Causes of Dilated Cardiomyopathy (DCM)
Dilated cardiomyopathy (DCM) is caused by a heterogeneous group of genetic and acquired disorders that lead to ventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. 1
Primary Genetic Causes (30-50% of cases)
Sarcomere and cytoskeletal gene mutations
- Titin gene mutations (most common)
- Lamin A/C (LMNA) - associated with conduction disorders
- Desmin - associated with conduction disorders
- Dystrophin - X-linked DCM 1
Neuromuscular disorders
- Duchenne muscular dystrophy
- Becker muscular dystrophy
- Myotonic dystrophy
Syndromic diseases 1
Acquired/Secondary Causes
Infectious
- Viral myocarditis (most common infectious cause)
- Coxsackievirus, adenovirus, parvovirus B19, HIV
- Bacterial (including Chagas disease)
- Fungal
- Parasitic 1
Toxic
- Alcohol - dose-dependent cardiotoxicity
- Recreational drugs - cocaine, methamphetamines
- Heavy metals - cobalt, lead, mercury
- Iron overload - hemochromatosis 1
Drug-Induced
- Chemotherapeutic agents
- Anthracyclines (doxorubicin)
- Trastuzumab
- Psychiatric medications
- Clozapine, lithium
- Other medications with cardiotoxic potential 1
Endocrine/Metabolic
- Thyroid disorders
- Hypothyroidism
- Hyperthyroidism
- Acromegaly
- Diabetes mellitus
- Electrolyte disturbances - hypocalcemia 1
Nutritional Deficiencies
- Selenium
- Thiamine
- Carnitine 1
Autoimmune/Inflammatory
- Organ-specific - inflammatory cardiomyopathy
- Systemic disorders
- Systemic lupus erythematosus
- Polymyositis
- Sarcoidosis 1
Other Specific Causes
- Tachycardia-induced cardiomyopathy
- Persistent supraventricular arrhythmias
- Frequent premature ventricular contractions 1
- Peripartum cardiomyopathy
- Occurs in last month of pregnancy or within 5 months postpartum 1
- Stress-induced (Takotsubo) cardiomyopathy
- Transient ventricular dysfunction following emotional or physical stress
Clinical Implications
- The identification of specific causes is crucial as it may lead to etiology-directed therapies that can improve outcomes 1
- Genetic causes are found in approximately 30-50% of DCM cases, with higher prevalence in children 1
- Patients with genetic forms may have a long preclinical phase with few symptoms before developing overt DCM 1
- Some genetic disorders may initially present with arrhythmias or conduction defects before ventricular dilatation becomes apparent (especially LMNA mutations) 1
- Patients with inflammatory/infectious causes may benefit from immunosuppressive or antiviral therapies
- Removal of offending agents (alcohol, drugs, toxins) may lead to partial or complete recovery in toxin-induced DCM
Diagnostic Approach
- Comprehensive evaluation should include:
- Detailed family history (for genetic forms)
- Exposure history (toxins, drugs)
- Cardiac imaging (echocardiography, CMR)
- Laboratory testing for metabolic, infectious, and autoimmune causes
- Genetic testing when familial or suspected genetic etiology
- Endomyocardial biopsy when inflammation or infection is suspected 1
Understanding the specific cause of DCM is essential for tailoring treatment approaches, providing prognostic information, and guiding family screening when genetic causes are identified.