Ultrasound-Accelerated Catheter-Directed Thrombolysis for Acute Submassive Pulmonary Embolism

doi:10.1016/j.jvir.2014.12.017

Journal of Vascular and Interventional Radiology

Volume 26, Issue 7, July 2015, Pages 1001-1006

https://doi.org/10.1016/j.jvir.2014.12.017 Get rights and content

Abstract

Purpose

To evaluate the safety and efficacy of ultrasound-accelerated catheter-directed thrombolysis (USAT) in patients with submassive pulmonary embolism (PE).

Materials and Methods

This retrospective study comprised 45 consecutive patients (15 prospective, 30 retrospective) who underwent USAT for submassive PE from June 2012–May 2014. Inclusion criteria were right ventricular dysfunction (RVD) as indicated by right ventricle-to-left ventricle (RV:LV) ratio > 0.9, symptoms of < 2 weeksʼ duration, and absence of absolute contraindication to thrombolysis. All patients underwent pulmonary artery catheterization with a standardized protocol (24 mg recombinant tissue plasminogen activator). Hemodynamic evaluation immediately after USAT, RV:LV ratio evaluation at 48–72 hours after USAT by computed tomography angiography and echocardiography, and adverse event reporting for a minimum of 30 days were performed. Outcomes and complications are reported as per the Society of Interventional Radiology Reporting Standards for Endovascular Treatment of Pulmonary Embolism.

Results

USAT was technically successful in 100% (n = 45) of patients. Main pulmonary artery pressure significantly decreased from 49.8 mm Hg to 31.1 mm Hg (P < .0001). RVD significantly improved with mean RV:LV ratios decreasing from 1.59 to 0.93 (P < .0001). There were 6 complications: 4 minor bleeding episodes at access sites and 2 major bleeding complications (flank and arm hematoma). All-cause mortality at 30 days was 0%. There were no readmissions for PE at 30 days after discharge.

Conclusions

Ultrasound-accelerated catheter-directed thrombolysis using a standardized low-dose protocol is a safe and efficacious method of treatment of submassive PE to reduce acute pulmonary hypertension and RVD.

Section snippets

Materials and Methods

This study included 45 consecutive patients (25 men and 20 women; mean age, 56.5 y) with submassive PE treated at a single institution from June 2012–May 2014. Demographics are presented in Table 1, and risk factors for venous thromboembolism are listed in Table 2 (25). The first 15 patients were enrolled in a prospective multicenter trial (SEATTLE II [A Prospective, Single-arm, Multi-center Trial of EkoSonic Endovascular System and Activase for Treatment of Acute Pulmonary Embolism],

Results

Endovascular placement of catheters and infusion were technically successful in 100% (n = 45) of patients. There were no complications related to catheter placement (ie, perforation, sustained arrhythmia, dissection). Compared with baseline, main systolic pulmonary artery pressure significantly decreased from 49.8 mm to 31.1 mm, and the difference before and after the procedure was highly statistically significant (18.9 mm; 95% confidence interval, 14.9–22.8 mm, P < .0001). Complete concordance

Discussion

Investigators are working to identify the ideal therapy, one with the lowest potential risk of hemorrhagic complications while decreasing RVD and subsequent mortality, in patients presenting with submassive PE. A recently published European double-blind randomized controlled trial (14) evaluating systemic thrombolysis with a single weight-based bolus of tenecteplase ranging from 30–50 mg versus placebo in intermediate-risk PE revealed a 66% reduction in hemodynamic collapse and all-cause

