Mechanical Thrombus Disruption Research Articles

Pharmacomechanical thrombectomy in management of pulmonary embolism

BackgroundAcute pulmonary embolism is recorded as one of the most common and critical medical conditions, resulting in a notable mortality rate requiring a multidisciplinary management. In this series, we address the management of massive and sub-massive pulmonary embolism utilizing catheter-based intervention, in particular the conjunction of mechanical thrombus disruption and aspiration with pharmacological thrombolysis (pharmacomechanical thrombectomy).Results37 patients were diagnosed with massive and sub-massive pulmonary embolism based on the clinical and radiological findings. Pre-procedural vital parameters were obtained, including oxygen saturation, pulse rate, and blood pressure. Under continuous monitoring and conscious sedation, a pulmonary angiography via right common femoral vein access was performed for pre-procedural assessment. Pharmacomechanical thrombectomy was performed using the AngioJet Ultra System (Boston Scientific). Using the power pulse option, a fibrinolytic agent was infused into the thrombus. After 5–10 min, mechanical thrombectomy is performed with a maximum 3 passes through the thrombus. This technique is performed in the main pulmonary artery and lower branch. The procedure is repeated on the other side. The maximum duration of thrombectomy is 2–3 min on each side. Procedure success was based on improvement of vital signs and not related to post-procedure angiographic findings. All patients showed immediate improvement of vital signs (blood pressure, 02 saturation, and pulse rate) with progressive improvement over the following days. There were no procedure-related complications.ConclusionPharmacomechanical thrombectomy is a safe and effective technique in the treatment of massive and submassive pulmonary embolism. It can be a first-line treatment even in patients without absolute contraindication to systemic thrombolysis.

Transcatheter Intervention of Coronary Obstructions in Infants, Children, and Young Adults.

This study assesses the characteristics of coronary obstructions that underwent transcatheter intervention in a pediatric catheterization laboratory, the procedural details, and patient outcomes. Acute cardiac failure due to coronary obstructions in children is rare. The role of catheter based intervention is largely unreported. Single center retrospective review between January 2000 and December 2016. Thirty-three patients (median age 2y/o [0-38], weighing 9.6kg [2.2-91]) underwent 39 transcatheter interventions on 39 lesions, mainly left main coronary (16/39; 39%) and right coronary (9/39; 23%) arteries. Most patients had congenital heart disease (29/33; 88%). Cath indications included ventricular dysfunction (17), cardiac arrest (7), failure to wean from cardiopulmonary bypass (5), and other (4). Almost half (18/39; 46%) were performed on ECMO support. Obstructions were post-surgical (16; 4 with coronary manipulation), thrombotic (13; 5 < 30days from cardiac surgery), and miscellaneous lesions (10). Interventions included 25 bare metal stents implanted in 22 lesions in 17 patients (mainly post-surgical lesions; 3at Damus-Kaye-Stansel anastomosis), nine balloon angioplasty only, four lytic therapy ± mechanical disruption of thrombus, and four technical failures. There were no procedure-related deaths. Most patients survived to discharge or transplant (24/33; 73%). Six patients who received stents had follow-up catheterization (median 15.5months [1-106]); all were without restenosis. Most coronary obstructions intervened upon in a pediatric cath lab were on young, critically ill patients with congenital heart disease secondary to surgical manipulation/injury or thrombosis. Transcatheter intervention should be considered a potential treatment strategy in this population.

Recanalization of occluded large arteries with broadened therapeutic window for acute cerebral infarction

ObjectiveTo investigate the safety and efficacy of recanalization with a broadened therapeutic window for acute occlusion of large cerebral arteries. MethodsWe assessed 38 patients who underwent the hyper-selective intra-arterial administration of low-dose urokinase, along with mechanical thrombus disruption or mechanical thrombus disruption recanalization (34 stents in 33 patients) of occluded vessels, 20 with onset time-to-treatment (OTT) >6h (observation group; mean OTT, 20.10±15.67h) and 18 with OTT ≤6h (control group). NIHSS scores, mRS scores (≤2) at 3 months, recanalization rates, severe cerebral infarctions on CT, and symptomatic hemorrhagic conversions after surgery were compared. ResultsPostoperative recanalization rates were 100% in both groups, and other results were equivalent. ConclusionsRecanalization at longer OTT was safe and effective with acute occlusions of large cerebral arteries. Time to recanalization could be safely prolonged for up to 20h in these patients.

