Ultrasound-assisted Catheter-directed Thrombolysis Research Articles

Fixed-Dose Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Associated with COVID-19.

Background. Fixed-dose ultrasound-assisted catheter-directed thrombolysis (USAT) rapidly improves hemodynamic parameters and reverses right ventricular dysfunction caused by acute pulmonary embolism (PE). The effectiveness of USAT for acute PE associated with coronavirus disease 2019 (COVID-19) is unknown. Methods and results. The study population of this cohort study consisted of 36 patients with an intermediate-high- or high-risk acute PE treated with a fixed low-dose USAT protocol (r-tPA 10–20 mg/15 h). Of these, 9 patients tested positive for COVID-19 and were age–sex-matched to 27 patients without COVID-19. The USAT protocol included, beyond the infusion of recombinant tissue plasminogen activator, anti-Xa-activity-adjusted unfractionated heparin therapy (target 0.3–0.7 U/mL). The study outcomes were the invasively measured mean pulmonary arterial pressure (mPAP) before and at completion of USAT, and the National Early Warning Score (NEWS), according to which more points indicate more severe hemodynamic impairment. Twenty-four (66.7%) patients were men; the mean age was 67 ± 14 years. Mean ± standard deviation mPAP decreased from 32.3 ± 8.3 to 22.4 ± 7.0 mmHg among COVID-19 patients and from 35.4 ± 9.7 to 24.6 ± 7.0 mmHg among unexposed, with no difference in the relative improvement between groups (p = 0.84). Within 12 h of USAT start, the median NEWS decreased from six (Q1–Q3: 4–8) to three (Q1–Q3: 2–4) points among COVID-19 patients and from four (Q1–Q3: 2–6) to two (Q1–Q3: 2–3) points among unexposed (p = 0.29). One COVID-19 patient died due to COVID-19-related complications 14 days after acute PE. No major bleeding events occurred. Conclusions. Among patients with COVID-19-associated acute PE, mPAP rapidly decreased during USAT with a concomitant progressive improvement of the NEWS. The magnitude of mPAP reduction was similar in patients with and without COVID-19.

Ultrasound-assisted catheter-directed thrombolysis versus anticoagulation alone for management of submassive pulmonary embolism

BackgroundPatients with submassive pulmonary embolism (PE) are vulnerable to sudden deterioration, recurrent PE, and progression to pulmonary hypertension and chronic right ventricular (RV) dysfunction. Previous studies have suggested a clinical benefit of using ultrasound-assisted catheter-directed thrombolysis (USCDT) to invasively manage patients with submassive PE. However, there is sparse data comparing the clinical outcomes of these patients when treated with USCDT versus anticoagulation (AC) alone. We sought to compare the outcomes of USCDT versus AC alone in the management of submassive PE. Methods192 consecutive patients who underwent USCDT for submassive PE between January 2013 and February 2019 were identified. ICD9/ICD10 codes were used to detect 2554 patients diagnosed with PE who did not undergo thrombolysis. Propensity matching identified 192 patients with acute PE treated with AC alone. Clinical outcomes were compared between the two groups. Baseline demographics, laboratory values, and pulmonary embolism severity index scores were similar between the two cohorts. ResultsThere was a significant reduction in mean systolic pulmonary artery pressure (sPAP) in the USCDT group compared to the AC group (∆11 vs ∆3.9 mmHg, p < 0.001). There was significant improvement in proportion of RV dysfunction in all patients, but the difference was larger in the USCDT group (∆43.3% vs ∆17.3%, p < 0.001). Patients who underwent USCDT had lower 30-day (4.3% vs 10.5%, p = 0.03), 90-day (5.5% vs 12.4%, p = 0.03), and 1-year mortality (6.2% vs 14.2%, p = 0.03). ConclusionsIn patients with acute submassive PE, USCDT was associated with improved 30-day, 90-day, and 1 year mortality as compared to AC alone. USCDT also improved RV function and reduced sPAP to a greater degree than AC alone. Further studies are needed to verify these results in both short- and long-term outcomes.

