Standard Catheter-directed Thrombolysis Research Articles

Ultrasound-Assisted Versus Standard Catheter-Directed Thrombolysis for Acute Pulmonary Embolism: Insights From National Inpatient Sample

BackgroundPulmonary embolism is one of the leading causes of morbidity and mortality in the United States. Catheter-directed therapies have emerged as a promising treatment for managing intermediate- and high-risk patients; however, data comparing standard catheter-directed thrombolysis (SCDT) and ultrasound-assisted thrombolysis (USAT) are limited. This study aimed to investigate trends, outcomes, and predictors of mortality of both modalities from a nationally representative sample. MethodsThis analysis used data from the National Inpatient Sample years 2016-2020. The primary outcome was in-hospital mortality. A multivariable regression model was used to compare the outcomes. ResultsAmong 39,430 patients who received catheter-directed thrombolysis, 26,710 (76.8%) received SCDT and 8060 (23.2%) received USAT. The utilization of SCDT and USAT increased during the study years except for 2020. In-hospital mortality was lower among patients who received USAT (2.7% vs 3.8%; P = .04) compared with patients who received SCDT in the unadjusted analysis. On multivariable regression analysis, there was no difference in the incidence of in-hospital mortality between USAT and SCDT (odds ratio, 0.75; 95% CI, 0.52-1.08; P = .13). There were no significant differences between SCDT and USAT groups in the rate of bleeding adverse events including intracranial hemorrhage (0.6% vs 0.4%; P = .47), and nonintracranial major bleeding (4.2% vs 4.1%; P = .72). ConclusionsUltrasound-assisted thrombolysis was associated with similar in-hospital mortality and bleeding complications compared with SCDT for acute pulmonary embolism. Further studies are warranted to confirm evaluate the long-term outcomes with both modalities.

Predictors of chronic thromboembolic pulmonary hypertension in patients with submassive pulmonary embolism treated with catheter-directed thrombolysis versus anticoagulation alone: A secondary analysis of the SUNSET sPE trial

ObjectiveChronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is a morbid complication with suboptimal treatment. We aimed to evaluate the biomarker profile and functional outcomes in patients with submassive PE (sPE) treated with catheter-directed thrombolysis (CDT) compared with anticoagulation alone (ACA). We performed a secondary biomarker and survey analysis of the SUNSET sPE (standard vs ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism) randomized trial comparing standard CDT to ultrasound-assisted thrombolysis in patients with sPE. MethodsAs a part of the SUNSET sPE study, patients who did not receive an intervention were enrolled in the medical (ACA) arm. The biomarkers associated with CTEPH in the literature (ie, CCL2, CXCL10, PTX3, GDF-15, RAGE, BCA-1, TFPI) were collected and measured using a multiplex assay at diagnosis, discharge, and 3-month follow-up. Patients underwent a 6-minute walk test and answered quality-of-life questionnaires (pulmonary embolism quality of life; University of California, San Diego, shortness of breath questionnaire; 36-item short-form survey) at 3 months after diagnosis. Comparisons were made using the Student t test. Nonparametric tests were used when the distributions were not normal. Significance was set at P ≤ .05. ResultsA total of 72 patients (age, 56 ± 15 years; 40.3% women) were included in the present analysis. Of these 72 patients, 53 underwent CDT and 19 were included in the ACA arm. The baseline right ventricle/left ventricle ratios were similar between the two groups (CST, 1.8; ACA, 1.7). The survival and complication rates were similar between the two groups. At discharge, CXCL10 (768.9 ± 148.6 pg/mL vs 3032.0 ± 1201.0 pg/mL; P = .018) and PTX3 (3203.5 ± 1298.0 pg/mL vs 12,716.2 ± 6961.5 pg/mL; P = .029) were lower in the CDT group and displayed a quicker return to baseline than in the ACA group. This trend, although not significant, was also seen with the other biomarkers. At 3 months, the 6-minute walking distance and quality-of-life scores were similar between both groups. ConclusionsIn patients with sPE, the biomarkers of CTEPH were lower with CDT compared with ACA. At 3 months, both groups demonstrated similar biomarker levels, 6-minute walking distances, and quality-of-life scores.

Comparison of the Clinical Efficacy and Safety of Standard and Ultrasound-Assisted Thrombolysis for Pulmonary Embolism: A Systematic Review and Meta-Analysis.

