Reduce Thrombus Burden Research Articles

Resolvin D4 attenuates the severity of pathological thrombosis in mice

AbstractDeep vein thrombosis (DVT) is a common cardiovascular disease with a major effect on quality of life, and safe and effective therapeutic measures to efficiently reduce existent thrombus burden are scarce. Using a comprehensive targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics approach, we established temporal clusters of endogenously biosynthesized specialized proresolving mediators (SPMs) and proinflammatory and prothrombotic lipid mediators during DVT progression in mice. Administration of resolvin D4 (RvD4), an SPM that was enriched at the natural onset of thrombus resolution, significantly reduced thrombus burden, with significantly less neutrophil infiltration and more proresolving monocytes in the thrombus, as well as an increased number of cells in an early apoptosis state. Moreover, RvD4 promoted the biosynthesis of other D-series resolvins involved in facilitating resolution of inflammation. Neutrophils from RvD4-treated mice were less susceptible to an ionomycin-induced release of neutrophil extracellular traps (NETs), a meshwork of decondensed chromatin lined with histones and neutrophil proteins critical for DVT development. These results suggest that delivery of SPMs, specifically RvD4, modulates the severity of thrombo-inflammatory disease in vivo and improves thrombus resolution.

Effects of Cangrelor as Adjunct Therapy to Percutaneous Coronary Intervention

Percutaneous coronary intervention (PCI) in patients with angiographic evidence of intracoronary thrombus is associated with in-hospital and 30-day adverse clinical outcomes. Cangrelor, a direct, rapid-onset acting intravenous P2Y12 receptor inhibitor, has been proved to be effective by reducing peri-PCI ischemic complications in subjects who underwent PCI. This study aimed to assess the angiographic and in-hospital clinical outcomes in all-comer patients receiving cangrelor immediately before PCI at a tertiary care center. The study analyzed consecutive unselected subjects treated with cangrelor at the time the decision was made to proceed with PCI. At the end of the procedure, all patients were transitioned to oral antiplatelet therapy. The target lesion angiographic assessment of Thrombolysis in myocardial infarction flow grade (TIMI-Flow), TIMI-thrombus grade (TIMI-Thrombus), myocardial blush grade, and TIMI-myocardial perfusion grade (TMPG) was performed before and post-PCI. Clinical events were recorded during the procedure and at discharge. In total, 223 patients (244 lesions) were included in the analysis (106, 97, and 20 patientswith TIMI-Flow 0/1, TIMI-Flow 2/3, and cardiogenic shock, respectively). The overall mean age was 63 ± 12 years, 70% men and 38% with diabetes mellitus. Acute myocardial infarction was the main presentation (72%). The use of cangrelor improved TIMI-Flow, MGB, TMPG, and TIMI-Thrombus in patients with initial TIMI-Flow 0 to 2. Major bleeding rate was 2.0%. In conclusion, cangrelor was effective and safe in restoring TIMI-Flow 3, reducing thrombus burden and improving myocardial blush grade and TMPG when administered to unselected subjects who underwent PCI. Therefore, cangrelor should be considered in patients presenting with intracoronary thrombus before intervention.

A new technique to salvage myocardium following the failure of thrombus aspiration in acute myocardial infarction: a case report

BackgroundThe failure of aspiration thrombectomy may negatively impact outcomes in patients with acute myocardial infarction (AMI), but the available options are limited.Case presentationA 41-year-old man with chest pain for 2 h presented with ST-segment elevation myocardial infarction. Coronary angiography revealed a large filling defect extending from the distal left main (LM) coronary artery into the proximal left circumflex (LCX) coronary artery. The whole thrombus moved and occluded the proximal left anterior descending (LAD) artery, while the guidewire crossed the lesion. Dedicated manual aspiration thrombectomy (MAT) and balloon dilation failed to reduce thrombus burden. We considered thrombus extraction as impossible when it moved forward to occlude the middle LAD. To reduce infarct size, a new balloon-pushing technique was successfully performed to move the thrombus to the terminal LAD based on the actual condition of the LAD. The final angiogram demonstrated no stenosis in the LM artery and stent deployment was not performed. A 1-week follow-up coronary angiography revealed the complete resolution of thrombus and flow restoration in the left coronary artery. Intravascular ultrasound (IVUS) showed nonsignificant residual stenosis of the LM artery. No adverse events occurred during a 12-month follow-up period.ConclusionThis case suggests that the new balloon-pushing technique is a useful remedy if repeated MAT fails during AMI.

