Related Experiment Video
Updated: Oct 8, 2025
Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension
Published on: February 11, 2017
Unmasking right ventricular-arterial uncoupling during fluid challenge in pulmonary hypertension
Nils Kremer1, Zvonimir Rako1, Philipp Douschan2
1Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
Background:
Patients with pulmonary hypertension (PH) frequently show preserved right ventricular (RV) function at rest. However, volume challenge may uncover pending RV dysfunction. We aimed to assess the physiological and prognostic impact of RV-pulmonary arterial (RV-PA) uncoupling during volume challenge in patients with precapillary PH.
Methods:
We prospectively assessed 32 patients with PH (pulmonary arterial hypertension, n = 27; inoperable chronic thromboembolic disease, n = 5) and 4 controls using invasive pressure-volume (PV) catheterization. PV loops were recorded during preload reduction (balloon occlusion of inferior vena cava; baseline) and acute volume loading (200 ml saline in 20 s). Contractility (multi-beat end-systolic elastance [Ees]), arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were obtained at baseline and at maximum volume loading (MVL).
Results:
Median [interquartile range] time to MVL was 19 [18-22] s. Ees/Ea significantly declined from baseline (0.89 [0.69-1.23]) to MVL (0.16 [0.12-0.34]; p < 0.001) in patients with PH but remained stable in controls (baseline: 1.08 [0.94-1.80]; MVL: 1.01 [0.80-2.49]; p = 0.715). The same pattern was observed for Ees, while Ea remained unchanged. The percent decline of RV-PA coupling (ΔEes/Ea) during fluid challenge was significantly associated with pulmonary resting hemodynamics, RV ejection fraction (RVEF), and RV end-diastolic volume. Kaplan-Meier analysis revealed that patients with PH who had a smaller ΔEes/Ea (<-65%) had a significantly better prognosis (log-rank p = 0.0389). In multivariate Cox regression analysis, clinical worsening was predicted by ΔEes/Ea (hazard ratio: 0.96 [95% confidence interval: 0.93-1.00]) and RVEF (hazard ratio: 0.95 [95% confidence interval: 0.92-0.98]).
Conclusions:
Assessment of PV loops during fluid challenge uncovers exhausted RV coupling reserve with severely reduced contractility in PH. RV-PA uncoupling during volume challenge can be predicted by pulmonary resting hemodynamics and RVEF. RV-PA uncoupling during fluid challenge and RVEF (as a noninvasive correlate) are predictors of clinical worsening.
Clinical Trial Registration:
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868 (January 19, 2018).
