Clinical Variables Associated with Pre-Fontan Aortopulmonary Collateral Burden.

Aortopulmonary collaterals (APCs) develop universally, but to varying degrees, in patients with single ventricle congenital heart disease (CHD). Despite their ubiquitous presence, APCs remain poorly understood. We sought to evaluate the association between APC burden and common non-invasive clinical variables. We conducted a single center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent pre-Fontan cardiac magnetic resonance (CMR) imaging from 3/2018 to 3/2021. CMR was used to quantify APC flow, which was normalized to aortic (APC/QAo) and pulmonary vein (APC/QPV) blood flow. Univariate, multivariable, and classification and regression tree (CART) analyses were done to investigate the potential relationship between CMR-quantified APC burden and clinical variables. A total of 29 patients were included, all of whom had increased APC flow (APC/QAo: 26.9, [22.0, 39.1]%; APC/QPV: 39.4 [33.3, 46.9]%), but to varying degrees (APC/QAo: range 11.9-44.4%; APC/QPV: range 17.7-60.0%). Pulmonary artery size (Nakata index, at pre-Fontan CMR) was the only variable associated with APC flow on multivariable analysis (APC/QAo: p = 0.020, R2 = 0.19; APC/QPV: p = 0.0006, R2 = 0.36) and was the most important variable associated with APC burden identified by CART analysis (size inversely related to APC flow). APC flow is universally increased but highly variable in patients with single ventricle CHD and Glenn circulation. Small branch pulmonary artery size is a key factor associated with increased APC burden; however, the pathogenesis of APCs is likely multifactorial. Further research is needed to better understand APC pathogenesis, including predisposing and mitigating factors.

A multicenter study of three-dimensional echocardiographic evaluation of normal pediatric left ventricular volumes and function.

BACKGROUND: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. METHODS: Six hundred and ninety-eight healthy children (ages 0-18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor-independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA)-based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). RESULTS: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV was 0.99, 0.99, and 0.99, respectively. The ICC for interobserver variability for EDV, ESV, and SV was 0.98, 0.94, and 0.98, respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). CONCLUSIONS: We report pediatric z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.

Cardiac MRI-Derived Myocardial Deformation Parameters Correlate with Pulmonary Valve Replacement Indications in Repaired Tetralogy of Fallot.

Right ventricular (RV) volumetric cardiac magnetic resonance (CMR) criteria serve as indicators for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF). Myocardial deformation and tricuspid valve displacement parameters may be more sensitive measures of RV dysfunction. This study's aim was to describe rTOF RV deformation and tricuspid displacement patterns using novel CMR semi-automated software and determine associations with standard CMR measures. Retrospective study of 78 pediatric rTOF patients was compared to 44 normal controls. Global RV longitudinal and circumferential strain and strain rate (SR) and tricuspid valve (TV) displacement were measured. Correlation analysis between strain, SR, TV displacement, and volumes was performed between and within subgroups. The sensitivity and specificity of strain parameters in predicting CMR criteria for PVR was determined. Deformation variables were reduced in rTOF compared to controls. Decreased RV strain and TV shortening were associated with increased RV volumes and decreased RVEF. Longitudinal and circumferential parameters were predictive of RVESVi (> 80 ml/m2) and RVEF (< 47%), with circumferential strain (> - 15.88%) and SR (> - 0.62) being most sensitive. Longitudinal strain was unchanged between rTOF subgroups, while circumferential strain trended abnormal in those meeting PVR criteria compared to controls. RV deformation and TV displacement are abnormal in rTOF, and RV circumferential strain variation may reflect an adaptive response to chronic volume or pressure load. This coupled with associations of ventricular deformation with traditional PVR indications suggest importance of this analysis in the evolution of rTOF RV assessment.

Echocardiographic Identification of Pulmonary Artery Flow Reversal: An Indicator of Adverse Outcomes in Single Ventricle Physiology.

