The Association Of Functional Classification With Right Atrial Function In Connective Tissue Disease Patients With Pulmonary Arterial Hypertension:Study With Multimodality Echocardiography

Objective:The aim of this study was to analyze right atrial(RA)myocardial deformation and volumetric phasic function quantitatively using two-dimensional echocardiography(2DE)combined with speckle tracking imaging(STI)and three-dimensional echocardiography(3DE)in connective tissue disease(CTD)patients with pulmonary arterial hypertension(PAH),to explore the correlation between RA STI myocardial strain parameters and 3DE volume parameters,and to further define the relationship between RA function parameters and WHO functional class as well as the predictive value of those parameters on WHO functional class in CTD-PAH patients.Methods:98 CTD patients were selected in this study as case group.CTD patients were divided into 4 groups according to the presence or absence of combined PAH and WHO classification of PAH patients:?CTD patients not combined with PAH(CTD-NPAH group)(n=35),?CTD-PAH WHO-FC class?/?(n=27),?CTD-PAH WHO-FC class?(n=19),?CTD-PAH WHO-FC class?(n=17).We selected 30 healthy volunteers who were matched age and gender with CTD patients to serve as controls(n=30).General data,clinical data and biochemical data were collected.Transthoracic echocardiography was performed on all study subjects who met the inclusion criterion with Philips EPIC7C ultrasound diagnostic instrument for 2DE,STI and 3DE examinations.1.Following parameters were acquired by two-dimensional echocardiography:right ventricular basal dimension(RVBD),right ventricular wall thickness(RVWT),right ventricular fractional area change(RVFAC),tricuspid annular systolic excursion(TAPSE),tricuspid regurgitation velocity(TRV),right atrial area index(RAAI),inferior veno cana diameter(IVCD),pulmonary arterial systolic pressure(PASP),tricuspid annulus systolic velocity(Tricuspid S'),tricuspid annulus early-diastolic velocity(Tricuspid e'),tricuspid flow early and late diastolic velocity(Tricuspid E,Tricuspid A),calculated Tricuspid E/A and E/e',left ventricular end-diastolic dimension(LVEDD),left atrial end-systolic dimension(LAESD),left ventricular end-diastolic volume index(LVEDVI),left ventricular ejection fraction(LVEF).2.Following right ventricular function parameters were acquired by 2D-STI and 3DE:right ventricular free wall global longitudinal strain(RVFWS),right ventricular end-diastolic volume index(RVEDVI),right ventricular ejection fraction(RVEF).3.Following right atrial function parameters were acquired by 2D-STI:The zero-strain reference point was set at the QRS(end diastole)and the analysis of2D-STI generated an average longitudinal strain(LS)curve.(1)LStot,strain during reservoir phase,measured at end-systole describing overall RA myocardial lengthening during RA filling.(2)LSact,strain during contraction phase,measured at onset of atrial contraction(p wave).(3)LScdt,strain during conduit phase,measured as the difference of LStot minus LSact.Three different waves on the strain rate(SR)curve were analyzed:(4)the first wave was positive(SRs)reflecting reservoir function;(5)the second was negative(SRe)corresponding with the conduit phase of the atrial cycle;(6)the third wave was negative(SRa)representing the booster pump function.4.Following right atrial function parameters were acquired by 3DE:Following RA phasic volumes were determined:maximal volume(Vmax);pre-atrial contraction volume(Vpre);and minimal volume(Vmin).From RA volumes,we calculated total emptying volume(EVtot)as the difference between Vmax and Vmin;passive emptying volume(EVpas)as the difference between Vmax and Vpre;and active emptying volume(EVact)as the difference between Vpre and Vmin.Accordingly,total emptying fraction(EFtot)representing reservoir function,passive emptying fraction(EFpas)representing conduit function,and active emptying fraction(EFact)corresponding to booster pump function were calculated.All parameters were indexed to the body surface area to ensure a comparable evaluation.Results:1.Right ventricular function:(1)Right ventricular systolic function parameters:Compared with control group and CTD-NPAH group,RVFAC,S',RVEF,RVFWS and TAPSE were decreased,while RVBD,RVWT and RVEDVI were increased in CTD-PAH patients(P<0.05).RVBD,RVWT and RVEDVI showed gradual increase alone with increased WHO-FC,while RVFAC,RVEF,RVFWS showed gradual decrease alone with increased WHO-FC(P<0.05).