Cardiac Biomarkers in Patients With Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial
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.
Article Details
Authors (29)
Brian R. Lindman
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
Philippe Pibarot
Laval University, Quebec, QC, Canada
Allan Schwartz
J. Bradley Oldemeyer
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
Yan Ru Su
Kashish Goel
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
David J. Cohen
Cardiovascular Research Foundation, New York
William F. Fearon
Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford, CA
Vasilis Babaliaros
Emory University, Atlanta
David Daniels
Division of Cardiology, California Pacific Medical Center, San Francisco (D.D.).
Adnan Chhatriwalla
St Luke’s Mid America Heart Institute, Kansas City, MO (A.C.).
Hussam S. Suradi
Division of Cardiology, Rush University Medical Center, Chicago, IL (H.S.S.).
Pinak Shah
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
Molly Szerlip
Baylor Scott and White the Heart Hospital Plano, Plano, TX
Michael J. Mack
Baylor Scott and White the Heart Hospital Plano, Plano, TX
Thom Dahle
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
William W. O’Neill
Center for Structural Heart Disease, Henry Ford Health System, Detroit, MI (W.W.O.).
Charles J. Davidson
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
Raj Makkar
Cedars-Sinai Medical Center, Los Angeles, California, United States
Tej Sheth
Population Health Research Institute, McMaster University, Hamilton, ON, Canada
Jeremiah Depta
Sands-Constellation Heart Institute, Rochester Regional Health, NY (J.D.).
James T. DeVries
Heart and Vascular Center, Section of Cardiovascular Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (J.T.D.).
Jeffrey Southard
UNIV OF CALIFORNIA DAVIS, West Sacramento, California, United States
Andrei Pop
Department of Cardiology, AMITA Alexian Brothers Medical Center, Elk Grove Village, IL (A.P.).
Paul Sorajja
Valve Science Center (M.E.-S., A.P., C.W., P.S., V.B., J.L.C.), Minneapolis Heart Institute Foundation, MN.
Rebecca T. Hahn
Yanglu Zhao
From Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ (P.G.); Columbia University Medical Center/New York Presbyterian Hospital (A.S., R.T.H., M.B.L.), the Cardiovascular Research Foundation (D.J.C., R.T.H., B.R., M.B.L.), and Weill Cornell Medicine (B.R.), New York, and St. Francis Hospital and Heart Center, Roslyn (D.J.C.) — all in New York; University of Colorado Health, Medical Center of the Rockies, Loveland (J.B.O.); Laval University, Quebec, QC (P.P.), St. Paul’s Hospital, University of British Columbia, Vancouver (P.B., J.L.), and McMaster University, Hamilton, ON (T.S.) — all in Canada; Vanderbilt University Medical Center, Nashville (B.R.L., K.G.); Emory University, Atlanta (V.B.); the Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, Stanford (W.F.F.), VA Palo Alto Health Care System, Palo Alto (W.F.F.), California Pacific Medical Center, San Francisco (D.V.D.), Cedars–Sinai Medical Center, Los Angeles (R.R.M.), and Edwards ...
Martin B. Leon
Cardiovascular Research Foundation, New York
Philippe Généreux
Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, NJ