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.”
Mario Zerkowski
Con Vyndamax hace 32 meses. Los laboratorios quieten recuperar velozmente sus inversiones en estudios etc y conrsn precios imposibles de pagar
Nancy Greene
In Dr Bryson’s article, the section: “When to suspect ATTR-CM” should include Bilateral Carpal Tunnel Syndrome as a key warning sign.
I suddenly developed severe bilateral CTS at age 70, and was treated by my orthopedic doctor, occupational therapists. and a neurologist. When I finally turned to an expert hand surgeon, he just happened to be aware of the link between my condition and Amyloidosis, and biopsied tissue during surgery. My sample came back positive; I’m now on Vyndamax.
I participate in online ATTR patient groups. For an increasing number of us, our bilateral CTS was the first symptom of our disease, which was diagnosed by hand surgeons who happened to know of the link.