Some current clinical trials use late loss as a key data point. Can you help us understand what late loss is? Late loss is the difference in millimeters between the diameter of a stented segment post-procedure compared with the follow-up angiogram at six or nine months. We expect some in-growth of tissue or neointima, and that number is going to be variable. Obviously, we want some growth to cover the stent struts, but enough suppression so that we significantly reduce restenosis. For bare stents, late loss is probably between 0.8 mm and 1 mm. For effective drug-eluting stents (DES), it appears to be below 0.5 to 0.6 mm. Why is late loss important? It's important because it's a measure of how effective a drug is in suppressing neointimal formation1 inside the stent. It's also a measure of safety, because healthy vessels with sustained, long-term results require uniform neointima and endothelial2 healing to cover the stent struts which otherwise would be exposed, potentially leading to platelet aggregation and sub-acute thrombosis (SAT). Late loss is also a measure of healing because neointimal and endothelial tissue growth are evidence of healing. Is there a preferred measurement or an appropriate amount of late loss in DES? We know that the number should certainly be reduced from that of a bare metal stent. When we plot a graph of late loss vs. clinical outcomes in terms of patients with recurrent symptoms or evidence of restenosis, the result should be below 0.5 or 0.6 mm. Previously, it had been thought that the lower the number, the better; however, there seems to be a law of diminishing returns with respect to late loss. There seems to be a break point below which one will see outstanding performance of the drug-eluting stent. It's not a matter of 0.1 vs 0.2-that may be a measurable difference in the core lab, but it might not translate into improved outcomes in your stent population. Can you talk more about what late loss means to safety and healthy healing,i.e.,late loss as an effective measure of safety? Obviously, you have to have some growth. An early study looking at late loss suggested that late loss was 0, but that is not a safe number, because you want some growth around the stent struts. Otherwise, they remain bare and would cause a continual thrombotic or clotting risk. You want the number to be positive. You do want it reduced, but you don't want it to be 0-or even worse, negative, which means that the actual wall has expanded around the stent. In other words, a negative late loss is where the vessel starts to pull away from the stent, creating a nexus for thrombotic material or thrombosis. What are the ramifications of negative late loss? You mentioned that it poses a thrombotic threat? We've all been concerned that we could push the envelope too far, and that eventually at the stented site there would be no in-growth whatsoever or, even more extreme, creating almost an aneurysm segment-an area that's larger than the reference area. Fortunately, we see that rarely with our current stent generation. What should cath lab staff take away from this discussion about late loss? Remember that late loss is a summation of events of a large population of patients who have stents. As my biology professor once said, Most of biology is a Gaussian curve. A bell-shaped curve is actually the response that you're seeing. This number we quote is just the mean. There will be patients who have larger late losses and they'll have restenosis, and there will be patients who have very low late losses. Just remember that this number is your measure of how effectively you are reducing some of that so-called scar tissue or neointimal proliferation. It is a prerequisite in reducing restenosis-it is a very important number for those of us who deal with the clinical ramifications. Sponsored by Boston Scientific Corporation. 1. Neointima: endothelium, smooth muscle cells and extracellular matrix. 2. Endothelial layer: innermost layer of cells in the lumen post-stent implant. Endothelial cells come from the bloodstream; they are smooth, lubricious, highly resistant to plaque, and resilient to target lesion revascularization (TLR).