Criteria

Mayo staging system for immunoglobulin light chain (AL) amyloidosis (2012)​[94]

Based on the following three prognostic markers:

  • N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥1800 ng/L

  • Cardiac troponin T (cTnT) ≥0.025 micrograms/L

  • Difference between involved and uninvolved serum free light chains (dFLC) ≥180 mg/L.

Each prognostic marker is assigned a score of 1. Stage is determined based on the total score:

  • Stage I: total score = 0

  • Stage II: total score = 1

  • Stage III: total score = 2

  • Stage IV: total score = 3

Conversion tables for use of B-type natriuretic peptide (BNP) instead of NT-proBNP, and for use of cardiac troponin I (cTnI) or high-sensitivity cTnT (hs-cTnT) instead of cTnT, have been published.[62][105]

Mayo staging system for immunoglobulin light chain (AL) amyloidosis (2004) with European modifications[93][95]

Based on the following risk factors:

  • N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥332 ng/L

  • Cardiac troponin T (cTnT) ≥0.035 microgram/L; or cardiac troponin I (cTnI) ≥0.1 microgram/L

Stage is determined based on the presence of these risk factors (an NT-proBNP cutoff of 8500 ng/L is used to subclassify stage III):

  • Stage I: no risk factors

  • Stage II: 1 risk factor

  • Stage IIIA: 2 risk factors (with NT-proBNP 332 to <8500 ng/L)

  • Stage IIIB: 2 risk factors (with NT-proBNP ≥8500 ng/L)

Conversion tables for use of B-type natriuretic peptide (BNP) instead of NT-proBNP, and high-sensitivity cTnT (hs-cTnT) instead of cTnT or cTnI, have been published.[62][105]

Haematological treatment response criteria for AL amyloidosis[106]

  • Complete response (CR): normal serum free light chain (FLC) levels with a normal kappa/lambda ratio and negative serum and urine immunofixation

  • Very good partial response (VGPR): difference between involved and uninvolved serum FLC (dFLC) <40 mg/L

  • Partial response (PR): dFLC decrease ≥50%

  • No response: response is less than PR

A modification to this criteria has been proposed that uses negative serum and urine immunofixation, along with involved FLC ≤20 mg/L or dFLC ≤10 mg/L, as a criteria for CR (i.e., instead of a normal serum FLC ratio), which may provide improved survival discrimination.[107]

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/ SNMMI expert consensus recommendations: diagnostic criteria[108]​​

Histological diagnosis of cardiac amyloidosis: Endomyocardial biopsy (amyloidogenic light chain, amyloidogenic transthyretin [ATTR], other subtypes)

  • Endomyocardial biopsy positive for cardiac amyloidosis with Congo red staining with apple-green birefringence under polarised light; typing by immunohistochemistry and/or mass spectrometry at specialised centres.

Histological diagnosis of cardiac amyloidosis: Extracardiac biopsy (ATTR)

  • ATTR cardiac amyloidosis is diagnosed when the following criteria are met:

    1. Extracardiac biopsy proven AL amyloidosis, and

    2. Typical cardiac imaging features.

Histological diagnosis of cardiac amyloidosis: Extracardiac biopsy (amyloidogenic light chain)

  • Amyloidogenic light chain cardiac amyloidosis is diagnosed when the following criteria are met:

    1. Extracardiac biopsy proven AL amyloidosis, and

    2. Typical cardiac imaging features, or

    3. Abnormal cardiac biomarkers: abnormal age-adjusted NT-pro BNP or abnormal Troponin T/I/Hs-Troponin (with all other causes for these changes excluded).

Clinical diagnosis of ATTR cardiac amyloidosis: 99mTc-PYP, DPD, HMDP

  • ATTR cardiac amyloidosis is diagnosed when the following criteria are met:

    1. 99mTc-PYP, DPD, HMDP Grade 2 or 3 myocardial uptake of radiotracer, and

    2. Absence of a clonal plasma cell process as assessed by serum FLCs and serum and urine immunofixation, and

    3. Typical cardiac imaging features.

Typical imaging features of cardiac amyloidosis: any of the following imaging features (with all other causes for these cardiac manifestations, including hypertension, reasonably excluded)

  • Echocardiography (ATTR/amyloidogenic light chain)

    1. Left ventricular (LV) wall thickness >12 mm

    2. Relative apical sparing of global LS ratio (average of apical LS/average of combined mid+basal LS >1)

    3. ≥ Grade 2 diastolic dysfunction.

  • Cardiac magnetic resonance (ATTR/amyloidogenic light chain)

    1. LV wall thickness >upper limit of normal for sex

    2. Global extracellular volume >0.40

    3. Diffuse late gadolinium enhancement

    4. Abnormal gadolinium kinetics typical for amyloidosis, myocardial nulling prior to blood pool nulling.

  • PET: 18F-florbetapir or 18F-florbetaben PET (ATTR/amyloidogenic light chain)

    1. Target to background (LV myocardium to blood pool) ratio >1.5

    2. Retention index >0.030 minute^-1.

European society of cardiology working group on myocardial and pericardial disease: invasive (all types) cardiac amyloidosis diagnostic criteria[109]

  • Cardiac biopsy positive for amyloid, or

  • Extracardiac biopsy positive for amyloid, plus

  • Echocardiographic/cardiac magnetic resonance criteria.

Echocardiographic and cardiac magnetic resonance criteria are:

  • Echocardiography; unexplained LV thickness (≥12 mm) plus 1 or 2:

    1. Characteristic echocardiography findings (≥2 of the following must be present):

      1. Grade 2 or worse diastolic dysfunction

      2. Reduced tissue Doppler s', e', and a' waves velocities (<5 cm/second)

      3. Decreased global longitudinal LV strain (absolute value <-15%).

    2. Multiparametric echocardiographic score ≥8 points:

      1. Relative LV wall thickness (IVS+PWT)/LVEDD >0.6 (3 points)

      2. Doppler E wave/eʹ wave velocities >11 (1 point)

      3. Tricuspid annular plane systolic excursion ≤19 mm (2 points)

      4. Left ventricular global longitudinal strain absolute value ≤-13% (1 point)

      5. Systolic longitudinal strain apex to base ratio >2.9 (3 points).

  • Cardiac magnetic resonance

    1. Characteristic CMR findings (a and b must be present):

      1. Diffuse subendocardial or transmural late gadolinium enhancement

      2. Abnormal gadolinium kinetics

      3. ECV ≥0.40% (strongly supportive, but not essential/diagnostic).

European society of cardiology working group on myocardial and pericardial disease: non-invasive (ATTR only) cardiac amyloidosis diagnostic criteria[109] 

  • Grade 2 or 3 cardiac uptake at diphosphonate scintigraphy, plus

  • Negative serum free light chains and negative serum and urine immunofixation, plus

  • Echocardiographic/cardiac magnetic resonance criteria (per European society of cardiology working group on myocardial and pericardial disease: invasive (all types) cardiac amyloidosis diagnostic criteria).

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