Treatment of Cardiac Amyloidosis
Treatment of cardiac amyloidosis should be tailored to the specific amyloid type, with daratumumab-CyBorD as the preferred regimen for AL amyloidosis and tafamidis as the first-line therapy for ATTR cardiomyopathy. 1
Diagnosis and Classification
Before initiating treatment, proper diagnosis and classification of cardiac amyloidosis is essential:
- Confirm amyloidosis through tissue biopsy with Congo red staining showing apple-green birefringence under polarized microscopy
- Determine amyloid type:
- For AL amyloidosis: Serum free light chain assay, serum/urine immunofixation electrophoresis (not just protein electrophoresis), and bone marrow biopsy
- For ATTR amyloidosis: Technetium-99m pyrophosphate scan and genetic testing to differentiate wild-type from hereditary forms
Treatment by Amyloid Type
AL Amyloidosis Treatment
First-line therapy:
- Daratumumab-CyBorD (daratumumab with cyclophosphamide, bortezomib, and dexamethasone) is the preferred regimen 2
- Alternative: CyBorD alone (cyclophosphamide, bortezomib, and dexamethasone)
For eligible patients:
- Consider high-dose melphalan with autologous stem cell transplantation (SCT) 2
- Patient selection is critical, with cardiac involvement being a major determinant of risk
Monitoring during treatment:
- Regular assessment of hematologic response
- Monitor for cardiac decompensation, which may include heart failure, atrial arrhythmias, or thromboembolism
- Track cardiac biomarkers
ATTR Amyloidosis Treatment
TTR stabilizers:
- Tafamidis - FDA-approved for ATTR cardiomyopathy to reduce cardiovascular mortality and hospitalization 3
- Diflunisal - Alternative TTR stabilizer (not FDA-approved for this indication)
TTR silencers (for hereditary ATTR with polyneuropathy):
- Patisiran - FDA-approved siRNA administered intravenously every three weeks
- Vutrisiran - FDA-approved siRNA
- Inotersen - FDA-approved antisense oligonucleotide administered subcutaneously weekly
- All TTR silencers require vitamin A supplementation (3,000 IU daily)
Advanced options:
- Organ transplantation (heart, liver, or combined) for selected patients with 5-year survival rates of 50-80%
Management of Cardiac Complications
Heart Failure Management
- Diuretics are the mainstay for managing fluid overload, but use with caution to avoid hypotension
- Standard heart failure medications require special consideration:
- Beta-blockers: Use with caution or avoid due to risk of hypotension
- ACE inhibitors/ARBs: Use with caution due to risk of hypotension
- Calcium channel blockers: Generally avoid due to negative inotropic effects
- Digoxin: Use with caution due to increased toxicity risk from binding to amyloid fibrils
Arrhythmia Management
- Anticoagulation is indicated for patients with atrial fibrillation
- Consider anticoagulation even in sinus rhythm if evidence of atrial mechanical dysfunction
- Amiodarone may be used for rhythm control in selected patients
Multidisciplinary Approach
Cardiac amyloidosis management requires collaboration between:
- Cardiologists
- Hematologists
- Neurologists
- Nephrologists
- Palliative care specialists
Pitfalls and Caveats
Diagnostic pitfalls:
- Don't rely solely on SPEP/UPEP to exclude AL amyloidosis; use serum free light chain assay and immunofixation electrophoresis 2
- Misdiagnosis can have catastrophic consequences
Treatment pitfalls:
- Corticosteroids can worsen fluid retention and heart failure
- Proteasome inhibitors may cause cardiac toxicity
- Immunomodulatory agents can cause paradoxical increases in cardiac biomarkers
Monitoring pitfalls:
- Failure to monitor for treatment-related cardiotoxicity
- Inadequate assessment of hematologic response in AL amyloidosis
Early diagnosis and prompt initiation of appropriate therapy are crucial for improving outcomes in cardiac amyloidosis, as patients treated earlier have significantly better survival rates 1.