Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial.

AIMS: To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an 'all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. METHODS AND RESULTS: Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas-volumetric parameters were found between ZES and EES, respectively. CONCLUSION: No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: an attempt to decipher the human optical coherence tomography images in the ABSORB trial.

BACKGROUND: With the use of optical coherence tomography (OCT), alterations of the reflectance characteristics of everolimus-eluting bioresorbable vascular scaffold (BVS) struts have been reported in humans. In the absence of histology, the interpretation of the appearances of the struts by OCT remains speculative. We therefore report OCT findings with corresponding histology in the porcine coronary artery model immediately after and at 28 days and 2, 3, and 4 years after BVS implantation. METHODS AND RESULTS: Thirty-five polymeric BVS (3.0×12.0 mm) were singly implanted in the main coronary arteries of 17 pigs that underwent OCT and were then euthanized immediately (n=2), at 28 days (n=2), at 2 years (n=3), at 3 years (n=5), or at 4 years (n=5) after implantation. All BVS-implanted arteries in these animals were evaluated by histology except for 5 arteries examined at 2 years with gel permeation chromatography to assess the biodegradation of the polymeric device. Fourteen arteries with BVS from an additional 6 pigs were examined by gel permeation chromatography at 1 (n=1), 1.5 (n=2), and 3 (n=2) years. Corresponding OCT and histology images were selected with the distal and proximal radiopaque markers used as landmarks. At 28 days, by OCT, 82% of struts showed sharply defined, bright reflection borders, best described as a box-shaped appearance. Histologically, all struts appeared intact with no evidence of resorption. At 2 years, by OCT, 60±20 struts were discernible per BVS with 80.4% of the strut sites as a box-shaped appearance. Despite their defined appearance by OCT, by histology, these structures appeared to be composed of proteoglycan, with polymeric material being at such low level as to be no longer quantifiable by chromatography. At 3 years, by OCT, recognizable struts decreased to 28±9 struts per BVS: 43.7% showed dissolved black box; 34.8%, dissolved bright box; 16.1%, open box; and 5.4%, preserved box appearance. Histology shows that connective tissue cells within a proteoglycan-rich matrix replaced the areas previously occupied by the polymeric struts and coalesced into the arterial wall. At 4 years, by OCT, 10±6 struts were recognizable as either dissolved black or dissolved bright box. In histology, these struts are minimally discernible as foci of low-cellular-density connective tissue. Relative to the prediction of histological type by OCT appearance, the preserved box appearance of OCT corresponds well with 2-year histology (86.4%), whereas the dissolved bright and black box appearances correspond to 3-year histology (88.0% and 90.7%, respectively). Struts indiscernible by OCT correspond to the integrated strut footprints seen at 4 years (100%). CONCLUSIONS: Struts that are still discernible by OCT at 2 years are compatible with largely bioresorbed struts, as demonstrated by histological and gel permeation chromatography analysis. At 3 and 4 years, both OCT and histology confirm complete integration of the struts into the arterial wall.

Stent strut thickness and acute vessel injury during percutaneous coronary interventions: an optical coherence tomography randomized clinical trial.

AIMS: Compare the degree of acute vascular injury caused by a polymer-free, thin-strut drug-eluting stent (DES) to that caused by a bioresorbable polymer, thick-strut DES using optical coherence tomography (OCT). METHODS AND RESULTS: Fifty patients requiring nonurgent PCI were randomized to receive either a thin or a thick-strut DES. OCT was performed before and after stent implantation. OCT-based injury score (IS) after implantation was numerically higher within thick-strut stents 0.32 vs. 0.23, but the difference was NS (P = 0.61). Edge dissections were present in 36% of the patients without differences between groups. Tissue prolapse (TP) area was larger with thin-strut stents (2.26 vs. 1.83 mm2, P = 0.04). Stent expansion and symmetry index were similar between the two platforms (85% vs. 94%, P = 0.08; and 0.82 vs. 0.80, P = 0.25). No differences were observed in total malapposition area (1.85 mm2 in thin-strut stents vs. 1.47 mm2, P = 0.48). Regarding the influence of plaque-type, IS tended to be higher (non-significant) with thick strut DES in fibrocalcific plaques. Stent malapposition area was smaller in fibrous plaques, especially with thin strut stents (P = 0.03). CONCLUSION: There was no difference in the extent of OCT-based vessel injury associated with thin and thick-strut DES platforms. TP was larger with the thin strut DES, potentially reflecting a deeper stent embedment in the vessel wall.

