Assessment of Disaster Preparedness at the Household Level in a Pediatric Cardiology Clinic Population.

Natural and human-provoked disasters pose serious health risks to children, particularly children and youth with special healthcare needs, including many cardiology patients. The American Academy of Pediatrics (AAP) provides preparedness recommendations for families, but little is known about recommendation adherence. Caregivers of children seen in a pediatric cardiology clinic network were recruited to complete an electronic survey. Participants self-reported child medical history and their household's implementation of AAP recommended disaster preparedness items. Families received a link to AAP resources and a child ID card. Data were analyzed using descriptive statistics with Fisher's exact and Wilcoxon rank sum tests. 320 caregivers participated in the study, of whom 124 (38.8%) indicated that their child has a diagnosed cardiac condition, and 150 (46.9%) indicated that their child had special healthcare needs. The average preparedness item completion rate was 70.7% for household preparedness, 40.1% for reunification preparedness, and 26.3% for community preparedness. Households of children with medical needs had similar rates of preparedness compared to overall rates. Of all respondents, 27.8% previously received disaster preparedness resources, 67.7% would like resources on discussing disaster preparedness, and 93.0% intend to talk with their household about disaster preparedness after completing the survey. These results demonstrate a gap between AAP recommendations and household-level disaster preparedness, including patients with cardiac conditions and those with special healthcare needs. Families expressed that they were interested in getting resources for disaster preparedness. Pediatric cardiologists may consider asking about disaster preparedness and providing disaster preparedness resources tailored to the needs of their patients.

Computation of a probabilistic and anisotropic failure metric on the aortic wall using a machine learning-based surrogate model.

Scalar-valued failure metrics are commonly used to assess the risk of aortic aneurysm rupture and dissection, which occurs under hypertensive blood pressures brought on by extreme emotional or physical stress. To compute failure metrics under an elevated blood pressure, a classical patient-specific computer model consists of multiple computation steps involving inverse and forward analyses. These classical procedures may be impractical for time-sensitive clinical applications that require prompt feedback to clinicians. In this study, we developed a machine learning-based surrogate model to directly predict a probabilistic and anisotropic failure metric, namely failure probability (FP), on the aortic wall using aorta geometries at the systolic and diastolic phases. Ascending thoracic aortic aneurysm (ATAA) geometries of 60 patients were obtained from their CT scans, and biaxial mechanical testing data of ATAA tissues from 79 patients were collected. Finite element simulations were used to generate datasets for training, validation, and testing of the ML-surrogate model. The testing results demonstrated that the ML-surrogate can compute the maximum FP failure metric, with 0.42% normalized mean absolute error, in 1 s. To compare the performance of the ML-predicted probabilistic FP metric with other isotropic or deterministic metrics, a numerical case study was performed using synthetic "baseline" data. Our results showed that the probabilistic FP metric had more discriminative power than the deterministic Tsai-Hill metric, isotropic maximum principal stress, and aortic diameter criterion.

Racial and ethnic differences in response to treatment for Marfan syndrome.

OBJECTIVE: To determine whether racial/ethnic differences exist for the treatment of Marfan syndrome aortopathy. The 2014 Pediatric Heart Network randomised trial of losartan versus atenolol in Marfan syndrome paediatric and young adult patients showed no treatment differences in the rate of aortic root growth over 3 years; however, they did not examine racial/ethnic differences, and recent data suggest that angiotensin receptor blockers may have different pharmacologic effects in different racial/ethnic populations. METHODS: We performed a secondary analysis of public-use data from the Pediatric Heart Network randomised trial comparing the differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic patients) amongst the treatment groups for the primary outcome of rate of aortic root enlargement by z score and secondary outcome of rate of change of absolute diameter of aortic root, z score and absolute diameter of ascending aorta, and blood pressure changes. RESULTS: For aortic root enlargement by z score amongst non-Hispanic White patients, patients on losartan exhibited an annual z score change of -0.090 ± 0.016, compared to -0.146 ± 0.015 for those on atenolol (p = 0.01), favouring atenolol. For Hispanic and non-Hispanic Black patients, there was no difference in primary or secondary outcomes between treatment groups. CONCLUSION: Non-Hispanic White patients had a small, but statistically significantly greater decrease in aortic root z score favouring atenolol over losartan. There were no significant differences amongst Hispanic or non-Hispanic Black patients, which may be due to relatively small size numbers. These findings may have important implications for medication selection by race/ethnicity in Marfan syndrome patients, which has not previously been evaluated in studies.

Heterogeneous Pulmonary Phenotypes in Filamin A Mutation-Related Lung Disease.

