What are the treatment options for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis must be tailored to the specific type (AL or ATTR), with daratumumab-based regimens being the preferred first-line therapy for AL amyloidosis and tafamidis or acoramidis for ATTR amyloidosis. 1

Determining Amyloid Type

Before initiating treatment, it's essential to identify the specific type of amyloidosis:

1. Tissue diagnosis: Obtain tissue sample through biopsy (abdominal fat pad, gingiva, rectum, bone marrow, or affected organs) 1
2. Amyloid typing:
   • Mass spectrometry (gold standard) with 88% sensitivity and 96% specificity 1
   • Immunohistochemistry to differentiate between AL, ATTR, and other types 1
3. For suspected AL amyloidosis: Complete monoclonal protein screen with:
   • Serum free light chain (sFLC) assay
   • Serum immunofixation electrophoresis (SIFE)
   • Urine immunofixation electrophoresis (UIFE) 1

Treatment Algorithm for AL Cardiac Amyloidosis

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

2. For transplant-eligible patients:

   • Evaluate for high-dose melphalan with autologous stem cell transplantation (HDM/SCT)
   • Eligibility criteria: Lower risk for treatment-related morbidity and mortality
   • Cardiac involvement is a major determinant of risk 1

3. Monitoring during treatment:

   • Assess hematologic response regularly
   • Monitor for cardiac decompensation (heart failure, arrhythmias)
   • Watch for treatment-related cardiotoxicity 1

4. For advanced disease:

   • Consider heart transplantation in selected cases
   • For hereditary forms, combined heart-liver transplantation may be needed 2

Treatment Algorithm for ATTR Cardiac Amyloidosis

1. First-line therapy: TTR stabilizers

   • Tafamidis: FDA-approved, available as tafamidis meglumine (80 mg daily) or tafamidis (61 mg daily) 3
   • Acoramidis: Newer TTR stabilizer with ~96% stabilization efficiency 3

2. Patient selection for TTR stabilizers:

   • Indicated for wild-type or variant ATTR-CM
   • NYHA class I-III heart failure symptoms
   • Not recommended for: NYHA class IV symptoms, severe aortic stenosis, or eGFR <25 mL/min/1.73 m² 3

3. For hereditary ATTR:

   • Genetic counseling and family screening
   • Consider liver transplantation (especially for younger patients) 4

Supportive Heart Failure Management

1. Volume management:

   • Diuretics: Mainstay of therapy but use cautiously due to risk of hypotension 1
   • Monitor for intravascular volume depletion

2. Medications to use with caution or avoid:

   • ACE inhibitors/ARBs: Use with extreme caution or avoid due to hypotension risk 1
   • β-blockers: May be used cautiously to control heart rate in atrial fibrillation but avoid with severe restrictive physiology 1
   • Calcium channel blockers: Avoid due to binding to amyloid fibrils 1
   • Digoxin: Avoid due to binding to amyloid fibrils and risk of toxicity even with normal serum levels 1

3. Anticoagulation:

   • Indicated for patients with atrial fibrillation
   • Consider even in sinus rhythm if evidence of atrial mechanical dysfunction or intracardiac thrombus 1

Monitoring and Follow-up

1. Cardiac biomarkers: B-type natriuretic peptide and cardiac troponins for disease monitoring 5

2. Imaging surveillance:

   • Echocardiography with strain assessment
   • Cardiac MRI when appropriate 6

3. Multidisciplinary collaboration:

   • Cardiology and hematology for AL amyloidosis
   • Consider geriatrics and palliative care involvement 1

Common Pitfalls to Avoid

1. Diagnostic delays: Cardiac amyloidosis is often diagnosed late, which significantly worsens outcomes 7

2. Misdiagnosis: MGUS with ATTR cardiac amyloidosis requires careful typing to avoid misdiagnosis 1

3. Inappropriate medication use: Standard heart failure medications may cause harm in cardiac amyloidosis 1

4. Overlooking anticoagulation needs: Higher risk of intracardiac thrombus even in sinus rhythm 1

5. Failing to monitor treatment toxicity: Chemotherapy agents for AL amyloidosis can have significant cardiac toxicity 1

By following this treatment approach and working within a multidisciplinary team, outcomes for patients with cardiac amyloidosis can be significantly improved compared to historical prognoses.