Venous and Arterial Thoracic Outlet Syndrome Requiring Surgical Intervention: Two Case Reports

Background: Thoracic outlet syndrome represents a spectrum of diseases depending on the structures involved. Most cases of thoracic outlet syndrome (TOS) are neurogenic while arterial and venous TOS constitute only 5% of the cases. Paget-Schroetter syndrome represents an acute complication of venous thoracic outlet syndrome (vTOS) commonly occurring in physically active individuals participating in strenuous upper body exercises. Arterial thoracic outlet syndrome (aTOS) is usually associated with bony abnormalities. We discuss one patient of each type who presented with acute thrombosis to illustrate the different associated factors and treatment options. Case Report(s): An 18-year-old Hispanic male presented with six days of left upper extremity (LUE) edema and pain that began following an upper body exercise. He was treated by pharmacomechanical thrombectomy followed by ultrasound assisted catheter-directed thrombolysis. Subsequently the patient underwent trans axillary surgical decompression of the thoracic outlet. A 59-year-old South Asian woman presented with worsening LUE pain, weakness and paresthesia of 10 days duration. She underwent pharmacomechanical thrombectomy with angioplasty followed by supraclavicular thoracic outlet decompression. Conclusions: Treatment of TOS presenting with thrombosis should consist of prompt thrombectomy followed by surgical decompression.

EKOS™ Jena Experience: Safety, Feasibility, and Midterm Outcomes of Percutaneous Ultrasound-Assisted Catheter-Directed Thrombolysis in Patients with Intermediate-High-Risk or High-Risk Pulmonary Embolism.

Background Percutaneous catheter-based ultrasound-assisted thrombolysis (UACDT) is recommended for patients with intermediate-high-risk or high-risk pulmonary embolism (PE) in whom systemic thrombolysis has failed or is contraindicated. Aim To evaluate the safety and efficiency of UACDT in patients with intermediate-high-risk or high-risk PE. Methods Between October 2017 and January 2020, we performed UACDT using the EkoSonic™ Endovascular System (EKOS™) in 51 patients (21 males, age 63 ± 18 years) with a sPESI of 1.3 ± 0.7. The EKOS™-catheter was implanted within 24 h after admission. Over 15 hours, 11.5 mg of alteplase was administered per catheter. We evaluated right ventricular stress and cardiac biomarkers before and after UACDT. Results 24 h post-UACDT, median RV/LV ratio decreased from 1.13 to 0.96 (p < 0.001) and the mean sPAP decreased from 47 ± 3 to 32 ± 2 mmHg + CVP (p < 0.0002). There were 6 major bleeding events resulting in transfusion. No stroke, myocardial infarction, right heart decompensation, or recurrent PE occurred. 31 patients (63%) were discharged without any signs of right ventricular stress. After at least 3 months, 73% of our patients did not show any signs of right ventricular dysfunction. The mean RV/LV ratio decreased to 0.75 ± 0.03 (p < 0.0001) in comparison with pre-UACDT, sPAP to 23 mmHg + CVP (p < 0.0001), and BNP to 40 pg/ml (p < 0.0001). Conclusions The treatment with UACDT reduced right heart stress during the first 24 hours and midterm in patients with intermediate-high-risk or high-risk PE at an acceptable rate of severe complications.

Advances in Ultrasound-assisted Catheter-directed Thrombolysis for the Treatment of Pulmonary Thromboembolism

Advances in Ultrasound-assisted Catheter-directed Thrombolysis for the Treatment of Pulmonary Thromboembolism

Fixed-Dose Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Associated with COVID-19

Fixed-Dose Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Associated with COVID-19

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.

Response Team Management of Acute Serious Pulmonary Embolism.

Response Team Management of Acute Serious Pulmonary Embolism.

Pulmonary Embolism in Pregnancy: Ultrasound-Assisted Catheter-Directed Thrombolytic Therapy for the Treatment of a Pulmonary Embolus—A Case Report

Abstract In the United States, pulmonary embolism (PE) accounts for approximately 10% of all pregnancy related deaths. The standard treatment for a patient with high-risk PE is systemic thrombolysis. Systemic thrombolysis in pregnancy is associated with the risk of maternal hemorrhage and fetal complications, including spontaneous abortion, preterm delivery, and fetal bleeding. Currently, there is limited evidence for a standardized approach for the treatment and management of intermediate- and high-risk PEs in pregnancy. A 36-year-old gravida 3 para 2002 woman at 31+1 weeks of gestation with a history of deep vein thrombosis in her prior pregnancy presented with shortness of breath. A computed tomography angiogram revealed a large pulmonary embolus with a saddle component that extended into the bilateral upper and lower lobes and into the secondary and tertiary pulmonary branches. A subsequent bedside echocardiogram demonstrated a dilated right ventricle with severely reduced right ventricular systolic function. The patient was successfully treated with bilateral ultrasound-assisted catheter-directed thrombolysis. She subsequently delivered a healthy male infant at term. Reported cases of ultrasound-assisted catheter-directed thrombolysis in pregnant patients is limited. Our case demonstrates that localized thrombolysis is a viable treatment option for life-threatening PE in pregnancy. Catheter-directed thrombolysis can be efficacious in treating intermediate- and high-risk PEs in pregnancy while simultaneously reducing the risk of bleeding complications.

