PYP Scan for Cardiac Amyloidosis Diagnosis
99mTc-PYP scintigraphy is highly useful and diagnostic for ATTR cardiac amyloidosis when combined with exclusion of monoclonal protein, but it is NOT appropriate for diagnosing AL amyloidosis. 1
Diagnostic Utility and Indications
PYP scanning is specifically indicated for confirming ATTR cardiac amyloidosis after ruling out light chain disease. The test achieves diagnostic accuracy when Grade 2 or 3 myocardial uptake is present on visual scoring AND serum/urine immunofixation plus free light chains are negative. 1
When PYP Scan is Appropriate:
- Screening for ATTR in new symptomatic heart failure with left ventricular wall thickness ≥12-14 mm, particularly when there is voltage-to-mass discordance on ECG 1
- Asymptomatic TTR gene carriers for early detection of cardiac involvement 1
- Patients with clinical red flags including bilateral carpal tunnel syndrome, lumbar spinal stenosis, peripheral neuropathy, or unexplained heart failure with preserved ejection fraction 1
When PYP Scan is NOT Appropriate:
- Suspected AL amyloidosis (when elevated free light chains or monoclonal protein is present) - rated "Rarely Appropriate" 1
- Monitoring disease progression in biopsy-proven cardiac amyloidosis - rated "Rarely Appropriate" 1
- Quantifying amyloid burden - PET tracers are preferred for this purpose 1
Interpretation Criteria
A positive PYP scan requires BOTH visual and quantitative criteria:
- Visual grading (Perugini score) ≥2 on planar imaging 2
- Heart-to-contralateral lung ratio >1.5 at 1 hour OR >1.3 at 3 hours 2
- SPECT imaging should be added to planar imaging to differentiate true myocardial uptake from blood pool activity 2
Critical Diagnostic Pitfalls
The most dangerous pitfall is assuming ATTR diagnosis when monoclonal protein is present. A positive PYP scan in the context of ANY abnormal monoclonal protein evaluation (MGUS, elevated free light chains, abnormal immunofixation) should NOT be considered diagnostic for ATTR cardiac amyloidosis. 1, 2 These patients require referral to a specialist amyloid center and consideration of endomyocardial biopsy for definitive tissue typing. 1
Over 10% of patients with monoclonal gammopathy can have ATTR deposits, making tissue diagnosis essential when both PYP is positive and monoclonal protein studies are abnormal. 2
Excess blood pool activity on 1-hour images can lead to false positive interpretations, which is why SPECT imaging and delayed imaging are important. 2
Diagnostic Algorithm
First: Screen for monoclonal protein with serum/urine immunofixation electrophoresis AND serum free light chains 1, 3, 2
If monoclonal protein is absent AND clinical suspicion is high: Proceed with 99mTc-PYP scintigraphy 1, 3
If PYP shows Grade 2-3 uptake with H/CL ratio >1.5: ATTR cardiac amyloidosis is confirmed (no biopsy needed) 1
If PYP shows intermediate uptake (ratio 1.2-1.49): Pursue additional testing including cardiac MRI, consider endomyocardial biopsy - 25% of these patients have confirmed cardiac amyloidosis 4
If monoclonal protein IS present: PYP scan alone is insufficient; endomyocardial biopsy with mass spectrometry is required 1, 5
After ATTR diagnosis: Perform TTR gene sequencing to differentiate hereditary (ATTRv) from wild-type (ATTRwt) 1, 3
Comparison to Other Imaging Modalities
PYP has some uptake in AL amyloidosis patients, but significantly less than in ATTR, which is why it cannot reliably exclude AL disease. 1 This is the mechanistic reason why monoclonal protein screening must precede PYP interpretation.
Cardiac MRI and echocardiography are rated "Appropriate" for initial screening, while PYP is specifically diagnostic for ATTR subtyping. 1 The diagnostic pathway should begin with echo or MRI to identify infiltrative cardiomyopathy, then proceed to PYP for ATTR confirmation after excluding AL disease. 5, 2
Bone scintigraphy tracers (PYP in USA, DPD/HMDP outside USA) are mechanistically bone tracers that happen to bind ATTR deposits, providing diagnostic capability with possible early detection. 1