In a 62‑year‑old woman with newly diagnosed heart failure with preserved ejection fraction, lumbar spinal stenosis, cervical spinal stenosis, and right lateral thigh neuropathy, what management steps would a cardiologist take after a technetium‑99m pyrophosphate (PYP) scan showing grade 1 uptake (H/CL ratio 0.84)?

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Last updated: September 11, 2026 • View editorial policy

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Management of Grade 1 PYP Scan (H/CL 0.84) in HFpEF Patient

A cardiologist would interpret this PYP scan as equivocal for ATTR cardiac amyloidosis and immediately order serum and urine immunofixation plus serum free light chains to exclude AL amyloidosis, while considering referral to an amyloidosis specialist given the patient's concerning extracardiac features (spinal stenosis, neuropathy) that may represent systemic ATTR deposition. 1

Interpretation of the PYP Results

The scan shows:

  • Visual grade 1 (myocardial uptake less than rib uptake)
  • H/CL ratio 0.84 (below the diagnostic threshold of ≥1.5 at 1 hour)

According to the 2021 ASNC/AHA/ASE expert consensus, this combination is classified as "equivocal for ATTR cardiac amyloidosis" rather than "not suggestive" or "strongly suggestive." 1 Grade 1 uptake specifically warrants further evaluation because it can be seen in both AL amyloidosis and early ATTR disease.

Critical Next Steps

1. Mandatory Plasma Cell Dyscrasia Screening

The cardiologist must order:

  • Serum free light chains (sFLC) assay
  • Serum immunofixation
  • Urine immunofixation

This is non-negotiable for any patient with grade 1 uptake, as grade 0 and grade 1 uptake may be observed in AL cardiac amyloidosis. 1 Missing AL amyloidosis has catastrophic consequences, as treatment differs fundamentally from ATTR.

2. Clinical Context Assessment

The patient's history is highly suspicious for systemic ATTR amyloidosis:

  • Lumbar spinal stenosis - ATTRwt deposits in ligaments and spinal structures
  • Cervical spine stenosis - another common site of ATTR deposition
  • Right lateral thigh neuropathy - peripheral neuropathy is a hallmark of ATTR

These orthopedic and neurologic manifestations are known to precede cardiac involvement by several years in wild-type ATTR amyloidosis. 2, 3 The combination of HFpEF with these extracardiac features substantially increases pretest probability for ATTR, even with an equivocal scan.

3. Consider Early/Subclinical ATTR-CM

Recent evidence demonstrates that:

  • ATTR can deposit in extracardiac tissues (subcutaneous fat, skeletal muscle, ligaments) before detectable myocardial uptake on PYP scanning 2
  • Some patients with confirmed ATTR-CM present with no ventricular hypertrophy and negative PYP scans 3
  • The H/CL ratio of 0.84 is below diagnostic threshold but not zero, suggesting possible early deposition

Common pitfall: Dismissing equivocal scans as negative without considering the clinical context and extracardiac manifestations.

Algorithmic Approach

If plasma cell dyscrasia workup is negative:

  1. Refer to amyloidosis specialist or multidisciplinary amyloidosis center
  2. Consider advanced imaging:
    • Cardiac MRI with late gadolinium enhancement and ECV mapping (can detect early amyloid deposition)
    • Repeat PYP scan in 6-12 months if clinical suspicion remains high
  3. Consider fat pad biopsy or other tissue biopsy from symptomatic sites (e.g., carpal tunnel if present) with Congo red staining and immunohistochemistry
  4. TTR gene sequencing to distinguish hereditary from wild-type ATTR

If plasma cell dyscrasia workup is positive or equivocal:

  • Immediate hematology referral
  • Bone marrow biopsy
  • Endomyocardial biopsy may be needed to distinguish AL from ATTR if imaging remains equivocal

Why This Matters for Outcomes

ATTR-CM prevalence in HFpEF with ventricular wall thickening is 6.3% overall, rising to 21% in patients ≥90 years old and 10.1% in men. 4 Early diagnosis is critical because:

  • Disease-modifying therapies (tafamidis, patisiran, inotersen) dramatically improve survival and quality of life in ATTR-CM
  • Median life expectancy without treatment is poor once cardiac involvement develops
  • Standard HFpEF therapies alone are insufficient for ATTR-CM

The equivocal scan in this clinical context (HFpEF + spinal stenosis + neuropathy) should not be dismissed as negative. The extracardiac features suggest systemic ATTR deposition that may be in the early stages of cardiac involvement, potentially before reaching PYP-positive thresholds. 2, 3

Documentation and Follow-up

The cardiologist should document:

  • Equivocal PYP result requiring further workup
  • High clinical suspicion for ATTR given extracardiac manifestations
  • Plan for plasma cell dyscrasia exclusion
  • Consideration of amyloidosis specialist referral
  • Need for close follow-up and possible repeat imaging

Do not simply report this as "negative for amyloidosis" and move on with standard HFpEF management. 1

References

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