Individuals with single ventricle congenital heart disease (CHD) undergo multiple staged surgical palliations. Staged single ventricle palliation with a superior cavopulmonary connection (SCPC) in infancy followed by a Fontan in early childhood relies on passive, unobstructed pulmonary blood flow and normal pulmonary vasculature. We hypothesized that patients with echocardiographic identification of retrograde flow in a branch pulmonary artery (PA) after SCPC or Fontan are at increased risk for adverse outcomes. We conducted a retrospective chart review of patients seen at Children's Wisconsin from 1999 to 2019. Inclusion criteria included a history of single ventricle congenital heart disease and surgical palliation with a superior cavopulmonary connection (SCPC). We created two cohorts based on transthoracic echocardiographic identification of branch PA flow patterns: those with color Doppler-defined pulmonary artery flow reversal (PA reversal cohort) and those with normal anterograde flow (Non-reversal cohort). We identified 21 patients in the PA reversal cohort and 539 patients in the Non-reversal cohort. The PA reversal cohort had increased hospital length of stay after SCPC palliation (p < 0.001) and decreased transplant-free survival (p = 0.032), but there was no difference in overall survival (p = 0.099). There was no difference in hospital length of stay after Fontan (p = 0.17); however, the PA reversal cohort was significantly less likely to progress to Fontan palliation during early childhood (p = 0.005). Echocardiographic color Doppler identification of branch PA flow reversal in patients with single ventricle physiology is a high-risk indicator for adverse short- and long-term outcomes.

Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

OBJECTIVES: To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. DESIGN: Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. SETTING: A 16-bed cardiac ICU at an university-affiliated hospital. PATIENTS: Forty-two patients (20 Down syndrome, 22 controls) were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. CONCLUSIONS: This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

Imaging adult patients with Fontan circulation.

PURPOSE OF REVIEW: Survival after the Fontan procedure for palliation of single ventricle congenital heart disease has improved. However, adults with Fontan circulation are at risk for several complications including heart failure, thromboembolism, and protein-losing enteropathy. This review discusses the role of noninvasive imaging for surveillance and early detection of anatomic and functional abnormalities of the Fontan circulation that can impact the risk for Fontan failure over time. RECENT FINDINGS: Echocardiography is the first-line imaging modality for the adult Fontan patient. Use of established techniques, such as tissue Doppler imaging, and newer techniques, such as myocardial deformation and three-dimensional imaging, has improved the ability of echocardiography to serially assess ventricular and valvular function in this population. Strain imaging, in particular, is effective for early detection of subclinical ventricular dysfunction, is reproducible and can be incorporated into a routine clinical echocardiography protocol. Cardiac magnetic resonance (CMR) imaging complements echocardiography and overcomes the limitation of poor acoustic windows in adult patients, especially with regards to visualizing the cavopulmonary anastomoses and pulmonary arteries. High resolution imaging with CMR provides reliable assessment of ventricular size and function. Novel techniques utilizing CMR, such as computational fluid dynamics, have provided important insights into Fontan fluid dynamics, and the impact of Fontan geometry on flow efficiency through the circulation. SUMMARY: Recent advances in echocardiography and CMR have improved detection of structural and functional abnormalities in adults with Fontan circulation and are essential in monitoring for complications in this growing population.

Cardiac Magnetic Resonance Imaging in Pediatric Turner Syndrome.

OBJECTIVE: To compare the detection of cardiac lesions with the use of cardiac magnetic resonance imaging (CMR) and conventional echocardiography in children with Turner syndrome. STUDY DESIGN: Twenty-four girls with Turner syndrome, 8-18 years of age, were recruited through the Pediatric Endocrinology Program. Participants underwent CMR and echocardiography within a 2-year period, and discrepancies between the results of each modality were identified. RESULTS: Fifteen of 24 (63%) girls had a cardiac lesion identified on CMR or echocardiography. Both modalities identified the same lesion in 10 of 15 (67%); however, 6 of 15 (40%) participants had a lesion identified on CMR but not echocardiography. Participants with a missed lesion had a trend towards greater body mass index. Aortic dilation and bicuspid aortic valve were the most commonly missed lesions by echocardiography. CONCLUSIONS: CMR identifies significant cardiac lesions missed by echocardiography in pediatric patients with Turner syndrome, particularly along the aorta. These findings support the current guidelines that recommend screening CMR in addition to echocardiogram. Early identification of cardiac abnormalities in patients with Turner syndrome will allow for a greater understanding of the natural history in these patients and potentially identify candidates for earlier intervention.

The association between cardiac magnetic resonance-derived aortic stiffness parameters and aortic dilation in young adults with bicuspid aortic valve: With and without coarctation of aorta.

