Fontan completion in reverse order out of necessity: secondary Glenn after primary extracardiac inferior cavopulmonary artery connection.

The primary extracardiac inferior cavopulmonary connection is an unusual novel palliation for single-ventricle physiology, which we first performed in the setting of unfavourable upper-body systemic venous anatomy for a standard bi-directional Glenn, and in lieu of leaving our patient with shunt-dependent physiology. After an initial 16-month satisfactory follow-up, increasing cyanosis led to the discovery of a veno-venous collateral that was coiled, but, more importantly, to impressive growth of a previously diminutive superior caval vein, which allowed us to perform completion Fontan with a good outcome. Performing the single-ventricle staging in a reverse manner, first from below with a primary inferior cavopulmonary connection, followed by Fontan completion from above with a standard superior caval vein bi-directional Glenn, is also possible when deemed necessary.

When the bi-directional Glenn is an unfavourable option: primary extracardiac inferior cavopulmonary connection as an alternative palliation.

The superior cavopulmonary anastomosis - bi-directional Glenn - is the standard palliation for single ventricle physiology. When upper body systemic venous anatomic concerns such as superior caval vein stenosis, hypoplasia, or inadequate collateral tributaries are present, a Glenn may be precluded or have a high risk of poor outcome. A primary inferior cavopulmonary connection with an extracardiac conduit is an alternative palliation that provides a generous pathway for pulmonary blood flow, with the additional benefit of including hepatic venous return. We report a case of primary extracardiac inferior cavopulmonary connection in a patient unsuitable for Glenn, with successful post-operative outcome and early follow-up.

Alternative strategies in newborns and infants with major co-morbidities to improve congenital heart surgery outcomes at an emerging programme.

INTRODUCTION: Debilitating patient-related non-cardiac co-morbidity cumulatively increases risk for congenital heart surgery. At our emerging programme, flexible surgical strategies were used in high-risk neonates and infants generally considered in-operable, in an attempt to make them surgical candidates and achieve excellent outcomes. MATERIALS AND METHODS: Between April, 2010 and November, 2013, all referred neonates (142) and infants (300) (average scores: RACHS 2.8 and STAT 3.0) underwent 442 primary cardiac operations: patients with bi-ventricular lesions underwent standard (n=294) or alternative (n=19) repair/staging strategies, such as pulmonary artery banding(s), ductal stenting, right outflow patching, etc. Patients with uni-ventricular hearts followed standard (n=96) or alternative hybrid (n=34) staging. The impact of major pre-operative risk factors (37%), standard or alternative surgical strategy, prematurity (50%), gestational age, low birth weight, genetic syndromes (23%), and major non-cardiac co-morbidity requiring same admission surgery (27%) was analysed on the need for extracorporeal membrane oxygenation, mortality, length of intubation, as well as ICU and hospital length of stays. RESULTS: The need for extracorporeal membrane oxygenation (8%) and hospital survival (94%) varied significantly between surgical strategy groups (p=0.0083 and 0.028, respectively). In high-risk patients, alternative bi- and uni-ventricular strategies minimised mortality, but were associated with prolonged intubation and ICU stay. Major pre-operative risk factors and lower weight at surgery significantly correlated with prolonged intubation, hospital length of stay, and mortality. DISCUSSION: In our emerging programme, flexible surgical strategies were offered to 53/442 high-risk neonates and infants with complex CHDs and significant non-cardiac co-morbidity, in order to buffer risk and achieve patient survival, although at the cost of increased resource utilisation.

A Multi-Center Evaluation of the Pharmacokinetics and Safety of Intravenous Ibuprofen in Infants 1-6 Months of Age.

