The Estimated Fick Method Systematically Over-Estimates Cardiac Index Compared to Thermodilution in Children.

Cardiac index (CI) may be derived from the Fick method, using measured or estimated oxygen consumption (VO2), or from thermodilution. In children, LaFarge VO2 estimates correlate poorly with measured VO2 values. In a large adult cohort, there was only modest correlation between estimated Fick CI (eFick CI) and thermodilution CI (TDCI). We evaluated the extent of agreement between eFick CI using LaFarge estimates of VO2 and TDCI in a pediatric cohort. A retrospective, single-center chart review of patients 3-18 years of age who underwent cardiac catheterization with documented eFick CI and TDCI from 2004 to 2020 included 201 catheterizations from 161 unique patients. The mean patient age at catheterization was 12.2y (SD 4.4y). The most frequent diagnosis was cardiomyopathy, followed by congenital heart disease and pulmonary hypertension. TDCI and eFick CI differed by > 20% in 49% of catheterizations. eFick CI systematically exceeded TDCI by a mean percentage difference of 24% (SD 31%). Higher mean CI ((eFick CI + TDCI)/2) and older age were predictive of greater percent difference between eFick CI and TDCI. For each increase in mean CI by 1.0 L/min/m2, the expected percent difference in CI increased by 9.9% (p < 0.001). In pediatric patients undergoing cardiac catheterization, eFick CI with LaFarge VO2 systematically exceeds TDCI. The difference between methods is frequently > 20%, which may have clinically significant implications. Discrepancies between eFick CI and TDCI increase at higher mean CI.

Interventions on residual lesions in patients with heterotaxy syndrome following orthotropic heart transplantation: A single-center experience.

BACKGROUND: Heterotaxy syndrome (HS) is a defect in lateralization which often results in complex intra and extracardiac abnormalities. Orthotropic heart transplantation (OHT) in HS involves intricate and individualized modifications to surgical technique. Post-OHT outcomes are worse in patients with HS, however, the impact of post-OHT residual lesions has not yet been characterized. METHODS: Patients with HS who underwent OHT at Ann & Robert H. Lurie Children's Hospital of Chicago between January 2012 and June 2023 were identified. Patients were excluded if follow-up data was not available due to follow up at a different institution of early mortality. Pre-OHT clinical data, surgical data, and post-OHT surgical and catheterization data were collected. RESULTS: Two early mortalities were excluded from analysis, leaving 15 patients in the study cohort. Median age at OHT was 3.7 years (range: 0.7-15.4). Nine out of 15 patients were diagnosed with residual lesions requiring intervention at a median of 188 days post transplantation. All interventions on residual lesions occurred via catheterization. Overall mortality rate was 27% (4/15) with all deaths occurring in patients with residual lesions (4/9 patients, 44%). 83% (10/12) of lesions were diagnosed via catheterization, and 83% (10/12) of lesions of occurred in the first year after transplant. CONCLUSIONS: Patients with HS are at high risk for residual lesions after OHT, which may contribute to increased mortality. Comprehensive invasive diagnostics were required to diagnose residual lesions, which were all addressed percutaneously.

Histopathology, mRNA expression profile, and donor-derived cell-free DNA for assessment of rejection in pediatric heart transplantation.

BACKGROUND: The relationship between histopathologic and molecular ("MMDx"®) assessments of endomyocardial biopsy (EMB) and serum donor-derived cell-free DNA (ddcfDNA) in acute rejection (AR) assessment following pediatric heart transplantation (HT) is unknown. METHODS: EMB sent for MMDx and histopathology from November 2021 to September 2022 were reviewed. MMDx and histopathology results were compared. DdcfDNA obtained ≤1 week prior to EMB were compared with histopathology and MMDx results. The discrimination of ddcfDNA for AR was assessed using receiver-operating curves. FINDINGS: In this study, 177 EMBs were obtained for histopathology and MMDx, 101 had time-matched ddcfDNA values. MMDx and Histopathology displayed moderate agreement for T-cell-mediated rejection (TCMR, Kappa = 0.52, p < .001) and antibody-mediated rejection (ABMR, Kappa = 0.41, p < .001). Discordant results occurred in 24% of cases, most often with ABMR. Compared with no AR, ddcfDNA values were elevated in cases of AR diagnosed by both histopathology and MMDx (p < .01 for all). Additionally, ddcfDNA values were elevated in injury patterns on MMDx, even when AR was not present (p = .01). DdcfDNA displayed excellent discrimination (AUC 0.83) for AR by MMDx and/or histopathology. Using a threshold of ≥0.135%, ddcfDNA had a sensitivity of 90%, specificity of 63%, PPV of 52%, and NPV of 94%. CONCLUSIONS: Histopathology and MMDx displayed moderate agreement in diagnosing AR following pediatric HT, with most discrepancies noted in the presence of ABMR. DdcfDNA is elevated with AR, with excellent discrimination and high NPV particularly when utilizing MMDx. A combination of all three tests may be necessary in some cases.

