BACKGROUND:Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited. OBJECTIVES:The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS. METHODS:This was a retrospective multicenter study of patients <18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed. RESULTS:Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were attempted in 15, only 4 achieved pacing at implantation. During a median follow-up of 6.9 years (IQR: 1.2-13.3 years), 7 (35%) had thromboembolic events. Of these, none had atrial pacing, 6 were not on anticoagulation, and 1 was on aspirin. Genetic testing identified SCN5A variants in 13 patients (65%). Analyses suggest SCN5A loss-of-function may be one mechanism driving AS. Ventricular arrhythmias and cardiac arrest were more commonly seen in patients with biallelic SCN5A variants. CONCLUSIONS:AS may be associated with loss-of-function SCN5A variants. Patients demonstrate atrial and ventricular arrhythmias, and may present challenges during device placement. Patients without the capacity for atrial pacing are at risk for thromboembolic events and warrant anticoagulation.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. Results: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P <0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6–52.2]; P =0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3–10.8], P =0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). Conclusions: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.

Several studies suggest that anxiety disorders (AD) involve dysregulation of the autonomic nervous system (ANS) and hypothalamic-pituitary (HPA) axis. However, it is unknown if alterations in these biological systems are premorbid markers of AD risk or a state-dependent feature of anxiety. This study examined ANS and HPA-axis response to a laboratory stressor in healthy child offspring of parents with (n = 55) and without (n = 98) a history of AD. High frequency heart rate variability (HF-HRV) was assessed during sitting and standing baseline conditions and during a speech task where participants remained standing. Salivary cortisol was measured at baseline and at 15, 30, 45 and 60 min post-speech. Subjective anxiety was assessed with a visual analogue scale. Children of parents with AD displayed reduced HRV and a blunted cortisol response to the speech task compared to children of non-anxious parents. No risk group effect was found for anxiety ratings. These preliminary data suggest that healthy children of anxious parents exhibit altered stress reactivity to an acute laboratory stressor. Further research is needed to confirm findings and identify mechanisms that may account for altered self-regulation processes to a stressor in children at familial risk for AD.

AbstractPotentially fatal arrhythmias add to the mental health challenges of adolescence. This systematic review sought to summarise current knowledge regarding the mental health of adolescents and pre-adolescents diagnosed with inherited arrhythmia syndromes. Searches combining psychological problems with inherited cardiac arrhythmia diagnoses identified 16 studies with paediatric (<18 years) inherited arrhythmia patients. All studies were cross-sectional; 8/16 required an implantable cardioverter defibrillator. Methods were quantitative (n=11), qualitative (n=4), or mixed (n=1), with 14–100% of participants having an inherited arrhythmia syndrome. Mean/median age in 13/16 studies was 12–16 years. Patients and parents reported lower quality of life, particularly in relation to physical function, social relationships, restriction of peer activities, bodily pain, and mental and emotional health. Self-perceptions and behaviour were similar to healthy populations. Rates of anxiety and depression (15–33% of these patients) were not increased in these studies where patients were assessed 2+ years after diagnosis. Higher mental health risk occurred among patients who have a diagnosed sibling, those with cardiomyopathy, and those who report decreased quality of life. Mental health research among youth with inherited arrhythmias is extremely limited and of low quality. Data, primarily from patients 2–4 years after diagnosis or treatment with an implantable cardioverter defibrillator, indicate that quality of life may be decreased and 15–33% experience mental health issues. Future research is required to examine the mental health and quality of life of paediatric patients with inherited arrhythmia syndromes, whether or not they have an implantable cardioverter defibrillator, from time of diagnosis.

Medical Journal of AustraliaVolume 207, Issue 3 p. 107-110 Medical Education How to measure a QT interval Kathryn Waddell-Smith, Kathryn Waddell-Smith Starship Children's Health, Auckland, New ZealandSearch for more papers by this authorRobert M Gow, Robert M Gow Children's Hospital of Eastern Ontario, Ottawa, CanadaSearch for more papers by this authorJonathan R Skinner, Corresponding Author Jonathan R Skinner jskinner@adhb.govt.nz Starship Children's Health, Auckland, New ZealandCorrespondence: jskinner@adhb.govt.nzSearch for more papers by this author Kathryn Waddell-Smith, Kathryn Waddell-Smith Starship Children's Health, Auckland, New ZealandSearch for more papers by this authorRobert M Gow, Robert M Gow Children's Hospital of Eastern Ontario, Ottawa, CanadaSearch for more papers by this authorJonathan R Skinner, Corresponding Author Jonathan R Skinner jskinner@adhb.govt.nz Starship Children's Health, Auckland, New ZealandCorrespondence: jskinner@adhb.govt.nzSearch for more papers by this author First published: 07 August 2017 https://doi.org/10.5694/mja16.00442Citations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume207, Issue3August 2017Pages 107-110 RelatedInformation

n abnormally prolongedQT interval is associated with an increased risk of sudden cardiac death. ASome professional bodies recommend national population-based screening programs to detect QT prolongation. Familial long QT syndrome (LQTS) may remain undetected because of misdiagnosis (eg, as a seizure disorder) or through failure to measure the QT interval correctly. Psychiatrists fear the QT prolongation caused by many psychotropic medications, and it may also be seen during periods of hypothermia; electrolyte imbalance (such as hypokalaemia, hypomagnesaemia and hypocalcaemia); in the setting of raised intracranial pressure or postcardiac arrest; with other medications, such as type 1A, 1C and III antiarrhythmic agents; and with antihistamines and macrolide antibiotics.

A previously healthy 15-month-old girl was admitted to the pediatric ward with recurring febrile episodes and a palpable large abdominal neuroblastoma. The initial echocardiogram showed a small to moderate sized pericardial effusion with no echocardiographic features of cardiac tamponade. The patient was transferred to the intensive care unit 1 week following admission for persistent tachycardia and respiratory distress. The echocardiogram then demonstrated a large asymmetric pericardial effusion with inflow respiratory variation through the mitral and tricuspid valves. Right atrial and ventricular collapse were not appreciated due to cardiac malposition from the large abdominal mass. The patient was tachycardic and tachypneic. There were several confounding factors, including presumed sepsis, contributing to the patient's deterioration, making it difficult to ascertain the hemodynamic significance of the pericardial effusion. Reliable inspiratory and expiratory blood pressures could not be obtained, thus making manual determination of pulsus paradoxus difficult. However, the amplitude of the pulse oximetry plethysmography concurrently showed significant respiratory variation, suggestive of cardiac tamponade (Figure 1). The patient subsequently underwent pericardiocentesis. Repeat echocardiogram the following day showed minimal residual effusion with no evidence of tamponade. Additionally, the amplitude of the pulse oximetry waveform demonstrated no variability with the respiratory cycle (Figure 2; available at www.jpeds.com). Pulsus paradoxus is an exaggeration (>10 mmHg) of the physiologic systolic blood pressure decline occurring during inspiration. It is highly suggestive of decreased left ventricular cardiac output from tamponade.1Tamburro R.F. Ring J.C. Womback K. Detection of pulsus paradoxus associated with large pericardial effusions in pediatric patients by analysis of the pulse-oximetry waveform.Pediatrics. 2002; 109: 673-677Crossref PubMed Scopus (22) Google Scholar However, this maneuver can be particularly difficult to elucidate in young pediatric patients.2Frey B. Butt W. Pulse oximetry for assessment of pulsus paradoxus: a clinical study in children.Intensive Care Med. 1998; 24: 242-246Crossref PubMed Scopus (43) Google Scholar Pulse oximetry waveform has been shown to correlate with pulsus paradoxus by examining the waveform amplitude during the respiratory cycle. The amplitude variation reflects arterial pulsations and is directly related to changes in arterial blood pressure. A ratio of the peak expiration compared with inspiration plethysmography value of 1.5 yields a sensitivity of 0.83 and specificity of 1.0 for the detection of cardiac tamponade.1Tamburro R.F. Ring J.C. Womback K. Detection of pulsus paradoxus associated with large pericardial effusions in pediatric patients by analysis of the pulse-oximetry waveform.Pediatrics. 2002; 109: 673-677Crossref PubMed Scopus (22) Google Scholar, 3Stone M.K. Bauch T.D. Rubal B.J. Respiratory changes in the pulse-oximetry waveform associated with pericardial tamponade.Clin Cardiol. 2006; 29: 411-414Crossref PubMed Scopus (6) Google Scholar Although echocardiography is an important test to diagnose pericardial effusions, patient or environmental factors may limit its use, and it may not be available immediately to the noncardiologist. Examination of the pulse oximetry waveform provides a noninvasive and readily available bedside tool for clinicians. It can be used as a surrogate to assess the hemodynamic significance of pericardial effusions when standard determination of pulsus paradoxus is difficult, and can aid in clinical decision-making.

