A Randomized Trial of an Exclusive Human Milk Diet in Neonates with Single Ventricle Physiology.

OBJECTIVE: To determine whether weight gain velocity (g/kg/day) 30 days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet. STUDY DESIGN: In this multicenter, randomized, single blinded, controlled trial, term neonates 7 days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed. RESULTS: We enrolled 107 neonates (exclusive human milk = 55, control = 52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12 g/day [IQR, 5-18 g/day] vs 8 g/day [IQR, 0.4-14 g/day], respectively; P = .03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P = .04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups. CONCLUSIONS: Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (www. CLINICALTRIALS: gov, Trial ID: NCT02860702).

Safety of Continuing Anticoagulation Prior to Cardiac Catheterization in Pediatric Patients: A Los Angeles Center Experience.

This is the first report specifically describing outcomes of pediatric patients who underwent cardiac catheterization while on uninterrupted anticoagulation. One hundred forty-four cardiac catheterizations were identified that met inclusion criteria at our institution from 11/2014 to 10/2019. The median age and weight of the patients were 6.3 [0.01-20.9] years and 19.3 [2.1-172.5] kg, respectively. Seventy-eight (54%) catheterizations involved inpatients. The most common cardiac diagnoses among the cohort were single ventricle (n = 41), conotruncal defects (n = 37), and structurally normal heart (n = 16). The most common indications for anticoagulation were arterial/venous thrombus (n = 45), Fontan physiology (n = 32), and mechanical valve thrombus prophylaxis (n = 27). The anticoagulation medications used were warfarin (n = 57), heparin (n = 52), enoxaparin (n = 25), fondaparinux (n = 5), rivaroxaban (n = 2), and both heparin and warfarin (n = 3). Interventions were performed in 96 cases (67%). The median length of the procedure was 122.5 [15-760] minutes, and the median time to achieve hemostasis was 18.0 [range: 5-76, IQR: 13-25] minutes. Adverse events were present in 11 cases (7.6%), and of those only 2 cases (1.4%) were bleeding-related complications. Our single-center data suggest that performing cardiac catheterization on pediatric patients while on uninterrupted anticoagulation is safe and does not substantially increase the risk of bleeding complications based on a cohort of patients that varied in age, size, diagnosis, medical complexity, and type of intervention performed. Patients on warfarin therapy for a mechanical valve are most likely to benefit from this practice, as the ability to continue warfarin therapy avoids the need for bridging and other interruption-related complications.

Routine Surveillance Catheterization is Useful in Guiding Management of Stable Fontan Patients.

We developed a Fontan surveillance catheterization protocol as part of routine assessment of stable patients 10 years after Fontan completion. The surveillance catherization includes hemodynamic assessment with inhaled nitric oxide, angiography, liver biopsy, and transcatheter intervention if indicated. We aimed to describe hemodynamic and liver biopsy findings, response to pulmonary vasoreactivity testing, rates of transcatheter intervention, and changes in medical therapy following surveillance catheterization in stable Fontan patients. A single-center retrospective review of Fontan patients undergoing surveillance catheterization between November 2014 and May 2019 was performed. Liver biopsies were independently scored by two pathologists. Sixty-three patients underwent surveillance catheterization (mean age 14.6 ± 3.0 years). The mean Fontan pressure was 11.8 ± 2.1 mmHg. The mean cardiac index was 2.9 ± 0.6 L/min/m2. In the 51 patients who underwent pulmonary vasoreactivity testing, there was a significant decrease in median pulmonary vascular resistance (1.8 [range 0.8-4.1] vs 1.4 [range 0.7-3.0] Wood units × m2; p < 0.001). The mean cardiac index increased (3.0 ± 0.6 vs 3.2 ± 0.7 L/min/m2, p = 0.009). The Fontan pressure did not change significantly. Fifty-seven patients underwent liver biopsy, and all but one showed fibrosis. Nineteen patients (33.3%) demonstrated bridging fibrosis or cirrhosis. Twenty-five patients underwent 34 transcatheter interventions. Pulmonary artery or Fontan stent placement was performed in 19 patients. Phosphodiesterase type 5 inhibitors were initiated in nine patients following surveillance catheterization. Routine surveillance catheterization with liver biopsy in adolescent Fontan patients reveals information that can guide interventional and medical management. Further long-term follow-up and assessment are indicated to assess the benefit of these interventions.

