A Preliminary Study of One Year Safety and Tolerability of Attention-Deficit/Hyperactivity Disorder Medications in Youth with Fontan Palliation or Heart Transplant.

There are no published studies that examine the safety and tolerability of medication to treat attention-deficit/hyperactivity disorder (ADHD) in children with histories of Fontan palliation (Fontan) or heart transplant (HT), despite the high prevalence of ADHD in these populations. To address this gap, we examined the cardiac course, somatic growth, and incidence of side effects for one year after medication initiation amongst children with Fontan or HT and comorbid ADHD. The final sample comprised 24 children with Fontan (12 medication-treated, 12 control) and 20 children with HT (10 medication-treated, 10 control). Demographic, somatic growth (height and weight percentile-for age), and cardiac data (blood pressure, heart rate, results of 24 h Holter monitoring, electrocardiograms) were extracted from electronic medical records. Medication-treated and control subjects were matched by cardiac diagnosis (Fontan or HT), age, and sex. Nonparametric statistical tests were utilized to compare between- and within-group differences prior to, and one year post, medication initiation. There were no differences in somatic growth or cardiac data when comparing medication-treated participants to matched controls, regardless of cardiac diagnosis. Within the medication group, a statistically significant increase in blood pressure was observed, though the group average remained within clinically acceptable limits. While results are preliminary in nature due to our very limited sample size, our findings suggest that ADHD medications can be tolerated with minimal cardiac or somatic growth effects amongst complex cardiac patients. Our preliminary results favor treating ADHD with medication, which has considerable implications for long-term academic/employment outcomes and quality of life for this population. Close collaboration between pediatricians, psychologists, and cardiologists is essential to individualizing and optimizing interventions and outcomes for children with Fontan or HT.

Ventricular global function index is associated with clinical outcomes in pediatric pulmonary hypertension.

BACKGROUND: Multiple right ventricular (RV) metrics have prognostic value in pulmonary hypertension (PH). A cardiac magnetic resonance imaging (CMR) derived global ventricular function index (GFI) provided improved prediction of composite adverse outcome (CAO) in adults with atherosclerosis. GFI has not yet been explored in a PH population. We explored the feasibility of GFI as a predictor of CAO in a pediatric PH population. METHODS: Two center retrospective chart review identified pediatric PH patients undergoing CMR from Jan 2005-June 2021. GFI, defined as the ratio of the stroke volume to the sum of mean ventricular cavity and myocardial volume, was calculated for each patient. CAO was defined as death, lung transplant, Potts shunt, or parenteral prostacyclin initiation after CMR. Cox proportional hazards regression was used to estimate associations and assess model performance between CMR parameters and CAO. RESULTS: The cohort comprised 89 patients (54% female, 84% World Health Organization (WHO) Group 1; 70% WHO-FC ≤ 2; and 27% on parenteral prostacyclin). Median age at CMR was 12 years (IQR 8.1-17). Twenty-one (24%) patients experienced CAO during median follow up of 1.5 years. CAO cohort had higher indexed RV volumes (end systolic-145 vs 99 mL/m2, p = 0.003; end diastolic-89 vs 46 mL/m2, p = 0.004) and mass (37 vs 24 gm/m2, p = 0.003), but lower ejection fraction (EF) (42 vs 51%, p < 0.001) and GFI (40 vs 52%, p < 0.001). Higher indexed RV volumes (hazard ratios [HR] 1.01, CI 1.01-1.02), lower RV EF (HR 1.09, CI 1.05-1.12) and lower RV GFI (HR 1.09, CI 1.05-1.11) were associated with increased risk of CAO. In survival analysis, patients with RV GFI < 43% demonstrated decreased event-free survival and increased hazard of CAO compared to those with RV GFI ≥ 43%. In multivariable models, inclusion of GFI provided improved prediction of CAO compared to models incorporating ventricular volumes, mass or EF. CONCLUSIONS: RV GFI was associated with CAO in this cohort, and inclusion in multivariable models had increased predictive value compared to RVEF. GFI uses readily available CMR data without additional post-processing and may provide additional prognostic value in pediatric PH patients beyond traditional CMR markers.