BACKGROUND:Inherited autosomal dominant mutations in cardiac sodium channels (NaV1.5) cause various arrhythmias, such as long QT syndrome and Brugada syndrome. Although dozens of mutations throughout the protein have been reported, there are few reported mutations within a voltage sensor S4 transmembrane segment and few that are homozygous. Here we report analysis of a novel lidocaine-sensitive recessive mutation, p.R1309H, in the NaV1.5 DIII/S4 voltage sensor in a patient with a complex arrhythmia syndrome.METHODS AND RESULTS:We expressed the wild type or mutant NaV1.5 heterologously for analysis with the patch-clamp and voltage clamp fluorometry (VCF) techniques. p.R1309H depolarized the voltage-dependence of activation, hyperpolarized the voltage-dependence of inactivation, and slowed recovery from inactivation, thereby reducing the channel availability at physiologic membrane potentials. Additionally, p.R1309H increased the "late" Na(+) current. The location of the mutation in DIIIS4 prompted testing for a gating pore current. We observed an inward current at hyperpolarizing voltages that likely exacerbates the loss-of-function defects at resting membrane potentials. Lidocaine reduced the gating pore current.CONCLUSIONS:The p.R1309H homozygous NaV1.5 mutation conferred both gain-of-function and loss-of-function effects on NaV1.5 channel activity. Reduction of a mutation-induced gating pore current by lidocaine suggested a therapeutic mechanism.

Twelve hours after birth, an otherwise healthy newborn infant is noted to have an irregular pulse during routine examination in the well-child unit. The infant was born at term after an uncomplicated pregnancy and vaginal delivery. An electrocardiogram (ECG) reveals frequent single premature wide complexes corresponding to the pulse irregularity. The infant has good perfusion, easily palpable pulses in all 4 limbs, and no murmur. He is afebrile and has been feeding and voiding normally. He is transferred to the intensive care unit for monitoring and further evaluation. In the following hours, the infant exhibits frequent wide-complex couplets, progressing to runs of wide-complex beats lasting up to 45 seconds at a time (Figure). Periods of wide-complex arrhythmia are unrelated to activity level, and the infant continues to demonstrate good perfusion. An arterial line is placed and reveals that while in sinus rhythm at a heart rate of 146 beats per minute, the blood pressure is 75/40 mm Hg. The heart rate is 161 beats per minute and the blood pressure is 65/35 mm Hg during the wide-complex rhythm. Figure. Electrocardiogram of an infant 21 hours after birth, which shows a run of monomorphic wide-complex tachycardia. Further analysis of the patient’s ECG during periods of sinus …

An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.

