Altered contractility, Ca2+ transients, and cell morphology seen in a patient-specific iPSC-CM model of Ebstein's anomaly with left ventricular noncompaction.

Patients with two congenital heart diseases (CHDs), Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The genetic etiology and pathogenesis of combined EA/LVNC remain largely unknown. We investigated a familial EA/LVNC case associated with a variant (p.R237C) in the gene encoding Kelch-like protein 26 (KLHL26) by differentiating induced pluripotent stem cells (iPSCs) generated from affected and unaffected family members into cardiomyocytes (iPSC-CMs) and assessing iPSC-CM morphology, function, gene expression, and protein abundance. Compared with unaffected iPSC-CMs, CMs containing the KLHL26 (p.R237C) variant exhibited aberrant morphology including distended endo(sarco)plasmic reticulum (ER/SR) and dysmorphic mitochondria and aberrant function that included decreased contractions per minute, altered calcium transients, and increased proliferation. Pathway enrichment analyses based on RNASeq data indicated that the "structural constituent of muscle" pathway was suppressed, whereas the "ER lumen" pathway was activated. Taken together, these findings suggest that iPSC-CMs containing this KLHL26 (p.R237C) variant develop dysregulated ER/SR, calcium signaling, contractility, and proliferation.NEW & NOTEWORTHY We demonstrate here that iPSCs derived from patients with Ebstein's anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural and functional changes that offer insight into disease pathogenesis, including altered ER/SR and mitochondrial morphology, contractility, and calcium signaling.

Impact of Reintervention During Stage 1 Palliation Hospitalization: A National, Multicenter Study.

BACKGROUND: Stage 1 palliation (S1P) for hypoplastic left heart syndrome remains associated with high morbidity and mortality. Previous studies on burden of reinterventions did not include patients who remain hospitalized before stage 2 palliation (S2P). This study described the rate of reintervention during S1P hospitalization and sought to determine the impact of reintervention on outcomes. METHODS: All participants enrolled in phase II of the National Pediatric Cardiology Quality Improvement Collaborative after S1P were included in this study. The primary outcome was the rate of reintervention during hospitalization after S1P and before hospital discharge or S2P. Reintervention was defined as 1 or more unplanned interventional cardiac catheterizations or surgical reoperations. RESULTS: Between March 1, 2016 and October 1, 2019, 1367 participants underwent S1P and 339 (24.8%) had a reintervention; most commonly to address the source of pulmonary blood flow. Gestational age, weight at S1P, atrioventricular septal defect, heterotaxy, preoperative pulmonary artery bands, hybrid S1P, and an additional bypass run or early extracorporeal membrane oxygenation were significantly associated with reintervention. Participants in the reintervention group experienced higher rates of nearly all postoperative complications, were less likely to be discharged before S2P (57.1% vs 86%; P < .001), and more likely to experience in-hospital mortality (17% vs 5%; P < .001). CONCLUSIONS: Unplanned reintervention during hospitalization after S1P palliation occurred in 25% of participants in a large, registry-based national cohort. Participants who underwent reintervention were more likely to remain as inpatient and were less likely to survive to S2P. Reintervention was associated with a multitude of postoperative complications that affect survival and long-term outcome.

A Systematic Review of Ebstein's Anomaly with Left Ventricular Noncompaction.

Traditional definitions of Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), two rare congenital heart defects (CHDs), confine disease to either the right or left heart, respectively. Around 15-29% of patients with EA, which has a prevalence of 1 in 20,000 live births, commonly manifest with LVNC. While individual EA or LVNC literature is extensive, relatively little discussion is devoted to the joint appearance of EA and LVNC (EA/LVNC), which poses a higher risk of poor clinical outcomes. We queried PubMed, Medline, and Web of Science for all peer-reviewed publications from inception to February 2022 that discuss EA/LVNC and found 58 unique articles written in English. Here, we summarize and extrapolate commonalities in clinical and genetic understanding of EA/LVNC to date. We additionally postulate involvement of shared developmental pathways that may lead to this combined disease. Anatomical variation in EA/LVNC encompasses characteristics of both CHDs, including tricuspid valve displacement, right heart dilatation, and left ventricular trabeculation, and dictates clinical presentation in both age and severity. Disease treatment is non-specific, ranging from symptomatic management to invasive surgery. Apart from a few variant associations, mainly in sarcomeric genes MYH7 and TPM1, the genetic etiology and pathogenesis of EA/LVNC remain largely unknown.

