High-Risk Pulmonary Embolism: A Second Opportunity for Thrombolysis

OUTCOMES FROM CATHETER-DIRECTED EMBOLECTOMY VERSUS SURGICAL PULMONARY EMBOLECTOMY FOR PATIENTS WITH ACUTE PE

This study describes the use of retrievable IVC filters in a select group of trauma patients at high risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). Retrievable IVC filters were placed in selected trauma patients who met high-risk criteria for deep vein thrombosis and PE according to institutional clinical management guidelines. All filters were placed percutaneously in the interventional radiology suite. Indications for filter placement were based on injury complex, weight-bearing status, and contraindications to enoxaparin or pneumatic compression devices. IVC filters were either removed or maintained. Retrievable IVC filters were placed in 35 patients after blunt trauma. Twenty-six patients (74%) sustained at least one orthopaedic injury; 17 patients (49%) were diagnosed with a pelvis fracture. Activity was limited to bed rest or spinal precautions in 18 patients (51%). Enoxaparin was contraindicated in 32 patients (91%) and injuries precluded the use of pneumatic compression devices in 11 (31%). IVC filters were removed in 18 patients (51%), with no reported complications. Patients with orthopaedic injuries and pelvis fractures were less likely to have their filters maintained (p = 0.040). Retrievable IVC filters offer a versatile option for prophylaxis in trauma patients at high risk for PE. Filter retrieval potentially spares the longterm complications of permanent filters in younger trauma patients. Retrievable filters warrant consideration in patients who meet high-risk criteria for deep vein thrombosis or PE who cannot receive effective mechanical prophylaxis and in whom contraindications to anticoagulation are expected to be temporary.

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

The exhaled end-tidal CO2/O2 ratio and the D-dimer concentration are diagnostic markers of pulmonary embolism (PE). To develop a non-invasive technique to monitor for PE in surgical patients. We examine the change imparted by anaesthesia-surgery on the end-tidal CO2/O2 compared with the D-dimer. We enrolled 125 participants undergoing an orthopaedic or oncological operation thought to confer high risk for postoperative PE. We obtained preoperative blood samples in the anaesthesia clinic, and breath samples in the preoperative holding area on the same day of surgery; we repeated blood and breath samples on the postoperative day of discharge. Blood samples were immediately analysed for fibrinogen and D-dimer (Vidas; bioMérieux, Durham, NC, USA) concentrations. Breath samples were obtained from 1 min of spontaneous tidal breaths delivered via mouthpiece while the participant breathed room air. All participants had follow-up at 30 days. We enrolled 125 participants and had complete data in 104. No participant developed PE or deep venous thrombosis within 30 days. The mean preoperative D-dimer was 927 +/- 928 ng ml(-1), and the mean postoperative D-dimer was 1879 +/- 1263 ng ml(-1) and the mean relative change was +234 +/- 292%. The mean preoperative end-tidal CO2/O2 was 0.31 +/- 0.05 and the mean postoperative end-tidal CO2/O2 was 0.32 +/- 0.07 and the mean relative change was +1.6 +/- 20%. The increase in D-dimer did not correlate with the increase in fibrinogen (r2 = 0.015). The stress impact of anaesthesia-surgery causes less change in end-tidal CO2/O2 compared with the D-dimer. Further work will be required to determine if end-tidal CO2/O2 can be used to monitor for postoperative PE.

