From the Guidelines
The most effective diagnostic approach for amyloidosis involves a combination of tissue biopsy, blood and urine tests, imaging studies, and genetic testing, with tissue biopsy being the gold standard for diagnosis, as recommended by the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis 1. To diagnose amyloidosis, the following steps can be taken:
- Clinical clues for AL amyloidosis, such as restrictive cardiomyopathy, macroglossia, unexplained proteinuria, hepatomegaly, and acquired factor X deficiency with coagulopathy, should be identified 1.
- Evidence of amyloid tissue deposits can be obtained through biopsy of a surrogate site or affected organ, serum free light chains, bone marrow biopsy, and serum and urine immunofixation electrophoresis (IFE) 1.
- If the biopsy of a surrogate site is negative, Congo red staining, identification, and assessment of the plasma cell monoclonal protein burden should be performed 1.
- Multiple myeloma or B-cell lymphoproliferative disorders should be excluded through bone marrow biopsy and monoclonal protein screening 1.
- Imaging studies, such as echocardiography, cardiac MRI, and nuclear medicine scans like technetium-99m pyrophosphate (99mTc-PYP), can help detect cardiac involvement and other organ damage 1.
- Genetic testing is important for hereditary forms of amyloidosis, particularly for transthyretin (TTR) gene mutations 1.
- A comprehensive diagnostic approach is necessary, as amyloidosis can affect multiple organ systems and presents with varied clinical manifestations 1.
From the Research
Diagnostic Tests for Amyloidosis
The diagnostic tests for amyloidosis include:
- Tissue examinations such as biopsy of affected tissues, which can be carried out using various methodologies including immunohistochemistry, immunofluorescence, immunoelectron microscopy, Western blotting, and proteomic analysis 2
- Noninvasive techniques including serological and imaging studies 2
- Rectal biopsy, which is the preferred initial procedure for obtaining tissue for study 3
- Subcutaneous fat pad, gingival, skin, and bone marrow biopsies, which are alternative noninvasive biopsy sites 3
- Morphological, cytochemical, and immunohistochemical studies to precisely identify the class of amyloid present 3
- Immunofluorescence and genetic analysis for the diagnosis of hereditary transthyretin cardiac amyloidosis 4
- Echocardiography and electrocardiography to detect cardiac involvement in patients with amyloidosis 5
Types of Amyloidosis and Diagnostic Approaches
The type of amyloidosis determines the diagnostic approach, with different types requiring different tests, such as:
- Immunoglobulin light chain amyloidosis (AL amyloidosis) 3, 6
- Transthyretin amyloidosis (ATTR amyloidosis) 2, 4
- AA amyloidosis (associated with chronic inflammatory disease) 5
Comprehensive Diagnostic Algorithm
A comprehensive multidisciplinary diagnostic algorithm for the early and efficient detection of amyloidosis has been proposed, which includes: