A Simple Way to Tell When Asymptomatic Aortic Stenosis Isn’t So Benign

A blood biomarker may identify individuals with asymptomatic non-severe aortic stenosis (AS) who can benefit from more frequent check-ups, as well as those who can safely defer care, a study suggested.

People who had N-terminal pro-brain natriuretic peptide (NT-proBNP) levels checked at year 1 in the old SEAS study had varying rates of aortic valve events (AVEs) — a composite of aortic valve replacement, cardiovascular death, or incident heart failure due to AS progression — over the next 2 years depending on AS severity and adjusted NT-proBNP:

• Mild AS and normal NT-proBNP: 1.39 per 100 patient-years
• Mild AS and increased NT-proBNP: 7.05 per 100 patient-years
• Moderate AS and normal NT-proBNP: 10.38 per 100 patient-years
• Moderate AS and increased NT-proBNP: 26.20 per 100 patient-years

Elevated NT-proBNP in tandem with a 1.5-fold or greater NT-proBNP level change from baseline to 1 year was associated with excess valve events in both patients with mild AS (adjusted HR 8.12, 95% CI 3.53-18.66) and those with moderate AS (adjusted HR 4.05, 95% CI 2.84-5.77), according to Olav Nielsen, MD, PhD, of Bispebjerg University Hospital in Copenhagen, Denmark, and colleagues.

Similarly, an increased NT-proBNP level at year 1 was associated with an increased risk of cardiovascular death in mild and moderate AS alike, the investigators reported in JAMA Cardiology.

“Therefore, our findings suggest the potential utility of using NPs as an alternative or add-on test to risk stratify a substantial population of patients who are monitored for many years,” Nielsen’s group said.

Current guidelines recommend clinical and echocardiographic follow-up every 1 to 3 years for these patients.

“The low incidence of AVEs associated with a normal NT-proBNP level at year 1 suggests that echocardiography may be safely deferred. Similarly, increased NT-proBNP levels, and especially levels that increase more than 1.5-fold over 1 year, identify patients who likely deserve more frequent or more intense scrutiny,” the authors noted.

Nielsen and colleagues suggested annual or biannual NT-proBNP measurements to strike a balance between reducing unnecessary and time-consuming echocardiograms for asymptomatic AS patients at very low risk, and promoting earlier testing in those at higher risk.

“Such a strategy can also address other conditions that affect [natriuretic peptide] levels and prognosis, including atrial fibrillation, ischemic heart disease, kidney dysfunction, and hypertension,” the researchers suggested. However, they acknowledged that it is unknown whether it is cost-effective to pursue this strategy.

Conducted from 2003 to 2008, SEAS was a randomized trial investigating combination simvastatin and ezetimibe therapy (Vytorin) for mild-to-moderate AS. The investigational drug not only failed to best placebo, but was associated with numerically more cancer deaths.

The present post hoc analysis included the 1,644 SEAS participants (60.6% men, mean age 67.5 years) who had available blood samples at baseline and year 1. All were asymptomatic AS patients with preserved ejection fraction who did not require statin therapy at study entry.

Increased NT-proBNP levels were measured in 20.5% of patients with mild AS and 37.1% of those with moderate AS at year 1. From baseline to year 1, these groups had NT-proBNP increase by a median 10% and 21%, respectively.

“The proportion of patients with abnormal NT-proBNP levels may be more frequent in everyday clinical practice than in the present study, but this differing number does not invalidate the favorable prognosis of a normal and stable NT-proBNP level in patients with non-severe AS,” Nielsen’s team maintained.

Follow-up beyond the year-1 time point lasted a median 42.2 months. Aortic valve replacement accounted for more than 80% of the observed AVEs, the study authors reported. Transcatheter aortic valve implantation was not available during this era.

Nielsen and colleagues noted that NT-proBNP did not bias any clinical decision-making during the conduct of SEAS because blood sample analyses had been delayed up to 8 years after the end of the trial, due to a lack of financial support.

However, one limitation was the inability to adjust for latent ischemic heart disease and cardiac amyloidosis that could affect NT-proBNP levels, symptoms, and outcomes.