Background: Anticoagulation therapy (ACT) remains the cornerstone of acute pulmonary embolism (PE) management and reduces the mortality risk to <1% in low-risk PE. However, AC is inadequate in intermediate and high-risk acute PE, thus requiring additional therapies. So, there has been a search for better advancement in therapeutic approaches, including catheter-directed thrombolysis (CDT) or thrombectomy, surgical embolectomy (SE), or mechanical thrombectomy (MT). We performed this network meta-analysis to analyze the outcome of different therapeutic approaches for acute intermediate and high-risk PE. Method: We conducted a Bayesian network meta-analysis to synthesize direct and indirect evidence from pertinent studies published until May 2024 using PubMed, Embase, and Scopus databases comparing different therapies for intermediate and high-risk PE patients. This study is registered with PROSPERO, and data analysis was performed using the “BUGSnet” package in R. Result: This analysis included 1,639,413 patients with intermediate or high-risk PE from 72 studies. The probability of CDT being ranked highest was for short-term mortality (catheter-directed intervention: 93), long-term mortality (Ultrasound-assisted Thrombolysis (USAT): 86.17), major bleeding (USAT: 85.58), and intracranial hemorrhage (USAT: 86.06) whereas surgical embolectomy for any and gastro-intestinal bleedings (93.76 and 78.7) respectively. The risk of short-term mortality and intracranial hemorrhage were lower among the patients treated with USAT [(OR: 0.38, CrI: 0.17 to 0.81) and (OR: 0.27, CrI: 0.10 to 0.69)] than those treated with AC only and MT in a random effects model. Conclusion: Based on the findings of this network meta-analysis, compared to other advanced PE management modalities, catheter-based interventions, especially ultrasound-assisted thrombolysis, could potentially reduce short and long-term mortality risk without increasing bleeding risk.

We hypothesized that ultrasound-assisted thrombolysis (USAT) is non-inferior to surgical pulmonary embolectomy (SPE) to improve right ventricular (RV) function in patients with acute pulmonary embolism (PE). In a single-centre, non-inferiority trial, we randomly assigned 27 patients with intermediate-high or high-risk acute PE to undergo either USAT or SPE stratified by PE risk. Primary and secondary outcomes were the baseline-to-72-h difference in right-to-left ventricular (RV/LV) ratio and the Qanadli pulmonary occlusion score, respectively, by contrast-enhanced chest-computed tomography assessed by a blinded CoreLab. The trial was prematurely terminated due to slow enrolment. Mean age was 62.6 (SD 12.4) years, 26% were women, and 15% had high-risk PE. Mean change in RV/LV ratio was -0.34 (95% CI -0.50 to -0.18) in the USAT and -0.53 (95% CI -0.68 to -0.38) in the SPE group (mean difference: 0.152; 95% CI 0.032-0.271; Pnon-inferiority = 0.80; Psuperiority = 0.013). Mean change in Qanadli pulmonary occlusion score was -7.23 (95% CI -9.58 to -4.88) in the USAT and -11.36 (95% CI -15.27 to -7.44) in the SPE group (mean difference: 5.00; 95% CI 0.44-9.56, P = 0.032). Clinical and functional outcomes were similar between the 2 groups up to 12 months. In patients with intermediate-high and high-risk acute PE, USAT was not non-inferior when compared with SPE in reducing RV/LV ratio within the first 72 h. In a post hoc superiority analysis, SPE resulted in greater improvement of RV overload and reduction of thrombus burden.