Device specificity of vascular healing following implantation of bioresorbable vascular scaffolds and bioabsorbable polymer metallic drug-eluting stents in human coronary arteries: the ESTROFA OCT BVS vs. BP-DES study.

AIMS: We sought to compare vascular healing with bioresorbable everolimus-eluting vascular scaffolds (BVS) and drug-eluting stents with bioabsorbable polymers (BP-DES) at six and 12 months both implanted in the same patients. METHODS AND RESULTS: This was a multicentre and prospective study including patients with at least two comparable lesions to treat. In every patient both BVS and BP-DES (SYNERGY, Orsiro or BioMatrix Flex) were implanted by lesion randomisation. Patients included were evaluated with optical coherence tomography at six or 12 months (2:1). Finally, 68 patients had an examination at six months and 27 patients at 12 months. The rates of uncovered struts at six months were 1.7±3.2% for BVS and 5.3±5.6% for BP-DES (p=0.0001), and at 12 months 0.48±0.72% and 4.8±5%, respectively (p=0.001). Rates of strut malapposition were significantly lower with BVS. There was no significant intra-patient correlation with BP-DES/BVS for endpoints. Evaginations were more frequent and larger with BVS. Discontinuities in BVS were observed in 19.4% at six months and 14.3% at 12 months. CONCLUSIONS: Vascular healing with BVS and BP-DES could be more device-specific than patient-specific. At follow-up, BVS presented fewer uncovered or non-apposed struts than BP-DES but more frequent and larger evaginations. Discontinuities in BVS were relatively frequent at both time points.

3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents.

OBJECTIVES: This study sought to compare the long-term safety and efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with in-stent restenosis (ISR) of drug-eluting stents (DES). BACKGROUND: Treatment of patients with DES-ISR remains a challenge. METHODS: The RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial is a prospective multicenter randomized clinical trial comparing DEB and EES in patients with DES-ISR. The pre-specified comparison of the 3-year clinical outcomes obtained with these interventions is the main objective of the present study. RESULTS: A total of 309 patients with DES-ISR were randomized to DEB (n = 154) or EES (n = 155). At angiographic follow-up, the in-segment minimal lumen diameter was larger in the EES arm (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p < 0.01). Three-year clinical follow-up was obtained in all enrolled patients (100%). The combined clinical outcome measure of cardiac death, myocardial infarction and target lesion revascularization was significantly reduced in the EES arm (19 [12.3%] vs. 31 [20.1%]; p = 0.04; hazard ratio: 0.57 [95% confidence interval: 0.34 to 0.96]), driven by a lower need for target lesion revascularization (11 [7.1%] vs. 24 [15.6%]; p = 0.015; hazard ratio: 0.43 [95% confidence interval: 0.21 to 0.87]). The need for "late" (>1 year) target lesion revascularization (2.6% vs. 4%) and target vessel revascularization (4% vs. 6.6%) was similar in the 2 arms. Rates of cardiac death (3.9% vs. 3.2%), myocardial infarction (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%) at 3 years were also similar in both arms. CONCLUSIONS: The 3-year clinical follow-up of this randomized clinical trial demonstrates that in patients with DES-ISR, EES reduce the need for repeat interventions compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents [RIBS IV]; NCT01239940).

Long-Term Results of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With Bare-Metal In-Stent Restenosis: 3-Year Follow-Up of the RIBS V Clinical Trial.

OBJECTIVES: The aim of this study was to compare the long-term efficacy of everolimus-eluting stents (EES) and drug-eluting balloons (DEB) in patients with bare-metal stent in-stent restenosis (ISR). BACKGROUND: The relative long-term clinical efficacy of current therapeutic modalities in patients with ISR remains unknown. METHODS: The 3-year clinical follow-up (pre-specified endpoint) of patients included in the RIBS V (Restenosis Intra-Stent of Bare-Metal Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent Implantation) randomized clinical trial was analyzed. All patients were followed yearly using a pre-defined structured questionnaire. RESULTS: A total of 189 patients with bare-metal stent ISR were allocated to either EES (n = 94) or DEB (n = 95). Clinical follow-up at 1, 2, and 3 years was obtained in all patients (100%). Compared with patients treated with DEB, those treated with EES obtained better angiographic results, including larger minimal luminal diameter at follow-up (primary study endpoint; 2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm; p < 0.001). At 3 years, the rates of cardiac death (2% vs. 1%), myocardial infarction (4% vs. 5%) and target vessel revascularization (9% vs. 5%) were similar in the DEB and EES arms. Importantly, however, at 3 years, the rate of target lesion revascularization was significantly lower in the EES arm (2% vs. 8%; p = 0.04; hazard ratio: 0.23; 95% confidence interval: 0.06 to 0.93). The need for "late" (>1 year) target vessel (3 [3.2%] vs. 3 [3.2%]; p = 0.95) and target lesion (1 [1%] vs. 2 [2.1%]; p = 0.54) revascularization was low and similar in the 2 arms. Rates of definite or probable stent thrombosis (1% vs. 0%) were also similar in the 2 arms. CONCLUSIONS: The 3-year clinical follow-up of the RIBS V clinical trial confirms the sustained safety and efficacy of EES and DEB in patients treated for bare-metal stent ISR. In this setting, EES reduce the need for target lesion revascularization at very long-term follow-up. (RIBS V [Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent] [RIBS V]; NCT01239953).

