Cardiac amyloidosis

• Deposition of abnormally folded protein in the extracellular compartment
• Proteins implicated are:
  • • Transthyretin (ATTR)
      • • Wild type presents late
        • Variant type is due to genetic mutation and presents earlier and with neuropathy as well eg. v122I variant)
    • Primary light chain amyloid
      • • Commonly associated with MGUS or myeloma

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Clinical features

• Heart failure, syncope, bradycardia
• Increased risk of calcific aortic stenosis (12% of patients with severe AS being considered for a TAVI have amyloid)
• Patient may be previously hypertensive and now hypotensive or normotensive
• Can be peripheral neuropathy and dysautonomia
• ATTR is associated with deafness, carpal tunnel, spinal stenosis
• AL amyloid is associated with macroglossia, bruising, CKD

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Diagnosis

• Usually made through non-invasive tests
• There is a role for biopsy – fat or endomyocardial
• Often elevated troponin and BNP (disproportionate to degree of HF)
• ECG may show pseudo-infarct low voltage QRS, AV conduction disease
• Echo
  • • Concentric LVH (wall thickness >12mm)
    • Bi-atrial dilatation
    • Small pericardial effusion (rarely of any haemodynamic significance)
    • Atrial septal thickening
    • Granular or sparkling myocardium (non-specific)
    • Reduced longitudinal strain with apical sparing
    • Reduced stroke / end-diastolic volume but typically preserved LVEF
    • Aortic stenosis
• Cardiac MRI can be very specific for amyloid
• Cardiac CT can also be useful (measuring the ECV, if <31% amyloid is unlikely) – reasonable sensitivity and specificity
• DPD bone scintigraphy – The Perugini grading scale
  • • A semi-quantitative method of scoring cardiac uptake following injection of 99mTc-DPD
    • >99% sensitive for cardiac TTR amyloid
    • 68% sensitive in other types
    • Grades 0 to 3
    • It doesn’t tell you which type of amyloid
• Check for monoclonal proteins – do myeloma screen (serum and urine immunofixation not just electrophoresis, and serum free light chains)
• Family screening if genetic mutation found
• Differential
  • • Appearance can be confused with hypertensive heart disease, HCM and the cardiac changes associated with aortic stenosis
    • Cardiac sarcoid and cardiac lymphoma are also differentials

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Prognosis and treatment

• BNP and troponin are prognostic markers (if BNP >8500 = poor prognosis)
• Maintain euvolemia. Avoid CCBs
• For AL cardiac amyloid
  • • 70% mortality at 2 years
    • Chemotherapy +/- stem cell transplant
    • Discuss with haematology
• For TTR amyloid
  • • Little role for usual heart failure therapies (betablockers poorly tolerated as conduction disease common)
    • Rate limiting medications may be contraindicated eg. digoxin, CCBs
    • Try diuretics
    • Consider device if conduction problems
    • Consider TAVI if co-existing AS
    • Some novel therapies – tafamidis (available on NHS. Costs £10,000 for 30 tablets, used if genetically proven and NYHA I or II), ASO, siRNA