Why Do PYP Scans Miss Heart Amyloidosis in V30M?

A PYP heart scan (also known as bone scintigraphy or a DPD scan) is a common imaging test used to detect transthyretin (ATTR) amyloidosis in the heart. While it is highly accurate for the wild-type form of the disease and many other mutations, it frequently produces false negative results in patients with the ATTRv V30M mutation (the “v” stands for variant, meaning it is the hereditary form of the disease) ^[1][2]. A false negative means the scan shows no amyloid buildup in the heart, even when amyloid is actually present. Because of this, doctors must rely on other tools like Echocardiograms or Cardiac MRIs to accurately check heart function in V30M patients ^[3][4].

The “Why”: Amyloid Fibril Types

To understand why a PYP scan might miss cardiac amyloidosis in V30M patients, it helps to look at the microscopic structure of the amyloid deposits themselves. Transthyretin amyloid fibrils in the heart can be classified into two structural types: Type A and Type B ^[5].

• Type A fibrils are made of a mix of full-length and broken (fragmented) transthyretin proteins. These fibrils strongly attract and bind to the radioactive tracers used in PYP and DPD scans ^[5].
• Type B fibrils are composed only of full-length transthyretin proteins. For reasons scientists are still studying, Type B fibrils do not bind well to the bone scan tracers ^[5][6].

In ATTRv V30M amyloidosis, especially in patients who develop symptoms at a younger age (early-onset disease, typically before age 50), the heart amyloid deposits are often primarily Type B ^[5][7]. Because the PYP tracer cannot firmly attach to these Type B fibrils, the scan comes back looking clear, resulting in a false negative ^[8][2]. By contrast, patients with late-onset V30M are more likely to have Type A fibrils, which the PYP scan can detect more easily ^[7].

What This Means for Your Testing

Because PYP and DPD scans can be unreliable for the V30M mutation, a negative scan should never be used as the sole reason to rule out heart involvement ^[6][9]. If you experience physical symptoms of heart involvement—such as shortness of breath, unusual swelling in your legs, or heart palpitations—it is critical to investigate further even if a PYP scan was clear.

Instead, your care team should use imaging tests that do not rely on these specific tracers:

• Echocardiogram (Echo): An ultrasound of the heart that shows the thickness of the heart walls and how well the heart is pumping ^[4].
• Cardiac MRI (CMR): A magnetic resonance imaging scan that provides highly detailed pictures of the heart tissue. Specialized CMR techniques, such as Late Gadolinium Enhancement (LGE) and Extracellular Volume (ECV) mapping, are excellent at detecting amyloid infiltration even when a PYP scan is negative ^[3][10]. LGE involves receiving a safe, non-radioactive IV contrast dye during the MRI to highlight the amyloid.

If these non-invasive imaging tests are inconclusive, a tissue biopsy of the heart muscle remains the gold standard for definitively diagnosing amyloid in the heart ^[9].

If you have the V30M mutation, having normal or inconclusive PYP scan results does not mean your heart is free of amyloidosis. Working with a cardiologist who understands the specific testing needs of V30M amyloidosis is the best way to ensure accurate monitoring of your heart health ^[11][12]. If your doctor tries to rule out heart issues based solely on a negative PYP scan, you can advocate for yourself by mentioning that V30M is known to cause false negatives and requesting an Echocardiogram or Cardiac MRI ^[9].