Recurrent Pulmonary Embolism Research Articles

Oral direct thrombin inhibitors or oral factor Xa inhibitorsversus conventional anticoagulants for the treatment of pulmonary embolism.

Pulmonary embolism (PE) is a potentially life-threatening condition in which a clot can migrate from the deep veins, most commonly in the leg, to the lungs. Conventional treatment of PE used unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and vitamin K antagonists (VKAs). Recently, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors. DOACs have characteristics that may be favourable to conventional treatment, including oral administration, a predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. This review reports the efficacy and safety of these drugs in the long-term treatment of PE (minimum duration of three months). This is an update of a Cochrane Review first published in 2015. OBJECTIVES: To assess the efficacy and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of PE. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 2 March 2022. We checked the reference lists of relevant articles for additional studies. We included randomised controlled trials (RCTs) in which people with a PE confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with a conventional anticoagulant or compared with each other for the long-term treatment of PE (minimum duration three months). We used standard Cochrane methods. Our primary outcomes were recurrent PE, recurrent venous thromboembolism (VTE), and deep vein thrombosis (DVT). Secondary outcomes were all-cause mortality, major bleeding, and health-related quality of life. We used GRADE to assess the certainty of evidence for each outcome. We identified five additional RCTs with 1484 participants for this update. Together with the previously included trials, we have included ten RCTs with a total of 13,073 participants. Two studies investigated an oral DTI (dabigatran) and eight studies investigated oral factor Xa inhibitors (three rivaroxaban, three apixaban, and two edoxaban). The studies were of good methodological quality overall. Meta-analysis showed no clear difference in the efficacy and safety of oral DTI compared with conventional anticoagulation in preventing recurrent PE (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.50 to 2.04; 2 studies, 1602 participants; moderate-certainty evidence), recurrent VTE (OR 0.93, 95% CI 0.52 to 1.66; 2 studies, 1602 participants; moderate-certainty evidence), DVT (OR 0.79, 95% CI 0.29 to 2.13; 2 studies, 1602 participants; moderate-certainty evidence), and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; 2 studies, 1527 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision due to the low number of events. There was also no clear difference between the oral factor Xa inhibitors and conventional anticoagulation in the prevention of recurrent PE (OR 0.92, 95% CI 0.66 to 1.29; 3 studies, 8186 participants; moderate-certainty evidence), recurrent VTE (OR 0.83, 95% CI 0.66 to 1.03; 8 studies, 11,416 participants; moderate-certainty evidence), DVT (OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 8151 participants; moderate-certainty evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; 1 study, 4817 participants; moderate-certainty evidence) and major bleeding (OR 0.71, 95% CI 0.36 to 1.41; 8 studies, 11,447 participants; low-certainty evidence); the heterogeneity for major bleeding was significant (I2 = 79%). We downgraded the certainty of the evidence to moderate and low because of imprecision due to the low number of events and inconsistency due to clinical heterogeneity. None of the included studies measured health-related quality of life. Available evidence shows there is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent PE, recurrent VTE, DVT, all-cause mortality, and major bleeding. The certainty of evidence was moderate or low. Future large clinical trials are required to identify if individual drugs differ in effectiveness and bleeding risk, and to explore effect differences in subgroups, including people with cancer and obesity.

A thrombophilic allele of clotting Factor VII/VIIa promoting recurrent pulmonary emboli, clinical details, and a structural model of the altered protein: a case report