Fibrinogen Levels and Bleeding Risk in Patients Undergoing Ultrasound-Assisted Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism

Fibrinogen Levels and Bleeding Risk in Patients Undergoing Ultrasound-Assisted Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism

Ultrasound-assisted catheter directed thrombolysis for pulmonary embolus during extracorporeal membrane oxygenation.

Acute pulmonary embolism (PE) is the third most common cause of cardiovascular death. For patients who are hemodynamically unstable, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been shown to provide hemodynamic stability, and allow time for definitive treatment and recovery. Ultrasound-assisted catheter directed thrombolysis (USAT) has the potential to be a safe adjunct and expedite right ventricular (RV) recovery for patients requiring VA-ECMO for PE. A review of all VA-ECMO patients from January 2017 to September 2019 was performed. A total of 49 of these patients were cannulated due to a PE. USAT therapy was used as an adjunct in 6 (12%) of these patients. These 6 patients were given standardized USAT therapy with EKOs catheters at 1 mg/h of tissue plasminogen activator with an unfractionated heparin infusion for additional systemic anticoagulation. Outcomes, including in-hospital death, 90-day survival, RV recovery, and complications, were examined in the cohort of patients that received USAT as an adjunct to ECMO. Median age was 54 years old. Five of the six patients presented with a massive PE and had a PE severity score of Class V. One patient presented with a submassive PE with a Bova score of 2, but was cannulated to VA-ECMO in the setting of worsening RV function. All patients demonstrated recovery of RV function, were free from in-hospital death, and were alive at 90-day follow-up. Ekosonic endovascular system therapy may be a safe and feasible adjunct for patients on VA-ECMO for PE, and allow for survival with RV recovery with minimal complications.

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.

Clinical outcomes of very elderly patients treated with ultrasound-assisted catheter-directed thrombolysis for pulmonary embolism: a systematic review.

Pulmonary embolism (PE) is a significant cause of death in the very elderly (≥ 75years) population. Ultrasound-assisted catheter-directed thrombolysis (USCDT) emerges to improve thrombolysis safety and efficacy. However, outcomes in very elderly patients are unknown, as randomized controlled trials exclude this population. Recently, we demonstrated acute kidney injury (AKI) and ischemic hepatitis in an octogenarian intermediate-risk PE patient treated with USCDT. Considering the lack of evidence, we undertook a systematic review to evaluate the clinical outcomes in very elderly PE patients treated with USCDT. We searched for very elderly PE patients treated with USCDT from 2008 to 2019. Additionally, we conducted another systematic review without age restriction to update previous evidence and compare both populations. We also did an exploratory analysis to determine if thrombolysis was followed based on current guidelines or impending clinical deterioration factors. We identified 18 very elderly patients (age 79.2, 75-86), mostly female and with intermediate-risk PE. We found an intracranial hemorrhage (ICH), and a right pulmonary artery rupture. Additionally, two significant bleedings complicated with transient AKI, and one case of AKI and ischemic hepatic injury. The patients who survived all had clinical and echocardiographic in-hospital improvement. Despite low rt-PA doses, ICH and major bleeding remain as feared complications. Thrombolysis decision was driven by impending clinical deterioration factors instead of international guideline recommendations. Our data do not suggest prohibitive risk associated with USCDT in very elderly intermediate and high-risk PE patients. Despite long-term infusions and right ventricular dysfunction, AKI and ischemic hepatic injury were infrequent.

