cardiac amyloidosis

Epidemiology

• 90% of patients with primary amyloidosis have cardiac involvement
• AL amyloidosis, transthyretin cardiac amyloidosis

Pathology

• heart is often enlarged
• thickened ventricular myocardium due to infiltration
• atria tend to enlarge
• conduction system abnormalities
• amyloid deposits in the cardiac valves
• mitral & tricuspid regurgitation common
• diastolic dysfunction: restrictive cardiomyopathy
• intractable biventricular failure

Clinical manifestations

• congestive heart failure
• arrhythmias
• sudden death
• angina
• pericardial effusion
• hepatomegaly & peripheral edema associated with right heart failure
• murmurs of mitral & tricuspid regurgitation
• manifestations of systemic amyloidosis
  • peripheral neuropathy, bilateral carpal tunnel syndrome

Laboratory

• urinalysis
• complete blood count (CBC) generally shows anemia
• serum & urine protein electrophoresis to rule out myeloma
• biopsy
  • aspiration of abdominal fat pad (first line)
  • myocardial biopsy (last resort)
• amyloid amyloid typing
  • Val122Ile mutation in transthyretin gene is most common variant in hereditary cardiac amyloidosis*
    • TTR gene sequencing

* MGUS may co-occur with hereditary cardiac amyloidosis

Diagnostic procedures

• Electrocardiography:
  • low QRS voltage
• Echocardiography
  • increased ventricular wall thickness
  • no cavity dilatation
  • granular appearance of ventricular myocardium
  • atria are usually dilated
  • cardiac valves may be thickened
  • mitral & tricuspid regurgitation is common
  • prolonged ventricular relaxation in early stages with important contribution to ventricular filling from atrial contraction
  • in later stages, rapid early filling suggest restrictive cardiomyopathy
  • >= grade 2 diastolic dysfunction,

Radiology

• cardiac magnetic resonance imaging
• cardiac technetium-99m pyrophosphate scintigraphy diagnostic for transthyretin cardiac amyloidosis

Differential diagnosis

• cardiac sarcoidosis

Management

• colchicine for familial forms of cardiac amyloidosis
• treatment of light chain amyloidosis (AL amyloidosis)
• intermittent combination of prednisone & melphalan
  • most successful when initiated prior to onset of heart failure & when myeloma is present
• disease recurs in cardiac transplants within 2 years
• stem cell transplantation may be an option for patients with AL amyloidosis identified before the onset of heart failure
• mean survival of untreated patients with heart failure is 6 months

More general terms

• amyloidosis

More specific terms

• transthyretin cardiac amyloidosis; amyloid transthyretin cardiomyopathy (ATTR-CM)

Additional terms

• restrictive cardiomyopathy