Background: Interstitial lung disease (ILD) has been recently reported in a few patients with pathogenic variants in the Filamin A (FLNA) gene with variable presentation and prognosis. This study evaluated the respiratory manifestations and clinical features in children with FLNA disease. Methods: We conducted a retrospective review of pediatric patients with variants in FLNA in a tertiary children's hospital. The clinical features, genotype, management, and outcomes were analyzed. Results: We identified 9 patients with variants in FLNA aged 15 months to 24 years, 4 females and 5 males. Six patients had abnormal chest imaging ranging from mild interstitial prominence to atelectasis, interstitial densities, and hyperinflation. Three patients with ILD presented during the neonatal period or early infancy with respiratory distress or respiratory failure requiring supplemental oxygen or assisted ventilation via tracheostomy. We report male twins with the same FLNA variant and lung disease, but different ages and clinical features at presentation eventually culminating in respiratory failure requiring assisted ventilation. All patients had FLNA variants identified by FLNA sequencing, had abnormal echocardiograms, and none of the patients underwent lung biopsy or lung transplantation. The outcomes were variable and could be as severe as chronic respiratory failure. Conclusion: The wide spectrum of respiratory manifestations and abnormal chest imaging in our study highlights the importance of evaluation for lung disease in patients with variants in FLNA. FLNA sequencing in suspected cases with ILD may obviate the need for a lung biopsy, prompt surveillance for progressive lung disease, and evaluation for associated clinical features.

Treatment of attention deficit/hyperactivity disorder in children with CHD.

INTRODUCTION: The prevalence of attention deficit/hyperactivity disorder in the general population is common and is now diagnosed in 4%-12% of children. Children with CHD have been shown to be at increased risk for attention deficit/hyperactivity disorder. Case reports have led to concern regarding the use of attention deficit/hyperactivity disorder medications in children with underlying CHD. We hypothesised that medical therapy for patients with CHD and attention deficit/hyperactivity disorder is safe. METHODS: A single-centre, retrospective chart review was performed evaluating for adverse events in patients aged 4-21 years with CHD who received attention deficit/hyperactivity disorder therapy over a 5-year span. Inclusion criteria were a diagnosis of CHD and concomitant medical therapy with amphetamines, methylphenidate, or atomoxetine. Patients with trivial or spontaneously resolved CHD were excluded from analysis. RESULTS: In 831 patients with CHD who received stimulants with a mean age of 12.9 years, there was only one adverse cardiovascular event identified. Using sensitivity analysis, our median follow-up time was 686 days and a prevalence rate of 0.21% of adverse events. This episode consisted of increased frequency of supraventricular tachycardia in a patient who had this condition prior to initiation of medical therapy; the condition improved with discontinuation of attention deficit/hyperactivity disorder therapy. CONCLUSION: The incidence of significant adverse cardiovascular events in our population was similar to the prevalence of supraventricular tachycardia in the general population. Our single-centre experience demonstrated no increased risk in adverse events related to medical therapy for children with attention deficit/hyperactivity disorder and underlying CHD. Further population-based studies are indicated to validate these findings.

Simultaneous Presentation of Crohn's Disease and Takayasu Arteritis in a Teenage Patient.

A 14-year-old female with no significant medical history presented with hypertensive urgency, in the setting of 4 to 6 weeks of diarrhea, abdominal pain, headaches, anemia, weight loss, and high blood pressures. Her evaluation revealed signs of a systemic inflammatory process that was most suspicious for inflammatory bowel disease. However, when her hypertension was evaluated with a renal Doppler ultrasound, there were signs of narrowing, stenosis, and hypoplasia that led to a diagnostic angiogram of the abdominal aorta. Full body positron emission tomography scan revealed multiple areas of stenosis and aortic thickening with enhancement compatible with Takayasu arteritis. She received prednisone, methotrexate, and infliximab with marked improvement in her clinical symptoms and inflammatory markers.

A Novel Anisotropic Failure Criterion With Dispersed Fiber Orientations for Aortic Tissues.