(2)Right ventricular diastolic function parameters:Compared with control group and CTD-NPAH group,Tricuspid e'decreased in CTD-PAH patients,RAAI,IVCD and E/e'increased,E/A first raised and then dropped(P<0.05).RAAI was further increased in WHO-FC III and IV compared with other three groups(P<0.05).2.Right atrial function(1)Right atrial 2D-STI parameters:LStot,LScdt and SRe were decreased in CTD patients compared with control group,and there were differences among subgroups which showed gradual decrease alone with increased WHO-FC(P<0.05).Compared with control group and CTD-NPAH group,SRs decreased in CTD-PAH patients and gradually decreased with the development of cardiac insufficiency(P<0.05),LSact increased first and then decreased(P<0.05).(2)Right atrial 3DE parameters:There were no significant differences of all the 3DE parameters between control group and CTD-NPAH group(P>0.05).VImax,VIpre and VImin were significantly increased in CTD-PAH patients when compared with control group and CTD-NPAH group,and gradually increased with the development of cardiac insufficiency(all P<0.05).Compared with control group and CTD-NPAH group,EVItot and EVIact were increased in CTD-PAH patients,EFItot and EFIpas were decerased,EFIact increased first and then decreased(P<0.05).EFItot gradually decreased with the development of cardiac insufficiency(P<0.05).3.Correlations between LStot,RAVImax,EFItot and other parameters:Among CTD-PAH patients,LStot showed a negative correlation with PASP,IVCD,RAAI,RVBD,RVWT,RVEDVI,E/A and E/e',while a positive correlation with RVFAC,RVFWS,RVEF,TAPSE and Tricuspid e'.RAVImax was positively correlated with PASP,RVBD,RAAI,RVWT,RVEDVI,E/A and E/e'while negatively correlated with RVFAC,RVFWS,RVEF,TAPSE,Tricuspid e'.A positive correlation was found between EFItot and RVFAC,RVFWS,while a negative correlation was found between EFItot and PASP,RVBD,RAAI,RVWT,RVEDVI.LStot and EFItot showed positive correlations with BNP,VImax was positively correlated with BNP and uric acid.4.Correlations between RA 2D-STI and 3DE parameters:In CTD patients,LStot was negatively correlated with VImax and EVItot while positively correlated with EFItot;LScdt was negatively correlated with VIpre while positively correlated with EFIpas;LSact was negatively correlated with VImin while positively correlated with EFIact.5.Parameters of the ROC curve and Logistic regression analysis:In receiver-operator characteristic analysis,LStot had a sensitivity of 91.7%and a specificity of 81.5%(AUC0.913)for prediction of WHO-FC??with a cut-off value of29.05%in CTD-PAH patients;EFItot had a sensitivity of 80.6%and a specificity of 70.4%(AUC0.822)for prediction of WHO-FC??with a cut-off value of 28.16%;VImax had a sensitivity of 77.8%and a specificity of 96.3%(AUC0.927)for prediction of WHO-FC??with an increase of>41.28ml/m~2.Logistic regression analysis showed LStot was an independent predictor of WHO-FC?III in CTD-PAH patients.Conclusions:1.2D-STI showed RA dysfunction in CTD patients even without manifest PAH.2.CTD-PAH is associated with impaired RA reservoir and conduit function,and gradually decreased reservoir function with the deterioration of WHO-FC.However,RA active contraction function is enhanced in WHO-FC I/II while reduced in WHO-FC III and IV CTD-PAH patients.3.CTD-PAH patients exhibited diastolic and systolic dysfunction of right ventricle.Among CTD-PAH patients,RA volume and strain parameters(LStot,VImax and EFItot)were correlated with right ventricular functional and overload parameters.Furthermore,those parameters were also associated with BNP and uric acid.4.Both 2D-STI and 3DE can objectively estimate the change of RA function in CTD-PAH patients,and there is a good correlation between these two methods.RA function parameters(LStot,VImax and EFItot)confer optimal predictive effect on WHO-FC?III and risk stratification,thus were simple,effective and non-invasive parameters for evaluating right heart dysfunction and prognosis in CTD-PAH patients.5.RA LStot is a powerful independent predictor of clinical WHO-FC and may therefore be useful for predicting functional status,exercise capacity and disease progression in CTD-PAH patients.