Treatment of Cardiac Amyloidosis
The first-line treatment for cardiac amyloidosis must be tailored to the specific type, with tafamidis (VYNDAQEL 80mg or VYNDAMAX 61mg daily) or acoramidis (Attruby) recommended for ATTR cardiac amyloidosis, and daratumumab plus CyBorD (cyclophosphamide, bortezomib, dexamethasone) for AL amyloidosis. 1
Diagnosis and Classification - Critical First Step
Accurate typing of cardiac amyloidosis is essential before initiating treatment:
Initial screening:
- Serum and urine immunofixation electrophoresis
- Serum free light chain assay 1
For ATTR amyloidosis confirmation:
- Bone scintigraphy (Tc-99m-PYP)
- TTR gene sequencing to differentiate hereditary variant (ATTRv) from wild-type (ATTRwt) 1
For definitive diagnosis:
- Tissue confirmation through biopsy with Congo red staining showing apple-green birefringence under polarized microscopy 1
Treatment Approach by Amyloidosis Type
1. ATTR Cardiac Amyloidosis Treatment
First-Line Therapies:
Tafamidis (80 mg VYNDAQEL or 61 mg VYNDAMAX orally once daily)
Acoramidis (Attruby)
- Novel TTR stabilizer
- Reduces all-cause mortality by up to 42%
- Reduces cardiovascular hospitalizations by ~50% over 30-42 months 1
Alternative Options:
- Diflunisal - TTR stabilizer (not FDA-approved for this indication) 1
- TTR silencers (require vitamin A supplementation):
- Patisiran
- Inotersen
- Vutrisiran 1
2. AL Cardiac Amyloidosis Treatment
- Standard of care: Daratumumab + CyBorD (cyclophosphamide, bortezomib, dexamethasone)
- Achieves very good partial responses or better in 78.5% of patients 1
- For eligible patients: Consider high-dose melphalan with stem cell transplantation 3
Symptomatic Management
Heart Failure Management
- Diuretics: Mainstay for volume management
- Loop diuretics (torsemide or bumetanide preferred over furosemide when intestinal wall edema is present) 1
- ACE inhibitors/ARBs: May be used for anti-proteinuric effects if blood pressure permits
- Use with caution as traditional heart failure medications may be poorly tolerated 1
Neuropathic Pain Management
- Pregabalin
- Gabapentin
- Duloxetine
- Tricyclic antidepressants (use cautiously due to risk of worsening orthostatic hypotension) 1
Orthostatic Hypotension Management
- Midodrine
- Droxidopa
- Pyridostigmine (preferred in patients with heart failure) 1
Anticoagulation
- Anticoagulation is recommended for atrial fibrillation regardless of CHA₂DS₂-VASc score 1
Advanced Treatment Options
Heart transplantation: Consider for selected patients with advanced/stage D heart failure
- Contraindications: significant extracardiac manifestations and uncontrolled disease 1
Combined heart and liver transplantation: Consider for selected patients with hereditary ATTR 1
Mechanical circulatory support: Generally poorly tolerated due to small LV cavity and biventricular involvement 1
Monitoring
- Regular assessment every 6-12 months:
- Cardiac biomarkers
- Echocardiography
- Functional status 1
Important Considerations and Pitfalls
Diagnostic delay: Cardiac amyloidosis is often diagnosed late, leading to worse outcomes. Early diagnosis is critical for effective treatment 4
Treatment intolerance: Patients with advanced cardiac disease may have difficulty tolerating therapies, requiring close monitoring and dose adjustments 3
Economic considerations: Tafamidis has low economic value at current list prices (>$180,000 per QALY gained) 1, which may impact access for some patients
Pregnancy considerations: Tafamidis may harm unborn babies; pregnant women should report pregnancies to the Pfizer reporting line 2
Breastfeeding: Not recommended during treatment with tafamidis 2
The management of cardiac amyloidosis has evolved significantly in recent years, with disease-modifying therapies now available that can substantially improve outcomes when initiated early in the disease course.