Protein-Losing Enteropathy in the Failing Fontan: Treatment With Angiotensin Receptor Neprilysin Inhibitor.

Angiotensin receptor neprilysin inhibitor is the standard of care for systolic heart failure in adults. In addition, its use in adults with failing systemic right ventricles and diastolic heart failure is promising. This study reports our experience with this drug for protein-losing enteropathy secondary to Fontan failure in pediatrics.

Ruptured Sinus of Valsalva Aneurysm with Resultant Myocardial Pouch Formation in the Fetal Heart-A Diagnostic Challenge.

Sinus of Valsalva aneurysms (SVAs) are infrequently seen in the pediatric population. When these aneurysms rupture, a significant hemodynamic burden is placed on the heart and increases the likelihood of cardiac failure. Here, we report a case of a ruptured SVA into the ventricular myocardium in a fetus with a form of double-inlet left ventricle. To the best of our knowledge, this has not previously been described.

A 12-Year-Old with Sudden Cardiac Arrest.

Sudden Cardiac Arrest in 12-Year-Old BoyA 12-year-old boy suddenly lost consciousness while playing catch in his backyard. He was found pulseless and received cardiopulmonary resuscitation and defibrillation before being transferred to the emergency department. How do you approach the evaluation, and what is the diagnosis?

Serial assessment of right ventricular function can detect acute cellular rejection in children with heart transplantation.

BACKGROUND: Echocardiographic markers of ACR are essential for early recognition and management. The literature's primary focus has been on the LV with little attention given to the RV. This study aimed to investigate echocardiographic right ventricular indices in the detection of ACR and to evaluate their utility as prognostic indicators of graft integrity. METHODS: We performed a retrospective chart review of children with biopsy-proven ACR following orthotopic heart transplant and an echocardiogram within 24 h of biopsy. Selected echocardiographic markers were compared at baseline, during ACR, and at follow-up. RESULTS: Forty-eight patients (56% male) had a total of 84 ACR episodes. Decrease in RV FAC (mean - 17.1%, p < .001) and TAPSE (mean - 8.9%, p < .001) with increase in left ventricular posterior wall thickness in diastole and systole (LVPWTd) (mean + 9.0%, p = .012) and LVPWTs (mean + 8.3%, p = .016) were found during ACR. Interestingly, these parameters improved following the episode of rejection. Additionally, these markers were compared after recovery between children with and without graft failure. RV dysfunction (FAC and TAPSE) and changes in LV posterior wall thickness were not found to have prognostic significance for graft integrity in children with heart transplantation. CONCLUSIONS: RV echocardiographic functional parameters should be considered as valuable adjuncts in rejection surveillance. Further, the presence of RV dysfunction does not have prognostic significance for graft integrity but is reversible as ongoing damage was not detectable by such.

Coronary Sinus Ostial Obstruction in Single-Ventricle Congenital Heart Disease: Two Patients With Different Outcomes.

Coronary sinus ostial obstruction is an exceedingly rare anomaly that is particularly important to diagnose in patients with single-ventricle heart disease before surgical palliation. We present 2 cases, an infant and an adult, diagnosed with coronary sinus ostial obstruction, with different clinical outcomes due to timing of diagnosis. (Level of Difficulty: Intermediate.).

Risk Factors for Increased Post-operative Length of Stay in Children with Coarctation of Aorta.

Coarctation of the aorta is a relatively common congenital heart disease occurring in 0.4-0.6 per 1000 live births with a low mortality rate. This is a retrospective study, with data abstracted from the Pediatric Health Information System database (PHIS). The study sample included pediatric patients less than or equal to 3 months of age discharged from a PHIS participating hospital between January 1, 2004 and December 31, 2018 who underwent surgical repair of isolated COA. The primary outcome for the study was post-operative hospital length of stay (PH-LOS), and the secondary outcome was in-hospital mortality. Patient demographics, comorbidities, procedures, and outcomes were assessed for statistical differences between eras. A total of 5354 patients were included in the study. The study highlights an increasing trend in PH-LOS and NICU hospital length of stay (NICU-LOS) across the investigated eras. Prematurity (before 37 weeks gestation) was an independent risk factor associated with both longer post-operative length of the stay and higher mortality. In addition, congenital anomalies, respiratory and abdominal surgeries have a significant impact on the post-operative hospital stay. In conclusion, this study is the largest published systematic assessment of PH-LOS in patients with isolated COA repair during infancy to date and identifies independent risk factors of increased PH-LOS.

A Fetal Presentation of a Ruptured Right Ventricular Diverticulum.

Ruptured diverticula and ventricular aneurysms are rare in the fetus, with a limited number of case reports published previously. Additional fetal complications secondary to these ventricular wall abnormalities can be seen. Interventional measures can be considered and attempted either in utero or postnatally to improve the chance of survival. We present a case of a ruptured diverticulum in a fetus and the clinical course.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa following endocarditis and aortic valve surgery in an infant-Case report and exhaustive systematic review of pediatric cases.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) continues to be a rare diagnosis in children. Etiology, presentation, and management strategies are considerably different from adults. We report a fatal case of P-MAIVF with classical transthoracic and transesophageal echocardiographic findings complemented by CT imaging. The natural course of uncomplicated/asymptomatic P-MAIVF is largely unknown since most patients are offered surgery. We present an extensive literature review of pediatric P-MAIVF and highlight important differences from the adult form of this disease.

Ebstein anomaly combined with unique pulmonary venous abnormality in a 9-month-old child.

Ebstein anomaly is a rare CHD known for its wide spectrum of presentation with the age of diagnosis dependent on the malformation's severity. Here, the authors describe a case of delayed diagnosis of Ebstein anomaly, secondary to lack of medical attention, which resulted in severe tricuspid regurgitation and pulmonary hypertension. Furthermore, the case was complicated by a unique pulmonary venous abnormality.

Implementation of a statewide, multisite fetal tele-echocardiography program: evaluation of more than 1100 fetuses over 9 years.

OBJECTIVES: We sought to describe the implementation and effectiveness of a statewide fetal tele-echocardiography program serving a resource-limited population. STUDY DESIGN: In 2009, our heart center established six satellite clinics for fetal tele-echocardiography around the state. We retrospectively reviewed all fetal tele-echocardiograms performed through 2018. Yearly statewide prenatal detection rates of operable congenital heart disease were queried from the Society of Thoracic Surgeons database. RESULT: In 1164 fetuses, fetal tele-echocardiography identified all types of congenital heart disease, with a sensitivity of 74% and specificity of 97%. For the detection of ductal-dependent congenital heart disease, fetal tele-echocardiography was 100% sensitive and specific. Between 2009 and 2018, annual statewide prenatal detection rates of congenital heart disease requiring heart surgery in the first 6 months of life rose by 159% (17-44%; R2 = 0.88, p < 0.01). CONCLUSIONS: The present study provides a framework for an effective, large-scale fetal tele-echocardiography program.

Spectrum of Off-Label Nitric Oxide Utilization After Pediatric Cardiac Surgery Among Centers of Varying Surgical Volume.

OBJECTIVE: Nitric oxide is utilized after pediatric cardiac surgery as an off-label medication without much evidence, is expensive, and varies among centers of varying surgical volume. The objective of our study was to describe the spectrum of nitric oxide utilization and to evaluate the effect of nitric oxide utilization on outcomes among patients cared for in centers of varying surgical volume using Pediatric Health Information system. METHODS: Patients aged ≤18 years undergoing heart surgery were included (2004-2015). Multivariable mixed-effects logistic regression models were fitted to evaluate association of center volume with odds of nitric oxide utilization among patients undergoing heart operations. Centers were classified into 3 volume categories based on tertiles of number of cardiopulmonary bypass cases performed (low volume: 34 792 patients, 21 centers; medium volume: 38 362 patients, 13 centers; high volume: 30 560 patients, 7 centers). RESULTS: A total of 103 714 patients from 41 hospitals were included. Of these, 15 708 (15.1%) patients received nitric oxide after cardiac surgery. Of the patients receiving nitric oxide, only 3936 (25.1%) patients were associated with a diagnosis of pulmonary hypertension. In adjusted models, low- and medium-volume centers were associated with higher nitric oxide utilization after heart operations as compared to high-volume centers (low vs high, odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.38-1.60; medium vs high, OR: 1.33, 95% CI: 1.26-1.41). Despite higher nitric oxide utilization, the mortality was worse among patients treated in low- and medium-volume centers, as compared to high-volume centers (low vs high, OR: 1.42, 95% CI: 1.26-1.60; medium vs high, OR: 1.14, 95% CI: 1.04-1.25). CONCLUSIONS: This study demonstrates variation in nitric oxide utilization after heart operations among centers of varying surgical volume. Further, it raises questions on the benefit of nitric oxide administration after pediatric cardiac surgery.

Short-Axis Diastolic Ventricular Area Ratio as a New Index in Screening Patients with Repaired Tetralogy of Fallot.

