Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole‐exome sequencing (WES) was carried out on patients from three different families that presented with life‐threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans‐2,3‐enoyl‐CoA reductase‐like protein. Both patients had cardiac arrest, stress‐induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation. A third patient from a consanguineous Sudanese family diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) had a homozygous splice site mutation (c.331+1G>A) in TECRL. Analysis of intracellular calcium ([Ca2+]i) dynamics in human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) generated from this individual (TECRLH om‐hiPSCs), his heterozygous but clinically asymptomatic father (TECRLH et‐hiPSCs), and a healthy individual (CTRL‐hiPSCs) from the same Sudanese family, revealed smaller [Ca2+]i transient amplitudes as well as elevated diastolic [Ca2+]i in TECRLH om‐hiPSC‐CMs compared with CTRL‐hiPSC‐CMs. The [Ca2+]i transient also rose markedly slower and contained lower sarcoplasmic reticulum (SR) calcium stores, evidenced by the decreased magnitude of caffeine‐induced [Ca2+]i transients. In addition, the decay phase of the [Ca2+]i transient was slower in TECRLH om‐hiPSC‐CMs due to decreased SERCA and NCX activities. Furthermore, TECRLH om‐hiPSC‐CMs showed prolonged action potentials (APs) compared with CTRL‐hiPSC‐CMs. TECRL knockdown in control human embryonic stem cell‐derived CMs (hESC‐CMs) also resulted in significantly longer APs. Moreover, stimulation by noradrenaline (NA) significantly increased the propensity for triggered activity based on delayed afterdepolarizations (DADs) in TECRLH om‐hiPSC‐CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT. Patient‐specific hiPSC‐CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias.

BackgroundLong-term complications of sympathomimetic drug overdosing have not been adequately investigated in infants and young children. Despite reports discouraging their use in children, these formulations are frequently administered for “cold-like symptoms”. Their frequent adverse events are different forms of arrhythmias, including multifocal atrial tachycardia.Case presentationA 3-year-old toddler developed multifocal atrial tachycardia following an iatrogenic overdose of epinephrine accidentally administered intravenously. His ECG showed wandering atrial pacemaker (p-waves with different origins and configurations) that persisted for at least one year. This event demonstrated the sensitivity of young children to the sympathomimetic drugs, especially overdosing.ConclusionsHealth care providers and parents should be warned of toxicities associated with sympathomimetic drug overdosing. Future studies are needed to determine whether wandering atrial pacemaker is a potential long-term complication of high-dose sympathomimetics.

ImportanceBoarding in the emergency department (ED) is a critical indicator of quality of care for hospitals. It is defined as the time between the admission decision and departure from the ED. As a result of boarding, patients stay in the ED until inpatient beds are available; moreover, boarding is associated with various adverse events.

BackgroundThe impact of obesity and dyslipidemia on cardiovascular health in adolescents and young adults with diabetes is incompletely understood. This study evaluated the effects of these co-morbidities on markers of inflammation and endothelial dysfunction in young patients with the disease.MethodsThe study investigated sets of inflammatory, endothelial, and adipocyte biomarkers in 79 patients with type 1 diabetes, 55 patients with type 2 diabetes, and 47 controls.ResultsMean (±SD) age was 20±6 y (median = 17, range = 12–31). Patients with diabetes had higher levels of cytoadhesive molecules (sICAM-1 and sVCAM-1, p<0.001), adiponectin (p<0.001), and haptoglobin (p = 0.023). Their heart rate variability assessment revealed lower standard deviation of beat-to-beat intervals and lower total power (p≤0.019), reflecting autonomous nervous dysfunction. Hemoglobin A1c >8.0% (estimated average blood glucose >10 mmol/L) was associated with higher adiponectin (p<0.001) and obesity was associated with lower adiponectin (p<0.001); thus, obesity damped the effect of hyperglycemia on adiponectin. Obesity was associated with higher sICAM-1 (p≤0.015), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP), p<0.001. Similarly, high-density lipoprotein (HDL) <1.02 mmol/L was associated with higher sICAM-1, TNFα, IL-6, and hsCRP (p≤0.009) and lower adiponectin (p<0.001). Adiponectin correlated negatively with the inflammatory biomarkers in patients with diabetes.ConclusionSubclinical inflammation and endothelial dysfunction are common among young patients with diabetes. Poor diabetes control is associated with higher adiponectin. Obesity and dyslipidemia are associated with lower adiponectin and higher inflammatory and endothelial biomarkers. Intuitively, these predictors of cardiovascular disease are amenable to proper glycemic control, nutritional choices, and regular exercise.

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Abnormalities in arterial function and LDL oxidation may persist for at least 2 weeks after a slight inflammatory reaction induced by influenza vaccination. These could explain in part the earlier reported increase in cardiovascular risk during the first weeks after an acute inflammatory disorder.

Aortic root dilatation develops early in MFS and was present in 35% by the age of 5 years and 68% by 19 years. Even though new aortic root dilation is relatively rare, it is not possible to safely discharge patients with MFS as about one-third of the patients in our series who developed new pathological aortic root dilation did so after the age of 19 years.

Aims  Sudden death and aborted sudden death have been observed in patients with biallelic variants in TECRL. However, phenotypes have only begun to be described and no data are available on medical therapy after long-term follow-up. Methods and results  An international, multi-centre retrospective review was conducted. We report new cases associated with TECRL variants and long-term follow-up from previously published cases. We present 10 cases and 37 asymptomatic heterozygous carriers. Median age at onset of cardiac symptoms was 8 years (range 1–22 years) and cases were followed for an average of 10.3 years (standard deviation 8.3), right censored by death in three cases. All patients on metoprolol, bisoprolol, or atenolol were transitioned to nadolol or propranolol due to failure of therapy. Phenotypes typical of both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) were observed. We also observed divergent phenotypes in some cases despite identical homozygous variants. None of 37 heterozygous family members had a cardiac phenotype. Conclusion  Patients with biallelic pathogenic TECRL variants present with variable cardiac arrhythmia phenotypes, including those typical of long QT syndrome and CPVT. Nadolol and propranolol may be superior beta-blockers in this setting. No cardiac disease or sudden death was present in patients with a heterozygous genotype.