What is the appropriate workup and management for a patient with suspected restrictive cardiomyopathy?

Workup and Management of Restrictive Cardiomyopathy

The comprehensive workup for suspected restrictive cardiomyopathy should include detailed history, physical examination, 3-generation family history, electrocardiography, echocardiography, advanced imaging, and targeted testing to identify the underlying etiology, as this directly impacts treatment options and prognosis. 1

Initial Diagnostic Evaluation

History and Physical Examination

• Obtain a detailed cardiac history and 3-generation family history to identify relatives with cardiomyopathy or sudden death 1
• Document symptoms of:
  • Biventricular heart failure (dyspnea, orthopnea, edema)
  • Arrhythmias (palpitations)
  • Syncope
  • Chest pain
• Assess for systemic diseases associated with restrictive cardiomyopathy:
  • Amyloidosis (macroglossia, periorbital purpura, carpal tunnel syndrome)
  • Sarcoidosis (lymphadenopathy, pulmonary symptoms)
  • Hemochromatosis (skin pigmentation, diabetes, arthropathy)
  • Scleroderma (skin changes, Raynaud's phenomenon)
  • Neuromuscular disorders 2

Initial Testing

• 12-lead ECG: Look for conduction abnormalities, arrhythmias, low voltage (amyloidosis), or LVH patterns 3
• Transthoracic echocardiography (TTE): Gold standard initial test to assess:
  • Ventricular wall thickness
  • Diastolic function (restrictive filling pattern)
  • Atrial enlargement
  • Ventricular size (typically normal or reduced)
  • Systolic function (often preserved early in disease)
  • Valvular function 1, 3
• 24-48 hour ambulatory ECG monitoring: To detect ventricular arrhythmias and atrial fibrillation 3
• Laboratory studies:
  • Complete blood count with differential (eosinophilia)
  • Renal and liver function tests
  • Serum protein electrophoresis and free light chain assay (amyloidosis)
  • Iron studies (hemochromatosis)
  • Inflammatory markers (sarcoidosis)
  • Specific biomarkers: cardiac troponins and NT-proBNP 1

Advanced Diagnostic Testing

Cardiovascular Magnetic Resonance (CMR)

• Indicated when:
  • Echocardiography is inconclusive
  • Suspicion of infiltrative/storage disease
  • Need to assess myocardial fibrosis or specific tissue characterization
• Look for:
  • Late gadolinium enhancement patterns (specific for amyloidosis, sarcoidosis)
  • T1 mapping abnormalities
  • Extracellular volume quantification 1, 3

Nuclear Imaging

• Tc-DPD or Tc-PYP scintigraphy: High specificity for transthyretin cardiac amyloidosis
• FDG-PET/CT: Valuable for diagnosing cardiac sarcoidosis (89% sensitivity, 78% specificity) 1

Cardiac Catheterization

• Right and left heart catheterization to:
  • Confirm restrictive hemodynamics
  • Differentiate from constrictive pericarditis
  • Characteristic "square root sign" in pressure tracings
  • Elevated and equalized end-diastolic pressures 1

Endomyocardial Biopsy

• Indicated when non-invasive testing is inconclusive and specific diagnosis would alter management
• Essential for definitive diagnosis of:
  • Amyloidosis (Congo red staining)
  • Sarcoidosis (non-caseating granulomas)
  • Hemochromatosis (iron deposition)
  • Other infiltrative diseases 2, 4

Genetic Testing

• Consider in patients with family history of cardiomyopathy
• Particularly important for:
  • Hereditary transthyretin amyloidosis
  • Sarcomeric protein gene mutations
  • Desminopathies 4

Management Approach

General Measures

• Heart failure management:
  • Diuretics for congestion (use cautiously to avoid reducing preload excessively)
  • Heart rate control to optimize ventricular filling
  • Anticoagulation for all patients with atrial fibrillation 1

Disease-Specific Therapy

• Cardiac amyloidosis:
  • Tafamidis for transthyretin amyloidosis (reduces mortality and cardiovascular hospitalizations by 32%) 5
  • Chemotherapy for light chain amyloidosis
  • Consider autologous stem cell transplantation in selected cases 6
• Sarcoidosis:
  • Corticosteroids and immunosuppressive therapy
  • ICD for high-risk patients 1
• Hemochromatosis:
  • Iron chelation therapy 6, 7

Arrhythmia Management

• ICD implantation:
  • Recommended for patients with restrictive cardiomyopathy and sustained ventricular arrhythmias causing hemodynamic instability who are expected to survive >1 year with good functional status (Class I recommendation) 1
  • Consider in patients with light-chain amyloidosis or hereditary transthyretin amyloidosis with ventricular arrhythmias (Class IIa recommendation) 1

Advanced Therapies

• Consider cardiac transplantation in selected patients with:
  • Progressive heart failure despite optimal medical therapy
  • Absence of significant extracardiac disease
  • Good functional status otherwise 6

Follow-up and Monitoring

• Repeat echocardiography every 1-2 years in stable patients, sooner if clinical status changes
• Regular assessment for arrhythmias with ECG and ambulatory monitoring
• Monitor for progression of heart failure symptoms
• Disease-specific monitoring based on etiology 3

Important Considerations and Pitfalls

• Differentiate restrictive cardiomyopathy from constrictive pericarditis, as the latter is potentially curable with pericardiectomy 8
• Early recognition is critical, as disease-modifying therapies are now available for certain etiologies (particularly amyloidosis) 7
• Prognosis is generally poor without specific therapy, with 5-year survival rates similar in adults and children 1
• Risk factors for mortality include NYHA functional class, left atrial size, and male sex 1