Plaque sealing and passivation with a mechanical self-expanding low outward force nitinol vShield device for the treatment of IVUS and OCT-derived thin cap fibroatheromas (TCFAs) in native coronary arteries: report of the pilot study vShield Evaluated at Cardiac hospital in Rotterdam for Investigation and Treatment of TCFA (SECRITT).

AIMS: The aim of the pilot SECRITT trial was to evaluate the safety and feasibility of sealing the high risk IVUS and optical coherence tomography-derived thin cap fibroatheroma (TCFA), with a dedicated nitinol self-expanding vShield device. METHODS AND RESULTS: After screening with angiography, fractional flow reserve (FFR), intravascular ultrasound virtual histology (IVUS-VH) and optical coherence tomography (OCT), 23 patients met enrolment criteria (presence of non-obstructive VH-derived TCFA lesion with thin cap on OCT) and were randomised to vShield (n=13) versus medical therapy (n=10). In the shielded group, baseline percent diameter stenosis was 33.2±13.5%, FFR was 0.93±0.06. At six-month follow-up in shielded patients percent diameter stenosis further decreased to 18.7±16.9% and FFR remained the same 0.93±0.05. Average late loss was 0.24±0.13 mm. Average baseline fibrous cap thickness was 48±12 µm. After shield placement at six-month follow-up neo-cap formation was observed with average cap thickness of 201±168 µm. There were no dissections after shield placement and no plaque ruptures. In addition, mean stent area of 8.76±2.16 mm2 increased to 9.45±2.30 mm2, that is by 9% at six-month follow-up. The number of malapposed struts decreased from 10.7% to 7.6% and the number of uncovered struts at six months was 8.1%. There were no device-related major adverse cardiovascular events (MACE) events at six-month follow-up. CONCLUSIONS: High risk plaque passivation and sealing with a vShield self-expanding nitinol device appears feasible and safe. A long-term larger randomised study with streamlined screening criteria is needed to evaluate the efficacy of this approach over medical therapy.

Detection of very early stent healing after primary angioplasty: an optical coherence tomographic observational study of chromium cobaltum and first-generation drug-eluting stents. The DETECTIVE study.

BACKGROUND: Lack of stent coverage appears to be associated with stent thrombosis, a problem of particular concern in patients with ST elevation myocardial infarction (STEMI). METHODS: The DETECTIVE European Multicenter Registry was set up to address the early modality of stent healing in the setting of STEMI. The Registry compared, with an early optical coherence tomography (OCT) evaluation performed at 3-7 days, the patterns of coverage and apposition of the first generation of drug-eluting stents (DESs) and cobalt chromium non-drug-eluting stents (CCSs) that were deployed in culprit lesions and in non-culprit segments. The Registry included only patients with a multi-vessel disease to allow, at 3-7 days from the first angioplasty, a deferred OCT examination and a staged intervention in another vessel. RESULTS: 28 stented lesions (15 patients) eventually entered the final OCT assessment. 13 stents were first-generation DESs, while the remaining 15 were CCSs. 18 stents (64%) were deployed at culprit STEMI lesions, and the remaining 10 (36%) were deployed at non-culprit sites. The distribution of clinical and procedural variables in DES and CCS as well as in culprit and non-culprit sites was not different. In total, 27,019 struts were analysed in 28 stents. The percentage of stent uncoverage in the overall analysis was 11.7%, while the percentage of malapposition and that of struts covered with thrombus were 4.8% and 2.2%, respectively. A low percentage of strut uncoverage was found in all the four studied subgroups: DES 12.8%, CCS 10.9%, stents deployed in culprit lesions 13.2% and stents deployed in non-culprit lesions 8.7%. CONCLUSIONS: In conclusion, our data show that in patients with STEMI, a very high percentage of stent struts is covered by an early thin rim of tissue within 7 days after stent positioning. The present data bring new insights in the mechanism and timing of strut coverage.