Reduce Thrombus Burden Research Articles

Combined use of optical coherence tomography and intravascular ultrasound imaging in patients undergoing coronary interventions for stent thrombosis

ObjectiveThis prospective study sought to assess the diagnostic value of optical coherence tomography (OCT) compared with intravascular ultrasound (IVUS) in patients presenting with stent thrombosis (ST).Design and settingAlthough the role...

Intracoronary administration of abciximab via an intracoronary perfusion catheter in patients with a thrombotic coronary occlusion—a single center experience

Aims: At concentrations superior to those achieved with the standard intravenous dose for coronary procedures, abciximab has an active dethrombotic effect by displacing platelet-bound fibrinogen. This analysis investigates whether administration of abciximab by local intracoronary infusion through the ClearWay (CX) RX perfusion catheter improves coronary blood flow (TIMI flow) by reducing thrombus burden. Methods and Results: This retrospective study included 68 patients who presented with an acute coronary syndrome due to an intracoronary thrombus between May 2009 and April 2011. The primary endpoint was defined as improvement in Thrombolysis In Myocardial Infarction (TIMI) flow after intracoronary application of abciximab via the ClearWay (CW) RX perfusion catheter. The population (mean age 58±11 years) consisted of 54 patients (79%) with an ST-elevation myocardial infarction and 14 patients (21%) with a non-ST-elevation myocardial infarction. The balloon-diameter of the perfusion catheter was 1 mm in 25 (37%), 1.5 mm in 23 (34%), 2.0 mm in 14 (20%), and 3.0 mm in 6 patients (9%), respectively. Successful positioning of the balloon within the thrombus was not possible in 4 patients (6%). After infusion of abciximab using the perfusion catheter TIMI flow improved by one grade in 17 patients (25%), by two grades in 9 patients (13%), and by three grades in 7 patients (10%), TIMI flow remained unchanged in 21 patients (31%), and even worsened by one grade in 4 patient (6%) (χ test, Pb.001). The procedure was complicated by an air embolization in 5 patients (7%). Air embolization occurred using a 2 mm balloon (three patients) or a 3 mm balloon (two patients), but not using a 1 mm or 1.5 mm balloon (χ, Pb.003). After the use of the perfusion catheter in these patients TIMI flow improved by one degree in 2 of these patients, was unchanged in 2 of these patients and worsened by one grade in one patient. After additional treatment with thrombectomy (54 patients, 79%), initial balloon dilatation (46 patients, 68%), direct stenting (22 patients, 32%), and stent implantation (64 patients, 94%), the final TIMI flow was TIMI 3 in 57 patients (84%), TIMI 2 in 4 patients (6%), TIMI 1 in 6 patients (9%), and TIMI 0 in 1 patient (1%). Conclusion: The intracoronary infusion of abciximab using the ClearWay (CX) RX perfusion catheter helps to improve myocardial perfusion in patients with acute coronary syndrome due to an intracoronary thrombus. The use of perfusion catheters with a balloon ≥2 mm can be associated with air embolism.

Abstract 9505: Short-Term Statin Therapy Improves Murine Deep Venous Thrombosis Resolution While Reducing Thrombus Inflammation: An i n vivo Multi-Targeted Imaging Study