BACKGROUND: Enteral ibuprofen was first approved as a prescription drug in 1974 for the US market. An intravenous (IV) ibuprofen formulation is approved for use in children older than 6 months of age, but there are limited studies specifically evaluating the pharmacokinetics and safety in children 1-6 months of age. AIMS: The primary purpose of this study was to evaluate the pharmacokinetics of IV ibuprofen in infants younger than 6 months of age. The secondary objective was to evaluate the safety of single and repeated doses of IV ibuprofen in infants younger than 6 months of age. METHODS: This was an industry-sponsored multi-center study. Institutional Review Board approval and informed parental consent were obtained prior to enrollment. Hospitalized neonates and infants younger than 6 months of age with fever or expected postoperative pain were eligible. Enrolled patients received 10 mg/kg of IV ibuprofen every 6 h, with up to four doses per day. Patients were randomized to two sparse sampling technique pharmacokinetic sample time groups. Group 1 samples were drawn at 0, 30 min, and 2 h, while group 2 samples were drawn at 0 min, 1, and 4 h after administration. RESULTS: A total of 24 children were enrolled in the study, with 15 male patients and 9 female patients. The median age of the cohort was 4.4 months (range 1.1-5.9 months), and the median weight was 5.9 kg (range 2.3-8.8 kg). The arithmetic mean and standard error for peak plasma ibuprofen concentration was 56.28 ± 2.77 µg/mL. Plasma levels declined rapidly with a mean elimination half-life of 1.30 h. Time to peak ibuprofen effect and concentration were similar when compared with older pediatric patients. Clearance and volume of distribution were also similar to those reported in older pediatric patients. No drug-related adverse events were reported. CONCLUSIONS: The pharmacokinetic and short-term safety profiles of IV ibuprofen in pediatric patients 1-6 months of age are comparable to those in children older than 6 months of age. TRIAL REGISTRATION: Clinicaltrials.gov Trial Registration number and date: NCT02583399-Registered July 2017.

Racial and Ethnic Disparity in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 in Mississippi, USA.

We aimed to study the disparity in the clinical profile and outcomes of hospitalized Multisystem Inflammatory Syndrome in Children (MIS-C) patients at our center. The second goal was to examine the temporal association with preceding SARS-CoV-2 infection by race/ethnicity in our community in Mississippi. We found the racial disparity in the prevalence of MIS-C exceeded its temporal association with SARS-CoV-2 infections. We included 51 consecutive MIS-C patients hospitalized, whose median age was 9 (interquartile range [IQR] 5-12) years, 58% were male, 71% were black, 25% were white, and 4% belonged to other groups. We found a delay between onset of symptoms and hospitalization in black patients compared with white patients with a median of 2 (IQR 0-7) vs median of 0 (0-5) urgent care visits (P = .022), respectively. Black patients were hospitalized longer (median 8, IQR 2-39 days) than whites (median 5, IQR 3-14 days), P = .047. A total of 38.9% of blacks and 23.1% of whites were admitted to intensive care unit (P = .498); 36.1% of blacks had severe cardiac involvement vs 23.1% of white patients, P = .531. Future studies of MIS-C are required to improve health equity for children.

Compound Heterozygous Missense Variants in RPL3L Genes Associated with Severe Forms of Dilated Cardiomyopathy: A Case Report and Literature Review.

Whole exome sequencing has identified an infant girl with fulminant dilated cardiomyopathy (DCM), leading to severe acute heart failure associated with ribosomal protein large 3-like (RPL3L) gene pathologic variants. Other genetic tests for mitochondrial disorders by sequence analysis and deletion testing of the mitochondrial genome were negative. Secondary causes for DCM due to metabolic and infectious etiologies were ruled out. She required a Berlin-Excor left ventricular assist device due to worsening of her heart failure as a bridge to orthotopic heart transplantation. At three months follow-up after heart transplantation, she has been doing well. We reviewed the literature on published RPL3L-related DCM cases and their outcomes. Bi-allelic variants in RPL3L have been reported in only seven patients from four unrelated families in the literature. RPL3L is a newer and likely pathogenic gene associated with a severe form of early-onset dilated cardiomyopathy with poor prognosis necessitating heart transplantation.

Further Evidence of Autosomal Recessive Inheritance of RPL3L Pathogenic Variants with Rapidly Progressive Neonatal Dilated Cardiomyopathy.

Neonatal dilated cardiomyopathy (DCM) is rare with high etiologic heterogeneity. Recently, biallelic, autosomal recessive, pathogenic variants in RPL3L (ribosomal protein L3-like) have been reported in the literature with severe early-onset DCM. In the present brief report, we identified two pathogenic RPL3L variants, each harbored in unaffected heterozygous parents: mother (RPL3L c.1076_1080delCCGTG (p.Ala359Glyfs*4)) and father (RPL3L c.80G > A (p.Gly27Asp)). Pathogenic variants were segregated as autosomal recessive to two offspring born with compound heterozygous RPL3L variants and affected by neonatal DCM. This is the second report in the literature to the best of our knowledge and our findings support the pathogenicity of biallelic RPL3L pathologic variants associated with rapidly progressive neonatal DCM and heart failure with a poor prognosis.

Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination: What Do We Know So Far?