Combined Primary PCI with Multiple Thrombus Burden Reduction Therapy Improved Cardiac Function in Patients with Acute Anterior Myocardial Infarction.

High thrombus burden induced slow-flow and no-reflow during primary percutaneous coronary intervention (PCI) and is associated with a poor prognosis. We aimed to investigate whether a combined thrombus burden reduction therapy during primary PCI, could improve microcirculation and enhance cardiac function in the long-term.Anterior wall STEMI patients with high thrombus burden were randomly assigned to receive a combined thrombus burden reduction therapy or thrombus aspiration alone. The primary end points included the percentage of patients with TMPG (TIMI myocardial perfusion grade) 3, STR (ST-segment resolution) above 70%, the index of microcirculatory resistance (IMR) and left ventricular ejection fraction (LVEF) difference.Twenty-two patients in the combined interventional group and 24 in the control group completed 1-year follow-up. The percentages of patients with TMPG 3 (68.2% versus 33.3%, P = 0.006) and STR above 70% (63.6% versus 25%, P = 0.016) were significantly higher in the combined group. IMR was significantly lower in the combined interventional group (31.50 ± 13.39 U versus 62.72 ± 22.80 U, P = 0.002). At 3 months and 1 year, the overall LVEF value was better in the combined interventional group (42.1% versus 40.0%, P = 0.049; 41.9% versus 39.8%, P = 0.042), respectively. The IMR value was negatively correlated with the EF value at 3 months (r = -0.145, P = 0.013) and 1 year (r = -0.333, P = 0.031).A combined thrombus burden reduction therapy during primary PCI can safely reduce thrombus burden, improve myocardial tissue perfusion, and improve cardiac function among STEMI patients with high thrombus burden. IMR might be a good predictor for post-myocardial infarction cardiac function.

Abstract 354: Early Intentional Restoration of Blood Flow Reduces Thrombus Burden and Vein Wall Scarring Following Dvt: Implications for Preventing the Post-thrombotic Syndrome

Background: Despite anticoagulation therapy, up to 50% of deep vein thrombosis (DVT) patients still develop the post-thrombotic syndrome (PTS), a condition that arises from thrombus obstruction and vein wall damage, leading to venous hypertension. While catheter-based intervention may reduce PTS, the CaVenT and ATTRACT trials demonstrated little clinical benefit of intentional restoration of blood flow (RBF) for reducing PTS. However, these trials have not explored the time-dependence of RBF, a key factor as aging VT are associated with greater vein wall injury. Methods: To investigate the temporal effects of intentional RBF following VT, we modified a classic complete ligation inferior vena cava (IVC) stasis VT protocol in C57BL/6 mice by de-ligating the day 0 ligature at day 2 to allow RBF. Compared to intravital microscopy, the sensitivity and specificity of noninvasive ultrasound (US) to detect RBF was 82.1% and 94.4%, respectively. Serial US was then performed on mice. Mice were classified as early RBF (RBF by day 4), late RBF (RBF after day 4), no RBF, or sham de-ligation groups. Follow day 8 sacrifice, thrombus burden (mg/cm) and vein wall scarring (VWS) were measured. Kruskal-Wallis followed by Dunn’s test was used to compare statistical significance between groups. Results: After de-ligation, RBF through VT increased gradually over time (Fig. A). The early RBF group exhibited significant reductions in VT burden (N=9) and VWS (N=5) at day 8 ( p <0.05 vs. comparator groups, Fig B-C). In contrast, the late RBF group did not experience significant reductions in thrombus burden (N=6) nor VWS (N=4), with measures similar to mice with no RBF (N=3-4), or sham de-ligation (N=8-9). Conclusions: Intentional early RBF reduces venous thrombus burden and VWS, factors that drive PTS. Mechanistic studies to address these findings are going. The overall results suggest that anti-PTS benefits of catheter-based intervention may be enhanced in subjects receiving early RBF.

