Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

A rare case of severe Ebstein's anomaly and hepatoblastoma in a neonate.

Primary liver tumours in neonates with single-ventricle palliation are exceedingly rare. We present the first reported case of neonatal hepatoblastoma with severe Ebstein's anomaly following Starnes procedure. The patient's postoperative course highlights the challenges and complications in simultaneous management of these diagnoses. Transition from shunted single-ventricle physiology to bidirectional cavopulmonary connection improved end-organ function, permitting more aggressive hepatic malignancy treatment.

Phenotypes and genotypes in a cohort of children with single-ventricle CHD.

OBJECTIVE: CHD is known to be associated with increased risk for neurodevelopmental disorders. The combination of CHD with neurodevelopmental disorders and/or extra-cardiac anomalies increases the chance for an underlying genetic diagnosis. Over the last 15 years, there has been a dramatic increase in the use of broad-scale genetic testing. We sought to determine if neurodevelopmental disorders in children with single-ventricle CHD born prior to the genetic testing revolution are associated with genetic diagnosis. METHODS: We identified 74 5-12-year-old patients with single-ventricle CHD post-Fontan procedure. We retrospectively evaluated genetic testing performed and neurodevelopmental status of these patients. RESULTS: In this cohort, there was an overall higher rate of neurodevelopmental disorders (80%) compared to the literature (50%). More of the younger (5-7-year-old) patients were seen by genetic counsellors compared to the older (8-12-year-old) cohort (46% versus 19% p value = 0.01). In the younger cohort, the average age of initial consultation was 7.7 days compared to 251 days in the older cohort. The overall rate of achieving a molecular diagnosis was 12% and 8% in the younger and older cohorts, respectively; however, the vast majority of did not have broad genetic testing. CONCLUSION: The minority of patients in our cohort achieved a genetic diagnosis. Given a large increase in the number of genes associated with monogenic CHD and neurodevelopmental disorders in the last decade, comprehensive testing and consultation with clinical genetics should be considered in this age range, since current testing standards did not exist during their infancy.

Pre-operative enteral feeding in single-ventricle CHD patients and necrotising enterocolitis risk.

INTRODUCTION: Enteral feeding prior to cardiac surgery has benefits in pre-operative and post-operative patient statuses. In 2020, to increase pre-operative feeding for single-ventricle patients prior to stage 1 palliation, an enteral feeding algorithm was created. The aim of this study is to monitor the impact of our practice change with the primary outcome of necrotising enterocolitis incidence from birth to 2 weeks following surgical intervention. METHODS: This is a single-site, retrospective cohort study including patients from 1 March, 2018 to 1 July, 2022. Variables assessed include demographics, age at cardiac surgery, primary cardiac diagnosis, necrotising enterocolitis pre-operative and 2 weeks post-operative cardiac surgery, feeding route, feeding type, volume of trophic enteral feeds, and near-infrared spectroscopy. RESULTS: Following implementation of a pre-operative enteral feeding algorithm, the rate of neonates fed prior to surgery increased (39.5-75%, p = .001). The feedings included a mean volume of 28.24 ± 11.16 ml/kg/day, 83% fed breastmilk only, 44.4% tube fed, and 55.5% of infants had all oral feedings. Comparing enterally fed neonates and those not enterally fed, the necrotising enterocolitis incidence from birth to 2 weeks post-op was not significantly increased (p = 0.926). CONCLUSION: As a result of implementing our feeding algorithm, the frequency of infants fed prior to stage I Norwood or Hybrid surgeries increased to 75%, and there was no significant change in the incidence of necrotising enterocolitis. This study confirmed that pre-operative enteral feeds are safe and are not associated with increased incidence of necrotising enterocolitis.

Hereditary haemorrhagic telangiectasia and SMAD4 mutation in a patient with complex single ventricle heart disease.

We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient's staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.

Preoperative versus postoperative survival in patients with univentricular heart: a nationwide, retrospective study of patients born in 1990-2015.

