High-Throughput Genomics Identify Novel FBN1/2 Variants in Severe Neonatal Marfan Syndrome and Congenital Heart Defects.

Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.

Apical muscular ventricular septal defect closure via hybrid approach using a right ventricular stay suture.

Transcatheter closure of large apical muscular ventricular septal defects (VSDs) can be performed via transfemoral or hybrid approach. A very large apical muscular VSD was closed via a hybrid approach. A strategy for deployment of a right ventricular stay suture was utilized to minimize the risk of device embolization without the use of bypass and without externalization of a portion of the device.

The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set.

BACKGROUND: In infants requiring 3-stage single-ventricle palliation for hypoplastic left heart syndrome, attrition after the Norwood procedure remains significant. The effect of the timing of stage 2 palliation (S2P), a physician-modifiable factor, on long-term survival is not well understood. We hypothesized that an optimal interval between the Norwood and S2P that both minimizes pre-S2P attrition and maximizes post-S2P survival exists and is associated with individual patient characteristics. METHODS: The National Institutes of Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single Ventricle Reconstruction Trial public data set was used. Transplant-free survival (TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using parametric hazard analysis. Factors associated with death or heart transplantation were determined for each interval. To account for staged procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3 years given survival to S2P) was calculated using parametric conditional survival analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3 years was then predicted and adjusted for attrition before S2P by multiplying by the estimate of TFS to S2P. The optimal timing of S2P was determined by generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the interval from the Norwood to S2P. RESULTS: Of 547 included patients, 399 survived to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up. The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1-6.0) months. The risk-adjusted, 3-year, TFS was 68±7%. A Norwood-S2P interval of 3 to 6 months was associated with greatest 3-year TFS overall and in patients with few risk factors. In patients with multiple risk factors, TFS was severely compromised, regardless of the timing of S2P and most severely when S2P was performed early. No difference in the optimal timing of S2P existed when stratified by shunt type. CONCLUSIONS: In infants with few risk factors, progressing to S2P at 3 to 6 months after the Norwood procedure was associated with maximal TFS. Early S2P did not rescue patients with greater risk factor burdens. Instead, referral for heart transplantation may offer their best chance at long-term survival. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.

Infants listed for heart transplantation experience high waitlist and early post-transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual-level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model. CART analysis was used to create a model which, at the time of listing, would predict which infants listed for heart transplantation would survive at least 3 months post-transplantation. A total of 48 infants were included; 13 died while waiting, and six died within 3 months of heart transplant. CART analysis identified RRT, blood urea nitrogen, and hematocrit as terminal nodes with alanine transaminase as an intermediate node predicting death. No patients listed on RRT (n = 10) survived and only three of 12 (25%) patients listed on ECLS survived >3 months post-transplant. CART analysis overall accuracy was 83%, with sensitivity of 95% and specificity 76%. This study shows that CART analysis can be used to generate accurate prediction models in small patient populations. Model validation will be necessary before incorporation into decision-making algorithms used to determine transplant candidacy.

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome.

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.

D-Transposition of the Great Arteries with Ventricular Septal Defect and Left Ventricular Outflow Tract Obstruction (D-TGA/VSD/LVOTO): A Survey of Perceptions, Preferences, and Experience.

Several procedures have been introduced to manage this complex congenital heart malformation. It is not clear that any one approach is best for all patients. Decision-making for a given patient may be influenced by multiple patient factors. There is little doubt that surgeon and institutional experience and preference also play a role. We have focused our survey on three procedures, i.e., the Rastelli, Nikaidoh (aortic root translocation), and réparation à l'étageventriculaire (REV) procedures. The questionnaire was directed to all Congenital Heart Surgeon Society member surgeons. A total of 61 clinical practitioners responded to our survey. Of them, 45 (73.8 %) were staff congenital heart surgeons, 11 (18 %) were staff pediatric cardiologists, 1 (1.6 %) was a staff adult congenital cardiologist, 1 (1.6 %) was a fellow pediatric cardiologist, 2 (3.3 %) were fellow or resident congenital heart surgeons, and 1 (1.6 %) was a nurse practitioner. Most respondents believe that the Rastelli procedure should be considered the first option (n = 28, 45.9 %), while 24 (39.3 %) respondents believe that the Nikaidoh procedure should be considered the first option. Asked "To which surgeon do you prefer to refer your patient" (one who will perform Rastelli, Nikaidoh, or REV), all staff cardiologists (n = 12, 100 %) responded "doesn't matter." This survey revealed a wide diversity among clinical practitioners in terms of management of patients with TGA/VSD/LVOTO and preferred surgical approaches. A multi-institutional study of surgical management of TGA/VSD/LVOTO may help to define principles for optimal matching of procedures to patients.

