Cardiac Amyloidosis
When to Suspect Amyloidosis¶
- Increased LV wall thickness without a sufficient loading condition
- HFpEF with restrictive physiology
- Apical-sparing strain pattern
- Biatrial enlargement or thickened interatrial septum
- Conduction disease or atrial fibrillation
- Low voltage relative to LV thickness
- Carpal tunnel syndrome, lumbar stenosis, biceps rupture, neuropathy, or orthostasis
Warning
Normal ECG voltage does not exclude cardiac amyloidosis.
Diagnostic Algorithm¶
- Obtain serum free light chains plus serum and urine immunofixation.
- If any monoclonal study is abnormal → evaluate urgently for AL amyloidosis; PYP cannot independently establish ATTR.
- If monoclonal studies are negative → perform Tc-99m PYP scintigraphy with SPECT.
- Grade 2–3 myocardial uptake with a compatible phenotype establishes ATTR-CM noninvasively.
- After ATTR is diagnosed → perform TTR genetic testing.
The critical trap
Bone-avid tracer uptake is not specific for ATTR when a monoclonal protein is present. AL must be excluded before calling the scan diagnostic of ATTR.
Tc-99m PYP Interpretation¶
| Grade | Myocardial uptake |
|---|---|
| 0 | None |
| 1 | Less than rib uptake |
| 2 | Equal to rib uptake |
| 3 | Greater than rib uptake with reduced bone activity |
- Grade 0: ATTR-CM unlikely
- Grade 1: equivocal; consider CMR or biopsy
- Grade 2–3: diagnostic of ATTR-CM only when AL is excluded and SPECT confirms myocardial uptake
SPECT or SPECT/CT is required to distinguish myocardial uptake from residual blood pool or overlying bone.
Heart-to-Contralateral Ratio¶
The H/CL ratio supports interpretation but should not be used alone:
- ≥1.5 at 1 hour is abnormal in an appropriate protocol
- ≥1.3 at 3 hours is abnormal in an appropriate protocol
Visual grading and SPECT localization take priority.
False Positives¶
- Residual blood pool
- Recent myocardial infarction
- Rib fracture or overlying bone activity
- Hydroxychloroquine toxicity
- AL amyloidosis
- Incorrect ROI placement
False Negatives¶
- Early ATTR disease
- Some hereditary TTR variants
- Inadequate acquisition or processing
- Minimal myocardial amyloid burden
Board Pearls¶
- Rule out AL before interpreting PYP as ATTR.
- SPEP alone is insufficient; use serum and urine immunofixation plus free light chains.
- Grade 2 planar uptake without SPECT confirmation may represent blood pool.
- CMR supports cardiac amyloidosis but does not reliably determine amyloid type.
- Genetic testing follows confirmation of ATTR and distinguishes variant from wild-type disease.