Evaluating the 12-Lead Electrocardiogram for Diagnosing ARVC in Young Populations: Implications for Preparticipation Screening of Athletes.

BACKGROUND: Arrhythmogenic right-ventricular cardiomyopathy (ARVC) is an identified cause of sport-related sudden cardiac arrest (SCA). Identifying athletes with ARVC and restricting them from exercise is believed to reduce the risk of SCA. The electrocardiogram (ECG) is considered to be an important component of screening for ARVC; however, the sensitivity of the 12-lead ECG to identify ARVC in young asymptomatic persons is unknown. METHODS: In this retrospective study, we identified 70 patients (49 ARVC-positive, based on Task Force Criteria, and 21 age-matched ARVC-negative persons from a paediatric arrhythmia database (<18 years of age); ECGs were analyzed for abnormalities, based on International Criteria for Interpretation of ECGs in Athletes, and ECG findings were adjudicated by group consensus. RESULTS: Of the 49 ARVC-positive patients (median age: 17 [interquartile range: 16-18], 65% male), 22% were found to have abnormal ECGs; the most common ECG findings were T-wave inversions. Patients with symptoms were more likely to have abnormal ECGs than asymptomatic patients (28% compared with 17%, respectively; P = 0.002). Of 16 gene-positive patients, 31% had abnormal ECGs. Patients with abnormal ECGs had larger right-ventricular end-diastolic volume indexes on magnetic resonance imaging than those with normal ECGs (P = 0.03). CONCLUSIONS: The ECG was insensitive for detecting ARVC in young (age <18 years), asymptomatic patients, and is unlikely to provide significant diagnostic value for identifying ARVC on routine preparticipation screening of adolescent athletes.

INTRODUCTION: La cardiomyopathie ventriculaire droite arythmogène (CVDA) est une cause établie d'arrêt cardiaque soudain (ACS) du sportif. On croit que le fait de repérer les athlètes atteints de CVDA et de limiter leur exercice réduit le risque d'ACS. On considère que l'électrocardiogramme (ECG) est une composante importante du dépistage de la CVDA. Toutefois, on ignore la sensibilité de l'ECG à 12 dérivations pour détecter la CVDA chez les jeunes personnes asymptomatiques. MÉTHODES: Dans cette étude rétrospective, nous avons repéré 70 patients (49 personnes dont les résultats sont positifs à la CVDA selon les critères de la Task Force, et 21 personnes appariées selon l'âge dont les résultats étaient positifs à la CVDA) d'une base de données sur l'arythmie en pédiatrie (< 18 ans); nous avons analysé les ECG pour détecter les anomalies selon les Critères de consensus internationaux de l'interprétation de l'ECG chez l'athlète, et nous sommes prononcés sur les résultats des ECG par consensus. RÉSULTATS: Parmi les 49 patients dont les résultats étaient positifs à la CVDA (âge médian : 17 [intervalle interquartile : 16-18], 65 % de sexe masculin), nous avons observé que 22 % d'entre eux avaient des résultats anormaux à l'ECG; les résultats les plus fréquents à l'ECG montraient des inversions de l'onde T. Les patients symptomatiques étaient plus susceptibles d'avoir des résultats anormaux à l'ECG que les patients asymptomatiques (28 % et 17 %, respectivement; P = 0,002). Parmi les 16 patients qui avaient des résultats génétiques positifs, 31 % avaient des résultats anormaux à l'ECG. Les patients qui avaient des résultats anormaux à l'ECG avaient des indices plus grands du volume télédiastolique du ventricule droit en fin de diastole à l'imagerie par résonance magnétique que ceux qui avaient des résultats normaux à l'ECG (P = 0,03). CONCLUSIONS: L'ECG n'a pas montré la sensibilité pour détecter la CVDA chez les jeunes (< 18 ans) patients asymptomatiques et n'a pas été susceptible de fournir une valeur diagnostique significative pour détecter la CVDA au dépistage systématique préalable à l'activité sportive des athlètes adolescents.

Sudden Cardiac Arrest during Participation in Competitive Sports.

BACKGROUND: The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes. METHODS: In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members. RESULTS: Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening. CONCLUSIONS: In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac arrest during participation in competitive sports was 0.76 cases per 100,000 athlete-years. The occurrence of sudden cardiac arrest due to structural heart disease was uncommon during participation in competitive sports. (Funded by the National Heart, Lung, and Blood Institute and others.).

Identification of a novel protein interaction motif in the regulatory subunit of casein kinase 2.

Casein kinase 2 (CK2) regulates multiple cellular processes and can promote oncogenesis. Interactions with the CK2ß regulatory subunit of the enzyme target its catalytic subunit (CK2α or CK2α') to specific substrates; however, little is known about the mechanisms by which these interactions occur. We previously showed that by binding CK2ß, the Epstein-Barr virus (EBV) EBNA1 protein recruits CK2 to promyelocytic leukemia (PML) nuclear bodies, where increased CK2-mediated phosphorylation of PML proteins triggers their degradation. Here we have identified a KSSR motif near the dimerization interface of CK2ß as forming part of a protein interaction pocket that mediates interaction with EBNA1. We show that the EBNA1-CK2ß interaction is primed by phosphorylation of EBNA1 on S393 (within a polyserine region). This phosphoserine is critical for EBNA1-induced PML degradation but does not affect EBNA1 functions in EBV replication or segregation. Using comparative proteomics of wild-type (WT) and KSSR mutant CK2ß, we identified an uncharacterized cellular protein, C18orf25/ARKL1, that also binds CK2ß through the KSSR motif and show that this involves a polyserine sequence resembling the CK2ß binding sequence in EBNA1. Therefore, we have identified a new mechanism of CK2 interaction used by viral and cellular proteins.