Accurate failure criteria play a fundamental role in biomechanical analyses of aortic wall rupture and dissection. Experimental investigations have demonstrated a significant difference of aortic wall strengths in the circumferential and axial directions. Therefore, the isotropic von Mises stress and maximum principal stress, commonly used in computational analysis of the aortic wall, are inadequate for modeling of anisotropic failure properties. In this study, we propose a novel stress-based anisotropic failure criterion with dispersed fiber orientations. In the new failure criterion, the overall failure metric is computed by using angular integration (AI) of failure metrics in all directions. Affine rotations of fiber orientations due to finite deformation are taken into account in an anisotropic hyperelastic constitutive model. To examine fitting capability of the failure criterion, a set of off-axis uniaxial tension tests were performed on aortic tissues of four porcine individuals and 18 human ascending thoracic aortic aneurysm (ATAA) patients. The dispersed fiber failure criterion demonstrates a good fitting capability with the off-axis testing data. Under simulated biaxial stress conditions, the dispersed fiber failure criterion predicts a smaller failure envelope comparing to those predicted by the traditional anisotropic criteria without fiber dispersion, which highlights the potentially important role of fiber dispersion in the failure of the aortic wall. Our results suggest that the deformation-dependent fiber orientations need to be considered when wall strength determined from uniaxial tests are used for in vivo biomechanical analysis. More investigations are needed to determine biaxial failure properties of the aortic wall.

Identification of in vivo nonlinear anisotropic mechanical properties of ascending thoracic aortic aneurysm from patient-specific CT scans.

Accurate identification of in vivo nonlinear, anisotropic mechanical properties of the aortic wall of individual patients remains to be one of the critical challenges in the field of cardiovascular biomechanics. Since only the physiologically loaded states of the aorta are given from in vivo clinical images, inverse approaches, which take into account of the unloaded configuration, are needed for in vivo material parameter identification. Existing inverse methods are computationally expensive, which take days to weeks to complete for a single patient, inhibiting fast feedback for clinicians. Moreover, the current inverse methods have only been evaluated using synthetic data. In this study, we improved our recently developed multi-resolution direct search (MRDS) approach and the computation time cost was reduced to 1~2 hours. Using the improved MRDS approach, we estimated in vivo aortic tissue elastic properties of two ascending thoracic aortic aneurysm (ATAA) patients from pre-operative gated CT scans. For comparison, corresponding surgically-resected aortic wall tissue samples were obtained and subjected to planar biaxial tests. Relatively close matches were achieved for the in vivo-identified and ex vivo-fitted stress-stretch responses. It is hoped that further development of this inverse approach can enable an accurate identification of the in vivo material parameters from in vivo image data.

Myocarditis in the pediatric population: A review.

Myocarditis has a variable clinical presentation and there is still debate regarding accurate diagnostic criteria. Adding to the controversy surrounding this diagnosis, there is no clear consensus for the treatment or ongoing follow-up of patients with myocarditis. All of this makes the diagnosis and management of myocarditis a particular challenge in the pediatric population. Furthermore, the literature with respect to this topic is dynamic and ever-changing. In this review article, we aim to review and summarize the common clinical presentations of myocarditis, along with the latest recommendations for diagnostic criteria, treatment, and follow-up of patients with myocarditis.

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

PURPOSE: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. METHODS: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. RESULTS: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. CONCLUSION: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

Biomechanical properties of the thoracic aorta in Marfan patients.

BACKGROUND: Marfan syndrome (MFS), a genetic disorder of the connective tissue, has been strongly linked to dilation of the thoracic aorta, among other cardiovascular complications. As a result, MFS patients frequently suffer from aortic dissection and rupture, contributing to the high rate of mortality and morbidity among MFS patients. Despite the significant effort devoted to the investigation of mechanical and structural properties of aneurysmal tissue, studies on Marfan aneurysmal biomechanics are scarce. Ex vivo mechanical characterization of MFS aneurysmal tissue can provide a better insight into tissue strength outside the physiologic loading range and serve as a basis for improved risk assessment and failure prediction. METHODS: The mechanical and microstructural properties of MFS aneurysmal thoracic aorta (MFS, n=15, 39.5±3.91 years), non-MFS aneurysmal thoracic aorta (TAA, n=8, 52.8±4.9 years), healthy human thoracic aorta (HH, n=8, 75.4±6.1 years), and porcine thoracic aorta (n=10) are investigated. Planar biaxial tensile testing and uniaxial failure testing were utilized to characterize the mechanical and failure properties of the tissue, respectively. Verhoeff-Van Gieson (VVG) and PicroSirius Red stains were utilized to visualize the elastin and collagen fiber architecture, respectively. RESULTS: MFS tissue was found to have age-dependent but diameter-independent mechanical, structural, and morphological properties, also showing extensive elastin fiber degradation. Non-MFS thoracic aneurysmal aorta was thicker and stiffer than age-matched MFS tissue. Moreover, non-MFS thoracic aneurysmal mechanics resembled closely the mechanics of older healthy human tissue. Younger MFS tissue (<40 years) exhibited similar mechanical and structural properties to aged porcine tissue. CONCLUSIONS: Both age and aneurysmal presence were found to be factors associated with increased stiffness in aortic tissue, and aortic diameter was not a significant determinant of mechanical property deterioration. Additionally, the presence of MFS was found to induce stiffening of the thoracic aorta, although not to the extent of the non-MFS aneurysm.

