Late ISA is defined as one or more stent struts clearly separated from the vessel wall with evidence of blood speckles behind the strut without overlapping side branches that was not present immediately after stent implantation by IVUS exam.

Late ISA is not a recently described phenomenon. Hong et al. previously reported that the incidence of late ISA after BMS implantation was 5.4%. Predictors of late ISA were primary stenting in acute myocardial infarction, and directional coronary atherectomy before stenting. In addition, late ISA did not have negative impact on clinical outcomes including death, myocardial infarction, and target lesion revascularization. It is also reported that the brachytherapy was associated with the higher incidence of late ISA. Several mechanisms for late ISA have been postulated: positive arterial remodeling with an increase in total vessel area out of proportion to the increase in persistent plaque and media area, dissolution of plaque and thrombus behind the stent so that a gap forms between the stent and vessel wall, chronic stent recoil without any change in arterial dimensions.

After advent of DES, the incidence of late ISA was getting higher up to 20% after DES implantation compared with BMS implantation. Several studies reported that the association between late ISA and VLST. Cook et al. reported the structural changes in the stented vessel segment associated with VLST. They compared intravascular ultrasound (IVUS) findings of 13 patients with VLST with 144 controlled patients, and revealed that late ISA was present in 10/13 (77%) patients with VLST versus 12% in the control group. However, it could not confirm whether late ISA might be a risk factor for VLST because aforementioned studies did not provide the prevalence of ISA in patients without VLST. Siqueria et al. analyzed the serial IVUS images of 195 consecutive patients undergoing DES implantation in native coronary artery lesion. They found that the incidence of late ISA was 5.1% (10 patients) and two patients suffered from VLST during follow up. Recently meta-analysis on the late ISA was published. Patients with DES had four times higher risk for late ISA (OR=4.36, 95% CI 1.74-10.94) compared with BMS, and the risk of VLST in patient with late ISA was higher compared with those without late ISA (OR=6.51, 95% CI 1.34-34.91). The mechanism by which late ISA may contribute to stent thrombosis remains unclear. It has been stated that late ISA may serve as a local nidus for thrombus formation by allowing fibrin and platelet deposition.

In contrary, several studies failed to identify the association between the late ISA and adverse clinical outcomes including VLST. Hong et al. evaluated the 705 native lesions (sirolimus eluting stent : 538 lesions, paclitaxel eluting stent : 167 lesions) by serial IVUS exam, and found the late ISA occurred in 85 lesions (12.1%) in overall, 71 lesions (13.2%) in sirolimus eluting stents, and 14 lesions (8.4%) in paclitaxel eluting stents. Total stent length, primary stenting in acute myocardial infarction, and chronic total occlusion were identified as predictors of late ISA. However, during 10-month follow-up after detection of late ISA, no patients with late ISA suffered from major adverse cardiac events. Furthermore, during the 3 year follow up, there was no significant difference regarding major cardiac event including VLST between in patient with and without late ISA. In other published trials, no adverse clinical events have been associated with late ISA after DES implantation. However, the number of patients studied was small and thus these studies underpowered to detect the causal association.

To sum up, it is obvious that late ISA is common after DES implantation, but there is a large amount of uncertainty whether the late ISA might be a risk factor for the VLST, mainly due to low incidence of this phenomenon. Therefore, further large studies to clarify this issue are required.