Pediatric donor heart utilization variability among organ procurement organizations.

BACKGROUND: Organ procurement organizations (OPOs) are responsible for the medical management of organ donors. Given the variability in pediatric donor heart utilization among OPOs, we examined factors that may explain this variability, including differences in donor medical management, organ quality, and candidate factors. METHODS: The Organ Procurement and Transplant Network database was queried for pediatric (<18 years) heart donors and candidates receiving pediatric donor heart offers from 2010 to 2019. OPOs were stratified by pediatric donor heart utilization rate, and the top and bottom quintiles were compared based on donor management strategies and outcomes. A machine learning algorithm, combining 11 OPO, donor, candidate, and offer variables, was used to determine factors most predictive of whether a heart offer is accepted. RESULTS: There was no clinically significant difference between the top and bottom quintile OPOs in baseline donor characteristics, distance between donor and listing center, management strategies, or organ quality. Machine learning modeling suggested neither OPO donor management nor cardiac function is the primary driver of whether an organ is accepted. Instead, number of prior donor offer refusals and individual listing center receiving the offer were two of the most predictive variables of organ acceptance. CONCLUSIONS: OPO clinical practice variation does not seem to account for the discrepancy in pediatric donor heart utilization rates among OPOs. Listing center acceptance practice and prior number of donor refusals seem to be the important drivers of heart utilization and may at least partially account for the variation in OPO heart utilization rates given the regional association between OPOs and listing centers.

Percutaneous Mitral Valve Repair in Pediatric Patients.

Rigorous clinical trials have demonstrated the safety and efficacy of Transcatheter Edge-to-Edge Repair to treat severe secondary mitral regurgitation (MR) in adults with primary cardiomyopathy who have failed guideline-directed medical therapy, as well as those with primary MR at high surgical risk. To date, there are only three case reports describing this procedure in the pediatric population. We report a case series of four pediatric patients, including the youngest and smallest reported, who underwent this procedure.

Fontan-associated liver disease after heart transplant.

BACKGROUND: Fontan associated liver disease (FALD) potentially impacts Fontan patients undergoing heart transplant. This multi-center study sought to identify pre-transplant risk factors and characterize any post-transplant liver recovery in those patients undergoing heart-alone transplant. METHODS: Review of Fontan patients at 12 pediatric institutions who underwent heart transplant between 2001-2019. Radiologists reviewed pre and post-transplant liver imaging for fibrosis. Laboratory, pathology and endoscopy studies were reviewed. RESULTS: 156 patients underwent transplant due to decreased ventricular function (49%), protein losing enteropathy (31%) or plastic bronchitis (10%); median age at transplant was 13.6 years (interquartile range IQR 7.8, 17.2) with a median of 9.3 years (IQR 3.2, 13.4) between the Fontan operation and transplant. Few patients had pre-transplant endoscopy (18%), and liver biopsy (19%). There were 31 deaths (20%). The median time from transplant to death was 0.5 years (95% Confidence Interval CI 0.0, 3.6). The five-year survival was 73% (95% CI 64%, 83%). Deaths were related to cardiac causes in 68% (21/31) and infection in 6 (19%). A pre-transplant elevation in bilirubin was a predictor of death. Higher platelet levels were protective. Immediate post-transplant elevations in creatinine, AST, ALT, and INR were predictive of death. Advanced liver fibrosis identified on ultrasound, computed tomography, or magnetic resonance imaging was not predictive of death. Liver imaging suggested some improvement in liver congestion post-transplant. CONCLUSIONS: Elevated bilirubin, but not fibrosis on liver imaging, was associated with post-heart transplant mortality in Fontan patients in this multicenter retrospective study. Additionally, heart transplant may alter the progression of FALD.

Transcatheter Occlusion of Left-To-Right Shunts in Premature Infants with Bronchopulmonary Dysplasia.

