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PubMed This is a summary of 15 peer-reviewed journal articles Updated
Cardiology · Wild-type Transthyretin Amyloidosis

Understanding Your Stage and Outlook

At a Glance

Staging for wild-type ATTR (wtATTR) amyloidosis uses blood tests like NT-proBNP, Troponin, and eGFR to measure heart and kidney stress, not to predict exact life expectancy. Doctors use the NAC and Mayo staging systems to determine disease severity and guide your treatment plan.

Once a diagnosis of wild-type transthyretin amyloidosis (wtATTR) is confirmed, your care team will use “staging” to understand the severity of the disease and how it may progress. Staging is not a prediction of your life expectancy—rather, it is a tool doctors use to measure how much stress the amyloid deposits are putting on your heart and kidneys right now, which helps guide your treatment decisions [1][2].

The Two Main Staging Systems

There are two primary systems used worldwide to categorize wtATTR. Both use simple blood tests to look for markers of organ stress [1][3].

1. The NAC Staging System

Developed by the National Amyloidosis Centre, this system focuses on how well your heart and kidneys are working together [1]. It uses two markers:

  • NT-proBNP: A protein released when the heart muscle is stretched or under pressure (a marker of heart stress) [1][4].
  • eGFR: A measure of how well your kidneys are filtering waste (a marker of kidney clearance) [1].
Stage Criteria
Stage I NT-proBNP ≤\leq 3,000 pg/mL AND eGFR ≥\geq 45 mL/min
Stage II One of the above is outside the healthy range
Stage III NT-proBNP > 3,000 pg/mL AND eGFR < 45 mL/min
Stage IV NT-proBNP > 10,000 pg/mL (Recent updates have added Stage IV to identify patients who need the most intensive monitoring) [5][6]

2. The Mayo Staging System

This system focuses purely on the heart by measuring two different cardiac proteins [3]:

  • NT-proBNP: (Cutoff: 3,000 pg/mL) [3].
  • Troponin T: A protein released when heart cells are damaged (Cutoff: 0.05 ng/mL) [3][7].

In the Mayo system, you are in Stage I if both are below the cutoff, Stage II if one is above, and Stage III if both are elevated [3].

The Role of Imaging: Global Longitudinal Strain (GLS)

While blood tests show the “chemistry” of heart stress, specialized imaging shows the “mechanics” of how your heart is moving.

Your doctor may look at Global Longitudinal Strain (GLS) on your echocardiogram. While a standard heart ultrasound measures how much blood is pumped out (Ejection Fraction), GLS measures how well the heart muscle fibers are actually shortening and squeezing [8][9].

  • Prognostic Value: A lower (more abnormal) GLS score can be an early warning sign that the heart is struggling, even if your Ejection Fraction still looks “normal” [8][10].

Why Staging Matters for Your Treatment

Staging helps your doctor decide which treatments are right for you and how aggressively to manage your symptoms.

  • Early Stages (Stage I & II): The focus is often on starting “stabilizer” medications (like tafamidis) as soon as possible to keep the disease from progressing [11][12].
  • Advanced Stages (Stage III & IV): While stabilizers are still used, doctors may focus more heavily on managing fluid (using diuretics) and closely monitoring for heart rhythm issues [13][3].

Important Note: These stages were developed by looking at large groups of patients. Every individual journey is different. Many patients remain stable in a specific stage for a long time, especially with the help of modern therapies [14][15].

Previous: Diagnosis and Avoiding Misdiagnosis | Next: Standard of Care and New Directions

Common questions in this guide

What is the NAC staging system for wtATTR amyloidosis?
The NAC staging system measures how well your heart and kidneys are working together. It uses two blood markers: NT-proBNP, which shows heart stress, and eGFR, which shows how well your kidneys are filtering waste. These markers help categorize the disease into stages I through IV.
How is the Mayo staging system different from the NAC system?
While the NAC system looks at both the heart and kidneys, the Mayo staging system focuses entirely on heart health. It measures two cardiac proteins: NT-proBNP and Troponin T. If these proteins are elevated above a certain level, it indicates greater heart stress.
What does Global Longitudinal Strain (GLS) show on my echocardiogram?
Global Longitudinal Strain, or GLS, is an imaging measurement taken during an echocardiogram that shows how well your heart muscle fibers are shortening and squeezing. A lower GLS score can be an early warning sign that your heart is struggling, even if its overall pumping ability looks normal.
Will my wtATTR stage determine my treatment options?
Yes, your stage helps doctors decide the best approach for managing the disease. In earlier stages, the focus is often on starting stabilizer medications to slow progression. In more advanced stages, doctors may prioritize managing fluid buildup with diuretics and closely monitoring heart rhythms.
Does my stage predict my exact life expectancy?
No, staging does not provide an exact prediction of your life expectancy. Staging is simply a tool doctors use to measure current organ stress and guide your therapy. Many patients remain stable in their specific stage for a long time, especially with modern treatments.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my NT-proBNP, Troponin, and eGFR, what is my exact stage according to the Mayo or NAC systems?
  2. 2.How does my kidney function (eGFR) impact which medications are safest for me?
  3. 3.Was my 'Global Longitudinal Strain' (GLS) measured on my last echocardiogram, and what does it tell us about my heart's pumping efficiency?
  4. 4.If I am in an intermediate or advanced stage, how does that change the urgency of starting or adjusting my therapy?
  5. 5.How often should we repeat these blood tests to monitor if the disease is progressing or stabilizing?

