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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1550-1564 |
| Number of pages | 15 |
| Journal | Circulation |
| Volume | 151 |
| Issue number | 22 |
| DOIs | |
| State | Published - Jun 3 2025 |
Funding
Dr Lindman reports serving as a consultant for Anteris, AstraZeneca, Medtronic, and Kardigan; and serving as a consultant for and receiving institutional grant or contract support from Edwards Lifesciences. Dr Pibarot reports receiving institutional grant or contract support from Cardiac Success, Edwards Lifesciences, Medtronic, Novartis Pharma, and Pi-Cardiac. Dr Schwartz reports no disclosures. Dr Oldemeyer reports serving as a consultant for ABIOMED and as an investigator and on the case review and steering committees for Edwards Lifesciences. Dr Fearon reports receiving institutional grant or contract support from Abbott Vascular, CathWorks Inc, and Medtronic; holding stock options in HeartFlow Inc; being an employee of Veterans Affairs of Palo Alto; and serving as a consultant for ShockWave. Dr Babaliaros reports serving as a consultant for Abbott Vascular and Edwards Lifesciences and holding stock options in TransMural Systems. Dr Daniels reports serving as a consultant for Edwards Lifesciences. Dr Chhatriwalla reports serving as a consultant for Abbott Vascular, serving as a review committee member for ABIOMED, receiving grant or contract support from Boston Scientific Corporation, performing data and safety monitoring for Corematrix Cardiovascular, and serving as a consultant for and receiving travel honoraria from Edwards Lifesciences and Medtronic. Dr Suradi reports serving as a consultant for Edwards Lifesciences and Gore Medical. Dr Shah reports receiving institutional grant or contract support from Abbott Vascular and serving as a consultant for Boston Scientific Corporation, Edwards Lifesciences, and Xenter. Dr Szerlip reports being a steering committee member for Abbott Vascular, a speaker and advisory board member for Boston Scientific Corporation, a speaker for Edwards Lifesciences, and a steering committee member and advisory board member for Medtronic. Dr Mack reports being a trial coprincipal investigator for Edwards Lifesciences and a study chair for Medtronic. Dr Dahle reports being a speaker and proctor for Boston Scientific Corporation and Medtronic and a principal trial investigator and speaker and proctor for Edwards Lifesciences. Dr O’Neill reports serving as a consultant for Abbott Fund and Boston Scientific Corporation, receiving grant or contract support from ABIOMED, and serving as a consultant for and receiving grant or contract support from Edwards Lifesciences. Dr Davidson reports receiving institutional grant or contract support from Abbott Vascular, receiving institutional grant or contract support from and serving as an advisor for Edwards Lifesciences, and serving as a consultant for Philips. Dr Makkar reports receiving grant or contract support from Abbott Vascular and Edwards Lifesciences and serving as a consultant for Cordis Corporation and Medtronic. Dr Sheth reports receiving grant or contract support from Abbott Vascular and receiving institutional grant or contract support from and serving as a consultant for Edwards Lifesciences. Dr Depta reports serving as a consultant for Boston Scientific Corporation and Edwards Lifesciences. Dr DeVries has no relevant interests to disclose. Dr Southard reports serving as a proctor and consultant for Edwards Lifesciences. Dr Pop reports serving as a consultant for and receiving institutional grant or contract support from Edwards Lifesciences. Dr Sorajja reports serving as a consultant for 4C Medical Technologies, Abbott Structural, Adona Medical, Boston Scientific Corporation, CroiValve, Cultiv8, Edwards Lifesciences, Egg Medical, Evolution-Med, Foldax, GE Medical, Haemonetics, InQ8, Laza, Medtronic, Philips, Polares, W.L. Gore & Associates, vDyne, Unorthodox Ventures, Valcare Medical, and xDot. Dr Cohen reports serving as a consultant for and receiving institutional grant or contract support from Abbott Vascular, Boston Scientific Corporation, Edwards Lifesciences, and Medtronic, and receiving institutional grant or contract support from JenaValve. Dr Zhao is an employee of Edwards Lifesciences. Dr Goel reports serving as a consultant for Abbott Vascular and Edwards Lifesciences. Dr Su reports serving as the core laboratory director of and receiving institutional grant or contract support from Edwards Lifesciences. Dr Hahn reports serving as a speaker for Abbott Vascular, Baylis Medical Company, and Philipps; serving as the chief scientific officer of the echocardiographic core laboratory for the Cardiovascular Research Foundation; and serving as a speaker and echocardiographic data reviewer/adjudicator for Edwards Lifesciences. Dr Leon reports receiving institutional grant or contract support from Abbott Fund, ABIOMED, Anora Heart Inc, Boston Scientific Corporation, and Medtronic; serving as a consultant for Anteris, Croivalve, Foldax, Laminar, and MiRus LLC; serving as a principal investigator and receiving institutional grant or contract support from Edwards Lifesciences; holding stock options in Pi-Cardia and Xenter MD; and holding stock in SoloPace. Dr Généreux reports serving as a consultant for 4C Medical, Abbott Vascular, ABIOMED, Haemonetics Corporation, Medtronic, Opsens Inc, ShockWave Medical, and Teleflex Inc; serving as a principal investigator and consultant for Edwards Lifesciences; and serving as a consultant and holding stock options in Pi-Cardia, Puzzle Medical Inc, and Saranas Inc. EARLY TAVR was funded by Edwards Lifesciences, Irvine, CA. The study was supported by grants R01HL164526 and R01AG073633 from the National Institutes of Health to Dr Lindman.
Keywords
- aortic valve
- aortic valve stenosis
- biomarkers
- natriuretic peptide, brain
- transcatheter aortic valve replacement
- troponin T
- watchful waiting
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
