What are the main causes of cardiomyopathy?

Main Causes of Cardiomyopathy

Cardiomyopathy is caused by a diverse range of genetic, acquired, and secondary factors that affect the heart muscle structure and function, with the most common causes being genetic mutations, coronary artery disease, hypertension, infections, and toxins. 1

Genetic Causes

• Sarcomere protein gene mutations - Most common cause of hypertrophic cardiomyopathy (HCM)
  • Mutations in genes encoding cardiac myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) account for the majority of cases 2
  • Other affected genes include cardiac troponin I and T (TNNI3, TNNT2), tropomyosin alpha-1 chain (TPM1), and myosin light chain 3 (MYL3) 2
• Cytoskeletal protein mutations - Common in dilated cardiomyopathy (DCM)
  • Genetic causes account for approximately 50% of DCM cases 2
• Desmosomal protein mutations - Primary cause of arrhythmogenic cardiomyopathy 2

Metabolic and Storage Disorders

• Anderson-Fabry disease - Most common metabolic disorder in adults with HCM (0.5-1% prevalence in patients >35-40 years) 2
• Glycogen storage diseases - Including Pompe and Danon disease 2
• Lysosomal storage diseases 2
• Mitochondrial disorders - Caused by mutations in nuclear or mitochondrial DNA 2
• Amyloidosis - Including:
  • Light chain (AL) amyloidosis
  • Hereditary transthyretin (TTR) amyloidosis
  • Wild-type (senile) TTR amyloidosis 2

Inflammatory/Infectious Causes

• Myocarditis - Viral, bacterial, or autoimmune inflammation 2
• Chagas disease - Caused by Trypanosoma cruzi infection 1

Toxic/Drug-Induced Causes

• Alcohol - Chronic excessive consumption 1
• Chemotherapeutic agents - Particularly anthracyclines 1
• Cocaine and other illicit drugs 1
• Hydroxychloroquine, steroids, and tacrolimus 2

Tachycardia-Induced Cardiomyopathy

• Atrial fibrillation - Most common arrhythmia causing tachycardia-induced cardiomyopathy 2
• Frequent premature ventricular complexes (PVCs) - PVC burden ≥10% can result in cardiomyopathy 2
• Supraventricular tachycardias - Including inappropriate sinus tachycardia 2

Endocrine Disorders

• Pheochromocytoma - Associated with LV hypertrophy 2
• Acromegaly - Can cause reversible hypertrophy 2
• Thyroid disorders - Both hyper- and hypothyroidism 1
• Diabetes - Can cause transient ventricular hypertrophy in infants of diabetic mothers 2

Neuromuscular Diseases

• Friedreich's ataxia - Most common neuromuscular disease causing HCM 2
• Muscular dystrophies - Various forms can affect cardiac muscle 2
• Desmin gene mutations - Typically cause dilated and restrictive cardiomyopathies 2

Malformation Syndromes

• Noonan syndrome - Most common malformation syndrome associated with HCM 2
• LEOPARD syndrome - Characterized by multiple abnormalities including HCM 2
• Costello syndrome - Associated with HCM 2

Stress-Induced Cardiomyopathy

• Takotsubo cardiomyopathy - Typically triggered by severe emotional or physical stress 2

Other Causes

• Peripartum cardiomyopathy - Occurs in the last month of pregnancy or within five months postpartum 1
• Hypertension - Long-standing uncontrolled hypertension 1
• Valvular heart disease - Chronic pressure or volume overload 1
• Coronary artery disease - Ischemic damage to myocardium 1

Clinical Implications

It's important to identify the specific cause of cardiomyopathy as it guides treatment approaches. For example:

• Tachycardia-induced cardiomyopathy requires aggressive rhythm control, with catheter ablation often being curative 2
• Genetic cardiomyopathies may warrant family screening and genetic counseling 1
• Metabolic causes may have specific enzyme replacement therapies 2
• Toxic causes require removal of the offending agent 1

Understanding the etiology is crucial for prognosis assessment, as some causes (like tachycardia-induced) may be largely reversible while others (like certain genetic forms) may have a progressive course despite optimal therapy.