Abstract 356 Transcatheter aortic valve replacement leads to plasmatic alterations in patients resulting in enhanced endothelial function in aortic ring bioassay

Background: Transcatheter-assisted aortic valve replacement (TAVI) is proven to be a successful therapy for patients with severe symptomatic aortic valve stenosis. Previous studies revealed endothelial dysfunction in aortic valve stenosis which can be converted by valve replacement. It is known that nitric oxide (NO) bioavailability and the effect other circulating plasmatic factors are relevant for endothelial homeostasis. Still, underlying mechanism of endothelial improvement due to TAVI are still unknown.

Purpose: Here, we aimed to verify that plasmatic factors may be modulated by TAVI and result in enhanced endothelial function in aortic ring bioassay in short term analysis.

Methods: Thoracic aortic segments from male 12-week-old wildtype mice (C57Bl/6) were excised as target organ to analyse the impact of plasmatic factors on endothelial function. Blood samples were collected from patients before and one to three days after TAVI and used immediately afterwards. Aortic segments were analysed with plasma from the same patients before and after TAVI. The aortic rings were co-incubated with plasma, placed in the organ bath and processed according to established standard procedure using phenylephrine and acetylcholine to assess endothelial function of the target organ.

Results: The organ bath technology investigates the changes in relaxation of the aorta under influence of acetylcholine according to standardized protocols. Co-incubation of aortic rings with human plasma showed that endothelium-dependent relaxation with acetylcholine was significantly improved after aortic valve replacement compared to analysis before valve replacement (Maximum relaxation before TAVI 71.33 ± 17.79% vs. maximum relaxation after TAVI 83.86 ± 16.18%, p = 0.0079).

Conclusions: The organ bath experiments with murine aortic segments as target organ show increased endothelium dependent relaxation of the aorta with plasma after TAVI compared to plasma before valvular intervention. This is attributable to modulated circulating systematic plasmatic factors and may mirror altered nitric oxide bioavailability. This elucidates underlying signaling cascades causing endothelial dysfunction in aortic valve stenosis and may explain endothelial improvement after valvular replacement.

Clin Res Cardiol (2021) DOI DOI https://doi.org/10.1007/s00392-021-01843-w
Transcatheter aortic valve replacement leads to plasmatic alterations in patients resulting in enhanced endothelial function in aortic ring bioassay
M. Nankinova¹, I. Gyamfi-Poku¹, T. Zeus¹, M. Kelm¹, C. Quast¹
¹Klinik für Kardiologie, Pneumologie und Angiologie, Universitätsklinikum Düsseldorf, Düsseldorf;
Background: Transcatheter-assisted aortic valve replacement (TAVI) is proven to be a successful therapy for patients with severe symptomatic aortic valve stenosis. Previous studies revealed endothelial dysfunction in aortic valve stenosis which can be converted by valve replacement. It is known that nitric oxide (NO) bioavailability and the effect other circulating plasmatic factors are relevant for endothelial homeostasis. Still, underlying mechanism of endothelial improvement due to TAVI are still unknown. Purpose: Here, we aimed to verify that plasmatic factors may be modulated by TAVI and result in enhanced endothelial function in aortic ring bioassay in short term analysis. Methods: Thoracic aortic segments from male 12-week-old wildtype mice (C57Bl/6) were excised as target organ to analyse the impact of plasmatic factors on endothelial function. Blood samples were collected from patients before and one to three days after TAVI and used immediately afterwards. Aortic segments were analysed with plasma from the same patients before and after TAVI. The aortic rings were co-incubated with plasma, placed in the organ bath and processed according to established standard procedure using phenylephrine and acetylcholine to assess endothelial function of the target organ. Results: The organ bath technology investigates the changes in relaxation of the aorta under influence of acetylcholine according to standardized protocols. Co-incubation of aortic rings with human plasma showed that endothelium-dependent relaxation with acetylcholine was significantly improved after aortic valve replacement compared to analysis before valve replacement (Maximum relaxation before TAVI 71.33 ± 17.79% vs. maximum relaxation after TAVI 83.86 ± 16.18%, p = 0.0079). Conclusions: The organ bath experiments with murine aortic segments as target organ show increased endothelium dependent relaxation of the aorta with plasma after TAVI compared to plasma before valvular intervention. This is attributable to modulated circulating systematic plasmatic factors and may mirror altered nitric oxide bioavailability. This elucidates underlying signaling cascades causing endothelial dysfunction in aortic valve stenosis and may explain endothelial improvement after valvular replacement.
https://dgk.org/kongress_programme/jt2021/aP1306.html