Catheter-directed therapy has been increasingly used in acute pulmonary embolism (PE). Whether ultrasound-assisted thrombolysis (USAT) is superior to standard catheter-directed thrombolysis (SCDT) remains unclear. This is a systemic review and meta-analysis of comparative trials on USAT and SCDT for PE to determine whether either modality yielded better clinical efficacy and safety. Major databases including PubMed, Embase, Cochrane Central, and Web of Science were searched through March 16, 2023. Studies that reported outcomes of SCDT and USAT for acute PE were included. Studies reported data on therapeutic efficacy (a reduction in the right ventricle [RV]/left ventricle [LV] ratio, a reduction in the systolic pulmonary artery pressure [mm Hg], change in Miller index, length of intensive care unit [ICU] and hospital stay) and safety outcomes (in-hospital mortality, overall and major bleeding events). A total of 9 studies with 2610 patients were included in the meta-analysis. The analysis showed significantly greater improvement in the RV/LV ratio in the SCDT group than in the USAT group (mean difference [MD]: -0.155; 95% confidence interval [CI]: -0.249 to -0.006). No statistically significant differences were found between groups comparing change in systolic pulmonary artery pressure (MD: 0.592 mm Hg; 95% CI: -2.623 to 3.807), change in Miller index (MD: -4.1%; 95% CI: -9.5 to 1.3%), hospital stay (MD: 0.372 days; 95% CI: -0.972 to 1.717), and ICU stay (MD: -0.073.038 days; 95% CI: -1.184 to 1). No significant difference was noted in safety outcomes, including in-hospital mortality (pooled odds ratio: 0.984; 95% CI: 0.597 to 1.622), and major bleeding (pooled odds ratio: 1.162; 95% CI: 0.714 to 1.894). In our meta-analysis of observational and randomized studies, USAT is not superior to SCDT in patients with acute PE.INSPLAY registration number: INPLASY202240082. This study compared SCDT and USAT in patients with acute pulmonary embolism. We found no additional benefit in PA pressure change, thrombus reduction, hospital stay, mortality and major bleeding rate. Additional study using consistent treatment protocol is necessary for further investigation.

A Meta-analysis of Standard Versus Ultrasound-Assisted Catheter-Directed Thrombolysis in the Management of Acute Pulmonary Embolism.

Standard catheter-directed thrombolysis (SCDT) harnesses the therapeutic benefit of systemic thrombolytics while minimizing bleeding complications in patients presenting with pulmonary embolism (PE). Ultrasound-assisted catheter-directed thrombolysis (USAT) theoretically improves upon SCDT by disrupting fibrin and increasing the surface area exposed to thrombolytic agent. However, it is unclear if this translates into improved outcomes. A systematic search of prior publications comparing SCDT and USAT in patients with intermediate or high-risk PE was conducted. Primary outcomes of interest were bleeding events, ICU and hospital length of stay. Secondary outcomes included changes in pulmonary artery systolic pressure (PASP), mean pulmonary artery pressure (mPAP), and right ventricle to left ventricle diameter (RV/LV) ratio. Studies that lacked comparison groups were excluded. Bias assessments were performed using the Cochrane tools for randomized and nonrandomized studies. Data was collated utilizing the Cochrane Review Manager software, and all analyses assumed random effects. Our search yielded 7 observational studies and 1 randomized control trial. The studies included a total of 543 patients who underwent either SCDT (n = 273) or USAT (n = 270) for intermediate or high-risk PE. The synthesized analysis showed no significant differences in bleeding between the groups. There were no differences in ICU or hospital lengths of stay, changes in PASP, or mPAP. Reductions in RV/LV ratio were greater with SCDT (mean difference, -0.16; 95% CI, -0.27 to -0.06; P = .003). In comparison to SCDT, USAT did not result in improved clinical or hemodynamic outcomes in patients presenting with PE. Results were limited by heterogeneity among the included studies.

Clinical efficacy and safety of ultrasound-assisted thrombolysis vs. standard catheter-directed thrombolysis in patients with acute pulmonary embolism: A study level meta-analysis of clinical trials.