Increases in oxygen saturation following discharge from Fontan palliation - an indicator of resolution of pulmonary arteriovenous malformations?

BACKGROUND: Pulmonary arteriovenous malformations in single ventricle congenital heart disease are poorly understood. Previous studies investigating pulmonary arteriovenous malformations predominantly focus on patients with heterotaxy syndrome and interrupted inferior caval vein. It is unknown if development and resolution of pulmonary arteriovenous malformations are similar for patients with and without heterotaxy syndrome. METHODS: In this retrospective single-institution study, we identified patients with a history of single ventricle congenital heart disease and Fontan palliation. We then matched patients with heterotaxy syndrome (intact and interrupted inferior caval vein) and non-heterotaxy hypoplastic left heart syndrome. To compare development of pulmonary arteriovenous malformations, we identified the frequency of positive diagnoses pre-Fontan. To compare resolution of pulmonary arteriovenous malformations, we recorded oxygen saturation changes for 12 months following Fontan. RESULTS: A total of 124 patients were included. Patients with heterotaxy and interrupted inferior caval vein were more likely to have a pre-Fontan contrast echocardiogram performed (p < 0.01) and more likely to be diagnosed with pulmonary arteriovenous malformations pre-Fontan (p < 0.01). There was no difference in oxygen saturation prior to Fontan, yet all patient groups had increased their oxygen saturations in the first year after Fontan discharge. CONCLUSIONS: Pulmonary arteriovenous malformations are variably diagnosed prior to Fontan palliation; however, all study groups had increased oxygen saturations after Fontan discharge, potentially indicating resolution of pulmonary arteriovenous malformations in all groups. The prevalence of pulmonary arteriovenous malformations pre-Fontan is likely underestimated. A quantitative, systematic approach to diagnosis and follow-up of pulmonary arteriovenous malformations is needed to better understand susceptibility and pathophysiology.

Pediatric Heart Network Echocardiographic Z Scores: Comparison with Other Published Models.

BACKGROUND: Different methods have resulted in variable Z scores for echocardiographic measurements. Using the measurements from 3,215 healthy North American children in the Pediatric Heart Network (PHN) echocardiographic Z score database, the authors compared the PHN model with previously published Z score models. METHODS: Z scores were derived for cardiovascular measurements using four models (PHN, Boston, Italy, and Detroit). Model comparisons were performed by evaluating (1) overlaid graphs of measurement versus body surface area with curves at Z = -2, 0, and +2; (2) scatterplots of PHN versus other Z scores with correlation coefficients; (3) Bland-Altman plots of PHN versus other Z scores; and (4) comparison of median Z scores for each model. RESULTS: For most measurements, PHN Z score curves were similar to Boston and Italian curves but diverged from Detroit curves at high body surface areas. Correlation coefficients were high when comparing the PHN model with the others, highest with Boston (mean, 0.99) and lowest with Detroit (mean, 0.90). Scatterplots suggested systematic differences despite high correlations. Bland-Altman plots also revealed poor agreement at both extremes of size and a systematic bias for most when comparing PHN against Italian and Detroit Z scores. There were statistically significant differences when comparing median Z scores between the PHN and other models. CONCLUSIONS: Z scores from the multicenter PHN model correlated well with previous single-center models, especially the Boston model, which also had a large sample size and similar methodology. The Detroit Z scores diverged from the PHN Z scores at high body surface area, possibly because there were more subjects in this category in the PHN database. Despite excellent correlation, significant differences in Z scores between the PHN model and others were seen for many measurements. This is important when comparing publications using different models and for clinical care, particularly when Z score thresholds are used to guide diagnosis and management.

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.

Novel KLHL26 variant associated with a familial case of Ebstein's anomaly and left ventricular noncompaction.

