Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service.

OBJECTIVES: This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Retrospective observational study. SETTING: Pulmonary hypertension referral centre in the UK. PARTICIPANTS: Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed. RESULTS: Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6-18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients. CONCLUSIONS: Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI).

BACKGROUND: The aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED). METHODS: Economic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE. RESULTS: Of the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population. CONCLUSIONS: Given the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders. CLINICALTRIALS: Trial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.

Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.

Causality assessment of circulating Vitamin D level on venous thromboembolism: A Mendelian randomization study.

BACKGROUND AND AIMS: The associations of vitamin D level with venous thromboembolism (VTE) reported in observational studies, whereas these causal associations were uncertain in European population. Therefore, we used Mendelian randomization (MR) method to explore the causal associations between 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of VTE and its subtypes [including deep vein thrombosis (DVT) and pulmonary embolism (PE)]. METHODS AND RESULTS: We used three kinds of genetic instruments to proxy the exposure of 25(OH)D, including genetic variants significantly associated with 25(OH)D, expression quantitative trait loci of 25(OH)D target genes, and genetic variants within or nearby 25(OH)D target genes. MR analyses did not provide any evidence for the associations of 25(OH)D levels with VTE and its subtypes (p > 0.05). The summary-data-based MR (SMR) analyses indicated that elevated expression of VDR was associated with decreased risk of VTE (OR = 0.81; 95% CI, 0.65-0.998; p = 0.047) and PE (OR = 0.67; 95% CI, 0.50-0.91; p = 0.011), and expression of AMDHD1 was associated with PE (OR = 0.93; 95% CI, 0.88-0.99; p = 0.027). MR analysis provided a significant causal effect of 25(OH)D level mediated by gene AMDHD1 on PE risk (OR = 0.09; 95% CI, 0.01-0.60; p = 0.012). CONCLUSION: Our MR analysis did not support causal association of 25(OH)D level with the risk of VTE and its subtypes. In addition, the expression of VDR and AMDHD1 involved in vitamin D metabolism showed a strong association with VTE or PE and might represent targets for these conditions.

Assessment of the relationship between C-reactive protein to albumin ratio and late-term mortality in patients with acute pulmonary embolism.

OBJECTIVE: In recent years, an increasing number of evidences suggests that inflammation plays a significant role in the pathophysiology of pulmonary embolism. Although the association between inflammatory markers and pulmonary embolism prognosis has been previously reported, no studies have investigated the ability of the C-reactive protein/albumin ratio, defined as an inflammation-based prognostic score, to predict death in patients experiencing a pulmonary embolism. MATERIALS AND METHODS: This retrospective study included 223 patients experiencing a pulmonary embolism. The study population was divided into two groups according to their C-reactive protein/albumin ratio values and analyzed whether the C-reactive protein/albumin ratio was an independent predictor of late-term mortality. Then, the performance of the C-reactive protein/albumin ratio in predicting patients' outcomes was further compared with its components. RESULTS: Out of 223 patients, death was observed in 57 patients (25.60%) during an average follow-up of 18 months (range: 8-26). The average C-reactive protein/albumin ratio was 0.12 (0.06-0.44). The group with a higher C-reactive protein/albumin ratio was older and had a higher troponin level and simplified Pulmonary Embolism Severity Index score. Independent predictors of late-term mortality were found to be C-reactive protein/albumin ratio (hazard ratio: 1.594, 95% CI: 1.003-2.009; p < 0.001), cardiopulmonary disease, simplified Pulmonary Embolism Severity Index score and fibrinolytic therapy. Receiver operating characteristic curve comparisons for both 30-day and late-term mortality demonstrated that the C-reactive protein/albumin ratio was a better predictor than both albumin and C-reactive protein, separately. CONCLUSION: The present study revealed that the C-reactive protein/albumin ratio is an independent predictor of both 30-day and late-term mortality in patients experiencing a pulmonary embolism. As a marker that can be easily obtained, and calculated, and does not require additional costs C-reactive protein/albumin ratio can be an effective parameter used for prognosis estimation of pulmonary embolism.

Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

The utility of risk assessment tools for acute pulmonary embolism in children.

BACKGROUND AND AIM: Pulmonary embolism (PE) is a potentially life-threatening disease in children. The objective of the study is to evaluate the utility of adult-based pulmonary embolism rule-out criteria (PERC), Pediatric PE Model, and D-dimer in the diagnosis of PE in children. MATERIAL AND METHODS: The study consisted of patients under 18 years of age who were consulted to the Pediatric Pulmonology Clinic for the evaluation of PE. Patients were divided into two groups based on the confirmation of PE. The group with the presence of PE (n = 20) consisted of children who were diagnosed with PE. The group with the absence of PE (n = 28) consisted of children with clinically suspected PE but negative diagnostic imaging. Adult validated clinical decision PERC rule and Pediatric PE Model were retrospectively applied to the patients. RESULTS: In the study, PERC demonstrated a sensitivity of 60% and a specificity of 46% for the diagnosis of PE in children. When PE Model was evaluated for the children, it was found a 50% sensitivity and 75% specificity. Combining PE Model and PERC rule with D-dimer did not increase the specificity and sensitivity. Smoking was found to be relevant for PE in the childhood. Twenty-five percent of the patients had a genetic tendency for PE. All of the patients had an underlying disease as well. CONCLUSION: None of the current risk assessment tools (PE Model, PERC, D-dimer) were found to be accurate in predicting PE. Further larger population studies are still required to develop a better diagnostic approach.

Prevalence, Outcome, and Optimal Management of Free-Floating Right Heart Thrombi in the Context of Pulmonary Embolism, a Systematic Review and Meta-Analysis.

Free-floating right-heart thrombus (FFRHT) in the context of a pulmonary embolism (PE) is a rare but serious encounter with no guidelines addressing its management. We performed a systematic review and meta-analysis addressing prevalence, clinical behavior, and outcomes of FFRHT associated with PE. Among the included 397 patients with FFRHT and PE, dyspnea was the main presenting symptom (73.3%). Obstructive shock was documented in 48.9% of cases. Treatment with thrombolytic therapy, surgical thrombectomy, and percutaneous thrombectomy was documented in 43.8%, 32.7%, and 6.5% of patients, respectively. The overall mortality rate was 20.4%. Syncope (p: 0.027), chest pain (p: 0.006), and obstructive shock (p: 0.037) were significantly associated with mortality. Use of thrombolytic therapy was significantly associated with survival (p: 0.008). A multivariate logistic regression model to determine mortality predictors revealed that syncope (OR: 1.97, 95% CI: 1.06-3.65, p: 0.03), and obstructive shock (OR: 2.23, 95% CI: 1.20-4.14, p: 0.01) were associated with increased death odds. Treatment with thrombolytic therapy (OR: 0.22, 95% CI: 0.086-0.57, p: 0.002) or surgical thrombectomy (OR: 0.35, 95% CI: 0.137-0.9, p: 0.03) were associated with reduced death odds. Meta-analysis of observational studies revealed a pooled prevalence of FFRHT among all PE cases of 8.1%, and overall mortality of 23%. Although uncommon, the presence of FFRHT in the context of PE is associated with high obstructive shock and mortality rates. Favorable survival odds are observed with thrombolytic therapy and surgical thrombectomy. Data are derived from case reports and observational studies. Clinical trials elucidating these findings are needed.

Understanding patient assessment and treatment in deep vein thrombosis.

Deep vein thrombosis (DVT) commonly develops in the deep veins of the legs, but it can potentially form in any part of the body. There are several risk factors associated with DVT including prolonged immobility, malignancy, recent surgery and family history. One of the main risks of DVT is that the thrombus that has formed in a vein may travel through the body and become lodged in the pulmonary system, causing a pulmonary embolism, which is life-threatening. In the UK, specialist services and diagnostic pathways have been developed to speed up the diagnosis and treatment of DVT, many of which are now nurse-led. This article uses a case study to outline the assessment of patients with suspected DVT and the treatment of patients with a confirmed diagnosis of DVT.