BackgroundThe clotting or hemostasis system is a meticulously regulated set of enzymatic reactions that occur in the blood and culminate in formation of a fibrin clot. The precisely calibrated signaling system that prevents or initiates clotting originates with the activated Factor Seven (FVIIa) complexed with tissue factor (TF) formed in the endothelium. Here we describe a rare inherited mutation in the FVII gene which is associated with pathological clotting.Case presentationThe 52-year-old patient, with European, Cherokee and African American origins, FS was identified as having low FVII (10%) prior to elective surgery for an umbilical hernia. He was given low doses of NovoSeven (therapeutic Factor VIIa) and had no unusual bleeding or clotting during the surgery. In fact, during his entire clinical course he had no unprovoked bleeding. Bleeding instances occurred with hemostatic stresses such as gastritis, kidney calculus, orthopedic surgery, or tooth extraction, and these were handled without factor replacement. On the other hand, FS sustained two unprovoked and life-threatening instances of pulmonary emboli, although he was not treated with NovoSeven at any time close to the events. Since 2020, he has been placed on a DOAC (Direct Oral Anticoagulant, producing Factor Xa inhibition) and has sustained no further clots.Possible mechanism of (unauthorized) FVII activationFS has a congenitally mutated FVII/FVIIa gene, which carries a R315W missense mutation in one allele and a mutated start codon (ATG to ACG) in the other allele, thus rendering the patient effectively homozygous for the missense FVII. Structure based comparisons with known crystal structures of TF-VIIa indicate that the patient's missense mutation is predicted to induce a conformational shift of the C170's loop due to crowding of the bulky tryptophan to a distorted "out" position (Fig. 1). This mobile loop likely forms new interactions with activation loop 3, stabilizing a more active conformation of the FVII and FVIIa protein. The mutant form of FVIIa may be better able to interact with TF, displaying a modified serine protease active site with enhanced activity for downstream substrates such as Factor X.ConclusionsFactor VII can be considered the gatekeeper of the coagulation system. Here we describe an inherited mutation in which the gatekeeper function is altered. Instead of the expected bleeding manifestations resulting from a clotting factor deficiency, the patient FS suffered clotting episodes. The efficacy of the DOAC in treating and preventing clots in this unusual situation is due to its target site of inhibition (anti-Xa), which lies downstream of the site of action of FVIIa/TF.

Return emergency department visits for recurrent pulmonary embolism symptoms in children and adolescents

AbstractRates of pulmonary embolism (PE) in children have steadily increased over the past 2 decades. Patient outcomes after hospital discharge are poorly understood, and many patients experience recurrent or persistent chest pain or dyspnea, prompting a return to care. This retrospective cohort study of patients diagnosed with PE at a large children’s hospital over a 9.5-year period was performed to evaluate rates of return to the emergency department (ED) for PE-related symptoms, and to determine the utility of repeat computed tomography angiography (CTA) in this population. Ninety-six patients were diagnosed with PE during the study period. Forty-two percent of patients (n = 40) returned to the ED for PE-related symptoms and a total of 74 repeat CTAs were performed. Among those who had return visits, the mean number of return visits was 3 and the mean number of repeat CTAs was 1.8. The median time to return to the ED was 34 days. Logistic regression analysis identified increased age and female sex as risk factors for return ED visits. Eight percent of the cohort experienced PE recurrence. Recurrent PE was observed only in those with persistent or new thrombotic risk factors and was uncommon in those who remained on appropriate anticoagulation. Future work should focus on the development of a risk stratification system to identify patients at low risk of recurrence in order to minimize repeat CTA imaging.

Case Series of Patients With Intermediate-High Risk Pulmonary Embolism in the Setting of Trauma Undergoing Mechanical Thrombectomy