Central Venous Waveform Patterns in the Fontan Circulation Independently Contribute to the Prediction of Composite Survival.

It is well appreciated that the Fontan circulation perturbs central venous hemodynamics, with elevated pressure being the clearest change associated with Fontan comorbidities, such as Fontan-associated liver disease (FALD) and protein-losing enteropathy (PLE). Our group has better quantity of these venous perturbations through single- and multi-location analyses of flow waveforms obtained from magnetic resonance imaging of Fontan patients. Here, we determine if such analyses, which yield principal components (PC) that describe flow features, are associated with Fontan survival. Patients with a Fontan circulation (N = 140) that underwent free-breathing and mechanically ventilated cardiac MRI were included in this study. Standard volumetric and functional hemodynamics, as well as flow analysis principal components, were subjected to univariate and bivariate Cox regression analyses to determine composite clinical outcome, including plastic bronchitis, PLE, and referral and receipt of transplant. Unsurprisingly, ventricular function measures of ejection fraction (EF; HR = 0.88, p < 0.0001), indexed end-systolic volume (ESVi; HR 1.02, p < 0.0001), and indexed end-diastolic volume (EDVi; HR = 1.02, p = 0.0007) were found as specific predictors of clinical events, with specificities uniformly > 0.75. Additionally a feature of IVC flow (PC2) indicating increased flow in systole was found as a highly sensitive predictor (HR = 0.851, p = 0.027, sensitivity 0.93). In bivariate prediction, combinations of ventricular function (EF, ESVi, EDVi) with this IVC flow feature yielded best overall prediction of composite outcome. This suggests that central venous waveform analysis relays additional information about Fontan patient survival and that coupling sensitive and specific measures in bivariate analysis is a useful approach for obtaining superior prediction of survival.

Flow profile characteristics in Fontan circulation are associated with the single ventricle dilation and function: principal component analysis study.

The Fontan circulation is characterized as a nonpulsatile flow propagation without a pressure-generating ventricle. However, flow through the Fontan circulation still exhibits oscillatory waves as a result of pressure changes generated by the systemic single ventricle. Identification of discrete flow patterns through the Fontan circuit may be important to understand single ventricle performance. Ninety-seven patients with Fontan circulation underwent phase-contrast MRI of the right pulmonary artery, yielding subject-specific flow waveforms. Principal component (PC) analysis was performed on preprocessed flow waveforms. Principal components were then correlated with standard MRI indices of function, volume, and aortopulmonary collateral flow. The first principal component (PC) described systolic versus diastolic-dominant flow through the Fontan circulation, accounting for 31.3% of the variance in all waveforms. The first PC correlated with end-diastolic volume (R = 0.34, P = 0.001), and end-systolic volume (R = 0.30, P = 0.003), cardiac index (R = 0.51, P < 0.001), and the amount of aortopulmonary collateral flow (R = 0.25, P = 0.027)-lower ventricular volumes and a smaller volume of collateral flow-were associated with diastolic-dominant cavopulmonary flow. The second PC accounted for 19.5% of variance and described late diastolic acceleration versus deceleration and correlated with ejection fraction-diastolic deceleration was associated with higher ejection fraction. Principal components describing the diastolic flow variations in pulmonary arteries are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to preserved ventricular volume and function, respectively.NEW & NOTEWORTHY The exact physiological significance of flow oscillations of phasic and temporal flow variations in Fontan circulation is unknown. With the use of principal component analysis, we discovered that flow variations in the right pulmonary artery of Fontan patients are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to more ideal ventricular volume and systolic function, respectively.

Relationships between Physiologic and Neuropsychologic Functioning after Fontan.