Cardiac magnetic resonance imaging in detection of progressive graft dysfunction in pediatric heart transplantation.

BACKGROUND: Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method. METHODS: Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression were performed. RESULTS: Forty-seven PHT with median age at CMR of 15.7 years (11.6, 19.3) and time from transplant of 6.4 years (4.1, 11.0) were studied. Cardiac allograft vasculopathy (CAV) was present in 11/44 (22.0%) and historical rejection in 14/41 (34.2%). CAV was associated with higher global T2 (49.0 vs. 47.0 ms; p = 0.038) and peak T2 (57.0 vs. 53.0 ms; p = 0.013) on CMR. Historical rejection was associated with higher global T2 (49.0 vs. 47.0 ms; p = 0.007) and peak T2 (57.0 vs. 53.0 ms; p = 0.03) as well as global extracellular volume (31.0 vs. 26.3%; p = 0.03). Higher fibrosis score on EMB correlated with smaller indexed left ventricular mass (rho = -0.34; p = 0.019) and greater degree of MVD with lower indexed left ventricular end-diastolic volume (rho = -0.35; p = 0.017). CONCLUSION: Adverse ventricular remodeling and abnormal myocardial characteristics on CMR are present in PHT with CAV, historical rejection, as well as greater fibrosis and MVD on EMB. CMR has the potential use for screening of CGF.

One children's hospital planning and development process to adhere to the FDA recommendation that babies and young children undergo thyroid function testing after receiving an injection of iodine-containing contrast media for medical imaging.

The United States (US) Food and Drug Administration (FDA) has issued multiple statements and guidelines since 2015 on the topic of thyroid function testing in babies and children through 3 years old after receiving iodinated contrast media for medical imaging exams. In April 2023, the FDA adjusted this recommendation to target babies and young children younger than 4 years of age who have a history of prematurity, very low birth weight, or underlying conditions which affect thyroid gland function, largely in response to solid arguments from expert statements from the American College of Radiology (ACR) which is endorsed by the Society for Pediatric Radiology (SPR), Pediatric Endocrinology Society (PES), and the Society for Cardiovascular Angiography & Intervention (SCAI). Herein we describe our approach and development of a clinical care guideline along with the steps necessary for implementation of the plan including alterations in ordering exams requiring iodinated contrast media, automatic triggering of lab orders, reporting, and follow-up, to address the 2022 FDA guidance statement to monitor thyroid function in children after receiving iodinated contrast media. The newly implemented clinical care guideline at Ann and Robert H. Lurie Children's Hospital of Chicago remains applicable following the 2023 updated recommendation from the FDA. We will track patients less than 3 months of age who undergo thyroid function testing following computed tomography (CT), interventional radiology, and cardiac catheterization exams for which an iodinated contrast media is administered as a clinical care quality initiative.

Echocardiogram-Guided Balloon Valvuloplasty of the Aortic Valve in Neonates and Infants Reduces Contrast Exposure with Maintained Efficacy and Less Aortic Regurgitation.

