Noninvasive Evaluation Of Pulmonary Hemodynamics And Interventional Therapy For Chronic Thromboembolic Pulmonary Hypertension

PART 1:Noninvasive evaluation of Pulmonary hemodynamics for Chronic thromboembolic pulmonary hypertensionObjective To study the changes of pulmonary hemodynamics and find biomarkers and imaging examination parameters to evaluate the pulmonary hemodynamics for CTEPH patients.Method Patients who were diagnosed CTEPH in the respiratory center of China-Japan Friendship Hospital from September 2016 to February 2020 were retrospectively studied.The basic information of patients,the history of acute venous thromboembolism,anticoagulant and pulmonary hypertension targeted drugs,complications(Thrombophilia,DVT),WHO function classification(WHO-FC),6MWD,blood biomarkers(NT-proBNP,TBIL and DBIL),transthoracic echocardiographic parameters(RA diameter,RV basal diameter,RV/LV ratio,RV free wall thickness,PASP,TRV,TAPSE and pericardial effusion),parameters measured by CTPA axial image(RA diameter,spinal ventricular septal angle),parameters measured by CMR(RVEDVI,RVESVI,RVEF,RVEDRI and RVESRI),blood flow parameters measured by 4D Flow MRI(PDF,PDE,PRI and PRV)and hemodynamic parameters measured by right heart catheterization(RAP,RVP,PAP,CO and PVR)were collected.The Correlation between the biomarkers,imaging examination parameters and the hemodynamic parameters measured by right heart catheterization were analyzed.Result1.Baseline data A total of 166 CTEPH patients,including 87 males(52.4%)and 79 females(47.6%),with a median age of 58.0(50.0,65.0)years old,the BMI was(24.1±3.7)kg/m2,41 cases(24.7%)had history of acute VTE,the median interval between acute VTE and CTEPH diagnosis was 36.0(12.0,60.0)months,the median interval between symptoms and CTEPH diagnosis was 12.0(3.0,32.5)months,48 cases(28.9%)were complicated with DVT and 11 cases(6.6%)were complicated with Thrombophilia,47 cases(28.3%)were treated by PEA,49 cases(29.5%)were treated by BPA for 111 BPA sessions.119 cases(71.7%)took warfarin and 44 cases(26.5%)took rivaroxaban,WHO-FC ? and ? were 48.2%and 13.9%respectively.77 cases(46.4%)took at least one kind of PH-targeted drugs,including 70 cases who took single PH-targeted drugs and 7 cases who took two kinds of PH-targeted drugs.2.Biomarkers evaluation 6MWD(r=-0.515,P<0.001)was significant negative correlation with PVR,the plasma concentration of NT-proBNP(r=0.587,P<0.001),TBIL(r=0.391,P<0.001)and DBIL(r=0.388,P<0.001)were significant positive correlation with PVR.Compared with TBIL normal group(TBIL?21 ?mol/L),6MWD[358(200,420)vs 414(359,468)m,P<0.05],SvO2[61.1%(54.0%,69.0%)vs 64.0%(60.0%,69.0%),P<0.05]and CI[1.6(1.3,2.0)vs 1.8(1.5,2.2)L·min-1·m-2,P<0.05]were decreased in the high group(TBIL>21.0?mol/L).the plasma concentration of NT-proBNP[1743(875,3164)vs 516(154,1240)ng/L,P<0.05],RV/LV basal diameter ratio[1.6(1.3,1.8)vs 1.2(1.1,1.4),P<0.05]and PVR[(14.9±5.8)vs(11.1 ±4.4)WU,P<0.05]were increased in the high group.3.Imaging evaluation In parameters measured by transthoracic echocardiography,RV/LV basal diameter ratio has the best correlation with PVR(r=0.476,P<0.001)and CI(r=-0.314,P<0.001).PASP measured by transthoracic echocardiography(r=0.660,P<0.001)was significant correlation with PASP measured by RHC.Compared with no pericardial effusion group,6MWD[365(200,414)vs 394(335,450)m,P<0.05]and SvO2[61.0%(56.0%,68.0%)vs 64.0%(60.0%,70.0%),P<0.05]were decreased in pericardial effusion group.the plasma concentration of NT-proBNP[2134(1147,3753)vs 666(161,1363)ng/L,P<0.05]and PVR[(14.6±5.5)vs(12.0±5.1)WU,P<0.05]were increased in pericardial effusion group.The spinal ventricular septal angle measured by CTPA axial image was significant correlation with Cl(r=-0.422,P<0.001),mPAP(r=0.580,P<0.001),PVR(r=0.697,P<0.001)and RVEF measured by CMR(r=-0.737,P<0.001).ROC curve analysis shows when the spinal ventricular septal angle?62.73 degree,the sensitivity and specificity of predicting PVR?1000dyn·s·cm-5 was 70.4%and 81.5%respectively,and when the spinal ventricular septal angle?55.5 degree,the sensitivity and specificity of predicting RVEF<40%was 94.4%and 71.4%respectively.In parameters measured by CMR,right ventricular end diastolic volume index(RVEDVI)(r=-0.531,P<0.001),right ventricular end systolic volume index(RVESVI)(r=-0.503,P<0.001),right ventricular ejection fraction(RVEF)(r=0.534,P<0.001),right ventricular end diastolic remodeling index(RVEDRI)(r=-0.492,P<0.001)and right ventricular end systolic remodeling index(RVESRI)(r=-0.398,P<0.001)were significantly correlation with CI.RVEDVI(r=0.520,P<0.001),RVESVI(r=0.484,P<0.001),RVEF(r=-0.555,P<0.001),RVEDRI(r=0.400,P<0.001)and RVESRI(r=0.506,P<0.001)were significantly