title: Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696.
abstract: BACKGROUND
  Elevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction, but less is known about the association in heart failure with preserved ejection fraction.
  
  
  RESULTS
  We examined the prevalence of elevated high-sensitivity troponin T (hs-TnT) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan. We assessed the association between hs-TnT and cardiac structure and function, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks. Elevated hs-TnT in the myocardial injury range (>0.014 μg/L) was found in 55% of patients and was associated with older age, history of diabetes mellitus, higher N-terminal pro-brain natriuretic peptide, lower estimated glomerular filtration rate, and larger left atrial size, left ventricular volume, and mass. LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks (12% reduction; P=0.05) and at 36 weeks (14% reduction; P=0.03) compared with valsartan.
  
  
  CONCLUSIONS
  Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure, function, and elevated baseline N-terminal pro-brain natriuretic peptide. Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00887588.
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Brian L
authors.initials: BL
authors.lastname: Claggett
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Burkert M
authors.initials: BM
authors.lastname: Pieske
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kraigher-Krainer
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Amil M
authors.initials: AM
authors.lastname: Shah
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Prescott
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Victor
authors.initials: V
authors.lastname: Shi
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: Marty
authors.initials: M
authors.lastname: Lefkowitz
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.).
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.S.J., B.L.C., A.M.S., S.D.S.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (P.S.J., J.J.V.M.); Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (A.A.V.); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (M.R.Z.); Medical University of South Carolina, Charleston (M.R.Z.); Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); Department of Cardiology, Medical University Graz, Graz, Austria (B.M.P., E.K.-K.); and Novartis Pharmaceuticals, East Hanover, NJ (M.F.P., V.S., M.L.). ssolomon@rics.bwh.harvard.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000613:Aminobutyrates / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004338:Drug Combinations; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000627:therapeutic use; D013777:Tetrazoles / Q000627:therapeutic use*; D020107:Troponin T / Q000097:blood*; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D010446:Peptide Fragments; D013777:Tetrazoles; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068756:Valsartan; D015260:Neprilysin; D014633:Valine; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: heart failure; neprilysin; troponin T