Right ventricular (RV) end-diastolic volume measured by cardiovascular magnetic resonance imaging (CMR) is a criterion for pulmonary valve replacement in patients with tetralogy of Fallot (TOF). We sought to determine if the ratio of echocardiographic, short-axis RV-to-left ventricular (LV) end-diastolic areas (EDA) could be used to predict RV volume on CMR. We retrospectively reviewed the echocardiograms of all patients with repaired TOF who underwent CMR at our institution from 2011 to 2015 and also had an echocardiogram within 6 months of the CMR. The short-axis RV and LV EDAs were measured and the ratio of the two was calculated. Results were compared with CMR RV end-diastolic volume index (RVEDVi) and RV:LV end-diastolic volume ratio. The sensitivity and specificity values predicting RV volumes > 150 ml/m2 were calculated. Fifty-eight studies met inclusion criteria. There were 47 studies with RVEDVi < 150 ml/m2 and 11 with RVEDVi > 150 ml/m2. RV:LV EDA and CMR RV:LV end-diastolic volume ratio correlated strongly (r = 0.76, p < 0.0001). An RV:LV EDA ≥ 1.57 had a 90% sensitivity to predict RVEDVi > 150 ml/m2 (area under the curve = 0.74, 95% CI 1.5-27.9; p = 0.012). An RV:LV EDA ≥ 1.88 had an 81% specificity to detect RV volume index > 150 ml/m2. Short-axis RV:LV EDA correlates well with an increased RVEDVi as measured by CMR. This new and simple measure can be used to predict optimal timing for CMR in anticipation of pulmonary valve replacement in repaired TOF.

Necrotizing Enterocolitis in Infants with Hypoplastic Left Heart Syndrome Following Stage 1 Palliation or Heart Transplant.

Previous studies of necrotizing enterocolitis (NEC) among infants with hypoplastic left heart syndrome (HLHS) were conducted in single centers or had small sample sizes. This study aimed to determine the mortality rate and the risk factors for NEC among infants with HLHS who were discharged over a 10-year period (2004-2013) from 41 Pediatric Health Information System affiliated children's hospitals. Either stage 1 palliation and/or heart transplant were completed prior to patient's death or hospital discharge. We compared the characteristics of infants with HLHS who did not develop NEC and those who developed medical or surgical NEC and of patients who had medical vs. surgical NEC. The primary outcome was mortality over time and by birth weight category (low birth weight [LBW], birth weight < 2500 vs. ≥ 2500 g). Multivariable analyses were performed to identify the risk factors for developing NEC and for mortality among infants with HLHS. The study evaluated 5720 infants with HLHS including 349 patients (6.1%) with medical or surgical NEC. Fifty-two patients (0.9%) required laparotomy or percutaneous abdominal drainage. On univariable analysis, the overall mortality rate for infants who developed NEC was significantly higher than infants who did not develop NEC (23.5 vs. 13.9%, P < 0.001). On multivariable analysis, neither medical nor surgical NEC was a significant predictor of mortality in the study population. LBW infants were at higher risk for mortality in both the univariable and the multivariable models. Nevertheless, LBW did not significantly predispose infants with HLHS to develop NEC. Our results provide a national benchmark incidence of NEC, its risk factors, and outcomes among a large cohort of infants with HLHS and establish that NEC is not a significant risk factor for mortality in this population.

Chromosomal Abnormalities Affect the Surgical Outcome in Infants with Hypoplastic Left Heart Syndrome: A Large Cohort Analysis.

Patients with hypoplastic left heart syndrome (HLHS) can have associated genetic abnormalities. This study evaluated the incidence of genetic abnormalities among infants with HLHS and the short-term outcomes of this population during the first hospitalization. This is a retrospective analysis of the multi-center Pediatric Heath Information System database of infants with HLHS who underwent Stage I Norwood, Hybrid, or heart transplant during their first hospitalization from 2004 through 2013. We compared clinical data between infants with and without genetic abnormality, among the three most common chromosomal abnormalities, and between survivors and non-survivors. Multivariable analysis was completed to evaluate predictors of mortality among patients with genetic abnormalities. A total of 5721 infants with HLHS were identified; 282 (5%) had associated genetic abnormalities. The three most common chromosomal abnormalities were Turner (25%), DiGeorge (22%), and Downs (12.7%) syndromes. Over the study period, the number of patients with genetic abnormalities undergoing cardiac operations increased without any significant increases in mortality. Infants with genetic abnormalities compared to those without abnormalities had longer hospital length of stay and higher morbidity and mortality. Variables associated with mortality were lower gestational age, longer duration of vasopressor therapy, need for dialysis, and cardiopulmonary resuscitation; and complicated clinical course as suggested by necrotizing enterocolitis, septicemia. Presence of any genetic abnormality in infants with HLHS undergoing cardiac surgery is associated with increased mortality and morbidity. Timely genetic testing, appropriate family counseling, and thorough preoperative case selection are suggested for these patients for any operative intervention.