AimTo compare the clinical efficacy of ultrasound-assisted thrombolysis (USAT) vs. standard catheter-directed thrombolysis (SCDT) in patients with acute pulmonary embolism (aPE).MethodsThis study analyzed the clinical outcomes of patients with non-low-risk aPE who received USAT or SCDT. The primary outcomes were all-cause death, total bleeding, and major bleeding. Secondary outcomes included pulmonary thrombotic load score (Miller), improvement in right ventricular-to-left ventricular ratio (RV/LV), dose and duration of the thrombolytic drug tissue plasminogen activator (tPA), length of stay (LOS) in the ICU, and total LOS in the hospital.ResultsA total of seven articles and 451 patients were included in this study. 241 patients were in the USAT group and 210 patients were in the SCDT group. There were no significant differences in all-cause mortality, total bleeding, and major bleeding between the two groups. Miller scores for pulmonary thrombus also showed no difference between the two groups, but pulmonary artery systolic pressure (PASP) was lower in the SCDT group after-treatment. The reduction of RV/LV from baseline was more pronounced in the SCDT group than in the USAT group (OR: −0.14, 95%CI: −0.20 to 0.07, P < 0.0001, I2 = 0%). Total dose of tPA and duration of infusion in the USAT group were lower than those in the SCDT group, but there was no significant statistical difference. LOS in the ICU was similar between the two groups, while LOS in the hospital was lower in the SCDT group.ConclusionThis study did not detect any differences in all-cause mortality, total bleeding, and major bleeding between non-low-risk aPE patients treated with USAT or SCDT. Improvement in right ventricular function was better in the SCDT group, and hospital LOS was lower in the SCDT group.

Efficacy and safety outcomes of ultrasound assisted thrombolysis versus standard catheter direct thrombolysis in patients with submassive or massive pulmonary embolism: an updated meta-analysis

Abstract Background The use of catheter-based thrombolysis in comparison to systemic thrombolytics has emerged as a potentially lifesaving therapy for patients with sub massive or massive pulmonary embolism (PE). The addition of ultrasound waves to accelerate lytic dispersion in ultrasound assisted thrombolysis (USAT) has been proposed to improve outcomes as compared to standard catheter-directed thrombolysis (SCDT). These two modalities have been compared in small studies, but larger population data on the outcomes of these therapies is still lacking. Purpose To assess the efficacy and safety of USAT versus SCDT in patients with submassive or massive pulmonary embolism. Methods A review of electronic databases (PubMed, Scopus, Embase, and Cochrane) was performed using keywords USAT, SCDT and PE and studies were included if efficacy and safety outcomes were compared between the two types of therapies. Efficacy outcomes that were evaluated included the reduction in right ventricle/left ventricle ratio (RV/LV ratio), pulmonary artery systolic pressure (PASP) and Miller score. Safety outcomes that were evaluated included major bleeding, mortality and length of ICU stay. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for continuous variables. Risk ratio (RR) and 95% CI were reported for dichotomous variables using the random effects model in comprehensive meta-analysis and RevMan 5.4.1 softwares. Results Six studies with a total of 381 patients (USAT n=204; SCDT n=177) were included. No statistical difference in efficacy outcomes of USAT over SCDT was noted in the degree of RV/LV ratio reduction (SMD: −0.507; CI: −1.386–0.373; p&amp;gt;0.05; I2=92%), PASP reduction (SMD: 0.037; CI: −0.404–0.478; p&amp;gt;0.05; I2=59%), or Miller score reduction (SMD: 0.303; CI: −0.481– 1.087; p&amp;gt;0.05; I2=82%). Safety outcomes were also not statistically different with similar rates of major bleeding (RR: 1.44; CI: 0.54–3.85; p&amp;gt;0.05; I2=4%), mortality (RR: 1.46; CI: 0.35–6.05; p&amp;gt;0.05; I2=0%) and length of ICU stay (SMD: −0.01; CI: −0.29–0.27; p&amp;gt;0.05; I2=31%) in both treatment groups. Conclusion Our data suggest that despite the technological advancement of USAT, there is no additional benefit over SCDT in terms of efficacy and safety. Further studies are warranted for both procedures investigating financial and clinical outcomes in real world practice. Funding Acknowledgement Type of funding sources: None.

