Mitral valve orifice area predicts outcome after biventricular repair in patients with hypoplastic left ventricles.

BACKGROUND: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). METHODS: Single-center retrospective analysis of preoperative CMRs on patients with HLV (≤50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. RESULTS: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 ± 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score <-2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score <-2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. CONCLUSION: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.

Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

OBJECTIVES: The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). DESIGN, SETTING, PATIENTS: Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. INTERVENTIONS: Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. MEASUREMENTS AND MAIN RESULTS: Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. CONCLUSIONS: Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.

The experience of fathers of children hospitalised with advanced heart disease.

BACKGROUND: There are little reported data on the perspectives of fathers caring for children with chronic conditions. Although survival of children with advanced heart disease has improved, long-term morbidity remains high. This study describes the experience and prognostic awareness of fathers of hospitalised children with advanced heart disease. METHODS: Cross-sectional survey study of parents caring for children hospitalised with advanced heart disease admitted for ≥ 7 days over a one-year period. One parent per patient completed surveys, resulting in 27 father surveys. Data were analysed using descriptive methods. RESULTS: Nearly all (96%) of the fathers reported understanding their child's prognosis "extremely well" or "well," and 59% felt they were "very prepared" for their child's medical problems. However, 58% of fathers wanted to know more about prognosis, and 22% thought their child's team knew something about prognosis that they did not. Forty-one per cent of fathers did not think that their child would have lifelong limitations, and 32% anticipated normal life expectancies. All 13 fathers who had a clinical discussion of what would happen if their child got sicker found this conversation helpful. Nearly half (43%) of the fathers receiving new prognostic information or changes to treatment course found it "somewhat" or "a little" confusing. CONCLUSIONS: Fathers report excellent understanding of their child's illness and a positive experience around expressing their hopes and fears. Despite this, there remain many opportunities to improve communication, prognostic awareness, and participation in informed decision-making of fathers of children hospitalised with advanced heart disease.

Angiotensin receptor blockers and ß blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.

BACKGROUND: Angiotensin receptor blockers (ARBs) and ß blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. METHODS: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus ß blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus ß blocker; and indirectly, ß blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. FINDINGS: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with ß-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with ß blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in ß-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between ß blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042). INTERPRETATION: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a ß blocker. The effects of ß blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and ß blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery. FUNDING: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.

The teammate trial: Study design and rationale tacrolimus and everolimus against tacrolimus and MMF in pediatric heart transplantation using the major adverse transplant event (MATE) score.

BACKGROUND: Currently there are no immunosuppression regimens FDA-approved to prevent rejection in pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as a potential alternative to standard tacrolimus (TAC) as the primary immunosuppressant to prevent rejection that may also reduce the risk of cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD) and cytomegalovirus (CMV) infection. However, the 2 regimens have never been compared head-to-head in a randomized trial. The study design and rationale are reviewed in light of the challenges inherent in rare disease research. METHODS: The TEAMMATE trial (IND 127980) is the first multicenter randomized clinical trial (RCT) in pediatric HT. The primary purpose is to evaluate the safety and efficacy of EVL and low-dose TAC (LD-TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). Children aged <21 years at HT were randomized (1:1 ratio) at 6 months post-HT to either regimen, and followed for 30 months. Children with recurrent rejection, multi-organ transplant recipients, and those with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 were excluded. The primary efficacy hypothesis is that, compared to TAC/MMF, EVL/LD-TAC is more effective in preventing 3 MATEs: acute cellular rejection (ACR), CKD and CAV. The primary safety hypothesis is that EVL/LD-TAC does not have a higher cumulative burden of 6 MATEs (antibody mediated rejection [AMR], infection, and post-transplant lymphoproliferative disorder [PTLD] in addition to the 3 above). The primary endpoint is the MATE score, a composite, ordinal surrogate endpoint reflecting the frequency and severity of MATEs that is validated against graft loss. The study had a target sample size of 210 patients across 25 sites and is powered to demonstrate superior efficacy of EVL/LD-TAC. Trial enrollment is complete and participant follow-up will be completed in 2023. CONCLUSION: The TEAMMATE trial is the first multicenter RCT in pediatric HT. It is anticipated that the study will provide important information about the safety and efficacy of everolimus vs tacrolimus-based regimens and will provide valuable lessons into the design and conduct of future trials in pediatric HT.

Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry.

OBJECTIVE: To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. STUDY DESIGN: We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. RESULTS: Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension. CONCLUSIONS: Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.

Magnetic resonance three-dimensional steady-state free precession imaging of the thoracic duct in patients with Fontan circulation and its relationship to outcomes.

BACKGROUND: Lymphatic complications are common in patients with Fontan circulation. Three-dimensional balanced steady-state free precession (3D bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely used for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct (TD) visualization using 3D bSSFP images and assess whether TD characteristics are associated with clinical outcomes. METHODS: This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Frequency matching of age at CMR was used to construct a comparison group of patients with repaired tetralogy of Fallot (rTOF). TD characteristics included maximum diameter and a qualitative assessment of tortuosity. Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplantation, and death. A composite outcome was defined as presence of any of these events. RESULTS: The study included 189 Fontan patients (median age 16.1 years, IQR 11.0-23.2 years) and 36 rTOF patients (median age 15.7 years, IQR 11.1-23.7 years). The TD diameter was larger (median 2.50 vs. 1.95 mm, p = 0.002) and more often well visualized (65% vs. 22%, p < 0.001) in Fontan patients vs. rTOF patients. TD dimension increased mildly with age in Fontan patients, R = 0.19, p = 0.01. In Fontan patients, the TD diameter was larger in those with PLE vs. without PLE (age-adjusted mean 4.11 vs. 2.72, p = 0.005), and was more tortuous in those with NYHA class ≥ II vs. class I (moderate or greater tortuosity 75% vs. 28.5%, p = 0.02). Larger TD diameter was associated with a lower ventricular ejection fraction that was independent of age (partial correlation = - 0.22, p = 0.02). More tortuous TDs had a higher end-systolic volume (mean 70.0 mL/m2 vs. 57.3 mL/m2, p = 0.03), lower creatinine (mean 0.61 mg/dL vs. 0.70 mg/dL, p = 0.04), and a higher absolute lymphocyte count (mean 1.80 K cells/µL vs. 0.76 K cells/µL, p = 0.003). The composite outcome was present in 6% of Fontan patients and was not associated with TD diameter (p = 0.50) or tortuosity (p = 0.09). CONCLUSIONS: The TD is well visualized in two-thirds of patients with Fontan circulation on 3D-bSSFP images. Larger TD diameter is associated with PLE and increased TD tortuosity is associated with an NYHA class ≥ II.

Impact of Right Ventricular Surface Area-to-Volume Ratio on Ventricular Remodeling After Pulmonary Valve Replacement.

Optimal reverse remodeling of the right ventricle (RV), a sentinel goal of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot, is not fully predicted by volume-based pre-PVR parameters. Our objectives were to characterize novel geometric RV parameters in patients receiving PVR and in controls, and to identify associations between these parameters and chamber remodeling post-PVR. Secondary analysis was performed on cardiac magnetic resonance (CMR) data from 60 patients enrolled in a randomized trial of PVR with and without surgical RV remodeling. 20 healthy age-matched subjects served as controls. The primary outcome was optimal post-PVR RV remodeling (end-diastolic volume index (EDVi) ≤ 114 ml/m2 and ejection fraction (EF) ≥ 48%) vs. suboptimal remodeling (EDVi ≥ 120 ml/m2 and EF ≤ 45%). RV geometry was markedly different at baseline in PVR patients compared with controls, with lower systolic surface area-to-volume ratio (SAVR) (1.16 ± 0.26 vs.1.44 ± 0.21 cm2/mL, p < 0.001) and lower systolic circumferential curvature (0.87 ± 0.27 vs. 1.07 ± 0.30 cm- 1, p = 0.007) but similar longitudinal curvature. In the PVR cohort, higher systolic SAVR was associated with higher RVEF both pre- and post-PVR (p < 0.001). Among PVR patients, 15 had optimal and 19 had suboptimal remodeling post-PVR. Multivariable modeling showed that among the geometric parameters, higher systolic SAVR (OR 1.68 per 0.1 cm2/mL increase; p = 0.049) and shorter systolic RV long-axis length (OR 0.92 per 0.1 cm increase; p = 0.035) were independently associated with optimal remodeling. Compared with controls, PVR patients have lower SAVR and lower circumferential but not longitudinal curvature. Higher pre-PVR systolic SAVR is associated with optimal remodeling post-PVR.

