Intermediate-high Risk Pulmonary Embolism Research Articles

Ultrasound assisted, catheter-directed thrombolysis for acute intermediate-high and high risk pulmonary embolism: focus on safety for oncological patients

Abstract Background Catheter-based revascularization procedures have been developed as an alternative to systemic thrombolysis or surgical embolectomy for intermediate-high and high risk pulmonary embolism (PE) patients with. Little is known about the outcomes of oncological patients, who are notably at higher bleeding risk, undergoing such procedure. Purpose The USAT IH-PE registry is a retrospective and prospective multicenter registry of patients treated with ultrasound-facilitated, catheter-directed thrombolysis. We sought to determine whether patients with active cancer experience more bleeding complications and need for transfusions. Methods: Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate–high-risk PE (86%), mostly female (57%), with a mean age of 63.7 ± 14.5 years. Most patients (77.8%) had a bilateral involvement of the main pulmonary arteries on CT scan and 9 patients (8.8%) had at least one prior episode of PE. 28.4% had active cancer. We compared the oncological and non-oncological subpopulations. The primary endpoints were bleeding complications (defined as BARC > IIIa) and need for transfusion. Results Overall, 12% of patients experienced bleeding complications, of which 4.9% were BARC ≥ 3. When comparing bleeding complications, defined as BARC > IIIa or the need for transfusion, no significant difference was found between patients with active cancer and those without (OR 0.61, 95% CI 0.01-6.62, p=1, and OR 2.43, 95% CI 0.61-9.48, p=0.18, respectively). Conclusions In the USAT IH-PE registry, where a significant proportion of patients have active cancer, no significant difference in bleeding complications was observed in these subjects. This finding confirms the safety of the procedure, even in a subpopulation traditionally considered at higher risk for bleeding.

Elective endovascular reperfusion therapies in intermediate-high risk pulmonary embolism after PERT assesment

Abstract Background The ideal management of patients with intermediate-high risk (IHR) pulmonary embolism (PE) is still unknown. A multidisciplinary approach by Pulmonary Embolism Response Teams (PERT) in combination with the advent of endovascular therapies sounds promising. Purpose Evaluate in-hospital events of elective endovascular reperfussion therapies in selected IHR PE patients after PERT assesment in a single center initial experience. Methods Analysis of consecutive patients with PE admitted from Jan/2017 to Jan/2024. The in-hospital evolution of an elective invasive strategy defined by an institutional PERT (since April/2021) in IHR PE patients was compared against the current standard of care (isolated anticoagulation and reperfusion only after hemodynamic collapse). Patients with limitations of therapeutic efforts due to comorbidities were excluded. Results 361 patients with PE were treated with 76 (21.1%) stratified as IHR. After excluding 14 patients due to limitations of therapeutic efforts (78±9.4 years; 64.3% active cancer), 62 were included for analysis. An elective endovascular treatment was performed in 20 (31.3%) patients; these were younger and with fewer comorbidities. However, they had more tachypnea, greater central distribution of thrombotic burden and signs of right ventricle overload assessed by flattening of the interventricular septum. Baseline characteristics, clinical presentation and management are described in table 1. Within the invasive group, endovascular reperfusion was performed with local thrombolysis (70%), aspiration thrombectomy (15%) or their combination (15%). During hemodynamic evaluation, hidden shock was detected in 42.9% (6/14), with improvements in cardiac index observed after reperfusion therapy (n=8; 2.1 vs. 2.5). Improvement was also observed in pulmonary artery systolic pressure (n=14, 56.9 vs. 37.1mmHg; p<0.001) and right ventricular function (n=15, TAPSE 16 vs. 22mm; p<0.001). Compared with the current standard of care, an elective invasive approach was associated with a shorter hospital stay (6.5 vs. 9 days; p=0.02), less hemodynamic collapse (0% vs. 19.1%; p=0.04), need for mechanical ventilation (0% vs. 19.1%; p=0.04) and in-hospital mortality (0% vs. 21.4%; p=0.04) without differences in the incidence of major bleeding (Fig 1). After multivariate logistic regression analysis, the mortality benefit persisted in favor of an invasive strategy (p=0.014). Conclusions An "elective" invasive strategy in selected patients with IHR PE after PERT assessment was safe and resulted in less major in-hospital cardiovascular events in a single-center initial experience. Although these results should be taken with caution given the limitations of this study (single-center, small observational sample), they are in line with recent reports and are the focus of ongoing large randomized clinical trials.Table 1

Routine use of ultrasound-assisted catheter-directed thrombolysis for the management of intermediate-high risk pulmonary embolism: a service evaluation project

