Cardiac amyloidosis

Red flags on echo, the ESC score, apical sparing — and the two blood tests that must come next.

Numbers to remember

• Suspect when LV wall ≥12 mm with a red flag ^[30]
• ESC echo score ≥8 points: RWT >0.6 (3), E/e′ >11 (1), TAPSE ≤19 mm (2), GLS ≤13% (1), apex-to-base strain ratio >2.9 (3) ^[30]
• Relative apical sparing ratio >1.0 — sensitivity 93%, specificity 82% ^[130]
• Grade 2–3 bone-scintigraphy uptake plus no monoclonal protein → ATTR without biopsy ^[132]

Questions echo must answer

Amyloid cardiomyopathy (transthyretin, ATTR, or light-chain, AL) is under-diagnosed. It presents as "HFpEF", "hypertensive heart disease", low-flow AS or "HCM in an older person". Tafamidis reduces mortality in ATTR ^[75], and AL is a haematological emergency. The job of echo is to raise the suspicion and trigger the right tests, not to make the diagnosis alone ^[30,131].

1. Is the wall thick without a reason?LV wall ≥12 mm, often with RV free-wall thickening and thick valves and interatrial septum.
2. Does the myocardium behave like amyloid?Low annular velocities (s′, e′, a′ often <5 cm/s), restrictive filling, apical-sparing strain ^[30,130].
3. Is output falling?Small cavity, low SVI, low-flow AS pattern.
4. Atria and thrombusAtrial dilatation with poor atrial function. Thrombus can occur even in sinus rhythm ^[30,131].
5. Next testSerum and urine immunofixation plus serum free light chains, then bone scintigraphy ^[30,131,132].

Acquisition protocol

1. PLAX / PSAXMeasure IVSd, PWd and RWT; valve and interatrial septum thickness; small pericardial effusion.
2. Tissue DopplerSeptal and lateral s′, e′ and a′. Values below 5 cm/s are a strong clue ^[30].
3. Mitral inflowE/A, DT, E/e′. Grade the diastolic function ^[2,32].
4. StrainGLS bull's-eye. Calculate the relative apical sparing ratio = apical LS / (basal LS + mid LS) ^[130]. Also calculate the ESC apex-to-base ratio ^[30].
5. RVFree-wall thickness >5 mm, TAPSE, S′.
6. OutputLVOT VTI, SVI. If the aortic valve is calcified, apply the low-flow AS pathway ^[5,58].
7. LALAVI and LA strain. Consider TOE before cardioversion even when anticoagulated ^[30,131].

• LV wall ≥12 mm?
• RWT
• s′, e′ and a′ at both annuli
• Diastolic grade
• GLS and apical-sparing ratio
• ESC multiparametric score
• RV free wall, TAPSE
• SVI (low-flow?)
• Pericardial effusion
• Recommended: FLC and immunofixation, then scintigraphy

Diagnosis & severity

ESC 2021 position statement: echocardiographic criteria ^[30]

In a patient with unexplained LV wall thickness ≥12 mm, echo is suggestive if either (a) or (b) applies.

(a) At least two of the following: grade ≥2 diastolic dysfunction; reduced s′, e′ and a′ (<5 cm/s); GLS absolute value <15%.

(b) A multiparametric score ≥8 points:

Relative apical sparing ^[130]

Apical LS / (basal LS + mid LS) >1.0 separated cardiac amyloidosis from other causes of LV hypertrophy with a sensitivity of 93% and specificity of 82%.

Non-biopsy diagnosis of ATTR ^[132]

Grade 2–3 myocardial uptake on bone scintigraphy with no monoclonal protein (serum and urine immunofixation and serum free light chains) was sufficient for ATTR without biopsy. If a monoclonal protein is present, tissue diagnosis is needed.

Thresholds that change management

• Echo suggestive → free light chains and immunofixation the same day. AL amyloidosis progresses quickly and needs haematology ^[30,131].
• No monoclonal protein and grade 2–3 scintigraphy → ATTR, confirmed without biopsy. Arrange genetic testing for variant ATTR and start disease-modifying therapy (tafamidis reduced all-cause mortality and cardiovascular hospitalisation in ATTR-ACT) ^[75,132].
• AF or atrial standstill → anticoagulate regardless of CHA₂DS₂-VA. Consider TOE before cardioversion ^[30,131,182].
• Low-flow AS with amyloid → TAVI is still effective. Calculate SVI and use calcium scoring or dobutamine when the gradient is discordant ^[5,172].
• Avoid high-dose beta-blockers, non-dihydropyridine calcium-channel blockers and digoxin toxicity. Output depends on heart rate when SV is small ^[131].

Pitfalls & mimics

• Low-voltage ECG is absent in many ATTR patients. A normal voltage does not exclude amyloid.
• Apical sparing is seen in other conditions (AS, HCM, hypertensive disease) and can be absent early. It is a clue, not proof ^[130].
• Hypertensive heart disease has high voltage and preserved s′. HCM has asymmetric hypertrophy, SAM and younger age.
• Scintigraphy is falsely positive in AL in a minority. That is why the monoclonal screen must be negative ^[132].
• Pseudo-normal inflow in intermediate disease. Use e′, LAVI and LA strain.