Management of Hematochezia in Infants with Congenital Heart Disease Admitted to the Acute Care Cardiology Unit: A Multicenter Retrospective Pilot Study.

OBJECTIVE: To assess the evaluation and prevalence of benign hematochezia (BH) vs necrotizing enterocolitis (NEC) in infants with congenital heart disease (CHD) <6 months old admitted to the acute care cardiology unit. STUDY DESIGN: This was a multicenter retrospective review of patient characteristics and evaluation of all hematochezia events in patients with CHD <6 months admitted to acute care cardiology unit at 3 high-volume tertiary care centers from February 2019 to January 2021. NEC was defined by the Bell staging criteria. Patients with gastrointestinal disorders were excluded. RESULTS: In total, 180 hematochezia events occurred in 121 patients; 42 patients had more than 1 event. In total, 61% of affected patients had single-ventricle physiology (38% hypoplastic left heart syndrome). Median age and weight at hematochezia were 38 days (IQR 24, 79) and 3.7 kg (IQR 3.2, 4.4). In total, 77% of hematochezia events were BH, and 23% were NEC. There were no surgical interventions for NEC or deaths from NEC. Those with NEC were significantly younger (34 vs 56 days, P < .01) and smaller (3.7 vs 4 kg, P < .01). Single-ventricle physiology was significantly associated with NEC. Initial bloodwork and diagnostic imaging at each center were assessed. There was no significant difference in white blood cell count or C-reactive protein in those with NEC compared with BH. Blood culture results were all negative. CONCLUSIONS: The majority of infants with CHD with hematochezia have BH over NEC, although single-ventricle and surgical patients remain at greater risk. Infants <45 days are more vulnerable for developing NEC. Bloodwork was noncontributory in the identification of cardiac NEC. Expansion to a prospective study to develop a treatment algorithm is important to avoid overtreatment.

Feeding Practices in Infants with Hematochezia and Necrotizing Enterocolitis on Acute Care Cardiology Units.

Infants with congenital heart disease (CHD) are at risk for developing both benign hematochezia and necrotizing enterocolitis (NEC). Despite these risks there are very few studies that investigate modifiable risk factors such as feeding practices. It remains unclear what feeding practices should be avoided due to higher incidence of CHD-NEC. We aim to assess the feeding practices across three high volume tertiary centers to establish a relationship between various feeding practices and development of NEC. A multicenter retrospective review of feeding practices at the time of documented hematochezia event that occurred between 1/2019 and 1/2021 in infants with CHD who were less than 6 months of age. NEC was defined as Bells Stage 2 or greater. Age, weight, ventricular morphology, primary diagnoses, feeding route, feed change, and formula type were evaluated. 176 hematochezia events occurred in 121 patients, 72% of these events were considered benign hematochezia with the remaining 28% being true NEC. Single ventricle (SV) physiology (p < 0.05), younger age, < 45 days of life, (p < 0.001), and feeding route were statistically associated with true NEC (p < 0.01). Formula type and recent change in feed administration were not associated with NEC. The caloric density of feeds at the time of hematochezia was nearing significance. The majority of hematochezia events are benign in nature, however, there should be heightened awareness in patients who are SV, younger in age, and those who are post-pylorically fed. There may be some risk in using higher caloric density feeds (> 24 kcal/oz), however, additional research is needed to fully establish this relationship.

Echocardiography Provides a Reliable Estimate of Total Cardiac Volume for Pediatric Heart Transplantation.

BACKGROUND: Donor-to-recipient size matching for heart transplantation typically involves comparing donor and recipient body weight; however, weight is not linearly related to cardiac size. Attention has shifted toward the use of computed tomography- (CT-) derived total cardiac volume (TCV), that is, CT-TCV, to compare donor and recipient heart organ size. At this time, TCV size matching is near impossible for most centers due to logistical limitations. To overcome this impediment, echocardiogram-derived TCV (ECHO-TCV) is an attractive, alternative option to estimate CT-TCV. The goal of this study is to test whether ECHO-TCV is an accurate and reliable surrogate for TCV measurement compared with the gold standard CT-TCV. METHODS: ECHO-TCV and CT-TCV were measured in a cohort spanning the neonatal to young adult age range with the intention to simulate the pediatric heart transplant donor pool. ECHO-TCV was measured using a modified Simpson's summation-of-discs method from the apical 4-chamber (A4C) view. The gold standard of CT-TCV was measured from CT scans using three-dimensional reconstruction software. The relationship between ECHO-TCV and CT-TCV was evaluated and compared with other anthropometric and image-based markers that may predict CT-TCV. Inter-rater reliability of ECHO-TCV was tested among 4 independent observers. Subanalyses were performed to identify imaging views and timing that enable greater accuracy of ECHO-TCV. RESULTS: Banked imaging data of 136 subjects with both echocardiogram and CT were identified. ECHO-TCV demonstrated a linear relationship to CT-TCV with a Pearson correlation coefficient of r = 0.96 (95% CI, 0.95-0.97; P < .0001) and mean absolute percent error of 8.6%. ECHO-TCV correlated most strongly with CT-TCV in the subset of subjects <4 years of age (n = 33; r = 0.98; 95% CI, 0.96-0.99; P < .0001). The single-score intraclass correlation coefficient across all 4 raters is 0.96 (interquartile range, 0.93-0.98). ECHO-TCV measured from a standard A4C view at end diastole with the atria in the plane of view had the strongest correlation to CT-TCV. CONCLUSIONS: ECHO-TCV by the A4C view was found to be both an accurate and reliable alternative measurement of CT-TCV and is derived from readily available donor ECHO images. The ECHO-TCV findings in this study make the ECHO method an attractive means of direct donor-to-recipient TCV size matching in pediatric heart transplantation.