Background: Bicuspid aortic valve (BAV) is associated with progressive aortic dilation. Studies in aortopathies have shown a correlation between increased aortic stiffness and aortic dilation. We aimed to evaluate aortic stiffness measures as predictors of progressive aortic dilation by cardiac magnetic resonance (CMR) in BAV patients. Methods: This is a retrospective study of 49 patients with BAV (median age 21.1 years at first CMR visit) with ≥2 CMR at the Wisconsin Adult Congenital Heart Disease Program (WAtCH). Circumferential aortic strain, distensibility, and ß-stiffness index were obtained from CMR-derived aortic root cine imaging, and aortic dimensions were measured at aortic root and ascending aorta. A linear mixed-model and logistic regression were used to identify important predictors of progressive aortic dilation. Results: Over a median of 3.8 years follow-up, the annual growth rates of aortic root and ascending aorta dimensions were 0.25 and 0.16 mm/year, respectively. Aortic strain and distensibility decreased while ß-stiffness index increased with age. Aortic root strain and distensibility were associated with progressive dilation of the ascending aorta. Baseline aortic root diameter was an independent predictor of >1 mm/year growth rate of the aortic root (adjusted OR 1.34, 95 % CI 1.03-1.74, p = 0.028). Most patients (61 %) had coexisting coarctation of aorta. Despite the higher prevalence of hypertension in patients with aortic coarctation, hypertension or coarctation had no effect on baseline aorta dimensions, stiffness, or progressive aortic dilation. Conclusion: Some CMR-derived aortic stiffness parameters correlated with progressive aortic dilation in BAV and should be further investigated in larger and older BAV cohorts.

Three-Dimensional Echocardiography Right Ventricular Volumes and Ejection Fraction Reference Values in Children: A North American Multicentre Study.

BACKGROUND: Three-dimensional echocardiography (3DE) evaluation of right ventricular (RV) volumes and ejection fraction (EF) is increasingly used for clinical serial assessments and management in children. This study aims to generate sex-specific reference values and z-score equations for RV volumetric parameters, independent of age and body size indices, derived from multiple populations across North America. METHODS: We prospectively recruited 455 healthy children (ages 0 to 18 years) from 5 centres. 3DE of the RV were acquired using various vendors with analyses performed offline using vendor-independent software. 3DE datasets with all walls of the RV endocardium visible were included. We reported data on RV EF, and generated z scores for end-systolic volumes (ESV), end-diastolic volumes (EDV) and stroke volume (SV). Differences between the sexes were explored. RESULTS: Of 455 3DE datasets, 312 (68%) met imaging criteria for analysis. Median age was 10.1 years (interquartile ratio [IQR]: 5.6, 14.0) with 17% being younger than 3 years of age. The mean and standard deviation for RV EDV, ESV, and SV for male and female patients were reported. We provided a downloadable z-score calculator with height and weight as independent variables to facilitate clinical utility. Although statistically significant differences between male and female RVEF was present (female 52.9 ± 3.9% vs male 51.6 ± 3.5%, P = 0.006), after adjusting for age, height, and weight, the magnitude of difference was clinically insignificant. CONCLUSIONS: Sex-specific reference values for pediatric RV volumes and EF, and z-score equations were derived from children 3DE datasets across 5 centres in North America.

The use of Arginine Vasopressin in neonates following the Norwood procedure.

BACKGROUND: Following the Norwood palliation, neonates may require an escalation of inotropic and vasoactive support. Arginine Vasopressin may be uniquely useful in supporting this population. MATERIALS AND METHODS: A retrospective evaluation of neonates at this institution between November, 2007 and October, 2010 who received Arginine Vasopressin following the Norwood procedure. Data were recorded from the patient records at one hour prior to, and then 1, 2, 3, 4, 6, and 24 hours following Arginine Vasopressin initiation. RESULTS: We included 28 neonates. The mean dose of Arginine Vasopressin was 0.0005 plus or minus 0.0003 units per kilogram per minute. There was an early response (less than 6 hours) characterised by an 8% increase in systolic blood pressure (p = 0.0004), a 100% increase in urine output (p = 0.02), and a 29% decrease in total fluid administration (p = 0.04). The late response (at 24 hours) revealed further increases in systolic blood pressure and urine output as well as a 53% decrease in serum lactate (p = 0.007) and increase in arterial pH from 7.36 to 7.45 (p less than 0.0001). These changes were not accompanied by increases in heart rate or inotrope score. CONCLUSIONS: The initiation of Arginine Vasopressin in post-operative Norwood patients was temporally associated with an improvement in markers of perfusion including systolic blood pressure, urine output, lactate, and pH. Further studies are required to ascertain the efficacy of Arginine Vasopressin in this population.

