Tc-99m PYP Imaging for Cardiac Amyloidosis

Tc-99m PYP Imaging for Cardiac Amyloidosis

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Introduction

Cardiac amyloidosis is an under-recognized cause of heart failure with preserved ejection fraction, restrictive cardiomyopathy, and unexplained left ventricular hypertrophy. Tc-99m pyrophosphate (PYP) imaging has emerged as a pivotal, non-invasive test for diagnosing transthyretin cardiac amyloidosis (ATTR-CM) and has dramatically reduced the need for endomyocardial biopsy in appropriate clinical settings.

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What is Tc-99m PYP Imaging?

Tc-99m PYP imaging is a nuclear scintigraphy technique that uses technetium-99m–labeled pyrophosphate, a bone-seeking tracer. In the heart, this tracer shows avid uptake in myocardium infiltrated by transthyretin amyloid, while uptake is minimal or absent in light-chain (AL) amyloidosis.

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Why is it Important?

Provides non-invasive diagnosis of ATTR-CM

Helps differentiate ATTR from AL amyloidosis

Avoids unnecessary endomyocardial biopsy

Enables early diagnosis and treatment, especially in HFpEF patients

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Indications for PYP Imaging

Tc-99m PYP imaging should be considered in patients with:

HFpEF with unexplained LV wall thickening

Low-voltage ECG with increased wall thickness on echo

Elderly patients with heart failure and carpal tunnel syndrome

History of biceps tendon rupture or lumbar spinal stenosis

Aortic stenosis with disproportionate LV hypertrophy

Suspected infiltrative or restrictive cardiomyopathy

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How the Scan is Performed

Intravenous injection of Tc-99m pyrophosphate

Imaging performed at 1 hour (± delayed 3-hour images)

Planar imaging plus SPECT acquisition

SPECT is essential to confirm true myocardial uptake and exclude blood-pool activity

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Interpretation of Tc-99m PYP Scan

1. Visual Assessment (Perugini Grading)

Grade 0: No myocardial uptake

Grade 1: Myocardial uptake less than ribs (equivocal)

Grade 2: Myocardial uptake equal to ribs (positive)

Grade 3: Myocardial uptake greater than ribs with minimal rib activity (strongly positive)

Grades 2 and 3 are considered diagnostic for ATTR-CM in the correct clinical context.

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2. Quantitative Assessment

Heart-to-Contralateral (H/CL) ratio

H/CL ≥ 1.5 at 1 hour strongly supports ATTR-CM

Quantification should always be interpreted alongside SPECT images

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Diagnostic Algorithm (Key Rule)

Grade 2–3 uptake + absence of monoclonal protein

→ Diagnostic of ATTR cardiac amyloidosis

Any myocardial uptake + presence of monoclonal protein

→ AL amyloidosis must be excluded with tissue biopsy

This step is critical to avoid misdiagnosis, as AL amyloidosis requires urgent hematologic treatment.

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Common Pitfalls and Limitations

Blood-pool activity mimicking myocardial uptake (always review SPECT)

Recent myocardial infarction or rib fractures causing false-positive uptake

Grade 1 uptake is not diagnostic and requires further evaluation

PYP imaging does not reliably detect AL amyloidosis

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Role in Contemporary Practice

Tc-99m PYP imaging is now central to modern diagnostic pathways for cardiac amyloidosis. When combined with monoclonal protein testing, it allows confident, biopsy-free diagnosis of ATTR-CM in most patients and facilitates early initiation of disease-modifying therapy.

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Take-Home Messages

Tc-99m PYP scan is a cornerstone test for ATTR-CM

Always combine imaging with monoclonal protein evaluation

SPECT confirmation is mandatory

Grade 2–3 uptake without monoclonal protein = ATTR-CM

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