Residual Pulmonary Vasodilative Reserve Predicts Outcome In Idiopathic Pulmonary Hypertension

Objective Idiopathic pulmonary arterial hypertension(IPAH)remains a devastating and incurable,albeit treatable condition.Treatment response is not uniform and parameters that help to anticipate a rather benign or a malignant course of the disease are warranted.Acute pulmonary vasoreactivity testing during right heart catheterization is recommended to identify a minority of patients with IPAH with sustained response to calcium channel blocker therapy.This study aimed to evaluate the prognostic significance of a residual pulmonary vasodilative reserve in patients with IPAH not meeting current vasoresponder criteria.Methods We obtained data on all participants from august 2008 to may 2017 in Shanghai pulmonary hospital.Observational right heart catheter study in 400(n=400)patients with IPAH not meeting current vasoresponse criteria.Pulmonary vasodilative reserve was assessed by inhalation of 5 mg iloprost-aerosol.Results The study included 400 patients.Their mean age was 37.4 years(37.400±17.40),137 were men,263 were women,with the BSA of 37.40±17.40 m2.Their 6-MWD is 378.04±107.81 m,and a mean NT-pro-BNP is 700.50 pg/ml(228.50,1832.25).The hemodynamic variable was tested by univariate Cox proportional hazards regression analysis.several hemodynamic parameters at baseline and during vasoreactivity testing predictive of mortality(p<0.05)during univariate analysis were observed,They were Baseline-mRAP?Baseline-PVR?Baseline-CO?Iloprost-mRAP?Iloprost-PVR?Ilfoprost-CO?Delta PVR?Delta CO.Then,these parameters were tested by multivariate Cox proportional hazards regression analysis,and we found that Baseline-mRAP?Iloprost-CO?Delta PVR were the only hemodynamic parameters to predict mortality independently(p<0.05).The next ROC curve analysis showed that Baseline-CO had good sensitivity,but poor specificity,Iloprost-mRAP had good specificity,but poor sensitivity,Delta PVR had good specificity and poor sensitivity.Subsequent survival analysis showed that Delta PVR had a good predictive value for survival with a cut-off value of 7.105 wood units(p<0.05).In the study of gender differences,no independent predictor of mortality was found in men,but in women,Delta PVR had independent prognostic value for mortality(p<0.05).With a cut-off value of 7.105 as the boundary,Delta PVR was a perfect survival prognostic value for women.In the analysis of BMPR2 mutation,no independent prognostic value was found in non-mutated patients,and Delta PVR had independent prognostic value for death in mutated patients(p<0.05).With a cut-off value of 11.12 as the boundary,Delta PVR was a perfect survival prognostic value.In the final study of gender differences in BMPR2 mutations,no prognostic markers were found in either male or female patients with BMPR2 mutations.Conclusion Representing residual pulmonary vascular reserve capacity,delta-PVR was an independent prognostic indicator of mortality.In patients with BMPR2 mutations,delta-PVR had independent prognostic value for mortality.In women,delta-PVR was still an independent prognostic indicator of mortality.In women with BMPR2 mutations,no independent prognostic value of delta-PVR for death was found,possibly due to small sample size.