Demonstrating responsiveness of the pediatric cardiac quality of life inventory in children and adolescents undergoing arrhythmia ablation, heart transplantation, and valve surgery.

PURPOSE: Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific pediatric cardiac health-related quality of life (HRQOL) instrument that is reliable, valid, and generalizable. We aim to demonstrate PCQLI responsiveness in children undergoing arrhythmia ablation, heart transplantation, and valve surgery before and after cardiac intervention. METHODS: Pediatric cardiac patients 8-18 years of age from 11 centers undergoing arrhythmia ablation, heart transplantation, or valve surgery were enrolled. Patient and parent-proxy PCQLI Total, Disease Impact and Psychosocial Impact subscale scores were assessed pre- and 3-12 months follow-up. Patient clinical status was assessed by a clinician post-procedure and dichotomized into markedly improved/improved and no change/worse/much worse. Paired t-tests examined change over time. RESULTS: We included 195 patient/parent-proxies: 12.6 ± 3.0 years of age; median follow-up time 6.7 (IQR = 5.3-8.2) months; procedural groups - 79 (41%) ablation, 28 (14%) heart transplantation, 88 (45%) valve surgery; clinical status - 164 (84%) markedly improved/improved, 31 (16%) no change/worse/much worse. PCQLI patient and parent-proxies Total scores increased (p ≤ 0.013) in each intervention group. All PCQLI scores were higher (p < 0.001) in the markedly improved/improved group and there were no clinically significant differences in the PCQLI scores in the no difference/worse/much worse group. CONCLUSION: The PCQLI is responsive in the pediatric cardiac population. Patients with improved clinical status and their parent-proxies reported increased HRQOL after the procedure. Patients with no improvement in clinical status and their parent-proxies reported no change in HRQOL. PCQLI may be used as a patient-reported outcome measure for longitudinal follow-up and interventional trials to assess HRQOL impact from patient and parent-proxy perspectives.

It is important to have quality of life (QOL) measures that are sensitive to change in QOL before and after procedures and to be sensitive to change over time. The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a QOL measure specifically developed for children with cardiac disease. This study assessed the responsiveness of the PCQLI to detect change in QOL over time. QOL in Children and adolescents who were being treated for abnormal heart rhythms, heart transplantation, and aortic, pulmonary, or mitral valve surgery were assessed before and after their procedure. Children and adolescents with improved clinical status post-procedure, and their parents, reported better QOL after the procedure. Patients with no improvement from a cardiac standpoint and their parents reported no change in QOL after their procedure. The PCQLI may be used to assess QOL before and after cardiac procedures or medical treatment and follow QOL over time.

Impact of donor-specific anti-HLA antibody on cardiac hemodynamics and graft function 3 years after pediatric heart transplantation: First results from the CTOTC-09 multi-institutional study.

The aim of this study (CTOTC-09) was to assess the impact of "preformed" (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

Contemporary outcomes of pediatric cardiac transplantation with a positive retrospective crossmatch.

BACKGROUND: A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM. This study's hypothesis is that children with a + XM have similar long-term survival, but higher rate of complications such as rejection, coronary allograft vasculopathy (CAV), and infection, compared to patients with a negative (-) XM. METHODS: The Pediatric Heart Transplant Society Registry (PHTS) database was queried from 2010-2021 for all patients <18 years of age with a known XM. Baseline demographics were compared between + XM and - XM groups using appropriate parametric and non-parametric group comparisons. Cox Proportional Hazards Modeling was used to identify risk factors for post-transplant graft loss, rejection, and CAV. RESULTS: Of 4599 pediatric heart transplants during the study period, XM results were available for 3914 (85%), of which 373 (9.5%) had a + XM. Univariate analysis showed lower 10-year survival for patients with + XM (HR = 1.3, p = .04). Multivariate analyses revealed no significant difference in 10-year survival in the 2 groups; however, time to first rejection (p = .0001) remained significantly shorter in the + XM group. CONCLUSIONS: Pediatric patients transplanted across a + XM experience earlier rejection; however, after multivariate adjustment, + XM is not independently associated with intermediate-term graft loss. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.

