A Path to Implement Precision Child Health Cardiovascular Medicine.

Congenital heart defects (CHDs) affect approximately 1% of live births and are a major source of childhood morbidity and mortality even in countries with advanced healthcare systems. Along with phenotypic heterogeneity, the underlying etiology of CHDs is multifactorial, involving genetic, epigenetic, and/or environmental contributors. Clear dissection of the underlying mechanism is a powerful step to establish individualized therapies. However, the majority of CHDs are yet to be clearly diagnosed for the underlying genetic and environmental factors, and even less with effective therapies. Although the survival rate for CHDs is steadily improving, there is still a significant unmet need for refining diagnostic precision and establishing targeted therapies to optimize life quality and to minimize future complications. In particular, proper identification of disease associated genetic variants in humans has been challenging, and this greatly impedes our ability to delineate gene-environment interactions that contribute to the pathogenesis of CHDs. Implementing a systematic multileveled approach can establish a continuum from phenotypic characterization in the clinic to molecular dissection using combined next-generation sequencing platforms and validation studies in suitable models at the bench. Key elements necessary to advance the field are: first, proper delineation of the phenotypic spectrum of CHDs; second, defining the molecular genotype/phenotype by combining whole-exome sequencing and transcriptome analysis; third, integration of phenotypic, genotypic, and molecular datasets to identify molecular network contributing to CHDs; fourth, generation of relevant disease models and multileveled experimental investigations. In order to achieve all these goals, access to high-quality biological specimens from well-defined patient cohorts is a crucial step. Therefore, establishing a CHD BioCore is an essential infrastructure and a critical step on the path toward precision child health cardiovascular medicine

Pre-participation Cardiac Screening in Young Athletes: Models and Criteria

This is the second of two review articles focusing on the value of preparticipation cardiac screening in young athletes. The article focuses on the efficacy of the resting 12-lead electrocardiogram (ECG), physical examination, and medical history questionnaire, which commonly make up the first stage of a cardiac screening protocol. The review then focuses on specific structural and electrical abnormalities which are responsible for sudden cardiac death (SCD) in young athletes – the most common of which is hypertrophic cardiomyopathy. The identification of appropriate ‘red flag’ signs and symptoms is essential for teasing out potential pathological conditions and allowing differentiation from often benign physiological adaptations. The final section provides guidance on how the resting 12-lead ECG can be used to separate pathological from physiological adaptations in young athletes

Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

Design and evaluation of a person-centric heart monitoring system over fog computing infrastructure

Heart disease and stroke are becoming the leading cause of death worldwide. Electrocardiography monitoring devices (ECG) are the only tool that helps physicians diagnose cardiac abnormalities. Although the design of ECGs has followed closely the electronics miniaturization evolution over the years, existing wearable ECG have limited accuracy and rely on external resources to analyze the signal and evaluate heart activity. In this paper, we work towards empowering the wearable device with processing capabilities to locally analyze the signal and identify abnormal behavior. The ability to differentiate between normal and abnormal heart activity significantly reduces (a) the need to store the signals, (b) the data transmitted to the cloud and (c) the overall power consumption. Based on this concept, the HEART platform is presented that combines wearable embedded devices, mobile edge devices, and cloud services to provide on-the-spot, reliable, accurate and instant monitoring of the heart. The performance of the system is evaluated concerning the accuracy of detecting abnormal events and the power consumption of the wearable device. Results indicate that a very high percentage of success can be achieved in terms of event detection ratio and the device being operative up to a several days without the need for a recharge

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 138 reports, articles, and other documents introduced into the NASA scientific and technical information system in Jun. 1980

Computer Aided ECG Analysis - State of the Art and Upcoming Challenges

In this paper we present current achievements in computer aided ECG analysis and their applicability in real world medical diagnosis process. Most of the current work is covering problems of removing noise, detecting heartbeats and rhythm-based analysis. There are some advancements in particular ECG segments detection and beat classifications but with limited evaluations and without clinical approvals. This paper presents state of the art advancements in those areas till present day. Besides this short computer science and signal processing literature review, paper covers future challenges regarding the ECG signal morphology analysis deriving from the medical literature review. Paper is concluded with identified gaps in current advancements and testing, upcoming challenges for future research and a bullseye test is suggested for morphology analysis evaluation.Comment: 7 pages, 3 figures, IEEE EUROCON 2013 International conference on computer as a tool, 1-4 July 2013, Zagreb, Croati