10.5 Cardiac Amyloid Imaging (Tc-99m PYP)

10.5 Cardiac Amyloid Imaging (Tc-99m PYP)

Cardiac Amyloidosis: ATTR vs AL

Cardiac amyloidosis results from extracellular deposition of insoluble amyloid fibrils in the myocardium, producing a thick, restrictive, stiff ventricle with heart failure. The two main systemic types relevant to cardiac imaging are:

• ATTR (transthyretin amyloidosis): either wild-type (senile, age-related) or hereditary mutant transthyretin. ATTR primarily affects the heart and soft tissues.
• AL (light-chain amyloidosis): a plasma-cell dyscrasia producing monoclonal light chains that form amyloid; it can involve the heart, kidneys, and nerves and is treated with chemotherapy.

Distinguishing ATTR from AL is essential because their treatments differ fundamentally — ATTR with tafamidis and other transthyretin stabilizers, AL with anti-plasma-cell regimens. Historically, endomyocardial biopsy was required. Bone-avid tracer scintigraphy now permits non-invasive ATTR diagnosis when AL is excluded.

Radiopharmaceutical and Mechanism

Tc-99m pyrophosphate (PYP) is the bone-avid tracer most used in the United States for ATTR cardiac imaging; Tc-99m DPD and Tc-99m HMDP/HDP serve the same role in Europe and elsewhere. These tracers bind calcium-rich amyloid fibrils (specifically the ATTR type) in the myocardial interstitium. Note that PYP, DPD, and HMDP are not FDA-approved for ATTR-CA diagnosis; their cardiac use is off-label but guideline-endorsed by ASNC and other societies. Typical administered activity is approximately 15–20 mCi (550–740 MBq) IV.

Imaging Protocol

1. Inject Tc-99m PYP intravenously (antecubital vein, flush well to avoid residual arm activity confounding the chest).
2. Acquire planar images of the chest in anterior, LAO, and left lateral (LLAT) views.
3. Image at 1 hour and/or 3 hours post-injection. ASNC practice points favor 3-hour imaging, which reduces residual blood-pool signal and improves specificity; some labs image at both time points.
4. Acquire SPECT/CT (or SPECT) of the chest after planar imaging. SPECT is critical to localize uptake to the myocardium rather than overlying ribs or blood pool.

Visual Grading (0–3)

The semi-quantitative visual score compares myocardial uptake to rib (bone) uptake on planar and SPECT images:

Per ASNC, grade 2 or 3 on planar or SPECT at 3 hours is classified ATTR-positive. Grade 0–1 is ATTR-negative. Grade 1 scans are the least reliable: SPECT may reveal blood-pool (false positive) or confirm absent myocardial uptake.

Heart-to-Contralateral-Lung (H/CL) Ratio

A quantitative heart-to-contralateral-lung (H/CL) ratio is calculated by drawing equal ROIs over the heart and the contralateral (right) chest on the anterior planar image. H/CL > 1.5 is strongly suggestive of ATTR amyloidosis. The ratio is most useful for equivocal grade 1 scans; if the visual grade is clearly 2 or 3, the ratio is not required. H/CL should not be reported when there is no myocardial uptake on SPECT (a blood-pool-only false positive).

The Mandatory AL Exclusion

A positive PYP scan (grade 2–3 or H/CL > 1.5) confirms ATTR cardiac amyloidosis only after AL amyloidosis is excluded, because AL amyloid can also produce bone-avid tracer uptake in over 20% of cases. AL exclusion requires:

• Serum free light-chain assay
• Serum and urine immunofixation electrophoresis

If a monoclonal plasma-cell dyscrasia is present, the PYP result is non-diagnostic for ATTR and biopsy is required. Conversely, a negative PYP does not exclude AL amyloid.

SPECT and the Blood-Pool Trap

False-positive planar uptake most often comes from residual blood-pool activity (free PYP circulating in the blood) rather than true myocardial uptake. SPECT differentiates diffuse myocardial wall uptake (true amyloid) from blood-pool activity (activity in the blood-filled LV cavity). Delaying imaging to 3 hours allows blood-pool clearance. The technologist must therefore always acquire SPECT, especially for grade 1–2 planar reads, and ensure adequate injection-to-imaging time.

Differentiating From a Routine Bone Scan

On a bone scan, PYP/MDP localizes symmetrically to the skeleton. In ATTR cardiac amyloidosis the striking finding is diffuse myocardial uptake that may equal or exceed rib uptake — a pattern distinctly different from focal bone metastases or symmetric normal skeletal uptake. Recognizing this pattern and grading it correctly is the technologist's contribution to an accurate ATTR read.

flowchart TD
    A[Inject Tc-99m PYP] --> B[Planar + SPECT at 1-3 h]
    B --> C[Visual grade vs ribs + H/CL ratio]
    C --> D{Grade 2-3 or H/CL >1.5?}
    D -->|No| E[ATTR-negative]
    D -->|Yes| F[Exclude AL: serum free light chains + immunofixation]
    F --> G{Monoclonal dyscrasia present?}
    G -->|No| H[ATTR cardiac amyloidosis confirmed]
    G -->|Yes| I[Biopsy required; PYP non-diagnostic for ATTR]