Retrospective Cohort Study of Additional Procedures and Transplant-Free Survival for Patients With Functionally Single Ventricle Disease Undergoing Staged Palliation in England and Wales.

BACKGROUND: Reinterventions may influence the outcomes of children with functionally single-ventricle (f-SV) congenital heart disease. METHODS AND RESULTS: We undertook a retrospective cohort study of children starting treatment for f-SV between 2000 and 2018 in England, using the national procedure registry. Patients were categorized based on whether they survived free of transplant beyond 1 year of age. Among patients who had transplant-free survival beyond 1 year of age, we explored the relationship between reinterventions in infancy and the outcomes of survival and Fontan completion, adjusting for complexity. Of 3307 patients with f-SV, 909 (27.5%), had no follow-up beyond 1 year of age, among whom 323 (35.3%) had ≥1 reinterventions in infancy. A total of 2398 (72.5%) patients with f-SV had transplant-free survival beyond 1 year of age, among whom 756 (31.5%) had ≥1 reinterventions in infancy. The 5-year transplant-free survival and cumulative incidence of Fontan, among those who survived infancy, were 93.4% (95% CI, 92.4%-94.4%) and 79.3% (95% CI, 77.4%-81.2%), respectively. Both survival and Fontan completion were similar for those with a single reintervention and those who had no reinterventions. Patients who had >1 additional surgery (adjusted hazard ratio, 3.93 [95% CI, 1.87-8.27] P<0.001) had higher adjusted risk of mortality. Patients who had >1 additional interventional catheter (adjusted subdistribution hazard ratio, 0.71 [95% CI, 0.52-0.96] P=0.03) had a lower likelihood of achieving Fontan. CONCLUSIONS: Among children with f-SV, the occurrence of >1 reintervention in the first year of life, especially surgical reinterventions, was associated with poorer prognosis later in childhood.

Textbook Outcome for Superior Cavopulmonary Connection: A Metric for Single Ventricle Heart Surgery.

Background: To develop a more holistic measure of congenital heart center performance beyond mortality, we created a composite "textbook outcome" (TO) for the Glenn operation. We hypothesized that meeting TO would have a positive prognostic and financial impact. Methods: This was a single center retrospective study of patients undergoing superior cavopulmonary connection (bidirectional Glenn or Kawashima ± concomitant procedures) from 2005 to 2021. Textbook outcome was defined as freedom from operative mortality, reintervention, 30-day readmission, extracorporeal membrane oxygenation, major thrombotic complication, length of stay (LOS) >75th percentile (17d), and mechanical ventilation duration >75th percentile (2d). Multivariable logistic regression and Cox proportional hazards modeling were used. Results: Fifty-one percent (137/269) of patients met TO. Common reasons for TO failure were prolonged LOS (78/132, 59%) and ventilator duration (67/132, 51%). In multivariable analysis, higher weight [odds ratio, OR: 1.44 (95% confidence interval, CI: 1.15-1.84), P = .002] was a positive predictor of TO achievement while right ventricular dominance [OR 0.47 (0.27-0.81), P = .007] and higher preoperative pulmonary vascular resistance [OR 0.58 (0.40-0.82), P = .003] were negative predictors. After controlling for preoperative factors and excluding operative mortalities, TO achievement was independently associated with a decreased risk of death over long-term follow-up [hazard ratio: 0.50 (0.25-0.99), P = .049]. Textbook outcome achievement was also associated with lower direct cost of care [$137,626 (59,333-167,523) vs $262,299 (114,200-358,844), P < .0001]. Conclusion: Achievement of the Glenn TO is associated with long-term survival and lower costs and can be predicted by certain risk factors. As outcomes continue to improve within congenital heart surgery, operative mortality will become a less informative metric. Textbook outcome analysis may represent a more balanced measure of a successful outcome.

Long-term outcomes of atrioventricular septal defect and single ventricle: A multicenter study.