In patients with pulmonary embolism (PE) in the setting of trauma, administration of fibrinolytic therapy is contraindicated due to high risk of hemorrhage. Several studies have demonstrated the safety and efficacy of mechanical thrombectomy among all-comers with PE as an alternative to catheter-directed thrombolytics. However, the risks and benefits of mechanical thrombectomy treatment for pulmonary embolism in a trauma population are not well established. A retrospective analysis was performed in all patients who presented to Level 1 Trauma Center with acute trauma who were found to have a pulmonary embolism (PE) treated with mechanical thrombectomy. From May 2019 to December 2020, six patients were identified. Average age was 54 years, and four patients were male. Four patients had a saddle PE on computed tomography. All patients had an intermediate-high risk PE with troponin I elevation >0.04 ng/mL (average 0.42 ng/mL). Pulmonary Embolism Severity Index (PESI) score in all six patients was class III or IV. In all patients, the mechanical thrombectomy was performed with mean-PA pressure changing from average 40.33 to 31.5 mmHg. Average Intensive Care Unit (ICU) length of stay post-procedure was five days with two patients not requiring ICU stay. No patient had post-operative bleeding during their index stay. Average hemoglobin drop after mechanical thrombectomy was 1.33 g/dL. One patient died <30 days post-procedure due to septic shock and another >90 days later (5 months) from cardiac arrest from recurrent PE. The other four patients were still living >90 days post-procedure. No immediate or delayed postoperative complications were identified. Mechanical thrombectomy appears to be a safe and effective treatment for patients with recent trauma who have an intermediate-high risk pulmonary embolism.

(977) Post-Operative Use of Direct Oral Anticoagulants is Associated with Increased Risk of Recurrent Pulmonary Embolism Following Pulmonary Thromboendarterectomy

(977) Post-Operative Use of Direct Oral Anticoagulants is Associated with Increased Risk of Recurrent Pulmonary Embolism Following Pulmonary Thromboendarterectomy

Clinical outcomes of ultrasound-assisted coagulation monitoring-adjusted catheter-directed thrombolysis for acute pulmonary embolism

BackgroundUltrasound-assisted catheter-directed thrombolysis (USAT) may reverse right ventricular dysfunction due to acute pulmonary embolism (PE) with a favorable safety profile. MethodsWe studied intermediate-high- and high-risk acute PE patients who underwent USAT at the University Hospital Zurich, 2018–2022. The USAT regimen included alteplase 10 mg per catheter over 15 h, therapeutic-dosed heparin, and dosage adaptations based on routinely monitored coagulation parameters, notably anti-factor Xa activity and fibrinogen. We focused on the mean pulmonary arterial pressure (mPAP) and the National Early Warning Score (NEWS) before and after USAT, and reported the incidence of hemodynamic decompensation, PE recurrence, major bleeding, and death over 30 days. ResultsWe included 161 patients: 96 (59.6 %) were men and the mean age was 67.8 (SD 14.6) years. Mean PAP decreased from a mean of 35.6 (SD 9.8) to 25.6 (SD 8.2) mmHg, whereas the NEWS decreased from a median of 5 (Q1-Q3 4–6) to 3 (Q1-Q3 2–4) points. No cases of hemodynamic decompensation occurred. One (0.6 %) patient had an episode of recurrent PE. Two (1.2 %) major bleeding events occurred, including one (0.6 %) intracranial, fatal hemorrhage in a patient with high-risk PE, severe heparin overdosing, and a recent head trauma (with negative CT scan of the brain performed at baseline). No other deaths occurred. ConclusionsUSAT resulted in a rapid improvement of hemodynamic parameters among patients with intermediate-high risk acute PE and selected ones with high-risk acute PE, without any recorded deaths related to PE itself. A strategy including USAT, therapeutic-dosed heparin, and routinely monitored coagulation parameters may partly explain the overall very low rate of major bleeding.

Comparative Overview of Different Radiological Imaging Techniques in the Diagnosis of Pulmonary Embolism

