Measuring standard cardiac biomarkers did not predict whether patients with asymptomatic severe aortic stenosis would benefit from nonsurgical aortic valve replacement, according to a recent study published in Circulation.
“The paradigm in the past had always been wait until symptoms develop and then we will treat the patient. What we’re finding now is that watchful waiting may not be the best strategy. It doesn’t mean that you necessarily have to have an urgent treatment for severe aortic stenosis, but that you should start planning to replace the valve soon and likely over the next six months. Waiting for symptoms is not the best strategy,” said Charles Davidson, MD, ‘85 GME, professor of Medicine in the Division of Cardiology and vice chair for Clinical Affairs in the Department of Medicine, who was a co-author of the study.
According to the American Heart Association, more than 13 percent of Americans over 75 years will develop severe aortic stenosis, which occurs when the opening of the aortic valve narrows and restricts proper blood flow from the left ventricle into the body, which can lead to death or stroke.
The EARLY TAVR trial, of which Davidson was also a co-author, had demonstrated that early transcatheter aortic valve replacement (TAVR) intervention — when the aortic valve is replaced from a groin artery with a balloon-expandable valve — improved outcomes compared to standard clinical surveillance and delayed TAVR in patients with severe aortic stenosis.
In the current follow-up study, Davidson and his collaborators aimed to determine whether elevated levels of standard cardiac biomarkers could identify asymptomatic patients with severe aortic stenosis who would be most likely to benefit from early TAVR intervention.
Plasma samples from 798 patients enrolled in the EARLY TAVR trial were analyzed for elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) — proteins produced by the heart that when elevated can indicate heart failure — and high-sensitivity cardiac troponin T (hs-cTnT), which can detect heart muscle damage.
The investigators found that higher NT-proBNP and hs-cTnT levels were broadly associated with higher rates of cardiac events, but the benefit of early TAVR was greater for patients with paradoxically lower, rather than higher, biomarker levels. This underscores the lack of predictive ability of traditional serum markers in asymptomatic patients, according to Davidson.
“Usually, the biomarkers lead you down a path of advancing pathology, but in this study, it found not to be a helpful way to guide recommendations for mechanical therapy,” Davidson said.
The findings suggest that the biomarkers offer limited value for guiding timing of TAVR treatment in this patient population. Although it can encourage physicians to discuss with patients the benefits of early intervention to prevent future hospitalizations and cardiac events, including stroke, it cannot be the sole decision marker.
On May 1, the body of data from this trial led to FDA approval and label for the Sapien 3 transcatheter heart valve for early TAVR intervention in asymptomatic aortic stenosis even with a negative stress test.
“We don’t have revised updated guideline recommendation for early TAVR, as of yet. However, the strong evidence coupled with FDA approval will need to be considered. Guidelines are helpful for patients because it adds confidence that this is a consensus recommendation. Practically speaking, it’s helpful for insurance approvals that are needed for treatment, particularly for the non-Medicare population or those on Medicare Advantage plans,” Davidson said.
The EARLY TAVR randomized clinical trial was funded by Edwards Lifesciences.
