Acute Antibody-Mediated Rejection Following Heart Transplantation

Acute antibody-mediated rejection (AMR) in heart transplantation is often associated with hemodynamic compromise, and is associated with increased mortality and development of accelerated transplant coronary artery disease (TCAD). The diagnosis of AMR has historically been controversial and outcomes with aggressive immunosuppressive therapy including plasmapheresis and cyclophosphamide are poor. Advances in diagnostic techniques like the demonstration of immunopathologic evidence for antibody-mediated rejection by deposition of the complement split product C4d in tissue and detection of anti-HLA antibodies by flow cytometry will assist in further characterizing AMR. Immunosuppression targeting B-lymphocytes and use of m-TOR inhibitors to alter the predilection to develop TCAD and improve survival in AMR remains to be proven.     

Pancreatitis Following Heart Transplantation: Report of a Case

Serious complications involving the alimentary tract following cardiac transplantations are commonly reported, and may be associated with significant morbidity and mortality. One of the most serious gastrointestinal complications in such patients is acute pancreatitis. There is still little known concerning its pathogenesis, early diagnosis, and the most appropriate treatment for this clinical condition. Many authors have reported a high mortality caused by difficulties in making an accurate diagnosis resulting in the use of inappropriate therapy for so called crypto-symptomatic acute pancreatitis. The factor suspected to be responsible for the increased frequency of the gastroenterological diseases and for their masked onset seems to be immunosuppression, especially by corticosteroids. The case of a 46-year-old male patient with cardiac transplant, who, 3 years after the transplantation, developed mild acute pancreatitis, is presented. The immunosuppressive regimen he followed was based on cyclosporine. The acute pancreatitis was treated conservatively with a satisfactory outcome. In the course of the illness the patient developed a pancreatic pseudocyst that was managed successfully by percutaneous drainage. The patient is currently being followed up, and both his medical ailments and health-related quality of life are being monitored, while he continues to show mild symptoms of chronic pancreatitis.     

Predictors of Organ Allograft Tolerance Following Hematopoietic Cell Transplantation

Using the miniature swine large animal model we have attempted to determine the relationship between tolerance and the presence of donor cells in the bone marrow, thymus and lineages of peripheral blood in a series of hematopoietic cell transplant recipients receiving delayed donor allografts without immunosuppression. Twenty-two animals receiving hematopoietic cell transplantation and a delayed organ allograft were analyzed. Assays for presence of donor CFUs in bone marrow (by PCR), thymic chimerism (by FACS and PCR/Southern Blot), peripheral blood chimerism (by FACS), and in vitro responsiveness to donor MHC were performed. Presence of donor BM CFUs, thymic chimerism and multilineage peripheral blood chimerism at the time of organ transplantation all correlated precisely with subsequent allograft tolerance (p < 0.001, p < 0.001, p < 0.005 respectively). These parameters were therefore accurate predictors (Positive Predictive Value (PPV) = 100% in all) of tolerance. In vitro assays of responsiveness were also highly associated (p < 0.002, p < 0.002 respectively), but were not as accurate predictors of subsequent organ tolerance (CML PPV = 80%). Engraftment, as indicated by the presence of donor derived CFU in the bone marrow, detectable thymic chimerism and multilineage peripheral blood chimerism are reliable predictors of subsequent donor allograft acceptance in hematopoietic cell transplant recipients.     

Incidence and Clinical Significance of Hyperkalemia Following Heart Transplantation

