{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:00:50Z","timestamp":1791892850848,"version":"4.3.4"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Edwards Lifesciences","award":["NCT03042104."],"award-info":[{"award-number":["NCT03042104."]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>A core laboratory measured NT-proBNP (N-terminal pro\u2013B-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.04) and heart failure hospitalization alone (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03042104.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.074425","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T14:02:32Z","timestamp":1743429752000},"page":"1550-1564","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Cardiac Biomarkers in Patients With Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial"],"prefix":"10.1161","volume":"151","clinical-trial-number":[{"clinical-trial-number":"nct03042104","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6879-5343","authenticated-orcid":true,"given":"Brian R.","family":"Lindman","sequence":"first","affiliation":[{"name":"Structural Heart and Valve Center (B.R.L.), Vanderbilt University Medical Center, Nashville, TN."},{"name":"Division of Cardiovascular Medicine (B.R.L., Y.R.S., K.G.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3607-279X","authenticated-orcid":true,"given":"Philippe","family":"Pibarot","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Qu\u00e9bec Heart and Lung Institute, Laval University, Canada (P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center\/NewYork-Presbyterian Hospital, New York (A.S., D.J.C., R.T.H., M.B.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-024X","authenticated-orcid":true,"given":"J. Bradley","family":"Oldemeyer","sequence":"additional","affiliation":[{"name":"University of Colorado Health, Loveland (J.B.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5096-1198","authenticated-orcid":true,"given":"Yan Ru","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (B.R.L., Y.R.S., K.G.), Vanderbilt University Medical Center, Nashville, TN."},{"name":"Cardiology Core Laboratory for Translational and Clinical Research (Y.R.S.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3457-6887","authenticated-orcid":true,"given":"Kashish","family":"Goel","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (B.R.L., Y.R.S., K.G.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-724X","authenticated-orcid":true,"given":"David J.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center\/NewYork-Presbyterian Hospital, New York (A.S., D.J.C., R.T.H., M.B.L.)."},{"name":"Cardiovascular Research Foundation, New York, NY (D.J.C., M.B.L.)."},{"name":"St Francis Hospital and Heart Center, Roslyn, NY (D.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1799-1368","authenticated-orcid":true,"given":"William F.","family":"Fearon","sequence":"additional","affiliation":[{"name":"Interventional Cardiology Section, Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (W.F.F.)."},{"name":"VA Palo Alto Health Care System, CA (W.F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-0846","authenticated-orcid":true,"given":"Vasilis","family":"Babaliaros","sequence":"additional","affiliation":[{"name":"Emory School of Medicine, Atlanta, GA (V.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Daniels","sequence":"additional","affiliation":[{"name":"Division of Cardiology, California Pacific Medical Center, San Francisco (D.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5309-3058","authenticated-orcid":true,"given":"Adnan","family":"Chhatriwalla","sequence":"additional","affiliation":[{"name":"St Luke\u2019s Mid America Heart Institute, Kansas City, MO (A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6012-9648","authenticated-orcid":true,"given":"Hussam S.","family":"Suradi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Rush University Medical Center, Chicago, IL (H.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1642-7557","authenticated-orcid":true,"given":"Pinak","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (P. Shah)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4907-1825","authenticated-orcid":true,"given":"Molly","family":"Szerlip","sequence":"additional","affiliation":[{"name":"Baylor Scott &amp; White Heart Hospital, Plano, Richardson, TX (M.S., M.J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3148-9158","authenticated-orcid":true,"given":"Michael J.","family":"Mack","sequence":"additional","affiliation":[{"name":"Baylor Scott &amp; White Heart Hospital, Plano, Richardson, TX (M.S., M.J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-2597","authenticated-orcid":true,"given":"Thom","family":"Dahle","sequence":"additional","affiliation":[{"name":"CentraCare Heart &amp; Vascular Center, St Cloud, MN (T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5896-728X","authenticated-orcid":true,"given":"William W.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Center for Structural Heart Disease, Henry Ford Health System, Detroit, MI (W.W.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0783-9995","authenticated-orcid":true,"given":"Charles J.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, IL (C.J.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Makkar","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (R.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tej","family":"Sheth","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada (T.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5095-2649","authenticated-orcid":true,"given":"Jeremiah","family":"Depta","sequence":"additional","affiliation":[{"name":"Sands-Constellation Heart Institute, Rochester Regional Health, NY (J.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-5831","authenticated-orcid":true,"given":"James T.","family":"DeVries","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Section of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (J.T.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-8888","authenticated-orcid":true,"given":"Jeffrey","family":"Southard","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, UC Davis Health System, University of California\u2013Davis, Sacramento (J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Pop","sequence":"additional","affiliation":[{"name":"Department of Cardiology, AMITA Alexian Brothers Medical Center, Elk Grove Village, IL (A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-854X","authenticated-orcid":true,"given":"Paul","family":"Sorajja","sequence":"additional","affiliation":[{"name":"Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, MN (P. 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