Mechanical Thrombus Fragmentation Research Articles

Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran vs warfarin: Results of a multicenter randomized RE-SPIRE trial

BackgroundThrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought to evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high and intermediate to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT). MethodsThe RE-SPIRE is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high and intermediate to high PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT) were randomized into two groups within the next 48 hours. The first group continued treatment with dabigatran 150 mg twice a day for 6 months; the second group continued treatment with warfarin under the control of international normalized ratio (2.0-3.0) for 6 months. Both groups received low molecular weight heparins for 2 days after surgery. Then, group 1 continued to receive low molecular-weight-heparin for 5 to 7 days, followed by a switch to dabigatran at a dosage of 150 mg two times a day. Group 2 received both low-molecular-weight heparin and warfarin up to an international normalized ratio of >2.0, followed by heparin withdrawal. The follow-up period was 6 months. ResultsThere were 63 patients who completed the study (32 in the dabigatran group and 31 in the warfarin group). In both groups, there was a statistically significant decrease in the mean pulmonary artery pressure. The mean pulmonary artery pressure at the 6-month follow-up after surgery was 24 mm Hg (interquartile range, 20.3-29.25 mm Hg) in the dabigatran group and 23 mm Hg (interquartile range, 20.0-26.3 mm Hg) in the warfarin group. The groups did not differ statistically in the deep vein thrombosis dynamics. Partial recanalization occurred in 52.0% vs 73.1% in the dabigatran and warfarin groups, respectively (P = .15). Complete recanalization occurred in 28.0% vs 19.2% in the dabigatran and warfarin groups, respectively (P = .56). The groups did not differ in the frequency of major bleeding events according to the International Society for Thrombosis and Hemostasis (0% vs 3.2% in the dabigatran and warfarin groups, respectively; P = 1.00). However, there were more nonmajor bleeding events in the warfarin group than in the dabigatran group (16.1% vs 0%, respectively; P = .02). ConclusionsThe results of the study show that dabigatran is comparable in effectiveness to warfarin. Dabigatran has greater safety in comparison with warfarin in the occurrence of all cases of bleeding in the postoperative and long-term periods. Thus, dabigatran may be recommended for the treatment and prevention of PE after CDT with RDT in patients with high and intermediate to high PE risk.

Feasibility and safety of catheter-directed thrombolysis via superficial cubital vein for the treatment of acute massive and submassive pulmonary embolism.

IntroductionProximal venous approaches (femoral or jugular) for catheter-directed thrombolysis (CDT) of acute pulmonary embolism (PE) dominate in clinical practice.AimWe investigated the feasibility and safety of CDT in acute PE by using the superficial cubital venous approach.Material and methodsAll patients with acute PE received intravenous unfractionated heparin plus CDT. CDT included mechanical thrombus fragmentation and the local application of adjuvant thrombolytic therapy through the pigtail catheter – alteplase administered as 2.5 mg bolus in each main branch of the pulmonary artery plus adjuvant 25 mg for 12 h in the more severely affected branch of the pulmonary artery.ResultsTwenty-seven consecutive patients presenting with acute massive (high risk) PE (n = 10) or submassive (intermediate risk) PE (n = 17) were enrolled in the study. The mean age of the enrolled cohort was 60.6 (14.1) years and most patients were female (n = 14, 52%). The procedural success of CDT application through the cubital vein was achieved in all patients. After the procedure, the systolic pulmonary artery pressure decreased from 61.4 (18.3) to 35.8 (12.3) mm Hg (p < 0.001) while the mean pulmonary artery pressure decreased from 35.7 (10.8) to 21.1 (6.5) mm Hg (p < 0.001). Similarly, the mean arterial pressure increased from 81.9 (12.8) to 89.0 (10.3) mm Hg (p = 0.031). Miller angiographic obstruction score and Miller index decreased significantly after the CDT intervention (p < 0.001). There were no deaths, major bleeding events, or hemorrhagic strokes.ConclusionsCDT by using the cubital approach is a simple, safe, and feasible treatment option for PE. This approach was associated with significant improvement in hemodynamic parameters without fatal outcomes or major periprocedural complications.