OBJECTIVE: To investigate potential relationships between neuropsychologic functioning and cardiac, gastroenterologic/hepatologic, and pulmonary complications in the single ventricle heart disease (SVHD) post-Fontan population. STUDY DESIGN: Following the initiation of a Fontan Multidisciplinary Clinic, patients with SVHD were evaluated systematically according to a clinical care pathway, and data from multiple subspecialty evaluations were collected prospectively from 2016 to 2019. Biomarkers of cardiology, pulmonary, and hepatology/gastroenterology functioning were abstracted, along with neuropsychologic testing results. Bivariate correlations and regression analyses examined cross-sectional relationships between physiologic predictors and neuropsychologic outcomes. RESULTS: The sample included a cohort of 68 youth with SVHD age 3-19 years, after Fontan palliation. Sleep-disordered breathing was related to poorer visual-motor integration skills (r = -0.33; P < .05) and marginally related to poorer executive functioning (r = -0.33; P = .05). Lower arterial blood oxygen content was related to poorer executive functioning (r = .45; P < .05). Greater atrioventricular valve regurgitation was related to lower parent-rated adaptive functioning (ρ = -0.34; P < .01). These results were maintained in regression analyses controlling for history of stroke and/or seizures. CONCLUSIONS: We demonstrated associations between neuropsychologic functioning and potentially modifiable aspects of physiologic functioning in a prospectively evaluated cohort of patients with SVHD with Fontan physiology. Our findings emphasize the importance of multidisciplinary screening and care after a Fontan procedure and suggest avenues for intervention that may improve patient outcomes and quality of life.

Evidence of Systemic Absorption of Enteral Budesonide in Patients with Fontan-Associated Protein-Losing Enteropathy.

To evaluate for evidence of systemic glucocorticoid absorption in cases of Fontan-associated protein-losing enteropathy (PLE) treated with enteral budesonide, we reviewed the charts of 27 patients with Fontan-associated PLE followed at Children's Hospital Colorado from 2005 to 2018. Cases were excluded for lack of budesonide thserapy or a treatment duration of less than 6 months. Charts were examined by two endocrinologists for review of prior biochemical endocrine evaluations, alterations in linear growth, and physical exam findings consistent with steroid excess. Twelve patients met inclusion criteria. Eight had prior documented cortisol screening. Three patients were tested while on treatment with a median fasting AM cortisol of 0.9 mcg/dL; two of these had a concomitantly measured ACTH, both below the detectable limit. Five patients were tested while weaning or having discontinued budesonide, with a median fasting AM cortisol of 9.1 mcg/dL. Eleven patients had decreases in height velocity associated with starting budesonide. Six patients had documentation of cushingoid features by an endocrinologist. In this cohort of children treated with budesonide for PLE following Fontan, clinical signs of systemic glucocorticoid absorption were frequent. Cortisol secretion was suppressed while on therapy, with adrenal recovery noted once budesonide was discontinued. Growth failure and cushingoid features were common findings. While these findings should be confirmed in larger cohorts, we recommend that the evaluation for systemic absorption of exogenous steroids be considered in patients treated with long-term enteral budesonide given the potential risk for adrenal crisis in times of physiologic stressors.

Exercise Performance at Increased Altitude After Fontan Operation: Comparison to Normal Controls and Correlation with Cavopulmonary Hemodynamics.

Exercise performance declines as patients who have undergone Fontan operation enter adolescence. However, the effect of altitude on functional capacity after Fontan remains inadequately studied. Our aim was to describe exercise performance in a cohort of patients with Fontan physiology living at increased altitude and compare to a normal control group and relate these data to invasively derived hemodynamics. We hypothesized that peak oxygen consumption ([Formula: see text]) would be decreased, in association with elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVRi). Patients were evaluated in a multidisciplinary clinic for patients with Fontan physiology. Evaluation included cardiopulmonary exercise test and cardiac catheterization at predetermined intervals. Descriptive statistics were calculated. Associations of catheterization and exercise testing measures with [Formula: see text] were estimated with Spearman correlation coefficients. One hundred patients with age- and gender-matched controls were included in the analysis. The mean age was 13.3 ± 3.9 years, with mean weight of 47.1 ± 18.4 kg. The mean [Formula: see text] was 29.0 ± 7.8 ml/kg/min, significantly lower than the control group, 40.2 ± 8.4 ml/kg/min (p < 0.0001). There was no statistically significant linear correlation between [Formula: see text] and mPAP or PVRi. We characterized exercise performance in a large cohort with Fontan physiology living at increased altitude and showed a decrease in [Formula: see text] compared to controls. Our data do not support the hypothesis that moderately increased altitude has a detrimental effect on exercise performance, nor is there a substantial link between poor cavopulmonary hemodynamics and exercise in this setting.

