De Novo and Progressive Pulmonary Vein Stenosis Following Pediatric Heart Transplantation: A Multicenter Retrospective Study.

BACKGROUND: Pulmonary vein stenosis (PVS) is a rare condition in which neointimal proliferation leads to venous and arterial hypertension. Little is known about PVS after heart transplant (HTx) in children. We sought to describe the characteristics and outcomes of children who develop PVS after HTx. METHODS: We performed a retrospective review of patients ≤18 years old who underwent HTx at two HTx centers between April 2012 and October 2023. Patients with PVS were identified via database queries. Cardiac diagnosis, PVS location and extent, and outcomes were recorded. RESULTS: Over 11.5 years, 422 patients underwent HTx across both centers. Nineteen patients with PVS (10 male) were identified, 15 with de novo PVS. Sixteen had underlying congenital heart disease (CHD), two with anomalous pulmonary venous return. PVS was diagnosed at a median of 2 months (range 2 weeks to 14 years) after HTx. At time of initial diagnosis, 13 patients had one-vessel PVS. At final follow-up, 7/19 (37%) had increases in the number of vessels involved. Six patients underwent surgery, and nine patients had stent or balloon angioplasty. Two patients were treated for pulmonary hypertension following PVS diagnosis. Three patients died from right heart failure secondary to PVS. CONCLUSIONS: This is the largest study to describe the characteristics of post-HTx PVS in children. PVS occurs in 4.5% of HTx, and underlying CHD is a strong risk factor. Multiple vessels can be involved and may require catheter-based or surgical intervention. Clinicians must be vigilant in monitoring the development of PVS in this population.

Common atrial reservoir strain during the interstage period is a predictor of poor outcomes prior to Fontan completion in hypoplastic left heart syndrome.

BACKGROUND: The atrium augments ventricular function, but the significance of atrial function in hypoplastic left heart syndrome (HLHS) has not been well evaluated. OBJECTIVE: We investigated the association of atrial reservoir strain (common atrial strain [CAS]) to death or need for transplantation in patients with HLHS. METHODS: In this retrospective single-center study, echocardiograms from three timepoints (pre-stage 1 palliation [S1P], 4-8 weeks post-S1P, and pre-Glenn) were analyzed in infants with classic HLHS. Patients were separated based on transplant-free survival to Fontan (survivors) versus death or heart transplant prior to Fontan (composite outcome). Echocardiographic parameters evaluated included CAS, right ventricle (RV) global longitudinal strain (RVGLS), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE). An equal variance t-test, regression, and receiver operating characteristic (ROC) analyses were performed. RESULTS: A total of 45 HLHS patients (25 survivors, 20 patients meeting endpoint) were included in this study. There were no significant differences in any of the functional parameters during the pre-stage 1 or post-stage 1 timepoints. Pre-Glenn CAS and RVGLS were significantly worse in those meeting composite endpoint compared to survivors. CAS was significantly correlated to RVGLS during the pre-S1P and pre-Glenn timepoints. A pre-Glenn CAS < 19.5 had an area under the curve of  .78 and a 75% sensitivity and 83% specificity for death or need for transplantation. CONCLUSION: Pre-Glenn CAS is significantly lower in patients with mortality or need for the transplantation prior to Fontan completion and may carry prognostic significance in patients with HLHS.

An Infant with High-Output Heart Failure and Pulmonary Hypertension Resulting from a Giant Cutaneous Hemangioma.

We present the clinical course of an 8-month-old infant with a giant cutaneous hemangioma resulting in high-output heart failure and pulmonary hypertension. The lesion was successfully embolized and excised, with rapid resolution of heart failure and improvement in pulmonary hypertension.

Prognostic Value of RV Function Analysis During the Interstage Period in Patients with Hypoplastic Left Heart Syndrome.