We report familial cardiac conduction disease (FCCD) in a 3-generation pedigree, including some family members with congenital junctional ectopic tachycardia (JET) (Fig. 1A). The proband presented during a febrile illness at 3.5-years of age with variable atrio-ventricular (AV) block (1st, 2nd, and 3rd degrees) together with left anterior fascicular block (LAFB) and right bundle branch block (RBBB) (Fig. 1B). Viral studies and echocardiogram were normal and he received a pacemaker; he subsequently developed clinical junctional tachycardia. Family history revealed a maternal grandmother with RBBB diagnosed at 5 years of age. The electrocardiogram (ECG) from the proband's mother revealed sinus rhythm (SR), 1st degree AV block and a nonspecific intraventricular conduction delay. Clinical genetic testing of SCN5A did not reveal any disease-associated mutations. Subsequently she gave birth to identical twin girls. Both girls had rapid JET in the immediate post-natal period that was initially difficult to control. There was rate dependent RBBB and LAFB in both children prior to use of antiarrhythmic drugs. The arrhythmia has resolved in one twin but persists in the other as a catecholamine dependent accelerated junctional rhythm/congenital JET that is modified by propranolol therapy (Fig. 1C). The resting ECGs now both show LAFB and intermittent incomplete RBBB. The mother has subsequently developed symptomatic palpitations and shows electrocardiographic features consistent with typical atrioventricular nodal re-entrant tachycardia (AVNRT) on symptom-rhythm correlation observed on loop recorder. Thus, the conduction defects in this family were of varying severity and the relationship to congenital JET in the three children is important as it is well recognized that congenital JET may progress to heart block [ 1 Henneveld H. Hutter P. Bink-Boelkens M. et al. Junctional ectopic tachycardia evolving into complete heart block. Heart. 1998; 80: 627-628 Crossref PubMed Scopus (23) Google Scholar , 2 Villain E. Vetter V.L. Garcia J.M. et al. Evolving concepts in the management of congenital junctional ectopic tachycardia. A multicenter study. Circulation. 1990; 81: 1544-1549 Crossref PubMed Scopus (211) Google Scholar ]. At this stage the conduction abnormalities are minor in the twins who presented with the JET and have not progressed.

The Cardiac Arrest Survivors with Preserved Ejection Fraction (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease, and aims to identify the underlying conditions responsible for the cardiac arrest through systematic clinical testing. A combination of exercise testing, drug provocation, electrophysiological testing, advanced cardiac imaging, and targeted genetic testing can unmask the cause of cardiac arrest when a cause is not apparent. Patients with a previous UCA from 14 sites across Canada were prospectively enrolled. Patients were free of evidence of coronary artery disease, left ventricular dysfunction or evident repolarization syndromes. ICD events, including appropriate shocks and anti-tachycardia pacing (ATP), were compared between diagnosed and undiagnosed patients. Time to first event was calculated using a Cox regression model. The first 200 survivors of unexplained cardiac arrest were evaluated to determine the results of investigation and follow-up risk of recurrence (age 48.6 ± 14.7 years, 41% female). Advanced testing determined a probable or definite diagnosis in 41% of patients. Of those that received a diagnosis, 28 (35%) had an underlying structural condition, and 53 (65%) had a primary electrical disease. During a median follow-up of 3.15±2.34 years, 23% of patients had either a shock or appropriate antitachycardia pacing or both from their ICD. Cox regression curves were constructed to determine time to first event (Figure 1). The annual ICD appropriate intervention rate was 7.3%, with no clear difference in intervention rate between diagnosed and undiagnosed subjects (p=0.208), or between those diagnosed with a primary electrical versus structural etiology (p=0.492). Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause of cardiac arrest. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate ICD therapy during medium-term follow-up.