A comparison of intracoronary treatment strategies for thrombus burden removal during primary percutaneous coronary intervention: a COCTAIL II substudy.

Manual thrombus aspiration and local drug delivery of abciximab have been proposed as a strategy to reduce thrombus burden during percutaneous coronary intervention in patients with ST elevation myocardial infarction; however, the effectiveness of these approaches, is uncertain. In this COCTAIL II substudy, we compared the effect of these strategies on prestenting and poststenting thrombus burden assessed by optical coherence tomography. COCTAIL II trial enrolled patients with ST elevation myocardial infarction randomized to intralesion (IL, by the ClearWay catheter) versus intracoronary (IC, by the guide catheter) abciximab bolus with or without aspiration thrombectomy (AT). The following parameters were used to quantify atherothrombotic burden: thrombus volume (TVol), maximum thrombus area (TA), and thrombus burden (TB). Primary endpoint was the comparison of prestenting TVol after the use of local drug delivery (group IL+IL abciximab plus AT) versus nonlocal drug delivery (group IC abciximab plus AT+IC). The final population consisted of 59 patients undergoing both prestenting and poststenting optical coherence tomography assessment. The amount of thrombus was not significantly different in the groups with local drug delivery of abciximab versus nonlocal drug delivery in both prestenting (TVol: 18.87±26.70 vs. 19.02±18.45; TB: 26.73±12.8 vs. 25.18±13.25; and maximum TA: 59.25±18.84 vs. 53.34±19.30) and poststenting (TVol: 8.46±9.15 vs. 8.05±6.81; TB: 6.68±3.54 vs. 6.24±3.66; and maximum TA: 15.47±7.61 vs. 16.52±11.55) evaluations. A good correlation between thrombus measurements after thrombus removal techniques and intrastent thrombus was observed. Either local drug delivery of abciximab or manual thrombus aspiration showed comparable results in terms of prestenting and poststenting thrombus burden removal.

Blocking of platelet glycoprotein receptor Ib reduces \u201cthrombo-inflammation\u201d in mice with acute ischemic stroke

BackgroundIschemic stroke causes a strong inflammatory response that includes T cells, monocytes/macrophages, and neutrophils. Interaction of these immune cells with platelets and endothelial cells facilitates microvascular dysfunction and leads to secondary infarct growth. We recently showed that blocking of platelet glycoprotein (GP) receptor Ib improves stroke outcome without increasing the risk of intracerebral hemorrhage. Until now, it has been unclear whether GPIb only mediates thrombus formation or also contributes to the pathophysiology of local inflammation.MethodsFocal cerebral ischemia was induced in C57BL/6 mice by a 60-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab). Rat immunoglobulin G (IgG) Fab was used as control treatment. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 1 after tMCAO.ResultsBlocking of GPIb reduced stroke size and improved functional outcome on day 1 after tMCAO without increasing the risk of intracerebral hemorrhage. As expected, disruption of GPIb-mediated pathways in platelets significantly reduced thrombus burden in the cerebral microvasculature. In addition, inhibition of GPIb limited the local inflammatory response in the ischemic brain as indicated by lower numbers of infiltrating T cells and macrophages and lower expression levels of inflammatory cytokines compared with rat IgG Fab-treated controls.ConclusionIn acute ischemic stroke, thrombus formation and inflammation are closely intertwined (“thrombo-inflammation”). Blocking of platelet GPIb can ameliorate thrombo-inflammation.

