Skirball Center for Cardiovascular Research

Orangeburg, NY, United States

Skirball Center for Cardiovascular Research

Orangeburg, NY, United States
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Hsu P.-F.,Taipei Veterans General Hospital | Hsu P.-F.,National Yang Ming University | Sung S.-H.,National Yang Ming University | Sung S.-H.,Taipei Veterans General Hospital | And 10 more authors.
Diabetes Care | Year: 2013

OBJECTIVE-Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown. RESEARCH DESIGN AND METHODS-The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998-2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization. RESULTS-Therewere 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients)among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63- 2.67]), all-cause hospitalization (2.51 [2.00-3.16]), and total mortality (2.48 [1.41-4.38]). CONCLUSIONS-Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes. © 2013 by the American Diabetes Association.


Nakazawa G.,CVPath Institute Inc. | Granada J.F.,Skirball Center for Cardiovascular Research | Alviar C.L.,Skirball Center for Cardiovascular Research | Tellez A.,Skirball Center for Cardiovascular Research | And 7 more authors.
JACC: Cardiovascular Interventions | Year: 2010

Objectives: In this study, we hypothesized that an antihuman-CD34 antibody immobilized on the surface of commercially available sirolimus-eluting stents (SES) could enhance re-endothelialization compared with SES alone. Background: Previous experience with antihuman-CD34 antibody surface modified Genous stents (GS) (OrbusNeich Medical, Fort Lauderdale, Florida) has shown enhanced stent endothelialization in vivo. Methods: In the phase 1 study, stents were deployed in 21 pig coronary arteries for single stenting (9 vessels: 3 GS, 3 SES, and 3 bare-metal stents) and overlapping stenting with various combinations (12 vessels: 4 GS+GS, 4 SES+SES, and 4 GS+SES) and harvested at 14 days for scanning electron and confocal microscopy. In phase 2, immobilized anti-CD34 antibody coating was applied on commercially available SES (SES-anti-CD34, n = 7) and compared with GS (n = 8) and SES (n = 7) and examined at 3 and 14 days by scanning electron/confocal microscopy analysis. Results: In phase 1, single stent implantation showed greatest endothelialization in GS (99%) and in bare-metal stent (99%) compared with SES (55%, p = 0.048). In overlapping stents, endothelialization at the overlapping zone was significantly greater in GS+GS (95 ± 6%) and GS+SES (79 ± 5%) compared with the SES+SES (36 ± 14%) group (p = 0.007). In phase 2, SES-anti-CD34 resulted in increased endothelialization compared with SES alone at 3 days (SES-anti-CD34 36 ± 26%; SES 7 ± 3%; and GS 76 ± 8%; p = 0.01), and 14 days (SES-anti-CD34 82 ± 8%; SES 53 ± 20%; and GS 98 ± 2%; p = 0.009). Conclusions: Immobilization of anti-CD34 antibody on SES enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents. © 2010 American College of Cardiology Foundation.


Eppihimer M.J.,Boston Scientific Corporation | Sushkova N.,Boston Scientific Corporation | Grimsby J.L.,Boston Scientific Corporation | Efimova N.,Boston Scientific Corporation | And 7 more authors.
Circulation: Cardiovascular Interventions | Year: 2013

Background-Emerging drug-eluting stent technologies are evolving toward the elimination of polymeric component used as the method for modulating drug delivery. Although this technological approach seems to be biologically appealing, the impact of durable polymers and metallic stent surfaces on vascular healing remains unclear. In the present study, we aimed to compare the independent effect of a durable polymer and a metallic stent surface on thrombogenicity and endothelial cell coverage using different in vitro and in vivo experimental models. Methods and Results-Platinum chromium (PtCr) and polyvinylidene fluoride-co-hexafluoropropene (PVDF-HFP)-coated surfaces were evaluated in this study. Thrombogenicity was assessed by exposing all surfaces to human blood under shear flow conditions. The inflammatory potential of the material was evaluated by measuring cytokine release from THP-1 cells exposed to all surfaces for 24 hours. Endothelial cell coverage was evaluated by detection of CD31 after the stents were exposed to human coronary artery endothelial cells for =14 days. Platelet adhesion (P<0.01) and activation (P=0.03) on PVDF-HFP were greater than on PtCr. In vivo, PVDF-HFP revealed more neointimal area (P<0.01) and residual parastrut fibrin (P=0.01) at 30 days compared with PtCr. PtCr displayed higher endothelialization rates and higher vascular endothelial-cadherin expression at 7 and 14 days (P=0.02) compared with PVDF-HFP. Conclusions-Thrombogenicity and vascular healing differ among metallic and polymeric stent surfaces. PVDF-HFP exhibits higher degrees of platelet activation-adhesion and thrombus accumulation in vivo compared with PtCr. PtCr displayed higher degrees of endothelial surface coverage compared with PVDF-HFP surfaces. © 2013 American Heart Association, Inc.