Stent treatment of ostial branch pulmonary artery stenosis: initial and medium-term outcomes and technical considerations to avoid and minimise stent malposition.

OBJECTIVE: Stenting of ostial pulmonary artery stenosis presents several unique challenges. These include difficulty in defining anatomy and need for precise stent placement in order to avoid missing the ostial stenosis or jailing either the contralateral branch pulmonary artery or the ipsilateral upper lobe branch. DESIGN: A retrospective review of outcomes was conducted in 1.5 or 2-ventricle patients who underwent stent placement for ostial branch pulmonary artery stenosis. Specific catheterisation lab techniques were reviewed. RESULTS: Forty-seven branch pulmonary arteries underwent stent placement for ostial stenosis in 43 patients. The median age and weight were 3.7 (0.3-18.1) years and 14.2 (5.6-70.0) kg, respectively. Three (2-8) angiographic projections were needed to profile the ostial stenosis. Open-cell stents were used in 23 and stents were modified in 5 cases. Following stent implantation, the minimum diameter improved from 3.6 (0.8-10.5) to 8.1 (4.2-16.5) mm (p < 0.001). The gradient improved from 21 (0-66) to 4 (0-27) mmHg (p < 0.001). Stent malposition occurred in eight (17%) of the stents placed. Five migrated distally causing suboptimal ostial coverage necessitating placement of a second stent in four. Three migrated proximally and partially jailed the contralateral pulmonary artery. Intentional jailing of the upper lobe branch occurred in four additional cases. At a follow-up of 2.4 (0.3-4.9) years, 15 stents underwent further dilation and 1 had a second stent placed within the exiting stent. CONCLUSION: Ostial branch pulmonary artery stenosis may require additional angiography to accurately define the ostial stenosis. Treatment with stents is effective but carries high rates of stent malposition.

Elevated Pulmonary Artery Pressure, Not Pulmonary Vascular Resistance, is an Independent Predictor of Short-Term Morbidity Following Bidirectional Cavopulmonary Connection.

Single ventricle palliation relies on the pulmonary vasculature accommodating non-pulsatile systemic venous return. Mean pulmonary artery pressure (MPAP) and indexed pulmonary vascular resistance (PVRi) are two measures that impact pulmonary blood flow following bidirectional cavopulmonary connection (BCPC). The purpose of the study was to determine which hemodynamic features are associated with adverse outcomes after BCPC. Pre-operative hemodynamic data and post-operative morbidity and mortality in 250 patients undergoing BCPC at a single center from 2008 to 2014 were reviewed. Patients were then separated into 5 physiologic states based on MPAP, PVRi, and degree of pulmonary to systemic blood flow (Qp:Qs). There were 9 (3.6%) deaths, and 49 patients (20%) sustained major morbidity. An ROC curve identified MPAP > 16 mmHg as an inflection point. Pre-BCPC sildenafil and oxygen use, ventricular dysfunction, and MPAP > 16 mmHg (OR 4.1 [95% CI 1.8-9.2]) were independently associated with morbidity. MPAP > 16 mmHg (OR 6.7 [95% CI 1.6-28]) and pre-BCPC oxygen use were associated with hospital mortality. PVRi was not associated with morbidity or mortality. Of the five physiologic states, patients with high MPAP, low PVRi, and low Qp:Qs fared the worst, with the highest risk of major morbidity (OR 8.6 [3.0-24.9]) and highest risk of mortality (OR 8.0 [1.5-41.3]) when compared to their reference groups (low MPAP, low PVRi). Elevated MPAP, need for pre-operative oxygen support, sildenafil use, and systemic ventricular systolic dysfunction predict morbidity following BCPC. Specifically, patients with elevated MPAP not due to elevated PVRi or pulmonary blood flow had the highest risk of morbidity and mortality.

Unmasking the borderline coarctation: the utility of isoproterenol in the paediatric cardiac catheterisation laboratory.