C-13 | Meta-analysis of Standard vs. Ultrasound-Assisted Thrombolysis in the Management of Acute Pulmonary Embolism

Standard catheter-directed thrombolysis (SCDT) harnesses the therapeutic benefit of systemic thrombolytics by infusing the lytic agent directly into the thrombus, thereby, minimizing the dose and bleeding complications in patients presenting with massive and sub-massive PE. Ultrasound-assisted thrombolysis (USAT) theoretically improves SCDT by disrupting fibrin and increasing the surface area exposed to the agent, but it comes at an increased cost. The purpose of this study is to determine if USAT improves outcomes compared to SCDT.

Efficacy of ultrasound assisted catheter-directed thrombolysis compared to catheter-directed thrombolysis in vitro.

Catheter-directed thrombolysis (CDT) is an effective and safe endovascular method used in critical limb ischemia and many other thromboembolic events. Ultrasound-assisted catheter-directed thrombolysis (US-CDT) is an emerging technique considered to accelerate thrombolysis and therefore is supposed to improve outcome. To evaluate the efficacy of US-CDT in comparison to standard CDT in vitro. A total of 69 sets of human venous blood were evaluated, each comprising a tube just treated with CDT, a tube treated with US-CDT, and a control tube. All tubes were kept under physiological conditions. Except for the controls, in all tubes 5 mg of tissue-type plasminogen activator was administered over the predetermined treatment interval. Thrombus mass was weighted at the end of the lysis intervals at 6 h or 24 h, respectively. CDT led to a mean thrombus reduction of 32% and ultrasound-assisted lysis led to a mean thrombus reduction of 41% (P < 0.001 for both). Thrombus reduction was significantly higher after US-CDT compared to CDT (P = 0.001). The better efficacy of US-CDT was mostly already apparent at early phases during thrombolysis and did further mildly increase over time (r = 0.24; P = 0.047). In vitro US-CDT is significantly superior to standard CDT; this effect is apparent at an early timepoint of lysis and slightly further increases over time.

Abstract 14165: Ultrasound-Accelerated Thrombolysis May Be the Preferred Catheter-Based Lytic Therapy for Pulmonary Embolism

Introduction: Pulmonary embolism (PE) is estimated to cause 100,000 deaths annually in the US. Systemic use of fibrinolytic drugs carries risks of significant bleeding. Catheter directed thrombolysis (CDT) delivers thrombolytic drugs directly to the site of the clot and in lower doses which may improve its safety profile. We aimed to investigate the safety and efficacy of CDT in intermediate risk PE and contemporary trends of follow-up cardiac testing in these patients. Methods: 75 patients who underwent CDT for intermediate risk PE at a single center from 2014-2021 were studied retrospectively. Outcomes included procedure related complications and mortality. Continuous variables are presented as mean±SD, categorical variables as percentages. Logistic regression and survival analysis was used. Data was analyzed in Stata/BE 17.0. Results: Demographics (Table 1), lab and imaging data (Table 2) were assessed for 75 patients. Troponin and BNP were elevated in 63.5% and 60% respectively. RV dilation was present in 86.7%. Ultrasound accelerated thrombolysis (EKOS) was performed in 80% and standard CDT in 20%. One procedural complication occurred, a patient undergoing standard CDT suffered a cardiac arrest and died. Major bleeding occurred in four patients but did not contribute to mortality. Mortality at 30 days and one year were 6.8% (5/73) and 13% (9/69) respectively. Only three deaths were attributed to cardiovascular causes. Those who underwent EKOS had 85.6% lower odds of death in 30 days (OR 0.14 (0.03-0.79), p=0.02) compared to CDT; however, our results are limited by a small sample size. Follow up imaging was assessed at 1 year (Table 3). Echo was most frequently performed in 45.3% of patients. Conclusions: EKOS for intermediate risk PE is a safe procedure with no procedural mortalities in our study. As follow up was poor, with less than 50% of the cohort receiving imaging, future directions should be aimed at ensuring these patients are monitored for long-term sequelae of PE.