INTRODUCTION: Patent ductus arteriosus (PDA) and atrial septal defects (ASDs) cause pulmonary overcirculation, potentially worsening bronchopulmonary dysplasia (BPD) in premature infants. Transcatheter device occlusion of these defects is feasible and safe, though no case-controlled studies have assessed respiratory outcomes in infants with BPD. We hypothesized infants with BPD and ASDs or PDAs would experience improved respiratory outcomes following device occlusion of these lesions as compared to those who did not. METHODS: We conducted a single-center, retrospective case-control study of premature infants diagnosed with BPD and either a small to large ASD or a small to moderate PDA from 2015 to 2021. The intervention group underwent transcatheter device occlusion of their defects and the control group did not. We compared changes in BPD severity over time between these two groups. RESULTS: The control and intervention groups demonstrated comparable baseline demographics. Of the 15 patients in the intervention group, 9 underwent PDA device occlusion and 6 underwent ASD device occlusion at median postmenstrual age of 42 weeks (IQR 41-45 weeks). Despite having higher severity BPD at baseline, there was a more pronounced improvement in BPD severity in the intervention group as compared to the control group. DISCUSSION: Premature infants with BPD and an ASD or PDA who underwent transcatheter occlusion of their lesion demonstrated a faster rate of improvement of their BPD severity as compared to a control cohort with similar lesions who did not undergo device occlusion of their lesion.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Emergency department care of patients with Duchenne muscular dystrophy.

Patients with Duchenne muscular dystrophy are living longer and are increasingly seen in Emergency Departments. Though the most common cause of death remains progressive respiratory failure, increased life expectancies have unmasked the significance of progressive myocardial dysfunction, now associated with nearly 40% of mortalities in the DMD population. Cardiac complications such as arrhythmias and cardiomyopathy are becoming ever more widely recognized. Emergency physicians may encounter DMD patients with untreated, undiagnosed or worsening of known heart disease. This review will initially familiarize the emergency physician with the pathophysiology and lifetime trajectory of care for these patients before describing specific emergency department evaluation and treatment.

Standard volume infusion unmasked diastolic dysfunction in pediatric heart transplant recipients during surveillance cardiac catheterization, but without echocardiographic correlates.

BACKGROUND: Adult experience evaluating left ventricular diastolic function (LVDFx) includes volume administration during catheterization while obtaining pulmonary capillary wedge pressures (PCWP) or left ventricular end diastolic pressures (LVEDP). Catheterization is inherently challenging in pediatric patients, making echocardiographic assessment ideal. Pediatric echocardiographic studies predicting LVDFx have variable hemodynamic and hydration conditions and have produced inconsistent results. We evaluated the association between simultaneous echocardiographic and catheterization assessment of LVDFx, using a fluid bolus for optimal loading conditions. METHODS: Prospective cohort study of pediatric heart transplant recipients receiving echocardiogram simultaneous with routine cardiac catheterization. Mitral valve inflow velocities, septal and lateral wall tissue Doppler indices, and PCWP and/or LVEDP were obtained and repeated following a 10 ml/kg bolus. Echocardiographic parameters were evaluated for an association with changes in PCWP or LVEDP following the bolus. Abnormal LVDFx was defined as PCWP or LVEDP ≥12 mm Hg. RESULTS: Twenty-nine patients underwent catheterization. Median pre-bolus PCWP and LVEDP were 11.0 mm Hg and 10.0 mm Hg, respectively. After bolus, median PCWP and LVEDP increased to 14.0 mm Hg (p < .001) and 13 mm Hg (p < .001), respectively. Of 21 patients with normal pre-bolus catheterization hemodynamics, 14 (66.7%) increased to abnormal following fluid bolus. Using area under an ROC, no echocardiographic parameter of LVDFx, or their ratios, were associated with predetermined abnormal LVEDP and/or PCWP. CONCLUSION: After bolus, our cohort demonstrated significant increases in LVEDP and/or PCWP, unmasking diastolic dysfunction. Fluid challenges should be considered in pediatric patients undergoing cardiac catheterization with suspected diastolic dysfunction. Echocardiographic measurements were unable to discriminate between normal and abnormal LVEDP and/or PCWP.

