title: Early echocardiographic predictors of outcomes in the mouse transverse aortic constriction heart failure model.
abstract: BACKGROUND
  Mouse transverse aortic constriction (TAC) is a widely-used model of pressure overload-induced heart failure. An intrinsic limitation of the model is variability in the response to pressure overload even when employing a standard severity of stenosis. Few literature studies have explicitly reported the use of entry criteria or early predictors to mitigate variability and enrich outcomes in this model.
  
  
  METHODS
  Eleven-week-old male C57BL/6J mice underwent TAC or sham surgery. Left ventricular (LV) function and dimensions were assessed by M-mode echocardiography at baseline (pre) and 3, 9 and 12weeks post-procedure (end-study). At 24h post-procedure, transverse aortic flow velocities were obtained for estimating trans-TAC pressure gradients. Invasive LV hemodynamic assessments were performed and terminal heart and lung weights obtained at end-study.
  
  
  RESULTS
  TAC mice displayed early development of LV hypertrophy and wall thickening followed by the later development of LV chamber dilation, and progressive development of LV systolic and diastolic dysfunction. The use of a pre-defined trans-TAC pressure gradient criterion of 45-60mmHg did not affect end-study organ weight, echocardiographic and invasive hemodynamic outcomes. A post-hoc receiver operator characteristic (ROC) analysis identified early 3week echocardiographic measures of LVmass(echo) and ejection fraction, with threshold changes of ~+30% and -10% normalized to baseline respectively, as good predictors for multiple end-study organ weight, echocardiographic and invasive hemodynamic outcomes.
  
  
  CONCLUSIONS
  This ROC analysis has identified early predictive threshold changes which may serve, alone or in combination, as entry criteria to enrich outcome in this model.
authors.affiliation: In Vivo Pharmacology, MRL, Kenilworth, NJ, USA.
authors.forename: Caryn
authors.initials: C
authors.lastname: Hampton
authors.affiliation: In Vivo Pharmacology, MRL, Kenilworth, NJ, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Rosa
authors.affiliation: Translational Imaging Biomarkers, MRL, Kenilworth, NJ, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Campbell
authors.affiliation: Translational Imaging Biomarkers, MRL, Kenilworth, NJ, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kennan
authors.affiliation: Laboratory Animal Resources, MRL, Kenilworth, NJ, USA.
authors.forename: Loise
authors.initials: L
authors.lastname: Gichuru
authors.affiliation: Laboratory Animal Resources, MRL, Kenilworth, NJ, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ping
authors.affiliation: Laboratory Animal Resources, MRL, Kenilworth, NJ, USA.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Shen
authors.affiliation: Cardiometabolic Disease Biology, MRL, Kenilworth, NJ, USA.
authors.forename: Kersten
authors.initials: K
authors.lastname: Small
authors.affiliation: Cardiometabolic Disease Biology, MRL, Kenilworth, NJ, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Madwed
authors.affiliation: In Vivo Pharmacology, MRL, Kenilworth, NJ, USA. Electronic address: lyncli@comcast.net.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
mesh_terms: D000818:Animals; D003250:Constriction; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods*; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011237:Predictive Value of Tests; D011897:Random Allocation; D016277:Ventricular Function, Left / Q000502:physiology
keywords: Heart failure; Methods; Receiver operator characteristic (ROC) analysis; Trans-aortic pressure gradient; Transverse aortic constriction (TAC)