Surgical palliation strategy does not affect interstage ventricular dysfunction or atrioventricular valve regurgitation in children with hypoplastic left heart syndrome and variants.

BACKGROUND: All 3 palliation strategies, Norwood, Sano, and Hybrid, currently used for hypoplastic left heart syndrome pose a risk of myocardial injury at different times and through different mechanisms. We sought to compare these strategies to understand longitudinal differences in interstage ventricular dysfunction and their subsequent impact on transplant-free survival and atrioventricular valve regurgitation (AVVR) as well as the relationship between adverse events and ventricular function. METHODS AND RESULTS: Serial echocardiographic reports and clinical data were reviewed for 138 children with hypoplastic left heart syndrome who underwent stage I surgical palliation (Sano: 11; Norwood: 73; Hybrid: 54) between 2004 and 2011. Stage II palliation was achieved in 92 (67%) patients (Sano: 7; Norwood: 51; Hybrid: 34). Interstage transplant-free survival, ventricular dysfunction, and AVVR were equivalent among palliation strategies. Patients with preserved ventricular function had a higher rate of transplant-free survival and freedom from AVVR, regardless of palliation strategy. Patients who had cardiac arrest, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation (adverse events) experienced more transient and persistent ventricular dysfunction compared to those without adverse events. Surgical palliation strategies were not identified as risk factors for ventricular dysfunction or AVVR. CONCLUSIONS: Surgical palliation strategy does not affect mortality, interstage ventricular function, or interstage AVVR in children with hypoplastic left heart syndrome. Therefore, the different timing and mechanisms of myocardial injury among palliation strategies do not affect outcomes. Ventricular dysfunction adversely affects transplant-free survival and atrioventricular valve function. Adverse events are associated with the development of ventricular dysfunction. To improve outcomes, interstage treatment should focus on the preservation of ventricular function.

Hybrid versus Norwood strategies for single-ventricle palliation.

BACKGROUND: Hybrid and Norwood strategies differ substantially in terms of stage II palliative procedures. We sought to compare these strategies with an emphasis on survival and reintervention after stage II and subsequent Fontan completion. METHODS AND RESULTS: Of 110 neonates with functionally single-ventricle physiology who underwent stage I palliation between 2004 and 2010, 75 (69%) infants (Norwood, n=43; hybrid, n=32) who subsequently underwent stage II palliation were studied. Survival and reintervention rates after stage II palliation, anatomic and physiologic variables at pre-Fontan assessment, and Fontan outcomes were compared between the groups. Predictors for reintervention were analyzed. Freedom from death/transplant after stage II palliation was equivalent between the groups (Norwood, 80.4% versus hybrid, 85.6% at 3 years, P=0.66). Hybrid patients had a higher pulmonary artery (PA) reintervention rate (P=0.003) and lower Nakata index at pre-Fontan evaluation (P=0.015). Aortic arch and atrioventricular valve reinterventions were not different between the groups. Ventricular end-diastolic pressure, mean PA pressure, and ventricular function were equivalent at pre-Fontan assessment. There were no deaths after Fontan completion in either group (Norwood, n=25, hybrid, n=14). CONCLUSIONS: Survival after stage II palliation and subsequent Fontan completion is equivalent between the groups. The hybrid group had a higher PA reintervention rate and smaller PA size. Both strategies achieved adequate physiology for Fontan completion. Evolution of the hybrid strategy requires refinement to provide optimal PA growth.

Left atrial decompression during venoarterial extracorporeal membrane oxygenation for left ventricular failure in children: current strategy and clinical outcomes.

From 2005 to 2011, 23 of 178 (12.9%) patients with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) had left atrial (LA) decompression to help improve left ventricular (LV) function, LA/LV dilatation, and/or lung edema. LA decompression was achieved with LA cannulation (n = 16), surgically created adjustable atrial septal defect (n = 3), or balloon atrial septostomy (n = 4). Sixteen (70%) patients had LA decompression at the time of ECMO initiation and all had LA decompression within 12 hours of ECMO initiation. ECMO duration was 5.9 ± 4.5 days and 16 (70%) patients were successfully decannulated. Subsequent intensive care unit and hospital survival was achieved in 13 (57%) and 12 (52%) patients, respectively. Earlier timing of LA decompression appeared to be associated with a high probability of weaning from ECMO and reasonable LV functional recovery.

