Prevention of sudden cardiac death in childhood-onset hypertrophic cardiomyopathy

BACKGROUND: Sudden cardiac death (SCD) is the most common cause of death in children with HCM. Although recent population-based studies have shown that SCD rates are lower than previously thought, it still occurs more frequently than in adult patients, highlighting the importance of accurate identification of those at risk. AIMS OF REVIEW: This review highlights risk factors for SCD in childhood HCM, current risk stratification guidelines, and novel personalized models for risk prediction. KEY SCIENTIFIC CONCEPTS OF REVIEW: The traditional approach to risk prediction in childhood-onset HCM, using cumulative risk factor thresholds and adopted by current international guidelines, has involved extrapolation of adult data, but recent evidence has demonstrated that this approach does not accurately discriminate high-risk from low-risk individuals. In response to this knowledge gap, novel pediatric-specific risk stratification models have been developed that allow calculation of individualized estimates of SCD risk and enable a personalized and shared decision-making approach to ICD implantation

La relación personal en el tratamiento de la diversidad

El autor centra su aportación en diferentes características de los organismos vivos, para incorporarlas a las perspectivas interpretativas y operativas, y de los métodos actuales de intervención educativa. En el texto también se trata el enfoque positivo desde la dimensión técnica y no «voluntarista», teniendo en cuenta que los especialistas que adoptan la perspectiva del enfoque positivo dan mucha importancia al tema de la calidad de vida.L'autor centra la seva aportació en diferents característiques dels organismes vius, per incorporar- les a les perspectives interpretatives i operatives, i dels mètodes actuals d'intervenció educativa. Al text també es tracta l'enfocament positiu des de la seva dimensió tècnica i no «voluntarista», tenint en compte que els especialistes que adopten la perspectiva de l'enfocament positiu donen molta importància al tema de la qualitat de vida.The author focuses on the different characteristics of the alive organisms in order to include them into the interpretative and operative views of the current methods of educational intervention. He also deals with the positive focus, from the technical and «no voluntary» dimension, taking into account that those specialists having this kind of view do emphasize a lot on the quality of life issue

An Improved Implementation and Abstract Interface for Hybrid

Hybrid is a formal theory implemented in Isabelle/HOL that provides an interface for representing and reasoning about object languages using higher-order abstract syntax (HOAS). This interface is built around an HOAS variable-binding operator that is constructed definitionally from a de Bruijn index representation. In this paper we make a variety of improvements to Hybrid, culminating in an abstract interface that on one hand makes Hybrid a more mathematically satisfactory theory, and on the other hand has important practical benefits. We start with a modification of Hybrid's type of terms that better hides its implementation in terms of de Bruijn indices, by excluding at the type level terms with dangling indices. We present an improved set of definitions, and a series of new lemmas that provide a complete characterization of Hybrid's primitives in terms of properties stated at the HOAS level. Benefits of this new package include a new proof of adequacy and improvements to reasoning about object logics. Such proofs are carried out at the higher level with no involvement of the lower level de Bruijn syntax.Comment: In Proceedings LFMTP 2011, arXiv:1110.668

Childhood Hypertrophic Cardiomyopathy: A Disease of the Cardiac Sarcomere

Hypertrophic cardiomyopathy is the second most common cause of cardiomyopathy presenting during childhood and whilst its underlying aetiology is variable, the majority of disease is caused by sarcomeric protein gene variants. Sarcomeric disease can present at any age with highly variable disease phenotype, progression and outcomes. The majority have good childhood-outcomes with reported 5-year survival rates above 80%. However, childhood onset disease is associated with considerable life-long morbidity and mortality, including a higher SCD rate during childhood than seen in adults. Management is currently focused on relieving symptoms and preventing disease-related complications, but the possibility of future disease-modifying therapies offers an exciting opportunity to modulate disease expression and outcomes in these young patients

Risk stratification in childhood hypertrophic cardiomyopathy

The true prevalence of hypertrophic cardiomyopathy (HCM) in childhood is unknown, but population-based studies have reported an annual incidence between 0.24–0.47 per 100,000 children. The aetiology of disease is more heterogeneous than that seen in adult populations, with up to 30% of patients having an inborn error of metabolism, malformation syndrome or neuromuscular syndrome. However, as in adults, most cases are caused by mutations in the cardiac sarcomere protein genes, even in young children. The long-term outcome of childhood HCM is highly variable and has been shown to depend partly on the age of presentation and underlying aetiology. Outside of infancy, the most frequent cause of mortality is sudden cardiac death (SCD), and one of the greatest challenges in managing young patients with HCM is identifying those at greatest risk of an arrhythmic event

The diagnostic yield of cardiac screening in first-degree relatives of sudden arrhythmic death syndrome or unexplained cardiac arrest probands: A systematic review of the literature

Background: First-degree relatives of Sudden Arrhythmic Death Syndrome (SADS) or Unexplained Cardiac Arrest (UCA) are recommended to undergo clinical evaluation for potential inherited cardiac conditions (ICC). However, data on the yield of family screening in these populations remains scarce. Aim of review: This systematic review aimed to explore the diagnostic yield of clinical screening of first-degree relatives of SADS or UCA probands. A secondary aim was to compare the diagnostic yield of adult-aged and pediatric-aged relatives. Key scientific concepts of review: Included studies described the clinical cardiac screening and yield of first-degree relatives of SADS and UCA probands. Quality of selected studies was assessed using a modified Joanna Briggs Institute checklist. 14 studies met inclusion criteria for this review, together including 1646 first-degree relatives of SADS probands and 656 first-degree relatives of UCA probands. Overall diagnostic yield described ranged from 0 to 32 %. The combined mean diagnostic yield of SADS relatives did not differ significantly from that of relatives of UCA probands. Three studies described outcomes of clinical screening in pediatric relatives, with an overall reported yield of 9.4 % ± 3.4 %, not significantly different from adult populations. Whilst there is a clear indication for clinical screening of first-degree relatives following SADS or an UCA, a lack of well-designed large population-based studies means that the evidence base is not robust. The yield in reported literature varies considerably, with no difference between SADS and UCA cohorts and a similar yield in pediatric and adult relatives. This supports screening for all first-degree relatives regardless of age