Abstract 17995: Inhibition of Aortic Valve Calcification by Local Delivery of Bisphosphonates

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Introduction: The mainstay of treatment for symptomatic aortic valve (AV) stenosis is AV replacement.

Hypothesis: Although bisphosphonates are compounds known to prevent medial vascular calcification, their effects on aortic calcification remain unknown. The aim of this study was to evaluate in an experimental model the effectiveness of zoledronate on the inhibition of calcium formation.

Methods: Sixteen New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. At that time all animals underwent cardiac ultrasound to assess aortic stenosis and PET/computed tomography (CT) with 18F-NaF to assess calcification severity. Thereafter, 8 animals were subsequently treated with local delivery of a mixture containing 500 μg/l zoledronate that was delivered on the cusps of the aortic valve, by a dedicated balloon catheter. A placebo mixture was administered on the rest 8 animals (control group). At 28 days all animals underwent a follow-up cardiac imaging with PET-CT 18F-NaF. 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

Results: A total of 48 cusps were examined. The cusps treated with zoledronate had less calcium compared to the placebo group (16.40±0.90 vs 24.88±1.90%, p<0.0001). The ascending aortas (AA) of both groups showed similar expression of calcium (23.58±4.43 vs 23.12±5.05%, p=0.78). Regarding PET/CT analysis in the zoledronate group, TBRmean and TBRmax at the AA showed a significant increase of calcification (1.31±0.11 versus 1.63±1.84, p=0.001 and 1.42±0.11 versus 1.64±0.20, p= 0.001). In the same group TBRmean and TBRmax at the AV did not show any significant change in calcification (1.20±0.12 versus 1.17±0.78, p=0.29 and 1.30±0.33 versus 1.40±0.67, p=0.08). Interestingly, TBRmean showed a regression of calcification of the AV compared to AA (-0.34±0.07 versus 0.30±0.11, p=0.01).

Conclusions: Inhibition of aortic valve calcification by local delivery of zoledronic acid is feasible and effective.

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