What is the diagnostic workup and management for cardiac amyloidosis?

From the Guidelines

The diagnostic workup for cardiac amyloidosis should begin with clinical suspicion based on symptoms like heart failure with preserved ejection fraction, unexplained left ventricular hypertrophy, or conduction abnormalities, and initial testing should include electrocardiography, echocardiography with strain imaging, cardiac biomarkers, and serum/urine protein electrophoresis with immunofixation, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

The diagnostic approach to cardiac amyloidosis involves a combination of clinical evaluation, imaging, and laboratory tests. Key considerations include:

• Clinical suspicion based on symptoms such as heart failure with preserved ejection fraction, unexplained left ventricular hypertrophy, or conduction abnormalities.
• Initial testing with electrocardiography, echocardiography with strain imaging, cardiac biomarkers (troponin and NT-proBNP), and serum/urine protein electrophoresis with immunofixation.
• Cardiac MRI with gadolinium enhancement showing characteristic late gadolinium enhancement patterns is highly sensitive for diagnosing cardiac amyloidosis, as noted in the expert consensus recommendations for multimodality imaging in cardiac amyloidosis 1.
• Nuclear scintigraphy using technetium-labeled tracers (99mTc-PYP, 99mTc-DPD, or 99mTc-HMDP) is particularly useful for diagnosing transthyretin amyloidosis and may obviate the need for biopsy when combined with absence of monoclonal protein.

Management of cardiac amyloidosis depends on the type of amyloidosis:

• For transthyretin amyloidosis, tafamidis (20 or 80 mg daily) is approved to reduce mortality and hospitalization, with patisiran (0.3 mg/kg IV every 3 weeks) or inotersen (300 mg subcutaneous weekly) considered for advanced cases.
• Light chain amyloidosis requires chemotherapy regimens like bortezomib-based combinations, often with dexamethasone and cyclophosphamide, as discussed in the comprehensive review of AL amyloidosis 1.
• Heart failure management includes careful use of diuretics, avoiding calcium channel blockers and digoxin, and cautious use of beta-blockers, with anticoagulation recommended for atrial fibrillation due to high thromboembolism risk, as highlighted in the current diagnostic and treatment strategies for specific dilated cardiomyopathies 1.

The choice of treatment should be guided by the specific type of amyloidosis, with consideration of the patient's overall clinical condition and potential for treatment-related complications, emphasizing the importance of a personalized approach to management, as outlined in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

From the FDA Drug Label

VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

The diagnostic workup and management for cardiac amyloidosis are not directly addressed in the provided drug label.

• The label only discusses the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) with tafamidis.
• It does not provide information on the diagnostic workup for cardiac amyloidosis. 2

From the Research

Diagnostic Workup for Cardiac Amyloidosis

• Cardiac amyloidosis is a rare disease caused by the extracellular deposition of abnormal proteins-amyloids in the myocardium, with high morbidity and mortality, and prognosis hinging on early detection and treatment 3.
• The diagnostic workup for cardiac amyloidosis involves laboratory and imaging tests to facilitate early detection, including screening for serum and/or urine monoclonal protein, serum cardiac biomarker measurement, and cardiac imaging for findings consistent with amyloid infiltration 4.
• Clinical recognition requires a high index of suspicion, inclusive of extracardiac manifestations, and diagnostic workup includes echocardiography, cardiac magnetic resonance, bone scintigraphy, and if required, organ biopsy 5, 6.

Imaging Techniques for Cardiac Amyloidosis

• Modern cardiac imaging techniques, including the use of nuclear scintigraphy with bone-seeking radiotracer, have reduced reliance on the gold standard endomyocardial biopsy 4.
• 99mTc-pyrophosphate imaging is a simple and effective method for identifying cardiac amyloidosis, particularly in patients with heart failure but preserved ejection fraction 7.
• Interpretation and diagnostic accuracy of 99mTc-pyrophosphate imaging require an in-depth knowledge of amyloidosis etiology, clinical manifestations, disease progression, and treatment 7.

Management of Cardiac Amyloidosis

• Disease-modifying therapeutic approaches have evolved significantly, particularly for transthyretin (ATTR) amyloidosis, and pharmacologic therapies that slow or halt disease progression are becoming available 4.
• The management of cardiac amyloidosis includes symptomatic management of heart failure and other cardiovascular complications, risk stratification, follow-up surveillance, and use of ATTR disease-modifying therapies 4.
• Patients with cardiac amyloidosis require optimal clinical care settings, and a multidisciplinary approach is essential for the management of this complex multisystem disease 4.

Types of Cardiac Amyloidosis

• There are three main types of cardiac amyloidosis: light chain (AL), familial or senile (ATTR), and secondary amyloidosis associated with chronic inflammation 3.
• AL amyloidosis is caused by monoclonal production of light-chains, while ATTR amyloidosis is caused by dissociation of the transthyretin tetramer into monomers 5.
• The diagnosis and management of cardiac amyloidosis depend on the specific type of amyloidosis, and accurate diagnosis is crucial for effective treatment 7.