Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

Griffith, Bartley P.; Goerlich, Corbin E.; Singh, Avneesh K.; Rothblatt, Martine; Lau, Christine L.; Shah, Aakash; Lorber, Marc I.; Grazioli, Alison; Saharia, Kapil; Hong, Susie N.; Joseph, Susan; Ayares, David; Mohiuddin, Muhammad M.

doi:10.1056/nejmoa2201422

Cited by 388 publications

(361 citation statements)

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“…However, despite the excellent early function of the pig heart, the final outcome was disappointing. Based on the admittedly limited data provided in the recent report, 1 what factors do we believe contributed to the failure of this patient to thrive, and to his ultimate demise?…”

Section: Introductionmentioning

confidence: 93%

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The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?

Cooper

Yamamoto

Hara

et al. 2022

Xenotransplantation

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The clinical course of the first patient to receive a gene-edited pig heart transplant was recently reported by the University of Maryland team. Although the pig heart functioned well for >40 days, serum anti-pig antibodies then increased, and the patient sadly died after 60 days. Because of his debilitated pre-transplant state, the patient never thrived despite excellent graft function for several weeks, and the cause of his demise continues to be uncertain. A few days before an increase in anti-pig antibodies was observed, the patient had received intravenous human immunoglobulin (IVIg), and whether this played a role in his cardiac deterioration has been discussed. Furthermore, mcfDNA testing indicated an increase in pig cytomegalovirus (CMV), and its possible role in the development of cardiac dysfunction has also been considered.On the basis of the limited data provided in the publication and on our previous investigations into whether IVIg contains anti-TKO pig antibodies and therefore might be deleterious to TKO pig organ xenografts, we suggest that the steady rise in anti-pig antibody titer was more consistent with the failure of the immunosuppressive regimen to prevent elicited anti-TKO pig antibody production, rather than from the passive transfusion of IVIg or the presence of pig CMV in the graft. Although the outcome of the Maryland experience was disappointing, valuable lessons were learned. Our attention was drawn to the potential risks of heart transplantation in a "deconditioned" patient, the administration of IVIg, the transmission of pig CMV, and of the difficulties in interpreting myocardial biopsy findings.

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Section: Introductionmentioning

confidence: 93%

“…The first clinical pig heart transplant, carried out by our colleagues at the University of Maryland at Baltimore on January 7, 2022, 1 attracted considerable public attention and stimulated interest in the potential of xenotransplantation as a therapeutic option for patients with terminal organ failure.…”

Section: Introductionmentioning

confidence: 99%

The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?

Cooper

Yamamoto

Hara

et al. 2022

Xenotransplantation

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“…S jögren syndrome is now the second most common autoimmune disease despite being infrequently diagnosed, according to a presentation by Frederick B. Vivino, MD, MS, at the Congress of Clinical Rheumatology. 1 The syndrome is a chronic, multisystem autoimmune disease characterized by lacrimal and salivary gland inflammation, with resultant dryness of the eyes and mouth and occasional glandular enlargement. 2 Other signs and symptoms can include seropositive polyarthritis, polymyalgia rheumatica, leukocytoclastic vasculitis, demyelinating disease, peripheral neuropathy, inflammatory myositis, salivary gland swelling, or accelerated caries.…”

Section: Often Undiagnosed Syndrome Now Most Commonmentioning

confidence: 99%

“…2 It can occur in primary form, not associated with other autoimmune rheumatic diseases; and a secondary form, often associated with rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis. 1 Vivino says the difficulty of the diagnosis and classification of the syndrome is due in part to three sets of criteria still being used: the 2002 American European Consensus Group criteria, 2012 American College of Rheumatology-Sjögren' s International Collaborative Clinical Alliance (ACR-SICCA) criteria, and an ACR-European League against Rheumatism (EULAR) document from 2016.…”

Section: Gallstone Disease May Be a Predictormentioning

confidence: 99%

Clinical Rounds

2022

Nursing

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“…Because the heart is a life-supporting organ, pig cardiac xenografts should be used initially as a "bridge-totransplant" in patients for whom a subsequent allograft offers a viable "exit strategy," but for whom mechanical circulatory support options are limited or associated with predictably poor outcomes. Thus far, the longest reported survival of a baboon with a life-supporting pig orthotopic heart transplant is <9 mo [3][4][5] ; based on Mr Bennett's case, long-term graft function is by no means assured (Griffith et al 6 ). Graft and patient survival of months duration could provide short-to medium-term bridging for patients otherwise acceptable for allotransplantation as long as cardiac xenograft dysfunction proves predictable.…”

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confidence: 99%