Variable clinical severity in TANGO2 deficiency: Case series and literature review.

Biallelic pathogenic variants in the TANGO2 (transport and Golgi organization 2 homolog) gene have been identified as causing a rare metabolic disorder characterized by susceptibility to recurrent rhabdomyolysis, lactic acidosis, encephalopathy, and life-threatening tachyarrhythmias. Recently published reports suggest variable clinical severity and phenotypes. This study details five new patients from two families with biallelic pathogenic variants in the TANGO2 gene identified by whole exome sequencing and includes the largest number of affected individuals from a single family reported to date. We document significant intrafamilial variability and highlight that milder phenotypes may be underrecognized. We present biochemical and clinical data to help highlight the features that aid in consideration of this condition in the differential with disorders of fatty acid oxidation. We also present a comprehensive literature review summarizing the molecular, clinical, and biochemical findings for 92 individuals across 13 publications. Of the 27 pathogenic variants reported to date, the recurrent exons 3-9 deletion represents the most common variant seen in 42% of individuals with TANGO2 deficiency. Common clinical features seen in >70% of all individuals include acute metabolic crisis, rhabdomyolysis, neurologic abnormalities, developmental delay, and intellectual disability. Findings such as elevated creatine kinase, hypothyroidism, ketotic hypoglycemia, QT prolongation, or abnormalities of long-chain acylcarnitines and urine dicarboxylic acids should raise clinical suspicion for this life-threatening condition.

Outcomes in Patients with Alagille Syndrome and Complex Pulmonary Artery Disease.

OBJECTIVE: To assess outcomes in a large cohort of patients with Alagille syndrome (ALGS) who underwent pulmonary artery reconstruction surgery for complex pulmonary artery disease. STUDY DESIGN: Patients with ALGS who underwent pulmonary artery reconstruction surgery at Lucile Packard Children's Hospital Stanford were reviewed. Patients were examined as an overall cohort and based on the primary cardiovascular diagnosis: severe isolated branch pulmonary artery stenosis, tetralogy of Fallot (TOF) without major aortopulmonary collateral arteries (MAPCAs), or TOF with MAPCAs. RESULTS: Fifty-one patients with ALGS underwent pulmonary artery surgery at our center, including 22 with severe branch pulmonary artery stenosis, 9 with TOF without MAPCAs, and 20 with TOF and MAPCAs. Forty-one patients (80%) achieved a complete repair. Five of the patients with TOF with MAPCAs (25%) underwent complete repair at the first surgery, compared with 8 (89%) with TOF without MAPCAs and 19 (86%) with isolated branch pulmonary artery stenosis. At a median follow-up of 1.7 years after the first surgery, 39 patients (76%) were alive, 36 with a complete repair and a median pulmonary artery:aortic systolic pressure of 0.38. Nine patients (18%), including 8 with isolated branch pulmonary artery stenosis, underwent liver transplantation. CONCLUSIONS: Most patients with ALGS and complex pulmonary artery disease can undergo complete repair with low postoperative right ventricular pressure. Patients with TOF/MAPCAs had the worst outcomes, with higher mortality and more frequent pulmonary artery interventions compared with patients with TOF without MAPCAs or isolated branch pulmonary artery stenosis. Complex pulmonary artery disease is not a contraindication to liver transplantation in patients with ALGS.

Hyperoxia During Cardiopulmonary Bypass Is Associated With Mortality in Infants Undergoing Cardiac Surgery.