Pulmonary thrombosis in Covid-19: before, during and after hospital admission

Disordered coagulation, endothelial dysfunction, dehydration and immobility contribute to a substantially elevated risk of deep venous thrombosis, pulmonary embolism (PE) and systemic thrombosis in coronavirus disease 2019 (Covid-19). We evaluated the prevalence of pulmonary thrombosis and reported RV (right ventricular) dilatation/dysfunction associated with Covid-19 in a tertiary referral Covid-19 centre. Of 370 patients, positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 39 patients (mean age 62.3 ± 15 years, 56% male) underwent computed tomography pulmonary angiography (CTPA), due to increasing oxygen requirements or refractory hypoxia, not improving on oxygen, very elevated D-dimer or tachycardia disproportionate to clinical condition. Thrombosis in the pulmonary vasculature was found in 18 (46.2%) patients. However, pulmonary thrombosis did not predict survival (46.2% survivors vs 41.7% non-survivors, p = 0.796), but RV dilatation was less frequent among survivors (11.5% survivors vs 58.3% non-survivors, p = 0.002). Over the following month, we observed four Covid-19 patients, who were admitted with high and intermediate-high risk PE, and we treated them with UACTD (ultrasound-assisted catheter-directed thrombolysis), and four further patients, who were admitted with PE up to 4 weeks after recovery from Covid-19. Finally, we observed a case of RV dysfunction and pre-capillary pulmonary hypertension, associated with Covid-19 extensive lung disease. We demonstrated that pulmonary thrombosis is common in association with Covid-19. Also, the thrombotic risk in the pulmonary vasculature is present before and during hospital admission, and continues at least up to four weeks after discharge, and we present UACTD for high and intermediate-high risk PE management in Covid-19 patients.

1083: Ultrasound-Assisted Catheter-Directed Thrombolysis: Optimizing Safety, Quality, and Value

Li, Fanny1; De Leon, Noelle1; Schell-Chaple, Hildy1; Zhao, Lucia1; Kolli, K. Pallav1; Fong, Charlene1 Author Information

Ultrasound-assisted catheter-directed thrombolysis versus systemic anticoagulation alone for submassive pulmonary embolism.

Pulmonary embolism (PE) is a significant contributor to morbidity and mortality in the United States. Catheter-directed, ultrasound-assisted thrombolysis (USAT) uses high-frequency, low-energy ultrasound waves to disaggregate uncrosslinked fibrin fibers and increase thrombus penetration of a locally delivered thrombolytic to treat an acute PE. The purpose of this study is to compare the efficacy and safety of catheter-directed USAT versus systemic anticoagulation alone in submassive PE. This was a single-center, retrospective study of patients with a diagnosis of acute submassive PE from April 4, 2014 to May 1, 2019 at a large, academic medical center. Subjects were split into two different groups based on treatment with either USAT with systemic anticoagulation or systemic anticoagulation alone. The primary outcome was the incidence of severe or life-threatening GUSTO bleeding within 72h or until hospital discharge if sooner. A total of 130 subjects were included (n = 40 in the USAT group and n = 90 in systemic anticoagulation alone group). Significantly fewer subjects in the USAT group had an active diagnosis of cancer at the time of presentation (7.5% vs 28.9%, p = 0.006). There was no difference in severe or life-threatening GUSTO bleeding or any component of the GUSTO bleeding definitions. Administration of USAT with systemic anticoagulation was well-tolerated when compared to systemic anticoagulation alone, but bias may have led to selection of patients for USAT with a lower bleeding risk and higher functional status at baseline.

Massive pulmonary embolism in patients with extreme bleeding risk: a case series on the successful use of ultrasound-assisted, catheter directed thrombolysis in a district general hospital

Massive pulmonary embolism (PE), characterised by profound arterial hypotension, is a life-threatening emergency with a 90-day mortality of over 50%. Systemic thrombolysis can significantly reduce the risk of death or cardiovascular collapse in these patients, by around 50%, but these benefits are offset by a fivefold increased risk of intracranial haemorrhage and major bleeding, which may limit its use in patients at high risk of catastrophic haemorrhage. We describe a case series of 3 patients presenting with massive PE, each with extreme risk of bleeding and contra-indication to systemic thrombolysis, treated successfully with ultrasound-assisted, catheter directed thrombolysis (U-ACDT). Our experience of this novel technique using the EkoSonic Endovascular System (Ekos, BTG, London, UK) on carefully selected patients has demonstrated the potential to improve clinical status in shocked patients, with minimal bleed risk. There have been several clinical studies evaluating the Ekos system. Both the ULTIMA and SEATTLE II studies have shown significant reductions in RV/LV ratio by CT scanning when compared to standard anticoagulation in patients with intermediate-risk PE, with minimal bleeding complications. However, there is a pressing need for a randomised trial demonstrating improvement in robust clinical outcomes when comparing U-ACDT to simple anticoagulation. We believe that this case series adds new insight and highlights the potential of catheter directed thrombolysis in this high-risk patient cohort and consideration should be made to its use in cases where systemic thrombolysis is felt to be too high risk.

