What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

Treatment for cardiac amyloidosis must be tailored to the specific amyloid type, with tafamidis as first-line therapy for ATTR amyloidosis and daratumumab-based regimens for AL amyloidosis to reduce mortality and improve quality of life. 1

Accurate Diagnosis and Typing

Proper treatment depends on accurate typing of cardiac amyloidosis:

• AL amyloidosis: Requires serum free light chain assay, serum and urine immunofixation electrophoresis 1
• ATTR amyloidosis: Diagnosed using bone scintigraphy in patients without evidence of monoclonal light chains 1
• Genetic testing is necessary to differentiate hereditary variant (ATTRv) from wild-type (ATTRwt) 1

Treatment Based on Amyloid Type

AL Amyloidosis Treatment

• First-line therapy: Daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 1, 2
• For eligible patients: High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) may be considered 1
  • Not recommended for patients with advanced cardiac involvement 1
• Treatment aims to eradicate pathological plasma cells and remove affected light chains 1

ATTR Amyloidosis Treatment

• First-line therapy: Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg orally once daily) 1, 3
  • Only FDA-approved therapy shown to improve cardiovascular outcomes in ATTR-CM
  • Reduces all-cause mortality (29.5% vs 42.9%) and cardiovascular-related hospitalizations (0.48 vs 0.70 per year) 1
• Alternative TTR stabilizer: Diflunisal for patients who cannot use tafamidis 1
• Newer option: Acoramidis (Attruby) - reduces all-cause mortality by up to 42% and cardiovascular hospitalizations by ~50% 1
• For ATTRv polyneuropathy: Consider TTR silencers (patisiran, inotersen, or vutrisiran) 1

Management of Cardiac Complications

• Heart failure symptoms: Judicious diuresis, avoiding overdiuresis to prevent hypotension 1
• Atrial fibrillation: Anticoagulation indicated regardless of CHA₂DS₂-VASc score 1
• Medications to avoid: Digoxin and calcium channel blockers 1
• Use with caution: Beta-blockers and ACE inhibitors/ARBs 1

Advanced Therapies for End-Stage Disease

• Heart transplantation: Consider for end-stage disease in selected patients 1
• Combined heart-liver transplantation: For hereditary ATTR 1
• Heart transplantation followed by bone marrow transplantation: For selected AL amyloidosis patients 1

Monitoring and Follow-up

• Regular assessment of neurological function and cardiac status every 6-12 months 1
• Monitor cardiac biomarkers (BNP/NT-proBNP and troponins) for disease progression and treatment response 1

Important Clinical Considerations

• Tafamidis may interact with BCRP substrates (e.g., methotrexate, rosuvastatin, imatinib) - monitor for toxicities 3
• Coordinated care between cardiology, hematology, and other specialties is essential 1
• Early diagnosis is critical as cardiac amyloidosis is rapidly progressive with median survival ranging from <6 months for untreated AL amyloidosis to 3-5 years for ATTR amyloidosis 4
• The economic value of tafamidis is low at current list prices (>$180,000 per QALY gained) 1

Common Pitfalls to Avoid

• Delayed diagnosis due to lack of clinical suspicion, especially in patients with heart failure with preserved ejection fraction 5
• Initiating treatment without accurate amyloid typing
• Overdiuresis leading to hypotension
• Using standard heart failure medications without caution
• Missing the opportunity for early intervention with disease-modifying therapies