Cardiac Amyloidosis and ATTR Cardiomyopathy
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Direct answer
Cardiac amyloidosis is infiltration of the myocardium by misfolded proteins, most often immunoglobulin light chains (AL) or transthyretin (ATTR), causing a restrictive cardiomyopathy. The key clue is low limb-lead voltage despite thick ventricular walls on echo, and apical sparing on strain imaging is typical. A pyrophosphate scan with no monoclonal protein identifies ATTR cardiomyopathy, which is treated with tafamidis, whereas AL disease needs plasma cell directed therapy.
What you must remember
- AL and ATTR: AL is a plasma cell disorder producing light chains, while ATTR is a transthyretin misfolding disease that occurs as a wild-type form in older men and as a hereditary variant.
- Low voltage with thick walls: limb-lead voltage out of proportion to the left ventricular wall thickness, the classic ECG discordance of amyloid.
- Apical sparing: longitudinal strain preserved at the apex but reduced at the base and mid segments, a pattern not seen in hypertrophic cardiomyopathy.
- Sparkling myocardium: a granular echo texture with biatrial enlargement, a thickened interatrial septum and restrictive filling.
- Pyrophosphate scan: technetium-99m pyrophosphate uptake of grade 2 or 3 with no monoclonal protein on screening points to ATTR.
- Congo red: apple-green birefringence under polarised light is the histological hallmark of amyloid.
- Drugs to avoid: digoxin binds amyloid fibrils and precipitates toxicity, and beta-blockers and non-dihydropyridine calcium channel blockers are poorly tolerated.
- ATTR prodrome: carpal tunnel syndrome, lumbar spinal stenosis and biceps tendon rupture can precede heart failure by years.
Where the examiner sets the traps
Amyloid questions usually test the ECG clue, the drug to avoid or the confirmatory test.
- Trap: reading low voltage with thick walls as hypertrophic cardiomyopathy Correct: hypertrophic cardiomyopathy usually keeps voltage in step with wall thickness, whereas amyloid shows low voltage despite thick walls.
- Trap: using digoxin for atrial fibrillation or heart failure in cardiac amyloidosis Correct: digoxin binds amyloid fibrils and precipitates toxicity, so it is avoided.
- Trap: assuming ATTR is always hereditary Correct: wild-type ATTR is not inherited, which is why a monoclonal protein screen must still exclude AL before the diagnosis is made.
Frequently asked questions
What is the typical ECG finding in cardiac amyloidosis?
The typical ECG finding in cardiac amyloidosis is low limb-lead voltage despite increased ventricular wall thickness on echo. Pseudo-infarct Q waves, conduction disease and atrial fibrillation are also common, so an unexplained low-voltage ECG should prompt an echo review.
What is apical sparing in cardiac amyloidosis?
Apical sparing is an echo strain pattern in which longitudinal strain is preserved at the apex of the left ventricle but reduced at the base and mid segments. It is characteristic of cardiac amyloidosis and helps distinguish it from hypertrophic cardiomyopathy, where this pattern is not seen.
Which scan confirms ATTR cardiomyopathy without biopsy?
Technetium-99m pyrophosphate scintigraphy with grade 2 or 3 myocardial uptake, in the absence of a monoclonal protein on serum and urine screening, confirms ATTR cardiomyopathy without biopsy. A monoclonal protein must be excluded first, because AL amyloidosis needs a different and urgent treatment pathway.
Why is digoxin avoided in cardiac amyloidosis?
Digoxin is avoided in cardiac amyloidosis because amyloid fibrils bind the drug, which increases the risk of toxicity even at standard doses. Beta-blockers and non-dihydropyridine calcium channel blockers are also poorly tolerated, since the stiff ventricle depends on heart rate and preload.