What are the treatment options for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

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

Diagnosis and Classification

Before initiating treatment, accurate diagnosis and typing of cardiac amyloidosis is essential:

1. Tissue diagnosis: Definitive diagnosis requires demonstration of amyloid deposits by Congo red staining showing apple-green birefringence under polarized light 1
2. Amyloid typing: Critical for treatment selection
   • AL amyloidosis: Requires demonstration of monoclonal light chains in serum/urine and bone marrow showing clonal plasma cells
   • ATTR amyloidosis: Can be diagnosed non-invasively with bone scintigraphy (Tc-PYP scan) in the absence of monoclonal proteins

Treatment of AL Cardiac Amyloidosis

AL amyloidosis treatment targets the underlying plasma cell dyscrasia:

1. First-line therapy: Daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) 1

   • Goal: Eradicate pathological plasma cells and remove affected light chains
   • Rapid hematologic response is critical to improve survival

2. Autologous stem cell transplantation (ASCT):

   • Consider in eligible patients without advanced cardiac involvement
   • Often preceded by high-dose melphalan
   • Patient selection is critical as transplant-related mortality is high in advanced cardiac disease

3. Monitoring during therapy:

   • Regular assessment of hematologic response
   • Cardiac biomarkers (troponin, BNP/NT-proBNP)
   • Echocardiography to assess cardiac function

Treatment of ATTR Cardiac Amyloidosis

1. Tafamidis: FDA-approved TTR stabilizer 2

   • Reduces all-cause mortality and cardiovascular hospitalizations
   • Available in two formulations: tafamidis meglumine 20 mg and tafamidis 61 mg
   • Indicated for both wild-type and hereditary ATTR cardiomyopathy

2. Advanced options:

   • Heart transplantation for end-stage disease in selected patients
   • Combined heart-liver transplantation for hereditary ATTR

Supportive Heart Failure Management

Cardiac amyloidosis requires modified heart failure management:

1. Volume management:

   • Diuretics are the mainstay of therapy
   • Careful monitoring for hypotension and renal dysfunction

2. Medications to use with caution or avoid:

   • β-blockers: May worsen cardiac output; use cautiously if at all
   • ACE inhibitors/ARBs: Often poorly tolerated due to hypotension
   • Calcium channel blockers: Contraindicated due to binding to amyloid fibrils
   • Digoxin: Increased risk of toxicity due to binding to amyloid fibrils

3. Anticoagulation:

   • Consider in all patients with atrial fibrillation
   • May be beneficial even in sinus rhythm due to high risk of atrial thrombi

Multidisciplinary Approach

Cardiac amyloidosis management requires collaboration between:

• Cardiologists
• Hematologists (for AL amyloidosis)
• Neurologists (for ATTR with neuropathy)
• Nephrologists (for renal involvement)
• Palliative care specialists

Common Pitfalls to Avoid

1. Delayed diagnosis: Early recognition is critical for treatment success
2. Misdiagnosis: Ensure proper typing of amyloid protein before initiating therapy
3. Inappropriate medication use: Standard heart failure medications may be poorly tolerated
4. Overlooking extracardiac manifestations: Assess for multi-organ involvement
5. Underestimating treatment toxicity: Cardiac amyloidosis patients are particularly vulnerable to side effects

Monitoring and Follow-up

• Regular assessment of cardiac function with echocardiography
• Monitoring of biomarkers (BNP/NT-proBNP, troponin)
• For AL amyloidosis: regular assessment of free light chains and hematologic response
• For ATTR amyloidosis: monitoring for disease progression and treatment response

The treatment landscape for cardiac amyloidosis has evolved significantly, with disease-modifying therapies now available that can improve survival and quality of life when initiated early in the disease course.