B08

Right ventricular (RV) function is the main determinant of symptomology and prognosis in pulmonary hypertension (PH). Measuring RV load-independent contractility (end-systolic elastance, Ees) as the inherent parameter of RV function is highly sophisticated and demanding. In the first funding period, we successfully established gold-standard pressure-volume (PV) loops of the RV and established a world-reference center in PV-loop-assessment. We showed that Ees, arterial elastance (arterial afterload, Ea), the interplay of RV to pulmonary afterload and the RV-pulmonary arterial (RV-PA) coupling (assessed by Ees/Ea relation and end-diastolic stiffness [Eed]) are associated with a) prognosis, b) ventilatory insufficiency, c) different RV-contraction patterns, (assessed with sophisticated cardiac magnetic resonance imaging [cMRI]), and d) severity of lung-disease associated PH. In addition, we validated non-invasive RV-PV-loops, which, based on our research, were integrated in the new PH-guidelines and defined the important range RV contractile reserve in chronic pressure overload. In the second funding period we established a completely 2D/3D echo-based method to measure RV-PA coupling and applied for a patent. This work paves the way to link highly sophisticated, time-consuming physiologic measurements, i.e. PV-loops, with non-invasive outpatient and inpatient clinical routine. In an experimental and human study, we recently revealed that inhaled Iloprost not only lowers afterload, but also increases RV Ees and Ees/Ea. This study is based on a collaboration with projects C01 and A08. In addition, our data close an important gap of knowledge in regard to sex-differences in pulmonary arterial hypertension (PAH). Recently we showed that female patients have higher values of contractility than male patients in idiopathic PAH and PAH. This finding is one of the explanations as to why female patients have a better prognosis than male patients, despite having a higher incidence of disease. Chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) represent a continuum of pulmonary vascular disease (PVD). In a collaborative research project with CP01 we showed that a simple surrogate of RV-PA coupling may help to identify patients with PVD due to chronic thromboembolism and may predict impaired pulmonary exercise haemodynamics in these patients. Recently, our study regarding volume load on diseased RV with chronic pressure overload paved the way to identify patients with a sufficient RV contractile reserve to cope with additional volume load, a question with high clinical impact and interest, i.e. in intensive care units. A RV-ejection fraction (RVEF) of higher than 48 % predicts a functioning RV reserve and an increase in contractility after increase in end-diastolic volume (Frank-Stralings-Law), whereas patients with lower RVEF present with decrease in Ees after volume load.

In the upcoming funding period, we aim to 1) establish a new app-based pressure-device (Corlog) to measure PV-loops in daily clinical routine a) based volume assessment from 3Decho and b) based on simultaneous volume assessment in CMRI and to calculate Ees/ea during real life situations, 2) establish a right ventricular hemodynamic database from routine right heart catheters. This database will mainly include right ventricular pressure/time tracings. Based on these tracings we will collaborate with specialists on artificial intelligence to define only based on the RV pressure over time curve a) an estimation of pulmonary capillary wedge pressure and b) oscillatory wave and oscillatory power.

3) establish measurements of a neglected important component of afterload in the pulmonary vessels, the impedance. This work will be done by pressure/flow assessments from the pulmonary artery (PA) based on a high fidelity catheter (pressure wire) and flow, derived from CMRI. Impedance will be evaluated in terms quality of life, outcome and hemodynamics. In addition, the impact of the reflective wave on the RV and outcome will be evaluated. 4) Based on findings of 3) PA denervation will be established and performed on clinical grounds. In an observational study we will evaluate the impact of denervation on outcome, quality of life, and hemodynamics, including oscillatory wave and impedance. 5) In collaboration with project B10N we will further evaluate the important impact of atrial fibrillation (AF) on RV function in PH. Patients with an indication for a pulmonary venous isolation will be evaluated in terms of RV function, including contractility before and after isolation and will be followed up for quality of life and outcome.