Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.

INTRODUCTION: Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG. Cardiomyopathy is an important phenotype in CDG. The clinical manifestations and progression of cardiomyopathy in CDG patients have not been well characterized. This study aims to delineate common patterns of cardiomyopathy across a range of genetic causes of CDG and to propose baseline screening and follow-up evaluation for this patient population. METHODS: Patients with molecular confirmation of CDG who were enrolled in the prospective or memorial arms of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study were ascertained for the presence of cardiomyopathy based on a retrospective review of their medical records. All patients were evaluated by clinical geneticists who are members of FCDGC at their respective academic centers. Patients were screened for cardiomyopathy, and detailed data were retrospectively collected. We analyzed their clinical and molecular history, imaging characteristics of cardiac involvement, type of cardiomyopathy, age at initial presentation of cardiomyopathy, additional cardiac features, the treatments administered, and their clinical outcomes. RESULTS: Of the 305 patients with molecularly confirmed CDG participating in the FCDGC natural history study as of June 2023, 17 individuals, nine females and eight males, were identified with concurrent diagnoses of cardiomyopathy. Most of these patients were diagnosed with PMM2-CDG (n = 10). However, cardiomyopathy was also observed in other diagnoses, including PGM1-CDG (n = 3), ALG3-CDG (n = 1), DPM1-CDG (n = 1), DPAGT1-CDG (n = 1), and SSR4-CDG (n = 1). All PMM2-CDG patients were reported to have hypertrophic cardiomyopathy. Dilated cardiomyopathy was observed in three patients, two with PGM1-CDG and one with ALG3-CDG; left ventricular non-compaction cardiomyopathy was diagnosed in two patients, one with PGM1-CDG and one with DPAGT1-CDG; two patients, one with DPM1-CDG and one with SSR4-CDG, were diagnosed with non-ischemic cardiomyopathy. The estimated median age of diagnosis for cardiomyopathy was 5 months (range: prenatal-27 years). Cardiac improvement was observed in three patients with PMM2-CDG. Five patients showed a progressive course of cardiomyopathy, while the condition remained unchanged in eight individuals. Six patients demonstrated pericardial effusion, with three patients exhibiting cardiac tamponade. One patient with SSR4-CDG has been recently diagnosed with cardiomyopathy; thus, the progression of the disease is yet to be determined. One patient with PGM1-CDG underwent cardiac transplantation. Seven patients were deceased, including five with PMM2-CDG, one with DPAGT1-CDG, and one with ALG3-CDG. Two patients died of cardiac tamponade from pericardial effusion; for the remaining patients, cardiomyopathy was not necessarily the primary cause of death. CONCLUSIONS: In this retrospective study, cardiomyopathy was identified in ∼6% of patients with CDG. Notably, the majority, including all those with PMM2-CDG, exhibited hypertrophic cardiomyopathy. Some cases did not show progression, yet pericardial effusions were commonly observed, especially in PMM2-CDG patients, occasionally escalating to life-threatening cardiac tamponade. It is recommended that clinicians managing CDG patients, particularly those with PMM2-CDG and PGM1-CDG, be vigilant of the cardiomyopathy risk and risk for potentially life-threatening pericardial effusions. Cardiac surveillance, including an echocardiogram and EKG, should be conducted at the time of diagnosis, annually throughout the first 5 years, followed by check-ups every 2-3 years if no concerns arise until adulthood. Subsequently, routine cardiac examinations every five years are advisable. Additionally, patients with diagnosed cardiomyopathy should receive ongoing cardiac care to ensure the effective management and monitoring of their condition. A prospective study will be required to determine the true prevalence of cardiomyopathy in CDG.

Arrhythmogenic cardiomyopathy is under-recognized in end-stage pediatric heart failure: A 36-year single-center experience.

