Reduce Thrombus Burden Research Articles

Coronary Plaque Erosion: Epidemiology, Diagnosis, and Treatment.

Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.

Abstract 122: Deletion Of Pyruvate Dehydrogenase Kinases Reduces Susceptibility To Experimental Venous Thrombosis By Limiting Glycolysis In Neutrophils

Background: Neutrophils by releasing extracellular traps (NETs) provide a scaffold for platelet activation and coagulation, thereby facilitating venous thrombosis (VT) development. Emerging evidence suggests that neutrophil activation and NETs formation (NETosis) is an energy-intensive process, accompanied by an increased rate of aerobic glycolysis (lactate formation in the presence of oxygen). The metabolic enzymes pyruvate dehydrogenase kinases (PDKs) inhibit the pyruvate dehydrogenase complex to divert the pyruvate flux (final product of glycolysis) from oxidative phosphorylation towards aerobic glycolysis. Recently, we reported the role of PDK2 and PDK4 (PDK2/4) in platelet activation and arterial thrombosis. The regulatory role of PDKs in neutrophils and VT has not been explored. Aim: To test the hypothesis that PDK2/4 promotes NETosis and VT by promoting glycolysis in neutrophils. Methods: Double-deficient PDK2/4 -/- and wild-type (WT) mice were subjected to 48 hours of inferior vena cava stenosis to test the susceptibility to VT. In vitro , neutrophils were stimulated with Phorbol 12-myristate 13-acetate (PMA) and the glycolytic proton efflux rate (glycoPER) was measured using the Seahorse XF Analyzer. Results: The PDK2/4 -/- mice were less susceptible to DVT as measured by the primary outcome of reduced thrombus burden (weight, length and % incidence) and marker of NETs such as citrullinated histones (P<0.05 vs WT). In the WT platelet aggregation assay mediated by PMA-stimulated WT or PDK2/4 -/- neutrophils, we observed reduced platelet aggregation evoked by PMA-stimulated PDK2/4 -/- neutrophils (P<0.05 vs WT). Impaired aggregation was associated with reduced release of cathepsin G and elastase from PMA-stimulated PDK2/4 -/- neutrophils (P<0.05 vs WT). Mechanistically, PMA-stimulated PDK2/4 -/- neutrophils exhibited reduced NETosis that was associated with decreased calcium mobilization and Erk1/2 phosphorylation (P<0.05 vs WT), known contributors of NETosis. Furthermore, PMA-stimulated PDK2/4 -/- neutrophils displayed reduced glycoPER (P<0.05 vs WT), suggesting reduced aerobic glycolysis. Conclusions: These findings for the first time demonstrate the regulatory role of PDK2/4 in NETosis and acute progression of VT.

The efficacy of excimer laser coronary atherectomy in ST-elevation myocardial infarction: a report from the STELA registry

Abstract Backgrounds Previous studies have demonstrated potential effect of excimer laser coronary atherectomy (ELCA) to reduce thrombus burden within the vessel, and ELCA has been used during primary PCI for acute coronary syndrome. Especially, the culprit lesions of ST-segment elevation myocardial infarction (STEMI) are generally accompanied by large thrombus burden. Nevertheless, the clinical effectiveness of ELCA use for the culprit lesions of STEMI has not been elucidated. Purpose To investigate the clinical outcomes of the STEMI patients who were treated with ELCA during primary PCI in comparison with those treated without ELCA. Methods We conducted the registry study of STEMI for the assessment of the efficacy of ELCA, which was an observational multicenter registry of the consecutive patients undergoing primary PCI for STEMI within 24 hours from the onset between 2015 and 2019. The patients were divided into two groups according to the use of ELCA during primary PCI: ELCA group and non-ELCA group. The primary endpoint was the major adverse cardiovascular event (MACE), which was defined as the composite of cardiovascular death (CVD), target vascular revascularization and non-fatal AMI. Propensity score (PS) matching was performed to adjust the bias of confounding factors using 1:1 nearest-neighbor matching without replacement. PS was yielded from clinical characteristics, baseline angiographic findings, and hemodynamic status that were imbalanced between the two groups. Results A total of 2593 patients, 424 patients in ELCA group and 2169 patients in non-ELCA group, were included in the analysis. PS matched cohort comprised 824 patients including 412 ELCA and 412 non-ELCA group. Median follow-up duration in the total cohort was 816 (394-1388) days. In the total cohort, baseline characteristics showed that younger age, less prevalent hypertension, and more frequent prior statin use in ELCA group than in non-ELCA group. In terms of clinical outcomes, ELCA group showed a significantly lower rate of CVD than non-ELCA group (4.3% vs 7.5%, P for log-rank = 0.03), whereas MACE rate was similar between the two groups (HR:1.00 95%CI 0.74-1.34, P=0.99). In the PS matched cohort, the baseline characteristics were well balanced. Clinical outcomes including MACE and CVD were comparable between the two groups (MACE HR:1.13 95%CI 0.76-1.66, P=0.53 and CVD HR0.70 95%CI 0.38-1.29 P=0.25). In the subgroup analysis, MACE rate was lower in ELCA group than in non-ELCA group in the patients who presented with Killip class III or IV (P for interaction <0.01) (Abstract Picture 1). Conclusions The use of ELCA was not associated with improved MACEs in both total cohort and the PS matched cohort, whereas subgroup analysis suggested a potential benefit of ELCA in patients with heart failure. Further prospective investigations are warranted.Forest Plots for Subgroup Analysis

Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: hemodynamic outcomes at three months

BackgroundMechanical thrombectomy has been shown to reduce thrombus burden and pulmonary artery pressure (PAP) and to improve right ventricular (RV) function in patients with high-risk or intermediate-high-risk pulmonary embolism (PE). As hemodynamic data after mechanical thrombectomy for PE are scarce, we aimed to assess the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload.MethodsIn this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after 20 patients completed three months of follow-up.ResultsTwenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients were at high (17%) or intermediate-high (76%) risk and had bilateral PE (79%). Before thrombectomy, systolic PAP (sPAP) was severely elevated (mean 51.3 ± 11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p < 0.001) immediately after the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p = 0.002). RV/left ventricular (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p < 0.001). The proportion of patients with a tricuspid annular plane systolic excursion (TAPSE)/sPAP ratio < 0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p = 0.007). There were no procedure-related major adverse events.ConclusionsMechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.

Abstract 243: Local Periadventitial Delivery Of Dexamethasone Improves Murine Deep Vein Thrombosis Resolution

Background: Post deep vein thrombosis (DVT), up to 30-50% of patients will develop post-thrombotic syndrome (PTS), despite anticoagulation. Currently no preventive therapies, including catheter-based thrombectomy/thrombolysis (CDT), have shown to reduce PTS. Local steroid therapy adjunct to CDT is being tested clinically for DVT patients in the DEXTERITY trials, but minimal mechanistic data exists on DVT resolution. Here, we investigate effects of local dexamethasone (DEX) therapy on murine DVT resolution. Method: C57/BL6 male mice (n=146) underwent inferior vena cava (IVC) complete ligation to develop stasis DVT on day 0 (D0) followed by mechanical de-ligation on D2 to spur restoration of blood flow (RBF). On D2, mice were injected with PBS/DEX (0.1, 0.2, or 0.5 mg/mouse, 60μl volume, across four zones) in the periadventitial tissue of thrombosed IVC, with or without de-ligation (Fig. A-B). Mice underwent D4&amp;D8 serial ultrasound imaging of IVC blood flow to assess RBF-defined as IVC mean flow velocity &gt; 0 mL/sec. D8 thrombus burden was measured followed by histological/picrosirius red assessment of vein wall fibrosis. Results: N=6-11 mice per group underwent IVC DVT creation. Low-dose (0.1 mg) but not higher doses of DEX reduced thrombus burden (p=0.02) and weight (p=0.01) on D8 (Fig. C-D). Low-dose DEX increased D4 RBF rates and mean flow velocity (MFV) (Fig. E-F). Complete IVC stasis without de-ligation but with DEX non-significantly reduced thrombus burden and weight (Fig. G-H). Low-dose DEX further decreased vein wall fibrosis (Fig. I; p=0.001). D8 thrombi exhibited reduced macrophage content with DEX (Fig. J; n=15-18 sections/group, p=0.007). Conclusion: Following stasis DVT induction, locally delivered low-dose DEX improves DVT resolution by reducing thrombus burden, vein wall injury, macrophage content, and increases RBF rate. These data provide a scientific foundation for ongoing DEXTERITY trail testing adjunct DEX for DVT patients undergoing CDT.