Abstract Background Intermediate-high risk Pulmonary Embolism (PE) has considerable morbidity. Conservative management could be sub-optimal. Ultrasound-Assisted Catheter-Directed Thrombolysis (UACDT) is used in our centre for the routine management of this presentation. Purpose We assessed the procedure safety and short-term outcomes by reviewing locally performed procedures. Methods This is an observational retrospective cohort study, with a historic control group. Our centre is a District General Hospital (DGH) in the United Kingdom, and we receive referrals from local acute hospitals. Since the introduction of this service in June 2018 until November 2023, 129 patients (2 patients/month) received routine management with UACDT for intermediate-high risk PE. The controls are 75 acute PE patients of comparable risk classes, managed from January to December 2016. We assessed procedural and in-hospital outcomes including minor, major bleeding/complications and death. We also assessed Length of Stay (LoS) in hospital, recurrent Venous Thrombo-Embolism (VTE) and re-admission rates for recurrent PE at 30 days. Reduction of oxygen requirements and improved estimated systolic Pulmonary Artery Pressure (sPAP) post-procedure were assessed as surrogate measures. Continuous variables were analysed with a Mann-Whitney U test, and categorical variables with a Chi-square Test. Results Baseline demographics are listed in Table 1. Mean duration between CT Pulmonary Angiography (CTPA) and the UACDT procedure was 1.6 (±SD 1.4) days, including inter-hospital transfer. Only 6% (8/129) of UACDT cohort received ≤12 mg standard alteplase dose. In the control group, 4% (3/75) of patients received standard 100mg systemic thrombolysis. There was no significant difference in the rates of minor (p= 0.9), major bleeding/complications (p= 0.8), or death (p= 1.0) between both groups. There was also no significant difference in rates of recurrent VTE (p= 1.0) or re-admission within 30 days for PE (p=0.1) (Table 2). LoS in hospital data were ratified, to exclude inappropriate delays (e.g. physiotherapy requirements, etc). We used the date when the patient was declared medically fit for discharge, and no significant difference was noted (p= 0.2). This was confirmed with a regression analysis of UACDT treatment effect (p= 0.9, CI= -3.5 to 3.1). Nonetheless, there was a 25% reduction of median LoS in hospital from 8 days in the controls to 6 days with UACDT. The proportion of patients requiring O2 was also reduced from 69% (89/129) to 41% (54/129) on day 1 post-procedure. A significant reduction of the estimated sPAP by TTE post-procedure was detected by a mean of 10.4 (±SD 13.9) mmHg (p= <0.01). Conclusion UACDT is generally safe with low complications rate. Compared to the control group, there was a reduction in absolute deaths and median LoS in hospital. This can be secondary to the significant acute reduction of systolic pulmonary artery pressure identified.

Efficacy and safety of reduced-dose and slow-infusion intravenous alteplase regimen in patients with acute pulmonary embolism at intermediate-high-risk

Abstract Background In patients with intermediate-high-risk (IHR) pulmonary embolism (PE), full-dose systemic thrombolytic treatment (STT) has been documented to lower the risk of hemodynamic decompensation and mortality, at the expense of an elevated risk of life-threatening bleeding. In this study, we aimed to evaluate the safety of reduced-dose STT regimen while maintaining effective reperfusion. Methods This single-center study comprised 124 retrospectively evaluated patients (female 58.9 % and mean age 55.4+15.8 years) diagnosed with acute PE at IHR status in accordance with European Society of Cardiology (ESC) 2019 acute PE guidelines in whom intravenous (i.v.) alteplase treatments were utilized. Patients fulfilling at least one of the following criteria have been included in the study: systolic blood pressure ≤ 110 mm Hg, heart rate > 100 bpm, SaO2 < 90 % on room air, respiratory rate > 20 breaths per minute, or serum lactate > 2 mmol/L. Exclusion criteria were any contraindication for STT and symptom onset > 14 days. Standard protocol for initial STT was i.v. infusion of alteplase of 25 mg over 4-6 hours. After completion of the infusion, a second STT in the same manner if one of the following criteria were present; heart rate > 100 bpm, SaO2 < 90 % or signs of organ hypoperfusion. Results Syncope and concomitant deep vein thrombosis were documented in 27.4 % and 49.2 % of patients, respectively. Baseline vital measures were as follows; heart rate: 112 +16.6 bpm, systolic blood pressure: 123+14.9 mm Hg, SaO2: 89 % (85-93), serum lactate 2.35 (1.6-2.9) mmol/L. Median alteplase dose and infusion duration were 50 (25-50) mg and 6 (4-10) hours, respectively. There were significant improvements in clinical parameters, pulmonary thrombus burden, pressure strain and right ventricular size and function as assessed by computed tomography and echocardiography (p< 0.001 for all). Minor and major bleeding events occurred in 3.2 % and 4.8 % of patients, respectively. One major bleed was due to cerebellar hemorrhage, but did not require surgery and patient was discharged without sequela. There were 6 (4.8 %) in-hospital deaths in which 2 were attributed to major hemorrhages and 4 due to hemodynamic decompensation. Conclusion In patients with acute IHR PE, reduced-dose and slow-infusion i.v. alteplase regimen seems to be a clinically relevant and safe reperfusion alternative to full-dose STT protocols associated with well-known major bleeding risks.

Right ventricular-pulmonary artery coupling for prognostication in acute pulmonary embolism.