The Fontan outcomes network: first steps towards building a lifespan registry for individuals with Fontan circulation in the United States.

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.

Surveillance Testing and Preventive Care After Fontan Operation: A Multi-Institutional Survey.

More children with single ventricle heart disease are surviving after Fontan surgery. This circulation has pervasive effects on multiple organ systems and has unique modes of failure. Many centers have created multidisciplinary programs to care for these patients. Our aim was to survey such programs to better understand current approaches to care. We hypothesized that significant variability in surveillance testing strategy would be present. Eleven academic institutions with established Fontan care programs performing a combined estimated 300 Fontan surgeries per year, with a total population of 1500-2000 Fontan patients, were surveyed using a REDCap survey regarding surveillance testing and basic practice philosophies. Fontan care programs were structured both as consultative services (64%) and as the primary clinical team (9%). Electrocardiograms (73%) and echocardiograms (64%) were most commonly obtained annually. Serum studies, including complete blood count (73%), complete metabolic panel (73%), and Brain-type natriuretic peptide (54%), were most commonly obtained annually. Hepatic testing consisted of liver ultrasound in most centers, obtained biennially (45%) or > every 2 years (45%). Liver biopsy was not routinely recommended (54%). Neurodevelopmental outcomes were assessed at most institutions (54%), with a median frequency of every 3-4 years. There is considerable variability in the surveillance testing regimen and management strategy after a Fontan procedure at surveyed programs. There is an urgent need for surveillance guidelines to reduce variability, define quality metrics, streamline collaborative practice, and prospective research to better understand the complex adaptations of the body to Fontan physiology.

Noninvasive wave intensity analysis predicts functional worsening in children with pulmonary arterial hypertension.

The purpose of the present study was to characterize pulmonary vascular stiffness using wave intensity analysis (WIA) in children with pulmonary arterial hypertension (PAH), compare the WIA indexes with catheterization- and MRI-derived hemodynamics, and assess the prognostic ability of WIA-derived biomarkers to predict the functional worsening. WIA was performed in children with PAH ( n = 40) and healthy control subjects ( n = 15) from phase-contrast MRI-derived flow and area waveforms in the main pulmonary artery (MPA). From comprehensive WIA spectra, we collected and compared with healthy control subjects forward compression waves (FCW), backward compression waves (BCW), forward decompression waves (FDW), and wave propagation speed ( c-MPA). There was no difference in the magnitude of FCW between PAH and control groups (88 vs. 108 mm5·s-1·ml-1, P = 0.239). The magnitude of BCW was increased in patients with PAH (32 vs. 5 mm5·s-1·ml-1, P < 0.001). There was no difference in magnitude of indexed FDW (32 vs. 28 mm5·s-1·ml-1, P = 0.856). c-MPA was increased in patients with PAH (3.2 vs. 1.6 m/s, P < 0.001). BCW and FCW correlated with mean pulmonary arterial pressure, right ventricular volumes, and ejection fraction. Elevated indexed BCW [heart rate (HR) = 2.91, confidence interval (CI): 1.18-7.55, P = 0.019], reduced indexed FDW (HR = 0.34, CI: 0.11-0.90, P = 0.030), and increased c-MPA (HR = 3.67, CI: 1.47-10.20, P = 0.004) were strongly associated with functional worsening of disease severity. Our results suggest that noninvasively derived biomarkers of pulmonary vascular resistance and stiffness may be helpful for determining prognosis and monitoring disease progression in children with PAH. NEW & NOTEWORTHY Wave intensity analysis (WIA) studies are lacking in children with pulmonary arterial hypertension (PAH) partially because WIA, which is necessary to assess vascular stiffness, requires an invasive pressure-derived waveform along with simultaneous flow measurements. We analyzed vascular stiffness using WIA in children with PAH who underwent phase-contrast MRI and observed significant differences in WIA indexes between patients with PAH and control subjects. Furthermore, WIA indexes were predictive of functional worsening and were associated with standard catheterization measures.

