What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis depends on the specific type (AL or ATTR) and requires a targeted approach with daratumumab-based regimens for AL amyloidosis and tafamidis for ATTR amyloidosis as first-line therapies to reduce mortality and improve quality of life. 1

Diagnosis and Classification

Before initiating treatment, accurate typing of cardiac amyloidosis is essential:

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

Treatment of AL Cardiac Amyloidosis

AL amyloidosis results from a clonal plasma cell disorder requiring plasma cell-directed therapies:

1. First-line therapy: Daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 1

   • Goal: Eradicate pathological plasma cells and remove affected light chains
   • Monitoring: Regular assessment of hematologic response and cardiac biomarkers

2. Autologous stem cell transplantation (ASCT):

   • Consider for selected patients based on risk stratification
   • Not recommended for patients with advanced cardiac involvement (high NT-proBNP, troponin)
   • Requires careful patient selection to minimize treatment-related mortality 1

3. Alternative regimens for patients intolerant to first-line therapy:

   • Bortezomib-based regimens
   • Immunomodulatory agents (used cautiously due to potential cardiac toxicity)

Treatment of ATTR Cardiac Amyloidosis

TTR Stabilizers:

1. Tafamidis (Vyndaqel/Vyndamax):

   • First-line therapy for ATTR-CM
   • FDA-approved to reduce cardiovascular mortality and hospitalizations 2
   • Dosing: Either Vyndaqel 80 mg (four 20-mg capsules) or Vyndamax 61 mg once daily 2
   • Demonstrated 30% reduction in all-cause mortality compared to placebo 3

2. Diflunisal:

   • Alternative for patients who cannot use tafamidis
   • NSAID that binds to TTR tetramer, preventing dissociation
   • Contraindicated in patients with significant kidney impairment (eGFR <45 mL/min/1.73 m²) 3

3. Acoramidis (Attruby):

   • Novel TTR stabilizer that reduced all-cause mortality by up to 42% 3

TTR Silencers (for ATTRv with polyneuropathy):

1. Patisiran:

   • RNA interference therapy administered IV every 3 weeks (0.3 mg/kg)
   • Requires premedication with corticosteroids, acetaminophen, and antihistamines 3

2. Inotersen:

   • Antisense oligonucleotide administered SC weekly (284 mg)
   • Requires monitoring for thrombocytopenia and glomerulonephritis 3

3. Vutrisiran:

   • Administered SC every 3 months (25 mg) 3

Management of Cardiac Complications

1. Volume management:

   • Judicious diuresis for heart failure symptoms
   • Caution against overdiuresis to avoid hypotension 1

2. Anticoagulation:

   • Indicated for patients with atrial fibrillation regardless of CHA₂DS₂-VASc score
   • Consider even in sinus rhythm if atrial mechanical dysfunction is present 1

3. Medications to avoid:

   • Digoxin (binds to amyloid fibrils causing toxicity)
   • Calcium channel blockers (can cause exaggerated hypotension) 1

4. Use with caution:

   • Beta-blockers (may be useful to increase diastolic filling time)
   • ACE inhibitors/ARBs (may cause hypotension) 1

Advanced Therapies

1. Organ transplantation:

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

2. Experimental options:

   • Doxycycline plus TUDCA
   • Epigallocatechin-3-gallate (EGCG) from green tea 3

Monitoring and Follow-up

• Regular assessment of cardiac biomarkers (BNP/NT-proBNP, troponins)
• Echocardiographic evaluation every 6-12 months
• For AL amyloidosis: monitoring of free light chains and hematologic response
• For patients on TTR stabilizers/silencers: vitamin A supplementation (3,000 IU daily) 3

Treatment Algorithm

1. Confirm amyloid type (AL vs. ATTR)
2. For AL amyloidosis: Initiate Dara-CyBorD and assess eligibility for ASCT
3. For ATTR amyloidosis: Start tafamidis (or alternative if contraindicated)
4. Manage cardiac complications with appropriate medications
5. Consider advanced therapies for end-stage disease
6. Regular monitoring for disease progression and treatment response

Early diagnosis and prompt initiation of appropriate therapy are critical to improving survival and quality of life in patients with cardiac amyloidosis.