Symptomatic severe aortic valve stenosis is a disease primarily found in patients of advanced age with substantially reduced life expectancy.1,2 The standard therapy is still the aortic valve replacement (AVR) during an open heart procedure.3 The patients are operated on via median sternotomy with cardiopulmonary bypass in cardioplegic arrest. Through a transverse aortotomy, the calcified aortic valve is excised. After sizing of the aortic annulus, the largest suitable prosthesis is implanted into the supra-annular position.
In contrast, transcatheter aortic valve implantation (TAVI) is a treatment for patients with symptomatic severe aortic valve stenosis ineligible for conventional AVR.4–9 A stented biological aortic valve is implanted through a catheter without the need for cardiopulmonary bypass via transapical, transaortic, transfemoral, or transsubclavian access.10 The patients’ calcified aortic valve is not resected but squeezed between the aortic wall and the transcatheter valve. This may lead to several complications in TAVI patients, such as paravalvular leakage (PVL), pacemaker necessity, and ostial coronary occlusion.11–16
To minimize the incidence of TAVI-related complications, various aortic valve stents have been designed (balloon-expandable valves or self-expanding valves), but these problems remain unsolved. Our research group works on the development of different resection tools for human calcified aortic valves during the TAVI procedure to improve the outcome of patients by minimizing TAVI-related complications.
The aim of this study was to investigate ex vivo different resection tools (laser scalpel, punching device, and scissors) for human calcified aortic valves concerning cross-section morphology.
With the use of 12 human calcified aortic valves, the effect of laser scalpel, punching device, and scissors (four aortic valves for each group) on cross-section morphology was investigated. The 12 heart valves were resected during conventional aortic valve resection and then subjected to the cutting experiments in the laboratory. All valves were severely calcified. The 12 heart valves were randomly distributed into the three groups to average possible nonvisible baseline differences concerning degree of calcification. Scanning electron microscopy (SEM) was applied to illustrate the cutting surface area. Samples were fixed in 0.1-M cacodylate buffer containing 2.5% glutaraldehyde and 0.5% paraformaldehyde at pH 7.4 for 24 hours. After dehydration in graded alcohols, the samples were critical point dried, mounted, and sputter coated with platinum-palladium. The samples were analyzed with a scanning electron microscope SEM 505 (Phillips, Eindhoven, The Netherlands).
For histological analyses, different aortic valve cross-section areas were fixed in 4% formaldehyde for 24 hours and gently decalcified. After embedding in paraffin, 1-μm–thick paraffin sections of the area of interest were stained with Elastica van Gieson-stain.
For laser cutting of calcified aortic valves, we used an Excimer laser (Spectranetics CVX-300; Spectranetics, Colorado Springs, CO USA) to deliver ultraviolet laser pulses with a wavelength of 308 nm, a flux of 30 mJ/mm2, as well as a repetition rate of 80 Hz and a pulse duration of 125 to 200 nanoseconds (full width at half maximum). The laser pulses were guided through a self-designed laser scalpel, made up of multiple single laser fibers. The tip of the scalpel was “scoop” shaped, and the single fibers formed a 130-degree curve with a diameter of approximately 7.5 mm (Fig. 1). During cutting, the tip of the laser was in direct contact with the calcified aortic valve tissue.
Conventional surgical scissors were used for cutting the human calcified aortic valve in typical procedure (Fig. 1).
A prototype aortic valve punching device was used to cut the aortic valve with one single punch (Fig. 1). The resulting circular cutting line (diameter of 19 mm) was planar and was originally designed for surgical resection of the calcified aortic valve in open heart surgery.