Association Between Pulsatility Index and the Development of Necrotizing Enterocolitis in Infants with Congenital Heart Disease.

Infants with congenital heart disease are known to have higher rates of necrotizing enterocolitis (NEC) which is associated with poorer outcomes. Although the etiology is recognized as distinct from the premature neonatal population, there is not a universal consensus regarding etiology or specific risk factors. In this retrospective single-institution case-control study, we assessed whether aortic pulsatility index (PI) as detected via ultrasound might be associated with NEC in neonates undergoing cardiac surgical repair within the first month of life. The study identified 30 participants who developed NEC and 50 matched controls. Baseline demographic and surgical characteristics were similar between groups. Patients who developed NEC had higher mortality (26% vs 4%, p < 0.01). Standard PI and the modified pulsatility values were calculated manually and underwent logistic regression. The median log PI of the NEC cohort was higher compared to the lowest control PI (0.68 vs 0.48, p = 0.03); the median log PI of the NEC cohort was significantly lower than the highest PI of the control cohort (0.61 vs 0.98, p = 0.05). The modified pulsatility index demonstrated similar trends with the median log MODPI of the NEC cohort being significantly greater than that of the control cohort (3.9 vs. 3.1, p = 0.01). Infants with congenital heart disease who develop NEC have a higher PI and MODPI when compared to the lowest control PI. This suggests that infants with a higher baseline PI may be at increased risk for developing NEC.

Diversity of Dystrophin Gene Mutations and Disease Progression in a Contemporary Cohort of Duchenne Muscular Dystrophy.

Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1-6). Subjects with mutations starting at exon positions 40-54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18-∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12-15) in subjects with mutations that started between exons 55-79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.

Immune Reconstitution Inflammatory Syndrome Complicating Cryptococcal Meningitis in a Pediatric Heart Transplant Patient.

Immune reconstitution inflammatory syndrome can be a complication of cryptococcal meningitis after immune reconstitution from antiretroviral therapy in HIV or reduced immune suppression in transplant recipients. In this case report, the authors discuss the diagnosis and management of cryptococcal-associated immune reconstitution inflammatory syndrome in a 10-year-old pediatric heart transplant recipient.

Orthotopic heart transplant in a pediatric patient with mixed connective tissue disease.

BACKGROUND: Patients with autoimmune inflammatory syndromes such as mixed connective tissue disease (MCTD) and systemic lupus erythematosus have previously been considered marginal candidates for orthotopic heart transplant (OHT). METHODS: A retrospective chart review was completed for this case report. RESULTS: We present the case of an 11-year-old girl with known MCTD who developed congestive heart failure refractory to medical therapy and underwent OHT. CONCLUSIONS: Despite her autoimmune condition, this patient has not experienced antibody-mediated rejection post-transplant and her inflammatory symptoms have greatly improved.

Hypoxemia in infants with trisomy 21 in the neonatal intensive care unit.

OBJECTIVE: Newborns with trisomy 21 (T21) often require NICU hospitalization. Oxygen desaturations are frequently observed in these infants, even in the absence of congenital heart defects (CHD). We hypothesized that NICU patients with T21 have more hypoxemia than those without T21. DESIGN: All infants with T21 without significant CHD discharged home from the NICU between 2009 and 2018 were included (n = 23). Controls were matched 20:1 for gestational age and length of stay. We compared daily severe hypoxemia events (SpO2 < 80% for ≥10 s) for the whole NICU stay and the pre-discharge week. RESULTS: Infants with T21 showed significantly more daily hypoxemia events during their entire NICU stay (median 10 versus 7, p = 0.0064), and more so in their final week (13 versus 7, p = 0.0008). CONCLUSION: NICU patients with T21 without CHD experience more severe hypoxemia events than controls, particularly in the week before discharge. Whether this hypoxemia predicts or contributes to adverse outcomes is unknown.

Survival After Heart Transplant Listing for Infants on Mechanical Circulatory Support.

