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Aims To create a large animal coronary chronic total occlusion (CTO) model. Presence of microvessels within the CTO lumen facilitates guidewire crossing. The patterns and time profiles of matrix changes and microvessel formation during coronary CTO maturation are unknown. Methods and results CTO were created in 15 swine by percutaneous deployment of a collagen plug. Matrix changes were assessed by histology. Intraluminal neovascularisation was assessed by histology and several imaging modalities, including conventional and 3D spin angiography, micro-computed tomography (micro-CT) imaging, and contrast-enhanced magnetic resonance imaging (MRI), at six and 12 weeks following CTO creation. Matrix changes included an intense inflammatory reaction at six weeks which had partially abated by 12 weeks. A proteoglycan-rich matrix at six weeks was partially replaced with collagen by 12 weeks. Similar changes were noted in the proximal cap which was acellular. Three patterns of microvessel formation were identified and defined based on the presence and extent of a "lead" neovessel. No major differences in pattern or extent of neovascularisation were noted between six and 12 weeks. Conclusions Heterogeneity in neovascularisation patterns occurs during coronary CTO development in a porcine model. Non-invasive imaging to determine the predominant type of neovascularisation prior to and during CTO revascularisation may improve guidewire crossing success rates. This model may be useful for further exploration of CTO pathophysiology, and may aid in further refinements of in vivo imaging of CTO and development of novel therapeutic approaches to revascularisation of CTO, such as manipulations of the proximal cap, matrix composition, neovessel induction, and device testing.

Objectives The purpose of this study was to characterize the 3-dimensional structure of intravascular and extravascular microvessels during chronic total occlusion (CTO) maturation in a rabbit model. Background Intravascular microchannels are an important component of a CTO and may predict guidewire crossability. However, temporal changes in the structure and geographic localization of these microvessels are poorly understood. Methods A total of 39 occlusions were created in a rabbit femoral artery thrombin model. Animals were sacrificed at 2, 6, 12, and 24 weeks (n ≥8 occlusions per time point). The arteries were filled with a low viscosity radio-opaque polymer compound (Microfil) at 150 mm Hg pressure. Samples were scanned in a micro-computed tomography system to obtain high-resolution volumetric images. Analysis was performed in an image processing package that allowed for labeling of multiple materials. Results Two distinct types of microvessels were observed: circumferentially oriented “extravascular” and longitudinally oriented “intravascular” microvessels. Extravascular microvessels were evident along the entire CTO length and maximal at the 2-week time point. There was a gradual and progressive reduction in extravascular microvessels over time, with very minimal microvessels evident beyond 12 weeks. In contrast, intravascular microvessel formation was delayed, with peak vascular volume at 6 weeks, followed by modest reductions at later time points. Intravascular microvessel formation was more prominent in the body compared with that in the proximal and distal ends of the CTO. Sharply angulated connections between the intravascular and extravascular microvessels were present at all time points, but most prominent at 6 weeks. At later time points, the individual intravascular microvessels became finer and more tortuous, although the continuity of these microvessels remained constant beyond 2 weeks. Conclusions Differences are present in the temporal and geographic patterns of intravascular and extravascular microvessel formation during CTO maturation.

To compare the long-term outcomes and recurrence rate of extensive versus limited subconjunctival pterygium excision with conjunctival autograft.This retrospective study included 135 consecutive patients (161 eyes) who had pterygium excision with conjunctival autograft at the cornea performed at the cornea service of the Toronto Western Hospital. Ninety-one had limited pterygium excision, and 70 had extensive pterygium excision with conjunctival sparing. Main outcome measures included the recurrence rate.The recurrence rate in the limited excision group was 12.1% compared with only 4.3% in the extensive pterygium excision group (p = 0.14). The mean time to recurrence was shorter with limited excision compared to extensive excision (4.0 vs. 5.3 months, respectively, p = 0.16). Limited pterygium excision had a hazard ratio of recurrence of 3.2 compared with the extensive excision method. Recurrence-free survival analysis showed a significant advantage for the extensive excision group (p = 0.045, log-rank test). Cox proportional hazards regression found that younger age (p = 0.0003), larger area of corneal involvement (p = 0.004), worse preoperative visual acuity (p = 0.01), and limited pterygium excision (p = 0.04) significantly increased the risk for recurrence.Both limited and extensive pterygium excision groups had low recurrence rates. The extensive subconjunctival pterygium excision group tended toward fewer recurrences, which occurred later.

Aims Percutaneous revascularisation of chronic total occlusions (CTO) is limited by failure of guidewire crossing. Neovascularisation within the proximal CTO segment may be important for guidewire crossing and dramatically declines in CTO beyond six weeks of age. The aims of the current study were to determine whether local delivery of a pro-angiogenic growth factor increases neovascularisation in mature CTO and facilitates guidewire crossings. Methods and results CTO (n=51) were created in the femoral arteries of 44 New Zealand white rabbits using the thrombin injection model. At 12 weeks, CTO were treated with poly-lactic-glycolic-acid (PLGA) microspheres containing either bovine serum albumin (BSA) (n=15) or recombinant mouse VEGF164 (n=14), or received no intervention (controls, n=12). Contrast-enhanced magnetic resonance angiography (CEMRA) was performed prior to treatment and at three weeks post treatment. Animals were sacrificed at three weeks post treatment and arterial samples were excised for micro-computed tomography imaging (µCT) and histologic morphometric analysis. Guidewire crossing was assessed at three weeks post treatment in an additional 10 VEGF164-treated CTO. In comparison to BSA-treated and control non-intervened CTO, VEGF164-treated CTO showed a significant increase in relative blood volume index in the proximal segment of the CTO lesion as determined by CEMRA and by µCT. Histologic measurements of microvessel area were also higher in VEGF164-treated CTO. Guidewire crossing across the proximal fibrous cap was successful in eight out of 10 VEGF164-treated CTO. Conclusions Angiogenic therapy appears to be a promising strategy to improve neovascularisation and guidewire crossing rates in CTO.

The purpose of this study was to determine the prevalence, clinical characteristics, and management of coronary chronic total occlusions (CTOs) in current practice.There is little evidence in contemporary literature concerning the prevalence, clinical characteristics, and treatment decisions regarding patients who have coronary CTOs identified during coronary angiography.Consecutive patients undergoing nonurgent coronary angiography with CTO were prospectively identified at 3 Canadian sites from April 2008 to July 2009. Patients with previous coronary artery bypass graft surgery or presenting with acute ST-segment elevation myocardial infarction were excluded. Detailed baseline clinical, angiographic, electrocardiographic, and revascularization data were collected.Chronic total occlusions were identified in 1,697 (18.4%) patients with significant coronary artery disease (50% stenosis in ≥1 coronary artery) who were undergoing nonemergent angiography. Previous history of myocardial infarction was documented in 40% of study patients, with electrocardiographic evidence of Q waves corresponding to the CTO artery territory in only 26% of cases. Left ventricular function was normal in50% of patients with CTO. Half the CTOs were located in the right coronary artery. Almost half the patients with CTO were treated medically, and 25% underwent coronary artery bypass graft surgery (CTO bypassed in 88%). Percutaneous coronary intervention was done in 30% of patients, although CTO lesions were attempted in only 10% (with 70% success rate).Chronic total occlusions are common in contemporary catheterization laboratory practice. Prospective studies are needed to ascertain the benefits of treatment strategies of these complex patients.