Quantitative Cutting Edge Analysis
Quantitative analyses of the histological cross-section areas were performed to evaluate differences between the three different aortic valve resection devices. Exemplarily, in Figure 2, the method for quantitative analysis of the roughness of the cutting area is illustrated. In a first step, the histological image was transformed into a gray-scale image (Fig. 2A). Then, at a randomly chosen point of the cutting area (square in Fig. 2A), an intensity line profile was generated perpendicular to the cutting edge with a width of 5 μm (Fig. 2B, triangles). Finally, a sigmoid edge function
Equation (Uncited)Image Tools
was simulated (Fig. 2B, solid line) fitting this line profile best, where f0, f1, and f2 are simulation parameters indicating a constant offset, the edge height, and the edge width, respectively. The edge width Δx as a quantitative value for the roughness of the cutting edge was calculated via Δx = f2 × 2 × 1n(3). As a comparison, cutting edges generated via the scissors and the punching device are plotted in Figures 2C and D, respectively.
The generation of an intensity profile and a simulation of a best-fitting edge were performed at 17 different points for each of the three histological samples.
Calculation and Statistics
Calculations and statistics were performed using GraphPad 4.0 software (GraphPad Software Inc., San Diego, CA USA). The Kruskal-Wallis test with the Dunn test for multiple comparisons was performed when comparing the three groups. Significance was defined as P < 0.05. Values were presented as median and interquartile ranges.
Scanning electron microscopy illustrated that the cutting surface area of the calcified aortic valves varies exceptionally between the three different resection tools: laser scalpel, scissors, and punching device (Fig. 3). The cross-section areas created by a laser scalpel were smooth, regular, and uniform, whereas these areas were rough, irregular, and inhomogeneous when using the scissors or the punching device.
The histological analyses confirmed the SEM illustrations and revealed a regular and uniform cutting area attained by the laser scalpel (Fig. 3). The cross-sectional areas created by the scissors or the punching device were more inhomogeneous.
Quantitative cutting edge analyses of the cross-section morphology delivered median cutting edge widths of 2.12 μm (interquartile range, 2.00–2.34 μm) for the laser scalpel, 2.76 μm (interquartile range, 2.52–3.35 μm) for the scissors, and 3.66 μm (interquartile range, 3.20–4.75 μm) for the punching device (Fig. 4).
Analysis of the edge widths—as a quantitative value for the roughness of the cutting area—demonstrated significant differences between the three resection tools laser scalpel, scissors, and punching device. The best results were obtained for the laser scalpel compared with the punching device (P < 0.001) and for the laser scalpel compared with the scissors (P < 0.05), whereas the scissors compared with the punching device showed no significant differences (P > 0.05) (Tables 1, 2, Fig. 4).
Transcatheter aortic valve resection may decrease the occurrence of TAVI-related complications, such as PVL, pacemaker necessity, and coronary ostial occlusion.11–16 The main reason for these TAVI-related complications is probably the in situ left native calcified aortic valve that is squeezed between the aortic wall and the implanted transcatheter valve. This causes uncontrolled movement of the calcified aortic leaflets.
Our study confirmed that laser resection of human calcified aortic valve tissue gave the best results concerning homogeneous cross-section morphology compared with the punching device and the scissors in an ex vivo model. To the best of our knowledge, this type of comparative study has been carried out for the first time. Aortic valve resection was first introduced by our group in 2005 using a water-jet scalpel and a resection chamber using a Hol:YAG laser.17 In 2009, Wendt et al18 reported on a minimally invasive aortic valve resection tool equipped with rotating and foldable Nitinol (Nitinol Devices & Components, Inc., Fremont, CA USA) cutting edges. Other aortic valve resection devices were presented by Bombien et al19 in 2010 using a valve isolation chamber and by Astarci et al20 in 2011 using a circular blade. All these projects have not yet obtained clinical approval. The question of whether the laser-cut surface will create a milieu for better tissue ingrowth compared with mechanical resection methods has to be addressed in future midterm in vivo experiments.
The next step will be to perform AVR via an advanced and miniaturized resection device in an acute porcine in vivo model. The operation will be a typical TAVI procedure with additional aortic valve resection. Here, besides feasibility tests of the device, the question of hemodynamical stability during acute aortic regurgitation will be of great interest.