Pediatric heart transplant waiting times in the United States since the 2016 allocation policy change.

We describe waiting times for pediatric heart transplant (HT) candidates after the 2016 revision to the US allocation policy. The OPTN database was queried for pediatric HT candidates listed between 7/2016 and 4/2019. Of the 1789 included candidates, 65% underwent HT, 14% died/deteriorated, 8% were removed for improvement, and 13% were still waiting at the end of follow-up. Most candidates were status 1A at HT (81%). Median wait times differ substantially by listing status, blood type, and recipient weight. The likelihood of HT was lower in candidates <25 kg and in those with blood type O; The <25 kg, blood type O subgroup experiences longer wait times and higher wait list mortality. For status 1A candidates, median wait times were 108 days (≤25 kg, blood type O), 80 days (≤25 kg, non-O), 47 days (>25 kg, O), and 24 days (>25 kg, non-O). We found that centers with more selective organ acceptance practices, based on a lower median Pediatric Heart Donor Assessment Tool (PH-DAT) score for completed transplants, experience longer status 1A wait times for their listed patients. These data can be used to counsel families and to select appropriate advanced heart failure therapies to support patients to transplant.

Cardiac MRI predictors of good long-term outcomes in patients with repaired TOF.

BACKGROUND: Risk stratification in patients with repaired tetralogy of Fallot (rTOF) have focused on poor clinical outcomes while predictors of a benign clinical course have not been characterized. OBJECTIVE: The goal of this study was to Identify cardiac magnetic resonance (CMR) markers of a good clinical course late after TOF repair. METHODS: Clinical and CMR data from the International Multicenter TOF Registry (INDICATOR) were analyzed. The primary outcome was time to the earliest occurrence of a composite of death, aborted sudden death, and sustained ventricular tachycardia (VT). The secondary outcome was time to the earliest occurrence of atrial arrhythmia, nonsustained VT, and NYHA class >II. Multinomial regression was used to identify predictors of the 3-category outcome: (a) good outcome, defined as freedom from the primary AND secondary outcomes at age 50 years; (b) poor outcome, defined as presence of the primary outcome before age 50 years; and (c) intermediate outcome, defined as not fulfilling criteria for good or poor outcomes. RESULTS: Among 1088 eligible patients, 96 had good outcome, 60 experienced poor outcome, and 932 had intermediate outcome. Patients were age 25.8±10.8 years at the time of the index CMR. Median follow-up was 5.8 years (IQR 3.0, 9.9) after CMR in event-free patients. By univariate analysis, smaller right ventricular (RV) end-systolic and end-diastolic volume index, smaller left ventricular end-systolic volume index, higher right and left ventricular ejection fraction, lower right and left ventricular mass index, and lower left ventricular mass/volume ratio were associated with good outcome. Multivariable modeling identified higher RV ejection fraction (OR 2.38 per 10% increase, P = .002) and lower RV mass index (OR 1.72, per 10 g/m2 decrease, P = .002) as independently associated with good outcome after adjusting for age at CMR. Classification and regression tree analysis identified important thresholds associated with good outcome that were specific to patients age ≥37 years at the time of CMR; these were RV ejection fraction ≥42% and RV mass index <39 g/m2. CONCLUSIONS: Adults with rTOF and no more than mild RV dysfunction combined with no significant RV hypertrophy are likely to be free from serious adverse clinical events into their sixth decade of life and may require less frequent cardiac testing.

Longitudinal changes in ventricular size and function are associated with death and transplantation late after the Fontan operation.

BACKGROUND: Cross-sectional studies have reported that ventricular dilation and dysfunction are associated with adverse clinical outcome in Fontan patients; however, longitudinal changes and their relationship with outcome are not known. METHODS: This was a single-center retrospective analysis of Fontan patients with at least 2 cardiovascular magnetic resonance (CMR) scans without intervening interventions. Serial measures of end-diastolic volume index (EDVI), end-systolic volume index (ESVI), ejection fraction (EF), indexed mass (massi), mass-to-volume ratio, and end-systolic wall stress (ESWS) were used to estimate within-patient change over time. Changes were compared for those with and without a composite outcome (death, heart transplant, or transplant listing) as well as between patients with left (LV) and right ventricular (RV) dominance. RESULTS: Data from 156 patients were analyzed with a mean age at 1st CMR of 17.8 ± 9.6 years. 490 CMRs were included with median of 3 CMRs/patient (range 2-9). On regression analysis with mixed effects models, volumes and ESWS increased, while mass, mass-to-volume ratio, and EF decreased over time. With a median follow-up of 10.2 years, 14% met the composite outcome. Those with the composite outcome had a greater increase in EDVI compared to those without (4.7 vs. 0.8 ml/BSA1.3/year). Compared with LV dominance, RV dominance was associated with a greater increase in ESVI (1.4 vs. 0.5 ml/BSA1.3/year), a greater decrease in EF (- 0.61%/year vs. - 0.24%/year), and a higher rate of the composite outcome (21% vs. 8%). CONCLUSIONS: Ventricles in the Fontan circulation exhibit a steady decline in performance with an increase in EDVI, ESVI, and ESWS, and decrease in EF, mass index, and mass-to-volume ratio. Those with death or need for heart transplantation have a faster increase in EDVI. Patients with rapid increase in EDVI (> 5 ml/BSA1.3/year) may be at a higher risk of adverse outcomes and may benefit from closer surveillance. RV dominance is associated with worse clinical outcomes and remodeling compared to LV dominance.

Hemodynamic and anatomic changes after fetal aortic valvuloplasty are associated with procedural success and postnatal biventricular circulation.

BACKGROUND: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV). METHODS: This retrospective study included patients who underwent FAV between 2000 and 2019, with echocardiograms performed pre-FAV, immediately post-FAV, and in late gestation. RESULTS: Of 118 fetuses undergoing FAV, 106 (90%) underwent technically successful FAV, of which 55 (52%) had biventricular circulation. Technically successful FAV was associated with improved aortic valve growth (p < 0.001), sustained antegrade aortic arch (AoA) flow (p = 0.02), improved mitral valve (MV) inflow pattern (p = 0.002), and favorable patent foramen ovale (PFO) flow pattern (p = 0.004) from pre-FAV to late gestation. Compared to patients with univentricular outcome, patients with biventricular outcome had less decrement in size of the left ventricle (LV) (p < 0.001) and aortic valve (p = 0.005), as well as more physiologic PFO flow (p < 0.001) and antegrade AoA flow (p < 0.001) from pre-FAV to late gestation. In multivariable analysis, echocardiographic predictors of biventricular outcome were less decline in LV end diastolic dimension (p < 0.001), improved PFO flow (p = 0.004), and sustained antegrade AoA flow (p = 0.002) from pre-FAV to late gestation. CONCLUSION: Stabilization of left heart growth and improved hemodynamics following successful FAV through late gestation are associated with postnatal biventricular circulation.

Associations With Extubation Failure and Predictive Value of Risk Analytics Algorithms With Extubation Readiness Tests Following Congenital Cardiac Surgery.

OBJECTIVES: Extubation failure is associated with morbidity and mortality in children following cardiac surgery. Current extubation readiness tests (ERT) do not consider the nonrespiratory support provided by mechanical ventilation (MV) for children with congenital heart disease. We aimed to identify factors associated with extubation failure in children following cardiac surgery and assess the performance of two risk analytics algorithms for patients undergoing an ERT. DESIGN: Retrospective cohort study. SETTING: CICU at a tertiary-care children's hospital. PATIENTS: Children receiving MV greater than 48 hours following cardiac surgery between January 1, 2017, and December 31, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred fifty encounters were analyzed with 49 occurrences (8%) of reintubation. Extubation failure occurred most frequently within 6 hours of extubation. On multivariable analysis, younger age (per each 3-mo decrease: odds ratio [OR], 1.06; 95% CI, 1.001-1.12), male sex (OR, 2.02; 95% CI, 1.03-3.97), Society of Thoracic Surgery-European Association for Cardiothoracic Surgery category 5 procedure (p equals to 0.005), and preoperative respiratory support (OR, 2.08; 95% CI, 1.09-3.95) were independently associated with unplanned reintubation. Our institutional ERT had low sensitivity to identify patients at risk for reintubation (23.8%; 95% CI, 9.7-47.6%). The addition of the inadequate delivery of oxygen (IDO2) index to the ERT increased the sensitivity by 19.0% (95% CI, -2.5 to 40.7%; p = 0.05), but the sensitivity remained low and the accuracy of the test dropped by 8.9% (95% CI, 4.7-13.1%; p < 0.01). CONCLUSIONS: Preoperative respiratory support, younger age, and more complex operations are associated with postoperative extubation failure. IDO2 and IVCO2 provide unique cardiorespiratory monitoring parameters during ERTs but require further investigation before being used in clinical evaluation for extubation failure.