BackgroundHyperkalemia (HK) is a life-threatening complication following solid organ transplantation, and patients often need potassium-chelating agents and deviations from standard posttransplant protocols. This is the first study to report the incidence and clinical impact of hyperkalemia following heart transplantation.MethodsWe retrospectively included patients who underwent heart transplantation at our institution between April 2014 and December 2018. Patients with multiorgan transplantation were excluded. Clinical outcomes of patients who had serum potassium >5.5 mEq/L in the first year posttransplant (HK group) were compared to patients who did not have serum potassium >5.5 mEq/L in the first year posttransplant (non-HK group).ResultsA total of 143 patients were included in this study. During the first year posttransplant, cumulative incidence of serum potassium >5.0, >5.5, and >6.0 mEq/L was 96%, 63%, and 24%, respectively. Fifty-five percent of patients required treatment with potassium-chelating agents. Sulfamethoxazole-trimethoprim was discontinued because of HK in 39% of patients. Overall survival of patients in the HK group (n = 89) was comparable to that of patients in the non-HK group (n = 54, 91% vs 98% at 1 year, P = .19), whereas infection-free survival was significantly lower in the HK group (34% vs 53% at 1 year, P = .010). Multivariate analysis revealed pretransplant renal dysfunction (odds ratio = 2.62; 95% confidence interval, 1.18-5.80; P = .018) and use of mechanical circulatory support (odds ratio = 2.90; 95% confidence interval, 1.08-7.76; P = .035) as significant predictors of posttransplant hyperkalemia.ConclusionsThe incidence of HK following heart transplantation was high, with more than half of patients requiring any therapeutic interventions, and HK was related to an increase in infection events.     

Malignancy After Heart Transplantation: Incidence, Prognosis and Risk Factors

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984–2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.     

Lack of Effect of MICA Antibodies on Graft Survival Following Heart Transplantation

Little is known about the effect of MICA antibodies (Abs) on cardiac allograft function and survival. Pretransplant and posttransplant serum from 491 and 196 adult cardiac allograft recipients, respectively, has been investigated for MICA Abs, donor specificity and the effect of MICA Abs on graft survival, acute rejection episodes (AR) and cardiac allograft vasculopathy (CAV). Patients with HLA Abs (11.6%) were excluded from the analysis. A total of 11.8% of patients had MICA Abs, without HLA Abs, before their transplant. Actuarial graft survival demonstrated slightly better survival of patients with donor-specific MICA Abs at 1 and 5 years (88.9% and 83.3%) than patients negative for MICA Abs (72% and 63.7%, p = 0.051). After transplantation, 15.8% of patients produced MICA Abs, and in 17 patients these were produced de novo . There was no effect of pretransplant or posttransplant production of MICA Abs on numbers of AR episodes in year 1, or CAV assessed at years 3 and 5. Immunocytochemistry of cardiac biopsies from 11 patients did not demonstrate a presence of MICA. Sera from only 4/69 patients with MICA Abs fixed complement prior to transplantation and from 7/38 patients following transplantation. In conclusion, this study suggests that MICA Abs do not adversely affect the outcome of cardiac transplantation.     

Clinical and Plasma Proteomic Markers Correlating With Chronic Kidney Disease After Liver Transplantation

Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline glomerular filteration rate (GFR) >60 at the time of LT and are now >3 years post‐LT. Risk factors for post‐LT CKD were compared between three different groups defined by current GFR: >90 (n = 40), 60–90 (n = 146) and <60 (n = 156) mL/min. Age, cyclosporine use and pre‐LT GFR were independently associated with new onset CKD. A subset (n = 64) without viral/immune disease or graft dysfunction underwent multianalyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n = 22) and validation (n = 42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multicenter study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function .     

Twenty-Year Experience With Heart Transplantation for Infants and Children With Restrictive Cardiomyopathy: 1986–2006

Idiopathic restrictive cardiomyopathy (RCM) is a rare cardiomyopathy in children notable for severe diastolic dysfunction and progressive elevation of pulmonary vascular resistance (PVR). Traditionally, those with pulmonary vascular resistance indices (PVRI) >6 W.U. × m² have been precluded from heart transplantation (HTX). The clinical course of all patients transplanted for RCM between 1986 and 2006 were reviewed. Preoperative, intraoperative and postoperative variables were evaluated. A total of 23 patients underwent HTX for RCM, with a mean age of 8.8 ± 5.6 years and a mean time from listing to HTX of 43 ± 60 days. Preoperative and postoperative (114 ± 40 days) PVRI were 5.9 ± 4.4 and 2.9 ± 1.5 W.U. × m², respectively. At time of most recent follow-up (mean = 5.7 ± 4.6 years), the mean PVRI was 2.0 ± 1.0 W.U. × m². Increasing preoperative mean pulmonary artery pressure (PA) pressure (p = 0.04) and PVRI > 6 W.U. × m² (χ²= 7.4, p < 0.01) were associated with the requirement of ECMO postoperatively. Neither PVRI nor mean PA pressure was associated with posttransplant mortality; 30-day and 1-year actuarial survivals were 96% and 86%, respectively. Five of the seven patients with preoperative PVRI > 6 W.U. × m² survived the first postoperative year. We report excellent survival for patients undergoing HTX for RCM despite the high proportion of high-risk patients.     

The Clinical Impact of an Early Decline in Kidney Function in Patients Following Heart Transplantation

Renal dysfunction is a well-known complication following heart transplantation. We examined an early decline in kidney function as a predictor of progression to end-stage renal disease and mortality in heart transplant recipients. We performed a retrospective cohort study of 233 patients who received a heart transplant between July 1985 and July 2004, and who survived >1 month. The decline in estimated creatinine clearance (CrCl) was used to predict the outcomes of need for chronic dialysis or mortality >1-year posttransplant. The earliest time to chronic dialysis was 484 days. A 30% decline in CrCl between 1 month and 12 months predicted the need for chronic dialysis (p = 0.01), all-cause mortality (p < 0.0001) and time to first CrCl ≤30 mL/min at >1-year posttransplant (p = 0.02). A 30% decline in CrCl between 1 month and 3 months also independently predicted the need for chronic dialysis (p = 0.04) and time to first CrCl ≤ 30 mL/min at >1-year posttransplant (p = 0.01). In conclusion, an early drop in CrCl within the first year is a strong predictor of chronic dialysis and death >1-year postheart transplantation. Future studies should focus on kidney function preservation in those identified at high risk for progression to end-stage kidney disease and mortality.     

Association of Clinical Risk Factors with Functional Status Following Lung Transplantation

A fundamental goal of lung transplantation is the regaining of functional capacity, yet little is known about what factors are associated with the achievement of this goal. The aim of this study is to test the association of clinical risk factors with functional status 1 year following lung transplantation. We conducted a cohort study of 321 lung transplants and assessed functionality by the distance achieved during a standard 6-min walk test (6MWT). Preoperative recipient risk factors were evaluated for association with functional status and adjusted for confounding using multivariable linear regression models. In these multivariable analyses, recipient female gender (p<0.001), recipient pretransplant body mass index (BMI) of greater than 27 kg/m2 (p=0.017) and shorter pretransplant 6MWT distances (p=0.006) were independently associated with shorter distances achieved during 6MWT after lung transplant, while cystic fibrosis (CF) (p=0.003), and bilateral lung transplant (p=0.014) were independently associated with longer distances achieved. Approximately 51% of the variance in 6MWT distance was explained by these risk factors in the linear regression models (R2=0.51). These findings may have implications in patient counseling, selection, procedure choice, and may lead to interventions aimed at improving the functional outcomes of lung transplantation.     

RIFLE Criteria for Acute Kidney Dysfunction Following Heart Transplantation: Incidence and Risk Factors

Background and PurposeThere are few data regarding the occurrence of (RIFLE)-based acute kidney dysfunction (AKD) after heart transplantation (HT) and its risk factors. The aim of this study was to apply RIFLE criteria in patients who developed AKD following HT to compare patients with and without AKD and to determine incidence and risk factors of AKD.Patients and MethodsWe retrospectively analyzed the records of 65 patients who underwent HT between 2003 and 2012. We investigated 3 levels of renal dysfunction outlined in RIFLE criteria: risk (R), injury (I), and failure (F). Appropriate class was assigned comparing baseline creatinine level to peak levels in the first 7 days after HT. Perioperative variables of heart transplant recipients were collected.ResultsThe mean age at transplantation was 32.8 ± 16.6 years with 72.7% males. The incidence of AKD was 61%, risk occured in 18%, injury in 16%, and failure in 27% of the patients. Patients who had AKD were significantly older (37.9 ± 15.6 vs 24.6 ± 15.0 years: P = .008), had higher body mass index (24.7 ± 6.7 vs 18.6 ± 4.3; P = .002), and more frequently had history of hypertension (92% vs 8%; P = .011) and smoking (100% vs 0%; P = .008) when compared with those who did not have AKD. When compared with patients who did not develop AKD postoperatively, preoperative higher creatinine levels (1.1 ± 0.3 vs 0.8 ± 0.4; P = .025), intraoperative higher mean arterial pressures (99.2 ± 14.1 vs 89.0 ± 11.4 mm Hg; P = .011), a higher frequency of intraoperative acidosis (81% vs 19%; P = .041), higher lactate levels (5.1 ± 3.8 vs 2.8 ± 1.7 mmol/L; P = .038), and postoperative more frequent use of cyclosporine (91% vs 9%; P = .025) were seen in those who developed AKD. Logistic regression analysis revealed that age (odds ratio [OR], 1.057; 95% confidence interval [CI], 1.010–1.106; P = .018) and use of cyclosporine (OR, 0.099; 95% CI, 0.010–0.935; P = .043) were independent risk factors for AKD.ConclusionsOur results suggest that based on RIFLE criteria, AKD occur in more than half of HTs postoperatively. Older age and use of cyclosporine are associated with AKD following HT.     

Risk Factors for and Clinical Course of Non-Anastomotic Biliary Strictures After Liver Transplantation

Non-anastomotic biliary stricture (NAS) formation is a major complication of liver transplantation. We prospectively determined the time to development of responsiveness to treatment, and clinical outcomes following NAS formation. In addition, an extensive analysis of the association of recipient, donor, and clinical variables with NAS formation was performed. A total of 749 consecutive patients was studied in a prospective, protocol-based fashion. Seventy-two patients (9.6%) developed NAS at a mean of 23.6 +/- 34.2 weeks post-transplantation. Non-anastomotic biliary stricture formation resolved in only 6% of affected patients. Although patient survival was not affected, retransplantation and graft loss rates were significantly greater in recipients who developed NAS. In contrast to previous reports, a pretransplant diagnosis of HCV was associated with a low frequency of NAS formation. The incidence of NAS was independently associated with pretransplant diagnoses of PSC and autoimmune hepatitis. Hepatic artery thrombosis, and prolonged warm and cold ischemia times were also independent risk factors for NAS formation. We conclude that NAS developed in approximately 10% of primary liver transplant recipients. A pretransplant diagnosis of autoimmune hepatitis has been identified as a novel independent risk factor for NAS formation. Development of NAS significantly attenuates graft but not patient survival.     

Survival Outcomes Following Liver Transplantation (SOFT) Score: A Novel Method to Predict Patient Survival Following Liver Transplantation

It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD‐predicted waitlist mortality. Univariate and multivariate analysis on 21 673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30 321 waitlisted candidates reevaluated the predictive ability of the Model for End‐Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3‐month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3‐month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.     

Heart Transplantation:

The gap between the number of potential recipients of a cardiac graft and the availability of donor hearts is still growing. A proper selection of heart transplant candidates is mandatory to ensure that patients in critical need, who are likely to benefit from this procedure, are identified. The work-up of a patient with terminal chronic heart failure includes a comprehensive cardiac and systemic evaluation. Critical in the decision is the exclusion of irreversible pulmonary hypertension. Furthermore, underlying diseases that could compromise short-and long-term prognosis after transplantation should be carefully assessed. The mortality on the waiting list and the growing pool of patients with chronic heart failure that is excluded from transplantation has stimulated the search for alternative treatment modalities. Besides a pharmacologic approach, the last few years have witnessed a tremendous evolution in so-called mechanical devices, designed to improve both morbidity and mortality of these patients. Although several of these devices have only just entered the clinical phase, internal cardioverter defibrillators, left ventricular assist devices and biventricular pacemakers can no longer be viewed as experimental tools.     

OPTN/SRTR 2019 Annual Data Report: Heart

The new adult heart allocation policy was approved in 2016 and implemented in October 2018. This year's Annual Data Report provides early insight into the effects of this policy. In 2019, new listings continued to increase, with 4086 new candidates. Also in 2019, 3597 heart transplants were performed, an increase of 157 (4.6%) from 2018; 509 transplants occurred in children and 3088 in adults. Short- and long-term posttransplant mortality rates improved. Overall, Mortality rates for adult recipients were 6.4% at 6 months and 7.9% at 1 year for transplants in 2018, 14.4% at 3 years for transplants in 2016, and 20.1% at 5 years for transplants in 2014. Mortality rates for pediatric recipients were 6.3% at 6 months and 8.2% at 1 year for transplants in 2018, 10.3% at 3 years for transplants in 2016, and 17.8% at 5 years for transplants in 2014.     

Tracheostomy Following Lung Transplantation Predictors and Outcomes

The effect of tracheostomy on patients receiving lung transplantation is unknown. We reviewed our experience by performing a retrospective analysis on all lung transplant recipients at our institution. Patients were assigned to each study group based on whether or not they received a tracheostomy in the acute postoperative period. One hundred and fourteen lung transplants were performed, and 16 of those patients received a tracheostomy. In the tracheostomy group, more patients had undergone bilateral-lung transplantation (81% vs. 34%, p = 0.001), more required cardiopulmonary bypass (75% vs. 38%, p = 0.005), more acquired postoperative pneumonia (88% vs. 30%, p < 0.001), had greater reperfusion injury at 48 h (PaO2/FiO2 of 233 vs. 345, p = 0.047), had longer initial periods on the ventilator (21 +/- 7 vs. 2 +/- 0.5 days, p < 0.001), more required re-intubation (56% vs. 18%, p = 0.001), spent longer times in the intensive care unit (30 +/- 7 vs. 5.5 +/- 0.9 days, p < 0.001), and had longer lengths of stay (67 +/- 10 vs. 22 +/- 2 days, p < 0.001). Despite these differences between the two groups, a significant difference in survival at 180 days (75 vs. 81%) did not exist (p = 0.89). Although tracheostomy is more likely in sicker patients, it is not associated with poor long-term outcomes.     

Successful Heart Transplantation From a Donor With Ullrich Congenital Muscular Dystrophy

Heart transplantation is the most effective therapy for children with end‐stage heart disease; however, its use is limited by the number of donor organs available. This shortage may be further compounded by concerns about organ quality, leading to refusal of potential donor organ offers. We report on the successful transplantation and 5‐year follow‐up of a heart from a donor with Ullrich congenital muscular dystrophy (UCMD). The candidate was critically ill at the time of the transplant and the donor organ was declined repeatedly on the match run list due to concerns about organ quality, despite having normal cardiac function by echocardiography on minimal inotropic support. We believe the diagnosis of “muscular dystrophy” in the donor combined with a lack of understanding about the specifics of the diagnosis of UCMD enabled our candidate to receive a primary offer for this organ. We are unaware of any previous reports of the use of a heart from a donor with UCMD for orthotopic heart transplantation in adults or children.     

Anemia: A Continuing Problem Following Kidney Transplantation

Cardiovascular disease is a leading cause of death among kidney transplant recipients. Anemia, a risk factor for cardiovascular complications among patients with chronic kidney disease, has not been well characterized in kidney transplant recipients. We performed a retrospective cohort study of the prevalence of and factors associated with anemia among 240 patients who underwent kidney transplantation at our institution. The mean hematocrit (Hct) rose from 33% at 1 month after transplantation to 40% at 12 months after transplantation. The proportion of patients with Hct < 36% was 76% at transplantation and 21% and 36%, 1 year and 4 years after transplantation, respectively. Six months after transplantation, women had higher likelihood (OR = 3.61) of Hct < 36%, while higher Hct at 3 months (OR = 0.67 for 1% higher Hct) and diabetes (OR = 0.14) were associated with a lower likelihood of Hct < 36%. Similar associations were seen 12 months after transplantation. Even among patients with Hct < 30%, only 36% had iron studies, 46% received iron supplementation and 40% received recombinant human erythropoietin. Awareness of factors associated with a lower Hct may prompt better anemia screening and management, potentially improving cardiovascular outcomes among kidney transplant recipients.