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Long-term outcomes and predictors of mortality in patients with pulmonary embolism undergoing catheter-directed thrombolysis: a 10-year retrospective study
2024, Current Problems in Cardiology
Data regarding long-term outcomes of catheter-directed thrombolysis (CDT) post intermediate risk pulmonary embolism (PE), the choice of anticoagulation, and factors affecting mortality are not well studied.
We conducted a ten-year retrospective observational chart review of patients undergoing CDT for intermediate-risk PE. Patients were followed for a period of 1 to a maximum of 5 years from the PE event. Multivariate regression analysis was used to identify independent predictors of mortality post-CDT.
We had a total of 373 patients in our study. Significant 5-year mortality was observed (18.7 %) in our patient population, with a 9.2 % cardiopulmonary cause of death. Rate was highest in patients without anticoagulation (78.5 %) and least in patients on apixaban [10.9 %, absolute risk reduction - 63.8 % (40.91 % - 86.60 %)]. Age, female sex and no anticoagulation were independently associated with mortality.
CDT for intermediate-risk PE has a high 5-year mortality with no anticoagulation as the only modifiable risk factor.
Navigating the Complexity of High-Risk Pulmonary Embolism—Is Mechanical Thrombectomy the Answer We Need?
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Citation Excerpt :
The primary endpoint, namely the difference in the right ventricle/left ventricle (RV/LV) ratio from baseline to 24 hours, was significantly improved in the endovascular group compared with heparin alone (0.30 ± 0.20 vs 0.03 ± 0.16; P < 0.001). Several other non-randomized non-comparative studies including patients with haemodynamically unstable PE or haemodynamically stable PE with RV dysfunction have found similar results in terms of improvement in RV function (Fig. 1) [14,20–31]. A meta-analysis of available studies showed an average reduction in systolic pulmonary artery pressure of 15.8 mmHg (95% confidence interval [CI] 12.2–19 mmHg), and a reduction of 34% (95% CI 25–42%) in the RV/LV ratio [32].
Systemic thrombolysis for acute pulmonary embolism reduces the risk of death and cardiovascular collapse but is associated with an increased rate of bleeding. The desire to minimize the risk of bleeding events has driven the development of catheter-based strategies for pulmonary reperfusion in pulmonary embolism. These catheter-based strategies utilize lower-dose fibrinolytic regimens or purely mechanical thromboaspiration to expedite removal of the embolus. The most comprehensive data on catheter-based techniques come from trials of ultrasound-facilitated catheter fibrinolysis. This technique relieves right ventricular pressure overload with a lower risk of major bleeding and intracranial haemorrhage than historical rates observed with systemic fibrinolysis in intermediate- to high-risk pulmonary embolism. Two aspiration thrombectomy devices recently demonstrated significant reductions in right ventricle/left ventricle ratio and a low major adverse event rate in patients with intermediate-risk pulmonary embolism. However, further research is required to determine the optimal application of ultrasound-facilitated catheter fibrinolysis and other catheter-based therapies in patients with acute pulmonary embolism.
La thrombolyse systémique dans la prise en charge des embolies pulmonaires aigues réduit le taux de décès et de déstabilisation hémodynamique au prix d’un sur-risque de complications hémorragiques. C’est dans l’optique de limiter le risque de saignement grave, intracrânien notamment qu’ont été développées les stratégies de reperfusion pulmonaire endoluminale. Ces stratégies utilisent soit des doses réduites de thrombolytiques, soit des procédés de thrombo-aspiration mécanique du thrombus. Les procédures de thrombolyse in situ, facilitées par ultrasons, sont celles qui ont été le plus étudiées. La thrombolyse in situ facilitée par ultrasons permet de réduire la dysfonction ventriculaire droite avec un faible risque hémorragique, intra-crânienne notamment, dans les embolies pulmonaires à risque intermédiaire et à haut risque. Deux dispositifs de thrombo-aspiration mécanique ont récemment montré une réduction du rapport des diamètres ventricule droit/ventricule gauche et un faible taux d’accidents hémorragiques dans les embolies pulmonaires à risque intermédiaire. Cependant, l’évaluation de ces techniques comparativement à un groupe contrôle ou à une autre stratégie de reperfusion pulmonaire n’est pas disponible et reste nécessaire.
Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report
2021, Chest
Citation Excerpt :
Given the lack of high-quality evidence, and the endorsement of the prior guidance statement, no evidence-to-decision framework was undertaken for this PICO. Small randomized trials of ultrasound-assisted CDT vs anticoagulation alone revealed more rapid improvement of right ventricular parameters and a low reported risk of procedure-related bleeding, but these studies were small and did not assess patient-important efficacy outcomes.78,93–97 An older randomized trial of 34 patients with massive PE found that infusion of recombinant tissue plasminogen activator into a pulmonary artery as opposed to a peripheral vein did not accelerate thrombolysis, but caused more frequent bleeding at the catheter insertion site.98