OBJECTIVE: The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. METHODS: Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. RESULTS: Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. CONCLUSIONS: The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired.

The impact of additional antegrade pulmonary blood flow at bidirectional Glenn shunt on long-term outcomes.

OBJECTIVES: We investigated the impact of additional antegrade pulmonary blood flow on the long-term outcomes after bidirectional Glenn shunt. METHODS: From 2001 to 2015, 279 patients underwent bidirectional Glenn shunt as an interim palliation for a functionally single ventricle. After excluding patients with a previous Kawashima or Norwood operation, 202 patients with preexisting antegrade pulmonary blood flow before bidirectional Glenn shunt were included in this study. Antegrade pulmonary blood flow was eliminated in 110 patients (no antegrade pulmonary blood flow group) and maintained in 92 patients (antegrade pulmonary blood flow group). The impact of antegrade pulmonary blood flow at bidirectional Glenn shunt on long-term outcome was analyzed using inverse probability of treatment weighting. RESULTS: Median age and body weight at bidirectional Glenn shunt were 8 months and 7.8 kg, respectively. Prolonged chest tube drainage or readmission for effusion after bidirectional Glenn shunt was more frequent in the antegrade pulmonary blood flow group (odds ratio, 3.067; 95% confidence interval, 1.036-9.073; P = .043). In the no antegrade pulmonary blood flow group, B-type natriuretic peptide level was decreased further until the Fontan operation (P = .012). In the no antegrade pulmonary blood flow group, oxygen saturation was lower just after bidirectional Glenn shunt, although it was increased further until Fontan operation (P < .001), despite still lower oxygen saturation before Fontan operation compared with antegrade pulmonary blood flow group (P < .001). The McGoon ratio was decreased in both groups without intergroup difference, although the McGoon ratio before Fontan operation was higher in the antegrade pulmonary blood flow group (2.3 ± 0.4 vs 2.1 ± 0.4, P = .008). Overall transplant-free survival was worse in the antegrade pulmonary blood flow group (hazard ratio, 2.37; confidence interval, 1.089-5.152; P = .030). CONCLUSIONS: Maintaining antegrade pulmonary blood flow at bidirectional Glenn shunt was beneficial for higher oxygen saturation and larger pulmonary artery size before Fontan operation. However, it was unfavorable for overall transplant-free survival with a sustained higher risk of death or transplant until the elimination of antegrade pulmonary blood flow.

Socioeconomic Status and Long-term Outcomes in Single Ventricle Heart Disease.

BACKGROUND: Low socioeconomic status (SES) has emerged as an important risk factor for higher short-term mortality and neurodevelopmental outcomes in children with hypoplastic left heart syndrome and related anomalies; yet little is known about how SES affects these outcomes over the long-term. METHODS: We linked data from the Single Ventricle Reconstruction trial to US Census Bureau data to analyze the relationship of neighborhood SES tertiles with mortality and transplantation, neurodevelopment, quality of life, and functional status at 5 and 6 years post-Norwood procedure (N = 525). Cox proportional hazards regression and linear regression were used to assess the association of SES with mortality and neurodevelopmental outcomes, respectively. RESULTS: Patients in the lowest SES tertile were more likely to be racial minorities, older at stage 2 and Fontan procedures, and to have more complications and fewer cardiac catheterizations over follow-up (all P < .05) compared with patients in higher SES tertiles. Unadjusted mortality was highest for patients in the lowest SES tertile and lowest in the highest tertile (41% vs 29%, respectively; log-rank P = .027). Adjustment for patient birth and Norwood factors attenuated these differences slightly (P = .055). Patients in the lowest SES tertile reported lower functional status and lower fine motor, problem-solving, adaptive behavior, and communication skills at 6 years (all P < .05). These differences persisted after adjustment for baseline and post-Norwood factors. Quality of life did not differ by SES. CONCLUSIONS: Among patients with hypoplastic left heart syndrome, those with low SES have worse neurodevelopmental and functional status outcomes at 6 years. These differences were not explained by other patient or clinical characteristics.