Percutaneous large-bore aspiration embolectomy with veno-arterial extracorporal membrane oxygenation support or standby in patients with high-risk pulmonary embolism and contraindications to thrombolysis: a preliminary single centre experience.

Large-bore catheter aspiration embolectomy reduces thrombus burden and right ventricle strain and improves haemodynamics after pulmonary embolism (PE). Sparse data are available for patients with high-risk PE and contraindications to thrombolysis or thrombolysis failure, particularly if veno-arterial extracorporal membrane oxygenation (VA-ECMO) is required. All patients with acute high-risk PE and contraindications to thrombolysis undergoing FlowTriever® percutaneous embolectomy and VA-ECMO circulatory support (or standby) at the University Hospital Zurich between April 2021 and August 2022 were retrospectively analysed. The primary outcome was the combination of recurrent PE, heart failure hospitalization, and all-cause death at 30 days. The analysis included 15 patients: mean age was 63.1 years and 14 (93%) were men. Overall, four (27%) patients presented with cardiac arrest, eight (53%) with ongoing obstructive shock, and three (20%) with persistent arterial hypotension. Veno-arterial extracorporal membrane oxygenation was implanted prior to aspiration embolectomy in eight (53%) patients. Three of seven patients without initial VA-ECMO support experienced periprocedural cardiac arrest, of whom two received ECMO support before completion of embolectomy. Veno-arterial extracorporal membrane oxygenation weaning was successful in all patients after a mean of 5.4 days. There was one periprocedural death in a patient who did not receive VA-ECMO support following a periprocedural cardiac arrest. The primary outcome at 30 days occurred in five (33.3%; 95% confidence interval 13.0-61.3%) patients. This study provides preliminary evidence for the feasibility of percutaneous large-bore aspiration embolectomy in combination with VA-ECMO support (or standby) in patients with high-risk PE and contraindications to thrombolysis.

Percutaneous Management of High-Risk Pulmonary Embolism.

Acute pulmonary embolism (PE) leads to an abrupt increase in pulmonary vascular resistance and right ventricular afterload, and when significant enough, can result in hemodynamic instability. High-risk PE is a dire cardiovascular emergency and portends a poor prognosis. Traditional therapeutic options to rapidly reduce thrombus burden like systemic thrombolysis and surgical pulmonary endarterectomy have limitations, both with regards to appropriate candidates and efficacy, and have limited data demonstrating their benefit in high-risk PE. There are growing percutaneous treatment options for acute PE that include both localized thrombolysis and mechanical embolectomy. Data for such therapies with high-risk PE are currently limited. However, given the limitations, there is an opportunity to improve outcomes, with percutaneous treatments options offering new mechanisms for clot reduction with a possible improved safety profile compared with systemic thrombolysis. Additionally, mechanical circulatory support options allow for complementary treatment for patients with persistent instability, allowing for a bridge to more definitive treatment options. As more data develop, a shift toward a percutaneous approach with mechanical circulatory support may become a preferred option for the management of high-risk PE at tertiary care centers.

Has low-dose intracoronary thrombolysis gained ground in primary percutaneous intervention?

Reducing thrombus burden would improve patient's outcomes. Low-dose intracoronary thrombolytic agent administration has been considered to improve myocardial microcirculation, cardiac function, and major adverse cardiovascular events in patients presenting with ST-segment elevation myocardial infarction and high thrombus burden. This paper discusses published meta-analyses on intracoronary thrombolysis in primary percutaneous intervention.

Decreased device related thrombus and enhanced neo-endocardial tissue maturation with a new generation left atrial appendage closure (LAAC) device. An anticoagulation and antiplatelet free canin study

Abstract Introduction Device related thrombus (DRT) has been reported in up to 7% of patients post LAAC even while on anticoagulation. Clinical predictors of DRT are poorly understood and may be related to patient, procedural and device factors. A next generation WATCHMAN LAAC device (NG) is identical in shape and geometry to the current WATCHMAN FLX device (CW) but has a device coating designed to make it hemocompatible and less thrombogenic. Objective To evaluate the incidence and burden of WM surface thrombus formation as detected longitudinally by TEE and at necropsy in a canine model implanted with the NG device. Methods The study included 12 canine (6 implanted with CW and 6 implanted with NG) that underwent serial TEE follow up at 14, 28 and 45 days to evaluate surface thrombus on WM face. This was a challenged canine model designed to induce thrombus with no anticoagulation or antiplatelet use throughout the study. D-dimer levels were measured at 7 days and 45 days and compared to baseline measurements. Results All devices were successfully implanted. TEE follow up at 14 days showed noticeably reduced thrombus burden on the NG device compared to CW (fig.1) with even further diminution by 28 days in the NG (6/6) as compared to only in 1/6 in the CW group (fig.2). After 45 days in-life, the post-fixation trim en-face images show a smooth, glistening neoendocardial covering (absence of acute thrombus material) in all (6/6) NG compared to only 2/6 in the CW (fig.3). The CW had 3/6 devices with exuberant, bulging calcified thrombus mass one of which was considered to be a mobile DRT. D Dimer levels at 7 and 45 days were significantly lower relative to baseline in the NG compared to CW. Conclusion The NG device compared to the CW device was associated with markedly less thrombus formation at 14 days and no thrombus formation at 28 days post implant on no anticoagulant and no antiplatelet therapy along with a more mature uniform tissue coverage at 45 days. The WATCHMAN FLX Pro device coating is a promising step to reduce DRT even without the use of anticoagulation and antiplatelets and merits further investigation in human studies. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boston Scientific

Initial experience with a continuous mechanical aspiration system for thrombus removal before percutaneous coronary intervention.

Here we investigate the safety and efficacy of a continuous mechanical aspiration system when used before percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Historically, trials of routine manual aspiration thrombectomy in ACS patients have reported mixed results. This may be due to the technical limitations of manual aspiration, which suffers from decreasing vacuum power as aspiration is performed. This is a retrospective case series of all patients treated with continuous mechanical aspiration (Indigo CAT RX Aspiration System; Penumbra Inc.) before PCI between August 2017 and July 2020 at five centers in the United States. Data regarding angiographic assessments, procedure, and safety were examined. Seventy-two patients (mean age 60 ± 12.5 years, 34.7% female) with ST Elevation Myocardial Infarction (STEMI) (80.6%) or Non-ST Elevation Myocardial Infarction (NSTEMI) (19.4%) were included. Target vessels were the right coronary (43.1%), left anterior descending (33.3%), and left circumflex (23.6%). Preprocedure, 94.4% had a high thrombus burden (thrombolysis in myocardial infarction [TIMI] thrombus grade ≥ 3). Median aspiration time was 35 s and median access-to-reperfusion time was 10 min. After CAT RX alone, 86.1% had complete perfusion (TIMI flow grade 3). After the procedure, 94.4% had TIMI thrombus grade <3% and 97.2% had TIMI flow grade 3. There were no cases of ischemic stroke. Cardiovascular mortality at 30 days was 1.4%. In our initial experience, aspirating thrombus from ACS patients using the Indigo CAT RX Aspiration System before PCI was safe and effective for reducing thrombus burden and restoring flow.

Management of no Reflow during Percutaneous Transcoronary Angioplasty with Catheter-Directed Intracoronary Thrombolysis: A Retrospective Observational Study.

Intracoronary thrombus is common in patients with ST-elevation myocardial infarction (STEMI). Percutaneous coronary intervention (PCI) is the treatment of choice for these patients. Intracoronary thrombus is still a challenge during PCI in STEMI, even with dual antiplatelets, glycoprotein IIb/IIIa inhibitor, and anticoagulation. Intracoronary thrombus can cause distal or nonculprit vessel embolization and no-reflow state. No reflow results in large infarct size, adverse left ventricular remodeling, arrhythmias, and death. Recently, catheter-directed intracoronary thrombolysis (ICT) is gaining acceptance in patients with no-reflow due to a large thrombus burden. Evaluation of catheter-directed ICT in patients with acute STEMI who develop no reflow due to large thrombus burden during PCI. This was a retrospective observational study conducted after approval of the institutional ethics committee in a tertiary care hospital of north India from April 15, 2021 to April 14, 2022, included 1020 adult patients who had undergone coronary evaluation. 37.25% patients had PCI, among these 10% had PCI for acute STEMI. Thrombolysis in myocardial infarction (TIMI) Grade 5 in 79.17% and Grade 4 in 20.83%. ICT was done with low-dose tenecteplase (15 ± 5 mg). The TIMI flow III in 91.67% and II in 8.33% of patients was achieved after intracoronary thrombolysis. Major risk factor was tobacco smoking in 41.67%, and the major complication was left ventricular failure in 33.33%. Catheter-directed ICT is safe and effective in reducing thrombus burden, thus improving myocardial reperfusion in STEMI. This condition has a grave prognosis and can lead to adverse cardiac outcomes. There are many drugs that have been tried to manage no reflow. The use of ICT to treat no-reflow state can be life saving with minimal systemic side effects.

Intracoronary pharmacological therapy versus aspiration thrombectomy in STEMI (IPAT-STEMI): A systematic review and meta-analysis of randomized trials.

BackgroundThrombus load in STEMI patients remains a challenge in practice. It aggravates coronary obstruction leading to impaired myocardial perfusion, worsened cardiac function, and adverse clinical outcomes. Various strategies have been advocated to reduce thrombus burden.ObjectivesThis meta-analysis aimed to evaluate the effectiveness of intracoronary-administered thrombolytics or glycoprotein IIb/IIIa inhibitors (GPI) in comparison with aspiration thrombectomy (AT) as an adjunct to percutaneous coronary intervention (PCI) among patients presenting with ST-segment elevation myocardial infarction (STEMI).MethodsA comprehensive literature search for randomized trials that compared intracoronary-administered thrombolytics or GPI with AT in STEMI patients who underwent PCI, was conducted using various databases (e.g., MEDLINE, EMBASE, CENTRALE). Primary outcome was procedural measures (e.g., TIMI flow grade 3, TIMI myocardial perfusion grade (TMPG) 3, Myocardial blush grade (MBG) 2/3, ST-segment resolution (STR)).ResultsTwelve randomized trials enrolled 1,466 patients: 696 were randomized to intracoronary-administered pharmacological interventions and 553 to AT. Patients randomized to PCI alone were excluded. Thrombolytics significantly improved TIMI flow grade 3 (odds ratio = 3.71, 95% CI: 1.85–7.45), complete STR (odds ratio = 3.64, 95% CI: 1.60–8.26), and TMPG 3 (odds ratio = 5.31, 95% CI: 2.48–11.36). Thrombolytics significantly reduced major adverse cardiovascular events (MACE) (odds ratio = 0.29, 95% CI: 0.13–0.65) without increasing bleeding risk. Trial sequential analysis assessment confirmed the superiority of thrombolytics for the primary outcome. Intracoronary GPI, either alone or combined with AT, did not improve procedural or clinical outcomes.ConclusionsCompared with AT, intracoronary-administered thrombolytics significantly improved myocardial perfusion and MACE in STEMI patients.

COVID-19 and cancer: start the resolution!

Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an ongoing pandemic causing significant morbidity and mortality worldwide. The “cytokine storm” is a critical driving force in severe COVID-19 cases, leading to hyperinflammation, multi-system organ failure, and death. A paradigm shift is emerging in our understanding of the resolution of inflammation from a passive course to an active biochemical process driven by endogenous specialized pro-resolving mediators (SPMs), such as resolvins, protectins, lipoxins, and maresins. SPMs stimulate macrophage-mediated debris clearance and counter pro-inflammatory cytokine production, a process collectively termed as the “resolution of inflammation.” Hyperinflammation is not unique to COVID-19 and also occurs in neoplastic conditions, putting individuals with underlying health conditions such as cancer at elevated risk of severe SARS-CoV-2 infection. Despite approaches to block systemic inflammation, there are no current therapies designed to stimulate the resolution of inflammation in patients with COVID-19 or cancer. A non-immunosuppressive therapeutic approach that reduces the cytokine storm in patients with COVID-19 and cancer is urgently needed. SPMs are potent immunoresolvent and organ-protective lipid autacoids that stimulate the resolution of inflammation, facilitate clearance of infections, reduce thrombus burden, and promote a return to tissue homeostasis. Targeting endogenous lipid mediators, such as SPMs, offers an entirely novel approach to control SARS-CoV-2 infection and cancer by increasing the body’s natural reserve of pro-resolving mediators without overt toxicity or immunosuppression.

Mechanical Thrombectomy for Treatment of Cerebral Venous Sinus Thrombosis in Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Reports of a rare form of cerebral venous sinus thrombosis with profound thrombocytopenia have emerged following introduction of the adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccines. Between March and June 2021, seven cases of refractory vaccine-induced immune thrombotic thrombocytopenia were referred to our institution for mechanical thrombectomy. The condition of 1 patient deteriorated during interhospital transfer, and the remaining 6 underwent successful recanalization. No procedure-related adverse events were reported. At the time of this writing, 3 patients have been discharged with a good functional outcome (mRS 0-1), one required rehabilitation for mild dysarthria and vocal cord palsy (mRS 3), and 2 have died due to severe mass effect. Our anecdotal experience suggests that endovascular therapy may be safe and effective in reducing thrombus burden in selected cases of postvaccination cerebral venous sinus thrombosis.

Intralesional delivery of glycoprotein IIb/IIIa inhibitors in acute myocardial infarction: Review and recommendations.

Plaque rupture leads to a cascade of events culminating in collagen disruption, tissue factor release, platelet activation and thrombus formation. Pro-inflammatory conditions, hyperglycemia and smoking predispose to high thrombus burden (HTB) which is an independent predictor of slow or no-reflow. In patients with acute myocardial infarction (AMI), glycoprotein IIb/IIIa inhibitors (GPI) reduce thrombus burden and improve myocardial perfusion. These agents are typically administered systemically via the intravenous route or locally via an intracoronary (IC) route. However, as higher local concentrations of GPI are associated with enhanced platelet inhibition, intralesional (IL) GPI administration may be particularly effective in cases of HTB. Modest-sized randomized trials comparing IL and IC GPI delivery have reported conflicting outcomes. Some trials have demonstrated improved coronary flow and myocardial perfusion with reduced major adverse cardiac events with IL compared with IC GPI administration, whereas others have shown no significant benefits. Furthermore, although no direct comparison has been made between IL delivery using an aspiration catheter, microcatheter or a dedicated balloon-based "weeping" infusion-catheter, improved outcomes have been most consistent following GPI administration at the site of the lesion and thrombus with the dedicated infusion catheter. This review provides an update on the role and outcomes of IL GPI administration in patients with AMI and HTB. Based on the evidence we offer an algorithm demonstrating when to consider IL administration in patients with AMI undergoing intervention. We conclude with a perspective on the management of patients with STEMI and COVID-19 in whom a prothrombotic state often results in HTB.

Low Incidence of Ischemic Stroke Associated With Thrombus Aspiration in STEMI Patients Undergoing Primary PCI.

Thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) was recommended to minimize distal embolization and to reduce thrombus burden prior to PPCI. Subsequent randomized trials showed no mortality benefit from TA and suggested an increased risk of stroke up to 180 days following TA, although it was not obvious that the procedure alone caused the strokes. This study retrospectively analyzed the periprocedural stroke rate in a series of STEMI patients treated with TA and PPCI at a single, large, tertiary hospital, where a rigorous uniform protocol of aspiration was used in all patients. Of 3734 patients, 1404 patients (38%; group 1) underwent TA as part of the PPCI procedure and 2330 patients (62%; group 2) did not undergo TA. There were no significant clinical differences between the 2 groups. In total, there were 20 strokes (0.54%), with 3 (0.2%) occurring in group 1, and 17 (0.7%) occurring in group 2 (P=.04). The majority of strokes occurred within 5 days of the procedure, and 3 (0.08%) were hemorrhagic. There were 22 intraprocedural deaths (0.6%), related to cardiogenic shock. There were no intraprocedural strokes. Very low stroke rates immediately post STEMI were seen in patients undergoing TA and PPCI in this real-world study. TA can be performed safely in STEMI patients undergoing PPCI with a short-term stroke risk equivalent to risk without TA. Further studies may be needed to explain the increased incidence of late stroke noted after TA and elucidate causative mechanisms.

Time-Restricted Salutary Effects of Blood Flow Restoration on Venous Thrombosis and Vein Wall Injury in Mouse and Human Subjects.

Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality of life. Although catheter-based interventions enabling the restoration of blood flow (RBF) have demonstrated little benefit on postthrombotic syndrome, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. In experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution. First, experimental stasis DVT was generated in C57/BL6 mice (n=291) by inferior vena cava ligation. To promote RBF, mice underwent mechanical deligation with or without intravenous recombinant tissue plasminogen activator administered 2 days after deligation. RBF was assessed over time by ultrasonography and intravital microscopy. Resected thrombosed inferior vena cava specimens underwent thrombus and vein wall histological and gene expression assays. Next, in a clinical study, we conducted a post hoc analysis of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) pharmacomechanical catheter-directed thrombolysis (PCDT) trial (NCT00790335) to assess the effects of PCDT on Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores for specific symptom-onset-to-randomization timeframes. Mice that developed RBF by day 4, but not later, exhibited reduced day 8 thrombus burden parameters and reduced day 8 vein wall fibrosis and inflammation, compared with controls. In mice without RBF, recombinant tissue plasminogen activator administered at day 4, but not later, reduced day 8 thrombus burden and vein wall fibrosis. It is notable that, in mice already exhibiting RBF by day 4, recombinant tissue plasminogen activator administration did not further reduce thrombus burden or vein wall fibrosis. In the ATTRACT trial, patients receiving PCDT in an intermediate symptom-onset-to-randomization timeframe of 4 to 8 days demonstrated maximal benefits in Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores (between-group difference=8.41 and 1.68, respectively, P<0.001 versus patients not receiving PCDT). PCDT did not improve postthrombotic syndrome scores for patients having a symptom-onset-to-randomization time of <4 days or >8 days. Taken together, these data illustrate that, within a restricted therapeutic window, RBF improves DVT resolution, and PCDT may improve clinical outcomes. Further studies are warranted to examine the value of time-restricted RBF strategies to reduce postthrombotic syndrome in patients with DVT.

Large-Bore Aspiration Thrombectomy versus Catheter-Directed Thrombolysis for Acute Pulmonary Embolism: A Propensity Score–Matched Comparison

PurposeTo compare effectiveness and safety of large-bore aspiration thrombectomy (LBAT) with catheter-directed thrombolysis (CDT) for treatment of acute massive and submassive pulmonary embolism (PE). Materials and MethodsThis retrospective review included patients with acute PE treated with LBAT or CDT using tissue plasminogen activator (tPA) between December 2009 and May 2020. A propensity score based on Pulmonary Embolism Severity Index class and PE severity (massive vs submassive) was calculated, and 26 LBAT cases (age 60.2 y ± 17.1, 14/26 women) were matched with 26 CDT cases (age 59.7 y ± 14.2, 14/26 women). ResultsThe CDT group had 22.1 mg ± 8.1 tPA infused over 21.2 h ± 6.6. Both groups demonstrated similar initial and final systolic pulmonary artery pressure (PAP) (LBAT: 54.5 mm Hg ± 12.9 vs CDT: 54.5 mm Hg ± 16.3, P = .8, and LBAT: 42.5 mm Hg ± 14.1 vs CDT: 42.6 mm Hg ± 12.1, P = .8, respectively) and similar reductions in heart rate (LBAT: −5.4 beats/min ± 19.2 vs CDT: −9.6 beats/min ± 15.8, P = .4). CDT demonstrated a higher reduction in Miller score (−10.1 ± 3.9 vs −7.5 ± 3.8, P = .02). LBAT resulted in 1 minor hemorrhagic complication and 2 procedure-related mortalities, and CDT resulted in 1 minor and 1 major hemorrhagic complication. ConclusionsLBAT and CDT resulted in similar reductions of PAP and heart rate when used to treat acute PE. CDT reduced thrombus burden to a greater degree. Although hemorrhagic complications rates were not significantly different, the LBAT group demonstrated a higher rate of procedure-related mortality. Larger studies are needed to compare the safety of these techniques.

Thrombus Aspiration Plus Intracoronary Abciximab vs Intracoronary Abciximab Alone in Patients with STEMI Undergoing Primary PCI

Background: Thrombus embolization during the Percutaneous Coronary Intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI is bolus intracoronary Abciximab and manual aspiration thrombectomy. There are several factors which influence the decision of primary PCI in a patient with AMI in developing countries. Cost of therapy and affordability is probably the most important factor. The additional cost for thrombus aspiration needs to be considered against the additional advantages in terms of better clinical outcome. &#x0D; Objectives: To compare the use of a combination of intracoronary Abciximab with manual thrombus aspiration to intracoronary Abciximab alone, in patients with STEMI undergoing primary PCI.&#x0D; Patients and Methods: This is a prospective observational study of patients with STEMI who underwent primary PCI between June 2018 to May 2019. A pre-approved study protocol was designed to determine the eligibility of STEMI patients to be included in the study. Patients with The patients have analysed in two groups: 84 patients received a combination of intracoronary Abciximab with manual thrombus aspiration &amp; 80 patients received intracoronary Abciximab alone. &#x0D; The primary endpoint was the assessment of myocardial perfusion parameters namely Myocardial Blush Grade (MBG) in the culprit vessel &amp; ST-segment resolution of &gt;70% on ECG at 90 min after PCI. Secondary endpoints were the improvement in LV ejection fraction, cardiovascular mortality &amp; recurrent MI at one-month post-procedure.&#x0D; Results: Result of the 84 patients who received combination of intracoronary Abciximab with manual thrombus aspiration, the primary endpoints namely the myocardial blush grade (MBG) of 2/3 was achieved in 72 patients (90.74%) &amp; ST-segment resolution of &gt;70% at 90 min was seen in 66 patients (78.57%) (p&lt;0.001). Of the 80 patients who received only intracoronary Abciximab without thrombus aspiration, MBG 2/3 was achieved in 38 patients (47.5%) &amp; ST-segment resolution of &gt;70% at 90 min was seen in 28 patients (35%). At one month of follow up the secondary endpoints namely the LVEF in the combination group improved from 43.42±3.73 to 47.88±4.16% (p=0.12)and in the Abciximab group improved from 44.78±3.34 to 46.20±3.63%. Recurrent MI was seen in one patient in the combination group (p&lt;0.001) &amp; two patients in the ic Abciximab group. There was no cardiovascular mortality noted in the present study (p&lt;0.001).&#x0D; Conclusion: Intracoronary Abciximab + manual thrombus aspiration reduces thrombus burden with better results in microvascular perfusion assessed by ST-segment resolution of &gt;70% at 90 min &amp; higher Myocardial Blush Grade compared to intracoronary Abciximab alone in patients with STEMI undergoing primary PCI.

Feasibility and Safety of Low-Dose Intra-Coronary Tenecteplase During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction (ICE T-TIMI 49)

Following primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction, microvascular perfusion is often impaired secondary to thrombotic embolization. Intracoronary (IC) fibrinolytic administration may reduce thrombotic burden and distal embolization. The ICE-T-TIMI-49 study evaluated the feasibility and safety of low-dose IC tenecteplase (TNK) during PPCI. The study randomized 40 PPCI patients to a volume matched bolus of IC TNK (4mg) (n = 20) or IC saline placebo (n = 20) before and following PPCI. The primary end point was percent diameter stenosis of the culprit lesion following first bolus. The primary end point did not differ between IC placebo (median 100%, interquartile range [IQR] 83.0,100.0) and IC TNK (median 100% stenosis, IQR 91.0,100.0; p = 0.522). However, the proportion of patients with reduction in thrombus following first bolus tended to be greater with IC TNK (placebo: 12.5% vs IC TNK: 40.0%, p = 0.133). Following PPCI, the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC) was lower (faster) with placebo (16.0 frames [IQR 12.0,24.0] vs 24.0 frames [22.0,32.0], p = 0.045) due to a trend towards greater frequency of hyperemia (cTFC <14), a marker of distal embolization (50.0% vs 8.3%, p = 0.056). There was no difference in TIMI major bleeds and no intracranial hemorrhage. In conclusion, treatment with low-dose IC TNK appears safe and well tolerated during PPCI. Although IC TNK administration did not improve percent stenosis, a trend towards reduced thrombus burden was demonstrated with less hyperemia (a marker of distal embolization). Our findings provide support for a large randomized study.