This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.
We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.
The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.
New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.
Meta-Analysis of Catheter Directed Ultrasound-Assisted Thrombolysis in Pulmonary Embolism
2019, American Journal of Cardiology
Citation Excerpt :
Fifty-one studies were excluded after full text review because they did not meet the inclusion criteria of the meta-analysis. Finally, 28 studies were included for quality appraisal and the meta-analysis (Figure 1).5–32 A total of 2,135 patients were included in the 28 included studies.
Ultrasound-assisted catheter directed thrombolysis (USAT) has been shown to improve hemodynamic function and reduce bleeding complications in patients with acute massive or submassive pulmonary embolism. We performed a meta-analysis to better evaluate the efficacy and safety of USAT. We conducted an extensive literature search in PUBMED, MEDLINE, and EMBASE databases from January 1, 2008 to December 31, 2018. Efficacy outcomes of interest were pulmonary artery systolic pressure, mean pulmonary pressure, ratio of right ventricular to left ventricular diameter, cardiac index, tricuspid annular plane systolic excursion, Miller Index Score, and Qanadli Score. Safety outcomes were in-hospital mortality, long-term mortality, major and minor bleeding complications, and recurrent pulmonary embolism. Meta-analysis was performed using Cochrane Collaboration Review Manager (version 5.1). Effect size was estimated using random effects model, with 95% confidence intervals (CIs). Twenty-eight studies (n = 2,135) met inclusion criteria. Compared with pretreatment parameters, post-USAT was associated with a reduction in the mean Miller Index Score and Qanadli Score by 10.55 (95% CI −12.98 to −8.12) and 15.64 (95% CI −19.08 to −12.20), respectively. Cardiac index and tricuspid annular plane systolic excursion improved by 0.68 L/m² (95% CI 0.49 to 0.87) and 3.68 mm (95% CI 2.43 to 4.93), respectively. Pulmonary artery systolic pressure and mean pulmonary pressure after therapy were reduced by a mean difference of 16.69 mm Hg (95% CI −19.73 to −13.65) and 12.13 mm Hg (95% CI −14.67 to −9.59) respectively. The right ventricular to left ventricular diameter dimension ratio decreased by 0.35 (95% CI −0.40 to −0.30) after therapy. In-hospital mortality in patients who underwent USAT was 2.9%, and total long-term mortality was 4.1%. Major and minor bleeding complications were seen in in 5.4% and 6.0% of patients, respectively. Recurrent events occurred in 0.2% of patients after USAT. In conclusion, USAT is a safe and effective procedure associated with significant hemodynamic and clinical improvement in patients with massive and submassive pulmonary embolism.
Systematic Review: The Role of Thrombolysis in Intermediate-Risk Pulmonary Embolism
2019, Journal of Emergency Medicine
This systemic review provides practicing emergency physicians updated information about the role of thrombolysis in the treatment of intermediate-risk pulmonary embolism.
A PubMed literature search from January 1, 2005 to December 31, 2018 was conducted and limited to human clinical trials written in English with relevant keywords. High-quality studies were identified and then underwent a structured review. Recommendations are made based on the literature review.
Sixty-three articles met criteria for rigorous review, of which 13 were appropriate for citation in this review. Of these 13, there were 6 prospective studies and 7 retrospective studies.
Thrombolysis, either catheter-directed or systemic, is a treatment option in the management of patients with intermediate-risk pulmonary embolism and a high likelihood of clinical deterioration. Each method of thrombolysis carries risks and benefits. Based on the available evidence, transfer to a facility for the purpose of catheter-directed thrombolysis is not recommended.

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: None of the other authors have identified a conflict of interest.

¹: K.M.S. is a paid consultant for BTG.

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Clinical StudyUltrasound-Accelerated Catheter-Directed Thrombolysis for Acute Submassive Pulmonary Embolism

Abstract

Purpose

Materials and Methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Lancet

Lancet

Chest

Thromb Res

Chest

Am J Med Sci

Am J Cardiol

Thromb Res

J Vasc Interv Radiol

J Vasc Interv Radiol

J Vasc Interv Radiol

J Am Coll Cardiol

J Vasc Interv Radiol

Ultrasound Med Biol

Acute infarct of the right ventricle secondary to a massive pulmonary thromboembolism

Arch Inst Cardiol Mex

Pulmonary embolism: one-year follow-up with echocardiography Doppler and five-year survival analysis

Circulation

Clinical Study
Ultrasound-Accelerated Catheter-Directed Thrombolysis for Acute Submassive Pulmonary Embolism