Genetic Testing Resources and Practice Patterns Among Pediatric Cardiomyopathy Programs.

The use of genetic testing has enhanced the diagnostic accuracy of heritable genetic cardiomyopathies. However, it remains unclear how genetic information is interpreted and incorporated into clinical practice for children with cardiomyopathy. The primary aim of this study was to understand how clinical practice differs regarding sequence variant classifications amongst pediatric cardiologists who treat children with cardiomyopathy. A secondary aim was to understand the availability of genetic testing and counseling resources across participating pediatric cardiomyopathy programs. An electronic survey was distributed to pediatric heart failure, cardiomyopathy, or heart transplantation physicians between August and September 2022. A total of 106 individual providers from 68 unique centers responded to the survey. Resources for genetic testing and genetic counseling vary among large pediatric cardiomyopathy programs. A minority of centers reported having a geneticist (N = 16, 23.5%) or a genetic counselor (N = 21, 31%) on faculty within the division of pediatric cardiology. A total of 9 centers reported having both (13%). Few centers (N = 13, 19%) have a formal process in place to re-engage patients who were previously discharged from cardiology follow-up if variant reclassification would alter clinical management. Clinical practice patterns were uniform in response to pathogenic or likely pathogenic variants but were more variable for variants of uncertain significance. Efforts to better incorporate genetic expertise and resources into the clinical practice of pediatric cardiomyopathy may help to standardize the interpretation of genetic information and better inform clinical decision-making surrounding heritable cardiomyopathies.

Cardiac imaging and biomarkers for assessing myocardial fibrosis in children with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis, as diagnosed on cardiac magnetic resonance imaging (cMRI) by late gadolinium enhancement (LGE), is associated with adverse outcomes in adults with hypertrophic cardiomyopathy (HCM), but its prevalence and magnitude in children with HCM have not been established. We investigated: (1) the prevalence and extent of myocardial fibrosis as detected by LGE cMRI; (2) the agreement between echocardiographic and cMRI measurements of cardiac structure; and (3) whether serum concentrations of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-T are associated with cMRI measurements. METHODS: A cross-section of children with HCM from 9 tertiary-care pediatric heart centers in the U.S. and Canada were enrolled in this prospective NHLBI study of cardiac biomarkers in pediatric cardiomyopathy (ClinicalTrials.gov Identifier: NCT01873976). The median age of the 67 participants was 13.8 years (range 1-18 years). Core laboratories analyzed echocardiographic and cMRI measurements, and serum biomarker concentrations. RESULTS: In 52 children with non-obstructive HCM undergoing cMRI, overall low levels of myocardial fibrosis with LGE >2% of left ventricular (LV) mass were detected in 37 (71%) (median %LGE, 9.0%; IQR: 6.0%, 13.0%; range, 0% to 57%). Echocardiographic and cMRI measurements of LV dimensions, LV mass, and interventricular septal thickness showed good agreement using the Bland-Altman method. NT-proBNP concentrations were strongly and positively associated with LV mass and interventricular septal thickness (P < .001), but not LGE. CONCLUSIONS: Low levels of myocardial fibrosis are common in pediatric patients with HCM seen at referral centers. Longitudinal studies of myocardial fibrosis and serum biomarkers are warranted to determine their predictive value for adverse outcomes in pediatric patients with HCM.

Single-drug immunosuppression is associated with noninferior medium-term survival in pediatric heart transplant recipients.