Decreased Global Myocardial Work Efficiency Correlates with Coronary Vasculopathy in Pediatric Heart Transplant Patients.

Coronary angiography remains the standard for diagnosis of cardiac transplant vasculopathy (CAV), but it is invasive. Non-invasively derived left ventricle (LV) global myocardial work (GMW) indices have not been evaluated. We aimed to assess for correlations between LV GMW and the presence of CAV in a pediatric population. 24 heart transplant patients and 24 normal controls were prospectively enrolled. Patients were age-matched into groups with: orthotopic heart transplant and CAV (OHT-CAV; 6 patients, 33% male, mean age 13.5 years [SD 4.2]), orthotopic heart transplant without CAV (OHT; 18 patients, 67% male, mean age 11.1 years [SD 4.8]), and normal healthy controls (42% male, mean age 12.8 years [SD 5.0]). Transplant patients underwent cardiac catheterization with coronary angiography within 3 months of echocardiogram. Post-processing of echocardiograms with speckle-tracking echocardiography and derivation of GMW indices was performed. OHT-CAV patients had decreased global work efficiency (GWE) compared to OHT (mean difference = 7.01 [1.76, 12.25], adjusted p < 0.01). LV global longitudinal strain (GLS) and LV ejection fraction were not different between groups. Both global work index and GWE were decreased in OHT-CAV and OHT when compared to normal controls (OHT-CAV 1311.23 mmHg% vs OHT 1426.22 mmHg% vs controls 1802.81 mmHg%, adjusted p < 0.01; OHT-CAV 83.87% vs. OHT 90.87% vs. controls 95.41%, adjusted p < 0.01). GWE correlated negatively with the presence of CAV (r = - 0.44 [- 0.72, - 0.05]). This pilot study demonstrates decreased GWE correlates with pediatric CAV. This supports the need for further investigation of this promising diagnostic tool.

Improving Compliance with Dyslipidemia Screening Guidelines in a Single-center U.S. Outpatient Pediatric Cardiology Clinic.

The development of atherosclerotic cardiovascular disease begins in childhood. The American Academy of Pediatrics (AAP) endorsed guidelines recommending universal hyperlipidemia screening of children ages 9-11 and again at 17-21 years. An AAP Periodic Survey of Fellows demonstrated less than half of pediatricians report adherence to these guidelines. This quality improvement initiative's objective was to improve compliance with AAP hyperlipidemia guidelines in an outpatient pediatric cardiology clinic at a single academic center to 80% over a 2-month time frame. METHODS: We report the results of an IRB-approved chart review at a single-center outpatient pediatric cardiology practice. We defined pediatric cardiologists' compliance as documented prior lipid screening, ordering a lipid panel, or documented recommendation for follow-up screening. Two plan-do-study-act (PDSA) cycles were undertaken. The first intervention included an informational session to provide pediatric cardiologists with AAP recommendations. The second intervention involved weekly email reminders and a statement for physicians in the electronic medical record. RESULTS: We collected data from 600 individual charts of patients seen over 35 clinic days. We received charts before the first PDSA intervention. Baseline compliance with outpatient hyperlipidemia screening was 0%. After the first PDSA cycle, the average screening rate improved to 49%. After the second PDSA cycle, the average screening rate improved to 89%, and there was a centerline shift in the data, indicating improvement. CONCLUSION: We improved the pediatric cardiologists' compliance with the AAP-recommended hyperlipidemia screening guidelines from 0% to 89% through 2 intervention cycles. Further efforts may be required to sustain this change.