Cardiac dysfunction is associated with mortality in children with hypoplastic left heart syndrome (HLHS). We evaluated the ability of qualitative and quantitative RV functional parameters to predict outcomes in HLHS patients. In this retrospective, single-center study, echocardiograms from 3 timepoints (pre-stage 1 palliation, 4-8 weeks post-stage 1 palliation, and pre-Glenn) were analyzed in infants with HLHS. Patients were stratified into two groups based on outcome of transplant-free survival post-Glenn (survivors) versus mortality or transplantation prior to Fontan (non-survivors). Images were retrospectively reviewed to obtain RV global longitudinal strain (RVGLS), RV-free wall strain (RVFWS), fractional area change (FAC), tricuspid annular systolic plane excursion (TAPSE), tissue motion annular displacement of the tricuspid valve (TMAD-TV) and qualitative systolic function assessment during the predetermined timepoints. An equal variance t-test and chi-square were used to determine significant differences and ROC curve analysis was performed to derive optimal cutoff values to predict mortality/transplant. A total of 47 patients met inclusion criteria, of which, 21 patients met composite endpoint. There were no significant differences in any RV functional parameter during the pre- or post-stage 1 palliation timepoints. The absolute values of RVFWS, RVGLS, and TMAD-TV were significantly greater in survivors than non-survivors during the pre-Glenn timepoint. A pre-Glenn RVGLS > -15.6 (AUC 0.79), RVFWS > -18.6 (AUC 0.75), and TMAD-TV < 12.6% (AUC 0.82) were sensitive and specific for predicting death or need for transplantation prior to Fontan completion. RVGLS, RVFWS, and TMAD-TV may help identify higher-risk HLHS patients during the interstage period.

Simulation Based Mastery Learning of Transesophageal Echocardiography.

Transesophageal echocardiography (TEE) education is part of pediatric cardiology fellow training. Simulation-based mastery learning (SBML) is an efficient and valuable education experience. The aim of this project was to equip trainees with the basic knowledge and skill required to perform a pediatric TEE. The secondary aim was to assess the utility of using SBML for pediatric TEE training. The target group is trainees from pediatric cardiology and cardiac anesthesia who participated in a TEE bootcamp. A baseline knowledge pretest was obtained. The knowledge session consisted of preparation via reading material, viewing recorded lectures and completing an iterative multiple-choice examination, which was repeated until a minimum passing score of 90% was achieved. The skills session involved a review of TEE probe manipulation and image acquisition, followed by rapid cycle deliberate practice using simulation to acquire TEE skills at 3 levels, advancing in complexity from level 1 to level 3. Eight individuals (7 pediatric cardiology fellows at varying training levels and one anesthesia attending) participated in the TEE bootcamp. All reached a minimum knowledge post test score of at least 90% before the skills session. All subjects reached mastery in TEE probe manipulation. All reached mastery in image acquisition for the skill level that they attempted (level 1-8/8, level 2-8/8, level 3-4/4, with 4 participants not attempting level 3). A TEE bootcamp using SBML is a powerful medical education strategy. SBML is a rigorous approach that can be used to achieve high and uniform TEE learning outcomes among trainees of different training levels and backgrounds.

Clinical Predictors of Subacute Myocardial Dysfunction in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19.

Multisystem Inflammatory Syndrome in Children (MIS-C) often involves a post-viral myocarditis and associated left ventricular dysfunction. We aimed to assess myocardial function by strain echocardiography after hospital discharge and to identify risk factors for subacute myocardial dysfunction. We conducted a retrospective single-center study of MIS-C patients admitted between 03/2020 and 03/2021. Global longitudinal strain (GLS), 4-chamber longitudinal strain (4C-LS), mid-ventricular circumferential strain (CS), and left atrial strain (LAS) were measured on echocardiograms performed 3-10 weeks after discharge and compared with controls. Among 60 MIS-C patients, hypotension (65%), ICU admission (57%), and vasopressor support (45%) were common, with no mortality. LVEF was abnormal (< 55%) in 29% during hospitalization but only 4% at follow-up. Follow-up strain abnormalities were prevalent (GLS abnormal in 13%, 4C-LS in 18%, CS in 16%, LAS in 5%). Hypotension, ICU admission, ICU and hospital length of stay, and any LVEF < 55% during hospitalization were factors associated with lower strain at follow-up. Higher peak C-reactive protein (CRP) was associated with hypotension, ICU admission, total ICU days, and with lower follow-up GLS (r = - 0.55; p = 0.01) and CS (r = 0.41; p = 0.02). Peak CRP < 18 mg/dL had negative predictive values of 100% and 88% for normal follow-up GLS and CS, respectively. A subset of MIS-C patients demonstrate subclinical systolic and diastolic function abnormalities at subacute follow-up. Peak CRP during hospitalization may be a useful marker for outpatient cardiac risk stratification. MIS-C patients with hypotension, ICU admission, any LVEF < 55% during hospitalization, or a peak CRP > 18 mg/dL may warrant closer monitoring than those without these risk factors.