BACKGROUND: Ebstein's anomaly (EA) is a rare congenital heart disease of the tricuspid valve and right ventricle. Patients with EA often manifest with left ventricular noncompaction (LVNC), a cardiomyopathy. Despite implication of cardiac sarcomere genes in some cases, very little is understood regarding the genetic etiology of EA/LVNC. Our study describes a multigenerational family with at least 10 of 17 members affected by EA/LVNC. METHODS: We performed echocardiography on all family members and conducted exome sequencing of six individuals. After identifying candidate variants using two different bioinformatic strategies, we confirmed segregation with phenotype using Sanger sequencing. We investigated structural implications of candidate variants using protein prediction models. RESULTS: Exome sequencing analysis of four affected and two unaffected members identified a novel, rare, and damaging coding variant in the Kelch-like family member 26 (KLHL26) gene located on chromosome 19 at position 237 of the protein (GRCh37). This variant region was confirmed by Sanger sequencing in the remaining family members. KLHL26 (c.709C > T p.R237C) segregates only with EA/LVNC-affected individuals (FBAT p < .05). Investigating structural implications of the candidate variant using protein prediction models suggested that the KLHL26 variant disrupts electrostatic interactions when binding to part of the ubiquitin proteasome, specifically Cullin3 (CUL3), a component of E3 ubiquitin ligase. CONCLUSION: In this familial case of EA/LVNC, we have identified a candidate gene variant, KLHL26 (p.R237C), which may have an important role in ubiquitin-mediated protein degradation during cardiac development.

Survival After Norwood Procedure in High-Risk Patients.

BACKGROUND: Multiple single-ventricle populations are noted to be at increased risk for mortality after the Norwood procedure. Preoperative risk factors include low birth weight, restrictive/intact atrial septum, obstructed pulmonary veins, ventricular dysfunction, and atrioventricular valve regurgitation. We report outcomes of the Norwood procedure in standard- and high-risk patients in the recent era. METHODS: All patients born with hypoplastic left heart syndrome between 2006 and 2016 who underwent a Norwood procedure at our institution were included. Patient data were retrospectively reviewed, and Kaplan-Meier analysis was used to evaluate survival between groups. RESULTS: The cohort included 177 patients. Fifty patients were determined high-risk preoperatively: low birth weight (n = 18), ventricular dysfunction/atrioventricular valve regurgitation (n = 13), intact or restrictive atrial septum/obstructed anomalous pulmonary venous return (n = 14), and multiple factors (n = 5). There were 2 (1.6%) deaths before Glenn in the standard-risk group, with a total of 10 (20%) from the high-risk groups (P < .0001). Survival at 1 year differed greatly between groups, with highest being standard risk at 89% and lowest in the intact septum/obstructed veins group at 54%. The difference between groups in long-term survival was significant (P < .001). CONCLUSIONS: Outcomes after the Norwood procedure have improved for standard-risk patients. Those with preoperative risk factors account for most of the early deaths after the Norwood procedure. This high-risk status does not resolve after Glenn, because longer-term survival continues to diverge from the standard-risk group.

Ventricular Fibrillation and Myocardial Depression Following Pulmonary Valve Replacement in Tetralogy of Fallot With an Intramural Coronary Artery and Coronary Artery Compression by Chest Tube.

We describe the case of a 10-year-old male with a history of repaired Tetralogy of Fallot and known intramural right coronary artery (RCA) who presented for bioprosthetic pulmonary valve replacement. The operation was complicated by postoperative ventricular fibrillation arrest. Selective coronary angiography revealed external compression of the mid-RCA by a mediastinal chest tube that improved immediately upon removal of the tube. Ultimately, the patient required additional unroofing of the intramural coronary for full recovery. This case highlights the need to thoroughly investigate malignant ventricular dysrhythmias following pediatric cardiac surgery and to rule out coronary insufficiency, which may be due to both extrinsic and/or intrinsic lesions.

Challenges With Left Ventricular Functional Parameters: The Pediatric Heart Network Normal Echocardiogram Database.