Masked Hypertension in Pediatric Heart Transplant Recipients.

BACKGROUND: Masked hypertension (HTN), especially, isolated nocturnal HTN (INH) has been shown to be a risk factor for cardiovascular disease (CVD) but is not studied well in pediatric heart transplant (PHT) patients. Ambulatory blood pressure monitoring (ABPM) is known to identify patients with HTN but is not used routinely in PHT. METHODS: A single-center, prospective, cross-sectional study of PHT recipients was performed to observe the incidence of masked HTN using 24-h ABPM. The relationship between ABPM parameters and clinical variables was assessed using Spearman correlation coefficient. p value < 0.05 was considered significant. RESULTS: ABPM was performed in 34 patients, mean age 14 ± 5 years, median 5.5 years post-PHT. All patients had normal cardiac function, left ventricular mass index and blood pressure measurements in the clinic. Four patients had known prior HTN and on medications, one of them was uncontrolled. Of the remaining 30 patients, 18 new patients were diagnosed with masked HTN, of which 14 had INH. Diurnal variation was abnormal in 82% (28/34) patients. 24-h diastolic blood pressure (DBP) index correlated with glomerular filtration rate (GFR) (r = - 0.44, p = 0.01). There was no correlation between other ABPM parameters with tacrolimus trough levels. CONCLUSIONS: ABPM identified masked HTN in 60% of patients, with majority being INH. Abnormal circadian BP patterns were present in 82% and an association was found between GFR and DBP parameters. HTN, especially INH, is under-recognized in PHT recipients and ABPM has a role in their long-term care.

COVID-19 infection in pediatric solid organ transplant patients.

BACKGROUND: Adult SOT recipients with COVID-19 have higher mortality rates when compared to general population. There is paucity of data on outcomes in pediatric SOT recipients. METHODS: This is a cross-sectional study investigating the prevalence of COVID-19 infection and outcomes in pediatric SOT (heart, liver, and kidney) recipients. We extracted demographic and clinical characteristics and COVID-19 testing (PCR or [Ab] test) results from medical records. Clinical characteristics were compared between patients who were positive for COVID-19 (PCR or Ab) and those who did not, using Mann-Whitney, Student's t test, or chi-square test. p value <.05 was statistically significant. RESULTS: A total of 108 SOT recipients with a median age of 13.1 (8.4, 17.8) years and median 4.2 (2.7, 7.9) years from transplant were checked for COVID-19 via a PCR or Ab test. A positive PCR was confirmed in 10 patients (9.3%), while 12 patients (11.1%) were positive for COVID-19 Ab. The patients who tested positive in our cohort were 9/50 (18%) heart, 6/68 (8.8%) kidney, and 7/50 (14%) liver transplant recipients. There were no differences in the clinical characteristics between patients with and without COVID-19 infection. All patients were either asymptomatic (50%) or had self-limiting symptoms. No changes were made to the immunosuppressive regimen. Only one patient was hospitalized and none had an oxygen requirement. CONCLUSIONS: In our cohort of pediatric SOT recipients, COVID-19 infection was asymptomatic or mild. This data may aid clinicians in counseling patients and families in this increased-risk population.

Safety of Enalapril in Infants: Data from the Pediatric Heart Network Infant Single Ventricle Trial.

OBJECTIVE: To assess the safety profile of angiotensin-converting enzyme inhibitor therapy in infants with single ventricle. STUDY DESIGN: The Pediatric Heart Network conducted a double-blind trial involving infants with single ventricle physiology randomized to receive enalapril or placebo and followed to 14 months of age. Data including demographics, drug administration, hemodynamic monitoring, laboratory measurements, adverse events, and survival were extracted from the public use data set and compared between the placebo and enalapril-treated groups. RESULTS: The Infant Single Ventricle trial randomized 230 patients, with 115 patients in each group. Initial enalapril dose was 0.10 mg/kg/d and median maximal dose was 0.38 mg/kg/d. There was no significant difference in change in blood pressure at study drug initiation or when resuming study drug after Glenn surgery. The incidence of hyperkalemia and neutropenia did not differ between groups. Renal dysfunction occurred in 3% of the enalapril group and none of the placebo patients, which was not statistically significant. There was a high frequency of serious adverse events in both groups. There was no difference in the frequency of heart transplant or death between groups. CONCLUSIONS: Enalapril did not have sustained hemodynamic effects at initiation or up-titration of drug. Creatinine and potassium were not different between groups, although renal dysfunction occurred more often in the patients on enalapril. Although efficacy of enalapril in neonates with single ventricle has not been demonstrated, the safety profile of angiotensin-converting enzyme inhibitors appears to be low risk in infants and children with significant heart disease.

