Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and destabilizing transthyretin (TTR) variants appeared to have higher all-cause mortality than patients with stable variants, according to a recent letter to the editor published in JAMA Cardiology.
“The link between TTR-destabilizing genetic variants and all-cause mortality highlights the critical importance of identifying carriers of pathogenic variants in TTR,” the letter’s authors said.
What is ATTR-CM?
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a rare progressive disease of the heart muscle that leads to congestive heart failure. It occurs when the transthyretin protein produced by the liver is unstable. Symptoms include fatigue; shortness of breath; irregular heart rate or palpitations; swelling of the legs, ankles and stomach; brain fog; wheezing; and dizziness. It often goes underdiagnosed because of a lack of awareness and knowledge of the disease. There is currently no cure for ATTR-CM.
The letter focused on the results from a recent study focusing on the association between TTR tetramer stability and mortality in patients with ATTR-CM. The extensive study analyzed 27 years of data from more than 100.000 Danish patients with ATTR-CM.
Read more about ATTR-CM testing and diagnosis
The study’s authors divided the total population into two groups: one group with stabilizing TRR variants such as p.T139M and destabilizing variants such as p.V142I, p.H110N and p.D119N. Results showed that patients with stabilizing variants had higher TTR plasma levels.
Researchers observed that TRR plasma levels were inversely correlated with all-cause mortality. The findings complemented previous studies that suggested a direct correlation between TTR tetramer instability and increased mortality.
The letter’s authors said that the study further underscored the importance of determining the TTR variant in each individual case in order to offer targeted and individualized therapy to every patient.
“Overall, the study by Christoffersen and colleagues contributes to existing literature on the consequences of amyloidosis and provides the basis for important testable hypotheses that hopefully can be extended to improve the prioritization of patients for the initiation of therapies that stabilize TTR to prevent amyloid-associated cardiovascular disease and mortality,” the letter said
The TTR protein is a tetramer, which means it is composed of four different subunits. TRR stability refers to the protein’s capacity to maintain its tetrameric structure without breaking into four subunits (monomers).
The dissolution of the TTR tetramer into monomers facilitates amyloid formation and deposition, contributing to the development of ATTR-CM.