Background The effectiveness of catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) has been rarely investigated in subgroups of patients at a higher risk of complications. Furthermore, this group of patients has been excluded from prior and ongoing phase 3 trials with CDT. Purpose To assess the efficacy and safety of catheter-directed thrombolysis for pulmonary embolism among specific patient subpopulations. Material and methods We conducted an individual patient-level analysis of patient data from 16 cohort studies and randomized trials of CDT for intermediate- and high-risk acute PE. Studies were identified on the basis of a systematic review of the literature. We focused on early clinical outcomes, including haemodynamic decompensation, intracranial bleeding, major bleeding, and death, as well as on the changes in the mean pulmonary artery pressure (mPAP) before and after CDT. We predefined three subgroups of at-risk patients: (i) older age (i.e. ≥75 years), (ii) active cancer, and (iii) surgery in the prior 4 weeks. Results We studied 1244 patients, of whom 586 (47.1%) were women. The median age was 61 (Q1-Q3; 50-71) years. There were 202 (16.3% of total available) patients aged 75 years or older, 101 (10%) with active cancer, and 108 (14.8%) with prior surgery. A total of 946 (89.3%) patients had intermediate-risk PE, and 113 (10.7%) were classified in the high-risk group. Patients aged ≥75 years more frequently suffered haemodynamic decompensation (7.5% vs 1.6% aged <75 years; p< 0.001), major bleeding (12.7% vs 4.5%; p<0.001), and death (9.2% vs 2.2%; p<0.001); Table 1. In a multivariable logistic regression model, age remained associated with death, major bleeding, and haemodynamic decompensation after adjustment for a key prognostic factor (high-risk PE). The same, except for decompensation, was observed after conditioning for sex, high-risk PE, and cancer status. Patients with active cancer showed a tendency to a higher 30-day case fatality when compared with patients with no active cancer, without reaching statistical significance; Table 1. Recent surgery did not appear to influence the outcome rate in this cohort. No differences were found among the three subgroups regarding the reduction of the mPAP following CDT ; Table 2. Conclusions Our results point to age as a strong predictor of early mortality and decompensation in patients undergoing CDT, even after adjusting for the higher rate of high-risk PE in the elderly. The clinical net benefit of CDT in the elderly when accounting for bleeding and the risk of haemodynamic decompensation remains unclear.Efficacy and safety outcomes of CDTmPAP values before and after CDT

Background Increased right ventricular (RV) dilation measured by the ratio of RV diameter (RVD) to left ventricular (LV) diameter (LVD) (RV:LV) is associated with pulmonary embolism (PE) severity and mortality. Data regarding the individual contributions of RVD and LVD are limited. Purpose To examine RVD and LVD as independent contributors to death or need for cardiopulmonary resuscitation (CPR) in intermediate- or high-risk PEs treated with surgical or catheter-based strategies Methods We measured basal RVD and LVD on presenting transthoracic echocardiograms (TTE) using the diastolic 4-chamber view on 127 PEs managed with surgical embolectomy (n=95, 75%), extracorporeal membrane oxygenation (n=23, 18%), or catheter-directed embolectomy (n=9, 7%) for intermediate- (64%) or high-risk (36%) PE (based on European Society of Cardiology criteria) between 2005 and 2022. The primary outcome was the composite of death (n=2) or survivors requiring CPR (n=10). Results A total of 127 patients were analyzed. Subjects were 57±14 years, 38% women, BMI 34±8. Mean RVD and LVD were 4.4±0.9 cm and 3.9±0.8 cm respectively. All presented with severe RV dysfunction on TTE and elevated cardiac biomarkers (Troponin-I or B-type natriuretic peptide). Mean RV:LV was 1.2±0.3 (range 0.7 to 2.8). Using logistic regression, higher RV:LV was associated with increased odds of death or CPR (odds ratio (OR) 15 [95% confidence interval (CI): 2.5, 82] per 1-unit increase, p=0.002. RV:LV >1.2 was the cutoff most associated with death or CPR, OR 7.2 [95% CI: 1.5, 34.5], p=0.01. Increasing RVD [OR 3.8 (95% CI: 1.1, 12.8), p=0.03] and decreasing LVD [OR 4.9 (95% CI: 1.3, 16.9), p=0.02] were independent predictors of death or CPR. RVD >5.0 cm (OR 5.9 [95% CI: 1,5, 23.2], p 0.01) and LVD <3.6 cm (OR 7.0 [95% CI: 1.7, 27.9], p=0.006) were the cutoff values most associated with the primary outcome. These cutoff values remained significant predictors even after adjustment for body surface area. Other parameters or RV size and function (diastolic area, systolic area and fractional area change) did not predict death or CPR. All of the subjects meeting the primary outcome had high-risk PE. Discussion In addition to RV:LV greater than 1.2, RVD and LVD were independently associated with death or CPR among high- or intermediate risk PEs. The independent contribution of declining LVD on PE mortality is a novel finding and highlights PE associatient LV pathophysiology (hyperdynamic and underfilled) antecedent to hemodynamic collapse. PE literature focuses on RV dilation as a predictor of PE mortality. LVD may represent a useful measure to risk stratify PE patients and predict hemodynamic decompensation. Funding Acknowledgement Type of funding sources: None.