Persistent hypogammaglobulinemia in pediatric solid organ transplant recipients.

INTRODUCTION: Hypogammaglobulinemia has not been well studied in pediatric solid organ transplant (SOT) recipients. We evaluated plasma immunoglobulin (Ig) and lymphocyte phenotypes among 31 pediatric heart and kidney recipients for two years post-transplant and from 10 non-transplanted children. METHODS: Plasma IgM, IgG, and IgA were quantified by immunoturbidimetric assays, IgG subclasses were quantified by bead-based multiplex immunoassay, and lymphocyte phenotypes were assessed by flow cytometry. RESULTS: Median age at transplant for SOT recipients was similar to that of the control cohort (15 vs. 12.5 years, respectively; P = .61). Mean plasma IgG and IgM levels for SOT recipients fell significantly below the control cohort means by 1 month post-transplant (P < .001 for both) and remained lower than control levels at 12-18 months post-transplant. Heart recipients had lower frequencies of a CD4+ naïve T lymphocytes relative to kidney recipients. CONCLUSIONS: Hypogammaglobulinemia was prevalent and persistent among pediatric SOT recipients and may be secondary to immunosuppressive medications, as well as loss of thymus tissue and CD45RA+   CD4+ T cells in heart recipients. Limitations of our study include but are not limited to small sample size from a single center, lack of samples for all participants at every time point, and lack of peripheral blood mononuclear cell samples for the non-transplanted cohort.

Use of bivalirudin as a primary anticoagulant in a child during Berlin Heart EXCOR ventricular assist device support.

We describe our experience of bivalirudin use, a newer direct thrombin inhibitor, in an infant who was supported with Berlin Heart EXCOR VAD (Berlin VAD) as bridge to transplant for 122 days without complications and without need for pump exchange. An 11-month-old girl with dilated cardiomyopathy with acute heart failure was awaiting cardiac transplant. Lack of improvement despite maximizing medical therapy and anticipating a prolonged waitlist time, she was supported with Berlin LVAD as a bridge to transplant. Anticoagulation with bivalirudin was started and titrated with a goal partial thromboplastin time of 60-90 seconds. Therapeutic anticoagulation was achieved with bivalirudin for 50% of the days (61/122 days) on a dose of 2.1 mg/kg/hour and in a narrow dose range of 1.9 to 2.3 mg/kg/hour for 80% of the days (98/122 days). Antiplatelet regimen was started initially with aspirin and clopidogrel added later. She was supported for 122 days on a single pump without any evidence of thrombus or need for pump change. Berlin VAD explant and orthotopic heart transplant with biatrial anastomosis were performed uneventfully. Explanted Berlin VAD had no evidence of clot/fibrin or thrombus formation. The child was discharged to home uneventfully 15 days after cardiac transplant.

Pediatric Cardiomyopathies.