OBJECTIVES: Patients undergoing cardiac surgery using cardiopulmonary bypass have variable degrees of blood oxygen tension during surgery. Hyperoxia has been associated with adverse outcomes in critical illness. Data are not available regarding the association of hyperoxia and outcomes in infants undergoing cardiopulmonary bypass. We hypothesize that among infants undergoing cardiac surgery, hyperoxia during cardiopulmonary bypass is associated with greater odds of morbidity and mortality. DESIGN: Retrospective study. SETTING: Single center at an academic tertiary children's hospital. PATIENTS: All infants (< 1 yr) undergoing cardiopulmonary bypass between January 1, 2015, and December 31, 2017, excluding two patients who were initiated on extracorporeal membrane oxygenation in the operating room. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 469 infants with a median age of 97 days (interquartile range, 14-179 d), weight 4.9 kg (interquartile range, 3.4-6.4 kg), and cardiopulmonary bypass time 128 minutes (interquartile range, 91-185 min). A Pao2 of 313 mm Hg (hyperoxia) on cardiopulmonary bypass had highest sensitivity with specificity greater than 50% for association with operative mortality. Approximately, half of the population (237/469) had hyperoxia on cardiopulmonary bypass. Infants with hyperoxia were more likely to have acute kidney injury, prolonged postoperative length of stay, and mortality. They were younger, weighed less, had longer cardiopulmonary bypass times, and had higher Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery mortality scores. There was no difference in sex, race, preoperative creatinine, single ventricle physiology, or presence of genetic syndrome. On multivariable analysis, hyperoxia was associated with greater odds of mortality (odds ratio, 4.3; 95% CI, 1.4-13.2) but failed to identify an association with acute kidney injury or prolonged postoperative length of stay. Hyperoxia was associated with greater odds of mortality in subgroup analysis of neonatal patients. CONCLUSIONS: Hyperoxia occurred in a substantial portion of infants undergoing cardiopulmonary bypass for cardiac surgery. Hyperoxia during cardiopulmonary bypass was an independent risk factor for mortality and may be a modifiable risk factor. Furthermore, hyperoxia during cardiopulmonary bypass was associated with four-fold greater odds of mortality within 30 days of surgery. Hyperoxia failed to identify an association with development of acute kidney injury or prolonged postoperative length of stay when controlling for covariables. Validation of our data among other populations is necessary to better understand and elucidate potential mechanisms underlying the association between excess oxygen delivery during cardiopulmonary bypass and outcome.

Pulmonary hemorrhage in children with Alagille syndrome undergoing cardiac catheterization.

OBJECTIVES: To evaluate the incidence, severity, and outcomes of pulmonary hemorrhage in children with Alagille syndrome (AGS) undergoing cardiac catheterization, and to find variables associated with hemorrhage in this population. BACKGROUND: Children with AGS have a high incidence of bleeding complications during invasive procedures. It has been our impression that catheterization-associated pulmonary hemorrhage is more common in children with AGS, but there are no published data on this topic. METHODS: This was a retrospective single institution study of children with AGS undergoing catheterization from 2010 to 2018. Pulmonary hemorrhage was defined as angiographic or fluoroscopic evidence of extravasated blood in the lung parenchyma, or blood suctioned from the endotracheal tube with documentation of pulmonary hemorrhage by the anesthesiologist or intensivist. Univariate comparisons were made between catheterizations that did and did not have pulmonary hemorrhage. RESULTS: Thirty children with AGS underwent 87 catheterizations, 32 (37%) with interventions on the branch pulmonary arteries (PA). There were 26 (30%) procedures with hemorrhage, the majority (65%) of which were self-limited or required less than 24 hr of mechanical ventilation. Moderate and severe hemorrhage occurred only in children with tetralogy of Fallot (TOF; 5 of 14, 36%). A higher right ventricle to aorta systolic pressure ratio (1.0 [0.85-1.1] vs. 0.88 [0.59-1.0], p = .029) and interventions on the branch PAs (14 of 26, 54% vs. 18 of 61, 30%, p = .032) were associated with hemorrhage. CONCLUSIONS: Pulmonary hemorrhage was common in children with AGS undergoing both intervention and diagnostic cardiac catheterization, and was associated with TOF, higher RV to aorta pressure ratio, and interventions on the branch PAs.