Background: Improving DVT resolution may limit the development of the post-thrombotic syndrome (PTS). Utilizing confocal intravital fluorescence microscopy (IVFM), we investigated the in vivo effects of short-term statin therapy on thrombus burden, permeability, and inflammation in subacute murine DVT. Methods: In 24 male C57Bl/6J mice with topical FeCl 3 -induced femoral DVT, atorvastatin (1.14 mg/kg/day, ≈ 80 mg/day/human subject, n=12) or PBS (n=12) was administered on days 1-4 via gavage. On day 3, macrophage-targeted nanoparticles (CLIO-AF555, ex/em 555/565 nm) and an MMP activity sensor (MMPsense680, 680/700 nm) were i.v. injected. On day 4, FITC-dextran (490/520 nm) was injected to define thrombus anatomy and to evaluate thrombus permeability. 30 minutes after FITC-dextran injection, IVFM was performed. The in vivo thrombus burden, and average thrombus macrophage, MMP activity, and permeability target-to-background ratio (TBR) in the mid-thrombus zone (z-stack of 40 um thickness) were determined from CLIO, MMPsense and FITC signals. Histopathology and fluorescence microscopy studies were performed. Results: Atorvastatin decreased DVT area on IVFM (0.17±0.01 mm 2 vs. 0.20±0.03 mm 2 in PBS animals, p=0.001), and by microscopy (% thrombus area, 42.2±12.6% statin vs. 71.0±12.7% PBS, p<0.001). Thrombus sections from statin-treated animals showed reduced PAI-1 immunoreactivity (14.8±4.7% positive area vs. 30.7±5.0% in PBS mice, p=0.022). Notably, statin therapy reduced thrombus inflammation compared to PBS-treated animals (macrophage TBR 1.7±0.2 vs. 3.1±0.3, p=0.001; and MMP activity TBR 1.3±0.1 vs. 1.8±0.2, p=0.021, respectively). Thrombus permeability was similar in the two groups (p=NS). Correlative fluorescence microscopy and immunohistochemistry corroborated the in vivo imaging findings. Conclusions: Short-term statin therapy in subacute DVT reduces thrombus burden and improves DVT resolution in vivo . The observed benefits of statin treatment are linked to its anti-thrombotic properties, and occur in the setting of reduced thrombus inflammation and similar thrombus permeability. Statin therapy may offer a clinically translatable approach to improve DVT resolution and to limit PTS.

Local Delivery Versus Intracoronary Infusion of Abciximab in Patients With Acute Coronary Syndromes

We investigated whether local abciximab delivery to the site of intracoronary thrombus is more effective than intracoronary bolus infusion in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention and downstream clopidogrel administration. The intracoronary route of administration does not allow an optimal contact between the plaque components and abciximab, which is rapidly washed out by the coronary flow. A total of 50 patients with ACS and a significant lesion in the culprit artery indicative of local thrombosis were randomly assigned to receive local intracoronary delivery of abciximab through a dedicated perfusion catheter or intracoronary infusion through the guiding catheter. The primary end point was the change in thrombus score after angioplasty by optical coherence tomography. After the intervention, the mean percentage change of the thrombus score was significantly higher among patients of the local delivery group compared with those of the intracoronary infusion group (33.8% vs. 3.9%, p = 0.002). Post-procedural corrected Thrombolysis in Myocardial Infarction frame count was shorter in the local delivery group compared with the intracoronary infusion group (15.3 ± 10.2 vs. 21.1 ± 9.9, p = 0.049). Procedure-related myocardial infarction was observed in 10% and 43% of patients in the local delivery and intracoronary infusion groups, respectively (p = 0.018). At 1 year, MACE were observed in 5.9% and 27.2% of patients in the local delivery and intracoronary infusion groups, respectively (p = 0.046). Local intracoronary delivery of abciximab by means of a dedicated perfusion catheter reduces thrombus burden with the potential to improve coronary microcirculation.

ClearWayRX System to reduce intracoronary thrombus in patients with acute coronary syndromes according to Optical Coherence Tomography after Abciximab Intracoronary Local infusion trial (COCTAIL): study rationale and design

Prompt reperfusion with percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes (ACS) improves clinical outcomes through salvage of myocardial tissue. Although use of intracoronary glycoprotein IIb/IIIa inhibition with PCI can result in improved rates of normal epicardial flow and myocardial perfusion, several unmet needs remain. The purpose of this trial is to evaluate the efficacy and safety of an intracoronary bolus of abciximab delivered using the ClearWayRX Therapeutic Perfusion Catheter followed by a dosing regimen of intravenous abciximab infusion after PCI, compared with intracoronary abciximab infusion, via the guiding catheter, followed by a dosing regimen of intravenous abciximab infusion after PCI in patients with ACS. Patients with ACS (either unstable angina/non-ST-elevation myocardial infarction or ST-elevation myocardial infarction with open infarct-related artery) and visible thrombus referred for PCI will be randomized to receive one of the two treatment regimens: local intracoronary infusion of abciximab through the ClearWayRX System or intracoronary infusion of abciximab via the guiding catheter. Both groups will receive intravenous infusion of abciximab during the 12-h period following the procedure. Optical coherence tomography assessment will be performed prior to abciximab administration and after the intracoronary infusions to document the change in the thrombus score. In addition, postintervention assessments of coronary microcirculatory function will be evaluated by means of the corrected thrombolysis in myocardial infarction frame count flow and the 'myocardial blush grade'. If local intracoronary infusion of abciximab through the ClearWayRX System significantly reduces thrombus burden, it will lend support to the use of this delivery system as a valuable tool in patients with ACS treated with PCI.