Maternal Predictors of Disparate Outcomes in Children With Single Ventricle Congenital Heart Disease.

Background Significant variability in morbidity and mortality persists for children with functionally single ventricle congenital heart disease (SV-CHD) despite standardization in medical and surgical care. We hypothesized that maternal health factors may be associated with an increased risk of poor outcomes in children with SV-CHD. Methods and Results This retrospective, observational, cohort study included term maternal-infant pairs with a diagnosis of SV-CHD who underwent surgical palliation from 2006 to 2015 at Primary Children's Hospital. Pairs lacking maternal variables of interest or infant follow-up data were excluded. The association of maternal risk factors of abnormal pre-pregnancy body mass index, abnormal gestational weight gain (<7 or >20 kg), hypertensive disorders, and gestational diabetes mellitus with death/transplant and hemodynamics were analyzed using regression models. Of 190 infants, 135 (71%) maternal-infant dyads had complete data for inclusion. Death or transplant occurred in 48 infants (36%) during an average follow-up of 2.2 years (0.1-11.7 years). Abnormal gestational weight gain was associated with an increased risk of death and/or transplant in logistic regression (odds ratio, 3.22; 95% CI, 1.32-7.86; P=0.01), but not Cox regression (hazard ratio, 1.9; 95% CI, 1.0-3.7; P=0.055). Mean pulmonary artery pressures were higher in the setting of abnormal gestational weight gain (16.5±2.9 versus 14.7±3.0 mm Hg; P<0.001), and abnormal pre-pregnancy body mass index (15.7±3.5 versus 14.2±2.1 mm Hg; P<0.001) in the systemic right ventricle group. Conclusions Abnormal gestational weight gain (excessive or inadequate) is a novel risk factor for worse outcomes in SV-CHD. The fetoplacental environment may alter the trajectory of vascular development to impact outcomes in infants with SV-CHD.

GDF-15 (Growth Differentiation Factor 15) Is Associated With Hospitalization and Mortality in Patients With a Fontan Circulation.

Background We investigated serial serum levels of GDF-15 (growth differentiation factor 15) in Fontan patients and their relation to outcome. Methods and Results In this single-center prospective study of consecutive Fontan patients, serial serum GDF-15 measurement and clinical assessment was done at baseline (n=81) and after 2 years (n=51). The association between GDF-15 and the combined end point of all-cause mortality, heart transplant listing, and Fontan-related hospitalization was investigated. Median age at baseline was 21 years (interquartile range: 15-28 years). Median GDF-15 serum levels at baseline were 552 pg/mL (interquartile range: 453-729 pg/mL). GDF-15 serum levels correlated positively with age, age at Fontan initiation, New York Heart Association class, and serum levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and É£GT (γ-glutamyltransferase) and negatively with exercise capacity. During a median follow-up of 4.8 years (interquartile range: 3.3-5.5 years), the combined end point occurred in 30 patients (37%). Multivariate Cox regression showed that patients with the highest baseline GDF-15 (n=20, defined as the upper quartile) had a higher risk of hospitalization or death than the lowest 3 quartiles (hazard ratio [HR], 2.76; 95% CI, 1.27-6.00; P=0.011). After 2 years of follow-up, patients in whom serum level of GDF-15 increased to >70 pg/mL (n=13) had a higher risk of hospitalization or death than the lowest 3 quartiles (HR, 2.69; 95% CI, 1.03-6.99; P=0.043). Conclusions In Fontan patients, elevated serum levels of GDF-15 are associated with worse functional status and predict Fontan-related events. Furthermore, serial measurements showed that an increase in GDF-15 serum level was associated with increased risk for adverse outcome.

Red Blood Cell Transfusion After Stage I Palliation Is Associated With Worse Clinical Outcomes.

