Carlos A. Gongora

Clinical ResearchTranslationalImpact of Paclitaxel Dose on Tissue Pharmacokinetics and Vascular Healing: A Comparative Drug-Coated Balloon Study in the Familial Hypercholesterolemic Swine Model of Superficial Femoral In-Stent Restenosis

OBJECTIVES This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 μg/mm(2), Lutonix = 2 μg/mm(2) and Ranger = 2 μg/mm(2)) in the experimental setting. BACKGROUND The optimal therapeutic dose for PCB use has not been determined yet. METHODS Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment. RESULTS All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2) PCB groups. CONCLUSIONS Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated.

Biological effect of orbital atherectomy and adjunctive paclitaxel-coated balloon therapy on vascular healing and drug retention: early experimental insights into the familial hypercholesterolaemic swine model of femoral artery stenosis

AIMS The efficacy of paclitaxel-coated balloons (PCB) for the treatment of superficial femoral artery (SFA) disease has been demonstrated in the clinical setting. Due to the high frequency of arterial calcification found in this vascular territory, the adjunctive use of atherectomy plus PCB has been proposed. In this study, we aimed to evaluate the biological effect on vascular healing and drug retention of this combination approach in the familial hypercholesterolaemic swine (FHS) model of femoral artery stenosis. METHODS AND RESULTS Eleven femoral arteries (six superficial and five profunda arteries) were included. Vessels were injured (x2) over a 28-day period and all animals were maintained on a high cholesterol diet for 60 days following initial injury. Vessels were randomised to PCB (n=5) or orbital atherectomy system (OAS) plus PCB (n=6). At 28 days following therapy, vessels were followed with angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Vessels were harvested for histological and pharmacokinetic analysis. Angiographic findings were comparable at termination between both groups. The OCT findings were comparable at termination. There were no differences in the vascular healing profile between both groups. The paclitaxel levels at termination were comparable between both groups (PCB=5.16 vs. OAS+PCB=3.03 ng/mg). CONCLUSIONS In the experimental setting, the combination of OAS+PCB appears to be safe by demonstrating a vascular healing profile and drug tissue levels comparable to PCB only. The vascular effect of PCB may be enhanced by the use of OAS by decreasing plaque burden and cholesterol crystals.

Four-year polymer biocompatibility and vascular healing profile of a novel ultrahigh molecular weight amorphous PLLA bioresorbable vascular scaffold: an OCT study in healthy porcine coronary arteries

AIMS The vascular healing profile of polymers used in bioresorbable vascular scaffolds (BRS) has not been fully characterised in the absence of antiproliferative drugs. In this study, we aimed to compare the polymer biocompatibility profile and vascular healing response of a novel ultrahigh molecular weight amorphous PLLA BRS (FORTITUDE®; Amaranth Medical, Mountain View, CA, USA) against bare metal stent (BMS) controls in porcine coronary arteries. METHODS AND RESULTS Following device implantation, optical coherence tomography (OCT) evaluation was performed at 0 and 28 days, and at one, two, three and four years. A second group of animals underwent histomorphometric evaluation at 28 and 90 days. At four years, both lumen (BRS 13.19±1.50 mm2 vs. BMS 7.69±2.41 mm2) and scaffold areas (BRS 15.62±1.95 mm2 vs. BMS 8.65±2.37 mm2) were significantly greater for BRS than BMS controls. The degree of neointimal proliferation was comparable between groups. Histology up to 90 days showed comparable healing and inflammation profiles for both devices. CONCLUSIONS At four years, the novel PLLA BRS elicited a vascular healing response comparable to BMS in healthy pigs. Expansive vascular remodelling was evident only in the BRS group, a biological phenomenon that appears to be independent of the presence of antiproliferative drugs.

ADJUSTED ODDS OF INPATIENT MORTALITY FOR NON-ST ELEVATION MYOCARDIAL INFARCTION IS NOT AFFECTED BY DAY OF ADMISSION: A NATIONWIDE ANALYSIS

Background: Day and month of admission has been shown to be an important predictor in other cardiac related admissions. We aim to show the impact of admission day in patients hospitalized for non-ST elevation myocardial infarction (NSTEMI) in the United States. Methods: This was a retrospective

PATIENTS WITH NON ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UTILIZING MEDICARE/MEDICAID HAVE LOWER ADJUSTED ODDS OF IN-HOSPITAL MORTALITY: A NATIONWIDE ANALYSIS

Background: There have been no studies looking at the type of insurance utilized by patients in Non-ST-segment Elevation Myocardial infarction (NSTEMI). The aim of this study was to look at insurance as an independent risk factor in outcome of NSTEMI patients. Methods: This was a retrospective

COMPARISON OF OUTCOMES AFTER INTRAVASCULAR ULTRASOUND-GUIDED VERSUS ANGIOGRAPHY-GUIDED DRUG-ELUTING STENT IMPLANTATION IN COMPLEX LESIONS CORONARY INTERVENTIONS: A META-ANALYSIS OF 1522 PATIENTS FROM RANDOMIZED TRIALS

There are conflicting data regarding the benefit of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) over angiography-guided PCI in complex coronary interventions. Electronic databases were searched to identify all relevant trials published through October, 2015. We

TCT-607 Atherosclerotic Swine Model Reveals Favorable Impact of Abluminal Bioresorbable Polymer on the Time Course of Para-Strut Inflammation in Comparison to BMS and Durable Polymer DES

TARGET I RCT (n1⁄4227), TARGET I long stent cohort (n1⁄450), and TARGET II registry (n1⁄4730) was prospectively collected and analyzed in 1007 patients with de novo native coronary lesions. All patients were exclusively treated with FIREHAWK stent and the follow-up visits are at 1-, 6-, 12-month, and annually up to 5 years. Results: 992 (98.5%) patients completed 2-year clinical follow-up. Between 1 and 2 years, 62% of patients discontinued DAPT and there were only 7 newly occurred TLF events including 3 cardiac death, 1 TV-MI and 3 iTLR (table). Importantly, no definite/probable stent thrombosis (ST) was observed in this cohort 5 days after implantation of FIREHAWK stents. Lesion length >1⁄430mm was an independent predictor of TLF at 2 years (HR [95%CI]: 2.44 [1.32, 4.53], p< 0.01).

TCT-85 Factors Influencing Stent Recoil and Underexpansion In Vivo Independent of Atherosclerosis: A Multimodality Imaging Study in Normal Porcine Coronary Arteries

Stent underexpansion and malapposition continue to be important factors in suboptimal outcomes of stent treatment of obstructive coronary disease. It is well established that stents rarely achieve intended post-implant diameters that would be expected from the maximum applied pressure and the stent

TCT-288 First in Vivo Evaluation of Efficacy of a Novel Peripheral Drug-Coated Balloon in a Familial Hypercholesterolemic Swine Model of In-Stent Restenosis

Drug coated balloons (DCBs) employ different coating technologies to deliver the antirestenotic drug without permanent polymer carrier. The ideal formulation should maximize the neointimal inhibition with the least drug possible, while ensuring adequate healing and containing the particulate release

BIOCOMPATIBILITY OF A NOVEL NON-DRUG ELUTING BIOABSORBABLE STENT IN PORCINE CORONARY ARTERIES: AN OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY STUDY

Bioabsorbable arterial stents (BAS) are emerging as a new paradigm for treatment of coronary disease by promoting vascular restoration rather than just alleviating the obstruction but caging the vessel segment with a metal stent. We aimed to evaluate mechanical integrity and biocompatibility of a