Right ventricular septal pacing via transmural approach for resynchronization in a child with postoperative heart block.

An infant with transposition of the great arteries was paced for postoperative heart block (single-site, right ventricular [RV] epicardial). She developed severe left ventricular (LV) dysfunction and septal dyskinesis. Resynchronization was performed at the age of 4 with an LV epicardial lead and an RV septal endocardial lead. The endocardial lead was affixed to the interventricular septum, then tunneled through the RV free wall and attached to an abdominal pulse generator. QRS duration decreased (176 to 122 ms) and LV ejection fraction improved (26 to 61%) and remained stable for 8 years. We present a case of successful resynchronization in congenital heart disease using a transmural RV septal lead.

Odontomas in Frogs.

Odontomas are variably differentiated, hamartoma-like proliferations of odontogenic epithelium, pulp ectomesenchyme (odontoblasts), and dental matrix. Frogs are polyphyodont and homodont. Their teeth also differ from mammals in that they are restricted to the upper jaw in adults and lack a periodontal ligament and cementum, attaching directly to the underlying bone. Odontomas were identified in an African clawed frog (Xenopus laevis), a false tomato frog (Dyscophus guineti), and a tomato frog of unknown species (Dyscophus sp.). All of the examined odontomas were composed of numerous tooth-like structures comprising an arc of dentinal matrix lined on the convex surface by ameloblasts and on the concave surface by odontoblasts. Masson's trichrome and immunohistochemistry with pan-cytokeratin supported these findings. The pathogenesis of these lesions may be displacement of the dental lamina, which has been shown in research studies to lead to de novo proliferation of dental elements in frogs.

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.

Kinetics of procalcitonin and C-reactive protein and the relationship to postoperative infection in young infants undergoing cardiovascular surgery.

BACKGROUND: The utility of procalcitonin (PCT) and C-reactive protein (CRP) as infectious biomarkers following infant cardiothoracic surgery is not well defined. METHODS: We designed a prospective cohort study to evaluate PCT and CRP after infant cardiothoracic surgery. PCT and CRP were drawn preoperatively and 24/72 h postoperation or daily in delayed sternal closure patients. Presence of infection within 10 d of surgery, vasoactive-inotropic scores at 24 and 72 h, and length of intubation, intensive care unit stay, and hospital stay were documented. RESULTS: PCT and CRP were elevated at 24 h. PCT then decreased while CRP increased in patients undergoing delayed sternal closure or cardiopulmonary bypass. In the delayed sternal closure group, PCT was significantly higher on postoperative days 2-5 in patients who ultimately developed infection. Higher PCT was independently associated with increased vasoactive-inotropic score at 72 h. CRP did not correlate with infection or postoperative support. CONCLUSION: PCT rises after cardiothoracic surgery in infants but decreases by 72 h while CRP remains elevated. Sternal closure may affect CRP but not PCT. PCT is independently associated with circulatory support requirements at 72 h postoperation and with development of infection. PCT may have greater utility as a biomarker in this population.

Tricuspid atresia associated with truncus arteriosus versus aortopulmonary window: combining fetal and postnatal echocardiography to make the diagnosis.

The coincident occurrence of tricuspid atresia and aortopulmonary window (APW) is exceedingly rare, with one previous case reported in the literature. We present a patient with tricuspid atresia, pulmonary atresia, and APW. Postnatal echocardiograms demonstrated no visible pulmonary valve, and additional defects including a bicuspid aortic valve, right aortic arch and anomalous coronary arteries raised suspicion for tricuspid atresia with persistent truncus arteriosus. However, fetal echocardiography and direct visualization of the anatomy confirmed the alternate diagnosis. The patient underwent successful palliation consisting of APW repair, atrial septectomy and a 3.5 mm modified Blalock-Taussig shunt, followed by a bidirectional cavopulmonary connection.

Pulmonary Hypertension in Congenital Heart Disease: A Scientific Statement From the American Heart Association.

Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research needs of patients with pulmonary hypertension associated with congenital heart disease.

Alkaline phosphatase activity after cardiothoracic surgery in infants and correlation with post-operative support and inflammation: a prospective cohort study.

INTRODUCTION: Limited evidence suggests that serum alkaline phosphatase activity may decrease after cardiac surgery in adults and children. The importance of this finding is not known. Recent studies, however, have identified a potential role for alkaline phosphatase as modulator of inflammation in multiple settings, including during adult cardiopulmonary bypass. We sought to describe the change in alkaline phosphatase activity after cardiothoracic surgery in infants and to assess for a correlation with intensity and duration of post-operative support, markers of inflammation, and short-term clinical outcomes. METHODS: Sub-analysis of a prospective observational study on the kinetics of procalcitonin in 70 infants (≤ 90 days old) undergoing cardiothoracic surgery. Subjects were grouped based on the use of cardiopulmonary bypass and delayed sternal closure. Alkaline phosphatase, procalcitonin, and C-reactive protein (CRP) levels were obtained pre-operation and on post-operative day 1. Mean change in alkaline phosphatase activity was determined in each surgical group. Generalized linear modeling and logistic regression were employed to assess for associations between post-operative alkaline phosphatase activity and post-operative support, inflammation, and short term outcomes. Primary endpoints were vasoactive-inotropic score at 24 hours and length of intubation. Secondary endpoints included procalcitonin/CRP levels on post-operative day 1, length of hospital stay, and cardiac arrest or death. RESULTS: Mean decrease in alkaline phosphatase was 30 U/L (p = 0.01) in the non-bypass group, 114 U/L (p < 0.0001) in the bypass group, and 94 U/L (p < 0.0001) in the delayed sternal closure group. On multivariate analysis, each 10 U/L decrease in alkaline phosphatase activity on post-operative day 1 was independently associated with an increase in vasoactive-inotropic score by 0.7 (p < 0.0001), intubation time by 6% (p < 0.05), hospital stay by 5% (p < 0.05), and procalcitonin by 14% (P < 0.01), with a trend towards increased odds of cardiac arrest or death (OR 1.3; p = 0.06). Post-operative alkaline phosphatase activity was not associated with CRP (p = 0.7). CONCLUSIONS: Alkaline phosphatase activity decreases after cardiothoracic surgery in infants. Low post-operative alkaline phosphatase activity is independently associated with increased procalcitonin, increased vasoactive/inotropic support, prolonged intubation time, and prolonged hospital stay. Alkaline phosphatase may serve as a biomarker and potential modulator of post-operative support and inflammation following cardiothoracic surgery in infants.

The association between pulmonary vascular disease and respiratory improvement in infants with type I severe bronchopulmonary dysplasia.

OBJECTIVE: To describe the association between echocardiographic measures of pulmonary vascular disease and time to respiratory improvement among infants with Type I severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: We measured the pulmonary artery acceleration time indexed to the right ventricular ejection time (PAAT/RVET) and right ventricular free wall longitudinal strain (RVFWLS) at 34-41 weeks' postmenstrual age. Cox-proportional hazards models were used to estimate the relationship between the PAAT/RVET, RVFWLS, and the outcome: days from 36 weeks' postmenstrual age to room-air or discharge with oxygen (≤0.5 L/min). RESULT: For 102 infants, the mean PAAT/RVET and RVFWLS were 0.27 ± 0.06 and -22.63 ± 4.23%. An abnormal measurement was associated with an increased time to achieve the outcome (PAAT/RVET: 51v24, p < 0.0001; RVFWLS; 62v38, p = 0.0006). A normal PAAT/RVET was independently associated with a shorter time to outcome (aHR = 2.04, 1.11-3.76, p = 0.02). CONCLUSION: The PAAT/RVET may aid in anticipating timing of discharge in patients with type I severe BPD.

Predictors of Bicuspid Aortic Valve-Associated Aortopathy in Childhood: A Report From the MIBAVA Consortium.

