Paroxysmal complete atrioventricular block in pediatric heart transplant recipients following cardiac catheterization: A case series

Late‐onset paroxysmal AVB has been described as a rare complication after HT and has been associated with AR or CAV. We describe 4 pediatric HT recipients who developed paroxysmal AVB hours after routine cardiac catheterization in the absence of AR, CAV, or underlying conduction system disease. Four pediatric HT recipients who were >1 year post‐transplant had episodes of paroxysmal AVB hours after surveillance cardiac catheterization with EMB. Telemetry demonstrated high‐grade block, ranging from 2:1 AVB to complete AVB without ventricular escape for several seconds. None of the patients had significant AR or rapidly progressive CAV. Supplemental testing did not reveal underlying conduction system disease. Three of the 4 patients received permanent pacemakers, although subsequent interrogations showed minimal ventricular pacing. These pediatric HT recipients had paroxysmal AVB hours after cardiac catheterization in the absence of significant AR, CAV, or underlying conduction system disease. Subsequent pacemaker interrogations showed minimal ventricular pacing, suggesting these were isolated episodes. These cases suggest that mechanisms in addition to AR and CAV may cause paroxysmal AVB in pediatric HT recipients, warranting further investigation.     

Donors' characteristics and impact on outcomes in pediatric heart transplant recipients

Organ availability and acceptability limit pediatric HTx. What characteristics define an unacceptable or high‐risk pediatric donor remains unclear. The purpose of this study was to characterize a large cohort of pediatric donors and determine the donor risk factors, including cumulative risk, that affect recipient survival. Data from the PHTS, a prospective multicenter study, were used to examine the impact of donor factors on the outcomes of patients listed <18 yr of age who received a HTx between 1993 and 2009. Donor data were available for 3149 of 3156 HTx (99.8%). Donor cause of death, need for inotropes, or CPR did not affect survival outcomes (p = 0.05). Ischemic time also did not have an impact on overall recipient survival; however, longer ischemic times negatively impacted one‐yr post‐transplant survival (p < 0.0001). There was no impact of cumulative risk factors on survival (p = 0.8). Although used in a minority of cases, hormonal therapy in the donor positively impacted survival (p = 0.03). In multivariate analysis, the only donor factor associated with decreased survival was smaller donor BSA, the other factors being related to the recipient characteristics. When analyzed by recipient age, there were no donor‐related factors that affected survival for those who received a transplant at <6 months of age. Longer ischemic time (p < 0.0001) and greater age difference between the recipient and donor (p = 0.0098) were donor‐related factors impacting early‐phase survival for recipients who received a graft at ≥10 yr of age. Factors perceived to define a marginal or high‐risk pediatric heart donor including inotrope use, CPR and donor cause of death may have less impact on outcomes than previously thought. Longer ischemic times did impact one yr, but not overall survival, and this impact was much greater with older donors. Parameters for accepting a donor heart can potentially be expanded, especially in the infant age group, but strong consideration should always be given to the interaction between ischemic time and donor age.     

Bone mineral status in pediatric heart transplant recipients: A retrospective observational study of an “at risk” cohort

Sachdeva R, Soora R, Bryant JC, Seibert JJ, Blaszak RT, Frazier EA. Bone mineral status in pediatric heart transplant recipients: A retrospective observational study of an “at risk” cohort.
Pediatr Transplantation 2010:14: 383–387. © 2009 John Wiley & Sons A/S. Abstract: There is a paucity of literature assessing the burden of bone loss in PHT recipients. We sought to describe the bone mineral status in PHT recipients by doing a retrospective medical record review of those who underwent evaluation of BMD when clinically indicated. Data collected included patient demographics, BMD evaluations, serum calcium, phosphorus, alkaline phosphatase, cumulative steroid dose, osseous complications and their management. Of 149 PHT recipients, 26 underwent BMD evaluation. This evaluation was done at a median of 3.4 yrs after PHT. There total serum calcium, phosphorus and alkaline phosphatase were similar at transplant and BMD study. The median BMD Z‐scores were: whole body ?0.09 (1.5 to ?5.13) and lumbar spine ?1.1 (1.5 to ?5.16). Bone loss (Z‐score 相似文献   

Fatal cardiac arrest in pediatric heart transplant recipients: Query of the UNOS database