OBJECTIVES: Few data exist on mortality among patients with univentricular heart (UVH) before surgery. Our aim was to explore the results of intention to perform surgery by estimating preoperative vs postoperative survival in different UVH subgroups. DESIGN: Retrospective. SETTING: Tertiary centre for congenital cardiology and congenital heart surgery. PARTICIPANTS: All 595 Norwegian children with UVH born alive from 1990 to 2015, followed until 31 December 2020. RESULTS: One quarter (151/595; 25.4%) were not operated. Among these, only two survived, and 125/149 (83.9%) died within 1 month. Reasons for not operating were that surgery was not feasible in 31.1%, preoperative complications in 25.2%, general health issues in 23.2% and parental decision in 20.5%. In total, 327/595 (55.0%) died; 283/327 (86.5%) already died during the first 2 years of life. Preoperative survival varied widely among the UVH subgroups, ranging from 40/65 (61.5%) among patients with unbalanced atrioventricular septal defect to 39/42 (92.9%) among patients with double inlet left ventricle. Postoperative survival followed a similar pattern. Postoperative survival among patients with hypoplastic left heart syndrome (HLHS) improved significantly (5-year survival, 42.5% vs 75.3% among patients born in 1990-2002 vs 2003-2015; p<0.0001), but not among non-HLHS patients (65.7% vs 72.6%; p=0.22)-among whom several subgroups had a poor prognosis similar to HLHS. A total of 291/595 patients (48.9%) had Fontan surgery CONCLUSIONS: Surgery was refrained in one quarter of the patients, among whom almost all died shortly after birth. Long-term prognosis was largely determined during the first 2 years. There was a strong concordance between preoperative and postoperative survival. HLHS survival was improved, but non-HLHS survival did not change significantly. This study demonstrates the complications and outcomes encountering newborns with UVH at all major stages of preoperative and operative treatment.

Association of Home Monitoring and Unanticipated Interstage Readmissions in Infants With Hypoplastic Left Heart Syndrome.

Background The impact of home monitoring on unanticipated interstage readmissions in infants with hypoplastic left heart syndrome has not been previously studied. We sought to examine the association of our institution's Infant Single Ventricle Management and Monitoring Program (ISVMP) with readmission frequency, cumulative readmission days, and readmission illness severity and to identify patient-level risk factors for readmission. Methods and Results We performed a retrospective single-center cohort study comparing infants with hypoplastic left heart syndrome enrolled in ISVMP (December 2010-December 2019) to historical controls (January 2007-November 2010). The primary outcome was number of readmissions per interstage days. Secondary outcomes were cumulative interstage readmission days and occurrence of severe readmissions. Inverse probability weighted and multivariable generalized linear models were used to examine the association between ISVMP and the outcomes. We compared 198 infants in the ISVMP to 128 historical controls. Infants in the ISVMP had more than double the risk of interstage readmission compared with controls (adjusted incidence rate ratio, 2.38 [95% CI, 1.50-3.78]; P=0.0003). There was no difference in cumulative interstage readmission days (adjusted incidence rate ratio, 1.02 [95% CI, 0.69-1.50]; P=0.90); however, infants in the ISVMP were less likely to have severe readmissions (adjusted odds ratio, 0.28 [95% CI, 0.11-0.68]; P=0.005). Other factors independently associated with number of readmissions included residing closer to our center, younger gestational age, genetic syndrome, and discharge on exclusive enteral feeds. Conclusions Infants in the ISVMP had more frequent readmissions but comparable readmission days and fewer severe unanticipated readmissions. These findings suggest that home monitoring can reduce interstage morbidity without increasing readmission days.

Incidence and recovery of post-surgical heart block in children following cardiac surgery.

BACKGROUND: A subset of patients who develop post-surgical heart block have recovery of atrioventricular node function. Factors predicting recovery are not understood. We investigated our centre's incidence of post-surgical heart block and examine factors associated with recovery of atrioventricular node function. METHODS: We conducted a single-centre retrospective study of patients 0 - 21 years who underwent cardiac surgery between January 2010 and December 2019 and experienced post-operative heart block. Data including patient and clinical characteristics and operative variables were collected and analysed. RESULTS: Of 6333 surgical hospitalisations, 128 (2%) patients developed post-operative heart block. Of the 128 patients, 90 (70%) had return of atrioventricular node function, and 38 (30%) had pacemaker placement. Of the 38 patients who underwent pacemaker placement, 6 (15.8%) had recovery of atrioventricular node function noted on long-term follow-up. Median time from onset of heart block to late atrioventricular node recovery was 13 days (Interquartile range: 5 - 117). Patients with single-ventricle physiology (p = 0.04), greater weight (p = 0.03), and shorter cardiopulmonary bypass time (p = 0.015) were more likely to have recovery. The use of post-operative steroids was similar between all groups (p = 0.445). Infectious or wound complications were similar between pacemaker groups (p = 1). CONCLUSIONS: Two per cent of patients who underwent congenital cardiac surgery developed post-operative heart block, and 0.6% underwent pacemaker placement. Early recovery of atrioventricular node was associated with greater weight at the time of surgery, single-ventricle physiology, and shorter cardiopulmonary bypass time. Late recovery of atrioventricular node conduction following pacemaker placement occurred in 15.8% of patients.