Background Packed red blood cell transfusion may improve oxygen content in single-ventricle neonates, but its effect on clinical outcomes after Stage 1 palliation is unknown. Methods and Results Retrospective multicenter analysis of packed red blood cell transfusion exposures in neonates after Stage 1 palliation, excluding those with intraoperative mortality or need for extracorporeal membrane oxygenation. Transfusion practice variability was assessed, and multivariable regression used to identify transfusion risk factors. After propensity score adjustment for severity of illness, clinical outcomes were compared between transfused and nontransfused subjects. Of 396 subjects, 323 (82%) received 930 postoperative red blood cell transfusions. Packed red blood cell volume (median 9-42 mL/kg [P<0.0001]), donor exposures (1-2 [P<0.0001]), transfusion number (1-3 [P<0.0001]), and pretransfusion hemoglobin (12.1-13 g/dL, P=0.0049) varied between sites. Cyanosis (P=0.02), chest tube output (P=0.0003), and delayed sternal closure (P=0.0033) increased transfusion risk. Transfusion was associated with prolonged mechanical ventilation (6 [interquartile range 4, 12] versus 3 [1, 5] days, P=0.02) and intensive care unit stay (19 [12, 33] versus 9 [6, 19] days, P=0.016). When stratified by number of transfusions (0, 1, or >1), duration of mechanical ventilation (3 [1, 5] versus 4 [3, 6] versus 9 [5, 16] days [P<0.0001]) and intensive care unit stay (9 [6, 19] versus 13 [8, 25] versus 21 [13, 38] days [P<0.0001]) increased for those transfused more than once. Most subjects who died were transfused, though the association with mortality was not significant. Conclusions Packed red blood cell transfusion after Stage 1 palliation is common, and transfusion practice is variable. Transfusion is a significant predictor of longer intensive care unit stay and mechanical ventilation. Further studies to define evidence-based transfusion thresholds are warranted.

Atrioventricular Valve Regurgitation in Single Ventricle Heart Disease: A Common Problem Associated With Progressive Deterioration and Mortality.

The Fontan procedure has provided patients with single ventricle physiology extended survival into adulthood and in many cases has improved their quality of life. Atrioventricular valve regurgitation (AVVR) is common in single ventricle patients and is associated with increased risk of mortality. AVVR is more common in patients with a systemic tricuspid or common atrioventricular valve but is generally progressive irrespective of underlying valve morphology. AVVR can be attributable to diverse structural and functional abnormalities at multiple levels of the valvar apparatus, as well as ventricular dysfunction and dilation. Multiple imaging modalities including recent advances in 3-dimensional echocardiography and cross-sectional imaging have been used to further understand AVVR. Surgery to address AVVR must be tailored to the underlying mechanism and the timing of surgical repair should be chosen carefully. In this review, we discuss the etiologies, treatment options, surgical timing, and outcomes of valve repair or replacement for AVVR in patients with single ventricle congenital heart disease, with a focus on those with a Fontan circulation as AVVR is associated with increased risk for Fontan failure and mortality. In-depth understanding of the current literature will help guide clinicians in their approach and management of AVVR in this population.

Proceedings From the 2019 Stanford Single Ventricle Scientific Summit: Advancing Science for Single Ventricle Patients: From Discovery to Clinical Applications.

Abstracts Because of remarkable advances in survival over the past 40 years, the worldwide population of individuals with single ventricle heart disease living with Fontan circulation has grown to ≈70 000, with nearly half aged >18 years. Survival to at least 30 years of age is now achievable for 75% of Fontan patients. On the other hand, single ventricle patients account for the largest group of the 6000 to 8000 children hospitalized with circulation failure, with or without heart failure annually in the United States, with the highest in-hospital mortality. Because there is little understanding of the underlying mechanisms of heart failure, arrhythmias, pulmonary and lymphatic vascular abnormalities, and other morbidities, there are no specific treatments to maintain long-term myocardial performance or to optimize overall patient outcomes.