Advances in thrombolytics for treatment of acute ischemic stroke

Over the past 50 years, thrombolytic agents have been devised with the aim of recanalizing occluded coronary vessels, and later on, applied in the setting of acute ischemic stroke. Pharmacologic agents have generally targeted the plasminogen-plasmin transformation, facilitating the natural process of fibrinolysis. Newer agents with varying degrees of fibrin selectivity and pharmacologic half-life have influenced both recanalization rates and hemorrhagic complications, inside and outside the CNS. Intra-arterial (IA) administration of fibrinolytic agents increases delivery of the drug to the thrombus at a higher concentration with smaller quantities and therefore lowers systemic exposure. Mechanical thrombus disruption or extraction allows for drug delivery to a greater surface area of the thrombus. Delays associated with IA therapy may worsen the risk/benefit ratio of thrombolysis; therefore, combinations of IA-IV treatments have been studied. To date, there are no direct comparative trials to show that endovascular administration is more efficacious or carries a lower risk of hemorrhagic complications than IV tissue plasminogen activator.

Intra-arterial thrombolytic therapy for acute intracranial large artery occlusive disease in patients selected by magnetic resonance image

Background and purpose We reported an experience of intra-arterial thrombolysis (IAT) study triaged by emergent MRI. Methods Patients were recruited if vascular occlusions were identified by emergent MRA. Urokinase was infused hyperselectively within 6 h after onset to a maximum dose of 900,000 IU or recanalization achieved with mechanical thrombus disruption. Heparin infusion was discontinued after 2 hemorrhage in the first 7 patients. TIMI grade 2 and 3 recanalization was recognized as successful. Favorable outcomes were mRS 0–3 at 3 months. Results Among 4225 ischemic stroke patients during the 29 months study period, 52 patients met the inclusion criteria with 49 screened by MRA and 3 screened by CT, 30 patients were enrolled and 25 were treated. Three patients (10%) were unable for the MRI examination due to time or equipment limit. There were 5 ICA, 13 MCA, and 7 VBA occlusions. Among 27 patients screened from MRA, 25 patients had the same occluded vessels and 2 patients had compatible occluded vessels confirmed by cerebral angiography. The median NIHSS was 26 and median time from symptom onset to IAT was 283 min. Successful recanalization was achieved in 68% (17/25). Intracerebral hemorrhage was recognized as symptomatic in 3 (12%) and asymptomatic in 8 (32%) at 3 months. Mortality was 32%. 36% patients had a mRS of 0–3 at 3 months. Patients with lower initial NIHSS score (20.9 vs. 28.4, P = 0.02) and MCA occlusions (69.3%, 9/13, P < 0.001) tend to have favorable outcomes. Conclusions Though the incidence was low, IAT triage with emergent MRI appeared to be feasible. MRI screening might be incorporated in the future IAT studies. Mechanical thrombus disruption and heparin infusion in IAT might need further investigation in this area.

Treatment for Mechanical Valve Thrombosis in the Right Heart: Combined Pharmacological and Mechanical Thrombolysis

We report clinical results of combined pharmacological and mechanical thrombolysis for mechanical prosthetic valve thrombosis (PVT) in the right heart. Between January 1992 and December 2008, combined thrombolysis, which consisted of an intravenous infusion of urokinase together with mechanical disruption of thrombus in a prosthetic valve by temporarily increasing the cardiac pacing rate, was performed in three patients with four cases of mechanical PVT in the right heart. The prosthetic valve in all three patients was a bileaflet mechanical valve, and was located in the tricuspid position in two patients and in the pulmonary position in the remaining patient. PVT was diagnosed by echocardiography and cineradiography. Thrombolysis was successful in all four cases in the three patients, and no hemorrhagic complications or clinically symptomatic pulmonary embolisms were observed. Mechanical disruption of thrombus using a pacemaker appears to be an effective adjunctive modality to thrombolysis with fibrinolytic agents for PVT in the right heart. Combined pharmacological and mechanical thrombolysis may improve success rates and reduce the time required for thrombolysis of PVT.