BACKGROUND: The reliability of left ventricular (LV) systolic functional indices calculated from blinded echocardiographic measurements of LV size has not been tested in a large cohort of healthy children. The objective of this study was to estimate interobserver variability in standard measurements of LV size and systolic function in children with normal cardiac anatomy and qualitatively normal function. METHODS: The Pediatric Heart Network Normal Echocardiogram Database collected normal echocardiograms from healthy children ≤18 years old distributed equally by age, gender, and race. A core lab used two-dimensional echocardiograms to measure LV dimensions from which a separate data coordinating center calculated LV volumes and systolic functional indices. To evaluate interobserver variability, two independent expert pediatric echocardiographic observers remeasured LV dimensions on a subset of studies, while blinded to calculated volumes and functional indices. RESULTS: Of 3,215 subjects with measurable images, 552 (17%) had a calculated LV shortening fraction (SF) < 25% and/or LV ejection fraction (EF) < 50%; the subjects were significantly younger and smaller than those with normal values. When the core lab and independent observer measurements were compared, individual LV size parameter intraclass correlation coefficients were high (0.81-0.99), indicating high reproducibility. The intraclass correlation coefficients were lower for SF (0.24) and EF (0.56). Comparing reviewers, 40/56 (71%) of those with an abnormal SF and 36/104 (35%) of those with a normal SF based on core lab measurements were calculated as abnormal from at least one independent observer. In contrast, an abnormal EF was less commonly calculated from the independent observers' repeat measures; only 9/47 (19%) of those with an abnormal EF and 8/113 (7%) of those with a normal EF based on core lab measurements were calculated as abnormal by at least one independent observer. CONCLUSIONS: Although blinded measurements of LV size show good reproducibility in healthy children, subsequently calculated LV functional indices reveal significant variability despite qualitatively normal systolic function. This suggests that, in clinical practice, abnormal SF/EF values may result in repeat measures of LV size to match the subjective assessment of function. Abnormal LV functional indices were more prevalent in younger, smaller children.

Surgical unroofing of intramural anomalous aortic origin of a coronary artery in pediatric patients: Single-center perspective.

BACKGROUND: Intramural anomalous aortic origin of a coronary artery (AAOCA) is associated with an increased risk of sudden cardiac death. This is amenable to surgical coronary unroofing, but outcomes studies are lacking. OBJECTIVE: To perform a comprehensive review of our institutional experience with pediatric patients with AAOCA who underwent surgical repair with unroofing of the intramural segment, focusing on preoperative and postoperative course and testing as well as intraoperative findings. METHODS: A retrospective cohort study was conducted to evaluate patients with AAOCA status post-coronary unroofing at Children's Hospital of Wisconsin. Data extraction included symptoms, preoperative and postoperative imaging and testing, surgical findings, and postoperative clinical course. RESULTS: From January 1999 to December 12, 2015, 63 patients underwent unroofing at a median age of 13 years (0.5-18 years). The majority underwent unroofing of an intramural right coronary (79%); 21% had an intramural left AAOCA. Symptoms suggestive of possible ischemia were present in about 50%. Additional structural cardiac anomalies were present in 33%. Transthoracic echocardiography was diagnostic in 60 of 63 (95%) and correlated with surgical findings in all cases. There was no surgical mortality associated with the unroofing, and no additional coronary reinterventions were performed. The median duration of postoperative follow-up was 3.1 years (7 days to 13.6 years). Symptoms either persisted or developed in 46% postoperatively. Postoperative exercise stress testing, stress echocardiography, and cardiac magnetic resonance imaging were performed in 76%, 8%, and 20%, respectively, of the cohort. None identified findings consistent with reversible coronary ischemia. Three patients had sudden cardiac arrest (1 death) after surgery without an identified residual coronary abnormality. CONCLUSIONS: Transthoracic echocardiography, with carefully designed coronary imaging protocols, can be diagnostic in accurately identifying intramural AAOCA in pediatric patients. Unroofing can be performed safely with no early morbidity, but symptoms can persist (including rare life-threatening events) without evidence of ischemia by postoperative provocative testing.

Transplacental treatment of fetal tachycardia: A systematic review and meta-analysis.

