What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis must be tailored to the specific type of amyloid protein involved, with daratumumab-CyBorD being the preferred first-line therapy for AL amyloidosis and tafamidis for ATTR amyloidosis. 1

Diagnosis and Classification

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

1. Initial Screening:

   • Serum and urine immunofixation electrophoresis
   • Serum free light chain assay 1
   • If monoclonal light chains are present → suspect AL amyloidosis
   • If no monoclonal light chains → proceed to bone scintigraphy for ATTR amyloidosis 1

2. Confirmation:

   • For suspected ATTR: Bone scintigraphy (Tc-99m-PYP scan) 1
   • For suspected AL: Tissue biopsy (fat pad, bone marrow, or cardiac) 1
   • TTR gene sequencing to differentiate hereditary from wild-type ATTR 1

Treatment of AL Cardiac Amyloidosis

First-line Therapy:

• Daratumumab-CyBorD (daratumumab, cyclophosphamide, bortezomib, and dexamethasone) is the preferred first-line treatment 1
• This regimen targets the abnormal plasma cells producing amyloidogenic light chains

Alternative Therapies:

• CyBorD (cyclophosphamide, bortezomib, and dexamethasone) if daratumumab is unavailable 1
• High-dose melphalan with autologous stem cell transplantation for selected eligible patients 1, 2

Eligibility for Stem Cell Transplantation:

• Consider for patients with:
  • Limited organ involvement
  • Good performance status
  • Absence of advanced cardiac disease 1

Treatment of ATTR Cardiac Amyloidosis

FDA-Approved Therapy:

• Tafamidis (either 61 mg once daily or 80 mg once daily as four 20-mg capsules) 3
  • Reduces cardiovascular mortality and hospitalizations
  • Indicated for both wild-type and hereditary ATTR-CM 3
  • Most effective when started early in the disease course 4

Newer Approved Option:

• Acoramidis (Attruby) - FDA-approved in November 2024
  • Near-complete TTR stabilizer (~96%)
  • Reduces all-cause mortality by up to 42% and cardiovascular hospitalizations by ~50% 4

Investigational Therapies:

• TTR silencers (patisiran, inotersen) - currently approved only for ATTRv with polyneuropathy 4
• TTR disruptors (doxycycline plus TUDCA, EGCG) - limited evidence for cardiovascular outcomes 4

Supportive Heart Failure Management

Recommended:

• Judicious diuresis for congestion management (with caution to avoid hypotension) 1
• Anticoagulation for patients with atrial fibrillation or history of embolic events 1

Use with Caution:

• Beta-blockers - only for rate control in atrial fibrillation; use cautiously as cardiac output may be heart rate dependent 1
• ACE inhibitors/ARBs - use with extreme caution due to risk of hypotension 1

Avoid:

• Digoxin - binds to amyloid fibrils causing increased toxicity risk 1
• Calcium channel blockers - can cause exaggerated hypotension and negative inotropic effects 1

Advanced Therapies for End-Stage Disease

• Cardiac transplantation - consider for selected patients with AL amyloidosis 1
• Combined heart-liver transplantation - consider for hereditary ATTR amyloidosis 1, 2

Monitoring and Follow-up

• Regular assessment of cardiac biomarkers (BNP, troponin)
• Echocardiography to evaluate disease progression
• For AL amyloidosis: Monitor hematologic response with serum free light chains 1
• For ATTR amyloidosis: Monitor for disease progression and treatment response

Common Pitfalls to Avoid

1. Delayed diagnosis - Maintain high index of suspicion in patients with HFpEF, especially with:

   • Left ventricular wall thickness ≥14 mm
   • Low QRS voltage on ECG despite increased wall thickness
   • History of carpal tunnel syndrome or spinal stenosis 1

2. Mismanagement of heart failure - Standard heart failure therapies may be poorly tolerated

   • Avoid aggressive diuresis leading to hypotension
   • Monitor closely for arrhythmias and conduction abnormalities 1

3. Failure to identify amyloid type - Treatment strategies differ dramatically between AL and ATTR

4. Missing hereditary forms - Always perform TTR gene sequencing in ATTR cases to identify hereditary variants requiring genetic counseling 1