Treatment Options for Cardiac Amyloidosis
Treatment for cardiac amyloidosis should be tailored to the specific type of amyloid protein involved, with tafamidis being the first-line therapy for ATTR cardiomyopathy and daratumumab-based regimens being the preferred first-line treatment for AL amyloidosis. 1
Classification of Cardiac Amyloidosis
Proper classification is essential before initiating treatment:
- AL amyloidosis: Caused by immunoglobulin light chain deposits
- ATTR amyloidosis: Caused by transthyretin protein deposits
- ATTRwt (wild-type)
- ATTRv (variant/hereditary)
Diagnostic workup should include:
- Tissue diagnosis with Congo red staining
- Immunohistochemistry for amyloid typing
- Mass spectrometry (gold standard for typing)
- Cardiac biomarkers (BNP/NT-proBNP, Troponin)
- Genetic testing for hereditary forms
Treatment for ATTR Cardiac Amyloidosis
FDA-Approved Therapies
- Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg daily): The only FDA-approved treatment for ATTR cardiomyopathy (both wild-type and hereditary) 2
- Reduces cardiovascular mortality and cardiovascular-related hospitalization
- Well-tolerated with no significant side effects reported in clinical trials
Emerging Therapies
- Acoramidis: Recently approved TTR stabilizer 1
- TTR gene silencing approaches: Suppress TTR protein production 3
- TTR stabilizers: Prevent TTR tetramer dissociation into fibrils 3
Historical Treatments
- Liver transplantation: Previously the only option for ATTRv disease (5-year survival rate of 50-80%) 1
- Heart transplantation: For end-stage disease, often with combined heart-liver transplantation for ATTRv 3
Treatment for AL Cardiac Amyloidosis
First-Line Therapies
- Daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD): Preferred first-line treatment 1
- Achieves high rates of deep hematologic responses
Alternative Options
- CyBorD alone: For patients who cannot tolerate daratumumab 1
- High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT): For eligible patients without significant cardiac involvement 1
- Eligibility criteria: LVEF >40%, ability to handle fluid shifts
- Only about 25% of newly diagnosed patients are eligible
- Median survival >15 years in those achieving complete response
Supportive Care for Cardiac Amyloidosis
Heart Failure Management
- Diuretics: Mainstay of symptom management, used judiciously 1
- Medications to use with caution or avoid:
- β-blockers
- Digoxin
- Calcium channel blockers
- ACE inhibitors/ARBs
Anticoagulation
- Indicated for atrial fibrillation, embolic stroke/TIA, or intracardiac thrombus
- Benefits must be weighed against increased bleeding risk in amyloid angiopathy 1
Palliative Care Integration
Palliative care should be integrated early in the disease course for:
- Assessment of goals, values, and preferences
- Symptom management
- Psychological relief
- Support system for family 3
Patients should be referred to palliative care at any stage when physical symptoms (intractable heart failure, neuropathy, orthostasis, GI distress) or emotional/spiritual distress interfere with quality of life 3
Monitoring and Follow-up
- Monthly monitoring: CBC, biochemistry, NT-proBNP, troponin, and serum-free light chain quantification
- Every 6 months: Echocardiography with strain measurements and Holter ECG 1
- Monitor for treatment-related toxicities, especially cardiac effects
Multidisciplinary Approach
Cardiac amyloidosis management requires collaboration between:
- Cardiologists
- Hematologists
- Neurologists
- Nephrologists
- Palliative care specialists 1
This team-based approach is essential for optimizing treatment outcomes and improving quality of life for patients with this complex disease.