BACKGROUND: Patients are usually maintained on at least 2 immunosuppressive drugs (ISDs) after the first year post heart transplant. Anecdotally, some children are switched to single-drug monotherapy (a single ISD) for various reasons and varying durations. Outcomes associated with differences in immunosuppression after heart transplantation are unknown for children. OBJECTIVES: A priori we defined a noninferiority hypothesis for monotherapy compared to ≥2 ISDs. The primary outcome was graft failure, a composite of death and retransplantation. Secondary outcomes included rejection, infection, malignancy, cardiac allograft vasculopathy and dialysis. METHODS: This international, multicenter, retrospective, observational cohort study used data from the Pediatric Heart Transplant Society. We included patients who underwent first-time heart transplant <18 years of age between 1999 and 2020 with ≥1 year of follow-up data available. RESULTS: Our analysis included 3493 patients with a median time post-transplant of 6.7 years. There were 893 patients (25.6%) switched to monotherapy at least once with the remaining 2600 patients always on ≥2 ISDs. The median time on monotherapy after the first year post-transplant was 2.8 years (range 1.1-5.9 years). We found an adjusted hazard ratio (HR) of 0.65 (95%CI: 0.47-0.88) favoring monotherapy compared to ≥2 ISDs (p = 0.002). There were no meaningful differences in the incidence of secondary outcomes between groups, except for a lower rate of cardiac allograft vasculopathy in patients on monotherapy (HR 0.58, 95%CI: 0.45-0.74). CONCLUSIONS: For pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was noninferior to standard therapy with ≥2 ISDs in the medium term. CONDENSED ABSTRACT: Some children are switched to a single immunosuppressive drug (ISD) for various reasons after heart transplant, but outcomes associated with differences in immunosuppression are unknown for children. We assessed graft failure in children on a single ISD (monotherapy) compared to ≥2 ISDs in a cohort of 3493 children with a first heart transplant. We found an adjusted hazard ratio of 0.65 (95%CI: 0.47-0.88) favoring monotherapy. We concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was non-inferior to standard therapy with ≥2 ISDs in the medium term.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children.

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein-as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens-are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

Intraventricular Septation in the Context of Dilated Cardiomyopathy Associated With TTN Mutation.

A 6-month-old infant boy presented with symptomatic heart failure. Dilated cardiomyopathy was found in association with a mutation in TTN. Structural heart disease included novel septation of the left ventricle with a fenestrated membrane resulting from aberrant congenital mitral valve apparatus formation. (Level of Difficulty: Advanced.).

Heterogeneous outcomes of liver disease after heart transplantation for a failed Fontan procedure.

BACKGROUND: Fontan-associated liver disease (FALD) uniformly affects patients with long-term Fontan physiology. The effect of isolated heart transplant (HT) on the course of FALD post-HT is not well understood. METHODS: We evaluated serial liver imaging pre- and post-HT to assess liver changes over time in a single-center retrospective analysis of Fontan HT recipients who had pre- and ≥1-year post-HT liver imaging. Available patient demographic and clinical data were reviewed, including available liver biopsy results. RESULTS: Serial liver imaging was available in 19 patients with a median age at HT of 12 years (range 3-23), the median age from Fontan to HT of 5.7 years (range 0.8-16), and the median time from imaging to follow up of 27 months (range 12-136 months). Pre-HT liver imaging was classified as follows: normal (n=1), congested (n=9), fibrotic (n=7), and cirrhotic (n=2). The majority of transplanted patients (15/19) had improvement in their post-HT liver imaging, including 13 patients with initially abnormal imaging pre-HT having normal liver imaging at follow-up. One patient had persistent cirrhosis at 26-month follow-up, one patient had unchanged fibrosis at 18-month follow-up, and one patient progressed from fibrosis pre-HT to cirrhosis post-HT at 136 months. No patients had overt isolated liver failure during pre- or post-HT follow-up. Liver biopsy did not consistently correlate with imaging findings. CONCLUSIONS: Post-HT liver imaging evaluation in Fontan patients reveals heterogeneous liver outcomes. These results not only provide evidence for the improvement of FALD post-HT but also show the need for serial liver imaging follow-up post-HT.

Clinical outcomes of children receiving ABO-incompatible versus ABO-compatible heart transplantation: a multicentre cohort study.

