What are the etiologies of dilated cardiomyopathy?

Causes of Dilated Cardiomyopathy

Dilated cardiomyopathy results from genetic mutations in 30-50% of cases, with acquired causes including viral myocarditis, alcohol toxicity, peripartum cardiomyopathy, autoimmune disease, and tachycardia-induced cardiomyopathy comprising the remainder. 1, 2

Primary Classification Framework

Dilated cardiomyopathy is defined by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to explain the dysfunction. 1 The American Heart Association divides cardiomyopathies into primary (genetic, nongenetic, acquired) and secondary (systemic diseases with cardiac involvement). 1

Genetic and Familial Causes (30-50% of Cases)

Genetic mutations are the single most important cause category, accounting for up to 50% of all dilated cardiomyopathy cases. 2

Key Genetic Patterns

• Autosomal dominant inheritance is the most common pattern, typically presenting in the third decade with progressive disease. 2
• Cytoskeletal-sarcomere protein genes are most frequently implicated, disrupting the mechanical link between contractile apparatus and cellular structure. 2
• LMNA (lamin A/C) mutations cause particularly aggressive disease with high arrhythmia risk and early need for device therapy. 2, 3
• Dystrophin gene mutations (X-linked) present in male adolescents/young adults with rapid progression; elevated creatine kinase is a distinguishing feature. 2, 4
• Titin truncating variants are among the most common genetic causes and carry specific prognostic implications. 3

Critical Screening Point

Echocardiographic screening of first-degree relatives identifies dilated cardiomyopathy in approximately 30% of families, even when the proband appears to have sporadic disease. 2 This means that many "idiopathic" cases are actually familial when proper screening is performed. 1

Acquired Causes

Viral Myocarditis (Most Common Infectious Cause in Western Countries)

• Parvovirus B19 and human herpes virus 6 are the most frequent viral causes in Western Europe. 1
• Coxsackie B and enteroviruses remain important in acute and fulminant myocarditis. 1
• Viral myocarditis accounts for up to 75% of myocardial infarction with non-obstructive coronary arteries (MINOCA) presentations. 2
• Recent viral syndrome preceding heart failure symptoms suggests myocarditis, though serum antibody titers have low yield. 2

Alcohol-Induced Cardiomyopathy

• Particularly common in men aged 30-55 years with heavy drinking history and probable genetic susceptibility. 2
• Patients frequently underreport alcohol consumption; careful questioning about current and past use is essential. 2

Tachycardia-Induced Cardiomyopathy

A premature ventricular contraction (PVC) burden ≥24% is independently associated with dilated cardiomyopathy, though the pathogenic threshold may be as low as 10%. 2, 4

• Radiofrequency ablation restores normal left ventricular ejection fraction in approximately 82% of patients within 6 months. 2, 4
• The right ventricular outflow tract is the most common PVC origin (≈52% of cases). 2
• Sustained tachyarrhythmias (atrial fibrillation with ventricular rate ≥130 bpm) can also induce dilated cardiomyopathy. 2

Peripartum Cardiomyopathy

• Presents during the last month of pregnancy or within 5 months postpartum. 4
• Risk factors include multiparity, advanced maternal age, obesity, and hypertension. 4

Toxic Exposures

• Cocaine and methamphetamine can cause dilated cardiomyopathy. 2
• Cancer chemotherapy agents (anthracyclines) are well-established cardiotoxins. 1

Secondary Causes (Systemic Diseases)

Infiltrative and Storage Diseases

• Cardiac sarcoidosis often affects the heart without clinical evidence of extracardiac disease. 1
• Hemochromatosis: Measure fasting transferrin saturation to screen, as mutated alleles are common in Northern European descent. 2, 4
• Amyloidosis causes restrictive physiology but can present with dilated phenotype. 1

Autoimmune and Inflammatory

• Systemic lupus erythematosus increases heart failure hospitalization risk 1-3 fold, highest in women <45 years. 4
• Rheumatoid arthritis and other connective tissue disorders can cause dilated cardiomyopathy. 2

Endocrine Disorders

• Both hyperthyroidism and hypothyroidism can cause or contribute to heart failure; measure thyroid-stimulating hormone in all patients. 2, 4
• Diabetes mellitus is a recognized secondary cause. 1

Infectious (Geographic Variation)

• Chagas disease (Trypanosoma cruzi) causes progressive myocardial damage through parasite persistence and autoimmune responses; prognosis is poor with 50% mortality within 4 years of heart failure onset. 4
• HIV-associated cardiomyopathy occurs in approximately 8% of asymptomatic HIV-positive individuals. 2

Neuromuscular Disorders

• Myotonic dystrophy type 1 (DM1) causes dilated cardiomyopathy in approximately 80% of patients, with cardiac manifestations being a leading cause of death. 4
• Cardiac involvement in DM1 is particularly high-risk in younger patients aged 2-30 years, manifesting primarily as progressive conduction defects and tachyarrhythmias. 4

Phenotypic Evolution

Patients with arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, or left ventricular non-compaction can later develop a dilated ventricular phenotype through remodeling processes. 2 This means certain cardiomyopathies do not remain static and may evolve from one phenotypic category to another over the clinical course. 2

Critical Diagnostic Pitfall

Approximately 5-15% of patients with acquired dilated cardiomyopathy harbor a likely pathogenic or pathogenic gene variant. 5 Therefore, the diagnostic approach must always consider both genetic and acquired factors simultaneously, not sequentially. 5 A three-generation family history is essential when assessing cardiomyopathy causes. 4