Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients.

Background: Right ventricular ( RV ) dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 ( ACE 2), a key enzyme of the renin-angiotensin system ( RAS ), using recombinant human ACE 2 ( rhACE 2) could alleviate RAS -mediated vasoconstriction and vascular remodeling.
Methods: This prospective observational study investigated the association between concentrations of RAS peptides (Ang II or Ang(1-7)) and markers of RV function, as assessed by echocardiography (ratio of RV to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure ( PASP )).
Results: Fifty-seven mechanically ventilated patients were enrolled. Incidence rates of acute cor pulmonale ( ACP ) and pulmonary circulatory dysfunction ( PCD ) were consistent with previous studies. In the 45 evaluable participants, no notable or consistent changes in RAS peptides concentration were observed over the observation period, and there was no correlation between Ang II concentration and either PASP or RV size. The model of the predicted posterior distributions for the pre- and post-dose values of Ang II demonstrated no change in the likelihood of PCD after hypothetical dosing with rhACE 2, thus meeting the futility criteria. Similar results were observed with the other RAS peptides evaluated.
Conclusions: Pre-defined success criteria for an association between PCD and the plasma RAS peptides were not met in the mechanically ventilated unselected patients.
Competing Interests: A.M.D. reports fees from GlaxoSmithKline plc. AVB’s institution received fees from GlaxoSmithKline plc. K.H., W.P., A.F., D.A.H., A.L.L., and D.C.B. are employees of GlaxoSmithKline plc. and hold shares in the company. F.B. has nothing to disclose.