Clinical Study On Oxygen Metabolism In Patients With Pulmonary Hypertension

Part I:Prevalence of iron deficiency in different subtypes of pulmonary hypertensionObjectives:Pulmonary hypertension is a fatal disease resulting from various causes.Studies from abroad have shown iron deficiency(ID)is closely associated with disease progression.It is common in pulmonary arterial hypertension(PAH)which belongs to group 1 pulmonary hypertension.However,ID prevalence in Chinese patients suffering from pulmonary hypertension is unclear so far.This study was carried out to delineate the prevalence of ID in different subtypes of pulmonary hypertension and to explore its relevant factors.Methods:Hospitalized patients diagnosed with pulmonary hypertension by right heart catheterization from September 2015 to March 2017 were retrospectively enrolled.Patients with pulmonary hypertension were divided into four study groups including idiopathic arterial pulmonary hypertension,congenital heart disease related pulmonary arterial hypertension,connective tissue disease related pulmonary arterial hypertension(CTD-PAH)and chronic thromboembolic pulmonary hypertension based on etiology.Parameters including laboratory tests,transthoracic echocardiography and right heart catheterization were collected and compared.ID was defined as transferrin saturation<20%in male and transferrin saturation<25%in female.Logistic regression analysis was performed to determine factors associated with ID.Results:A total of 251 patients who were diagnosed with pulmonary hypertension were enrolled,ID was found in 38.3%of all patients,the prevalence was highest in CTD-PAH(P=0.001 compared to other study groups).Univariate logistic regression analysis showed that female sex(OR=11.420,95%CI:4.712-27.682,P<0.001),age(OR=0.958,95%CI:0.937-0.980,P<0.001),CTD-PAH diagnosis(OR=3.657,95%CI:1.383-9.667,P=0.009),and high sensitive C reactive protein(OR=1.110,95%CI:1.018-1.211,P=0.019)were associated with ID.After adjusting for age,sex and high sensitive C reactive protein,the diagnosis of CTD-PAH was still associated with ID(OR=3.005,95%CI:1.015-8.896,P=0.047).Conclusions:ID is most prevalent in CTD-PAH among the four different subtypes of pulmonary hypertension in China.CTD-PAH is independently associated with ID,adjusted for age,sex and high sensitive C reactive protein.Part Ⅱ:Obstructive sleep apnea in patients with chronic thromboembolic pulmonary hypertensionObjectives:Due to its effects,like an exaggerated negative intrathoracic pressure,sympathetic activation,systemic inflammation,oxidative stress,and endothelial dysfunction,obstructive sleep apnea(OSA)has been involved as a cause in multiple cardiovascular diseases.These diseases include coronary artery disease,hypertension,heart failure,and pulmonary hypertension.Furthermore,OSA often coexists with chronic thromboembolic pulmonary hypertension(CTEPH)in clinical practice.However,few studies focus on OSA and its relationship with CTEPH.This study aims to determine whether OSA has an influence on the clinic status of patients with CTEPH,and to identify what possible factors are associated with OSA in CTEPH.Methods:Patients who were newly diagnosed with CTEPH and received overnight polysomnography monitoring from September 2015 to December 2017 were enrolled.OSA was defined as apnea hypopnea index of ≥ 5/h and the obstructive events at>50%.Baseline clinical characteristics and parameters were collected and compared between CTEPH patients with and without OSA.In addition,logistic regression analysis was performed to identify possible factors associated with OSA in CTEPH.Results:Fifty-seven patients with CTEPH were eventually enrolled.Among them,32 patients were diagnosed with OSA by polysomnography.CTEPH patients with OSA showed an older age,a higher body mass index(BMI),a higher hemoglobin level,a lower oxygen saturation and a worse World Health Organization(WHO)functional class(all P<0.05)when compared to CTEPH patients without OSA.In addition,sleep data including apnea hypopnea index,oxygen desaturation index and minimum oxygen saturation were also