Clinical Study Of Pulmonary Hypertension Due To Left Heart Disease

Part I:Relationship between hypoxia inducible factor-1?,hypoxia inducible factor-2a,heart-type fatty acid binding protein and pulmonary hypertension due to left heart diseaseObjective:The relationships between plasma levels of HIF-1?,HIF-2a,H-FABP and PASP were observed,to explore its significance in the formation of pulmonary hypertension due to left heart disease.Methods:66 patients with heart failure(HF)with reduced left ventricular ejection fraction(HF-RLVEF)were selected,including 36 patients with pulmonary hyper-tension due to left heart disease(PH-LHD group)(PASP>40mmHg),30 patients with left heart disease without PH(LHD group).The 30 patients in the control group came from the normal population of the physical examination center in the same period.According to different etiology,they were divided into PH-CHD group(PH caused by coronary heart disease)and PH-DCM group(PH caused by dilated cardiomyopathy).The patients in PH-LHD group were divided into 3 groups(group A,group B,groupC)according to the degree of LVEF and 3 groups(group ?,group ?,group ?)according to the degree of PASP.Medical history,physical and routine examinations were performed on selected patients.The patients in PH-LHD group and LHD group were examined by echocardiography before and after treatment.Plasma samples were collected from patients with PH-LHD(before and after treatment),LHD group(be-fore treatment)and normal control group(before treatment)for the detection of HIF-1?,HIF-2?,H-FABP and NT-proBNP.The differences of relative indexes between different groups and the differences of relative indexes before and after treatment were compared.The statistical software of SPSS22.0 was used to analyze whether there was statistical significance among the groups.The correlations between HIF-1?(HIF-2? or H-FABP)concentration and echocardiographic parameters,PASP and NT-proBNP were analyzed.Results:Before treatment,the LAD,LVEDd,RVEDd,PASP,NT-proBNP of PH-LHD group were significantly higher than those of LHD group(P<0.05),the LVEF,TAPSE,RVFAC of PH-LHD group were significantly lower than those of LHD group(P<0.05).Before treatment,the HIF-1a,HIF-2a,H-FABP in PH-LHD group were significantly higher than those in LHD group and control group(P<0.0 5),the HI F-1a,HIF-2a and H-FABP in LHD group were significantly higher than those in control group(P<0.05).Before treatment,the LVEDd,RVEDd,PASP,NT-proBNP in PH-DCM group were significantly higher than those in PH-CHD group(P<0.05),the age and RVFAC in PH-DCM group were significantly lower than those in PH-CHD group(P<0.05).The PH-LHD group was grouped according to the degree of LVEF.The TAPSE,RVFAC of group A(LVEF 30%-49%)were significantly higher than those of group B(LVEF20%-29%)(P<0.05),the LVEDd,RVEDd,PASP of group A were significantly lower than those of group B(P<0.05).The TAPSE,RVFAC of group B were significantly higher than those of group C(LVEF<20%)(P<0.05),the LAD,LVEDd,RVEDd,PASP,HIF-1?,HIF-2?,H-FABP and NT-proBNP of group B were significantly lower than those of group C(P<0.05).The TAPSE,RVFAC of group A were significantly higher than those of group C(P<0.05),the LAD,LVEDd,RVEDd,PASP,HIF-1?,HIF-2?,H-FABP and NT-proBNP of group A were significantly lower than those of group C(P<0.05).The PH-LHD group was grouped according to the different degree of PASP.The LVEF,TAPSE,RVFAC of group I(PASP41-50 mmHg)were significantly higher than those of group II(PASP 51-60 mmHg)(P<0.05),the RVEDd,HIF-la of group I were significantly lower than those in group ?(P<0.05).The LVEF,TAPSE,RVFAC of group II were significantly higher than those of group III(PASP>60mmHg)(P<0.05),the LAD,RVEDd,HIF-1?,HIF-2a,H-FABP and NT-pro BNP of group II were significantly lower than those of group ?(P<0.05).The LVEF,TAPSE,RVFAC of group I were significantly higher than those of groupIII(P<0.05),the LAD,LVEDd,RVEDd,HIF-la,HIF-2a,H-FABP and NT-proBNP of group I were significantly lower than those of group ?