Abstract 2550: Intraluminal Neovascularization of Arterial Chronic Total Occlusions: a Novel Therapeutic Approach
Percutaneous coronary interventions (PCI) have low success rates in chronic total occlusions (CTO), primarily due to failure of guidewire crossing. Previous studies have suggested that intraluminal microvessels may be an important factor in successful guidewire crossing in CTOs. The aims of this study were to determine 1) the temporal profile of intraluminal neovascularization during CTO formation and 2) the angiogenic effects of direct VEGF delivery.
Methods: CTOs were created in New Zealand White rabbits (n=51) by thrombin injection into surgically exposed femoral arteriy with verification at 6 – 8 weeks by ultrasound. At 2, 6, 12 and 18 –24 weeks of CTO age, contrast enhanced magnetic resonance angiography (CEMRA) was performed to determine relative blood volume index (RBVI) in the CTO region, which was followed by ex-vivo micro-CT imaging and histological analysis. To determine the effects of angiogenic therapy in 12-week-old CTO (8 per group), recombinant mouse VEGF164 was incorporated into biodegradable microspheres which were locally injected into the proximal part of the CTO, control animals received empty microspheres. RBVI was determined by CEMRA at 12 weeks (baseline) and again at 15 weeks.
Results: A definite temporal pattern of intraluminal neovascularization occurred within the CTO with a 2-fold increase in total microvessel cross-sectional area from 2 to 6 weeks (0.014±0.002 to 0.023±0.005 mm2, p=0.0008) and a 3-fold increase in RBVI (5.1±1.9% to 16.9±2.7%, p=0.0008). However, this was followed by significant reductions in both RBVI (3.5±1.1%, p<0.0001) and total microvessel CSA (0.017 ± 0.002 mm2, p=0.011), at later time periods. Micro-CT imaging demonstrated corkscrew-like recanalization channels at the proximal end at 6 weeks that regressed at later time points. Delivery of VEGF-containing microspheres significantly increased RBVI over the 3 week period compared with control group (15.23±1.2% vs. 2.36±1.11%, p<0.0001).
Conclusions: Intraluminal neovascularization occurs early during CTO maturation but regresses at later time points. Local administration of VEGF increases blood flow and enhances intraluminal neovascularization within CTO, and may offer a novel therapeutic approach to improve PCI success rates in CTO.