Abstract 11701: Ultrasound Acceleration Does Not Provide Detectable Benefit During Catheter-Directed Thrombolysis for Massive or Submassive Pulmonary Embolism: A Meta-Analysis of the Available Evidence

Introduction: Compared with systemic thrombolysis, catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) reduces the risk of mortality and major bleeding due to lower thrombolytic doses. The only FDA-approved device for CDT is a more expensive ultrasound-accelerated CDT (USAT) device, which uses high frequency ultrasound waves to disrupt the fibrin mesh of the thrombus. No trials comparing CDT vs USAT exist. We conducted a meta-analysis of all published studies that employed CDT and/or USAT for acute PE, stratified by PE severity. Hypothesis: Ultrasound acceleration will improve mortality, bleeding risk, and right heart strain in acute PE over standard CDT. Methods: We performed a retrospective non-time-limited literature search of PubMed for all studies of either catheter-directed thrombolysis technique. Outcome measures (30-day mortality, major bleeding, RV/LV ratio, pulmonary artery systolic pressure) were extracted. Meta-analyses were performed using RevMan Review Manager 5.3 (Cochrane Collaboration). Random Effects Model was used to calculate proportion, mean difference, and Chi-square with 95% confidence intervals. Results: Of 1260 patients in the 34 identified studies, 311 had massive PE, and 928 underwent USAT. There was no difference between CDT and USAT in 30-day mortality in massive PE (27% [7, 48] vs 30% [-2, 62], Chi2=0.02, p=0.90, I2=40%) or submassive PE (5% [-5, 15] vs 3% [0, 7], Chi2=0.16, p=0.69, I2=0%), in major bleeding in massive PE (21% [0, 43] vs 16% [2, 31], Chi2=0.15, p=0.70, I2=58%), in pulmonary artery systolic pressure in massive PE (md 25.73 [16.06, 35.40] vs 19.75 [5.38, 34.12], Chi2=0.46, p=0.50, I2=89%) or submassive PE (15.71 [10.31, 21.89] vs 15.62 [9.77, 21.47] Chi2=0.01, p=0.91, I2=85%). Conclusions: Both techniques are efficacious in improving mortality, bleeding, and right heart strain. However, few studies report outcomes for standard CDT, and between-study heterogeneity is high. Differences in 30-day mortality, major bleeding events, and markers of right heart strain were not detected between techniques in our met-analysis. Practitioners are left without evidence of benefit for ultrasound acceleration, pending the results of the ongoing randomized-controlled trial .

Endovascular Therapy for Venous Thromboembolic Diseases.

Thrombolytic therapy plays an important role in treating venous thromboembolic events in patients with unstable hemodynamics or compromised limb circulation. Standard catheter-directed thrombolysis requires a lower dosage of thrombolytic agents than systemic thrombolysis, thus lowering the risk of bleeding. Pharmacomechanical catheter- directed thrombolysis further decreases the dose of thrombolytic agents and duration of infusion. Percutaneous mechanical thrombolysis may potentially become an alternative for patients not suitable for thrombolytic agents. With an increasing number of devices and ongoing trials, endovascular therapy is a promising development that may improve both safety and efficacy in treating venous thromboembolic diseases.

A Novel Use of Suction Thrombectomy for Embolic Protection During Mechanical Ileocaval Thrombectomy

We have reported on a novel use of the AngioVac suction thrombectomy device (AngioDynamics, Latham, NY) for vacuum-assisted embolic protection in a case of extensive mechanical thrombectomy of a caval–visceral deep vein thrombosis (DVT) that was refractory to standard catheter-directed thrombolysis. To the best of our knowledge, this is the first report of the use of a vacuum-assisted suction thrombectomy device for successful embolic protection. A 15-year-old girl had developed extensive, symptomatic bilateral ileocaval and renal vein DVTs refractory to outpatient management with anticoagulation therapy after pharmacomechanical thrombectomy and catheter-directed lysis. Initially, she had been treated successfully with overnight lytic therapy for the ileocaval DVT, and she was discharged with anticoagulation therapy. However, she had presented again with worsening bilateral lower extremity symptoms and kidney injury due to progression of the DVT. To prevent end-organ failure, extensive endovascular mechanical thrombectomy was planned. With the patient's significant thrombus burden through the visceral and retrohepatic inferior vena cava (IVC), pulmonary embolic protection during mechanical thrombectomy was our chief concern. Given the extent of the clot, IVC filter placement was impossible. Therefore, an AngioVac suction thrombectomy cannula and circuit was established via bilateral internal jugular vein access in an attempt to debulk the thrombus from a superior approach and provide pulmonary embolic protection. Mechanical thrombectomy (ClotTriever; Inari Medical, Irvine, Calif) was used to successfully debulk the IVC and bilateral ileofemoral venous segments from the bilateral popliteal veins. Although the use of the AngioVac from above proved unable to debulk the thrombus, it was successful in preventing significant embolism during ClotTriever mechanical thrombectomy (Fig 1). After mechanical thrombectomy (Fig 2), the patient's creatinine had returned to normal. She continued anticoagulation therapy, with Doppler ultrasound imaging showing reduction of the DVT and improvement of her lower extremity symptoms. We believe the present case has illustrated successful pulmonary embolic protection using a large-bore suction thrombectomy device with venoveno bypass during endovascular mechanical thrombectomy of caval, visceral, and bilateral ileofemoral DVTs. The AngioVac cannula and circuit can be safely and effectively used for central embolic protection in the case of large-volume caval mechanical thrombectomy.Fig 2Doppler ultrasound image showing reduction of the deep vein thrombosis (DVT) after mechanical thrombectomy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Randomized Trial Comparing Standard Versus Ultrasound-Assisted Thrombolysis for Submassive Pulmonary Embolism: TheSUNSET sPE Trial.

