Rudolph Virchow in 1854 adopted the term "amyloid“ to refer to tissue deposits of material that stained in a similar manner to cellulose when exposed to iodine
Amyloidosis is a generic term that refers to the extracellular tissue deposition of fibrils composed of low molecular weight subunits (most of which are in the molecular weight range of 5 to 25 kD) of a variety of proteins.
At least 25 different human and eight different animal protein precursors of amyloid fibrils are now known
Many kinds of Amyloidosis
Primary (AL amyloidosis)
= plasma cell dyscrasia leading to overproduction of Immunoglobulin light chains
Clinical evidence of cardiac involvement occurs in up to 50 percent of patients
Secondary (AA amyloidosis)
Deposition of fragments of serum amyloid A protein, an acute phase reactant
Associated with chronic inflammatory disorders (eg RA).
Almost never produces clinically apparent heart disease (< 5%)
Senile systemic and Heritable amyloidosis
= Transthyretin deposits
+ Cardiac involvement, but much slower time course than AL
Clinical Manifestations of AL amyloidosis
Nephrotic syndrome with or without renal insufficiency
Peripheral neuropathy, typically axonal, which can be associated with autonomic neuropathy. Carpal tunnel syndrome is commonly seen
Hepatomegaly, with elevated liver enzyme levels
Purpura, characteristically elicited in a periorbital distribution (raccoon eyes) by a valsalva maneuver or minor trauma, is present in only a minority of patients, but is highly characteristic of AL amyloidosis
Cardiac exam findings
Elevation of the jugular venous pressure, sometimes with a low-volume pulse.
Right sided heart failure hepatomegaly and LE edema
A right-sided third heart sound is occasionally heard
Fourth heart sound, which coincides with atrial systole, argues against the diagnosis since atrial infiltration causes atrial dysfunction
Amyloidosis rarely causes significant valve disease, but a murmur of tricuspid or mitral regurgitation is occasionally heard.
Left ventricular wall thickening with evidence of diastolic dysfunction is the earliest echocardiographic abnormality,
In more advanced disease, wall thickening progresses resulting in a restrictive cardiomyopathy with a nondilated or small LV cavity, biatrial enlargement
Amyloid infiltration of the heart results in increased echogenicity.
"granular, sparkling" appearance of the myocardium, unusually high quality myocardial visualization
Only a minority of patients has this pattern 26% = low sensitivity
The diagnosis of cardiac amyloidosis is confirmed either by
demonstrating amyloid deposits on endomyocardial biopsy
or, in patients with appropriate cardiac findings, by demonstrating amyloid deposits on histologic examination of a biopsy from other tissues (eg, abdominal fat pad, rectum, or kidney).