The impact of physical activity modification on the well-being of a cohort of children with an inherited arrhythmia or cardiomyopathy.

BACKGROUND: We evaluated a cohort of 35 children diagnosed with long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy with regard to physical and psychosocial well-being. MATERIAL AND METHODS: Patients wore an accelerometer to record their time involved in moderate- to vigorous-intensity physical activity and completed the Pediatric Quality of Life Inventory and the Pediatric Cardiac Quality of Life Inventory. Parents were also asked to describe if their child had changed their physical activity because of their diagnosis and how difficult and upsetting it was for the child to adapt to the physical activity recommendations. RESULTS: Patients were involved in less moderate- to vigorous-intensity physical activity per day (35 min/day versus 55 min/day) and had lower Pediatric Quality of Life Inventory total health scores (79 versus 84) compared to normative data. Overall, 51% of the cohort modified their physical activity in some way because of their diagnosis and changing physical activity was associated with lower Pediatric Quality of Life Inventory and Pediatric Cardiac Quality of Life Inventory scores. CONCLUSION: Our cohort was involved in less moderate- to vigorous-intensity physical activity and had lower Pediatric Quality of Life Inventory total health scores compared to normative paediatric data. Modifying one's physical activity was associated with worse health-related quality of life scores, highlighting a vulnerable sub-group of children. These findings are useful for families and healthcare professionals caring for children who are adjusting to a new cardiac diagnosis of an inherited arrhythmia or cardiomyopathy.

Physical activity restriction for children and adolescents diagnosed with an inherited arrhythmia or cardiomyopathy and its impact on body mass index.

BACKGROUND: Historically, individuals diagnosed with an inherited arrhythmia or cardiomyopathy have been advised to avoid participating in competitive sports. Consequently, these individuals may be more susceptible to weight gain and obesity. METHODS: A retrospective longitudinal chart review was performed for a population of children with a genetic or clinical diagnosis of the long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy. We recorded the physical activity recommendation, postdiagnosis sports participation, and body mass index (BMI) over time. RESULTS: A total of 109 charts were reviewed. Some level of physical activity restriction was documented for the majority of phenotype-positive children (80%) but was less common for phenotype-negative children (37%) (P < 0.001). Overall, 38% ( n = 41) of the study population were reportedly participating in a moderate or high dynamic sports following their diagnosis. Nonetheless, the BMI did not differ over time based on physical activity restriction or sports participation, and the proportion of overweight and obese children at follow-up was consistent with that seen in the Canadian pediatric population. CONCLUSION: Physical activity restriction was recommended for the majority of phenotype-positive children with an inherited arrhythmia or cardiomyopathy. However, many children continue to participate in competitive sports. Children prescribed physical activity restriction appear to face similar concerns relating to obesity as other Canadian children. This study highlights the need to further assess the effectiveness of physical activity recommendations and its impact on the cardiovascular health.

Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk for an Inherited Arrhythmia or Cardiomyopathy.

Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

Validation of FoodChek™ - Salmonella for Rapid Detection of Salmonella in Eggs, Derivative Products, and the Environment.

The FoodChek™ - Salmonella assay is an immunomagnetic lateral flow assay for the rapid detection (shorter than 24 h) of the most frequently isolated Salmonella (groups B-E) in eggs, egg-derivative products, and environmental surfaces. The FoodChek - Salmonella assay correctly identified 99.6% (239/240) of the samples tested in the matrix studied, and the statistical analysis of the method comparison study results demonstrated that it performs as well as U.S. culture-based reference methods. Ninety-nine percent of the 103 Salmonella strains tested belonging to serogroups B-E were detected during the inclusivity study. Concerning the exclusivity, 31 nontarget strains were tested. No cross-reactivity was observed in FoodChek - Salmonella assay enrichment conditions. In addition, the assay shows strong robustness, good stability, and consistency among lots. The present study proves that the assay is an effective tool for the rapid detection of Salmonella spp. in whole liquid eggs, liquid egg white (liquid egg albumen), shell eggs, dried whole eggs, dried egg yolks, and environmental surfaces as stainless steel, plastic, rubber, ceramic tiles, and sealed concrete.

Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy.

Individuals affected by restrictive cardiomyopathy (RCM) often develop heart failure at young ages resulting in early heart transplantation. Familial forms are mainly caused by mutations in sarcomere proteins and demonstrate a common genetic etiology with other inherited cardiomyopathies. Using next-generation sequencing, we identified two novel missense variants (p.S1624L; p.I2160F) in filamin-C (FLNC), an actin-cross-linking protein mainly expressed in heart and skeletal muscle, segregating in two families with autosomal-dominant RCM. Affected individuals presented with heart failure due to severe diastolic dysfunction requiring heart transplantation in some cases. Histopathology of heart tissue from patients of both families showed cytoplasmic inclusions suggesting protein aggregates, which were filamin-C specific for the p.S1624L by immunohistochemistry. Cytoplasmic aggregates were also observed in transfected myoblast cell lines expressing this mutant filamin-C indicating further evidence for its pathogenicity. Thus, FLNC is a disease gene for autosomal-dominant RCM and broadens the phenotype spectrum of filaminopathies.

Late intervention in an asymptomatic pediatric patient with anomalous left coronary artery.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is most commonly diagnosed within the first year of life with congestive heart failure symptomatology reflecting left ventricle (LV) dysfunction. The late diagnosis of ALCAPA is presented in a 5-year-old without significant LV dysfunction, mild LV dilatation and only mild mitral regurgitation that did not change significantly after surgery. The timing of surgical intervention in the late diagnosis of ALCAPA remains unclear despite risks of significant ongoing myocardial injury secondary to coronary artery hypoperfusion and progressive mitral valve dysfunction. Intervention in this case allows for revascularization which may reverse ventricular and valvular dysfunction.