Background: Imaging techniques such as chest X-ray (CXR), computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scintigraphy, and magnetic resonance imaging (MRI) are some methods used to detect and manage acute pulmonary embolism (PE). The aim of this review was a comparative analysis of the various imaging techniques used to evaluate PE. Methods and Results: The incidence, distribution, clinical features, classification of PE and clinical assessment of the current methods for diagnosis of PE were discussed. CTPA is the gold standard for fast turnaround and accurate diagnosis. Additional probable reasons for sudden chest pain can also be learned through a CT scan. Lung perfusion anomalies can be identified and measured using dual-energy CT. Chest radiographs are only marginally beneficial, occasionally revealing PE or infarction signs, but are helpful in ruling out other possible causes of chest pain. These patients' ventilation-perfusion mismatches are evident in the V/Q scan, which has many grading schemes with conventional ranges from normal to high. While MRI, which is only available in specialist facilities and calls for higher degrees of competence, also offers accurate diagnosis. Conclusion: Early diagnosis and treatment of PE is challenging due to asymptomatic conditions or overlapping symptoms. Diagnosis of PE in expectant mothers and those with suspected PE recurrence is typically difficult. Over-diagnosis and overtreatment, particularly regarding sub-segmental PE, and the lowered clinical suspicion threshold remain a major concern in PE diagnosis. The routine use and integration of the above diagnostic techniques need to be encouraged in clinical practice to overcome the diagnostic hurdles. The introduction of new diagnostic techniques or improved risk stratification processes might enhance the management of PE.

Effectiveness, Retrievability, and Safety of Celect vs. ALN Inferior Vena Cava Filters: A Randomized Prospective Multicenter Controlled Study

The purpose of this study is to compare IVC Celect and ALN filters in regard to their efficacy, retrievability, and one-year follow-up after retrieval. Materials and Methods: This is a prospective randomized study, conducted in three centers between April 2020 and May 2021. A total of 115 participants were randomized, of which 15 participants were excluded for various reasons. Each group of 50 participants was finally assigned a type of filter (Celect n = 50 and ALN = 50). Tilt angles at placement and retrieval, rates of overall filter retrieval, complications, complex retrieval, and clinical follow-up at 12 months were compared. Results: One hundred participants (59 men and 41 women) were included. The mean age was 62.4 ± 13.3, with no significant differences between both groups (p 0.503). The mean of dwelling time was 44.7 ± 93 days. (p 0.520) Filter retrieval was successful in all participants (100%). The main complication in CT prior to removal was tilt &gt;15° (31%) and filter tip embedment (16%). No significant differences were observed in the type of retrieval (standard or complex) between both filters (p 0.24); however, fluoroscopy time was significantly longer in the complex removal of the Celect filter: 29.1 ± 12 min vs. 17.5 ± 10.3 (p 0.005). After one year, no recurrent pulmonary embolism was observed in both types of filters. Conclusions: The ALN filter had a significantly lower rate of tip and filter tip embedding, with no differences in complexity or removal success rate. There were significant differences in the fluoroscopy time consumed for standard and complex retrievals between both filters, with less time for the ALN filter.

Percutaneous large-bore aspiration embolectomy with veno-arterial extracorporal membrane oxygenation support or standby in patients with high-risk pulmonary embolism and contraindications to thrombolysis: a preliminary single centre experience.

Large-bore catheter aspiration embolectomy reduces thrombus burden and right ventricle strain and improves haemodynamics after pulmonary embolism (PE). Sparse data are available for patients with high-risk PE and contraindications to thrombolysis or thrombolysis failure, particularly if veno-arterial extracorporal membrane oxygenation (VA-ECMO) is required. All patients with acute high-risk PE and contraindications to thrombolysis undergoing FlowTriever® percutaneous embolectomy and VA-ECMO circulatory support (or standby) at the University Hospital Zurich between April 2021 and August 2022 were retrospectively analysed. The primary outcome was the combination of recurrent PE, heart failure hospitalization, and all-cause death at 30 days. The analysis included 15 patients: mean age was 63.1 years and 14 (93%) were men. Overall, four (27%) patients presented with cardiac arrest, eight (53%) with ongoing obstructive shock, and three (20%) with persistent arterial hypotension. Veno-arterial extracorporal membrane oxygenation was implanted prior to aspiration embolectomy in eight (53%) patients. Three of seven patients without initial VA-ECMO support experienced periprocedural cardiac arrest, of whom two received ECMO support before completion of embolectomy. Veno-arterial extracorporal membrane oxygenation weaning was successful in all patients after a mean of 5.4 days. There was one periprocedural death in a patient who did not receive VA-ECMO support following a periprocedural cardiac arrest. The primary outcome at 30 days occurred in five (33.3%; 95% confidence interval 13.0-61.3%) patients. This study provides preliminary evidence for the feasibility of percutaneous large-bore aspiration embolectomy in combination with VA-ECMO support (or standby) in patients with high-risk PE and contraindications to thrombolysis.

