What are the treatment options for cardiac amyloidosis?

Treatment Options for Cardiac Amyloidosis

The optimal treatment for cardiac amyloidosis depends on the specific type (AL or ATTR), with daratumumab-based regimens being first-line for AL amyloidosis and tafamidis being the only FDA-approved treatment for ATTR cardiac amyloidosis. 1, 2

Diagnosis and Classification

Before initiating treatment, proper classification of cardiac amyloidosis is essential:

• Tissue diagnosis: Endomyocardial biopsy with Congo red staining showing apple-green birefringence under polarized microscopy is the gold standard 2
• Typing of amyloid:
  • Immunohistochemistry with antibodies against amyloid proteins
  • Mass spectrometry (considered gold standard for typing)
  • Nuclear imaging with Technetium Tc 99m for distinguishing AL from ATTR 2

Treatment Options by Amyloid Type

AL (Light-Chain) Cardiac Amyloidosis

The primary goal is to eradicate the pathological plasma cells producing the amyloidogenic light chains:

1. First-line therapy:

   • Daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 1, 2

2. Alternative regimens:

   • CyBorD (cyclophosphamide, bortezomib, dexamethasone) when daratumumab is unavailable 1
   • High-dose melphalan with autologous stem cell transplantation (ASCT) in eligible patients 1

3. Treatment considerations:

   • No absolute contraindications based on ejection fraction or cardiac status
   • Close cardiac monitoring required for decompensated heart failure, arrhythmias, and thromboembolism 1
   • Goal of therapy: eradicate pathological plasma cells and remove affected light chains from circulation 1

ATTR (Transthyretin) Cardiac Amyloidosis

1. FDA-approved therapy:

   • Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg daily) - reduces cardiovascular mortality and hospitalization in both wild-type and hereditary ATTR-CM 2, 3

2. Emerging therapies:

   • Acoramidis (investigational TTR stabilizer) 2
   • TTR silencing agents
   • Amyloid degradation therapies 4

3. Advanced options:

   • Heart transplantation for end-stage heart failure 2
   • Combined heart-liver transplantation for hereditary ATTR (liver produces the mutant TTR protein) 2, 5

Heart Failure Management

• Diuretics: Judicious use as the mainstay of symptom management 2
• Medications to avoid or use with caution:
  • β-blockers (cardiac output is heart rate dependent)
  • Digoxin and calcium channel blockers (bind to amyloid fibrils)
  • ACE inhibitors/ARBs (risk of hypotension) 2

Monitoring and Follow-up

1. For AL amyloidosis:

   • Monthly: CBC, biochemistry, NT-proBNP, troponin, serum-free light chain quantification
   • Assessment of hematologic response (goal: very good partial response or better) 2

2. For all types:

   • Echocardiography with strain measurements every 6 months
   • Holter ECG every 6 months 2

Advanced Therapies for End-Stage Disease

• Heart transplantation: Consider for select patients with advanced/stage D heart failure
  • Contraindicated with significant extracardiac manifestations 2
  • For AL amyloidosis: must be combined with chemotherapy and stem cell transplantation 5
  • For ATTR amyloidosis: consider combined heart-liver transplantation for hereditary forms 5

Multidisciplinary Approach

Cardiac amyloidosis management requires collaboration between:

• Cardiologists (for heart failure management)
• Hematologists (for AL amyloidosis treatment)
• Neurologists (for ATTR with neuropathy)
• Palliative care specialists (for symptom management) 2

Treatment Pitfalls to Avoid

1. Misdiagnosis or delayed diagnosis (often confused with other cardiomyopathies)
2. Failure to determine amyloid type before initiating therapy
3. Inappropriate use of standard heart failure medications that may worsen symptoms
4. Delayed referral to specialized centers for advanced therapies
5. Inadequate monitoring for treatment toxicities, especially in AL amyloidosis

Early diagnosis and prompt initiation of appropriate therapy are crucial for improving outcomes in this traditionally poor-prognosis disease.