Granada J.F.,Skirball Center for Cardiovascular Research | Milewski K.,Skirball Center for Cardiovascular Research | Zhao H.,Abbott Laboratories | Stankus J.J.,Abbott Laboratories | And 7 more authors.
Circulation: Cardiovascular Interventions | Year: 2011

Background-Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine. Methods and Results-A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm 2) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm 2, n=16), low-dose (300 μg/cm 2, n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups. Conclusions-The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine. © 2011 American Heart Association, Inc.


Cheng Y.,Skirball Center for Cardiovascular Research | Aboodi M.S.,Skirball Center for Cardiovascular Research | Annest L.S.,BioVentrix | Wechsler A.S.,Drexel University | And 3 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2014

Objective The loss of normal apical rotation is associated with left ventricular (LV) remodeling and systolic dysfunction in patients with congestive heart failure after myocardial infarction. The objective of the present study was to evaluate the effect of epicardial ventricular reconstruction, an off-pump, less-invasive surgical reshaping technique, on myocardial strain, LV twist, and the potential alteration of myocardial fiber orientation in an ovine model of LV anteroapical aneurysm. Methods LV anteroapical myocardial infarction was induced by coil embolization of the left anterior descending artery. Eight weeks after occlusion, epicardial ventricular reconstruction was performed using left thoracotomy under fluoroscopic guidance in 8 sheep to completely exclude the scar. The peak systolic longitudinal/circumferential strains and LV twist were evaluated using speckle tracking echocardiography before (baseline), after device implantation, and at 6 weeks of follow-up. Results Epicardial ventricular reconstruction was completed in all sheep without any complications. Immediately after device implantation, LV twist significantly increased (4.18 ± 1.40 vs baseline 1.97 ± 1.92; P =.02). The ejection fraction had increased 17% and LV end-systolic volume had decreased 40%. The global longitudinal strain increased from -5.3% to -9.1% (P <.05). Circumferential strain increased in both middle and apical LV segments, with the greatest improvement in the inferior lateral wall (from -11.4% to -20.6%, P <.001). These effects were maintained ≤6 weeks after device implantation without redilation. Conclusions Less invasive than alternative therapies, epicardial ventricular reconstruction on the off-pump beating heart can restore LV twist and systolic strain and reverse LV remodeling in an ovine anteroapical aneurysm model. © 2014 by The American Association for Thoracic Surgery.


Murata A.,Skirball Center for Cardiovascular Research | Wallace-Bradley D.,Skirball Center for Cardiovascular Research | Tellez A.,Skirball Center for Cardiovascular Research | Alviar C.,Skirball Center for Cardiovascular Research | And 9 more authors.
JACC: Cardiovascular Imaging | Year: 2010