This is a cross-sectional study of 29 published cases of acute myopericarditis following COVID-19 mRNA vaccination. The most common presentation was chest pain within 1-5 days after the second dose of mRNA COVID-19 vaccination. All patients had an elevated troponin. Cardiac magnetic resonance imaging revealed late gadolinium enhancement consistent with myocarditis in 69% of cases. All patients recovered clinically rapidly within 1-3 weeks. Most patients were treated with non-steroidal anti-inflammatory drugs for symptomatic relief, and 4 received intravenous immune globulin and corticosteroids. We speculate a possible causal relationship between vaccine administration and myocarditis. The data from our analysis confirms that all myocarditis and pericarditis cases are mild and resolve within a few days to few weeks. The bottom line is that the risk of cardiac complications among children and adults due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection far exceeds the minimal and rare risks of vaccination-related transient myocardial or pericardial inflammation.

Complex febrile seizures followed by complete recovery in an infant with high-titer 2009 pandemic influenza A (H1N1) virus infection.

We describe a 2009 H1N1 virus infection with a high viral load in a previously healthy infant who presented with complex febrile seizures and improved on oseltamivir without neurologic sequelae. Febrile seizures may be a complication in young children experiencing infection with high viral loads of 2009 H1N1 influenza virus.

Fundamentals of management of acute postoperative pulmonary hypertension.

In the last several years, there have been numerous advancements in the field of pulmonary hypertension as a whole, but there have been few changes in the management of children with pulmonary hypertension after cardiac surgery. Patients at particular risk for postoperative pulmonary hypertension can be identified preoperatively based on their cardiac disease and can be grouped into four broad categories based on the mechanisms responsible for pulmonary hypertension: 1) increased pulmonary vascular resistance; 2) increased pulmonary blood flow with normal pulmonary vascular resistance; 3) a combination of increased pulmonary vascular resistance and increased blood flow; and 4) increased pulmonary venous pressure. In this review of the immediate postoperative management of pulmonary hypertension, various strategies are discussed including medical therapies, monitoring, ventilatory strategies, and weaning from these supports. With early recognition of patients at particular risk for severe pulmonary hypertension, management strategies can be directed at preventing or minimizing hemodynamic instability and thereby prevent the development of ventricular dysfunction and a low output state.

Staged Palliation of Cyanotic Obstructive Lesions With a Modified Right Ventricular Outflow Procedure.

BACKGROUND: Traditional palliation for biventricular cyanotic congenital heart lesions often involves staging with systemic-to-pulmonary arterial shunts to secure pulmonary blood flow (PBF) in the newborn period prior to complete repair. However, shunts may lead to life-threatening events secondary to shunt occlusion or acute coronary steal. They may be associated with morbidity secondary to diastolic runoff, systemic steal and volume loading, and do not provide pulsatile flow which has the potential to promote pulmonary artery (PA) growth. We have alternatively performed modified right ventricular outflow (mRVO) procedures by establishing antegrade right ventricle-to-PA flow. METHODS: Retrospective review of data on all patients who underwent the mRVO procedure from 2013 to 2016, including anatomy, number of interstage catheterizations, reoperations, intensive care unit admissions, hypercyanotic episodes, interval to complete repair, and mortality. RESULTS: Seventeen nonconsecutive patients included tetralogy of Fallot (n = 14), pulmonary valve stenosis (n = 2), and 1 with pulmonary atresia-intact septum; 14 had significant branch PA stenosis. Median age of first mRVO procedure was 14 days (range 5-193), and median duration of follow-up was 15.3 months (range 4-47 months). No patients had post-palliation acute hypercyanotic episodes. Nine were admitted to the ICU for persistent interstage hypoxemia, 7 of whom required reintervention prior to complete repair, which was achieved in 11 patients. Two late deaths unrelated to mRVO occurred. CONCLUSIONS: The mRVO procedure is a potential option with satisfactory results. It avoids potential shunt-related sudden death. The physiology of the mRVO palliation may provide unique benefits by providing antegrade pulsatile PBF, facilitates catheter interventions, and avoids branch PA distortion and stenosis.

Antegrade cerebral perfusion at 25 °C for arch reconstruction in newborns and children preserves perioperative cerebral oxygenation and serum creatinine.