Outcomes of Infants Supported With Extracorporeal Membrane Oxygenation Using Centrifugal Versus Roller Pumps: An Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To determine whether mortality differs between roller and centrifugal pumps used during extracorporeal membrane oxygenation in infants weighing less than 10 kg. DESIGN: Retrospective propensity-matched cohort study. SETTING: All extracorporeal membrane oxygenation centers reporting to the Extracorporeal Life Support Organization. PATIENTS: All patients less than 10 kg supported on extracorporeal membrane oxygenation during 2011-2016 within Extracorporeal Life Support Organization Registry. INTERVENTIONS: Centrifugal and roller pump recipients were propensity matched (1:1) based on predicted probability of receiving a centrifugal pump using demographic variables, indication for extracorporeal membrane oxygenation, central versus peripheral cannulation, and pre-extracorporeal membrane oxygenation patient management. MEASUREMENTS AND MAIN RESULTS: A total of 12,890 patients less than 10 kg were supported with extracorporeal membrane oxygenation within the Extracorporeal Life Support Organization registry during 2011-2016. Patients were propensity matched into a cohort of 8,366. Venoarterial and venovenous extracorporeal membrane oxygenation runs were propensity matched separately. The propensity-matched cohorts were similar except earlier year of extracorporeal membrane oxygenation (standardized mean difference, 0.49) in the roller pump group. Within the propensity-matched cohort, survival to discharge was lower in the centrifugal pump group (57% vs 59%; odds ratio, 0.91; 95% CI, 0.83-0.99; p = 0.04). Hemolytic, infectious, limb injury, mechanical, metabolic, neurologic, pulmonary, and renal complications were more frequent in the centrifugal pump group. Hemorrhagic complications were similar between groups. Hemolysis mediated the relationship between centrifugal pumps and mortality (indirect effect, 0.023; p < 0.001). CONCLUSIONS: In this propensity score-matched cohort study of 8,366 extracorporeal membrane oxygenation recipients weighing less than 10 kg, those supported with centrifugal pumps had increased mortality and extracorporeal membrane oxygenation complications. Hemolysis was evaluated as a potential mediator of the relationship between centrifugal pump use and mortality and met criteria for full mediation.

A Quality Bundle to Support High-Risk Pediatric Ventricular Assist Device Implantation.

Pediatric ventricular assist device (VAD) implantation outcomes are increasingly promising for children with dilated cardiomyopathy and advanced decompensated heart failure (ADHF). VAD placement in patients with clinical features such as complex congenital cardiac anatomy, small body size, or major comorbidities remains problematic. These comorbidities have been traditionally prohibitive for VAD consideration leaving these children as a treatment-orphaned population. Here we describe the quality bundle surrounding these patients with ADHF considered high risk for VAD implantation at our institution. Over a 7-year period, a quality bundle aimed at the peri-operative care for children with high-risk features undergoing VAD implantation was incrementally implemented at a tertiary children's hospital. Patients were considered high risk if they were neonates (< 30 days), had single-ventricle physiology, non-dilated cardiomyopathy, biventricular dysfunction, or significant comorbidities. The quality improvement bundle evolved to include (1) structured team-based peri-operative evaluation, (2) weekly VAD rounds addressing post-operative device performance, (3) standardized anticoagulation strategies, and (4) a multidisciplinary system for management challenges. These measures aimed to improve communication, standardize management, allow for ongoing process improvement, and incorporate principles of a high-reliability organization. Between January 2010 and December 2017, 98 patients underwent VAD implantation, 48 (49%) of which had high-risk comorbidities and a resultant cohort survival-to-transplant rate of 65%. We report on the evolution of a quality improvement program to expand the scope of VAD implantation to patients with high-risk clinical profiles. This quality bundle can serve as a template for future large-scale collaborations to improve outcomes in these treatment-orphaned subgroups.

Extracorporeal membrane oxygenation-supported cardiopulmonary resuscitation following stage 1 palliation for hypoplastic left heart syndrome.