Pediatric cardiomyopathies are rare diseases with an annual incidence of 1.1 to 1.5 per 100 000. Dilated and hypertrophic cardiomyopathies are the most common; restrictive, noncompaction, and mixed cardiomyopathies occur infrequently; and arrhythmogenic right ventricular cardiomyopathy is rare. Pediatric cardiomyopathies can result from coronary artery abnormalities, tachyarrhythmias, exposure to infection or toxins, or secondary to other underlying disorders. Increasingly, the importance of genetic mutations in the pathogenesis of isolated or syndromic pediatric cardiomyopathies is becoming apparent. Pediatric cardiomyopathies often occur in the absence of comorbidities, such as atherosclerosis, hypertension, renal dysfunction, and diabetes mellitus; as a result, they offer insights into the primary pathogenesis of myocardial dysfunction. Large international registries have characterized the epidemiology, cause, and outcomes of pediatric cardiomyopathies. Although adult and pediatric cardiomyopathies have similar morphological and clinical manifestations, their outcomes differ significantly. Within 2 years of presentation, normalization of function occurs in 20% of children with dilated cardiomyopathy, and 40% die or undergo transplantation. Infants with hypertrophic cardiomyopathy have a 2-year mortality of 30%, whereas death is rare in older children. Sudden death is rare. Molecular evidence indicates that gene expression differs between adult and pediatric cardiomyopathies, suggesting that treatment response may differ as well. Clinical trials to support evidence-based treatments and the development of disease-specific therapies for pediatric cardiomyopathies are in their infancy. This compendium summarizes current knowledge of the genetic and molecular origins, clinical course, and outcomes of the most common phenotypic presentations of pediatric cardiomyopathies and highlights key areas where additional research is required. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02549664 and NCT01912534.

Ventricular Arterial Coupling: A Novel Echocardiographic Risk Factor for Disease Progression in Pediatric Dilated Cardiomyopathy.

In adult heart failure (HF) patients, a higher ventricular arterial (VA) coupling ratio measured non-invasively is associated with worse HF prognosis and response to treatment. There are no data regarding the relationship of VA coupling to outcome in pediatric dilated cardiomyopathy (DCM) patients. We investigated the association of VA coupling ratio with worse outcome (mechanical circulatory support, transplant, or death) in 48 children with DCM and 97 age-gender matched controls. Mean age at presentation was 9 ± 7 years; DCM patients had a higher arterial elastance (3.8 ± 1.7 vs 2.7 ± 0.7 respectively p = 0.001), a lower LV elastance (1.1 ± 0.65 vs 4.5 ± 1.4, respectively p = 0.001) and higher VA coupling ratio (5.0 ± 3.9 vs 0.34 ± 0.14, respectively p = 0.001). Outcome events occurred in 27/48 (56%) patients. Patients with an outcome event had a higher NYHA class (p = 0.001), lower LV elastance (0.8 ± 0.47 vs 1.6 ± 0.57, respectively p = 0.001), higher arterial elastance (4.5 ± 1.8 vs 2.9 ± 1.1, respectively p = 0.002), and a higher VA coupling ratio (7.1 ± 3.8 vs 2.2 ± 1.5, respectively p = 0.001) compared to those without. In a multivariate CART analysis, VA coupling was the top and only discriminator of poor outcome. In conclusion, a higher VA coupling ratio is associated with worse outcome in pediatric patients with DCM. VA coupling is promising as a bedside analysis tool that may provide insight into the mechanisms of HF in pediatric DCM and identify potential targets for therapy.

Plasmacytoma-like Posttransplant Lymphoproliferative Disorder in a Pediatric Heart Transplant Recipient.

Posttransplant lymphoproliferative disorder (PTLD) is a diversely manifesting group of lymphoid or plasmacytic proliferations found in solid organ and bone marrow transplant recipients. PTLD occurs as a result of immunosuppression and is often driven by the Epstein Barr virus. Although most commonly of B-cell origin, similar to B-cell lymphomas, PTLD can rarely present as a plasmacytic process, resembling multiple myeloma. Although more common in adults, 8 cases of plasmacytoma-like PTLD have been reported in pediatric renal and combined small bowel-liver transplant recipients. Here, we present a rare report of a plasmacytoma-like PTLD case in a pediatric heart transplant recipient.

Cardiomyopathy Phenotypes and Outcomes for Children With Left Ventricular Myocardial Noncompaction: Results From the Pediatric Cardiomyopathy Registry.