Detection of Listeria spp. using ACTERO listeria enrichment media.

ACTERO Listeria Enrichment Media (ACTERO Listeria) is a selective medium developed for a single-step recovery and enrichment of Listeria spp. from environmental samples. Robustness testing of the ACTERO Listeria medium demonstrated good performance when minor changes were introduced to the incubation temperature and time. All 54 Listeria strains tested, representing the most frequently isolated Listeria species from food (L. monocytogenes, L. ivanovii, L. seeligeri, L. welshimeri, and L. grayi), were successfully enriched in ACTERO Listeria. None of the 30 nontarget strains tested in the exclusivity study was recovered after incubation in ACTERO Listeria. Recovery of Listeria was consistent across three independently produced lots of the ACTERO Listeria, and the prepared medium was stable for 45 days when stored at 4 degrees C in the dark. Matrix studies performed with environmental sponge samples from plastic and stainless steel surfaces demonstrated similar recovery of Listeria spp. in a single-step enrichment using ACTERO Listeria from plastic, and significantly better recovery from stainless steel surfaces when compared to the U.S. Department of Agriculture-Food Safety and Inspection Service reference method. The results of this study prove that ACTERO Listeria Enrichment Media can be effectively used in replacement of the two-step enrichment suggested by the reference method without affecting the recovery of Listeria spp. from environmental samples.

Exome sequencing identifies a novel variant in ACTC1 associated with familial atrial septal defect.

BACKGROUND: The genetics of congenital heart disease (CHD) remain incompletely understood. Exome sequencing has been successfully used to identify disease-causing mutations in familial disorders in which candidate gene analyses and linkage mapping have failed. METHODS: We studied a large family characterized by autosomal dominant isolated secundum atrial septal defect (ASD) (MIM No. 612794). Candidate gene resequencing and linkage analysis were uninformative. RESULTS: Whole-exome sequencing of 2 affected family members identified 44 rare shared variants, including a nonsynonymous mutation (c.532A>T, p.M178L, NM_005159.4) in alpha-cardiac actin (ACTC1). This mutation was absent from 1834 internal controls as well as from the 1000 Genomes and the Exome Sequencing Project (ESP) databases, but predictions regarding its effect on protein function were divergent. However, p.M178L was the only rare mutation segregating with disease in our family. CONCLUSIONS: Our results provide further evidence supporting a causative role for ACTC1 mutations in ASD. Massively parallel sequencing of the exome allows for the detection of novel rare variants causing CHD without the limitations of a candidate gene approach. When mutation prediction algorithms are not helpful, studies of familial disease can help distinguish rare pathologic mutations from benign variants. Consideration of the family history can lead to genetic insights into CHD.

Hypertension and obstructive sleep apnea in Caucasian children.

AIM: To evaluate the prevalence of hypertension and/or left ventricular hypertrophy (LVH) in children with a diagnosis of obstructive sleep apnea (OSA). METHODS: A cross-sectional case series of consecutive, otherwise healthy children aged > 4 years, with polysomnography-proven OSA [apnea hypopnea index (AHI) > 1.5/h] is described. Echocardiography was performed on all subjects and left ventricular mass was calculated. Study subjects underwent additional investigation with 24-h ambulatory blood pressure (BP) monitoring. RESULTS: Thirty children (21 males) were studied. Mean age was 8.9 years. Mean body mass index was 19.87 kg/cm(2). Mean AHI was 14.3/h. 10/30 (33%) of the study population met criteria for pre-hypertension (n = 3) or masked hypertension (n = 7) based on standard ambulatory monitoring criteria. All 10 children had systolic hypertension throughout the night with 5 of these also having elevated daytime systolic readings. There was a relationship between AHI and BP showing an increase of 1.162 percentile units in mean diastolic night BP (age, gender and height specific) per unit increase in AHI (P = 0.018). There were no subjects with LVH and/or right ventricular hypertrophy. CONCLUSION: In our population of otherwise healthy Caucasian children, there was a high prevalence of hypertension that would not have been identified using standard office/clinic protocols.

Noonan syndrome in a premature infant with hypertrophic cardiomyopathy and death in infancy.

We report an extremely premature infant with Noonan syndrome who developed rapidly progressive obstructive hypertrophic cardiomyopathy, which contributed to the death of the infant. The complications of prematurity combined with progressive, severe hypertrophic cardiomyopathy associated with Noonan syndrome lead to a poor prognosis.

Nonductal dependent coarctation: a 20-year study of morbidity and mortality comparing early-to-late surgical repair.

OBJECTIVE: The objective of this study was to evaluate the effect of the timing of surgical repair of nonductal dependent coarctation on the short-term outcome. METHODS: The medical records of 76 patients, diagnosed and treated for a nonductal dependent mild-to-moderate coarctation at a tertiary care institute over a 20-year period, were retrospectively reviewed with the age at repair compared against outcome measures. Multiple logistic regression was performed to assess the timing of repair, the presence of congestive heart failure or associated cardiac defects on the outcome measures. RESULTS: The mean age of surgery for the mild-to-moderate coarctation repair was 3.1 years (range: three days to 12 years). The most common cause for referral to a pediatric cardiologist was the clinical finding of a cardiac murmur. The timing of surgical repair was not found to be a predictor of morbidity or mortality. There was no significant difference in outcome measures defined as residual hypertension, residual coarctation gradient, persistent cardiomegaly, postoperative neurological sequelae, the requirement for a second surgery or the need for balloon dilatation for residual postoperative coarctation and the need for antihypertensive medications within five years postsurgery. CONCLUSION: The timing of surgical repair in the setting of nonductal dependent, mild-to-moderate coarctation of the aorta, does not adversely affect the short term (less than 20 years) outcome in children.