Fluid Restriction Contributes to Poor Nutritional Adequacy in Patients With Congenital Heart Disease Receiving Renal Replacement Therapy.

OBJECTIVES: Critically ill patients receiving renal replacement therapy (RRT) in the pediatric cardiac intensive care unit (CICU) are at high risk for inadequate nutrition delivery. The objective of this study is to evaluate barriers to adequate energy and protein delivery in critically ill patients with congenital heart disease receiving RRT. METHODS: This is a single-center retrospective cohort study of patients receiving RRT in the CICU from 2011 to 2019. Energy and protein adequacy was recorded over the first 7 days of RRT. Adequacy was defined as delivery of >80% of the energy and protein targets during this time period. Patients who achieved adequacy were compared to those who did not. Multivariable logistic regression models were constructed to determine factors independently associated with energy and protein adequacy while receiving RRT. RESULTS: Sixty patients were included for analysis. Fifty-five patients (92%) achieved energy adequacy and 37 patients (62%) achieved protein adequacy. A higher weight-for-age z-score (WAZ) on admission to the CICU was the only independent predictor of inadequate energy intake (odds ratio 0.07, 95% confidence interval 0.01-0.58, P = .014); median WAZ was -1.17 versus +1.24 for those with adequate versus inadequate energy intake, respectively. Fluid restriction to <80% of maintenance fluid at the time of RRT initiation was more likely in patients with higher WAZ. Fluid restriction was the only independent predictor of inadequate protein intake (odds ratio 0.13, 95% confidence interval 0.02-0.7, P = .018); 5% versus 30% were fluid restricted in those with adequate versus inadequate protein intake, respectively. Azotemia was not associated with inadequate protein intake. Initiation of RRT did not allow for liberalization of fluid intake over the time period evaluated. CONCLUSIONS: Protein delivery was inadequate in 38% of children undergoing RRT in the CICU. Fluid restriction was associated with inadequate protein intake and higher WAZ was associated with inadequate energy intake.

Life-Threatening Hemoptysis in a Pediatric Referral Center.

OBJECTIVES: Hemoptysis is uncommon in children, even among the critically ill, with a paucity of epidemiological data to inform clinical decision-making. We describe hemoptysis-associated ICU admissions, including those who were critically ill at hemoptysis onset or who became critically ill as a result of hemoptysis, and identify predictors of mortality. DESIGN: Retrospective cohort study. Demographics, hemoptysis location, and management were collected. Pediatric Logistic Organ Dysfunction-2 score within 24 hours of hemoptysis described illness severity. Primary outcome was inhospital mortality. SETTING: Quaternary pediatric referral center between July 1, 2010, and June 30, 2017. PATIENTS: Medical/surgical (PICU), cardiac ICU, and term neonatal ICU admissions with hemoptysis during or within 24 hours of ICU admission. INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: There were 326 hemoptysis-associated ICU admissions in 300 patients. Most common diagnoses were cardiac (46%), infection (15%), bronchiectasis (10%), and neoplasm (7%). Demographics, interventions, and outcomes differed by diagnostic category. Overall, 79 patients (26%) died inhospital and 109 (36%) had died during follow-up (survivor mean 2.8 ± 1.9 yr). Neoplasm, bronchiectasis, renal dysfunction, inhospital hemoptysis onset, and higher Pediatric Logistic Organ Dysfunction-2 score were independent risk factors for inhospital mortality (p < 0.02). Pharmacotherapy (32%), blood products (29%), computerized tomography angiography (26%), bronchoscopy (44%), and cardiac catheterization (36%) were common. Targeted surgical interventions were rare. Of survivors, 15% were discharged with new respiratory support. Of the deaths, 93 (85%) occurred within 12 months of admission. For patients surviving 12 months, 5-year survival was 87% (95% CI, 78-92) and mortality risk remained only for those with neoplasm (log-rank p = 0.001). CONCLUSIONS: We observed high inhospital mortality from hemoptysis-associated ICU admissions. Mortality was independently associated with hemoptysis onset location, underlying diagnosis, and severity of critical illness at event. Additional mortality was observed in the 12-month posthospital discharge. Future directions include further characterization of this vulnerable population and management recommendations for life-threatening pediatric hemoptysis incorporating underlying disease pathophysiology.

