Simultaneous pediatric heart-kidney transplant outcomes in the US: A-25 year National Cohort Study.

BACKGROUND: Pediatric sHKTx remains uncommon in the US. We examined outcomes of pediatric sHKTx compared to PHTx alone. Our objective was to identify a threshold eGFR that justified pediatric sHKTx. METHODS: Data from the SRTR heart and kidney databases were used to identify 9245 PHTx, and 63 pediatric sHKTx performed between 1992 and 2017 (age ≤21 years). RESULTS: The median age for sHKTx was 16 years, and included 31 males (31/63 = 49%). Over half of sHKTx (36/63 = 57%) were performed in cases where pretransplant dialysis was initiated. Among patients who required pretransplant dialysis, the risk of death in sHKTx recipients was significantly lower than PHTx alone (sHKTx vs. PHTx: HR 0.4, 95% CI [0.2, 0.9], p = .01). In those without pretransplant dialysis, there was no improvement in survival between sHKTx and PHTx (p = .2). When stratified by eGFR, PHTx alone recipients had worse survival than sHKTx in the group with eGFR ≤35 ml/min/1.73 m2 (p = .04). The 1- and 5-year actuarial survival rates in pediatric sHKTx recipients were 87% and 81.5% respectively and was similar to isolated PHTx (p = .5). One-year rates of treated heart (11%) and kidney (7.9%) rejection were similar in sHKTx compared to PHTx alone (p = .7) and pediatric kidney transplant alone (p = .5) respectively. CONCLUSION: Pediatric sHKTx should be considered in HTx candidates with kidney failure requiring dialysis or eGFR ≤35 ml/min/1.73 m2 . The utility of sHKTx in cases of kidney failure not requiring dialysis warrants further study.

Ventricular assist device support for children with chemotherapy-induced cardiomyopathy and advanced heart failure: Perspectives gained from a single-center experience.

BACKGROUND: Guidance and data on ventricular assist device (VAD) support for children with chemotherapy-induced cardiomyopathy, particularly within the first 2 years after chemotherapy, are limited. METHODS: We performed a single-center retrospective case series, reviewing medical records of children <18 years of age with chemotherapy-induced cardiomyopathy and advanced heart failure (HF) who received durable VAD support. RESULTS: Six patients met inclusion criteria-5 HeartWare™ HVAD, 1 Berlin Heart EXCOR® . Median age at cancer diagnosis was 6 years (IQR 4.5-10 years). Median dose of anthracycline received was 540 mg/m2 (IQR 450-630 mg/m2 ). All patients developed HF within 1 year after initiation of cancer treatment (median 8 months, IQR 6-11.5 months) and were initiated on durable VAD support at a median of 8 months after completion of cancer treatment (IQR 3.3-43.5 months). Four patients had significant right ventricular dysfunction needing oral pulmonary vasodilator therapy, one patient had a major bleeding complication, and two patients had thromboembolic strokes while on VAD support. Median duration of VAD support was 7.5 months (IQR 3-11.3 months). Two patients underwent VAD explant due to recovery of LV function, one died due to cancer progression, and three underwent heart transplantation. CONCLUSIONS: Durable VAD support should be considered as a therapeutic option for children who have advanced HF due to chemotherapy-induced cardiomyopathy, even within 2 years of completing cancer treatment. A multi-disciplinary approach is essential for appropriate patient selection prior to implant and to ensure comprehensive care throughout the duration of VAD support.

Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study.

OBJECTIVES: Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. DESIGN: Retrospective cohort study. SETTING: Single tertiary-quaternary referral center. PATIENTS: All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. CONCLUSIONS: Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure.

INTRODUCTION: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. METHODS: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. RESULTS: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. CONCLUSIONS: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Pediatric heart-liver transplant outcomes in the United States: A 25-year National Cohort Study.