Late Clinical Outcomes of Hybrid Catheter Intervention for Acute Massive Pulmonary Thromboembolism.

Purpose: We aimed to investigate the long-term outcomes of patients undergoing hybrid catheter intervention for acute massive pulmonary thromboembolism.Material and Methods: Twenty-five patients with hemodynamic impairment were treated with mechanical thrombus fragmentation, an intrapulmonary injection of mt-PA, and manual clot aspiration between August 1999 and June 2002. All patients were discharged after the procedure. Patients’ statuses were checked by medical record examinations and telephone interviews. The median follow-up was 141 months (115-168 months).Results: Ten patients died during follow-up, five for malignancy, three for septic shock, one for cerebral infarction, and one for heart failure. One patient had recurrence of pulmonary thromboembolism because of drug withdrawal by self-judgment. No chronic pulmonary thromboembolism was observed. The 1-year, 5-year, and 10-year survival rates were 87.5 ±6.8%, 83.3±7.6%, and 74.5±9.0%, respectively.Conclusion: Patients who undergo hybrid catheter intervention for acute massive pulmonary thromboembolism show good long-term outcomes.

Percutaneous mechanical thrombectomy combined with catheter-directed thrombolysis in the treatment of acute pulmonary embolism and lower extremity deep venous thrombosis: A novel one-stop endovascular strategy

ObjectiveThis study was performed to evaluate the efficacy and feasibility of percutaneous mechanical thrombectomy (PMT) combined with catheter-directed thrombolysis (CDT) in patients with acute pulmonary embolism (APE) and lower extremity deep venous thrombosis (LEDVT).MethodsIn total, 20 consecutive patients with APE and LEDVT were prospectively selected for PMT combined with CDT. Mechanical thrombus fragmentation and aspiration using a pigtail rotation catheter followed by CDT was performed in each patient. Details regarding the patients’ clinical presentation and outcome, pulmonary status parameters (pulmonary arterial pressure, partial pressure of oxygen in arterial blood, Miller score, thigh and calf circumference, and shock index), and lower extremity parameters (thrombus-lysis grade and Villalta scale score) were recorded.ResultsAll 20 patients’ clinical manifestations significantly improved. Both the clinical success rate and technical success rate were 100%. No major adverse events occurred during hospitalization. Four patients developed iliac vein compression syndrome and underwent stent implantation in the iliac vein. No pulmonary embolism recurred within 16.5±6.8 months of follow-up.ConclusionsThe combination of PMT and CDT is a safe and effective treatment for APE and LEDVT with good short- and intermediate-term clinical outcomes.

Interventional Treatment of Pulmonary Embolism.

Pulmonary embolism (PE) is a serious and prevalent cause of vascular disease. Nevertheless, optimal treatment for many phenotypes of PE remains uncertain. Treating PE requires appropriate risk stratification as a first step. For the highest-risk PE, presenting as shock or arrest, emergent systemic thrombolysis or embolectomy is reasonable, while for low-risk PE, anticoagulation alone is often chosen. Normotensive patients with PE but with indicia of right heart dysfunction (by biomarkers or imaging) constitute an intermediate-risk group for whom there is controversy on therapeutic strategy. Some intermediate-risk patients with PE may require urgent stabilization, and ≈10% will decompensate hemodynamically and suffer high mortality, though identifying these specific patients remains challenging. Systemic thrombolysis is a consideration, but its risks of major and intracranial hemorrhages rival overall harms from intermediate PE. Multiple hybrid pharmacomechanical approaches have been devised to capture the benefits of thrombolysis while reducing its risks, but there is limited aggregate clinical experience with such novel interventional strategies. One method to counteract uncertainty and generate a consensus multidisciplinary prognostic and therapeutic plan is through a Pulmonary Embolism Response Team, which combines expertise from interventional cardiology, interventional radiology, cardiac surgery, cardiac imaging, and critical care. Such a team can help determine which intervention-catheter-directed fibrinolysis, ultrasound-assisted thrombolysis, percutaneous mechanical thrombus fragmentation, or percutaneous or surgical embolectomy-is best suited to a particular patient. This article reviews these various modalities and the background for each.