BACKGROUND: One indication for intervention in coarctation of the aorta is a peak-to-peak gradient >20 mmHg. Gradients may be masked in patients under general anaesthesia and may be higher during exercise. Isoproterenol was given during cardiac catheterisation to simulate a more active physiologic state. OBJECTIVES: We aimed to describe the haemodynamic effects of isoproterenol in patients with coarctation and the impact of intervention on the elicited gradients. METHODS: A retrospective study was performed on two-ventricle patients who underwent cardiac catheterisation for coarctation with isoproterenol testing. RESULTS: 25 patients received isoproterenol before and after intervention. With isoproterenol, the mean diastolic (p=0.0015) and mean arterial (p=0.0065) blood pressures proximal to the coarctation decreased significantly. The mean systolic, diastolic, and mean arterial blood pressures distal to the coarctation decreased significantly (p20 mmHg. Post intervention, the median gradient decreased to 2 (0-29) mmHg, versus baseline, p=0.005, and with isoproterenol it decreased to 8 (0-27) mmHg, versus pre-intervention isoproterenol, p<0.0001. There were significant improvements in the gradients by Doppler (<0.0001) and by blood pressure cuff (p=0.0313). The gradients on isoproterenol best correlated with gradients by blood pressure cuff in the awake state (R2=0.76, p<0.0001). CONCLUSIONS: Isoproterenol can be a useful tool to assess the significance of a coarctation and the effectiveness of an intervention. Percutaneous interventions can effectively reduce the gradients elicited by isoproterenol.

Tailoring stents to fit the anatomy of unique vascular stenoses in congenital heart disease.

BACKGROUND: Unique and small anatomical features often preclude the use of available vascular stents in pediatric patients with congenital heart disease (CHD). OBJECTIVES: To report our experience and outcomes tailoring stents to fit unique anatomy, particularly in small children and infants with CHD. METHODS: Stent tailoring techniques included trimming, folding, and flaring. Patients receiving a tailored stent November 2002 to February 2015 were included in a retrospective analysis. RESULTS: Forty-one tailored stents were implanted in 30 patients with median age and weight of 0.8 years (6 days to 17 years) and 8.1 kg (2.9-47.9 kg). Thirty stents were placed intraoperatively and 11 percutaneously. Sites included branch pulmonary arteries (BPA; n = 32), pulmonary veins (n = 6), SVC (n = 1), and the ventricular septum (n = 2). Twenty-three (56%) stents were trimmed with or without folding to avoid jailing of side branches, 16 (39%) stents were folded or flared with or without trimming to avoid excessive proximal protrusion, and two (5%) stents were folded back at both ends for implantation in ventricular septal defects. Final stent lengths were 6-15 mm. Minimal vessel diameters increased from 2.8 ± 1.4 mm to 6.7 ± 2.6 mm (P < 0.001). Complications included two intraoperative BPA tears, three pinhole balloon leaks, two intraoperative stent dislodgements, one transient heart block, and one lung reperfusion injury. Follow-up catheterization included 36 re-dilations and implantation of four additional stents over a median of 4.1 years. In-stent restenosis was the indication in 25 (69.4%) re-interventions. CONCLUSION: Tailored stents can be safely implanted to fit unique anatomy in small patients. Re-interventions can effectively treat restenosis and accommodate ongoing vessel growth.

Reduction in Radiation Dose in a Pediatric Cardiac Catheterization Lab Using the Philips AlluraClarity X-ray System.

The objective of this study was to compare radiation doses and imaging quality using Philips AlluraClarity (Philips Healthcare, Best, The Netherlands) X-ray system and an older generation reference system. AlluraClarity is a new generation fluoroscopy system designed to reduce radiation without compromising image quality, but reports of its use in pediatric patients are limited. Dose area products (DAP, mGy cm2) and DAP/kg were compared in patients catheterized using Allura Xper and AlluraClarity systems over a year of use for each. Randomly selected studies from each system were assessed for image quality. The 430 patients imaged with Clarity were larger than the 332 imaged with Xper (median BSA: 0.74 vs. 0.64 m2, p = 0.06), and median total fluoroscopic times (TFT) were similar (15.8 vs. 16.1 min, p = 0.37). Median DAPs were 8661 mGy cm2 (IQR: 18,300 mGy cm2) and 4523 mGy cm2 (IQR: 11,596 mGy cm2) with Xper and Clarity, respectively (p < 0.001). There was a reduction in median DAP in all procedure categories. After adjustment for BSA, TFT, and procedure type, using Clarity was associated with a 57.5% (95% CI 51.5-62.8%, p < 0.001) reduction in DAP for all procedures. Reductions did not significantly differ by weight (<10 kg, 10-40 kg, ≥ 40 kg). There was an adjusted percent reduction in DAP for each procedure category ranging from 39.0% (95% CI 25.6-50.1%, p < 0.001) for cardiac biopsies with or without coronary angiography to 67.6% (95% CI 61.2-72.8%, p < 0.001) for device occlusions. Mean overall imaging quality scores (4.3 ± 0.8 with Clarity vs. 4.4 ± 0.6 with Xper, p = 0.62) and scores based on specific quality parameters were similar in the two groups. Use of AlluraClarity substantially reduced radiation doses compared to the older generation reference system without compromising imaging quality in a pediatric cardiac catheterization lab.

Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects.

After the Fontan procedure, patients with univentricular hearts can experience long-term complications due to chronic low-shear non-pulsatile pulmonary blood flow. We sought to evaluate hemorheology and its relationship to hemodynamics in children with univentricular hearts. We hypothesized that low-shear blood viscosity and red blood cell (RBC) aggregation would be associated with increased pulmonary vascular resistance (PVR) and decreased pulmonary blood flow (PBF). We performed a cross-sectional analysis of 62 children undergoing cardiac catheterization-20 with isolated atrial septal defect (ASD), 22 status post Glenn procedure (Glenn), and 20 status post Fontan procedure (Fontan). Shear-dependent blood viscosity, RBC aggregation and deformability, complete blood count, coagulation panel, metabolic panel, fibrinogen, and erythrocyte sedimentation rate were measured. PVR and PBF were calculated using the Fick equation. Group differences were analyzed by ANOVA and correlations by linear regression. Blood viscosity at all shear rates was higher in Glenn and Fontan, partially due to normocytic anemia in ASD. RBC aggregation and deformability were similar between all groups. Low-shear viscosity negatively correlated with PBF in Glenn and Fontan only (R (2) = 0.27, p < 0.001); it also negatively correlated with pulmonary artery pressure in Glenn (R (2) = 0.15, p = 0.01), and positively correlated with PVR in Fontan (R (2) = 0.28, p = 0.02). Our data demonstrate that elevated low-shear blood viscosity is associated with negative hemodynamic perturbations in a passive univentricular pulmonary circulation, but not in a pulsatile biventricular pulmonary circulation.

The Valeo stent: a pre-mounted, open-cell, large stent for use in small children with CHD.

OBJECTIVES: The aim of the present study was to determine the outcomes of using the Valeo stent (Bard Peripheral Vascular, Tempe, Arizona, United States of America) in small children with CHD. BACKGROUND: Stenting vascular stenoses is safe and effective in adults and older children with CHD but is limited in smaller children. The design of the Valeo stent addresses these limitations but has not been extensively described. METHODS: Bench testing was conducted to determine the maximum diameter of the stent, foreshortening, and side-cell diameter. A retrospective analysis of Valeo stents implanted between October, 2012 and October, 2014 was performed. Patient profile, pre-implant/post-implant catheterization data, and stent geometry were reviewed. RESULTS: Bench testing: medium and large Valeo stents can be dilated up to 13 mm and 20 mm diameters, respectively. Side-cells are dilatable up to 12 mm. Valeo stents are of low profile - delivered through 6- or 7-Fr sheaths - and show minimal foreshortening. Retrospective analysis: a total of 81 stents were implanted in 61 patients with CHD. The median weight was 15.3 kg, and the median age was 58.9 months. Stents were implanted in the pulmonary artery, systemic vein, aorta, and pulmonary vein. Overall, mean vessel diameters increased from 4.1 to 7.7 mm (121.7%). There was effective mean gradient reduction: 3.7-0.5 mmHg (63%) in the venous systems, 28.2-12.5 mmHg (63.7%) in the pulmonary arteries, and 17.4-4 mmHg (77.1%) in the aorta. The mean stent foreshortening was 2.5%, and the mean recoil was 5.9%. Side-cells that crossed other vessels were dilated in four cases, and stents were re-mounted onto different-sized balloons in seven cases. CONCLUSIONS: The features of the Valeo stent, such as low profile, large maximum diameter, open-cell design, minimal foreshortening, and recoil, make it suitable for treating vascular stenoses in small children with CHD.

Intervention for recoarctation in the single ventricle reconstruction trial: incidence, risk, and outcomes.

