Impact of lowering pulmonary vascular resistance on right and left ventricular deformation in pulmonary arterial hypertension

Abstract

Aims: As pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality, particularly among patients with right ventricular (RV) dysfunction, we aimed to determine the impact of therapy to reduce pulmonary vascular resistance (PVR) on RV and LV deformation in PAH.

Methods and results: Right ventricular free wall longitudinal strain (FWLS) and LV global circumferential strain (CS) were measured at baseline, 12 weeks, and 24 weeks in 68 patients with advanced PAH randomized to imatinib or placebo in the Imatinib in Pulmonary arterial hypertension, a Randomized Efficacy Study (IMPRES) trial, and compared with 30 healthy controls. Compared with controls, PAH was associated with impaired RV FWLS (-15.9 ± 5.4 vs. -30.8 ± 4.3, respectively; P < 0.0001) and LV septal CS (-24.2 ± 8.2 vs. -31.4 ± 5.3, respectively, P < 0.0001), but not LV global CS. Improvement in PVR and mean pulmonary artery pressure (MPAP) over a 24-week period was significantly associated with improvement in RV FWLS (r = 0.39, P = 0.02; 0.33, P = 0.04 respectively), LV global CS (r = 0.61, P = 0.0001; r = 0.60, P = 0.0001, respectively), and LV septal CS (r = 0.50, P = 0.005; r = 0.56, P = 0.002, respectively). These associations were most robust with LV global and septal CS. Imatinib therapy was associated with improvement in RV FWLS compared with placebo.

Conclusions: PAH is associated with impaired biventricular deformation. Reduction in PVR is associated with improvements in both RV and LV deformation, coupled to improvements in MPAP and stroke volume index, with LV global and septal CS the strongest correlates of these changes. RV FWLS is sensitive to treatment effect, demonstrating greater improvement with imatinib compared with placebo.

Trial registration: NCT00902174.

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

Figure 1

Representative examples of deformation measurements in a patient with PAH. (A) RV global longitudinal strain (RV GLS); white – segments comprising RV free wall (FWLS), light grey – segments comprising RV septal wall (SLS). (B) LV circumferential strain (LV global CS); light grey – segments comprising LV septal segments (Septal), white – segments comprising non-septal LV segments (Non-septal). The right-most panel demonstrates average and segmental strain curves for both RV LS (top) and LV CS (bottom). From top to bottom: RV longitudinal strain: (A.1) IMPRES patient. (A.2) Control patient; LV circumferential strain: (B.1) IMPRES patient. (B.2) Control patient.

Figure 2

Study population, including IMPRES patients with PAH and healthy controls. LS – longitudinal strain; CS – circumferential strain.

Figure 3

Scatter plot showing the correlation between change in deformation measures (left – RV FWLS; right – LV global CS) and change in invasively measured hemodynamics (MPAP, SVI, PVR). Correlation coefficients (Pearson’s correlation for SVI; Spearman’s correlations for MPAP and PVR) and p value are provided.

Figure 4

Cardiac deformation (left – RV FWLS; right –LV global CS) at baseline, 12 weeks, and 24 weeks in IMPRES patients treated with imatinib versus placebo. Values provided are mean and standard errors. P value is for the combined difference between groups, derived from mixed-effects repeated measures models, adjusting for baseline value.