Development of a validated risk score for interstage death or transplant after stage I palliation for single-ventricle heart disease.

OBJECTIVE: To develop a risk score to predict mortality or transplant in the interstage period. BACKGROUND: The "interstage" period between the stage 1 and stage 2 palliation is a time of high morbidity and mortality for infants with single-ventricle congenital heart disease. METHODS: This was an analysis of patients with single-ventricle congenital heart disease requiring arch reconstruction who were enrolled in the National Pediatric Cardiology Quality Improvement Collaborative registry from 2008 to 2015. The primary composite endpoint was interstage mortality or transplant. Multivariable logistic regression and classification and regression tree analysis were performed on two-thirds of the patients ("learning cohort") to build a risk score for the composite endpoint, that was validated in the remaining patients ("validation cohort"). RESULTS: In the 2128 patients analyzed in the registry, the overall event rate was 9% (153 [7%] deaths, 42 [2%] transplants). In the learning cohort, factors independently associated with the composite endpoint were (1) type of Norwood; (2) postoperative ECMO; (3) discharge with Opiates; (4) No Digoxin at discharge; (5) postoperative Arch obstruction, (6) moderate-to-severe Tricuspid regurgitation without an oxygen requirement, and (7) Extra Oxygen required at discharge in patients with moderate-to-severe tricuspid regurgitation. This model was used to create a weighted risk score ("NEONATE" score; 0-76 points), with >75% accuracy in the learning and validation cohorts. In the validation cohort, the event rate in patients with a score >17 was nearly three times those with a score ≤17. CONCLUSIONS: We introduce a risk score that can be used post-stage 1 palliation to predict freedom from interstage mortality or transplant.

Invasive Cardiac Procedures in Interstage Single Ventricle Patients in Emergent Hospitalizations.

Single ventricle congenital heart disease (SV CHD) patients are at risk of morbidity and mortality between the first and second palliative surgical procedures (interstage). When these patients present acutely they often require invasive intervention. This study sought to compare the outcomes and costs of elective and emergent invasive cardiac procedures for interstage patients. Retrospective review of discharge data from The Vizient Clinical Data Base/Resource Manager™, a national health care analytics platform. The database was queried for admissions from 10/2014 to 12/2017 for children 1-6 months old with ICD-9 or ICD-10 codes for SV CHD who underwent invasive cardiac procedures. Demographics, length of stay (LOS), complication rate, in-hospital mortality and direct costs were compared between elective and emergent admissions using t test or χ2, as appropriate. The three most frequently performed procedures were also compared. 871 admissions identified, with 141 (16%) emergent. Age of emergent admission was younger than elective (2.9 vs. 4 months p < 0.001). Emergent admissions including cardiac catheterization or superior cavo-pulmonary anastomosis had longer LOS (58.7 vs. 25.8 day, p < 0.001 and 54.8 vs .22.6 days, p < 0.001) and higher costs ($134,774 vs. $84,253, p = 0.013 and $158,679 vs. $81,899, p = 0.017). Emergent admissions for interstage SV CHD patients undergoing cardiac catheterization or superior cavo-pulmonary anastomosis are associated with longer LOS and higher direct costs, but with no differences in complications or mortality. These findings support aggressive interstage monitoring to minimize the need for emergent interventions for this fragile patient population.

Early Integration of Palliative Care in Families of Children with Single Ventricle Congenital Heart Defects: A Quality Improvement Project to Enhance Family Support.