Optimal management, prevalence, and clinical behavior of saddle pulmonary embolism: A systematic review and meta-analysis.

INTRODUCTION: The central location, size, and instability of saddle pulmonary embolism (SPE) have raised significant concerns regarding its clinical, hemodynamic effects as well as optimal management. Pulmonary embolism (PE) guidelines barely address such concerns. We aimed to pool the available data on the clinical behavior and outcomes of SPE and study the effects of various treatment modalities on mortality outcomes. METHODS: PubMed, Scopus, and Google Scholar were searched for articles (any date up to February 28, 2022) reporting patients with SPE. Data on SPE demographics, clinical characteristics, management, and outcomes were extracted and analyzed. RESULTS: Results from all SPE cases: A total of 5251 patients from 194 studies were included in the review. Dyspnea (57 %) was the most prevalent symptom. Massive and submassive PE comprised 9.7 % and 45.8% of cases, respectively. Thrombolytic therapy (TT) was administered in 18.1 %, and thrombectomy was performed in 16 % of cases. SPE-related mortality was observed in 4.6 %, late decompensation in 9.5 %, and PE recurrence in 4.5 % of cases. Female sex (61.5 % vs. 41.3 %, p = 0.019), hypoxemia (90 % vs. 59.2 %, p < 0.001), massive PE features (89.7 % vs. 30.1 %, p < 0.001), associated chronic kidney disease (CKD) (10.3 % vs. 1.4 %, p = 0.002), and the need for mechanical ventilation (28.2 % vs. 13.1 %, p = 0.02) were significantly associated with increased mortality. The use of TT was significantly associated with increased survival (27.1 % vs. 12.5 %, p < 0.001). In a multivariate logistic regression model, massive PE features significantly increased the odds of death (OR: 29.3, CI: 4.86-181.81, p < 0.001), whereas, treatment with anticoagulation (AC) alone (OR: 0.1, CI: 0.027-0.356, p < 0.001), TT (OR: 0.065, CI: 0.019-0.26, p < 0.001), surgical thrombectomy (ST) (OR: 0.047, CI: (0.010-0.23), p < 0.001), or percutaneous thrombectomy (PT) (OR: 0.12, CI: 0.020-0.84, p = 0.032) significantly decreased odds of death. Results from a meta-analysis of observational studies: Meta-analysis of the included 17 observational studies revealed an overall 10 % (95 % CI: 4.56-16.89) SPE prevalence among all PE cases. The overall SPE-related mortality rate was 8 % (95 % CI: 5.26-10.96). Massive PE was observed in 13.3 % (95 % CI: 5.56-23.70), PE recurrence in 5.1 % (95 % CI: 2.22-9.05), and late decompensation in 11 % (95 % CI: 3.43-22.34) of patients. CONCLUSIONS: SPE comprises 10 % of all PE cases. Despite its ominous radiologic appearance, the clinical, hemodynamic, and mortality outcomes of SPE seem comparable to that of other PE types in general. The presence of massive PE features is the main predictor of mortality in SPE patients. AC, TT, ST, and PT are all associated with decreased odds of death from SPE.

Pulmonary embolism diagnosis part 1: clinical assessment at the front door.

This first of two practice reviews addresses pulmonary embolism (PE) diagnosis considering important aspects of PE clinical presentation and comparing evidence-based PE testing strategies. A companion paper addresses the management of PE. Symptoms and signs of PE are varied, and emergency physicians frequently use testing to 'rule out' the diagnosis in people with respiratory or cardiovascular symptoms. The emergency clinician must balance the benefit of reassuring negative PE testing with the risks of iatrogenic harms from over investigation and overdiagnosis.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study.

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.

Cardiopulmonary exercise testing for treatment effect assessment in chronic thromboembolic pulmonary hypertension patients.