Clinical Significance and Outcome in Patients with Asymptomatic Versus Symptomatic Subsegmental Pulmonary Embolism

The clinical significance and optimal therapy of patients with subsegmental pulmonary embolism (SSPE) remain controversial. We used the data in the RIETE Registry to compare the baseline characteristics, treatment, and outcomes during anticoagulation and after its discontinuation in patients with asymptomatic vs. symptomatic SSPE. From January 2009 to September 2022, there were 2135 patients with a first episode of SSPE, of whom 160 (7.5%) were asymptomatic. Most patients in both subgroups received anticoagulant therapy (97% vs. 99.4%, respectively). During anticoagulation, 14 patients developed symptomatic pulmonary embolism (PE) recurrences, 28 lower-limb deep vein thrombosis (DVT), 54 bled, and 242 died. The patients with asymptomatic SSPE had similar rates of symptomatic PE recurrences (hazard ratio (HR): 2.46; 95% CI: 0.37-9.74), DVT (HR: 0.53; 95% CI: 0.03-2.80), or major bleeding (HR: 0.85; 95% CI: 0.21-2.42) to those with symptomatic SSPE, but had a higher mortality rate (HR: 1.59; 95% CI: 1.25-2.94). The rate of major bleeding outweighed the rate of PE recurrences (54 major bleeds vs. 14 PE recurrences), and the rate of fatal bleeds outweighed the rate of fatal PE recurrences (12 vs. 6 deaths). After discontinuing anticoagulation, the patients with asymptomatic SSPE had a similar rate of PE recurrences (HR: 1.27; 95% CI: 0.20-4.55) and a non-significantly higher mortality rate (HR: 2.06; 95% CI: 0.92-4.10). The patients with asymptomatic SSPE had similar rates of PE recurrences to those with symptomatic SSPE, during and after discontinuing anticoagulation. The unexpectedly higher rate of major bleeding than recurrences highlights the need for randomized trials to find the best management.

Cancer-associated thrombosis: comparison of characteristics, treatment, and outcomes in oncologic and nononcologic patients followed by a pulmonary embolism response team.

The risk of venous thromboembolism (VTE) in patients with cancer is currently 12 times higher than in the general population, and even 23 times higher when they receive chemotherapy. The main goal of the pulmonary embolism response team at the Center for the Management of Pulmonary Embolism (PERT‑CELZAT) is to improve prognosis through interdisciplinary care, with a particular focus on patients with contraindications to standard pharmacologic treatment, requiring individual decision‑making, including a wider use of interventional therapeutic methods. The objectives of the study were to report and compare the characteristics and outcomes of pulmonary embolism (PE) in patients with and without cancer treated by the PERT‑CELZAT. The analysis included 235 patients diagnosed with VTE who were consulted by local PERT between September 2017 and December 2021. The study group was divided into 2 cohorts: oncologic patients (OP) and nononcologic patients (NOP). There were 81 patients in the OP group (mean [SD] age, 66.2 [14.1] years) and 154 patients in the NOP group (mean age, 57.4 [17.4] years). The OPs were older and more frequently diagnosed with incidental PE. In‑hospital mortality for all patients reached 6.4% (15/235), 3.7% in the OP and 7.8% in the NOP group (P = 0.27). In‑hospital events, such as major bleeding, minor bleeding, recurrent PE, and deep venous thrombosis occurred with similar frequency in both groups. Posthospital mortality up to 12 months after the PE diagnosis was 12.8% (10/78) in the OP and 4.2% (6/142) in the NOP group (P = 0.03). In a long‑term survival analysis, cancer was associated with increased risk of mortality (hazard ratio, 2.44 [95% CI, 1.51-3.95]; P <0.001) when adjusted for age. The multidisciplinary therapeutic approach may provide the OPs with VTE an in‑hospital survival rate noninferior to that of the NOPs. The OPs died more often in the following months, because of their underlying neoplastic disease.

