The Association of Gestational Age and Size with Management Strategies and Outcomes in Symptomatic Neonatal Tetralogy of Fallot.

 In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011-2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: - 27.1, - 14.1; p < 0.001) and 15 days (95%CI: - 22.1, - 8.2; p < 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7, p < .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5, p = 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy.

Low birth weight and very low birth weight neonates with congenital heart disease: timing of surgery, reasons for delaying or not delaying surgery.

Conventional management of low birth weight and very low birth weight neonates was composed of deferring corrective surgery by aggressive medical management or palliative surgery which does not require cardiopulmonary bypass. However, while waiting for weight gain, these neonates are at risk for various comorbidities. In the current era, this "wait and let the baby grow" approach has not been shown to result in better clinical outcomes. Early primary repair hence has become the standard strategy for congenital heart disease requiring surgery in these neonates. However, there still exist some circumstances, which are considered to be unfavorable for corrective surgery due to medical, physiologic, surgeon's technical and institutional-systemic factors. We reviewed the recent literature and examined the reasons for delaying or not delaying surgery.

Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease.

BACKGROUND: Brain injury is common in neonates with complex neonatal congenital heart disease (CHD) and affects neurodevelopmental outcomes. OBJECTIVES: Given advancements in perioperative care, we sought to determine if the rate of preoperative and postoperative brain injury detected by using brain magnetic resonance imaging (MRI) and associated clinical risk factors have changed over time in complex CHD. METHODS: A total of 270 term newborns with complex CHD were prospectively enrolled for preoperative and postoperative brain MRIs between 2001 and 2021 with a total of 466 MRI scans. Brain injuries in the form of white matter injury (WMI) or focal stroke and clinical factors were compared across 4 epochs of 5-year intervals with logistic regression. RESULTS: Rates of preoperative WMI and stroke did not change over time. After adjusting for timing of the postoperative MRI, site, and cardiac group, the odds of newly acquired postoperative WMI were significantly lower in Epoch 4 compared with Epoch 1 (OR: 0.29; 95% CI: 0.09-1.00; P = 0.05). The adjusted probability of postoperative WMI declined significantly by 18.7% from Epoch 1 (24%) to Epoch 4 (6%). Among clinical risk factors, lowest systolic, mean, and diastolic blood pressures in the first 24 hours after surgery were significantly higher in the most recent epoch. CONCLUSIONS: The prevalence of postoperative WMI has declined, whereas preoperative WMI rates remain constant. More robust postoperative blood pressures may explain these findings by minimizing periods of ischemia and supporting cerebral perfusion. These results suggest potential modifiable clinical targets in the postoperative time period to minimize the burden of WMI.

Atrial Appendage Anastomosis in Hypoplastic Left Heart Syndrome With Restrictive Atrial Septum: A Novel Approach.

Intact atrial septum (IAS), occurring in ∼10% of patients with hypoplastic left heart syndrome (HLHS), conveys significant neonatal morbidity and mortality. Perinatal interventions have been described, but outcomes remain poor. We present a fetus with HLHS with IAS who underwent immediate novel postnatal atrial appendage anastomosis, thus achieving rapid left atrial decompression. (Level of Difficulty: Advanced.).

Fetal brain growth and risk of postnatal white matter injury in critical congenital heart disease.

OBJECTIVE: To test the hypothesis that delayed brain development in fetuses with d-transposition of the great arteries or hypoplastic left heart syndrome heightens their postnatal susceptibility to acquired white matter injury. METHODS: This is a cohort study across 3 sites. Subjects underwent fetal (third trimester) and neonatal preoperative magnetic resonance imaging of the brain to measure total brain volume as a measure of brain maturity and the presence of acquired white matter injury after birth. White matter injury was categorized as no-mild or moderate-severe based on validated grading criteria. Comparisons were made between the injury groups. RESULTS: A total of 63 subjects were enrolled (d-transposition of the great arteries: 37; hypoplastic left heart syndrome: 26). White matter injury was present in 32.4% (n = 12) of d-transposition of the great arteries and 34.6% (n = 8) of those with hypoplastic left heart syndrome. Overall total brain volume (taking into account fetal and neonatal scan) was significantly lower in those with postnatal moderate-severe white matter injury compared with no-mild white matter injury after adjusting for age at scan and site in d-transposition of the great arteries (coefficient: 14.8 mL, 95% confidence interval, -28.8 to -0.73, P = .04). The rate of change in total brain volume from fetal to postnatal life did not differ by injury group. In hypoplastic left heart syndrome, no association was noted between overall total brain volume and change in total brain volume with postnatal white matter injury. CONCLUSIONS: Lower total brain volume beginning in late gestation is associated with increased risk of postnatal moderate-severe white matter injury in d-transposition of the great arteries but not hypoplastic left heart syndrome. Rate of brain growth was not a risk factor for white matter injury. The underlying fetal and perinatal physiology has different implications for postnatal risk of white matter injury.