BACKGROUND: Pediatric HLT remains uncommon in the United States and criteria for HLT are unclear. The objectives of this study were to review the indications, and outcomes of pediatric HLT. METHODS: Data from the Scientific Registry of Transplant Recipients heart and liver databases were used to identify 9245 pediatric isolated heart transplants (PHT), 14 134 pediatric isolated liver transplant (PLT), and 20 pediatric HLT (16 patients underwent sHLT [same organ donor] and four patients with a history of PHT followed by PLT [different organ donors]; age ≤21 years) between 1992 and 2017. Outcomes included patient survival, and 1-year rates of acute heart and liver rejection. RESULTS: The median age for pediatric HLT was 15.6 (IQR: 10.5, 17.9) years, and included 12 males (12/20 = 60%). In the HLT group, the most common indication for HT was CHD (12/20 = 60%), and the most common indication for liver transplant was cirrhosis (9/20 = 45%). The 1, 3, and 5 year actuarial survival rates in pediatric simultaneous HLT recipients (n = 16) were 93%, 93%, and 93%, respectively, and was similar to isolated PHT alone (88%, 81%, and 75.5%, respectively and isolated PLT alone (84%, 82%, and 80%), respectively. There was no heart or liver rejection reported in the HLT group versus 9.9% in heart and 10.6% in liver transplant-only groups, respectively. CONCLUSION: Pediatric HLT is an uncommon but acceptable option for recipients with combined end-organ failure, with intermediate survival outcomes comparable to those of single-organ recipients.

Hospital outcomes for pediatric heart transplant recipients undergoing tracheostomy: A multi-institutional analysis.

Tracheostomy is associated with increased mortality and resource utilization in children with CHD. However, the prevalence and hospital outcomes of tracheostomy in children with HTx are not known. We describe the prevalence and compare the post-HTx hospital outcomes of pediatric patients with Pre-TT and Post-TT to those without tracheostomy. A multi-institutional retrospective cohort study was performed using the Pediatric Health Information System database. Hospital mortality, mediastinitis, LOS, and costs were compared among patients with Pre-TT, Post-TT, and no tracheostomy. Pre-TT was identified in 29 (1.1%) and Post-TT was identified in 41 (1.6%) of 2603 index HTx hospitalizations. Patients with Pre-TT were younger and more likely to have CHD, a non-cardiac birth defect, or an airway anomaly compared to those without Pre-TT. Pre-TT was not independently associated with increased post-HTx in-hospital mortality. Age at HTx < 1 year, CHD, and Post-TT were associated with increased in-hospital mortality. Pre-TT that occurred during the HTx hospitalization and Post-TT were associated with increased resource utilization. Tracheostomy was not associated with mediastinitis.

The pediatric solid organ transplant experience with COVID-19: An initial multi-center, multi-organ case series.

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

Iron Deficiency Is Associated with Adverse Outcomes in Pediatric Heart Failure.

OBJECTIVE: To evaluate the prevalence of iron deficiency and its association with outcomes in children with heart failure. STUDY DESIGN: A single-center retrospective cohort study of patients with heart failure aged 1-21 years from July 2012 to June 2017 with available serum iron studies was performed. Subjects were analyzed in 2 groups: biventricular systolic heart failure (BiV) and single-ventricle congenital heart disease with systolic heart failure (SV). Iron deficiency was defined as ≥2 of the following: serum iron <50 µg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, or transferrin saturation <15%. The primary outcome was a composite adverse event (CAE) of ventricular assist device implantation, heart transplantation, or death, at 3 and 6 months from time of iron studies. RESULTS: Of the 107 subjects (77 BiV, 30 SV) included in the study, 56% were iron deficient. Demographics, etiology of heart failure, and chronicity of heart failure symptoms were not associated with iron deficiency. On multivariable analysis, in group BiV, iron deficiency was associated with CAE at 3 months (79% iron deficiency in CAE group vs 37% iron deficiency in non-CAE, P = .001, OR 7, 95% CI 2-21) and 6 months (76% iron deficiency in CAE vs 35% iron deficiency in non-CAE, P = .002, OR 7, 95% CI 2-24). In group SV, iron deficiency was associated with CAE at 6 months (79% iron deficiency in CAE vs 29% iron deficiency in non-CAE, P = .014, OR 8, 95% CI 2-32). CONCLUSIONS: Iron deficiency was present in 56% of the pediatric patients with heart failure who were evaluated with iron studies. Iron deficiency was associated with greater risk of ventricular assist device implantation, heart transplantation, or death.

Educational and learning morbidity in pediatric heart transplant recipients: A pediatric heart transplant society study.