Impact of obstructive sleep apnea on outcomes of pulmonary embolism: A systematic review and meta‑analysis.

The current review aimed to assess the effect of obstructive sleep apnea (OSA) on the severity and outcomes of pulmonary embolism (PE). PubMed, Embase, ScienceDirect, CENTRAL and Google Scholar were searched for studies assessing the impact of OSA on severity and outcomes of PE. A total of 12 studies were included. Meta-analysis revealed that simplified PE severity index of >1 and pulmonary artery obstruction index score was significantly higher in patients with OSA as compared with controls, but there was no difference in right ventricle to left ventricle short-axis diameter. The need for non-invasive ventilation was significantly higher in patients with OSA but there was no difference in the need for mechanical ventilation. Patients with OSA had a significantly higher incidence of recurrence of PE. Meta-analysis also showed a statistically significantly lower risk of in-hospital mortality in patients with OSA as compared with controls, but without any difference in the risk of late mortality. Adjusted data on mortality indicated a significantly lower risk of mortality in PE patients with comorbid OSA. Limited data shows that comorbid OSA increases the severity of PE but has no effect on right ventricular function. OSA may increase the risk of recurrent PE. Paradoxically, the presence of OSA may also reduce the risk of in-hospital mortality. Results must be interpreted with caution owing to high inter-study heterogeneity and lack of matching of baseline characteristics. Current evidence needs to be confirmed by high-quality prospective studies.

Comparison of various prognostic scores for identification of patients with intermediate-high risk pulmonary embolism

BackgroundVarious risk assessment tools have been proposed to identify stable patients with acute pulmonary embolism (PE) who are at high risk of early adverse outcome (i.e., intermediate-high risk). MethodsWe evaluated the ability of the 2019 ESC, Bova, modified FAST and PEITHO-3 models for predicting a 30-day complicated course (death, haemodynamic collapse, and/or recurrent PE) in a cohort of 848 stable patients with acute PE. We also tested whether replacement of echocardiographic right ventricle (RV) dysfunction by computed tomographic (CT) RV enlargement provides comparable prognostic information for identifying these patients. ResultsA complicated course occurred in 63 (7.4 %) of the 848 patients with PE during the first month of follow-up. The proportion of patients designated as having intermediate-high risk PE was 6.7 % with the ESC model, 4.4 % with the Bova score, 15.7 % with the FAST score, and 5.2 % with the PEITHO-3 model. However, among patients identified as intermediate-high risk, the 30-day complicated course rate was higher with the Bova score (21.6 %) than with the ESC model (17.5 %), the PEITHO-3 model (15.9 %), or the modified FAST score (14.3 %). When echocardiographic RV dysfunction was replaced by CT RV enlargement in the models, the proportion of patients classified as having intermediate-high risk PE and the rate of an adverse outcome among them slightly increased. ConclusionsThe Bova score might identify patients with intermediate-high risk PE slightly better than the ESC, PEITHO-3, and modified FAST score. When echocardiography is not readily available, CT-assessed RV enlargement might be used for identifying intermediate-high risk PE.ClinicalTrials.gov number: NCT02238639.