Trajectories in Neurodevelopmental, Health-Related Quality of Life, and Functional Status Outcomes by Socioeconomic Status and Maternal Education in Children with Single Ventricle Heart Disease.

Trajectories of neurodevelopment and quality of life were analyzed in children with hypoplastic left heart syndrome according to socioeconomic status (SES) and maternal education. Lower SES and less maternal education were associated with greater early delays in communication and problem-solving and progressive delays in problem-solving and fine motor skills over time.

Parent-Reported Symptoms and Perceived Effectiveness of Treatment in Children Hospitalized with Advanced Heart Disease.

OBJECTIVE: To characterize parent-reported symptom burden and effectiveness of symptom management in children hospitalized with advanced heart disease. STUDY DESIGN: Prospective survey study of 161 parents whose child was admitted to a single institution with advanced heart disease between March 2018 and February 2019 using the Survey about Caring for Children with Heart Disease. RESULTS: Of the 161 patients, 54% were under 2 years old with a diagnosis of single ventricle physiology (39%), pulmonary hypertension (12%), and other congenital heart disease (28%). Over one-half (56%) of parents reported that their child was experiencing a high degree ("a great deal"/"a lot") of symptoms. The most frequently reported symptoms were pain (68%), fatigue (63%), and breathing difficulties (60%). Of the symptoms that were treated, parents perceived successful treatment to be least likely for their child's sleep disturbance (24%), depression (29%), and fatigue (35%). Parents who reported their child's functional status as New York Heart Association class III/IV were more likely to report that their child was experiencing "a great deal" of symptoms, compared with those who reported class I/II (51% vs 19%, P < .001). Parents who reported their child was experiencing a high degree of suffering from fatigue were also more likely to report a high symptom burden (P < .001). CONCLUSIONS: Parents of children with advanced heart disease reported high symptom burden with a broad spectrum of symptoms. Parents reported fatigue and psychiatric symptoms frequently and rarely reported treatment as successful. Parents' view of their child's symptom burden was concordant with their perception of their child's functional status.

Impact of pulmonary valve replacement on left ventricular rotational mechanics in repaired tetralogy of Fallot.

BACKGROUND: In repaired tetralogy of Fallot (rTOF), abnormal left ventricular (LV) rotational mechanics are associated with adverse clinical outcomes. We performed a comprehensive analysis of LV rotational mechanics in rTOF patients using cardiac magnetic resonance (CMR) prior to and following surgical pulmonary valve replacement (PVR). METHODS: In this single center retrospective study, we identified rTOF patients who (1) had both a CMR ≤ 1 year before PVR and ≤ 5 years after PVR, (2) had no other intervening procedure between CMRs, (3) had a body surface area > 1.0 m2 at CMR, and (4) had images suitable for feature tracking analysis. These subjects were matched to healthy age- and sex-matched control subjects. CMR feature tracking analysis was performed on a ventricular short-axis stack of balanced steady-state free precession images. Measurements included LV basal and apical rotation, twist, torsion, peak systolic rates of rotation and torsion, and timing of events. Associations with LV torsion were assessed. RESULTS: A total of 60 rTOF patients (23.6 ± 7.9 years, 52% male) and 30 healthy control subjects (20.8 ± 3.1 years, 50% male) were included. Compared with healthy controls, rTOF patients had lower apical and basal rotation, twist, torsion, and systolic rotation rates, and these parameters peaked earlier in systole. The only parameters that were correlated with LV torsion were right ventricular (RV) end-systolic volume (r = - 0.28, p = 0.029) and RV ejection fraction (r = 0.26, p = 0.044). At a median of 1.0 year (IQR 0.5-1.7) following PVR, there was no significant change in LV rotational parameters versus pre-PVR despite reductions in RV volumes, RV mass, pulmonary regurgitation, and RV outflow tract obstruction. CONCLUSION: In this comprehensive study of CMR-derived LV rotational mechanics in rTOF patients, rotation, twist, and torsion were diminished compared to controls and did not improve at a median of 1 year after PVR despite favorable RV remodeling.

