What is the treatment for cardiac thickening in amyloidosis?

Treatment of Cardiac Thickening in Amyloidosis

Treatment must be tailored to the specific amyloid type, with disease-directed therapy targeting the underlying protein deposition combined with cautious supportive heart failure management. 1

Identify the Amyloid Type First

The treatment strategy fundamentally depends on which type of amyloidosis is causing the cardiac thickening, as each requires distinct disease-modifying approaches 1:

AL (Light Chain) Amyloidosis

For AL amyloidosis with cardiac involvement, bortezomib-based chemotherapy regimens are the primary disease-directed treatment. 2

• First-line therapy: Bortezomib combined with dexamethasone and an alkylating agent (melphalan or cyclophosphamide) 2
• Alternative regimens: Melphalan with dexamethasone, or cyclophosphamide with thalidomide and dexamethasone 1
• For advanced cardiac involvement: Consider daratumumab with minimal dexamethasone to reduce cardiotoxicity 2
• Autologous stem cell transplantation: May be considered in highly selected patients without significant cardiac involvement (LVEF >40% and no decompensated heart failure), though treatment-related mortality is high at 13% at 100 days, with 42% being cardiac deaths 1
• Important limitation: Only a small subset of patients achieve actual cardiac response (decreased wall thickness, improved LV function) despite 40-60% achieving hematologic response 1

ATTR (Transthyretin) Amyloidosis

For ATTR cardiac amyloidosis, tafamidis is the FDA-approved treatment that reduces cardiovascular mortality and hospitalization. 3

• Dosing: Either tafamidis meglumine (VYNDAQEL) 80 mg orally once daily OR tafamidis (VYNDAMAX) 61 mg orally once daily 3
• Critical note: VYNDAMAX and VYNDAQEL are NOT substitutable on a per mg basis 3
• Mechanism: TTR stabilizers prevent misfolding and inhibit amyloid fibril formation 1
• Alternative stabilizer: Diflunisal may reduce amyloid fibril formation 1, 2
• For hereditary ATTR: Combined cardiac and liver transplantation may be considered in selected patients, with 5-year survival of 50-80% 1, 2

Supportive Heart Failure Management

Judicious diuresis is the mainstay of heart failure therapy in cardiac amyloidosis, as standard heart failure medications are poorly tolerated or contraindicated. 1

Safe Approaches

• Diuretics: Use cautiously to manage congestion, but avoid overdiuresis that causes hypotension from underfilling a stiff heart 1
• Anticoagulation: Strongly indicated for atrial fibrillation, history of embolic stroke/TIA, or demonstrable intracardiac thrombus 1
  • Use warfarin (INR 2-3) or direct thrombin inhibitors 1
  • Consider even in sinus rhythm due to high risk of atrial thrombus from mechanical "standstill" 1

Medications to AVOID

Digoxin should be completely avoided because it binds to amyloid fibrils and causes toxicity even with normal serum levels. 1, 2

• Calcium channel blockers (nifedipine, verapamil): Contraindicated due to binding to amyloid fibrils causing exaggerated hypotension and negative inotropy 1, 2
• ACE inhibitors/ARBs: Should probably be avoided due to hypotension risk 1
• Beta-blockers: Should probably be avoided in AL amyloidosis; may be used cautiously only for rate control in atrial fibrillation, but avoid when cardiac output is low with severe restrictive physiology 1

Monitoring Treatment Response

In AL amyloidosis, monitor both hematologic and cardiac response using NT-proBNP, troponin, and echocardiography. 2

• Cardiac response criteria: Decrease in NT-proBNP by >30% and to <300 ng/L, with potential decrease in wall thickness and improvement in LV function 2
• Complete hematologic response: Absence of amyloidogenic light chains 2

Advanced Interventions for End-Stage Disease

• Cardiac transplantation for AL amyloidosis: Generally not recommended due to high recurrence risk and dismal prognosis (5-year survival only 20-30%) 1
• Combined cardiac and bone marrow transplantation: May improve survival to 35-55% at 5 years in very selected AL patients 1
• For hereditary ATTR: Liver transplantation cures the disease process since TTR is synthesized in the liver, with 5-year survival of 50-80% 1, 2

Critical Pitfalls to Avoid

The most common error is applying standard heart failure protocols to cardiac amyloidosis patients, which can precipitate hemodynamic collapse 1. The restrictive physiology and amyloid binding properties create a unique situation where medications that typically improve heart failure outcomes become dangerous 1.