Mechanisms of In-Stent Restenosis After Drug-Eluting Stent Implantation

We used intravascular ultrasound (IVUS) to (1) clarify the mechanisms of luminal loss after drug-eluting stent (DES) implantation and (2) classify morphological patterns of in-stent restenosis (ISR).On the basis of IVUS-identified luminal narrowing (in-stent minimum lumen area <4 mm(2)), IVUS-defined ISR was classified as focal (luminal narrowing ≤10 mm in length), multifocal (≥1 focal lesions), and diffuse (luminal narrowing >10 mm in length) with or without stent edge involvement. Significant intimal hyperplasia (IH) was defined as IH area >50% of stent. Overall, 76 lesions had IVUS-defined ISR; 32 (42%) had stent underexpansion (minimal stent area <5 mm(2)); and 71 (93%) had IH area >50% of stent. Total stent length negatively correlated with minimal stent area (r=-0.613, P<0.001) as well as with stent area at the minimum lumen site (r=-0.436, P<0.001) but not with minimum lumen area (r=-0.084, P=0.472). Underexpansion was present at the minimum lumen site in 15 of 43 (35%) lesions with stent length >28 mm, even though there was significant IH in 34 (79%) lesions; conversely, in 32 of 33 (97%) lesions with stent length ≤28 mm, the minimum lumen site was not associated with stent underexpansion but significant IH. IVUS-defined focal ISR was most common (47%). Compared with focal ISR, normalized vessel, stent, lumen, and plaque volumes were smaller in diffuse and multifocal than focal ISR, with no difference in IH extent.In most DES restenosis, IH was the dominant mechanism of ISR. Nevertheless, underexpansion associated with longer stent length remained an important preventable mechanism of ISR.