What is the initial treatment for Cardiac Amyloidosis?

Initial Treatment for Cardiac Amyloidosis

The initial treatment for cardiac amyloidosis depends on the specific type, with tafamidis (80 mg VYNDAQEL or 61 mg VYNDAMAX orally once daily) being the first-line treatment for ATTR cardiac amyloidosis, while daratumumab-CyBorD is the standard of care for newly diagnosed AL amyloidosis. 1

Treatment Based on Amyloidosis Type

ATTR Cardiac Amyloidosis (Wild-type or Hereditary)

• First-line therapy:

  • Tafamidis 80 mg (four 20-mg capsules of VYNDAQEL) or 61 mg (one capsule of VYNDAMAX) orally once daily 2
  • Reduces cardiovascular mortality and cardiovascular-related hospitalizations 2
  • Long-term data shows significantly better survival with early tafamidis treatment compared to delayed treatment (hazard ratio 0.59,95% CI 0.44-0.79, P<0.001) 3

• Efficacy considerations:

  • Both 80 mg and 20 mg doses reduce mortality and hospitalizations, but longer-term data supports 80 mg as the optimal dose 4
  • Real-world data confirms tafamidis is associated with reduced heart failure exacerbations and all-cause mortality 5
  • Most effective when initiated early, particularly in NYHA class I-II patients 6, 3

AL Cardiac Amyloidosis

• First-line therapy:

  • Daratumumab (anti-CD38 monoclonal antibody) plus CyBorD (cyclophosphamide, bortezomib, dexamethasone) 1
  • Produces very good partial responses or better in 78.5% of patients vs. 49.2% with CyBorD alone 1

• Alternative regimens:

  • CyBorD alone
  • Bortezomib-melphalan-dexamethasone
  • For advanced cardiac involvement: single-agent daratumumab with minimal dexamethasone 1

Treatment Considerations by NYHA Functional Class

NYHA Class I-II

• Tafamidis is strongly recommended (Class I, Level of Evidence: B) 6
• Shows clear mortality benefit in this population 3

NYHA Class III

• Recommendations vary between guidelines:
  • ESC: Recommends tafamidis regardless of NYHA class 6
  • AHA: Includes NYHA class III in recommendations 6
  • JCS: Provides weaker recommendation (Class IIb, Level of Evidence: B) 6
  • Caution: Subgroup analysis showed increased frequency of hospitalizations in NYHA class III patients in ATTR-ACT trial 6

NYHA Class IV

• Limited evidence for benefit
• Consider advanced therapies in selected patients

Supportive Care for Cardiac Symptoms

1. Diuretic management:

   • Use cautiously to avoid overdiuresis and volume contraction 6
   • Monitor for hypotension

2. Medications to avoid:

   • Digoxin (binds to amyloid fibrils causing toxicity) 6
   • Calcium channel antagonists (bind to amyloid fibrils causing hypotension) 6

3. Anticoagulation:

   • Warfarin or direct thrombin inhibitors are indicated for patients with atrial fibrillation or history of embolic events 6
   • Target INR 2-3 if using warfarin 6

Monitoring Response to Treatment

• For ATTR amyloidosis:

  • NT-proBNP levels (higher baseline levels predict poorer treatment response) 7
  • Echocardiography including strain measurements every 6 months 6
  • Holter ECG every 6 months 6

• For AL amyloidosis:

  • Monthly monitoring during initial hematological treatment 6:
    • Complete blood count, basic biochemistry
    • NT-proBNP and troponin
    • Serum-free light chain quantification

Advanced Therapies

• Heart transplantation:

  • Consider for selected patients with advanced/stage D heart failure 1
  • Contraindicated with significant extracardiac manifestations 1

• Combined heart and liver transplantation:

  • May be considered for selected patients with hereditary ATTR 6
  • Liver transplantation cures the amyloidosis disease process in hereditary ATTR 6

Key Pitfalls to Avoid

1. Delayed diagnosis and treatment: Early initiation of therapy is crucial for better outcomes 3

2. Mistyping the amyloidosis: Treatment strategies differ significantly between AL and ATTR types 1

3. Inappropriate medication use: Avoid digoxin and calcium channel blockers which can cause toxicity 6

4. Overdiuresis: Can lead to hypotension and worsening symptoms 6

5. Missing neurologic involvement: In ATTR amyloidosis, assess for polyneuropathy which may affect treatment decisions 6

By following this treatment algorithm based on amyloidosis type and cardiac functional status, outcomes for patients with cardiac amyloidosis can be optimized with current evidence-based therapies.