Is cardiac amyloidosis (cardiac amyloidosis) curable?

Cardiac Amyloidosis: Is It Curable?

Cardiac amyloidosis is not currently curable, but disease-modifying therapies can significantly improve survival and quality of life when initiated early, with heart transplantation offering the only potential cure in highly selected cases. 1

Types of Cardiac Amyloidosis and Treatment Approaches

Cardiac amyloidosis is primarily categorized into two main types, each requiring different treatment strategies:

Light Chain (AL) Amyloidosis

• First-line therapy: Daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 2
• Alternative therapy: CyBorD alone if daratumumab is unavailable 2
• For eligible patients: High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 2
  • Only approximately 25% of newly diagnosed patients are eligible
  • Treatment-related mortality is high (13% at 100 days) 1
  • Median survival improved to 6.4 years in patients without cardiac involvement but only 1.6 years with cardiac involvement 1

Transthyretin (ATTR) Amyloidosis

• First-line therapy: Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg daily) 2
  • Reduces cardiovascular mortality and hospitalizations
• Emerging therapy: Acoramidis (Attruby) - reduces all-cause mortality by up to 42% 2
• TTR silencing agents: Patisiran and inotersen for hereditary ATTR 3

Potential Curative Options

Heart Transplantation

• May be considered in select patients with advanced/stage D heart failure 1
• Contraindicated with significant extracardiac manifestations 1
• For AL amyloidosis:
  • Generally not recommended due to high risk of recurrence in the transplanted heart 1
  • Poor prognosis with 5-year survival of only 20-30% 1
  • Survival improves if followed by bone marrow transplantation (5-year survival 35-55%) 1

Combined Transplantation

• For hereditary ATTR amyloidosis:
  • Combined heart and liver transplantation may be considered 2
  • Liver transplantation can cure the disease process as TTR protein is synthesized in the liver 1, 2
  • 5-year survival rate of 50-80% for combined transplantation 1

Prognostic Factors and Monitoring

• Cardiac involvement is the single most important prognostic indicator in amyloidosis 1
• Biomarkers for monitoring:
  • Troponin and NT-proBNP are powerful indicators of disease burden and prognosis 1
  • Cardiac response should be assessed 6-12 months after hematologic response 2
  • Monthly monitoring includes CBC, basic biochemistry, NT-proBNP, troponin, and serum-free light chain quantification 2

Important Caveats and Pitfalls

1. Delayed diagnosis: Delays in diagnosis are common and detrimental to outcomes 3
2. Medication cautions:
   • Avoid digoxin and calcium channel blockers in patients with cardiac involvement 2
   • Use diuretics cautiously to prevent overdiuresis and volume contraction 2
3. Treatment challenges:
   • Patient frailty and therapeutic side effects often complicate management 4
   • Bortezomib requires monitoring for peripheral neuropathy (occurs in 20% of patients) 2
   • Balance between systemic congestion and low blood pressure is difficult 5

Palliative Care

• Should be integrated early for symptom management and quality of life improvement 2
• For patients with advanced cardiac involvement (NT-proBNP >8,500 pg/mL), single-agent daratumumab with minimal dexamethasone can be considered 2
• May be an option for symptomatic relief even if heart transplantation or mechanical circulatory support is the chosen pathway 1

While cardiac amyloidosis remains incurable for most patients, early diagnosis and appropriate disease-modifying therapy can significantly improve survival and quality of life. The prognosis has dramatically improved in recent years with novel therapies, and in rare selected cases, transplantation may offer a potential cure, particularly for hereditary ATTR amyloidosis.