OBJECTIVES: To report on survival from a large multicenter cohort of neonates with hypoplastic left heart syndrome requiring extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation after stage 1 palliation operation. DESIGN: Retrospective analysis of data from the Extracorporeal Life Support Organization data registry (1998 through 2013). We computed the survival to hospital discharge for neonates (age < 30 d) who required extracorporeal membrane oxygenation after stage 1 palliation and evaluated factors associated with mortality using multivariate logistic regression analysis. SETTING: Multicenter data reported to Extracorporeal Life Support Organization registry. PATIENTS: Infants with hypoplastic left heart syndrome after stage 1 palliation who received extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 307 extracorporeal membrane oxygenation runs in the setting of extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation in 293 neonates with hypoplastic left heart syndrome following stage 1 palliation operation. The median age at cannulation was 9 days (interquartile range, 5-14 d). Survival to hospital discharge was 36%. In univariate analysis, gestational age, weight, extracorporeal membrane oxygenation duration, presence of air embolism, hemorrhagic complications, renal failure, and pulmonary complications (pulmonary hemorrhage and pneumothorax) were all associated with nonsurvival. In multivariate analysis, lower body weight at cannulation (odds ratio, 3.9; 95% CI, 1.9-8.3), duration of the extracorporeal membrane oxygenation (odds ratio, 3.4; 95% CI, 1.9-7.3), and renal failure while on extracorporeal membrane oxygenation (odds ratio, 2; 95% CI, 1.2-3.5) increased odds of mortality. CONCLUSIONS: Mortality for neonates with hypoplastic left heart syndrome supported with extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation after stage 1 palliation is high. Lower body weight, increased duration of extracorporeal membrane oxygenation support, and renal failure increased mortality.

Pulmonary deadspace and postoperative outcomes in neonates undergoing stage 1 palliation operation for single ventricle heart disease.

OBJECTIVES: Increased pulmonary dead space fraction (VD/VT) has been associated with prolonged mechanical ventilation after surgery for congenital heart disease. The association of VD/VT with clinical outcomes in neonates undergoing stage 1 palliation for single ventricle congenital heart disease has not been reported. We describe changes in VD/VT, differences in VD/VT based on shunt type (right ventricle to pulmonary artery conduit vs modified Blalock-Taussing shunt) and association of VD/VT with postoperative outcomes in patients undergoing stage 1 palliation. DESIGN: Retrospective chart review for demographic, hemodynamics, outcome information, and VD/VT values were collected at 6-hour intervals during the first 48 postoperative hours in neonates undergoing stage 1 palliation. VD/VT was calculated using mixed expired CO2 (PeCO2) obtained from capnography and paired arterial blood gas CO2 values. SETTING: Cardiac ICU in a tertiary care pediatric hospital. PATIENTS: Newborns with single ventricle congenital heart disease undergoing stage 1 palliation during 2003-2004. MEASUREMENTS AND MAIN RESULTS: Of the 51 patients, 31 had right ventricle to pulmonary artery and 20 had Blalock-Taussing shunt. Although VD/VT was lower in the Blalock-Taussing shunt group over all time points (p = 0.02), maximal VD/VT on day 1 (0.49 ± 0.07) and on day 2 (0.46 ± 0.08) were not different between the shunt groups. VD/VT decreased significantly over time in both shunt groups (p = 0.001 for right ventricle to pulmonary artery; p < 0.001 for Blalock-Taussing shunt). Higher maximal VD/VT during first 48 postoperative hours was independently associated with fewer ventilator (ß = -26.6; p = 0.035) and hospital-free days in the first month after stage 1 palliation (ß = -40.4; p = 0.002) after adjusting for potential confounders in a multivariable linear regression model. CONCLUSIONS: Increased pulmonary dead space exists early after stage 1 palliation operation for single ventricle congenital heart disease. Higher VD/VT during the first 48 postoperative hours was associated with longer duration of ventilation and hospital LOS and may be a useful marker of postoperative outcomes in this population.

Short-Term Outcomes, Functional Status, and Risk Factors for Requiring Extracorporeal Life Support After Norwood Operation: A Single-Center Retrospective Study.

