What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

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

Diagnosis and Classification

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

1. Tissue diagnosis: Obtain tissue sample 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. Type identification:

   • AL amyloidosis: Confirm with serum free light chain assay (sFLC), serum immunofixation (SIFE), and urine immunofixation (UIFE) plus bone marrow biopsy showing clonal plasma cells 1
   • ATTR amyloidosis: Confirm with bone scintigraphy and genetic testing to differentiate hereditary (ATTRv) from wild-type (ATTRwt) 2

Treatment Algorithm by Amyloidosis Type

AL Amyloidosis Treatment

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

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

   • Patient selection is critical as cardiac involvement increases treatment-related mortality
   • Collaboration between cardiologists and hematologists is essential during treatment

3. Monitoring during treatment:

   • Regular assessment of hematologic response
   • Close monitoring for cardiac decompensation, arrhythmias, and thromboembolism
   • Watch for specific cardiotoxicities of treatments (see below)

ATTR Amyloidosis Treatment

1. First-line therapy: Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg orally once daily) 2, 3

   • Reduces all-cause mortality and cardiovascular-related hospitalizations in NYHA class I-III patients
   • FDA-approved for treatment of cardiomyopathy of wild-type or hereditary ATTR-CM

2. Alternative options (if tafamidis is not accessible or tolerated):

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

3. For hereditary ATTR: Consider combined heart and liver transplantation in selected patients 2

Supportive Heart Failure Management

1. Volume management: Judicious use of diuretics is the mainstay of therapy 1

   • Use cautiously to avoid hypotension from underfilling a stiff heart

2. Medications to use with caution or avoid:

   • Avoid: Digoxin (binds to amyloid fibrils causing toxicity even with normal serum levels) 1
   • Avoid: Calcium channel blockers (bind to amyloid fibrils causing exaggerated hypotension) 1
   • Use with caution: Beta-blockers (may worsen symptoms as cardiac output is heart rate dependent) 1
   • Use with caution: ACE inhibitors/ARBs (may cause hypotension) 1

3. Anticoagulation:

   • Recommended for patients with atrial fibrillation regardless of CHA₂DS₂-VASc score 2
   • Consider in patients with sinus rhythm who have evidence of atrial mechanical dysfunction 1

Monitoring Cardiotoxicity of Disease-Directed Therapy

Be aware of potential cardiac toxicities with AL amyloidosis treatments 1:

• Corticosteroids: Peripheral edema, pulmonary edema, fluid overload
• Proteasome inhibitors (bortezomib, carfilzomib, ixazomib): Heart failure, LVEF reduction
• Immunomodulatory agents (thalidomide, lenalidomide, pomalidomide): Bradycardia, increased cardiac biomarkers
• Cyclophosphamide: Myocarditis, pericardial effusion, arrhythmias
• Daratumumab: Cardiac failure (12%), arrhythmias (8%)

Advanced Options

For end-stage cardiac amyloidosis:

• Heart transplantation may be considered for selected patients 1
• For hereditary ATTR, combined heart-liver transplantation may be appropriate 2

Key Pitfalls to Avoid

1. Diagnostic delay: Early diagnosis is critical for improved outcomes
2. Mistyping: Proper identification of amyloid type is essential for appropriate treatment
3. Overdiuresis: Can lead to hypotension in patients with restrictive physiology
4. Inappropriate medication use: Standard heart failure medications may be poorly tolerated
5. Missing concurrent organ involvement: Amyloidosis often affects multiple organ systems

Regular multidisciplinary collaboration between cardiologists, hematologists, and other specialists is essential for optimal management of this complex disease.