Educational development is an important component of quality of life for children with heart transplant. Aims include determining prevalence of and risk factors for modified education placement in a large representative sample of pediatric heart transplant recipients. Participants included 1495 patients (age 6-18 years) from the PHTS database. Data on education placement and clinical predictors were collected at listing and at 1 and 3 years post-transplant. At listing, 88% of patients were in typical education placement, while 12% were in modified education. Males (P = .02), those with CHD (P < .0001), those with non-private insurance (P < .0001), and those with longer hospital stay (P = .001) were more likely to be in a modified education placement at time of listing. Age, race, listing status, mechanical support, and waitlist time were not significantly associated with placement. The prevalence of typical education placement was similar (87% at 1-year and 86% at 3-year) post-transplant. Predictors of modified education placement at 3-year follow-up included placement at listing (OR = 12.9 [95% CI 7.6-21.9], P < .0001), non-private insurance (OR = 2.0 [95% CI 1.3-3.2], P = .001), CHD (OR = 1.8 [95% CI 1.1-2.7, P = .01), history of post-transplant infection (OR = 1.9 [95% CI 1.2-2.9, P = .007), and number of post-transplant infections (OR = 1.3 [95% CI 1.1-1.5, P = .002). Among pediatric heart transplant recipients, males, those with non-private insurance, those with CHD, and those who experience post-transplant infections are at greatest risk for modified academic placement, which persists for several years post-transplant and deserves targeted intervention.

Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report.

Pediatric recipients of SOT have a significantly increased risk of Clostridiodes (formerly Clostridium) difficile infection (CDI), which is associated with adverse outcomes after SOT. Alterations to the intestinal microbiota community structure increase the risk of CDI. FMT is a safe and effective treatment for recurrent CDI in immunocompetent children and adults. While there are increasing data that FMT in immunosuppressed patients is safe and effective without increased risk of infection, data regarding safety and efficacy of FMT in children after SOT are limited. To our knowledge, we report the youngest immunocompromised patient to undergo FMT and the third overall case of FMT in a child after HTx. Our patient presented with five episodes of rCDI in 6 months, and 16S rRNA genetic analysis revealed significant loss of overall microbiota community structure and diversity prior to FMT compared with a donor and a healthy, age-matched control. After FMT, marked and prolonged (at least 16 months) shifts in the recipient microbiota community structure and diversity were evident, approaching that of donor and healthy, age-matched control. FMT was well tolerated, restored microbial diversity without any graft or transplant complications, and prevented further rCDI episodes after more than 4 years of follow-up.

Missed Diagnosis of New-Onset Systolic Heart Failure at First Presentation in Children with No Known Heart Disease.

OBJECTIVE: To determine frequency of missed heart failure diagnosis at first presentation among children with no known heart disease admitted with new-onset heart failure. STUDY DESIGN: Using a retrospective design, we reviewed electronic medical records of all patients aged <21 years with no known heart disease, hospitalized with new-onset heart failure during 2003-2015 at a tertiary-quaternary care institution. We assessed records for missed diagnosis of heart failure (primary outcome), associated process breakdowns, and clinical outcomes using a structured data collection instrument. RESULTS: Of 191 patients meeting inclusion criteria, 49% (94/191) were missed on first presentation. Most common incorrect diagnostic labels given to "missed" patients were bacterial infection (29%; 27/94), followed by viral illness (22%; 21/94) and gastroenteritis/hepatitis (21%; 20/94). On multivariable analysis, presentation to primary care provider (PCP), longer duration of symptoms (median 7 days), more than 2 symptoms of heart failure, and nausea/emesis were associated with missed diagnosis. On examining process breakdowns, 49% had errors in history-taking and 50% had no documentation of differential diagnoses. There was no difference in hospital mortality, length of stay, or mechanical circulatory support in missed vs not-missed cohorts. Unnecessary noninvasive and invasive tests were performed in 18% and 4% of patients, respectively. CONCLUSIONS: Nearly one-half of children with no known heart disease hospitalized with systolic heart failure were missed at first presentation and underwent significant nonrelevant treatment and testing. Initial presentation to the PCP, longer duration of symptoms before presentation, and nausea/emesis were associated with missed diagnosis.

Diuretic Responsiveness and Its Prognostic Significance in Children With Heart Failure.

BACKGROUND: Loop diuretics are considered first-line therapy for congestion in children with heart failure, although some patients remain volume overloaded during treatment. We sought to characterize loop diuretic responsiveness (DR) in children hospitalized with acute decompensated failure and to determine whether a decreased response was associated with worse outcomes. METHODS AND RESULTS: DR was calculated for 108 consecutive children ˂21 years of age who were hospitalized with acute decompensated heart failure. DR was defined as net fluid (mL) output per 1 mg of furosemide equivalents during the first 72 hours of treatment with a loop diuretic. The primary outcome was the composite end point of inpatient death or use of mechanical circulatory support. The median DR was 6.0 mL/mg (interquartile range -2.4 to 15.7 mL/mg). Thirty-two percent of patients remained in a positive fluid balance after 72 hours of treatment with a loop diuretic. Death or use of mechanical circulatory support occurred in 29 patients (27%). Low DR was associated with the composite end point, even after adjusting for net urine output and loop diuretic dose indexed to weight (odds ratio 5.3; P = .003). Patients with low DR also experienced longer length of hospital stay than patients with greater DR (median 33 days vs 11 days; P = .002). CONCLUSION: In children hospitalized with acute decompensated heart failure, early diminished loop DR during decongestion therapy is common and portends a poor prognosis.