Balloon aortic valvuloplasty (BAV) is performed in children with significant aortic stenosis (AS). Traditionally, contrast angiography measures the annulus and assesses aortic regurgitation (AR) after each dilation. Echocardiographic guidance is hypothesized to reduce contrast and radiation exposure, without compromising efficacy or safety. Patients < 10 kg undergoing BAV from 2013 to 2022 were retrospectively investigated. Agreement between echocardiographic and angiographic annulus measurements was assessed. Echocardiogram-guided (eBAV) and traditional angiogram-guided (tBAV) outcomes were compared controlling for weight, critical AS, and other congenital heart disease (CHD). Twelve eBAV and 19 tBAV procedures were performed. The median age was 33 days, median weight was 4.3 kg, 7 patients (23%) had critical AS, and 9 patients (29%) had other CHD. Annulus measurements by intraprocedural echocardiography and angiography displayed excellent correlation (ICC 0.95, p < 0.001). eBAV patients received less contrast (0.5 vs 3.5 ml/kg, p < 0.01). Five recent eBAV procedures were performed contrast free. Radiation exposure was not statistically different between the eBAV and tBAV groups (155 vs 313 µGy·M2, p = 0.12). One eBAV patient (8%) and 3 tBAV patients (16%, p = 0.62) experienced serious adverse events. Technical success (gradient < 35 mmHg and increase in AR by ≤ 1 grade) occurred in 11 eBAV patients (92%) and 16 tBAV patients (84%, p = 0.22). AR increased in 2 eBAV patients (17%) and 8 tBAV patients (44%, p = 0.02). eBAV was associated with similar efficacy and significantly lower contrast exposure and risk of aortic regurgitation. There was strong agreement between aortic valve annulus measurements by intraprocedural echocardiography and angiography, ultimately permitting contrast free BAV.

Left Atrial Hypertension and Respiratory Failure Requiring Venoarterial ECMO After Transcatheter Pulmonary Valve Replacement.

A 33-year-old woman with aortic valve stenosis status-post Ross at age 6 years developed symptomatic right heart failure from right ventricle to pulmonary artery conduit stenosis. Conduit rehabilitation and transcatheter pulmonary valve replacement resulted in acute left atrial hypertension and respiratory failure requiring venoarterial extracorporeal membrane oxygenation and atrial septal defect creation as a bridge to recovery.

Differences in outcomes between surgical pericardial window and pericardiocentesis in children with postpericardiotomy syndrome.

Children with postpericardiotomy syndrome may develop hemodynamically significant pericardial effusions warranting drainage by surgical pericardial window or pericardiocentesis. The optimal approach is unknown. We performed a retrospective observational study at two pediatric cardiac centers. We included 42 children aged <18 years who developed postpericardiotomy syndrome following cardiac surgery between 2014 and 2021. Thirty-two patients underwent pericardial window and 10 underwent pericardiocentesis. Patients in the pericardial window group presented with postpericardiotomy syndrome sooner than those who underwent pericardiocentesis (median 7.5 days vs. 14.5 days, P = 0.03) and tended to undergo earlier intervention (median 8 days vs. 16 days, P = 0.16). No patient required subsequent drainage. There were no differences between groups in days of pericardial tube duration (median 4 days), complications, and subsequent days of intensive care or hospitalization. For children with postpericardiotomy syndrome with a pericardial effusion warranting drainage, these data suggest that pericardial window and pericardiocentesis have similar efficacy, safety, and resource utilization.

A Volume Challenge Reveals the Diagnosis of Pediatric Restrictive Cardiomyopathy.

A healthy 11-year-old girl presented with exercise intolerance of unclear etiology, and her physical exam was notable for a 3/6 systolic ejection murmur at the left upper sternal border with radiation to the back. Extensive noninvasive workup consisted of ECG, transthoracic echocardiogram, and cardiac MRI/MRA, which were all nondiagnostic. She was ultimately referred for cardiac catheterization. Baseline invasive hemodynamics demonstrated a normal cardiac index and pulmonary vascular resistance but was notable for mildly elevated right and left end-diastolic pressures. A diagnosis remained elusive, so a 500 mL volume challenge was performed, which unmasked right and left ventricular waveform transformations to reveal the pathognomonic "square root sign" of restrictive cardiomyopathy with concordant RV/LV respirophasic variation. These findings and her clinical history allowed for the rare pediatric diagnosis of restrictive cardiomyopathy early in her clinical course, prior to the development of overt signs of pathologic myocardial remodeling, such as pulmonary hypertension and biatrial enlargement.

Combined Echo and Fluoroscopy-Guided Pulmonary Valvuloplasty in Neonates and Infants: Efficacy and Safety.