Multimodal Therapy for the Treatment of Severe Ischemic Stroke Combining Endovascular Embolectomy and Stenting of Long Intracranial Artery Occlusion

Embolic occlusion of cerebral arteries is a major cause for stroke. Intravenous thrombolysis showed positive results in this condition, however even when strict criteria are used, the risk of hemorrhagic transformation is possible. Microsurgical embolectomy has been described earlier. Purpose. We performed multimodal therapy of cerebral artery occlusion. Case Report. We present a case of a 49-year-old female patient who—according to the National Institute of Health Stroke Scale (NIHSS)—was rated as 19 due to acute occlusion of the horizontal segment of the left middle cerebral artery (MCA). After failed i.v. thrombolysis, only a part of the clot could be evacuated by the endovascular approach—without restoration of blood flow. Normal patency of the left MCA was re-established after stenting. Within 72 hours, the patient had an NIHSS score of 14, with a small haematoma in the left hemisphere. Conclusion. In our case multimodal therapy combining i.v. thrombolysis, mechanical disruption of thrombus, MCA stenting and platelet function antagonists, resulted in successful recanalization of the acutely occluded left MCA.

Simple microwire and microcatheter mechanical thrombolysis with adjuvant intraarterial urokinase for treatment of hyperacute ischemic stroke patients

Mechanical thrombolysis may effectively enhance the efficacy of thrombolysis for hyperacute ischemic stroke patients. To assess the feasibility and results of simple mechanical-based thrombolysis using microwire and microcatheter with adjuvant low-dose intraarterial (i.a.) urokinase (UK) for the treatment of hyperacute ischemic stroke. Nineteen consecutive patients with hyperacute proximal middle cerebral artery (MCA) occlusions treated by a standardized protocol using microwire and microcatheter for mechanical thrombus disruption with adjuvant i.a. UK were reviewed. Simple to-and-fro passages through the clot with the microwire and microcatheter followed by disruptions by a J- or pigtail-shaped wire tip with alternating small-dose injections of UK distal, within, and proximal to the clot were performed. The recanalization rates, post-thrombolysis hemorrhage, and clinical outcome (baseline and discharge National Institute of Health Stroke Scale [NIHSS], mortality, 3-month modified Rankin scale [mRS]) were evaluated. Recanalization was achieved in 18 of 19 patients (94.7%). The mean UK dose was 375,789 IU (range 130,000-580,000 IU). Two patients (10.5%) developed symptomatic hemorrhage. One of the hemorrhages included a patient who developed subarachnoid hemorrhage. Mortality rate was 15.8% (n = 3). The median baseline NIHSS scores showed improvement from 17 to 10 at presentation and discharge, respectively. At three months, good outcome was noted in 11 of 19 patients (57.9%, mRS 0-2). Simple mechanical-based thrombolysis using microwire and microcatheter with adjuvant low-dose i.a. UK is safe and effective in achieving recanalization with good long-term outcome.

