Imaging right ventricular function to predict outcome in pulmonary arterial hypertension

Abstract

Background

Right ventricular (RV) function is a major determinant of outcome in pulmonary arterial hypertension (PAH). However, uncertainty persists about the optimal method of evaluation.

Methods

We measured RV end-systolic and end-diastolic volumes (ESV and EDV) using cardiac magnetic resonance imaging and RV pressures during right heart catheterization in 140 incident PAH patients and 22 controls. A maximum RV pressure (Pmax) was calculated from the nonlinear extrapolations of early and late systolic portions of the RV pressure curve. The gold standard measure of RV function adaptation to afterload, or RV–arterial coupling (Ees/Ea) was estimated by the stroke volume (SV)/ESV ratio (volume method) or as Pmax/mean pulmonary artery pressure (mPAP) minus 1 (pressure method) (n = 84). RV function was also assessed by ejection fraction (EF), right atrial pressure (RAP) and SV.

Results

Higher Ea and RAP, and lower compliance, SV and EF predicted outcome at univariate analysis. Ees/Ea estimated by the pressure method did not predict outcome but Ees/Ea estimated by the volume method (SV/ESV) did. At multivariate analysis, only SV/ESV and EF were independent predictors of outcome. Survival was poorer in patients with a fall in EF or SV/ESV during follow-up (n = 44, p = 0.008).

Conclusion

RV function to predict outcome in PAH is best evaluated by imaging derived SV/ESV or EF. In this study, there was no added value of invasive measurements or simplified pressure-derived estimates of RV–arterial coupling.

Introduction

It has been realized in recent years that right ventricular (RV) function is a major determinant of functional state, exercise capacity and survival in patients with pulmonary arterial hypertension (PAH) [1]. However, how to measure RV function and what variables might be most clinically relevant at the bedside remains uncertain [1], [2].

The gold standard measure of RV systolic functional adaptation to increased loading conditions is end-systolic elastance (Ees) (or end-systolic pressure (ESP) divided by end-systolic volume (ESV)), corrected for arterial elastance (Ea) (or stroke volume (SV) divided by ESP). The Ees/Ea ratio defines RV–arterial coupling, or the matching of contractility to afterload. Ees is a measure of RV contractility and unlike other measures of RV function is load independent. Ea is a measure of the afterload faced by the RV and incorporates resistance, compliance and impedance of the pulmonary circulation. The optimal balance between RV work and oxygen consumption occurs at an Ees/Ea ratio of 1.5–2 [1], [2].

The reference method for the determination of Ees requires instantaneous and simultaneous measurements of RV pressure and volume and generation of a family of pressure–volume loops at decreasing venous return [3]. This is not practical at the bedside. However Ees can also be estimated from a single P–V loop [4]. This method relies on the calculation of a maximum RV pressure (Pmax) from the extrapolation of early and late systolic portions of a RV pressure curve and the continuous recording of RV pressure and relative change in volume to define ESP and ESV. From these, Ees and Ea are easily calculated. The estimation of RV–arterial coupling by an Ees/Ea ratio can further be simplified for pressure and expressed as a SV/ESV ratio [5], i.e. the volume method. Alternatively the ratio can be simplified for volumes and expressed as Pmax divided by mean pulmonary artery pressure (mPAP), taken as a surrogate for ESP, minus 1 [6], i.e. the pressure method. A RV pressure curve is easily obtained during a right heart catheterization. RV volumes are ideally determined by magnetic resonance imaging (CMR).

From RV volumes it is naturally also easy to calculate a SV and an ejection fraction (EF) as SV/EDV. Cardiac CMR studies have shown that decreased SV and RV EF are predictive of poor outcome [7], and that a deterioration in RV EF during PAH therapy predicts a poor survival irrespective of improvements in pulmonary vascular resistance (PVR) [8]. However, EF is preload-dependent while Ees/Ea is theoretically not. Therefore, estimates of Ees should be superior in determining clinical state and outcome. Accordingly, a recent study on a limited number of patients referred for investigation of PH showed Ees/Ea estimated by SV/ESV to be an independent predictor of outcome while EF was not [9].

We therefore investigated the prognostic utility of RV–arterial coupling determined by both the volume and the pressure methods, compared to more usual determinations of EF and right heart catheterization-derived RAP and SV in a large cohort of patients with PAH, and in addition examined changes over time of these measurements with targeted therapies and their impact on survival.