S. Dimbil

Revealing a new mode of sensitization induced by mechanical circulatory support devices: Impact of anti-AT1R antibodies

Increased levels of angiotensin II type 1 receptor (AT1R) antibody have been shown to be associated with allograft rejection. This study aims to determine the rate of development of antibody to AT1R after mechanical circulatory support device (MCS) implantation, and if the development of strong binding AT1R antibodies is associated with survival.

Change in lymphocyte to neutrophil ratio predicts acute rejection after heart transplantation

AIMSnMost immunosuppressive drugs provide targeted immunosuppression by selective inhibition of lymphocyte activation and proliferation. This study evaluated whether a change in the lymphocyte to neutrophil ratio (LNR) is related to acute rejection.nnnMETHODSnIn 74 cardiac transplant recipients peripheral blood lymphocyte and neutrophil counts were measured soon after (baseline) and three, six, and 12months after heart transplantation. The primary endpoint was the incidence of acute rejection.nnnRESULTSnSignificant acute rejection after heart transplantation occurred in 20 patients (27%) during a median follow-up of 49.4 [IQR 37.4-61.1] months. LNR significantly increased over time (0.1149±0.1354 at baseline, 0.2330±0.2266 at 3months, 0.2961±0.2849 at 6months, and 0.3521±0.2383 at 12months; P<0.001), especially during the first 3months in the group without acute rejection. The area under the curve of the change in LNR during the first three months (ΔLNR) for acute rejection was 0.565 (95% CI 0.420 to 0.710, P=0.380) on ROC curve analysis. The best cutoff value of Δ LNR to differentiate those with and without acute rejection was ≤0.046 by ROC curve analysis. Kaplan-Meier analysis revealed that the low ΔLNR group (≤0.046) had a significantly higher rate of acute rejection than the high ΔLNR group (>0.046) (37.5% vs. 19.0%, log-rank: P=0.0358). The low ΔLNR for the first 3months was an independent predictor of clinically significant acute rejection after adjusting for cytomegalovirus donor seropositive and recipient seronegative.nnnCONCLUSIONSnThe results of this study suggest that ΔLNR over the first 3months after heart transplantation is a strong and independent predictor of acute rejection after heart transplantation. ΔLNR can be used as an early biomarker for predicting of acute rejection after heart transplantation.

Use of durable mechanical circulatory support on outcomes of heart–kidney transplantation†

OBJECTIVESnPrevious studies have demonstrated that preheart transplant mechanical circulatory support (MCS) can lead to a small but significant increase in mortality. However, data on outcomes of patients with MCS who require simultaneous heart-kidney transplant are limited.nnnMETHODSnA retrospective review of simultaneous heart-kidney transplantations (HKTxs) performed at a single institution over a 5-year period was performed. Patients were divided based on the preoperative use of durable MCS. Renal graft-related end points were evaluated, including glomerular filtration rate following transplantation, prevalence of delayed renal graft function and freedom from antibody and cellular-mediated graft rejection. Patient-specific outcomes, including survival and frequency of non-fatal major adverse cardiac events at 1 year, were additionally assessed.nnnRESULTSnDuring the study period, 50 HKTxs were performed, 14 of which had preoperative MCS. HKTx patients with and without MCS implantations had a similar prevalence of delayed graft function (57.1% vs 50.0%; Pu2009=u20090.757). A numerical trend was observed towards a reduced glomerular filtration rate 1-month post-transplant in patients without an MCS device (81.2u2009±u200932.8 vs 64.4u2009±u200927.5; Pu2009=u20090.072), but no significant difference was observed at 6 and 12u2009months. No significant difference was observed on the need for post-transplant renal replacement therapy, non-fatal major adverse cardiac events, freedom from graft rejection and overall survival at 1 year.nnnCONCLUSIONSnThe use of preoperative MCS in patients undergoing combined HKTx was not found to affect renal graft function post-transplantation and does not seem to be associated with increase in morbidity or mortality.

Characterizing Predictors and Severity of Vasoplegia Syndrome After Heart Transplantation

BACKGROUNDnVasoplegia is characterized as a severe vasodilatory shock after cardiac surgery, and can be associated with substantial morbidity. Increased systemic inflammation and endothelial dysfunction, often related to prolonged cardiopulmonary bypass times, anesthesia, or mechanical circulatory support have been shown to be associated with the development of vasoplegia. We sought to identify risk factors and the impact of various degrees of vasoplegia after heart transplantation.nnnMETHODSnA retrospective review was conducted of 244 consecutive patients who underwent heart transplantation over a 3-year period. Patients were divided into three groups: no vasoplegia, mild vasoplegia (requiring one vasopressor), and moderate/severe vasoplegia (more than two vasopressors). One-year survival, freedom from rejection, and postoperative complication rates were assessed. Risk factors for vasoplegia subgroups were retrospectively identified.nnnRESULTSnVasoplegia syndrome was observed in 34.3% of patients after heart transplantation (mild, 74.1%; moderate/severe, 25.9%). Cardiopulmonary bypass time was significantly longer and pretransplant creatinine was significantly higher in the moderate/severe vasoplegia group. There was a strong trend toward greater use of mechanical circulatory support among moderate/severe vasoplegia patients compared with mild and no vasoplegia patients. After heart transplantation, 1-year survival, freedom from rejection, and need for hemodialysis were not significantly different between groups.nnnCONCLUSIONSnVasoplegia syndrome is common after heart transplantation. Risk factors for increased severity include longer cardiopulmonary bypass times and elevated preoperative creatinine. Although higher rates of mortality or graft rejection were not detected, vasoplegia was associated with prolonged intubation, greater blood product usage, and lengthened hospital stay. Further studies involving larger cohorts are warranted.

The ratio of circulating regulatory cluster of differentiation 4 T cells to endothelial progenitor cells predicts clinically significant acute rejection after heart transplantation

BACKGROUNDnThe aim of this study was to determine the value of the ratio of the percentage of circulating regulatory cluster of differentiation 4 T cells (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC ratio) for predicting clinically significant acute rejection.nnnMETHODSnPeripheral blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using flow cytometry at a mean of 42 ± 13 days after transplant. The primary end point was clinically significant acute rejection, defined as an event that led to an acute augmentation of immunosuppression in conjunction with an International Society for Heart and Lung Transplantation grade ≥ 2R in a right ventricular endomyocardial biopsy specimen or non-cellular rejection (specimen-negative rejection) with hemodynamic compromise (decrease in left ventricular ejection fraction by > 25%).nnnRESULTSnSignificant rejection occurred in 27 recipients (29.7%) during a median of 49.4 months (interquartile range, 37.0-62.0 months). The mean %Tregs and %EPCs were not significantly different between those with and without an episode of significant rejection, but the mean Treg/EPC ratio was significantly lower in recipients with significant rejection (44.9 vs 106.7, p = 0.001). Receiver operating characteristic curve analysis showed anxa0area under the curve value for significant rejection for a Treg/EPC ratio of 0.712. The best cutoff value of the Treg/EPC ratio that distinguished between those with or without significant rejection was ≤ 18 by receiver operating characteristic curve analysis. Kaplan-Meier analysis revealed that patients with a Treg/EPC ratio of ≤ 18 had a significantly higher rate of rejection than those with a Treg/EPC ratio > 18 (61.5% vs 16.9%, log-rank p < 0.0001). A low Treg/EPC ratio was an independent predictor of significant rejection.nnnCONCLUSIONSnA low Treg/EPC ratio measured soon after heart transplantation is an independent predictor of acute rejection. The Treg/EPC ratio has potential as an early biomarker after heart transplantation for predicting acute rejection.