The incidence of death by CA after PHTx is unknown. We aimed to determine the incidence and factors for fatal CA after PHTx, and whether a PM affects survival. Retrospective cohort study utilizing the United Network of Organ Sharing registry of patients transplanted ≤18 years. Multivariable analyses in hazard‐function domain and Kaplan‐Meier analyses were performed for an outcome of death due to CA. There were 7719 PHTx patients queried. CA was the reported cause of death in 11%. Age ≥13 years at time of transplant, presence of a PM, and depressed EF were identified as significant factors for fatal CA. Death due to CA beyond 10 years post‐transplant was associated with depressed EF, CAV, and presence of a PM. Kaplan‐Meier analysis demonstrated higher likelihood of fatal CA in patients with CAV and in those with a PM vs those without. In total, 15% of patients with a PM died from CA. CA is a relatively common cause of death after PHTx. The benefit of a PM remains unclear, but its presence does not confer complete protection. Patients with associated factors warrant vigilant surveillance and consideration for retransplantation.     

Hypoalbuminemia and poor growth predict worse outcomes in pediatric heart transplant recipients

Children with end‐stage cardiac failure are at risk of HA and PG. The effects of these factors on post‐transplant outcome are not well defined. Using the PHTS database, albumin and growth data from pediatric heart transplant patients from 12/1999 to 12/2009 were analyzed for effect on mortality. Covariables were examined to determine whether HA and PG were risk factors for mortality at listing and transplant. HA patients had higher waitlist mortality (15.81% vs. 10.59%, p = 0.015) with an OR of 1.59 (95% CI 1.09–2.30). Survival was worse for patients with HA at listing and transplant (p ≤ 0.01 and p = 0.026). Infants and patients with congenital heart disease did worse if they were HA at time of transplant (p = 0.020 and p = 0.028). Growth was poor while waiting with PG as risk factor for mortality in multivariate analysis (p = 0.008). HA and PG are risk factors for mortality. Survival was worse in infants and patients with congenital heart disease. PG was a risk factor for mortality in multivariate analysis. These results suggest that an opportunity may exist to improve outcomes for these patients by employing strategies to mitigate these risk factors.     

Screening for rejection in symptomatic pediatric heart transplant recipients: the sensitivity of BNP

Abstract:  As the pediatric OHT population expands, there is increasing demand for convenient, yet sensitive screening techniques to identify children with acute rejection when they present to acute care facilities. In children, symptoms of acute rejection or other causes of graft dysfunction are often non-specific and can mimic other childhood illnesses. The aim of this study was to assess the utility of BNP as a biomarker to assist providers in clinical decision-making when evaluating symptomatic pediatric heart transplant patients. One hundred twenty-two urgent care and emergency room visits from 53 symptomatic pediatric OHT patients were retrospectively reviewed to evaluate the relationship between BNP levels, symptoms, and clinical diagnosis at these visits. An ROC curve was generated to determine the accuracy of BNP as a screening tool for acute rejection in this patient population. In this group of patients, a BNP value of >700 pg/mL was 100% sensitive and 92% specific for detecting allograft acute rejection (NPV of 100%). We concluded that BNP is a highly sensitive screening test for acute rejection in symptomatic pediatric heart transplant patients.     

Safety of mTOR inhibitor continuation in pediatric heart transplant recipients undergoing surgical procedures

mTOR inhibitors have been associated with SWC when used in the perioperative period. Limited literature is available to guide providers in managing chronic mTOR inhibitor use in the perioperative period, especially in the pediatric setting. The primary aim of this study was to describe the prevalence of SWC with mTOR inhibitor continuation during the perioperative period for major surgeries. Heart transplant recipients ≤25 years old at the time of primary heart transplant receiving sirolimus maintenance therapy during a surgical procedure and within the study period were included. Surgeries identified within the study period included otolaryngology procedures (46.2%), such as tonsillectomies with or without adenoidectomies, cardiac surgeries (30.8%) including a sternal revision, pulmonary vein repair, and pacemaker placement in two patients, orthopedic surgeries (15.4%) including a posterior spinal fusion and an Achilles tendon lengthening with ankle and subtalar joint release, and a neurosurgery (7.7%), which was a ventriculoperitoneal shunt revision. Thirteen surgical encounters were examined. One SWC was observed, an infected pacemaker requiring systemic antibiotics and removal of the device. The results of this study suggest that sirolimus may be continued in the perioperative period based on the low rate of SWC observed.     

School re-entry of the pediatric heart transplant recipient

Pediatric cardiac transplant has become increasingly frequent in the last decade and survival rates have improved remarkably. Outcome research on this population suggests that the majority of children have the capacity for healthy adaptation although 25-40% have been shown to have some type of psychiatric difficulties. As school plays a major role in these children's lives, early intervention and close liaison with schools is indicated to reduce psychological morbidity, enhance adaptation within the school environment and enhance overall adjustment. This paper proposes a model for a school re-entry program for this population. The school re-entry program is aimed at children who are undergoing cardiac transplant and will be entering or re-entering the school system. They may range in academic age from preschool to college level and have been attending private or public schools with placements in regular education programs, regular education programs with resource support, special education programs, and alternative school programs. Others may not have been attending school because of the severity of their medical condition and have been receiving in-home tutoring. Each child is offered school re-entry assistance by a multi-disciplinary team composed of members from the Cardiology Transplant Service. The re-entry program includes cognitive and psychosocial assessment, liaison with the child's school pre- and post-transplant, academic planning and provision of academic, emotional, and behavioral support before, during, and immediately after transplant, a school re-entry visit, and an ongoing school consultation. The goal is to address issues necessary for a successful school re-entry including appropriate academic placement and support, psychosocial adjustment, education of school personnel and ongoing health needs of the student. The next step is to formally evaluate the efficacy of this program in successful school re-entry.     

Permanent pacemaker implantation in pediatric heart transplant recipients: A systematic review and evidence quality assessment

Bradyarrhythmias are a common complication following pediatric OHT and may require permanent pacemaker implantation (PPM). The purpose of this study was to investigate the incidence, predictors, and outcomes of children undergoing PPM implantation following OHT. A PRISMA‐compliant systematic literature review was performed using the PubMed database and the Cochrane Library (end‐of‐search date: January 27, 2019). The Newcastle‐Ottawa scale and the Joanna Briggs Institute tool were used to assess the quality of cohort studies and case reports, respectively. We analyzed data from a total of 11 studies recruiting 7198 pediatric patients who underwent heart transplant. PPM implantation was performed in 1.9% (n = 137/7,198; 95% CI: 1.6‐2.2) of the patients. Most patients underwent dual‐chamber pacing (46%, 95% CI: 32.6‐59.7). Male‐to‐female ratio was 1.3:1. Mean patient age at the time of OHT was 10.1 ± 6.3. Overall, biatrial anastomosis was used in 62.2% (95% CI: 52.8‐70.6) of the patients. The bicaval technique was performed in the remaining 37.8% (95% CI: 29.4‐47.1). Sinus node dysfunction was the most frequent indication for PPM implantation (54.4%; 95% CI: 42.6‐65.7) followed by AV block (45.6%; 95% CI: 34.3‐57.3). The median time interval between OHT and PPM implantation ranged from 17 days to 12.5 years. All‐cause mortality was 27.9% (95% CI: 18.6‐39.6) during a median follow‐up of 5 years. PPM implantation is rarely required after pediatric OHT. The most common indication for pacing is sinus node dysfunction, and patients undergoing biatrial anastomosis may be more likely to require PPM.     

BK polyomavirus infection in pediatric heart transplant recipients: a prospective study

BKV infection and nephropathy complicate pediatric HTx, but the incidence and time course of the disease are unknown. We assessed the incidence of BKV infection and its association with kidney dysfunction in pediatric HTx recipients. A single center prospective study compared pediatric (<18 years) HTx recipients, with and without BKV infection, who received an allograft between September 2013 and December 2014. Screening of urine for BKV was performed prior to transplant, and at week 1, and at months 3, 6, 9, 12, and 15 months post‐transplantation. Serum for BKV DNA was assayed if BK viruria was present. Statistics included Fisher's exact test and Student's t test. Twelve patients were enrolled. Two patients were removed per parent request. Two (20%) had BK viruria and one (10%) had BK viremia. No patients developed BKVN. BK viruria was present within 2 months following transplantation. There were no identifiable risk factors for BKV infection and no statistically significant difference in renal function between the groups; however, there was a trend toward worsening renal function in those with BKV infection. BKV infection can occur early following heart transplantation. Screening for BK viruria should be considered in HTx recipients.     

A comprehensive strategy in donor acceptance: Impact on pediatric waitlist and heart transplant outcomes

Significant inter‐ and intra‐center practice variability is present in pediatric donor heart acceptability. This may contribute to variation in the donor refusal rate and may impact waitlist time, morbidity, mortality, and transplant rates. In order to reduce practice variability, our center developed and implemented a comprehensive strategy regarding donor acceptance in September 2017. The aim of this study was to assess the impact of this strategy on waitlist time and outcomes as well as early post‐transplant outcomes. We performed a single‐center, retrospective analysis of all pediatric (<18 years) patients listed for single‐organ heart transplant at our center from September 2015 to September 2018. Patients were divided into those listed before (Group 1) and after implementation of the comprehensive strategy (Group 2). The primary end‐point was waitlist time. Secondary end‐points included waitlist removal due to death or clinical deterioration, donor refusals per listed patient, early post‐transplant outcomes (graft failure, mechanical ventilation time, inotropic support, length of hospital stay) and 1‐year post‐transplant survival. Of 78 listed patients, 54 were transplanted (29 in Group 1), 9 were removed due to death or clinical deterioration (7 in Group 1) and 15 were removed due to clinical improvement (12 in Group 1). The waitlist time was significantly shorter in Group 2 (17 days, IQR 7‐53) vs Group 1 (90 days, IQR 14‐162); P = .006. The number of donor refusals was lower in Group 2 (1, IQR 0‐2.2) vs Group 1 (4, IQR 2‐19); P < .001. The percentage of refused donors with normal function (Left ventricular ejection fraction > 50%) was lower in Group 2 vs Group 1 (53% vs 84%; P < .001). Difference in removal from the waitlist for death or deterioration in Group 2 vs Group 1 (n = 2, 7% vs n = 7, 20%, P = .18) did not reach statistical significance. There was no difference in post‐transplant outcomes between groups. The waitlist time and donor refusals significantly decreased after implementation of a comprehensive donor acceptance strategy without impacting transplant outcomes. This analysis supports the need for a comprehensive approach to donor organ acceptance within a pediatric transplant center.     

Choledochal cyst in two pediatric heart transplant patients

Abstract:  Choledochal cyst is a relatively uncommon entity in Western countries. No reports of choledochal cyst in heart transplant patients have been reported to date. We report two cases of choledochal cyst in pediatric heart transplant recipients, one with post-transplant lymphoproliferative disorder (PTLD) within the cyst. The first patient had abdominal pain, increased liver enzymes and was seropositve for Epstein-Barr virus. A choledochal cyst with PTLD was removed 4 years after heart transplantation. The second patient presented 14 years after heart transplantation with a choledochal cyst that was excised for severe abdominal pain. This previously unreported association between choledochal cysts in conjunction with PTLD and heart transplantation is interesting and a possible common pathogenesis is proposed. The management and alternative treatments were briefly noted. We recommend an aggressive treatment for patients with suspected choledochal cyst after heart transplantation because of the increased potential for malignant transformation.     

Perioperative renal failure in pediatric heart transplant recipients: outcome and risk factors

PRF is encountered in 10-13% of adult heart transplants. Only one study of a single center's experience with PRF has been reported in pediatric patients. This study examines the effect of PRF on pediatric heart transplant outcome using the UNOS database. A total of 3598 patients met inclusion criteria, of whom 254 (7%) had PRF. The PRF group comprised 31 recipients requiring PRE and 223 recipients requiring POST. Compared with No-PRF patients, PRE patients had similar survival rate and POST patients had decreased survival rate at 30 days, one, five, and 10-yr post-transplant (p < 0.001). PRF patients also had significantly lower graft survival at one, five, and 10 yr (p < 0.001). Risk factors for developing PRF included ECMO, ventilator, and inotropic support at listing and CHD as the listing diagnosis. PRF increased the duration of hospital stay and the incidence of chronic severe renal dysfunction. PRF that requires POST (whether or not it began pretransplant) has a significant negative impact on pediatric heart transplant outcome. Specific characteristics identify patients at particular high risk of developing PRF.     

Emergency department utilization in pediatric heart transplant recipients

We used the NEDS database (2010) to evaluate ED utilization in PED HT recipients compared to other patient populations with focus on characteristics of ED visits, risk factors for admission, and charges. We analyzed 433 ED visits by PED HT recipients (median age 8 [range: 0‐18] years). The most common primary diagnosis category was infectious (n=163, 37.6%), with pneumonia being the most common infectious etiology. When compared to all PED visits, HT visits were more likely to result in hospital admission (32.6% versus 3.9%, P<.001), had greater hospital LOS (median of 3 days [IQR 2‐4] versus 2 days [IQR 1‐4], P=.001), and accumulated greater total hospital charges (median $26 317 [IQR $11 438‐$46 407] versus $12 332 [IQR $7092‐$22 583], P<.001). When compared to visits by other SOT recipients, results varied with similar rates of hospital admission for HT, LUNGT, and KT visits and similar LOS for HT and KT visits but differing total hospital charges. Although PED HT recipients account for a small percentage of overall ED visits, they are more likely to be hospitalized and require greater resource utilization compared to the general PED population, but not when compared to other SOT recipients.     

Early post-transplant vaccination with pandemic influenza A/H1N1 vaccine in pediatric heart transplant recipients

Pandemic influenza A/H1N1 virus has the potential to cause severe disease in pediatric transplant patients. A pandemic vaccine against H1N1 is effective in immunocompetent children. We investigated the immunogenicity of this vaccine when given in the first six months after heart transplantation. Four patients younger than two yr received two doses of vaccine and one patient older than seven yr received one dose. Titers were obtained using the HAI at baseline and after final immunization. Five patients were enrolled, ages 0.5-7 yr. Median age at the time of transplant was five months (range 3 wk-7 yr). All patients received induction with anti-thymoglobulin and maintenance immunosuppression with tacrolimus, MMF, and prednisone. Patients were immunized with the adjuvanted H1N1 vaccine after heart transplant at median time of nine wk (range 5-23 wk) post-transplant. Three of five developed protective titers against H1N1. A proportion of pediatric patients may respond to influenza vaccine even when immunized in the early post-transplant period.     

Decline in ventricular function as a result of general anesthesia in pediatric heart transplant recipients

Echocardiography is frequently performed under anesthesia during procedures such as cardiac catheterization with EMB in pediatric HTx recipients. Anesthetic agents may depress ventricular function, resulting in concern for rejection. The aim of this study was to compare ventricular function as measured by echocardiography before and during GA in 17 pediatric HTx recipients. Nearly all markers of ventricular systolic function were significantly decreased under GA, including EF (?4.2% ±1.2, P < .01) and RV FAC (?0.05 ± 0.02, P = .04). Subjects in the first post‐transplant year (n = 9) trended toward a more significant decrease in EF vs those beyond the first post‐transplant year (n = 8; ?6.0% ±1.2 vs ?2.1 ± 2.0, P = .1). This information quantifies a decline in biventricular function that should be expected in pediatric HTx recipients while under GA and can assist the transplant clinician in avoiding unnecessary treatment of transient GA‐induced ventricular dysfunction.     

Feasibility and interpretation of global longitudinal strain imaging in pediatric heart transplant recipients

Evaluation of myocardial mechanics after heart transplant is important in monitoring allograft function and identifying rejection. Speckle tracking global longitudinal strain (GLS) may be more sensitive to early regional changes from rejection. This study aimed to determine feasibility of GLS in pediatric hearts during surveillance echocardiograms, compare their GLS to published norms (?18% to ?22%), and assess association of GLS with other indices of graft function. Retrospective review of transplant echocardiograms from 2013 to 2014. Philips QLAB was used for post‐acquisition GLS analysis. Multiple linear regression was used to assess the association of GLS with echocardiographic/catheterization indices, and B‐type natriuretic peptide (BNP). Forty‐seven patients (84 studies) were included. Calculation of GLS was feasible in 82 studies (97%) with inter‐ and intra‐observer variability of 0.71 and 0.69. Patients (n=9) with rejection had GLS of ?16.4% (SD=3.5%) compared to those without [?16.8% (SD=3.7%)]. GLS worsened linearly with increasing Ln(BNP) (P=<.001), left ventricular volume in diastole (P=<.001), septal a’ wave (P=<.001), and pulmonary capillary wedge pressure (P=<.001). Speckle tracking‐based GLS is feasible and reproducible in pediatric heart recipients and is reduced at baseline. The role of GLS and BNP in detecting early systolic dysfunction warrants further investigation.     

The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients

Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA‐TL are 1.5–3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA‐TL of 0.8–2.0 μg/mL in pediatric HTR. MPA‐TL were retrospectively collected 2–12 months post‐transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA‐TL. A total of 355 MPA‐TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA‐TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m²) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One‐yr survival was 100%. Targeting a lower range for MPA‐TL was not associated with significant rejection or infection. Despite lower MPA‐TL, MMF was discontinued in 3/22 patients for adverse effects.