Time course of vascular response after an a priori strategy of bare metal stent implantation post-dilated with a paclitaxel-coated balloon: Implementation of a three-dimensional analysis algorithm with optical coherence tomography.

BACKGROUND: An a priori combined therapy of a bare metal stent post-dilated with a paclitaxel- -coated balloon (PCB) was investigated with optical coherence tomography (OCT) at 2 and 6 months regarding vessel response. Previous studies have shown inconsistent results and the time course of vessel healing after such an interventional strategy is unknown. METHODS: Thirty-three de novo lesions in 32 patients were electively treated. Six-month OCT analysis was available in 24 lesions. Two-month OCT follow-up was obtained in 16 lesions. Sequential OCT at 2 and 6 months was available in 7 patients. A novel 3-dimensional picture of vessel segments as spread outs was implemented. RESULTS: Severe incomplete stent apposition (ISA) accompanied by significantly lower strut coverage were found at 2-month compared with 6-month follow-up (ISA struts: 11.4 ± 11.8% vs. 1.8 ± 4.8%, p = 0.001; uncovered struts: 14.5 ± 14.8% vs. 2.0 ± 5.3%, p = 0.001). ISA size diminished over time and the possibly observed phenomenon of positive vessel remodeling (remodeling volume: 4.9 ± 5.9 mm3 at 2-months vs. 2.0 ± 2.6 mm3 at 6-months; p = 0.042) was largely reversible in most lesions. CONCLUSIONS: Bare metal stenting with adjunctive application of paclitaxel by a coated bal-loon shows transient severe incomplete strut apposition, most likely due to focal positive ves-sel remodeling. Thus, caution is needed in bailout situations following a PCB angioplasty. A novel illustration of OCT parameters as "carpet views" enables a comprehensive analysis of investigated stents.

Stent coverage and neointimal proliferation in bare metal stents postdilated with a Paclitaxel-eluting balloon versus everolimus-eluting stents: prospective randomized study using optical coherence tomography at 6-month follow-up.

BACKGROUND: In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up. METHODS AND RESULTS: A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found. CONCLUSIONS: Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01056744.

Determinants of neointimal proliferation and stent coverage after intracoronary therapy with drug-eluting devices in stable coronary artery disease: role of endothelial progenitor cells and interleukin-1 family cytokines.

BACKGROUND: Endothelial progenitor cells (EPCs) and cytokines seem to play a pivotal role in arterial healing after stent implantation. Using optical coherence tomography (OCT) as a high-resolution imaging technique, we aimed to assess the influence of circulating EPCs and levels of Il-1 cytokines on stent coverage and in-stent proliferation. METHODS: Eighty-nine patients were randomly treated with either Xience V drug-eluting stent (DES; n = 48) or bare-metal stent (BMS) postdilated with the SeQuent Please drug-eluting balloon (DEB; n = 41). EPC populations (CD34+/CD133+ and CD34+/CD133+/KDR+ EPC) and cytokines (Il-1ra, Il-18, and Il-1α) were measured before percutaneous coronary intervention using flow cytometry or immunoassay. Vessel remodeling was analyzed using coronary angiography and OCT at 6-month follow-up. RESULTS: Indexed neointimal volume and maximal proliferation thickness correlated inversely with EPC levels in the entire study population (r = -0.220; P=.04 and r = -0.253; P=.02) and the BMS + DEB subgroup (r = -0.344; P=.03 and r = -0.374; P=.02). Late lumen loss (LLL) was associated with the proatherogenic Il-18 concentration in the main population (r = 0.342; P=.01) and the BMS + DEB group (r = 0.471; P=.01). In the DES subgroup, associations with proliferation and LLL were lacking. Associations for stent strut coverage were not observed. CONCLUSIONS: A high EPC count seems to be a favorable individual patient factor, since it was associated with less instent proliferation. Contrarily, high Il-18 levels lead to more LLL, which emphasizes its proatherogenic properties.

A prospective randomised study using optical coherence tomography to assess endothelial coverage and neointimal proliferation at 6-months after implantation of a coronary everolimus-eluting stent compared with a bare metal stent postdilated with a paclitaxel-eluting balloon (OCTOPUS Trial): rationale, design and methods.

BACKGROUND: Safety concerns regarding use of drug-eluting stent systems (DES) are related mostly to late stent thrombosis, which is facilitated by incomplete stent endothelial coverage. Specific information about time course and amount of endothelial strut coverage of different DES is required, in order to further refine the concept of antiplatelet therapy after DES implantation. Optical coherence tomography (OCT) is emerging as a new gold standard for endovascular imaging of stents, atherosclerosis progression, vulnerable plaque, and neointimal proliferation. The aim of this study is a comparative evaluation using OCT of the XIENCE V everolimus-eluting stent (Abbot Vascular, Santa Clara, CA, USA) on one hand, and the bare metal stent Coroflex Blue postdilated with the paclitaxel-eluting balloon Sequent Please (both from B Braun Melsungen AG, Melsungen, Germany) on the other hand, with respect to endothelial coverage and neointimal proliferation. METHODS: Eighty patients scheduled for elective percutaneous coronary intervention (PCI) of a native coronary stenosis suitable for DES implantation and OCT imaging are scheduled to be openly randomised 1:1 to either XIENCE or Coroflex Blue/Sequent Please. The study is conducted prospectively at a university high-volume PCI centre with OCT expertise. Angiographic follow-up and time-domain OCT imaging with motorised pull-back at 1 mm/s are planned six months after study stent implantation in all patients. OCT endpoints are: (1) endothelial coverage, expressed as % of struts without coverage and % of stent length containing non-covered struts, and respectively (2) neointimal proliferation, given as % neointimal volumetric proliferation within the whole stent and also as peak focal % neointimal area proliferation. The study is not powered for clinical endpoints, which are: subacute or late stent thrombosis and need for revascularisation of the stent segment. Given the high number of measurements (15 cross-section images / 1 mm stent length), OCT endpoints are likely to reach significance at the level p <0.05, if the drop-out rate in follow-up does not exceed 20%. CURRENT STATUS: The study is currently on-going and its termination is scheduled for February 2010. (ClinicalTrials.gov identifier: NCT01056744).