Echocardiographic Measurements of Right Ventricular Mechanics in Infants with Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age.

OBJECTIVE: To test the hypothesis that specific echocardiographic measurements of right ventricular (RV) mechanics at 36 weeks postmenstrual age (PMA) are associated with the severity of bronchopulmonary dysplasia (BPD). STUDY DESIGN: A subset of 93 preterm infants (born between 27 and 29 weeks of gestation) was selected retrospectively from a prospectively enrolled cohort. BPD was defined using the National Institutes of Health workshop definition, with modifications for oxygen reduction testing and altitude. The cohort was divided into no-BPD and BPD groups using previously published methodology for analyses. Echocardiographic measurements of RV function (ie, tricuspid annular plane systolic excursion, fractional area of change, systolic-to-diastolic ratio, tissue Doppler myocardial performance index, and RV strain), RV remodeling/morphology (end-systolic left ventricular eccentricity index), and RV afterload (pulmonary artery acceleration time measure) were evaluated at 36 weeks PMA. Multivariable logistic regression determined associations between RV measurements and BPD severity. RESULTS: Compared with the no-BPD cohort, the BPD group had lower birth weight z-scores (P = .04) and trended toward a male predominance (P = .08). After adjusting for birth weight z-score, gestational age, and sex, there were no between-group differences in echocardiographic measurements except for the eccentricity index (scaled OR [0.1-unit increase], 1.49; 95% CI, 1.13-2.12; P = .01). CONCLUSIONS: Among conventional and emerging echocardiographic measurements of RV mechanics, eccentricity index was the sole variable independently associated with BPD severity in this study. The eccentricity index may be a useful echocardiographic measurement for characterizing RV mechanics in patients with BPD at 36 weeks PMA.

Pulmonary Screening in Subjects after the Fontan Procedure.

OBJECTIVES: To review the pulmonary findings of the first 51 patients who presented to our interdisciplinary single-ventricle clinic after undergoing the Fontan procedure. STUDY DESIGN: We performed an Institutional Review Board-approved retrospective review of 51 patients evaluated following the Fontan procedure. Evaluation included history, physical examination, pulmonary function testing, and 6-minute walk. Descriptive statistics were used to describe the population and testing data. RESULTS: Sixty-one percent of the patients had a pulmonary concern raised during the visit. Three patients had plastic bronchitis. Abnormal lung function testing was present in 46% of patients. Two-thirds (66%) of the patients had significant desaturation during the 6-minute walk test. Patients who underwent a fenestrated Fontan procedure and those who underwent unfenestrated Fontan were compared in terms of saturation and 6-minute walk test results. Sleep concerns were present in 45% of the patients. CONCLUSIONS: Pulmonary morbidities are common in patients after Fontan surgery and include plastic bronchitis, abnormal lung function, desaturations with walking, and sleep concerns. Abnormal lung function and obstructive sleep apnea may stress the Fontan circuit and may have implications for cognitive and emotional functioning. A pulmonologist involved in the care of patients after Fontan surgery can assist in screening for comorbidities and recommend interventions.

Application of Principal Component Analysis to Heterogenous Fontan Registry Data Identifies Independent Contributing Factors to Decline.

Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that ultimately requires heart transplant. Our observational cohort study goal was to determine if principal component analysis (PCA) applied to data collected from a substantial Fontan cohort can predict functional decline (N=140). Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO2max), lymphatic biomarkers, and blood biomarkers were collected over 11 years at a single site; in that time, 16 events occurred that are considered here in a composite outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Our main findings suggest that the 6th PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by blood serum biomarkers and superior vena cava flow, is a superior measure of proportional hazard compared to EF, and displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and lymphatic dysfunction (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Our findings support our hypothesis that a multifactorial model must be considered to improve prognosis in the Fontan population.

Supplemental tube feeding does not mitigate weight loss in infants with shunt-dependent single-ventricle physiology.