Cerebral oxygen metabolism during total body flow and antegrade cerebral perfusion at deep and moderate hypothermia.

The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200mL/kg/min. After cooling to 18°C (n=6) or 25°C (n=7), flow was reduced to 100mL/kg/min (half-flow, HF) for 15min and ACP was initiated at 40mL/kg/min for 45min. Following rewarming, animals were weaned from bypass and survived for 4h. At baseline, HF, ACP, and 4 h post-CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO(2) ) and cerebral metabolic rate of oxygen (CMRO(2) ) were monitored. Regional cranial oxygen saturation (rSO(2) ) was continuously recorded throughout the procedure using near-infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO(2) trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO(2) at ACP matched that at HF. Cranial rSO(2) was significantly greater at HF and ACP (P<0.001, P<0.001) and matched baseline after CPB. At 25°C, CBF trended lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB. CEO(2) was equal at HF and ACP and trended higher after CPB compared with baseline. CMRO(2) at ACP was greater than that at HF (P=0.001). Cranial rSO(2) was significantly greater at HF (P=0.01), equal at ACP, and lower after CPB (P=0.03). Lactate was significantly higher at all time points (P=0.036, P<0.001, and P<0.001). ACP provided sufficient oxygen to the brain at a total body flow rate of 100mL/kg/min at deep hypothermia. Although ACP provided minimum oxygenation to the brain which met the oxygen requirement, oxygen metabolism was altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia needs further investigation.

Deep brain hyperthermia while rewarming from hypothermic circulatory arrest.

BACKGROUND: Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming. METHODS: Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 degrees C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 degrees C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded. RESULTS: During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 +/- 0.7 vs. 32.3 +/- 0.7 p < 0.05, respectively, 40 minutes: 37.5 +/- 0.3 vs. 34.7 +/- 0.8 p < 0.05, respectively). CONCLUSION: Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 degrees C and NPT should be closely monitored.

A randomized, controlled trial of aprotinin in neonates undergoing open-heart surgery.

BACKGROUND: Neonates undergoing open-heart surgery are especially at risk for massive bleeding and pronounced inflammation. The efficacy of aprotinin, a serine protease inhibitor, at ameliorating these adverse effects of cardiopulmonary bypass has not been clearly demonstrated in neonates. METHODS: Term neonates were enrolled and randomly assigned in a blinded fashion to receive saline (group P, placebo) or high-dose aprotinin (group A). Intraoperative management was standardized: surgeon, anesthesia, cardiopulmonary bypass and hemostasis therapy. Patients were admitted postoperatively to a pediatric cardiac intensive care unit. Primary outcome measure of efficacy was duration of the postoperative mechanical ventilation. Secondary outcome measures were total volume and units of blood products transfused intraoperatively and for 24 h after surgery, duration of chest tube in situ, and intensive care and hospital stays after surgery. RESULTS: Twenty-six neonates were enrolled; 13 received aprotinin and 13 received placebo. The study was halted prematurely because of US Food and Drug Administration's concerns about aprotinin's safety. Baseline patient, surgery and cardiopulmonary bypass characteristics were similar between groups. No outcome variables differed between groups (P > 0.05). Duration of postoperative ventilation was 115 +/- 139 h (group A); 126 +/- 82 h (group P); P = 0.29, and total blood product exposure was 8.2 +/- 2.6 U (group A); 8.8 +/- 1.4 U (group P); P = 0.1. Postoperative blood creatinine values did not differ between groups. In-hospital mortality rate was 4%. CONCLUSIONS: Aprotinin was not shown to be efficacious in neonates undergoing open-heart surgery. It is unclear whether adult aprotinin safety data are relevant to neonates undergoing open-heart surgery.