Pulmonary embolism (PE) remains a significant cause of cardiovascular mortality. Despite advancements in diagnosis and treatment, gender disparities in high-risk PE management and outcomes remain poorly understood. This study aimed to investigate gender-based differences in the presentation, treatment, and outcomes of patients with high-risk PE. We analyzed data from the National Inpatient Sample for patients with high-risk PE from 2016 to 2021. High-risk PE was defined as PE with cardiogenic shock, mechanical ventilation, mechanical circulatory support, or vasopressors. Multivariable logistic regression was used to examine gender-based differences in management and outcomes. Of 45,140 patients with high-risk PE, 51.4% were female. Female patients were older (mean age 65.2 vs. 63.4 years, p < 0.001) and more likely to present with cardiac arrest (35.4% vs. 30.4%, p < 0.001). After adjustment, females were more likely to receive systemic thrombolysis (aOR 1.17, 95% CI 1.11–1.23, p < 0.001) but less likely to undergo catheter-directed embolectomy (aOR 0.92, 95% CI 0.86–0.99, p = 0.034) or surgical embolectomy/thrombectomy (aOR 0.83, 95% CI 0.73–0.93, p = 0.002). Female patients experienced higher risk of all-cause mortality (aOR 1.22, 95% CI 1.18–1.27, p < 0.001) and major adverse cardiovascular and cerebrovascular events (aOR 1.21, 95% CI 1.16–1.25, p < 0.001). Significant gender disparities exist in the management and outcomes of high-risk PE. Female patients have higher mortality rates despite being more likely to receive systemic thrombolysis. Further research is needed to understand and address these disparities to improve outcomes for all patients with high-risk PE.

Background Implication of rapid-response teams have demonstrated significant improvement in several cardiovascular diseases, such as myocardial infarction and stroke. Thus, pulmonary embolism (PE) response teams (PERT) for the management of high-risk PE are encouraged in the guidelines. Purpose We aimed to assess the impact of a PERT initiative on hospital mortality. PERT was designed to manage patients with bilateral PE with RV/LV ratio &amp;gt;0.9 and positive biomarkers. Methods We prospectively recruited all consecutive patients with intermediate-high and high-risk bilateral PE who required PERT activation from February-2018 to September-2019 (PERT group, n=56 patients). We compared them with patients with bilateral PE admitted to our hospital in a previous 2-year period (2014–2016), managed with standard of care (SC-group, n=172 patients). As a secondary analysis, we focused on patients with a RV/LV ratio&amp;gt;0.9 (n=52, in the SC-group; n=55, 98% in the PERT-group). Results Results are shown on Table. The SC-group had a lower risk profile at admission (lower PESI score, heart rate, and higher oxygen saturation), compared to PERT-group. The proportion of patients with RV enlargement on CT (RV/LV &amp;gt;0.9) was lower in the retrospective cohort (p&amp;lt;0.001). Peak Troponin I was significantly higher in the PERT-group (Table). Reperfusion treatment was more frequently needed in PERT patients. On the contrary, there was no difference in the use of vasopressors (5.8% vs 12.5%, p=0.098) and orotracheal intubation (4.1% vs 5.4%, p=0.689) between groups. In-hospital mortality was lower in the PERT-group in the whole cohort (Table) and much lower when considering patients with RV/LV ratio&amp;gt;0.9 (17.6% vs 1.8%, p=0.005). Conclusion PERT initiative is associated with a significant reduction in mortality compared to the standard of care in patients with bilateral high-risk PE. Funding Acknowledgement Type of funding source: None

The role of Pulmonary Artery Pulsatility Index to assess the outcomes following catheter directed therapy in patients with intermediate-to-high and high-risk pulmonary embolism.