Infants with shunt-dependent single-ventricle (SV) physiology are at risk for poor weight gain before superior cavopulmonary connection (SCPC). Lower weight-for-age z-score is a risk factor for prolonged length of stay (LOS) after SCPC. We sought to characterize infant growth and feeding and determine the effect of method of feeding on outcomes. Chart review of infants with shunt-dependent SV physiology born between October 2007 and September 2010 was performed. The cohort was divided into three groups based on feeding method at discharge after initial palliation; 53 in the oral feeding (PO) group, 56 in the nasogastric (NG) tube group, and 26 in the gastrostomy tube (GT) group. Birth weight z-score did not differ among groups (p = 0.39), but infants fed by NG or GT were smaller than PO-fed infants at hospital discharge (p = 0.0001), a difference that persisted through SCPC (p < 0.0001). Predictors of need for GT included Norwood procedure (p = 0.008) and longer LOS after initial palliation (p < 0.001). Interstage mortality and age at SCPC did not differ among groups. Risk factors for longer LOS at SCPC included longer LOS and need for supplemental feeds at discharge from initial palliation as well as lower weight at SCPC. Poor growth is common among infants with shunt-dependent SV physiology. Infants who require GT have lower weight-for-age z-scores at hospital discharge and remain smaller at SCPC than those fed PO. Although GT after initial palliation is associated with longer LOS after SCPC, it is not associated with an increase in interstage morbidity or mortality.

Hemi-Fontan and bidirectional Glenn operations result in flow-mediated viscous energy loss at the time of stage II palliation.

Background: Superior cavopulmonary connection (SCPC) for stage II palliation of hypoplastic left heart syndrome (HLHS) is achieved most frequently by either a bidirectional Glenn (BDG) or hemi-Fontan (HF) operation. The comparison of flow hemodynamic efficiency at the region of surgical reconstruction and in proximal pulmonary arteries has been evaluated primarily using computational modeling techniques with conflicting reports. The purpose of this descriptive study was to compare flow hemodynamics following stage II (BDG vs HF) using 4-dimensional flow magnetic resonance imaging (4D-Flow MRI) with particular focus on flow-mediated viscous energy loss (EL') under matched hemodynamic conditions. Methods: Patients with hypoplastic left heart syndrome (HLHS) who underwent either HF or BDG as part of stage II palliation underwent pre-Fontan 4D-Flow MRI. Patients were matched by the pulmonary vascular resistance index, net superior vena cava (SVC) flow, right pulmonary artery (RPA) and left pulmonary artery (LPA) size, and age. Maximum EL' throughout the cardiac cycle was calculated along the SVC-RPA and SVC-LPA tracts. Results: Eight patients who underwent HF as part of their stage II single ventricle palliation were matched with 8 patients who underwent BDG. There were no differences between the 2 groups in median volumetric indices, including end-diastolic volume (P = .278) and end-systolic volume (P = .213). Moreover, no differences were observed in ejection fraction (P = .091) and cardiac index (P = .324). There also were no differences in peak EL' measured along the SVC-RPA tract (median, 0.05 mW for HF vs 0.04 mW for BDG; P = .365) or along the SVC-LPA tract (median, 0.05 mW vs 0.04 mW; P = .741). Conclusions: The second stage of surgical palliation of HLHS using either HF or BDG results in similar flow-mediated viscous energy loss throughout the SCPC junction. 4D-Flow MRI and computational methods should be applied together to investigate flow hemodynamic patterns throughout the Fontan palliation and overall efficiency of the Fontan circuit.

Myocardial strain-curve deformation patterns after Fontan operation.