Contemporary sequential segmental approach to congenital heart disease using four-dimensional magnetic resonance imaging with ferumoxytol: an illustrated editorial.

The ferumoxytol-enhanced 4D MR angiography with MUSIC (Multiphase Steady State Imaging with Contrast) technique provides a single data set that captures dynamic cardiovascular anatomy and ventricular function at the same time. Homogeneous opacification of all cardiovascular structures within the imaging volume allows full sequential segmental approach to the congenital heart diseases without any blind spots. The complex systemic and pulmonary venous anatomy is particularly well captured in the MUSIC. Cinematographic display of multiplanar sectional and 3D volume images is helpful in the morphological identification of the cardiac chambers, the assessment of the dynamic nature of the ventricular outflow tracts, and the assessment of the coronary arterial origins and courses.

Integration of Prenatal Cardiovascular Magnetic Resonance Imaging in Congenital Heart Disease.

Standard of care echocardiography can have limited diagnostic accuracy in certain cases of fetal congenital heart disease. Prenatal cardiovascular magnetic resonance (CMR) imaging has potential to provide additional anatomic imaging information, including excellent soft tissue images in multiple planes, improving prenatal diagnostics and in utero hemodynamic assessment. We conducted a literature review of fetal CMR, including its development and implementation into clinical practice, and compiled and analyzed the results. Our findings included the fact that technological and innovative approaches are required to overcome some of the challenges in fetal CMR, in part due to the dynamic nature of the fetal heart. A number of reconstruction algorithms and cardiac gating strategies have been developed over time to improve fetal CMR image quality, allowing unique investigations into fetal hemodynamics, oxygenation, and growth. Studies demonstrate that incorporating CMR in the prenatal arena influences postnatal clinical management. With further refinement and experience, fetal CMR in congenital heart disease continues to evolve and demonstrate ongoing potential as a complementary imaging modality to fetal echocardiography in the care of these patients.

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: Management of infants and neonates with tetralogy of Fallot.

OBJECTIVE: Despite decades of experience, aspects of the management of tetralogy of Fallot with pulmonary stenosis (TOF) remain controversial. Practitioners must consider newer, evolving treatment strategies with limited data to guide decision making. Therefore, the TOF Clinical Practice Standards Committee was commissioned by the American Association for Thoracic Surgery to provide a framework on this topic, focused on timing and types of interventions, management of high-risk patients, technical considerations during interventions, and best practices for assessment of outcomes of the interventions. In addition, the group was tasked with identifying pertinent research questions for future investigations. It is recognized that variability in institutional experience could influence the application of this framework to clinical practice. METHODS: The TOF Clinical Practice Standards Committee is a multinational, multidisciplinary group of cardiologists and surgeons with expertise in TOF. With the assistance of a medical librarian, a citation search in PubMed, Embase, Scopus, and Web of Science was performed using key words related to TOF and its management; the search was restricted to the English language and the year 2000 or later. Articles pertaining to pulmonary atresia, absent pulmonary valve, atrioventricular septal defects, and adult patients with TOF were excluded, as well as nonprimary sources such as review articles. This yielded nearly 20,000 results, of which 163 were included. Greater consideration was given to more recent studies, larger studies, and those using comparison groups with randomization or propensity score matching. Expert consensus statements with class of recommendation and level of evidence were developed using a modified Delphi method, requiring 80% of the member votes with 75% agreement on each statement. RESULTS: In asymptomatic infants, complete surgical correction between age 3 and 6 months is reasonable to reduce the length of stay, rate of adverse events, and need for a transannular patch. In the majority of symptomatic neonates, both palliation and primary complete surgical correction are useful treatment options. It is reasonable to consider those with low birth weight or prematurity, small or discontinuous pulmonary arteries, chromosomal anomalies, other congenital anomalies, or other comorbidities such as intracranial hemorrhage, sepsis, or other end-organ compromise as high-risk patients. In these high-risk patients, palliation may be preferred; and, in patients with amenable anatomy, catheter-based procedures may prove favorable over surgical palliation. CONCLUSIONS: Ongoing research will provide further insight into the role of catheter-based interventions. For complete surgical correction, both transatrial and transventricular approaches are effective; however, the smallest possible ventriculotomy should be utilized. When possible, the pulmonary valve should be spared; and if unsalvageable, reconstruction can be considered. At the conclusion of the operation, adequate relief of the right ventricular outflow obstruction should be confirmed, and identification of a significant fixed anatomical obstruction should prompt further intervention. Given our current knowledge and the gaps identified, we propose several key questions to be answered by future research and potentially by a TOF registry: When to palliate or proceed with complete surgical correction, as well as the ideal type of palliation; the optimal surgical approach for complete repair for the best long-term preservation of right ventricular function; and the utility, efficacy, and durability of various pulmonary valve preservation and reconstruction techniques.

Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy.

As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated by the actin-binding proteins Leiomodins (LMODs), among which LMOD2 has recently been identified as a key regulator of thin filament elongation to reach a mature length. Few reports have implicated homozygous loss of function variants of LMOD2 in neonatal dilated cardiomyopathy (DCM) associated with thin filament shortening. We present the fifth case of DCM due to biallelic variants in the LMOD2 gene and the second case with the c.1193G>A (p.W398*) nonsense variant identified by whole-exome sequencing. The proband is a 4-month male infant of Hispanic descent with advanced heart failure. Consistent with previous reports, a myocardial biopsy exhibited remarkably short thin filaments. However, compared to other cases of identical or similar biallelic variants, the patient presented here has an unusually late onset of cardiomyopathy during infancy. Herein, we present the phenotypic and histological features of this variant, confirm the pathogenic impact on protein expression and sarcomere structure, and discuss the current knowledge of LMOD2-related cardiomyopathy.

Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery.

BACKGROUND: Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. METHODS AND RESULTS: We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/10(9) cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. CONCLUSIONS: Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.

Thrombotic complications and thromboprophylaxis across all three stages of single ventricle heart palliation.

OBJECTIVES: To describe the incidence of thrombotic complications across all 3 stages of single ventricle palliation and the association between thromboprophylaxis use and thrombotic risk. STUDY DESIGN: Two separate cross-sectional studies were performed that included 195 patients born between 2003-2008 and 162 patients who underwent Fontan after 2000. RESULTS: The incidence of thrombotic complications was 40% and 28% after initial palliation and superior cavopulmonary connection (SCPC), respectively; 5-year freedom from thrombotic complications after Fontan was 79%. Thromboprophylaxis was initiated for 70%, 46%, and 94% of patients after initial palliation, SCPC, and Fontan, respectively. Thromboprophylaxis with enoxaparin (vs no thromboprophylaxis) was associated with a reduction in risk of thrombotic complications after initial palliation (hazard ratio [HR] 0.5, P = .05) and SCPC (HR 0.2, P = .04). Thromboprophylaxis with warfarin was associated with a reduction in thrombotic complications after Fontan (HR 0.27, P = .05 vs acetylsalicylic acid; HR 0.18, P = .02 vs no thromboprophylaxis). Thrombotic complications were associated with increased mortality after initial palliation (HR 5.5, P < .001) and SCPC (HR 12.5, P < .001). Three patients experienced major bleeding complications without permanent sequelae (2 enoxaparin, 1 warfarin). CONCLUSIONS: Given the negative impact of thrombotic complications on survival, the low risk of serious bleeding complications, and the association between thromboprophylaxis and lowered thrombotic complication risk across all 3 palliative stages, routine use of thromboprophylaxis from the initial palliation to the early post-Fontan period in this population may be indicated.

Branch pulmonary artery stenosis after arterial switch operation: The effect of preoperative anatomic factors on reintervention.

BACKGROUND: We hypothesized that preoperative patient characteristics and branch pulmonary artery (PA) size might influence the rate of postoperative branch PA reintervention in patients with transposition of the great arteries who undergo the arterial switch operation (ASO). METHODS: The retrospective single-center study included 262 consecutive (2008-2017) newborns who underwent the ASO. Demographic characteristics, echocardiography, and clinical outcomes were reviewed. Competing risk analysis modeled incidence of branch PA reintervention and cause-specific hazard regression for predictors analyses. RESULTS: Median age and weight were 7 (range, 5-11) days and 3.4 (range, 3.1-3.8) kg, respectively. Various types of early branch PA reinterventions (concomitant revision or reintervention during the intensive care unit stay) were required in 28 (10.7%) patients. These patients had prolonged ventilation (P < .001), intensive care unit duration (P < .001), worse right ventricular function (P = .043), and high in-hospital mortality (P = .010). Branch PA dimensions significantly decreased immediately after ASO compared with baseline measurements. The median follow-up duration was 20.8 (range, 0.9-44.7) months. Branch PA reintervention was common among survivors without early reinterventions (9.4%), and even more frequent among those with early reinterventions (25%). Subsequent reintervention (all catheter-based) was necessary for more than one-third of patients after initial branch PA reintervention. The multivariable analysis showed preoperative dimension of the left PA (hazard ratio, 0.527 [95% CI, 0.337-0.823]; P = .005), and right PA (hazard ratio, 0.503 [95% CI, 0.318-0.796]; P = .003) were independently associated with late branch PA reinterventions. CONCLUSIONS: Branch PA reintervention was common and often required surgical or catheter-based reinterventions after ASO. PA branch diameters became significantly smaller after ASO. Smaller preoperative branch PA predicted late branch PA reintervention, indicating a smaller margin of geometrical tolerance to this effect.