Background Infants with heart failure remain at significant risk for wait list mortality, despite mechanical circulatory support (MCS). It is unclear if the outcomes are influenced by modality of support or underlying diagnosis. We sought to compare the outcomes of infants <10 kg, focusing on modality of support and underlying diagnosis. Methods and Results Using the Pediatric Heart Transplant Society database, we evaluated survival following first MCS device in children <10 kg who were listed for heart transplant between 2010 and 2018. There were 2049 children <10 kg, with the predominant diagnosis being congenital heart disease (CHD) (59.8% [n=1226]) and 28.1% (n=577) requiring MCS. Extracorporeal membrane oxygenation (ECMO) was the most common form of MCS at listing, with ventricular assist device (VAD) more common after listing. There was no difference in the use of ECMO at or after listing for cardiomyopathy versus CHD (8.9% versus 7.2%; P=0.2; 5.4% versus 6.4%; P=0.4). However, there was a significant difference in the use of VAD both at listing (8% versus 2.4%; P<0.001) and after (22.8% versus 5.1%; P<0.001) between the 2 groups. When comparing these groups, patients with CHD were smaller and younger and had a higher proportion with previous cardiac surgery. Survival at 3 months demonstrated better survival for VAD therapy compared with ECMO (74.3% versus 48.6%; P<0.001). In patients <5 kg, survival did not differ between ECMO and VAD (P=0.01) for the CHD or the cardiomyopathy group (P=0.38), but patients with cardiomyopathy demonstrated better survival on both forms of support. Conclusions Survival for patients <10 kg on ECMO is inferior compared with VAD. Patients with cardiomyopathy <5 kg had better survival with both modes of MCS compared with those with CHD. These findings support the need for small, durable devices for neonates and infants, with particular focus in patients with CHD.

Implantable Cardioverter Defibrillator Use in Males with Duchenne Muscular Dystrophy and Severe Left Ventricular Dysfunction.

Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF) < 35% and/ or shortening fraction (SF) < 16% on final echocardiogram. SLVD was present in 57/436 (13.1%) patients, of which 12 (21.1%) died during the study period. Of these 12, (mean EF 20.9 ± 6.2% and SF 13.7 ± 7.2%), 8 received GDMT, 5 received steroids, and none received an ICD. ICDs were placed in 9/57 (15.8%) patients with SLVD (mean EF 31.2 ± 8.5% and SF 10.3 ± 4.9%) at a mean age of 20.4 ± 6.3 years; 8/9 received GDMT, 7 received steroids, and all were alive at study end; mean ICD duration was 36.1 ± 26.2 months. Nine ICDs were implanted at six different institutions, associated with two appropriate shocks for ventricular tachycardia in two patients, no inappropriate shocks, and one lead fracture. ICD use may be associated with improved survival and minimal complications in DMD cardiomyopathy with SLVD. However, inconsistent GDMT utilization may be a significant confounder. Future studies should define optimal indications for ICD implantation in patients with DMD cardiomyopathy.

Effects of donor cause of death, ischemia time, inotrope exposure, troponin values, cardiopulmonary resuscitation, electrocardiographic and echocardiographic data on recipient outcomes: A review of the literature.

BACKGROUND: Heart transplantation has become standard of care for pediatric patients with either end-stage heart failure or inoperable congenital heart defects. Despite increasing surgical complexity and overall volume, however, annual transplant rates remain largely unchanged. Data demonstrating pediatric donor heart refusal rates of 50% suggest optimizing donor utilization is critical. This review evaluated the impact of donor characteristics surrounding the time of death on pediatric heart transplant recipient outcomes. METHODS: An extensive literature review was performed to identify articles focused on donor characteristics surrounding the time of death and their impact on pediatric heart transplant recipient outcomes. RESULTS: Potential pediatric heart transplant recipient institutions commonly receive data from seven different donor death-related categories with which to determine organ acceptance: cause of death, need for CPR, serum troponin, inotrope exposure, projected donor ischemia time, electrocardiographic, and echocardiographic results. Although DITs up to 8 hours have been reported with comparable recipient outcomes, most data support minimizing this period to <4 hours. CVA as a cause of death may be associated with decreased recipient survival but is rare in the pediatric population. Otherwise, however, in the setting of an acceptable donor heart with a normal echocardiogram, none of the other data categories surrounding donor death negatively impact pediatric heart transplant recipient survival. CONCLUSIONS: Echocardiographic evaluation is the most important donor clinical information following declaration of brain death provided to potential recipient institutions. Considering its relative importance, every effort should be made to allow direct image visualization.