Interventional treatment of mesenteric venous occlusion.

SummaryBackgroundMesenteric venous thrombus may be an incidental finding during imaging studies and asymptomatic patients are treated conservatively or with anticoagulant therapy only. Patients with symptomatic acute thrombosis causing bowel ischemia require urgent treatment, which frequently includes extensive surgery. Interventional treatment may be an alternative. Purpose: To present results of interventional treatment in patients with symptomatic occlusion of the mesenteric veins.Material/MethodsEight patients, four men and four women aged 24–74 years (mean 53 years) were treated due to symptomatic portomesenteric venous occlusion of thrombotic origin. Transhepatic (n=5), trans-splenic (n=2), and transjugular (n=4) accesses were used. Patients were treated with mechanical thrombus fragmentation (n=4), pharmacological thrombolysis (n=3) and stent placement (n=8). Additional transjugular intrahepatic portosystemic shunt (TIPS) was created to facilitate the outflow from the treated veins (n=4).ResultsThe majority of the patients required combination of different treatment methods. Resolution of symptoms with initial clinical success was achieved in seven of the eight patients, and one patient died the day after the procedure due to sepsis. Two other patients had procedure-related complications; one of them required embolization. Two patients had documented long-term clinical success with patent stents and no symptoms at one year following intervention.ConclusionsEndovascular treatment of portomesenteric occlusion in patients with acute symptomatology showed good short-term clinical success rate.

Combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary embolism

The aim of this study is to evaluate the effectiveness and safety of combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary embolism (PE). Forty-six patients (19 men and 27 women, average age 52.3 ± 13.4 years) with acute PE and right ventricular dysfunction were treated by mechanical thrombus fragmentation with a percutaneous transluminal coronary angioplasty guide catheter. Urokinase was injected into the culprit pulmonary artery after catheter thrombus fragmentation in all patients. Clinical success was achieved in all patients. After the treatment, the average pulmonary artery pressure was decreased from 57.2 ± 6.2 to 36.3 ± 4.1 mmHg (P < 0.01). The oxygen saturation rate was raised from 81.4 ± 4.3% to 97.0 ± 2.0% (P < 0.01), and the right ventricular function was improved. There was no in-hospital mortality and there were no major complications, such as haemorrhage. Patients were treated with warfarin for 6 months with no signs of PE recurrence during the follow up. In PE patients with right ventricular dysfunction and unstable haemodynamics, combined catheter thrombus fragmentation and thrombolysis appears to be a useful therapeutic strategy. In PE patients with right ventricular dysfunction and stable haemodynamics, randomized trials are still required to show that combination of catheter-directed thrombus fragmentation and thrombolysis is superior to standard anticoagulation.

Natriuretic peptide type-B can be a marker of reperfusion in patients with pulmonary thromboembolism subjected to invasive treatment

This study was intended to investigate changes in cardiac biomarkers and pulmonary hemodynamic effects of invasive treatment in patients with intermediate-risk (hemodynamic stability with evidence of right ventricle dysfunction and/or myocardial injury) pulmonary embolism. Also, to also evaluate if natriuretic peptide type-B (NT-proBNP) plasma levels are associated with right ventricle function and pulmonary arterial pressures. Interventional study: Fourteen normotensive adult patients with acute and radiologically massive pulmonary embolism plus positive biomarkers and evidences of right ventricle dysfunction underwent invasive pulmonary angiography for invasive treatment consisting on mechanical thrombus fragmentation and catheter-directed intrathrombus thrombolysis. Angiography was repeated after 12-24 h to reevaluate perfusion status. Plasma biomarkers were monitored before and 8-h after intervention. Biomarkers were initially elevated in all patients. Eleven patients (78.6%) exhibited significant angiographic reperfusion. NT-proBNP and mean pulmonary arterial pressure decreased significantly in all of them [3693 (1803, 8862) to 1951 (1309, 7918) pg/ml; P = 0.008) and 40.0 (24.0, 46.0) to 22.0 (14.0, 27.0) mmHg; P = 0.003, respectively]. No significant variation was observed in troponin-T levels. In patients with high-risk pulmonary embolism, NT-proBNP plasma levels experience rapid and significant reduction after successful invasive treatment. In pulmonary embolism, serial measurements of NT-proBNP could be useful as a tracking tool to assess the success or failure of the thrombolytic treatment.

