Grant: Project Grant

Blockages of the coronary or femoral arteries begin as soft blood clots but over time they can harden becoming what are called chronic total occlusions (CTOs). In the heart, patients can often survive the formation of CTOs but have degraded lifestyles and reduced life expectancy due to poor cardiac performance. To fix this problem, clinicians often try to open the vessels up again using a catheter that is put in through an artery in the leg and worked up into the coronary artery until it reaches the blockage. A thin wire then goes into the CTO and is used to guide balloon catheter that re-opens the vessel. However, because of the stiffness of the CTOs this is often unsuccessful and this remains one of the most challenging problems facing cardiologists. To address this problem, we developed an approach that involves the injection of a drug (enzyme) that softens the CTO so that it is easier to slide a wire through it to re-open it. This new approach is now in clinical trials and evidence is showing that it improves the success rates for unblocking difficult CTOs. For this procedure, the drug injection occurs on one day and then the unblocking procedure is attempted the following day to allow enough time for the drug to work. In other parallel work we have investigated using a specialized form of ultrasound to help improve the drug effects. We have shown in bench-top experiments as well as in animal models of CTOs that when ultrasound is used to 'pop' small injected bubbles nearby the clot, it is damaged in a way that makes the drug work better and faster. Here we propose to build on this work to develop a new catheter based ultrasound device that can be used to enhance the performance of this emerging CTO drug therapy. It will use a new approach to generating ultrasound waves at the tip of a catheter, which will be used to vibrate bubbles and accelerate drug effects. This work will further improve CTO treatment success rates and have them done in a single day.