What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis requires specific therapy directed at the underlying amyloid type, with daratumumab-CyBorD being the preferred treatment for AL amyloidosis and tafamidis for ATTR amyloidosis. 1

Diagnosis and Classification

Before initiating treatment, proper diagnosis and classification of the amyloid type is essential:

1. Tissue diagnosis: Obtain tissue confirmation through 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:

   • For suspected AL amyloidosis: Serum free light chain (sFLC) assay, serum and urine immunofixation electrophoresis (SIFE, UIFE), and bone marrow biopsy 1
   • For suspected ATTR amyloidosis: Technetium-99m pyrophosphate (PYP) scan and genetic testing to differentiate between wild-type and hereditary forms 1

Treatment Based on Amyloid Type

AL Amyloidosis Treatment

1. First-line therapy:

   • Daratumumab-CyBorD (daratumumab with cyclophosphamide, bortezomib, and dexamethasone) is the preferred regimen 1
   • Alternative: CyBorD alone (cyclophosphamide, bortezomib, and dexamethasone) 1

2. Stem cell transplantation:

   • Consider high-dose melphalan with autologous stem cell transplantation (HDM/SCT) for eligible patients 1
   • Patient selection is critical - cardiac involvement is a major determinant of risk 1
   • Eligibility assessment should include cardiac function evaluation

3. Monitoring:

   • Regular assessment of hematologic response
   • Monitoring for cardiac decompensation during therapy
   • Cardiac biomarkers (BNP, troponin) to track disease progression 1

ATTR Amyloidosis Treatment

1. TTR stabilizers:

   • Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg orally once daily) - FDA approved for ATTR cardiomyopathy to reduce cardiovascular mortality and hospitalization 2, 3
   • Acoramidis (Attruby) - Recently approved TTR stabilizer 3
   • Diflunisal - Alternative stabilizer (not FDA approved for this indication) 3

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

   • Patisiran - IV administration every three weeks 3
   • Vutrisiran - FDA approved for ATTRv polyneuropathy 3
   • Inotersen - Weekly subcutaneous administration 3

3. Advanced options:

   • Organ transplantation: Heart transplantation for end-stage disease
   • Combined heart-liver transplantation for hereditary ATTR 3

Supportive Heart Failure Management

Heart failure management in cardiac amyloidosis differs from standard approaches:

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

2. Medications to use with caution or avoid:

   • Beta-blockers: Use cautiously or avoid, especially in AL amyloidosis, as cardiac output is heart rate dependent 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

Multidisciplinary Approach

Cardiac amyloidosis management requires collaboration between:

• Cardiologists
• Hematologists (for AL amyloidosis)
• Neurologists (for ATTR with neuropathy)
• Nephrologists (for renal involvement)
• Palliative care specialists 1

Treatment Monitoring and Follow-up

1. AL amyloidosis:

   • Monitor hematologic response to therapy
   • Track cardiac biomarkers (BNP, troponin)
   • Watch for treatment-related cardiotoxicity 1

2. ATTR amyloidosis:

   • Regular cardiac assessment (echocardiography, biomarkers)
   • For patients on TTR silencers: vitamin A supplementation (3,000 IU daily) 3

Common Pitfalls to Avoid

1. Diagnostic delays: Early diagnosis is critical for improved outcomes
2. Misdiagnosis: Ensure proper typing of amyloid (AL vs. ATTR)
3. Inappropriate medication use: Standard heart failure medications may be poorly tolerated
4. Overlooking multisystem involvement: Assess for non-cardiac manifestations
5. Missing ATTR in elderly patients: Consider cardiac amyloidosis in elderly patients with heart failure with preserved ejection fraction

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