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Objective: Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH., Methods: Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z 0 ), characteristic impedance (Z C , a measure of proximal PA stiffness) and proximal and distal PA compliance (C PA )., Results: In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m 2 at rest; p=0.003) and PA compliance was decreased (C PA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m 2 at rest; p=0.0002). Z 0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10 -6 ). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise., Conclusions: In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z 0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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., Competing Interests: Dr Bellofiore, Dr Vanderpool, Dr Chesler and Professor Naeije report no relationships that could be construed as a conflict of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To compare noninvasive estimates of pulmonary artery pressure (PAP) obtained via echocardiography (ECHO) to invasive measurements of PAP obtained during right heart catheterization (RHC) across a range of PAP. To examine the accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP measured by RHC (RAPRHC), and determine if adding RAPECHO improves the accuracy of noninvasive PAP estimations., Animals: 14 healthy female beagle dogs., Methods: Comparison of ECHO and RHC measures of PAP, both at normal PAP and increased PAP generated by microbead embolization., Results: Noninvasive estimates of PAP were moderately but significantly correlated (r of 0.68-0.78; p < 0.0006) with invasive measurements of PAP. Wide variance was noted for all estimations, with increased variance at higher PAP. The addition of RAPECHO improved correlation and bias in all cases. RAPRHC was significantly correlated with RAPECHO (r = 0.38; p = 0.04) as estimated by the ellipse area method. Median RAPRHC was significantly different between 3 subjective assessments of right atrial size (p = 0.037)., Conclusions: Spectral Doppler assessments of tricuspid and pulmonic regurgitation are imperfect methods for predicting PAP as measured by catheterization despite an overall moderate correlation between invasive and noninvasive values. Noninvasive measurements may be better utilized as part of a comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated based on subjective assessment of RA size. Including estimated RAPECHO in estimates of PAP improves the correlation and relatedness between noninvasive and invasive measures of PAP, but notable variability in accuracy of estimations persists., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A low relative area change (RAC) of the proximal pulmonary artery (PA) over the cardiac cycle is a good predictor of mortality from right ventricular failure in patients with pulmonary hypertension (PH). The relationship between RAC and local mechanical properties of arteries, which are known to stiffen in acute and chronic PH, is not clear, however. In this study, we estimated elastic moduli of three PAs (MPA, LPA and RPA: main, left and right PAs) at the physiological state using mechanical testing data and correlated these estimated elastic moduli to RAC measured in vivo with both phase-contrast magnetic resonance imaging (PC-MRI) and M-mode echocardiography (on RPA only). We did so using data from a canine model of acute PH due to embolization to assess the sensitivity of RAC to changes in elastic modulus in the absence of chronic PH-induced arterial remodeling. We found that elastic modulus increased with embolization-induced PH, presumably a consequence of increased collagen engagement, which corresponds well to decreased RAC. Furthermore, RAC was inversely related to elastic modulus. Finally, we found MRI and echocardiography yielded comparable estimates of RAC. We conclude that RAC of proximal PAs can be obtained from either MRI or echocardiography and a change in RAC indicates a change in elastic modulus of proximal PAs detectable even in the absence of chronic PH-induced arterial remodeling. The correlation between RAC and elastic modulus of proximal PAs may be useful for prognoses and to monitor the effects of therapeutic interventions in patients with PH., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pulmonary hypertension (PH) can impact right ventricular (RV) function and alter pulmonary artery (PA) stiffness. The response of the RV to an acute increase in pulmonary pressure is unclear. In addition, the relation between total pulmonary arterial compliance and local PA stiffness has not been investigated. We used a combination of right heart catheterization (RHC) and magnetic resonance imaging (MRI) to assess PA stiffening and RV function in dogs before and after acute embolization. We hypothesized that in moderate, acute PH the RV is able to compensate for increased afterload, maintaining adequate coupling. Also, we hypothesized that in the absence of PA remodeling the relative area change in the proximal PA (RAC, a noninvasive index of local area strain) correlates with the total arterial compliance (stroke volume-to-pulse pressure ratio). Our results indicate that, after embolization, RV function is able to accommodate the demand for increased stroke work without uncoupling, albeit at the expense of a reduction of efficiency. In this acute model, RAC showed excellent correlation with total arterial compliance. We used this correlation to assess PA pulse pressure (PP) from noninvasive MRI measurements of stroke volume and RAC. We demonstrated that in acute pulmonary embolism MRI estimates of PP are remarkably close to measurements from RHC. These results, if confirmed in chronic PH and clinically, suggest that monitoring of PH progression by noninvasive methods may be possible.