BACKGROUND: ABO-incompatible heart transplantation increases donor availability in young children and is evolving into standard of care in children younger than 2 years. Previous smaller studies suggest similar outcomes to ABO-compatible heart transplantation, but persisting alterations of the immune system in ABO-incompatible recipients might increase the risk of some infections or benefit the graft owing to reduced HLA reactivity. We aimed to assess long-term outcomes in young children after they received ABO-incompatible or ABO-compatible heart transplantation. METHODS: In this multicentre, prospective cohort study, we analysed data from the Pediatric Heart Transplant Society registry to compare children who received ABO-incompatible or ABO-compatible heart transplantation before age 2 years between Jan 1, 1999, and June 30, 2018. Given significantly different clinical demographics between the two groups, we also matched each ABO-incompatible recipient to two ABO-compatible recipients using propensity score matching. We assessed patient and graft survival, coronary allograft vasculopathy, malignancy, acute rejection (any episode resulting in augmentation of immunosuppression), and infections (requiring intravenous antibiotic or antiviral therapy or life-threatening infections treated with oral therapy). FINDINGS: We included 2206 children who received a heart transplant before age 2 years, with 11 332·6 patient-years of cumulative observation time. Children who received an ABO-incompatible transplant (n=364) were younger and a larger proportion had congenital heart disease and ventilator and mechanical circulatory support than the ABO-compatible recipients (n=1842). After matching, only differences in blood group (more O in ABO-incompatible and more AB in ABO-compatible groups) and use of polyclonal induction therapy with anti-thymocyte globulins persisted. The two matched groups had similar post-transplantation graft survival (p=0·74), freedom from coronary allograft vasculopathy (p=0·75), and malignancy (p=0·51). ABO-incompatible recipients showed longer freedom from rejection (p=0·0021) in the overall cohort, but not after matching (p=0·48). Severe infections (p=0·0007), bacterial infections (p=0·0005), and infections with polysaccharide encapsulated bacteria (p=0·0005) that share immunological properties with blood group antigens occurred less frequently after ABO-incompatible heart transplantation. INTERPRETATION: ABO-incompatible heart transplantation for children younger than 2 years is a clinically safe approach, with similar survival and incidences of rejection, coronary allograft vasculopathy, and malignancy to ABO-compatible recipients, despite higher-risk pre-transplant profiles. ABO-incompatible transplantation was associated with less bacterial infection, particularly encapsulated bacteria, suggesting that the acquired immunological changes accompanying ABO tolerance might benefit rather than jeopardise transplanted children. FUNDING: Pediatric Heart Transplant Society.

Altered Biatrial Phasic Function after Heart Transplantation in Children.

PURPOSE: We used two-dimensional echocardiographic speckle-tracking to investigate whether left and right atrial (LA and RA) phasic function in pediatric heart transplantation (HT) patients is altered and explored the relationship to HT-related clinical variables. METHODS: Eighty-six subjects (36 HT and 50 normal children) were prospectively enrolled in two centers. Clinical data included age at HT, bypass time, ischemia time, donor age, and incidence of rejection. Atrial deformation indices including strain and strain rates (SRs) were measured using two-dimensional echocardiographic speckle-tracking. Components of phasic atrial function-reservoir (εr, SRr), conduit (εcd, SRcd), and booster (εct, SRct) were calculated. Comparisons with controls were made using t test or Kruskal-Wallis test, and correlations to clinical variables were explored. RESULTS: The mean age and body surface area of HT subjects were 10.2 ± 6.2 years and 1.2 ± 0.6 m2, respectively. The mean heart rates were higher in HT (96 ± 18 vs 88 ± 21 in controls). There were reductions in RA and LA reservoir (εr, SRr), conduit (εcd, SRcd), and booster (εct, SRct) function in HT compared with controls. There was no relationship of LA and RA deformation indices with mean age at HT, bypass time, or ischemia time. The LA εcd correlated weakly with donor age (r = -0.49, P = .04) and RA SRr, and SRcd showed association with duration of HT (P < .05). Nineteen HT recipients had follow-up studies 0.24 ± 0.18 years after the first examination, and deformational indices were not significantly changed. CONCLUSIONS: Atrial strain determination is feasible in pediatric HT recipients and demonstrates disruption of reservoir, conduit, and booster function of both atria in this population; we speculate this may be a consequence of ventricular diastolic dysfunction.

A current era analysis of ABO incompatible listing practice and impact on outcomes in young children requiring heart transplantation.

BACKGROUND: Heart transplantation from ABO incompatible (ABOi) donors has evolved into a progressively accepted therapy in young children. We assessed the recent practice of ABOi listing impact on waitlist and post-transplant outcomes. METHODS: Using the Pediatric Heart Transplant Society registry, we compared clinical presentation, waitlist parameters, and post-transplant survival of children < 2 years of age listed for ABOi vs ABO compatible (ABOc) heart transplant between January 2010 and June 2018 with sub-analysis of blood group O recipients. RESULTS: Among 2,039 patients, ABOi listing increased significantly with time from 49% (2010) to 72% (2017). ABOi-listed patients had lower age and body surface area, and higher proportion of congenital heart disease, mechanical ventilation, and high urgency status (all p < 0.01). Use of mechanical circulatory support was similar between groups. Of 1,288 patients reaching transplant, 239 (18.6%) received an ABOi organ (15%-40%/year). Death while waiting, removal from the waitlist, and waitlist survival were similar between groups. Time to transplant was significantly shorter for ABOi listing in blood group O patients (p < 0.02), approaching significance (p = 0.057) for all blood groups. Post-transplant survival was similar except for lower survival of patients listed ABOc but transplanted ABOi. These patients showed increasing need for mechanical circulatory support and high urgency listing while waiting. CONCLUSIONS: In the current era, primary listing for ABOi heart transplant has become routine for the majority of children < 2 years old, resulting in shorter waitlist time, especially in blood group O. Post-transplant survival is similar despite ABOi-listed children still showing a higher risk profile.

