title: Suppression of Tumorigenicity 2 in Heart Failure With Preserved Ejection Fraction.
abstract: Soluble suppression of tumorigenicity 2 (sST2) receptor is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity-driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF.
  
  
  
  At enrollment, patients (n=174) from the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HFpEF had sST2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST2 levels. Median sST2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9-49.2 ng/mL; reference range 4-31 ng/mL) and 30.8 ng/mL (range 25.3-39.3 ng/mL; reference range 2-21 ng/mL), respectively. Among HFpEF patients, higher sST2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis (P<0.05 for all). sST2 was not associated with left ventricular structure or left ventricular systolic or diastolic function.
  
  
  
  In HFpEF, sST2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that ST2 may be a marker of systemic inflammation in HFpEF and potentially of extracardiac origin.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Omar F
authors.initials: OF
authors.lastname: AbouEzzeddine
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKie
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Dunlay
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke University Medical Center, Durham, NC.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: University of Vermont, Burlington, VT.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Mayo Clinic, Rochester, MN redfield.margaret@mayo.edu.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D015150:Echocardiography, Doppler; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000037:antagonists & inhibitors / Q000097:blood*; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage; D017472:Receptors, Interleukin-1; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D058986:Phosphodiesterase 5 Inhibitors; D017472:Receptors, Interleukin-1; D000068677:Sildenafil Citrate
keywords: biomarker; diastolic heart failure