The aim of this trial was to determine whether ultrasound-assisted thrombolysis (USAT) is superior to standard catheter-directed thrombolysis (SCDT) in pulmonary arterial thrombus reduction for patients with submassive pulmonary embolism (sPE). Catheter-directed therapy has been increasingly used in sPE and massive pulmonary embolism as a decompensation prevention and potentially lifesaving procedure. It is unproved whether USAT is superior to SCDT using traditional multiple-side-hole catheters in the treatment of patients with pulmonary embolism. Adults with sPE were enrolled. Participants were randomized 1:1 to USAT or SCDT. The primary outcome was 48-hour clearance of pulmonary thrombus assessed by pre- and postprocedural computed tomographic angiography using a refined Miller score. Secondary outcomes included improvement in right ventricular-to-left ventricular ratio, intensive care unit and hospital stay, bleeding, and adverse events up to 90days. Eighty-one patients with acute sPE were randomized and were available for analysis. The mean total dose of alteplase for USAT was 19 ± 7mg and for SCDT was 18 ± 7mg (P=0.53), infused over 14 ± 6 and 14 ± 5 hours, respectively (P=0.99). In the USAT group, the mean raw pulmonary arterial thrombus score was reduced from 31 ± 4 at baseline to 22 ± 7 (P< 0.001). In the SCDT group, the score was reduced from 33 ± 4 to 23 ± 7 (P< 0.001). There was no significant difference in mean thrombus score reduction between the 2 groups (P=0.76). The mean reduction in right ventricular/left ventricular ratio from baseline (1.54 ± 0.30 for USAT, 1.69 ± 0.44 for SCDT) to 48 hours was 0.37 ± 0.34 in the USAT group and 0.59 ± 0.42 in the SCDT group (P=0.01). Major bleeding (1 stroke and 1 vaginal bleed requiring transfusion) occurred in 2 patients, both in the USAT group. In the SUNSET sPE (Standard vs. Ultrasound-Assisted Catheter Thrombolysis for Submassive Pulmonary Embolism) trial, patients undergoing USAT had similar pulmonary arterial thrombus reduction compared with those undergoing SCDT, using comparable mean lytic doses and durations of lysis.

Contemporary Catheter-Based Treatment Options for Management of Acute Pulmonary Embolism.

IntroductionAcute pulmonary embolism (PE) remains an important cause of cardiovascular mortality and morbidity in the USA and worldwide. Catheter-based therapies are emerging as a new armamentarium for improving outcomes in these patients.Purpose of reviewThe purpose of this review is to familiarize the clinicians with (1) various types of catheter-based modalities available for patients with acute PE, (2) advantages, disadvantages, and appropriate patient selection for the use of these devices, and (3) evidence base and the relevance of such therapies in the COVID-19 pandemic.Recent findingsThere are four main types of catheter-based therapies in acute PE: (1) standard catheter-directed thrombolysis (CDT), (2) ultrasound-assisted CDT, (3) pharmacomechanical CDT, and (4) mechanical thrombectomy without thrombolysis. Ultrasound-assisted thrombolysis is the most widely studied modality in this group; however, evidence base for other catheter-based technologies is rapidly emerging.SummaryCurrent use of catheter-based therapies is most suitable for patients with intermediate and high-risk acute PE. The adoption of a multidisciplinary approach like the pulmonary embolism response team (PERT) is desirable for appropriate patient selection and possibly/potentially improving patient outcomes. We discuss the current status of these therapies.