Hyperglycemia after pediatric cardiac surgery: impact of age and residual lesions.

OBJECTIVE: We evaluated the effect of patient age and significant residual cardiac lesions on the association between hyperglycemia and adverse outcomes in children after cardiac surgery. The incidence, severity, and duration of hyperglycemia in this patient population and perioperative factors predisposing to hyperglycemia were also delineated. DESIGN: Retrospective, observational cohort study. SETTING: Eighteen-bed pediatric cardiac critical care unit. PATIENTS: Seven hundred seventy-two children undergoing cardiac surgery with cardiopulmonary bypass during 2006 and 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative glucose levels were reviewed in all children who underwent cardiac surgery with cardiopulmonary bypass at our institution during 2006 and 2007 who met all inclusion criteria and none of the exclusion criteria (n = 772). The composite morbidity-mortality outcome included hospital death, cardiac arrest, renal/hepatic failure, lactic acidosis, extracorporeal membrane oxygenation use, or infection. Hyperglycemia occurred in 90% of patients and resolved within 72 hrs in most without exogenous insulin. Preoperative factors, including prostaglandins, mechanical ventilation, and cyanosis, were significantly associated with increased odds of significant hyperglycemia (>180 mg/dL for >12 hrs or any level >270 mg/dL) as were increased surgical complexity and perioperative steroid administration. Thirty-one percent of the entire cohort reached the composite outcome and the odds were significantly increased after 54 hrs of mild (elevated, but <180 mg/dL), 12 hrs of moderate (180-270 mg/dL), or any period of severe hyperglycemia (>270 mg/dL). Neonates (<1 month of age) tolerated longer periods of hyperglycemia before showing increased odds of reaching the composite morbidity-mortality end point. In the setting of important residual cardiac lesions, mild or moderate hyperglycemia was not as strongly associated with adverse outcomes. CONCLUSIONS: Age and residual cardiac lesions are important modifiers of the association between hyperglycemia and suboptimal outcomes after pediatric cardiac surgery. Use of insulin therapy for glucose control in this patient population may need to be carefully targeted toward high-risk subsets of patients.

Airway pressure release ventilation improves pulmonary blood flow in infants after cardiac surgery.

OBJECTIVE: We hypothesized that spontaneous inspiratory effort transmitted to the pleural space during airway pressure release ventilation would result in increased lung perfusion after surgery for tetralogy of Fallot or following a cavopulmonary shunt as a consequence of transient decreases in intrapleural pressure. DESIGN: Prospective crossover cohort study. SETTING: A tertiary care cardiac pediatric intensive care unit. PATIENTS: Children after tetralogy of Fallot repair, cavopulmonary shunt, or Fontan operation. INTERVENTIONS: Lung perfusion and cardiac output were measured during airway pressure release ventilation and pressure control ventilation with pressure support, both with and without spontaneous ventilation. Oxygen consumption was measured (mass spectrometer) and lung perfusion/cardiac output calculated (Fick equation). Constant levels of CO2 and mean airway pressure were targeted in all study phases. MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled in the study, nine after repair of tetralogy of Fallot and 11 after a cavopulmonary shunt. In the absence of spontaneous ventilation, there were no differences in lung perfusion or any of the measured gas exchange or hemodynamic parameters. In the presence of spontaneous ventilation for all patients, mean pulmonary blood flow increased from 2.4 to 2.9 L·min⁻¹M⁻² (p = .02). Oxygen delivery increased from 594 to 774 mL/min/m² (p = .05) in the patients with tetralogy of Fallot patients and from 473 to 518 L·min⁻¹M⁻² (p = .07) in the cavopulmonary shunt group. CONCLUSION: Ventilation with airway pressure release ventilation (at comparable mean airway pressure) improves lung perfusion compared with pressure control ventilation in children after tetralogy of Fallot repair and cavopulmonary shunt operations. Although this study focused on tetralogy of Fallot and cavopulmonary shunt operations, the improved cardiopulmonary interactions may be beneficial in other situations in which hemodynamics are impaired by positive pressure ventilation.