Systolic ejection click versus split first heart sound: Are our ears deceiving us?

OBJECTIVE: Bicuspid aortic valve (BAV) disease is associated with potential lifetime complications, but auscultation of a BAV click is commonly missed or mistaken for a benign split first heart sound. Our objective was to determine whether pediatric cardiologists could reliably distinguish between BAV clicks and benign split first heart sounds. DESIGN: Quality evaluation project using de-identified recordings from an outpatient pediatric cardiology clinic. OUTCOME MEASURES: Twenty-one cardiologists listened to five de-identified recordings of pediatric heart sounds (three with BAV clicks, two with mitral components of benign split first heart sounds) and indicated whether they believed each recording was a BAV or split first heart sound. The accuracy of diagnoses was determined using percent agreement and calculated kappa coefficients for the cohort and subgroups based on those with less than 10 years of experience versus those with ≥10 years. To assess precision, a kappa extension was used for multiple raters to assess interrater agreement. RESULTS: Among participants, diagnostic accuracy of BAV click was 38%, while accuracy of split first heart sound was 41%. No participant correctly diagnosed all sounds. No difference in agreement was observed when stratifying by experience. Kappa was -0.11 (CI 95% -0.31 to 0.08) for all raters, -0.03 (CI 95% -0.39 to 0.33) for those with less than 10 years' experience, and -0.15 (CI 95% -0.38 to 0.08) for those with ≥10 years' experience. The kappa statistic among the 21 raters was 0.01 (95% CI -0.03 to 0.04), indicating poor precision among the raters. CONCLUSIONS: In this sample of pediatric cardiologists, the diagnostic accuracy of BAV clicks versus split first heart sounds was worse than chance. There was no association between years of experience and diagnostic accuracy. While further study is needed, these data suggest that an echocardiogram may be valuable when either a systolic ejection click or split first heart sound is heard.

Sickle Cell Disease with Cyanotic Congenital Heart Disease: Long-Term Outcomes in 5 Children.

Sickle cell disease is a risk factor for cerebrovascular accidents in the pediatric population. This risk is compounded by hypoxemia. Cyanotic congenital heart disease can expose patients to prolonged hypoxemia. To our knowledge, the long-term outcome of patients who have combined sickle cell and cyanotic congenital heart disease has not been reported. We retrospectively reviewed patient records at our institution and identified 5 patients (3 girls and 2 boys) who had both conditions. Their outcomes were uniformly poor: 4 died (age range, 12 mo-17 yr); 3 had documented cerebrovascular accidents; and 3 developed ventricular dysfunction. The surviving patient had developmental delays. On the basis of this series, we suggest mitigating hypoxemia, and thus the risk of stroke, in patients who have sickle cell disease and cyanotic congenital heart disease. Potential therapies include chronic blood transfusions, hydroxyurea, earlier surgical correction to reduce the duration of hypoxemia, and heart or bone marrow transplantation.

Exome sequencing of patients with histiocytoid cardiomyopathy reveals a de novo NDUFB11 mutation that plays a role in the pathogenesis of histiocytoid cardiomyopathy.

Histiocytoid cardiomyopathy (Histiocytoid CM) is a rare form of cardiomyopathy observed predominantly in newborn females that is fatal unless treated early in life. We have performed whole exome sequencing on five parent-proband trios and identified nuclear-encoded mitochondrial protein mutations in three cases. The molecular genetic basis of Histiocytoid CM remains unknown despite several hypotheses in medical literature. The findings presented in this manuscript may represent components of genetic etiologies for this heterogeneous disease. Two probands had de novo non-sense mutations in the second exon of the X-linked nuclear gene NDUFB11. A third proband was doubly heterozygous for inherited rare variants in additional components of complex I, NDUFAF2 and NDUFB9, confirming that Histiocytoid CM is genetically heterogeneous. In a fourth case, the proband with Histiocytoid CM inherited a mitochondrial mutation from her heteroplasmic mother, as did her brother who presented with cardiac arrhythmia. Strong candidate recessive or compound heterozygous variants were not found for this individual or for the fifth case. Although NDUFB11 has not been implicated before in cardiac pathology, morpholino-mediated knockdown of ndufb11 in zebrafish embryos generated defective cardiac tissue with cardiomegaly, looping defects, and arrhythmia which suggests the role of NDUFB11 in the pathogenesis of this abnormal cardiac pathology. Taken together, the unbiased whole exome sequencing approach confirms the suspected genetic heterogeneity of Histiocytoid CM. Therefore, the novel NDUFB11 mutation may cause a complex 1 deficiency in synergy with additional unknown mtDNA variants.