(P<0.05).After treatment,the LVEF,TAPSE,RVFAC in group PH-LHD were higher than those before treatment,the LAD,LVEDd,RVEDd,PASP,HIF-1?,HIF-2?,H-FABP and NT-proBNP were lower than those before treatment(P<0.05).HIF-lahad moderate positive correlation with LAD,LVEDd,NT-proBNP,strong positive correlation with RVEDd,PASP,H-FABP,a extremely positive correlation with HIF-2a and strong negative correlation with LVEF,TAPSE,RVFAC(P<0.01).HIF-2? had moderate positive correlation with LAD,LVEDd,NT-proBNP,strong positive correlation with RVEDd,PASP,H-FABP and strong negative correlation with LVEF,TAPSE,RVFAC(P<0.01).H-FABP had moderate positive correlation with LAD,LVEDd,NT-proBNP,strong positive correlation with RVEDd,PASP,a moderate negative correlation with LVEF,and strong negative correlation with TAPSE,RVFAC(P<0.01).Conclusion:HIF-la,HIF-2? and H-FABP were significantly increased in patients with PH-LHD,and gradually increased with the decrease of LVEF and the increase of PASP.HIF-1?,HIF-2? and H-FABP can be used to evaluate the severity of pulmonary vascular lesions and HF in PH-LHD patients.Part ?:Clinical evaluation of combined cardiopulmonary ultrasound in patients with pulmonary hypertension due to left heart diseaseObjective:Patients with pulmonary hypertension due to left heart disease(PH-LHD)were evaluated by combined cardiopulmonary ultrasound.The purpose of this study was to study the correlations between B line grade score and pulmonary artery systolic pressure(PASP),echocardiographic parameters,to study the correlations between ventricular morphologic parameters measured by echocardiography(LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs)and PASP,B line grade score,and to study the diagnostic value of ventricular morphologic parameters in PH-LHD and right heart failure(RHF).Methods:From April 2018 to August 2018,88 patients with heart failure(HF)with reduced left ventricular ejection fraction(HF-RLVEF)were selected.The patients were divided into PH-LHD group and LHD without PH group(LHD group).The patients were divided into coronary heart disease(CHD)associated with PH group(PH-CHD group)and non-PH-CHD group according to etiology.All patients underwent echocardiographic and pulmonary ultrasound to compare the differences of the clinical characteristics and cardiopulmonary ultrasound indexes of PH-LHD group and LHD group,to compare the differences of above indexes in different etiology groups,to compare the differences of above indexes before and after treatment in PH-LHD group.Patients with PH-LHD were divided into groups according to diffe-rent degrees of LVEF,PASP,and the differences of the above indexes were compared.The correlations between PASP and echocardiographic parameters,B line grade score were analyzed.The correlations between B line grade score and PASP,echocardio-graphic parameters were analyzed.The chest was divided into 12 examination areas,and the B line grade score of each examination areas,the left chest,the right chest and the whole chest between PH-LHD group and LHD group were compared.The B line grade score of above examination areas were compared in PH-LHD group before and after treatment.The sensitivity and specificity of LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs in the diagnosis of PH-LHD and RHF were evaluated.SPSS22.0 software was used to analyze whether there were statistical differences between groups.Results:The LAD,LVEDd,RVEDd,PASP,LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs of PH-LHD group were statistically higher than those of LHD group,the LVEF,TAPSE,RVFAC were statistically lower than those of LHD group(P<0.01).The B line grade scores in 12 chest examination areas,left chest,right chest and whole chest in group PH-LHD were statistically higher than those in LHD group(P<0.01).After treatment,the LAD,LVEDd,RVEDd,PASP,LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs in PH-LHD group were statistically lower than those before treatment,the LVEF,TAPSE,RVFAC were statistically higher than those before treatment,the B line grade scores in 12 examination areas,left chest,right chest and whole chest were significantly lower than those before treatment(P<0.01).PH-LHD group was divided into four groups according to different degree of LVEF.The RVEDd,PASP,LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs of group A(LVEF40%-49%)were significantly lower than those of group B(LVEF30%-39%)(P<0.05),and the TAPSE,RVFAC of group A were significantly higher than those of group B(P<0.05).The RVEDd,LVEId,B line grade score of group B were signifi-cantly lower than those of group C(LVEF20%-29%)(P<0.05),the TAPSE,RVFAC of group B were significantly higher than those of group C(P<0.05).The LAD,LVEDd,RVEDd,PASP,RVTDd/LVTDd,RVTDs/LVTDs,B line grade score in group C were significantly lower than those in group D(LVEF<20%)(P<0.05),the TAPSE,RVFAC of group C were significantly higher than those of group D(P<0.05).The PH-LHD group was divided into three groups according to the different degree of PASP.The RVEDd,LVEId,RVAD s/LVAD s,RVTDd/LVTDd,RVTDs/LVTDs,B line grade score of group I(PASP41-50mmHg)in group PH-LHD were significantly lower than those in group II(PASP 51-60mmHg)(P<0.05),the LVEF,TAPSE,RVFAC in group I were significantly higher than those in group ?(P<0.05).The LAD,RVEDd,RVTDs/LVTDs,B line grade score of group ? were significantly lower than those of group III(PASP>60mmHg)(P<0.05),the TAPSE of group II was significantly higher than that of group ?(P<0.05).The LAD,LVEDd,RVEDd,LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs,B line grade score of group I were significantly lower than those of group ?(P<0.05),the LVEF,TAPSE,RVFAC of group I were significantly higher than those of group ?(P<0.05).PASP had extremely strong positive correlation with RVEDd(P<0.0 1),strong positive corre-lation with LAD,LVEDd,LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs and B line grade score(P<0.01),extremely strong negative correlation with LVEF,TA PSE,R VFAC(P<0.01).B line grade score had strong positive correlation with RVEDd,PASP(P<0.01),moderate positive correlation with LAD,LVEDd,LVEld,RVTDd/LVTDd and RVTDs/LVTDs(P<0.01),strong negative correlation with LVEF,TAPSE,RVFAC(P<0.01).LVEId,RVADs/LVADs,RVTDd/LVTDd,RVTDs/LVTDs had high sensitivity and specificity in diagnosing PH-LHD and RHF.Conclusion:Combined cardiopulmonary ultrasound can be used to evaluate pulmonary vascular lesions,shape of ventricular remodeling,degree of pulmonary edema in ptients with PH-LHD.Dynamic cardiopulmonary ultrasound can be used to guide the clinical treatment of PH-LHD and evaluate the therapeutic effect.There are significant correlations between PASP or B line grade score and ventricular morphologic parameters measured by echocardiography.Ventricular morphologic parameters have high sensitivity and specificity in the diagnosis of PH-LHD and RHF.Part?:Clinical characteristics of dilated cardiomyopathy with pulmonary hypertensionObjective:To evaluate the clinical characteristics of patients with dilated cardiomyo-pathy(DCM)with pulmonary hypertension(PH),to explore the risk factors of patients with PH-DCM.Methods:Two hundred and fifty DCM patients were retrospectively analyzed.The characteristics of basic clinical data,ultrasound index,biochemical index,RDW,PDW,MPV and P-LCR were analyzed.The correlations between above indexes and PASP or LVEF were investigated.The risk factors of PH-DCM were analyzed by logistic regression analysis.Results:The length of history and the proportion of patients with right heart failure(RHF)in PH-DCM group were significantly higher than those in DCM group(P<0.01).The LAD,LVEDd,RATD,RVEDd,P ASP,NT-proBNP,TBIL,UA,Cr,CYC5 RDW-SD,RDW-CV,MPV,PDW,P-LCR in group PH-DCM were significantly higher than those in group DCM,the LVEF and PA were significantly higher than those in group DCM,(P<0.01).In group PH-DCM,there was a strong positive correlation between PASP and LAD,LVEDd,RVEDd,NT-proBNP,UA,Cr,CYC(P<0.01),a moderate posi-tive correlation between PASP and the length of history,RATD,TBIL,RDW-SD,RDW-CV,PDW,P-LCR,and a strong negative correlation between PASP and LVEF,PA(P<0.01).In the 250 patients,there was a moderate positive correlation between LVEF and PA(P<0.01),a strong negative correlation between LVEF and PASP,NT-proBNP(P<0.01),and a moderate negative correlation between LVEF and length of history,L AD,LVEDd,RATD,RVED d,T BIL,UA,Cr,CYC,RDW-CV and P-LCR(P<0.01).The patients in group