Late gestation predictors of a postnatal biventricular circulation after fetal aortic valvuloplasty.

OBJECTIVES: Fetal aortic valvuloplasty (FAV) for severe aortic stenosis (AS) has shown promise in averting progression to hypoplastic left heart syndrome. After FAV, predicting which fetuses will achieve a biventricular (BiV) circulation after birth remains challenging. Identifying predictors of postnatal circulation on late gestation echocardiography will improve parental counseling. METHODS: Liveborn patients who underwent FAV and had late gestation echocardiography available were included (2000-2017, n = 96). Multivariable logistic regression and classification and regression tree analysis were utilized to identify independent predictors of BiV circulation. RESULTS: Among 96 fetuses, 50 (52.1%) had BiV circulation at the time of neonatal discharge. In multivariable analysis, independent predictors of biventricular circulation included left ventricular (LV) long axis z-score (OR 3.2, 95% CI 1.8-5.7, p < 0.001), LV ejection fraction (OR 1.3, 95% CI 1.0-1.8, p = 0.023), anterograde aortic arch flow (OR 5.0, 95% CI 1.2-20.4, p = 0.024), and bidirectional or right-to-left foramen ovale flow (OR 4.6, 95% CI 1.4-15.8, p = 0.015). CONCLUSION: Several anatomic and physiologic parameters in late gestation were found to be independent predictors of BiV circulation after FAV. Identifying these predictors adds to our understanding of LV growth and hemodynamics after FAV and may improve parental counseling.

Stratification of Bleeding Risk Using Thromboelastography in Children on Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Patients undergoing extracorporeal membrane oxygenation are at high risk for bleeding and thrombotic complications. Current laboratory methods for assessing the coagulation system may be imprecise and complicate clinical decision-making. We hypothesize that thromboelastography may be more strongly associated with bleeding events than traditional methods and can aid extracorporeal membrane oxygenation coagulation management. DESIGN: In a retrospective study, 40 patients with congenital heart disease requiring extracorporeal membrane oxygenation support yielded a total of 159 patient days of data for thromboelastography analysis. SETTING: Pediatric cardiac ICU at a single institution. SUBJECTS: Pediatric patients (≤ 18 yr) with congenital heart disease requiring extracorporeal membrane oxygenation support. INTERVENTIONS: None. METHODS: Thromboelastography was performed on whole blood samples collected 6-12 hours following extracorporeal membrane oxygenation initiation and daily for the duration of extracorporeal membrane oxygenation. Bleeding during each 24-hour period was defined as need for re-exploration or need for blood transfusion. Associations between thromboelastography variables and bleeding over each 24-hour period (bleeding vs nonbleeding days) were assessed using mixed effects logistic regression and classification and regression tree analysis. MEASUREMENTS AND MAIN RESULTS: Bleeding occurred in 25 patients (63%), contributing 87 bleeding days (55% extracorporeal membrane oxygenation days) for analysis. The probability of bleeding within the 24-hour period was not associated with activated partial thromboplastin time (p = 0.6) or anti-Xa levels (p = 0.3) on that day. The strongest correlate of bleeding was a maximum amplitude less than 55.4 mm on thromboelastography (odds ratio, 3.28; 95% CI, 1.63-6.60; p < 0.001). Bleeding occurred on 73% versus 35% of extracorporeal membrane oxygenation days for maximum amplitude less than 55.4 mm versus greater than or equal to 55.4 mm, respectively. Bleeding occurred on all days when a combination of maximum amplitude less than 55.4 mm and a reaction time greater than 12.9 minutes was present. The lowest risk of bleeding (28% of patient days) was associated with maximum amplitude greater than or equal to 55.4 mm and plasma fibrinogen greater than 345 mg/dL. CONCLUSIONS: Thromboelastography-derived variables maximum amplitude and reaction time, along with plasma fibrinogen levels, can help predict bleeding events in children on extracorporeal membrane oxygenation support. Research based on larger patient samples is needed to confirm the specific thresholds identified for bleeding risk stratification for extracorporeal membrane oxygenation anticoagulation management.