What is the treatment approach for cardiac amyloidosis?

Treatment Approach for Cardiac Amyloidosis

Treatment for cardiac amyloidosis must be tailored to the specific type of amyloid protein involved, with tafamidis being the first-line treatment for ATTR cardiomyopathy and daratumumab-based regimens for AL amyloidosis. 1

Classification Before Treatment

Proper classification is essential before initiating treatment:

1. AL amyloidosis: Caused by immunoglobulin light chain deposits
2. ATTR amyloidosis: Caused by transthyretin protein deposits
   • ATTRwt (wild-type)
   • ATTRv (variant/hereditary)

Diagnostic Workup

• Tissue diagnosis (abdominal fat pad, gingiva, rectum, bone marrow, or affected organs)
• Immunohistochemistry
• Mass spectrometry (gold standard for typing)
• Cardiac biomarkers (BNP/NT-proBNP with 93% sensitivity, 90% specificity) 2, 1
• Genetic testing for hereditary forms

Imaging Techniques

• Echocardiography
• Nuclear imaging with Technetium Tc 99m
• Cardiac MRI with late gadolinium enhancement 2, 1

Treatment for AL Cardiac Amyloidosis

First-line treatment options:

• Daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) - achieves high rates of deep hematologic responses 1
• CyBorD alone (cyclophosphamide, bortezomib, dexamethasone) for patients who cannot tolerate daratumumab 1
• High-dose melphalan with autologous stem cell transplantation for eligible patients without significant cardiac involvement 1, 3

Treatment for ATTR Cardiac Amyloidosis

FDA-Approved Treatment

• Tafamidis - the only FDA-approved treatment for ATTR cardiomyopathy 1, 4, 3
  • Dosage: VYNDAQEL 80 mg orally once daily OR VYNDAMAX 61 mg orally once daily 4
  • Reduces cardiovascular mortality and hospitalization 1, 4
  • Well-tolerated with no significant side effects reported in clinical trials 1

Other Approaches

• TTR gene silencing approaches - suppress TTR protein production 1, 3
• Heart transplantation for end-stage disease 1, 3
  • Often combined with liver transplantation for ATTRv
  • 5-year survival rate: 50-80%

Symptom Management

• Diuretics - used judiciously as the mainstay of symptom management 1
• Anticoagulation - indicated for atrial fibrillation, embolic stroke/TIA, or intracardiac thrombus 1
• Use with caution or avoid: β-blockers, digoxin, calcium channel blockers, and ACE inhibitors/ARBs due to potential adverse effects 1

Monitoring and Follow-up

Monthly monitoring should include:

• Complete blood count
• Biochemistry
• NT-proBNP
• Troponin
• Serum-free light chain quantification 1

Every 6 months:

• Echocardiography with strain measurements
• Holter ECG 1

Important Considerations and Pitfalls

• Early diagnosis is crucial - treatments can modify but not reverse disease progression 3, 5
• Treatment-related mortality is a significant concern, particularly in patients with advanced cardiac involvement 1
• Medication management requires caution - patients with cardiac amyloidosis may be sensitive to standard heart failure medications 1
• Multidisciplinary approach - collaboration between cardiologists, hematologists, neurologists, nephrologists, and palliative care specialists is essential 1, 3
• Referral to specialized centers may be necessary for timely diagnosis, treatment initiation, and participation in clinical trials 3

Treatment Outcomes

• AL amyloidosis: Median survival exceeds 15 years in those achieving complete response with high-dose melphalan and stem cell transplantation 1
• ATTR amyloidosis: Tafamidis significantly reduces cardiovascular mortality and hospitalization 1, 4
• Untreated prognosis: Median survival from diagnosis is less than 6 months for AL and 3-5 years for ATTR amyloidosis 6