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Cardiac Amyloidosis

In morning report this week, we discussed a case of a patient presenting with new heart failure with findings of restrictive cardiomyopathy that we found out later was due to cardiac amyloidosis.

Below are some key learning points that we discussed.

  1. Diagnostic Approach to Heart Failure with Preserved Ejection Fraction
  • DDx of HFpEF includes:
    • HTN
    • Valvular disease
    • Infiltrative diseases (Amyloid, Hemochromatosis, sarcoidosis, Glycogen storage diseases)
  • CAD
  • Hypertrophic cardiomyopathy
  • Pericardial disease (constrictive pericarditis)
  • Other causes of restrictive CM: e.g., carcinoid, scleroderma, endomyocardial fibrosis (e.g. secondary to hypereosinophilia or drugs), radiation, chemo, cancer

Approach to Restrictive Cardiomyopathy

Types of Amyloidosis

  1. Systemic Amyloidosis/ Light chain (AL) Amyloidosis: most common
  2. Transthyretin (TTR) Amyloidosis
  3. Serum Amyloid A (AA) = Secondary
    • Caused by chronic inflammation such as infection (TB), inflammation (untrreated RA); rarely cardiac
  4. Aβ2MG amyloidosis (Hemodialysis associated amyloidosis)

Signs and Symptoms of Amyloidosis

  • Amyloid is systemic! Involving multiple organs.
  • Extra cardiac manifestations:
    • Kidneys (proteinuria, renal failure)
    • Liver (Elevated ALP, hepatic failure)
    • GI tract (Dysphagia, constipation, malabsorption, GI bleeding)
    • HEENT: Macroglossia, may have OSA, carpal tunnel syndrome, voice/nail changes
    • Nerves (peripheral neuropathy, autonomic dysfunction)
    • MSK: Shoulder pad sign
    • Cardiac dysfunction:
      • HFpEF >>HFrEF
      • Conduction disease with heart block, tachyarrhythmias and low voltage on ECG
      • LVH and LV mass on TTE
      • Elevated BNP, elevated troponin (destruction cardiomyocytes)
      • Combination of increased LV mass & low voltage is very specific for amyloid!

Investigations

  • CBC, lytes, creatinine, urinalysis/ACR/24 hour urine, liver function tests
  • SPEP, serum immunofixation and free light chain assay
  • BNP, troponin, ECG –> In AL cardiac amyloidosis, staging is based on troponin and BNP
  • Echocardiogram +/- cardiac MRI
  • Biopsy is gold standard: bone marrow biopsy +/- cardiac or noncardiac biopsy
    • E.g., Fat pad biopsy (AL amyloid; sensitivity of ~70%) or Endomesial biopsy (gold standard, most invasive)
  • If no plasma cell dyscrasia, may do nuclear update assessment and then consider genetic testing for TTR mutation

Management of AL Cardiac Amyloidosis

  • Goal: 1) Treat consequences of organ dysfunction
      2) Slow progression- target clonal plasma cells
  • Cardiac (BNP, troponin) and hematologic parameters are prognostic

CHF treatment

  • Avoid BB/CCB/Digoxin
  • Intolerance of ACE inhibitors
  • Spironolactone
  • Salt restriction
  • Midodrine
  • Consider heart transplant/LVAD, CRT-D

Chemotherapy for AL Amyloidosis

  • Most common regimen is CyBorD = bortezomib with cyclophophadmide, dexamethasone
  • In one study, only 17% with cardiac involvement responded
  • Rarely, stem cell transplant may be considered
  • ATTR amyloid treated differently

Further Reading:

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