Acute pulmonary embolism (PE) increases pulmonary pressure and impair right ventricular (RV) function. Echocardiographic investigation can quantify this mismatch as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio. The aim of the study was to investigate the prognostic capabilities of TAPSE/PASP ratio in patients with acute PE. We utilized the RIETE registry to analyze consecutive hemodynamically stable PE patients. We used multivariable logistic regression analyses to assess the association between the TAPSE/PASP ratio and 30-day all-cause mortality across the strata of European Society of Cardiology (ESC) risk categories. We included 4,478 patients, of whom 1,326 (30%) had low-risk, 2,425 (54%) intermediate-low risk, and 727 (16%) intermediate-high risk PE. Thirty-day mortality rates were 0.7%, 2.3% and 3.4%, respectively. Mean TAPSE/PASP ratio was 0.65±0.29 in low-risk patients, 0.46±0.30 in intermediate-low risk, and 0.33±0.19 in intermediate-high risk patients. In multivariable analyses, there was an inverse association between TAPSE/PASP ratio and 30-day mortality (adjusted OR 1.32 [95%CI 1.14-1.52] per 0.1 decrease in TAPSE/PASP). TAPSE/PASP ratio below optimal cut-points was associated with increased mortality in low- (<0.40, aOR: 5.88; 95%CI:1.63-21.2), intermediate-low (<0.43, aOR: 2.96; 95%CI:1.54-5.71) and intermediate-high risk patients (<0.34, aOR: 4.37; 95%CI:1.27-15.0). TAPSE/PASP <0.44 showed net reclassification improvement of 18.2% (95%CI:0.61-35.8) vs. RV/LV ratio >1, and 27.7% (95%CI:10.2-45.1) vs. ESC risk strata. Decreased TAPSE/PASP ratio was associated with increased mortality. The ratio may aid in clinical decision-making, particularly for intermediate-risk patients for whom the discriminatory capability of the current risk stratification tools is limited.

Bringing PERT to Pediatrics: Initial Experience and Outcomes of a Pediatric Multidisciplinary Pulmonary Embolism Response Team (PERT)

IntroductionMultidisciplinary Pulmonary Embolism Response Teams (PERTs) streamline care of adults with life-threatening pulmonary embolism (PE). Given rarity of pediatric PE, developing a clinical, educational, and research PERT paradigm is a novel and underutilized concept in pediatrics. Research QuestionIs PERT feasible in pediatrics, and does it improve PE care? Study Design and MethodsA strategy-to-execution proposal to launch a pediatric PERT was developed for institutional buy-in. Key stakeholders collectively implemented PERT. Data were collected for the two-year pre- and post-PERT eras, and outcomes were compared. ResultsPERT implementation took 12 months. Our PERT, led by hematology, comprises of pediatric experts in emergency medicine, critical care, interventional cardiology, anesthesiology, and interventional radiology. Data on 30 patients pre-PERT and 31 post-PERT were analyzed. Pre-PERT, 10%(3/30), 13%(4/30), 20%(6/30), and 57%(17/30), and post-PERT, 3%(1/31), 10%(3/31), 16%(5/31), and 71%(22/31) were categorized as high-risk, intermediate-LOW risk, intermediate-HIGH risk, and low-risk PE, respectively. Post-PERT, there were 13 unique PERT activations. PERT was activated on all eligible PE patients and, additionally, on four low-risk PEs. Time-to-echocardiogram was shorter post-PERT (4.7 hrs vs 2 hrs, P=0.0147). Anticoagulation was ordered (90 min vs 54 min, P=0.003) and given sooner (154 min vs 113 min, P=0.049) post-PERT. There were no differences in time-to-reperfusion therapies (12 hrs pre-PERT vs 8.7 hrs post-PERT, P=0.1). Five (83.3%) of six eligible (intermediate-HIGH and high-risk) patients received reperfusion therapies in the post-PERT era compared to three (37.5%) of eight eligible patients in the pre-PERT era (P=0.0001). There were no differences in major bleeding, mortality, or length of stay in either era. InterpretationThe pediatric PERT paradigm was successfully created and adopted locally. Our PERT enhanced access to experts, facilitated timely advanced therapies, and held value for low-risk PE. The University of Texas Southwestern Medical Center (UTSW) and Children’s Health System of Texas pediatric PERT may serve as a best-practice model for streamlining care for pediatric PE.

Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism.

