Blood test may help predict heart failure risk in ATTR-CM patients
Blood levels of protein MR-proADM may be biomarker, study finds
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A blood test measuring levels of the protein MR-proADM may help predict heart failure events (worsening of symptoms requiring immediate medical care) and death in people with transthyretin amyloid cardiomyopathy (ATTR-CM), a study showed.
The MR-proADM test, used to evaluate risk and outcomes in people with suspected infections, meaningfully improved the accuracy of existing ATTR-CM outcome prediction measures.
“One of the biggest challenges with this disease is knowing which patients are at the greatest risk of worsening disease,” Pablo García-Pavía. MD, PhD, the study’s senior author and a cardiologist at the Spanish National Centre for Cardiovascular Research, said in an institute press release. “Our results indicate that MR-proADM can help identify those patients who are at a greater risk of heart failure events and death.”
The study, “MR-ProADM Predicts Mortality and Heart Failure Events in ATTR Cardiac Amyloidosis,” was published in Circulation.
In ATTR-CM, misfolded transthyretin proteins form toxic clumps, known as amyloid deposits, in the heart, making the heart muscle stiff and unable to pump blood effectively. ATTR-CM can be caused by inherited mutations in the gene encoding transthyretin (inherited form) or be independent of mutations and associated with age (wild-type form).
Need for new prediction measures
Certain blood markers can predict the risk of death in ATTR-CM patients. But most of these were developed years ago, when patients were typically diagnosed at more advanced stages of the disease.
Because more ATTR-CM patients are now being diagnosed earlier and have access to newer, targeted treatments, they are living longer. As a result, there is growing interest in predicting not only the risk of death, but also the risk of heart failure events.
García-Pavía’s team evaluated 12 circulating biomarkers previously studied in heart failure to assess their ability to predict all-cause mortality (death by any cause) and heart failure events in people with ATTR-CM.
“Having access to tools that can fine-tune prognosis is essential for tailoring follow-up and treatment to each patient,” said Belén Peiró-Aventín, MD, the study’s first author and a doctor at Hospital Universitario Puerta de Hierro Majadahonda in Spain.
Researchers collected blood samples from 337 adults (81.9% men; median age 78.3) diagnosed with ATTR-CM at two Spanish hospitals. Most (86.4%) had the wild-type form of the disease.
More than one-quarter of the participants (27.3%) were taking Vyndamax (tafamidis), an approved ATTR-CM medication designed to stabilize transthyretin and prevent the formation of amyloid deposits. About two-thirds were receiving treatment with diuretics, or water pills, which help reduce fluid buildup and blood pressure in people with heart failure.
During a median follow-up of 19.7 months (about 1.5 years), 19.6% died, 24% experienced heart failure events, and one (0.3%) underwent a heart transplant. Overall, median survival was 6.2 years, and the estimated survival rates were 93% at one year, 74.5% at three years, and 62.8% at five years.
The team tested each of the 12 biomarkers individually to assess their ability to predict all-cause mortality and a composite outcome, which combined all-cause death, worsening heart failure, and heart transplant. MR-proADM, a protein involved in blood vessel and fluid regulation, performed best and was selected for further studies.
The team found that over half of the participants (51.6%) had MR-proADM levels above 0.79 nanomole/L (nmol/L), a cutoff value previously identified in chronic heart failure studies.
Participants with MR-proADM levels above this cutoff were significantly more likely to have more severe disease, a history of heart failure-related hospitalizations, higher blood levels of NT-proBNP (a marker of heart stress), and signs of impaired kidney function. These patients also had significantly higher rates of death, worsening heart failure events, and the composite outcome.
A statistical analysis adjusted for influencing factors confirmed significant associations between higher MR-proADM levels and all-cause death and the composite outcome.
An MR-proADM level of 1.1 nmol/L was identified as the optimal threshold for predicting outcomes. Patients with lower levels had higher survival rates at both one year (96.9% vs. 82.8%) and three years (87.6% vs. 40.5%) compared with those with levels at or above the threshold.
Adding MR-proADM results to three standard outcome prediction tools in ATTR-CM, the Mayo, NAC (National Amyloid Center), and Columbia staging systems improved the accuracy of each.
MR-proADM’s predictive potential in ATTR-CM was confirmed in two separate patient groups: one comprised of 210 ATTR-CM patients in the U.S., and the other consisting of 416 ATTR-CM patients from the Phase 3 ATTR-ACT clinical trial (NCT01994889), whose data supported Vyndamax approval.
In the second group, patients with MR-proADM levels of at least 1.1 nmol/L were significantly more likely to die and to reach the composite outcome, regardless of whether they were taking Vyndamax.
“Incorporating MR-proADM into routine clinical testing and established staging systems could improve risk stratification and guide clinicians in selecting the most appropriate therapeutic strategy in patients with ATTR-CM,” the team wrote. “Our work paves the way for tailored risk assessment and targeted management strategies in ATTR-CM.”
García-Pavía said the outcome of the study “takes us a step closer to a more personalized treatment for heart failure.”
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