BACKGROUND: Antegrade cerebral perfusion (ACP) typically is used with deep hypothermia for cerebral protection during aortic arch reconstructions. The impact of ACP on cerebral oxygenation and serum creatinine at a more tepid 25 °C was studied in newborns and children. METHODS: Between 2010 and 2014, 61 newborns and children (<5 years old) underwent aortic arch reconstruction using moderate hypothermia (25.0±0.9 °C) with ACP and a pH-stat blood gas management strategy. These included 44% Norwood-type operations, 30% isolated arch reconstructions, and 26% arch reconstructions with other major procedures. Median patient age at surgery was 9 days (range, 3 days-4.7 years). Cerebral oxygenation (NIRS) was monitored continuously perioperatively for 120 hours. Serum creatinine was monitored daily. RESULTS: Median cardiopulmonary bypass (CPB) and cross clamp times were 181 minutes (range, 82-652 minutes) and 72 minutes (range, 10-364 minutes), respectively. ACP was performed at a mean flow rate of 46±6 mL/min/kg for a median of 48 minutes (range, 10-123 minutes). Cerebral and somatic NIRS were preserved intraoperatively and remained at baseline postoperatively during the first 120 hours. Peak postoperative serum creatinine levels averaged 0.7±0.3 mg/dL for all patients. There were 4 (6.6%) discharge mortalities. Six patients (9.8%) required ECMO support. Median postoperative length of hospital and intensive care unit (ICU) stay were 16 days(range, 4-104 days) and 9 days (range, 1-104 days), respectively. Two patients (3.3%) received short-term peritoneal dialysis for fluid removal, and none required hemodialysis. Three patients (4.9%) had an isolated seizure which resolved with medical therapy, and none had a neurologic deficit or stroke. CONCLUSIONS: ACP at 25 °C preserved perioperative cerebral oxygenation and serum creatinine for newborns and children undergoing arch reconstruction. Early outcomes are encouraging, and additional study is warranted to assess the impact on late outcomes.

Percutaneous Closure of Perimembranous Ventricular Septal Defects Using the Second-Generation Amplatzer Vascular Occluders.

Earlier attempts at percutaneous closure of perimembranous ventricular septal defects (Pm VSDs) were abandoned because of incidence of heart block likely as a result of device rigidity and/or oversizing. This is retrospective review and data reporting of patients who underwent percutaneous closure using the softer second-generation Amplatzer vascular occluders; namely the Amplatzer vascular plug, second generation, (AVP II) and the Amplatzer duct occluder, second generation (ADO II) in our institution. A total of 20 patients were identified; AVP II was used in 9 patients and ADO II in 11 patients. Median weight was 13.45 kg (range 6.5 to 76); age 28.5 months (range 11 to 352). After procedure, 4 were noted to have aortic insufficiency; trivial in 3 and mild in 1 (unrelated to the device). Mild tricuspid regurgitation possibly device or procedure related was seen in 4. Residual flow through the device was common after procedure and disappeared in all but 3, graded as trivial in 1, small in 2. Average follow-up period was 7.54 months ± 7.5 (1 day to 25 months). There was no incidence of heart block, bacterial endocarditis, hemolysis, device embolization, or fracture. The aortic insufficiency resolved in 1 patient and was estimated to be trivial in the remaining 3 patients. In conclusion, percutaneous closure of Pm VSDs using the softer new generation devices as the AVP II and the ADO II is feasible and safe. Longer follow-up and larger series are needed.

Clinical outcomes of 84 children with congenital heart disease managed with extracorporeal membrane oxygenation after cardiac surgery.

The purpose of our research was to study the clinical outcomes of children with congenital heart disease (CHD) requiring extracorporeal membrane oxygenation (ECMO) support after cardiac surgery at a tertiary care children's hospital. Retrospective review of all patients with CHD who required postcardiotomy ECMO between January 2001 and September 2004 (45 months) was undertaken. Various outcome predictors were tested for any association with survival to hospital discharge using univariate analysis. A total of 84 children were placed on ECMO after CHD surgery; 39 (46.4%) were placed on ECMO in the operating room. Median age of the patients was 128 days (1 day to 5 years) and median weight was 4.53 kg (2-18 kg). Active cardiopulmonary resuscitation was ongoing at the time of cannulation in 27 children (32%). Fifty-two children (61.9) survived > 24 hours after decannulation and 31 (36.9%) survived to discharge. High arterial serum lactate levels at the time of ECMO initiation were strongly correlated with nonsurvival (p = 0.004). Nonsurvivors had longer duration on ECMO than survivors (p = 0.003). The odds of survival dropped significantly after 144 hours (day 6) of ECMO. ECMO support results in improved outcomes in patients who suffered hemodynamic collapse post cardiac surgery. Underlying cardiac lesion, age, weight, gender, initial arterial pH, location of ECMO initiation, need for hemofiltration and placement of ECMO after active ongoing cardiopulmonary resuscitation did not increase the mortality risk. Initial arterial serum lactate level and inability to wean off by 6 days were strongly correlated with nonsurvival.