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients. METHODS: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity of AS and AI, history of coarctation, and aortic dimensions. Associations were determined using multivariable regression analysis. A subset of patients undergoing aortic interventions (balloon dilation or Ross) were assessed longitudinally. RESULTS: Data were obtained from 2122 patients (68% male; median age 10.2 years). Fifty percent of patients had ascending aorta dilatation. Right and noncoronary cusp fusion, increasing AS and AI, and older age were independently associated with ascending aorta dilatation. A history of coarctation was associated with less ascending aorta dilatation. In patients with neither AS nor AI, 37% had ascending aorta dilatation (4% severe). No complications related to aortic dilatation occurred in this cohort. Aortic Z scores were determined, and a Z-score calculator was created for this population. CONCLUSIONS: In this large pediatric cohort of patients with BAV, valve morphology, AS, and AI are independently associated with ascending aorta dilatation, suggesting that hemodynamic factors influence aortopathy. However, even in BAVs with no AS or AI, there is significant ascending aorta dilatation independent of valve morphology. Interventions that led to changes in degree of AI and AS did not seem to influence change in aortic dimensions. The current BAV cohort can be used as a reference group for expected changes in aortic dimensions during childhood.

Supra-Annular Mitral Implantation of Melody Valve: Minimizing Left Ventricular Outflow Tract Obstruction.

Utilization of the Melody valve for mitral valve replacement has been previously reported; however, left ventricular outflow tract obstruction is a frequent concern. In this report, a technique for supra-annular placement of the Melody valve in the mitral position is described which will minimize the risk of left ventricular outflow tract obstruction.

Electrocardiograms for cardiomyopathy risk stratification in children with anthracycline exposure.

BACKGROUND: Early recognition of anthracycline-induced cardiomyopathy may reduce morbidity and mortality in children, but risk stratification tools are lacking. This study evaluates whether electrocardiogram (ECG) changes precede echocardiographic abnormalities in children with anthracycline-induced cardiomyopathy. METHODS: We performed a retrospective analysis of 589 pediatric cancer patients who received anthracyclines at a tertiary referral center. ECG endpoints were sum of absolute QRS amplitudes in the 6 limb leads (ΣQRS(6 L)) and corrected QT interval (QTc). Cardiomyopathy was defined by echocardiogram as ejection fraction < 50%, shortening fraction < 26%, or left ventricular end-diastolic diameter z-score > 2.5. RESULTS: Median age at start of therapy was 7.8 years (IQR 3.7-13.6); median follow-up time was 3.6 years (IQR 1.1-5.8). 19.5% of patients met criteria for cardiomyopathy. Male sex, race, older age at first dose, and larger body surface area were associated with development of cardiomyopathy. A 0.6 mV decrease in ΣQRS(6 L) and 10 ms increase in QTc were associated with an increased risk of developing cardiomyopathy with hazard ratios of 1.174 (95% CI = 1.057-1.304, p = 0.003) and 1.098 (95%CI = 1.027-1.173, p = 0.006) respectively. Kaplan-Meier estimates showed a lower chance of cardiomyopathy-free survival for QTc ≥ 440 ms and ΣQRS(6 L) ≤ 3.2 mV over time. After controlling for confounders, total anthracycline dose predicted a decrease in ΣQRS(6 L) and an increase in QTc independent of cardiomyopathy status (p = 0.01 and p < 0.001 respectively). Cardiotoxic radiation did not predict changes in ECG parameters. Cardiomyopathy was associated with increased mortality (34% versus 12%, p < 0.001). CONCLUSION: In children receiving anthracyclines, decrease in ΣQRS(6 L) and QTc prolongation are associated with increased risk of developing cardiomyopathy. ECG is a potential non-invasive risk stratification tool for prediction of anthracycline-induced cardiomyopathy and requires prospective validation.

Descending Aortic Translocation and Right Pulmonary Artery Reimplantation for Midline Descending Aorta and Crossed Pulmonary Arteries in an Infant.

Left mainstem bronchial compression by a midline descending thoracic aorta is a rare anatomic variant. Translocation of the descending thoracic aorta to the ascending aorta has recently been described to treat this condition. We performed an aortic translocation and right pulmonary artery reimplantation in a 4-month-old infant with severe pulmonary hypertension secondary to right pulmonary artery stenosis and left bronchial compression by a midline descending thoracic aorta. The procedure was successful in ameliorating the patient's left mainstem bronchial compression and pulmonary hypertension. Descending aortic translocation should be considered when the left bronchus is compressed causing respiratory symptoms.