BACKGROUND: Recoarctation after the Norwood procedure increases risk for mortality. The Single Ventricle Reconstruction (SVR) trial randomized subjects with a single right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. We sought to determine the incidence of recoarctation, risk factors, and outcomes in the SVR trial. METHODS AND RESULTS: Recoarctation was defined by intervention, either catheter based or surgical. Univariate analysis and multivariable Cox proportional hazard models were performed with adjustment for center. Of the 549 SVR subjects, 97 (18%) underwent 131 interventions (92 balloon aortoplasty, 39 surgical) for recoarctation at a median age of 4.9 months (range, 1.1-10.5 months). Intervention typically occurred at pre-stage II catheterization (n=71, 54%) or at stage II surgery (n=38, 29%). In multivariable analysis, recoarctation was associated with the shunt type in place at the end of the Norwood procedure (hazard ratio, 2.0 for right ventricle-pulmonary artery shunt versus modified Blalock-Taussig shunt; P=0.02), and Norwood discharge peak echo-Doppler arch gradient (hazard ratio, 1.07 per 1 mm Hg; P<0.01). Subjects with recoarctation demonstrated comorbidities at pre-stage II evaluation, including higher pulmonary arterial pressures (15.4±3.0 versus 14.5±3.5 mm Hg; P=0.05), higher pulmonary vascular resistance (2.6±1.6 versus 2.0±1.0 Wood units·m(2); P=0.04), and increased echocardiographic volumes (end-diastolic volume, 126±39 versus 112±33 mL/BSA(1.3), where BSA is body surface area; P=0.02). There was no difference in 12-month postrandomization transplantation-free survival between those with and without recoarctation (P=0.14). CONCLUSIONS: Recoarctation is common after Norwood and contributes to pre-stage II comorbidities. Although with intervention there is no associated increase in 1-year transplantation/mortality, further evaluation is warranted to evaluate the effects of associated morbidities.

Impact of stent implantation on pulmonary artery growth.

BACKGROUND: Goals of stent implantation (SI) in children with pulmonary artery (PA) stenosis are to relieve obstruction and improve flow to the distal vasculature. We evaluated stent impact on distal PA growth. METHODS: We compared data of children who underwent unilateral SI using the nonstenotic contralateral PA (CPA) as a control (1998-2005; f/u data through 2009). Main/lobar diameters measured at initial and f/u catheterizations were analyzed. RESULTS: For single ventricle (SV) patients (N = 18), the stented PA diameter (SPA D) increased 118%. At initial f/u catheterization (14 ± 9.6 months), both upper lobe (UL) and lower lobe (LL) growth of SPA was comparable to those of the CPA (UL:7% vs. 7%; P = 0.97); (LL:5% vs. 10%; P = 0.33). Subsequent f/u in 11/18 patients (mean 26 ± 20 months) revealed similar results: both UL and LL growth of SPA were comparable to those of the CPA (UL:51% vs. 27%; P = 0.3); (LL:18% vs. 21%; P = 0.62). For two-ventricle (2V) patients (N = 21), the SPAD increased 100%. At f/u, UL, and LL growth on SPA was similar to those of the CPA (UL: 32% vs. 21%; P = 0.37); (LL: 17% vs. 18%; P = 0.88). Subsequent f/u in 10/21 patients (mean 34 ± 14 months) showed UL growth of SPA was significantly greater than that of the CPA (44% vs. 21%; P = 0.05). LL growth of SPA was similar to that of the CPA (19% vs. 14%; P = 0.56). CONCLUSION: SI for PA stenosis is effective in promoting normal lobar growth in SV and 2V patients. Greater lobar growth was seen in 2V compared to SV pts at first f/u. Early, aggressive PA stenting is beneficial in promoting lobar branch growth.

Relationship of pulmonary artery wedge pressure to left atrial pressure and pulmonary vascular resistance in preoperative Fontan patients.

