Dose volume histogram assessment of late stent malapposition after intravascular brachytherapy

Purpose: Positive remodeling and decreased neointima proliferation are among the causes for Late Stent Malapposition (LSM). It was our interest to investigate a possible relationship between dose and incidence of LSM. Methods: Index and follow up IVUS examinations of 238 patients (152 treated with Intravascular Brachytherapy (IVBT), 86 control) enrolled in IVBT trials were reviewed to identify patients with LSM. 7.2% of patients treated with IVBT and 2.3% of patients in the control group were found to have LSM on their 6-month follow-up IVUS. Using the index IVUS study. Dose Volume Histograms (DVH) were constructed for a segment of the adventitia comprising an arc deep to the area where LSM is present at follow up. For control, two areas: an arc deep to complete apposition (Control 1) and a segment within the stent but 5 mm apart from the LSM (Control 2). Volumes were defined by IVUS images that were 1 mm apart and the media-adventitial contour was taken to be 0.5 mm thick from the border. Results: DVH of 90% and 50% adventitial volume of LSM area received a significantly (p<0.05) higher dose compared to both controls. Calculated are 12 LSM sites in 9 patients and 9 control sites. At all 12 sites Mean Cross Sectional Area of External Elastic Membrane (EEM CSA) was significantly larger in the LSM group at follow up compared to index (p-0.001). Conclusions: DVH analysis showed a positive correlation between radiation dose to the adventitia and incidence of LSM. The myofibroblasts in the adventitia are known to be the target for irradiation. Proliferation of myofibroblasts leads to neointima formation. LSM may be due to the higher dosages delivered to 50% and 90% of the adventitia volume (LSM area) which may have led to profound neointima suppression. In turn the neointima could not compensate positive remodeling reflected by an increase in EEM CSA.