Outcomes Following Surgery to Address Shone Syndrome in Children.

BACKGROUND: Shone syndrome is characterized by coincident mitral valve stenosis and left ventricular outflow tract obstruction. Although first described in 1963, little research has expounded surgical outcomes. We sought to evaluate our experience with this cohort, emphasizing outcomes including mortality, morbidity, and cardiac function. METHODS: A retrospective chart review of 46 patients who underwent operation for Shone syndrome between 1990 and May 2018 was conducted. Index operations included 32 repairs of the left ventricular outflow tract, four mitral valve repair/replacements, nine combined repairs, and one non-Shone's repair. Median age at index procedure was 22 days (2 days-10 years). Mean follow-up was 9.1 years (2 months-21 years), and 70 additional operations (51 reoperations) were required. Three patients were lost to follow-up. RESULTS: Overall survival was 95.7% with two late deaths. Freedom from death or transplant was 93.5%. Thirteen (28.3%) patients remained free from reoperation. Thirty-three patients required 51 reoperations of the left ventricle outflow tract (n = 12), mitral valve (n = 16), combined repairs (n = 21), and transplant (n = 1). At most recent follow-up, patients exhibited mitral stenosis (n = 21), aortic stenosis (n = 7), and diminished LV function (n = 2). CONCLUSION: Surgical correction of Shone's offers excellent survival benefit, but reoperation burden is high, with >70% of patients requiring reintervention in the follow-up period. A total of 65% of patients developed recurrent obstruction of left ventricular inflow or outflow, however, ventricular function is preserved in the majority of patients. All but one patient had no functional deficits, classified as New York Heart Association I with > 60% requiring no medication.

Evaluating Chest Pain and Heart Murmurs in Pediatric and Adolescent Patients.

Chest pain and heart murmurs are common issues primary care providers must evaluate and manage. Both are a source of anxiety for patients, parents, and providers, necessitating evaluation and understanding to ensure appropriate management. Most pediatric chest pain can be treated symptomatically and with reassurance. This article examines the approach to pediatric chest pain including identification of key historical points, common causes of chest pain, and when to refer. The article also delineates our approach to auscultation, describes common benign murmurs, and offers suggestions on when to refer for further evaluation.

Echocardiography vs cardiac magnetic resonance imaging assessment of the systemic right ventricle for patients with d-transposition of the great arteries status post atrial switch.

OBJECTIVE: Patients with Dextro-transposition of the great arteries status post atrial switch (dTGA s/p atrial switch) are "at-risk" for systemic right ventricular (RV) dysfunction. Due to complex RV geometry, echocardiography (Echo) does not allow accurate determination of ejection fraction (EF), but cardiac magnetic resonance imaging (CMR) allows quantitative right ventricular assessment. Measures of ventricular deformation may be precursors to global ventricular dysfunction. The primary aim of this study was to characterize imaging and clinical findings for adult patients with dTGA s/p atrial switch. DESIGN: This was a retrospective cohort study of patients with dTGA s/p atrial switch operation (February 1966 to August 1988) with CMR performed at Children's Hospital of Wisconsin (from September 2005 to May 2015). Eligible patients had clinic visit, Echo, and exercise stress test within 1 year of CMR. RESULTS: This study enrolled twenty-seven patients (16 males, 11 females) with dTGA s/p atrial switch (18 with Mustard operation and 9 with Senning operation; median age 30 years; 74% New York Heart Association class 1 and 26% class 2). Seventy-four percentage had normal RV systolic function (RV EF >45% by CMR). No correlation was observed between Echo strain data and clinical status (EF, exercise endurance, VO2 max, or New York Heart Association class). Cardiac magnetic resonance imaging RV global circumferential strain GCS and RV EF had moderate negative correlation (r = -0.65, P < .001). Global circumferential strain was significantly different for those with RV EF above and below 45%, while global peak longitudinal strain (GLS) was not. Patients had reduced CMR myocardial strain values compared with healthy controls. CONCLUSIONS: Reduced RV CMR GCS (for those with RV EF <45%) suggests that CMR evaluation may enhance early detection of detrimental changes in the systemic RV myocardium.