Simultaneous Treatment with Intravenous Recombinant Tissue Plasminogen Activator and Endovascular Therapy for Acute Ischemic Stroke Within 3 Hours of Onset

Because intravenous (IV) recombinant tissue plasminogen activator (rtPA) does not always lead to a good outcome in a considerable proportion of patients, combined IV rtPA and rescue endovascular therapy (ET) have been performed in several recent studies. However, rescue therapy after completion of IV rtPA often results in late ineffective recanalization. We examined the efficacy and safety of combined IV rtPA and simultaneous ET as primary rather than rescue therapy for hyperacute middle cerebral artery (MCA) occlusion. A total of 29 patients eligible for IV rtPA, who were diagnosed as having MCA (M1 or M2) occlusion within 3 hours of onset, underwent thrombolysis. In the combined group, patients were treated by IV rtPA (0.6 mg/kg for 60 minutes) and simultaneous ET (intra-arterial rtPA, mechanical thrombus disruption with microguidewire, and balloon angioplasty) initiated as soon as possible. In the IV group, patients were treated by IV rtPA only. The improvement of the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours was 11 +/- 4.8 in the combined group versus 5 +/- 4.3 in the IV group (P < .001). In the combined group, successful recanalization was observed in 14 (88%) of 16 patients with no symptomatic intracranial hemorrhage, and 10 (63%) of 16 patients had favorable outcomes (modified Rankin Scale [mRS] 0, 1) at 3 months. Aggressive combined therapy with IV rtPA and simultaneous ET markedly improved the clinical outcome of hyperacute MCA occlusion without significant adverse effect. Additional randomized study is needed to confirm our results.

Endovascular Thrombectomy and Thrombolysis for Severe Cerebral Sinus Thrombosis

Most patients with cerebral sinus thrombosis (CST) recover after treatment with heparin, but a subgroup has a poor prognosis. Those patients may benefit from endovascular thrombolysis. Prospective case series. Patients with sinus thrombosis were selected for thrombolysis if they had an altered mental status, coma, straight sinus thrombosis, or large space-occupying lesions. Urokinase was infused into the sinuses (bolus 120 to 600 x 10(3) U; then 100 x 10(3) U/h) via a jugular catheter, in 15 cases combined with mechanical thrombus disruption or removal. We treated 20 patients (16 women), mean age 32 years. Twelve patients were comatose and 14 had hemorrhagic infarcts before thrombolysis. Twelve patients recovered (Rankin score 0 to 2), 2 survived with handicaps, and 6 died. Factors associated with a fatal outcome were leukemia (3/6 versus 0/14, P=0.02) and large hemorrhagic infarcts (4/6 versus 2/14, P=0.04). Seizures were less frequent in the fatal cases (P=0.05). Patients who died had a larger mean lesion surface than survivors (30.5 versus 13.6 cm(2); P=0.03), larger midline shift (5.2 versus 1.7 mm; P=0.02), and a more rapid course (2.7 versus 8.2 days; P=0.01). Five patients who died had large hemispheric infarcts and edema before thrombolysis, causing herniation. Five patients had increased cerebral hemorrhage (3 minor, 2 major) after thrombolysis. Thrombolysis can be effective for severe sinus thrombosis, but patients may deteriorate because of increased cerebral hemorrhage. Patients with large infarcts and impending herniation did not benefit.

Acute treatment of cerebral venous and dural sinus thrombosis

Management of thrombosis of the dural sinus and cerebral veins (CVT) includes treatment of the underlying condition, antithrombotic treatment, symptomatic treatment, and the prevention or treatment of complications. Intravenous heparin or subcutaneous low-molecular-weight heparin should be used in acute CVT to prevent thrombus propagation and pulmonary embolism and to increase the chances of recanalization. Anticoagulation is safe and can be used in patients with acute CVT who have intracranial hemorrhagic lesions. Endovascular thrombolysis (with or without mechanical thrombus disruption) is an experimental treatment to be used in experienced centers for severe cases or patients who fail to improve on anticoagulation. Local thrombolysis is not useful in patients with large infarcts and impending herniation. In patients with severe headache and papilledema, intracranial hypertension can be reduced and symptoms relieved through a therapeutic lumbar puncture. Hemicraniectomy may be lifesaving in patients with parenchymal lesions leading to herniation. In patients with acute seizures and supratentorial lesions, antiepileptic drugs should be prescribed. Prophylactic use of these drugs can also be considered for patients with one of these risk factors but should be avoided in patients with neither of them. To reduce the risk of recurrent deep venous thrombosis of the limbs, vitamin K antagonists are given for a variable period depending on the patient's inherent risk of thrombosis, aiming at an International Normalized Ratio of 2 to 3.5. If CVT is related to a transient risk factor (eg, pregnancy, infection), we recommend anticoagulants for 3 months. In patients with idiopathic CVT or CVT associated with "mild" thrombophilia, the period of anticoagulation must be extended to 6 to 12 months. In patients with "severe" thrombophilia (eg, two or more prothrombotic abnormalities or antiphospholipid syndrome), anticoagulants should be given for life. Patients with persistent symptoms of increased intracranial hypertension, visual loss, or both can be treated with repeated lumbar punctures or a lumboperitoneal shunt. For the prevention of remote seizures, antiepileptic drugs are recommended for patients with seizures in the acute phase and for those who experience a seizure after the acute phase. These drugs can also be considered for patients without seizures who have supratentorial hemorrhagic lesions or motor deficits.