Objectives: This study aimed to evaluate the accuracy of optical coherence tomography (OCT) in analyzing the neointimal response to several drug-eluting stent (DES) types by comparing OCT images acquired in vivo with corresponding histological specimens using a nondiseased porcine injury model. Background: Optical coherence tomography is emerging as a promising endovascular imaging tool for the evaluation of neointimal response after DES implantation. Methods: A total of 84 stents were implanted-22 ML Vision (Abbott Vascular, Santa Clara, California), 22 Xience V (Abbott Vascular), 20 Endeavor (Medtronic, Minneapolis, Minnesota), and 20 Taxus Liberté (Boston Scientific, Natick, Massachusetts) stents-in normal porcine coronary arteries and were harvested at 28 (n = 42) and 90 (n = 42) days, with the different stent types equally distributed between the 2 follow-up periods. At termination, morphometric evaluation using OCT imaging was performed in all stented arteries. Histological morphometric analysis was performed and correlated with OCT. Results: A total of 622 OCT-histology matched frames acquired from all stent designs were analyzed. The luminal (13.7%) and stent (6.1%) areas were consistently larger by OCT compared with histology. The mean neointimal thickness was very similar between techniques (∼3.27% variation). There was a high correlation between OCT and histology for the evaluation of neointimal area (R2 = 0.804), luminal area (R2 = 0.825), and neointimal thickness (R2 = 0.789). Correlation for total stent area was poor (R2 = 0.352). Although the proportion of individual struts determined to be uncovered by OCT and histology was similar, there was significant variation in the estimation of strut coverage between OCT and histology when the neointimal thickness was between 20 and 80 μm. This variation converged for neointimal thicknesses between 80 and 100 μm. Conclusions: Subtle differences in neointimal formation induced by current DES can be reproducibly analyzed in vivo by OCT. However, OCT measurement of stent area seems to have less correlation with histology. © 2010 American College of Cardiology Foundation.


Kim J.-S.,Skirball Center for Cardiovascular Research | Kim J.-S.,Yonsei University | Afari M.E.,Skirball Center for Cardiovascular Research | Ha J.,Yonsei University | And 7 more authors.
European Heart Journal Cardiovascular Imaging | Year: 2014

AimsAlthough optical coherence tomography (OCT) is capable to detect microscopic peri-strut changes that seem to be related to neointimal inhibition and healing, its ability to characterize these components is still limited. In this study, we aimed to compare different OCT morphological characteristics with different in-stent neointimal tissue types analysed by histology.MethodsA total of 69 stents (39 drug eluting and 30 bare metal stents) were implanted in coronary arteries of 27 swine. By OCT, neointimal type was classified as homogeneous, heterogeneous, or layered according to its pattern of backscatter and optical intensity. The resulting optical patterns were correlated with several histological findings [external elastic lamina (EEL) disruption, fibrin deposition, circumferential rim of peri-strut inflammatory cell infiltration, and fibrous connective deposition] in every single cross-section (CS) analysed.ResultsA total of 197 matched OCT and histological CS were analysed. The heterogeneous (0.44 ± 0.21 mm) and layered (0.65 ± 0.16 mm) patterns had a significantly higher degree of neointimal thickness compared with the homogeneous pattern (0.25 ± 0.16 mm, P < 0.001). Fibrous connective tissue deposition was more frequently present in the homogeneous pattern (71.6%, P < 0.001), whereas significant fibrin deposits were more commonly seen in the heterogeneous pattern (56.9%, P = 0.007). Peri-strut inflammation was less frequently found in the homogeneous pattern (19.8%, P < 0.001) in comparison with the layered (73.9%) or heterogeneous patterns (43.1%). The presence of EEL rupture was also more commonly seen in layered (73.9%) and heterogeneous (46.6%) patterns than in the homogeneous pattern (22.4%, P < 0.001).ConclusionThe optical characteristics of neointimal formation seen in OCT properly correlated with the presence of several histological findings involved in stent healing. The biological implications of these findings in clinical outcomes require further investigation. © The Author 2013.


Buszman P.P.,Skirball Center for Cardiovascular Research | Tellez A.,Skirball Center for Cardiovascular Research | Afari M.E.,Skirball Center for Cardiovascular Research | Peppas A.,Skirball Center for Cardiovascular Research | And 6 more authors.
JACC: Cardiovascular Interventions | Year: 2013

