Bill D. Gogas

Restenosis Delineating the Numerous Causes of Drug-Eluting Stent Restenosis

In the past decade, tremendous progress has been made in reducing the incidence of restenosis with the advent of the drug-eluting stent (DES). With “plain old balloon angioplasty,” rates of acute and chronic vessel occlusion were unacceptably high at ≈30% to 60%, secondary to acute and chronic recoil and constrictive remodeling. The advent of bare-metal stents (BMS) appeared to eliminate the issue of acute and chronic recoil but introduced a new entity, neointimal hyperplasia (NIH), with classical papers unequivocally demonstrating a strong and linear relationship between NIH formation and late lumen loss (LLL). The restenosis rates with BMS were reported to be between 16% and 44%, with higher rates of stenosis attributable to several risk factors, in particular, long lesion length and small vessel caliber.1 DES were thus conceived as the next step in tackling this iatrogenic entity of NIH, with large-scale reductions in restenosis rates reported at 0% in highly selective lesions and up to 16% in a broader range of patients and lesions with first-generation DES.1 In contrast to plain old balloon angioplasty and BMS, in which an almost classical gaussian distribution of LLL is seen postprocedurally, the LLL after DES implantation appears to follow a bimodal pattern of distribution (Figure 1).2 Figure 1. The bimodal distribution of LLL (A, B) and percentage diameter stenosis (C, D) after Cypher (left) and Taxus (right) implantation. LLL indicates late lumen loss. Reproduced with permission from Byrne et al.2 Despite the significant advances in the technology to reduce DES restenosis, conservative estimates still suggest that the incidence of in-stent restenosis (ISR) requiring target vessel revascularization (TVR), so-called DES failure, to be ≈5% to 10%, with one estimate suggesting ≈200 000 repeat revascularizations in the United States alone.3 Whereas the pattern of restenosis in BMS has been shown …

IVUS-based imaging modalities for tissue characterization: similarities and differences

Gray-scale intravascular ultrasound (IVUS) is the modality that has been established as the golden standard for in vivo imaging of the vessel wall of the coronary arteries. The use of IVUS in clinical practice is an important diagnostic tool used for quantitative assessment of coronary artery disease. This has made IVUS the de-facto invasive imaging method to evaluate new interventional therapies such as new stent designs and for atherosclerosis progression-regression studies. However, the gray-scale representation of the coronary vessel wall and plaque morphology in combination with the limited resolution of the current IVUS catheters makes it difficult, if not impossible, to identify qualitatively (e.g. visually) the plaque morphology similar as that of histopathology, the golden standard to characterize and quantify coronary plaque tissue components. Meanwhile, this limitation has been partially overcome by new innovative IVUS-based post-processing methods such as: virtual histology IVUS (VH-IVUS, Volcano Therapeutics, Rancho Cordova, CA, USA), iMAP-IVUS (Bostoc Scientific, Santa Clara, CA, USA), Integrated Backscatter IVUS (IB-IVUS) and Automated Differential Echogenicity (ADE).

Clinical and intravascular imaging outcomes at 1 and 2 years after implantation of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels. Late lumen enlargement: does bioresorption matter with small vessel size? Insight from the ABSORB cohort B trial

