New Preclinical Tool May Help Predict Heart Problems in ATTR Amyloidosis
Investigating how plasma from people with transthyretin (ATTR) amyloidosis affects heart cells from rats may help researchers predict future heart-related health events and deaths in these patients, a study suggests.
The findings were published in Clinical Research in Cardiology, in the study “Impaired in vitro growth response of plasma-treated cardiomyocytes predicts poor outcome in patients with transthyretin amyloidosis.”
ATTR amyloidosis is characterized by the abnormal buildup of the protein transthyretin in multiple organs. When these deposits form as a result of an inherited mutation and mainly cause symptoms of nerve damage, the condition is referred to as familial amyloid polyneuropathy (FAP). Another familial form, called hereditary ATTR amyloidosis with cardiomyopathy (ATTRv-CA), is more commonly associated with heart symptoms.
The toxic transthyretin deposits can have a detrimental effect on cardiac health, with nearly all patients experiencing some form of heart problem in their lifetime.
Generally, when heart cells are under stress, they will undergo hypertrophy (get bigger). An established method for studying hypertrophy in heart cells involves treating heart cells from rats with a compound called phenylephrine.
In the new study, researchers at the University Hospital Heidelberg, in Germany, tested the effects of treating these rat cells with plasma (the non-cellular part of blood) from people with ATTR amyloidosis.
The researchers used plasma from 89 patients who were screened at their hospital between October 2016 and November 2017. Of these, 23 had FAP, 36 had ATTRv-CA, and the remaining 30 had a non-inherited form of the disease. For comparison, the researchers also assessed plasma from 16 individuals without known disease.
Generally, treating the cells with plasma from ATTR amyloidosis patients induced hypertrophy to a slight degree. In contrast, when the cells were treated with both patient plasma and phenylephrine, the hypertrophy-inducing effects of phenylephrine were lessened.
By comparing the effect of plasma treatment with or without phenylephrine, the researchers calculated a novel metric which they called the hypertrophic index (HI). Compared to control serum, serum from patients with ATTRv-CA and non-familial ATTR resulted in a significantly decreased HI.
The researchers then looked at clinical data for the patients, using statistical analyses to see whether HI could be used to predict future heart-related health events. Over a median follow-up time of 14.8 months, nine patients died, five were listed for urgent heart transplants, and 20 were hospitalized for serious heart-related events.
Patients with a low HI were significantly more likely to be hospitalized for heart-related events, and they were significantly more likely to die or require a heart transplant. Risk of major cardiac events (MACE), a composite encompassing death, transplant, and hospitalization, also was significantly increased in individuals with low HI.
Low HI remained significantly predictive of MACE in further statistical analyses that accounted for other relevant factors, such as age, sex, and various markers of heart health and disease status.
“In the present work we established a novel functional biomarker to predict future cardiac events in patients with ATTR [amyloidosis],” the researchers concluded, noting that HI could be used in conjunction with other, established markers of heart health to make better prognoses for patients and plan care accordingly.
The researchers stressed that these findings are preliminary, and the results will need to be validated in independent studies before HI can be widely applied as a prognostic marker. They also noted a need for further research into the exact mechanisms governing altered hypertrophy in ATTR amyloidosis.