BACKGROUND: Left ventricular noncompaction (LVNC) is a distinct form of cardiomyopathy characterized by hypertrabeculation of the left ventricle. The LVNC phenotype may occur in isolation or with other cardiomyopathy phenotypes. Prognosis is incompletely characterized in children. METHODS AND RESULTS: According to diagnoses from the National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry from 1990 to 2008, 155 of 3,219 children (4.8%) had LVNC. Each LVNC patient was also classified as having an associated echocardiographically diagnosed cardiomyopathy phenotype: dilated (DCM), hypertrophic (HCM), restrictive (RCM), isolated, or indeterminate. The time to death or transplantation differed among the phenotypic groups (P = .035). Time to listing for cardiac transplantation significantly differed by phenotype (P < .001), as did time to transplantation (P = .015). The hazard ratio for death/transplantation (with isolated LVNC as the reference group) was 4.26 (95% confidence interval [CI] 0.78-23.3) for HCM, 6.35 (95% CI 1.52-26.6) for DCM, and 5.66 (95% CI 1.04-30.9) for the indeterminate phenotype. Most events occurred in the 1st year after diagnosis. CONCLUSIONS: LVNC is present in at least 5% of children with cardiomyopathy. The specific LVNC-associated cardiomyopathy phenotype predicts the risk of death or transplantation and should inform clinical management.

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/m(2) ) 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.

Acute Kidney Injury in Pediatric Acute Decompensated Heart Failure.

OBJECTIVE: Acute kidney injury in adult patients with acute decompensated heart failure is associated with increased mortality. There is limited literature in pediatric patients with acute decompensated heart failure and acute kidney injury. We aim to study acute kidney injury in the pediatric acute decompensated heart failure population and its association with specific outcomes. DESIGN: Retrospective, case-control study. SETTING: Cardiac ICU in a children's tertiary care hospital. PATIENTS: Index admissions of patients younger than 21 years with acute decompensated heart failure between January 2008 and December 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Index admissions of patients younger than 21 years with acute decompensated heart failure between January 2008 and December 2012 were reviewed, and the presence or absence of acute kidney injury at admission was determined based on the Pediatric Risk, Injury, Failure, Loss, End-Stage criteria. Descriptive statistics and multivariate analyses were performed to determine the association between acute kidney injury and a composite outcome of cardiac transplantation and/or mortality. Fifty-seven patients, with median age 12 years (interquartile range, 1.1, 16), were included for study. The median left ventricular ejection fraction was 27% (interquartile range, 18, 48). Twenty-one patients (36%) underwent cardiac transplantation and five patients (8.7%) died. Of the 57 patients, 44 (77%) had evidence of acute kidney injury (41% Risk; 39% Injury; 20% Failure). Of the 44 patients with acute kidney injury, 25 (57%) met the composite outcome, compared with 1 (7%) without acute kidney injury. Multivariate analyses demonstrated that a left ventricular ejection fraction up to 25% was significantly associated with the presence of acute kidney injury (adjusted odds ratio, 12.3; 95% CI, 1.4-109; p = 0.03), and acute kidney injury was significantly associated with the composite outcome (adjusted odds ratio, 19.1; 95% CI, 2.3-160; p < 0.001). CONCLUSIONS: Acute kidney injury is common during the initial presentation of pediatric patients with acute decompensated heart failure. A left ventricular ejection fraction up to 25% is associated with acute kidney injury. The presence of acute kidney injury in this population is significantly associated with cardiac transplantation and/or death.

Serial Measurement of Amino-Terminal Pro-B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Outcome in Children With Primary Myocardial Dysfunction and Acute Decompensated Heart Failure.

