Intraplaque therapies for facilitating percutaneous recanalization of chronic total occlusions

Chronic total occlusions (CTOs) are found in up to 30% of angiograms performed on patients with coronary disease. The technical difficulty of performing percutaneous coronary interventions (PCIs) in CTOs, primarily because of the inability to cross CTOs with a guide wire, is reflected in low rates of PCI for CTo (approximately 9% of PCI procedures). The main barrier to successful CTO crossing is the dense collagenous extracellular matrix, particularly at the entrance, known as the 'proximal fibrous cap'. Current interventional strategies to overcome this barrier are based primarily on forceful penetration of the CTO plaque by the use of dedicated CTO guide wires. These extra-stiff wires are designed to transfer maximal force to the tip to create a path within the plaque. However, these wires can also cause vascular complications such as dissections; overall procedural success rates remain modest. Several groups are working on new approaches to actually alter the biology and structural characteristics of the CTO plaque to facilitate guide wire crossing. Preliminary data suggest that plaque-directed therapies aimed at 'priming' it for wire crossing may increase PCI success in these challenging cases. New techniques for plaque modification, either by 'softening' the collagenous matrix (collagenase) or by exposing and enlarging existing microvessels (intravascular thrombolysis, contrast injection) or by inducing new microvessels (angiogenic growth factor[s]) are described in the present review.