Refractory rapidly progressive diffuse in-stent restenosis with left main involvement: a case report

Drug-eluting stents (DES) have significantly reduced the incidence of in-stent restenosis (ISR). However, a subset of patients still develop refractory, rapidly progressive, and diffuse ISR, which poses substantial therapeutic challenges and reflects its complex underlying mechanisms. We report a 46-year-old male who underwent five percutaneous coronary interventions (PCI) over five years, with repeated diffuse ISR in the left anterior descending artery (LAD). Initial PCI was followed by DCB therapy after first ISR, achieving temporary symptom relief. Four years later, ISR progressed to chronic total occlusion, requiring further stenting and DCB therapy. Within five months, he developed 99% LM stenosis and recurrent LAD ISR. Despite a SYNTAX score of 36 favoring CABG, the patient refused surgery. Under intra-aortic balloon pump support, a balloon-only PCI (stent-less) strategy was performed. IVUS revealed diffuse fibrous proliferation and neoatherosclerosis. During follow-up, the patient remained clinically stable overall. This case highlights a potential systemic hyperproliferative phenotype, in which repeated vascular injury triggers accelerated neoatherosclerosis and intimal hyperplasia. It challenges the conventional view of ISR as a local mechanical problem and underscores the importance of mechanism-driven risk stratification and individualized management, particularly when standard surgical therapy is declined.