Objectives This study sought to evaluate vascular drug uptake, distribution and response of second-generation paclitaxel coated balloon (PCB) (Cotavance, MEDRAD Interventional, Indianola, Pennsylvania) and compare it with first-generation technology, containing identical excipient and drug concentration. Background Original PCB technologies displayed a heterogeneous deposition of crystalline paclitaxel-iopromide inside the balloon folds, whereas second-generation PCBs consisted of more homogeneous, circumferential coatings. Methods Paclitaxel tissue uptake was assessed in 20 iliofemoral arteries of a domestic swine. Vascular healing response was assessed in the familial hypercholesterolemic model of iliofemoral in-stent restenosis. Three weeks after bare-metal stent implantation, vascular segments were randomly revascularized with first-generation PCBs (n = 6), second-generation PCBs (n = 6), or plain balloon angioplasty (PBA) (n = 6). At 28 days, angiographic and histological evaluation was performed in all treated segments. Results One-hour paclitaxel tissue uptake was 42% higher in the second-generation PCBs (p = 0.03) and resulted in more homogeneous segment-to-segment distribution compared with first-generation PCBs. Both angiography (percentage of diameter stenosis: second-generation 11.5 ± 11% vs. first-generation 21.9 ± 11% vs. PBA 46.5 ± 10%; p < 0.01) and histology (percentage of area stenosis: second-generation 50.5 ± 7% vs. first-generation 54.8 ± 18% vs. PBA 78.2 ± 9%; p < 0.01) showed a decrease in neointimal proliferation in both PCB groups. Histological variance of the percentage of area stenosis was lower in second-generation compared with first-generation PCBs (51.7 vs. 328.3; p = 0.05). The presence of peristrut fibrin deposits (0.5 vs. 2.4; p < 0.01) and medial smooth muscle cell loss (0 vs. 1.7; p < 0.01) were lower in the second-generation compared with first-generation PCBs. Conclusions In the experimental setting, second-generation PCB showed a comparable efficacy profile and more favorable vascular healing response when compared to first-generation PCB. The clinical implications of these findings require further investigation. © 2013 by the American College of Cardiology Foundation.


Granada J.F.,Skirball Center for Cardiovascular Research | Granada J.F.,Corbic Medical Center | Delgado J.A.,Corbic Research Institute | Uribe M.P.,Corbic Research Institute | And 4 more authors.
JACC: Cardiovascular Interventions | Year: 2011

Objectives: We aimed to evaluate the safety and feasibility of a robotic angioplasty system in delivery and manipulation of coronary guidewires, balloons, and stents in patients undergoing elective percutaneous coronary intervention (PCI). Background: A remote-control, robotic-assisted angioplasty system is under development to address some of the procedural challenges and occupational hazards associated with traditional PCI. Methods: Patients with coronary artery disease and clinical indication for elective PCI were enrolled. The coronary angioplasty procedure was performed with the CorPath 200 robotic system (Corindus, Inc., Natick, Massachusetts). The system consists of a remote interventional cockpit and a multicomponent bedside unit that enables the operator to advance, retract, and rotate guidewires and rapid exchange catheters. The primary endpoint was device clinical success (≤30% residual stenosis) without in-hospital major adverse cardiac events. Technical success was defined as the ability of the system to complete all the planned angioplasty steps on the basis of procedural segments. Patients were followed up to 30 days after angioplasty procedure. Results: A total of 8 patients were enrolled in the study. The primary endpoint was achieved in all patients (100%). The technical success of the robotic system was 97.9% in completing 47 of 48 planned steps. There were no device- or procedure-related complications and no in-hospital or 30-day major adverse cardiac events. The operators rated the robotic system performances as equal to or better than manual procedures in 97.5% of the cases. The operator radiation exposure was 97% lower than the levels found at the standard table position. Conclusions: Early clinical experience with a robotic-assisted angioplasty system demonstrated feasibility, safety, and procedural effectiveness comparable to manual operation. In addition, the total operator exposure to radiation was significantly low. A larger study is warranted to verify the safety and effectiveness of robotic-assisted percutaneous coronary intervention. © 2011 American College of Cardiology Foundation.


Granada J.F.,Skirball Center for Cardiovascular Research | Buszman P.P.,Skirball Center for Cardiovascular Research
Current Cardiology Reports | Year: 2012

The treatment of severe hypertension by the surgical obliteration of the renal sympathetic nerves was proposed almost 80 years ago. This approach, although highly effective in reducing blood pressure was associated with a significant amount of side effects and it was rapidly replaced by better tolerated medical therapy. The rapid progress in catheter based technologies occurring within the last 20 years facilitated the development of the first radio frequency renal artery denervation catheter. At the present time, several small trials have demonstrated the safety and efficacy of this approach among patients with refractory hypertension. Besides its effect on reducing blood pressure, other pleiotropic effects (ie, improving glycemia in diabetic patients) have been proposed. In this review, we discuss the anatomical and physiological rationale for this therapy, provide an update on the latest clinical data available and describe additional emerging technologies in this field. © 2012 Springer Science+Business Media, LLC.

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