Very Low Incidence of Ischaemic Stroke Associated with Thrombus Aspiration in a Large Series of STEMI Patients Treated with Primary PCI

Background: Thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI) was recommended to minimise distal embolisation and ischaemia, improve myocardial reperfusion, and reduce thrombus burden prior to PPCI. Subsequent larger randomised trials showed no benefit and suggested an increased risk of stroke with TA, mostly in the first 48 hours. Aim: To describe the rate of ischaemic stroke in STEMI patients treated with TA and PPCI at two large Western Sydney hospitals. Methods: We conducted a retrospective analysis of all STEMI patients treated with TA and PPCI from 2008 to 2015 at Westmead and Blacktown Hospitals. Patients received protocol dose heparin and dual antiplatelet therapy. TA was performed using 6Fr and 7Fr catheters. The guide catheter was selectively engaged prior to removal of the aspiration catheter. Negative suction was maintained during removal, followed by generous aspiration of the guide catheter. The incidence of ischaemic stroke within the first 48 hours was retrieved from patient records. Results: Of 1463 patients (mean age 68 ± 11; 58% male), 2 patients had ischaemic stroke in the first 48 hours post index procedure (incidence rate 0.14%). Both patients were intubated prior to PPCI due to poor Glasgow Coma Scale scores. 1, 6 and 12 month stroke rates will be presented at the meeting. Conclusion: Very low ischaemic stroke rates were seen in this real-world study. TA can be performed safely in STEMI patients undergoing PPCI with a stroke risk equivalent to reported risk in PPCI without TA.

The Role of Manual Aspiration Thrombectomy in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI.

In STEMI, primary PCI restores macrovascular coronary blood flow effectively but microvascular perfusion remains a challenge. Thrombus has the potential to embolize to the microvasculature limiting effective coronary blood flow. Thrombus burden is associated with a higher mortality and manual aspiration thrombectomy has the potential to reduce thrombus burden. The first large trial of routine aspiration thrombectomy (TAPAS, N = 1071) showed an improvement in myocardial blush and an unexpected reduction in mortality. Reinforcing the enthusiasm for this finding meta-analysis of small trials also showed a reduction in mortality, which led to routine manual thrombectomy becoming a class IIa recommendation in the American and European Guidelines for STEMI. Subsequently; however, large trials such as TOTAL (N = 10,732) and TASTE (N = 7244) and meta-analysis showed an increase in the risk of stroke with routine manual thrombectomy but no improvement in mortality, myocardial infarction, stent thrombosis, or severe heart failure. As such, manual thrombectomy should not be routinely used instead saving it as a bailout procedure as indicated.

The 2005 Caprini Score Predicts Both Baseline Venous Thromboembolism Risk and Effectiveness of Chemoprophylaxis: A Meta-Analysis of 13,412 Surgical Patien

Conclusions: Apixaban is less effective in reducing thrombus burden than enoxaparin at 2and 14-day time points in this nonstasis murine model of DVT. This may be due to anti-inflammatory pleiotropic effects of enoxaparin that apixaban may not have in acute DVT. Further study is ongoing to determine whether vein wall remodeling is affected by Xa inhibition and whether this is an effect of apixaban itself or a class effect of anti-Xa inhibitors.