Risk Factors for Cardiac and Non-cardiac Causes of Death in Males with Duchenne Muscular Dystrophy.

As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9-24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger [14.9 (IQR: 11.0-19.1) years] than those dying of cardiac [18 (IQR 15.5-24) years, p = 0.03] and non-cardiac [19 (IQR: 16.5-23) years, p = 0.002] causes. GC use was lower for those dying of cardiac causes compared to those living [2/8 (25%) vs. 304/378 (80.4%), p = 0.001]. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8, p = 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3, p = 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.

ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation.

The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.

Pediatric heart transplant from an incompletely treated influenza A-positive donor.

There is a shortage of pediatric donor hearts for waitlisted children, and yet nearly 50% of organs offered are not transplanted. Donor quality is often cited as a reason for declining organs offered from donors infected with influenza, presumably due to concern about disease transmission at transplant leading to severe disease. We previously described an excellent outcome after heart transplant from a donor infected with influenza B that had been treated with a complete course of oseltamivir. In this report, we describe a similar outcome after transplantation of an organ from an influenza A-positive donor with symptomatic disease incompletely treated with oseltamivir. Due to the availability of effective antiviral treatment, we suggest that influenza A is also a manageable donor infection that need not preclude heart placement.

Use of advanced heart failure therapies in Duchenne muscular dystrophy.

BACKGROUND: As survival and neuromuscular function in Duchenne Muscular Dystrophy (DMD) improve with glucocorticoid therapy and respiratory advances, the proportion of cardiac deaths is increasing. Little is known about the use and outcomes of advanced heart failure (HF) therapies in this population. METHODS: A retrospective cohort study of 436 males with DMD was performed, from January 1, 2005-January 1, 2018, with the primary outcome being use of advanced HF therapies including: implantable cardioverter defibrillator (ICD), left ventricular assist device (LVAD), and heart transplantation (HTX). RESULTS: Nine subjects had an ICD placed, 2 of whom (22.2%) had appropriate shocks for ventricular tachycardia; 1 and 968 days after implant, and all of whom were alive at last follow-up; median 18 (IQR: 12.5-25.5) months from implant. Four subjects had a LVAD implanted with post-LVAD survival of 75% at 1 year; 2 remaining on support and 1 undergoing HTX. One subject was bridged to HTX with ICD and LVAD and was alive at last follow-up, 53 months after HTX. CONCLUSION: Advanced HF therapies may be used effectively in select subjects with DMD. Further studies are needed to better understand risk stratification for ICD use and optimal candidacy for LVAD implantation and HTX, with hopes of improving cardiac outcomes.

Respiratory failure secondary to congenital pulmonary arterial thrombus with lung dysplasia.

Respiratory failure requiring extracorporeal membranous oxygenation in the newborn is commonly seen secondary to severe pathology such as congenital diaphragmatic hernia, meconium aspiration syndrome, pulmonary hypertension and pulmonary hypoplasia. However, atypical causes of respiratory failure, such as pulmonary arterial thrombi, are often refractory to traditional management and require careful multidisciplinary evaluation. We report a case of respiratory failure secondary to congenital pulmonary arterial thrombosis of unknown aetiology in an otherwise healthy neonate. We discuss the abnormal anatomy and pathophysiology that presented in our patient secondary to this condition and discuss our diagnostic process, management and outcomes. Additionally, we review the literature for reported cases and discuss current hypotheses on the development of congenital pulmonary arterial thrombi. Given the rare occurrence of this event, we hope to contribute to the understanding of future similar cases and emphasise the importance of keeping pulmonary arterial thrombi in the clinical differential.