Review of the impact of donor characteristics on pediatric heart transplant outcomes.

Heart transplantation (HTx) is a treatment option for end-stage heart failure in children. HTx is limited by the availability and acceptability of donor hearts. Refusal of donor hearts has been reported to be common with reasons for refusal including preexisting donor characteristics. This review will focus on the impact of donor characteristics and comorbidities on outcomes following pediatric HTx. A literature review was performed to identify articles on donor characteristics and comorbidities and pediatric HTx outcomes. There are many donor characteristics to consider when accepting a donor heart. Weight-based matching is the most common form of matching in pediatric HTx with a donor-recipient weight ratio between 0.7 and 3 having limited impact on outcomes. From an age perspective, donors <50 years can be carefully considered, but the impact of ischemic time needs to be understood. To increase the donor pool, with minimal impact on outcomes, ABO-incompatible donors should be considered in patients that are eligible. Other factors to be considered when accepting an organ is donor comorbidities. Little is known about donor comorbidities in pediatric HTx, with most of the data available focusing on infections. Being aware of the potential infections in the donor, understanding the testing available and risks of transmission, and treatment options for the recipient is essential. There are a number of donor characteristics that potentially impact outcomes following pediatric HTx, but these need to be taken into consideration along with their interactions with recipient factors when interpreting the outcomes following HTx.

Vasopressin After the Fontan Operation.

BACKGROUND: Prolonged pleural effusion following Fontan operation is common and increases morbidity and hospital length of stay. Vasopressin (VP), a neurohypophysial hormone, has numerous effects on the cardiovascular system. The most notable is increased peripheral vascular resistance, but it may also reduce capillary leakage by tightening endothelial intercellular junctions and reducing capillary hydrostatic pressure We reviewed our experience with the perioperative administration of VP following Fontan operation. METHODS: We retrospectively reviewed the records of 62 consecutive patients who underwent Fontan operation from January 2004 to June 2014. In January 2010, VP was introduced as part of the standard perioperative management of patients undergoing Fontan operation at our center. For this retrospective observational study, patients were grouped according to the use (VP; N = 40) or nonuse (non-VP; N = 22) of VP (0.3-0.5 mU/kg/min) in the perioperative period. The primary end point analyzed was chest tube output. Secondary end points analyzed included fluid balance and length of hospital stay, with groups compared using Mann-Whitney U test. RESULTS: There was no hospital mortality. Median total chest tube output was 22 mL/kg in the VP group and 68 mL/kg in the non-VP group (P < .001). The median total duration of chest tube indwelling time was five days in the VP group and was 11 days in the non-VP group (P < .001). Median fluid balance on first postoperative day was 13 and 38 mL/kg, respectively (P < .001). Median hospital stay for VP and non-VP groups was 9 and 16 days, respectively (P = .002). CONCLUSIONS: The more recent group of patients undergoing Fontan operations, all of whom received VP perioperatively, had less chest tube output and shorter duration of chest tube drainage after the Fontan operation relative to the earlier patient group whose perioperative management did not include VP. They also experienced less positive fluid balance in the early postoperative period and shorter hospital length of stay than the patients from the earlier era.

Iatrogenic pseudoaneurysm of the innominate artery in a neonate.

A 2.8-kg infant underwent urgent repair of a large iatrogenic pseudoaneurysm of the innominate artery, which was compressing the airway and superior vena cava, creating critical respiratory instability. The pseudoaneurysm was repaired with complete resolution of all respiratory symptoms.

Surgical Decision Making in Neonatal Ebstein's Anomaly: An Algorithmic Approach Based on 48 Consecutive Neonates.

