What is the treatment for amyloidosis heart failure?

Treatment of Amyloidosis Heart Failure

The treatment of amyloidosis heart failure requires a specific approach based on the type of amyloidosis, with AL amyloidosis primarily treated with daratumumab-CyBorD (daratumumab with bortezomib, cyclophosphamide, and dexamethasone) and ATTR amyloidosis treated with tafamidis for NYHA class I-III symptoms to reduce mortality and hospitalization. 1, 2

Diagnosis and Classification

• Accurate diagnosis and classification of amyloidosis type is essential as treatment differs significantly between types 1
• Screening for serum and urine monoclonal light chains with serum and urine immunofixation electrophoresis and serum free light chains is necessary to differentiate AL from ATTR amyloidosis 1
• For patients without evidence of monoclonal light chains, bone scintigraphy (Tc-99m-PYP scan) should be performed to confirm ATTR cardiac amyloidosis 1
• If TTR amyloid is detected, genetic testing with TTR gene sequencing is recommended to differentiate hereditary variant from wild-type transthyretin cardiac amyloidosis 1

Treatment of AL (Light Chain) Amyloidosis Heart Failure

First-Line Therapy

• Daratumumab-CyBorD (daratumumab with bortezomib, cyclophosphamide, and dexamethasone) is the preferred first-line therapy for AL amyloidosis based on the ANDROMEDA trial, which showed very good partial responses or better in 78.5% of patients compared to 49.2% with CyBorD alone 1
• Daratumumab is the only FDA-approved agent specifically for AL amyloidosis treatment 1

Stem Cell Transplantation

• High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) may be considered for selected patients without advanced cardiac involvement 1
• Patients with EF <40% are generally not candidates for stem cell transplantation due to risk of hemodynamic decompensation 1
• Only about 25% of newly diagnosed AL amyloidosis patients are eligible for this intensive treatment 1

Monitoring and Cardiac Toxicity

• Collaboration with cardiologists is crucial to monitor for cardiac decompensation, decompensated heart failure, atrial arrhythmias, or thromboembolism during treatment 1
• Many AL amyloidosis treatments have cardiac toxicities that require careful monitoring (see below) 1

Treatment of ATTR (Transthyretin) Amyloidosis Heart Failure

Pharmacologic Therapy

• Tafamidis is FDA-approved for treatment of wild-type or hereditary ATTR cardiomyopathy in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization 2
• In patients with NYHA class I to III symptoms, tafamidis is indicated to reduce cardiovascular morbidity and mortality (Class 1 recommendation) 1, 3
• Tafamidis demonstrated lower all-cause mortality (29.5% versus 42.9%) and lower cardiovascular-related hospitalization (0.48 versus 0.70 per year) after 30 months compared to placebo 3
• Benefit has not been observed in patients with NYHA class IV symptoms, severe aortic stenosis, or impaired renal function (eGFR <25 mL/min/1.73 m²) 3

Advanced Therapies

• Combined cardiac and liver transplantation may be considered for hereditary ATTR amyloidosis, with a 5-year survival rate of 50% to 80% 1, 4

Supportive Heart Failure Management

Diuretic Therapy

• Judicious diuresis remains the mainstay of heart failure therapy in cardiac amyloidosis 1
• Diuretics should be used cautiously due to risk of hypotension from underfilling of a stiff heart 1, 4

Medications to Use with Caution or Avoid

• ACE inhibitors and ARBs should be used with caution or avoided due to risk of hypotension 1
• β-blockers should be used cautiously if at all when cardiac output is low and there is severe restrictive physiology; they probably should be avoided in AL amyloidosis 1
• Digoxin should be avoided as it binds to amyloid fibrils and can cause toxicity even with normal serum levels 1
• Calcium channel antagonists should be avoided as they bind to amyloid fibrils, resulting in exaggerated hypotensive and negative inotropic responses 1

Anticoagulation

• Anticoagulation is reasonable in patients with cardiac amyloidosis and atrial fibrillation to reduce the risk of stroke regardless of the CHA₂DS₂-VASc score (Class 2a recommendation) 1, 3
• Anticoagulation should also be considered in patients with a history of embolic stroke or transient ischemic attacks, and in those with demonstrable intracardiac thrombus 1
• Risk of intracardiac thrombus is high even in sinus rhythm when atria develop mechanical "standstill" due to amyloid infiltration 1

Monitoring Treatment Response

• Regular follow-up should include assessment of NT-proBNP and troponin levels, echocardiography including strain measurements, electrocardiogram and Holter monitoring, and NYHA functional class 3
• In AL amyloidosis, hematologic response (absence of amyloidogenic light chains) and organ response should be monitored 1, 4

Common Pitfalls and Caveats

• Delayed diagnosis is common and leads to worse outcomes; maintain high index of suspicion in patients with heart failure and increased left ventricular wall thickness 1, 5
• Standard heart failure medications may be poorly tolerated or ineffective in amyloid cardiomyopathy 6, 5
• Cardiac amyloidosis requires a multidisciplinary approach involving cardiology, hematology, neurology, and other specialties 1, 7
• Cost of tafamidis therapy is a significant barrier, with 2020 list prices providing low economic value (>$180,000 per QALY gained) 3
• Patients with persistent heart failure symptoms despite guideline-directed medical therapy should be evaluated for cardiac amyloidosis 5

I hope this helps provide a comprehensive approach to treating amyloidosis heart failure.