PurposeTo provide insight into the current use and results of ultrasound-facilitated catheter-directed thrombolysis (USAT) in patients with high-risk pulmonary embolism (PE).IntroductionSystemic thrombolysis is an effective treatment for hemodynamically unstable, high-risk PE, but is associated with bleeding complications. USAT is thought to reduce bleeding and is therefore advocated in patients with high-risk PE and contraindications for systemic thrombolysis.MethodsWe conducted a retrospective cohort study of all patients who underwent USAT for high-risk PE in the Netherlands from 2010 to 2017. Characteristics and outcomes were analyzed. Primary outcomes were major (including intracranial and fatal) bleeding and all-cause mortality after 1 month. Secondary outcomes were all-cause mortality and recurrent venous thromboembolism within 3 months.Results33 patients underwent USAT for high-risk PE. Major bleeding occurred in 12 patients (36%, 95% CI 22–53), including 1 intracranial and 3 fatal bleeding. All-cause mortality after 1 month was 48% (16/33, 95% CI 31–66). All-cause mortality after 3 months was 50% (16/32, 95% CI 34–66), recurrent venous thromboembolism occurred in 1 patient (1/32, 3%, 95% CI 1–16).ConclusionsThis study was the first to describe characteristics and outcomes after USAT in a study population of patients with high-risk PE only, an understudied population. Although USAT is considered a relatively safe treatment option, our results illustrate that at least caution is needed in critically ill patients with high-risk PE. Further research in patients with high-risk PE is warranted to guide patient selection.

Aim. To compare the PESI and GRACE scores in assessing the risk of hospital outcomes in patients with pulmonary embolism.Material and methods. The study included 383 patients with pulmonary embolism (PE), hospitalized during the period of April 4, 2003 on September 18, 2014; 190 (49,6%) are men, the average age is 57,4 years±14,4 years. We considered the patient’s anamnesis, complaints, results of biochemical and instrumental tests, as well as the treatment carried out to the patients.Results. According to the risk stratification of PESI score, 86 (22,5%) patients had a very low risk of death, 88 (22,9%) had a low risk, 94 (24,5%) had an intermediate risk, 60 (15,%) — high risk and 55 (14,4%) patients have a very high risk. The combination of three ECG signs (SI-QIII, right bundle branch block and T-wave inversion in V1-V3) was significantly more common in patients with a very high PE risk — 14,5% (p=0,025). The most reliable sign of the most echographic (echoCG) criteria was dilatation of right ventricle (RV) (p=0,009) in a group of patients with a very high PE risk. According to the GRACE scale, 112 (29,2%) patients were assigned to the low risk group, and 271 (70,8%) patients — to the high risk group. ECG signs were observed more frequently in the high risk group: SI-QIII, T-wave inversion in III, V1-V3 leads, right bundle branch block (p&lt;0,05). Pulmonary hypertension and RV dilatation according to echoCG prevailed in the high risk group (98,4% and 85,1%, respectively), p&lt;0,05. The minimum value of points on the GRACE score for the deceased patients was 118 points. The GRACE scale showed high predictive ability with a sensitivity of 96% and a specificity of 63% (AUC=0,811, CI 95% 0,0738-0,884). However, the PESI score had a slightly greater predictive value with a sensitivity of 100% and a specificity of 53% (AUC=0,879 compared with AUC=0,811 for the GRACE scale). Analysis of the PESI and GRACE scores showed a moderate correlation between them (r=0,668).Conclusion. The GRACE score showed a high predictive value for adverse outcomes in PE patients with a sensitivity of 96% and a specificity of 63%. The minimum score on the GRACE score for deceased patients was 118 points.