Coronary Microembolization

Coronary microembolization from the erosion or rupture of a vulnerable atherosclerotic plaque occurs spontaneously in acute coronary syndromes and iatrogenically during percutaneous coronary interventions. Typical consequences of coronary microembolization are microinfarcts with an inflammatory response, contractile dysfunction, and reduced coronary reserve. Apart from transient elevations of creatine kinase and troponin, microemboli can be visualized by intracoronary Doppler and the resulting microinfarcts by late-enhancement nuclear magnetic resonance. Statins, antiplatelet agents, and coronary vasodilators protect against microembolization and microinfarction when started before percutaneous coronary interventions. Distal protection devices can retrieve atherothrombotic debris and prevent its embolization into the microcirculation, but their effect on clinical outcome has been disappointing so far, except for saphenous vein bypass grafts. Devices for aspiration of thrombi and thrombus-derived vasoconstrictor, thrombogenic, and inflammatory substances, however, reduce thrombus burden, improve perfusion, and provide protection in patients with acute myocardial infarction.

Thrombectomy during PCI for acute myocardial infarction

Macro and microembolization during percutaneous coronary intervention (PCI) in ST elevation acute myocardial infarction (STEAMI) is frequent and may result in obstruction of the microvascular network with subsequent reduction in efficacy of reperfusion. Numerous mechanistic studies have shown that the presence and size of the culprit thrombus is the most powerful predictor of incidence of embolization and slow flow/no reflow. Techniques that have been used to reduce the incidence of these events include thrombectomy devices and embolic protection devices. Although numerous prospective randomized clinical trials have been performed to evaluate the role of thrombectomy devices in patients with STEAMI, the results of these trials are conflicting and they speak to both sides of the controversy. The Achilles heal of the majority of these trials is the premise that thrombectomy devices should be routinely used in all patients presenting with STEAMI even irrespective of the presence and size of the thrombus. Such a hypothesis is naively optimistic and it ignores the basic knowledge available to us regarding the relationship between thrombus burden and embolization. Nonetheless, clinicians are faced every day with the reality of making difficult decisions on how to best treat patients presenting with STEAMI and large thrombus burden. The current available "evidence-based medicine" cannot and should not be generalized to these patients because only a minority of these patients was included in these randomized clinical trials. In these patients, thrombectomy devices should be strongly considered as an integral part of the armamentarium available to reduce thrombus burden prior to definitive treatment. Whether a future clinical trial will provide a definitive answer in terms of clinical outcome difference is doubtful because such a trial will need to include large number of selected patients with STEAMI who both have large amount of myocardium at jeopardy and large thrombus burden, a difficult and possibly undoable study.

Below Radar

Below Radar

A pilot study with a new, rapid‐exchange, thrombus‐aspirating device in patients with thrombus‐containing lesions: The Diver C.E. study

