What are the treatment options for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

For cardiac amyloidosis, the preferred treatment approach is daratumumab with bortezomib, cyclophosphamide, and dexamethasone (Dara-CyBorD) for AL amyloidosis, and tafamidis for ATTR amyloidosis. 1

Diagnosis and Classification

Before initiating treatment, proper diagnosis and classification of amyloid type is essential:

1. Tissue diagnosis: Obtain tissue 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: Mass spectrometry-based analysis is the gold standard (88% sensitivity, 96% specificity) 1

3. Monoclonal protein screening: For suspected AL amyloidosis, complete:

   • Serum free light chain assay (sFLC)
   • Serum immunofixation electrophoresis (SIFE)
   • Urine immunofixation electrophoresis (UIFE) 1

4. Genetic testing: For ATTR amyloidosis, genetic sequencing of TTR gene to differentiate between hereditary (ATTRv) and wild-type (ATTRwt) 2

Treatment Algorithm by Amyloid Type

AL Amyloidosis Treatment

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

2. For transplant-eligible patients:

   • Consider high-dose melphalan with autologous stem cell transplantation (HDM/SCT)
   • Cardiac involvement is a major determinant of transplant eligibility risk 1

3. Alternative regimens (if first-line not tolerated):

   • Cyclophosphamide, bortezomib, and dexamethasone (CyBorD)
   • Bortezomib-melphalan-dexamethasone (BMD) 1

ATTR Amyloidosis Treatment

1. TTR stabilizers:

   • Tafamidis: FDA-approved for ATTR-CM

     • Available as tafamidis meglumine (80 mg daily) or tafamidis (61 mg daily) 3
     • Reduces all-cause mortality (29.5% vs 42.9% with placebo)
     • Decreases cardiovascular hospitalizations (0.48 vs 0.70 per year) 2

   • Acoramidis: Near-complete TTR stabilizer (~96%)

     • Reduces all-cause mortality by up to 42%
     • Reduces cardiovascular hospitalizations by ~50% 2

2. Eligibility criteria for TTR stabilizers:

   • NYHA class I-III heart failure symptoms
   • Not recommended for NYHA class IV, severe aortic stenosis, or eGFR <25 mL/min/1.73 m² 2

3. For hereditary ATTR: Consider liver transplantation (to remove source of variant TTR) or combined heart-liver transplantation in advanced disease 4

Supportive Heart Failure Management

Cardiac amyloidosis requires careful management of heart failure symptoms:

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

   • Use diuretics cautiously due to risk of hypotension from underfilling of stiff heart

2. Medications to use with caution or avoid:

   • ACE inhibitors/ARBs: Use with extreme caution or avoid due to hypotension risk 1
   • Beta-blockers: May be used cautiously to control heart rate in atrial fibrillation, but avoid in severe restrictive physiology 1
   • Calcium channel blockers: Avoid due to binding to amyloid fibrils causing exaggerated hypotension 1
   • Digoxin: Avoid due to binding to amyloid fibrils causing increased toxicity risk 1

3. Anticoagulation:

   • Indicated for patients with atrial fibrillation
   • Consider even in sinus rhythm if evidence of atrial mechanical dysfunction or intracardiac thrombus 1

Monitoring and Follow-up

1. Hematologic response (for AL amyloidosis):

   • Regular assessment of light chain levels
   • Monitoring for treatment-related cardiotoxicity 1

2. Cardiac function:

   • Regular echocardiography
   • Cardiac biomarkers (BNP, troponin)
   • Watch for cardiac decompensation, atrial arrhythmias, or thromboembolism 1

3. Treatment toxicity:

   • Monitor for specific toxicities of each agent (see below)

Potential Treatment Toxicities

AL Amyloidosis Therapies

• Corticosteroids: Peripheral edema, pulmonary edema, fluid overload 1
• Bortezomib: Grade 3 HF in 6.4%, >10% decrease in LVEF in 23% 1
• Cyclophosphamide: Myocarditis, myopericarditis, pericardial effusion, arrhythmias 1
• Daratumumab: Cardiac failure in 12%, cardiac arrhythmia in 8%, AF in 6% 1

ATTR Therapies

• Tafamidis: Generally well-tolerated; cost is a significant barrier ($225,000 annually) 2

Advanced Therapies for End-Stage Disease

For patients with end-stage cardiac amyloidosis:

• Heart transplantation: Consider for selected patients with advanced disease 1
• Combined transplantation: Heart-liver (for hereditary ATTR) or heart-kidney (with renal involvement) 4

Common Pitfalls to Avoid

1. Misdiagnosis: Failing to distinguish between AL and ATTR amyloidosis, especially in patients with MGUS and suspected ATTR 1

2. Inappropriate medication use: Using standard heart failure medications that may be harmful in cardiac amyloidosis 1

3. Delayed diagnosis: Not considering amyloidosis in patients with HFpEF and increased ventricular wall thickness 1

4. Overlooking anticoagulation needs: Not recognizing the high risk of intracardiac thrombus even in sinus rhythm 1

5. Inadequate monitoring: Failing to monitor for treatment toxicity, especially cardiac decompensation during chemotherapy 1