Percutaneous balloon pulmonary valvuloplasty (PBPV) is the treatment of choice for isolated pulmonary valve stenosis. While this procedure is highly efficacious and has an excellent safety profile, as currently practiced, patients are obligatorily exposed to the secondary risks of ionizing radiation and contrast media. To mitigate these risks, we developed a protocol which utilized echo guidance for portions of the procedure which typically require fluoroscopy and/or angiography. Ten cases of echo-guided pulmonary valvuloplasty (EG-PBPV) for isolated pulmonary stenosis in children less than a year of age were compared to a historical cohort of nineteen standard cases using fluoroscopy/angiography alone, which demonstrated equivalent procedural outcomes and safety, while achieving a median reduction in radiation (total dose area product) and contrast load of 80% and 84%, respectively. Our early experience demonstrates that EG-PBPV in neonates and infants has results equivalent to standard valvuloplasty but with less radiation and contrast.

Deployed Dimensions of the GORE® CARDIOFORM ASD Occluder as Function of Defect Size.

The GORE® CARDIOFORM ASD occluder (ASDO) is approved for closure of ASDs up to 35 mm diameter. With an adaptable central waist, each device size is suitable over a range of defect diameters. Understanding deployed dimensions across various defect sizes will assist operators. Therefore, this study investigates the deployed dimensions of the ASDO as a function of defect size. A 2-mm-thick ASD model with circular defects ranging from 5 to 35 mm was 3D printed. Diameter, width, and left-right disc diameter were measured by fluoroscopy after ASDO devices were deployed in applicable defects. Linear regression evaluated relationships between device size, defect size, and deployed dimensions. Six ASDOs of each size (27, 32, 37, 44, and 48 mm) were deployed in all applicable defects. There was significant ASDO size-defect size interaction in determining deployed ASDO diameter. Diameter was positively associated with defect size for 48-mm (B = 0.13, p < 0.001) and 44-mm (B = 0.11, p < 0.001) ASDOs, while no association was seen for 27-mm, 32-mm, or 37-mm ASDOs. No such interaction existed for deployed width or left-right disc difference. Controlling for ASDO size, width (B = - 0.12, p < 0.001) and left-right disc difference (B = - 0.06, p < 0.001) were negatively associated with defect size. In smaller defects, the 44-mm and 48-mm ASDOs display progressive diameter foreshortening, and all devices display progressive increase in width and left-right disc asymmetry. Anticipating the degree of diameter foreshortening may be critical when attempting closure of fenestrated lesions and/or in patients with limited total atrial septal length.

Transcatheter biventricular conversion in an adult patient with a 1.5 ventricle Glenn palliation and superior vena cava syndrome.

Covered stents have a continually expanding spectrum of applications for patients with congenital heart disease. Here we report use of covered stents to successfully perform a first-in-human percutaneous biventricular conversion of a 1.5 ventricle Glenn palliation in an adult born with pulmonary atresia. This case demonstrates that in patients considered borderline for biventricular repair, surgery can potentially be modified to promote growth of underdeveloped structures and setup for transcatheter biventricular conversion.

Use of a Dilatable exGraft Conduit in Single-Ventricle Palliation.

Surgically paced prosthetic conduits are commonly used in the treatment of congenital heart disease. A major limitation of available prosthetic grafts is that they do not grow with the patient. We describe a human case of percutaneous balloon dilation of a surgically placed exGraft conduit (PECA Labs, Inc, Pittsburgh, PA) in a neonate with single-ventricle disease. The use of dilatable conduits could change the management of many congenital heart defects and greatly reduce both the morbidity of repeat cardiac reoperations and the deleterious effects of prolonged conduit dysfunction that accrue between surgical conduit revisions.

Diagnosis and Management of Anomalous Left Anterior Descending Coronary Artery from the Pulmonary Artery in an Asymptomatic Infant.

Anomalous origin of the left anterior descending coronary artery from the pulmonary artery is a rare variant of anomalous origin of the left main coronary artery from the pulmonary artery. We report on a seemingly asymptomatic patient with ALADCAPA and a small restrictive muscular ventricular septal defect diagnosed by echocardiogram in the neonatal period. Our patient underwent elective repair at 3.5 months of age after which feeding and growth improved dramatically. Multimodality imaging is helpful to confirm this rare anomaly; however, echocardiographic clues including lack of left coronary branching or an abnormal coronary course should raise suspicion for ALADCAPA. This case provides support for early repair in children with an incidental finding of this anomaly as subclinical ischemia may be under-recognized by available testing but may lead to symptoms later in life.

