ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis — Part 2
Authors, Journal, Affiliations, Type, DOI
- Lead Author: Sharmila Dorbala (Brigham and Women's Hospital / Harvard Medical School)
- Co-Chair: Jamieson M. Bourque (University of Virginia)
- Journal: Circulation: Cardiovascular Imaging
- Year: 2021; 14:e000030
- Societies: ASNC, AHA, ASE, EANM, HFSA, ISA, SCMR, SNMMI (8 societies)
- Type: Multi-society expert consensus (Part 2 of 2) — modified Delphi methodology, 7-member clinical expert rating panel
- DOI: https://doi.org/10.1161/HCI.0000000000000030
Overview
Part 2 complements Part 1 by formalising two deliverables absent from existing guidelines: (1) Expert consensus diagnostic criteria for cardiac amyloidosis with precise imaging thresholds (Table 1); and (2) Appropriate utilization ratings across 32 clinical scenarios using modified Delphi methodology (Table 2). The central finding is that echocardiography is Appropriate in nearly all clinical scenarios, scintigraphy is Appropriate primarily for ATTR-suspected cases and Rarely Appropriate whenever AL amyloidosis is suspected or biopsy-proven, and CMR occupies an intermediate role with greatest strength in amyloid burden quantification. Evidence base was moderate-quality; PET recommendations were based on limited data.
Keywords
Cardiac amyloidosis, AL amyloidosis, ATTR amyloidosis, diagnostic criteria, appropriate use criteria, echocardiography, CMR, radionuclide imaging, 99mTc-PYP, modified Delphi, extracellular volume, apical sparing, TTR gene carrier, carpal tunnel syndrome
Key Takeaways
Formal Diagnostic Criteria for Cardiac Amyloidosis (Table 1)
1. Histological — Endomyocardial Biopsy (all subtypes)
- Endomyocardial biopsy positive for amyloid: Congo red staining with apple-green birefringence under polarised light; typing by immunohistochemistry and/or mass spectrometry at specialised centres
2. Histological — Extracardiac Biopsy + Imaging
- ATTR: extracardiac biopsy-proven ATTR amyloidosis AND typical cardiac imaging features (below)
- AL: extracardiac biopsy-proven AL amyloidosis AND (typical cardiac imaging features OR abnormal cardiac biomarkers: age-adjusted NT-proBNP or troponin T/I/hs-troponin with all other causes excluded)
3. Clinical (Non-Biopsy) ATTR Diagnosis via Scintigraphy
- Grade 2 or 3 myocardial uptake on 99mTc-PYP/DPD/HMDP AND
- Absence of clonal plasma cell process (serum FLCs + serum and urine immunofixation) AND
- Typical cardiac imaging features (below)
- Note: When Grade ≥2 scintigraphy is positive in the context of any abnormal FLC/immunofixation or MGUS, this is NOT diagnostic of ATTR — referral to specialist amyloid centre required
4. Typical Cardiac Imaging Features (any ONE of the following, with other causes excluded):
| Modality | Threshold | Notes |
|---|---|---|
| Echo — LV wall thickness | >12 mm | Without other cardiac cause |
| Echo — Apical sparing GLS ratio | Average apical LS / average (mid + basal) LS >1 | Relative apical sparing criterion |
| Echo — Diastolic dysfunction | Grade ≥2 | Off-label use of standard criteria |
| CMR — LV wall thickness | >ULN for sex on SSFP cine CMR | Women: 7 mm (LAX)/7 mm (SAX); Men: 9 mm (LAX)/8 mm (SAX) |
| CMR — Global ECV | >0.40 | Highly specific threshold |
| CMR — LGE | Diffuse LGE | Any pattern consistent with amyloidosis |
| CMR — Gadolinium kinetics | Myocardium nulls before blood pool | On TI scout/Look-Locker sequence |
| PET — 18F-florbetapir or 18F-florbetaben | Target-to-background (LV:blood pool) >1.5 | Off-label; 18F-flutemetamol not studied |
| PET — Retention index | >0.030 min⁻¹ | Off-label |
Appropriate Utilization Ratings (Table 2) — 32 Clinical Scenarios
Scoring: Appropriate (A) = 7–9; May Be Appropriate (M) = 4–6 or any disagreement; Rarely Appropriate (R) = 1–3
Scenario 1: Asymptomatic / Pre-Clinical Detection
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| Asymptomatic TTR gene carrier — initial | A (7) | M (6) | A (8) |
| Asymptomatic TTR gene carrier — recurrent | A (7) | M (6) | A (7.5) |
| Biopsy-proven systemic AL + abnormal biomarkers | A (9) | A (7) | R (1) |
| MGUS + abnormal FLC + abnormal biomarkers | A (8) | A (7) | R (2) |
Scenario 2: New Symptomatic Heart Failure
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| Elevated FLC levels | A (9) | A (8) | R (2.5) |
| African-Americans >60 yr, unexplained HF | A (9) | A (8) | A (8) |
| African-Americans >60 yr, increased LV wall thickness | A (9) | A (8) | A (9) |
| Non-African-Americans >60 yr, HF + increased LV wall thickness | A (9) | A (8) | A (8) |
| >60 yr with low-flow low-gradient AS | NA | A (8) | A (7) |
| HF + unexplained peripheral sensorimotor neuropathy | A (8) | A (8) | A (8) |
| Known or suspected familial amyloidosis | A (8) | A (8) | A (8) |
| Monoclonal gammopathy including multiple myeloma | A (8) | A (8) | R (2) |
Scenario 3: Biopsy-Proven AL Cardiac Amyloidosis
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| Quantify cardiac amyloid burden | A (7) | A (9) | R (1) |
| Monitor response/progression — every 6 months | M (5)† | R (3) | R (1) |
| Monitor response/progression — every 12 months | M (5) | M (6) | R (1) |
| Monitor response/progression — every 24 months | A (7) | A (8) | R (1) |
