Chapter 13 Restenosis and in-stent restenosis
PATHOPHYSIOLOGY
Figure 13.1 Mechanisms of restenosis following PCI.
Source: Chan AW and Moliterno DJ, Clinical Evaluation of Restenosis. In Atherothrombosis and Coronary Artery Disease, edited by V. Fuster, EJ Topol, and EG Nabel, p. 1416 (Figure 93.2).
DEFINITIONS OF RESTENOSIS
Angiographic restenosis
Various definitions for angiographic restenosis have been used. 50% or greater dichotomous diameter stenosis at follow-up angiography is a widely used criterion in clinical trials. However, reporting of the minimum luminal diameter (MLD) may avoid variation of restenosis rates reported in clinical trials due to inconsistent definitions of angiographic restenosis. The difference between pre-procedural MLD and immediate post-procedural MLD is defined as acute gain, and the difference between post-procedural MLD and MLD at follow-up is termed to late loss. Acute gain is lowest with PTCA, followed by atherectomy, and stenting (highest acute gain). Late loss is usually proportional to acute gain, such that the late loss index, defined as late loss divided by the acute gain, is similar after revascularization with PTCA, atherectomy, or stents (Fig. 13.3).
Clinical restenosis
Since angiographic definitions for restenosis are somewhat arbitrary, the importance of restenosis becomes clinically relevant only when it is linked to symptom(s) or functional parameter(s). Because the process of restenosis is usually gradual, and the newly formed lesion is ‘stabilized’ with fibrous tissue and smooth muscle cells, recurrent angina is the most common presenting feature, whereas myocardial infarction (MI) and sudden death are less frequent. Chest pain is reportedly present in 25–93% of patients six months following balloon angioplasty, with an average of approximately 50%.2 The proportion of patients presenting with recurrent chest pain who have restenosis demonstrable at angiography ranges from 48–92%. Hence, the positive predictive value (PPV) of symptoms alone is only modest.
Clinical restenosis is roughly correlated with the need for repeat revascularization (repeat PCI or bypass surgery). Traditionally, target lesion revascularization (TLR) has been used in many of the interventional trials designed to test various pharmacology, while target vessel revascularization (TVR) has been used in device trials in which the effect of the device on the vessel beyond the target lesions also needs to be considered. More recently, the term target vessel failure (TVF) has also become popular, and it refers to TVR plus death or myocardial infarction due to restenosis or reocclusion of the target vessel.