To integrate AVR via laser or punching device, the protection from debris is of enormous importance. With a punching device—as proposed in this article—the aortic valve will be cut within one single step. Afterward, the device will be removed while still closed with the remnants of the valve inside. But still, a protection device is needed during the cutting procedure. For this, an operation chamber will be developed for antegrade and retrograde isolation as proposed by Bombien et al.19 These isolation elements will not consist of inflatable balloons but rather two mesh- or polyester-covered stentlike self-expanding structures that are pressed against each other and the native valve sandwiched in between. After AVR, this chamber will be removed in a closed and isolated manner.
A great advantage of the laser scalpel is the multiple, thin, and flexible laser fibers transferring the energy directly to the cutting zone. Therefore, a device is thinkable containing those fibers, fitting through the TAVI delivery system and spreading to the desired shape in the vicinity of the aortic valve. In direct contact mode of the fibers with the tissue, the tissue-blood interface will not represent a barrier in the application.
We believe that partial or complete transcatheter aortic valve resection before TAVI will further improve the patient outcome, but a number of developments are still needed for aortic valve resection devices. Aortic valve resection must be safe, fast, and easy as well as applicable during the TAVI procedure. It has to be proven that the remaining ring of native aortic tissue, after partial aortic valve resection, allows a stable anchoring scaffold for the transcatheter valve. The aortic valve resection device should pass through the TAVI delivery sheath of 24F (diameter of 7.9 mm) when performing transapical or transaortic access. Our self-designed laser scalpel tip was scoop shaped, and the single fibers formed in a 130-degree curve with a diameter of 7.5 mm, which can easily pass through the TAVI delivery sheath.
On the one hand, an additional protection device is needed to minimize the risk for embolization of leaflet debris during valve resection. Such embolic protection devices are already available from the industry. On the other hand, we have limited experiences with the hemodynamic situation at the time of acute aortic regurgitation induced by transcatheter aortic valve resection.
Our team is working on an optimized aortic valve resection device that can be integrated into the TAVI procedure in a safe, fast, and easy way. The planned animal trials will hopefully demonstrate the feasibility of our device and elucidate the hemodynamic stability immediately after aortic valve resection and before TAVI.
These results are gained from the first ex vivo study testing different resection tools concerning cross-section morphology of human calcified aortic valves. At the moment, we are not able to answer the question as to the influences of roughness of the cutting area of the aortic valve before TAVI on PVL or thrombogenicity. Further studies are needed, which our research team plans to pursue.
The quantitative cutting edge analyses reveal cutting edge widths in the range of a few micrometers. We have to note that this quantitative value depicts only the roughness of the cutting edge within this histological section of 1 μm. To make a statement of real roughness of the cutting surface, a complete surface topography of this area has to be measured. However, in comparing the quality of different cutting edges, the presented method is adequate, and—as long as histological sections are generated in the same manner and thickness—the results are reproducible and accurate.
Laser cutting of human calcified aortic valves demonstrated the best results concerning homogeneous cross-section morphology compared with the punching device and the scissors in an ex vivo model. Nonetheless, the laser scalpel and the punching device reveal as potential candidates for AVR during TAVI procedure in the future.
The authors thank Frank Lichte, Institute of Anatomy, Christian-Albrechts-University of Kiel, Kiel, Germany, for his valuable assistance in SEM studies and Katharina Heß, MD, Institute of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany, for her valuable support.
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This interesting experimental study examined the efficacy of a number of different resection tools for excising human calcified aortic valves in an ex vivo model. The laser scalpel, scissors, and a punching device were used, and the cutting surface area was examined with standard histology and electron microscopy. The laser scalpel had better results than either the punching device or the scissors. There were no significant differences between the scissors and the punching device. They concluded that the laser cutting device may have some advantages over the other tools. The readers should keep in mind that this was an ex vivo experiment and in vivo studies will need to be performed to better assess these different tools. However, the authors are to be congratulated on their work and their efforts to objectively evaluate these devices.