OBJECTIVE: There is currently no consensus of opinion regarding the optimal surgical management of Ebstein's anomaly (EA) in neonates and young infants. Reported early mortality rates range from 25% to 100%. In this study, we present an algorithm for choosing the best management option for neonates with EA based on analysis of our experience. PATIENTS AND METHODS: From 1994 to June, 2011, 48 neonates with a diagnosis of EA were managed by the same surgical team. Of these, two died before intervention; the remaining 46 either were managed medically initially (n = 20) or underwent surgical intervention during the neonatal period (n = 26) or early infancy (n = 9). RESULTS: The mean weight was 3.6 ± 1.7 kg (1.9-8.6) and mean follow-up time was 6.3 ± 4.5 years (0.2-16). Of the 20 patients initially managed medically, 11 remain well without intervention and nine required complete repair in infancy, with 100% survival. Of the 26 neonatal operations, 23 (88%) were complete biventricular repairs, 1 Starnes' palliation, and two Blalock-Taussig shunts (BTSs) ± pulmonary valvotomy. Among those having a two-ventricle repair, anatomic pulmonary atresia (APA) was a risk factor for early mortality (46.1%, 6 of 13) compared with those without pulmonary atresia (EA/no-PA; 10%, 1 of 10), P < .05. CONCLUSIONS: Most symptomatic neonates with EA will require early operation. For those with APA and mild tricuspid regurgitation (TR), a modified BTS and reduction atrioplasty may be the best initial option. For those with functional pulmonary atresia and severe TR and pulmonary regurgitation, ligation of the main pulmonary artery and placement of a BTS may provide the best initial palliation. For the rest, either a biventricular repair or a single-ventricle palliation is indicated.

Apical Left Ventriculotomy is Safe in Infants and Young Children Requiring Cardiac Surgery.

OBJECTIVES: Incisions in the left ventricle have previously been associated with increased mortality and morbidity, particularly in infants. In order to determine whether this assumption is still true in the current era, we reviewed our recent experience with apical left ventriculotomy in neonates and infants. METHODS: The records of five consecutive patients requiring a left ventriculotomy between 2007 and 2010 were reviewed. Weight and age ranged from 2.6 to 16 kilograms and 5 days to 2 years. The diagnoses were three multiple ventricular septal defects, one rhabdomyoma, and one apical aneurysm. The primary end point was left ventricular ejection fraction, with other end points being intensive care unit length of stay, time to extubation, inotrope requirement, arrhythmias, and mitral valve function. RESULTS: There were no early or late deaths. Although lower than their preoperative values, early postoperative ejection fractions were greater than 50% in all patients. Two patients required no inotropes, and 3 required only minimal support. Hospital length of stay was 9 ± 7 days for multiple ventricular septal defect patients, with intensive care unit stays of 2 to 5 days. There were no postoperative arrhythmias requiring pharmacological therapy, and one patient had a significant reduction in mitral insufficiency postoperatively. CONCLUSIONS: Based on our experience, we believe that an apical left ventriculotomy does not significantly impair left ventricular function even in small infants, and is not associated with significant morbidity, based on short-term follow-up. Although the long-term effects are still unknown, early results suggest that a left ventriculotomy may safely be used when alternative approaches are inadequate for complex cardiac defects.

Early systemic-to-pulmonary artery shunt intervention in neonates with congenital heart disease.

OBJECTIVE: To determine the incidence, risk factors, and outcomes after early, unplanned intervention on systemic-to-pulmonary artery shunts in neonates. METHODS: We retrospectively studied all neonates undergoing systemic-to-pulmonary artery shunt placement at The Children's Hospital of Philadelphia between September 1, 2002, and May 1, 2005. Patients requiring transcatheter or surgical systemic-to-pulmonary artery shunt intervention before discharge were compared with those not undergoing shunt intervention. RESULTS: A total of 206 patients underwent shunt placement. Diagnoses included hypoplastic left heart syndrome (62.1%), pulmonary atresia (15%), tricuspid atresia (4.9%), tetralogy of Fallot (2.4%), and other lesions with obstruction to systemic (10.7%) or pulmonary blood flow (4.9%). Twenty-one interventions occurred in 20 patients (9.7%). Risk factors for intervention included heterotaxy syndrome (P = .04), congenital abnormality (P = .04), and a trend toward lower birthweight. In patients with a modified Blalock-Taussig shunt, similar risk factors were identified and the incidence of intervention decreased with increasing shunt size. In-hospital mortality was 30% (6/20) for the cases and 8.1% (15/186) for the nonintervention group (P = .02). Long-term survival was significantly lower in patients requiring intervention (P = .002). This group also had a higher incidence of infections (P < .001) and extracorporeal membrane oxygenation (P < .001), and longer hospital stay (P = .001). CONCLUSIONS: In neonates undergoing systemic-to-pulmonary artery shunt placement, approximately 10% underwent shunt intervention before discharge. Some factors, such as low birthweight, shunt size, noncardiac congenital abnormalities, and heterotaxy syndrome, may help identify patients at risk. Patients undergoing intervention experienced increased morbidity and mortality.