0459: Super-Minimalist Immediate Mechanical Intervention (Super-MIMI) study

To evaluate the safety of extended-delay stenting (>7 days between procedures) in the setting of percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). This ongoing prospective observational study is being conducted in STEMI patients with a high thrombus burden in the infarct-related artery (IRA). Patients are enrolled if the operator decides to try to restore the best TIMI flow with the thinnest tool and defer stent implantation for >7 days under optimal anticoagulation to reduce thrombus burden. The primary endpoint is the composite of reocclusion of the IRA or sudden death between the two procedures, and deterioration of the flow (from the final flow achieved after the first procedure to the initial flow at the second procedure). Between January 2014 and January 2015, 127 patients (of 135 we will enroll) were enrolled at 14 centres: 110 were men and the mean age±SD was 57.1±13.0 years. 98 patients underwent a primary PCI as the first procedure and 29 patients underwent PCI after fibrinolysis. The final TIMI flow at the first procedure was 3 in 119 patients, 2 in 7 patients, and 1 in 1 patient and the residual culprit lesion was 61±24%. Glycoprotein IIb/IIIa inhibitor in 42 patients. The second procedure was performed between 7 and 26 days after the first. None of the patients died between the two procedures; 1 patient experienced a reocclusion of the IRA In all cases, initial TIMI flow in the IRA (at the start of the second procedure) was the same as or better than the final flow after the first procedure. A stent was implanted in 80 patients, whereas no significant lesion was documented in 47 patients. Final results will be presented at the meeting. In PCI for acute STEMI, when the thrombus burden is high, stenting delayed by 7-26 days with intensive antithrombotic cover appears safe, with only 1 of 130 patients developing an IRA reocclusion.

Super-Minimalist Immediate Mechanical Intervention (Super-MIMI) study

Purpose To evaluate the safety of extended-delay stenting (> 7 days between procedures) in the setting of percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). Methods This ongoing prospective observational study is being conducted in STEMI patients with a high thrombus burden in the infarct-related artery (IRA). Patients are enrolled if the operator decides to try to restore the best TIMI flow with the thinnest tool (i.e. wire, aspiration, or thin balloon) and defer stent implantation for > 7 days under optimal anticoagulation to reduce thrombus burden. The primary endpoint is the composite of reocclusion of the IRA or sudden death between the two procedures, and deterioration of the flow (from the final flow achieved after the first procedure to the initial flow at the second procedure). Results Between January 2014 and January 2015, 127 patients (of 135 we will enroll) were enrolled at 14 centres: 110 were men and the mean age ± SD was 57.1 ± 13.0 years. Ninety-eight patients underwent a primary PCI as the first procedure and 29 patients underwent PCI after fibrinolysis. The final TIMI flow at the first procedure was 3 in 119 patients, 2 in 7 patients, and 1 in 1 patient. This final flow was spontaneous (same as initial flow, in the absence of intervention) in 43 patients, and after wire in 3 patients, thrombus aspiration in 60, and with a 1.5–2.5 mm diameter balloon in 21 patients. At the end of the first PCI, the residual culprit lesion was 61 ± 24%. Aspirin, P2Y12 inhibitors, and anticoagulants were used in all patients between the two procedures, and a glycoprotein IIb/IIIa inhibitor in 42 patients. The second procedure was performed between 7 and 26 days after the first. None of the patients died between the two procedures; 1 patient experienced a reocclusion of the IRA 15 min after the first procedure. In all cases, initial TIMI flow in the IRA (at the start of the second procedure) was the same as or better than the final flow after the first procedure. A stent was implanted in 80 patients, whereas no significant lesion was documented in 47 patients. Final results will be presented at the meeting. Conclusions In PCI for acute STEMI, when the thrombus burden is high, stenting delayed by 7–26 days with intensive antithrombotic cover appears safe, with only 1 of 127 patients developing an IRA reocclusion.

Endovascular Interventions for Acute and Chronic Lower Extremity Deep Venous Disease: State of the Art.

The societal and individual burden caused by acute and chronic lower extremity venous disease is considerable. In the past several decades, minimally invasive endovascular interventions have been developed to reduce thrombus burden in the setting of acute deep venous thrombosis to prevent both short- and long-term morbidity and to recanalize chronically occluded or stenosed postthrombotic or nonthrombotic veins in symptomatic patients. This state-of-the-art review provides an overview of the techniques and challenges, rationale, patient selection criteria, complications, postinterventional care, and outcomes data for endovascular intervention in the setting of acute and chronic lower extremity deep venous disease. Online supplemental material is available for this article.

Enhancing the Benefit of Bivalirudin in Percutaneous Coronary Intervention: Is High Risk of Bleeding the Key?

