Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy

Coutance, Guillaume; Ouldamar, S.; Rouvier, Philippe; Saheb, Samir; Suberbielle, Caroline; Bréchot, Nicolas; Hariri, Sarah; Lebreton, Guillaume; Leprince, Pascal; Varnous, Shaïda

doi:10.1016/j.healun.2015.03.002

Cited by 81 publications

(60 citation statements)

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“…Treated AMR in the first year after transplantation was shown to have good outcomes in one recent study (14), however late AMR with graft dysfunction has been shown to be associated with significant one year mortality (50–60%) despite treatment. (16–18) The poor outcomes in these studies were likely due to CAV and/or preceding subclinical AMR. Loupy et al (19) recently described the presence of undiagnosed sub-clinical AMR in 40% of a cohort of patients that developed allograft failure.…”

Section: Discussionmentioning

confidence: 89%

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Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation

Clerkin

Farr

Restaino

et al. 2017

The Journal of Heart and Lung Transplantation

112

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Introduction Donor specific anti-HLA antibodies (DSA) are common following heart transplantation and are associated with rejection, cardiac allograft vasculopathy (CAV), and mortality. Currently a non-invasive diagnostic test for pathologic AMR (pAMR) does not exist. Methods 221 consecutive adult patients underwent heart transplantation from January 1st, 2010 through August 31th, 2013 and followed through October 1st, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included the association of DSA (stratified by MHC Class and de-novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of CAV. Results During the study period 69 individual patients (31.2%) had DSA (24% had de-novo DSA) and there were 74 episodes of pAMR in 38 unique patients. The sensitivity of DSA at any MFI to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (OR 5.37, 95% CI 1.34–21.47, p=0.018), adjusting for age, gender, and timing of AMR. Circulating Class II DSA after transplantation increased the risk of future pAMR (HR 2.97, 95% CI 1.31–6.73, p=0.009). Patients who developed de-novo Class II DSA had a 151% increase in risk of graft loss (contingent on 30-day survival) compared with those who did not have DSA (95% CI 1.11–5.69, p=0.027). Conclusions DSA were inadequate to diagnose pAMR, but Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss.

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Section: Discussionmentioning

confidence: 89%

“…We also investigated the future risk of AMR among those who develop DSA. Graft dysfunction was defined as at least two of the following: 33% decrease in cardiac index and a cardiac index of less than 2.2 L/min/m 2 , 33% increase in pulmonary capillary wedge pressure, or 33% decrease in left ventricular ejection fraction (14, 15). …”

Section: Methodsmentioning

confidence: 99%

Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation

Clerkin

Farr

Restaino

et al. 2017

The Journal of Heart and Lung Transplantation

112

View full text Add to dashboard Cite

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“…Donor-specific anti-human leukocyte antigen (HLA) circulating antibodies (DSA) with C1q binding activity have been associated with a worse prognosis after HT; however, these markers lack the specificity to predict graft outcome in a given patient 15 . In addition to complemento identify non-invasive biomarkers that y enable the early stratification of patients a at t t ri ri r sk sk sk 2, 2, 2 5 5 5-8 -8 -8 t t to o o ailor individualized therapeutic approaches that prevent HT failure 6,9 .…”

Section: Downloaded Frommentioning

confidence: 99%

Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy

et al. 2018

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“…In addition, 1 study reported that sepsis killed 2 of 10 patients studied, but it was not categorized as a mortality factor after heart transplant. 22 Another study stated that 9 of 117 patients died due to sepsis, but it was not classified as a mortality factor. 23 Survival after heart transplant has improved over time.…”

Section: Discussionmentioning

confidence: 99%

“…Coutance and associates 22 found that the mortality of 20 patients was 80% at 1 month and 50% at 1 year, despite patients receiving a high immunosuppressive therapy regimen (100% received methylpred nisolone, 90% received intra venous immunoglobulin, 85% received plasmapheresis, and 45% received rituximab). Holmes and associates 2 used cyclosporine and mycophenolate for their immunosuppressive therapy, in which patient survival was lower than ours.…”

Section: Discussionmentioning

confidence: 99%

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Rojas¹,

Cruz-Ku²,

Yassen³

et al. 2018

Exp Clin Transplant

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Objectives: The identification of variables related to the survival of heart transplant patients is vital for a good medical practice. Few studies have examined this issue in a Latin American population. Therefore, the aim of this study was to analyze, retrospectively, the survival and mortality characteristics of patients after heart transplant. Materials and Methods: Information on patients was obtained through review of medical records; we collected information on all patients who underwent this procedure from 2010 to 2015. Sociodemographic, clinical, and surgical characteristics associated with posttransplant mortality were analyzed. Survival over 5 years was determined with the Kaplan-Meier method. Results: The overall survival rate of the 35 patients who underwent heart transplant was 85%. Those with low total cholesterol values (< 160 mg/dL) had a lower survival at 5 years than patients with higher values (74% vs 100%; P = .044). The overall mortality was 14.3%, and the main cause of death was acute graft rejection (40%). Lower total cholesterol level (< 160 mg/dL; P = .036), presence of chronic kidney disease stage 1 (P = .049), intraoperative bleeding (> 600 mL; P = .013), and number of sepsis incidents (P = .03) were more frequent in patients who died. Conclusions: The survival in our institute at 5 years is higher than shown in the reported literature, and the mortality is lower. In addition, a low total cholesterol value negatively affects survival of heart transplant patients at 5 years. Key words: Cardiac surgery, Cholesterol, Graft rejection, Sepsis IntroductionCompared with past decades, the International Society for Heart and Lung Transplantation and other institutions have recorded improved survival after heart transplant at 1, 5, and 10 years. 1,2 This is relevant because this surgical procedure remains the treatment of choice in patients with severe heart failure from different causes. 3 Data have also demonstrated survival greater than 20 years after heart transplant. 4 However, survival continues to be below 80% at 5 years in various institutions. 2,5 Survival after heart transplant is affected by several mortality factors from both the recipient and the donor. 6 For the recipient, age, body mass index, high preoperative creatinine level, ischemic time, cardiovascular diseases or hematologic-associated causes, and the patient's psychological state can affect survival. 2,7-10 For the donor, higher age, donor diabetes mellitus history, and sex mismatch or race mismatch can increase the recipients' mortality after heart transplant. 9,11 The principal causes of death after this procedure include cardiac graft vasculopathy, primary graft failure, graft rejection, infection, and neoplasia. 12,13 In recent years, new developments to minimize the causes of death have been implemented, thus raising survival rates. 14 These include the implementation of more protocols, strict sanitary policies, and the combination and use of better immunosuppressive therapy. 6 Most studies have been done on p...

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Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy

Cited by 81 publications

References 17 publications

Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation

Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation

Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy

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