Incorporation of the CardioMEMS™ System During an Exercise Physiology Test in a Pediatric Congenital Heart Disease Patient Contributing to Medical Decision-Making.

Exercise testing among the pediatric congenital heart disease population continues to transform and expand the way patients are evaluated and managed. We describe a case where a stress echocardiogram was performed while successfully collecting data from a previously implanted CardioMEMS™ HF system which helped guide decision-making.

Economic implications of outpatient cardiac catheterisation in infants with single ventricle congenital heart disease.

BACKGROUND: Resource utilisation for infants with single ventricle CHD remains high without well-studied ways to decrease economic burden. Same-day discharge following cardiac catheterisation has been shown to be safe and effective in children with CHD, but those with single ventricle physiology are commonly excluded. The purpose of this study was to investigate the economic implications of planned same-day discharge following cardiac catheterisation versus universal overnight hospital admission in infants with single ventricle CHD. METHODS AND RESULTS: A probabilistic decision-tree analysis with sensitivity analyses was performed. All included patients were categorised into four possible outcomes; discharge, readmission following discharge (within 48 hours), observation and prolonged hospitalisation. Baseline probabilities of each node of the tree were then combined with the cost data to evaluate the comparative dominance of one decision (immediately discharge) versus the other decision (routinely admit). Patients discharged on the same day as the procedure accrued the lowest attributed hospital cost ($5469), while patients readmitted to the hospital had the highest attributed cost ($11,851). Currently, no other studies have assessed the cost of hospitalisation following cardiac catheterisation in this population. Thus, we allowed for a wide range of cost variation, but same-day discharge dominated the decision outcome with a lower economic burden. CONCLUSION: Same-day discharge following routine cardiac catheterisation in patients with single ventricle physiology is less costly compared to universal overnight admission. This demonstrates an important cost-limiting step in a complex population of patients who have high resource utilisation.

Safety of outpatient cardiac catheterisation in infants with single-ventricle or shunt-dependent biventricular congenital heart disease.

OBJECTIVE: We aimed to investigate the incidence and causes of readmission of infants with single-ventricle and shunt-dependent biventricular CHD following routine, outpatient cardiac catheterisation. BACKGROUND: Cardiac catheterisation is commonly performed in patients with single-ventricle and shunt-dependent biventricular CHD for haemodynamic assessment and surgical planning. Best practices for post-procedural care in this population are unknown, and substantial variation exists between centres. Outpatient catheterisation reduces parental anxiety and decreases cost. Our institutional strategy is to discharge patients following a 4- to 6-hour post-procedure observation period. METHODS: Retrospective cohort study using the Society of Thoracic Surgeons Database identified patients 23 hours. There were no differences in baseline characteristics between discharged and admitted patients. Patients who underwent intervention were more likely to be admitted. Patients with hypoplastic left heart syndrome did not have major adverse events or readmissions. No intra- or peri-procedural deaths occurred. CONCLUSIONS: Outpatient cardiac catheterisation may be a safe option for infants with single-ventricle and shunt-dependent biventricular CHD, with low readmission rates and minimal morbidity.

Decreased false-positive adolescent pre-athletic screening with Seattle Criteria-interpreted electrocardiograms.

Sudden cardiac arrest is a rare but devastating cause of death in young adults. Electrocardiograms may detect many causes of sudden cardiac arrest, but are not routinely included in pre-athletic screening in the United States of America partly because of high rates of false-positive interpretation. To improve electrocardiogram specificity for identifying cardiac conditions associated with sudden cardiac arrest, an expert panel developed refined criteria known as the Seattle Criteria. Ours is the first study to compare standard electrocardiogram criteria with Seattle Criteria in 11- to 13-year-olds. In total, 1424 students completed the pre-athletic screening and electrocardiogram; those with a positive screen or abnormal electrocardiogram interpreted by a paediatric electrophysiologist completed further work-up. Electrocardiograms referred for additional evaluation were re-interpreted by a paediatric electrophysiologist using Seattle Criteria. Electrocardiogram abnormalities were identified in 98 (6.9%); Seattle Criteria identified 28 (2.0%). Formal evaluation confirmed four students at risk for sudden cardiac arrest (0.3%): long QT syndrome (n=2), Wolff-Parkinson-White (n=1), and pulmonary hypertension (n=1). All students with at-risk phenotypes for sudden cardiac arrest were identified by both standard electrophysiologist and Seattle Criteria. The false-positive interpretation rate decreased from 6.6 to 1.7% with Seattle Criteria. Downstream costs associated with screening using standard paediatric electrocardiogram interpretations and Seattle Criteria were projected at $24 versus $7, respectively. In conclusion, using Seattle Criteria for electrocardiogram interpretation decreases the rate of false-positive results compared with standard interpretation without omitting true-positive electrocardiogram findings. This may decrease unnecessary referrals and costs associated with formal cardiology evaluation.