BACKGROUND: Although ventricular failure is a late finding in adults with AC, we hypothesize that this is a presenting symptom in pediatric heart failure patients who undergo HT and that their ventricular arrhythmia burden could differentiate AC from other cardiomyopathies. METHODS: We performed a single-center retrospective cohort study reviewing 457 consecutive pediatric (≤18 years) HT recipients at our institution. Explanted hearts were examined to establish the primary diagnosis, based on pathologic findings. Demographic and clinical variables were compared between AC versus non-HCM cardiomyopathy cases. RESULTS: Forty-five percent (n = 205/457) had non-HCM cardiomyopathies as the underlying primary diagnosis. Ten cases (10/205 = 4.9%) were diagnosed with AC. All 10 had biventricular disease. In 8/10 patients (80%), AC diagnosis was unrecognized pre-HT. Compared with non-AC cardiomyopathies, the AC group was older at diagnosis (9.3 years vs. 4.3 years, p = .012) and transplant (11.1 years vs. 6.5 years, p = .010), had more ventricular arrhythmias (80.0% vs 32.8%, p = .003), and required more anti-arrhythmic use (80.0% vs 32.3%, p = .001). Genetic testing yielded causative pathogenic variants in all tested individuals (n = 5/5, 100%). CONCLUSION: AC is often an unrecognized cardiomyopathy pretransplant in children who undergo HT. Pediatric non-HCM phenotypes with heart failure who have a significant ventricular arrhythmia burden should be investigated for AC.

Pediatric Pericarditis: Update.

PURPOSE OF REVIEW: While there have now been a variety of large reviews on adult pericarditis, this detailed review specifically focuses on the epidemiology, clinical presentation, diagnosis, and management of pediatric pericarditis. We have tried to highlight most pediatric studies conducted on this topic, with special inclusion of important adult studies that have shaped our understanding of and management for acute and recurrent pericarditis. RECENT FINDINGS: We find that the etiology of pediatric pericarditis differs from adult patients with pericarditis and has evolved over the years. Also, with the current COVID-19 pandemic, it is important for pediatric clinicians to be aware of pericardial involvement both due to the infection and from vaccination. Oftentimes, pericarditis maybe the only cardiac involvement in children with COVID-19, and so caregivers should maintain a high index of suspicion when they encounter children with pericarditis.  Large-scale contemporary epidemiological data regarding incidence and prevalence of both acute and recurrent pericarditis is lacking in pediatrics, and future studies should focus on highlighting this important research gap. Most of the current management strategies for pediatric pericarditis are from experiences gathered from adult data. Pediatric multicenter trials are warranted to understand the best management strategy for those with acute and recurrent pericarditis. CASE VIGNETTE: A 6-year-old child with a past history of pericarditis almost 2 months ago comes in with a 2-day history of chest pain and fever. Per mother, he stopped his steroids about 2 weeks ago, and for the last 2 days has had a temperature of 102F and has been complaining of sharp mid-sternal chest pain that gets worse when he lies down and is relieved when he sits up and leans forward. On examination, he is tachycardic (heart rate 160 bpm), with normal blood pressure for age. He appears to be in pain (5/10), and on auscultation has a pericardial friction rub. His lab studies are notable for elevated white blood cell count and inflammatory markers (CRP and ESR). His electrocardiogram reveals sinus tachycardia and diffuse ST-elevation in all precordial leads. His echocardiogram demonstrates normal biventricular function and a trace pericardial effusion. His cardiac MRI confirms recurrent pericarditis. He is started on indomethacin and colchicine. He has complete resolution of his symptoms by day 3 of admission and is discharged with close follow-up.

Outcomes following use of pediatric and young adult donor hearts with bicuspid aortic valves: A single-center case series.