In hemodynamically stable patients with acute pulmonary embolism (PE), the Composite Pulmonary Embolism Shock (CPES) score predicts normotensive shock. However, it is unknown if CPES predicts adverse clinical outcomes. The objective of this study was to determine whether the CPES score predicts in-hospital mortality, resuscitated cardiac arrest, or hemodynamic deterioration. Patients with acute intermediate-risk PE admitted from October 2016 to July 2019 were included. CPES was calculated for each patient. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. Secondary outcomes included individual components of the primary outcome. The association of CPES with primary and secondary outcomes was evaluated. Among the 207 patients with intermediate-risk PE (64.7% with intermediate-high risk PE), 29 (14%) patients had a primary outcome event. In a multivariable model, a higher CPES score was associated with a worse primary composite outcome (adjusted hazard ratio [aHR], 1.81 [95% CI, 1.29-2.54]; P=0.001). Moreover, a higher CPES score predicted death (aHR, 1.76 [95% CI, 1.04-2.96]; P=0.033), resuscitated cardiac arrest (aHR, 1.99 [95% CI, 1.17-3.38]; P=0.011), and hemodynamic decompensation (aHR, 1.96 [95% CI, 1.34-2.89]; P=0.001). A high CPES score (≥3) was associated with the worse primary outcome when compared with patients with a low CPES score (22% versus 2.4%; P=0.003; aHR, 6.48 [95% CI, 1.49-28.04]; P=0.012). CPES score provided incremental prognostic value for the prediction of primary outcome over baseline demographics and European Society of Cardiology intermediate-risk subcategories (global Χ2 value increased from 0.63 to 1.39 to 13.69; P=0.005). In patients with acute intermediate-risk PE, the CPES score effectively risk stratifies and prognosticates patients for the prediction of clinical events and provides incremental value over baseline demographics and European Society of Cardiology intermediate-risk subcategories.

The Predictive Value of Qanadli and Miller Index Scores in Patients with Intermediate-High–Risk and High-Risk Pulmonary Emboli Undergoing Aspiration Thrombectomy

PurposeTo evaluate the correlation between clot burden and pulmonary artery pressures in patients undergoing suction thromboembolectomy for high-risk and intermediate-high–risk pulmonary embolism with secondary outcomes of 30-day mortality and intensive care unit (ICU) length of stay. Materials and MethodsInstitutional review board (IRB) exemption was granted for this retrospective study. The charts of 120 consecutive patients who underwent mechanical thromboembolectomy using the Flowtriever system (Inari Medical, Irvine, California) between February 2020 and August 2022 were retrospectively reviewed, and the following data were collected: (a) preprocedural B-type natriuretic peptide and creatinine levels, (b) echocardiographic findings, (c) preprocedural and postprocedural pulmonary artery pressures, (d) ICU length of stay, and (e) 30-day mortality. Clot burden was scored using Qanadli and Miller indices and correlated with the clinical outcomes. ResultsOf the 120 patients who underwent thromboembolectomy, pulmonary artery pressures and diagnostic-quality angiograms were available in 109 patients. In the 109 patients with adequate data, Qanadli, preprocedural Miller, and postprocedural Miller scores correlated with pulmonary artery pressures. Neither was independently associated with ICU length of stay. Freedom from 30-day mortality was 91%, and embolism-specific mortality was 92%. All-risk and high-risk patients who survived demonstrated a significantly lower preprocedural and postprocedural Miller score, respectively. ConclusionsThrombus burden as measured by the Qanadli and Miller scores appeared to be correlated with pulmonary artery pressures. Furthermore, catheter-directed thromboembolectomy led to a reduction in Miller scores, which appeared to be correlated with a reduction in pulmonary pressures. In high-risk patients, a reduced postprocedural Miller score and pulmonary pressure demonstrated improved 30-day survival. Further investigation into the association between Miller scores and patient mortality is warranted to stratify patients who would benefit from emergency intervention.

Effect of Filtered Blood Return on Outcomes of Pulmonary Aspiration Thrombectomy

ObjectivesTo assess the effects of filtered blood reinfusion (FBR) on procedural outcomes of aspiration thrombectomy for pulmonary embolism (PE). Materials and MethodsA total of 171 patients who underwent aspiration thrombectomy for intermediate-high–risk or high-risk PE between December 2018 and September 2022 were included, 84 of whom underwent thrombectomy with FBR and 87 without. Demographic data, vital signs, laboratory values, procedural details, pulmonary arterial pressures, transfusion needs, length of hospital stay, and procedure-related adverse events were recorded. ResultsThe groups did not differ at baseline, other than the FBR cohort having a higher percentage of women. There was no significant difference in postprocedural vital signs or pulmonary arterial pressure. Mean fluoroscopy time and volume of contrast medium used were lower in the FBR cohort. The drop in hemoglobin level was lower in the FBR group at both 12 (FBR, −1.065; No FBR, −1.742; P > .001) and 24 hours (FBR, −1.526; No FBR, −2.380; P > .001) after procedure; accordingly, fewer patients required transfusions in the FBR cohort (FBR, 8 (9.5%); No FBR, 20 (23.0%); P = .016). There was no difference in the number or severity of adverse events or duration of intensive care unit or hospital admission. ConclusionsFBR use during aspiration pulmonary thrombectomy reduced blood loss and transfusion requirements but had no significant effect on procedural success or adverse event rates.

Assessment of lytic therapy effect in patients with intermediate-high risk pulmonary embolism for prevention of chronic thromboembolic pulmonary hypertension: A randomized, double-blind trial.