correlated with PVR.In parameters measured by 4D flow MRI for right ventricle,the percentage of direct flow(PDF)(r=-0.493,P<0.001),the percentage of delayed ejection flow(PDE)(r=-0.551,P<0.001),the percentage of retained inflow(PRI)(r=-0.642,P<0.001)and the percentage of residual volume(PRV)(r=0.651,P<0.001)were significantly correlated with mPAP.PDF(r=-0.605,P<0.001),PDE(r=-0.568,P<0.001),PRI(r=-0.641,P<0.001)and PRV(r=0.702,P<0.001)were significantly correlated with PVR.PDF(r=0.592,P<0.001)and PRV(r=-0.498,P<0.001)were significantly correlated with cardiac index.ROC curve analysis shows when the percentage of residual volume(PRV)?67.15%,the sensitivity and specificity of predicting PVR?1000dyn·s·cm-5 was 85.7%and 89.5%respectively,when the percentage of direct flow(PDF)?3.5%,the sensitivity and specificity of predicting CI?2.0L·min-1·m-2 was 86.9%and 70.4%respectively.Conclusion The percentage of residual volume(PRV)measured by 4D flow MRI has a better correlation with PVR,which can be used to evaluate pulmonary hemodynamics for CTEPH patients.the percentage of direct flow(PDF)measured by 4D flow MRI has a better correlation with CI,which can be used to evaluate right heart function for CTEPH patients.PART 2:Efficacy and safety of Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertensionObjective To evaluate the efficacy and safety of hemodynamics guided Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension(CTEPH).Methods Patients who were diagnosed CTEPH in the Center of Respiratory Medicine for China-Japan Friendship Hospital from Feb 2018 to Feb 2020 were evaluated.The indications of BPA include:inaccessibility of the occlusions because the thrombus located in distal pulmonary artery,the age was older than 75 years old,residual pulmonary hypertension after PEA.The ineligibility for PEA and the indication for BPA were decided on the basis of a consensus among the multidisciplinary team for all CTEPH patients.The balloon size was chosen according to mPAP:the balloon diameter was 1.5-2mm when mPAP>50 mmHg,2-3mm when mPAP was 40-50 mmHg,and 3-4 mm when mPAP was 30-40 mmHg,the balloon diameter=the target pulmonary artery diameter(mm)×0.9 when mPAP<30 mmHg.General information,WHO function classification,6-min walk distance(6MWD),the plasma concentration of N-terminal pro-brain natriuretic peptide(NT-proBNP)and creatinine,oxygenation index,Echocardiography parameters,Hemodynamic parameters measured by right heart catheterization were collected and analyzed before the first and the last BPA session.Results A total of 49 inoperable CTEPH patients were treated by BPA,including 45 inoperable CTEPH patients and 4 residual pulmonary hypertension after PEA,16 patients(32.7%)were males and 33 patients(67.3%)were females,with an average age of(59.1 ±8.1)years old.BMI was(23.7±3.6)kg/m2,the median interval between CTEPH diagnosis and the first BPA was 14.0(6.0,48.5)months,WHO function classification ?,?,? and ? were 2 cases(4.1%),20 cases(40.8%),25 cases(51.0%)and 2 cases(4.1%)respectively.6-minute walking distance(6MWD)was 376(324,428)m,the plasma concentration of NT-proBNP was 652(149,1521)ng/L,the oxygenation index(OI)was(267.2±52.4),RV/LV basal diameter ratio measured by Echocardiography was 1.3(1.1,1.4),the mixed venous oxygen saturation(SvO2)was(62.3%±7.4%),mean pulmonary artery pressure(mPAP)was(41.7±11.5)mmHg,Pulmonary vascular resistance(PVR)was 12.4(9.5,16.4)WU and Cardiac index(CI)was 1.64(1.45,1.82)L·min-1·m-2.111 BPA sessions were performed for 682 subsegmental pulmonary arteries,27 patients underwent more than 2 BPA sessions,the median follow-up time was 5.0(2.0,8.0)months.6MWD[375(329,430)vs 450(405,502)m,P<0.05],Oxygenation index[(261.3±52.8)vs(316.4±67.0),P<0.05],SvO2[(62.2%±5.9%)vs(67.0%±5.6%),P<0.05]and CI[1.63(1.40,1.78)vs 1.83(1.55,2.01)L·min-1·m-2,P<0.05]were significant improved after BPA.The plasma concentration of NT-proBNP[504(144,1743)vs 113(53,381)ng/L,P<0.05],RV/LV basal diameter ratio measured by echocardiography[1.2(1.1,1.6)vs 1.1(1.0,1.3),P<0.05],mPAP[(44.4±10.2)vs(34.1±7.3)mmHg,P<0.05]and PVR[13.5(11.1,17.9)vs 8.0(6.6,10.7)WU,P<0.05]were significantly decreased after BPA.Complications:Hemoptysis occurred in 7 sessions(6.3%)and reperfusion pulmonary edema(RPE)occurred in 3 sessions(2.7%),2 patient needed non-invasive mechanical ventilation because of RPE,1 patient died from right heart failure caused by hemoptysis during perioperative period.Conclusion Hemodynamics guided BPA can significantly decrease the mPAP and PVR,improve oxygenation index,cardiac index and exercise tolerance for inoperable CTEPH patients.Hemodynamics guided BPA was an effective and relatively safe treatment for CTEPH patients.