Non-invasive left ventricular myocardial work indices in healthy adolescents at rest.

Global myocardial work (GMW) provides a metric of left ventricular (LV) function and energy consumption. Its non-invasive assessment by echocardiography correlates with invasive measures and normal values have been reported in healthy adults. We aimed to establish normal values in a healthy adolescent population. Fifty-two healthy adolescents (mean age = 14.5 ± 2.0 years, range 11-19 years, 62% male) with normal echocardiograms were included. Brachial cuff blood pressure was obtained immediately following apical imaging in the supine position. Post-processing of echocardiograms for speckle tracking strain measurement and derivation of global myocardial work indices from LV pressure-strain loops was performed. The mean global work index (GWI) was 1802.0 ± 264.4 mmHg% with mean global work efficiency of 95.5 ± 1.1%. The mean global constructive work (GCW) was 2054.5 ± 297.3 mmHg%, and the mean global wasted work 83.8 ± 28.1 mmHg%. On multivariable analysis, there were significant associations between both GWI and GCW with systolic blood pressure (ß coefficient = 0.57, p < 0.001; ß coefficient = 0.67, p < 0.001 respectively) and LV global longitudinal strain (GLS) (ß coefficient = - 0.56, p < 0.001; ß coefficient = - 0.52, p < 0.001 respectively). There were no associations with any of the work indices with age, sex, body surface area, heart rate or LV ejection fraction. This study provides echocardiographic reference ranges for non-invasive indices of GMW in normal adolescents.

Atrial Reservoir Strain is Associated with Decreased Cardiac Index and Adverse Outcomes Post Fontan Operation.

Fontan patients rely on atrial function for diastolic filling and to augment cardiac output. Emerging data suggests that diminished atrial function is predictive of poor outcomes in adults but studies evaluating the association between atrial mechanics in Fontan patients and outcomes are lacking. We sought to assess atrial function in Fontan patients using speckle tracking echocardiography to determine whether atrial function is associated with invasive hemodynamics and clinical outcomes. Single-center review of Fontan patients receiving both catheterization and echocardiogram from 2012-2017. Atrial reservoir, conduit and pump global longitudinal strain and strain rate were assessed by speckle tracking echocardiography. The primary outcome was a composite of all adverse clinical outcomes including cardiac hospitalizations, transplant and death. Eighty-three Fontan patients at a median age of 14.2 years (IQR 8.6, 21.7) at time of echocardiogram were included. Increased atrial reservoir strain (p = 0.04), atrial emptying fraction (p = 0.04) and atrial fractional area change (p = 0.04), were associated with higher cardiac index at baseline. There were no associations between atrial strain and systemic ventricular end diastolic pressure (EDP) at catheterization. Reservoir strain was inversely associated with the composite clinical outcome on multivariable Cox proportional hazard analysis (HR 0.96, p = 0.03). Reduced atrial function is associated with reduced cardiac index, but is not directly associated with ventricular EDP in Fontan patients. Reservoir strain is associated with an excess of adverse clinical outcomes in Fontan patients.

Congenitally corrected transposition and mitral atresia complicated by restrictive atrial septum.

Congenitally corrected transposition (ccTGA), also known as L-transposition of the great arteries (L-TGA), is a rare cardiac malformation accounting for approximately 0.05% of congenital heart disease, characterized by ventricular inversion, discordant ventriculo-arterial connections with a normal visceroatrial relationship. It was first described by Baron Rokitansky in 1875, and prenatal sonographic diagnosis can be difficult. Symptomatology and clinical presentation of this malformation are related to the associated intracardiac defects. We report a rare case of severe, complex cardiac disease: prenatally diagnosed ccTGA with atrial restriction, mitral atresia, Ebsteinoid tricuspid valve, and severe pulmonary valve stenosis, who subsequently developed left pulmonary vein stenosis.

Anticholinergic, anti-depressant and other medication use is associated with clinically relevant oesophageal manometric abnormalities.

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

Ambulatory Arrhythmia Detection with ZIO® XT Patch in Pediatric Patients: A Comparison of Devices.

