Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696

Circ Heart Fail. 2014 Nov;7(6):953-9. doi: 10.1161/CIRCHEARTFAILURE.114.001427. Epub 2014 Oct 2.

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.

Methods and 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.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00887588.

Keywords: heart failure; neprilysin; troponin T.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminobutyrates / therapeutic use*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Biphenyl Compounds
  • Drug Combinations
  • Female
  • Heart Failure / blood*
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Natriuretic Peptide, Brain / therapeutic use
  • Neprilysin / antagonists & inhibitors*
  • Peptide Fragments / therapeutic use
  • Tetrazoles / therapeutic use*
  • Troponin T / blood*
  • Valine / analogs & derivatives
  • Valine / therapeutic use
  • Valsartan

Substances

  • Aminobutyrates
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Peptide Fragments
  • Tetrazoles
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Valsartan
  • Neprilysin
  • Valine
  • sacubitril and valsartan sodium hydrate drug combination

Associated data

  • ClinicalTrials.gov/NCT00887588