The HeartWare cannula has shown roughness of 8.0 and 6.1 μm for the internal and the external surfaces, respectively. In contrast, the HeartMate II cannula showed a 374.3 μm roughness in both surfaces.
As a general indication, the Ti alloy used to manufacture the VAD cannulas is the Ti6Al4V alloy approved from the FDA. The thermal treatments used to fabricate and model the inflow cannulas are responsible of some metal segregation that modifies the composition of the cannula surfaces. In addition, also the Ti6Al4V alloy can contain other metals in low concentrations that, because of the thermodynamic surface segregation phenomenon, can be evidenced only with a surface-sensitive technique (XPS).
X-Ray Photoelectron Spectroscopy
X-ray photoelectron spectroscopy measurements have been performed to characterize the chemical composition of the surfaces. XPS enables in-depth chemical and structural characterizations and allows for a qualitative and quantitative analysis of elemental composition as well as oxidation states. It is important to bear in mind that XPS probes a few tenth of angstroms of surface. Therefore, the XPS composition can show major differences with respect to EDX results.
X-Ray Photoelectron Spectroscopy of the HeartMate II Cannula
Figure 6 shows the XPS of the internal surface of the HeartMate II cannula in the Ti 2p energy region. There are two strong and clear signals at 458.6 and 464.4 eV, typical of Ti 2p5/2 and Ti 2p3/2 spin–orbit components of the TiO2 phase.24–26 This result is rather important because the surface that will be in strong contact with the blood is TiO2 instead of Ti. The XPS atomic concentration analysis reveals also a relevant presence of silicon,17 being the surface ratio Si/Ti = 0.38, and some Al, being the ratio Al/Si = 0.05. No evidence of S was found. Therefore, the Ti6Al4V alloy used to manufacture the cannula contained some Si that segregated onto this cannula surface.
X-Ray Photoelectron Spectroscopy of the HeartWare Left Ventricular Assist Device Cannula
The XPS atomic concentration analysis of the HeartWare internal cannula reveals increased Si and Al surface concentrations Si/Ti = 0.41 and Al/Si = 0.14 as compared to the HeartMate II. No Si presence was observed with EDX analyses in both HeartMate II and HeartWare cannulas. Therefore, the Si presence is confined to the topmost surface layers. Titanium is present only as TiO2 on the surface.27,28 In addition, a small but evident presence of lead, Pb/Ti = 0.01, was also found on the internal surface (Figure 7A) with the Pb 4f7/2 and Pb 4f5/2 spin–orbit components at 138.5 and 143.4 eV, respectively, and typical of the PbO phase.29
Importantly, Figure 7B shows the XPS of the HeartWare cannula in the S 2p energy region. There is a strong and clear signal at 169.1 eV typical of the SO4 - group, as expected for a thin heparin film.30 This signal was absent in the HeartMate II cannula.
Our study is the first addressing the physicochemical characterization of LVADs’ surfaces with techniques that allow high vertical resolution, providing information on the bonding states of molecules and on the elemental composition of the surfaces; moreover, morphological and quantitative results have been obtained.
Thromboembolic complications may result from ingestion of thrombi grown around the inflow cannula at the implant site in the left ventricle, especially in the presence of stasis or suction.
To improve the biocompatibility of the foreign material, pseudo-endothelial artificial surfaces have been implemented in LVADs. Two major groups of coating can be distinguished: bioactive (heparin, nitric oxide) and biopassive (albumin, phosphorylcholine). Heparin interferes with the physiological hemostasis but the duration of the immobilized heparin on the surfaces of the LVAD is not known over the time and phenomena of superficial thrombosis are often observed on LVAD surfaces and no consistent benefits of coating of artificial surfaces has yet been shown.
Few data are available on the role of the physicochemical properties of foreign surfaces and thrombosis: Ellingensen27 reported that oxide layers increase the surface hydrophobicity thus causing greater adsorption of proteins. In contrast to this view, other authors indicated an increased compatibility of blood with the titania layer.28
The rates of pump thrombosis in the HeartMate II and HeartWare series have been identified as major issues.31,32 In the HeartWare LVAD ADVANCE trial, these events prompted the introduction of sintering with titanium microspheres and the intensification of antiplatelets. Exchange rates for suspected pump thrombus were analyzed for those events occurring before the anticoagulation adjustment and device design enhancements (on or before March 15, 2011) compared with those occurring post-adjustment and design enhancements (after March 15, 2011 through July 30, 2012). The total number of patients at risk pre-adjustment was n = 253, and the total number at risk post-adjustment was n = 211. Event rates decreased from 0.065 event/person per year (PPY) to 0.028/PPY.31,32
Similarly, Starling et al. 33 observed an increasing incidence of early thrombosis with the HeartMate II. The occurrence of confirmed pump thrombosis increased steeply after approximately March 2011, from 2.2% (95% confidence interval [CI]: 1.5–3.4) at 3 months after implantation to 8.4% (95% CI: 5.0 to 13.9) by January 2013. The risk of pump thrombosis peaked at 1.4% per month within 1 month after implantation before decreasing to a constant risk of 0.4% per month, with estimated occurrences of 4.7% during HeartMate II support for 6 months, 7.5% during 12 months of support and 12.3% during 24 months of support.
Our study has shown major differences between the HeartWare and HeartMate II. First, as far as the external surfaces, its roughness is much more pronounced for the HeartMate II device. Moreover, the HeartMate II cannula is totally covered with Ti nanospheres, while the HeartWare cannula shows only the lower external aspect covered with Ti sintered microspheres. In addition, the internal surfaces of the cannulas of these two devices are totally different: in fact, the HeartWare system shows no Ti microspheres and the surface roughness is ~8.0 μm while the HeartMate II cannula showed a ~374 μm roughness in both surfaces. Furthermore, no heparin was observed on the internal surface of the HeartMate II device.
In the light of these data, the HeartMate II and HeartWare LVAD have major differences in the physicochemical characteristics of their inflow cannula, albeit both sintered with titanium microspheres; whether these turn into major clinical outcomes warrants further studies. Structural inflow cannula changes and improvements of biocompatibility might turn into pivotal positive results in the clinical setting.
The combination of the analytical techniques applied in this study is unique in this field and could play interesting in evaluating innovations in structural changes and biocompatibility of artificial surfaces.
In conclusion, this is the first study addressing the physicochemical characteristics of LVADs. Both HeartWare and HeartMate II LVADs show sintered titanium microspheres on the inflow cannulas. The two surfaces are, however, significantly different both macroscopically (in terms of design of the inner and outer side of the cannula and of smooth and rough surfaces) and microscopically (sintering of titanium microspheres). In both HeartWare and HeartMate II inflow cannulas the surface titanium is present as TiO2 with no zero-valent Ti. In the light of these data, further studies are warranted to address the interaction of the artificial surfaces of LVADs and blood coagulation, their correlations with thromboembolic complications, and eventually the optimization of anticoagulation.
A. Gulino and F. Pappalardo thank INSTM and Regione Lombardia for the financial support of the BIOSUOVAD project, 2013. A. Gulino thanks the University of Catania. The authors are indebted to O. G. Turla, CCP, for his continuous support and for data collection.
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left ventricular assist device; X-ray photoelectron spectroscopy; scanning electron microscopy; energy dispersive X-ray; heart; thrombosis
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