A contemporary comparison of the effect of shunt type in hypoplastic left heart syndrome on the hemodynamics and outcome at Fontan completion.

OBJECTIVE: We previously reported no difference in morbidity or mortality in a cohort of infants undergoing stage 1 and 2 reconstructions for hypoplastic left heart syndrome with either a modified Blalock-Taussig shunt or a right ventricular to pulmonary artery conduit. This article compares the hemodynamics and perioperative course at the time of the Fontan completion and reports longer-term survival for this cohort. METHODS: We retrospectively reviewed the hospital records of all patients who underwent stage 1 reconstruction between January 2002 and May 2005 and subsequent surgical procedures, as well as cross-sectional analysis of hospital survivors. RESULTS: A total of 176 patients with hypoplastic left heart syndrome or a variant underwent stage 1 reconstruction with either modified Blalock-Taussig shunt (n = 114) or right ventricular to pulmonary artery conduit (n = 62). Shunt selection was at the discretion of the surgeon. The median duration of follow-up was 58 months (range 1-87 months). By Kaplan-Meier analysis, shunt type did not influence survival or freedom from transplant at 5 years (right ventricular to pulmonary artery conduit 61%; 95% confidence limit, 47-72 vs modified Blalock-Taussig shunt 70%; 95% confidence limit, 60-77; P = .55). A total of 107 patients underwent Fontan (69 modified Blalock-Taussig shunts and 38 right ventricular to pulmonary artery conduits) with 98% (105/107) early survival. Patients with a right ventricular to pulmonary artery conduit shunt pre-Fontan had higher pulmonary artery (13 +/- 8 mm Hg vs 11 +/- 3 mm Hg, P = .026) and common atrial (8 +/- 2.3 mm Hg vs 6.8 +/- 2.7 mm Hg, P = .039) pressures. By echocardiography evaluation, there was more qualitative moderate to severe ventricular dysfunction (right ventricular to pulmonary artery conduit 31% [12/36] vs modified Blalock-Taussig shunt 17% [11/67], P = .05) and moderate to severe atrioventricular valve regurgitation (right ventricular to pulmonary artery conduit 40% [14/35] vs modified Blalock-Taussig shunt 16% [11/67], P = .01) in the right ventricular to pulmonary artery conduit group. Use of diuretic therapy, angiotensin-converting enzyme inhibition, reflux medications, and tube feedings were not different between groups. Overall, 5 patients underwent heart transplantation (right ventricular to pulmonary artery conduit 4 vs modified Blalock-Taussig shunt 1, P = .1) before Fontan. There was no difference in age or weight at Fontan, bypass time, intensive care unit or hospital length of stay, postoperative pleural effusions, or need for reoperation between groups. CONCLUSIONS: Interim analyses continue to suggest there is no survival advantage of one shunt type compared with the other. Longer-term follow-up of a randomized patient population remains of utmost importance.

Reintervention for arch obstruction after stage 1 reconstruction does not adversely affect survival or outcome at Fontan completion.

OBJECTIVE: To determine the effect of reintervention for coarctation after stage 1 reconstruction for hypoplastic left heart syndrome and variants on survival, suitability for Fontan, and morbidity at Fontan. METHODS: A retrospective review of echocardiograms, catheterizations, hospital records of patients who underwent stage 1 reconstruction from January 2002 to May 2005, with a cross-sectional analysis of hospital survivors, was performed. Kaplan-Meier curves were derived for patients alive more than 30 days after stage 1 reconstruction. RESULTS: A total of 176 patients underwent stage 1 reconstruction. Forty-three patients (23%) underwent balloon angioplasty (n = 43) or surgical intervention (n = 4) for re-coarctation. Median time to intervention was 123 (1-316) days. Seven of 43 patients (16%) underwent more than 1 balloon angioplasty. Thirty-nine patients underwent intervention before stage 2 reconstruction, and 4 patients had intervention between stage 2 reconstruction and Fontan. Kaplan-Meier curves showed no difference in freedom from death or transplant between patients who did and did not undergo intervention for re-coarctation. Fontan completion was performed in 107 patients. By echocardiogram, the prevalence of moderate to severe ventricular dysfunction between groups was similar at Fontan; however, significant atrioventricular valve regurgitation was more common in patients who required intervention (28/33 vs 40/65, P = .02). Overall Fontan mortality was 2% and not different between groups. Length of stay was not different between patients with and without re-coarctation. CONCLUSIONS: Reintervention for coarctation after stage 1 reconstruction is common. Hemodynamic differences between groups did not affect Fontan completion, mortality, or hospital length of stay. Follow-up is necessary to determine the impact of re-coarctation on longer-term mortality and morbidity.

