What are the causes and management options for cardiomyopathy?

Cardiomyopathy Etiology and Management

Cardiomyopathies are caused by a diverse range of genetic, acquired, and secondary conditions that require specific diagnostic approaches and targeted management strategies based on the underlying etiology. 1

Types of Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM)

Diagnostic Criteria

• In adults: Left ventricular wall thickness ≥15 mm in one or more LV myocardial segments 1
• In children: LV wall thickness more than two standard deviations greater than predicted mean (z-score >2) 1
• In first-degree relatives of HCM patients: LV wall thickness ≥13 mm may be diagnostic 1

Etiologies

1. Genetic causes (60% of cases) 1, 2

   • Sarcomeric protein gene mutations (most common)
     • MYBPC3 (myosin-binding protein C)
     • MYH7 (myosin heavy chain 7)
     • TNNI3 (troponin I)
     • TNNT2 (troponin T)
     • TPM1 (tropomyosin 1 alpha chain)
     • MYL3 (myosin light chain 3)

2. Non-genetic causes (5-10%) 1

   • Metabolic disorders
   • Neuromuscular diseases
   • Infiltrative diseases (amyloidosis)
   • Chromosomal abnormalities
   • Genetic syndromes

3. Drug-induced causes 1

   • Anabolic steroids
   • Tacrolimus
   • Hydroxychloroquine

Dilated Cardiomyopathy (DCM)

Diagnostic Criteria

• Left ventricular or biventricular dilation and impaired contraction
• Not explained by abnormal loading conditions or coronary artery disease 3

Etiologies

1. Genetic causes (35% of cases) 4

   • Mutations in genes encoding:
     • Cytoskeletal proteins
     • Sarcomeric proteins
     • Nuclear envelope proteins

2. Infectious causes 1

   • Viral myocarditis (parvovirus B19, human herpes virus 6, coxsackie B)
   • Chagas disease (Trypanosoma cruzi)
   • HIV-associated cardiomyopathy

3. Toxic causes 1

   • Alcohol (alcoholic cardiomyopathy)
   • Cocaine
   • Chemotherapeutic agents (anthracyclines)

4. Autoimmune diseases 1

   • Systemic lupus erythematosus
   • Scleroderma
   • Rheumatoid arthritis
   • Dermatomyositis
   • Polyarteritis nodosa

5. Other causes 1, 4

   • Tachycardia-induced cardiomyopathy
   • Peripartum cardiomyopathy
   • Nutritional deficiencies (thiamine, selenium, carnitine)
   • Endocrine disorders (thyroid disease, acromegaly)
   • Electrolyte disturbances (hypocalcemia)

Diagnostic Approach

Initial Evaluation

• Detailed family history (particularly important for genetic forms) 1
• Electrocardiogram (ECG) to detect abnormalities 1
• Echocardiography to assess:
  • Wall thickness
  • Chamber dimensions
  • Systolic and diastolic function
  • Presence of outflow tract obstruction (in HCM) 1

Advanced Imaging

• Cardiac MRI for tissue characterization:
  • Detection of myocardial fibrosis
  • Identification of infiltrative disease
  • Differentiation between ischemic and non-ischemic etiologies 1
• Nuclear imaging for:
  • Myocardial perfusion assessment
  • Differentiation between DCM and ischemic cardiomyopathy 1

Laboratory Testing

• Genetic testing for suspected hereditary forms 1
• Specialized laboratory tests based on clinical suspicion 1
• Endomyocardial biopsy when inflammation or infection is suspected 1, 3

Management Strategies

Hypertrophic Cardiomyopathy Management

Pharmacological Therapy

• First-line therapy: Non-vasodilating beta-blockers (e.g., propranolol) titrated to maximum tolerated dose 5
• Alternative therapies if beta-blockers are ineffective or contraindicated:
  • Verapamil (starting 40 mg TID, max 480 mg daily)
  • Disopyramide (400-600 mg/day) in combination with beta-blockers for persistent symptoms
  • Diltiazem (starting 60 mg TID, max 360 mg daily) 5

Invasive Therapies

• Surgical myectomy (preferred in patients <50 years)
• Alcohol septal ablation (alternative in appropriate candidates)
• Consider for refractory symptoms with resting or provoked LVOTO ≥50 mm Hg 5

Medications to Avoid

• Arterial and venous dilators (nitrates, phosphodiesterase inhibitors)
• Digoxin 5

Dilated Cardiomyopathy Management

General Approach

• Standard heart failure therapy based on guidelines 4
• Treatment targeted at underlying etiology when identified 1, 3

Specific Etiologies

1. Cardiac Sarcoidosis 1

   • Corticosteroids are recommended
   • Alternative immunosuppressive therapies (methotrexate, azathioprine, mycophenolate mofetil) for those who cannot tolerate corticosteroids
   • ICD implantation is reasonable

2. Alcoholic Cardiomyopathy 1

   • Total abstinence from alcohol
   • Standard heart failure therapy
   • Consider thiamine supplementation

3. Cocaine-Related Cardiomyopathy 1

   • Abstinence from cocaine
   • Standard therapy for LV dysfunction after 6 months of abstinence
   • Consider non-selective β-blockers with α-antagonism for patients at risk of relapse

4. Chagas Cardiomyopathy 1

   • Antiparasitic treatment (benznidazole or nifurtimox)
   • Standard heart failure therapy

5. Autoimmune Cardiomyopathy 1

   • Treatment of the underlying autoimmune condition
   • Standard heart failure therapy

Prognosis and Follow-up

• Regular assessment of symptom status
• Periodic echocardiography to evaluate ventricular function
• ECG monitoring for arrhythmias
• Assessment of medication side effects and tolerance 5
• Consider ICD implantation for prevention of sudden cardiac death in high-risk patients 5, 6
• Consider cardiac resynchronization therapy for appropriate candidates 3
• Heart transplantation for refractory cases 6, 3

Prevention Strategies

• Lifestyle modifications:
  • Weight loss in obese patients
  • Sodium restriction
  • Regular exercise (with caution in certain HCM cases)
  • Avoiding dehydration and excess alcohol consumption 5
• Early detection and treatment of subclinical disease may alter disease course 1
• Genetic counseling and cascade screening for family members of patients with genetic forms 1