A number of disciplines rely on assessment of LVH to help determine disease severity and guide management decisions. Alternate methods of quantifying LV mass may result in inconsistent classification of LVH. Our study aims to examine reproducibility of various indexing methods and evaluate for errors of classification of LVH due to the indexing method. We hypothesized that different indexing Methods would lead to discrepant classification of LVH from calculated LV mass. A total of 230 transthoracic echocardiograms of children without complex congenital heart disease or cardiomyopathy were randomly selected from a single institution's pre-existing database: 100 with structurally normal hearts, 100 with hypertension, and 30 with LVH. LV mass in all children was indexed to body surface area (BSA), height and height2.7, and additionally to lean body mass (LBM) in children over 5 years of age. The primary variable of interest was indexed LV mass Z score. LVH was defined as a Z score ≥1.65. Reliability was evaluated using intraclass correlation coefficient (ICC (3,1)). Agreement between indexing Methods was explored using Bland-Altman analysis. Classification of LVH was evaluated by percent agreement and kappa coefficient. There were 126 males (54.7%); mean age was 9.83 years. Mean Z score varied significantly by method (p < 0.001), from -0.64 (BSA) to 1.41 (height2.7). Reliability analysis between Methods showed an ICC (95% CI) of 0.62 (0.21,0.81). Two-way Bland-Altman analyses of Z scores revealed bias (-2.16 to 1.56) and wide limits of agreement between Methods. The indexing method determined the proportion of individuals classified as having LVH. Indexing to BSA or LBM classified 4.78% or 6.96% of the group with LVH respectively, whereas 14.78% were categorized as LVH when indexed to height. Indexing to height2.7 resulted in 36.09% being classified as LVH. The percentage of absolute agreement was 68.7% amongst the entire cohort, with higher agreement among the three Methods in children under the age of 5 years (85.3%) compared to all four Methods in children over the age of 5 (61.7%). Kappa analysis (95% CI) showed low agreement for classification [0.39 (0.26,0.51)]. There was no significant difference in classification errors between the three populations ("normals," "hypertension," and "LVH"). Classification of LVH is heavily biased and depends directly on indexing technique. There is poor reliability and agreement between the four indexing Methods which are not interchangeable. Moving between Z score indexing Methods could lead to inaccurate clinical decisions.

BackgroundADHD medications increase clinical encounters for cardiovascular symptoms. Uncertain are the roles of differences in ADHD medications and restrictive practices by drug programs.MethodsWe conducted two nested case-control studies. The first was nested within a cohort of children de novo users of methylphenidate, amphetamines or atomoxetine and the second case-control study was nested within a subcohort of de novo amphetamine or atomoxetine users with no cardiovascular events prior to the first dispensing of either drug. The outcome for both studies was the composite of physician visits, emergency room visits or hospitalizations for cardiovascular reasons. Cases were matched on sex, age and date of entry within the cohorts, with up to 10 controls. Patients with an active dispensation of ADHD medications at the index date (and up to 90 days previously) were considered exposed. Conditional logistic regression was used to calculate odd ratios (OR).ResultsThe full cohort comprised 38,495 patients. Among these patients, 3595 (9.3%) had no prior cardiovascular events (the subcohort). In the full cohort, an association was demonstrated with exposure to amphetamine and atomoxetine (but not methylphenidate) and the cardiovascular encounter outcomes. When the sub-cohort was analyzed the associations with amphetamine or atomoxetine were no longer evident.ConclusionReimbursement policies need to be considered when conducting observational studies. Had the analysis been conducted without consideration of these policies the results would have incorrectly identified amphetamine and atomoxetine as important risk factors for cardiovascular encounters.

