Clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism: a multicenter study report.

BACKGROUND: Clinical characteristics of patients with pulmonary thromboembolism have been described in previous studies. Although very old patients with pulmonary thromboembolism are a special group based on comorbidities and age, they do not receive special attention. OBJECTIVE: This study aims to explore the clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism in a relatively large population. DESIGN AND PARTICIPANTS: The study included a total of 7438 patients from a national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES). Consecutive patients with acute pulmonary thromboembolism were enrolled and were divided into three groups. Comparisons were performed between these three groups in terms of clinical characteristics, comorbidities and in-hospital prognosis. Mortality predictors were analyzed in very old patients with pulmonary embolism. KEY RESULTS: In 7,438 patients with acute pulmonary thromboembolism, 609 patients aged equal to or greater than 80 years (male 354 (58.1%)). There were 2743 patients aged between 65 and 79 years (male 1313 (48%)) and 4095 patients aged younger than 65 years (male 2272 (55.5%)). Patients with advanced age had significantly more comorbidities and worse condition, however, some predisposing factors were more obvious in younger patients with pulmonary thromboembolism. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2, malignancy, anticoagulation as first therapy were mortality predictors for all-cause death in very old patients with pulmonary thromboembolism. The analysis found that younger patients were more likely to have chest pain, hemoptysis (the difference was statistically significant) and dyspnea triad. CONCLUSION: In very old population diagnosed with pulmonary thromboembolism, worse laboratory results, atypical symptoms and physical signs were common. Mortality was very high and comorbid conditions were their features compared to younger patients. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2 and malignancy were positive mortality predictors for all-cause death in very old patients with pulmonary thromboembolism while anticoagulation as first therapy was negative mortality predictors.

Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.

BACKGROUND: A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. METHODS: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. RESULTS: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10-14), ABO rs582094 (p-value = 1.16 × 10-10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10-17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. CONCLUSIONS: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

Validation of the IMPROVE bleeding risk assessment model in surgical patients: Results from the DissolVE-2 Study.

INTRODUCTION: IMPROVE Bleeding Risk Score (BRS) is known to be validated and widely accepted in medical patients. However, its relevance in surgical patients has so far not been explored. External validation of the IMPROVE BRS on bleeding in surgical patients can hopefully improve clinical practice (for surgical patients). METHODS: Data from 6986 surgical patients were collected from the DissolVE-2 cohort. The Kaplan-Meier method was used to assess the incidences of major bleeding and any bleeding among surgical patients within 14 days of admission. A cut-off value of BRS ≥7 indicated a higher risk of bleeding. Risk factors associated with major and any bleeding were analysed by the Cox regression method. Model discrimination was evaluated by area under the receiver operator characteristic curves (AUC). Calibration curves and Hosmer-Lemeshow χ2 statistics were used to measure the difference between predicted and observed bleeding risks. RESULTS: A total of 6399 surgical patients were included in the final validation cohort. The cumulative incidence rate of any bleeding was 3.9 % (95 % confidence interval [CI], 3.4-4.5), of which the incidence rate of major bleeding was 1.2 % (95 % CI, 0.9-1.6). Among patients with a BRS of ≥7, 16.3 % reported any bleeding, and 26.3 % reported major bleeding. The IMPROVE BRS had a better discriminative power (AUC = 0.69) and excellent goodness of fit (Hosmer-Lemeshow test, P = 0.208) for the prediction of major bleeding events as compared with any bleeding (AUC = 0.55; Hosmer-Lemeshow test, P = 0.004). The calibration plot suggested a more accurate prediction for major bleeding events. Moreover, the IMPROVE BRS had a higher AUC value of 0.83 and better goodness of fit (P = 0.2616) for major bleeding in patients undergoing abdominal surgery than other surgery types. CONCLUSION: The IMPROVE BRS is a simple and practical technique that can help in predicting the risk of major bleeding in surgical patients, improving functional and safety outcomes of hospitalized patients with surgery.

Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) patients may present with atherosclerotic lesions in their pulmonary arteries, but their clinical characteristics remain unclear. The metabolic pathways associated with the atherosclerotic lesions may explain their occurrence and have implications for interventions, but they have not been investigated. Methods: We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following a detailed pathological examination of the PEA specimen, the patients were divided into those with and without lesions, and age- and sex matching were performed subsequently using propensity score matching (n = 25 each). Metabolomic profiling was used to investigate the metabolites of the proximal lesions in the PEA specimens. Results: In our study population, 27.2% of all PEA specimens were found to contain atherosclerotic lesions. CTEPH patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism and had a longer timespan between embolism and surgery, whereas the classic risk factors of systemic and coronary circulation could not distinguish CTEPH patients with or without atherosclerotic lesions. Metabolomic profiling revealed that the formation of atherosclerotic lesions in CTEPH was closely related to altered glycine, serine, and threonine metabolic axes, possibly involved in cellular senescence, energy metabolism, and a proinflammatory microenvironment. Conclusion: The occurrence of atherosclerotic lesions in the pulmonary arteries of CTEPH was associated with symptomatic thromboembolic history and prolonged disease duration. The results revealed a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH for the first time. This study has characterized the clinical and metabolic profiles of this distinct group of CTEPH patients, providing new insights into disease pathogenesis and potential interventions.

Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study.

Background: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. Methods: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. Results: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). Conclusions: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence.

Right Ventricle Remodeling in Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed, but potentially curable pulmonary vascular disease. The increased pulmonary vascular resistance in CTEPH is caused by unresolved proximal thrombus and secondary microvasculopathy in the pulmonary vasculature, leading to adaptive and maladaptive remodeling of the right ventricle (RV), eventual right heart failure, and death. Knowledge on the RV remodeling process in CTEPH is limited. The progression to RV failure in CTEPH is a markedly slower process. A detailed understanding of the pathophysiology and underlying mechanisms of RV remodeling may facilitate early diagnosis and the development of targeted therapy. While ultrasound, magnetic resonance imaging, right heart catheterization, and serum biomarkers have been used to assess cardiac function, the current treatment strategies reduce the afterload of the right heart, but are less effective in improving the maladaptive remodeling of the right heart. This review systematically summarizes the current knowledge on adaptive and maladaptive remodeling of the right heart in CTEPH from molecular mechanisms to clinical practice.

LMWHs dosage and outcomes in acute pulmonary embolism with renal insufficiency, an analysis from a large real-world study.

BACKGROUND: Renal function is associated with prognoses for acute pulmonary embolism (PE). OBJECTIVE: To investigate the application of anticoagulants and dosage of LMWH among patients with renal insufficiency (RI), and the association between LWMH dosage and the patients' in-hospital outcomes. METHODS: Adult patients diagnosed with non-high risk acute PE from 2009 to 2015, with available data of creatinine clearance (CCr) were enrolled from a multicenter registry in China. Renal insufficiency (RI) was defined as CCr < 60 ml/min. LMWH dosage was converted into IU/kg daily dose and presented as adjusted dose (≤ 100 IU/kg/day) and conventional dose (> 100 IU/kg/day). All-cause death, PE-related death and bleeding events during hospitalization were analyzed as endpoints. RESULTS: Among the enrolled 5870 patients, RI occurred in 1311 (22.3%). 30 ≤ CCr < 60 ml/min was associated with higher rate of bleeding events and CCr < 30 ml/min was associated with all-cause death, PE-related death and major bleeding. Adjusted-dose LMWH was applied in 26.1% of patients with 30 ≤ CCr < 60 ml/min and in 26.2% of CCr < 30 ml/min patients. Among patients with RI, in-hospital bleeding occurred more frequently in those who were administered conventional dose of LMWH, compared with adjusted dose (9.2% vs 5.0%, p = 0.047). Adjusted dose of LMWH presented as protective factor for in-hospital bleeding (OR 0.62, 95%CI 0.27-1.00, p = 0.0496) and the risk of bleeding increased as length of hospital stay prolonged (OR 1.03, 95%CI 1.01-1.06, p = 0.0014). CONCLUSIONS: The proportion of adjusted usage of LMWH was low. The application of adjusted-dose LMWH was associated with lower risk of in-hospital bleeding for RI patients, in real-world setting of PE treatment. Anticoagulation strategy for RI patients should be paid more attention and requires evidence of high quality. TRIAL REGISTRATION: The CURES was registered in ClinicalTrias.gov, identifier number: NCT02943343 .