Children with single ventricle congenital heart defects (SVCHD) experience a significant risk of early mortality throughout their lifespan, particularly during their first year of life. Due to the intense care needed for these children and families, pediatric palliative care (PPC) team consults should be routine; however, medical staff are often reluctant to broach the idea of PPC to families. The involvement of PPC for many carries with it an association to end-of-life (EOL) care. Setting the standard of PPC involvement from the time of admission for the first palliative surgery led to increased family support, decreased days to consult, improved acceptance and communication. The purpose of this article is to describe a quality improvement project of early integration of PPC with families of children with SVCHD. Lessons learned will be presented, including the resources needed and the barriers encountered in assimilating PPC into the standard of care for all patients with SVCHD. The single ventricle (SV) and PPC teams collaborated to enhance the support given to SV families. Education was initiated with cardiology and PPC providers to understand the goal of consistent PPC consults beginning after birth for patients with SVCHD. Parents were educated during fetal consultation regarding the involvement of the PPC team. The SV team ensured compliance with the PPC initiative by identifying eligible patients and requesting consult orders from the primary providers. PPC consultation increased significantly over the 40 month study period to nearly 100% compliance for children with SVCHD who are undergoing pre-Fontan surgery. In addition, mean days to consult decreased dramatically during the study to a current average of 3 days into the patient's hospitalization; the data likely suggest that more PPC consults were routinely ordered versus urgently placed for unexpected complications. Data indicate that patients are being followed by the PPC team at an earlier age and stage in their SV journey which allows for more opportunity to provide meaningful support to these patients and families. The early involvement of the PPC team for children with SV physiology was operationally feasible and was accepted by families, thus allowing PPC providers to establish a therapeutic relationship early in the disease trajectory with the family. It allowed more continuity throughout the SV journey in a proactive fashion rather than a reactive manner.

Valve Replacement in Children with Single Ventricle Physiology.

Severe atrioventricular valve (AVV) or semilunar valve (SLV) regurgitation in the setting of a single ventricle physiology may proceed to valve replacement if repair strategies fail. Outcome data for these children are limited. We present transplant-free survival of a case series of children with single ventricle physiology undergoing either atrioventricular replacement (AVVR) or semilunar valve replacement (SLVR) from a multi-institutional, US-based registry (Pediatric Cardiac Care Consortium-PCCC). Outcomes were derived from PCCC and by linkage with the National Death Index (NDI) and Organ Procurement Transplant Network (OPTN). Fifty children with single ventricle physiology were identified to have received either AVVR (n = 38) or SLVR (n = 12). There were 17 in-hospital deaths including 8 intraoperative deaths (all intraoperative deaths were among children requiring AVVR). The in-hospital mortality was 42% and 8% for AVVR and SLVR, respectively. Among the 33 children surviving to hospital discharge, follow-up was available in 15 (46%). Death or cardiac transplant after hospital discharge occurred in 10-death in 4 (all among those requiring AVVR), cardiac transplant in 6 (2 following AVVR, 4 following SLVR). Valve replacement in children with single ventricle physiology, especially AVVR, is associated with poor outcomes. Alternative palliation strategies should be considered in children with single ventricle physiology with significant AVV or SLV regurgitations.

Outcomes of Multistage Palliation of Infants With Single Ventricle and Atrioventricular Septal Defect.

