What are the causes of dilated cardiomyopathy?

Causes of Dilated Cardiomyopathy

Dilated cardiomyopathy results from either genetic mutations (30-50% of cases) or acquired factors including viral myocarditis, cardiotoxins (especially alcohol and chemotherapy), endocrine disorders, peripartum state, tachyarrhythmias, autoimmune diseases, and nutritional deficiencies. 1, 2

Primary (Genetic/Familial) Causes

Genetic mutations account for 30-50% of all DCM cases, with 30-40% attributable to identifiable pathogenic variants in specific protein genes. 2, 3

• Cytoskeletal protein mutations affect the structural framework of cardiomyocytes and represent a major genetic category. 2, 4
• Sarcomeric protein mutations disrupt the contractile apparatus of the heart muscle. 2, 4
• Sarcolemmal protein mutations affect the cell membrane integrity and function. 2
• Nuclear envelope protein mutations disrupt nuclear structure and gene regulation. 2

Importantly, 5-15% of patients with apparently acquired DCM harbor pathogenic gene variants, meaning genetic testing should be considered even when an acquired cause is identified. 5

Secondary (Acquired) Causes

Infectious Causes

• Viral myocarditis represents a well-established pathway from acute inflammation to chronic DCM, with cell-mediated autoimmune mechanisms triggered by viral infection driving progression. 1, 5, 6
• Endomyocardial biopsy studies demonstrate persistent myocardial inflammation in DCM patients, supporting the myocarditis-to-DCM progression hypothesis. 6

Cardiotoxic Substances

• Alcohol is a common and reversible cause when consumption is stopped early. 1, 3, 4
• Chemotherapeutic agents (particularly anthracyclines and other cancer treatments) cause direct myocyte injury. 1, 5, 4
• Recreational drugs including cocaine and amphetamines damage myocardium through multiple mechanisms. 5, 4

Endocrine and Metabolic Disorders

• Diabetes mellitus contributes to secondary cardiomyopathy through metabolic derangements. 1
• Thyroid disorders (both hypo- and hyperthyroidism) affect cardiac contractility. 1
• Nutritional deficiencies including thiamine, carnitine, and selenium cause reversible DCM when severe. 1

Pregnancy-Related

• Peripartum cardiomyopathy presents during the last month of pregnancy or within 5 months postpartum, with risk factors including multiparity, advanced maternal age, obesity, and hypertension. 1, 3

Arrhythmia-Induced

• Tachycardia-induced cardiomyopathy results from chronic supraventricular or ventricular arrhythmias with rapid rates, causing reversible systolic dysfunction through myocardial energy depletion and abnormal calcium handling. 1, 5
• Frequent premature ventricular complexes can induce cardiomyopathy even without sustained tachycardia. 1
• Chronic ventricular pacing at high rates causes cardiomyopathy through dyssynchronous contraction. 1

Autoimmune and Inflammatory Disorders

• Systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, scleroderma, and polyarteritis nodosa all associate with DCM through immune-mediated myocardial damage. 1, 5

Infiltrative Diseases

• Amyloidosis, hemochromatosis, and sarcoidosis cause secondary cardiomyopathy as part of multiorgan systemic disease. 1

Stress-Related

• Stress-induced (Tako-tsubo) cardiomyopathy presents with acute, usually reversible LV dysfunction triggered by emotional or physical stress, mediated by catecholamine excess causing β2-adrenergic receptor signaling changes. 1

Hypertensive Heart Disease

• Long-standing uncontrolled hypertension leads to "burned-out" dilated cardiomyopathy after initial concentric hypertrophy, with progressive chamber dilation and declining ejection fraction. 1

Critical Diagnostic Consideration

The diagnostic approach must always consider both genetic and acquired factors simultaneously, as they frequently coexist and influence prognosis and family screening requirements. 5 A three-generational family history is essential to identify familial patterns. 7