Medically reviewed by Dr. Jyoti Rao, Consultant, Medical Affairs | Last reviewed August 2026
Key Takeaways
- The NAC staging system uses NT-proBNP and eGFR; the Mayo (Grogan) system uses cardiac troponin T and NT-proBNP.
- Both systems define three stages of increasing risk, and higher stage is associated with worse survival.
- The Mayo system was derived in wild-type ATTR; the NAC system applies across transthyretin amyloid cardiomyopathy.
- Staging supports prognosis and shared conversations but doesn't replace serial monitoring or individualized judgment.
Staging in ATTR-CM Is Biomarker-Based Risk Stratification
Staging systems in ATTR-CM convert routinely measured biomarkers into a small number of prognostic groups. They rest on the observation that natriuretic peptides, cardiac troponin, and renal function each track with disease severity and outcome. The point of staging isn't to diagnose—that’s already established—but to estimate risk in a reproducible way and to give clinicians and patients a shared vocabulary for trajectory. How risk accumulates over time in narrative terms is developed in prognostic indicators in ATTR-CM; this page covers the formal systems.
The NAC Staging System Uses NT-proBNP and eGFR
The National Amyloidosis Centre staging system stratifies transthyretin amyloid cardiomyopathy using two thresholds: an NT-proBNP cut-point of 3000 ng/L and an eGFR cut-point of 45 mL/min. Stage I is defined by NT-proBNP at or below 3000 ng/L together with eGFR at or above 45 mL/min; Stage III is defined by NT-proBNP above 3000 ng/L together with eGFR below 45 mL/min; the remaining patients are Stage II. The system was developed across both wild-type and variant transthyretin amyloidosis, and survival is progressively shorter from Stage I to Stage III. Because it incorporates renal function, the NAC system captures the cardiorenal interaction that often shapes the course of advanced disease.
The Mayo (Grogan) System Uses Troponin T and NT-proBNP
The Mayo Clinic staging system, derived in wild-type ATTR, uses cardiac troponin T and NT-proBNP, with thresholds of troponin T 0.05 ng/mL and NT-proBNP 3000 pg/mL. Stage I is defined by both biomarkers below their cut-points, Stage II by one value above, and Stage III by both above. As with the NAC system, higher stage corresponds to markedly worse survival. The two systems share NT-proBNP but differ in their second axis—renal function in the NAC system, troponin in the Mayo system—so they are complementary rather than interchangeable, and a given patient can be described by either.
NYHA Class Adds the Functional Dimension
Biomarker stage describes risk but not how a patient feels or functions, which is where New York Heart Association functional class is useful. NYHA class captures symptom burden and functional limitation and is used alongside staging in prognostic discussion and in many treatment and trial frameworks. Reading biomarker stage and functional class together gives a fuller picture than either alone, particularly when biomarkers and symptoms appear discordant.
The three staging systems are summarized below.
| System | Biomarkers | Stage I | Stage II | Stage III | Notes |
|---|---|---|---|---|---|
| NAC (Gillmore 2018) | NT-proBNP and eGFR | NT-proBNP at or below 3000 ng/L and eGFR at or above 45 mL/min | Neither (intermediate) | NT-proBNP above 3000 ng/L and eGFR below 45 mL/min | Across wild-type and variant ATTR |
| Mayo / Grogan (2016) | Troponin T and NT-proBNP | Both below cut-points | One above | Both above | Cut-points: troponin T 0.05 ng/mL, NT-proBNP 3000 pg/mL; derived in wild-type |
| NYHA | Functional class | \- | \- | \- | Symptom and functional limitation; read alongside biomarker stage |
How Staging Informs Prognosis and Conversations
Staging is clinically valuable because it makes prognosis communicable and anchors expectations at the start of and during care. A stage is a snapshot, however, and the trajectory matters as much as the starting point, so staging works best alongside serial follow-up rather than as a one-time label. In practice, it informs the intensity of clinical management, supports realistic discussion of cost, access, and persistence, and complements the narrative risk picture rather than overriding clinical judgment.
Practical Checklist for Using Stage
When applying a staging system, confirm:
- Which system is being used (NAC or Mayo), and are the biomarkers required for that system available?
- Are the values current, and could a transient illness be distorting them?
- Is NYHA functional class documented alongside the biomarker stage?
- Is the stage being read as part of a trend rather than a single snapshot?
- Does the stage match the clinical picture, or is there discordance to explain?
Clinical Decision Point
Stage should inform conversations and intensity of follow-up, not substitute for them. A single high-stage result in the setting of acute illness may overstate baseline risk, and a low stage doesn't guarantee stability. The most informative assessment combines a validated biomarker stage, functional class, and the trajectory observed across serial assessment that’s then interpreted against the individual patient rather than the number alone.
Frequently Asked Questions
What biomarkers are used to stage ATTR-CM?
The NAC system uses NT-proBNP and eGFR, with thresholds of 3000 ng/L and 45 mL/min. The Mayo (Grogan) system uses cardiac troponin T and NT-proBNP, with thresholds of 0.05 ng/mL and 3000 pg/mL, and was developed in wild-type ATTR. The original versions of both systems define three stages of increasing risk.
How do the NAC and Mayo systems differ?
They share NT-proBNP but differ in the second axis: the NAC system adds renal function (eGFR) and was developed across wild-type and variant disease, while the Mayo system adds troponin T and was derived in wild-type ATTR. They are complementary rather than interchangeable.
Does a higher stage mean worse prognosis?
Yes. In the original validation studies, higher stage was associated with progressively worse survival. Stage is a probabilistic estimate of risk at a point in time, not a fixed prediction for an individual patient.
Where does NYHA class fit?
NYHA functional class describes symptom burden and functional limitation and is used alongside biomarker staging. Reading stage and functional class together gives a fuller prognostic picture, especially when they appear discordant.
Can staging change over time?
Yes. Biomarkers and functional class change as disease and treatment evolve, so a stage is best interpreted as part of a trend across serial assessments rather than as a one-time label.
Related Reading
Part of the Spotlight On ATTR-CM resource center.
Outcomes and Burden
Next Clinical Decision
See the Evidence
References:
- A New Staging System for Cardiac Transthyretin Amyloidosis (National Amyloidosis Centre). European Heart Journal
- Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System (Mayo / Grogan). Journal of the American College of Cardiology
- World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM). Global Heart
- How to Monitor Disease Progression in ATTR Amyloid Cardiomyopathy: Implications for Clinical Practice and Trial Design. European Journal of Internal Medicine
This content is intended for healthcare professionals for educational purposes and isn't a substitute for individual clinical judgment. It was developed with AI assistance and reviewed by a qualified healthcare professional for clinical accuracy prior to publication.