Stenting the ductus arteriosus: Case selection, technique and possible complications

Ductal stenting is an attractive alternative to conventional shunt surgery in duct dependent congenital heart disease as it avoids thoracotomy and its related problems. With today's generation of coronary stents which have better profile, flexibility and trackability, ductal stenting may be achieved safely and with considerably less difficulty than previously described.As in Blalock-Taussig (BT) shunt, ductal stenting is indicated mainly in duct-dependent cyanotic lesions chiefly in the neonatal period. Unlike the Patent ductus arteriosus (PDA) as an isolated lesion, the ductus in cyanotic heart disease has a remarkable morphologic variability. The ductus tends to arise more proximally under the aortic arch, giving rise to a vertical ductus or occasionally it may arise from the subclavian artery. It also tends to be long and sometimes very tortuous, rendering stent implantation technically impossible. The ductus in these patients may also insert onto one of the branch pulmonary arteries with some stenosis at the site of insertion. The ductus in Tetralogy of Fallot with pulmonary atresia (TOF-PA) tend to exhibit these morphologic features and to a lesser degree in transposition of great arteries with ventricular septal defect and pulmonary atresia (TGA-VSD-PA) and the more complex forms of univentricular hearts. In the preliminary angiographic evaluation, it is important to delineate these morphologic features as the basis for case selection.Ductal stenting may be done by the retrograde femoral artery route or the antegrade transvenous route depending on the ductus morphology and the underlying cardiac lesion. The detailed techniques and essential hardware are described. Finally, major potential complications of the procedure are described. Acute stent thrombosis is the most serious and potentially catastrophic. Emergent treatment with thrombolytic therapy and mechanical disruption of thrombus are required. With proper case selection, appropriate technique and the right hardware ductal stenting provides reasonable short-medium term palliation in duct-dependent cyanotic heart disease.

Impact of Arterial Reocclusion and Distal Fragmentation during Thrombolysis among Patients with Acute Ischemic Stroke

Arterial reocclusion and distal embolization are known complications of ischemic stroke intervention, impacting treatment strategies and device design. We sought to determine their rates of occurrence and effects on long-term outcomes during endovascular treatment of patients with acute ischemic stroke. Retrospective analysis of data from 4 prospective acute stroke protocols was performed. Patients underwent the standard technique for parent vessel angiography followed by pharmacologic thrombolysis and/or sonographic thrombolysis and/or mechanical thrombus disruption. Certain patients also received systemic heparin or abciximab therapy. Demographic, clinical, and angiographic variables were assessed at onset, 24 hours, 1 week, and 1-3 months after the event. "Distal embolization" was defined qualitatively as appearance of an occlusion on a downstream vessel. "Arterial reocclusion" was defined as subsequent reocclusion of the target vessel after initial recanalization had been achieved. Arterial reocclusion occurred in 18% of these patients, whereas distal embolization occurred in 16% of the 91 patients treated in these protocols. Arterial reocclusion, but not distal embolization, was associated with a lower likelihood of favorable outcome at 1-3 months (P = .05; odds ratio, 3.9; 95% confidence interval, 0.01-0.98) after adjusting for age, initial National Institutes of Health Stroke Scale scores, sex, time to treatment, initial angiographic grade, symptomatic intracranial hemorrhage, and final recanalization. Arterial reocclusion and distal embolization occur in 16%-18% of patients with stroke undergoing endovascular intervention. Only arterial reocclusion is associated with poor long-term outcome. Prospective studies are needed to identify risk factors for their occurrence and possible preventive therapies.

