What is the treatment approach for heart amyloidosis?

Treatment Approach for Heart Amyloidosis

The treatment of cardiac amyloidosis requires a disease-specific approach based on amyloid type, with tafamidis being the only FDA-approved treatment for ATTR cardiomyopathy and daratumumab-based regimens being the preferred first-line therapy for AL amyloidosis. 1, 2, 3

Diagnosis and Classification

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

1. Tissue diagnosis with typing:

   • Endomyocardial biopsy with Congo red staining (shows apple-green birefringence)
   • Immunohistochemistry for amyloid typing
   • Mass spectrometry (gold standard for typing)

2. Imaging:

   • Echocardiography (ventricular wall thickening, diastolic dysfunction)
   • Nuclear imaging with Technetium Tc 99m (distinguishes AL from ATTR)
   • Cardiac MRI with late gadolinium enhancement

3. Laboratory testing:

   • Serum free light chain assay
   • Cardiac biomarkers (BNP/NT-proBNP, Troponin)
   • Genetic testing for hereditary forms

Treatment by Amyloid Type

1. AL (Light Chain) Amyloidosis

• First-line therapy: Daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 2, 4

  • Achieves high rates of deep hematologic responses

• Alternative therapy: CyBorD alone (cyclophosphamide, bortezomib, dexamethasone) for patients who cannot tolerate daratumumab 2

• For eligible patients: High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 2

  • Eligibility criteria: LVEF >40%, ability to handle fluid shifts and potential infections
  • Only about 25% of newly diagnosed patients are eligible
  • Treatment-related mortality ~3%
  • 70% achieve very good partial hematologic response or better
  • Median survival >15 years in those achieving complete response

2. ATTR (Transthyretin) Amyloidosis

• FDA-approved treatment: Tafamidis 2, 3, 4

  • Dosage: VYNDAQEL 80 mg or VYNDAMAX 61 mg orally once daily
  • Indicated for both wild-type and hereditary ATTR cardiomyopathy
  • Reduces cardiovascular mortality and cardiovascular-related hospitalization

• Emerging therapies (in clinical trials):

  • TTR gene silencing agents
  • TTR tetramer stabilizers
  • Anti-TTR fiber antibodies
  • Amyloid degradation agents 4, 5

Advanced Interventions for End-Stage Disease

• Heart transplantation: Consider in select patients with advanced/stage D heart failure 1

  • Contraindicated with significant extracardiac manifestations (see Table 14 in guidelines)

• Combined transplantation:

  • Heart-liver transplantation for hereditary ATTR (5-year survival 50-80%)
  • Heart transplantation followed by ASCT for AL amyloidosis (superior outcomes compared to heart transplantation alone) 5

• Temporary mechanical circulatory support:

  • Intra-aortic balloon pump or percutaneous microaxial catheter-based pump as bridge to transplantation 1
  • Axillary approach allows for ambulation while awaiting transplantation

Supportive Care and Symptom Management

• Heart failure management:

  • Judicious diuresis as mainstay of therapy
  • Avoid β-blockers (cardiac output is heart rate dependent)
  • Avoid digoxin and calcium channel blockers (bind to amyloid fibrils)
  • Use ACE inhibitors/ARBs with caution 2

• Anticoagulation:

  • Indicated for atrial fibrillation, embolic stroke/TIA, or intracardiac thrombus
  • Balance benefits against increased bleeding risk in amyloid angiopathy 2

• Palliative care integration:

  • Refer at any stage when physical symptoms interfere with quality of life
  • Focus on symptom management, psychological relief, and support for family 1
  • Team-based approach to help patients live as actively as possible

Monitoring

• Monthly monitoring:

  • CBC, biochemistry, NT-proBNP, troponin, serum-free light chain quantification

• Every 6 months:

  • Echocardiography with strain measurements
  • Holter ECG

• Monitor for treatment toxicities:

  • Cardiac toxicities: heart failure (6.4%), LVEF reduction (23%) for proteasome inhibitors
  • Paradoxical increase in cardiac biomarkers for immunomodulatory agents
  • Cardiac failure (12%) and arrhythmias (8%) for daratumumab 2

Multidisciplinary Approach

A collaborative approach involving cardiologists, hematologists, neurologists, and palliative care specialists is essential for optimal management of cardiac amyloidosis 1, 2, 6. Early referral to an expert center should be considered for timely diagnosis, initiation of treatment, and participation in clinical trials 4.