title: Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension.
abstract: OBJECTIVE
  Imatinib mesylate, as add-on therapy in patients with pulmonary arterial hypertension (PAH) who remain inadequately treated despite receiving at least two PAH-specific drugs, improves exercise capacity and haemodynamics. We evaluated whether 24 weeks of add-on therapy with imatinib compared with placebo also improves right ventricular (RV) function assessed by echocardiography.
  
  
  RESULTS
  Echocardiograms were obtained at baseline, 12 weeks, and 24 weeks in 74 patients randomized to imatinib or placebo in the Imatinib in Pulmonary arterial hypertension, a Randomized Efficacy Study (IMPRES) trial. Right ventricular function was assessed by tissue Doppler tricuspid annular peak systolic velocity (TA S'), tricuspid annular plane systolic excursion (TAPSE), RV Tei index, and RV fractional area change. Between-treatment-group differences in the changes from baseline to week-24 were assessed using an ANCOVA with the last observation carried forward. At week-24 patients randomized to imatinib demonstrated greater improvements in TA S' (1.6 ± 2.3 imatinib vs. 0.5 ± 2.4 cm/s placebo, P = 0.007) and RV Tei index (-0.11 ± 0.18 imatinib vs. 0.05 ± 0.18 placebo, P = 0.005) compared with placebo, but not in TAPSE (0.07 ± 0.44 imatinib vs. 0.03 ± 0.32 cm placebo, P = 0.08). Imatinib therapy was also associated with significant reduction in peak tricuspid regurgitation velocity, increase in LV size, and improvement in LV early diastolic relaxation velocity.
  
  
  CONCLUSIONS
  Among patients with advanced PAH who remain symptomatic on at least two PAH-specific drugs, treatment with imatinib compared with placebo is associated with significant improvements in echocardiographic measures of RV function, in addition to LV size and LV early diastolic relaxation.
  
  
  BACKGROUND
  NCT00902174 (Clinicaltrials.gov).
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA ashah11@partners.org.
authors.forename: Amil M
authors.initials: AM
authors.lastname: Shah
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Campbell
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.
authors.forename: Gabriela Querejeta
authors.initials: GQ
authors.lastname: Rocha
authors.affiliation: Scottish Pulmonary Vascular Unit, Regional Heart and Lung Centre, Glasgow, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Peacock
authors.affiliation: Division of Pediatric Cardiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: Debbie
authors.initials: D
authors.lastname: Quinn
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015150:Echocardiography, Doppler; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D013318:Stroke Volume / Q000187:drug effects; D014262:Tricuspid Valve Insufficiency / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D000068877:Imatinib Mesylate
keywords: Echocardiography; Pulmonary heart disease; Pulmonary hypertension; Trials