From the Guidelines
The diagnostic workup for cardiac amyloidosis should begin with a thorough clinical evaluation, including history, ECG, echocardiogram, and cardiac MRI, followed by tissue biopsy and laboratory tests to determine the specific amyloid type, as recommended by the 2023 ACC expert consensus decision pathway 1. The initial evaluation should focus on symptoms like heart failure, arrhythmias, and syncope. Initial testing should include:
- An electrocardiogram (ECG) to show low voltage and conduction abnormalities
- An echocardiogram to assess for increased ventricular wall thickness, diastolic dysfunction, and a "speckled" myocardial appearance
- Cardiac biomarkers such as troponin and NT-proBNP, which are often elevated Advanced imaging is crucial, particularly:
- Cardiac MRI with gadolinium enhancement to show characteristic late gadolinium enhancement patterns and abnormal T1 mapping values
- Nuclear imaging with technetium-labeled bone tracers (99mTc-PYP, DPD, or HMDP) for transthyretin (ATTR) amyloidosis, with grade 2-3 uptake strongly suggesting this subtype To confirm the diagnosis and determine the specific amyloid type, tissue biopsy is often necessary, either from:
- An affected organ (endomyocardial biopsy)
- Alternative sites like abdominal fat pad or bone marrow Additional laboratory tests should include:
- Serum and urine protein electrophoresis
- Serum free light chain assay
- Immunofixation to screen for light chain (AL) amyloidosis
- Genetic testing for TTR mutations to distinguish hereditary from wild-type ATTR amyloidosis, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The 2023 ACC expert consensus decision pathway 1 provides a comprehensive approach to the diagnosis of cardiac amyloidosis, emphasizing the importance of tissue biopsy and laboratory tests to determine the specific amyloid type.
From the Research
Diagnostic Workup for Cardiac Amyloidosis
The diagnostic workup for cardiac amyloidosis involves a combination of clinical suspicion, laboratory tests, and imaging techniques.
- Clinical suspicion is raised by the presence of "red flags" such as heart failure, arrhythmias, orthostatic hypotension, syncope, and pre-syncope 2, 3.
- Laboratory tests include biomarkers and mass spectrometry to identify the type of amyloidosis 4.
- Imaging techniques used in the diagnostic workup of cardiac amyloidosis include:
- Echocardiography to assess left ventricular wall thickening and heart failure 5, 2, 4.
- Cardiac magnetic resonance (CMR) imaging to evaluate myocardial tissue characteristics and identify amyloid deposits 5, 2, 3.
- Bone scintigraphy to detect amyloid deposits in the heart 5.
- Organ biopsy, including endomyocardial biopsy, to confirm the presence of amyloidosis and identify the type of amyloid 5, 4.
Diagnostic Algorithm
A practical approach to the diagnostic workup of cardiac amyloidosis involves a step-wise algorithm that includes:
- Clinical suspicion and identification of "red flags" 6, 2.
- Laboratory tests and biomarkers to support the diagnosis 3, 4.
- Imaging techniques to confirm the presence of amyloidosis and evaluate the extent of cardiac involvement 5, 2, 3.
- Organ biopsy to confirm the diagnosis and identify the type of amyloidosis 5, 4.
Importance of Early Diagnosis
Early diagnosis of cardiac amyloidosis is crucial to improve patient outcomes, as timely treatment can significantly improve survival 2, 3.