Background: The optimal treatment strategy for isolated side branch (SB) lesions remains uncertain. In this study, the aim was to evaluate the safety and efficacy of drug-coated balloon (DCB) angioplasty for the treatment of de novo isolated SB stenosis.

Methods: This single-center, retrospective study included patients with symptomatic isolated SB occlusion who underwent percutaneous coronary intervention using DCB. The primary endpoint was procedural success, and the secondary endpoint was the occurrence of major adverse cardiac events, defined as death from all causes, myocardial infarction, target vessel revascularization, or revascularization of target lesions.

Results: Forty-eight patients were included between April 2022 and June 2025. The mean age was 62.8 ± 13.9 years, and the majority were male (n = 35, 72.9%). The cohort exhibited a high cardiovascular risk profile. Procedural success was achieved in 97.9% (n = 47). Thrombolysis in myocardial infarction grade 3 flow was obtained in all patients, with a mean residual stenosis of 26% ± 14.9. One patient (2.1%) required bailout stenting, and no cases of acute thrombosis were observed. During a mean follow-up of 423 days, 8 patients (16.7%) underwent repeat coronary angiography for angina, 6 patients (12.5%) required additional medical therapy, and 1 patient (2.1%) experienced myocardial infarction.

Conclusion: These findings suggest that, with appropriate lesion preparation and patient selection, DCB angioplasty represents a safe and feasible revascularization strategy for isolated SB occlusions. However, larger, controlled, and long-term studies are needed to confirm these results.