The advent of temporary mechanical circulatory support for the failing left ventricle has been life-saving for selected patients awaiting heart transplantation (1
). Despite the success of this LVAD-bridging to transplant, many mechanically supported heart transplant candidates develop circulating anti-HLA antibodies with potential donor reactivity, manifest as an elevation of the PRA (2
). Having an increased PRA has been shown to increase transplant waiting times (15
) and leads to adverse clinical outcomes even after a crossmatch compatible transplant (7
Our data identify an increased PRA prior to LVAD implantation as a risk factor for developing a high-degree (PRA>90%) HLA allosensitization that tends to persist in time.. The patients who were sensitized prior to LVAD implantation included a higher proportion of women. It has been described that women are more likely to have an increased PRA level prior to LVAD implantation (16
). However, Massad et al documented that post LVAD implantation increases in PRA levels do not correlate with gender (16
). Our data also suggest that while female gender is a risk factor for elevated PRA, gender does not seem to be associated with increased risk of becoming or remaining highly sensitized following LVAD implantation.
Perioperative transfusions could represent a plausible confounding factor. It has been suggested that perioperative transfusion of cellular blood products increase sensitization after LVAD implantation (4
). However, we have previously shown that avoidance of perioperative cellular transfusions did not decrease the incidence or degree of HLA sensitization (18
). Conversely, transfusions may be associated with less alloimmunization and may mitigate the sensitization seen in bridge to transplant LVAD recipients (19
). Whatever the effect of transfusions on sensitization might be, there were no significant differences between the number of cellular transfusions administered to any group or subgroup of patients compared in our analysis.
In HM I patients, the duration of support in both the pre-LVAD sensitized patients and in those who were not sensitized prior to implantation was similar. The duration of support in the highly sensitized patients of the non pre-LVAD sensitized subgroup tended to be longer than in their counterparts in the pre-LVAD sensitized subgroup (). However, it has been shown that longer duration of support does not provide a continuous increased risk for allosensitization (16
). Pagani et al, demonstrated that the median duration of support time to peak PRA was less than forty days (20
). We have shown that sensitization is a phenomenon that typically occurs during the first 3 months of mechanical support (11
). Thus, it seems that post LVAD sensitization is a phenomenon that would occur relatively early after LVAD implantation and further prolongation of LVAD support would not add to the likelihood of becoming sensitized. Therefore, given the fact that the duration of support for both sensitized and non sensitized pre-HM1 LVAD subgroups was well beyond this time limit where sensitization would be expected, comparing the sensitization rate and degree between these groups seems appropriate.
However, the same rationale might not apply when comparing the rates and degree of de-
sensitization. The fact that the highly-sensitized patients of the pre-HM I non-sensitized subgroup had longer duration of support raises the possibility that they decreased their HLA antibodies while their highly sensitized counterparts in the sensitized pre-HM I subgroup did not because the latter were given less time to do so. However, Kumpati and colleagues showed that the temporal pattern of sensitization consisted of a rapid increase followed by a rapid progressive decrease, and their data showed a decrease in sensitization occurring within 4 months of becoming sensitized (21
). Our own data show a similar trend. Therefore, given the average duration of support in these two groups of patients we would not attribute the differences in decreasing the degree of sensitization to the observed trend for different duration of LVAD therapy.
The effects of the LVAD type on the host immune system could have potentially important clinical consequences when considering LVAD implantation as a bridge to transplant in patients at high risk for development of sensitization. Host interactions with device biomaterials, specifically the textured chamber surface found in the HM I LVAD, have been proposed as one of the mechanisms responsible for an increased immunologic and inflammatory response seen after LVAD support (3
). The pseudointima formed on the textured surface of the HM I device contains an abundance of T cells, macrophages, and monocytes and reflects the constant interaction of blood with the device (3
). Specifically, aberrant T-cell activation on the LVAD surface, defective T-cell proliferation and polyclonal B-cell hyperreactivity with CD40 ligand interactions have been observed post LVAD implantation (3
Newer generation axial-flow devices such as HM II have been hypothesized to result in lower immunologic and inflammatory response than HM 1. Plausible explanations are the lower overall textured surface area (which is limited to the inflow cannula in HM II device) and the absence of biologic valves. Yet, this issue has not been adequately investigated; one study of 14 patients receiving axial-flow DeBakey device reported that no patients became sensitized during mechanical support (24
). George et al (25
) compared sensitization rates between HM I devices (n=36) and axial flow devices (HM II or DeBakey, n= 24) and and found that HM I was associated with significantly increased incidence of allosensitization (28% vs 8%) which is consistent with the results of our study. These findings are encouraging given the current trend towards increased use of continuous flow assist devices.
The limitations of this study include those related to a retrospectively performed analysis. Data were obtained by means of chart and electronic database review, which has inherent limitations, such as access and accuracy of the data. The small number of HM II patients included in our study and the uneven number of patients in the two groups are additional limitations of our study.
In conclusion, presensitized patients seem to be at higher risk for becoming and remaining highly HLA allosensitized after LVAD implantation. Furthermore, HM II LVAD appears to cause less sensitization than HM I LVAD. Therefore, when considering LVAD implantation as a bridge to transplant in patients at increased risk for development of sensitization, newer-generation continuous-flow devices should be given preference. Further research is warranted to validate these results.