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An Indirect Test to Assess Risk of Cardiac Transthyretin Amyloidosis

Researchers have only recently started to understand the degree to which transthyretin amyloidosis contributes to heart failure. This condition is thought to be a majority cause of death in the very oldest people, but there is now evidence to show that heart disease in earlier old age is also caused by a build up of this form of amyloid in tissues. The growing presence of various amyloids is one of the fundamental differences between old tissue and young tissue, and any future rejuvenation toolkit must include the means to remove them. Since there is at least one viable clearance treatment under development for transthyetin amyloid, that worked on at Pentraxin Therapeutics, an important next step in the process of raising the funds needed to complete passage through the heavy-handed regulatory systems of the US and Europe is to gather more evidence of the need for such a therapy. That in turn requires better clinical tests, or indeed any viable clinical tests, as at present the evidence for transthyretin amyloid to cause heart disease is largely obtained from post-mortem studies. Here, researchers report on progress towards an indirect approach to testing for the risk of this form of amyloidosis in heart tissue:

Researchers have developed a new diagnostic test that may help doctors identify patients with a condition called cardiac amyloidosis. Cardiac amyloidosis is caused by abnormal folding of proteins that deposit in the heart. These protein deposits can also occur in other organ systems in the body and can cause life-threatening organ failure. Cardiac amyloidosis that results from the mis-folded protein transthyretin is called ATTR amyloidosis, and this form of the disease occurs in older patients. Amyloid deposition can cause electrical abnormalities and decrease the heart's ability to relax and contract, leading to congestive heart failure.

The diagnosis of ATTR amyloidosis can be challenging for doctors, and amyloidosis in many patients remains un-recognized, sometimes until the time of death. However, recent studies suggest that as many as 10 percent of older patients with certain types of congestive heart failure may have cardiac amyloidosis. In this study, researchers identified that a specific blood protein named retinol-binding protein 4 (RBP4) can be used to determine the likelihood of ATTR amyloidosis in a patient with congestive heart failure.

In addition the research team developed a mathematical calculator that incorporates RBP4 and other commonly ordered clinical tests that can be used to estimate the probability of ATTR amyloidosis in a given patient. An important advantage of this algorithm is that it can be used in the context of a doctor's office visit at the point-of-care. According to the researchers, this discovery could guide clinical decision making and increase recognition of this disease. Since many new drug therapies are in various stages of development now for ATTR amyloidosis, recognition and accurate diagnosis is essential to get a patient on the correct treatment.

Link: https://www.eurekalert.org/pub_releases/2017-02/bumc-otd020717.php

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