OBJECTIVES: In children, elevated amino-terminal pro-B-type natriuretic peptide levels are associated with impaired heart function. The predictive value of serial monitoring of amino-terminal pro-B-type natriuretic peptide levels in acute decompensated heart failure is unclear. DESIGN: Prospective observational study. SETTING: Single, tertiary referral pediatric critical care unit. PATIENTS: Patients aged 0-21 years with primary myocardial dysfunction and acute decompensated heart failure. INTERVENTIONS: Amino-terminal pro-B-type natriuretic peptide levels were obtained on enrollment, day 2, and day 7. Clinical, laboratory, and imaging data were collected on enrollment. Adverse cardiovascular outcome was defined as heart transplant, ventricular assist device placement, extracorporeal membrane oxygenation, or death at 1 year after admission. Aminoterminal pro-B-type natriuretic peptide levels and the percent change from day 0 to day 2 and day 0 to day 7 were calculated and compared between those with and without adverse cardiovascular outcome. MEASUREMENTS AND MAIN RESULTS: Sixteen consecutive patients were enrolled. Adverse cardiovascular outcome occurred in six patients (37.5%, four heart transplant and two ventricular assist device). In patients with an adverse cardiovascular outcome, median amino-terminal pro-B-type natriuretic peptide levels at day 7 were significantly higher (7,365 vs 1,196 pg/mL; p = 0.02) and the percent decline in amino-terminal pro-B-type natriuretic peptide was significantly smaller (28% vs 73%; p = 0.02) compared with those without an adverse cardiovascular outcome. Receiver operating curve analysis revealed that a less than 55% decline in amino-terminal pro-B-type natriuretic peptide levels at day 7 had a sensitivity and specificity of 83% and 90%, respectively, in predicting an adverse cardiovascular (area under the curve, 0.86; 95% CI, 0.68-1.0; p = 0.02). CONCLUSIONS: In conclusion, children with primary myocardial dysfunction and acute decompensated heart failure, a persistently elevated amino-terminal pro-B-type natriuretic peptide, and/or a lesser degree of decline in amino-terminal pro-B-type natriuretic peptide during the first week of presentation were strongly associated with adverse cardiovascular outcome. Serial amino-terminal pro-B-type natriuretic peptide monitoring may allow the early identification of children at risk for worse outcome.

Pediatric patient radiation dosage during endomyocardial biopsies and right heart catheterization using a standard "ALARA" radiation reduction protocol in the modern fluoroscopic era.

BACKGROUND: Surveillance endomyocardial biopsy (EMB) with right heart catheterization (RHC) is the standard of care for the assessment of post cardiac transplantation rejection. This procedure has traditionally relied upon fluoroscopy, which exposes both patient and staff to the risks of ionizing radiation. These risks may be of particular concern in the transplant patient who must undergo many such procedures lifelong. We present data on a new "ALARA - As Low As Reasonably Achievable" protocol to reduce radiation exposure during the performance of RHC with EMB. METHODS: All cardiac transplantation patients < 21 years of age who underwent RHC with EMB at The Children's Hospital at Montefiore from 6/11-12/11 were included. EMB was performed after all right heart pressures including wedge pressure and thermodilution cardiac output were measured. A novel ALARA protocol consisting of multiple features including ultra-low frame rates (2-3 fps), low fluoro dose/frame (10-18 nGy/frame), use of the "air-gap" technique for patients < 20 kg, and multiple other techniques aimed at minimizing use of fluoroscopy were employed in all cases. Demographics, procedural data and patient radiation exposure levels were collected and analyzed. RESULTS: 18 patients underwent 45 surveillance RHC with EMB in the study period and were the subject of this analysis. The mean age was 5.9 ± 6.1 years, weight was 20.4 kg ± 16.6 kg, and BSA was 0.75 ± 45 m(2) . PA fluoroscopy was used exclusively in 45/45. Vascular access was RFV (21/45; 47%), RIJV (17/45; 38%), LFV (4/45; 9%) and LIJV (3/45; 7%). The median number of EMB specimens obtained was 5 (range, 4-7). The median fluoroscopy time was 3.7 min (range, 1.2-9). The median air Kerma product (K) was 1.4 mGy (range, 0.4-14), and dose area product (DAP) was 15.8 uGym(2) (range, 3.5-144.5). The K and DAP are substantially lower than any prior published data for RHC/EMB in this patient group. There were no procedural complications. CONCLUSIONS: The use of a novel ALARA protocol for RHC and EMB in pediatric cardiac transplantation patients markedly reduced radiation exposure to levels far below any previously reported values without negatively affecting the safety or efficacy of these procedures.

Reverse ventricular remodeling and improved ventricular compliance after heart transplantation in infants and young children.