BACKGROUND: Valvular disease in pediatric and young adult donor hearts may be a relative contraindication to graft use. Outcomes following the use of donor hearts with bicuspid aortic valve (BAV) have not been previously reported in children. We describe 4 cases of pediatric heart transplantation (HTx) utilizing a donor heart with a BAV. CASE SERIES: Of the 469 HTx included in this study, 4 utilized a donor heart with a BAV. All recipients were female; median age was 11 years (range 0.3 to 19 years). In all cases, the BAV was not discovered until after HTx. All donors were less than 30 years old. The patients were followed for a median of 6 years (range 2 to 9 years) with all patients alive at last follow-up. Two patients have transitioned to adult care, and 2 patients continue to follow in our clinic. In follow-up, no patient has required an aortic valve intervention or had infective endocarditis. At last review, no patient had greater than mild aortic insufficiency or more than mild aortic stenosis. Three patients developed mild-to-moderate left ventricular hypertrophy in the first year post-transplant that improved over time. One patient experienced a peri-operative embolic stroke at time of transplant unrelated to the BAV. CONCLUSION: On short- and intermediate-term follow-up, pediatric and young adult donor hearts with BAV demonstrated acceptable graft longevity and valvular function. A functionally normal BAV in a pediatric heart transplant donor should not be a contraindication to organ acceptance.

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.

Role of a Pediatric Cardiologist in the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected patients across all age groups, with a wide range of illness severity from asymptomatic carriers to severe multi-organ dysfunction and death. Although early reports have shown that younger age groups experience less severe disease than older adults, our understanding of this phenomenon is in continuous evolution. Recently, a severe multisystem inflammatory syndrome in children (MIS-C), with active or recent COVID-19 infection, has been increasingly reported. Children with MIS-C may demonstrate signs and symptoms of Kawasaki disease, but also have some distinct differences. These children have more frequent and severe gastrointestinal symptoms and are more likely to present with a shock-like presentation. Moreover, they often present with cardiovascular involvement including myocardial dysfunction, valvulitis, and coronary artery dilation or aneurysms. Here, we present a review of the literature and summary of our current understanding of cardiovascular involvement in children with COVID-19 or MIS-C and identifying the role of a pediatric cardiologist in caring for these patients.

Adaptations of paediatric cardiology practice during the COVID-19 pandemic.

During the initial surge of the COVID-19 pandemic in the spring and summer of 2020, paediatric heart centres were forced to rapidly alter the way patient care was provided to minimise interruption to patient care as well as exposure to the virus. In this survey-based descriptive study, we characterise changes that occurred within paediatric cardiology practices across the United States and described provider experience and attitudes towards these changes during the pandemic. Common changes that were implemented included decreased numbers of procedures, limiting visitors and shifting towards telemedicine encounters. The information obtained from this survey may be useful in guiding and standardising responses to future public health crises.

Telehealth for Pediatric Cardiology Practitioners in the Time of COVID-19.

Due to the COVID-19 pandemic, there has been an increased interest in telehealth as a means of providing care for children by a pediatric cardiologist. In this article, we provide an overview of telehealth utilization as an extension of current pediatric cardiology practices and provide some insight into the rapid shift made to quickly implement these telehealth services into our everyday practices due to COVID-19 personal distancing requirements. Our panel will review helpful tips into the selection of appropriate patient populations and specific cardiac diagnoses for telehealth that put patient and family safety concerns first. Numerous practical considerations in conducting a telehealth visit must be taken into account to ensure optimal use of this technology. The use of adapted staffing and billing models and expanded means of remote monitoring will aid in the incorporation of telehealth into more widespread pediatric cardiology practice. Future directions to sustain this platform include the refinement of telehealth care strategies, defining best practices, including telehealth in the fellowship curriculum and continuing advocacy for technology.

Venous duct stenting in a 940-gram infant with infradiaphragmatic total anomalous pulmonary venous return.

An extremely low birthweight infant (940 grams) with a rare variant of obstructed infracardiac total anomalous pulmonary venous return underwent stenting of the venous duct as bridge to later surgical intervention. While technically challenging, this procedure represents a bridge to surgery for infants who might otherwise not be surgical candidates.

Association of Wolff-Parkinson-White With Left Ventricular Noncompaction Cardiomyopathy in Children.