Pulmonary artery wedge pressure (PAWp) as a surrogate for left atrial pressure (LAp) has been validated in patients with fully pulsatile two-ventricle circulations. This study was to validate PAWp as an accurate estimate of LAp for calculating pulmonary vascular resistance in single-ventricle patients after the bidirectional Glenn operation. A prospective study measuring direct branch pulmonary artery pressures, ipsilateral PAWp, and direct LAp to calculate pulmonary and systemic blood flows was conducted. Pulmonary vascular resistance (PVR) was calculated for each patient using the PAWp and compared to the PVR calculated by direct LAp measurements. Twenty-eight patients were enrolled; 27 were eligible for study inclusion. Ages ranged from 21 to 60 months and weights ranged from 9.5 to 20.8 kg. Underlying congenital heart defect diagnoses varied, with all patients either functionally or anatomically univentricular. Left mPAWp measured 4.4 ± 2.6, statistically different from simultaneous direct mLAp of 2.5 ± 2.4 mmHg (P < 0.001. Right mPAWp measured 4.3 ± 3.2 mmHg, statistically different from simultaneous direct mLAp of 2.8 ± 2.6 mmHg (P < 0.001. The PVR calculated using mPAWp was 1.2 ± 0.7 W.U., statistically different to 1.8 ± 0.95 W.U. using mLAp (P < 0.001). The average PVR measurement calculated using mPAWp underestimated the PVR calculated using mLAp by 0.6 W.U. It can be extrapolated that a PVR of 2.3 W.U. calculated using wedge measurements would estimate a PVR of 3 W.U. calculated using direct LA measurements. In this study, the PVR calculated using PAWp as a surrogate for LAp either equaled or underestimated the true PVR, up to 33% different. This difference is important in patients with univentricular physiology who rely on low PVR for cardiac output. Thus, based on this study, a PVR measurement of greater than 2.3 W.U. by the mPAWp method should prompt a direct LA pressure measurement, in order to more appropriately determine true surgical risk.

Shear Stress Causing Hemolytic Anemia and Congestive Heart Failure as an Initial Presentation of Cor Triatriatum in an Infant.

Among congenital cardiac defects, cor triatriatum sinistrum is a rare formation of 3 distinct atrial chambers in the heart. Depending on the size of the defect in the membranous septum, the symptoms can range from asymptomatic to severe pulmonary hypertension. Individuals can go years, sometimes to the second and third decades of life, before presenting with symptoms. Although it is well known to be associated with pulmonary veno-occlusive disease, the association with hemolytic anemia is much less well known. Identifying the subtle signs and symptoms of cor triatriatum in the emergency department can save a life. Here, we present the case of a 6-month-old infant with hemolytic anemia in the setting of right-sided congestive heart failure leading to the diagnosis of cor triatriatum. Anemia developed secondary to shearing stress caused by the heart defect itself. Complete resolution of symptoms occurred status post septectomy and repair of the defect.

Non-invasive biomarkers of Fontan-associated liver disease.

BACKGROUND & AIMS: Fontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored. METHODS: A retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed. RESULTS: Among 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m2, with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/µl for congestive hepatic fibrosis score [CHFS] 0-2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005). CONCLUSIONS: In this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population. LAY SUMMARY: In this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population.

Novel use of a vascular plug to anchor an azygous vein ICD lead.

We describe the case of a young patient with severe hypertrophic cardiomyopathy and marginal defibrillation thresholds (DFTs) at implant of a standard transvenous implantable cardioverter-defibrillator (ICD) system. The patient subsequently experienced multiple failed ICD shocks during a prolonged episode of spontaneous ventricular tachycardia/fibrillation. Placement of a second single-coil shocking lead in the azygous vein resulted in acceptable DFTs, but the new lead migrated superiorly within hours of the procedure. To stabilize the lead position, a vascular plug was placed in the distal azygous vein, and the shocking lead screw was actively fixated to the meshwork of the device. Subsequent testing confirmed both adequate defibrillation and stable lead position.

Need for Pulmonary Arterioplasty During Glenn Independently Predicts Inferior Surgical Outcome.

BACKGROUND: Bidirectional cavopulmonary anastomosis (BDCA) can be accomplished with low morbidity and mortality. The impact of concomitant pulmonary arterioplasty (PAplasty) is not known. We hypothesized that the need for and extent of PAplasty adversely affect BDCA outcomes. METHODS: Patients who underwent BDCA at our institution between 2006 and 2014 were included. Patient demographics, operative characteristics, mortality, and morbidity were analyzed. Serious physiologic adverse event following Glenn (GAE) was defined as need for extracorporeal support, BDCA takedown or percutaneous intervention during same admission, hospital length of stay 1 SD or more from mean, or need for supplemental oxygen at discharge. PAplasty was categorized according to extent. Data were analyzed using SAS 9.4 (SAS Institute, Cary, NC). RESULTS: A total of 424 patients (231 boys, 54%) underwent BDCA for single ventricle physiology at a median of 7 (5.5 to 8.9) months of age and 6.5 (5.7 to 7.7) kg weight. A total of 112 (26%) patients required PAplasty: 23 were patch closures of the divided distal PA (type 1), 45 were central PA augmentations (type 2), 23 extended to the hilum on 1-branch PA (type 3), and 21 were bilateral hilum to hilum augmentation (type 4). Patients who required PAplasty tended to be significantly younger and more likely to have single right ventricles. There was no difference in PA pressure or resistance between patients who did and did not require PAplasty. Major Society of Thoracic Surgeons morbidity (13% vs 6%; p = 0.001), GAE (45% vs 34%; p = 0.04), and in-hospital mortality (5.4% vs 1.9%; p = 0.03) were higher in patients who required PAplasty compared with those who did not. Among the operative variables evaluated, need for PAplasty (hazard ratio [HR], 1.6; p = 0.03) independently predicted hospital mortality. Need for circulatory arrest (HR, 4; p = 0.005) and PAplasty (HR, 2.4; p = 0.0006) were independent predictors of Society of Thoracic Surgeons morbidity and need for PAplasty independently predicted GAE (HR, 1.8; p = 0.03). CONCLUSIONS: The need for PAplasty at BDCA is an independent predictor of mortality and morbidity. It is important to consider this variable when developing outcome metrics for BDCA.

