From the Guidelines
Testing for ATTR-CM requires a multi-step diagnostic approach, starting with an echocardiogram to assess for increased left ventricular wall thickness, followed by nuclear scintigraphy with technetium-labeled bone tracers, such as Tc-99m PYP, if ATTR-CM is suspected. The initial evaluation should include an assessment of clinical symptoms, such as fatigue, dyspnea, or edema, and other cardiac abnormalities. If ATTR-CM is suspected, nuclear scintigraphy with technetium-labeled bone tracers (Tc-99m PYP, DPD, or HMDP) is the preferred non-invasive test, with grade 2 or 3 cardiac uptake strongly suggesting ATTR-CM, as stated in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Diagnostic Steps
- Echocardiogram to assess for increased left ventricular wall thickness and other cardiac abnormalities
- Nuclear scintigraphy with technetium-labeled bone tracers (Tc-99m PYP, DPD, or HMDP) if ATTR-CM is suspected
- Blood and urine tests to rule out light chain (AL) amyloidosis, including serum and urine immunofixation electrophoresis and serum free light chain assay
- Genetic testing for TTR gene mutations to differentiate between hereditary and wild-type ATTR-CM
Additional Supportive Tests
- Cardiac MRI with gadolinium enhancement, which may show a characteristic late gadolinium enhancement pattern
- Biomarkers like elevated troponin and NT-proBNP
- Endomyocardial biopsy with Congo red staining and immunohistochemistry remains the gold standard for definitive diagnosis in cases where non-invasive testing is inconclusive, as recommended by expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis 1.
Early diagnosis is crucial as specific treatments are now available that can slow disease progression, including tafamidis, which has been shown to reduce mortality and cardiovascular hospitalizations in ATTR-CM patients.
From the Research
Testing for ATTR-CM
To test for Transthyretin Amyloid Cardiomyopathy (ATTR-CM), several methods can be employed, including:
- Bone scintigraphy, such as 99mTc-labeled pyrophosphate scintigraphy, which is currently considered the first-line modality for identifying ATTR-CM 2
- Echocardiography, which can be useful for ATTR-CM screening, but has several limitations and should be combined with physical examination, laboratory findings, and other imaging data 2
- Technetium-99m pyrophosphate (PYP) imaging, which can be used to diagnose ATTR-CM noninvasively when light chain (AL) amyloidosis has been excluded 3
- Light chain testing, such as serum free light chain (FLC) and/or urine/serum immunofixation electrophoresis (IFE), to exclude AL amyloidosis 3
- Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and T1 mapping, which is emerging as a reference standard for diagnosis and characterization of cardiac amyloidosis 4
- The Mayo ATTR-CM score, which has a good diagnostic performance to distinguish ATTR-CA from AL-CA or no CA, and can be used to identify patients with ATTR-CA 5
Diagnostic Algorithms
Diagnostic algorithms for ATTR-CM may involve a combination of the above tests, as well as clinical evaluation and other imaging modalities. For example:
- The Mayo ATTR-CM score can be used to distinguish ATTR-CA from AL-CA or no CA, and has a better discrimination power compared to other scores and biomarkers 5
- A flexible yet robust algorithm for diagnosis and monitoring of patients with ATTR-CM in Asia has been proposed, taking into account regional practice variations and differing healthcare systems 6
- Unexplained left ventricular (LV) wall thickness, LV apical sparing, and a discrepancy between LV wall thickness and QRS voltage can be used as red flags/clues for ATTR-CM in various current diagnostic algorithms 2
Imaging Techniques
Imaging techniques play a crucial role in the diagnosis of ATTR-CM, including:
- Bone scintigraphy, such as 99mTc-labeled pyrophosphate scintigraphy 2
- Echocardiography, which can be used to evaluate LV wall thickness and other echocardiographic findings 2
- CMR with LGE and T1 mapping, which can be used to characterize cardiac involvement and predict outcome in ATTR-CM 4
- PYP imaging, which can be used to diagnose ATTR-CM noninvasively when AL amyloidosis has been excluded 3