Automated Prediction of Cardiorespiratory Deterioration in Patients With Single Ventricle.

BACKGROUND: Patients with single-ventricle physiology have a significant risk of cardiorespiratory deterioration between their first and second stage palliation surgeries. OBJECTIVES: The objective of this study is to develop and validate a real-time computer algorithm that can automatically recognize physiological precursors of cardiorespiratory deterioration in children with single-ventricle physiology during their interstage hospitalization. METHODS: A retrospective study was conducted from prospectively collected physiological data of subjects with single-ventricle physiology. Deterioration events were defined as a cardiac arrest requiring cardiopulmonary resuscitation or an unplanned intubation. Physiological metrics were derived from the electrocardiogram (heart rate, heart rate variability, ST-segment elevation, and ST-segment variability) and the photoplethysmogram (peripheral oxygen saturation and pleth variability index). A logistic regression model was trained to separate the physiological dynamics of the pre-deterioration phase from all other data generated by study subjects. Data were split 50/50 into model training and validation sets to enable independent model validation. RESULTS: Our cohort consisted of 238 subjects admitted to the cardiac intensive care unit and stepdown units of Texas Children's Hospital over a period of 6 years. Approximately 300,000 h of high-resolution physiological waveform and vital sign data were collected using the Sickbay software platform (Medical Informatics Corp., Houston, Texas). A total of 112 cardiorespiratory deterioration events were observed. Seventy-two of the subjects experienced at least 1 deterioration event. The risk index metric generated by our optimized algorithm was found to be both sensitive and specific for detecting impending events 1 to 2 h in advance of overt extremis (receiver-operating characteristic curve area: 0.958; 95% confidence interval: 0.950 to 0.965). CONCLUSIONS: Our algorithm can provide 1 to 2 h of advanced warning for 62% of all cardiorespiratory deterioration events in children with single-ventricle physiology during their interstage period, with only 1 alarm being generated at the bedside per patient per day.

Annuloplasty for Aortic Regurgitation in Univentricular Heart on Ventricular Assist Support.

Progressive aortic regurgitation is a common complication in patients supported with continuous flow ventricular assist devices. The risk of neoaortic regurgitation is likely to be particularly high in patients with univentricular hearts owing to the lack of fibrous support for the neoaortic valve. Previously described techniques for addressing neoaortic regurgitation in this setting have required cardiopulmonary bypass and cross clamping, or ligation of the neoaortic root. We present a simple technique of external partial annuloplasty of the neoaortic valve, which can be performed without the need for cardiopulmonary bypass or cross clamping.

Poor Late Outcomes After Tricuspid Valve Repair in a Single Ventricle: Experience of 103 Patients.

BACKGROUND: Outcomes of tricuspid valve repair in single-ventricle palliation are poor. We sought to identify the impact of repair technique and primary mechanisms of regurgitation on outcomes after surgery. METHODS: A retrospective review of medical records across 4 centers undertaking single-ventricle palliation in Australia and New Zealand was performed. Patients with a dominant right functional single ventricle undergoing tricuspid valve repair between January 1991 and March 2019 were identified. RESULTS: One hundred three patients met inclusion criteria, with a median follow-up duration of 6.7 years (interquartile range, 1.5-12.4). Mechanism of regurgitation was structural in 30 patients, functional in 28 patients, and a combination of both in 24 patients (21 missing). Surgical repair technique consisted of annuloplasty in 42 patients, leaflet and/or subvalvular repair in 12 patients, and a combination of both in 44 patients (5 missing). Thirty-four patients died, and 5 underwent heart transplantation. Fifty-two patients experienced valve repair failure (22 re-repairs, 7 replacements, and 23 recurrent regurgitation). Of 17 patients with early valve repair failure (within 30 days of repair), 14 died. Freedom from death or transplant at 5 years after repair for patients with a successful repair was 79% (95% confidence interval, 70%-90%) compared with 15% (95% confidence interval, 6%-37%) for those with a failed repair (P < .01; hazard ratio, 8.95; 95% confidence interval, 4%-18%). CONCLUSIONS: Tricuspid valve repair failure occurs frequently in patients with a single ventricle and is associated with a significant risk of mortality. The persistence of moderate regurgitation after repair mandates reoperation.