Bivalirudin is a potent direct thrombin inhibitor that can reduce thrombus burden during acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) by blocking formation of fibrin and by suppressing platelet aggregation [1]. When compared with heparin, bivalirudin has several theoretical mechanistic advantages that include activity against clot-bound thrombin, inhibition of thrombin-induced platelet activation, short plasma half-life, linear pharmacokinetics less affected by plasma proteins and renal insufficiency, and an unaffected platelet activation during PCI [1]. These properties of bivalirudin provide a more predictable inhibition of coagulant activity than does heparin, with less degree of inter-patient variability in anticoagulation response. Moreover, its binding to thrombin is non-competitive and reversible, and hemostatic capacity is more readily restored; hence bleeding, as well as ischemic complications, may be reduced [2]. In the first randomized trial (HAS [Hirulog Angioplasty Study]) comparing bivalirudin with heparin in over 4000 patients undergoing PCI for unstable or post-infarction angina, bivalirudin was at least as effective as high-dose heparin in preventing ischemic complications, and it carried a lower risk of bleeding [3]. Nevertheless, development of bivalirudin was suspended because of the unfavorable cost comparison with heparin. Only recently did the development of a less expensive manufacturing process encourage interest from researchers to further support the efficacy and safety of this anticoagulant therapy. Re-analysis of the original HAS using contemporary endpoints and intention-to-treat analysis showed a 22 % reduction in major adverse cardiac events (including death, ACS, and revascularization) and a 62 % reduction in bleeding with bivalirudin at 7 days [4]. In the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) trial [5], bivalirudin with provisional glycoprotein IIb/IIIa blockade (which was administered in about 7 % of patients) was proven to be statistically non-inferior to heparin plus planned glycoprotein IIb/IIIa inhibitors during PCI with regard to suppressing ischemic events after PCI, but was superior in preventing hemorrhagic complications. More recently, bivalirudin provided similar protection from ischemic events as glycoprotein IIb/IIIa inhibitors, but with lower bleeding rates in the ACUITY (Acute Catheterisation and Urgent Intervention Triage strategy) trial [6]. Although the evidentiary landscape in support of antithrombotic treatment choices during PCI has been enriched by these trials, recent data from clinical trials and pooled analyses questioned the role of bivalirudin in the setting of planned and primary PCI [7–12]. In the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial, the use of bivalirudin was associated with a This comment refers to the article available at doi:110.1007/s40256015-0113-8.

Abstract 24: Resolvin D2 Reduces Thrombus Burden and Attenuates Inflammatory Signaling Pathways in a Murine Model of Venous Thrombosis

Background: Specialized pro-resolving lipid mediators (SPM) derived from polyunsaturated fatty acids, such as Resolvin D2 (RvD2), play a critical role in the resolution of acute inflammation. In recent years, total organic synthesis of SPM have enabled investigation of their bioactivity in-vivo. It is known that the effects of RvD2 include limited neutrophil influx in-vivo, reduced neutrophil transmigration and counter-regulation of cytokines such as tumor necrosis factor-α TNF-α in mice. However, SPMs have not been studied in the context of experimental venous thrombosis (VT). Methods: Mice C57Bl/6, 10 week-old, 25grams. Groups: Control non-VT mice; VT-control-vehicle; VT-RvD2; Flow model: Electrolytic IVC model. Intra-peritoneal injection was used for RvD2 and vehicle administration 4 hours after surgery. Harvest was performed 2 days after surgery, acute VT. Thrombus weight, qRT-PCR for inflammatory cytokines panel and subsets of white blood cell (WBC) counts were performed at the site of thrombosis histologically. Results (Figure 1): We observed that RvD2 significantly reduced thrombus size when compared to vehicle controls (17.9mg±2.1mg vs. 4.5mg±0.8mg). The vein wall cytokine profile demonstrated a significant gene down-regulation of IL-6, CCL2, and TNF-a. In addition, the inflammatory cell counts showed reduction in all white cells subsets. No bleeding complications were observed. Conclusions: For the first time we have demonstrated that RvD2 reduces VT formation. The decreased thrombogenesis was accompanied by a decrease in WBC and proinflammatory cytokines. We demonstrated that RvD2 is a potent anti-inflammatory agent that reduced WBC and attenuated cytokines in the context of experimental VT. Further investigation of RvD2 in VT treatment and prophylaxis appears warranted.