| Guide eligibility for stem cell transplant | A (8) | M (5) | R (1) |
Scenario 4: Biopsy-Proven ATTR Cardiac Amyloidosis
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| Quantify amyloid burden | A (8) | A (9) | R (2) |
| Monitor response/progression — every 6 months | M (4)† | R (2) | R (2) |
| Monitor response/progression — every 12 months | A (7) | M (5) | R (2.5) |
| Monitor response/progression — every 24 months | A (8) | A (8) | R (3) |
| Contraindication to CMR (devices / renal insufficiency) | A (8) | NA | R (3) |
Scenario 5: Follow-Up — New or Worsening Symptoms
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| TTR gene carrier | A (8) | A (7) | A (8) |
| AL amyloidosis | A (8) | A (7) | R (1) |
| ATTR amyloidosis | A (8) | A (7) | A (7.5) |
Scenario 6: Other Emerging Indications
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| >60 yr, unexplained bilateral carpal tunnel syndrome | A (7) | M (5)† | M (6.5)† |
| Bilateral CTS + elevated FLC levels | A (7) | M (5) | M (5.5) |
| HF + unexplained biceps tendon rupture | A (7) | M (5) | M (6) |
| Unexplained neuropathy/arrhythmia, no HF symptoms (elderly men) | A (7) | M (5) | M (6) |
Scenario 7: Prior Testing Suggestive of Cardiac Amyloidosis
| Indication | Echo | CMR | Scintigraphy |
|---|---|---|---|
| Suggestive echo | NA | A (7) | M (6) |
| Suggestive CMR | A (8) | NA | M (6) |
| Suggestive bone scintigraphy | A (8) | A (7.5) | NA |
†Lack of consensus among experts
Key Clinical Interpretation Points
- Scintigraphy is Rarely Appropriate whenever AL amyloidosis is confirmed or strongly suspected — it cannot subtype amyloid when monoclonal protein is present; CMR and echo are the tools of choice in this setting
- CMR is the preferred modality for quantifying amyloid burden (rated A(9) in both AL and ATTR biopsy-proven disease)
- Echo is Appropriate for almost everything — the only May Be Appropriate indications involve high-frequency surveillance (every 6 months) and emerging red-flag conditions
- Monitoring interval: Every 24 months is Appropriate for both echo and CMR in biopsy-proven disease; every 6 months is May Be Appropriate (echo) or Rarely Appropriate (CMR) — more frequent monitoring is centre-dependent
- ATTR in long-term AL survivors: ATTR-CA has been reported in long-term AL survivors; scintigraphy may have a role in this rare scenario
- Red-flag conditions (bilateral carpal tunnel syndrome, biceps tendon rupture, unexplained neuropathy/arrhythmia in elderly men): echo Appropriate; CMR and scintigraphy May Be Appropriate — further research needed to define prevalence and imaging yield
- Referral to specialised amyloidosis centre explicitly recommended for: familial amyloidosis, AL cardiac amyloidosis, novel therapies, and any equivocal scintigraphy with coexisting monoclonal protein
Definitions Used in This Document (Key)
- Increased wall thickness: Echo mean LV wall thickness >12 mm with no other known cardiac cause
- Preserved LVEF: ≥40% per ACC/AHA HF guidelines
- Low-flow AS: Mean aortic gradient ≤40 mmHg or stroke volume index <35 mL/m² (with reduced or preserved EF)
- TTR gene carrier: Individual harbouring one of >120 TTR gene mutations associated with transthyretin amyloidosis
- MGUS: Monoclonal gammopathy of uncertain significance (<10% clonal plasma cells in bone marrow, no myeloma)
- Unexplained bilateral carpal tunnel syndrome: Bilateral CTS without rheumatoid arthritis or known trauma
- Unexplained biceps tendon rupture: Rupture without heavy lifting/trauma
Limitations of the Document
- Rating panel of only 7 clinical experts (RAND-UCLA methodology requires minimum 7; imaging experts expressly excluded to prevent modality bias)
- All panellists from academic settings — may not reflect community practice
- Evidence base moderate-quality for most criteria; PET thresholds based on limited pilot studies
- Appropriateness ratings assume accredited laboratories, state-of-the-art equipment, and qualified interpreters — lower-resource settings may have different optimal strategies
- Radiation risk and cost not considered in the rating process
- Not all clinical scenarios are represented; emerging indications (TAVR, hip/knee arthroplasty) acknowledged but not formally rated
Key Concepts Mentioned
- concepts/Cardiac-Amyloidosis-Imaging — primary concept page; diagnostic criteria and AUC tables integrated here
- concepts/LV-Diastolic-Function — Grade ≥2 diastolic dysfunction as imaging criterion for cardiac amyloidosis
Key Entities Mentioned
- entities/ATTR-Amyloidosis — formal diagnostic criteria; AUC for TTR carriers; red-flag clinical scenarios
- entities/Heart-Failure — HFpEF with increased LV wall thickness; African-Americans >60 yr as high-risk group
- entities/Atrial-Fibrillation — unexplained arrhythmia in elderly men as emerging red-flag indication
- entities/HCM — differential of increased LV wall thickness; echo apical sparing ratio differentiates
Wiki Pages Updated
- Created:
wiki/sources/imaging-amyloidosis-2nd-aha-2021.md(this file) - Updated:
wiki/concepts/Cardiac-Amyloidosis-Imaging.md - Updated:
wiki/entities/ATTR-Amyloidosis.md - Updated:
wiki/wikiindex.md - Updated:
wiki/sourceindex.md