Active right atrial emptying fraction predicts reduced survival and increased adverse events in childhood pulmonary arterial hypertension.

BACKGROUND: Right atrial (RA) function has been studied rarely in childhood pulmonary arterial hypertension (PAH). We sought to determine if RA and right ventricular (RV) area changes measured by echocardiography predicted outcomes. METHODS: We reviewed data from children with PAH undergoing cardiac catheterization and echocardiography. RA and RV areas were obtained from the apical 4-chamber view. Clinical worsening indicated initiation of parenteral prostanoid therapy, heart and/or lung transplantation, Potts shunt surgery or death. RESULTS: We studied 57 children (27 females), median age 3 years (range 0.30-17 years), body surface area 0.56 m2 (0.2-1.8), follow up 3 years (0.21-8.35), time to clinical worsening was 1.14 years (0.03-6.14) and mortality was 1.55 years (range 0.88-4.95). We determined from receiver operator curves that RA active emptying fraction (RA EaF) ≥60% predicted clinical worsening (sensitivity 78%, specificity 69%, AUC 0.7) and mortality (sensitivity 100%, specificity 65%, AUC 0.82). RV fractional area change (RVFAC) <25% predicted clinical worsening (sensitivity 72%, specificity 79%, AUC 0.85) and death (sensitivity 67%, specificity 69%, AUC 0.77). The combination of RA EaF ≥60% and RVFAC <33% were best predictors of clinical worsening (sensitivity 72%, specificity 82%, partial AUC 0.65) and mortality (sensitivity 100%, specificity 77%, partial AUC 0.75). CONCLUSION: In childhood PAH, RA EaF ≥ 60% and RVFAC <25% were associated with poor outcomes. RA EaF ≥60% and RVFAC <33% were best predictors of clinical worsening and may be useful markers in children with PAH who require closer observation and more intensive therapy.

Rapid 3D imaging of the lower airway by MRI in patients with congenital heart disease: A retrospective comparison of delayed volume interpolated breath-hold examination (VIBE) to turbo spin echo (TSE).

OBJECTIVE: When imaging the lower airway by MRI, the traditional technique turbo spin echo (TSE) results in high quality 2D images, however planning and acquisition times are lengthy. An alternative, delayed volume interpolated breath-holds examination (VIBE), is a 3D gradient echo technique that produces high spatial resolution imaging of the airway in one breath-hold. The objective of this study is to retrospectively evaluate the accuracy of lower airway measurements obtained by delayed VIBE when compared to TSE. DESIGN: Patients with congenital heart disease who underwent a cardiac MRI (CMR) that included a delayed VIBE sequence from 5/2008 to 9/2013 were included. Standard TSE imaging was performed and delayed VIBE was acquired 5 min after gadolinium contrast administration. Airway measurements were made on both sequences by two observers in a blinded fashion to the other observer and other technique. Intraclass correlations (ICC) were calculated to assess for agreement between both techniques and the observers. RESULTS: 29 studies met inclusion criteria with a mean patient age of 8.8 years (2 months to 63 years) and mean patient weight of 30.2 kg (3.5-110). All delayed VIBE and TSE sequences were found to be of diagnostic quality. Mean acquisition time was shorter for the delayed VIBE (13.1 seconds) than TSE (949.9 seconds). Overall there was very good agreement between the delayed VIBE and TSE measurements for both observers (ICC 0.78-0.94) with the exception of the distal right bronchus (ICC 0.67) The interobserver agreement was also excellent for both TSE (ICC 0.78-0.96) and VIBE (ICC 0.85-0.96). CONCLUSION: Delayed VIBE is rapid and at least as accurate as the alternative TSE imaging for assessment of the lower airway by MRI across a wide spectrum of patients.

Multivalvular Replacement and Ventricular Arrhythmias in a Female Child With Congenital Polyvalvular Disease.

We report the clinical course of a female child with a normal karyotype and chromosomal microarray who presented as an infant with clinical findings consistent with congenital polyvalvular disease (CPVD). This clinical entity describes patients with multiple congenitally dysplastic valves, often showing nodular or cystic malformation in at least two cardiac valves. This patient then developed medically refractory multifocal ventricular arrhythmia and required radiofrequency ablation at seven months of age. She had good tachycardia control but became symptomatic with right heart failure related to progressive tricuspid, pulmonary, and mitral valve dysfunction necessitating multivalvular replacement at 21 months of age.