Aim      To determine possibilities of the cardiopulmonary stress test (CPST) as an unbiassed, noninvasive method for evaluation of the effect of managing patients with chronic thromboembolic pulmonary hypertension (CTEPH).Material and methods  This study included 37 patients with CTEPH, 24 men (mean age, 53±15 years) and 13 women (mean age, 58±8.5 years). The diagnosis was verified and theCoperability was assessed according to 2015 European Society of Cardiology Clinical Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension (PH). The surgical treatment was used in 65 % (n=24) of CTEPH patients: the group with pulmonary thromboendarterectomy constituted 35 % (n=13); the group with balloon pulmonary angioplasty 30% (n=11); and the conservative tactics was used in 27 % (n=10) of patients.Results Baseline CPST parameters significantly correlated with parameters of right heart catheterization (RHC): mixed venous oxygen saturation (SvO2) significantly positively correlated with V´O2peak (r=0.640, p<0.05), V´O2 / heart rate (HR) (r=0.557; p<0.001), PETCO2 peak (r=0.598, p<0.05), and V´E / V´CO2 (r=0.587; p<0.001); cardiac output (CO) correlated with V´O2 / HR (r=0.555, p<0.001), PETCO2peak (r= -0.476; p<0.05 and r=0.555, p<0.001 for ´E / V´CO2). In repeated testing, the physical working capacity (V´O2peak) increased only in patients after the surgical treatment of CTEPH. Importantly in this process, significant correlations remained between a number of CPST and RHC parameters: SvO2 correlated with V´O2peak (r=0.743; p<0.05), V´O2 /HR (r=0.627; p<0.001), PETCO2peak (r=0.538; p<0.05), and V´E / V´CO2 (r=0.597; p<0.001); V´O2 / HR, PETCO2peak, and V´E / V´CO2 significantly correlated with CO (r=0.645, p<0.001; r= -0.516, p<0.001, and r=0.555, p<0.001, respectively.Conclusion      CPST can be used as a noninvasive instrument for evaluation of the effect of CTEPH treatment, particularly in the absence of echocardiographic data for residual PH.

An efficient and fast multi-band focused bioimpedance solution with EIT-based reconstruction for pulmonary embolism assessment: a simulation study from massive to segmental blockage.

Objective.Pulmonary embolism (PE) is an acute condition that blocks the perfusion to the lungs and is a common complication of Covid-19. However, PE is often not diagnosed in time, especially in the pandemic time due to complicated diagnosis protocol. In this study, a non-invasive, fast and efficient bioimpedance method with the EIT-based reconstruction approach is proposed to assess the lung perfusion reliably.Approach.Some proposals are presented to improve the sensitivity and accuracy for the bioimpedance method: (1) a new electrode configuration and focused pattern to help study deep changes caused by PE within each lung field separately, (2) a measurement strategy to compensate the effect of different boundary shapes and varied respiratory conditions on the perfusion signals and (3) an estimator to predict the lung perfusion capacity, from which the severity of PE can be assessed. The proposals were tested on the first-time simulation of PE events at different locations and degrees from segmental blockages to massive blockages. Different object boundary shapes and varied respiratory conditions were included in the simulation to represent for different populations in real measurements.Results.The correlation between the estimator and the perfusion was very promising (R = 0.91, errors <6%). The measurement strategy with the proposed configuration and pattern has helped stabilize the estimator to non-perfusion factors such as the boundary shapes and varied respiration conditions (3%-5% errors).Significance.This promising preliminary result has demonstrated the proposed bioimpedance method's capability and feasibility, and might start a new direction for this application.

Cost-effectiveness of diagnostic strategies for venous thromboembolism: a systematic review.