Mechanical Disruption of Thrombus Following Intravenous Tissue Plasminogen Activator for Ischemic Stroke

We prospectively evaluated the safety of aggressive mechanical disruption of thrombus following full-dose intravenous (IV) recombinant tissue plasminogen activator (rt-PA) to treat ischemic stroke in 24 patients with an initial National Institutes of Health stroke scale (NIHSS) score of >or=10. Clinical evaluations were performed at presentation and 24 hours, 7 to 10 days, and 1 to 3 months (using modified Rankin scale) after treatment. These end points were compared to matched historical controls treated with IV rt-PA alone. Of the 24 patients, mechanical disruption was undertaken in 17 patients with persistent angiographic occlusion using microcatheter exploration (n= 3), angioplasty (n= 5), snare maneuvers (n= 7), and combination of both (n= 2). Partial or complete recanalization was observed in 10 of the 17 patients. Neurological improvement at 24 hours (>or=4 point reduction in NIHSS score) was observed in 11 of 17 patients. Comparisons with matched controls suggest potential equivalence for symptomatic ICH (0% vs 12%), asymptomatic ICH (18% vs 15%), and early neurological improvement (65% vs 53%). The study shows that aggressive mechanical thrombus disruption in large artery occlusion in the setting of acute ischemic stroke is safe with acceptable rates of ICH and promotes angiographic recanalization.

Photoacoustic Fibrinolysis: Pulsed-Wave, Mid-Infrared Laser-Clot Interaction.

Objectives: The purpose of this study was to determine whether a mid-infrared laser can induce selective fibrinolysis and to analyze the effect of altered fibrin structure (thin vs. thick fibers) on laser-clot interaction. Background: Mechanical disruption of thrombus can be achieved with balloon angioplasty, sonication, and thermal energy. Thrombi avidly absorb light in the mid-infrared optical spectrum due to their high water content. This phenomenon provides a potential for mid-infrared lasers as a source for selective thrombolysis. As fibrin is the essential component of clot, a study of mid-infrared laser-fibrin interaction is warranted. Methods: Clots of varying fibrin structure were lased in cuvettes with a solid-state, pulsed-wave, mid-infrared laser (2.1 micron, 500 mJ/pulse, 250 msec pulse length). Total pulse energies of 5 Joules (J), 10 J, 37.5 J, 75 J, and 112.5 J were tested. Protein content of the extruded fluid was measured by optical density absorbance at 280 nm. Th e amount of released material was studied as a function of lasing energy and clot structure. SDS-polyacrylamide gel electrophoresis was applied for analysis of protein bands in order to identify unique protein bands released by the selective effect of laser fibrinolysis. Results: A threshold for mid-infrared laser induced fibrinolysis was found; application of up to 20 J of energy did not result in dissolution. As lasing energy was increased above 37.5 J, the structure of these gels was mechanically destroyed and 12.4 +/- 6.7% (mean +/- SEM) of the original content of protein was released. Electrophoresis revealed that lased gels did not release any unique protein band. Lased, thin fibers released significantly less protein than thick fibers, indicating that they are more resistant to the effect of this wavelength of energy. Conclusions: Mid-infrared laser can induce in-vitro photoacoustic dissolution of fibrin clots. However, this wavelength laser achieves fibrinolysis by me chanical destruction of the target clot rather than by a selective effect, as induced by the pulsed-dye laser. A threshold exists for energy levels required. Thin fibrin fibers, with their high elastic modulus (i.e., gel rigidity) appear more resistant than thick fibers to the effect of lasing at this wavelength.