Intermediate-high Risk Pulmonary Embolism Research Articles

Management of acute pulmonary embolism with sequential hybrid therapy of surgical thrombectomy and rivaroxaban intensive therapy: a case report

Acute pulmonary embolism (PE) is often associated with rapid hemodynamic deterioration or death. Therefore, early therapeutic intervention is important. A 45-year-old man was diagnosed with intermediate-high risk PE, and sequential hybrid therapy consisting of surgical thrombectomy and rivaroxaban intensive therapy was administered. During the course of treatment, echocardiography revealed improvement in pulmonary artery systolic pressure, and thrombus volume analysis by computed tomography revealed a drastic reduction in the size of the thrombus. Sequential hybrid therapy for acute PE not only stabilizes hemodynamics, but may also prevent conversion to chronic thromboembolic pulmonary hypertension by sufficiently reducing the volume of the thrombus.

Pulmonary Reperfusion Injury After Catheter-Directed Thrombectomy for Acute Pulmonary Embolism

An 82-year-old man had catheter-directed thrombectomy for intermediate-high–risk pulmonary embolism. Shortly after the procedure, the patient developed new alveolar and interstitial infiltrates found on chest computed tomography (CT) as well as life-threatening hemoptysis, likely related to pulmonary reperfusion injury after thrombus removal. Pulmonary reperfusion injury after minimally invasive thrombectomy in acute pulmonary embolism is a rare and life-threatening complication and should be considered in the differential diagnosis of acute pulmonary hemorrhage syndromes.

Right ventricular function assessment by 3D echocardiography and 2D speckle-tracking imaging in acute pulmonary embolism

Objective: To assess changes in right ventricular (RV) function parameters determined by three-dimensional (3D) echocardiography and two-dimensional (2D) speckle-tracking echocardiography in patients with acute pulmonary embolism without systemic hypotension, as compare to a control population. Subject and method: Fifty-seven intermediate-high risk pulmonary embolism patients were prospectively studied at the onset of the acute episode and after median follow-up periods of 30 days. A control group of age-and sex-matched subjects were selected. All patients and the controls underwent 2D and 3D transthoracic echocardiography within 24 hours of pulmonary embolism diagnosis and one month after hospital discharge. Tricuspid annular peak systolic velocity (s’), tricuspid annular plane systolic excursion (TAPSE), RV diameter, RV fractional area change (FAC), 3D RV ejection fraction (EF), 2D RV global strain and RV free wall strain were measured. Result: From Dec. 2019 to March 2022, fifty-seven patients with acute intermediate-high risk of early mortality PE were included. Mean age was 56 ± 14 years. Men accounted for 47.4% (27/57). Control group consisted of 34 subjects. Pulmonary embolism patients initially had RV dysfunction as assessed by 2D and 3D parameters: RV diameter: 29.3 ± 4.6mm; TAPSE: 14.6 (9.1-15.7) mm; FAC: 31.5 (30.5-39.9)%; 3DRVEFL 31.9 ± 7.7%; RVGS: -9.8 ± 3%, RVFWS: -8.9 ± 3.3%. At 30-day follow-up: s’, TAPSE, RV diameter, RV FAC were restored compared to the control group, systolic pulmonary artery pressures decreased significantly, right atrial pressure, also decreased significantly at follow-up, contrary to 3DRVEF and RV 2D global strain and free wall strain. Conclusion: After 1 month of anticoagulant therapy in patients with intermediate-high risk pulmonary embolism, RV function has not fully recovered as assessed by 3D RVEF and 2D strain imaging, while the traditional echocardiographic assessment could not detect this incomplete recovery. Further studies are needed to assess the prognostic role and implications of this residual 3DRVEF and 2D RV strain impairment after PE.

Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism.

Evidence supporting interventional pulmonary embolism (PE) treatment is needed. We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE in a large real-world population. FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement. Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m2 mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001). Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.

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.