Background The long-term results after second generation everolimus eluting bioresorbable vascular scaffold (Absorb BVS) placement in small vessels are unknown. Therefore, we investigated the impact of vessel size on long-term outcomes, after Absorb BVS implantation. Methods In ABSORB Cohort B Trial, out of the total study population (101 patients), 45 patients were assigned to undergo 6-month and 2-year angiographic follow-up (Cohort B1) and 56 patients to have angiographic follow-up at 1-year (Cohort B2). The pre-reference vessel diameter (RVD) was <2.5 mm (small-vessel group) in 41 patients (41 lesions) and ≥2.5 mm (large-vessel group) in 60 patients (61 lesions). Outcomes were compared according to pre-RVD. Results At 2-year angiographic follow-up no differences in late lumen loss (0.29±0.16 mm vs 0.25±0.22 mm, p=0.4391), and in-segment binary restenosis (5.3% vs 5.3% p=1.0000) were demonstrated between groups. In the small-vessel group, intravascular ultrasound analysis showed a significant increase in vessel area (12.25±3.47 mm2 vs 13.09±3.38 mm2 p=0.0015), scaffold area (5.76±0.96 mm2 vs 6.41±1.30 mm2 p=0.0008) and lumen area (5.71±0.98 mm2 vs 6.20±1.27 mm2 p=0.0155) between 6-months and 2-year follow-up. No differences in plaque composition were reported between groups at either time point. At 2-year clinical follow-up, no differences in ischaemia-driven major adverse cardiac events (7.3% vs 10.2%, p=0.7335), myocardial infarction (4.9% vs 1.7%, p=0.5662) or ischaemia-driven target lesion revascularisation (2.4% vs 8.5%, p=0.3962) were reported between small and large vessels. No deaths or scaffold thrombosis were observed. Conclusions Similar clinical and angiographic outcomes at 2-year follow-up were reported in small and large vessel groups. A significant late lumen enlargement and positive vessel remodelling were observed in small vessels.

A comparative assessment by optical coherence tomography of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds

AIMS The first generation of the everolimus-eluting bioresorbable vascular scaffold (BVS 1.0) showed an angiographic late loss higher than the metallic everolimus-eluting stent Xience V due to scaffold shrinkage. The new generation (BVS 1.1) presents a different design and manufacturing process than the BVS 1.0. This study sought to evaluate the differences in late shrinkage, neointimal response, and bioresorption process between these two scaffold generations using optical coherence tomography (OCT). METHODS AND RESULTS A total of 12 lesions treated with the BVS 1.0 and 12 selected lesions treated with the revised BVS 1.1 were imaged at baseline and 6-month follow-up with OCT. Late shrinkage and neointimal area (NIA) were derived from OCT area measurements. Neointimal thickness was measured in each strut. Strut appearance has been classified as previously described. Baseline clinical, angiographic, and OCT characteristics were mainly similar in the two groups. At 6 months, absolute and relative shrinkages were significantly larger for the BVS 1.0 than for the BVS 1.1 (0.98 vs. 0.07 mm² and 13.0 vs. 1.0%, respectively; P = 0.01). Neointimal area was significantly higher in the BVS 1.0 than in the BVS 1.1 (in-scaffold area obstruction of 23.6 vs. 12.3%; P < 0.01). Neointimal thickness was also larger in the BVS 1.0 than in the BVS 1.1 (166.0 vs. 76.4 µm; P < 0.01). Consequently, OCT, intravascular ultrasound, and angiographic luminal losses were higher with the BVS 1.0 than with the BVS 1.1. At 6 months, strut appearance was preserved in only 2.9% of the BVS 1.0 struts, but remained unchanged with the BVS 1.1 indicating different state of strut microstucture and/or their reflectivity. CONCLUSION The BVS 1.1 has less late shrinkage and less neointimal growth at 6-month follow-up compared with the BVS 1.0. A difference in polymer degradation leading to changes in microstructure and reflectivity is the most plausible explanation for this finding.

Three-dimensional optical frequency domain imaging in conventional percutaneous coronary intervention: the potential for clinical application

