Erfan Bashar
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Cardiac Amyloidosis

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Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.

Cardiac amyloidosis is an infiltrative cardiomyopathy: proteins misfold, aggregate as amyloid fibrils, and deposit diffusely through the myocardium. The deposits expand the extracellular space and stiffen the walls. More than 20 different proteins are known to form amyloid, but from a cardiac perspective three types dominate.

Three cardiac types

Light-chain (AL) amyloidosis is an onco-haematological disease. A pathological B-cell clone in the marrow produces excess immunoglobulin light chains that misfold and infiltrate tissues. Like other oncological processes, it progresses fast: cardiac involvement can advance dramatically over months. Whether the heart recovers depends on the haematological response — clone suppression reaching complete response or very good partial response is required for cardiac improvement.

Wild-type transthyretin (ATTRwt) amyloidosis comes from a normal protein gone unstable with ageing. Transthyretin, made chiefly by the liver, misfolds over years, so functional abnormality appears long after deposition begins. The disease is slower than AL and predominantly affects older men.

Hereditary transthyretin (ATTRv) amyloidosis comes from a clearly pathological mutation in the transthyretin gene that destabilises the protein. Different mutations favour different organs and ages of onset.

What infiltration does to the ventricle

Amyloid fills the space between cells until, in advanced disease, extracellular volume can reach roughly 50% — half the wall is deposit rather than contractile tissue, against a normal value below 30%. The mechanical consequences follow in order: diastolic dysfunction first, as stiff walls demand higher filling pressures; restrictive physiology in advanced disease, with enlarged atria, elevated wedge pressure, and falling stroke volume; systolic decline late, as working cells are progressively replaced. Restrictive physiology here is a haemodynamic description of advanced disease, not a separate restrictive cardiomyopathy entity — early amyloidosis may show only mild thickening with subtle longitudinal dysfunction.

The imaging signature

Tissue imaging shows the hallmark combination, explained step by step in the cardiac MRI note:

  • Native T1 raised diffusely across all segments, reflecting extracellular expansion everywhere.
  • Enhancement classically circumferential and subendocardial — the inner layer is affected first — becoming transmural in advanced disease.
  • Extracellular volume raised diffusely and severely, around 50%, in every segment. This homogeneous pancardiac elevation is the most characteristic finding and separates amyloid from focal fibrotic diseases.
  • Shape with function mismatch: wall thickness is increased while ejection fraction sits at the lower limit of normal at first — mild dysfunction on echocardiography overlying severe tissue disease on mapping.

Typing amyloid, usually without biopsy

A defined pathway now types the disease non-invasively in most cases:

  1. Tissue characterisation with cardiac MRI, as above.
  2. Light-chain assessment — serum free light chains with immunofixation of serum and urine. A clonal result points to AL.
  3. Bone scintigraphy (DPD, PYP, or HMDP tracers), which is highly specific for transthyretin cardiac amyloidosis when light-chain studies are negative.
  4. Transthyretin gene sequencing when scintigraphy is positive, to separate wild-type from hereditary disease.
  5. Endomyocardial biopsy, reserved for equivocal cases or suspected AL where non-invasive workup stays inconclusive.

Treatment principles

The teaching sources give principles rather than drug regimens, so this note stays at that level. AL treatment targets the clone: agents described in the teaching material include cyclophosphamide, prednisone, and bortezomib alongside other oncological drugs, and cardiac regression follows only when the haematological response is deep. For transthyretin disease, specific medications now exist; evidence of tissue regression on serial imaging has emerged since approximately 2018–2019. The slower ATTR course widens the intervention window, but late diagnosis still carries a poor outlook. Specific drug names, dosing, and pharmacology are deliberately left to guidelines and formularies rather than this note.

Following disease over time

Mapping doubles as a treatment monitor. When AL therapy suppresses the clone, extracellular volume can fall on follow-up scans, indicating regression of deposition. Serial T1 and ECV values predict the clinical course on therapy — improvement fares better than worsening — a relationship reported from the National Amyloidosis Centre in London in JAMA Cardiology.

Evidence anchors

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