This study aims to compare the effectiveness of thrombolytic therapy and anticoagulation in preventing chronic thromboembolic pulmonary hypertension (CTEPH). A total of 60 patients with intermediate-high risk pulmonary embolism (PE) were randomly assigned to receive either thrombolytic therapy (n = 30) or anticoagulation (n = 30). Echocardiographic assessments demonstrated no significant differences between the two treatment approaches in terms of right ventricular size (RVS) (on discharge in thrombolytic group: 31.17 ± 3.43 vs. anticoagulant group: 32.73 ± 5.27, p = 0.912), tricuspid annular plane systolic excursion (TAPSE) (on discharge in thrombolytic group: 17.66 ± 2.39 vs. anticoagulant group: 16.73 ± 2.93, p = 0.290), and systolic pulmonary artery pressure (SPAP) (on discharge in thrombolytic group: 32.93 ± 9.73 vs. anticoagulant group: 34.46 ± 9.30, p = 0.840). However, significant changes were observed in all assessed parameters within each treatment group (p < 0.001). The 6-month follow-up showed no significant difference between the two groups in terms of CTEPH incidence (p = 0.781) or functional class of the patients (p = 0.135). Based on the findings of this study, neither thrombolytic therapy nor anticoagulation demonstrated superiority over the other in reducing adverse outcomes associated with intermediate-high risk PE, including right ventricular size, SPAP, TAPSE, or CTEPH.

Interventional therapy of pulmonary embolism - update

Several catheter-based systems have been developed for interventional recanalization of pulmonary embolism. These include local ultrasound assisted thrombolysis (EKOS), in-toto-thrombectomy via retriever and aspiration system (FlowTriever) and the Indigo mechanical aspiration system. Safety and efficacy in the removal of thrombus have been demonstrated for all systems. Interventional recanalization strategies for high- and intermediate-high risk pulmonary embolism are potentially more effective in the removal of thrombus and restoration of right heart function than systemic thrombolysis with a lower risk of major bleeding complications. Preliminary data from registries and observational studies are very promising whereas the evidence for systemic thrombolysis treatment in high and intermediate-high risk pulmonary embolism is low. Randomized controlled clinical trials are currently performed comparing catheter based interventional therapies to systemic thrombolysis for the treatment of intermediate-high risk pulmonary embolisms. Primary outcome measurements include mortality, hemodynamic collapse, and major bleedings. Results are expected in 2025. The introduction of interventional therapies for pulmonary embolism was accompanied by an increased awareness of the complexity of pulmonary embolism management. The need for specialized interdisciplinary pulmonary embolism response teams (PERT-teams) and a well-structured approach including a PDCA cycle was recognized.

Effectiveness and safety of half-dose thrombolysis in intermediate-high risk pulmonary embolism: a single centre experience

Abstract Funding Acknowledgements None. Introduction According to current guidelines, full-dose systemic thrombolysis for pulmonary embolism (PE) is limited to patients either classified as high risk or presenting intermediate risk with hemodynamically instability. As evidenced by recent clinical trials, "low" half-dose (50 mg) tissue plasminogen activator (HDrtPA) appears to offer a safe, effective alternative with a low bleeding risk, especially if catheter directed therapies are not available. Purpose we aimed to evaluate if HDrtPA in intermediate-high risk PE could improve right ventricular (RV)-arterial coupling by means of TAPSE/PAPs ratio, right ventricular basal dimensions in 4 chambers (RVD1), and tricuspid velocity (TV) between admission and discharge, exploring eventual associated bleeding risk. Methods we retrospectively analized 90 intermediate-high risk PE patients consecutively admitted to our intensive cardiac care unit between January 2016 and May 2023. Diagnosis was achieved by computed tomography in all cases. All patients underwent echocardiographic assessment upon admission and at discharge along with baseline lab values. HDrtPA patients (Group A, n=28) received low-dose thrombolytic therapy (0,6 mg/kg maximum 50 mg in 1 hour) combined with unfractionated heparin. Standard anticoagulation patients (Group B) included patients exclusively treated with parenteral anticoagulants. Primary endpoint was echocardiographic improvement of RV-arterial coupling (TAPSE/PAPS), and of pulmonary pressures (tricuspid velocity, TV) and right ventricular basal dimension (RVD1) between admission and dis-charge in the two treatment arms. To perform this analysis, linear regression models with Inverse Probability Weighting (IPW) propensity scores were used. Secondary endpoint was presence of mayor or minor bleeding between groups, and a descriptive analysis of mortality due to paucity of events. Results in the whole population mean age was 73.48 ± 12.49 (mean ± sd) and n=43 (47.8%) were males. Between admission and discharge, group A (HDrtPA) had an improvement of TAPSE/PAPs (+0.16, p=0.05, CI 95%: -0.002; 0.325), of RVD1 (-6.00 mm, p &amp;lt;0.01, CI 95%: -2.59; 9.41). Reduction of TV values (-0.45 m/s, p=0.108, CI 95%: -1.02; 0.10) was not statistically significant at IPW propensity score, but deserves further investigations. No significant increase of major bleedings were recorded between two groups (Group A: 1/28 3.5%, Group B: 0/52 0%) with an acceptable number of minor, non fatal bleedings (Group A: 7/28: 25%, Group B 1/62 1.6%). Death occurred in 3 patients in group A (10%) and 1 patient in group B (1.6%). Conclusion half dose of tissue plasminogen activator (HDrtPA) offer a promising alternative to anticoagulation alone therapy in selected patients with high-intermediate risk pulmonary embolism. In our experience, this approach seems to acutely improve RV-arterial coupling and right ventricular dimensions, without an increase of major bleeding risk.

