Right ventricular end-diastolic stiffness heralds right ventricular failure in monocrotaline-induced pulmonary hypertension

Abstract

Recent studies suggest right ventricular (RV) stiffness is important in pulmonary hypertension (PH) prognosis. Smaller stroke volume (SV) variation after a certain RV end-diastolic pressure (EDP) respiratory variation as assessed by spectral transfer function (STF) may identify RV stiffness. Our aim was to evaluate RV stiffness in monocrotaline (MCT)-induced PH progression and to validate STF gain between EDP and SV as marker of stiffness. Seven-week-old male Wistar rats randomly injected with 60 mg/kg MCT or vehicle were divided into three groups (n = 12 each) according to cardiac index (CI): controls (Ctrl), preserved CI (MCT pCI), and reduced CI (MCT rCI). All underwent RV pressure-volume (PV) evaluation 24-34 days after MCT, under halogenate anesthesia and constant positive-pressure ventilation. End-diastolic stiffness (β_i), end-systolic elastance (Ees_i), arterial elastance for indexed volumes (Ea_i), and preload recruitable stroke work (PRSW) were obtained and beat-to-beat fluctuations during ventilation assessed by STF. Ea_i was the strongest determinant of CI, alongside β_i but not PRSW. MCT rCI showed impaired ventricular-vascular coupling (VVC) and higher β_i, along with low end-diastolic pressure (EDP) and stroke volume index (SV_i) STF gain, denoting impaired preload reserve. On multivariate analysis β_i and not Ees_i correlated with EDP-SV_i STF gain (P < 0.001). Receiver-operating characteristics (ROC) curve analysis of EDP-SV_i STF gain showed an area under curve of 0.84 for β_i prediction (P = 0.002). Afterload, impaired VVC and RV stiffness are major players in RV failure. RV stiffness can be assessed by STF gain analysis of respiratory fluctuations between EDP and SV_i, which may constitute a prognostic tool in PH.