Valvuloplasty with a paclitaxel-eluting balloon prevents restenosis in an experimental animal model of aortic stenosis.

Abstract Restenosis occurs invariably within 12 months following balloon valvuloplasty (BAV) in calcific aortic valve disease (CAVD), and is a limiting factor of this treatment. Cellular proliferation secondary to balloon injury is thought to play a pivotal role in the mechanism of restenosis. The study aim was to investigate the potential role of a paclitaxel-eluting valvuloplasty balloon to mitigate the progression of restenosis in an animal model of CAVD. Fifty-three rabbits were fed with an aortic stenosis (AS)-inducing diet (cholesterol 0.5% plus vitamin D3 50,000 IU/day) for three months. The surviving animals (n = 40) underwent echocardiographic and invasive assessments, followed by valvuloplasty, randomly using either a paclitaxel-coated (3 μg/mm2) or a plain balloon. At one month after BAV, the surviving animals (n = 28) underwent repeat assessments, followed by histology and micro-computed tomography (MicroCT) analysis of the aortic valve. The baseline and post-BAV transvalvular gradients, aortic valve area (AVA), left ventricular stroke work loss (SWL) and aortic valve resistance (AVR) were similar between the groups (14 rabbits were assigned to paclitaxel-eluting, and 14 to plain balloon). Significant differences between the groups were observed at one-month post-BAV, which was suggestive of diminished restenosis in the paclitaxel-balloon group (mean maximum transvalvular pressure gradient 7.7 ± 7.7 versus 3.6 ± 3.7 mmHg, p = 0.08; AVA 0.91 ± 0.59 versus 0.55 ± 0.22 cm2, p = 0.04; SWL 3.5 ± 4.0 versus 8.6 ± 8.0%, p = 0.047; AVR 86 ± 71 versus 177 ± 137 dynes/s/cm(-5), p = 0.039). Histology demonstrated decreased leaflet thickness (0.60 ± 0.15 versus 0.71 ± 0.17 mm, p = 0.03), proliferating cell nuclear antigen (PCNA) staining (grade 1.53 ± 0.04 versus 2.24 ± 0.55, p = 0.049), and calcification in the paclitaxel-balloon group. Use of a paclitaxel-eluting valvuloplasty balloon in an animal model of AS resulted in attenuated restenosis, secondary to decrease in valve proliferation and calcification.