Referral and outcomes of mechanical thrombectomy for pulmonary embolism - a single-centre experience

Abstract Funding Acknowledgements None. Introduction Acute pulmonary embolism (PE) is a significant cause of morbidity and mortality, and percutaneous catheter-based treatments have emerged as an effective treatment option alongside thrombolysis. However, data concerning long-term outcomes are scarce. Methods All patients referred to a tertiary centre for pulmonary angiography with the intent to perform mechanical thrombectomy in the context of acute PE between January 2016 and August 2023 were retrospectively included and clinical data and outcomes were collected. Results Fifty-two patients (58% female; mean age 66±18 years) were referred to pulmonary angiography in the setting of acute PE, of whom 40 patients (77%) underwent continuous aspiration mechanical thrombectomy with an overall success rate of 70%. Twenty-eight percent of patients had bilateral thrombus. Thirty-two patients had intermediate-high risk or high-risk PE, and the mean Pulmonary Embolism Severity Index (PESI) was 146 points. Thirteen patients (25%) underwent thrombolysis prior to angiography, while 15 patients (28%) had an absolute or relative contraindication for thrombolysis. Ventilation/perfusion scans were performed in ten patients (19%) during the follow-up period, of whom five patients (10%) had evidence of residual illness, with no significant differences between the thrombectomy and non-thrombectomy groups (p=0.8). The overall mortality rate over the complete follow-up period was 39%, while 25% of patients died within 48 hours of the procedure. Predictors of mortality on univariate analysis included older age (HR 1.06 [95% CI 1.00-1.11, p = 0.03]), history of chronic obstructive pulmonary disease (HR 3.88 [95% CI 1.41-10.69, p = 0.01]), history of previous deep vein thrombosis or PE (HR 3.40 [95% CI 1.34-8.63, p = 0.01]), thrombolysis prior to referral for mechanical thrombectomy (HR 5.94 [95% CI 1.93-18.26, p &amp;lt;0.01), shock or haemodynamic instability (HR 8.50 [95% CI 2.44-29,52, p &amp;lt;0.01]) and resuscitated cardiac arrest (HR 5.98 [95% CI 2.34-15.30, p &amp;lt;0.01]). On Cox multivariate analysis, the presence of shock or haemodynamic instability was a predictor of increased mortality (HR 5.23 [95% CI 1.12-24.3, p = 0.04]). Conclusions Intermediate and high risk acute PE is a clinical entity with a high morbidity and mortality rate regardless of treatment strategy, particularly during the index hospitalization and in patients with shock or haemodynamic instability.

Treatment of high- and intermediate-high-risk pulmonary embolism by the Pulmonary Embolism Response Team: Focus on catheter-directed therapies.

Multidisciplinary Pulmonary Embolism Response Teams (PERTs) were established to individualize the treatment of high-risk (HR) and intermediate-high-risk (IHR) pulmonary embolism (PE) patients, which pose a challenge in clinical practice. We retrospectively collected the data of all HR and IHR acute PE patients consulted by PERT CELZAT between September 2017 and October 2022. The patient population was divided into four different treatment methods: anticoagulation alone (AC), systemic thrombolysis (ST), surgical embolectomy (SE), and catheter-directed therapies (CDTx). Baseline clinical characteristics, risk stratification, PE severity parameters, and treatment outcomes were compared between the four groups. Of the 110 patients with HR and IHR PE, 67 (61%) patients were treated with AC only, 11 (10%) with ST, 15 (14%) underwent SE, and 17 (15%) were treated with CTDx. The most common treatment option in the HR group was reperfusion therapy, used in 20/24 (83%) cases, including ST in 7 (29%) patients, SE in 5 (21%) patients, and CTDx in 8 (33%) patients. In contrast, IHR patients were treated with AC alone in 63/86 (73%) cases. The in-hospital mortality rate was 9/24 (37.5%) in the HR group and 4/86 (4.7%) in the IHR group. The number of advanced procedures aimed at reperfusion was substantially higher in the HR group than in the IHR PE group. Despite the common use of advanced reperfusion techniques in the HR group, patient mortality remained high. There is a need further to optimize the treatment of patients with HR PE to improve outcomes.

Outcomes With Hybrid Catheter-Directed Therapy Compared With Aspiration Thrombectomy for Patients With Intermediate-High Risk Pulmonary Embolism.