Two-dimensional (2D) frequency domain optical coherence tomography (FD-OCT) has enhanced our understanding of coronary atherosclerotic disease and is increasingly being used in conventional percutaneous coronary intervention (PCI) to elucidate mechanisms of disease and improve our understanding of complex coronary anatomy. Since the first report of three-dimensional (3D) OCT applied in human coronary vessels,1 the technology has rapidly progressed.2–10 Currently, the main limitation of this technology is the need for off-line creation of 3D reconstructions—prototypes of current generation ‘real time’ (i.e. available peri-procedurally at the ‘push-of-a-button’) remain experimental, work in progress, and are limited by relatively poor image quality/resolution.4 As of now, the potential clinical application of 3D FD-OCT remains undefined. Recently, the application of this emerging technology to the coronary bifurcation has allowed visualization and assessment of jailed side branches (SideBs) at a level of detail not previously reported.2–7 The assessment of a jailed SideB, after implantation of a bioresorbable scaffold in the main branch (MainB) of a bifurcation, lead to the proposal of a new classification system based on the assessment of the number of compartments the SideB ostium was divided into, with examples of how this may potentially effect the neointimal response and subsequent coverage of the struts.2 More recently, the application of this technology to the coronary bifurcation in patients implanted with conventional metallic stents, utilizing the Terumo optical frequency domain imaging (OFDI) system, was described for the first time.3 Hypotheses related to types of coronary bifurcation (‘parallel’ and ‘perpendicular’ bifurcations) based on the bifurcation angle, and how this leads to certain specific characteristics of the carina, which potentially made the SideB more vulnerable to the effects of carina shift and potential SideB closure, were described. Furthermore, the potential practical application of 3D FD-OCT in guiding the …

New Insights Into the Coronary Artery Bifurcation: Hypothesis-Generating Concepts Utilizing 3-Dimensional Optical Frequency Domain Imaging

Coronary artery bifurcations are a common challenging lesion subset accounting for approximately 10% to 20% of all percutaneous coronary interventions. The provisional T-stenting approach is generally recommended as the first-line management of most lesions. Carina shift is suggested to be the predominant mechanism of side-branch pinching during provisional T-stenting and has been indirectly inferred from bench work and other intravascular imaging modalities. Offline 3-dimensional (3D) reconstructions of patients studied in the first-in-man trial of the high-frequency (160 frames/s) Terumo optical frequency domain imaging system were undertaken using volume-rendering software. Through a series of 3D reconstructions, several novel hypothesis-generating concepts are presented.

Progress in treatment by percutaneous coronary intervention: The stent of the future

First generation drug-eluting stents have considerably reduced in-stent restenosis and broadened the applications of percutaneous coronary interventions for the treatment of coronary artery disease. The polymer is an integral part of drug-eluting stents in that, it controls the release of an antiproliferative drug. The main safety concern of first generation drug-eluting stents with permanent polymers--stent thrombosis--has been caused by local hypersensitivity, delayed vessel healing, and endothelial dysfunction. This has prompted the development of newer generation drug-eluting stents with biodegradable polymers or even polymer-free drug-eluting stents. Recent clinical trials have shown the safety and efficacy of drug-eluting stents with biodegradable polymer, with proven reductions in very late stent thrombosis as compared to first generation drug-eluting stents. However, the concept of using a permanent metallic prosthesis implies major drawbacks, such as the presence of a foreign material within the native coronary artery that causes vascular inflammation and neoatherosclerosis, and also impedes the restoration of the vasomotor function of the stented segment. Bioresorbable scaffolds have been introduced to overcome these limitations, since they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. This update article presents the current status of these new technologies and highlights their future perspectives in interventional cardiology.

Natural history of optical coherence tomography-detected non-flow-limiting edge dissections following drug-eluting stent implantation

AIMS Angiographic evidence of edge dissections has been associated with a risk of early stent thrombosis. Optical coherence tomography (OCT) is a high-resolution technology detecting a greater number of edge dissections--particularly non-flow-limiting--compared to angiography. Their natural history and clinical implications remain unclear. The objectives of the present study were to assess the morphology, healing response, and clinical outcomes of OCT-detected edge dissections using serial OCT imaging at baseline and at one year following drug-eluting stent (DES) implantation. METHODS AND RESULTS Edge dissections were defined as disruptions of the luminal surface in the 5 mm segments proximal and distal to the stent, and categorised as flaps, cavities, double-lumen dissections or fissures. Qualitative and quantitative OCT analyses were performed every 0.5 mm at baseline and one year, and clinical outcomes were assessed. Sixty-three lesions (57 patients) were studied with OCT at baseline and one-year follow-up. Twenty-two non-flow-limiting edge dissections in 21 lesions (20 patients) were identified by OCT; only two (9%) were angiographically visible. Flaps were found in 96% of cases. The median longitudinal dissection length was 2.9 mm (interquartile range [IQR] 1.6-4.2 mm), whereas the circumferential and axial extensions amounted to 1.2 mm (IQR: 0.9-1.7 mm) and 0.6 mm (IQR: 0.4-0.7 mm), respectively. Dissections extended into the media and adventitia in seven (33%) and four (20%) cases, respectively. Eighteen (82%) OCT-detected edge dissections were also evaluated with intravascular ultrasound which identified nine (50%) of these OCT-detected dissections. No stent thrombosis or target lesion revascularisation occurred up to one year. At follow-up, 20 (90%) edge dissections were completely healed on OCT. The two cases exhibiting persistent dissection had the longest flaps (2.81 mm and 2.42 mm) at baseline. CONCLUSIONS OCT-detected edge dissections which are angiographically silent in the majority of cases are not associated with acute stent thrombosis or restenosis up to one-year follow-up.