Perkutane mechanische Thrombektomie mittels Rotationsthrombektomie Aktuelle Studienlage

Acute and subacute ischemia of the limbs is still one of the most frequent reasons for amputation. There are different therapy options for reperfusion therapy including balloon thrombectomy, local lysis and rotational thrombectomy. Balloon thrombectomy, the standard surgical treatment, has proven an effective tool for the treatment of acute vascular obstructions. Nevertheless technical problems and complications can occur. Localized lysis on the other hand could be time - consuming and cost intensive, requiring intensive care monitoring and reangiograms. To achieve a successful result, at least one lower limb artery or major collateral has to be reopened to establish a sufficient situation. During the last years considerable advances have been made in endovascular interventions for the treatment of acute and subacute limb ischemia. The Straub Rotarex is one of the modern peripheral mechanical thrombectomy device, which combines mechanical thrombus fragmentation and removal of the material using negative pressure. There are different clinical and experimental studies, which have shown promising results in restoring blood flow to the occluded vessels. Studies mainly exist for the lower extremities. Some case reports showed effective treatment of the subclavian and axillary arteries. The advantages of the Rotarex system is simple handling, a short intervention time and the avoidance of lytic substances with consequent reduced risk of hemorrhage complications. In this article an overview about the main Rotarex studies is given which analyzed the results of percutaneous rotational thrombectomy in patients with subacute an acute thrombotic occlusions in peripheral arteries.

Catheter fragmentation of acute massive pulmonary thromboembolism: distal embolisation and pulmonary arterial pressure elevation

The aim of this study was to evaluate the relationship between pulmonary arterial pressure and distal embolisation during catheter fragmentation for the treatment of acute massive pulmonary thromboembolism with haemodynamic impairment. 25 patients with haemodynamic impairment (8 men and 17 women; aged 27-82 years) were treated by mechanical thrombus fragmentation with a modified rotating pigtail catheter. After thrombus fragmentation, all patients received local fibrinolytic therapy, followed by manual clot aspiration using a percutaneous transluminal coronary angioplasty (PTCA) guide catheter. Pulmonary arterial pressure was continuously recorded during the procedure. The Friedman test and Wilcoxon test were applied for statistical analysis. Distal embolisation was confirmed by digital subtraction angiography in 7 of the 25 patients. A significant rise in mean pulmonary arterial pressure occurred after thrombus fragmentation (before: 34.1 mmHg; after: 37.9 mmHg; p<0.05), and this group showed a significant decrease in mean pulmonary arterial pressure after thrombus aspiration (25.7 mmHg; p<0.05). No distal embolisation was seen in 18 of the 25 patients, and a significant decrease in mean pulmonary arterial pressure was confirmed after thrombus fragmentation (before: 34.2 mmHg; after: 28.1 mmHg: p<0.01), and after thrombus aspiration (23.3 mmHg; p<0.01). In conclusion, distal embolisation and a rise in pulmonary arterial pressure can occur during mechanical fragmentation using a rotating pigtail catheter for the treatment of life-threatening acute massive pulmonary thromboembolism; thrombolysis and thrombus aspiration can provide partial recanalization and haemodynamic stabilization. Continuous monitoring of pulmonary arterial pressure may contribute to the safety of these interventional procedures.