Role of Interventional Radiologist in the Management of Acute Pulmonary Embolism.

Pulmonary embolism is a common cause of morbidity and mortality which continues to increase in overall incidence. Because it can occur with a wide range of clinical presentations, different guidelines have been developed for appropriate risk stratification of patients; interventional radiology plays a vital role in the management of both massive and submassive pulmonary embolism. Catheter-directed therapy, including mechanical and aspiration thrombectomy, standard catheter-directed thrombolysis, and ultrasound-accelerated thrombolysis, has many benefits, including lower thrombolytic doses and intraclot administration of thrombolytic therapy. While the role of catheter-directed therapy is still being developed, four important prospective studies have demonstrated its safety and efficacy. Additional studies comparing short- and long-term clinical outcomes in patients treated with catheter-directed therapy versus anticoagulation are the next step in understanding its role within the management of submassive pulmonary embolism. Furthermore, multidisciplinary pulmonary embolism response teams, in which interventional radiology plays a crucial role, are becoming essential to appropriately managing pulmonary embolism patients, including selection of those who may benefit from catheter-directed therapy.

Design and rationale of a randomized trial comparing standard versus ultrasound-assisted thrombolysis for submassive pulmonary embolism.

Catheter-directed interventions for the treatment of patients with submassive pulmonary embolism (sPE) have shown promise in rapidly improving right-sided heart strain and preventing decompensation to massive pulmonary embolism. Among various catheter interventions, ultrasound-assisted thrombolysis (USAT) has attracted interest as potentially having more efficient lytic effect that could achieve thrombolysis faster and with a reduced lytic dose. However, based on clinical evidence, it is unclear whether USAT is superior to standard catheter-directed thrombolysis (SCDT). We herein describe the study design of the Standard vs UltrasouNd-assiSted CathEter Thrombolysis for Submassive Pulmonary Embolism (SUNSET sPE) trial, an ongoing randomized clinical trial designed to address this question. Adults with sPE presenting or referred to our institution are considered for enrollment in the trial. At the discretion of the treatment team, all patients undergo a catheter-directed intervention plus concomitant therapeutic anticoagulation. Participants are randomized 1:1 to a USAT catheter or an SCDT catheter. Study assessors are blinded to treatment group. The primary outcome is clearance of pulmonary thrombus burden, assessed by postprocedure computed tomography angiography. Secondary outcomes include resolution of right ventricular strain by echocardiography; improvement in pulmonary artery pressures; and 3- and 12-month improvement in echocardiographic, functional capacity, and quality of life measures. The study is powered to detect a 50% improvement in pulmonary artery thrombus clearance. Our enrollment target is 40 patients per treatment arm. SUNSET sPE is an ongoing randomized, head-to-head, single-blinded clinical trial with the goal of assessing whether USAT results in superior thrombus clearance compared with SCDT in patients with sPE. We expect the results ofour study to inform future guidelines on choice of thrombolysis modality in this population of challenging patients.

Catheter-directed Thrombolysis for Intermediate-Risk Pulmonary Embolism.

Intermediate-risk pulmonary embolism is common and carries a risk of progression to hemodynamic collapse and death. Catheter-directed thrombolysis is an increasingly used treatment option, based largely on the assumptions that it is more efficacious than anticoagulation alone and safer than systemic thrombolysis. In this review, we critically analyze the published data regarding catheter-directed thrombolysis for the treatment of intermediate-risk pulmonary embolism. Catheter-directed thrombolysis reduces right heart strain and lowers pulmonary artery pressures more quickly than anticoagulation alone. The mortality for patients with intermediate-risk pulmonary embolism treated with catheter-directed thrombolysis is low, between 0% and 4%. However, similarly low mortality is seen with anticoagulation alone. Catheter-directed thrombolysis appears to be safer than systemic thrombolysis, and procedural complications are uncommon. Bleeding risk appears to be slightly higher than with anticoagulation alone. Randomized, controlled trials are needed to compare the efficacy and safety of catheter-directed thrombolysis versus anticoagulation for intermediate-risk pulmonary embolism. There is no evidence that catheter-directed thrombolysis decreases the incidence of chronic thromboembolic pulmonary hypertension. There is no evidence from clinical studies that ultrasound-assisted thrombolysis is more effective or safer than standard catheter-directed thrombolysis.