Prognostic value of echocardiographic indices in risk stratification of intermediate-risk pulmonary embolism

BackgroundRegarding risk stratification of intermediate-risk pulmonary embolism, data are still not sufficient. Transthoracic echocardiography parameters may be useful in risk evaluation in those patients. Some novel echocardiographic indices mainly tricuspid regurgitation peak gradient (TRPG), pulmonary artery acceleration time, and tricuspid annulus plane systolic excursion (TAPSE) were evaluated showing that they may be used for risk stratification of normotensive cases with acute pulmonary embolism (APE).ResultsThe studied cases were subdivided into two classes:Class I with intermediate-low-risk pulmonary embolism included 32 patients (53.3%) and class II with intermediate high-risk pulmonary embolism involved 28 cases (46.7%). Dyspnea, tachypnea, troponin level, RVD, RVD/LVD, TR velocity, and TRPG/TAPSE were statistically higher in cases of class II than that of class I (p < 0.001). On the other hand, TAPSE and PA acceleration time were markedly lower in the case of class II than that of class I (p < 0.001). Ten cases (35.7%) of group II required thrombolytic agents with a significant difference (p<0.001).ConclusionsRVD/LVD ratio, TAPSE, TRPG/TAPSE ratio, and PA acceleration time are echocardiographic parameters that might be helpful for risk stratification of cases with moderate-risk pulmonary embolism. The addition of elevated levels of cardiac troponins to imaging and clinical findings can improve PE-related risk identification.Trial registrationNCT04020250. Registered on 16 July 2019.

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.

Successful use of rivaroxaban achieving therapeutic anti-factor xa levels in a morbidly obese patient with acute intermediate-high risk pulmonary embolism.

Direct oral anticoagulants (DOACs) have become the standard of care for acute and long-term therapy for venous thromboembolism (VTE) due to their efficacy and safety profiles. The 2021 International Society on Thrombosis and Haemostasis guidelines recommend using standard DOAC dosages in patients with BMI >40 kg/m2 or weight >120 kg. Use of DOACs remains uncertain in morbidly obese patients with VTE, including acute PE. A morbidly obese woman in her 30s who presented with acute worsening of dyspnea was diagnosed with acute intermediate-high risk acute pulmonary embolism and concomitant proximal deep vein thrombosis, constituting a clinically challenging scenario for treating her with rivaroxaban. Standard doses of rivaroxaban for acute and extended phase treatment of venous thromboembolism in individuals with morbid obesity at BMI>70 kg/m2 may be effective, and safe.

Mean arterial pressure predicts 48 h clinical deterioration in intermediate-high risk patients with acute pulmonary embolism.

We assess the prognostic role of mean arterial pressure (MAP) for 48 h clinical deterioration in intermediate-high risk pulmonary embolism (PE) patients after admission. A post hoc analysis of intermediate-high-risk PE and intermediate-low-risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (Trial registry: ClinicalTrials.gov; No.: NCT01604538) was performed. Clinical deterioration within 48 h was defined as patient worsening from a stable to an unstable haemodynamic condition, need of catecholamine infusion, endotracheal intubation, or cardiopulmonary resuscitation. Of 450 intermediate-high risk PE patients (mean age 71.4 ± 13.8 years, 298 males), 40 (8.8%) experienced clinical deterioration within 48 h from admission. Receiver operating characteristic analysis established the optimal cut-off value for MAP, as a predictor of 48 h clinical deterioration, ≤81.5 mmHg [area under curve (AUC) of 0.77 ± 0.3] with sensitivity, specificity, positive predictive value, and negative predictive value were 77.5, 95.0, 63.2, and 97.7%, respectively. Multivariate Cox regression analysis showed that independent risk factors for 48 h clinical deterioration were age [hazard ratio (HR): 1.26, 95% confidence interval (CI): 1.19-1.28, P < 0.0001], history of heart failure (HR: 1.76, 95% CI: 1.72-1.81, P < 0.0001), simplified Pulmonary Embolism Severity Index (HR: 1.52, 95% CI: 1.49-1.58, P = 0.001), systemic thrombolysis (HR: 0.54, 95% CI: 0.30-0.65, P < 0.0001), and a MAP of ≤81.5 mmHg at admission (HR: 3.25, 95% CI: 1.89-5.21, P < 0.0001). The deteriorating group had a significantly higher risk of 30-day mortality (HR: 2.61, 95% CI: 2.54-2.66, P < 0.0001) compared with the non-deteriorating group. The mean arterial pressure appears to be a useful, bedside, and non-invasive prognostic tool potentially capable of promptly identifying intermediate-high risk PE patients at higher risk of 48 h clinical deterioration.