Safety and effectiveness of stoss therapy in children with vitamin D deficiency.

AIM: Paediatric vitamin D (25-hydroxyvitamin D (25OHD)) deficiency can lead to nutritional rickets and extra-skeletal complications. Compliance with daily therapy can be difficult, making high-dose, short-term vitamin D (stoss) therapy attractive to correct vitamin D deficiency. We compared the effectiveness and safety of standard versus stoss therapy in treating childhood 25OHD deficiency. METHODS: Children aged 2-16 years with 25OHD <50 nmol/L were randomised to either standard (5000 IU daily for 80 days) or stoss (100 000 IU weekly for 4 weeks) cholecalciferol. Participants underwent an evaluation of effectiveness and safety. The 25OHD level, random spot calcium: creatinine ratio (Ca:Cr) and compliance were measured at 12 weeks. RESULTS: A total of 151 children were enrolled in the study (68 standard and 83 stoss), median age 9 years (inter-quartile range (IQR): 6-12 years). Baseline 25OHD levels were 26 nmol/L (IQR: 19-35 nmol/L) and 32 nmol/L (IQR: 24-39 nmol/L) in the standard and stoss groups, respectively. At 12 weeks, the median 25OHD level was significantly greater in the standard versus stoss group (81 vs. 67 nmol/L; P = 0.005); however, >80% of participants in both groups achieved sufficiency (25OHD > 50 nmol/L) and had normal urinary Ca:Cr, with no significant difference seen between groups. Compliance was similar in the two groups. CONCLUSIONS: Compared to stoss, standard therapy achieved higher 25OHD levels at 12 weeks; however, in both groups, there was a similar proportion of participants who achieved 25OHD sufficiency, with no evidence of toxicity. Unlike other studies, simplifying the treatment regimen did not improve compliance. These results support stoss therapy as an effective and safe alternative therapy for the treatment of paediatric vitamin D deficiency.

Normalization of hemodynamics is delayed in patients with a single ventricle after pediatric heart transplantation.

OBJECTIVES: The time course for hemodynamic normalization after pediatric heart transplantation has not been well characterized. We hypothesized that patients with a single ventricle would normalize later than those with dilated cardiomyopathy. Establishing the expected course based on the underlying pathophysiology will allow identification of patients who are outliers, requiring further investigation. METHODS: We performed a retrospective review of patients with dilated cardiomyopathy, Glenn, and Fontan who underwent heart transplantation from January 2007 to December 31, 2017, and had 6-month and 1-year catheterization data. Hemodynamic data were examined for sustained normalization of pressures. Myocardial biopsies were reviewed for clinically significant rejection within the first year. RESULTS: Ninety-four patients comprised the cohort (47 dilated cardiomyopathy, 18 Glenn, 29 Fontan) with a median age of 6.8 (12) years. Patients with dilated cardiomyopathy were more likely to normalize hemodynamics by 6 months (85% vs 28% Fontan, 44% Glenn, P < .05), and 96% of patients with dilated cardiomyopathy had normalized hemodynamics by 1 year (vs 62% Fontan, 78% Glenn, P < .001). The pulmonary capillary wedge pressure at 6 months was higher in patients who underwent the Fontan and Glenn (median 12.8 [8.8] mm Hg and 11.2 [5.9] mm Hg, respectively) compared with patients with dilated cardiomyopathy (7.0 [3.3] mm Hg, P < .001). Patients with dilated cardiomyopathy demonstrated normalized hemodynamics earlier (121 ± 72 days) than patients who underwent the Fontan (329 ± 62 days) and Glenn (233 ± 11 days, P < .001). Eighteen patients (19%) experienced significant rejection, which was not increased in patients with delayed hemodynamic normalization. The 6-month pulmonary capillary wedge pressure was associated with delayed normalization (hazard ratio, 1.36; 95% confidence interval, 1.16-1.60; P < .001). CONCLUSIONS: Patients with a single ventricle demonstrated delayed hemodynamic normalization compared with dilated cardiomyopathy heart transplant recipients, without affecting survival or need for retransplantation.