Pulmonary Thromboembolism Proteomics And Interventional Therapy Research

Part Ⅰ Discovery and Validation of Circulatory Biomarkers of Acute Pulmonary ThromboembolismPurpose:Acute pulmonary thromboembolism(PTE)is a common fatal disease with high morbidity and mortality,and its clinical manifestations lack specificity,which can easily lead to misdiagnosis and missed diagnosis.Early diagnosis and risk stratification of acute PTE are helpful to select the optimal treatment according to different risk levels of patients,and current diagnostic and risk stratification strategies are still flawed Differential proteomics has broad application prospects in early diagnosis,exploring pathogenesis,monitoring disease progression and assessing treatment outcomes,and is important for the discovery of potential biological markers for the diagnosis and risk stratification of acute PTE.Methods:Blood samples were collected from patients with acute PTE in different risk strata and healthy volunteers.Sodium dodecyl sulphate-polyacrylamide gel electrophoresis combined with label-free quantitative liquid chromatography-tandem mass spectrometry was used to identify the protein expression profiles of each sample.The abundance and differences of protein expression in blood samples were analyzed and compared.Bioinformatics analyses such as GO,KEGG and PPI were performed.Finally,the value of candidate biomarkers in the diagnosis and risk stratification of acute PTE was verified by enzyme-linked immunosorbent assay.Results:A total of 5159 peptides and 559 proteins were identified by mass spectrometric analysis.Bioinformatic analysis suggested differential proteins between the groups mainly constituted cellular components such as hemoglobin complex,blood microparticles,specific granule lumen and fibrinogen complex,exerted molecular functions such as heme binding,iron ion binding,oxygen binding and oxygen carrier activity,and participated in biological processes such as immune response,acute phase response,platelet aggregation and protein polymerization.Based on the fold difference of proteins and bioinformatics analysis,a total of 30 up-regulated proteins that may be related to the diagnosis and risk stratification of acute PTE were screened.Enzyme-linked immunosorbent assay validation revealed that serum amyloid A1(SAA1),SAA2,and cystatin C were significantly higher in patients with acute PTE than in healthy controls,and serum SAA2 levels were significantly higher in patients with high-risk PTE than those with intermediate-risk PTEConclusion:Differential proteomics provided an important clue for the diagnosis and risk stratification of acute PTE.The levels of serum SAA1,SAA2 and cystatin C in patients with acute PTE were significantly higher than those in healthy controls,which might be conducive to the identification of patients with acute PTE,while SAA2 showed significant differences between patients with acute PTE in different risk strata,which might be used to guide the refined risk stratification of patients with acute PTE.Part Ⅱ Efficacy,Safety and Strategy of Interventional Therapy for Chronic Thromboembolic Pulmonary HypertensionPurpose:Chronic thromboembolic pulmonary hypertension(CTEPH)is a long-term complication of acute pulmonary thromboembolism,and balloon pulmonary angioplasty(BPA)is an emerging treatment option for inoperable CTEPH patients.Many foreign studies have reported the safety and efficacy of BPA in the treatment of CTEPH,but little attention has been paid to changes in cardiopulmonary function,while there is little BPA experience from China.This study aimed to assess the safety of BPA for CTEPH and its effects on hemodynamics and cardiopulmonary function in our center,and to preliminarily explore BPA interventional strategies that have received little attention in previous studies.Methods:Consecutive inoperable CTEPH patients treated with BPA from May 201 8 to June 2019 were enrolled.The number and location of target vessels,lesion type,balloon size and guiding wire type were recorded in detail.The changes of WHO functional class,N-terminal pro-brain natriuretic peptide,catheter-based hemodynamics,echocardiographic parameters,6-minute walk distance,cardiopulmonary exercise testing before and after BPA intervention during hospitalization were assessed.Results:A total of 101 BPA sessions were performed in 60 patients,and 558 pulmonary vessels were dilated cumulatively.The number of dilated vessels per session was significantly lower in the initial 40 than in the later 61 BPA sessions(4.6±1.9 vs 6.2±1.9,P<0.001),and BPA intervention was mainly used to treat right lower lobe lesions and web lesions,with the most commonly used balloon diameter of 2 mm(44.5%)and Pilot(58.9%)being the most commonly used guiding wire.No complications occurred in the initial period,and 8 cases of self-limiting hemoptysis and 2 cases of arteriovenous fistulas at the puncture site occurred in the later period.After single BPA session,WHO functional class(2.3±0.6 vs 1.9±0.4,P<0.001),N-terminal pro-brain natriuretic peptide(1057.2±1192.9 vs 542.6±644.3 pg/ml,P<0.001),6-minute walk distance(380.5± 104.0 vs 414.1 ±86.0 m,P<0.001),mean pulmonary artery pressure(49.7± 11.8 vs 44.7± 10.9 mmHg,P<0.001),right ventricular end-diastolic diameter(32.4±6.6 vs 31.1 ±6.3 mm,P=0.006),peak VO2(14.1±3.5 vs 15.0±3.5 ml/kg/min,P<0.001)and VE/VCO2 slope(47.3±12.5 vs 44.5±10.3,P=0.009)were significantly improved,and multiple BPA sessions were more effective.Conclusion:BPA can safely and effectively improve hemodynamics,exercise tolerance and cardiopulmonary function in patients with CTEPH,and relatively conservative treatment strategies are helpful to reduce the occurrence of complications.Multicenter studies are needed to further explore the safety,efficacy and optimal strategy of BPA interventional therapy in CTEPH.