Background: Recently, very late in-stent restenosis (VL-ISR) is occasionally observed beyond a few years after drug-eluting stents (DESs) implantation. This study evaluated the process of progression of VL-ISR by analyzing serial coronary angiograms (CAG) and its correlation with neointimal tissue characterization of VL-ISR lesions.
Methods: The subjects were 50 DES VL-ISR in which more than 4 serial CAGs over a period of 2 years, including baseline, 8 months later, 6 to 12 months before VL-ISR, and at the time of VL-ISR, were performed. The degree of percent diameter stenosis at each CAG was classified either as none or mild (<15%), moderate (15% to 50%), or severe (>50%). All VL-ISRs were imaged by optical coherence tomography, and qualitative neointimal morphological analysis was performed. Fibroatheroma-like neointima was defined as neointima containing poorly delineated low-intensity region with invisible struts in >1mm.
Results: From the progression pattern, 29 VL-ISRs (58%) were categorized as marked progression (none or mild⇒none or mild⇒severe) and 21 (42%) as gradual progression (none or mild⇒moderate⇒severe, and moderate⇒moderate⇒severe). Marked progression VL-ISRs featured higher prevalence of unstable angina at the time of VL-ISR (68% versus 22%, p<0.01). The prevalence of fibroatheroma-like neointima was significantly higher in marked progression than in gradual progression VL-ISR (36% versus 11%, p=0.01). Conversely, gradual progression VL-ISR featured higher prevalence of stable angina, and higher incidence of high-intensity intima (72% versus 40%, p=0.02), and calcified intima (33% versus 8%, p=0.04).
Conclusions: A feature of future VL-ISR after DES was mild stenosis on CAG 8 months after stent implantation. A thrombogenic atheromatous neointima has a high probability of undergoing rapid progression, leading to VL-ISR. Two types of stenosis progression provide a new insight into the mechanism of VL-ISR after DES implantation.