1
Clinical events at two-year follow-up SES Endeavor p- value SES Resolute p- value (n51) (n46) (n103) (n104) Target lesion revascularization, n (%) 5 (9.8) 8 (17.4) 0.43 7 (6.8) 5 (4.8) 0.75 Target vessel failure, n (%)† 6 (11.8) 8 (17.4) 0.62 7 (6.8) 7 (6.7) 0.73 Composite of cardiac death and MI, n (%) 1 (2.0) 2 (4.3) 0.60 0 2 (1.9) 0.49 Definite or probable stent thrombosis, n (%) 1 (2.0) 2 (4.3) 0.60 0 1 (0.9) 1.00 According to the ARC criteria. †Composite of cardiac death, myocardial infarctions (MI) and target vessel revascularization. Conclusions: Our study data indicate that the worse performance of Endeavor ZES relative to SES in terms of late lumen loss, might translate in more clinical events. In contrast, SES and Resolute ZES both show excellent angiographic outcome resulting in comparable low clinical event rates after two years in patients treated for total coronary occlusions. TCT-441 Enhanced Endothelial Tubule Formation in Response to Proly-Hydroxylase Inhibitor FG-2216: A Step Towards Therapeutic Angiogenesis in Chronic Total Occlusions Georgina Barnett 1 , Benjamin Wrigley 2 , Damien Kelly 2 , Emily Flashman 3 , Christopher Schofield 3 , Anthony Gershlick 2 1 University of Leicester, Leicester, United Kingdom, 2 University Hospitals of Leicester, Leicester, United Kingdom, 3 University of Oxford, Oxford, United Kingdom Background: Enhancement of coronary antegrade collateral vessels represents a poten- tially novel therapeutic option for the treatment of chronic total occlusions (CTO). We have investigated two prolyl-hydroxylase inhibitors (PHI) for their ability to stimulate endothelial angiogenesis via upregulation of hypoxia inducible factor. We previously reported that di-methyl oxalylglycine (DMOG) increased collateral neovascularisation in a porcine CTO model. We now describe the actions of FG-2216, another PHI which unlike DMOG has been previously used in anaemic renal patients. Methods: Low passage (p3) human umbilical vein endothelial cells (HUVECs) were cultured on growth factor reduced Matrigel in the presence of FG-2216 at a range of doses (from 0 to 500M). Endothelial cell (EC) tubule formation was measured at 6 hours by image analysis of photomicrographs (image J). Results: Compared to control, ECs treated with FG-2216 demonstrated an enhanced tubule formation on Matrigel with the number of internal loops formed by branching tubules increasing with dose, up to 500M (20.56 (0M) versus 107.3 (500M), p0.05) (Figure). Conclusions: A proportion of CTOs cannot be revascularised by conventional means and therapeutic enhancement of the collateral circulation may offer a novel approach. We have demonstrated increased tubule formation in primary human ECs in response to FG-2216. This novel proof of concept study represents a significant step towards the development of therapeutic angiogenesis. We are collecting mechanistic data to confirm the action of FG-2216 and will test its use as a stent-based therapy in models of CTO. TCT-442 The Impact of High Residual Platelet Reactivity After Clopidogrel Loading on Cardiac Mortality in Patients Treated by Percutaneous Coronary Intervention for Chronic Total Occlusion Renato Valenti 1 , Rossella Marcucci 1 , Angela Migliorini 1 , Anna Maria Gori 1 , Nazario Carrabba 1 , Betti Giusti 1 , Giampaolo Cerisano 1 , Guido Parodi 1 , Rita Paniccia 1 , Rosanna Abbate 2 , David Antoniucci 3 1 Careggi Hospital, Florence, Italy, 2 Careggi Hospital, Florence , Italy, 3 Careggi Hospital, Florence, Italy Background: There is evidence that clopidogrel nonresponsivenss is a strong marker of poor outcome in patients with coronary artery disease treated invasively. No data exist about the impact of high residual platelet reactivity (HRPR) after 600 mg clopidogrel loading on long-term clinical outcome in patients undergoing drug-eluting stent (DES) implantation for chronic total occlusion (CTO). Methods: The Florence CTO-PCI registry include consecutive patients treated for at least 1 CTO by DES supported percutaneous coronary intervention (PCI). Patients had prospective platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel and using adenosine 5’-diphosphate (ADP) as agonist. HRPR was defined as aggregation by 10 mol/L ADP 70. Clopidogrel therapy 75 mg daily was recommended for at least 1 year. The end point of the study was long-term cardiac mortality. Cardiac survival was assessed by Kaplan-Meier estimation and independent predictors of cardiac mortality were evaluated by forward stepwise Cox regression analysis. Results: From 2005 to 2010, 713 consecutive patients underwent CTO PCI and had “in vitro” platelet reactivity assessment. A successful PCI was achieved in 569 patients (80%). The incidence of HRPR after clopidogrel loading was 18%. There were no significant differences in baseline characteristics between patients with HRPR and patients with low residual platelet reactivity (LRPR). Successful CTO-PCI rates were similar between groups (76% vs. 81%). The 2-year cardiac survival rate was 98 1% in the LRPR group and 79 7% in the HRPR group (p0.001). By multivariable analysis, HRPR resulted as a independent predictor of cardiac death (HR 3.0; p0.007); the others variables related to cardiac death were age (HR 1.1; p0.001), left ventricular ejection fraction 0.40 (HR 6.8; p0.001) and diabetes (HR 2.4; p0.033). Conclusions: HRPR after clopidogrel loading is a strong prognostic marker of increased risk of cardiac death in patients undergoing PCI for CTO. TCT-443 Predictors of Reocclusion After Successful Drug-Eluting Stent Supported Percutaneus Coronary Intervention for Chronic Total Occlusion Renato Valenti 1 , Ruben Vergara 1 , Angela Migliorini 1 , Nazario Carrabba 1 , Guido Parodi 1 , Giampaolo Cerisano 1 , Piergiovanni Buonamici 1 , David Antoniucci 1 1 Careggi Hospital, Florence, Italy Background: Large registries have shown a survival benefit in patients with successful chronic total occlusion (CTO)-PCI as compared to unsuccessful and/or unattempted CTO-PCI. Sustained vessel patency may be considered as a main variable related to long-term survival. Few data exist about the angiographic outcome of patients who performed CTO-PCI, due to lack or very low angiographic follow-up rate of CTO registries. The aim of this study was to assess the incidence of reocclusion and identifications of predictors of angiographic failure after successful CTO-PCI in the drug-eluting stent (DES) era. Methods: From the large prospective Florence CTO-PCI registry, since 2004 to 2010, 1005 patients underwent a PCI for CTO (3 months). The protocol treatment includes routine 6- to 9-month angiographic FU. Clinical, angiographic, and procedural variables were included into the model of multivariable binary logistic regression analysis for the identification of the predictors of reocclusion. Results: From January 2004 to December 2010 1,005 patients underwent a PCI attempt for at least 1 CTO (3 months). Out of these, 770 (77%) had a successful PCI. Baseline and procedural characteristics: mean age 68 11, male 84%, diabetes 24%, previous myocardial infarction 51%, LVEF0.40 37%, 3-vessel disease 50%, everolimus-eluting stent (EES) 36%, stent lenght 40 mm 54%, long subintimal tracking and very distal re-entry (STAR) 4%. STAR technique was used exclusively after failed intraluminal anterograde or retrograde attempt. The angiographic FU rate was 80% (578 patients). Reocclusion rate was 7.6%, while binary restenosis (50%) or reocclusion rate was 21%. EES, was associated with a significant lower re-occlusion rate than other DES (2.4% vs. 9.9%; p0.001). A successful STAR technique was associated with a 55% of rocclusion rate (p0.001). At multivariable analysis STAR technique (OR 32; p0.001) and EES (OR 0.19; p0.002) were independently related to the risk of reocclusion. Conclusions: Successful EES supported CTO-PCI is associated with a very high patency rate (97.6%). Successful STAR technique is associated with a very low mid-term patency rate whatever the type of stent used. TUESDAY, OCTOBER 23, 8:00 AM–10:00 AM www.jacc.tctabstracts2012.com JACC Vol 60/17/Suppl B | October 22–26, 2012 | TCT Abstracts/POSTER/Chronic Total Occlusions B127 POSTERS