Achieving Therapeutic Anti-Xa Levels Using Rivaroxaban for Venous Thromboembolism in a Morbidly Obese Patient with a BMI >70

Background: Anticoagulation (AC) is the cornerstone of treatment for venous thromboembolism (VTE). Direct oral anticoagulants (DOACs) have become the standard of care during the acute and extended phases of therapy for VTE, mostly due to their ease of use, efficacy, and safety profiles. There is a 9.2% prevalence of severe obesity (BMI>40) in Americans as of 2017-2020 with a 6.2-fold increased risk of VTE in obese individuals. The 2021 International Society on Thrombosis and Haemostasis (ISTH) guidelines recommend using standard dosages of DOACs in patients with a BMI >40 kg/m2 or weight >120 kg. Despite these recommendations, their use in severely obese individuals at extremes of weight like our patient with a BMI > 70 kg/m2 remains uncertain. Case Presentation Herein, we present a 38-year-old morbidly obese female with no significant past medical history who presented with an acute worsening of dyspnea on exertion saturating 60% on room air. The diagnosis of intermediate-high risk pulmonary embolism (PE) was made based on computed tomographic angiography (CTA) with right ventricular strain and elevated cardiac biomarkers. A concomitant proximal DVT from the left common femoral to the distal peroneal vein was also noted. The patient's weight was 243kg with a calculated BMI of 72.3 kg/m2. After the patient had received parenteral anticoagulation with heparin for 4 days, it was decided to switch to Rivaroxaban 15mg BID for 21 days followed by 20 mg daily. With a history of irregular menses, the patient developed heavy menstrual bleeding (HMB) following the initiation of rivaroxaban. Her hemoglobin remained stable with no blood transfusion requirements. However, this led to the decision to switch to rivaroxaban 20 mg PO daily earlier than planned due to a lack of improvement in menstrual bleeding which was considered to be clinically relevant non-major bleeding (CRNMB). Despite this switch, there was no effect on efficacy and the patient did not develop any signs or symptoms of VTE recurrence during her prolonged hospital stay with a significant improvement in her oxygenation levels and VTE symptomatology. In our patient, we demonstrated the use of rivaroxaban in a morbidly obese individual with a BMI>70 by achieving therapeutic anti-Xa levels. Figure 1 shows the therapeutic peak and trough anti-Xa levels throughout the patient's hospitalization. The highest Anti Xa level of 314 mcg/mL was reported on day 19 correlating with the patient's menorrhagia, which self-limited with the transition from rivaroxaban 15 mg twice daily to 20 mg daily. Discussion: Two pivotal clinical trials, the EINSTEIN-DVT/PE trials, where 14% of patients in both arms weighed >100 kg, showed that patients on rivaroxaban (15 mg BID for 3 weeks, followed by 20 mg once daily) vs those on enoxaparin followed by a vitamin K antagonist, had no significant difference in recurrence rates of VTE and bleeding rates [Moore KT, et Al. Influences of Obesity, Am J Med 2017]. A recent post-hoc analysis of the EINSTEIN DVT/PE trials also portrayed no correlation between weight/BMI and risk of recurrent VTE or bleeding in those who received rivaroxaban. Our case illustrates the attainment of therapeutic anti-Xa levels with no recurrent VTE in our morbidly obese patient. Despite her heavy menstrual bleeding, the bleeding was controlled once the switch to rivaroxaban 20mg daily was completed. Another study in which its heaviest participant at 172 kg, showed compelling evidence that morbid obesity has minimal influence on the safety and efficacy of rivaroxaban [Speed V, et al. Fixed dose rivaroxaban. JTH 2020]. This remains true for our patient at 243 kg. Conclusion: Our case demonstrates that standard doses of rivaroxaban for the treatment of DVT/PE in individuals with morbid obesity with BMI>70 kg/m2 can be effective, and safer for the initial phase of treatment for VTE and in prevention of VTE recurrence. It also portrays that increased dosages attempting to account for high bodyweight/fat can potentially result in major bleeding events. Despite the 2021 ISTH guidelines, further prospective studies and randomized controlled trials are warranted, to assess the safety and efficacy of DOACs in VTE, particularly in such challenging clinical scenarios like morbid obesity. Alongside clinical assessment, additional studies will be essential to evaluate the need for universal and external validation of anti-Xa levels in patients taking DOACs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Case 06—A fatal dance: a case report of a pulmonary embolism with mobile right ventricular thrombus