BACKGROUND: Wolff-Parkinson-White (WPW) has been associated with left ventricular noncompaction (LVNC) in children. Little is known about the prevalence of this association, clinical outcomes, and treatment options. METHODS: Retrospective review of subjects with LVNC. LVNC was defined by established criteria; those with congenital heart disease were excluded. Electrocardiograms (ECGs) were reviewed for presence of pre-excitation. Outcomes were compared between those with isolated LVNC and those with WPW and LVNC. RESULTS: A total of 348 patients with LVNC were identified. Thirty-eight (11%) were found to have WPW pattern on ECG, and 84% of those with WPW and LVNC had cardiac dysfunction. In Kaplan-Meier analysis, there was significantly lower freedom from significant dysfunction (ejection fraction ≤ 40%) among those with WPW and LVNC (P < .001). Further analysis showed a higher risk of developing significant dysfunction in patients with WPW and LVNC versus LVNC alone (hazard ratio 4.64 [2.79, 9.90]). Twelve patients underwent an ablation procedure with an acute success rate of 83%. Four patients with cardiac dysfunction were successfully ablated, 3 having improvement in function. CONCLUSION: WPW is common among children with LVNC and is associated with cardiac dysfunction. Ablation therapy can be safely and effectively performed and may result in improvement in function.

Predictors and Consequences of Pediatric Hypertension: Have Advanced Echocardiography and Vascular Testing Arrived?

PURPOSE OF REVIEW: Pediatric hypertension is relatively common and associated with future adult hypertension. Elevated blood pressure in youth predicts future adult cardiovascular disease and blood pressure control can prevent progression of pediatric kidney disease. However, pediatric blood pressure is highly variable within a given child and among children in a population. RECENT FINDINGS: Therefore, modalities to index aggregate and cumulative blood pressure status are of potential benefit in identifying youth in danger of progression from a risk factor of subclinical phenotypic alteration to clinically apparent event. In this review, we advocate for the health risk stratification roles of echocardiographically assessed cardiac remodeling, arterial stiffness assessment, and assessment by ultrasound of arterial thickening in children and adolescents with hypertension.

Fgf signaling governs cell fate in the zebrafish pineal complex.

Left-right (L-R) asymmetries in neuroanatomy exist throughout the animal kingdom, with implications for function and behavior. The molecular mechanisms that control formation of such asymmetries are beginning to be understood. Significant progress has been made by studying the zebrafish parapineal organ, a group of neurons on the left side of the epithalamus. Parapineal cells arise from the medially located pineal complex anlage and migrate to the left side of the brain. We have found that Fgf8a regulates a fate decision among anterior pineal complex progenitors that occurs just prior to the initiation of leftward migration. Cell fate analysis shows that in the absence of Fgf8a a subset of cells in the anterior pineal complex anlage differentiate as cone photoreceptors rather than parapineal neurons. Fgf8a acts permissively to promote parapineal fate in conjunction with the transcription factor Tbx2b, but might also block cone photoreceptor fate. We conclude that this subset of anterior pineal complex precursors, which normally become parapineal cells, are bipotential and require Fgf8a to maintain parapineal identity and/or prevent cone identity.

Central Venous Pressure and Impaired Renal Function in Children and Young Adults With Cardiovascular Disease.