Intermediate-high-risk pulmonary embolism (IHR PE) is a challenging form of embolism obstruction that causes right ventricular(RV) dysfunction. The optimal management of IHR PE has not been established. This single-center prospective, observational study aimed to evaluate the efficacy and safety of complex catheter-directedtherapy (CDT)-catheter-directed mechanical aspiration thrombectomy (CDMT) supplemented with catheter-directed thrombolysis (hybrid CDT)in comparison to CDMT alone for IHR PE. A propensity score based on the pulmonary embolism severity index class and Miller obstruction index (MOI) was calculated, and 21 hybrid CDT cases (mean age 54.8 (14.7) years, 9/21 women) were matched with 21 CDMT cases (mean age 58.8 (14.9) years, 13/21 women). The baseline demographics, clinical,and treatment characteristics were analyzed. No significant differences were detected regarding baseline demographics and PE severity parameters. Hybrid CDT demonstrated a higher reduction in mean pulmonary artery pressure (mPAP) (hybrid CDT: median mPAP reduction 8mmHg (IQR: 6-10mmHg) vs CDMT: median mPAP reduction 6mmHg (IQR: 4-7mmHg); P = 0.019), MOI score (hybrid CDT: median change - 5 points (IQR: 5-6 points) vs CDMT median change - 3 points (IQR: 3-5 points); P = 0.019), and median RV: left ventricular ratio (hybrid CDT: median change 0.4 (IQR: 0.3-0.45) vs CDMT median change 0.26 (IQR: 0.2-0.4); P = 0.007). No major bleeding was observed. Both the hybrid CDT and CDMT alone treatments are safe and effective in managing IHR PE. Hybrid CDT is a promising technique for the management of IHR PE with insufficient thrombus load reduction by CDMT. NCT0447356-registration date 16 July 2020.

Prognostic Role of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure Ratio for the Identification of Early Clinical Deterioration in Intermediate-High–Risk Pulmonary Embolism Patients

The ratio of tricuspid annular plane systolic excursion (TAPSE) to echocardiographically measured systolic pulmonary artery pressure (PASP) has been proposed as a surrogate of RV-arterial coupling. In this analysis, we assess the prognostic role of TAPSE/PASP for early clinical deterioration and short-term mortality in an often clinically challenging population of intermediate high-risk PE patients. A post-hoc analysis of intermediate-high risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (ClinicalTrials.gov: NCT01604538) was performed. All patients underwent a transthoracic echocardiography (TTE) at admission. The primary and secondary outcomes were clinical deterioration within 48 hours from admission and 30-day all-cause mortality, respectively. Among 422 intermediate high-risk PE patients (mean age 71.2±5.3 years, 238 males), 37 (8.7%) experienced clinical deterioration within 48 hours of admission. The 30-day mortality rate was 6.6% (n=28). Receiver operating characteristic analysis established 0.33 as the optimal cut-off value for the TAPSE/PASP in predicting 48-h clinical deterioration (AUC of 0.79 ± 0.1). Sensitivity, specificity, PPV and NPV were 81%, 88.5%, 40.5% and 97.9%, respectively. Multivariate Cox regression analysis showed that a TAPSE/PASP≤0.33 was an independent predictor of 48-h clinical deterioration (HR: 2.06, 95% CI 1.98-2.11, p<0.0001) and 30-day mortality (HR: 2.28, 95% CI: 2.25-2.33, p<0.001). TAPSE/PASP shows promise as a non-invasive prognostic predictor to identify intermediate-high risk PE patients at higher risk of early clinical deterioration and short-term mortality.

Effectiveness and Safety of Large-Bore Aspiration Thrombectomy for Intermediate- or High-Risk Pulmonary Embolism

PurposeTo evaluate effectiveness and safety of large-bore mechanical thrombectomy of intermediate- or high-risk pulmonary embolism (PE) and factors associated with effectiveness. Materials and MethodsA retrospective review of 257 patients with intermediate- or high-risk PE who underwent mechanical thrombectomy using the Flowtriever system (Inari Medical, Irvine, California) between July 2019 and November 2021 was conducted. Data were analyzed using the linear regression and Kaplan-Meier methods with a Type 1 error set at 0.05. ResultsPatients’ mean age was 62 years, and 51% were male. PE risk was classified as high, intermediate-high, and intermediate-low in 37 (14%), 201 (78%), and 18 (7%) of the patients, respectively. Procedural technical success was 100%. The mean pulmonary artery pressure (MPAP) decreased from a mean of 32 mmHg (SD ± 9) before to 24 mmHg (SD ± 9) after thrombectomy (mean decrease, 8 mmHg [SD ± 6]; P < .0001). Immediate complications occurred in 2% of the patients. Postprocedural 30-day and all-time PE-attributable mortality in a mean of 1.3-year follow-up was 2% and 6%, respectively. In multivariate analysis, the presence of lower extremity DVT at presentation (β ± SE, −7.60 ± 3.22; P = .019) and a higher prethrombectomy MPAP (β ± SE, −0.19 ± 0.04; P < .001) were associated with lower degrees of decrease in MPAP in the intermediate-high–risk PE group. Among 14 patients with postthrombectomy PE-attributable mortality, 13 had postthrombectomy MPAPs of >20 mmHg. ConclusionsLarge-bore aspiration thrombectomy is a safe and effective treatment for reducing PAP in patients with intermediate- or high-risk PE. Postthrombectomy MPAPs of >20 mmHg might indicate postthrombectomy PE-attributable mortality in high-risk patients.

