Deleterious Effect of Coronary Brachytherapy on Vasomotor Response to Exercise

BACKGROUND: Intracoronary radiotherapy (brachytherapy) has been proposed as treatment option for in-stent restenosis. Long-term results of brachytherapy with regard to vascular integrity and vasomotor responsiveness are unknown. The purpose of the present study was to determine the vasomotor response after brachytherapy and to assess its influence on vasomotion during exercise. METHODS AND RESULTS: Biplane quantitative coronary angiography was performed at rest and during bicycle exercise in 27 patients with coronary artery disease. Fourteen patients underwent coronary stenting and were studied 10+/-3 months after intervention (control group). Thirteen patients were treated with brachytherapy (Guidant Galileo System) for in-stent restenosis with a mean dosis of 20 Gy at 1 mm into the vessel wall and were studied 9+/-1 months after radiation (brachytherapy group). Minimal luminal area, stent area, and proximal, distal, and a reference vessel area were determined. The reference vessel showed exercise-induced vasodilation (26+/-4%, P<0.001) in both groups. Vasomotion within the stented vessel segments was abolished. In control subjects, the proximal and distal segments showed exercise-induced vasodilation (17+/-2% and 22+/-7%, respectively; P<0.005). In contrast, there was exercise-induced vasoconstriction in the proximal and distal vessel segments of the brachytherapy group (-14+/-3% and -16+/-4%, respectively; P<0.01). Sublingual nitroglycerin was associated with maximal vasodilation of the proximal and distal vessel segments in both groups. CONCLUSIONS: Normal vessel segments elicit flow-mediated vasodilation during exercise. Stent implantation does not affect physiological response to exercise proximal and distal to the stent. Brachytherapy eliminates exercise-induced vasodilation, although dilatory response to nitroglycerin is maintained, suggesting endothelial dysfunction as the underlying mechanism.