From the Guidelines
The recommended workup for a patient suspected of having amyloidosis begins with a thorough clinical evaluation, followed by specific diagnostic tests to confirm the diagnosis and determine the type of amyloidosis, as outlined in the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis 1.
Initial Screening
Initial screening should include:
- Serum and urine protein electrophoresis with immunofixation
- Serum free light chain assay
- Complete blood count
- Comprehensive metabolic panel
- Cardiac biomarkers (troponin and BNP/NT-proBNP)
- 24-hour urine protein collection
Tissue Biopsy
Tissue biopsy remains the gold standard for diagnosis, with abdominal fat pad aspiration being the preferred initial biopsy site due to its minimal invasiveness and reasonable sensitivity (84% for AL-CM) 1. If this is negative but clinical suspicion remains high, targeted organ biopsy (such as kidney, heart, liver, or nerve) may be necessary.
Organ Involvement Assessment
Once amyloid deposits are confirmed with Congo red staining, typing of the amyloid protein is essential using immunohistochemistry, mass spectrometry, or genetic testing. Organ involvement assessment should include:
- Echocardiography
- Cardiac MRI (if available)
- Electrocardiogram
- Liver function tests
- Renal function tests
- Proteinuria quantification
Additional Specialized Tests
For patients with confirmed AL amyloidosis, bone marrow biopsy with flow cytometry is necessary to evaluate for plasma cell dyscrasia. Additional specialized tests may include SAP scintigraphy (where available), genetic testing for hereditary forms, and autonomic function tests. This comprehensive approach is necessary because amyloidosis is a heterogeneous disease with multiple subtypes requiring different treatment approaches, and accurate diagnosis and typing are crucial for appropriate management, as supported by recent guidelines 1 and expert recommendations 1.
From the Research
Diagnostic Approach
The diagnostic workup for a patient suspected of having amyloidosis involves a multidisciplinary approach, as stated in 2. This includes:
- Clinical evaluation to identify signs and symptoms suggestive of amyloidosis, such as macroglossia and periorbital purpura in light chain (AL) amyloidosis 3
- Laboratory tests, including serum and urine immunofixation electrophoresis to detect monoclonal proteins 4
- Imaging studies, such as bone scintigraphy, to detect cardiac amyloidosis 4
- Genetic testing to identify mutations associated with hereditary forms of amyloidosis, such as the Transthyretin gene 4
- Endomyocardial biopsy to confirm the diagnosis and type of amyloidosis, especially in cases where non-invasive tests are inconclusive 4
Importance of Early Diagnosis
Early diagnosis of amyloidosis is crucial, as it can significantly improve patient outcomes, as mentioned in 2 and 3. Delayed diagnosis can lead to irreversible organ damage and poor prognosis. Therefore, clinicians should be aware of the signs and symptoms that raise suspicion for amyloidosis and initiate a diagnostic workup promptly.
Typing and Staging
Once the diagnosis of amyloidosis is confirmed, typing and staging of the disease are essential to guide treatment, as recommended in 2. This includes identifying the type of amyloidosis, such as AL or transthyretin (ATTR) amyloidosis, and assessing the extent of organ involvement.
Treatment Options
Treatment options for amyloidosis depend on the type and extent of disease, as discussed in 5. These may include chemotherapy, stem cell transplantation, and organ transplantation, such as heart or liver transplantation, in selected cases. A multidisciplinary approach to management, including specialists from various fields, is necessary to provide optimal care for patients with amyloidosis.