In patients with acute coronary syndromes (ACS), distal embolization of thrombotic material is more likely to play a key role in the pathogenesis of myocardial no-reflow during percutaneous coronary intervention (PCI). Thus, interventional techniques able to reduce thrombus burden at the culprit vessel might improve final myocardial reperfusion. To evaluate a new rapid-exchange thrombus-aspirating catheter, the Diver C.E., in patients with thrombotic coronary lesions undergoing PCI. Fifty patients with acute myocardial infarction (n = 44) or with non-ST-elevation ACS and angiographic evidence of coronary thrombus (n = 6) undergoing urgent PCI were prospectively enrolled. The Diver C.E. was used to aspirate coronary thrombus from the culprit lesion after placement of the guidewire. Adjunctive balloon inflations and stent implantation were used to achieve good angiographic result. Angiographic coronary flow (by means of TIMI score and corrected TIMI frame count, cTFC), thrombus score (TS), and myocardial perfusion (by means of postintervention myocardial blush grade, MBG) were assessed in all patients. The device could be successfully employed in 96% of the cases (48/50) and yielded significant (P < 0.0001) acute reduction in thrombus burden (TS: predevice 3.5 +/- 0.8, postdevice 2.5 +/- 0.9) and improvement in coronary flow (TIMI grade: predevice 1.0 +/- 0.9, postdevice 2.0 +/- 0.9; CTFC predevice 71 +/- 31, postdevice 39 +/- 26). Final TIMI grade 0-1 was observed in one patient only (2%). A significant (P = 0.02) correlation was found between preintervention TS and efficacy of thrombus aspiration. A more pronounced acute reduction of thrombus burden after thrombus aspiration (TS reduction > or = 2) was associated with a better postintervention angiographic myocardial perfusion (MBG 2.3 +/- 0.9 vs 1.7 +/- 0.8; P = 0.05). This new, easy-to-use, device is able to reduce thrombus burden and to improve coronary flow in patients with thrombus-containing lesions. The improvement in myocardial perfusion associated to greater thrombus removal highlights the importance of thrombus aspiration in the management of thrombus-burdened coronary lesions.

X-Sizer for Thrombectomy in Acute Myocardial Infarction Improves ST-Segment Resolution: Results of the X-Sizer in AMI for Negligible Embolization and Optimal ST Resolution (X AMINE ST) Trial

We sought to compare, in a prospective randomized multicenter study, the effect of adjunctive thrombectomy using X-Sizer (eV3, White Bear Lake, Minnesota) before percutaneous coronary intervention (PCI) versus conventional PCI in patients with acute myocardial infarction (AMI) for <12 h and Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1. The primary end point was the magnitude of ST-segment resolution after PCI. Despite a high rate of TIMI flow grade 3 achieved by PCI in patients with AMI, myocardial reperfusion remains relatively low. Distal embolization of thrombotic materials may play a major role in this setting. We conducted a prospective, randomized, multicenter study in patients with AMI <12 h and initial TIMI flow grade 0 to 1 who were treated with primary PCI. The magnitude of ST-segment resolution 1 h after PCI was the primary end point. A total of 201 patients were included. Treatment groups were comparable by age (61 +/- 13 years), diabetes (22%), previous MI (8%), anterior MI (52%), onset-to-angiogram (258 +/- 173 min), and glycoprotein IIb/IIIa inhibitor use (59%). The magnitude of ST-segment resolution was greater in the X-Sizer group compared with the conventional group (7.5 vs. 4.9 mm, respectively; p = 0.033) as ST-segment resolution >50% (68% vs. 53%; p = 0.037). The occurrence of distal embolization was reduced (2% vs. 10%; p = 0.033) and TIMI flow grade 3 was obtained in 96% vs. 89%, respectively (p = 0.105). Myocardial blush grade 3 was similar (30% vs. 31%; p = NS). Six-month clinical outcome was comparable (death, 6% vs. 4% and major adverse cardiac and cerebral events, 13% vs. 13%, respectively). By multivariate analysis, independent predictors of ST-segment resolution >50% were: younger age, non-anterior MI, use of the X-Sizer, and a short time interval from symptom onset. Reducing thrombus burden with X-Sizer before stenting leads to better myocardial reperfusion, as illustrated by a reduced risk of distal embolization and better ST-segment resolution.

Dissolution of a saphenous vein graft thrombus with systemic glycoprotein IIb/IIIa receptor inhibitor prior to percutaneous coronary intervention

A60-year-old man with known coronary artery disease was admitted to the hospital with severe retrosternal pain persisting over two hours. In the week before admission he had suffered from short episodes of chest pain but the symptoms always had resolved spontaneously. The patient had undergone coronary artery bypass grafting of the proximal left anterior descending coronary artery (LAD) and the first diagonal branch 21 years ago, and had suffered from a myocardial infarction ten years ago, but no coronary angiography had been performed at that time. On admission, the ECG showed a non-significant infero-lateral ST segment depression without elevation of the cardiac enzymes. Anti-ischaemic therapy with aspirin, beta-blockers, and a weightadapted abciximab bolus with subsequent continuous infusion was started, and the chest pain resolved. The next day cardiac troponin I was raised to 103 μg/l and creatine kinase to 504 U/l. Due to a sudden recurrence of chest pain the patient was urgently transferred to the cardiac catheterisation laboratory. Coronary angiography revealed severe three-vessel disease without high-grade stenoses of the right coronary and circumflex artery, but a chronic proximal occlusion of the LAD with an open saphenous vein graft (SVG) on the mid part and an occluded SVG on the first diagonal branch with a large thrombus in the distal part (fig. 1A.). Due to the high periprocedural risk of embolisation the intervention was postponed and treatment with abciximab was continued for another 48 hours in combination with half-dose low molecular weight heparin, followed by full-dose low molecular weight heparin for another seven days. The subsequent clinical course was uneventful without recurrence of symptoms. Ten days after admission a repeated coronary angiography revealed a high-grade proximal stenosis of the SVG on the first diagonal branch with a total dissolution of the thrombus (fig. 1B.). Percutaneous transluminal coronary angioplasty of the culprit lesion was performed with insertion of a 3.5/18 mm bare stent (fig. 1C.). Heparin therapy was stopped, and clopidogrel was started for six months. Before discharge, the patient underwent a clinically negative exercise stress test without any significant ECG alterations. Percutaneous coronary intervention (PCI) is the treatment of choice in acute coronary syndromes. However, PCI in thrombotic SVG occlusions remains an unresolved issue because of technical difficulties, distal embolisation, high restenosis rate, and a poor outcome with low event-free survival rates [1]. The use of distal embolisation protection devices reduces major adverse events after stenting of stenotic SVG [2], and intracoronary application of glycoprotein (GP) IIb/IIIa blockers during angioplasty reduces thrombus burden [3]. GP IIb/IIIa receptor inhibitors prevent platelet aggregation, have a great potential to diminish formation of platelet thrombi in case of platelet activation, and are indicated in patients both undergoing PCI and with acute coronary syndromes not responding to conventional medical therapy when PCI is planned. Our case shows a successful dissolution of a SVG thrombus with GP IIb/IIIa receptor inhibition over 48 hours enabling a subsequent safe and complication-free PCI with a good angiographic result. Due to the high periprocedural risk of PCI in case of a SVG obstruction with concomitant intracoronary thrombus formation a conservative management with attempted dissolution with GP IIb/IIIa receptor inhibitors might be recommended as a first-line therapy as long as the patients are clinically stable.

Pathogenesis of the acute coronary syndromes and therapeutic implications

Atherosclerosis is characterized by the thickening and obstruction of the arterial lumen and thrombosis associated with vulnerable disrupted plaques seems to be responsible for the accelerated process of clinical syndrome presentation. Strategies to promote plaque stabilization and reduce thrombus burden have been one of the major targets of recent times. Modification of diet and lifestyle has important benefit in reducing coronary risk. Several pharmacological strategies for reducing cardiovascular morbidity and mortality have demonstrated effectiveness. Statins and angiotensin converting enzyme, fibrinolytics, inhibitors of the intrinsic coagulation cascade and anti-platelet agents have been developed to reduce the impact of atherosclerosis and inhibit thrombogenesis.

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts

Background Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. Methods We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had ≥60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. Results Median percent diameter stenosis improved from 69% to 45% ( P = .0001) after local delivery, and TIMI thrombus grade ≥1 incidence reduced from 68% to 34% ( P = .0001). TIMI flow grade was not significantly affected ( P = .12). All patients had a successful intervention (≤50% residual stenosis). Conclusions Local abciximab delivery before percutaneous SVG intervention is associated with significantly reduced thrombus burden, significantly improved percent diameter stenosis, and excellent acute procedural results. Further studies of this approach are warranted to define its clinical utility.

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts

Reduced thrombus burden with abciximab delivered locally before percutaneous intervention in saphenous vein grafts

Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty.

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and alter lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for > or = 4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus.