Pediatric Cardiac Transplant Patients Research Articles

The Effect of Neurodevelopmental Disorders on the Prognosis of Children Undergoing Heart Transplantation: A Retrospective Analysis of the National Inpatient Sample 2011–2019

Background: Many international governing bodies recommend against heart transplantation in patients with severe cognitive-behavioral disabilities, however no clear criteria are offered to define severity. Patients with neurodevelopmental disorders may face systematic discrimination when being evaluated for transplant. We set out to investigate whether children with neurodevelopmental disorders that undergo heart transplantation have poorer in-hospital outcomes compared to neurotypical children. Methods: A retrospective analysis of the National Inpatient Sample database was conducted to identify pediatric patients with neurodevelopmental disorders who underwent heart transplantation from 2011–2019. Baseline characteristics and in-hospital outcomes between patients were compared. Binary logistic regression was used to investigate the association between the documented presence of a neurodevelopmental disorder and in-hospital outcomes in children undergoing heart transplantation. Results: We identified a weighted sample of 3770 pediatric cardiac transplant patients, of whom 245 (6.5%) had a documented diagnosis of neurodevelopmental disorder. There was no significant difference in the odds of major adverse cardiovascular events (all-cause mortality, stroke complications or myocardial infarction), surgical complications, infection, venous thromboembolic events, delirium/restraint use, or cardiac dysrhythmia. Patients with neurodevelopmental disorders had lower overall length of stay (44.0 days interquartile range (IQR): 16.0–90.0 vs. 57.08 days IQR: 22.0–112.0, p < 0.050), and cost of stay ($956,031 IQR: 548,559.0–1,801,412.0 vs. $1,074,793 IQR: 599,089.8–2,129,086.0, p < 0.050). Patients with neurodevelopmental disorders had significantly lower odds of acute transplant complications (adjusted odds ratio (aOR): 0.39, 95% confidence interval (CI): 0.21–0.74, p < 0.050) vascular complications (aOR: 0.36, 95% CI: 0.19–0.66, p < 0.050) and acute kidney injury (AKI) (aOR: 0.52, 95% CI: 0.33–0.83, p < 0.050). Conclusions: These data suggest that patients with neurodevelopmental disorders have overall similar if not potentially improved post-transplant outcomes in the acute setting compared to neurotypical patients, possibly secondary to selection bias in the patient selection process.

Differences in Baseline Immunophenotype in Pediatric Cardiac Transplant Evaluation: How Informed Reductions in Immunosuppression can Improve Patient Outcomes

Lifelong multi-drug immunosuppression is essential in pediatric cardiac transplant with regimens varying between pediatric centers. Current data suggests pre-transplant immunologic phenotype differences may predispose patients to over-immunosuppression. At our tertiary care center, targeted reduction of immunosuppression has recently become common practice despite limited published data. We hypothesize that individualized reduction of immunosuppression in pediatric cardiac transplant patients based on baseline immunophenotype will lead to improved outcomes post-transplant.From January 2020 through July 2022, 52 pediatric patients were referred to our tertiary care center for cardiac transplant evaluation, which includes Immunology evaluation. Patient demographics, cardiac history, and pre-transplant immune evaluation (T/B/NK cell quantitation, quantitative immunoglobulins, vaccine responses and T cell functional testing, as available) were collected. Genetic testing was reviewed. 28 patients who completed cardiac transplant were followed up to 12 months for information on reduced immunosuppression (decreased/bypassed induction with antithymocyte globulin and/or decreased long-term immunosuppression goals), infections, and rejection post-transplant.Of patients referred for evaluation, 63% had congenital heart disease (CHD). Nearly 100% of CHD patients required cardiac surgery in the first year of life with thymectomy. Of all referred patients and of those with available total T cell count (CD3+ T cells), 54% were lymphopenic (CD3+ T cells < 1000/mm3), and 11% of the lymphopenic children were severely lymphopenic (CD3+ T cells < 300/mm3). Patient IgG levels outside of protein losing enteropathy (PLE) and vaccine responses were within normal limits. Available microarray results showed 5 children with abnormal chromosomal syndromes (including 22q11.2 deletion syndrome). Of those referred, 28 patients underwent cardiac transplant and review of outcomes for up to 12 months post-transplant is on-going.Immunologic abnormalities are inconsistent in cardiac patients and may be secondary to early thymectomy, PLE or chromosomal deletion syndromes. Our data demonstrates significant differences in pre-transplant immunologic phenotypes and will add to the limited literature on decreasing immunosuppression in severely lymphopenic cardiac patients. This retrospective study provides encouragement for partnership between immunology and cardiology teams to conduct larger, prospective multicenter studies to further understand individualization of immunosuppression regimens, the role of baseline immunophenotyping to inform these decisions and the resulting improvement in transplant outcomes.

Xenotransplantation: A historical-ethical account of viewpoints.

Formal clinical trials of pig-to-human organ transplant-known asxenotransplantation-may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical-ethical account of xenotransplantation and details if or how viewpoints have shifted over time.

Total Lymphoid Irradiation in The Treatment and Prevention of Pediatric Cardiac Allograft Rejection — A 23-Year Experience

Despite the development of increasingly efficacious immunosuppressive agents, allograft rejection is still a leading cause of morbidity and mortality in pediatric heart transplant patients. Total lymphoid irradiation (TLI) has emerged as a secondary treatment for recurrent cardiac allograft rejection refractory to medication in adults. However, there is limited evidence for long-term TLI efficacy and safety in the pediatric cohort. Our objectives were to evaluate 1) the long-term effects of TLI in treating recurrent pediatric cardiac allograft rejections at a single institution, and 2) the outcome of a unique prophylactic TLI protocol for re-transplant cardiac allograft in pediatric patients. This study included pediatric cardiac transplant patients who received TLI between 1996 and 2014, and who underwent regular right ventricular endomyocardial biopsies. TLI of 800 cGy in 10 fractions was delivered twice a week to the mantle and periaortic/splenic fields. Indication of TLI for treatment of allograft rejection included recurrent episodes (≥ 3) of rejection (defined as ISHLT Grade ≥ 1B/1R) or rejection episodes that failed to respond to medical therapy. Prophylactic TLI was indicated for patients who received a re-transplant cardiac allograft. Follow-up on these patients ended on January 23, 2020, comprising of 23 years of single institutional data. Comparisons in endpoints were performed using paired-sample, non-parametric tests. Eighteen patients underwent TLI for treatment of recurrent cardiac allograft rejection (n = 11, treatment cohort) and/or for rejection prevention in a re-transplant graft (n = 10, prophylactic cohort). Three patients completed 2 courses of TLI for both treatment and prevention of graft rejection. Median follow up was 10.1 years (range 0.5-23 years). In the treatment cohort, TLI demonstrated a trend to prolong the time to graft rejection, from a median of 62 days before TLI to 320 days after TLI (p = 0.054). In the prophylactic cohort, TLI increased ten-year graft survival from 11.1% to 44.4% (n = 9 due to a patient lost to follow-up; p = 0.38). Nine out of 10 patients underwent re-transplant due to graft coronary artery disease in the initial allograft – 1 patient developed coronary vessel narrowing in the re-transplant graft requiring a drug-eluting stent 17.1 years after prophylactic TLI, while the other 8 patients had no evidence of any narrowing, stenosis, or coronary allograft vasculopathy (CAV) in the re-transplant graft (mean CAV-free graft survival 9.4 years). During long-term follow-up, there was no incidence of hematological malignancies or blood dyscrasias. Our study showed that TLI was well tolerated and safe in long-term follow-up. It not only demonstrated a trend to prolong the time to graft rejection, but also showed promising results in preventing CAV and lengthening graft survival if given prophylactically. Further investigation into the role of treatment and prophylactic TLI is warranted.

Longitudinal Strain and Strain Rate Abnormalities Precede Invasive Diagnosis of Transplant Coronary Artery Vasculopathy in Pediatric Cardiac Transplant Patients.

Transplant coronary artery vasculopathy (TCAV) is the primary cause of late graft loss in pediatric heart transplant recipients. TCAV is diagnosed using angiography or intravascular ultrasound; however, noninvasive methods remain elusive. We sought to define patterns of myocardial mechanics in patients with TCAV and to determine whether this can detect TCAV before invasive methods. In this retrospective study, we queried our heart transplant database to identify all recipients with TCAV since 2006 (n = 41). Echoes were reviewed from the last normal catheterization and at TCAV diagnosis, and from time-matched transplant controls (n = 33) without TCAV. Peak global circumferential and longitudinal strain and systolic and diastolic strain rate (SSR and DSR) of the left ventricle were derived using velocity vector imaging. T tests were used to compare both groups longitudinally and between groups at both time points. Longitudinal strain, SSR, and DSR were diminished in the TCAV group compared to the transplant control group at both time points. No differences were found across time points in either group. Retrospective modeling using a longitudinal strain cutoff of 15 % on echoes 2 years prior to TCAV diagnosis predicted development or exclusion of TCAV with sensitivity of 53 %, specificity of 89 % with an area under the curve of 0.8. Decreases in longitudinal strain measurements demonstrate that alterations in myocardial mechanics occur in patients with TCAV at least 2 years prior to invasive diagnosis. These early changes may be due to microvascular disease. This modality could aid in earlier treatment and intervention for this challenging problem .

Eosinophilic esophagitis in children following cardiac transplantation: association with post-transplant lymphoproliferative disorder and other transplant outcomes.

Although cardiac transplantation is life-saving, morbidities from immunosuppression are significant. EoE is a complication of calcineurin inhibitors following liver transplant causing feeding intolerance, weight loss, vomiting, and dysphagia. There are limited reports of EoE following heart transplantation. We performed a retrospective single-center review of pediatric cardiac transplant patients from 2000 to 2010. A case-control analysis of patients with and without EoE was performed evaluating heart transplantation outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty-six transplants were performed in 84 patients; 34 (40%) underwent diagnostic endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7yr (IQR: 2.0-5.2). There were no differences in demographics or use of induction medications between patients with or without EoE. Patients with EoE had fewer episodes of treated rejection (1.0 vs. 2.5; p=0.04). Four of 10 (40%) EoE patients had PTLD compared with only 2/24 (8%) of those without EoE (p=0.048; OR 7.33 [95% CI: 1.1-50.2]). There were no differences in CAV or graft loss between groups. EoE should be considered as a cause of GI symptoms in children after cardiac transplantation and may be associated with fewer rejection episodes and increased rates of PTLD, thus representing a marker of over-immunosuppression.

Pre-Natal Diagnosis of Complex Congenital Cardiac Disease: Is There any Neuro-Developmental Benefit at 2 Years of Age?

s S95 assess cardiac anatomy. Due to the diminutive size of the cardiac structures at this early gestation, 2 Dimensional (2D) imaging alone is often insufficient to identify cardiac anatomy and great vessel relationships. We sought to evaluate the additive benefit of Color Doppler (CD) in addition to routine 2D imaging in early FE before 14 weeks GA. METHODS: From February 2009 we prospectively recruited pregnant women for first trimester FE for a variety of indications including increased nuchal translucency as well as healthy controls. All had 2D cardiac imaging combined with CD assessment. Trans abdominal scanning was used in all cases with trans vaginal scanning used additionally in most cases prior to the 11th week GA (n1⁄492/107, 86%). RESULTS: 254 pregnancies undergoing first trimester FE were included for review. Mean GA at FE was 10+6 weeks (range 6+1 to 13+6 weeks). Significant improvement in image resolution of the fetal heart was gained with every advancing week of gestation. CD significantly improved identification of cardiac arterial outflows and systemic venous inflows from the beginning of the 8th week GA through to the end of the 12th week GA (table 1). Pulmonary venous drainage was not identified in any patient until the 11th week GA. CONCLUSION: When performing early FE, prior to 14 weeks GA, identification of cardiac arterial outflows and systemic venous inflows is greatly improved by the use of color Doppler. When very early FE is performed the use of color Doppler should be routine. WCHRI 021 OPTICAL COHERENCE TOMOGRAPHY TO ASSESS FOR CORONARY ALLOGRAFT VASCULOPATHY IN PEDIATRIC TRANSPLANT RECIPIENTS A Manouzi, MC Hosking, A Fung, A De Souza, JE Potts, KC Harris Vancouver, British Columbia BACKGROUND: Optical Coherence Tomography (OCT) is a highresolution intravascular imaging technique (resolution w 10 microns) that has been used in adults to assess for coronary allograft vasculopathy. The purpose of this study is to describe technical modifications that permit its use in children and compare the coronaryfindings in pediatric transplant recipients to those seen in adults. METHODS: Pediatric cardiac transplant patients were assessed during their routine annual catheterization between December 2012 and April 2013.Modifications weremade to the traditional OCT protocol used in adults in order to adapt this technique to the pediatric population. OCT recordings (Ilumien System, LightLabs,Massachussets)were performed selectively in the right or left coronary artery. Serial measurements of the cross sectional area (CSA) of the lumen, intima and media were made along the length of the vessel. Entire imaging data was analyzed for the presence of mural thrombus, plaque and calcification. We defined the intima-to-media (I/M) area ratio as normal ( 1) or abnormal (>1) as has been done in adult transplant recipients. RESULTS: Seven patients with a history of cardiac transplant were evaluated. The mean age of children was 10.5 years (range 5.5-17) and coronary evaluation was performed a mean of 5.1 years (range 7 months to 15.7 years) following cardiac transplantation. OCT imaging demonstrated intimal thickening in 6/7 (86%) of patients, while conventional angiography was normal in all patients. The median I/M CSA ratio for all patients was 1.25 (0.94-1.79). The intima to lumen CSA ratio was 0.2 in all 7 patients. Intimal thickening was more pronounced in the proximal aspect of the coronaries (figure 1). In contrast to the findings in adults, no other vessel wall abnormalities were identified in this series of children. CONCLUSION: In pediatric cardiac transplant recipients, there are early coronary artery changes seen in the vessel wall with OCT, despite normal selective coronary angiograms. Intimal thickening is present in a significant proportion of children and is most apparent in the proximal coronaries. This is the first description of high-resolution, invivo imaging, of coronary changes in children following cardiac transplantation. 022 CORONARY ARTERY ABNORMALITIES IDENTIFIED WITH OPTICAL COHERENCE TOMOGRAPHY IN CHILDREN WITH KAWASAKI DISEASE A Manouzi, MC Hosking, A Fung, A De Souza, JE Potts, KC Harris Vancouver, British Columbia BACKGROUND: Optical Coherence Tomography (OCT) is an intravascular imaging technique allowing high-resolution

Could contrast-enhanced cardiovascular MRI potentially be used to screen pediatric cardiac transplant patients for transplant coronary artery disease?

“…recent studies suggest that contrast-enhanced cardiovascular MRI techniques can provide a noninvasive means to image and quantify the effects of increased angiogenesis and inflammation in coronar...

Use of a highly sensitive assay for cardiac troponin T and N-terminal pro-brain natriuretic peptide to diagnose acute rejection in pediatric cardiac transplant recipients

Biomarkers have been proposed to augment or replace endomyocardial biopsy (EMB) to diagnose acute transplant rejection (AR). A new, highly sensitive assay for troponin T detects levels of cardiac troponin T (cTnT) 10- to 100-fold lower than standard assays but has not been investigated in transplant patients. N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been evaluated in pediatric transplant patients. The purpose of this pilot study was to evaluate the association of cTnT and NT-proBNP with AR in pediatric cardiac transplant patients. Plasma was obtained at the time of EMB from pediatric patients ≥ 1 year old. N-terminal pro-brain natriuretic peptide was measured in fresh plasma at the time of biopsy, and cTnT was measured from frozen, stored samples using the highly sensitive assay for troponin T. Biomarker data were correlated with EMB results. Cellular AR was defined as an International Society for Heart and Lung Transplantation biopsy score of grade ≥ 2R. Fifty-three blood samples were obtained from 42 patients (mean age 11 years). Seven episodes of AR occurred in 5 patients. Biopsies with vs without AR were associated with higher cTnT (median [interquartile range {IQR}] 66 [45-139] vs 7 [2-13] pg/mL, P = .001) and NT-proBNP (median [IQR] 11,169 [280-23,317] vs 334 [160-650] pg/mL, P < .01). After successful treatment of AR in 5 patients, cTnT fell markedly (median [IQR] 53.5 [44.8-66.5] to 10.7 [1.5-16.4], P = .05). In this pilot study, we found marked elevation of cTnT and NT-proBNP among children with AR. Moreover, reduction in cTnT levels after treatment paralleled improvement in EMB results. If these findings are confirmed in larger prospective studies, monitoring with these biomarkers may obviate surveillance EMB.

393 Donor Specific HLA Antibodies Arising after Pediatric Cardiac Transplantation

The presence of donor specific HLA antibodies(DSA) is known be a risk for poor graft outcome but there is little evidence of long-term effect in pediatric cardiac transplant(Tx) patients(pts) and no data on the effect of transient vs persistent DSA found using newer antibody(Ab) testing methods.

Continuous arterial pressure waveform monitoring in pediatric cardiac transplant, cardiomyopathy and pulmonary hypertension patients

A continuous cardiac output monitor based on arterial pressure waveform (FloTrac/Vigileo; Edwards Lifesciences, Irvine, CA) is now approved for use in adults but not in children. This device is minimally invasive, calculates cardiac output continuously and in real time, and is easy to use. Our study sought to validate the FloTrac with the pulmonary artery catheter (PAC) intermittent thermodilution technique in pediatric cardiac patients. This was a prospective pilot study comparing cardiac output measurements obtained via the FloTrac and arterial pressure waveform analysis with intermittent thermodilution. Subjects carried the diagnosis of pulmonary hypertension or cardiomyopathy, or were in the postoperative course after orthotopic heart transplantation. Enrolled in the study were 31 subjects, and 136 data points were obtained. The age range was 8 months to 16 years. The mean body surface area (BSA) was 1.1 m(2). Bland-Altman plots for the mean cardiac outputs of all subjects with a BSA ≥ 1 m(2) showed limits of agreement of -2.7 to 8.0 l/min (± 5.4 l/min). Patients with a BSA ≤ 1 m(2) demonstrated even wider limits of agreement (± 8.5 l/min). The intraclass correlation for the PAC was 0.929 and 0.992 for the FloTrac. There was poor agreement between the PAC and FloTrac in measuring cardiac output in a population of children with pulmonary hypertension or cardiomyopathy, or after cardiac transplantation. This is in contrast to adult studies published thus far. This suggests that the utility of the FloTrac and measurements obtained from arterial pulse wave analysis in children is uncertain at this time.

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation. Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival. Between June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17). Viral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06). Viral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation.

Evaluation of the myocardial performance index and tissue doppler imaging by comparison to near-simultaneous catheter measurements in pediatric cardiac transplant patients

Parameters derived from Doppler echocardiography, such as the myocardial performance index (MPI) and the ratio of peak velocity of early diastolic prograde flow (E) across the atrioventricular valve (AVV) divided by the peak velocity of early diastolic tissue motion at the AVV annulus (E') (E:E' ratio), are routinely used to assess ventricular function. However, they have not been compared with measurements obtained by cardiac catheterization (CC) in children. We prospectively studied post-cardiac transplant children undergoing CC with near-simultaneous echocardiographic imaging for MPI and E:E'. CC data included right atrial pressure (RAp), pulmonary artery wedge pressure (PAWp) and cardiac index (CI). One investigator, who was blinded to the CC data, measured right ventricular (RV) and left ventricular (LV) MPI and E:E' offline. Correlations between echocardiographic and catheter measurements were calculated. Receiver-operating-characteristics (ROC) curves were created to evaluate the utility of echocardiographic measurements that exhibited statistically significant correlations with CC measurements. Twenty-four patients (age range 0.8 to 21 years) underwent 142 CCs during the study period. Of the 12 correlations studied, 3 met statistical significance (p < 0.05) (RV E:E' vs RAp, RV E:E' vs PAWp and LV MPI vs CI). The ROC areas for these correlations were 0.38, 0.42 and 0.68, respectively. There were no cut-off points where both the sensitivity and specificity for any measurement were >0.80. Our data suggest that MPI and E:E' are poor predictors of simultaneously obtained, catheter-derived hemodynamic parameters in post-transplant children. These limitations should be carefully considered before ascribing diagnostic value to these measurements.

Increase of B-type Natriuretic Peptide from Baseline Increases the Risk of Death or Retransplant in Pediatric Cardiac Transplant Patients, Midterm Results

BACKGROUND; Several studies have demonstrated the utility of B-type natriuretic peptide (BNP) in the months following cardiac transplant. The purpose of this study was to analyze longitudinal BNP data in pediatric cardiac transplant patients and determine the efficacy of BNP in routine follow-up of transplant to help predict the adverse event of death or re-transplant. From October 2002 to July 2007, 53 pediatric cardiac transplant patients were treated in an unmatched case-control study. Along with routine studies, BNP values were obtained at regular intervals. Six patients were excluded due to recent transplant, and three patients were excluded due to poor compliance. A baseline BNP was established for each subject utilizing the mean of all BNP values during year 2 post-transplant, or the first year of measured BNP in those patients whose transplant preceded the study by more than 1 year (time from transplant to first BNP 7.0 +/- 3.5 years). The median BNP of all data points since transplant was utilized as an additional surrogate baseline. Univariate logistic regression was used to evaluate BNP versus other covariates on cardiac death. Forty-four patients provided 1254 BNP data points spanning 173 patient years. Nine (20.5%) had an adverse event. Patients who experienced an adverse event had a higher baseline BNP (mean 365 +/- 290; median 375 +/- 352)) when compared to patients without an event (mean 128 +/- 78; median 121 +/- 62; p = 0.04 and p = 0.06)). All subjects with adverse events had a BNP value >or= 250 during the 90 days preceding the event compared to 32.4% of those who did not (odds ratio: 23.13, p < 0.01). A log fold increase in the BNP value compared to the baseline median BNP is a risk for cardiac death in the subsequent 90-day period (OR: 6.82, 95% confidence interval: 1.25-37.11, p = 0.03). Routine BNP monitoring in the post-cardiac transplant pediatric patient allows for the determination of a median BNP, which can be used as a baseline. A log fold increase from the median BNP, or a BNP value >or= 250, increases the risk of death or re-transplant and suggests a 90-day period of heightened clinical surveillance, perhaps necessitating increased medication or re-listing for repeat transplant.

Interventional cardiac catheterization procedures in pediatric cardiac transplant patients: Transplant surgery is not the end of the road

The objectives of this study are to report the spectrum of cardiac lesions in pediatric patients post-orthotopic heart transplantation (OHT), the characteristics of patients who develop these lesions, and the feasibility of transcatheter intervention in treating these lesions. Indications for OHT in the pediatric population range from cardiomyopathy to complex congenital heart defects with and without prior palliation. These patients may have residual vascular access and great vessel abnormalities. Data was collected through retrospective review of all OHT patients at our institution from 1988 to 2005. During the study period, 276 heart transplants were performed. Forty-seven patients, age 1.6 [0.1-26] years with a weight of 9.5 [3.5-96.0] kilograms, underwent 69 procedures. Patients with original diagnoses of hypoplastic left heart syndrome and failed palliations required intervention most frequently. Sixteen patients, all with a history of left sided disease, developed aortic arch obstruction. Fifteen were successfully treated with balloon angioplasty while one has recurrent supravalve aortic obstruction. Fourteen patients had superior vena cava obstruction treated with balloon angioplasty and/or stent placement. Twelve patients required no further intervention and two required further stent placement. Ilio-femoral vein occlusion was treated with balloon angioplasty alone in 4 patients and stent placement in 10 patients to achieve vessel patency. Other procedures included treatment of branch pulmonary artery and pulmonary vein stenosis. Anastomotic aortic arch and venous obstructive lesions should be sought following pediatric OHT as they occur in almost 20% of patients and can be successfully addressed using interventional techniques.

212: Ultrasound cardiac output monitor measurements in pediatric cardiac transplant patients

Purpose: The ultrasound cardiac output monitor (USCOM) is an FDA approved non-invasive device that can quickly determine cardiac output based on outflow tract velocity measured by continuous doppler and outflow valvular surface area deduced by patients’ height and weight. This investigation examines USCOM measurements in pediatric cardiac transplant patients. Methods and Materials: Following IRB approval and informed consent, USCOM readings were obtained during routine outpatient visits from June to August 2006. Measurements included cardiac index (CI), aortic valve diameter (AVD) and velocity through the aortic valve (VAV). Aortic valve velocities were compared to readings obtained by echocardiogram (ECHO) performed using the paired t-test with statistical significance at p-value 0.05. Results: 16 boys and 15 girls met study entry criteria. Mean age was 11.5 years and mean weight was 42.2 kg (range 12.3 to 146 kg). A single USCOM reading was obtained on each patient. Each USCOM measurement took less than 10 minutes to perform. USCOM derived mean CI was 4.42 L/min/m( /1.74). Mean USCOM VAV (1.13 /0.36 m/sec) was no different than that measured by ECHO (1.14 /0.16 m/sec), p 0.46. However, mean USCOM derived AVD (1.69 cm) was smaller than that measured by ECHO (2.32 cm). This is attributable to fact that the cardiac grafts are typically larger than the recipients’ expected AVD calculated using height and weight. All children appeared healthy and active on discharge from clinic. One child later requiring ICU admission for sepsis had a 50% decrement in CI from his USCOM baseline which also correlated with moderate to severe decrease in graft function on ECHO. Conclusions: VAV in children undergoing heart transplantation obtained by the USCOM device appeared no different from that measured by ECHO, though measured and calculated AVD may vary. USCOM derived CI appears to reasonably portray these patients’ clinical condition. USCOM may be a useful rapid screening tool to assess deviations from the baseline in pediatric heart transplant recipients.

Pediatric Cardiac Transplants: A Clinical Update

In the last 10 years more than 2,600 pediatric patients have received heart transplants. The survival rate at 10 years is 65% (Blume, 2003). There have been profound improvements in the survival and quality of life associated with pediatric heart transplants. Due to the increase in survival and quality of life, it is becoming more common for nurses to care for these unique patients. Nurses need to be aware of the complex management of pediatric heart transplant patients to aid in their care of these patients. This paper will discuss the transplant process, medications, common complications, and psychosocial impact associated with pediatric heart transplants to better prepare nurses involved in the care of pediatric cardiac transplant patients.

Lack of Correlation Between MMF Dose and MPA Level in Pediatric and Young Adult Cardiac Transplant Patients: Does the MPA Level Matter?

To determine the correlation between mycophenolate mofetil (MMF) dose and mycophenolic acid (MPA) level as well as its impact on rejection among young cardiac transplant recipients (OHT), trough concentrations of MPA and its metabolite, mycophenolic acid glucuronide (MPAG), were measured following MMF doses of 1200 mg/m2/d (max 3000 mg/d). Corresponding endomyocardial biopsy (EMB) grades and calcineurin inhibitor levels were recorded with simultaneous MPA/MPAG levels. Correlation coefficients were derived between MMF dose and MPA/MPAG levels. Contingency analysis evaluated the relation between MPA level and EMB score.Twenty-six patients (median age 15.4 years) had 120 MPA/MPAG levels measured. Average MMF dose was 1208.8 mg/m2/d with median MPA and MPAG concentrations: 2.1 (therapeutic: 1.0–3.5 μg/mL) and 48 μg/mL (reference range: 35–100 μg/mL), respectively. Only 50% of patients consistently achieved therapeutic levels with standard dosing. No correlation was found between MMF dose and MPA/MPAG levels. In the presence of therapeutic calcineurin inhibition, EMB grade ≥ 2 occurred more with MPA concentrations <2.5 μg/mL (p = 0.01).In young OHT patients, MMF dose does not correlate with MPA/MPAG levels, and standard MMF dosing fails to consistently achieve ‘therapeutic’ MPA concentrations. An MPA trough level <2.5 μg/mL was more frequently associated with EMB grade ≥ 2. Concentration rather than dose-driven management is a more prudent strategy when using MMF.

An Assessment of Vancomycin Pharmacokinetic Variability in Pediatric Cardiology Patients

To establish the steady-state pharmacokinetic profile of vancomycin in pediatric cardiology patients; determine an empiric vancomycin dose; and evaluate the correlation between fluid balance and volume of distribution (Vd), serum creatinine and clearance (CL), and daily dose of furosemide and Vd. Retrospective pharmacokinetic evaluation in 36 pediatric cardiology, cardiac surgery, or cardiac transplant patients treated with vancomycin. The pharmacokinetic profile for vancomycin including elimination half-life (t1/2), elimination rate constant (ke), volume of distribution (Vd), and clearance (CL) was calculated for each patient. The relationship between fluid balance and Vd, serum creatinine and CL, and the total daily dose of furosemide and Vd was evaluated. The patient population had an average half-life of 5.9±1.2 hr and a Vd of 0.4±0.12 L/kg. A statistically significant correlation was noted between serum creatinine and CL (r(2)=0.19, P<0.01). Additionally, a statistically significant correlation exists between the total daily furosemide dose and the Vd (r(2)=0.31, P<0.01). A dose of 10 mg/kg/dose every 12 hrs was predicted to result in the greatest number of serum vancomycin concentrations within the reference range. Routine monitoring of serum vancomycin concentrations is prudent for this population, and special consideration should be given to those with elevated serum creatinine and to those receiving large doses of furosemide.

Coronary artery vasculopathy in pediatric cardiac transplant patients: the therapeutic potential of immunomodulators.

The single largest cause of late graft loss in pediatric cardiac transplantation is transplant coronary artery vasculopathy (CAV). The mechanism of CAV remains unknown; it appears to have both immune and non-immune causes. The final common pathway of these mechanisms is endothelial activation, a prothrombotic environment, and endothelial damage with subsequent diffuse intimal proliferation. The disease process has largely been thought to be progressive and unresponsive to treatment. Re-transplantation has been advocated as the only definitive treatment. The appropriate management is largely unknown; intervention or surgical management has had limited utility, while medical management appears to have the most promise. Improvement in outcome can be achieved by optimizing non-immune factors and aggressive management of the immune mechanisms. Long-term survival of transplant patients after diagnosis with CAV is now being reported.