Guideline developers consider cost-effectiveness evidence in decision making to determine value for money. This consideration in the guideline development process can be informed either by formal and dedicated economic evaluations or by systematic reviews of existing studies. To inform the American Society of Hematology guideline on the diagnosis of venous thromboembolism (VTE), we conducted a systematic review focused on the cost-effectiveness of diagnostic strategies for VTE within the guideline scope. We systematically searched Medline (Ovid), Embase (Ovid), National Health Service Economic Evaluation Database, and the Cost-effectiveness Analysis Registry; summarized; and critically appraised the economic evidence on diagnostic strategies for VTE. We identified 49 studies that met our inclusion criteria, with 26 on pulmonary embolism (PE) and 24 on deep vein thrombosis (DVT). For the diagnosis of PE, strategies including d-dimer to exclude PE were cost-effective compared with strategies without d-dimer testing. The cost-effectiveness of computed tomography pulmonary angiogram (CTPA) in relation to ventilation-perfusion (V/Q) scan was inconclusive. CTPA or V/Q scan following ultrasound or d-dimer results could be cost-effective or even cost saving. For DVT, studies supporting strategies with d-dimer and/or ultrasound were cost-effective, supporting the recommendation that for patients at low (unlikely) VTE risk, using d-dimer as the initial test reduces the need for diagnostic imaging. Our systematic review informed the American Society of Hematology guideline recommendations about d-dimer, V/Q scan and CTPA for PE diagnosis, and d-dimer and ultrasound for DVT diagnosis.

A Comparison of GFR Calculated by Cockcroft-Gault vs. MDRD Formula in the Prognostic Assessment of Patients with Acute Pulmonary Embolism.

INTRODUCTION: Risk stratification is mandatory for optimal management of patients with acute pulmonary embolism (APE). Previous studies indicated that renal dysfunction predicts outcome and can improve risk assessment in APE. AIM: The aim of the study was a comparison of estimated glomerular filtration rate (eGFR) formulas, MDRD, and Cockcroft-Gault (CG), in the prognostic assessment of patients with APE. MATERIALS AND METHODS: Data from 2274 (1147 M/1127 F, median 71 years) hospitalised patients with APE prospectively included in a multicenter, observational, cohort study were analysed. A serum creatinine measurement as a routine laboratory parameter at the cooperating centers and eGFR calculation were performed on admission. Patients were followed for 180 days. The primary outcome was death from any cause within 30 days. RESULTS: The eGFR levels assessed by both, MDRD (eGFRMDRD) and CG formula (eGFRCG), were highest in patients with low-risk APE and lowest in high-risk APE. The eGFR (using both methods) was significantly lower in nonsurvivors compared to survivors. Using a threshold of <60 ml/min/1.73 m2, eGFRMDRD revealed the primary outcome with sensitivity 67%, specificity 52%, PPV 8%, and NPV 97%, while eGFRCG had a sensitivity 62%, specificity 62%, PPV 8.6%, and NPV 96%. The area under the ROC curve for eGFRCG tended to be higher than that for eGFRMDRD: 0.658 (95% CI: 0.608-0.709) vs. 0.631 (95% CI: 0.578-0.683), p = 0.12. A subanalysis of ROC curves in a population above 65 yrs showed a higher AUC for eGFRCG than based on MDRD. Kaplan-Meier analysis showed a worse long-term outcome in patients with impaired renal function. CONCLUSION: eGFRMDRD and eGFRCG assessed on admission significant short- and long-term mortality predictors in patients with APE. The eGFRCG seems to be a slightly better 30-day mortality predictor than eGFRMDRD in the elderly.

Development and validation of a novel risk assessment model to estimate the probability of pulmonary embolism in postoperative patients.