Patients requiring extracorporeal life support (ECLS) post-Norwood operation constitute an extremely high-risk group. We retrospectively described short-term outcomes, functional status, and assessed risk factors for requiring ECLS post-Norwood operation between January 2010 and December 2020 in a high-volume center. During the study period, 269 patients underwent a Norwood procedure of which 65 (24%) required ECLS. Of the 65 patients, 27 (41.5%) survived to hospital discharge. Mean functional status scale (FSS) score at discharge increased from 6.0 on admission to 8.48 (p < 0.0001). This change was primary in feeding (p < 0.0001) and respiratory domains (p = 0.017). Seven survivors (26%) developed new morbidity, and two (7%) developed unfavorable functional outcomes. In the regression analysis, we showed that patients with moderate-severe univentricular dysfunction on pre-Norwood transthoracic echocardiogram (odds ratio [OR] = 6.97), modified Blalock Taussig Thomas (m-BTT) shunt as source of pulmonary blood flow (OR = 2.65), moderate-severe atrioventricular valve regurgitation on transesophageal echocardiogram (OR = 8.50), longer cardiopulmonary bypass time (OR = 1.16), longer circulatory arrest time (OR = 1.20), and delayed sternal closure (OR = 3.86), had higher odds of requiring ECLS (p < 0.05). Careful identification of these risk factors is imperative to improve the care of this high-risk cohort and improve overall outcomes.

Clinical Predictive Tool for Pediatric Cardiac Patients on Extracorporeal Membrane Oxygenation Therapy and Ultrafiltration.

Fluid overload is common among pediatric cardiac patients receiving extracorporeal membrane oxygenation (ECMO) and is often treated with in-line ultrafiltration (UF) or continuous renal replacement therapy (CRRT). We assessed whether CRRT was associated with poor outcomes versus UF alone. Additionally, we identified characteristics associated with progression from UF to CRRT. Retrospective chart review of 131 patients age ≤18 years treated with ECMO at a single quaternary center. Data were collected to compare patient demographics, characteristics, and outcomes. A receiver operator curve (ROC) was used to create a tool predictive of the need for CRRT at the time of UF initiation. Patients who required CRRT had a higher creatinine and blood urea nitrogen at time of UF initiation ( p = 0.03 and p < 0.01), longer total ECMO duration ( p < 0.01), lower renal recovery incidence ( p = 0.02), and higher mortality ( p ≤ 0.01). Using ROC analysis, presence of ≤3 of 7 risk variables had a positive predictive value of 87.5% and negative predictive value of 50.0% for use of UF alone (area under the curve 0.801; 95% CI: 0.638-0.965, p = 0.002). Pediatric cardiac patients treated with ECMO and UF who require CRRT demonstrate worse outcomes versus UF alone. A novel clinical tool may assist in stratifying patients at UF initiation.

Functional Status Change Among Infants, Children, and Adolescents Following Extracorporeal Life Support: a Multicenter Report.

In our retrospective multicenter study of patients 0 to 18 years of age who survived extracorporeal life support (ECLS) between January 2010 and December 2018, we sought to characterize the functional status scale (FSS) of ECLS survivors, determine the change in FSS from admission to discharge, and examine risk factors associated with development of new morbidity and unfavorable outcome. During the study period, there were 1,325 ECLS runs, 746 (56%) survived to hospital discharge. Pediatric patients accounted for 56%. Most common ECLS indication was respiratory failure (47%). ECLS support was nearly evenly split between veno-arterial and veno-venous (51% vs . 49%). Median duration of ECLS in survivors was 5.5 days. Forty percent of survivors had new morbidity, and 16% had an unfavorable outcome. In a logistic regression, African American patients (OR 1.68, p = 0.01), longer duration of ECLS (OR 1.002, p = 0.004), mechanical (OR 1.79, p = 0.002), and renal (OR 1.64, p = 0.015) complications had higher odds of new morbidity. Other races (Pacific Islanders, and Native Americans) (OR 2.89, p = 0.013), longer duration of ECLS (OR 1.002, p = 0.002), and mechanical complications (OR 1.67, p = 0.026) had higher odds of unfavorable outcomes. In conclusion, in our multi-center 9-year ECLS experience, 56% survived, 40% developed new morbidity, and 84% had favorable outcome. Future studies with larger populations could help identify modifiable risk factors that could help guide clinicians in this fragile patient population.