PH-DCM were divided into 3 groups according to the degree of PASP,the Length of history,LAD,LVEDd,RATD,RVEDd,NT-pro BNP,TBIL,UA,Cr,CYC,RDW-SD,RDW-CV,MPV,PDW and P-LCR increased gradually,the L VEF,PA decreased gradually with the increase of PASP,the differences of some indexes were statistically significant(P<0.01).250 patients with DCM were divided into 4 groups according to the degree of LVEF decline,the Length of history,LAD,LVEDd,RATD,RVEDd,PASP,NT-proBNP,TBIL,Cr,CYC,RDW-SD,RDW-CV,MPV,PDW,P-LCR increased and the PA decreased gradually with the decrease of LVEF,the differences of some indexes were statistically significant(P<0.01).The clinical data,echocardiographic parameters and test indexes of the patients were included in multivariate Logistic regression analysis,the Length of history,symptoms and signs of RHF,LAD,RVEDd,LVEF,NT-proBNP,TBIL,PA,UA,CYC,RDW-SD,RDW-CV,PDW of DCM were correlated with PH.Conclusion:The length of history,the symptoms and signs of right heart failure,LAD,RVEDd,LVEF,NT-proBNP,TBIL,PA,UA,CYC,RDW-SD,RDW-CV and PDW can be used as predictors of secondary PH in DCM patients.Part?:Study on the clinical efficacy of specific phosphodiesterase inhibitor in patients with pulmonary hypertension due to left heart diseaseObjective:To evaluate the efficacy and safety of milrinone(a kind of specific phos-phodiesterase inhibitor)in the treatment of PH-LHD patients.Methods:From May 2016 to May 2017,60 patients with pulmonary hypertension due to left heart disease(PH-LHD)in our hospital were collected.They were ran-domly divided into treatment group A,treatment group B and control group C.There were 20 patients in each group.All three groups of patients were given routine treat-ment(Digitalis,Angiotensin converting enzyme inhibitors or angiotensin ? receptor antago nists,beta-blockers,Diuretics,etc.).The treatment group was treated with milrinone injection(5ug/kg/min was initially given intravenously for 10 minutes,then group A and group B were given 0.25 ug/kg/min,0.5ug/kg/min intravenous pump respectively).Cardiac ultrasound(LAD,LVEDd,LVEF,PASP,RVFAC,TAPSE et al.)and NT-proBNP,hsCRP were performed before and 5 days after treatment.The diffe-rences of the above indexes before and after treatment were compared among the three groups.The difference between the milrinone treatment group and the routine treatment group after treatment was compared.The difference between the different doses of milrinone after treatment was compared.The effects of milrinone at different doses on PH-LHD patients with different severity were compared.Adverse reactions were observed and recorded during treatment.Results:In group A and group B,the LVEF,TAPSE and RVFAC following treatment were statistically higher than those prior to treatment(P<0.05).The LAD,LVEDd,PASP,NT-proBNP and hsCRP following treatment were statistically lowerthan those prior to treatment(P<0.05).Following treatment,the TAPSE and RVFAC of group B were statistically higher than those of group A(P<0.05),the PASP of group B was statistically lower than that of group A(P<0.05).Following treatment,the TAPSE and RVFAC of group A were statistically higher than those of group C(P<0.05),the PASP,NT-proBNP and hsCRP of group A were statistically lower than those of group C(P<0.05).Following treatment,the LV EF,TAPSE and RVFAC of group B were statistically higher than those of group C(P<0.05),the LAD,LVEDd,PASP,NT-pro BNP and hsCRP of group B were statistically lower than those of group C(P<0.05).In group A and group B,the LVEF,TAPSE and RVFAC in patients with mild and moderate PH-LHD following treatment were statistically higher than those prior to treatment(P<0.01),the LAD,LVEDd,PASP,NT-proBNP and hsCRP were statis-tically lower than those prior to treatment(P<0.01).PASP was positively correlated with LAD,LVEDd,NT-proBNP and hsCRP(P<0.01),and negatively correlated with LV EF,TAPSE and RVFAC(P<0.01).The maintenance dose of milrinone did not cause any significant adverse reactions during the course of treatment.Conclusion:Milrinone could significantly reduce PASP,improve cardiac structure and function,and decrease NT-proBNP,hsCRP in patients with PH-LHD.