Lithotripsy of Calcified Aortic Valve Leaflets by a Novel Ultrasound Transcatheter-Based Device

Figures

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  Figure 1. Scheme illustrating the main components of the trans-catheter debridement device (TDD) in the configuration as it was employed for the in vivo trial. The device consists of two piezoelectric transducers that can be juxtaposed to deliver shockwaves on both sides of the region of treatment. The impulse-transducing cables are inserted into an intravascular catheter and operated by a handle at the other extremity to deploy and de-sheath the device.

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  Figure 2. Validation of the TDD on living porcine pericardium. (A,B) Show the two sides of a pericardial patch stained with 3-(4.5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT; purple color). The region encircled by the dotted rectangle indicates the part that was exposed to shockwaves and does not exhibit any staining reduction, suggesting maintenance of an excellent vitality of the tissue. (C) Shows the transversal section of another section of living pericardium treated with the TDD. It is evident from the high magnifications in the lower part of the panels that cells in the treated regions are in the same amount as in the untreated portions. Quantifications of nuclei are present in D, showing no difference in the nuclei counting in treated vs. untreated portions. Bar graph displays the mean and the SE of data (n = 3 independently treated pericardial samples; p > 0.05 by paired Student's t-test).

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  Figure 3. Treatment of calcific aortic valve disease (CAVD) leaflets by TDD. (A,B) Show the sequence of the human CAVD leaflets mounting in the debridement device. After preparation, leaflets were individually placed among the two piezoelectric transducers and immersed into a phosphate-buffered saline (PBS) solution for the treatment. After treatment, the orientation of the treated zones (TR) was marked with a surgical pen to distinguish them from the untreated portions (UT). These marks were taken as a reference for histological sectioning that occurred in a transversal orientation as indicated in the lower right panel in (B). (C,D) And the high magnifications of the histological regions represented therein (E,F) show the difference in the aspect of the calcifications in control (C,E) vs. the treated calcific leaflets (D,F). It is remarkable that in control tissues there was a net boundary between the calcific lesions (removed by sectioning; CLB) and the surrounding sclerotic tissue (red arrows in E). By contrast in treated tissues, the boundaries were less sharp (yellow arrows) and granular-like deposits (yellow asterisks) appeared around the lesions, suggesting a partial debridement of…

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  Figure 4. Angiographic and echocardiographic assessment of successful TDD deployment and leaflet treatment with a trans-femoral access in vivo. (A) Shows the deployment of the device through the femoral artery from an initial position at the level of the ascending aorta and down to the positioning of the piezo in the Valsalva sinus of the right aortic valve leaflet. (B) Shows three images of an echocardiographic sequence showing the motion of the valve leaflets in the presence of the piezo deployed at the level of the right leaflet. The pictures of the sequence show, respectively, the correct closure of the three leaflets before piezo deployment (left picture), the closure of the valve after piezo deployment (center picture), and the opening of the left (L) and the non-coronary (NC) leaflets or the blockade of the right (R) leaflet by the deployed piezo at systole (right picture). The complete sequence is provided as Supplementary Video 1. (C) Shows, finally, static images of the angiography and the echocardiographic sequences during activation of the piezo. It is evident on the right the interference of shockwaves with the ultrasounds, making it impossible to distinguish the structure of…

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  Figure 5. Histological sectioning of the right (a), non-coronaric (b), and left (c) leaflets of the aortic valve treated with TDD in Figure 4 from commissure to commissure and along a radial direction stained with hematoxylin/eosin and Masson's staining solutions. The right leaflet, treated with the TDD (a), showed evident signs of superficial damage (arrows in magnification inset) that were contained within the superficial portion of the fibrosa (Fib) identifiable on the aortic (Ao) side of the valve due to its intense blue staining. In no case the ventricular portion (V) or the ventricularis (Ve) or the spongiosa (Sp) layers exhibited signs of tissue damage.