BACKGROUND: Published palliation outcomes of infants with functional single ventricle (SV) and common atrioventricular septal defect (AVSD) are poor due to associated cardiac and extracardiac anomalies and development of atrioventricular valve (AVV) regurgitation. We report current palliation results. METHODS: From 2002 to 2012, 80 infants with functional SV with AVSD underwent multistage palliation. Competing-risks analyses modeled events after first-stage surgery and Glenn (death/transplantation vs next palliation surgery) and examined factors associated with survival and AVV intervention. RESULTS: Sixty-eight (80%) patients received neonatal palliation: modified Blalock-Taussig shunt (n = 33, 41%), Norwood (n = 20, 25%), and pulmonary artery band (n = 15, 19%), whereas 12 (15%) received primary Glenn. On competing-risks analysis, one-year following first-stage surgery, 29% of patients had died or received transplantation and 62% had undergone Glenn. Five years following Glenn, 9% of patients had died or received transplantation and 68% had undergone Fontan. Overall eight-year survival was 64% and was lower in patients with genetic syndromes (53% vs 82%), patients requiring concomitant total anomalous pulmonary venous connection repair (53% vs 69%), and those requiring neonatal palliation (48% vs 100%). Factors associated with mortality were unplanned reoperation (hazard ratio [HR]: 3.7 [1.7-8.0], P = .001) and extracorporeal membrane oxygenation use (HR: 7.1 [3.0-16.6], P < .001). Initial AVV regurgitation ≥ moderate was associated with AVV intervention (HR: 6.2 [2.4-16.1], P = .002) with eight-year freedom from death or AVV intervention of 25% in those patients. CONCLUSIONS: Patients with SV with AVSD are a distinct group and commonly have associated cardiac and extracardiac malformations that complicate care and affect survival. The development of AVV regurgitation requiring intervention is common but does not affect survival.

Atrioventricular Valve Repair in Single Ventricle Physiology: Timing Matters.

OBJECTIVES: Atrioventricular valve (AVV) regurgitation in patients with single ventricle (SV) physiology severely impacts prognosis; the appropriate timing for surgical treatment is unknown. We sought to study the results of surgical treatment of AVV regurgitation in SV patients and evaluate risk factors for mortality. METHODS: Medical records of 81 consecutive patients with moderate or severe AAV regurgitation who were submitted to AVV repair or replacement during any stage of univentricular palliation between January 2013 and May 2017 were examined. We studied demographic data and perioperative factors looking for predictors that might have influenced the results. Binary logistic regression was used to assess the impact on postoperative ventricular dysfunction and mortality. RESULTS: Median age and weight were seven months (interquartile range [IQR]: 3-24) and 5.2 kg (IQR: 3.7-11.2), respectively. Seventy (86.4%) patients underwent AVV repair, and 11 (13.6%) patients underwent AVV replacement. There was an association between AVV repair effectiveness and timing of intervention (P = .004). Atrioventricular valve intervention at the time of initial surgical palliation was associated with more ineffective repairs (P = .001), while AVV replacement was more common between Glenn and Fontan procedures (P = .004). Overall 30-day mortality was 30.5% (25 patients). In-hospital mortality was 49.4%, and it was higher when AVV repair was performed concomitant with initial (stage 1) palliation (64.1% vs 35.7%; P = .01) and when an effective repair was not achieved (75% vs 41%; P = .008). Multivariable analysis identified timing concomitant with stage 1 palliation as an independent risk factor for mortality (P = .01); meanwhile, an effective repair was a protective factor against in-hospital mortality (P = .05). CONCLUSION: Univentricular physiology with AVV regurgitation is a high-risk group of patients. Surgery for AVV regurgitation at stage 1 palliation was associated with less effective repair and higher mortality in this initial experience. On the other hand, effective repair determined better outcomes, highlighting the importance of experience and the learning curve in the management of such patients.

Bridge to Transplant with Ventricular Assist Device Support in Pediatric Patients with Single Ventricle Heart Disease.

Ventricular assist device (VAD) support for children with single ventricle (SV) heart disease remains challenging. We performed a single-center retrospective review of SV patients on VAD support and examined survival to transplant using the Kaplan-Meier method. Patients transplanted were compared with those who died on support. Between 2009 and 2017, there were 14 SV patients with 1,112 patient-days of VAD support. Stages of palliation included pre-Glenn (n = 5), Glenn (n = 5), and Fontan (n = 4). Eight patients (57%) were successfully bridged to transplant at a median 107 days. Deaths occurred early (n = 6, median 16 days) and in smaller patients (10.1 vs. 28.3 kg, P = 0.04). All Fontan patients survived to transplant, whereas only 20% of Glenn patients survived to transplant. Adverse events occurred in 79% (n = 11). Five patients met hospital discharge criteria, with two patients (one pre-Glenn, one Glenn) discharged and transplanted after 219 and 174 days of VAD support. All transplanted patients were discharged at a median 21 days posttransplant. SV patients in various stages of palliation can be successfully bridged to transplant with VAD support. With use of intracorporeal continuous-flow devices, longer-term support and hospital discharge are possible.