TCT-441 Enhanced Endothelial Tubule Formation in Response to Proly-Hydroxylase Inhibitor FG-2216: A Step Towards Therapeutic Angiogenesis in Chronic Total Occlusions

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Page 1: TCT-441 Enhanced Endothelial Tubule Formation in Response to Proly-Hydroxylase Inhibitor FG-2216: A Step Towards Therapeutic Angiogenesis in Chronic Total Occlusions

Clinical events at two-year follow-up

SES Endeavorp-

value SES Resolutep-

value

(n�51) (n�46) (n�103) (n�104)

Target lesionrevascularization,n (%)

5 (9.8) 8 (17.4) 0.43 7 (6.8) 5 (4.8) 0.75

Target vesselfailure, n (%)†

6 (11.8) 8 (17.4) 0.62 7 (6.8) 7 (6.7) 0.73

Composite ofcardiac deathand MI, n (%)

1 (2.0) 2 (4.3) 0.60 0 2 (1.9) 0.49

Definite orprobable stentthrombosis,n (%)�

1 (2.0) 2 (4.3) 0.60 0 1 (0.9) 1.00

�According to the ARC criteria.†Composite of cardiac death, myocardial infarctions (MI) and target vesselrevascularization.

Conclusions: Our study data indicate that the worse performance of Endeavor ZESrelative to SES in terms of late lumen loss, might translate in more clinical events. Incontrast, SES and Resolute ZES both show excellent angiographic outcome resulting incomparable low clinical event rates after two years in patients treated for total coronaryocclusions.

TCT-441

Enhanced Endothelial Tubule Formation in Response to Proly-HydroxylaseInhibitor FG-2216: A Step Towards Therapeutic Angiogenesis in ChronicTotal Occlusions

Georgina Barnett1, Benjamin Wrigley2, Damien Kelly2, Emily Flashman3,Christopher Schofield3, Anthony Gershlick2

1University of Leicester, Leicester, United Kingdom, 2University Hospitals ofLeicester, Leicester, United Kingdom, 3University of Oxford, Oxford, UnitedKingdom

Background: Enhancement of coronary antegrade collateral vessels represents a poten-tially novel therapeutic option for the treatment of chronic total occlusions (CTO). Wehave investigated two prolyl-hydroxylase inhibitors (PHI) for their ability to stimulateendothelial angiogenesis via upregulation of hypoxia inducible factor. We previouslyreported that di-methyl oxalylglycine (DMOG) increased collateral neovascularisation ina porcine CTO model. We now describe the actions of FG-2216, another PHI whichunlike DMOG has been previously used in anaemic renal patients.Methods: Low passage (p3) human umbilical vein endothelial cells (HUVECs) werecultured on growth factor reduced Matrigel in the presence of FG-2216 at a range of doses(from 0 to 500�M). Endothelial cell (EC) tubule formation was measured at 6 hours byimage analysis of photomicrographs (image J).Results: Compared to control, ECs treated with FG-2216 demonstrated an enhancedtubule formation on Matrigel with the number of internal loops formed by branchingtubules increasing with dose, up to 500�M (20.56 (0�M) versus 107.3 (500�M), p�0.05)(Figure).

Conclusions: A proportion of CTOs cannot be revascularised by conventional means andtherapeutic enhancement of the collateral circulation may offer a novel approach. We havedemonstrated increased tubule formation in primary human ECs in response to FG-2216.This novel proof of concept study represents a significant step towards the developmentof therapeutic angiogenesis. We are collecting mechanistic data to confirm the action ofFG-2216 and will test its use as a stent-based therapy in models of CTO.

TCT-442

The Impact of High Residual Platelet Reactivity After Clopidogrel Loading onCardiac Mortality in Patients Treated by Percutaneous Coronary Interventionfor Chronic Total Occlusion

Renato Valenti1, Rossella Marcucci1, Angela Migliorini1, Anna Maria Gori1,Nazario Carrabba1, Betti Giusti1, Giampaolo Cerisano1, Guido Parodi1,Rita Paniccia1, Rosanna Abbate2, David Antoniucci31Careggi Hospital, Florence, Italy, 2Careggi Hospital, Florence , Italy, 3CareggiHospital, Florence, Italy

