P368Quantitative echocardiographic assessment of preventive therapy for aortic valve calcification in a rat model of renal failure

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Background: valve calcification is an independent prognostic factor in patients with aortic valve disease. End-stage renal disease (ESRD) and secondary hyperparathyroidism increase the risk of cardiac and vascular calcifications. Since calcimimetics inhibit parathyroid hormone (PTH) secretion and may decrease these calcifications, we studied the preventive effects of the research calcimimetic R-568 on aortic valve calcifications in an in vivo rat model of progressive ESRD with secondary hyperparathyroidism, by means of echocardiographic calibrated integrated backscatter (cIB).Methods: 36 male Wistar rats were prospectively divided in four groups: groups 1 (n=10) and 2 (n=10) received a 0.5% adenine diet to induce renal failure. Groups 3 (n=8) and 4 (n=8) received a normal diet. Groups 2 and 4 received daily R-568 (30 mg/kg) during 8 weeks, while groups 1 and 3 received the vehicle. Blood parameters (calcium (Ca), phosphorus (P), PTH) and cIB values were measured at baseline and after 8 weeks. Ex-vivo micro-CT was used to confirm the calcifications.Results: There were no significant differences between baseline values. At week 8, we observed a significant decrease of cIB values of the aortic valve in the treated group 2 (15.1 ± 0.5) compared to group 1 (18.0 ± 1.0, P < 0.05). This was confirmed by a decreased calcified volume on ex-vivo micro-CT. In group 2, we found a significant decrease of plasma Ca x P (group 1: 200 ± 10 mg2/dl2; group 2: 122 ± 21 mg2/dl2; P < 0.05) and PTH (group 1: 2724 ± 506 pg/ml; group 2: 348 ± 130 pg/ml; P < 0.001).Conclusion: Calibrated integrated backscatter is a promising, non-ionising and non-invasive technique for the quantitative echo assessment of aortic valve calcifications in vivo. With this technique, it was shown that the calcimimetic R-568 was able to reduce aortic valve calcifications in a rat model of progressive ESRD with secondary hyperparathyroidism.

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