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.

Hospital Charges for Pediatric Heart Failure-Related Hospitalizations from 2000 to 2009.

Scarce data exist regarding costs of pediatric heart failure-related hospitalizations (HFRH) or how costs have changed over time. Pediatric HFRH costs, due to advances in management, will have increased significantly over time. A retrospective analysis of Healthcare Cost and Utilization Project Kids' Inpatient Database was performed on all pediatric HFRH. Inflation-adjusted charges are used as a proxy for cost. There were a total of 33,189 HFRH captured from 2000 to 2009. Median charges per HFRH rose from $35,079 in 2000 to $72,087 in 2009 (p < 0.0001). The greatest median charges were incurred in patients on extracorporeal membrane oxygenation ($442,134 vs $53,998) or ventricular assist devices ($462,647 vs $55,151). Comorbidities, including sepsis ($207,511 vs $48,995), renal failure ($180,624 vs $52,812), stroke ($198,260 vs $54,974) and respiratory failure ($146,200 vs $48,797), were associated with greater charges (p < 0.0001). Comorbidities and use of mechanical support increased over time. After adjusting for these factors, later year remained associated with greater median charges per HFRH (p < 0.0001). From 2000 to 2009, there has been an almost twofold increase in pediatric HFRH charges, after adjustment for inflation. Although comorbidities and use of mechanical support account for some of this increase, later year remained independently associated with greater charges. Further study is needed to understand potential factors driving these higher costs over time and to identify more cost-effective therapies in this population.

Arrhythmias in children with ventricular assist devices.

BACKGROUND: Children with decompensated heart failure are at high risk for arrhythmias, and ventricular assist device placement is becoming a more common treatment strategy. The impact of ventricular assist devices on arrhythmias and how arrhythmias affect the clinical course of this population are not well described. METHODS AND RESULTS: A single-centre retrospective analysis of children receiving a ventricular assist device between 1998 and 2011 was performed. In all, 45 patients received 56 ventricular assist devices. The median age at initial placement was 13 years (interquartile range 6-15). The median duration of support was 10 days (range 2-260). The aetiology of heart failure included cardiomyopathy, transplant rejection, myocarditis, and congenital heart disease. In all, 32 patients (71%) had an arrhythmia; 19 patients (42%) had an arrhythmia before ventricular assist device and eight patients (18%) developed new arrhythmias on ventricular assist device. Ventricular tachycardia was most common (25/32, 78%). There was no correlation between arrhythmia and risk of death or transplantation (p=0.14). Of the 15 patients who weaned from ventricular assist device, post-ventricular assist device arrhythmias occurred in nine (60%), with five (33%) having their first arrhythmia after weaning. Patients with ventricular dysfunction after ventricular assist device were more likely to have arrhythmias (p<0.02). CONCLUSIONS: Arrhythmias, especially ventricular, are common in children requiring ventricular assist device. They frequently persist for those able to wean from ventricular assist device.

A 25-year experience of endomyocardial biopsy safety in infants.

OBJECTIVES: To analyze the outcomes and risk factors associated with endomyocardial biopsy (EMB) in children less than one year of age. BACKGROUND: EMB has proven to be an integral diagnostic tool to evaluate suspected myocarditis, identify tumor histology, and provide tissue-graft surveillance after cardiac transplantation. The morbidity and mortality of EMB has been well established in the adult literature and reviewed in the general pediatric population, but there remains limited data for children in the first year of life. METHODS: We retrospectively reviewed the cardiology database at our institution to identify patients less than one year of age who underwent EMB between 1984 and 2008. Cardiac catheterization reports were reviewed for patient demographics, biopsy indication, procedural details, and complications. RESULTS: A total of 99 EMBs were performed, 49 for evaluation of suspected myocarditis, 43 for transplant rejection surveillance, 3 to identify tumor histology, and 4 for suspected endocardial fibroelastosis. Forty procedures were performed in children age < 6 months with 11 complications and 59 procedures performed in children age ≥ 6 months with four complications. In total, there were 12 EMB procedures (12.1%) with associated complications: 9 arrhythmias, 4 perforations requiring pericardiocentesis, 1 pneumothorax, and 1 death. Univariate analysis revealed a significant association between perforation and both weight <8 kg (P = 0.05) and age <6 months (P = 0.01). CONCLUSION: Endomyocardial biopsies can be performed safely in infants, although children under 6 months of age and less than 8 kg represent a high risk group and deserve special consideration due to the incidence of complications in this cohort.