Outcome analysis for a small, start-up congenital heart surgery program.

There will be a continuing need to start new congenital heart surgery programs to serve communities experiencing significant population growth. However, small congenital heart programs frequently underperform their larger counterparts. This study summarizes the clinical outcome data for the first 42 months of a small, start-up congenital heart surgery program. Clinical outcomes were summarized from the start of the program in September 2003 through March 2007. Risk adjustment analysis was performed using the risk adjustment in congenital heart surgery (Rachs-1) risk adjustment model and Society of Thoracic Surgeons (STS) congenital database. Three hundred eighty-six operations have been performed during this time period, including 47 newborns, 96 infants, 217 children/adolescents, and 26 adults (greater than 18 years). There have been two operative mortalities (0.5%). Assigning these cases to the Rachs-1 categories, there were 64 level I, 188 level II, 90 level III, 12 level IV cases, with 32 "others." The predicted mortality for the 354 categorized cases calculates to be 17.4 (Rachs-1) and 10.2 (STS). The data demonstrate that a start-up program with a relatively modest surgical volume can achieve satisfactory clinical results. This model has relied upon careful case selection and direct, senior-level surgeon involvement through an affiliation with a university-based program. These results suggest that a small congenital heart surgery program can be successfully started if the circumstances are carefully controlled.

Homograft valved right ventricle to pulmonary artery conduit as a modification of the Norwood procedure.

BACKGROUND: The use of a right ventricle to pulmonary artery (RV-PA) conduit in the Norwood procedure has been proposed to increase postoperative hemodynamic stability. A valve within the conduit should further decrease RV volume load. We report our clinical experience with this modification. METHODS AND RESULTS: From February 2002 through August 2005, we performed 88 consecutive Norwood procedures using RV-PA conduits. We used composite valved conduits made from cryopreserved homograft and polytetrafluoroethylene (PTFE) in 66 cases (54 pulmonary, 12 aortic homografts), other valved conduits in 14, and unvalved PTFE in 8 cases. Hospital survival was 88.6% overall and increased to 93.1% after the initial year. Early interventions were required in 18 patients (16 for cyanosis). Prestage II cardiac catheterization was performed at a mean age of 126 days. Mean Qp/Qs was 1, with mean aortic saturation 71%, mean O2 extraction 24%, and mean right ventricular end-diastolic pressure 9 mm Hg. Patient weight, use of an aortic homograft valve in the conduit, stage I palliation within the first year of our experience, and low O2 extraction and high transpulmonary gradient prestage II were risk factors for overall death. Early interventions were more frequent in aortic valve conduits compared with all other conduits. CONCLUSIONS: The valved RV-PA conduit was associated with low early mortality after the Norwood procedure. The majority of these patients had normal cardiac output and well-maintained RV function. There may be a higher risk for early conduit interventions and death when aortic valve homografts are used in the RV-PA conduit.

Pushing the envelope: a treat and repair strategy for patients with advanced pulmonary hypertension associated with congenital heart disease.

Pulmonary arterial hypertension (PAH) is a frequent complication of congenital heart disease as a consequence of altered pulmonary hemodynamics with increased pulmonary blood flow and pressure. The development of pulmonary vascular disease (PVD) in this patient population is an important concern in determining operative strategy. Early, definitive surgical repair, when possible, is the best therapy to prevent and treat PVD. However, this is not possible in some patients because they either presented late, after the development of PVD, or they have complex lesions not amenable to one-step surgical correction, including patients with single ventricle physiology, who have a continuing risk of developing PVD. These patients represent an important, high-risk subgroup and many have been considered inoperable. We present a case series of two patients with complex congenital heart disease and advanced PVD who successfully underwent a treat and repair strategy with aggressive PAH therapies before surgical correction. Both patients had normalization of pulmonary vascular resistance prior to surgical correction. Caution is warranted in applying this strategy broadly and long-term follow-up for these patients is crucial. However, this treat and repair strategy may allow for favorable outcomes among some patients who previously had no therapeutic options.

Management of the Preterm Infant with Congenital Heart Disease.

The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD.

Mitral Stenosis and Aortic Atresia--A Risk Factor for Mortality After the Modified Norwood Operation in Hypoplastic Left Heart Syndrome.

