What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis requires disease-specific therapy targeting the underlying amyloid protein type, with daratumumab-CyBorD being the preferred regimen for AL amyloidosis and tafamidis for ATTR cardiomyopathy. 1, 2

Diagnosis and Classification

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

1. Tissue confirmation: Obtain biopsy (abdominal fat pad, gingiva, rectum, bone marrow, or affected organs) with Congo red staining showing apple-green birefringence under polarized microscopy 1

2. Amyloid typing:

   • AL amyloidosis: Serum free light chain assay, serum/urine immunofixation electrophoresis, and bone marrow biopsy 1
   • ATTR amyloidosis: Technetium-99m pyrophosphate scan and genetic testing to differentiate wild-type from hereditary forms 1

Treatment by Amyloid Type

AL Amyloidosis Treatment

1. First-line therapy:

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

2. For eligible patients:

   • High-dose melphalan with autologous stem cell transplantation (HDM/SCT) should be considered 1, 3
   • Patient selection is critical - cardiac involvement is a major determinant of risk 1

3. Monitoring during treatment:

   • Regular assessment of hematologic response
   • Monitoring for cardiac decompensation
   • Tracking cardiac biomarkers (BNP, troponin) 1, 2

ATTR Amyloidosis Treatment

1. TTR stabilizers:

   • Tafamidis: FDA-approved for ATTR cardiomyopathy at 80 mg (VYNDAQEL) or 61 mg (VYNDAMAX) daily to reduce cardiovascular mortality and hospitalization 2, 4
   • Diflunisal: Alternative TTR stabilizer (not FDA-approved for this indication) 2

2. TTR silencers (for hereditary ATTR with polyneuropathy):

   • Patisiran: FDA-approved siRNA administered intravenously every three weeks 2
   • Vutrisiran: FDA-approved siRNA 2
   • Inotersen: FDA-approved antisense oligonucleotide administered subcutaneously weekly 2
   • All TTR silencers require vitamin A supplementation (3,000 IU daily) 2

3. For end-stage disease:

   • Consider heart transplantation (palliative)
   • For hereditary ATTR, consider liver transplantation or combined heart-liver transplantation 3, 5

Supportive Heart Failure Management

Cardiac amyloidosis requires specialized heart failure management:

1. Diuretics: Mainstay of therapy for fluid overload, but use cautiously to avoid hypotension 1, 2

2. Medications to use with caution or avoid:

   • Beta-blockers: Use cautiously as cardiac output is heart rate dependent; generally avoided in AL amyloidosis 1
   • ACE inhibitors/ARBs: Use with extreme caution or avoid due to hypotension risk 1
   • Calcium channel blockers: Avoid due to binding to amyloid fibrils causing exaggerated hypotension 1
   • Digoxin: Avoid due to binding to amyloid fibrils causing increased toxicity risk 1

3. Anticoagulation:

   • Indicated for patients with atrial fibrillation
   • Consider in patients with sinus rhythm who have evidence of atrial mechanical dysfunction 1, 2

Multidisciplinary Collaboration

Cardiac amyloidosis management requires coordination between:

• Cardiologists
• Hematologists
• Neurologists (especially for ATTR with neuropathy)
• Nephrologists (for renal involvement)
• Palliative care specialists 1, 2

Treatment Response Monitoring

1. AL amyloidosis:

   • Monitor hematologic response (serum free light chains)
   • Track cardiac biomarkers (BNP, troponin)
   • Watch for treatment-related cardiotoxicity 1, 2

2. ATTR amyloidosis:

   • Regular cardiac assessment
   • Monitor for disease progression
   • Ensure vitamin A supplementation for patients on TTR silencers 2

Common Pitfalls and Caveats

1. Diagnostic delays are common and detrimental - maintain high index of suspicion 6

2. Medication sensitivity - patients with cardiac amyloidosis are extremely sensitive to conventional heart failure medications 1

3. Treatment toxicity - many therapies have significant side effects requiring careful monitoring 1

4. Intracardiac thrombus risk is high even in sinus rhythm due to atrial mechanical dysfunction 1

5. Early treatment is crucial - patients treated earlier have better outcomes 2, 3

Early diagnosis and prompt initiation of disease-specific therapy are essential for improving survival and quality of life in patients with cardiac amyloidosis.