Ambulatory electrocardiogram monitoring devices can be used for 24-72 h to detect arrhythmias. A new device, the ZIO® XT Patch has cardiac monitoring capabilities that can be utilized for up to 14 days. The purpose of this study is to describe duration of ZIO use by age, and to compare its time to arrhythmia detection with the Holter monitor in a pediatric population. A single-center, retrospective review of patients < 18 years of age who underwent clinical investigation with ZIO from October 2014 to February 2016 was performed. An age-matched cohort was utilized to compare ZIO to Holter monitor results. Demographic and diagnostic data, time to first arrhythmia, and arrhythmia burden were analyzed. A total of 406 ZIO were prescribed; median age 12.7 years and 50% male subjects. Median duration of ZIO monitoring significantly increased with age (p < 0.001). 499 Holter monitors were prescribed on a statistically different age group. Arrhythmia detection rates were similar between groups, 10% (n = 42) by ZIO and 9% (n = 45) by Holter (p = NS). The majority of arrhythmias (57%) detected by ZIO were after 24 h (p < 0.0001). All arrhythmias detected by Holter monitor occurred within 24 h (p < 0.0001), mean duration of wear was 24.1 h, range 0.5-48 h. The ZIO® XT Patch may be considered as an ambulatory ECG monitor to diagnose arrhythmia in pediatric patients of all ages. Increasing patient age resulted in increasing duration of ZIO monitoring. Majority of arrhythmias detected with ZIO were identified after 24 h, which would have been missed by other short-term monitors.

Glutamate alterations associated with transcranial magnetic stimulation in youth depression: a case series.

OBJECTIVE: We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after 3 weeks of repetitive transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms. METHODS: We report 6 patients (4 females) 15 to 21 years of age with treatment-resistant MDD. Participants had a mean (SD) age of 18.7 (1.95) years and a mean (SD) IQ of 102.3 (3.39). Short echo proton magnetic resonance spectroscopy (¹H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5 cc) before and after rTMS treatment. Repetitive transcranial magnetic stimulation was localized to the left DLPFC and applied for 15 consecutive weekdays (120% resting motor threshold; 40 pulses over 4 seconds [10 Hz]; intertrain interval, 26 seconds; 75 trains; 3000 pulses). Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores. Short echo proton magnetic resonance spectroscopy data were analyzed with LCModel to determine glutamate concentration. RESULTS: After rTMS, treatment responders (n = 4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Hamilton Depression Rating Scale score reduction). Treatment nonresponders (n = 2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (-10%). Procedures were generally well tolerated with no adverse events. CONCLUSIONS: Repetitive transcranial magnetic stimulation is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement.

Influence of age of onset on limbic and paralimbic structures in depression.

AIM: Major depressive disorder (MDD) onset during childhood/adolescence is associated with a greater illness burden and distinct clinical profile. However, limited research exists on the effect of age of MDD onset on volumetric abnormalities in para/limbic structures during adulthood. METHODS: Subgenual anterior cingulate cortex (sgACC), hippocampus and caudate nucleus volumes were measured by manual tracing in depressed individuals (n = 45) and healthy controls (HC; n = 19). Volumetric comparisons were carried out between HC and MDD patients divided into those with pediatric (≤ 18 years; n = 17) and adult onset (≥ 19 years; n = 28). RESULTS: The adult MDD-onset group had smaller sgACC volumes than the pediatric-onset and HC groups (age, sex controlled). No differences in caudate and hippocampus volumes existed. sgACC and hippocampal volumes were inversely correlated with depression severity. CONCLUSIONS: Surprisingly, pediatric MDD-onset was not associated with more pronounced sgACC, hippocampus and caudate volume reductions. Nevertheless, age of illness onset appears to be a meaningful dimension of study in efforts to understand the neurobiological heterogeneity of MDD.

Age of onset and corpus callosal morphology in major depression.

BACKGROUND: The corpus callosum and related white matter projections have been implicated in major depressive disorder (MDD). Previously, we found a smaller genu in adolescents with MDD as compared to controls. To date, no study has examined the age of depression onset (adult vs. pediatric) as it relates to genu area in adults with MDD. METHODS: The area of the corpus callosum and its sub-regions were measured in 21 MDD subjects with pediatric age of onset (≤18 years) (29.48±7.62 years; 16 female, 5 male) and 31 MDD subjects with adult age of onset (≥19 years) (41.42±8.85; 17 female, 14 male) and 19 healthy controls (32.89± years 9.98; 11 female, 8 male) using magnetic resonance imaging (MRI). RESULTS: A difference in genu area was noted between groups (p=0.03), after co varying for age with post-hoc tests revealing that the difference was driven by the subjects with an MDD onset of pediatric age (p=0.035). No other sub-regions or total corpus callosum area demonstrated a significant difference. Genu area correlated with age in controls (p=0.02) but not in MDD patients (p=0.35). No significant correlation was found between the confound illness duration and genu area in MDD subjects with pediatric age of onset. LIMITATIONS: Confirmation and extension of our findings requires a larger sample size and usage of diffusion tensor imaging. CONCLUSIONS: Our findings provide additional evidence of abnormalities in the genu of the corpus callosum in early onset depression that persist into adulthood.