Blood tests for ATTR-CM
Reviewed by Transthyretin amyloid cardiomyopathy (ATTR-CM) is a condition in which transthyretin, a protein made by the liver, becomes misfolded and accumulates in the heart muscle as deposits called amyloid fibrils. This buildup, known as amyloidosis, causes the heart muscle to stiffen and reduces its ability to relax and contract, which over time can lead to heart failure.
No single blood test can confirm ATTR-CM. If the condition is suspected, doctors usually combine heart imaging, blood and urine tests, and a nuclear bone scan. ATTR-CM blood tests play two important roles: ruling out a different, more rapidly progressing form of amyloidosis and measuring signs of heart strain and damage. In some cases, a biopsy may be needed to confirm the diagnosis.
The dual role of blood tests in ATTR-CM evaluation
Blood tests for ATTR-CM serve two main purposes. The first and most urgent is ruling out AL amyloidosis using a combination of blood tests such as a serum free light chain assay and serum and urine immunofixation tests, which look for abnormal monoclonal proteins. The second is measuring heart strain and heart muscle injury by testing for cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin.
In addition to blood tests, nuclear bone scans are highly accurate for ATTR-CM. When a nuclear bone scan shows characteristic cardiac uptake and blood and urine tests find no monoclonal protein, ATTR-CM can often be diagnosed without a heart biopsy. Echocardiography or cardiac MRI is also used to look for changes consistent with cardiac amyloidosis.
On the other hand, some people with AL cardiac amyloidosis also show signs of ATTR-CM using nuclear bone scans alone. A positive scan on its own therefore cannot separate the two conditions.
Blood and urine tests are essential for distinguishing between the conditions, although finding a monoclonal protein does not by itself confirm AL amyloidosis. AL amyloidosis develops when abnormal plasma cells in the bone marrow produce misfolded light-chain proteins. When AL affects the heart and is left untreated, median survival is less than six months.
The treatment for AL amyloidosis uses drugs that target the abnormal plasma cells, and often includes chemotherapy and immunotherapy. Unlike AL amyloidosis, ATTR-CM generally progresses more slowly. Additionally, doctors usually treat ATTR-CM with medicines that stabilize or reduce transthyretin.
Because the two conditions require different treatment and can progress at different rates, an incorrect diagnosis can delay appropriate treatment. This is especially serious for people with AL amyloidosis, given how quickly the condition can progress.
Despite its importance, an analysis of U.S. Medicare records found that only 14% of people diagnosed with wild-type ATTR-CM had undergone the recommended combination of a nuclear bone scan and full monoclonal protein testing.
Blood tests also establish a cardiac health baseline. Blood test results recorded at diagnosis feed into staging systems that estimate a person’s outlook and help decide how closely someone should be followed.
Essential blood and urine tests
Excluding AL amyloidosis depends on a monoclonal protein screen. This screen is comprised of a small group of laboratory tests. These tests look for abnormal monoclonal proteins, including protein fragments called light chains.
Many experts call for three complementary tests, carried out in parallel with imaging:
- Serum protein electrophoresis with immunofixation (SPEP with IFE): A blood test that separates different proteins, while immunofixation checks whether an abnormal monoclonal protein is present.
- Urine protein electrophoresis with immunofixation (UPEP with IFE): A urine test that looks for monoclonal proteins or light chains excreted in the urine. It complements blood testing because some abnormalities may not clearly be identified by blood testing alone and may be easier to detect in urine.
- Serum free light chain assay: A blood test that measures two types of free light chain, kappa and lambda, and reports the balance between them. Serum free light chains in ATTR-CM workups with a lopsided ratio suggest that certain plasma cells are overproducing a light chain, but this result must be interpreted alongside kidney function.
The kidneys help clear light chains from the blood. Reduced kidney function can increase light chain levels and alter their ratio, even in people who do not have ATTR-CM or AL amyloidosis.
If the combined results suggest that a monoclonal protein is present, a positive bone scan is no longer enough on its own to distinguish between ATTR-CM and AL amyloidosis. A tissue biopsy with amyloid typing may then be needed to identify which proteins are actually building up in an individual’s heart.
