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Normal NT-proBNP levels tied to low clinical risk in asymptomatic, nonsevere aortic stenosis

JAMA Cardiology
Reuters Health - 22/02/2022 - In patients with asymptomatic nonsevere aortic stenosis (AS), normal concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) over the course of a year are associated with low aortic valve events (AVEs) and low all-cause mortality, researchers say.

"NT-proBNP remained a very strong prognostic marker even after multivariable adjustment, including echocardiographic variables such as changes in the maximum velocity over the aortic valve," Dr. Olav Nielsen of Bispebjerg Hospital and University of Copenhagen told Reuters Health by email. "Clinicians can rest assured that patients with asymptomatic AS who have persistently normal NT-proBNP concentrations during one year are at low clinical risk."

In such patients, he said, "it seems safe to defer an echocardiogram and instead repeat NT-proBNP measurement up to one year after for mild AS and six months for moderate AS."

"An elevated NT-proBNP is a signal to look for effects on left ventricular function secondary to AS," he added, "but also to examine and treat for concomitant underlying comorbidities that may cause the symptoms and therefore can affect a decision to refer to aortic valve replacement."

As reported in JAMA Cardiology, Dr. Nielsen and colleagues analyzed annual NT-proBNP concentrations from 1,644 patients (mean age, 67.5; 61%, men) with asymptomatic AS enrolled in the multicenter Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) randomized clinical trial, which ran from 2003-2008.

Moderate AS was defined as baseline maximal flow velocity greater than or equal to 3.0 m/s. The main outcome was AVEs - a composite of aortic valve replacement, cardiovascular death, or incident heart failure due to AS progression.

Age- and sex-adjusted NT-proBNP concentrations were within the reference range (normal) in 77.0% of patients at baseline and in 70.8% of patients at year 1.

Over two years of follow-up, the AVE rates per 100 patient-years for normal versus increased adjusted NT-proBNP levels at year 1 were 1.39 versus 7.05 for those with mild AS, and 10.38 versus 26.20 for moderate AS.

Similarly, all-cause mortality rates were 1.05 versus 4.17 for mild AS and 1.60 versus 4.78 for moderate AS.

In multivariable models, the combination of a 1-year increased adjusted NT-proBNP level and 1.5-fold or greater NT-proBNP level change from baseline was associated with the highest AVE rates in patients with mild AS (hazard ratio, 8.12), as well as moderate AS (HR, 4.05).

Dr. Nielsen said, "Further research should establish whether regular NT-proBNP assessment can be extended to several years of symptoms and NT-proBNP-guided 'watchful waiting.'"

"Furthermore," he added, "a randomized clinical trial is needed to test whether hospitalizations can be more effectively prevented and reduced when comparing the blood-sample-based monitoring of NT-proBNP with the usual standard of care, including annual echocardiograms.

Dr. Rigved Tadwalkar, a cardiologist at Providence Saint John's Health Center in Santa Monica, told Reuters Health by email that he agrees with the findings. "We have been using natriuretic peptides routinely for years in the evaluation of heart failure. While we have seen in population-based studies that increasing natriuretic peptide levels predict cardiovascular events - including myocardial infarction and mortality - in a variety of settings, the precise use of these biomarkers in non-heart failure patients has remained unclear."

"The study...elucidates a clearer role for NT-proBNP assessment in non-severe aortic stenosis," he said. "The data are informative; however, my hope is that clinicians do not use biomarkers as a sole or predominant means of assessing these patients prognostically. A multi-modality clinical assessment remains the primary means by which appropriate decisions are made in valvular disease."

"Additionally," he noted, "the study was conducted in a European population, where 99.7% of the participants identified as white. We would want to see similar findings reproduced in a more diverse population to better apply the findings to the Americas."

The SEAS study, but not the current study, was conducted with financial support from Merck and Co. Inc. Two coauthors received funds from the company.

SOURCE: https://bit.ly/3IcJGpD JAMA Cardiology, online February 16, 2022.

By Marilynn Larkin

© 2023 The Author(s). Published by Medicom Medical Publishers.
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