Major aortopulmonary collateral arteries in a case of unrepaired tricuspid and pulmonary atresia with single ventricle physiology.

Tricuspid and pulmonary atresia with single ventricle physiology and major aortopulmonary collateral arteries (MAPCAs) is a complex cyanotic congenital heart disease with heterogeneous pulmonary artery morphology and arborization. The complex anatomy and physiology, coupled with a dearth of existing literature, pose imitable challenges to treatment. Although the exact surgical algorithm is still unclear, the goal is a well-developed, low-resistance pulmonary vascular bed. A precise understanding of the blood supply to each lung is a requisite for successful surgery, and a multimodality and multidisciplinary approach is compulsory. Herein, we describe a case of tricuspid and pulmonary atresia with single ventricle, MAPCAs and aortopulmonary collateral arteries.

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.

Current evaluation and management of plastic bronchitis in the pediatric population.

OBJECTIVE: To describe a multidisciplinary approach for the treatment of plastic bronchitis (PB) in children. METHODS: Retrospective chart review of children with PB between 1997 and 2017. Data regarding clinical presentation, diagnosis, management, and outcomes were analyzed. RESULTS: Of 34 patients presenting with PB, 24 had single ventricle (SV) heart disease, 9 had pulmonary disease, and one had no underlying disease. Median (IQR: interquartile range) age at the time of PB diagnosis was 5.5 years (IQR: 9.0). Presenting symptoms included cough productive of casts (n = 27, 79%), wheezing (n = 5, 15%), dyspnea (n = 18, 53%), hypoxia (n = 31, 91%), and respiratory failure (n = 9, 26%). Diagnosis was made based on clinical evaluation, bronchoscopy findings, and/or pathology of casts. Treatment methods included bronchoscopy for cast removal (25% of SV patients, 91% of non-SV patients), chest physiotherapy (SV: 92%, non-SV: 45%), albuterol (SV: 79%, non-SV: 73%), inhaled steroids (SV: 75%, non-SV: 18%), nebulized hypertonic saline (SV: 29%, non-SV: 9%), nebulized heparin (SV: 8%, non-SV: 55%), nebulized tissue plasminogen activator (tPA; SV: 33%, non-SV: 9%), inhaled Dornase Alfa (SV: 54%, non-SV: 9%), antibiotics (SV: 46%, non-SV: 45%), systemic steroids (SV: 13%, non-SV: 45%), and lymphatic embolization (SV: 8%, non-SV: 45%). Of SV patients, 11 had no recurrence, 5 underwent heart transplantation, one awaits transplant, and 3 died due to cardiac disease. Three patients with respiratory disease had recurrent PB and one died from MRSA pneumonia. CONCLUSION: PB is a highly morbid disease with limited treatment options. Bronchoscopy and chest physiotherapy for airway clearance are among the most-utilized therapies.

Micro-RNA 150-5p predicts overt heart failure in patients with univentricular hearts.

BACKGROUND: In patients with left heart failure, micro-RNAs (miRNAs) have been shown to be of diagnostic and prognostic value. The present study aims to identify those miRNAs in patients with univentricular heart (UVH) disease that may be associated with overt heart failure. METHODS: A large panel of human miRNA arrays were used to determine miRNA expression profiles in the blood of 48 UVH patients and 32 healthy controls. For further selection, the most abundantly expressed miRNA arrays were related to clinical measures of heart failure and selected miRNAs validated by polymerase chain reaction were used for the prediction of overt heart failure and all-cause mortality. RESULTS: According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-150-5p was best related to heart failure parameters. According to ROC analysis, NT-proBNP levels (AUC 0.940, 95% CI 0.873-1.000; p = 0.001), miR-150-5p (AUC 0.905, 95% CI 0.779-1.000; p = 0.001) and a higher NYHA class ≥ III (AUC 0.893, 95% CI 0.713-1.000; p = 0.002) were the 3 most significant predictors of overt heart failure. Using a combined biomarker model, AUC increased to 0.980 indicating an additive value of miR-150-5p. Moreover, in the multivariate analysis, a higher NYHA class ≥ III (p = 0.005) and miR-150-5p (p = 0.006) turned out to be independent predictors of overt heart failure. CONCLUSION: In patients with UVH, miR-150-5p is an independent predictor of overt heart failure and thus may be used in the risk assessment of these patients.