Surgical Access to Jejunal Veins for Local Thrombolysis and Stent Placement in Portal Vein Thrombosis

Portal vein thrombosis is an infrequent entity, which may cause high morbidity and mortality. We report a case of portal vein thrombosis due to benign stenosis following partial pancreatoduodenectomy with segmental replacement of the portal vein by a Gore-tex graft. Using a surgical access to jenunal veins, local thrombolysis, mechanical fragmentation of thrombus, and stent placement were successfully performed.

Factors associated with outcome after interventional treatment of symptomatic iliac vein compression syndrome

Iliac vein compression syndrome (IVCS) results from compression of the left iliac vein by the overlying right iliac artery against the pelvic brim. In many cases, patients are symptomatic. In symptomatic cases, management consists of angioplasty and stenting. Although therapy is often initially successful, factors associated with long-term outcome have been poorly defined. The purpose of this study was to identify factors associated with stent patency. The medical records of all patients who underwent iliac vein percutaneous transluminal angioplasty and stenting from January 1996 to December 2006 for symptomatic IVCS were reviewed retrospectively. There were 50 women and 8 men, with a mean age of 42 years (median, 39 years; range, 17-71 years). Primary, assisted primary, and secondary patency rates were determined. Patient characteristics and clinical variables were evaluated by univariate and multivariate analysis to determine association with vein patency. Symptoms consisted of lower extremity swelling (81%) and lower extremity pain (67%). Iliac vein obstruction was treated with pharmacologic thrombolysis (31% of patients) and mechanical thrombus fragmentation (17% of patients). The primary, assisted primary, and secondary patency rates of angioplasty/stenting were 74.1%, 79.7%, and 85.8% at 1 year and 38.1%, 62.8%, and 73.8% at 5 years, respectively. Using a Cox proportional risk model, male sex (hazard ratio, 6.5; P = .001), recent trauma (hazard ratio, 5.3; P = .001), and age younger than 40 years (hazard ratio, 3.8; P = .015) were associated with decreased primary patency. In the absence of any risk factors, primary patency was 94.4% at 1 year and 63.0% at 5 years, decreasing to 28.6% and 0% for two or more risk factors. Patency rates for iliac vein percutaneous transluminal angioplasty and stenting in patients with IVCS can potentially be predicted on the basis of a multivariate model. Assessing risk factors allows for patient stratification and appropriate clinical decision making. Prospective validation of these variables is necessary.

Acute mesenteric ischemia: endovascular therapy

Acute mesenteric ischemia (AMI) is an abdominal emergency with a high mortality. Prompt revascularization can prevent intestinal infarction and reduce mortality. We report three cases of acute occlusive mesenteric ischemia without signs of intestinal necrosis, which were successfully managed with endovascular interventions. Mechanical thrombus fragmentation was performed and underlying chronic stenoses were treated with stent implantation. All the patients had pain relief immediately after the procedure, and none of them required surgery for bowel resection. The patients remained symptom free during a follow-up of 12-16 months. We suggest that endovascular treatment is a feasible option in patients with AMI and can prevent intestinal infarction.

Hybrid treatment of acute massive pulmonary thromboembolism: mechanical fragmentation with a modified rotating pigtail catheter, local fibrinolytic therapy, and clot aspiration followed by systemic fibrinolytic therapy.

We sought to evaluate the efficacy and safety of a hybrid treatment for acute massive pulmonary thromboembolism in patients with hemodynamic impairment by combining mechanical fragmentation, local thrombolysis, and clot aspiration. Within a period of 35 months, 25 patients with hemodynamic impairment (eight men and 17 women; age range, 35-77 years) were treated with mechanical thrombus fragmentation using a modified rotating pigtail catheter. After embolus fragmentation, all patients received an intrapulmonary injection of recombinant human-tissue plasminogen activator and then underwent manual clot aspiration with a large-lumen percutaneous transluminal coronary angioplasty guide catheter. All the patients survived, and their clinical status improved. Posttreatment angiography showed an improvement in pulmonary perfusion in all patients (mean Miller score before treatment, 22.2; after treatment, 13.6; p < 0.01). Mean pulmonary artery pressure decreased from 32.6 to 23.4 mm Hg (p < 0.01). Mean treatment time was 124.6 min. Hybrid treatment with mechanical fragmentation using a rotating pigtail catheter combined with local fibrinolysis and manual clot aspiration resulted in a rapid and safe improvement in the hemodynamic condition of patients with acute massive pulmonary thromboembolism. This hybrid treatment appears to be especially useful in patients at high risk for right ventricular failure and is a minimally invasive alternative to surgical embolectomy.