Clinical Outcomes of Patients with Intermediate-to-High-Risk Pulmonary Embolism Undergoing Ultrasound-Assisted Catheter-Based Fibrinolysis Therapy in a Mid-Term Follow-Up Period - A Retrospective Observational Study.

Endovascular therapy with ultrasound-assisted catheter-directed thrombolysis (UACDT) theoretically provides higher efficacy while reducing the bleeding risk compared with conventional systemic thrombolysis. The clinical outcomes of UACDT in treating intermediate-to-high-risk pulmonary embolism (PE) are lacking in an Asian population. Forty-two patients who presented with intermediate-to-high-risk PE received UACDT. The patients were divided into two groups based on the incidence of procedure-related bleeding events, and baseline demographics were compared between the two groups. A paired-Student's t test was conducted to evaluate the efficacy of UACDT. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for significant bleeding events. The average age was 58.93 ± 20.48 years, and 33.33% of the study participants were male. A total of 85.7% of the participants had intermediate-risk PE. Compared with pre-intervention pulmonary artery pressure, the mean pulmonary artery pressure decreased significantly (37.61 ± 9.57 mmHg vs. 25.7 ± 9.84 mmHg, p < 0.01) after UACDT. The cumulative total tissue plasminogen activator dosage and total infusion duration were 44.54 ± 20.55 mg and 39.14 ± 19.06 hours respectively. Overall, 21.43% of the participants had severe bleeding events during the endovascular fibrinolysis treatment period. Forward conditional multivariate logistic regression analysis revealed that the lowest fibrinogen level during thrombolysis was an independent factor associated with moderate-to-severe bleeding (odds ratio: 0.40, 95% confidence interval: 0.19-0.88, p = 0.02). UACDT exhibited high efficacy, but resulted in a higher-than-expected bleeding rate in this real-world study of an Asian population. The lowest fibrinogen level during thrombolysis was an independent risk factor associated with procedure-related bleeding events.

Predictors of Treatment Response Following Ultrasound-Facilitated Catheter-Directed Thrombolysis for Submassive and Massive Pulmonary Embolism: A SEATTLE II Substudy.

Little is known about which factors predict improvement in clinical and imaging parameters among patients undergoing catheter-directed thrombolysis for submassive or massive pulmonary embolism. The identification of such predictors may allow for more appropriate patient selection for ultrasound-facilitated catheter-directed thrombolysis. We conducted a retrospective cohort analysis of patients from the SEATTLE II trial (Prospective, Single-Arm, Multi-Center Trial of EkoSonic Endovascular System and Activase for Treatment of Acute Pulmonary Embolism) to identify clinical characteristics that independently predict pulmonary artery pressures, right ventricular-to-left ventricular (RV/LV) diameter ratio, and modified Miller angiographic index following ultrasound-assisted catheter-directed thrombolysis. Eligible patients had submassive or massive pulmonary embolism and an RV/LV diameter ratio ≥0.9 on chest computed tomography. Multivariable linear regression was used to identify independent clinical predictors of each outcome. One hundred fifty patients with massive (n=31) or submassive (n=119) pulmonary embolism were enrolled. Mean (±SD) baseline and postprocedure RV/LV diameter ratio, pulmonary artery systolic pressure, and modified Miller Score were 1.59 (±0.39) and 1.14 (±0.2), 51.45 (±16.0), and 37.47 (±11.9), and 23.0 (±5.7) and 15.7 (±5.9), respectively. The multivariable model adjusted R2 for absolute change in RV/LV ratio, pulmonary artery systolic pressure, modified Miller Score was 0.71, 0.57, and 0.43, respectively. After adjusting for age, gender, and baseline RV/LV ratio, pulmonary artery systolic pressure, and modified Miller Score, patients with higher body mass index, renal or hepatic dysfunction, active smoking, or a higher baseline heart rate showed less improvement. Patients with more life-threatening pulmonary embolism may derive the greatest benefit from ultrasound-assisted, catheter-directed thrombolysis.

ULTRASOUND ASSISTED CATHETER DIRECTED THROMBOLYSIS CAN BE SAFELY USED WITH INHALED EPOPROSTENOL AND REPEATED DURING THE SAME ADMISSION

Ultrasound assisted catheter directed thrombolysis (USCDT) is increasingly used in patients with sub-massive pulmonary embolism (PE). Repeat use of USCDT in patients during the same admission and with inhaled epoprostenol has not been described. 43 year-old man with known thromboangiitis obliterans