Prediction of Warfarin Dose in Pediatric Patients: An Evaluation of the Predictive Performance of Several Models.

OBJECTIVES: The objective of this study was to evaluate the performance of pediatric pharmacogenetic-based dose prediction models by using an independent cohort of pediatric patients from a multicenter trial. METHODS: Clinical and genetic data (CYP2C9 [cytochrome P450 2C9] and VKORC1 [vitamin K epoxide reductase]) were collected from pediatric patients aged 3 months to 17 years who were receiving warfarin as part of standard care at 3 separate clinical sites. The accuracy of 8 previously published pediatric pharmacogenetic-based dose models was evaluated in the validation cohort by comparing predicted maintenance doses to actual stable warfarin doses. The predictive ability was assessed by using the proportion of variance (R(2)), mean prediction error (MPE), and the percentage of predictions that fell within 20% of the actual maintenance dose. RESULTS: Thirty-two children reached a stable international normalized ratio and were included in the validation cohort. The pharmacogenetic-based warfarin dose models showed a proportion of variance ranging from 35% to 78% and an MPE ranging from -2.67 to 0.85 mg/day in the validation cohort. Overall, the model developed by Hamberg et al showed the best performance in the validation cohort (R(2) = 78%; MPE = 0.15 mg/day) with 38% of the predictions falling within 20% of observed doses. CONCLUSIONS: Pharmacogenetic-based algorithms provide better predictions than a fixed-dose approach, although an optimal dose algorithm has not yet been developed.

Impact of pre-stage II hemodynamics and pulmonary artery anatomy on 12-month outcomes in the Pediatric Heart Network Single Ventricle Reconstruction trial.

OBJECTIVE: To compare the interstage cardiac catheterization hemodynamic and angiographic findings between shunt types for the Pediatric Heart Network Single Ventricle Reconstruction trial. The trial, which randomized subjects to a modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS) for the Norwood procedure, demonstrated the RVPAS was associated with a smaller pulmonary artery diameter but superior 12-month transplant-free survival. METHODS: We analyzed the pre-stage II catheterization data for the trial subjects. The hemodynamic variables and shunt and pulmonary angiographic data were compared between shunt types; their association with 12-month transplant-free survival was also evaluated. RESULTS: Of 549 randomized subjects, 389 underwent pre-stage II catheterization. A smaller size, lower aortic and superior vena cava saturation, and higher ventricular end-diastolic pressure were associated with worse 12-month transplant-free survival. The MBTS group had a lower coronary perfusion pressure (27 vs 32 mm Hg; P<.001) and greater pulmonary blood flow/systemic blood flow ratio (1.1 vs 1.0, P=.009). A greater pulmonary blood flow/systemic blood flow ratio increased the risk of death or transplantation only in the RVPAS group (P=.01). The MBTS group had fewer shunt (14% vs 28%, P=.004) and severe left pulmonary artery (0.7% vs 9.2%, P=.003) stenoses, larger mid-main branch pulmonary artery diameters, and greater Nakata indexes (164 vs 134, P<.001). CONCLUSIONS: Compared with the RVPAS subjects, the MBTS subjects had more hemodynamic abnormalities related to shunt physiology, and the RVPAS subjects had more shunt or pulmonary obstruction of a severe degree and inferior pulmonary artery growth at pre-stage II catheterization. A lower body surface area, greater ventricular end-diastolic pressure, and lower superior vena cava saturation were associated with worse 12-month transplant-free survival.