Background: Catheter-Directed Interventions (CDIs) for Acute Pulmonary Embolism (PE) have been available for years. However, their use and effectiveness in patients with a concomitant diagnosis of liver cirrhosis is uncertain due to a paucity of data in this high-risk population. In this study, we aim to evaluate the safety, efficacy, and current trends in the use of CDIs for high-risk PE (HR-PE) in patients with liver cirrhosis. Methods: Nationwide Readmissions Database (2016-2021) was used to identify patients with liver cirrhosis presenting with HR-PE (shock, pressor or mechanical circulatory support requirement). Patients who received systematic thrombolysis were excluded. Mahalanobis Distance Matching within the Propensity Score Caliper was used to match patients who received CDIs vs those who did not recieve any catheter-directed intervention. Inverse Probability weighting (IPW) was utilized, and Pearson’s chi-squared test was applied to the PSM-2 matched cohorts to compare outcomes. Results: Among 427,802 hospitalizations of patients with HR-PE and concomitant diagnosis of liver cirrhosis, only 1,319 (0.3%) of the patients underwent CDI. After propensity matching (N: 668 in each group), patients receiving CDI had a significantly lower mortality (42.9% vs. 61.7%, aOR:0.44, p &lt;0.001). However, bleeding complications including major bleeding (12.1% vs 5.4%, aOR:1.9, p&lt;0.001), thoraco-respiratory bleeding (8.5% vs 3.3%, aOR:1.9, p &lt;0.001) and intracerebral hemorrhage (5.1% vs 1.8%, aOR:2.3, p:0.001) was higher in patients receiving CDIs. Short-term (30-day) readmission rates were lower in cirrhotic patients receiving CDI (12.4% vs 18.8%, p: 0.024). From 2016-2021, mortality associated with HR-PE in cirrhotic patients has not changed significantly (mean: 61.2%, p &gt;0.05). There has been increasing use of mechanical thrombectomy (MT) over thrombolysis in recent years (0.08% to 0.22%, p-trend &lt;0.001). Conclusion: CDIs for HR-PE in patients with liver cirrhosis are rare and areassociated with significant reduction in mortality at the expense of higher bleeding risk. Despite a slight increase in the utilization of mechanical thrombectomy, mortality has not significantly decreased over the years.

Background/Objectives: Pulmonary embolism (PE) is a major cause of cardiovascular mortality, particularly in high-risk cases complicated by hemodynamic instability. Systemic thrombolysis is the recommended treatment in such settings; however, the coexistence of thrombocytopenia represents a major therapeutic challenge due to concerns regarding bleeding risk. Evidence guiding thrombolytic therapy in thrombocytopenic patients with PE is limited. This study aimed to present a representative case and review the available literature addressing thrombolysis in PE complicated by thrombocytopenia. Methods: A qualitative review of published case reports was conducted using the PubMed and Scopus databases, and articles describing adult patients with objectively confirmed PE, documented thrombocytopenia, and treatment with thrombolytic therapy were included. Eight case reports met the inclusion criteria, and the clinical characteristics, severity markers, platelet dynamics, treatment strategies and outcomes were analyzed and compared with the reported case. Results: Most of the reported patients presented with high-risk pulmonary embolism, defined by hemodynamic instability, including shock or cardiac arrest. Thrombolysis was frequently administered despite platelet counts below conventional thresholds. Platelet levels at the time of thrombolysis varied widely, including cases of severe thrombocytopenia. Clinical and hemodynamic improvement was observed in most of the cases, while major bleeding complications were infrequent. The reported case demonstrated successful systemic thrombolysis with rt-PA in a postpartum patient with suspected heparin-induced thrombocytopenia and high-risk PE, without hemorrhagic events. Conclusions: Available evidence suggests that thrombolytic therapy may be a viable life-saving option in carefully selected thrombocytopenic patients with high-risk pulmonary embolism. Therapeutic decisions should prioritize clinical severity and hemodynamic status over platelet count alone, emphasizing individualized, multidisciplinary risk-benefit assessment.