Hyperglycaemia after Stage I palliation does not adversely affect neurodevelopmental outcome at 1 year of age in patients with single-ventricle physiology.

OBJECTIVE: Hyperglycaemia has been associated with worse outcome following traumatic brain injury and cardiac surgery in adults. We have previously reported no relationship between early postoperative hyperglycaemia and worse neurodevelopmental outcome at 1 year following biventricular repair of congenital heart disease. It is not known if postoperative hyperglycaemia results in worse neurodevelopmental outcome after infant cardiac surgery for single-ventricle lesions. METHODS: Secondary analysis of postoperative glucose levels in infants <6 months of age undergoing Stage I palliation for various forms of single ventricle with arch obstruction. The patients were enrolled in a prospective study of genetic polymorphisms and neurodevelopmental outcomes assessed at 1 year of age with the Bayley Scales of Infant Development-II yielding two indices: mental developmental index (MDI) and psychomotor developmental index (PDI). RESULTS: Stage I palliation was performed on 162 infants with 13 hospital and 15 late deaths (17.3% 1-year mortality). Neurodevelopmental evaluation was performed in 89 of 134 (66.4%) survivors. Glucose levels at admission to the cardiac intensive care unit and during the first 48 postoperative hours were available for 85 of 89 (96%) patients. Mean admission glucose value was 274+/-91 mg dl(-1); the maximum was 291+/-90 mg dl(-1), with 69 of 85 (81%) patients having at least one glucose value >200 mg dl(-1). Only two patients had a value <50 mg dl(-1). Mean MDI and PDI scores were 88+/-16 and 71+/-18, respectively. There were no statistically significant correlations between initial, mean, minimum or maximum glucose measurements and MDI or PDI scores. Only delayed sternal closure resulted in a statistically significant relationship between initial, minimum and maximum glucose values within the context of a multivariate analysis of variance model. CONCLUSIONS: Hyperglycaemia following Stage I palliation in the neonatal period was not associated with lower MDI or PDI scores at 1 year of age.

Risk factors for interstage death after stage 1 reconstruction of hypoplastic left heart syndrome and variants.

OBJECTIVE: The risk of death during the interstage period remains high after stage 1 reconstruction for single ventricle lesions, despite improved surgical results. The purpose of this study is to identify risk factors for interstage death and to describe the events leading to interstage death. METHODS: A nested case-control study was conducted of 368 patients who underwent stage 1 reconstruction at a single center between January 1998 and April 2005. RESULTS: Among the 313 (85%) hospital survivors, there were 33 (10.5%) interstage deaths. Cases more frequently presented with intact or restrictive atrial septum (9 [27%] vs 4 [4%]; P < .001), were older at the time of surgery (5 [2-40] vs 3 [1-42] days; P = .005), had more postoperative arrhythmias (12 [36%] vs 15 [15%]; P = .01), and a higher incidence of airway or respiratory complications (12 [36%] vs 19 [19%]; P = .04). By multivariate analysis, only intact atrial septum (odds ratio 7.6; 95% confidence intervals 1.9-29.6; P = .003) and age at operation greater than 7 days (odds ratio 3.8; 95% confidence intervals 1.3-11.2; P = .017) were predictors of interstage death. CONCLUSIONS: The presence of intact atrial septum and older age at the time of surgery are associated with a higher risk of interstage death. In addition, postoperative arrhythmia and airway complications are associated with a higher risk of interstage death in univariate analysis. The results of this study provide a focus for interstage monitoring and risk stratification of these high-risk infants, which may improve overall survival.