Intermediate-high risk pulmonary embolism: When teamwork really matters

Pulmonary embolism is a common disease associated with significant morbidity and mortality. Existing validated risk stratification tools have enabled the rapid identification of patients with low versus high-risk pulmonary embolism. Intermediate-high risk pulmonary embolism is defined as pulmonary embolism with haemodynamic stability, evidence of right ventricular dysfunction and elevated cardiac biomarkers. The therapeutic management of intermediate-high risk pulmonary embolism in the acute setting is challenging as these patients are often unwell, but do not fulfil criteria for high-risk pulmonary embolism. Although current guidelines recommend prompt first-line treatment with systemic anticoagulation and monitoring for deterioration, alternative strategies are being increasingly considered in this cohort. These include systemic or catheter-directed thrombolysis, surgical embolectomy, and mechanical circulatory support. In this case series, we discuss three cases of intermediate-high risk pulmonary embolism with a focus on multidisciplinary decision making in clinical management. Following on from this, we provide a brief narrative review of the current literature and guidelines surrounding this topic, considering the risks and benefits of alternative therapy options on patient outcomes.

Optional therapeutic management of intermediate-risk pulmonary embolism patients

Background: Few studies have evaluated the thrombolytic treatment in patients with intermediate-high risk pulmonary embolism, making this study more valuable. Material and methods: It was a prospective, non-randomized, open-label, single-center study. Eligible patients at the age of 18 or older with an acute pulmonary embolism (PE) confirmed by CT pulmonary angiography with onset until 14 day and signs of right ventricular (RV) overload on echocardiography took part in the study. Pulmonary Arterial CT Obstruction Index Rate (PACTOIR) was used to define the localization and the expansion zone of thromboembolism. This study included 18 patients with intermediate risk and acute submassive pulmonary thromboembolism. In thrombolysis (TT) group (n=9) were used 50 mg of tissue-plasminogen activator (t-PA) administered in infusion as 0.4 mg/h for 2 hours. In the standard anticoagulation group, unfractioned heparin (UFH) was administered as a bolus of 70 units/kg or a maximum of 5000 units, followed by continuous infusion at an initial rate of 16 units/kg or a maximum of 1000 units/h. Results: The mean age for TT group was 69 vs 63 for the UFH group. PACTOIR was 100% in 3 patients in the half-dose rt-PA group and in 2 patients in the UFH group. RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p &lt; 0.0001). Mean pulmonary artery systolic pressure was 55 mm Hg in both groups (p &lt; 0.05), with 53 [43–60] in TT group vs. 41.5 [37–45] mmHg in UFH group, P&lt;0.05. Also, RV/ LV ratio and systolic PAP decreased significantly in both groups. Severe bleeding with a need in red blood cell transfusion was seen in 0.11% (1 patient) in the TT group vs 0 in UFH group. The hospitalization length of stay was significantly shorter in the TT group (3.8±1.8, p &lt; 0.05). The rate of secondary endpoints was significantly higher in the UFH group with a high rate of pulmonary hypertension (0 vs. 19%, p=0.003). Conclusions: Half-dose thrombolytic therapy in patients diagnosed with submassive pulmonary embolism significantly reduced death and hemodynamic decompensation in the first 7 days compared to anticoagulant therapy only. With all that being said, it can be concluded that patients with high-intermediate risk PE could benefit from reduced-dose TT.

Prognostic impact of the e-TAPSE ratio in intermediate-high risk pulmonary embolism patients.

We assess the prognostic role of a new index (Age-T index), based on age and the tricuspid annular plane systolic excursion (TAPSE) for the estimation of 30-day mortality and risk of 48-h clinical deterioration since admission, in intermediate-high risk Pulmonary Embolism (PE) patients. A post-hoc analysis of intermediate-high risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (Trial registry: ClinicalTrials.gov; No.: NCT01604538) was performed. The Age-T index was calculated as the ratio between age and TAPSE. The primary outcome was the 30-day mortality risk while the risk of clinical deterioration within 48h in the same patients was chosen as the secondary outcome. Among 450 intermediate-high risk PE patients (mean age 71.4 ± 13.8 years, 298 males), 40 (8.8%) experienced clinical deterioration within 48h since admission and 32 (7.1%) died within 30-day. Receiver operating characteristic analysis established ≥ 4.9 as the optimal cut-off value for the Age-T index in predicting 30-day mortality (AUC of 0.76 ± 0.1). Sensitivity, specificity, PPV and NPV were 81.2, 85.6, 30.2 and 98.3%, respectively. Multivariate Cox regression analysis showed that an Age-T index ≥ 4.9 predicts 30-day mortality (HR: 3.24, 95% CI: 1.58-4.96, p < 0.001) and was also associated with a significantly higher risk of 48-h clinical deterioration (HR: 2.02, 95% CI 1.96-2.08, p < 0.0001) in intermediate-high risk PE patients. Age-T Index appears as a useful, bed-side and non-invasive prognostic tool to identify intermediate-high risk PE patients at higher risk of death and/or 48-h clinical deterioration.