Application and Utility of iPads in Pediatric Tele-echocardiography.

BACKGROUND: Telemedicine is used with increasing frequency to improve patient care in remote areas. The interpretation of medical imaging on iPad(®) (Apple, Cupertino, CA) tablets has been reported to be accurate. There are no studies on the use of iPads for interpretation of pediatric echocardiograms. We compared the quality of echo images, diagnostic accuracy, and review time using three different modalities: remote access on an iPad Air (iPad), remote access via a computer (Remote), and direct access on a computer linked through Ethernet to the server, the "gold standard" (Direct). MATERIALS AND METHODS: Fifty consecutive archived pediatric echocardiograms were interpreted using the three modalities. Studies were analyzed blindly by three pediatric cardiologists; review time, diagnostic accuracy, and image quality were documented. Diagnostic accuracy was assessed by comparing the study diagnoses with the official diagnosis in the patient's chart. Discrepancies between diagnoses were graded as major (more than one grade difference) or minor (one grade difference in severity of lesion). RESULTS: There were no significant differences in accuracy among the three modalities. There was one major discrepancy (size of patent ductus arteriosus); all others were minor, hemodynamically insignificant. Image quality ratings were better for iPad than Remote; Direct had the highest ratings. Review times (mean [standard deviation] minutes) were longest for iPad (5.89 [3.87]) and then Remote (4.72 [2.69]), with Direct having the shortest times (3.52 [1.42]) (p < 0.0001). CONCLUSIONS: Pediatric echocardiograms can be interpreted using convenient, portable devices while preserving accuracy and quality with slightly longer review times (1-2 min). These findings are important in the current era of increasing need for mobile health.

Exercise-induced ß2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition.

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling. Following 14 days ex vivo expansion with zoledronic acid and IL2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro and in vivo in leukemia-bearing xenogeneic mice. Infusing humans with the ß1+ß2-agonist isoproterenol and administering ß1 or ß1+ß2 antagonists prior to exercise revealed these effects to be ß2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced antileukemic effects of exercise. These findings provide a mechanistic link between exercise, ß2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematologic malignancies. SIGNIFICANCE: Exercise mobilizes effector γδ T-cells to blood via ß2-adrenergic signaling which allows for generation of a potent expanded γδ T-cell product that is highly cytotoxic against hematologic malignancies.

Cardiac Concerns in the Pediatric Athlete.

Cardiovascular disease remains the number one cause of death in Americans. It is no secret that exercise mitigates this risk. Exercise and regular physical activity are beneficial for physical health including aerobic conditioning, endurance, strength, mental health, and overall improved quality of life. Unfortunately, today many children and adolescents are sedentary, lacking the recommended daily amount of physical activity, leading to higher rates of obesity, cardiovascular disease, stroke, diabetes, anxiety, and depression. Given this rising concern, the World Health Organization launched a 12-year plan to improve physical activity in children and adolescents by reducing the inactivity rate by 15% in the world. How does this apply to children and adolescents with acquired or congenital heart disease?.

Single-Centre Case Series Assessment of Early Exercise Capacity Data Among Patients Who Received an Alterra Prestent and SAPIEN 3 Valve Placement.

Previous studies have used cardiopulmonary exercise test (CPET) data to objectively assess physiological changes in patients undergoing percutaneous pulmonary valve implantation. A retrospective review was performed to assess pre- and post-CPET data among patients undergoing Alterra Adaptive Prestent and SAPIEN 3 transcatheter heart valve (Alterra) placement. Of the 7 patients eligible for the study, 5 (71%) were male. The mean age was 22 years (range: 12-49 years). CPET data showed significant (P = 0.03) improvement in ventilatory efficiency (VE/VCO2) while only 2 (29%) patients had an improvement of percent predicted peak oxygen consumption (VO2). These findings suggest favourable haemodynamic changes though further investigation is needed.

Des résultats aux épreuves d'effort cardiorespiratoire ont été utilisés lors d'études antérieures pour mesurer de manière objective les changements physiologiques chez les patients ayant subi l'implantation percutanée d'une valvule pulmonaire. Nous présentons une étude rétrospective des résultats à ces épreuves avant et après l'intervention dans des cas d'implantation transcathéther d'une prothèse Alterra Adaptive Prestent et d'une valve cardiaque SAPIEN 3 (Alterra). Parmi les sept patients admissibles à l'étude, cinq (71 %) étaient de sexe masculin. L'âge moyen des sujets était de 22 ans (plage de 12 à 49 ans). Les résultats obtenus à l'épreuve d'effort cardiorespiratoire ont démontré une amélioration significative (P = 0,03) de l'efficacité respiratoire (VE/VCO2), mais seulement deux patients (29 %) ont présenté une amélioration du pourcentage prévu de la consommation maximale d'oxygène (VO2). Bien que ces observations semblent indiquer des changements hémodynamiques favorables, d'autres études sont nécessaires pour élucider la question.