Impact of rosuvastatin treatment on reduction of thrombus burden in rat acute inferior vena cava stenosis

This study tested the hypothesis that rosuvastatin reduces thrombus burden through inhibiting inflammation and suppressing reactive oxygen species (ROS) generation in an inferior vena cava stenosis (IVCST)-induced deep vein thrombosis (DVT) rat model. 12-week-old male Sprague-Dawley rats (n = 24) were equally divided into sham control (group 1: laparotomy only), IVCST (group 2: IVC stenosis), and IVCST + rosuvastatin (20 mg/kg/day, orally after induction of IVC stenosis) (group 3). IVC diameter was measured by days 0 and 14 and the right hindlimb thickness was measured by day 0, 7, and 14 prior to scarifying the animals. The results showed significantly increased IVC diameter and hindlimb thickness in group 2 than in groups 1 and 3, and significantly increased in group 3 than in group 1 by day 14 after the procedure (all p < 0.001). Additionally, WBC count and prevalence of helper T cells, cytotoxic T cells, regulatory T cells, and early and late apoptotic mononuclear cells (MNCs) in circulation were significantly higher in group 2 than in group 1, and were significantly suppressed in group 3 after treatment (all p < 0.001). Furthermore, inflammation at cellular (CD68+ cells) and protein (MMP-9, TNF-α) levels, oxidative stress (oxidized protein) and reactive oxygen species (NOX-1, NOX-2) in IVC also showed similar changes as those of immune cells in circulation among the three groups (all p < 0.01). Rosuvastatin treatment significantly reduced IVC thrombus burden through inhibiting inflammatory response and oxidative stress in a rodent model of DVT.

Mechanical Thrombectomy with Trerotola Compared with Catheter-directed Thrombolysis for Treatment of Acute Iliofemoral Deep Vein Thrombosis

Mechanical thrombectomy (MT) of acute deep vein thrombosis (DVT) is safe and effective in reducing thrombus burden. MT utilizing a percutaneous thrombectomy device confers a great advantage because it may reduce both the dose of the thrombolytic agent and the overall procedure time compared with a conventional catheter-directed thrombolysis (CDT). We examined the results of MT using the Trerotola device and evaluated factors affecting patient outcome. This retrospective study was performed using data from a database of patients who had undergone treatment for an acute iliofemoral DVT from January 2005 to December 2011, at 2 institutions. The patients' clinical characteristics and procedures were compared, and the outcomes of treatment with the Trerotola in the MT group were compared with those obtained with CDT. There were a total of 98 DVTs (left 76; right 22) in 90 patients (34 men); 53 DVTs were treated with MT and 45 with CDT. There were no statistical differences in the clinical characteristics among the MT with CDT, MT only and CDT group. Inferior vena cava filters were placed in 93 DVTs (95%), and iliac vein stenting was used in 64 (65%). Symptom improvement was seen in 78% (18 limbs) of the MT group, 80% (24 limbs) of the MT with CDT group, and 71% (32 limbs) of the CDT group (P = 0.498). The procedure time was shorter in the MT with CDT group (18.2 ± 8.2 hr) or in the MT only group (2.7 ± 2.0 hr) compared with the CDT group (29.3 ± 9.4 hr; P < 0.001). Urokinase dose was lower in MT only (0 million units) or in the MT with CDT group (5.13 ± 3.72 million units) than in the CDT group (7.51 ± 4.54 million units; P < 0.001). There was no difference in complications during the procedures or in primary patency rate during the follow-up period (mean 16.0 ± 19.1 months; range: 0-78 months). MT with the Trerotola device for acute iliofemoral DVT required shorter procedure times and lower urokinase doses than conventional CDT, while providing the same results.

