scholarly journals Evaluation of Myocardial Perfusion and Immune Cell Response in Cardiac Allograft Dysfunction of Heart-Transplant Patients

2020 ◽  
Author(s):  
Paul J. Kim ◽  
Francisco Contijoch ◽  
Gerald Morris ◽  
Darrin Wong ◽  
Patricia Nguyen
Keyword(s):  
T Cells ◽  
Myocardial Perfusion ◽  
Heart Transplant ◽  
Immune Cell ◽  
Cardiac Allograft ◽  
Normal Heart ◽  
Graft Dysfunction ◽  
Stress Myocardial Perfusion ◽  
Transplant Patients ◽  
Immune Cell Response

BackgroundWe investigated the myocardial perfusion differences and changes in immune cell response in heart-transplant patients with nonspecific graft dysfunction (NGD) compared to cardiac allograft vasculopathy (CAV) patients and normal heart-transplant patients.Methods and ResultsWe prospectively studied 17 heart-transplant patients (59.8±14.1 years, 78% male) from January to June 2016. Regadenoson stress cardiac MRI was performed in the patients and peripheral blood obtained contemporaneously to isolate peripheral blood mononuclear cells (PBMCs). Stress myocardial perfusion showed significantly decreased myocardial perfusion using maximum upslope method in NGD and CAV patients compared to normal heart-transplant patients. Myocardial scar by late gadolinium enhancement also was significantly increased in nonspecific graft dysfunction patients compared to normal. Evaluation of PBMCs by flow cytometry showed a trend towards increased activated HLA-DR+ T cells in NGD patients compared to normal. Clinical outcomes for cardiac hospitalization, allograft loss/retransplant, death were assessed at 3 years.ConclusionsNGD shows decreased stress myocardial perfusion by cardiac MRI and a trend towards increased activated T cells in PBMCs, suggestive of an immune-mediated cause for allograft dysfunction.

scholarly journals Specific recruitment of CD4+CD25++ regulatory T cells into the allograft in heart transplant recipients

2007 ◽  
Vol 292 (5) ◽  
pp. H2425-H2431 ◽  
Author(s):  
Caroline Schmidt-Lucke ◽  
Alexandra Aicher ◽  
Paola Romagnani ◽  
Björn Gareis ◽  
Sergio Romagnani ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Cell Types ◽  
Systemic Circulation ◽  
Cardiac Allograft ◽  
Transplant Recipients ◽  
Activated T Cells ◽  
Transplant Patients ◽  
Heart Transplant Recipients

Regulatory T cells (Treg) migrate into allografts and induce tolerance of the graft. Immunosuppressive Treg are found among CD4+CD25++ T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesized that activated T cells and Treg might modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated T cells and CD4+CD25++ Treg in the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients ( n = 22) compared with controls ( n = 18). Systemic levels of circulating Treg were significantly lower in CA recipients (8.9 ± 1.3 μl) compared with controls (15.8 ± 1.6 μl; P = 0.002). Similarly, the proportion of Treg related to the total leukocyte number was significantly lower in CA recipients ( P < 0.01). In contrast, systemic levels of circulating activated CD4+ T cells and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of Treg significantly decreased during transcardiac passage (3.0 ± 0.3 to 2.4 ± 0.3% of CD4+ T cells, P < 0.01), and FOXP3+ T cells invaded into the allograft. In contrast, numbers of activated CD4+ T cells increased during passage through the allograft, even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive Treg are reduced in transplant recipients. Recruitment of Treg into the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy.

scholarly journals Isolation and expansion of thymus‐derived regulatory T cells for use in paediatric heart transplant patients

2021 ◽  
Author(s):  
Marco Romano ◽  
Monica Sen ◽  
Cristiano Scottà ◽  
Rowa Y. Alhabbab ◽  
Andres Rico‐Armada ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Patients

Detection of Donor-Specific Antibodies Both in Serum and Cardiac Allograft Biopsy in Heart Transplant Patients

2018 ◽  
Vol 102 ◽  
pp. S677
Author(s):  
Bilkay Basturk ◽  
Atilla Sezgin ◽  
Elif Sade ◽  
B. Handan Ozdemir ◽  
Aysen Terzi ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Cardiac Allograft ◽  
Specific Antibodies ◽  
Transplant Patients ◽  
Allograft Biopsy ◽  
Donor Specific Antibodies

Abstract 13933: High Urgency Candidates for Heart Transplantation Does Not Correlate to the Development of Primary Graft Dysfunction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rafael Skorka ◽  
Keith Nishihara ◽  
Adriana Shen ◽  
Evan P Kransdorf ◽  
Lillian Benck ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Heart Transplant ◽  
Survival Rates ◽  
Control Group ◽  
High Dose ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Assist Device ◽  
Transplant Patients ◽  
High Urgency

Introduction: Primary Graft Dysfunction (PGD) after Heart Transplantation (HTx) is seen in approximately 7-30% of heart transplant patients as described by the literature. Many of these patients have severe PGD which requires support with ECMO. It has been reported that patients who are severely ill on high dose inotropes or on assists devices have greater propensity to develop severe PGD. Many of these patients have borderline blood pressure due to poor cardiac function which may contribute to PGD with its associated vasoplegia. In order to asses risk for the development of PGD we evaluated our patients in terms of their status at the time of transplant to assess risk. Methods: Between 2010 and 2019 we assessed 44 Heart Transplant patients who developed severe PGD immediately after HTx. The UNOS Status at the time of Transplant was recorded along with the presence of a durable assist device, temporary assist device, or no Inotropes or assist device. 30 Day and 1 Year survival were assessed for all status groups including a control group (no PGD, n=799). Results: High urgency status at the time of transplant was not the overwhelming majority of patients that developed severe PGD. Approximately 32% of these patients were patients who were waiting for transplant at home, who were not on Intravenous Inotropes and not on assist devices. 1 Year survival was compromised in all patients who developed severe PGD with survival rates that were significantly lower than patients without PGD in our program (47.7% vs 93.6%, p<0.001) (see Table). Conclusions: High urgency status is not solely associated with the development of severe PGD. Further assessment into these non-urgent patients who develop severe PGD is warranted and is under investigation. Inflammatory markers should be assessed in all patients who develop severe PGD.

