What are the treatment options for cardiac amyloidosis?

Treatment for Cardiac Amyloidosis

The treatment of cardiac amyloidosis depends on the specific type, with daratumumab-CyBorD being the preferred regimen for AL amyloidosis and tafamidis or acoramidis being the first-line therapy for ATTR cardiomyopathy. 1, 2

Diagnosis and Classification

Before initiating treatment, proper diagnosis and classification of cardiac amyloidosis is essential:

• AL Amyloidosis: Requires demonstration of a plasma cell disorder through:

  • Serum free light chain assay
  • Serum/urine immunofixation electrophoresis
  • Bone marrow biopsy showing clonal proliferation of lambda or kappa-producing plasma cells 1

• ATTR Amyloidosis: Diagnosed through:

  • Technetium-99m pyrophosphate scan
  • Genetic testing to differentiate between hereditary (ATTRv) and wild-type (ATTRwt) forms 2

Treatment of AL Cardiac Amyloidosis

AL amyloidosis treatment targets the underlying plasma cell disorder:

1. First-line therapy:

   • Daratumumab-CyBorD (daratumumab with cyclophosphamide, bortezomib, and dexamethasone) is the preferred regimen 1, 2
   • CyBorD alone (cyclophosphamide, bortezomib, and dexamethasone) is an alternative option

2. For eligible patients:

   • High-dose melphalan with autologous stem cell transplantation (SCT) may be considered
   • Patient selection is critical, with cardiac involvement being a major determinant of risk 1, 2

3. Monitoring during treatment:

   • Regular assessment of hematologic response
   • Monitoring for cardiac decompensation, including heart failure, atrial arrhythmias, or thromboembolism 1

Treatment of ATTR Cardiac Amyloidosis

ATTR amyloidosis treatment focuses on stabilizing transthyretin or reducing its production:

1. TTR Stabilizers:

   • Tafamidis (Vyndaqel/Vyndamax): FDA-approved for ATTR cardiomyopathy to reduce cardiovascular mortality and hospitalization 2, 3
   • Acoramidis (Attruby): Recently FDA-approved TTR stabilizer that reduced all-cause mortality by up to 42% and cardiovascular hospitalizations by ~50% 2
   • Diflunisal: Alternative TTR stabilizer (not FDA-approved for this indication) 2

2. TTR Silencers (for ATTRv polyneuropathy):

   • Patisiran
   • Vutrisiran
   • Inotersen
   • Note: Vitamin A supplementation (3,000 IU daily) is essential for patients on TTR silencers 2

3. Advanced options:

   • Organ transplantation: Liver transplantation for hereditary ATTR or combined cardiac and liver transplantation, with 5-year survival rates of 50-80% in selected patients 2

Supportive Management of Cardiac Amyloidosis

Regardless of amyloidosis type, supportive care is crucial:

1. Heart failure management:

   • Diuretics: Mainstay of therapy for fluid overload (use with caution to avoid hypotension) 2
   • Caution with standard heart failure medications:
     • Beta-blockers, ACE inhibitors/ARBs, calcium channel blockers, and digoxin should be used cautiously or avoided due to risk of hypotension or increased toxicity 2

2. Anticoagulation:

   • Indicated for patients with atrial fibrillation
   • Consider in patients with sinus rhythm who have evidence of atrial mechanical dysfunction 2

Monitoring and Follow-up

• Regular assessment of hematologic response in AL amyloidosis
• Monitoring for cardiac decompensation during therapy
• Tracking cardiac biomarkers
• Multidisciplinary collaboration between cardiologists, hematologists, neurologists, nephrologists, and palliative care specialists 1, 2

Treatment Considerations and Pitfalls

• Early diagnosis and treatment are crucial as patients treated earlier have better outcomes
• Corticosteroids (like dexamethasone and prednisone) can cause peripheral edema, pulmonary edema, and fluid overload in cardiac amyloidosis patients 1
• Proteasome inhibitors like bortezomib may cause Grade 3 heart failure in some patients 1
• No absolute contraindications to plasma cell-directed therapies based on ejection fraction or cardiac status in AL cardiac amyloidosis, but close monitoring is essential 1