Atypical infiltrates on endomyocardial biopsy are associated with adverse outcomes in pediatric heart transplantation.

BACKGROUND: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes. METHODS: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017. Multiorgan transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare vs predominant) on EMB were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (relisting or retransplant), or death. Presence of atypical infiltrates was evaluated: (1) overall using Cox regression with time-dependent covariates and (2) if present by 1 year post-HTx using Kaplan-Meier analysis. RESULTS: Atypical infiltrates were present in 24 out of 95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (hazard ratio (HR) 6.22, 95% confidence interval (CI) 2.60-14.89, p < 0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 nonconsecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p = 0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p < 0.0001). Patients with atypical infiltrates by 1-year post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p = 0.002). CONCLUSIONS: The presence of atypical infiltrates on EMB is associated with significantly worse outcomes in children following HTx. These patients require closer follow-up to assess for developing graft dysfunction.

Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study.

BACKGROUND: Few data exist on prevalence, morbidity, and mortality of pediatric heart failure hospitalizations. We tested the hypotheses that pediatric heart failure-related hospitalizations increased over time but that mortality decreased. Factors associated with mortality and length of stay were also assessed. METHODS AND RESULTS: A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed for pediatric (age ≤18 years) heart failure-related hospitalizations for the years 1997, 2000, 2003, and 2006. Hospitalizations did not significantly increase over time, ranging from 11,153 (95% confidence interval [CI] 8,898-13,409) in 2003 to 13,892 (95% CI 11,528-16,256) in 2006. Hospital length of stay increased from 1997 (mean 13.8 days, 95% CI 12.5-15.2) to 2006 (mean 19.4 days, 95% CI 18.2 to 20.6). Hospital mortality was 7.3% (95% CI 6.9-8.0) and did not vary significantly between years; however, risk-adjusted mortality was less in 2006 (odds ratio 0.70, 95% CI 0.61 to 0.80). The greatest risk of mortality occurred with extracorporeal membrane oxygenation, acute renal failure, and sepsis. CONCLUSIONS: Heart failure-related hospitalizations occur in 11,000-14,000 children annually in the United States, with an overall mortality of 7%. Many comorbid conditions influenced hospital mortality.

Ultrasound dilution: an accurate means of determining cardiac output in children.

BACKGROUND: Cardiac output is a useful measure of myocardial performance. Cardiac output monitoring is frequently performed in critically ill adults to guide physicians' treatment strategies. However, standard methods of determining cardiac output in children are not without risk and can be problematic secondary to their invasive nature and other technical problems. The COstatus system (Transonic Systems, NY), which is based on ultrasound dilution technology, works off in situ catheters and uses an innocuous indicator to allow for routine measurements of cardiac output and blood volumes in pediatric patients. The purpose of this study was to validate cardiac output measured by the COstatus system with those obtained by the clinical standard technique of pulmonary artery thermodilution. METHODS: This was a prospective evaluation performed at a single institution. Any child with a structurally normal heart undergoing hemodynamic evaluation in the cardiac catheterization laboratory was included. A prograde right heart catheterization was performed, and cardiac output was first determined by using the pulmonary artery thermodilution technique. Thermodilution results were then compared with cardiac output measurements obtained using the COstatus system. The results were analyzed by standard correlation, Bland-Altman, and Critchley and Critchley analyses. RESULTS: Twenty-eight patients were evaluated with a median age of 8 yrs and a median weight of 31 kg. The mean thermodilution cardiac index = 3.18 L/min (± 1.35 L/min), and the mean COstatus system cardiac index = 3.17 L/min (± 1.31 L/min). Standard Pearson correlation tests revealed an excellent correlation coefficient of 0.95 (p < .0001). Bland-Altman analysis revealed good clinical agreement with a mean difference of -0.004 L/min with a precision of 0.8 L/min at 2 SD. A percentage error of 25.4% was noticed in this study, which is less than the clinically acceptable limit. CONCLUSION: The ultrasound dilution technique of determining cardiac output using the COstatus system provides a less invasive method than the traditional pulmonary artery thermodilution for accurately determining cardiac output in children. This is the first validation of the COstatus system in pediatric patients. Further studies are required to establish its accuracy in pediatric patients with cardiac shunts and other hemodynamically unstable conditions.