Donor thyroid hormone therapy is associated with an increased risk of graft dysfunction after heart transplantation

Peled, Yael; Lavee, Jacob; Kassif, Yigal; Arad, Michael; Kogan, Alexander; Peled, Amir; Tirosh, Amir; Sternik, Leonid; Ram, Eilon

doi:10.1111/ctr.13887

Cited by 14 publications

(8 citation statements)

References 25 publications

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“…Thyroxine replacement was associated with early graft loss and 30-day mortality by analyzing data from 23,000 HTX recipients [ 30 ]. The withdrawal phenomenon has been hypothesized in this process as after implantation the heart will be placed in a relative thyroid hormone deficiency of the recipient caused by sick euthyroid syndrome, amiodarone treatment and glucocorticoid treatment [ 31 ]. Reliable data from prospective studies are still missing regarding the benefit of thyroid hormone replacement.…”

Section: Discussionmentioning

confidence: 99%

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation

Pállinger

Székely

Töreki

et al. 2023

IJMS

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The proinflammatory cascade that is activated at the time of brain death plays a crucial role in organ procurement. Our aim of this study was to explore the relationship between the clinical outcome of orthotopic heart transplantation, as well as cytokine and apolipoprotein profiles of the pericardial fluid obtained at donation. Interleukin, adipokine and lipoprotein levels in the pericardial fluid, as well as clinical data of twenty donors after brain death, were investigated. Outcome variables included primary graft dysfunction, the need for posttransplantation mechanical cardiac support and International Society for Heart and Lung Transplantation grade ≥ 2R rejection. Hormone management and donor risk scores were also investigated. Lower levels of IL-6 were observed in primary graft dysfunction (median: 36.72 [IQR: 19.47–62.90] versus 183.67 [41.21–452.56]; p = 0.029) and in the need for mechanical cardiac support (44.12 [20.12–85.70] versus 247.13 [38.51–510.38]; p = 0.043). Rejection was associated with lower ApoAII (p = 0.021), ApoB100 (p = 0.032) and ApoM levels (p = 0.025). Lower adipsin levels were detected in those patients receiving desmopressin (p = 0.037); moreover, lower leptin levels were found in those patients receiving glucocorticoid therapy (p = 0.045), and higher T3 levels were found in those patients treated with L-thyroxine (p = 0.047) compared to those patients not receiving these hormone replacement therapies. IL-5 levels were significantly associated with UNOS-D score (p = 0.004), Heart Donor Score (HDS) and Adapted HDS (p < 0.001). The monitoring of immunological and metabolic changes in donors after brain death may help in the prediction of potential complications after heart transplantation, thus potentially optimizing donor heart allocation.

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Section: Discussionmentioning

confidence: 99%

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation

Pállinger

Székely

Töreki

et al. 2023

IJMS

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“…38 Nonetheless, concerns have been raised regarding an early withdrawal effect that is associated with a higher risk of PGD in heart transplant recipients whose donors had received TH therapy. 16 Similarly, there are studies suggesting that donor T4 administration is detrimental to liver transplant recipients, for whom higher peaks of transaminases, higher rates of graft dysfunction and failure, and a greater need for post-operative plasmapheresis have been reported. 17,18 The conclusions of these studies have found support in recent studies in mice showing that both steroids and thyroxine have detrimental effects on the reperfused steatotic liver, with thyroid supplementation being associated with increased rates of hepatic necrosis.…”

Section: Donor Th Protocols and Formulationmentioning

confidence: 99%

“…Recently, it has been hypothesized that an early withdrawal effect in HTx recipients whose donors had received TH therapy could be associated with primary graft dysfunction (PGD). 16 Higher peak transaminases and higher rates of graft dysfunction and failure have also been reported in liver transplant recipients of livers procured from donors receiving hormonal therapy. 17,18 The primary aim of this study was to test the hypothesis that donor TH therapy is independently associated with early graft loss (EGL) in a large contemporary cohort of HTx recipients, a finding that would support the TH withdrawal effect hypothesis.…”

mentioning

confidence: 97%

Donor thyroid hormone therapy and heart transplantation outcomes: ISHLT transplant registry analysis

