Accurate assessment of load-independent right ventricular systolic function in patients with pulmonary hypertension

doi:10.1016/j.healun.2012.09.022

The Journal of Heart and Lung Transplantation

Volume 32, Issue 1, January 2013, Pages 50-55

https://doi.org/10.1016/j.healun.2012.09.022 Get rights and content

Background

End-systolic elastance (E_es), a load-independent measure of ventricular function, is of clinical interest for studies of the right ventricle (RV) in patients with pulmonary arterial hypertension (PAH). The objective of this study was to determine whether, in PAH patients, E_es can be estimated from mean pulmonary artery pressure (mPAP) and end-systolic volume (ESV) only.

Methods

Right heart catheterization was used to measure mPAP. Maximal isovolumic pressure (P_iso) was estimated from RV pressure curves with the so-called single-beat method. Cardiac magnetic resonance imaging (MRI) was used to assess RV end-diastolic and end-systolic volumes (EDV and ESV). E_es was then calculated as: E_es = (P_iso−mPAP) / (EDV−ESV), and as E_{es,V0 = 0} = mPAP/ESV (simplified method, with V0 = 0, is negligible volume at zero pressure). Right ventricular volume at zero pressure (V₀) was then defined as the intercept of the end-systolic pressure–volume relation (single-beat method) with the horizontal axis.

Results

E_{es,V0 = 0} was significantly lower compared with E_es (0.61 vs 1.34 mm Hg/ml, respectively, p<0.01). A modified Bland–Altman analysis showed a contractility-dependent difference between E_{es,V0 = 0} and E_es. Moreover, V₀ ranged from−8 up to 171 ml, and a moderate and good correlation was found between V₀ and EDV, and V₀ and ESV, respectively (r = 0.65 and r = 0.87, p< 0.01).

Conclusions

These findings show that V₀ is dependent on RV dilation. Therefore, the assumption that V₀ is negligible in PAH is incorrect. Consequently, for an accurate assessment of load-independent RV systolic function, RV volumes and pressure curves are required.

Section snippets

Subjects

Patients referred to the VU Medical Center for evaluation of PAH and patients with PAH undergoing follow-up analysis were retrospectively included in this study. Standard clinical care included right heart catheterization with digital recordings of pressures and cardiac MRI. A total of 28 patients were selected based on: (1) diagnosis of idiopathic pulmonary arterial hypertension (IPAH); and (2) available recordings of qualitative good RV pressure curves and cardiac magnetic resonance imaging

Results

Patient characteristics and both E_es and E_{es,V0 = 0} are shown in Table 1. The patients (n = 28) included represent IPAH patients over a wide range of disease severity, as reflected by the range in PVR (188 to 1,969 dynes/s/cm⁵), RV ejection fraction (18% to 65%) and stroke volume index (14 to 89 ml/m²). Of the 28 patients, 24 patients were being treated at the moment of inclusion, with the other 4 not yet treated.

Discussion

Our study has shown that, in PAH patients, the estimation of E_es based on mPAP and end-systolic volume strongly underestimates E_es. Therefore, this method cannot be applied in patients with PAH. Furthermore, V₀ was highly dependent on RV dilation as suggested by the close association between RV volumes and V₀. The assumption that V₀ is negligible in PAH patients is therefore incorrect.

Disclosure statement

The authors have no conflicts of interest to disclose.

This study was supported by the Netherlands Organisation for Scientific Research (NWO)-VIDI (Project No. 917.96.306 to A.V.-N.).

References (30)

S. Ghio et al.
Prognostic relevance of the echocardiographic assessment of right ventricular function in patients with idiopathic pulmonary arterial hypertension
Int J Cardiol
(2010)
A. Sachdev et al.
Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension
Chest
(2011)
M.C. van de Veerdonk et al.
Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy
J Am Coll Cardiol
(2011)
S.S. Najjar et al.
Age and gender affect ventricular–vascular coupling during aerobic exercise
J Am Coll Cardiol
(2004)
L.J. Dell'Italia et al.
Can indices of left ventricular function be applied to the right ventricle?
Prog Cardiovasc Dis
(1998)
C.H. Chen et al.
Noninvasive single-beat determination of left ventricular end-systolic elastance in humans
J Am Coll Cardiol
(2001)
N.F. Voelkel et al.
Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure
Circulation
(2006)
P.R. Forfia et al.
Tricuspid annular displacement predicts survival in pulmonary hypertension
Am J Respir Crit Care Med
(2006)
S.A. van Wolferen et al.
Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension
Eur Heart J
(2007)
V. Ferferieva et al.
The relative value of strain and strain rate for defining intrinsic myocardial function
Am J Physiol Heart Circ Physiol
(2012)

D.A. Kass et al.

Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure–volume relationships

Circulation

(1987)

W.L. Maughan et al.

Instantaneous pressure–volume relationship of the canine right ventricle

Circ Res

(1979)

H. Suga et al.

Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio

Circ Res

(1973)

K. Sunagawa et al.

Estimation of the hydromotive source pressure from ejecting beats of the left ventricle

IEEE Trans Biomed Eng

(1980)

M. Takeuchi et al.

Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle

Circulation

(1991)

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View full text

Original clinical scienceAccurate assessment of load-independent right ventricular systolic function in patients with pulmonary hypertension

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Disclosure statement

Int J Cardiol

Chest

J Am Coll Cardiol

J Am Coll Cardiol

Prog Cardiovasc Dis

J Am Coll Cardiol

Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure

Circulation

Tricuspid annular displacement predicts survival in pulmonary hypertension

Am J Respir Crit Care Med

Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension

Eur Heart J

The relative value of strain and strain rate for defining intrinsic myocardial function

Am J Physiol Heart Circ Physiol

Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure–volume relationships

Circulation

Instantaneous pressure–volume relationship of the canine right ventricle

Circ Res

Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio

Circ Res

Estimation of the hydromotive source pressure from ejecting beats of the left ventricle

IEEE Trans Biomed Eng

Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle

Circulation

Original clinical science
Accurate assessment of load-independent right ventricular systolic function in patients with pulmonary hypertension