title: Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study.
abstract: BACKGROUND
  The prevalence of heart failure with preserved ejection fraction is increasing. The prognosis worsens with pulmonary hypertension and right ventricular (RV) failure development. We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil.
  
  
  RESULTS
  Forty-four patients with heart failure with preserved ejection fraction (heart failure signs and symptoms, diastolic dysfunction, ejection fraction ≥50%, and pulmonary artery systolic pressure >40 mm Hg) were randomly assigned to placebo or sildenafil (50 mg thrice per day). At 6 months, there was no improvement with placebo, but sildenafil mediated significant improvements in mean pulmonary artery pressure (-42.0±13.0%) and RV function, as suggested by leftward shift of the RV Frank-Starling relationship, increased tricuspid annular systolic excursion (+69.0±19.0%) and ejection rate (+17.0±8.3%), and reduced right atrial pressure (-54.0±7.2%). These effects may have resulted from changes within the lung (reduced lung water content and improved alveolar-capillary gas conductance, +15.8±4.5%), the pulmonary vasculature (arteriolar resistance, -71.0±8.2%), and left-sided cardiac function (wedge pulmonary pressure, -15.7±3.1%; cardiac index, +6.0±0.9%; deceleration time, -13.0±1.9%; isovolumic relaxation time, -14.0±1.7%; septal mitral annulus velocity, -76.4±9.2%). Results were similar at 12 months.
  
  
  CONCLUSIONS
  The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility, RV function and dimension, left ventricular relaxation and distensibility (structural changes and/or ventricular interdependence), and lung interstitial water metabolism (wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage). These results enhance our understanding of heart failure with preserved ejection fraction and offer new directions for therapy.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01156636.
authors.affiliation: Cardiopulmonary Unit, University of Milan, San Paolo Hospital, Via A. di Rudinì 8, 20142 Milan, Italy. marco.guazzi@unimi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Guazzi
authors.forename: Marco
authors.initials: M
authors.lastname: Vicenzi
authors.forename: Ross
authors.initials: R
authors.lastname: Arena
authors.forename: Maurizio D
authors.initials: MD
authors.lastname: Guazzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D015995:Prevalence; D011687:Purines / Q000008:administration & dosage; D012129:Respiratory Function Tests / Q000379:methods; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects*; D013450:Sulfones / Q000008:administration & dosage*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate