Nicola Corcione

Expression of exogenous tissue factor pathway inhibitor in vivo suppresses thrombus formation in injured rabbit carotid arteries

OBJECTIVESnThe aim of the present study was to test the hypothesis that retrovirus-mediated in vivo tissue factor pathway inhibitor (TFPI) gene transfer to the arterial wall would efficiently inhibit thrombosis without causing significant changes in systemic hemostatic variables.nnnBACKGROUNDnAcute coronary syndromes (unstable angina and acute myocardial infarction) are usually caused by atherosclerotic plaque rupture, with consequent activation of the coagulation cascade and circulating platelets. Tissue factor (TF) exposure represents an early event in this pathophysiologic sequence, leading to activation of the extrinsic coagulation pathway and thrombin formation. Tissue factor pathway inhibitor is a naturally occurring inhibitor of the extrinsic pathway.nnnMETHODSnIn the present study, the gene coding for rabbit TFPI was inserted in a retroviral vector under control of a tetracycline-inducible promoter. Replication-defective, infectious, recombinant retroviruses were used to transfect rabbit carotid arteries with either TFPI or a reporter gene--green fluorescent protein (GFP).nnnRESULTSnRetroviral-mediated arterial gene transfer of TFPI resulted in potent inhibition of intravascular thrombus formation in stenotic and injured rabbit carotid arteries, whereas transfection of the contralateral carotid artery with GFP had no effect on thrombosis. No significant changes in systemic hemostatic variables (prothrombin time and partial thromboplastin time) were observed when thrombosis was inhibited.nnnCONCLUSIONSnThese data suggest that retroviral-mediated transfection of the arterial wall with TFPI might represent an attractive approach for the treatment of thrombotic disorders.

Long‐lasting antithrombotic effects of a single dose of human recombinant, active site‐blocked factor VII: insights into possible mechanism(s) of action

Summary.u2002 Tissue factor (TF) is important in initiating intravascular thrombosis. We demonstrated that active‐site blocked factor VII (FVIIai) inhibits intravascular thrombosis for at least 6 h following a single injection, despite FVIIai plasma half‐life was ∼45u2003min. The aims of the present study were: (a) to determine the duration of the antithrombotic effects of a single injection of FVIIai; and (b) to assess whether FVIIai prolonged effects can be explained by a slow dissociation rate from TF in the arterial wall. Cyclic flow variations (CFVs), obtained in stenotic rabbit carotid arteries with endothelial injury, were abolished by either FVIIai (100u2003µgu2003kg−1u2003min−1 for 10u2003min) or hirudin (1u2003mgu2003kg−1). After CFVs were abolished, carotid blood flow velocity was recorded continuously for 24u2003h. CFVs restored in all hirudin‐treated animals after 2.1u2003±u20030.3u2003h, while they restored in only four of nine FVIIai‐treated rabbits in 10.1u2003±u20032.2u2003h. Five animals in this group did not show restoration of CFVs up to 24u2003h. Immunohistochemistry revealed that FVIIai was still bound to the arterial wall 24 h following its administration, despite at this time FVIIai plasma levels were undetectable. Prothrombin time and partial thromboplastin time did not change significantly. FVIIai exerts potent, long‐lasting antithrombotic effects without affecting systemic hemostatic parameters; a possible mechanism is a slow dissociation rate of FVIIai from TF. These proprieties make FVIIai particularly attractive as an antithrombotic intervention.

Endovascular Therapy for Infrainguinal Artery Disease With Coronary Devices A Retrospective Observational Study Comparing Drug-Eluting Stents Versus Bioresorbable Vascular Scaffolds

Several devices are available for infrainguinal endovascular therapy, with drug-eluting stents (DES) among the most promising. Bioresorbable vascular scaffolds (BVS) may further improve outcomes. We have liberally used in our practice coronary DES and BVS for infrainguinal endovascular therapy and hereby report our preliminary results. We conducted an observational study by retrospectively identifying characteristics of patients undergoing infrainguinal implantation of coronary DES or BVS. We compared the risk of major adverse events (MAE: death, amputation, or target vessel revascularization [TVR]) and components of MAE in the overall sample and after propensity matching. We included a total of 204 patients (207 limbs), 148 (72.5%) treated with DES and 56 (27.5%) with BVS. Bivariate analysis showed that TVR was less common in the DES group (41.9% vs 18.4%, P = .014). However, propensity-matched analysis showed nearly identical risks of MAE, amputation, TVR, or symptom burden with DES and BVS (all P > .05). In conclusion, the present pilot experience with coronary BVS suggests that they could provide acceptable results for infrainguinal endovascular procedures, comparable to those obtained by their metallic counterpart.

Tirofiban Positively Regulates β1 Integrin and Favours Endothelial Cell Growth on Polylactic Acid Biopolymer Vascular Scaffold (BVS)

An unexpectedly high incidence of thrombosis in patients that received the polylactic acid bioresorbable vascular scaffold (BVS) suggests a delayed/incomplete endothelial repair with this stent. The anti-platelet agent tirofiban stimulates endothelial cell migration and proliferation, mediated by VEGF production. We investigated the tirofiban effect on the migration and adhesion of endothelial cells to BVS, in vitro. We performed human umbilical endothelial cell (HUVEC) cultures in the presence of BVS. Tirofiban, similarly to VEGF, increased the ability of HUVEC to grow on the vascular scaffold, compared to unstimulated or abciximab-treated cells. Tirofiban increased HUVEC expression of β1 and β3 integrins along with collagen and fibronectin. A role for β1 integrin in the “pro-adhesive and -migratory” signals elicited by tirofiban was suggested by use of an anti-β1-blocking antibody that prevented poly-levo-lactic acid vascular scaffold colonization. Our study suggests that tirofiban may improve the outcomes of patients receiving BVS by accelerating stent endothelization.

Impact of sex on the early and long-term outlook of patients undergoing carotid artery stenting with a single embolic protection device-stent combo

Aims: Whether men and women benefit similarly from carotid artery stenting (CAS) remains uncertain. We hypothesized that CAS, especially when performed with the same combination of embolic protection device (EPD) and stent, may have a different risk-benefit profile in men and women. Methods: We retrospectively collected data on all patients undergoing CAS with the Angioguard EPD and Precise RX stent. A total of 447 patients were included, 285 (64%) men and 162 (36%) women. Results: Despite several baseline, lesion and procedural differences, procedural success and clinical outcomes were similar (all p > 0.05), at both discharge and longterm follow-up (19±21 months). Specifically, the composite of death, myocardial infarction, stroke or transient ischemic attack occurred in 5 (2%) men and 2 (1%) women at discharge, and 32 Arturo Giordano1, Paolo Ferraro1, Nicola Corcione1, Michele Polimeno1, Stefano Messina1, Gabriele Giordano1, Rosario Mancusi1, Raffaella Avellino1, Giacomo Frati2, Giuseppe Biondi-Zoccai2 Affiliations: 1Unità Operativa di Interventistica Cardiovascolare, Presidio Ospedaliero Pineta Grande, Castel Volturno, and Unità Operativa di Emodinamica, Casa di Salute Santa Lucia, San Giuseppe Vesuviano Italy; 2Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. Corresponding Author: Dr. Giuseppe Biondi-Zoccai, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy; Email: giuseppe.biondizoccai@uniroma1.it Received: 29 September 2015 Accepted: 28 November 2015 Published: 11 December 2015 PEER REVIEWED | OPEN A CE S (11%) men and 12 (7%) women at follow-up (both p > 0.05). Even after propensity score matching, no significant differences were found (all p > 0.05). Conclusion: In conclusion, despite several baseline disparities, there are no differences in the early and long-term incidence of adverse events in men versus women undergoing CAS.

Chronic Total Occlusion of the Innominate Trunk: Successful Recanalization with Retrograde Technique and Dedicated Devices Borrowed from Percutaneous Coronary Interventions

The innominate trunk is a short vessel with crucial clinical relevance as in most patients it provides flow to the right subclavian artery and the right common carotid artery. Innominate trunk occlusions are particularly challenging, as results of endovascular therapy are suboptimal in terms of acute success, whereas open surgery poses a high risk of complications. The systematic application of techniques and devices developed for coronary occlusions holds the promise of substantially improving the management of subjects with peripheral artery disease. We hereby present a case of a patient with innominate trunk occlusion who underwent successful percutaneous revascularization by carefully and expertly exploiting techniques and devices well tested in the coronary realm. This clinical vignette suggests that this treatment approach may be feasible and risk-beneficial for otherwise challenging innominate trunk occlusions.