy, reduced ventricular cavities, disorganized muscle fibers, and diffuse interstitial fibrosis.

Macroscopic features:

Heart weight ranges from 500–700 g with a pointed apex.
Left ventricular wall thickness reaches 2.5–3 cm with decreased cavity size.
Valves and coronary arteries are normal.
Divided into asymmetric (interventricular septum thickness is 1.5–2 times the left ventricular wall thickness) and symmetric (uniform hypertrophy) forms.

Microscopic features:

Myofiber disarray (disarray).
Global and diffuse myocardial fibrosis.

What genetic mutations underlie the development of hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy is caused by pathogenic variants in genes encoding sarcomeric and non-sarcomeric proteins.

Sarcomeric protein gene mutations — associated with classic hypertrophic cardiomyopathy; the disease is defined as a disease of the sarcomere. The most frequent mutation involves the beta-myosin heavy chain gene.
Multiple mutations — the presence of 2, 3, or more pathogenic variants, most commonly combinations of sarcomeric gene mutations. Present in 5–7% of cases and associated with earlier onset, marked septal hypertrophy, and high risk of sudden cardiac death.
Non-sarcomeric gene mutations — pathogenic variants in genes encoding cytoskeletal proteins, ion channels, Z-disc components, and other intracellular structures, accounting for 15–20% of cases. Cytoskeletal mutations are often associated with congenital heart defects and left ventricular non-compaction.

Which form of cardiomyopathy is most common?

Dilated cardiomyopathy is the most frequent, accounting for approximately 60% of all idiopathic myocardial disorders.

Why does electrical instability occur in dilated cardiomyopathy?

At the ultrastructural level, separation of cardiomyocyte intercalated discs disrupts normal electrical impulse propagation.

What are the macroscopic features of dilated cardiomyopathy?

The heart assumes a globular shape with a blunted apex, weighing 600–1200 g due to marked dilation of all chambers, while valves and coronary arteries remain unaffected.

What pathology frequently causes sudden death in young athletes?

Arrhythmogenic right ventricular cardiomyopathy (dysplasia), in which the myocardium thins and is replaced by adipose and fibrous tissue.

Go deeper

Ultrastructural changes in cardiomyocytes in dilated cardiomyopathy
Pathogenesis of cor pulmonale in restrictive cardiomyopathy
Mechanisms of mural thrombus formation and thromboembolism
Role of Löffler eosinophilic endocarditis in endomyocardial fibrosis
Genetic aspects of arrhythmogenic right ventricular dysplasia