Abstract Presentation We report a case of a 44-year-old woman with past medical history of dyslipidemia under atorvastatin, overweight and depression, that presented to the emergency department with a 1-month history of dyspnea. On physical examination, blood pressure was within normal range, however she was hypoxemic, needing oxygen via nasal cannula, and tachycardic. Pulmonary auscultation revealed basal crackles. Blood workup showed discrete leukocytosis, increased C-reactive protein, mild hypertransaminasemia and increased troponin and NT-proBNP levels. An EKG revealed sinus tachycardia with 123 beats per minute. A D-shaped left ventricle, an enlarged right ventricle and right heart mobile thrombus were observed in a transthoracic echocardiogram. Diagnosis Scoring 2 points on simplified Wells’ Score and with a visible mobile right ventricular thrombus, pulmonary embolism was suspected and further confirmed by computed tomographic pulmonary angiography. Management: In the absence of hemodynamic instability this case fulfils criteria for intermediate-high risk pulmonary embolism. Therefore, anticoagulation with enoxaparin was started under strict electrocardiographic monitoring. Unfortunately, a day later the patient had a sudden cardiac arrest in asystole, with no recuperation after prolonged advanced life support and administration of rescue thrombolysis (alteplase 50mg). Learning points

Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism

The optimal treatment of intermediate-high-risk pulmonary embolism (PE) remains unknown. To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high-risk PE. The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High-Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high-risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020. Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy. The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes. The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group. This prematurely terminated randomized clinical trial of patients with intermediate-high-risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial. ClinicalTrials.gov Identifier: NCT05172115.

OUTCOMES FROM CATHETER-DIRECTED EMBOLECTOMY FOR INTERMEDIATE-RISK AND HIGH-RISK PULMONARY EMBOLISM

OUTCOMES FROM CATHETER-DIRECTED EMBOLECTOMY FOR INTERMEDIATE-RISK AND HIGH-RISK PULMONARY EMBOLISM

EVALUATION OF SERIAL BIOMARKERS IN INTERMEDIATE-RISK PATIENTS WITH ACUTE PULMONARY EMBOLISM

EVALUATION OF SERIAL BIOMARKERS IN INTERMEDIATE-RISK PATIENTS WITH ACUTE PULMONARY EMBOLISM

Changing biventricular mechanics during thrombectomy for intermediate high-risk pulmonary embolism.

Changing biventricular mechanics during thrombectomy for intermediate high-risk pulmonary embolism.

TCT-227 The Efficacy of Reperfusion Therapy Treating Acute Intermediate High-Risk Pulmonary Embolism Patients

TCT-227 The Efficacy of Reperfusion Therapy Treating Acute Intermediate High-Risk Pulmonary Embolism Patients

Percutaneous treatment of acute pulmonary embolism: state of the art

Acute pulmonary embolism (PE) is a common disease associated with high mortality rates that vary widely according to patient clinical presentation and hemodynamic status. According to international guidelines, systemic thrombolysis (ST) is the mainstem treatment in patients with high risk PE and intermediate-high risk PE evolving towards hemodynamic decompensation, showing lower mortality compared with anticoagulant therapy alone despite a high rate of bleeding events. Considering that a large proportion of patients presents contraindication to ST, catheter-directed therapies (CDTs) could tackle some unsolved issues, targeting the treatment to the pulmonary arteries, avoiding the dreaded complications of ST.The aim of this review is to describe the current indication for CDTs in terms of patient selection and timing of treatment, to describe contemporary available medical devices and techniques, discussing current knowledge of safety and efficacy and the importance of multidisciplinary team in PE management.

Prognostic significance of symptomatic deep vein thrombosis in patients with acute symptomatic pulmonary embolism regarding the European Society of Cardiology mortality risk model.

