Qualitative Assessments Of Right Ventricular Function In Acute Pulmonary Embolism By Echocardiography:An Experimental Study

Objective: Right ventricular dysfunction(RVD)is a determining factor in the risk assessment and a well-known prognostic marker in acute pulmonary embolism(APE).The objective of present study was to assess right ventricular function using echocardiography,and determine impacts of pulmonary embolus size on right ventricular function.Materials and Methods: The study protocol was approved by Institutional animal care of Guangxi Medical University and conformed to Chinese guidelines on animal experiments in research.Thirty-three healthy New Zealand rabbits were randomly divided into massive thrombus group,sub-massive thrombus group and control group,11 rabbits per group.After anesthesia via ear marginal venous,a total of 2 mL of venous blood collected from another ear marginal venous was injected into a rubber tube(10cm long with a 1-mm or2-mm inner diameter).Then put it into a thermostatic water bath at 37℃ for 40 minutes.Long cylindrical clots were removed from the rubber tube and washedthree times with saline solution.Blood clots were then cut into six segments with 6-mm long by operating knife blade and drawn back into the tubes which were filled up with saline solution for later injection.APE model was created by injecting a 10 mL mixture of autologous blood clots and normal saline through jugular vein catheterization(n=4,massive thrombus group:2mm × 2mm × 6mm,sub-massive thrombus group: 1mm × 1mm × 6mm).Control animals received normal saline as an equivalent volume.RV function in all rabbits was evaluated using echocardiography at 1h,3h and 6h respectively after embolization.Echocardiographic indices of right ventricular transverse diameter(RVTD),right/left ventricular end-diastolic diameter ratio(RV/LV),right ventricular fractional area change(RVFAC),tricuspid annular plane systolic excursion(TAPSE),right ventricular index of myocardial performance(Tei index),Isovolumic acceleration(IVA)and Right ventricular outflow tract systolic excursion(RVOT_SE)were measured,and the data were analyzed statistically.The change trend of right ventricular parameters at different time points(1h,3h,6h)in the massive embolus group was compared with that of the sub-massive embolus group using repeated measures analysis of variance(RM-ANOVA).Receiver operating curve(ROC)analysis was utilized for evaluation of RV parameter in the detection of right ventricular(RV)systolic dysfunction.The Bland-Altman analysis was used to assess inter-observer and intra-observer variability,and data were presented using Bland–Altman plots.Differences were considered statistically significant at the two-sided P < 0.05 level.Specimens from lung tissue were gathered and stained with hematoxylin-eosin(HE).Pathological changes of lung tissue in APE were observed through an optical microscope.Results: Among the 22 rabbits,1 case died of anesthesia accident,and 3cases died of acute heart failure after injection of thrombus immediately.The APE model was successfully made in 18 rabbits,among them,10 cases of sub-massive thrombus group,and 8 cases of massive thrombus group.The success rate of a model establishment in sub-massive thrombus group was90.9%,and in massive thrombus group was 72.7%.Compared with control group,rabbits in APE had different extent of RV dilation and systolic dysfunction.The difference of RVTD,RV/LV,RVFAC,TAPSE,Tei index,IVA and RVOT_SE between massive thrombus group and the control group was statistically significant(P <0.01).Contrasted with the control group,the value of RVFAC and IVA in sub-massive thrombus group decreased significantly(P<0.05),there was no significant difference in RVTD,RV/LV,TAPSE and Tei index between control group and sub-massive thrombus group(P>0.05).The result of RVTD,RVFAC,RV/LV,Tei index,and IVA showed a significant difference between sub-massive thrombus group and massive thrombus group(P < 0.01).However,massive thrombus group suggested a slightly decreased TAPSE,showing no significant difference compared with massive thrombus group(P>0.05).ROC analysis showed that IVA had high sensitivity(94.4%)and specificity(81.8%)in the assessment of RV dysfunction in APE.There were significant differences in right ventricular function parameters(RV/LV,RVFAC,TAPSE,Tei index,IVA and RVOT_SE)between the massive emboli group and the sub-massive emboli group at each time point(P<0.01).Without considering the size of the embolus,the Tei index increased with time,and IVA and TAPSE decreased with time(P < 0.01);RV/LV,RVFAC and RVOT_SE had no significant difference with time(P > 0.05).The time factors of Tei index,IVA and TAPSE were correlated with the size of the embolus,indicating that the decreasing trend of IVA and TAPSE,and increasingtrend of Tei index in massive thrombus group was more significant than that in sub-massive thrombus group(P < 0.01).The results of Bland-Altman analysis showed that the reproducibility between inter-observer and intra-observer was good.Pathologic results showed that the pulmonary vessels were obstructed by masses of the massive or sub-massive thrombi.In the area of the pulmonary infarction and erythrocyte effusion were observed simultaneously in the pulmonary alveolus.Conclusion: Echocardiography plays a critical role in the evaluation of the right ventricular geometry and function in APE.IVA may be a useful parameter to detect subtle alterations in RV function and has superior predictive value compared to traditional main RV chamber markers in APE.RVOT_SE provides a simple measure and might be useful to estimate the global impairment in APE.Pulmonary embolus size is an important factor in affecting the right ventricular function in APE,and the decreasing trend in right ventricular function followed the size of thrombus.