Myocardial deformation analysis by cardiac MRI (CMR) yielding global circumferential and longitudinal strain (GCS and GLS) is an increasingly utilized method to accurately quantify systolic function and predict clinical events in patients with Fontan circulation. The purpose of this study was to use principal component analysis (PCA) to investigate myocardial temporal deformation patterns derived from strain-time curves to learn about latent strain features beyond peak values. We conducted the study with specific attention to dominant single left or right ventricle (SLV and SRV) morphologies. Methods and Results: Patients remote from Fontan operation who underwent follow-up CMR were analyzed for standard volumetric and function hemodynamics including myocardial deformation parameters including GCS and GLS. We applied PCA to investigate in an unbiased fashion the strain-time curve morphology and to calculate patient specific shape scores. All variables were subjected to single variable Cox regression analysis to detect composite clinical outcome including death, heart transplant, protein losing enteropathy and plastic bronchitis. A total of 122 patients, (SLV = 67, SRV = 55) with a mean age of 12.7 years underwent comprehensive CMR analysis. The PCA revealed 3 primary modes of strain-curve variation regardless of single ventricle morphology and type of strain investigated. Principle components (PCs) described changes in (1) strain-time curve amplitude, (2) time-to-peak strain, and (3) post-systolic slope of the strain-time curve. Considering only SLV patients, GCS was only CMR variable predictive of clinical events (HR 1.46, p = 0.020). In the SRV group, significant CMR predictors of clinical events were derived indexed end-diastolic (HR 1.02, p = 0.023) and end-systolic (HR 1.03, p = 0.022) volumes, GCS (HR 1.91, p = 0.003) and its related first component score (HR 1.20, p = 0.005), GLS (HR 1.32, p = 0.029) and its third component score (HR 1.58, p = 0.017). CMR derived global strain measures are sensitive markers of clinical outcomes in patients with Fontan circulation, particularly in patients with the SRV morphology. Myocardial strain-time curve morphology specific to SLV and SRV patients inspired by unbiased PCA technique can further aid with predicting clinical outcomes.

Predicting Hemodynamic Performance of Fontan Operation for Glenn Physiology using Computational Fluid Dynamics: Ten Patient-specific Cases.

Single ventricle hearts have only one ventricle that can pump blood effectively and the treatment requires three stages of operations to reconfigure the heart and circulatory system. At the second stage, Glenn procedure is performed to connect superior vena cava (SVC) to the pulmonary arteries (PA). For the third and most complex operation, called Fontan, an extracardiac conduit is used to connect inferior vena cava (IVC) to the PL and thereafter no deoxygenated blood goes to the heart. Predicting Hemodynamic Performance of Fontan Operation using computational fluid dynamics (CFD) is hypothesized to improve outcomes and optimize this treatment planning in children with single-ventricle heart disease. An important reason for this surgical planning is to reduce the development of pulmonary arteriovenous malformations (PAVM) and the need to perform Fontan revisions. The purpose of this study was to develop amodel for Fontan surgical planning and use this model to compare blood circulation in two designed graft types of Fontan operation known as T-shape and Y-graft. The functionality of grafts was compared in terms of power loss (PL) and hepatic flow distribution (HFD), a known factor in PAVM development. To perform this study, ten single-ventricle children with Glenn physiology were included and a CFD model was developed to estimate the blood flow circulation to the left and right pulmonary arteries. The estimated blood flow by CFD was compared with that measured by cardiovascular magnetic resonance. Results showed that there was an excellent agreement between the net blood flow in the right and left pulmonary arteries computed by CFD and CMR (ICC= 0.98, P-value ≥0.21). After validating the accuracy of each CFD model, Fontan operations using T-shape and Y-graft conduits were performed in silico for each patient and the developed CFD model was used to predict the post-surgical PL and HFD. We found that the PL in the Y-graft was significantly lower than in the T-shape (P-value ≤0.001) and HFD was significantly better balanced in Y-graft compared to the T-shape (P-value=0.004).

Multi-Disciplinary Management and Surgical Resection of Intracardiac Fibromas Causing Bilateral Ventricular Outflow Tract Obstructions in an Infant.

Cardiac tumors remain rare in children with benign pathologies predominating. Indications for surgical management often result from compromised ventricular chamber size, biventricular outflow tract obstruction, impaired ventricular function, or the presence of medically refractory dysrhythmias. We present a case of a six-month-old infant with two intracardiac fibromas originating in the interventricular septum. The fibromas were causing significant biventricular outflow obstruction. The patient successfully underwent tumor resection on cardiopulmonary bypass The literature on pediatric cardiac tumors is reviewed. Multi-disciplinary medical planning is necessary for successful anesthetic and surgical treatment of this high-risk patient population.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. RESULTS: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (P=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity). CONCLUSIONS: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.