Outcome of patients with functional single ventricular heart after pacemaker implantation: What makes it poor, and what can we do?

BACKGROUND: Pacemaker implantation in patients with single ventricle is associated with poor outcomes. OBJECTIVE: The purpose of this study was to determine the reasons for the poor outcomes of pacemaker implantation. METHODS: We performed a retrospective chart review of patients with single ventricle who had undergone permanent pacemaker implantation. Patients were categorized into 3 groups based on the site of pacing and the proportion of ventricular pacing (VP) as follows: (1) atrial pacing group with atrial pacing only (n = 11); (2) low VP group with low daily VP proportion (<50%; n = 12); and (3) high VP group with high daily VP proportion (≥50%; n = 15). Pacing leads were placed at the epicardium in all patients. RESULTS: No patients in the atrial pacing or low VP groups died, whereas the survival rate in the high VP group was 58.9% and 39.3% at 10 and 20 years, respectively, after pacemaker implantation. Among the post-Fontan patients, plasma brain natriuretic peptide (BNP) levels significantly increased with the proportion of VP: 11.7, 20.3, and 28.4 pg/mL in the atrial pacing, low VP, and high VP groups, respectively (P = 0.04). In the high VP group, the plasma BNP level was significantly lower in patients with an apical pacing lead than in those with a nonapical pacing lead (27.0 pg/mL vs 82.8 pg/mL, respectively; P = .03). CONCLUSION: A higher proportion of VP was associated with poor outcome and higher plasma BNP levels, probably due to ventricular dyssynchrony. In epicardial ventricular pacing, apical pacing is better to avoid the increase in ventricular stress and plasma BNP level.

Risk factors for death or heart transplantation in single-ventricle physiology (tricuspid atresia, pulmonary atresia, and heterotaxy): A systematic review and meta-analysis.

BACKGROUND: In this study we sought to evaluate risk factors (RFs) for death or heart transplantation (D-HT) in single-ventricle (SV) physiology due to tricuspid atresia (TA), pulmonary atresia‒intact ventricular septum (PA-IVS), and heterotaxy with SV (HX), clinical conditions for which outcome data are limited. METHODS: To conduct a systematic review, we included citations that evaluated occurrence of D-HT in SV physiology of TA, PA-IVS, and HX in English articles published between January 1998 and December 2017 based on inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The Cochrane Risk of Bias in Non-Randomized Studies-Interventions (ROBINS-I) tool for non-randomized studies was used to assess the risk of bias. Meta-analysis was performed if RF data were available in more than 3 studies. RESULTS: Of 11,629 citations reviewed, 30 met inclusion criteria. All 30 were observational, retrospective studies. In all, 1,770 patients were included, 481 died and 21 underwent HT (63 lost to follow-up); 723 patients reached Fontan completion. We found that systemic ventricular dysfunction (odds ratio [OR] 20.7, confidence interval [CI] 10.0-42.5, I2 = 0%) and atrioventricular valve regurgitation (AVR) were associated with risk of D-HT (OR 3.7, CI 1.9-6.9, I2 = 14%). RF associations with D-HT could not be derived for right ventricle‒dependent coronary circulation, pulmonary arteriovenous malformations, total anomalous pulmonary venous return, arrhythmias, and pulmonary atresia. CONCLUSIONS: This systematic review and meta-analysis has identified a high mortality rate in children born with non-HLHS SV heart disease and points to potential under-utilization of HT. Systemic ventricular dysfunction and AVR were identified as RFs for D-HT in this subset of patients SV with TA, PA-IVS, and HX.