Background: Traditionally, low cardiac output has been considered the primary hemodynamic driver of renal function and injury. Adult data suggest that central venous pressure (CVP) is a more important factor. Objectives: The authors hypothesized that in children with cardiovascular disease, higher CVP predicts lower estimated glomerular filtration rate (eGFR) and worsening renal function (WRF). Methods: We performed a single-center cohort study of patients aged 3 months to 21 years with biventricular circulation undergoing cardiac catheterization. Pearson's correlation and linear and Cox regression analyses were performed to determine associations with eGFR at the time of catheterization and WFR within 180 days after catheterization. Results: 312 patients had median age 7.9 years (IQR: 2.3 to 14.5 years), median eGFR 97 mL/min/1.73 m2 (IQR: 81-118 mL/min/1.73 m2), median CVP 7 mm Hg (IQR: 5-9 mm Hg), and median cardiac index 3.7 mL/min/m2 (IQR: 2.9-4.6 mL/min/m2). Nearly half (48%) were transplant recipients. In multivariable analysis, CVP was independently associated with eGFR (ß = -2.65; 95% CI: -4.02, -1.28; P < 0.001), as was being a transplant recipient (ß = -10.20; 95% CI: -17.74, -2.65; P = 0.008), while cardiac index was not. Fifty-one patients (16%) developed WRF. In a proportional hazards model adjusting for cardiac index, only higher CVP (HR: 1.10; 95% CI: 1.04-1.17; P = 0.002) and greater contrast volume by weight (HR: 1.05; 95% CI: 1.01-1.10; P = 0.021) predicted WRF. CVP ≥7 mm Hg likewise predicted WRF (HR: 2.57; 95% CI: 1.29-5.12; P = 0.007). Conclusions: Among children with a spectrum of cardiovascular disease, higher CVP is associated with lower eGFR and development of WRF, independent of cardiac index.

Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children.

BACKGROUND: Despite growing cardiogenic shock (CS) research in adults, the epidemiology, clinical features, and outcomes of children with CS are lacking. OBJECTIVES: This study sought to describe the epidemiology, clinical presentation, hospital course, risk factors, and outcomes of CS among children hospitalized for acute decompensated heart failure (ADHF). METHODS: We examined consecutive ADHF hospitalizations (<21 years of age) from a large single-center retrospective cohort. Patients with CS at presentation were analyzed and risk factors for CS and for the primary outcome of in-hospital mortality were identified. A modified Society for Cardiovascular Angiography and Interventions shock classification was created and patients were staged accordingly. RESULTS: A total of 803 hospitalizations for ADHF were identified in 591 unique patients (median age 7.6 years). CS occurred in 207 (26%) hospitalizations. ADHF hospitalizations with CS were characterized by worse systolic function (P = 0.040), higher B-type natriuretic peptide concentration (P = 0.032), and more frequent early severe renal (P = 0.023) and liver (P < 0.001) injury than those without CS. Children presenting in CS received mechanical ventilation (87% vs 26%) and mechanical circulatory support (45% vs 16%) more frequently (both P < 0.001). Analyzing only the most recent ADHF hospitalization, children with CS were at increased risk of in-hospital mortality compared with children without CS (28% vs 11%; OR: 1.91; 95% CI: 1.05-3.45; P = 0.033). Each higher CS stage was associated with greater inpatient mortality (OR: 2.40-8.90; all P < 0.001). CONCLUSIONS: CS occurs in 26% of pediatric hospitalizations for ADHF and is independently associated with hospital mortality. A modified Society for Cardiovascular Angiography and Interventions classification for CS severity showed robust association with increasing mortality.

External assessment and refinement of a population pharmacokinetic model to guide tacrolimus dosing in pediatric heart transplant.

STUDY OBJECTIVE: The immunosuppressant tacrolimus is a first-line agent to prevent graft rejection following pediatric heart transplant; however, it suffers from extensive inter-patient variability and a narrow therapeutic window. Personalized tacrolimus dosing may improve transplant outcomes by more efficiently achieving and maintaining therapeutic tacrolimus concentrations. We sought to externally validate a previously published population pharmacokinetic (PK) model that was constructed with data from a single site. DATA SOURCE: Data were collected from Seattle, Texas, and Boston Children's Hospitals, and assessed using standard population PK modeling techniques in NONMEMv7.2. MAIN RESULTS: While the model was not successfully validated for use with external data, further covariate searching identified weight (p < 0.0001 on both volume and elimination rate) as a model-significant covariate. This refined model acceptably predicted future tacrolimus concentrations when guided by as few as three concentrations (median prediction error = 7%; median absolute prediction error = 27%). CONCLUSION: These findings support the potential clinical utility of a population PK model to provide personalized tacrolimus dosing guidance.

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.

Subnuclear development of the zebrafish habenular nuclei requires ER translocon function.

