Why Would a Person Have a Positive Cardiovascular Myocardial PYP Scan?
A positive myocardial technetium-99m pyrophosphate (PYP) scan most commonly indicates transthyretin cardiac amyloidosis (ATTR-CM), but only when monoclonal light chains are absent from serum and urine. 1, 2
Primary Indication: ATTR Cardiac Amyloidosis
The 2022 AHA/ACC/HFSA guidelines establish that 99mTc-PYP scanning is diagnostic of ATTR-CM when grade 2/3 cardiac uptake or heart-to-contralateral lung (H/CL) ratio >1.5 is present AND there is no evidence of monoclonal light chains 1, 2. This combination has very high specificity and positive predictive value for ATTR-CM 1.
Clinical Context for Ordering PYP Scan
PYP scanning should be performed when there is high clinical suspicion for cardiac amyloidosis, specifically:
- Left ventricular wall thickness ≥14 mm with fatigue, dyspnea, or edema
- Voltage-mass discordance: thick walls on echo but low QRS voltage on ECG
- Associated conditions: severe aortic stenosis, HFpEF, bilateral carpal tunnel syndrome, lumbar spinal stenosis, autonomic/sensory polyneuropathy 1, 2, 1
- Echocardiographic findings: apical sparing pattern on strain imaging, granular sparkling myocardium, biatrial enlargement 3
Critical Diagnostic Algorithm
The PYP scan result MUST be interpreted in context of monoclonal protein screening 1, 2:
First: Check serum free light chains (FLC), serum immunofixation electrophoresis (IFE), and urine IFE (>99% sensitive for AL amyloidosis) 1
If monoclonal proteins are ABSENT and PYP is positive (grade 2/3 or H/CL >1.5): Diagnosis is ATTR-CM without need for biopsy 1, 2
If monoclonal proteins are PRESENT: PYP positivity cannot distinguish between ATTR and AL amyloidosis—endomyocardial biopsy with immunohistochemistry or mass spectrometry is required 1, 4
Important Pitfalls and False Positives
AL Amyloidosis Can Cause Positive PYP
PYP scans may be positive even in AL amyloidosis 1, 2, 1. This is why the guidelines mandate that bone scintigraphy alone, without concomitant light chain testing, cannot distinguish ATTR-CM from AL-CM 1. Case reports document false-positive PYP scans (grade 2, H/CL 1.65) in biopsy-proven AL cardiac amyloidosis 5.
Other Rare Causes of Positive PYP
- Fabry disease: Case reports show myocardial PYP uptake in Fabry cardiomyopathy 6
- Hyperphosphatemia: Documented false-positive with Perugini grade 3 uptake, ruled out by endomyocardial biopsy 7
- Bacterial endocarditis: Historical case of positive PYP in endocarditis 8
- Prior myocardial infarction: May cause falsely low H/CL ratio due to limited uptake in infarcted zones; requires careful SPECT evaluation 9
Technical Considerations
SPECT imaging is essential for all positive or equivocal scans to confirm true myocardial retention versus blood pool or rib uptake signal 1, 9, 2. Visual grading (Perugini 0-3) and semi-quantitative H/CL ratio should both be employed 9.
Next Steps After Positive PYP
If ATTR-CM is diagnosed, TTR gene sequencing is mandatory to differentiate hereditary variant (ATTRv) from wild-type (ATTRwt) disease 1, 2. This distinction is critical because:
- ATTRv triggers genetic counseling and family screening
- Specific therapies (inotersen, patisiran) are approved only for ATTRv with polyneuropathy
- Tafamidis is indicated for both ATTRv and ATTRwt with NYHA class I-III symptoms 1
Prognostic Implications
Positive PYP uptake carries prognostic significance: patients with positive PYP SPECT have significantly higher incidence of cardiac death and fatal ventricular arrhythmias compared to those with negative scans (11% vs 4%, P=0.018), with PYP positivity being an independent predictor of adverse cardiac events 10.