Proximal and distal maximal luminal diameters as a guide to appropriate deployment of the ABSORB everolimus-eluting bioresorbable vascular scaffold: a sub-study of the ABSORB Cohort B and the on-going ABSORB EXTEND Single Arm Study.

Objectives: Due to the limited distensibility of the everolimus‐eluting bioresorbable vascular scaffold (ABSORB) compared to metallic platform stents, quantitative coronary arteriography (QCA) is a mandatory requirement for ABSORB deployment in the on‐going ABSORB EXTEND Single‐Arm Study. Visual assessment of vessel size in the ABSORB Cohort B study often lead to under and over‐sizing of the 3 mm ABSORB in coronary vessels (recommended range of the vessel diameter ≥2.5 mm and ≤3.3 mm), with an increased risk of spontaneous incomplete scaffold apposition post ABSORB deployment. We report whether mandatory QCA assessment of vessel size pre‐implantation, utilizing the maximal luminal diameter (Dmax) and established interpolated reference vessel diameter (RVD) measurements, has improved device/vessel sizing. Methods: Pre‐implantation post‐hoc QCA analyses of all 101 patients from ABSORB Cohort B (102 lesions) and first consecutive 101 patients (108 lesions) from ABSORB EXTEND were undertaken by an independent core‐laboratory; all patients had a 3 mm ABSORB implanted. Comparative analyses were performed. Results: Within ABSORB Cohort B, a greater number of over‐sized vessels (>3.3 mm) were identified utilizing the Dmax compared to the interpolated RVD (17 vessels, 16.7% vs. 3 vessels, 2.9%; P = 0.002). Comparative analyses demonstrated a greater number of appropriate vessel‐size selection (75 vessels, 69.4% vs. 48 vessels, 47.1%; P = 0.001), a trend towards a reduction in implantation in small (<2.5 mm) vessels (29 vessels, 26.9% vs. 40 vessels, 39.2%; P = 0.057) and a significant decrease in the implantation in large (>3.3 mm) vessels (4 vessels, 3.7% vs. 17 vessels, 16.7%; P = 0.002) in ABSORB EXTEND. Bland–Altman plots suggested a good agreement between operator and core‐laboratory calculated Dmax measurements. Conclusions: The introduction of mandatory Dmax measurements of vessel size prior to ABSORB implantation significantly reduced the under‐sizing of the 3.0 mm scaffold in large vessels validating the use of this technique in vessel sizing prior to ABSORB implantation.

Acute coronary occlusion following TAVI

Transcatheter aortic valve implantation (TAVI) has nowadays replaced open heart surgery as an alternative therapeutic tool in selected patients. Thirty‐five percent of patients with severe degenerative aortic valve stenosis (AS) remain untreated because of the existing comorbidities that increase their perioperative risk. TAVI is a relatively new technique that has “come to stay” in the everyday clinical practice considering, that is the only alternative to surgery and appears to have excellent long term results. Herein, we describe a vascular complication immediately after the implantation of the Edwards SAPIEN (Edwards Lifesciences, Irvine, CA) prosthesis, followed by ad hoc percutaneous coronary intervention.