OBJECTIVE: Multiple transplacental medications can be used to treat fetal tachycardia. We sought to perform a systematic review and meta-analysis to determine whether digoxin, flecainide, or sotalol was the most efficacious therapy for converting fetal tachycardia to sinus rhythm. METHOD: We performed a systematic review and meta-analysis to compare digoxin, flecainide, or sotalol as first-line therapy for fetal tachycardia. Studies were identified by a search of PubMed (Medline), Web of Science, and Scopus. RESULTS: There were 21 studies included. Flecainide (OR: 1.4, 95% CI: 1.1-2.0, I2  = 60%, P = 0.03) and sotalol (OR:1.4, 95% CI:1.1-2.0, I2  = 30%, P = 0.02) were superior to digoxin for conversion of fetal tachycardia to sinus rhythm. In those with hydrops, the benefit over digoxin was more notable for both flecainide (OR: 5.0, 95% CI: 2.5-10.0, I2  = 0%, P < 0.001) and sotalol (OR: 2.5, 95% CI: 1.7-5.0, I2  = 0%, P < 0.001). When limited to atrioventricular reentrant tachycardia, flecainide was superior to digoxin (OR:1.7, 95% CI:1.1-3.3, I2  = 62%, P = 0.03) and sotalol (OR:1.3, 95% CI:1.1-1.7, I2  = 0%, P = 0.01). CONCLUSION: Digoxin should not be first-line therapy for fetal tachycardia, particularly in the presence of hydrops fetalis. Flecainide should be the first-line therapy of choice in atrioventricular reentrant tachycardia. Further study may identify further sub-populations responding differently.

Echocardiographic Diagnosis, Surgical Treatment, and Outcomes of Anomalous Left Coronary Artery from the Pulmonary Artery.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare condition that can be difficult to diagnose by echocardiography alone. The purpose of this study was to describe the clinical and echocardiographic presentation of ALCAPA, create a set of critical echocardiographic diagnostic criteria, and report outcomes. METHODS: A retrospective review was conducted of all patients diagnosed with isolated ALCAPA at two major cardiac centers between 1990 and 2015. RESULTS: Of the 37 patients identified, only 54% presented in infancy. The anomalous coronary artery (CA) origin was clearly imaged in only 54% of echocardiographic examinations. However, other consistently identified echocardiographic markers were found, including left CA flow reversal (91%), collateral CA flow (85%), right CA dilation (81%), abnormal pulmonary artery flow (79%), mitral regurgitation (74%), left ventricular dysfunction (66%) and endocardial fibroelastosis (57%). Presenting echocardiograms had five of seven markers in 85% of patients. Left ventricular dysfunction was the most common marker in infants (89% vs 38%, P = .005); older children were more likely to have collateral formation visualized by color Doppler (100% vs 75%, P = .04). Following surgery, there were no early surgical deaths. The median follow-up duration was 10.3 years. At last follow-up, 92% had normal left ventricular function, 3% had moderate or worse mitral regurgitation, and 17% had required reintervention. CONCLUSIONS: Echocardiographic markers can reliably identify ALCAPA; these markers vary with the age of presentation. Surgical outcomes are excellent, and most patients will recover left ventricular and mitral valve function.

Translating clinical trials into clinical practice: a survey assessing the potential impact of the Pediatric Heart Network Infant Single Ventricle Trial.

BACKGROUND: A few studies have evaluated the impact of clinical trial results on practice in paediatric cardiology. The Infant Single Ventricle (ISV) Trial results published in 2010 did not support routine use of the angiotensin-converting enzyme inhibitor enalapril in infants with single-ventricle physiology. We sought to assess the influence of these findings on clinical practice. METHODS: A web-based survey was distributed via e-mail to over 2000 paediatric cardiologists, intensivists, cardiothoracic surgeons, and cardiac advance practice nurses during three distribution periods. The results were analysed using McNemar's test for paired data and Fisher's exact test. RESULTS: The response rate was 31.5% (69% cardiologists and 65% with >10 years of experience). Among respondents familiar with trial results, 74% reported current practice consistent with trial findings versus 48% before trial publication (p<0.001); 19% used angiotensin-converting enzyme inhibitor in this population "almost always" versus 36% in the past (p<0.001), and 72% reported a change in management or improved confidence in treatment decisions involving this therapy based on the trial results. Respondents familiar with trial results (78%) were marginally more likely to practise consistent with the trial results than those unfamiliar (74 versus 67%, p=0.16). Among all respondents, 28% reported less frequent use of angiotensin-converting enzyme inhibitor over the last 3 years. CONCLUSIONS: Within 5 years of publication, the majority of respondents was familiar with the Infant Single Ventricle Trial results and reported less frequent use of angiotensin-converting enzyme inhibitor in single-ventricle infants; however, 28% reported not adjusting their clinical decisions based on the trial's findings.

