A case of amyloidosis (questions)
What is amyloidosis?
Amyloidosis is a clinical disorder caused by extracellular deposition of insoluble abnormal fibrils, derived from aggregation of misfolded normally soluble protein.
What is the classification of amyloidosis?
1) Systemic AA amyloidosis. Formerly known as secondary amyloidosis, is a complication of chronic inflammatory conditions or any disorder associated with a sustained acute-phase response in which there is markedly increased production of serum amyloid A protein (SAA). Renal disease dominates the clinical picture in AA amyloidosis, and the condition almost always presents with proteinuria and renal failure. Regression of AA amyloid following suppression of SAA production may lead to reversal of organ dysfunction. Clinically significant involvement of the heart is very rare.
3) Hereditary systemic amyloidosis is caused by deposition of amyloid fibrils derived from genetic variants of transthyretin (TTR), apolipoprotein A-I, lysozyme, or fibrinogen alpha-chain and other extremely rare variants. Clinical syndromes include cardiomyopathy, nephropathy, or neuropathy, though the heart is most prominently involved in variant TTR type, which is associated with more than 100 different TTR mutations, most often with associated neuropathy. This entity is not rare; indeed, the amyloidogenic TTR Val122Ile variant is present in 4% of African Americans, and 23% of African Americans with cardiac amyloidosis have this variant.
4) Senile systemic amyloidosis (SSA) is caused by deposition of amyloid fibrils derived from normal wild-type transthyretin and almost always presents as a slowly progressive, infiltrative amyloid cardiomyopathy. Senile systemic amyloidosis is exceptionally rare in those younger than 60 years of age, but its prevalence ranges from 25% to 36% in those older than 80 years of age. There is a large male predominance, and senile systemic amyloidosis has a major predilection for the heart. Patients usually present with congestive heart failure, with carpal tunnel syndrome being the only common accompanying extracardiac manifestation.
Normal-voltage electrocardiogram (ECG) with a left anterior fascicular
block and thickened left ventricular (
What are the features suggestive of amyloidosis on cardiac testing?
1- The low precordial and limb lead voltage
2- pseudoinfarction pattern as evidenced by QS waves in 2 consecutive leads
2- Granular or sparkling appearance of the myocardium
3- Early stages: abnormal relaxation with decreased early diastolic filling velocity (E), increased late diastolic filling velocity (A), and reduced E/A ratio
4- Advanced stages have restrictive filling abnormalities characterized by shortened E deceleration time and isovolumetric relaxation time
5- Pericardial effusion
6- Valvular thickening
1- Findings of restrictive cardiomyopathies
2- Delayed post-gadolinium enhancement images reveal diffuse subendocardial enhancement
3- abnormal myocardial and blood-pool gadolinium kinetics
How would 99mTc-DPD myocardial uptake help to diagnose subtypes of amyloidosis?
DPD scintigraphy was demonstrated to be 100% accurate for distinction
between TTR-related and
In the absence of the 99m Tc-DPD isotope availability,
similar selectivity for transthyretin type amyloid can be expected from the
alternative bone-seeking isotope 99m Tc-pyrophosphate. In fact, myocardial
accumulation of either isotope is highly specific for cardiac amyloidosis.
Their purportedly low sensitivity for detection of cardiac amyloidosis in prior
studies ( as low as 20%) did not take into account the
various types of amyloidosis. There are clearly different uptake
characteristics of bone-seeking isotopes in AL and TTR
amyloidosis, ie poor in