Kremer Nils, Rako Zvonimir, Douschan Philipp, Gall Henning, Ghofrani Hossein A, Grimminger Friedrich, Guth Stefan, Naeije Robert, Rieth Andreas, Schulz Rainer, Seeger Werner, Tedford Ryan J, Vadász István, Vanderpool Rebecca, Wiedenroth Christoph B, Richter Manuel J, Tello Khodr
Department 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.
Department 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; Division of Pulmonology, Department of Internal Medicine and Ludwig Boltzmann Institute for Lung Vascular Research, Medical University of Graz, Graz, Austria.
J Heart Lung Transplant. 2022 Mar;41(3):345-355. doi: 10.1016/j.healun.2021.11.019. Epub 2021 Dec 5.
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.
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).
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]).
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.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868 (January 19, 2018).
肺动脉高压（PH）患者静息时右心室（RV）功能通常保持正常。然而，容量负荷试验可能会揭示潜在的右心室功能障碍。我们旨在评估毛细血管前性肺动脉高压患者在容量负荷试验期间右心室-肺动脉（RV-PA）解耦联对生理和预后的影响。
我们前瞻性地评估了32例肺动脉高压患者（肺动脉高压，n = 27；无法手术的慢性血栓栓塞性疾病，n = 5）和4例对照者，采用有创压力-容量（PV）导管插入术。在预负荷降低（下腔静脉球囊闭塞；基线）和急性容量负荷（20秒内输注200毫升生理盐水）期间记录PV环。在基线和最大容量负荷（MVL）时获得收缩性（多次搏动的收缩末期弹性[Ees]）、动脉弹性（Ea）和RV-PA耦联（Ees/Ea）。
达到MVL的中位[四分位间距]时间为19[18-22]秒。肺动脉高压患者的Ees/Ea从基线时的0.89[0.69-1.23]显著下降至MVL时的0.16[0.12-0.34]；p < 0.001），而对照组保持稳定（基线：1.08[0.94-1.80]；MVL：1.01[0.80-2.49]；p = 0.715）。Ees呈现相同模式，而Ea保持不变。液体负荷试验期间RV-PA耦联的下降百分比（ΔEes/Ea）与肺静息血流动力学、右心室射血分数（RVEF）和右心室舒张末期容积显著相关。Kaplan-Meier分析显示，ΔEes/Ea较小（<-65%）的肺动脉高压患者预后明显较好（对数秩检验p = 0.0389）。在多变量Cox回归分析中，临床恶化可通过ΔEes/Ea（风险比：0.96[95%置信区间：0.93-1.00]）和RVEF（风险比：0.95[95%置信区间：0.92-0.98]）预测。
液体负荷试验期间对PV环的评估揭示了肺动脉高压患者右心室耦联储备耗尽且收缩性严重降低。容量负荷试验期间的RV-PA解耦联可通过肺静息血流动力学和RVEF预测。液体负荷试验期间的RV-PA解耦联和RVEF（作为无创相关指标）是临床恶化的预测因素。
网址：https://www.clinicaltrials.gov。唯一标识符：NCT03403868（2018年1月19日）。