After heart transplantation (HT) in infants and young children, environmental and intrinsic factors may lead to changes in the geometry and compliance of the donor heart. Serial demographic, clinical, hemodynamic, and echocardiographic data were obtained from HT recipients younger than 4 years of age. Echocardiographic chamber measurement z-scores were compared using recipient body surface area from the time of HT to 1 week, 3 months, and last follow-up visit. Left ventricular end-diastolic volume (LVEDV) z-scores were correlated with pulmonary capillary wedge pressure (PCWP) at each time point. Heart transplantation was performed for 13 children between March 2009 and December 2012, 9 of whom (69%) were boys. The median age at HT was 8 months (range, 4-43 months), and the mean follow-up period was 13 ± 7 months. Left ventricular end-diastolic dimension z-scores decreased significantly (p = 0.03) between HT and 1 week, then increased from 1 week to 3 and 12 months. (-1.32 ± 1.7, -0.71 ± 1.8, 0.41 ± 2.1, 0.79 ± 2.3, respectively). A positive relationship (R(2) = 0.48) between the LVEDV z-score and PCPW was present at the last follow-up visit. For infants and young children, the allograft demonstrates appropriate growth by 1 year after HT. Left ventricular compliance improves over time.

Prevalence and Impact of Recurrent Rejection on Pediatric Heart Transplant Recipients: A PHTS Multi-Institutional Analysis.

BACKGROUND: Studies evaluating the prevalence and impact of recurrent rejection (RR) in pediatric heart transplant (HT) are sparse. OBJECTIVES: The purpose of this study was to describe prevalence and impact of RR on cardiac allograft vasculopathy (CAV) and graft loss after pediatric HT. METHODS: Data on HT from January 1, 2000, to June 30, 2020, in the Pediatric Heart Transplant Society database were included. Freedom from RR (≥2 rejection episodes) was compared by era (early: 2000-2009; current: 2010-2020). Outcomes for children experiencing RR were compared with those experiencing 0 or 1 rejection episodes and by type of RR (antibody-mediated rejection [AMR], acute cellular rejection [ACR], mixed [ACR/AMR]). RESULTS: Of 6,342 HT recipients, 1,035 (17%) experienced RR. In the current era, pediatric HT recipients were less likely to experience RR (P < 0.001). Freedom from CAV was similar for those experiencing RR to those experiencing 0 or 1 episode (96.6% vs 95.3% vs 96.6%); and similar regardless of the type of RR (AMR, ACR, or mixed) (65.5% vs 82.9% vs 100%) (P > 0.05). Freedom from graft loss was significantly lower for those experiencing RR to those experiencing 0 or 1 episode (56.3% vs 72.3% vs 82.3%) and lower for those experiencing recurrent mixed rejection or recurrent AMR compared with those experiencing recurrent ACR (65.3% vs 50% vs 81.8%). Black children experiencing RR subsequently had lower freedom from CAV and graft loss than White children (P < 0.05 for all). CONCLUSIONS: Although prevalence of RR has decreased, children experiencing RR are at greatly increased risk for losing their graft, particularly those who have recurrent mixed or antibody-mediated rejection.

Progressive Left Ventricular Remodeling for Predicting Mortality in Children With Dilated Cardiomyopathy: The Pediatric Cardiomyopathy Registry.

BACKGROUND: Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end-diastolic dimension (LVEDD), LV end-diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes. METHODS AND RESULTS: We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end-diastolic posterior wall thickness, and the LV end-diastolic posterior wall thickness:LVEDD ratio between baseline and follow-up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1-year follow-up had died, received a heart transplant, or were alive and transplant-free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD Z scores. Median LVFS and LVEDD Z scores improved among survivors (Z score changes of +2.6 and -1.1, respectively) but remained stable or worsened in the other 2 groups. The LV end-diastolic posterior wall thickness:LVEDD ratio increased in survivors only, suggesting beneficial reverse LV remodeling. The risk for death or cardiac transplantation up to 7 years later was lower when LVFS was improved at 1 year (hazard ratio [HR], 0.83; P=0.004) but was higher in those with progressive LV dilation (HR, 1.45; P<0.001). CONCLUSIONS: Progressive deterioration in LV contractile function and increasing LV dilation are associated with both early and continuing mortality in children with dilated cardiomyopathy. Serial echocardiographic monitoring of these children is therefore indicated. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005391.