Artificial intelligence-based iliofemoral deep venous thrombosis detection using a clinical approach

Early diagnosis of deep venous thrombosis is essential for reducing complications, such as recurrent pulmonary embolism and venous thromboembolism. There are numerous studies on enhancing efficiency of computer-aided diagnosis, but clinical diagnostic approaches have never been considered. In this study, we evaluated the performance of an artificial intelligence (AI) algorithm in the detection of iliofemoral deep venous thrombosis on computed tomography angiography of the lower extremities to investigate the effectiveness of using the clinical approach during the feature extraction process of the AI algorithm. To investigate the effectiveness of the proposed method, we created synthesized images to consider practical diagnostic procedures and applied them to the convolutional neural network-based RetinaNet model. We compared and analyzed the performances based on the model’s backbone and data. The performance of the model was as follows: ResNet50: sensitivity = 0.843 (± 0.037), false positives per image = 0.608 (± 0.139); ResNet152 backbone: sensitivity = 0.839 (± 0.031), false positives per image = 0.503 (± 0.079). The results demonstrated the effectiveness of the suggested method in using computed tomography angiography of the lower extremities, and improving the reporting efficiency of the critical iliofemoral deep venous thrombosis cases.

Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis

Background: Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action. Objectives: The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis. Methods: A search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework. Results: A total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = −11.36, 95% CI, −21.45, −1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10). Conclusion: For patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.

Association of bilateral inferior vena cava with azygos and hemiazygos continuation and aortic coarctation in a child

Introduction. Developmental variations of the inferior cava vein (IVC) rarely cause symptoms, and they were detected during routine examinations performed for other reasons. The prevalence in the general population is between 0.07% and 8.7%. Various anomalies of the IVC can be seen depending on abnormal regression or abnormal persistence of embryonic veins. They are usually associated with more complex intracardiac and atrioventricular septal defects, partial anomalous pulmonary venous connection, and pulmonary atresia. Case Outline. We presented the 18th-month-old patient with double IVC, IVC interruption, azygos, and hemiazygos continuation associated with aortic coarctation. The vein malformation was discovered during percutaneous balloon angioplasty of the aortic re-coarctation and confirmed by using cross-sectional imaging modalities. Our patient had no symptoms of IVC malformation. Conclusion. In clinical practice, double IVC should be suspected in patients with recurrent pulmonary emboli. Another important point in practice is the identification of those anomalies to avoid potential complications of retroperitoneal surgery and cannulation during cardiac surgery

Low-dose thrombolytic therapy versus unfractionated heparin in patients with intermediate-high risk pulmonary embolism.

Patients with intermediate-high risk pulmonary embolism (PE) who have acute right ventricular dysfunction and myocardial injury without overt hemodynamic compromise may be candidates for thrombolytic therapy (TT). In this study, we aimed to compare the clinical outcomes of low-dose prolonged TT and unfractionated heparin (UFH) in intermediate-high risk PE patients. This study enrolled 83 (female: 45 [54.2%], mean age: 70.07±10.7 years) retrospectively evaluated patients with the diagnosis of acute PE who were treated with low-dose and slow-infusion of TT or UFH. The primary outcomes of the study were de-fined as a combination of death from any cause and hemodynamic decompensation, and severe or life-threatening bleeding. Secondary endpoints were recurrent PE, pulmonary hypertension, and moderate bleeding. The initial management strategy of intermediate-high risk PE was TT in 41 (49.4%) patients and UFH in 42 (50.6%) cases. Low-dose prolonged TT was successful in all patients. While the frequency of hypotension decreased significantly after TT (22 vs. 0%, P<0.001), it did not decrease after UFH (2.4 vs. 7.1%, p=0.625). The proportion of hemodynamic decompensation was significantly lower in the TT group (0 vs. 11.9%, p=0.029). The rate of secondary endpoints was significantly higher in the UFH group (2.4 vs. 19%, P=0.016). Moreover, the prevalence of pulmonary hypertension was significantly higher in UFH group (0 vs. 19%, p=0.003). Prolonged TT regimen with low dose, slow infusion of tissue plasminogen activator was found to be associated with a lower risk of hemodynamic decompensation and pulmonary hypertension in patients with acute intermediate-high-risk PE compared to UFH.