Background: There is evidence that clopidogrel nonresponsivenss is a strong marker ofpoor outcome in patients with coronary artery disease treated invasively. No data existabout the impact of high residual platelet reactivity (HRPR) after 600 mg clopidogrelloading on long-term clinical outcome in patients undergoing drug-eluting stent (DES)implantation for chronic total occlusion (CTO).Methods: The Florence CTO-PCI registry include consecutive patients treated for at least1 CTO by DES supported percutaneous coronary intervention (PCI). Patients hadprospective platelet reactivity assessment by light transmittance aggregometry after aloading dose of 600 mg of clopidogrel and using adenosine 5’-diphosphate (ADP) asagonist. HRPR was defined as aggregation by 10 �mol/L ADP � 70. Clopidogrel therapy75 mg daily was recommended for at least 1 year. The end point of the study waslong-term cardiac mortality. Cardiac survival was assessed by Kaplan-Meier estimationand independent predictors of cardiac mortality were evaluated by forward stepwise Coxregression analysis.Results: From 2005 to 2010, 713 consecutive patients underwent CTO PCI and had “invitro” platelet reactivity assessment. A successful PCI was achieved in 569 patients(80%). The incidence of HRPR after clopidogrel loading was 18%. There were nosignificant differences in baseline characteristics between patients with HRPR and patientswith low residual platelet reactivity (LRPR). Successful CTO-PCI rates were similarbetween groups (76% vs. 81%). The 2-year cardiac survival rate was 98 � 1% in theLRPR group and 79 � 7% in the HRPR group (p�0.001). By multivariable analysis,HRPR resulted as a independent predictor of cardiac death (HR 3.0; p�0.007); the othersvariables related to cardiac death were age (HR 1.1; p�0.001), left ventricular ejectionfraction � 0.40 (HR 6.8; p�0.001) and diabetes (HR 2.4; p�0.033).Conclusions: HRPR after clopidogrel loading is a strong prognostic marker of increasedrisk of cardiac death in patients undergoing PCI for CTO.

TCT-443

Predictors of Reocclusion After Successful Drug-Eluting Stent SupportedPercutaneus Coronary Intervention for Chronic Total Occlusion

Renato Valenti1, Ruben Vergara1, Angela Migliorini1, Nazario Carrabba1,Guido Parodi1, Giampaolo Cerisano1, Piergiovanni Buonamici1,David Antoniucci11Careggi Hospital, Florence, Italy

Background: Large registries have shown a survival benefit in patients with successfulchronic total occlusion (CTO)-PCI as compared to unsuccessful and/or unattemptedCTO-PCI. Sustained vessel patency may be considered as a main variable related tolong-term survival. Few data exist about the angiographic outcome of patients whoperformed CTO-PCI, due to lack or very low angiographic follow-up rate of CTOregistries. The aim of this study was to assess the incidence of reocclusion andidentifications of predictors of angiographic failure after successful CTO-PCI in thedrug-eluting stent (DES) era.Methods: From the large prospective Florence CTO-PCI registry, since 2004 to 2010,1005 patients underwent a PCI for CTO (�3 months). The protocol treatment includesroutine 6- to 9-month angiographic FU. Clinical, angiographic, and procedural variableswere included into the model of multivariable binary logistic regression analysis for theidentification of the predictors of reocclusion.Results: From January 2004 to December 2010 1,005 patients underwent a PCI attemptfor at least 1 CTO (�3 months). Out of these, 770 (77%) had a successful PCI. Baselineand procedural characteristics: mean age 68 � 11, male 84%, diabetes 24%, previousmyocardial infarction 51%, LVEF�0.40 37%, 3-vessel disease 50%, everolimus-elutingstent (EES) 36%, stent lenght �40 mm 54%, long subintimal tracking and very distalre-entry (STAR) 4%. STAR technique was used exclusively after failed intraluminalanterograde or retrograde attempt. The angiographic FU rate was 80% (578 patients).Reocclusion rate was 7.6%, while binary restenosis (�50%) or reocclusion rate was 21%.EES, was associated with a significant lower re-occlusion rate than other DES (2.4% vs.9.9%; p�0.001). A successful STAR technique was associated with a 55% of rocclusionrate (p�0.001). At multivariable analysis STAR technique (OR 32; p�0.001) and EES(OR 0.19; p�0.002) were independently related to the risk of reocclusion.Conclusions: Successful EES supported CTO-PCI is associated with a very high patencyrate (97.6%). Successful STAR technique is associated with a very low mid-term patencyrate whatever the type of stent used.

TUESDAY, OCTOBER 23, 8:00 AM–10:00 AMwww.jacc.tctabstracts2012.com

JACC Vol 60/17/Suppl B | October 22–26, 2012 | TCT Abstracts/POSTER/Chronic Total Occlusions B127

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