Introduction: The genetics of unexplained cardiac arrest (UCA) remains largely elusive. We sought to identify genetic variants linked to UCA in a case-control genetic association study. Methods: Cases are UCA probands from the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER), which included individuals with a history of UCA or sudden cardiac death (SCD) with normal autopsy. Exclusion criteria were coronary/structural heart diseases, or a baseline ECG with type I Brugada or prolonged QTc (males>460ms, females>480ms). Controls were individuals without coronary/structural heart diseases, ventricular arrhythmia or family history of SCD, from the Montreal Heart Institute Biobank. We performed exome-wide genotyping using the Illumina HumanExome BeadChip (>250,000 mostly coding markers). Each case was matched with 3 controls from a 3139 individuals dataset using identity-by-descent. Association analysis was performed using the Cochran-Mantel-Haenszel test, controlling for sex. We validated genotyping of most significant variants using Sequenom technology. Results: After quality checks, we compared allele frequencies at 76157 polymorphic markers in 79 cases and 237 matched controls. Genotyping success rate was 99% in both groups. We identified 17 variants with P-values -4 , whereas we would have expected 7 under the null hypothesis of no association. This reflects an enrichment of variants associated with UCA. The strongest association with UCA risk was observed at a single nucleotide polymorphism (SNP) in POLRMT . Minor allele frequency (MAF) in cases and controls was 0.048 and 0.011, respectively (p = 9.7x10 -7 , odds ratio = 5.0). MAF in controls was similar to those reported in Exome Sequence Project (0.014) and 1000 Genomes (0.007). POLRMT encodes a mitochondrial DNA-directed RNA polymerase. Interestingly, POLRMT is located next to HCN2 , which encodes an ion channel previously implicated in ventricular arrhythmia. Conclusion: In this case-control study from the CASPER registry, a SNP in POLMRT is strongly associated with UCA. Replication studies are ongoing. If the association is confirmed, the mechanism of arrhythmogenesis might involve deregulation of gene expression of a nearby ion channel gene.

Canadian electrophysiology (EP) fellowship programs have evolved in an ad hoc fashion over 30 years. This evolution has occurred in many fields in medicine and is natural when innovators and pioneers attract research fellows who help change the status quo from predominantly research to a predominantly clinical application and focus. Fellows not only push their supervisors and their centres into new areas of inquiry but also function at the most advanced level to encourage and teach junior trainees and to provide examples of excellence to residents, medical students, and other health professionals. Funding for fellows has never been provided in the traditional way through the Ministry of Health or the Ministry of Advanced Education. Each Canadian centre has over the years found novel ways to fund fellowship programs, and many centres have used value-adds from procurement programs. These sources of funding are eroding as provincial government agencies are beginning to assume procurement responsibilities and local flexibility to fund fellowships is lost. In particular, provincial government agencies feel that valuable financial resources should be restricted to Canadian trainees only, despite the international consensus that fellowship is an essential time for advanced trainees to travel abroad to acquire a broad a range of experience, learn new techniques and approaches, make lifelong research connections, and hopefully return home with these skills and expertise. This article summarizes the long history of EP fellowship training in Canada, as well as EP fellowship experiences at home and abroad by Canadian electrophysiologists, in an attempt to contextualize these new realities.

Background— International guidelines recommend restriction of activities for many children and adolescents with inherited arrhythmia syndromes to moderate activity (<7 metabolic equivalents [METs]). We hypothesized that moderate levels of intensity would be exceeded during free-living daily activity in these individuals when assessed objectively by combined heart rate and accelerometry monitor (Actiheart). Methods and Results— Participants wore the Actiheart for ≤7 days on 2 occasions after a maximal exercise test that was used to calibrate the monitor individually against intensity levels. Of 16 participants, 13 (81%) had long QT syndrome, 9 (56%) were female, and median age was 12 years. Monitors were worn for a median (range) of 13 (6–14) days, and a mean (SD) of 11.3 (1.7) hours per day. Vigorous (7 MET) and very vigorous (10 MET) thresholds were exceeded by 15 and 13 participants, respectively. The median (interquartile range), individual, total weekly time spent >7 MET threshold was 113 (65–330) minutes, whereas such time spent >10 MET threshold was 53 (9–115) minutes. Total time >7 MET threshold was 2.3% of monitor wear time. There were no differences in time above threshold between male and female participants ( P =0.357) or among those with different levels of activity restriction ( P =0.769). Conclusions— Current recommended activity guidelines are frequently exceeded during routine free-living activities in young participants with inherited arrhythmia syndromes. Whether this indicates increased risk for these individuals or excessively restrictive guidelines remains to be determined.