Associations Between Day of Admission and Day of Surgery on Outcome and Resource Utilization in Infants With Hypoplastic Left Heart Syndrome Who Underwent Stage I Palliation (from the Single Ventricle Reconstruction Trial).

Newborns with hypoplastic left heart syndrome and other single right ventricular variants require substantial health care resources. Weekend acute care has been associated with worse outcomes and increased resource use in other populations but has not been studied in patients with single ventricle. Subjects of the Single Ventricle Reconstruction trial were classified by whether they had a weekend admission and by day of the week of Norwood procedure. The primary outcome was hospital length of stay (LOS); secondary outcomes included transplant-free survival, intensive care unit (ICU) LOS, and days of mechanical ventilation. The Student's t test with log transformation and the Wilcoxon rank-sum test were used to analyze associations. Admission day was categorized for 533 of 549 subjects (13% weekend). The day of the Norwood was Thursday/Friday in 39%. There was no difference in median hospital LOS, transplant-free survival, ICU LOS, or days ventilated for weekend versus non-weekend admissions. Day of the Norwood procedure was not associated with a difference in hospital LOS, transplant-free survival, ICU LOS, or days ventilated. Prenatally diagnosed infants born on the weekend had lower mean birth weight, younger gestational age, and were more likely to be intubated but did not have a difference in measured outcomes. In conclusion, in this cohort of patients with single right ventricle, neither weekend admission nor end-of-the-week Norwood procedure was associated with increased use of hospital resources or poorer outcomes. We speculate that the complex postoperative course following the Norwood procedure outweighs any impact that day of admission or operation may have on these outcomes.

Challenges and controversies in fetal diagnosis and treatment: hypoplastic left heart syndrome.

Today, almost 70% of babies with hypoplastic left heart syndrome (HLHS) will survive into adulthood, although significant long-term morbidity and mortality still exists. Prenatal diagnosis of HLHS is increasingly common, allowing improved counseling, and the potential for fetal intervention if indicated. Exciting progress continues to be made in the area of fetal diagnosis and intervention, specifically catheter intervention for intact atrial septum or severe aortic stenosis. Pediatric cardiologists should be keenly aware of the flaws of staged palliation for the treatment of HLHS, and need to keep abreast of the emerging data regarding fetal diagnosis and intervention.

Effect of feeding modality on interstage growth after stage I palliation: a report from the National Pediatric Cardiology Quality Improvement Collaborative.

OBJECTIVES: Achieving adequate growth after stage 1 palliation for children with single-ventricle heart defects often requires supplemental nutrition through enteral tubes. Significant practice variability exists between centers in the choice of feeding tube. The impact of feeding modality on the growth of patients with a single ventricle after stage 1 palliation was examined using the multiinstitutional National Pediatric Cardiology Quality Improvement Collaborative data registry. METHODS: Characteristics of patients were compared by feeding modality, defined as oral only, nasogastric tube only, oral and nasogastric tube, gastrostomy tube only, and oral and gastrostomy tube. The impact of feeding modality on change in weight for age z-score during the interstage period, from stage 1 palliation discharge to stage 2 palliation, was evaluated by multivariable linear regression, adjusting for important patient characteristics and postoperative morbidities. RESULTS: In this cohort of 465 patients, all groups demonstrated improved weight for age z-score during the interstage period with a mean increase of 0.3±0.8. In multivariable analysis, feeding modality was not associated with differences in the change in weight for age z-score during the interstage period (P=.72). Risk factors for poor growth were a diagnosis of hypoplastic left heart syndrome (P=.003), vocal cord injury (P=.007), and lower target caloric goal at discharge (P=.001). CONCLUSIONS: In this large multicenter cohort, interstage growth improved for all groups and did not differ by feeding modality. With appropriate caloric goals and interstage monitoring, adequate growth may be achieved regardless of feeding modality and therefore local comfort and complication risk should dictate feeding modality.