What Is Cardiac Amyloidosis?
Cardiac amyloidosis is a condition where abnormal proteins (called amyloid) deposit in the heart muscle. These protein deposits make the heart walls stiff and thick, gradually interfering with the heart’s ability to fill and pump blood effectively. Over time, this leads to heart failure.
The condition was historically considered rare. In reality, it has been significantly underdiagnosed. As awareness and diagnostic tools have improved, doctors are recognising it more frequently, particularly in older adults with unexplained heart failure or thickened heart walls.
Types of Cardiac Amyloidosis
There are two main types relevant to the heart:
- ATTR amyloidosis (transthyretin amyloidosis): This is caused by the misfolding of transthyretin, a protein made by the liver. ATTR can be hereditary (caused by a genetic mutation) or wild-type (age-related, with no genetic mutation). Wild-type ATTR is increasingly recognised in men over 65 with heart failure.
- AL amyloidosis (light-chain amyloidosis): This is caused by abnormal light-chain proteins produced by bone marrow plasma cells. AL amyloidosis is a different disease with different treatment and requires different diagnostic approaches.
Distinguishing between these two types is critical because they have very different treatments and prognoses.
Why Diagnosis Was Historically Difficult
Cardiac amyloidosis mimics other, more common causes of heart failure and thickened heart walls. Echocardiography (heart ultrasound) might show increased wall thickness, but this finding also occurs in hypertensive heart disease and hypertrophic cardiomyopathy. Many patients with cardiac amyloidosis spent years being treated for other conditions before receiving the correct diagnosis.
For a long time, the definitive diagnosis required a heart biopsy, an invasive procedure where a small piece of heart tissue is removed and examined under a microscope. While biopsies are still sometimes necessary (particularly for AL amyloidosis), the availability of a non-invasive nuclear scan has transformed the diagnostic pathway for ATTR cardiac amyloidosis.
How the 99mTc-PYP Scan Works
The 99mTc-PYP scan (technetium-99m pyrophosphate scan) is a nuclear medicine imaging study that can identify ATTR amyloid deposits in the heart without a biopsy.
Here is how it works: Technetium-99m pyrophosphate is a radioactive tracer that was originally developed decades ago for detecting heart attacks. Researchers discovered that this tracer also binds to transthyretin amyloid deposits in the heart. This binding is strong and specific enough to serve as a diagnostic tool.
The Procedure
The scan is simple from the patient’s perspective. The tracer is injected into a vein, and after a waiting period of about one to three hours, images of the chest are acquired using a gamma camera. The entire process is painless and requires no special preparation.
The images are evaluated using a standardised scoring system. If the tracer uptake in the heart is equal to or greater than the uptake in the ribs (a visual grading scale), it is considered strongly suggestive of ATTR cardiac amyloidosis. Combined with blood and urine tests that rule out AL amyloidosis (by confirming no abnormal light-chain proteins), a positive 99mTc-PYP scan can confirm the diagnosis of ATTR cardiac amyloidosis without a biopsy.
What Makes This Scan Significant
The impact of this scan on clinical practice has been substantial. Before its adoption, many patients underwent invasive biopsies, and many more were simply never diagnosed. The non-invasive nature of the 99mTc-PYP scan has lowered the barrier to diagnosis, meaning more patients are being identified and treated appropriately.
It is worth clarifying that the 99mTc-PYP scan is specifically useful for ATTR cardiac amyloidosis. It does not reliably diagnose AL cardiac amyloidosis, which requires a different diagnostic workup including bone marrow biopsy and specialised blood and urine tests. This is why your doctor will typically order both the nuclear scan and blood/urine tests to differentiate between the two types.
Who Should Be Evaluated?
Your doctor may consider cardiac amyloidosis and order a 99mTc-PYP scan if you have:
- Heart failure with thickened heart walls on echocardiography, especially if you are over 60
- Heart failure that does not respond as expected to standard treatments
- A history of carpal tunnel syndrome in both hands (this can be an early sign of ATTR amyloidosis, appearing years before heart symptoms)
- Spinal stenosis or biceps tendon rupture (other musculoskeletal associations)
- A family history of amyloidosis or a known TTR gene mutation
- Low voltage on ECG despite thickened heart walls on imaging (a classic but not universal finding)
Early diagnosis matters because treatments are now available for ATTR cardiac amyloidosis. Tafamidis, a medication that stabilises the transthyretin protein and slows disease progression, has been shown to reduce hospitalisations and mortality. The earlier the diagnosis, the earlier treatment can begin.
What Comes After Diagnosis
If the 99mTc-PYP scan and supporting tests confirm ATTR cardiac amyloidosis, your cardiologist will discuss treatment options, ongoing monitoring, and genetic testing (to determine if the hereditary form is present, which has implications for family members).
Management also involves adjusting heart failure medications. Some standard heart failure drugs are poorly tolerated in amyloidosis, so the treatment approach is tailored specifically for this condition.
Speaking With Your Doctor
If you have unexplained heart failure or your doctor has noted thickened heart walls, ask whether cardiac amyloidosis should be investigated. The 99mTc-PYP scan is a straightforward, non-invasive test that can provide a definitive answer for ATTR type amyloidosis.
For more information about this scan, visit our 99mTc-PYP scan page.