Prior Amiodarone Exposure Reduces Tacrolimus Dosing Requirements in Heart Transplant Recipients

2019 ◽  
Vol 29 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Nadine T. Breslin ◽  
David M. Salerno ◽  
Veli K. Topkara ◽  
Farhana Latif ◽  
Susan Restaino ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Organ Transplant ◽  
Patient Characteristics ◽  
Tacrolimus Concentration ◽  
Transplant Recipients ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Transplant Patients ◽  
Significant Difference ◽  
And Control

Introduction: Amiodarone use prior to heart transplant is independently associated with a higher rate of severe primary graft dysfunction and in-hospital mortality. Amiodarone may also alter the pharmacokinetics of medications metabolized via cytochrome P450. No data exist regarding the interaction between pretransplant amiodarone and tacrolimus concentrations. Design: Single-center retrospective study of transplant patients between January 1, 2014, and June 30, 2016. A therapeutic tacrolimus concentration was defined as a trough level between 8 and 15 ng/mL for 2 consecutive days. The primary outcome was the tacrolimus therapeutic weight-based dosing requirements (mg/kg/day) for patients receiving amiodarone prior to transplant when compared to those without prior receipt of amiodarone. Secondary outcomes include the incidence of cellular rejection and mortality within 6 months posttransplant. Results: Multi-organ transplant recipients (n = 3), retransplants (n = 9), those who died prior to a therapeutic level (n = 1), and those receiving amiodarone posttransplant (n = 7) were excluded from the analysis. Of the 80 patients included, 34 (42%) received amiodarone prior to transplant. Patient characteristics were similar, with the exception of primary graft dysfunction incidence (38% in amiodarone vs 8.5% in control, P = .001). The median therapeutic dose was 0.1 (interquartile range [IQR]: 0.07-0.12) versus 0.13 (IQR: 0.09-0.17) in the amiodarone and control groups, respectively, ( P < .01). No significant difference in mortality or rejection was noted. Conclusion: Patients receiving amiodarone prior to transplant require a lower weight-based dose of tacrolimus.

P761The effect of extracorporeal photopheresis on cardiac allograft rejection and on lymphocyte subclasses

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Teszak ◽  
A Assabiny ◽  
A Kiraly ◽  
Z Tarjanyi ◽  
N Parazs ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Lymphocytes ◽  
Heart Transplant ◽  
Allograft Rejection ◽  
Cytotoxic T Cells ◽  
Cardiac Allograft ◽  
Extracorporeal Photopheresis ◽  
Cardiac Allograft Rejection ◽  
Cellular Rejection

Abstract Background Cardiac allograft rejection is known to have a profound impact on graft survival and mortality after heart transplant. Previous data on the efficacy of extracorporeal photopheresis (ECP) in the management of cardiac allograft rejection is encouraging. Though, clear evidence on the exact indication and data regarding its effect on distinct lymphocyte subtypes are still lacking. Based on their cytokine production, both helper and cytotoxic T cells can differentiate into either regulatory cells participating in the suppression of rejection or into effector cells responsible for its maintenance. Regulatory T cells are essential for the termination of rejection, while B lymphocytes and natural killer (NK) cells contribute to it. Purpose We aimed to investigate the anti-rejection efficacy and the impact of ECP on peripheral blood lymphocyte subclasses in adult heart transplant recipients. Methods In a retrospective analysis of 12 consecutive patients treated with ECP for cardiac allograft rejection between 2013 and 2019, we examined the grade of rejection in endomyocardial biopsies (EMB) based on the International Society for Heart and Lung Transplantation classification. We analysed the absolute counts and the percentages of helper, cytotoxic and regulatory T cells, B lymphocytes and NK cells with fluorescence activated cell sorting. Measurements were performed both before and after the ECP treatment period. Data values were given as either mean±standard deviation or median [min–max]. Results The patients underwent 26 [2–39] ECP treatments in addition to standard immunosuppressant therapy. Whereas grade 2R cellular rejection was detected in 83% of the cases prior to initiating ECP, none of the examined EMB specimen revealed rejection greater than grade 1R cellular rejection post ECP therapy. The average grade of cellular rejection improved significantly (1.25±0.45 vs. 0.50±0.53; p=0.022). The absolute count and the percentage of helper T cells increased significantly post ECP therapy (0.34 G/l±0.26 G/l vs. 0.51 G/l±0.39 G/l; p=0.018 and 3.43%±2.24% vs. 5.98%±3.64%; p=0.017, respectively). There was also a significant rise in the percentage of cytotoxic T cells (2.33%±1.46% vs. 4.16±2.98%; p=0.027). We noticed an almost significant twofold increase in the percentage of regulatory T cells on completion of the ECP therapy (0.20%±0.22% vs. 0.37%±0.20%; p=0.060). Neither B lymphocyte nor NK cell counts revealed any significant changes. Conclusion ECP was effective in reducing the severity of cardiac allograft rejection episodes. The significant decrease in rejection rates might be indicative of the predominance of anti-inflammatory helper and cytotoxic T cell subpopulations and the increase of regulatory T cell count post ECP therapy. However, discussion of the results are limited by small sample size and the effect of medical therapy on the lymphocytes.

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