Ultrasound-enhanced thrombolysis.

Problems with current thrombolytic therapy include slow and incomplete thrombolysis and frequent bleeding complications. Increasing evidence from in vitro, animal, and initial patient studies indicates that application of ultrasound as an adjunct to thrombolytic therapy offers unique potential to improve effectiveness and decrease bleeding complications. Numerous studies in vitro demonstrate that low intensity ultrasound increases enzymatic fibrinolysis through mechanisms that include improving drug transport, reversibly altering fibrin structure, and increasing tPA binding to fibrin. These observations have been confirmed in animal models that demonstrated that ultrasound delivered transcutaneously or with an endovascular catheter accelerates thrombolysis in models of venous, arterial, and small vessel thrombosis. Ultrasound delivered at higher intensities using either an endovascular vibrating wire or transcutaneously in conjunction with stabilized microbubbles can cause mechanical fragmentation of thrombus without administration of plasminogen activator. Recent studies indicate that ultrasound at lower frequencies in the range of 20-40 kHz has a greater effect on thrombolysis with improved tissue penetration and less heating. These studies form the basis for clinical trials investigating the potential of ultrasound as an adjunct to improve thrombolytic therapy.

High-dose bolus injection of urokinase: Use during cardiopulmonary resuscitation for massive pulmonary embolism: Chest 1994; 106/4: 1281–1283

Bolus administration of high-dose thrombolytic agents has been reported for the treatment of acute pulmonary embolism. We describe the case of a 60-year-old woman who suffered a massive pulmonary embolism with cardiopulmonary arrest 21 h after an exploratory laparotomy. After 20 min of unsuccessful cardiopulmonary resuscitation (CPR), a bolus of 2,000,000 U of urokinase was injected via a peripheral vein. Ten minutes later, the circulatory system stabilized, and the patient survived without subsequent bleeding. In our opinion, bolus lysis made a definitive contribution to the success of the resuscitation. Several other case reports and small series showed successful treatment of pulmonary embolism during similar circumstances using high-dose bolus injection of thrombolytic agents. Mechanical thrombus fragmentation using a pulmonary artery catheter or pulmonary embolectomy has not been shown to be more successful during resuscitation. We conclude that bolus administration of thrombolytic agents during CPR for massive pulmonary thromboembolism may be an acceptable and successful technique, which also is available even in the community hospital setting.

High-Dose Bolus Injection of Urokinase

Bolus administration of high-dose thrombolytic agents has been reported for the treatment of acute pulmonary embolism. We describe the case of a 60-year-old woman who suffered a massive pulmonary embolism with cardiopulmonary arrest 21 h after an exploratory laparotomy. After 20 min of unsuccessful cardiopulmonary resuscitation (CPR), a bolus of 2,000,000 U of urokinase was injected via a peripheral vein. Ten minutes later, the circulatory system stabilized, and the patient survived without subsequent bleeding. In our opinion, bolus lysis made a definitive contribution to the success of the resuscitation. Several other case reports and small series showed successful treatment of pulmonary embolism during similar circumstances using high-dose bolus injection of thrombolytic agents. Mechanical thrombus fragmentation using a pulmonary artery catheter or pulmonary embolectomy has not been shown to be more successful during resuscitation. We conclude that bolus administration of thrombolytic agents during CPR for massive pulmonary thromboembolism may be an acceptable and successful technique, which also is available even in the community hospital setting.