Peled

Ram

Klempfner

et al. 2020

The Journal of Heart and Lung Transplantation

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BACKGROUND: Donor thyroid hormone (TH) supplementation therapy is widely used. Recent reports suggested an increased risk of graft dysfunction in heart transplant (HTx) recipients not receiving TH supplementation. Our aim was to determine the effect of a donor TH supplementation in a large contemporary HTx cohort. METHODS: We analyzed data reported to the International Society for Heart and Lung Transplantation Registry on adult HTx recipients transplanted from 2006 to 2016. Early graft loss (EGL) was defined as death or retransplant because of graft failure within 48 hours of transplant. Logistic regression and propensity score analyses were performed. RESULTS: There were 23,002 adult HTx recipients transplanted during the study period for whom data on the use of donor TH supplementation were provided to the Registry. There were 15,821 recipients whose donors had received TH supplementation, and 7,181 who had not. Multivariable analysis showed donor TH therapy to be associated with an increased risk for EGL (odds ratio, 1.51; 95% CI, 1.13−2.06; p < 0.001). Long-term survival was similar, irrespective of donor TH supplementation. Recipients whose donors had received TH supplementation exhibited a lower 8-year incidence of vasculopathy (hazard ratio, 0.90; 95% CI, 0.85−0.97; p = 0.003). These results remained consistent in a propensity-matched analysis. CONCLUSIONS: Donor TH therapy is independently associated with an increased risk of EGL. Whether this is a result of the donor allograft intrinsic characteristics related to the reasons why TH was used or whether this is a result of a TH withdrawal effect, which could be mitigated by administration of TH to the recipient, should be further studied.

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“…Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65 (5)(6)(7)). An independent association was found between fT4 and adverse outcomes after HTx, and perioperative low fT4 levels could be a prognostic marker of adverse outcomes in HTx (8).…”

Section: Introductionmentioning

confidence: 99%

Association of Thyroid-Stimulating Hormone (TSH) Levels With the Prognosis of Patients Undergoing Heart Transplantation: A Retrospective Study

Wei

Zhou

2021

Front. Cardiovasc. Med.

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Purpose: To investigate the impact of TSH levels using a more stringent cutoff of subclinical hypothyroidism (i.e., TSH > 2.5 mIU/L) on the short-term complications and long-term prognosis in patients who underwent heart transplantation (HTx).Methods: This is a retrospective study of consecutive patients with end-stage heart failure (HF) who underwent HTx. They were divided into three groups: thyroid-stimulating hormone (TSH) ≤ 2.50 mIU/L (L-TSH), 2.50 < TSH ≤ 4.91 mIU/L (M-TSH), and TSH > 4.91 mIU/L (H-TSH). The outcomes are all-cause death and cardiogenic death.Results: There are 63 (70%) males and 27 (30%) females. Nine (10%) patients died within 1 month after surgery, including five cardiogenic deaths. By 1 year, a total of 19 patients total were dead. The survival rate in the M-TSH group was significantly higher than that of the L-TSH group (P = 0.017). After adjusted by variables of sex, age, BMI, diabetes history, hypertension history, the multivariable Cox analysis showed that body mass index (HR = 0.804, 95%CI: 0.680–0.951, P = 0.011), and L-TSH (HR = 8.757, 95%CI: 1.786–42.948, P = 0.007 vs. M-TSH), and H-TSH (HR = 6.427, 95%CI: 1.137–36.327, P = 0.035 vs. M-TSH) were independently associated with all-cause death. The multivariable Cox analysis showed that body mass index (HR = 0.703, 95%CI: 0.564–0.878, P = 0.002), and L-TSH (HR = 17.717, 95%CI: 1.907–164.607, P = 0.011 vs. M-TSH) were independently associated with cardiogenic death.Conclusion: For patients with end-stage HF undergoing HTx, low and high baseline TSH levels are independently associated with 1-year all-cause death and low baseline TSH levels with cardiogenic death.

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Donor thyroid hormone therapy is associated with an increased risk of graft dysfunction after heart transplantation

Cited by 14 publications

References 25 publications

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation

Donor thyroid hormone therapy and heart transplantation outcomes: ISHLT transplant registry analysis

Association of Thyroid-Stimulating Hormone (TSH) Levels With the Prognosis of Patients Undergoing Heart Transplantation: A Retrospective Study

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