Cardiac Transplant Recipients Research Articles

De Novo Anti-HLA Antibodies After Heart Transplantation Are Associated With Adverse Events in the Long-term Follow-up of Cardiac Transplant Recipients

Background and ObjectivesLong-term morbidity and mortality after heart transplantation (HTx) remain very high. Several reports have suggested that anti-HLA antibodies (anti-HLA-AB) detected after HTx might be associated with poor survival, but the implication of isolated anti-HLA-AB is still under debate. The aim of the study was to analyze the incidence of de novo anti-HLA-AB and whether they are associated with adverse events after HTx. MethodsThis retrospective study analyzed the presence of anti-HLA-AB assessed by fluorimetry (Luminex) and quantified by a single-antigen bead assay in 119 HTx patients. Mortality, graft dysfunction, antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV) were recorded. Cardiovascular mortality of patients with and without anti-HLA-AB was compared according Kaplan-Meier curves. Cox regression analyses were performed to identify predictors for global mortality and for a combined endpoint (cardiovascular mortality, AMR, and CAV). Mean age of recipients and donors was 49 ± 15 and 38 ± 14 years, 70% were men, 29% were urgent transplants, and mean ischemic time was 195 ± 56 minutes. ResultsAnti-HLA-AB were detected in 23 patients (19%). These patients had higher rates of AMR (39% vs 1%; P < .05) and cardiovascular mortality (17% vs 2%; P < .05). By multivariate analysis, anti-HLA-AB were the only predictor of the combined endpoint (hazard ratio 3.1; confidence interval 1.3 to 7.5; P = .01). Kaplan-Meier curves showed the worse cardiovascular survival of patients with anti-HLA-AB (72% vs 97%; P = .003). ConclusionsPresence of anti-HLA-AB identifies a group of HTx patients with worse prognosis. Better understanding of the immunologic relevance of anti-HLA-AB is expected to improve long-term survival after HTx.

TEMPORAL CHANGES ON THE RISK OF NEW ONSET DIABETES FOLLOWING CARDIAC TRANSPLANTATION OVER 30 YEARS

New onset diabetes after transplantation (NODAT) promotes cardiovascular diseases. The recent changes in recipients and cardiac donor demography may increase their risk for developing NODAT. The objective of this study was to investigate the secular trends of the risk of NODAT at 1 year and 3 years over a 30 years follow-up in a large cohort of cardiac transplant (CTx) recipients, and to compare the recipient and donor characteristics over that period.

IMPACT OF OPTICAL COHERENCE TOMOGRAPHY ON MANAGEMENT OF PEDIATRIC HEART TRANSPLANT RECIPIENTS: DATA FROM THE INTERNATIONAL PEDIATRIC OCT REGISTRY

Cardiac allograft vasculopathy (CAV) is a leading risk factor for graft failure and mortality in pediatric cardiac transplant recipients. Optical coherence tomography (OCT) is a high-resolution intravascular imaging technique that has shown promise at detecting early signs of CAV which are not yet detectable by conventional angiography. We established an International Pediatric OCT Registry to: 1) evaluate the impact of OCT on clinical care; and 2) document the safety profile of this technique across pediatric centres.

Abstract PR398

Case report: Background: Bariatric surgery has been shown to attenuate metabolic syndrome, especially insulin resistance. We report a case of an obese patient with refractory insulin-dependent diabetes and a previous heart transplantation, submitted to laparoscopic vertical gastrectomy to achieve metabolic control. Case report: A male patient with 38y, 117Kg, 174cm, BMI 38.64, ASA P3, hypertension (165/98 mmHg), previous myocardial infarction and heart transplantation 8 years ago was submitted to laparoscopic vertical gastrectomy under general anesthesia. Preoperative findings: glucose 254mg.dl-1, glycated hemoglobin (GHb) 8.4%, hematocrit 29.4%, creatinine 1.7mg.dl-1, ejection fraction 49%. At theater, central venous and left radial artery catheterization were inserted. Monitoring included electrocardiography with ST analysis, pulse oximetry, central venous pressure, continuous invasive arterial pressure, cardiac output and index (CI), BIS, neuromuscular activity, capnography, temperature and urinary output. Infusion of 3ml.kg-1.h-1 per ideal body weight (IBW) Ringer’s lactate solution. Anesthesia was induced with midazolam 0.15mg.kg-1, fentanyl 0.2µg.kg-1 and rocuronium 0,6mg.kg-1 IBW. Lungs ventilated with 6ml.kg-1 IBW tidal volume and 10ml PEEP. Respiratory frequency adjusted to maintain target ETCO2 38 mmHg. Target-controlled infusion of propofol and remifentanil for maintenance according to hemodynamic and BIS parameters. Dexmedetomidine 0,3 µg.kg-1.h-1 for sympatholysis. Isoflurane 1-2% in 50% air for myocardial conditioning. IV insulin started and dosed according to capillary glucose monitored each 30 min and 100ml.h-1 5% dextrose in saline infusion to prevent hypoglycemia. Dobutamine 3-5µg.kg-1.min-1, norepinephrine 0.02-0.05µg.kg-1.min-1 IBW and Ringer’s lactate were administered, according to hemodynamic and cardiac values. Patient remained stable during surgery, with MAP 78±27(75-80)mmHg, HR 62±15(49-80), SvO2 65±17(60-75)%, CI 2,5±1.0(1,5-3,5), SpO2 98±1(96-99)%, BIS 55±23(48-60)%. After surgery, the patient was transferred to ICU. The postoperative period was uneventful. Four months later, he had lost 16kg, insulin was stopped and GHb fell to 6.4%, with metformin 500mg.day-1. Conclusions: There are more long-term cardiac transplant recipients undergoing noncardiac surgery. Although still controversial, metabolic surgery for diabetes control is now a more common practice. Data regarding the association of these 2 clinical scenarios are still scarce, implying new challenges to the management of these patients.