BACKGROUND: There are conflicting reports regarding the importance of mitral stenosis and aortic atresia as a risk factor for Norwood mortality. This study reviews outcomes of this anatomic subgroup at our institution and examines the utility of preoperative cardiac catheterization and its correlation with clinical outcomes and pathology findings. METHODS: This is a single-center, retrospective review of hypoplastic left heart syndrome patients who underwent modified Norwood operation between October 2005 and May 2013. RESULTS: Fourteen of 74 hypoplastic left heart syndrome patients (19%) had mitral stenosis and aortic atresia. Operative mortality for MS/AA was 29% versus 7% for all other hypoplastic left heart syndrome anatomic subgroups (p = 0.04). Although only 19% of the entire cohort, the mitral stenosis and aortic atresia subgroup constituted 50% of the total operative mortality and the only interstage deaths. Autopsies support myocardial ischemia as the mechanism of death. Although preoperative angiography defined the presence of ventriculo-coronary connections, it did not clearly risk stratify patients in regard to operative mortality. CONCLUSIONS: Mitral stenosis and aortic atresia is a risk factor for perioperative myocardial ischemia and mortality. Further exploration of myocardial reserve is warranted.

Anatomic Factors Associated With Truncal Valve Insufficiency and the Need for Truncal Valve Repair.

PURPOSE: Truncus arteriosus is a complex and heterogeneous form of congenital heart defect. Many of the risk factors from several decades ago, including late repair and interrupted aortic arch, have been mitigated through better understanding of the entity and improved surgical techniques. However, truncal valve dysfunction remains an important cause of morbidity and mortality. The purpose of this study was to evaluate the anatomic factors associated with truncal valve dysfunction and the need for truncal valve surgery. METHODS: This was a retrospective review of 72 infants who underwent repair of truncus arteriosus at our institution. The median age at surgery was nine days, and the median weight was 3.1 kg. Preoperative assessment of truncal valve insufficiency by echocardiography revealed no or trace insufficiency in 30, mild in 25, moderate in 10, and severe in 7. The need for truncal valve surgery was dictated by the severity of truncal valve insufficiency. RESULTS: Sixteen (22%) of the 72 patients undergoing truncus arteriosus repair had concomitant truncal valve surgery. Anatomic factors associated with the need for truncal valve surgery included an abnormal number of truncal valve cusps (P < .005), presence of valve dysplasia (P < .005), and the presence of an anomalous coronary artery pattern (P < .005). Fifteen (94%) of the sixteen patients who underwent concomitant surgery had two or all three of these anatomic factors (sensitivity = 94%, specificity = 85%). CONCLUSION: This study demonstrates that the presence of specific anatomic factors was closely associated with the presence of truncal valve insufficiency and the need for concomitant truncal valve surgery. Preoperative evaluation of these anatomic factors may provide a useful tool in determining who should undergo concomitant truncal valve surgery.

Electrical resynchronization: a novel therapy for the failing right ventricle.

BACKGROUND: Many patients with congenital heart disease develop right ventricular (RV) failure due to anatomy and prior therapy. RV problems may include right bundle-branch block (RBBB), volume loading, and chamber enlargement. Because the failing RV may have regional dyskinesis, we hypothesized that resynchronization therapy might augment its performance. METHODS AND RESULTS: We studied 7 patients with RV dysfunction and RBBB, using a predefined pacing protocol. QRS duration, cardiac index (CI), and RV dP/dt were measured in 4 different pacing states. Atrioventricular pacing improved CI and RV dP/dtmax and decreased QRS duration as compared with atrial pacing or sinus rhythm. CONCLUSIONS: Atrioventricular pacing in patients with RBBB and RV dysfunction augments RV and systemic performance. RV resynchronization is a promising novel therapy for patients with RV failure.

Preliminary results of fetal cardiac bypass in nonhuman primates.