Lower extremity edema in a child due to pectus excavatum.

A previously healthy 11-year-old girl was referred for pediatric cardiology evaluation because of the development of progressive bilateral lower extremity swelling over the course of 2 years. Her prior workup had included a negative result for proteinuria and a negative ultrasound for deep venous thrombosis. On physical examination, in addition to her edema, she was found to have a severe pectus excavatum deformity, which prompted cardiac magnetic resonance imaging. This study demonstrated compression of the inferior vena cava. She underwent uneventful pectus repair with use of a modified Ravitch procedure and experienced complete resolution of her lower extremity edema.

Necrotizing enterocolitis in infants with congenital heart disease: the role of red blood cell transfusions.

Necrotizing enterocolitis (NEC) is a rare but catastrophic complication that may occur in newborns with congenital heart disease (CHD). In the preterm population, transfusion of red blood cells (RBCs) and use of RBCs with longer storage time have been independently associated with the development of NEC. To date, it is not known whether similar associations exist for the term newborn with CHD. This retrospective study identified the incidence of NEC among 1,551 newborns admitted to the authors' cardiac intensive care unit between 7 January 2002 and 7 January 2010. The study was limited to term newborns (>36 weeks gestation). To understand the impact of RBC transfusions on the development of NEC, a nested 2:1 matched case-control analysis was undertaken to compare RBC transfusion patterns between an age-matched group and a cardiac lesion-matched control group. In the study population, NEC developed in 45 term infants during the postoperative period. Of these 45 infants, 30 (66.7%) had single-ventricle heart defects, whereas 22 (48.8%) required surgery for aortic arch obstruction. The median patient age at NEC diagnosis was 21 days. The RBC transfusion rate was higher among the patients who experienced NEC (0.21/day) than among the control subjects (0.10/day) (p = 0.048). A multivariate analysis indicated that onset of NEC was associated with a greater number of RBC transfusions (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.07-7.47; p = 0.045). The duration of RBC storage was not significantly longer in the NEC group (9 days) than in the control cohort (7 days) (p = 0.16). Increased exposure to RBC transfusions is associated with the development of NEC in term infants with CHD. Longer storage of RBCs does not appear to increase this risk. Although causality cannot be confirmed, these data prompt a careful review of RBC transfusion practices with this population.

The relationship between in-house attending coverage and nighttime extubation following congenital heart surgery*.

OBJECTIVES: Many cardiac ICUs have instituted 24/7 attending physician in-house coverage, which theoretically may allow for more expeditious weaning from ventilation and extubation. We aimed to determine whether this staffing strategy impacts rates of nighttime extubation and duration of mechanical ventilation. DESIGN: National data were obtained from the Virtual PICU System database for all patients admitted to the cardiac ICU following congenital heart surgery in 2011 who required postoperative mechanical ventilation. Contemporaneous data from our local institution were collected in addition to the Virtual PICU System data. The combined dataset (n = 2,429) was divided based on the type of nighttime staffing model in order to compare rates of nighttime extubation and duration of mechanical ventilation between units that used an in-house attending staffing strategy and those that employed nighttime residents, fellows, or midlevel providers only. MEASUREMENTS AND MAIN RESULTS: Institutions that currently use 24/7 in-house attending coverage did not demonstrate statistically significant differences in rates of nighttime extubation or the duration of mechanical ventilation in comparison to units without in-house attendings. Younger patients cared for in non-in-house attending units were more likely to require reintubation. CONCLUSIONS: Pediatric patients who have undergone congenital heart surgery can be safely and effectively extubated without the routine presence of an attending physician. The utilization of nighttime in-house attending coverage does not appear to have significant benefits on the rate of nighttime extubation and may not reduce the duration of mechanical ventilation in units that already use in-house residents, fellows, or other midlevel providers.

Hemolytic anemia after placement of an intraluminal pulmonary artery band.

A newborn with double outlet right ventricle, malposed great vessels, hypoplastic aortic arch, and coarctation of the aorta with no restriction to pulmonary blood flow underwent palliation with arch augmentation and placement of an intraluminal Dacron patch pulmonary artery band (PAB). She subsequently presented in shock because of profound hemolytic anemia. Her intraluminal PAB was taken down and replaced with a traditional extraluminal band with resolution of her hemolysis. It is possible that the use of Dacron for construction of the intraluminal PAB may have contributed significantly to this patient's hemolytic anemia.