statistically different between two groups(all P<0.05).Adjusted for age,sex and BMI,hemoglobin,oxygen saturation,N-terminal pro-brain natriuretic peptide,right atrium pressure,mean pulmonary arterial pressure,cardiac index,total pulmonary resistance and WHO function class III-IV were associated with OSA in CTEPH.Multivariate logistic regression analysis demonstrated cardiac index was independently associated with OSA in CTEPH in addition to age,sex and BMI(OR=0.051,95%Cl:0.003-0.868,P=0.040).Conclusions:OSA may aggravate the clinical status of CTEPH patients to some degree.In turn,a worse hemodynamics,oxygenation state and cardiac function are associated with OSA in CTEPH after being adjusted for age,sex and BMI.CTEPH patients with OSA show a significant decrease in cardiac index.Part Ⅲ:Value of Cardiopulmonary Exercise Testing in The Diagnosis of Pulmonary HypertensionObjectives:To observe the characteristics of cardiopulmonary exercise testing(CPET)in patients with pulmonary hypertension(PH)and to explore the threshold of CPET variables in detecting PH.Whether CPET thresholds can correctly identify the subset of patients in which PH was missed and misdiagnosed by echocardiography were also investigated.Methods:Treatment-naive,suspected of PH patients who were admitted in Fuwai Hospital from January 2017 to August 2018 were consecutively enrolled.All patients underwent right heart catheterization and CPET at baseline,and time interval between the two examinations was no more than one week.PH was defined as the mean pulmonary artery pressure(mPAP)≥25mmHg which was measured by right heart catheterization at rest.All patients were divided into PH group and non-PH group according to it.General clinical materials,echocardiography,hemodynamics and CPET parameters of the patients were collected and compared between the two groups.Logistic regression was performed to explore which CPET parameters could independently predict PH.Linear regression was also used to observe the correlation between CPET parameters and mPAP.Then receiver operating characteristic curve(ROC)analysis was used to obtain the threshold of the CPET parameters for diagnosis of PH.The CPET thresholds were used to detect PH in suspected patients who are misdiagnosed and missed by echocardiography.In this way,the sensitivity and specificity of the CPET thresholds to diagnose PH was further verified.Results:1.559 treatment-naive,suspected PH patients were included in the study with a mean age of 43±15years and 67.8%of patients were female.Peak tricuspid regurgitation velocity was 4.2±0.8m·s-1,mPAP was 49±20mmHg,and total pulmonary resistance was 787.4(442.0-1127.3)dyn·s·cm-5.2.Patients with PH had significantly worse CPET parameters compared to patients without PH.Multivariate logistic regression analysis showed that peak work rate(OR=0.973,95%CI:0.961-0.986,P<0.001),peak oxygen uptake(OR=0.949,95%CI:0.910-0.990,P=0.015),and end-tidal carbon dioxide partial pressure at anaerobic threshold(OR=0.865,95%CI:0.820-0.913,P<0.001)independently predicted PH after adjustment for age,gender,and body mass index.Linear regression analysis showed that the above three CPET parameters were negatively correlated with mPAP(r=-0.271,-0.176,-0.468,all P<0.001).3.ROC analysis showed that the combined CPET parameters including peak work rate,peak oxygen uptake and end-tidal carbon dioxide partial pressure at anaerobic threshold had the largest area under the curve(0.890,95%CI:0.852-0.927,P<0.001)for diagnosis of PH.The diagnostic threshold was 0.86,and the sensitivity and specificity were 81.8%and 86.5%respectively.Using this diagnostic threshold,67.9%of patients with PH missed by echocardiography and 83.7%of patients with PH misdiagnosed by echocardiography could be identified.Conclusions:Patients with PH have decreased cardiopulmonary reserve,worse exercise tolerance,and increased ineffective ventilation.The combination of peak power,peak oxygen uptake,and end-tidal carbon dioxide increased the sensitivity and specificity for diagnosing PH,and for identifying patients who are misdiagnosed and missed by echocardiography.