Pulmonary embolism (PE) is a leading cause of mortality in postoperative patients. Numerous PE prevention clinical practice guidelines are available but not consistently implemented. This study aimed to develop and validate a novel risk assessment model to assess the risk of PE in postoperative patients. Patients who underwent Grade IV surgery between September 2012 and January 2020 (n = 26,536) at the Affiliated Dongyang Hospital of Wenzhou Medical University were enrolled in our study. PE was confirmed by an identified filling defect in the pulmonary artery system in CT pulmonary angiography. The PE incidence was evaluated before discharge. All preoperative data containing clinical and laboratory variables were extracted for each participant. A novel risk assessment model (RAM) for PE was developed with multivariate regression analysis. The discrimination ability of the RAM was evaluated by the area under the receiver operating characteristic curve, and model calibration was assessed by the Hosmer-Lemeshow statistic. We included 53 clinical and laboratory variables in this study. Among them, 296 postoperative patients developed PE before discharge, and the incidence rate was 1.04%. The distribution of variables between the training group and the validation group was balanced. After using multivariate stepwise regression, only variable age (OR 1.070 [1.054-1.087], P < 0.001), drinking (OR 0.477 [0.304-0.749], P = 0.001), malignant tumor (OR 2.552 [1.745-3.731], P < 0.001), anticoagulant (OR 3.719 [2.281-6.062], P < 0.001), lymphocyte percentage (OR 2.773 [2.342-3.285], P < 0.001), neutrophil percentage (OR 10.703 [8.337-13.739], P < 0.001), red blood cell (OR 1.872 [1.384-2.532], P < 0.001), total bilirubin (OR 1.038 [1.012-1.064], P < 0.001), direct bilirubin (OR 0.850 [0.779-0.928], P < 0.001), prothrombin time (OR 0.768 [0.636-0.926], P < 0.001) and fibrinogen (OR 0.772 [0.651-0.915], P < 0.001) were selected and significantly associated with PE. The final model included four variables: neutrophil percentage, age, malignant tumor and lymphocyte percentage. The AUC of the model was 0.949 (95% CI 0.932-0.966). The risk prediction model still showed good calibration, with reasonable agreement between the observed and predicted PE outcomes in the validation set (AUC 0.958). The information on sensitivity, specificity and predictive values according to cutoff points of the score in the training set suggested a threshold of 0.012 as the optimal cutoff value to define high-risk individuals. We developed a new approach to select hazard factors for PE in postoperative patients. This tool provided a consistent, accurate, and effective method for risk assessment. This finding may help decision-makers weigh the risk of PE and appropriately select PE prevention strategies.

Association of Socioeconomic Disadvantage With Mortality and Readmissions Among Older Adults Hospitalized for Pulmonary Embolism in the United States.

Background In the United States, hospitalizations for pulmonary embolism (PE) are increasing among older adults insured by Medicare. Although efforts to reduce health disparities have intensified, it remains unclear whether clinical outcomes differ between socioeconomically disadvantaged and nondisadvantaged Medicare beneficiaries hospitalized with PE. Methods and Results In this study, there were 53 386 Medicare fee-for-service beneficiaries age ≥65 years hospitalized for PE between October 2015 and January 2017. Of these, 5494 (10.3%) were socioeconomically disadvantaged and 47 892 (89.7%) were nondisadvantaged. Socioeconomically disadvantaged adults were of similar age as nondisadvantaged adults (77.1 versus 77.0), more likely to be female (68.5% versus 54.2%), and less likely to receive advanced therapies (11.0% versus 12.1%). After adjustment for demographics, 90-day all-cause mortality rates were similar between disadvantaged and nondisadvantaged adults. In contrast, 1-year mortality rates were higher among socioeconomically disadvantaged adults (hazard ratio [HR], 1.16; 95% CI, 1.10-1.22), although these differences were partially attenuated after additional adjustments for comorbidities and PE severity (HR, 1.09; 95% CI, 1.02-1.16). Risk-adjusted 30-day and 90-day all-cause readmission rates were substantially higher among socioeconomically disadvantaged patients (30-day HR, 1.14 [95% CI, 1.06-1.22]; 90-day HR, 1.18 [95% CI, 1.12-1.25]). In addition, 90-day readmissions attributed to PE, deep vein thrombosis, and/or bleeding were higher among socioeconomically disadvantaged patients (HR, 1.16; 95% CI, 1.02-1.32). Conclusions Socioeconomically disadvantaged older adults hospitalized with PE have higher 1-year mortality rates compared with their nondisadvantaged counterparts. Nearly 1 in 3 socioeconomically disadvantaged older adults was readmitted within 90 days of a hospitalization for PE. Targeted strategies are needed to improve transitional and ambulatory care for this vulnerable population.