Questions For You

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References

References (15)
  1. 1

    A new staging system for cardiac transthyretin amyloidosis.

    Gillmore JD, Damy T, Fontana M, et al.

    European heart journal 2018; (39(30)):2799-2806 doi:10.1093/eurheartj/ehx589.

    PMID: 29048471
  2. 2

    Biomarkers and Prediction of Prognosis in Transthyretin-Related Cardiac Amyloidosis: Direct Comparison of Two Staging Systems.

    Cappelli F, Martone R, Gabriele M, et al.

    The Canadian journal of cardiology 2020; (36(3)):424-431 doi:10.1016/j.cjca.2019.12.020.

    PMID: 32145869
  3. 3

    Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System.

    Grogan M, Scott CG, Kyle RA, et al.

    Journal of the American College of Cardiology 2016; (68(10)):1014-20.

    PMID: 27585505
  4. 4

    Role of biomarkers in early diagnosis and prognosis of cardiac amyloidosis: A systematic review and meta-analysis.

    Albulushi A, Buraiki JA, Aly G, et al.

    Current problems in cardiology 2025; (50(1)):102883 doi:10.1016/j.cpcardiol.2024.102883.

    PMID: 39490645
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    Expansion of the National Amyloidosis Centre staging system to detect early mortality in transthyretin cardiac amyloidosis.

    Nitsche C, Ioannou A, Patel RK, et al.

    European journal of heart failure 2024; (26(9)):2008-2012 doi:10.1002/ejhf.3354.

    PMID: 38922779
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    Characteristics and natural history of early-stage cardiac transthyretin amyloidosis.

    Law S, Bezard M, Petrie A, et al.

    European heart journal 2022; (43(27)):2622-2632 doi:10.1093/eurheartj/ehac259.

    PMID: 35608040
  7. 7

    High-Sensitivity Cardiac Troponin I for Risk Stratification in Wild-Type Transthyretin Amyloid Cardiomyopathy.

    De Michieli L, Sinigiani G, Guida G, et al.

    Circulation. Heart failure 2025; (18(8)):e012816 doi:10.1161/CIRCHEARTFAILURE.125.012816.

    PMID: 40371473
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    Global Longitudinal Strain for Prognostic Staging in Wild-Type Transthyretin Cardiac Amyloidosis.

    Debonnaire P, L'Hoyes W, Donal E, et al.

    Circulation. Cardiovascular imaging 2026; (19(1)):e018862 doi:10.1161/CIRCIMAGING.125.018862.

    PMID: 41342126
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    Prognostic value of right ventricular global longitudinal strain in transthyretin amyloid cardiomyopathy.

    Usuku H, Takashio S, Yamamoto E, et al.

    Journal of cardiology 2022; (80(1)):56-63 doi:10.1016/j.jjcc.2022.02.010.

    PMID: 35282945
  10. 10

    Comparison of the standard and speckle tracking echocardiographic features of wild-type and mutated transthyretin cardiac amyloidoses.

    Minamisawa M, Koyama J, Sekijima Y, et al.

    European heart journal. Cardiovascular Imaging 2016; (17(4)):402-10 doi:10.1093/ehjci/jew003.

    PMID: 26873458
  11. 11

    Tafamidis in the Treatment of ATTR-related Cardiomyopathy: Indications and Grey Zones.

    Capovilla TM, Lalario A, Rossi M, et al.

    Heart failure clinics 2024; (20(3)):333-341 doi:10.1016/j.hfc.2024.03.007.

    PMID: 38844304
  12. 12

    Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy.

    Maurer MS, Schwartz JH, Gundapaneni B, et al.

    The New England journal of medicine 2018; (379(11)):1007-1016 doi:10.1056/NEJMoa1805689.

    PMID: 30145929
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    Tafamidis treatment in transthyretin cardiac amyloidosis: A retrospective cohort analysis of outcomes and associated factors.

    Krief J, Aguilhon S, Delbaere Q, et al.

    Archives of cardiovascular diseases 2026; doi:10.1016/j.acvd.2025.12.010.

    PMID: 41654426
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    Cardiac Biomarker Change at 1 Year After Tafamidis Treatment and Clinical Outcomes in Patients With Transthyretin Amyloid Cardiomyopathy.

    Kuyama N, Takashio S, Oguni T, et al.

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    Longitudinal Changes in Multiple Cardiac Biomarkers in Transthyretin Amyloidosis Cardiomyopathy Patients Treated Vs Untreated with Tafamidis.

    Shahi K, Miller RJH, Dykstra S, et al.

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    PMID: 41001259

This page provides educational information about wtATTR staging and prognosis. Always consult your cardiologist or specialist for medical advice regarding your specific test results, stage, and treatment plan.

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