What are the steps for testing for amyloidosis?

From the Guidelines

Testing for amyloidosis involves a comprehensive approach, including a thorough medical history, physical examination, blood and urine tests, tissue biopsy, and imaging studies, with the most recent guidelines recommending a step-wise approach to diagnosis, as outlined in the 2023 ACC expert consensus decision pathway 1. The diagnosis of amyloidosis requires the identification of amyloid deposits in tissues, which can be done through biopsy of affected organs or surrogate sites such as abdominal fat or bone marrow.

• Blood and urine tests, including serum free light chain assay, serum and urine protein electrophoresis, and immunofixation, are used to detect abnormal proteins.
• Tissue biopsy is the definitive diagnostic test, where samples are taken from affected organs and stained with Congo red dye to identify amyloid deposits.
• Imaging studies, such as echocardiogram, cardiac MRI, or nuclear medicine scans, help assess organ involvement and damage.
• Genetic testing is recommended for suspected hereditary forms of amyloidosis, as outlined in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
• Bone marrow biopsy may be performed if AL amyloidosis is suspected, and mass spectrometry can be used to determine the specific type of amyloid protein. The 2023 ACC expert consensus decision pathway provides a comprehensive approach to the diagnosis of cardiac amyloidosis, including the use of bone scintigraphy and genetic testing to confirm the presence of transthyretin cardiac amyloidosis 1. Overall, the diagnosis of amyloidosis requires a multidisciplinary approach, and the most recent guidelines provide a step-wise approach to diagnosis and management, prioritizing the use of tissue biopsy, imaging studies, and genetic testing to confirm the diagnosis and guide treatment.

From the Research

Testing for Amyloidosis

The steps for testing for amyloidosis involve a combination of non-invasive and invasive methods. The following are some of the key steps:

• Echocardiography: This is a widely available diagnostic imaging method that can help raise suspicion of cardiac amyloidosis (CA) if novel parameters of systolic dysfunction are used, which are based on strain measurement complemented with traditional morphologic and hemodynamic traits 2.
• Electrocardiography (ECG): ECG findings, such as low-voltage and pseudo-infarction patterns, can be associated with biopsy-proven cardiac amyloidosis 3.
• Cardiovascular Magnetic Resonance Imaging (CMR): This imaging technique can complement conventional echocardiography and allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis 4.
• Scintigraphic methods: These methods can also be used to diagnose cardiac amyloidosis and assess the extent of cardiac involvement 4.
• Endomyocardial biopsy: This is still the gold standard for diagnosing cardiac amyloidosis and can provide a definitive diagnosis 5, 2, 4.
• Serum biomarkers: Specific serum biomarkers can be used to diagnose and subtype cardiac amyloidosis 4.
• Hematology workup: A hematology workup can be used to diagnose AL amyloidosis and differentiate it from other types of amyloidosis 2.

Diagnostic Algorithm

The main objective of the diagnostic algorithm is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment 4. The algorithm involves a combination of non-invasive and invasive methods, including echocardiography, ECG, CMR, scintigraphic methods, endomyocardial biopsy, serum biomarkers, and hematology workup.

Key Findings

Some of the key findings that can be used to diagnose cardiac amyloidosis include:

• Thickened right and left ventricular myocardium 5
• Normal or small left ventricular cavity size in contrast to enlarged biatrial cavities 5
• Diffuse hyper-refractile 'granular sparkling' appearance 5
• 'Mismatch' ECG/ECHO 5
• Reduced magnitude of cyclic variation recorded with integrated backscatter 5
• Abnormal Tei index 5
• Low-voltage and pseudo-infarction patterns on ECG 3
• Increased myocardial thickness and speckled-appearing myocardium on echocardiogram 3