Cardiac Biomarkers in Patients With Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial

Authors

Brian R. Lindman, Structural Heart and Valve Center, Vanderbilt University Medical Center, Nashville, TN.
Philippe Pibarot, Department of Cardiology, Québec Heart and Lung Institute, Laval University, Canada.
Allan Schwartz, Columbia University Medical Center/NewYork-Presbyterian Hospital, New York.
J Bradley Oldemeyer, University of Colorado Health, Loveland.
Yan Ru Su, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN.
Kashish Goel, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN.
David J. Cohen, Columbia University Medical Center/NewYork-Presbyterian Hospital, New York.
William F. Fearon, Interventional Cardiology Section, Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA.
Vasilis Babaliaros, Emory School of Medicine, Atlanta, GA.
David Daniels, Division of Cardiology, California Pacific Medical Center, San Francisco.
Adnan Chhatriwalla, St Luke's Mid America Heart Institute, Kansas City, MO.
Hussam S. Suradi, Division of Cardiology, Rush University Medical Center, Chicago, IL.
Pinak Shah, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.
Molly Szerlip, Baylor Scott & White Heart Hospital, Plano, Richardson, TX.
Michael J. Mack, Baylor Scott & White Heart Hospital, Plano, Richardson, TX.
Thom Dahle, CentraCare Heart & Vascular Center, St Cloud, MN.
William W. O'Neill, Center for Structural Heart Disease, Henry Ford Health System, Detroit, MI.
Charles J. Davidson, Northwestern University Feinberg School of Medicine, Chicago, IL.
Raj Makkar, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Tej Sheth, Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
Jeremiah Depta, Rochester Regional HealthFollow
James T. DeVries, Heart and Vascular Center, Section of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Jeffrey Southard, Division of Cardiovascular Medicine, UC Davis Health System, University of California-Davis, Sacramento.
Andrei Pop, Department of Cardiology, AMITA Alexian Brothers Medical Center, Elk Grove Village, IL.
Paul Sorajja, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, MN.
Rebecca T. Hahn, Columbia University Medical Center/NewYork-Presbyterian Hospital, New York.
Yanglu Zhao, Edwards Lifesciences, Irvine, CA.
Martin B. Leon, Columbia University Medical Center/NewYork-Presbyterian Hospital, New York.
Philippe Généreux, Gagnon Cardiovascular Institute, Morristown Medical Center, NJ.

Department

Cardiology

Document Type

Article

Publication Title

Circulation

Abstract

Background: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) intervention was superior to clinical surveillance with delayed TAVR in patients with asymptomatic severe aortic stenosis. Cardiac biomarkers are associated with maladaptive remodeling, symptom onset, and worse outcomes after TAVR. Whether elevated biomarkers identify asymptomatic patients more likely to benefit from early intervention is unknown.

Methods: A core laboratory measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) levels. Associations between biomarker levels and risk of the trial primary end point (death, stroke, or unplanned cardiovascular hospitalization) and other secondary end points were examined with Kaplan-Meier curves and Cox proportional hazard models. Interaction tests were performed to assess whether the treatment effect of early TAVR, compared with clinical surveillance, differed according to biomarker levels.

Results: Among 901 patients randomized in EARLY TAVR, 798 (89%) had biospecimens measured (median NT-proBNP level, 287 [145, 601]; median hs-cTnT level, 14.6 [10.5, 21.0]). Higher levels of NT-proBNP and hs-cTnT were broadly associated with higher event rates for multiple end points. In general, there was no significant interaction between baseline biomarkers and treatment group with respect to any composite or individual end point examined, although trends broadly demonstrated a greater relative benefit of early TAVR at lower biomarker levels. There was a significant interaction between hs-cTnT level and treatment group with respect to death or heart failure hospitalization (P interaction=0.04) and heart failure hospitalization alone (P interaction=0.03) such that the relative benefit of early TAVR was greater for patients with normal, rather than elevated, levels of hs-cTnT at baseline. For some end points, higher baseline NT-proBNP level was associated with numerically greater absolute risk reduction with early TAVR than were lower NT-proBNP levels.

Conclusions: In patients with asymptomatic severe high-gradient aortic stenosis, higher NT-proBNP and hs-cTnT levels were broadly associated with higher event rates, as expected. However, the relative benefit of an early TAVR strategy was consistent regardless of baseline biomarker levels and, contrary to our hypothesis, tended to be more pronounced in patients with the lowest biomarker levels. These findings suggest limited value for single measurements of these biomarkers to guide the timing of TAVR in asymptomatic patients.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03042104.

First Page

1550

Last Page

1564

DOI

10.1161/CIRCULATIONAHA.125.074425

Volume

151

Issue

22

Publication Date

6-3-2025

Medical Subject Headings

Humans; Aortic Valve Stenosis (surgery, blood, mortality, diagnosis); Male; Biomarkers (blood); Female; Transcatheter Aortic Valve Replacement (mortality); Natriuretic Peptide, Brain (blood); Troponin T (blood); Peptide Fragments (blood); Aged; Aged, 80 and over; Severity of Illness Index; Asymptomatic Diseases; Treatment Outcome

PubMed ID

40163596

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