Antithrombotic treatment after intracerebral hemorrhage: Surveys among stroke physicians in Scandinavia and the United Kingdom.

It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. We conducted three web-based surveys among stroke physicians in Scandinavia and the United Kingdom. Eighty-nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. Considerable proportions of stroke physicians in Scandinavia and the United Kingdomwere uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials.

CTEPH: A Kaiser Permanente Northern California Experience

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening form of pulmonary hypertension and the only potentially curable form of the World Health Organization Pulmonary Hypertension classes. Thus, the prompt and accurate diagnosis of this condition is imperative. Despite widespread chronic symptoms following acute pulmonary embolism (PE), the condition is rarely considered, and an externally validated inexpensive diagnostic algorithm is lacking. MethodsA long-term, retrospective cohort study was conducted to assess the incidence of CTEPH following acute PE in a real-world study population. Additional data were collected regarding the practice patterns of diagnostic testing and imaging, particularly in patients with persistent or recurrent symptoms. Amongst diagnosed CTEPH patients, previously established risk factors were evaluated for degree of risk and commonly used diagnostic tests (electrocardiogram [ECG] right ventricular hypertrophy [RVH] pattern, B-type natriuretic peptide [BNP] elevations) employed during this period were evaluated and assessed for feasibility as screening tests. The study population was obtained from the MAPLE study cohort, comprised of patients presenting with acute PE in 21 community medical centers across the Kaiser Permanente Northern California system from January 2013 to April 2015. Diagnosis of CTEPH was confirmed via pulmonary vascular imaging (ventilation/perfusion [V/Q] scanning, computed tomography angiography, pulmonary angiography) and diagnostic right heart catheterization (RHC). Probable diagnoses were defined as a combination of suggestive echocardiographic and RHC findings. Additional inclusion criteria included age (≥18 years) with at least 2 years follow up and no previous diagnosis of CTEPH or PE during the prior 30 days. ResultsThere were 1973 patients who met inclusion criteria (mean age 62.4 years). Despite 75 % of patients developing symptoms consistent with CTEPH >3 months following acute PE, only 5.6 % of these symptomatic patients underwent V/Q scanning. There was overall a very low cumulative incidence of CTEPH (2.3 %), which was significantly higher amongst patients with symptoms compared to those without symptoms. When controlled for confounding in the multivariate analysis, only recurrent PE (HR 19.3, P < 0.001) and pulmonary artery systolic pressure >50 mmHg (HR 10.4, P < 0.001) were statistically significant predictors of CTEPH. Of the non-invasive diagnostic tests, ECG criteria for RVH were found to be poorly sensitive (2.6 %), but very specific (98.8 %) for CTEPH. Elevated levels of BNP alone were more sensitive than RVH ECG criteria (76.3 %) but poorly specific (44.4 %). ConclusionsThe diagnosis of CTEPH is uncommonly made following acute PE. Despite the frequency of persistent symptoms consistent with CTEPH following acute PE, the appropriate diagnostic work-up is rarely undertaken as evidenced in this cohort. This suggests that CTEPH is underappreciated and rarely considered, likely underestimating the true incidence in this cohort. Future studies are needed to elucidate the true prevalence of CTEPH and further investigate both the optimal diagnostic tools and timing of appropriate screening. These discoveries may help guide future development of diagnostic algorithms that can effectively rule out and accurately identify this potentially curable disease in a timely manner.

Rivaroxaban plus aspirin versus acenocoumarol to manage recurrent venous thromboembolic events despite systemic anticoagulation with rivaroxaban

IntroductionThe evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban. Materials and methodsThe study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events. ResultsA total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group – two DVTs and one ischemic stroke – and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008–2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005–1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group. ConclusionsIn this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.