Multidisciplinary Stroke Pathway for Children Supported With Ventricular Assist Devices.

Mechanical circulatory support (MCS), including ventricular assist device (VAD) support, is a leading cause of stroke in children; however, existing pediatric stroke recommendations do not apply to many pediatric VAD patients. We sought to develop a multidisciplinary pathway to improve timely and effective acute stroke care and examine the early performance of the pathway in expediting stroke care. Stakeholders from pediatric heart failure, cardiac intensive care, neurology, interventional radiology, neuroradiology, neurosurgery, pharmacy, and adult VAD care convened at Stanford University in August 2017 to discuss the challenges of providing high-quality acute stroke care to children on VAD support, and to develop multidisciplinary acute stroke pathways. Stakeholders identified multiple barriers to providing timely acute stroke care to pediatric VAD patients. These include delayed recognition of stroke, and lack of clarity related to the optimal imaging technique, when to emergently reverse antithrombotic therapy (AT), pediatric indications for thrombectomy and cranial decompression, and strategies to avoid unnecessary serial CTS. Four stroke pathways were created including evaluation and management of the pediatric patient with (1) an acute neurologic change before an imaging diagnosis; (2) an arterial ischemic stroke (AIS); (3) an intracerebral hemorrhage (ICH); and (4) a subdural hematoma (SDH). With the implementation of the stroke pathway, the median time-to-first-CT image decreased by 43 minutes from 66 to 23 minutes ( P < 0.001) while the proportion with a CT within 30 minutes increased from 0% to 67% ( P < 0.001). Despite a variety of challenges, multidisciplinary consensus can be achieved on a rapid stroke management pathway for children on VAD support that addresses important barriers to timely stroke care. Although too few stoke events occurred to differentiate clinical outcomes, the time-to-first-CT image was significantly shorter after pathway implementation.

Durability of Pulmonary Valve Replacement with Large Diameter Stented Porcine Bioprostheses.

There is limited information about durability of large diameter porcine bioprostheses implanted for pulmonary valve replacement (PVR). We studied patients who underwent surgical PVR from 2002-2019 with a stented porcine bioprosthetic valve (BPV) with a labeled size ≥27 mm. The primary outcome was freedom from reintervention. During the study period, 203 patients underwent PVR using a porcine BPV ≥27 mm, 94% of whom received a Mosaic valve (Medtronic Inc., Minneapolis, MN). Twenty patients underwent reintervention from 3.4-12.0 years after PVR: 5 surgical and 15 transcatheter PVR procedures. The indication for reintervention was regurgitation in 13 patients, stenosis in 2, mixed disease in 4, and endocarditis in 1. Estimated freedom from reintervention was 97±1% at 5 years and 82±4% at 10 years, and freedom from prosthesis dysfunction (moderate or severe regurgitation and/or a maximum Doppler gradient ≥50 mm Hg) over time was 91±2% at 5 years and 74±4% at 10 years. Younger age and smaller true valve diameter were associated with shorter freedom from reintervention, but valve oversizing was not. The durability of large stented porcine bioprostheses in the pulmonary position is generally excellent, particularly in adolescents and adults, similar to various other types of BPV. In the current study, relative valve size was not associated with valve longevity, although the low event-rate in this population was a limiting factor.

Adverse Events Associated with Cardiac Catheterization in Children Supported with Ventricular Assist Devices.

