What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

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

Diagnosis and Classification

Before initiating treatment, proper diagnosis and classification are essential:

1. Tissue diagnosis: Obtain tissue confirmation via biopsy (abdominal fat pad, gingiva, rectum, bone marrow, or affected organs)

   • Congo red staining showing apple-green birefringence under polarized microscopy
   • Mass spectrometry for definitive typing

2. Amyloid type determination:

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

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 risk determinant)
   • Can achieve long-lasting remission and high organ response rates

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

ATTR Amyloidosis Treatment

1. First-line therapy:

   • Tafamidis 80 mg (four 20-mg capsules) or 61 mg (one capsule) daily 2, 4
   • Reduces all-cause mortality (29.5% vs 42.9%) and cardiovascular hospitalizations
   • FDA-approved for both wild-type and hereditary ATTR-CM
   • Acoramidis (recently FDA-approved) is an alternative with ~96% TTR stabilization 2

2. Alternative therapies (if tafamidis is unavailable/not tolerated):

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

3. For hereditary ATTR: Consider liver transplantation (curative for the disease process) or combined heart-liver transplantation in selected cases 3

Supportive Heart Failure Management

1. Volume management:

   • Judicious diuresis is the mainstay of therapy
   • Careful monitoring to avoid overdiuresis 1

2. Medication precautions:

   • Avoid: Digoxin (binds to amyloid fibrils causing toxicity), calcium channel blockers (exaggerated hypotension) 1
   • Use with caution: ACE inhibitors/ARBs (hypotension risk), β-blockers (may worsen symptoms as cardiac output is heart rate dependent) 1, 2

3. Anticoagulation:

   • Recommended for patients with atrial fibrillation regardless of CHA₂DS₂-VASc score
   • Consider in patients with sinus rhythm who have evidence of atrial mechanical standstill 1

Multidisciplinary Approach

Cardiac amyloidosis management requires collaboration between:

• Cardiologists: Monitor for cardiac decompensation during therapy
• Hematologists: Direct AL amyloidosis treatment
• Neurologists: Assess for neuropathy (especially in ATTR)
• Nephrologists: Manage renal involvement
• Geriatrics/Palliative care: Review goals of care and symptom management 1

Treatment Challenges and Pitfalls

• Delayed diagnosis: Often leads to irreversible organ damage; early recognition is crucial 5
• Cardiac toxicity: Many AL amyloidosis treatments have cardiac side effects requiring close monitoring 1
• Hypotension: Common with standard heart failure medications; requires careful titration 1
• Treatment access: Tafamidis has high cost (>$180,000 per QALY gained) 2

Early diagnosis and prompt initiation of appropriate therapy are essential for improving survival and quality of life in patients with cardiac amyloidosis.