Pulmonary arteriovenous malformations in a patient with single ventricle and polysplenia syndrome.

A 5-month-old girl with single ventricle, interrupted inferior vena cava and polysplenia syndrome palliated with bilateral Blalock-Taussig shunts developed severe cyanosis despite apparently increased pulmonary blood flow. Angiography revealed diffuse pulmonary arteriolar capillary dilatation and early pulmonary venous filling, suggesting the presence of pulmonary arteriovenous malformations. Abdominal angiography at 6 months demonstrated a large extrahepatic portosystemic shunt, which was percutaneously closed with a vascular plug. Kawashima operation was performed 2 weeks after portosystemic shunt closure. Although cyanosis improved temporarily, the patient suffered from deteriorating cyanosis at 9 months of age and underwent Fontan completion. Thereafter, her oxygen saturation gradually improved to 95% over the course of 3 weeks. Both the congenital extrahepatic portosystemic shunt and Kawashima operation contributed to the development of pulmonary arteriovenous malformations.

The Neurodevelopmental Outcomes of Patients With Single Ventricles Across the Lifespan.

BACKGROUND: Moderate to severe neurodevelopmental impairments are recognized as a significant comorbidity in one-fourth to one-third of single-ventricle patients. This report reviews the nature of neurodevelopment across the lifespan, contributing factors, and interventions. METHODS: A focused review was performed of all articles in English that address the topic from 1980 to 2018. RESULTS: Innate patient factors, rather than intraoperative factors, affect the development of neurodevelopmental outcomes, yet a large portion of causality factors remains unexplained. There are also limits to how we currently measure neurodevelopmental outcomes. Limited studies in adulthood and a lack of longitudinal studies hamper our full understanding of how neurodevelopment progresses across time, but estimates are that adults with neurodevelopmental impairments will be affected by abnormal brain aging and early-onset dementia. Intervention services and their efficacy have not been researched in depth and have not been researched across the lifespan. CONCLUSIONS: Further research into neurodevelopmental testing that accurately predicts future functioning is needed. The complexity of implementing systematic and effective neurodevelopmental interventions in the busy lives of patients and families, who often have multiple other clinical demands, needs a complex and thoughtful solution within the context of a multidisciplinary care team approach. The role of targeted psychological and educational interventions that decrease maternal worry and improve family functioning should also continue to be explored in patients with a Fontan circulation.

Concurrent right atrial isomerism, complete atrioventricular septal defect, and single ventricle in an L-transposition of great arteries patient complicated by brain abscess.

We present a case of an 11-year-old Indonesian female who was referred to our facility after surgical excision of brain abscess. The patient has been previously diagnosed with right atrial isomerism, complete atrioventricular septal defect, and L-Transposition of great arteries. Multiple staged surgeries are required for the management of this condition.

Early prediction of critical events for infants with single-ventricle physiology in critical care using routinely collected data.

OBJECTIVE: Critical events are common and difficult to predict among infants with congenital heart disease and are associated with mortality and long-term sequelae. We aimed to achieve early prediction of critical events, that is, cardiopulmonary resuscitation, emergency endotracheal intubation, and extracorporeal membrane oxygenation in infants with single-ventricle physiology before second-stage surgery. We hypothesized that naïve Bayesian models learned from expert knowledge and clinical data can predict critical events early and accurately. METHODS: We collected 93 patients with single-ventricle physiology admitted to intensive care units in a single tertiary pediatric hospital between 2014 and 2017. Using knowledge elicited from experienced cardiac-intensive-care-unit providers and machine-learning techniques, we developed and evaluated the Cardiac-intensive-care Warning INdex (C-WIN) system, consisting of a set of naïve Bayesian models that leverage routinely collected data. We evaluated predictive performance using the area under the receiver operating characteristic curve, sensitivity, and specificity. We performed the evaluation at 5 different prediction horizons: 1, 2, 4, 6, and 8 hours before the onset of critical events. RESULTS: The area under the receiver operating characteristic curves of the C-WIN models ranged between 0.73 and 0.88 at different prediction horizons. At 1 hour before critical events, C-WIN was able to detect events with an area under the receiver operating characteristic curve of 0.88 (95% confidence interval, 0.84-0.92) and a sensitivity of 84% at the 81% specificity level. CONCLUSIONS: Predictive models may enhance clinicians' ability to identify infants with single-ventricle physiology at high risk of critical events. Early prediction of critical events may indicate the need to perform timely interventions, potentially reducing morbidity, mortality, and health care costs.

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.