Amyloidosis is a proteostatic disease , meaning a progressive disorder of extracellular deposition of insoluble protein fibrils in tissues.It affects , brain, kidney, nerves and almost any organ.Crucially, amyloid is an interstitial disease, accumulating strictly in the spaces between cells rather than inside them. This interstitial buildup exerts physical pressure, alters tissue architecture, and finally invading the cell and hence the organ function.
The process begins with normal transport proteins, most notably transthyretin (TTR) (same as prealbumin) Transthyretin is synthesized by the liver as a stable, four-part tetramer structure that safely circulates in the blood. Under stressful or aging conditions, this tetramer destabilizes unstable monomer pieces. These monomers undergo misfolding, polymerizing into rigid cross-beta-sheet amyloid fibrils. These abnormal ATTR fibrils escape cellular degradation.
Cardiac amyloidosis
Cardiac amyloidosis , presents as mainly as restrictive cardiomyopathy, but can be seen in any chronic heart failure associated with LVH, especially in Aortic stenosis, where it can involve both the valve and myocardium.There are multiple reasons why we diagnose amyloidosis more often than before. But , one thing is sure, it is not due to increasing incidence in the population , but more of a high awareness and availability of advanced cardiac imaging .
Image source : Agha AM,. Role of cardiovascular imaging for the diagnosis and prognosis of cardiac amyloidosis. Open Heart. 2018;5:
What is the confirmatory test for Amyloidosis ?
It was classically diagnosed by tissue biopsy with Congo red staining, showing “apple-green” birefringence under polarized light microscope. Mass Spectrometry, Immunofluorescence is then used to decode the protein composition. Currently , with typical patterns of cardiac imaging we can diagnose with confidence without biopsy. While echocardiography is good enough , MRI and technetium-99m pyrophosphate scans are crucial.
What are the specific treatment option for amyloidosis ?
Until recently, Amyloidosis, has been considered as irreversible degenerative disease .Now we have strategies to reduce progression or even regress the Amyloid deposition. Many drugs are still being studied with varying success.
Following table summarise the different pharmacological modalities to tackle Amyloidosis.
Final message
A limitation of currently approved anti-amyloid medication such as Tafamidis or Onpattro , is that it cannot be reversed and only be prevented.Emerging technologies like monoclonal antibody depleters hold promise to actively clear out existing deposits, potentially turning it to a truly reversible condition. Chronic fibrotic pathways from triggered fibroblasts are closely linked to Amyloidosis. Hence, antifibrotic drug research should go hand in hand with Amyloidosis.
Dr.S.Venkatesan MD 