Scroll horizontally to view all columns -->
| Test | Sample | What it looks for | Why it matters |
|---|---|---|---|
| SPEP with IFE | Blood | An abnormal monoclonal protein | Helps exclude AL amyloidosis |
| UPEP with IFE | Urine | Light chains passing into the urine | Can detect monoclonal proteins or light chains in urine that may not be found by blood tests |
| Serum free light chains | Blood | An unbalanced kappa to lambda ratio | Third arm of the screen; needs kidney-adjusted ranges |
Evaluating heart strain and damage
The second group of tests helps assess how ATTR-CM is affecting the heart. Doctors primarily use two biomarkers that reflect different heart-related processes.
NT-proBNP in ATTR-CM is released when increased pressure and volume stretch the walls of the heart’s pumping chambers. Higher levels can indicate greater strain on the heart and more severe heart failure, although kidney function and other conditions can also affect the results.
Troponin in cardiac amyloidosis works differently. It is released into the blood when heart muscle cells are injured, and various heart conditions can raise its levels. In ATTR-CM, higher levels can indicate ongoing heart muscle injury
These ATTR-CM biomarkers are used in two common staging systems:
- Mayo system: Developed for wild-type ATTR-CM, this system combines NT-proBNP with troponin T.
- U.K. National Amyloidosis Centre system: Used for both wild-type and hereditary ATTR-CM, this system combines NT-proBNP with estimated glomerular filtration rate (eGFR), a measure of kidney function.
These biomarkers do not diagnose ATTR-CM on their own and must be interpreted alongside other test results.
Staging helps a cardiology team assess disease severity, discuss outlook, and plan ongoing care. Those unsure what a stage means should ask their cardiology team to explain it in the context of their condition. The care team will decide how often follow-up is needed based on the stage, symptoms, treatment, and other health needs.
Genetic blood testing
Once ATTR-CM is confirmed, genetic testing is recommended to determine whether it is hereditary or wild-type. In wild-type ATTR-CM, the protein becomes unstable and misfolds with age. In hereditary ATTR-CM, the protein is more likely to misfold because of an inherited change in the TTR gene, the segment of DNA that carries the instructions for making transthyretin.
A genetic test can look for a disease-causing change in the TTR gene. This is done by taking a standard blood sample for DNA sequencing in a specialized lab. If a change is found, the condition is hereditary ATTR-CM, and if no disease-causing TTR variant is found, it is classified as wild-type ATTR. A genetic counselor can help patients understand what the result means for them and their family, including who else may want to consider testing. The medical team can then use the genetic result together with symptoms and other tests when planning treatment and follow-up.
TTR gene testing alongside genetic counseling is recommended for everyone with confirmed ATTR. This is true at any age. Studies that included people diagnosed in their 70s or older have identified disease-causing TTR genetic variants, with some of these people going on to start specific treatment.
These results can also matter to relatives of people with ATTR-CM. Hereditary ATTR is passed on in an autosomal dominant pattern. A person with a disease-causing TTR variant has a 50% chance of passing it to each child. Other first-degree relatives, including parents and siblings, may also carry the familial variant and should be offered genetic counseling and testing.
If a disease-causing variant is found, genetic counseling can help identify relatives who may wish to consider testing through cascade screening. This is a process in which relatives are offered testing themselves. People who carry a disease-causing TTR variant may be offered regular monitoring so that signs of disease can be detected early if they develop.
Knowing the genetic status can also shape treatment choices and eligibility for clinical trials. Those weighing what a positive TTR genetic test result might mean for them and their family should ask to speak with a genetic counselor.
Biomarker tracking during treatment
After diagnosis, blood tests can take on a further function.
Routine follow-ups generally involve repeating NT-proBNP, troponin, and kidney function tests. They may also include symptom reviews, imaging studies, and walking assessments, such as a six-minute walk test, which measures how far a person can walk in six minutes. Together, these assessments help healthcare teams track disease progression and determine whether a person’s condition is stable, improving, or worsening during treatment.
A meaningful rise in NT-proBNP over time can be one sign that ATTR-CM is progressing and may be associated with a less favorable outlook.
However, doctors do not rely solely on NT-proBNP levels because other health conditions can affect the results. They use blood tests alongside symptom reviews, physical assessments, and heart tests to monitor ATTR-CM over time.
Amyloidosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
