Effect of imatinib as add-on therapy on echocardiographic measures of right ventricular function in patients with significant pulmonary arterial hypertension

Eur Heart J. 2015 Mar 7;36(10):623-32. doi: 10.1093/eurheartj/ehu035. Epub 2014 Feb 23.

Abstract

Aims: 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.

Methods and 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.

Clinical trial registration: NCT00902174 (Clinicaltrials.gov).

Keywords: Echocardiography; Pulmonary heart disease; Pulmonary hypertension; Trials.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Antihypertensive Agents / therapeutic use*
  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects
  • Echocardiography, Doppler
  • Exercise Tolerance / drug effects
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnostic imaging
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / drug therapy
  • Hypertrophy, Left Ventricular / physiopathology
  • Imatinib Mesylate / therapeutic use*
  • Male
  • Middle Aged
  • Observer Variation
  • Stroke Volume / drug effects
  • Tricuspid Valve Insufficiency / diagnostic imaging
  • Tricuspid Valve Insufficiency / drug therapy
  • Tricuspid Valve Insufficiency / physiopathology
  • Vascular Resistance / drug effects
  • Ventricular Dysfunction, Right / diagnostic imaging
  • Ventricular Dysfunction, Right / drug therapy
  • Ventricular Dysfunction, Right / physiopathology

Substances

  • Antihypertensive Agents
  • Imatinib Mesylate

Associated data

  • ClinicalTrials.gov/NCT00902174