Infantile-onset Pompe disease complicated by sickle cell anemia: Case report and management considerations.

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two GAA variants, NM_000152.5: c.842G>C, p.(Arg281Pro) and NM_000152.5: c.2560C>T, p.(Arg854*) in trans, and homozygosity for the HBB variant causative of SCA, consistent with his diagnosis. An acute neonatal presentation of hypotonia and cardiomyopathy required ERT with alglucosidase alfa infusions preceded by immune tolerance induction (ITI), as well as chronic red blood cell transfusions and penicillin V potassium prophylaxis for treatment of IOPD and SCA. Clinical course was further complicated by multiple respiratory infections. We review the current guidelines and interventions taken to optimize his care and the pitfalls of those guidelines when treating patients with concomitant conditions. To the best of our knowledge, no other case reports of the concomitance of these two disorders was found. This report emphasizes the importance of newborn screening, early intervention, and treatment considerations for this complex patient presentation of IOPD and SCA.

Early preclinical experience of a mixed reality ultrasound system with active GUIDance for NEedle-based interventions: The GUIDE study.

Background: Use of ultrasound (US) to facilitate vascular access has increased compared to landmark-based procedures despite ergonomic challenges and need for extrapolation of 2-dimensional images to understand needle position. The MantUS™ system (Sentiar, Inc.,) uses a mixed reality (MxR) interface to display US images and integrate real-time needle tracking. Objective: The purpose of this prospective preclinical study was to evaluate the feasibility and usability of MantUS in a simulated environment. Methods: Participants were recruited from pediatric cardiology and critical care. Access was obtained in 2 vascular access training models: a femoral access model and a head and neck model for a total of 4 vascular access sites under 2 conditions-conventional US and MantUS. Participants were randomized for order of completion. Videos were obtained, and quality of access including time required, repositions, number of attempts, and angle of approach were quantified. Results: Use of MantUS resulted in an overall reduction in number of needle repositions (P = .03) and improvement in quality of access as measured by distance (P <.0001) and angle of elevation (P = .006). These findings were even more evident in the right femoral vein (RFV) access site, which was a simulated anatomic variant with a deeper more oblique vascular course. Use of MantUS resulted in faster time to access (P = .04), fewer number of both access attempts (P = .02), and number of needle repositions (P <.0001) compared to conventional US. Postparticipant survey showed high levels of usability (87%) and a belief that MantUS may decrease adverse outcomes (73%) and failed access attempts (83%). Conclusion: Use of MantUS improved vascular access among all comers, including the quality of access. This improvement was even more notable in the vascular variant (RFV). MantUS readily benefited users by providing improved spatial understanding. Further development of MantUS will focus on improving user interface and experience, with larger clinical usage and in-human studies.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. RESULTS: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (P=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity). CONCLUSIONS: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.

Exercise Performance in Adolescents With Fontan Physiology (from the Pediatric Heart Network Fontan Public Data Set).

In the pediatric population, exercise capacity differs between females and males and the gap widens through adolescence. However, specific age- and sex-based changes in adolescents with congenital heart disease and Fontan palliation have not been reported. The purpose of the current study is to identify age- and sex-specific changes in exercise performance at peak and ventilatory anaerobic threshold (AT) for adolescents with Fontan physiology. Retrospective review of the Pediatric Heart Network Fontan cross sectional study (Fontan 1) public use dataset. Comparisons were made for peak and AT exercise parameters for females and males at 2-year age intervals. In addition, normative values were generated by sex and age at 2-year intervals. χ2 test was used for comparison for categorical variables. Changes in exercise parameters between age groups by sex were compared by ANOVA with post-hoc analysis. Exercise testing was performed in 411 patients. AT was reached in 317 subjects (40% female), of whom, 166 (43% female) reached peak exercise. Peak oxygen consumption decreased 32% through adolescence in females and did not have the typical increase through adolescence for males. Oxygen consumption at AT also decreased with age in both sexes. In conclusion, age- and sex-based exercise performance for adolescents with Fontan physiology are predictably low, but there are additional significant decreases through adolescence for this population, especially in females. We have established normative exercise values for several parameters for this population which will better identify at risk patients and allow for earlier intervention.