title: Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with pulmonary vasculopathy.
  
  
  OBJECTIVE
  The purpose of this study was to determine whether sildenafil improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction.
  
  
  METHODS
  The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF, defined by carbon monoxide diffusing capacity &lt; 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafil treatment, and changes in 6MWD, St. George's Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks.
  
  
  RESULTS
  The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafil experienced less decrement in 6MWD (99.3 m; P = .01) and greater improvement in SGRQ (13.4 points; P = .005) and EuroQol visual analog scores (17.9 points; P = .04) than subjects receiving placebo. In the subgroup with RVH, sildenafil was not associated with change in 6MWD (P = .13), but was associated with greater relative improvement in SGRQ (14.8 points; P = .02) vs subjects receiving placebo. Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36.
  
  
  CONCLUSIONS
  Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafil also improves quality of life in subjects with RVH and RVSD.
authors.affiliation: University of Michigan Health System, Ann Arbor, MI. Electronic address: mrking@umich.edu.
authors.forename: MeiLan K
authors.initials: MK
authors.lastname: Han
authors.affiliation: University of Michigan Health System, Ann Arbor, MI.
authors.forename: David S
authors.initials: DS
authors.lastname: Bach
authors.affiliation: University of Michigan Health System, Ann Arbor, MI.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Hagan
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Eric
authors.initials: E
authors.lastname: Yow
authors.affiliation: University of Michigan Health System, Ann Arbor, MI.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Flaherty
authors.affiliation: University of Michigan Health System, Ann Arbor, MI.
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: University of Michigan Health System, Ann Arbor, MI.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006801:Humans; D017380:Hypertrophy, Right Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D010919:Placebos; D011687:Purines / Q000627:therapeutic use; D011788:Quality of Life; D012044:Regression Analysis; D012129:Respiratory Function Tests; D000068677:Sildenafil Citrate; D018709:Statistics, Nonparametric; D013450:Sulfones / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D016138:Walking / Q000502:physiology*
chemical_list: D010879:Piperazines; D010919:Placebos; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate