Abstract 16095: Attenuation of Aortic Valve Calcification With Local Delivery of Bisphosphonates
Introduction: Bisphosphonates have been proven to have a beneficial effect on inhibition of calcification in arterial wall of an experimental model.
Hypothesis: To evaluate the safety and effectiveness of local delivery of the bisphosphonate zoledronate on inhibition of calcium formation in an experimental animal model of aortic stenosis
Methods: Sixteen New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. Half of them were treated with local delivery of a mixture containing 500 μg/l zoledronate delivered on the cusps of the aortic valve (AV), by a dedicated balloon catheter. A placebo mixture was administered on rest eight animals, which were used as controls. PET/CT imaging was performed in the ‘zoledronate group” at 3 weeks of atherogenic diet and at 28 days after local drug delivery. 18F-NaF in a standard volume of 1ml was injected intravenously. PET imaging was preceded by CT for attenuation correction and anatomical localization of the PET images. The progression of calcification was assessed by calculating the difference in SUVmax, SUVmean, TBRmax and TBR mean at baseline and at follow up both for AV and ascending aorta (AA). After the second PET/CT examination all animals were sacrificed and all aortic valves were collected and analyzed by histology. The difference between the extent of calcification between the proximal part of the aorta and the cusps was calculated and assigned as ΔC.
Results: In all animals the local delivery of zoledronate and placebo mixtures was successful and uncomplicated. In the zoledronate group, SUVmax and SUVmean showed an attenuation of calcification in AV compared to AA (0.34±0.23 vs 0.11±0.20, p=0.09 for SUVmax and 0.21±0.55 vs 0.19±0.19, p=0.90 for SUVmean). TBR max and TBR mean showed a decrease in calcification in the AV compared to the AA (0.17±0.55 vs -0.24±0.53, p=0.21 for TBR max and 0.78±0.74 vs -0.12±0.50, p=0.032 for TBR mean). Histology confirmed the findings of PET/CT The animals treated with zoledronate had more extended calcification in their AA compared to the calcification observed at the AV. (ΔC: 6.72 vs 3.36, p<0.001)
Conclusions: Local delivery of zoledronate in the aortic cusps of an experimental model of aortic stenosis results in an attenuation of the progress of calcification
Author Disclosures: A. Synetos: None. K. Toutouzas: None. M. Drakopoulou: None. K. Stathogiannis: None. G. Agrogiannis: None. K. Anagnostopoulos: None. A. Papalois: None. D. Cokkinos: None. E. Patsouris: None. D. Tousoulis: None.
- © 2016 by American Heart Association, Inc.