Evaluation of In-Hospital Venous Thromboembolism Prevention and Management System Using Hospital-Level Metrics: A Nationwide Cross-Sectional Survey in China.

BACKGROUND: Countries in the world have taken actions to prevent venous thromboembolism (VTE) in hospitals. We have conducted a study in China to assess the establishment of hospital-based systems for VTE prevention and management. METHODS: A nationwide hospital survey was conducted in China to collect hospital-level metrics on their system for VTE prevention between 2019 and 2020. We analyzed hospital-level metrics potentially influencing the implementation of thromboprophylaxis using a multivariable regression model. Characteristics of the hospital, organizational structure, quality control, and staff training were analyzed. RESULTS: Among 435 hospitals responding to the survey, 328 (75.4%) were able to implement thromboprophylaxis. They performed VTE and bleeding risk assessments and had prophylactic interventions. Institutional VTE steering committee and unit-based working group were set up in 317 (72.9%) and 339 (77.9%) hospitals, respectively. More than 80% of the hospitals performed quality control and staff training. In contrast, digitalization of risk assessment was only accomplished in 196 (45.1%) hospitals. Proportions of the aforementioned metrics were consistently higher in tertiary hospitals than secondary hospitals (P < 0.01) except for quality control. There were geographical disparities in the establishment of VTE steering committees (P = 0.0004). In multivariable analysis, VTE steering committee was an independent factor for the implementation of thromboprophylaxis (odds ratio, 2.22, 95% confidence interval, 1.17-4.23). Working group, quality control, and training on VTE were also positively associated with the implementation of thromboprophylaxis. CONCLUSIONS: In-hospital VTE prevention has been undertaken in China, but system establishment remains suboptimal. Implementation of VTE prevention programs was associated with a decrease in thrombolytic events. Hospitals with VTE steering committees performed better on implementing preventive strategies. Suboptimal adoption of information digitization was identified, and the implementation of computer supporting techniques would be expected to improve the implementation of thromoboprophylaxis.

Higher Incidence of Chronic Thromboembolic Pulmonary Hypertension After Acute Pulmonary Embolism in Asians Than in Europeans: A Meta-Analysis.

Aim: To summarize the incidence of right heart catheter diagnosed chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE) in a meta-analysis. Methods: Cohort studies reporting the incidence of CTEPH after acute PE were identified via search of Medline, Embase, China National Knowledge Infrastructure and WanFang databases. Results: Twenty-two cohort studies with 5,834 acute PE patients were included. Pooled results showed that the overall incidence of CTEPH was 2.82% (95% CI: 2.11-3.53%). Subgroup analyses showed higher incidence of CTEPH in Asians than Europeans (5.08 vs. 1.96%, p = 0.01), in retrospective cohorts than prospective cohorts (4.75 vs. 2.47%, p = 0.02), and in studies with smaller sample size than those with larger sample size (4.57 vs. 1.71%, p < 0.001). Stratified analyses showed previous venous thromboembolic events and unprovoked PE were both significantly associated with increased risk of CTEPH (OR = 2.57 and 2.71, respectively; both p < 0.01). Conclusions: The incidence of CTEPH after acute PE is ~3% and the incidence is higher in Asians than Europeans. Efforts should be made for the early diagnosis and treatment of CTEPH in PE patients, particularly for high-risk population.

Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from the China pUlmonary thromboembolism REgistry Study (CURES).

Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies are not clear in Asian countries. We retrospectively analysed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicentre registry in China (CURES).Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analysed. Risk stratification was retrospectively classified by haemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines.Among 7438 patients, the proportions with high (haemodynamic instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. Computed tomographic pulmonary angiography was the most widely used diagnostic approach (87.6%) and anticoagulation was the most frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted pfor trend=0.0003), with a concomitant reduction in the use of initial systemic thrombolysis (from 14.8% to 5.0%, pfor trend<0.0001). The common predictors for all-cause mortality shared by haemodynamically stable and unstable patients were co-existing cancer, older age and impaired renal function.The considerable reduction of mortality over the years was accompanied by changes in initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.

Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up.

OBJECTIVE: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function. METHODS AND MATERIAL: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020. RESULTS: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (D LCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO. Pulmonary interstitial damage may be associated with abnormal D LCO. CONCLUSION: Pulmonary function, particularly D LCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO.

Healthcare professionals' knowledge, attitudes, and practices regarding graduated compression stockings: a survey of China's big-data network.

BACKGROUND: The accurate identification of venous thromboembolism prophylaxis implementation barriers is an important part of prophylaxis prevention. However, in China, data to help identify these barriers is limited. This study has two objectives: 1) to determine the knowledge, attitudes, and practices (KAPs) of healthcare professionals regarding graduated compression stockings (GCS) since the launch of the National Program for the Prevention and Management of Pulmonary Embolism (PE) and Deep Venous Thrombosis (DVT) in October 2018 and 2) to identify the obstacles and assist the program. METHODS: This was a cross-sectional study of 5070 healthcare professionals in China. We used exploratory factor and reliability analyses to evaluate the researcher-designed questionnaire's reliability and validity. The formal questionnaire, which included demographic data, knowledge, attitudes, and clinical practice patterns, was distributed to healthcare professionals. RESULTS: Of the 5070 respondents, 32.5% had a good knowledge of GCS, 78.5% had a positive attitude towards their use, and 34.0% exhibited normative behavior when applying them. The KAPs of healthcare professionals towards GCS were significantly correlated with one another. Binary logistic regression suggested that the training received by healthcare professionals was an important factor affecting their knowledge regarding GCS usage. CONCLUSIONS: The training provided for the use of GCS in China cannot meet medical staff needs and deserves more attention from policy makers. This represents an obstacle for venous thromboembolism prophylaxis, which restricts the effective implementation of the National Program for Prevention and Management of PE and DVT.

Effect on thromboprophylaxis among hospitalized patients using a system-wide multifaceted quality improvement intervention: Rationale and design for a multicenter cluster randomized clinical trial in China.

BACKGROUND: Venous thromboembolism (VTE) is a life-threatening disease that can affect each hospitalized patient. But the current in-hospital thromboprophylaxis remains suboptimal and there exists a large gap between clinical practice and guideline-recommended care in China. METHODS: To facilitate implementation of guideline recommendations, we conduct a multicenter, adjudicator-blinded, cluster-randomized clinical trial, aiming to assess the effectiveness of a system-wide multifaceted quality improvement (QI) strategy on VTE prophylaxis improvement and thromboembolism reduction in clinical setting. Hospitals are randomized into intervention or control group. In intervention group, hospitals receive the concept of appropriate in-hospital thromboprophylaxis plus a multifaceted QI which encompasses four components: (1) an electronic alert combining computer-based clinical decision support system and electronic reminders, (2) appropriate prophylaxis based on dynamic VTE and bleeding risk assessments, (3) periodical audit and interactive feedback on performance, (4) strengthened training and patient education. In control, hospitals receive the concept of recommended prophylaxis alone without QI. Thromboprophylaxis will be at the discretion of hospitals and conducted as usual. With a final sample size of 5760 hospitalized patients in 32 hospitals on mainland China, this trial will examine the effect of QI on improvement in thromboprophylaxis and patient-centered outcomes. This is an open-label trial that patients and healthcare professionals will know group allocation after enrollment, but endpoint adjudicators and statisticians will be blinded. RCT# NCT04211181 CONCLUSIONS: The system-wide multifaceted QI intervention is expected to facilitate implementation of recommended VTE prophylaxis in hospital, thereafter reducing VTE incidence and relevant adverse events among hospitalized patients in China.