OBJECTIVE: Fetal cardiac surgery has potential benefits for treatment of some congenital heart defects. However, placental dysfunction as a result of fetal bypass, fetal stress, and fetal exposure to external milieu needs to be overcome to optimize the outcomes of fetal cardiac bypass. In this study we evaluated the technical feasibility of cardiac bypass in the nonhuman primate fetus and the efficacy of different anesthetic approaches. METHODS: Twelve baboon fetuses, average gestation 146 +/- 8 days and weight 696 +/- 184 g, were used. Three fetuses were excluded from the study because of nuchal cord presentations. The animals were separated into two anesthesia groups: isoflurane (n = 6) and fentanyl and midazolam (n = 3). A miniature roller pump circuit without oxygenator was used for fetal bypass for 30 minutes. No blood transfusion was performed. Fetal blood gas samples were collected before bypass, during bypass, and at 15 and 60 minutes after bypass. RESULTS: All fetuses in the isoflurane group were successfully placed on the cardiac bypass circuit. However, 2 animals in the fentanyl and midazolam group were not placed on the bypass circuit because of sustained elevation in maternal uterine tone. All maternal baboons survived. Of the 6 fetuses in the isoflurane group, 5 survived for 60 minutes; however, placental function continued to deteriorate after bypass (Pa o 2 33 +/- 3 mm Hg before bypass, 23 +/- 6 mm Hg 15 minutes after, and 18 +/- 9 mm Hg 60 minutes after). CONCLUSION: The technical feasibility of cardiac bypass in nonhuman primate fetuses weighing less than 1000 g was confirmed. Isoflurane anesthesia appears to be superior to fentanyl and midazolam anesthesia for fetal cardiac surgery because of adequate uterine relaxation.

Flow simulations and validation for the first cohort of patients undergoing the Y-graft Fontan procedure.

OBJECTIVES: In this study, with the use of computational fluid dynamics, we evaluate the postoperative hemodynamic performance of the first cohort of patients undergoing a handcrafted Y-graft Fontan procedure and validate simulation predictions of hepatic blood flow distribution against in vivo clinical data. METHODS: An 18-12 × 2-mm handcrafted Y-graft modification of the Fontan procedure was performed in 6 patients. Early (at the time of discharge) and 6-month postoperative 3-dimensional magnetic resonance imaging data were collected. Patient-specific models were constructed for flow simulations. RESULTS: Hepatic blood flow distribution varied among patients. Lung perfusion data (n = 3) showed good agreement with simulations. Postoperative asymmetry in hepatic blood flow distribution was reduced 6 months postoperatively. In 1 patient, low wall shear stress was found in the left limb of the Y-graft, corresponding to the location of subsequent thrombosis in the patient. CONCLUSIONS: The credibility and accuracy of simulation-based predictions of postoperative hepatic flow distribution for the Fontan surgery have been validated by in vivo lung perfusion data. The performance of the Y-graft design is highly patient-specific. The anastomosis location is likely the most important factor influencing hepatic blood flow distribution. Although the development of thrombosis is multifactorial, the occurrence in 1 patient suggests that simulations should not solely consider the hepatic blood flow distribution but also aim to avoid low wall shear stress in the limbs.

Fate of right ventricle to pulmonary artery conduits after complete repair of pulmonary atresia and major aortopulmonary collaterals.

BACKGROUND: Surgical repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals (PA/VSD/MAPCAs) requires insertion of a conduit from the right ventricle to the reconstructed pulmonary arteries. Although there is extensive literature on conduit longevity for many forms of congenital heart defects, there is currently limited information for PA/VSD/MAPCAs. It is likely that conduits will have a different longevity in PA/VSD/MAPCAs because pulmonary artery pressures are higher after unifocalization than in other congenital heart defects. The purpose of this study was to evaluate the fate of right ventricle to pulmonary artery conduits after complete repair of PA/VSD/MAPCAs. METHODS: This was a retrospective review of 103 infants who underwent complete repair of PA/VSD/MAPCAs with insertion of an aortic homograft conduit. The average age at complete repair was 5.1 ± 2.8 months, average conduit size was 13 ± 2 mm, and average conduit z score was a positive 1.6 ± 0.9. RESULTS: Conduit z scores were linearly correlated with increasing homograft conduit size. The average longevity of small homografts (8 to 11 mm) was 15 ± 4 months, medium homografts (12 to 14 mm) was 39 ± 7 months, and large homografts (15 to 17 mm) was 50 ± 14 months. There was a negative correlation between increasing pulmonary artery pressure and conduit longevity. CONCLUSIONS: Conduit z scores and conduit size worked synergistically to predict the longevity of right ventricle to pulmonary artery conduits after complete repair of PA/VSD/MAPCAs. Pulmonary artery pressure was an additional modifier of longevity. These data provide a framework for expectations of aortic homograft conduits used in the repair of PA/VSD/MAPCAs.