Prevention of Arteriovenous Shunt Occlusion Using Microbubble and Ultrasound Mediated Thromboprophylaxis

BackgroundPalliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts.Methods and ResultsHeparin‐bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right‐sided side‐to‐side arteriovenous (AV, carotid‐jugular) shunt, and a left‐sided arterio‐arterial (AA, carotid‐carotid) interposition shunt in each animal. After shunt implantation, animals were randomly assigned to one of 3 groups. Transcutaneous, weekly 30‐minute treatments (total of 4 treatments) of either guided high MI US+MB (Group 1; n=6) using a 3% MRX‐801 MB infusion, or US alone (Group 2; n=6) were given separately to each shunt. The third group of 6 pigs received no treatments. The shunts were explanted after 4 weeks and analyzed by histopathology to quantify luminal thrombus area (mm2) for the length of each shunt. No pigs received antiplatelet agents or anticoagulants during the treatment period. The median overall thrombus burden in the 3 groups for AV shunts was 5.10 mm2 compared with 4.05 mm2 in AA (P=0.199). Group 1 pigs had significantly less thrombus burden in the AV shunts (median 2.5 mm2) compared with Group 2 (median 5.6 mm2) and Group 3 (median 7.5 mm2) pigs (P=0.006). No difference in thrombus burden was seen between groups for AA shunts.ConclusionTranscutaneous US with intravenous MB is capable of preventing thrombus accumulation in arteriovenous shunts without the need for antiplatelet agents, and may be a method of preventing progressive occlusion of palliative shunts.

Local Intracoronary Eptifibatide versus Mechanical Aspiration in Patients with Acute ST-Elevation Myocardial Infarction.

Objectives. We compared local delivery of intracoronary eptifibatide via perfusion catheter to thrombus aspiration in primary PCI. Background. Perfusion catheter increases local concentration of the drugs at the culprit site and prolongs their residency time. Methods. 75 patients with acute STEMI were randomized to three groups: 25 received local intracoronary eptifibatide and verapamil via perfusion catheter; 25 patients were managed by Diver CE thrombectomy device and 25 patients by primary PCI without thrombus aspiration. Primary end point was assessment of postprocedural TIMI flow, MPG, and corrected TIMI frame count (cTFC) in the culprit vessel. Results. Perfusion catheter was superior to thrombus aspiration and conventional PCI as regards MBG (68% versus 36% in Diver CE and 20% in the control arm; P value = 0.002), with shorter cTFC rates than thrombectomy and control groups (20.76 ± 4.44 versus 26.68 ± 8.40 and 28.16 ± 5.96, resp.; P = 0.001). TIMI flow was not different between the 3 groups. Eptifibatide led to less time to peak CK (13.12 hours versus 16.5 and 19.5 hours, respectively, P value = 0.001). Conclusion. Local intracoronary eptifibatide by perfusion catheter reduces thrombus burden with better results in microvascular perfusion assessed by cTFC and MBG compared to aspiration device or conventional PCI.

Thrombus aspiration in acute myocardial infarction

Rupture of an atherosclerotic plaque is the principal mechanism responsible for the development of an acute coronary syndrome. Thrombus formation ensues rapidly on the surface of the injured endothelium. When the infarct vessel is completely occluded, ST-elevation myocardial infarction is diagnosed and urgent reperfusion is required. While infarct artery patency can be restored in most patients, adequate reperfusion at the tissue level is achieved much less often because of distal embolization of plaque and thrombus. Manual thrombus aspiration has been shown to reduce thrombus burden and improve markers of reperfusion, such as epicardial flow (thrombolysis in myocardial infarction flow), myocardial blush grade and ST-elevation resolution, compared with conventional balloon angioplasty and stenting. In one study, mortality was also reduced, but this result could not be duplicated in other series. Additional research is needed to clarify the exact role of manual thrombectomy in the management of ST-elevatio...