Midterm outcomes of catheter-directed interventions for the treatment of acute pulmonary embolism.

Objective The hemodynamic benefits of catheter-directed thrombolysis for acute pulmonary embolism have not been clearly defined beyond the periprocedural period. The objective of this study is to report midterm outcomes of catheter-directed thrombolysis for treatment of acute pulmonary embolism. Methods Records of all patients undergoing catheter-directed thrombolysis for high- or intermediate-risk pulmonary embolism were retrospectively reviewed. Endpoints were clinical success, procedure-related complications, mortality, and longitudinal echocardiographic parameter improvement. Results A total of 69 patients underwent catheter-directed thrombolysis (mean age 59 ± 15 y, 56% male). Eleven had high-risk and 58 intermediate-risk pulmonary embolism. Baseline characteristics did not differ by pulmonary embolism subtype. Fifty-two percent of patients underwent ultrasound-assisted thrombolysis, 39% standard catheter-directed thrombolysis, and 9% other interventional therapy; 89.9% had bilateral treatment. Average treatment time was 17.7 ± 11.3 h with average t-Pa dose of 28.5 ± 19.6 mg. The rate of clinical success was 88%. There were two major (3%) and six minor (9%) periprocedural bleeding complications with no strokes. All echocardiographic parameters demonstrated significant improvement at one-year follow-up. Pulmonary embolism-related in-hospital mortality was 3.3%, and estimated survival was 81.2% at one year. Conclusions Catheter-directed thrombolysis is safe and effective for treatment of acute pulmonary embolism, with sustained hemodynamic improvement at one year. Further prospective large-scale studies are needed to determine comparative effectiveness of interventions for acute pulmonary embolism.

Dutch Randomized Trial Comparing Standard Catheter-Directed Thrombolysis and Ultrasound-Accelerated Thrombolysis for Arterial Thromboembolic Infrainguinal Disease (DUET)

Purpose: To report the results of the Dutch randomized trial comparing standard catheter-directed and ultrasound-accelerated thrombolysis (UST) for the treatment of arterial thromboembolic occlusions. Methods: The DUET study ( controlled-trials.com ; identifier ISRCTN72676102) was designed to assess whether UST can reduce therapy time significantly compared with standard thrombolysis (ST). Sixty patients (44 men; mean age 64 years) with recently (7–49 days) thrombosed infrainguinal native arteries or bypass grafts causing acute limb ischemia (Rutherford category I or IIa) were randomized to ST (n=32) or UST (n=28). The primary outcome was the duration of thrombolysis needed for uninterrupted flow (>95% thrombus lysis), with outflow through at least 1 below-the-knee artery. Continuous data are presented as means ± standard deviations. Results: Thrombolysis was significantly faster in the UST group (17.7±2.0 hours) than in the ST group (29.5±3.2 hours, p=0.009) and required significantly fewer units of urokinase (2.8±1.6×106 IU in the ST group vs. 1.8±1.0×106 IU in the UST group, p=0.01) for uninterrupted flow. Technical success was achieved in 27 (84%) patients in the ST group vs. 21 (75%) patients in the UST group (p=0.52). The combined 30-day death and severe adverse event rate was 19% in the ST group and 29% in the UST group (p=0.54). The 30-day patency rate was 82% in the ST group as compared with 71% in the UST group (p=0.35). Conclusion: Thrombolysis time was significantly reduced by UST as compared with ST in patients with recently thrombosed infrainguinal native arteries or bypass grafts.

Equivalent Outcomes Between Ultrasound-Assisted Thrombolysis and Standard Catheter-Directed Thrombolysis for the Treatment of Acute Pulmonary Embolism.

Equivalent Outcomes Between Ultrasound-Assisted Thrombolysis and Standard Catheter-Directed Thrombolysis for the Treatment of Acute Pulmonary Embolism.