What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis must be tailored to the specific amyloid type, with daratumumab-CyBorD being the preferred first-line therapy for AL amyloidosis and tafamidis or acoramidis for ATTR amyloidosis. 1, 2

Diagnosis and Classification

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

1. Tissue diagnosis: Obtain tissue confirmation through biopsy (abdominal fat pad, gingiva, rectum, bone marrow, or affected organs) with Congo red staining showing apple-green birefringence under polarized microscopy 1

2. Amyloid typing:

   • AL amyloidosis: Requires serum free light chain (sFLC) assay, serum and urine immunofixation electrophoresis (SIFE, UIFE), and bone marrow biopsy 1
   • ATTR amyloidosis: Bone scintigraphy and genetic testing to differentiate hereditary (ATTRv) from wild-type (ATTRwt) 2

Treatment by Amyloid Type

AL Amyloidosis Treatment

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

   • Goal: Eradicate pathological plasma cells and remove affected light chains from circulation

2. For eligible patients: Consider high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 1, 3

   • Patient selection based on risk assessment
   • Cardiac involvement is a major determinant of risk

3. Monitoring: Regular assessment of hematologic response and cardiac function during therapy 1

ATTR Amyloidosis Treatment

1. First-line therapy:

   • Tafamidis (Vyndaqel 80mg or Vyndamax 61mg orally once daily) for NYHA class I-III symptoms 2, 4
   • Reduces all-cause mortality (29.5% vs 42.9%) and cardiovascular-related hospitalizations 2
   • FDA-approved for both wild-type and hereditary ATTR-CM 4

2. Alternative therapies (if tafamidis is not accessible):

   • Diflunisal (with careful monitoring of renal function) 2
   • EGCG (green tea extract) 2

3. For hereditary ATTR: Consider liver transplantation or combined heart-liver transplantation in selected cases 3

Supportive Heart Failure Management

1. Volume management: Judicious diuresis is the mainstay of therapy 1

   • Use diuretics cautiously to avoid hypotension from underfilling a stiff heart

2. Anticoagulation: Recommended for patients with atrial fibrillation regardless of CHA₂DS₂-VASc score 2

   • Consider anticoagulation even in sinus rhythm if atrial mechanical dysfunction is present 1

3. Medications to use with caution or avoid:

   • Avoid: Digoxin (binds to amyloid fibrils causing toxicity even with normal levels) 1
   • Avoid: Calcium channel blockers (bind to amyloid fibrils causing exaggerated hypotension) 1
   • Use cautiously: Beta-blockers (cardiac output is heart rate dependent in restrictive physiology) 1
   • Use cautiously: ACE inhibitors/ARBs (risk of hypotension) 1

Monitoring and Follow-up

1. Cardiac biomarkers: BNP/NT-proBNP and troponins for monitoring disease progression and response to therapy 1

2. Multidisciplinary collaboration: Coordinate care between cardiology, hematology, and other specialties 1

   • Monitor for cardiac decompensation during chemotherapy
   • Assess candidacy for heart transplantation in appropriate cases

Special Considerations

1. Medication side effects: Monitor for cardiotoxicity of disease-directed therapies 1

   • Proteasome inhibitors: Risk of heart failure and LVEF reduction
   • Immunomodulatory agents: Paradoxical increase in cardiac biomarkers
   • Corticosteroids: Fluid retention and pulmonary edema

2. Advanced disease: For end-stage cardiac amyloidosis, consider:

   • Heart transplantation in selected cases 3
   • Combined heart-liver transplantation for hereditary ATTR 3

By following this treatment algorithm and working with a multidisciplinary team, outcomes for patients with cardiac amyloidosis can be significantly improved compared to the historically poor prognosis of this condition.