Clinical outcomes in sensitized heart transplant patients bridged with ventricular assist devices

Kidambi, S.; Mohamedali, Burhan; Bhat, Geetha

doi:10.1111/ctr.12540

Cited by 27 publications

(17 citation statements)

References 22 publications

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“…Presensitization to HLA is an important barrier to transplantation with sensitized patients experiencing longer wait times for suitable organs and higher waiting list mortality rates [15]. In addition, presensitized patients may exhibit reduced post-transplant survival [5] [17]. Recent studies have linked VAD-induced HLA-sensitization with an increased rate of PGD [4], increased risk of rejection [15] and mortality [5].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, presensitized patients may exhibit reduced post-transplant survival [5] [17]. Recent studies have linked VAD-induced HLA-sensitization with an increased rate of PGD [4], increased risk of rejection [15] and mortality [5]. Much less is known about the impact of VAD on non-HLA antibodies and their influence on transplant outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that leukodepeleted blood transfusions received by VAD patients at our center contributed to sensitization. However, previous studies suggest that such sensitization is independent of transfusions [2] [5] [34]. …”

Section: Discussionmentioning

confidence: 99%

“…Mechanical circulatory support, in the form of ventricular assist device (VAD) implants, has also been associated with sensitization in multiple studies [2] [3] [4]. In some reports, sensitization consequent to VAD increased the incidence of antibody-mediated rejection (AMR), thereby impacting on the overall clinical outcome [5]. To date, the immune mechanism causing continuous flow devices to elicit anti-HLA antibodies is still elusive.…”

Section: Introductionmentioning

confidence: 99%

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Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

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Clerkin

Kennel

et al. 2017

The Journal of Heart and Lung Transplantation

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Background Pre-transplant sensitization is a limiting factor in solid organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed the generation of Nabs following VAD implantation in pre-transplant sera and examined their contribution to the cardiac allograft outcome. Methods IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant (OHT) recipients, including 128 VAD and 78 no-VAD patients. Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by ELISA. Results No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared to no-VAD patients. This increase was likely due to presence of VAD, as revealed by lower serum IgG Nabs levels before implantation. Lastly, elevated pre-transplant IgG Nabs level was associated with the development of primary graft dysfunction in this patient series. Conclusions Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support the idea of a broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with the development of primary graft dysfunction suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

See

Clerkin

Kennel

et al. 2017

The Journal of Heart and Lung Transplantation

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“…Mechanical circulatory support is particularly problematic in the pediatric population due to distinct physiology and size constraints. 28,29 Additionally, the presence of, or development of, antibodies against HLA (allosensitization) may be linked to prior mechanical circulatory system device placement, 30 and is associated with worse outcomes after heart transplantation. 31 Procuring a negative cross-matched organ for highly-sensitized patients is difficult.…”

Section: Heart Xenotransplantationmentioning

confidence: 99%

Selection of Patients for Initial Clinical Trials of Solid Organ Xenotransplantation

et al. 2017

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Several groups have reported extended survival of genetically-engineered pig organs in nonhuman primates, varying from almost 10 months for life-supporting kidney grafts and >2 years for nonlife-supporting heart grafts to less than 1 month for life-supporting liver and lung grafts. We have attempted to define groups of patients who may not have an option to wait for an allograft. These include kidney, heart, and lung candidates who are highly-allosensitized. In addition, some kidney candidates (who have previously lost at least 2 allografts from rapid recurrence of native kidney disease) have a high risk of further recurrence and will not be offered a repeat allotransplant. Patients with complex congenital heart disease, who may have undergone previous palliative surgical procedures, may be unsuitable for ventricular assist device implantation. Patients dying of fulminant hepatic failure, for whom no alternative therapy is available, may be candidates for a pig liver, even if only as a bridge until an allograft becomes available. When the results of pig organ xenotransplantation in nonhuman primates suggest a realistic potential for success of a pilot clinical trial, highly-selected patients should be offered participation.

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Fontan‐associated liver disease

et al. 2022

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Clinical outcomes in sensitized heart transplant patients bridged with ventricular assist devices

Abstract: Sensitization appears to have a negative effect on mortality. This mortality appears to be concentrated in patients with AMR, and we postulate that the development of AMR in a sensitized patient may be a predictor of mortality.

Cited by 27 publications

References 22 publications

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation

Selection of Patients for Initial Clinical Trials of Solid Organ Xenotransplantation

Fontan‐associated liver disease

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