Deep vein thrombosis (DVT) can be symptomatic or asymptomatic in patients with acute pulmonary embolism (PE). The prognostic value of the symptomatic DVT at the presentation regarding the prognosis of PE is unknown. Data were extracted from the REgional Pulmonary Embolism Registry (REPER) which enrolled 1604 hospitalized patients after multidetector computed tomography (MDCT) diagnosed symptomatic acute PE. According to the ESC risk model, patients were classified into four subgroups. Patients who had leg edema with or without pain, and patients with leg pain and DVT confirmed by compression ultrasound were considered to have symptomatic DVT. This study aimed to compare all-cause hospital mortality between patients with symptomatic DVT and patients without symptoms or signs of DVT across the PE risk stratums. All-cause mortality in patients with symptomatic DVT compared to those who had no symptoms or signs of DVT were 2/196 (1.0%) vs. 11/316 (3.5%), P=0.145, 4/129 (3.1%) vs. 17/228 (7.5%), P=0.106, 14/196 (7.1%) vs. 54/290 (18.6%), P<0.001 and 16/55 (29.1%) vs. 51/139 (36.7%), P=0.402 in patients with low, intermediate-low, intermediate-high and high-risk PE, respectively. In multivariate analysis symptomatic DVT was associated with decreased in-hospital mortality only in patients with intermediate-high PE (OR 0.320, 95%CI 0.164-0.627; P=0.001). Intermediate-high risk PE patients with symptomatic DVT who were treated with thrombolysis had significantly lower hospital mortality than patients without symptoms or signs of DVT (2.2% vs. 11.4%, P=0.003). Intermediate-high risk PE patients with symptomatic DVT at presentation may benefit from thrombolysis and have lower hospital all-cause mortality in such circumstances.

P262 ULTRASOUND–ASSISTED THROMBOLYSIS OF HIGH RISK AND INTERMEDIATE–HIGH RISK PULMONARY EMBOLISM: A MULTICENTRE REAL WORLD EXPERIENCE IN LOMBARDY REGION

Abstract Introduction Acute pulmonary embolism (PE) is associated with high morbidity and mortality rate. Catheter–directed treatments (CDTs) seem a therapeutical option in case of sistemic thrombolysis (ST) contraindication or failure. Ultrasound–assisted thrombolysis (USAT) allows low–dose thrombolytic loco–regional infusion facilitated by ultrasounds. Methods and Results A multicentre retrospective observational cohort study was conducted among 4 Cardiovascular Interventional Centres in Lombardy Region to evaluate safety and efficacy of USAT in high risk and intermediate–high risk PE patients presenting with contraindications to ST. Patients at high risk were included in case of USAT because of ST contraindications. Patients at intermediate–high risk were included in case of rescue USAT. Loco–regional thrombolysis was performed using rTPA. Procedural success was defined as successful catheters‘ deployment in pulmonary arteries and patient survival during the procedure. Bleeding were defined according to BARC criteria. Echocardiographic evaluation to determine the prevalence of right ventricular (RV) dysfunction and pulmonary hypertension was performed at presentation, discharge and follow–up. Between 2011 and 2021, 109 patients were included. 21.1% presented with high risk PE, the remaining 78.9% with intermediate–high risk. Procedural success was obtained in 99.1% of the cases; major bleedings occurred in 9.2%, minor bleedings in 11.9% and vascular complications in 7.3% of the patients. 91.7% of patients were alive at discharge. In–hospital all–cause mortality was higher in high risk patients (26.1% vs 3.5%; p = 0.003) that showed a steep decline in survival as compared to intermediate–high risk patients that constantly maintained a high survival rate throughout the observation period. At six–months follow–up 3 patients in intermediate–high risk group died so that the overall mortality remains higher in high risk patients (26.1% vs 7%; p = 0.018). No re–hospitalization for recurrent PE at six–months occurred. Prevalence of RV dysfunction and pulmonary hypertension significantly decreased from hospital admission to discharge and to six–months follow–up (p–value &amp;lt;0.0001 for all comparisons). Conclusions Our experience shows good short and mid–term outcomes in USAT in high risk and intermediate–high risk PE patients with contraindications to ST, suggesting that it might be considered in a neglected subset of patients with no alternative therapeutical options.

Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study

BackgroundDue to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE). Methods and resultsThe Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. ConclusionsRegardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.