Children on ventricular assist device (VAD) support can present several unique challenges, including small patient size, univentricular or biventricular congenital heart disease (1V- or 2V-CHD) and need for biventricular VAD (BiVAD) support. While cardiac catheterization can provide valuable information, it is an invasive procedure with inherent risks. We sought to evaluate the safety of catheterization in pediatric patients on VAD support. We performed a retrospective review of patients on VAD support who underwent catheterization at Lucile Packard Children's Hospital between January 1, 2014 and September 1, 2019. Using definitions adapted from Pedimacs, adverse events (AEs) after catheterization were identified, including arrhythmia; major bleeding or acute kidney injury within 24 hours; respiratory failure persisting at 24 hours; and stroke, pericardial effusion, device malfunction, bacteremia or death within 7 days. AEs were categorized as related or unrelated to catheterization. Sixty procedures were performed on 39 patients. Underlying diagnoses were dilated cardiomyopathy (48%), 1V-CHD (35%), 2V-CHD (8%), and other (8%). Devices were implantable continuous flow (72%), paracorporeal pulsatile (18%) and paracorporeal continuous flow (10%). Catheterizations were performed on patients in the ICU (60%), on inotropic support (42%), with deteriorating clinical status (37%) and on BiVAD support (12%). There were 9 AEs possibly related to catheterization including 6 episodes of respiratory failure, 2 major bleeding events, and 1 procedural arrhythmia. AE occurrence was associated with ICU status ( P = 0.01), BiVAD support ( P = 0.04) and procedural indication to evaluate worsening clinical status ( P = 0.04). Despite high medical acuity, catheterization can be performed with an acceptable AE profile in children on VAD support.

Perioperative care of the infant with single ventricle physiology.

OPINION STATEMENT: Among patients with congenital heart defects, neonates with single ventricle disease continue to challenge clinicians despite significant improvements in survival over the past 30 years. The cardiac anatomical variants associated with the term "single ventricle" are characterized by severe hypoplasia (or absence) of either ventricle, typically in association with obstruction or atresia of either the pulmonary or systemic outflow tracts. Physiologically, the single ventricle receives both pulmonary and systemic venous blood and ejects simultaneously into the pulmonary and systemic circulations, a pattern commonly referred to as single ventricle physiology. Medical and surgical management strategies, though palliative, are aimed at achieving the optimal balance of systemic blood flow and pulmonary blood flow to maximize oxygen delivery. Patients with single ventricle physiology have a greater risk of dying than those with biventricular circulations and are generally committed to multiple palliative interventions throughout childhood with considerable risk. Surgical intervention in the newborn period involves Norwood Stage I palliation, placement of a systemic-to-pulmonary artery shunt, or banding of the pulmonary artery, depending on the status of the outflow tracts. Heart transplantation is offered as the initial approach in some centers. The management strategy and the actual delivery of care from the time of birth (or at time of diagnosis) through the postoperative period is crucial to optimize the short-term and long-term outcomes. Whereas survival following initial palliation in experienced centers is as high as 95%, emphasis is now appropriately shifting toward the control of in-hospital morbidity and optimizing long-term functional outcome. Centers are continually striving to gather and apply new knowledge related to the underlying anatomical and physiologic problems while seeking to improve decision making and care of the patient with single ventricle physiology.

Single Ventricular Assist Device Support for the Failing Bidirectional Glenn Patient.

BACKGROUND: Given poor outcomes, strategies to improve ventricular assist devices (VADs) for single-ventricle patients with bidirectional Glenn (BDG) palliation are needed. METHODS: This retrospective review describes an institutional experience with VAD support for patients with BDG from April 2011 to January 2019. Surgical strategies, complications, and causes of death are described. Survival to heart transplantation for various strategies are compared. RESULTS: A total of 7 patients with BDG (weights, 5.6 to 28.8 kg; ages, 7 months to 11 years) underwent VAD implantation. Three patients underwent implantation of Berlin Heart EXCOR devices (Berlin Heart, Inc, Spring, TX), 2 had HeartWare HVADs (Medtronic, Minneapolis, MN) implanted, and 2 patients underwent implantation of paracorporeal continuous flow devices. Four patients underwent ventricular inflow cannulation, and 3 underwent atrial inflow cannulation. At the time of VAD implantation, the BDG was left intact in 3 patients, taken down in 3 patients, and created de novo in 1 patient. Over a total of 420 VAD support days, 2 patients survived to heart transplantation, 1 patient with HeartWare ventricular cannulation and intact BDG (after 174 days) and another with Berlin Heart atrial cannulation and BDG take-down (after 72 days). There were 3 deaths within 2 weeks of VAD implantation (2 from respiratory failure, 1 from infection) and 2 deaths after 30 days as a result of strokes. CONCLUSIONS: The surgical strategy and postoperative management of VAD with BDG are still evolving. Successful support can be achieved with (1) both pulsatile and continuous flow pumps, (2) atrial or ventricular cannulation, and (3) with or without BDG take-down. Surgical strategy should be determined by individual patient anatomy, physiology, and condition.

