What does stage 2 in the National Amyloidosis Centre (NAC) staging system for AL amyloidosis represent?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: September 22, 2026 • View editorial policy

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question

NAC Stage 2 in Transthyretin Cardiac Amyloidosis

NAC Stage 2 represents an intermediate-risk category in transthyretin cardiac amyloidosis, defined as patients who have either elevated NT-proBNP (>3000 ng/L) OR reduced kidney function (eGFR <45 ml/min), but not both simultaneously.

Staging Criteria

The National Amyloidosis Centre (NAC) staging system for ATTR cardiac amyloidosis uses two biomarkers to stratify patients 1:

  • NT-proBNP: Cut-point at 3000 ng/L
  • eGFR: Cut-point at 45 ml/min

Stage 2 is defined as the "remainder" category - patients who don't meet criteria for Stage 1 (both biomarkers favorable) or Stage 3 (both biomarkers unfavorable) 1.

Specifically:

  • Stage 1: NT-proBNP ≤3000 ng/L AND eGFR ≥45 ml/min
  • Stage 2: Either NT-proBNP >3000 ng/L OR eGFR <45 ml/min (but not both)
  • Stage 3: NT-proBNP >3000 ng/L AND eGFR <45 ml/min

Prognostic Significance

Stage 2 patients have intermediate survival outcomes with median survival of approximately 46.7 months 1. In the original NAC cohort of 869 patients, Stage 2 represented 38% of the population 1.

The mortality risk is substantial:

  • 1-year mortality: 8.8% 2
  • After adjusting for age, Stage 2 patients have a 2-fold higher mortality risk compared to Stage 1 (HR 2.05,95% CI 1.54-2.72) 1
  • Stage 2 has better prognosis than Stage 3, which carries a 3.8-fold higher mortality risk than Stage 1 1

Clinical Context

This staging system applies to both wild-type ATTR (ATTRwt) and hereditary variant ATTR (ATTRv) cardiac amyloidosis 1. The prognostic value remains consistent across genotypes and has been validated in independent cohorts 1.

The NAC stage maintains its prognostic value throughout the disease course 3. Serial recalculation during follow-up is clinically meaningful - progression from Stage 1 to a higher stage predicts ongoing mortality with hazard ratios of 2.58-3.22 3.

Contemporary Relevance

Even in the era of disease-modifying therapy (tafamidis), the NAC staging system remains effective for risk stratification 4. In a contemporary cohort where 85% received tafamidis, 3-year survival for Stage 2 was 67.5% 4, demonstrating that staging retains clinical utility for treatment planning and prognostication.

Important Caveat

Do not confuse this with AL amyloidosis staging systems (Mayo 2004, Mayo 2012, European 2015), which use different biomarker thresholds and are designed for a completely different disease entity 5. The NAC staging system is specifically validated for transthyretin cardiac amyloidosis, not AL amyloidosis.

References

Related Questions

What is the recommended use of serum free light‑chain assay and serum immunofixation electrophoresis in the evaluation and monitoring of amyloidosis?
How is amyloidosis diagnosed?
In a 71‑year‑old woman with a very high atypical P‑ANCA (perinuclear anti‑neutrophil cytoplasmic antibodies) titer, markedly elevated free κ and λ light chains, increased γ‑globulin and total globulin, what is the likely diagnosis and what diagnostic work‑up and initial treatment should be pursued?
What is the significance of a non‑dependent air‑fluid level in the bladder on computed tomography, and what diagnostic and therapeutic steps should be taken?
In a 79-year-old man presenting with shoulder and neck pain, sinus pressure above and below the eyes, left lower back pain worsened by deep inspiration, hypothermia, hypertension, and warm extremities, what emergent diagnosis should be considered and what immediate management is indicated?
Should antitubercular therapy be discontinued now or should further investigations be performed to definitively exclude tuberculous meningitis in an 18‑year‑old female with one‑month history of headache and fever, normal MRI, and cerebrospinal fluid showing lymphocytic pleocytosis (16 cells/mm³), normal glucose (74 mg/dL) and mildly elevated protein (88 mg/dL) after five weeks of treatment?
In a patient currently receiving piperacillin‑tazobactam (Tazocin) with an ESBL‑producing Escherichia coli wound infection that is susceptible to both piperacillin‑tazobactam and meropenem, which antibiotic is the preferred treatment?
What is the TSH target and follow‑up plan for a 57‑year‑old patient who had papillary thyroid carcinoma, underwent total thyroidectomy and radioactive iodine ablation 20 years ago, has a normal serum thyroglobulin level and a small residual thyroid tissue focus?
What do the NCCN (National Comprehensive Cancer Network) recommendation grades IVa and IVb mean?
Which angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACE inhibitor) has the lowest risk of causing hyperkalaemia?
Is there scientific evidence supporting the use of 100 mg aspirin for secondary prevention after an ischemic event?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.