The dorsal habenular nuclei (Dh) of the zebrafish are characterized by significant left-right differences in gene expression, anatomy, and connectivity. Notably, the lateral subnucleus of the Dh (LsDh) is larger on the left side of the brain than on the right, while the medial subnucleus (MsDh) is larger on the right compared to the left. A screen for mutations that affect habenular laterality led to the identification of the sec61a-like 1(sec61al1) gene. In sec61al1(c163) mutants, more neurons in the LsDh and fewer in the MsDh develop on both sides of the brain. Generation of neurons in the LsDh occurs more rapidly and continues for a longer time period in mutants than in WT. Expression of Nodal pathway genes on the left side of the embryos is unaffected in mutants, as is the left sided placement of the parapineal organ, which promotes neurogenesis in the LsDh of WT embryos. Ultrastructural analysis of the epithalamus indicates that ventricular precursor cells, which form an epithelium in WT embryos, lose apical-basal polarity in sec61al1(c163) mutants. Our results show that in the absence of sec61al1, an excess of precursor cells for the LsDh exit the ventricular region and differentiate, resulting in formation of bilaterally symmetric habenular nuclei.

Relation of Low Chloride Concentration to Diuretic Efficiency and Transplant-Free Survival in Children Hospitalized With Heart Failure.

Serum chloride plays an important role in fluid homeostasis and is associated with impaired diuretic responsiveness and mortality in adults with heart failure (HF). We sought to characterize the relationship of serum chloride and diuretic efficiency (DE) and to determine its prognostic importance in children hospitalized with acute decompensated HF (ADHF). We studied DE, defined as net fluid output/kg+constant per mg of loop diuretic/kg, in 200 children hospitalized with ADHF. Median serum chloride at admission was 102 mmol/L (interquartile range 99 to 105 mmol/L), and hypochloremia (chloride ≤96 mmol/L) was present in 16% of the population at admission. Serum chloride correlated with serum sodium (r = 0.66; p < 0.001) and bicarbonate (r = -0.39; p < 0.001). In the adjusted analysis, lower chloride was associated with reduced DE (p < 0.001). Serum sodium was associated with DE on the unadjusted analysis; however, the association was eliminated when added to the model with chloride (p = 0.442). Lower chloride was also associated with features of inadequate decongestion during hospitalization: a positive fluid balance (p = 0.003), greater cumulative loop diuretic dose per weight (p = 0.001), addition of a thiazide diuretic during hospitalization (p < 0.001), less weight loss (p = 0.025), and longer length of stay (p = 0.003). Chloride concentration was independently associated with death or transplant 1 year after admission (hazard ratio 0.94; p < 0.001). As a dichotomous variable, hypochloremia was independently associated with reduced DE (p < 0.001) and decreased 1-year transplant-free survival (hazard ratio 2.3, p < 0.001). Lower serum chloride at hospital admission is strongly and independently associated with impaired DE and reduced transplant-free survival in children hospitalized with ADHF.

Redefining the Relationship: Palliative Care in Critical Perinatal and Neonatal Cardiac Patients.

Patients with perinatal and neonatal congenital heart disease (CHD) represent a unique population with higher morbidity and mortality compared to other neonatal patient groups. Despite an overall improvement in long-term survival, they often require chronic care of complex medical illnesses after hospital discharge, placing a high burden of responsibility on their families. Emerging literature reflects high levels of depression and anxiety which plague parents, starting as early as the time of prenatal diagnosis. In the current era of the global COVID-19 pandemic, the additive nature of significant stressors for both medical providers and families can have catastrophic consequences on communication and coping. Due to the high prognostic uncertainty of CHD, data suggests that early pediatric palliative care (PC) consultation may improve shared decision-making, communication, and coping, while minimizing unnecessary medical interventions. However, barriers to pediatric PC persist largely due to the perception that PC consultation is indicative of "giving up." This review serves to highlight the evolving landscape of perinatal and neonatal CHD and the need for earlier and longitudinal integration of pediatric PC in order to provide high-quality, interdisciplinary care to patients and families.