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

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

The Stanford acute heart failure symptom score for patients hospitalized with heart failure.

BACKGROUND: Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials. METHODS: Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019. RESULTS: The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%). CONCLUSION: This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

Impact of Phrenic Nerve Palsy and Need for Diaphragm Plication Following Surgery for Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals.

Injury to the phrenic nerves may occur during surgery for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA-VSD and MAPCAs). These patients may develop respiratory failure and require diaphragm plication. The purpose of this study was to evaluate the impact of phrenic nerve palsy on recovery following surgery for PA-VSD and MAPCAs. Between 2007 and 2016, approximately 500 patients underwent surgery for PA-VSD and MAPCAs at our institution. Twenty-four patients (4.8%) subsequently had evidence of new phrenic nerve palsy. Sixteen patients were undergoing their first surgical procedure, whereas 8 were undergoing reoperations. All 24 patients underwent diaphragm plication. A cohort of matched controls was identified based on identical diagnosis and procedures but did not sustain a phrenic nerve palsy. Eighteen of the 24 patients (75%) had clinical improvement following diaphragm plication as evidenced by the ability to undergo successful extubation (5 ± 2 days), transition out of the intensive care unit (32 ± 16 days), and discharge from the hospital (42 ± 19 days). In contrast, there were 6 patients (25%) who did not demonstrate a temporal improvement following diaphragm plication, as evidenced by intervals of 61 ± 38, 106 ± 45, and 108 ± 46 days, respectively (P < 0.05 for all 3 comparisons). The 6 patients who failed to improve following diaphragm plication had a significantly greater number of comorbidities compared to the 18 patients who demonstrated improvement (2.2 vs 0.6 per patient, P < 0.05). When compared with the control group, patients who improved following diaphragm plication spent an additional 22 days and patients who failed to improve an additional 90 days in the hospital. The data demonstrate a bifurcation of clinical outcome in patients undergoing diaphragm plication following surgery for PA-VSD and MAPCAs. This bifurcation appears to be linked to the presence or absence of other comorbidities.

Applying Lessons from an Inaugural Clinical Pathway to Establish a Clinical Effectiveness Program.

INTRODUCTION: Clinical effectiveness (CE) programs promote standardization to reduce unnecessary variation and improve healthcare value. Best practices for successful and sustainable CE programs remain in question. We developed and implemented our inaugural clinical pathway with the aim of incorporating lessons learned in the build of a CE program at our academic children's hospital. METHODS: The Lucile Packard Children's Hospital Stanford Heart Center and Center for Quality and Clinical Effectiveness partnered to develop and implement an inaugural clinical pathway. Project phases included team assembly, pathway development, implementation, monitoring and evaluation, and improvement. We ascertained Critical CE program elements by focus group discussion among a multidisciplinary panel of experts and key affected groups. Pre and postintervention compared outcomes included mechanical ventilation duration, cardiovascular intensive care unit, and total postoperative length of stay. RESULTS: Twenty-seven of the 30 enrolled patients (90%) completed the pathway. There was a reduction in ventilator days (mean 1.0 + 0.5 versus 1.9 + 1.3 days; P < 0.001), cardiovascular intensive care unit (mean 2.3 + 1.1 versus 4.6 + 2.1 days; P < 0.001) and postoperative length of stay (mean 5.9 + 1.6 versus 7.9 + 2.7 days; P < 0.001) compared with the preintervention period. Elements deemed critical included (1) project prioritization for maximal return on investment; (2) multidisciplinary involvement; (3) pathway focus on best practices, critical outcomes, and rate-limiting steps; (4) active and flexible implementation; and (5) continuous data-driven and transparent pathway iteration. CONCLUSIONS: We identified multiple elements of successful pathway implementation, that we believe to be critical foundational elements of our CE program.