Rolipram Improves Outcome in a Rat Model of Infant Sepsis-Induced Cardiorenal Syndrome.

While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram. Rat pups at 17-18-days old were subjected to cecal ligation and puncture (CLP) to induce fecal polymicrobial sepsis. Uptake of Evans Blue dye was used to assess renal microvascular leakage. Intravital videomicroscopy was used to assess renal microvascular perfusion and oxidant generation. Glomerular filtration rate (GFR) was used to assess renal function. Left ventricular (LV) catheterization and echocardiography were used to assess cardiac function. Impairment of both cardiac and renal function developed rapidly following CLP, indicating type 5 CRS. Most notable were the rapid decline in LV diastolic function, the decline in cardiac output, renal microvascular failure, and the decline in GFR. A dose-response study with rolipram determined 0.1 mg/kg, ip as the lowest most efficacious dose to protect the renal microcirculation. Rolipram was then evaluated using a clinically relevant delayed dosing paradigm (a single dose at 6 h post-CLP). With delayed dosing, rolipram restored the renal microcirculation and reduced microvascular leakage but did not reduce oxidant generation in the kidney nor restore GFR. In contrast, delayed dosing with rolipram restored cardiac function. Rolipram also improved 4-days survival. In summary, CLP in the rat pup produces a clinically relevant pediatric model of sepsis-induced CRS. The PDE4 inhibitor rolipram was effective in improving renal microvascular function and cardiac function, which improved mortality. These findings suggest that rolipram should be evaluated further as adjunctive therapy for the septic infant with CRS.

Improved Survival While Waiting and Risk Factors for Death in Pediatric Patients Listed for Cardiac Transplantation.

Our aim is to determine (a) the effect of changes in pre-transplant management and era of listing on survival of children listed for HTx and (b) risk factors for death while waiting. This retrospective study included all children listed between 1/1993 and 12/2009 at our center. Survival was determined using survival analysis and competing outcomes modeling. There were 254 listed patients of whom 144 (57%) had congenital heart disease, 208 (82%) were status 1, 52 used ECMO (20%), and 28 used ventricular assist device support (VAD) (11%) beginning in 2005. Overall mortality while waiting was 17% at 6 months, and 69% underwent transplant. Seven of 95 patients (7%) died waiting after 2004 compared to 36 of 159 (23%) before. ECMO and earlier year of listing were significant risk factors (p < 0.001) for wait-list mortality, whereas mortality was significantly lower (p = 0.002) after availability of VADs. Race, gender, blood type, and congenital diagnosis were not significant risk factors for death. Survival in pediatric patients listed for HTx has improved significantly in the current era at our institution. The availability of pediatric VADs has had a significant impact on survival while waiting in children listed for transplantation.

Tricuspid annular plane systolic excursion is reduced in infants with pulmonary hypertension.

BACKGROUND: Right ventricular (RV) function is reduced in infants with pulmonary hypertension (PH) but echocardiographic assessment can be challenging. We sought to determine the role of tricuspid annular plane systolic excursion (TAPSE) in infants with PH and compared it with other markers such as tricuspid annular S' and RV fractional area change (RVFAC). METHODS: Retrospective review of medical records of 30 infants treated for PH and 69 healthy controls from January 2012 to November 2012 was performed. Patients with significant congenital heart disease were excluded. Offline analysis of echocardiograms was performed to obtain TAPSE, tricuspid annular S', and RVFAC. TAPSE was indexed to body surface area (TAPSE/BSA). Logistic regression analysis was performed to evaluate the relation between echocardiographic markers and PH. RESULTS: TAPSE and TAPSE/BSA were significantly lower in PH patients. PH patients were younger than controls; however, TAPSE was significantly lower in PH patients after matching with controls by age. Tricuspid annular S' was decreased in PH patients, but RVFAC was similar. On multivariate analysis, tricuspid S' did not have a significant effect on the probability of PH (P = 0.067). The odds of PH significantly increased with each 1 mm decrease in TAPSE (OR 1.78, 95% CI 1.26-2.45). Inter-observer agreement for TAPSE showed concordance correlation coefficient of 0.89. CONCLUSIONS: TAPSE is a feasible and reproducible marker of RV systolic function in infants with PH and is superior to tricuspid annular S' and RVFAC. Longitudinal studies are needed to evaluate the role of TAPSE in serial evaluation of PH.