OR22 Identification and validation of non-HLA antibodies in allograft recipients

Aim Non-HLA antibodies (Ab) are associated with an increased risk of allograft rejection. Currently, only a few non-HLA Ab can be tested in the clinical setting however, many have been reported in the literature. Simultaneously screening allograft recipients for a panel of novel and previously published non-HLA Ab would further elucidate the prevalence of non-HLA Ab, their organ specificity, and their association with allograft rejection. Methods Endothelial cell cross matches (ECXM) were performed using sera obtained at the time of cardiac allograft rejection ( n = 37) to identify clinically relevant endothelial specific Ab. ECXM+ HLA DSA-sera ( n = 12) were further evaluated by protoarray analysis of 9000 human proteins (Invitrogen) to identify novel non-HLA Ab targets. Previously published non-HLA Ab and the novel non-HLA Ab targets identified by protoarray were validated in a cohort of cardiac transplant recipients ( n = 61) using a multiplex bead array (Immucor, Inc.) to detect Ab to over 45 non-HLA Ab targets. Results Thirty-two novel non-HLA Ab targets including 22 membrane proteins and 10 autoantigens were identified with protoarray analysis. Nineteen novel targets and 26 previously published non-HLA Ab were evaluated in a cardiac cohort ( n = 61). Previously published renal targets including nucleolin (NCL) and peroxisomal trans-2-enoyl-CoA reductase (PECR) Ab and multiple novel targets were increased (Mann-Whitney, p Conclusion Multiple non-HLA Ab are present in organ transplant patients some of which are associated with rejection. A panel to screen many non-HLA Ab simultaneously is beneficial to further elucidate the prevalence and organ specificity of non-HLA Ab in allograft rejection. N. Jiang: Employee; Company/Organization; Immucor, Inc. , I. Balazs: Employee; Company/Organization; Immucor, Inc , E.F. Reed: Grant/Research Support; Company/Organization; Immucor, Inc.

Ethnic Differences in Osteoporosis After Cardiac Transplantation

Cardiac transplantation is associated with a high risk of fracture. African Americans (AAs) are believed to have a lower risk of osteoporosis than Caucasians, but it is not clear whether they are also protected from osteoporosis resulting from the use of glucocorticoids and/or organ transplantation. We examined possible ethnic differences in 33 cardiac transplant recipients (16 AAs) in a cross-sectional analysis. In addition to bone mineral density and vertebral fracture assessment, we also compared biochemical variables, trabecular bone score, total body dual-energy X-ray absorptiometry, and disability. Overall fracture rates were low in both groups, with only 6 total subjects with fractures on vertebral fracture assessment or history of fracture. While T-scores were similar between groups, Z-scores were lower in AA with the difference reaching statistical significance when controlling for important covariates. The trabecular bone score was also lower in AAs than in Caucasians even when adjusting for age and tissue thickness (1.198 ± 0.140 vs 1.312 ± 0.140, p = 0.03).While AAs are generally thought to be protected from osteoporosis, our study instead suggests that AAs may be at higher risk of bone deterioration after cardiac transplantation and may need to be managed more aggressively than suggested by current guidelines.

Successful Management of Acute Kidney Injury with Peritoneal Dialysis in a Patient after Heart Transplantation with Burkholderia Septicemia

Acute kidney injury is a common cause of morbidity and mortality after cardiac transplantation. Knowledge of various preoperative, intraoperative and post-operative risk factors allow prevention, early diagnosis and successful management of acute kidney injury. CRRT in the form of acute peritoneal dialysis is a modality of dialysis which is extremely cost effective and is non-inferior to other extra corporeal therapies. We present the successful management of acute kidney injury with peritoneal dialysis in a cardiac transplant recipient in the immediate post operative period who developed sepsis and non-oliguric AKI.

Acute Kidney Injury as a Complication of Cardiac Transplantation: Incidence, Risk Factors, and Impact on 1-year Mortality and Renal Function.

Although chronic deterioration in renal function is frequently seen after cardiac transplantation, which is partly explained by the use of calcineurin inhibitors, data on the consequences of acute kidney injury (AKI) after cardiac transplantation are scarce. In the current study, the incidence of AKI and its impact on mortality and renal function was evaluated. Five hundred thirty-one cardiac transplant recipients (age ≥18 years) were evaluated for the postoperative incidence of AKI defined by the Kidney Disease Improving Global Outcome criteria. Secondary outcomes were renal function and mortality during the first postoperative year. Overall, 405 (76%) recipients met the AKI criteria of which 211 (40%) had AKI stage I, 119 (22%) stage II, 75 (14%) stage III, and 25 patients (5%) required renal replacement therapy (RRT). One-year mortality rates in patients without AKI, stages I, II, and III were 4.8%, 7.6%, 11.8%, and 14.7%, respectively (log-rank test for trend, P = 0.008). In patients that required RRT 1-year mortality was 28.2% (log-rank test P = 0.001). In multivariable analysis only AKI requiring RRT was an independent predictor of 1-year mortality (hazard ratio, 2.75; P = 0.03). Improvement in renal function, compared with baseline values, occurred in 27% of recipients 1 month after transplantation. This was less likely to occur after previous AKI (P ≤ 0.04). The AKI stages I to III were independently proportionally associated with a worse renal function 1 year after transplantation (P ≤ 0.01). Acute kidney injury is highly frequent after cardiac transplantation, and the stage of AKI is associated with increased mortality and impaired renal function in the first postoperative year.

Pregnancy in cardiac transplant recipients.

Successful pregnancy following cardiac transplantation has been described, although outcome data from individual centers are relatively sparse. We investigated maternal and fetal outcomes including change in left ventricular (LV) function and calcineurin inhibitor (CNI) dose in women who became pregnant from our institution. We identified every female patient <49years at the time of transplant who survived >3months post-surgery, between 1985 and 2014. Those who conceived had a review of their medical records and transplant charts. Those currently alive were interviewed. There were 22 pregnancies in 17 women with 20 live births (91%). Mean time from transplantation was 98±62.4months. Rejection complicated one pregnancy, and LV function remained normal in all others. Hypertension complicated 3 (13.6%), preeclampsia 3 (13.6%), and cholestasis 1 (4.5%). Mean birthweight was 2447±608 grams at 34.1±3.6weeks. Four women died following pregnancy. A significant increase in total daily dose of tacrolimus and cyclosporine A was required to maintain therapeutic levels through pregnancy (CyA, P<.001; and Tac, P=.001), with no deterioration in serum creatinine. We report a 91% live birth rate post-cardiac transplantation. Meticulous individualized care with frequent monitoring of CNI levels and LV function is necessary to optimize the maternal and fetal outcomes.

087 - Impact of Early Therapeutic Tacrolimus Levels on Outcomes in Cardiac Transplant Recipients

087 - Impact of Early Therapeutic Tacrolimus Levels on Outcomes in Cardiac Transplant Recipients

312 - Should We Use Dobutamine Stress Echocardiograms to Screen for Cardiac Allograft Vasculopathy in Cardiac Transplant Recipients?

312 - Should We Use Dobutamine Stress Echocardiograms to Screen for Cardiac Allograft Vasculopathy in Cardiac Transplant Recipients?

Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients

Cardiac allograft vasculopathy (CAV) is a major cause of mortality after cardiac transplantation. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is inversely associated with coronary artery disease. In 2 independent studies, we tested the hypothesis that reduced CEC is associated with mortality and disease progression in CAV. We tested the relationship between CEC and survival in a cohort of patients with CAV (n = 35). To determine whether reduced CEC is associated with CAV progression, we utilized samples from the Clinical Trials in Organ Transplantation 05 (CTOT05) study to determine the association between CEC and CAV progression and status at 1 year (n = 81), as assessed by average change in maximal intimal thickness (MIT) on intravascular ultrasound. Multivariable Cox proportional hazard models demonstrated that higher levels of CEC were associated with improved survival (hazard ratio 0.26, 95% confidence interval 0.11 to 0.63) per standard deviation CEC, p = 0.002). Patients who developed CAV had reduced CEC at baseline and 1-year post-transplant. We observed a significant association between pre-transplant CEC and the average change in MIT, particularly among patients who developed CAV at 1 year (β = -0.59, p = 0.02, R2 = 0.35). Reduced CEC is associated with disease progression and mortality in CAV patients. These findings suggest the hypothesis that interventions to increase CEC may be useful in cardiac transplant patients for prevention or treatment of CAV.

Myeloid-derived Suppressor Cells Recruit CD4+/Foxp3+ Regulatory T Cells in a Murine Cardiac Allograft

IntroductionMyeloid-derived suppressor cells (MDSCs) play an important role in regulating allograft rejection in organ transplantation. On the other hand, CD3+/CD4+/FOXP3+ regulatory T cells (Tregs) also are of vital importance in immunological tolerance. We previously revealed that adoptive transfer of MDSCs recruited Tregs in the spleen. However, it is still uncertain whether MDSCs are capable of recruiting Tregs to an allograft in vivo. ObjectivesWe conducted adoptive transfer experiments of MDSCs to clarify the effects of MDSCs on Tregs in vivo. MethodsGr-1+/CD11b+ MDSCs were isolated from rapamycin-treated cardiac transplant (CTx) recipients (3 mg/kg, intraperitoneally on postoperative days [POD] 0, 2, 4, and 6) on POD 7 by magnetic-activated cell sorting (purity >95%). In murine heterotopic cardiac transplantation, 2 × 106 MDSCs were transferred into the graft aorta 5 minutes before reperfusion. ResultsFlow cytometric analyses of a cardiac allograft on POD 7 showed that MDSCs derived from rapamycin-treated CTx mice (MDSCs-Rap) transfer led to significant recruitment of Tregs compared with a PBS-injected allograft. The level of programmed death ligand-1 (PD-L1) on MDSCs-Rap was higher than those from non-treated recipients.Furthermore, pathological findings also confirmed accumulation of Foxp3+ Tregs in an allograft. ConclusionInduced PD-L1 on MDSCs might result in recruitment of Tregs. These results suggested that functional MDSCs possessed an ability to induce Tregs in a cardiac allograft and developed a tendency to immunological tolerance.

(247) - Circulating Exosomes Expressing Cardiac Self-Antigens (Myosin and Vimentin) and miRNA Are Induced in Cardiac Transplant Recipients with Cardiac Allograft Vasculopathy

(247) - Circulating Exosomes Expressing Cardiac Self-Antigens (Myosin and Vimentin) and miRNA Are Induced in Cardiac Transplant Recipients with Cardiac Allograft Vasculopathy

(1179) - Pre-Transplant Amiodarone Exposure Increases Mortality in Cardiac Transplant Recipients: A Meta-Analysis

(1179) - Pre-Transplant Amiodarone Exposure Increases Mortality in Cardiac Transplant Recipients: A Meta-Analysis

(787) - Palliative Care Integration into Cardiac Transplant Recipient Care: A Retrospective Case Series

(787) - Palliative Care Integration into Cardiac Transplant Recipient Care: A Retrospective Case Series

(21) - Outcomes with Gene Expression Profiling for Cardiac Transplant Recipients within North America

(21) - Outcomes with Gene Expression Profiling for Cardiac Transplant Recipients within North America

Association Between Early Cardiac Rehabilitation and Long-term Survival in Cardiac Transplant Recipients

ObjectiveTo determine whether participation in early cardiac rehabilitation (CR) after heart transplant (HTx) affects long-term survival. Patients and MethodsA retrospective review was conducted in 201 patients who underwent HTx at Mayo Clinic between June 1, 2000, and July 31, 2013. Patients were excluded with multiorgan transplant, no CR data, and follow-up less than 90 days after HTx. Demographic and exercise data at baseline before HTx were collected. Post-HTx exercise capacity, biopsy, CR data, and medications were collected at 1 through 5 and 10 years. ResultsOverall survival at 1, 5, and 10 years was 98%, 88%, and 82%, respectively; 29 patients died. Number of CR sessions attended in the first 90 days after HTx predicted survival in multivariate regression, controlling for baseline post-HTx 6-minute walk test (6MWT) results and rejection episodes (hazard ratio, 0.90; 95% CI, 0.82-0.97; P=.007). Additional univariate predictors of survival included pre-HTx 6MWT results, weight at HTx, and body mass index and systolic blood pressure at CR enrollment. Pre-HTx 6MWT results, body mass index, and post-HTx were associated with improvement in peak oxygen consumption. ConclusionThis report demonstrates, for the first time, an association between CR and long-term survival in patients after HTx. Further work should clarify the most beneficial aspects of CR.

Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort

Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n=170). Controls without SCSC (n=324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR]=2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR=0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR=0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus.

Palliative Care Integration into Cardiac Transplant Recipient Care: A Retrospective Case Series (S796)

Palliative Care Integration into Cardiac Transplant Recipient Care: A Retrospective Case Series (S796)