March 23 (UPI) -- Age-adjusted biomarker thresholds accurately diagnose or rule out acute heart failure in patients seen for shortness of breath at hospital emergency departments, according to a multi-institutional study.
Researchers studied the protein NT-proBNP as a method of validating diagnosis of heart failure in a wide range of patients, publishing their findings on Tuesday in the Journal of the American College of Cardiology.
"Since we did the first U.S.-based studies of NT-proBNP for the identification or exclusion of heart failure, as well as for establishing the risk of bad outcomes, its use has been incorporated into diagnostic guidelines internationally," Dr. James Januzzi Jr., a researcher at the Massachusetts General Hospital Division of Cardiology in Boston, said in a press release. "But over the past 15 years, the characteristics of patients with heart failure have changed -- they tend to be older, are more likely to be women and to have additional complications -- making a contemporary re-assessment of the assay's performance necessary."
NT-proBNP, which is short for N-terminal pro-brain natriuretic peptide, and a related protein called B-type natriuretic peptide, or BNP, are produced when the cardiac muscle is under stress.
An earlier study, conducted in the MGH Emergency Department, suggested age-based diagnostic cutoffs for diagnosis of acute heart failure of 450 pg/ml for patients under 50, 900 pg/ml for those 50 to 75 and 1,800 pg/ml for those over 75, and that an NT-proBNP level of 300 or below appeared to rule out acute heart failure regardless of a person's age.
These results were supported by a larger, multi-institutional trial and have been largely adopted at hospitals worldwide. But the only NT-proBNP diagnostic cutoffs approved by the U.S. Food and Drug Administration are 125 pg/ml for patients under 75 and 450 pg/ml for those 75 and older. The levels are designed for outpatient treatment.
The researchers anticipate FDA approval of the age-based cutoffs for emergency department diagnosis, though.
"There is a need to reconsider which cutoffs should be used, as continued reliance on current, approved cutoffs has the potential for diagnostic inaccuracy, particularly for test specificity," the researchers wrote.
The new study was designed to validate the emergency-care-based cutoffs and find out whether they remain useful for assessment of the current population of patients with heart failure.
The researchers recruited 1,461 patients who were at least 22 years old and had come to hospital emergency departments with shortness of breath or other breathing difficulties in 2015 and 2016 at 19 sites in the United States and Canada,
Overall, 277 patients, 19 percent of overall participants, were determined to have acute heart failure after blood samples were measured for NT-proBNP levels. This determination was separate from the clinical diagnosis that guided participants' care.
In a comparison of participants' NT-proBNP levels with their eventual diagnoses, the usefulness of the age-based cutoff levels were confirmed. A level below 300 strongly excluded a heart failure diagnosis regardless of the age.
The results were consistent for age, gender, racial or ethnic background or the presence of conditions that include obesity or kidney disease.
"We found no specific population in which the test did not perform well, and what was most striking to me -- as someone who has been working with NT-proBNP since the early 2000s -- was how consistent these results were with those of prior studies," Januzzi said. "Given the changes in the types of patients with heart failure we see today, it's quite remarkable how reliable this test is."
The study was funded by Roche Diagnostics, which manufactures the NT-proBNP used in this study.