Among NFL football players who began their careers between 1982 and 1992, career participation in the NFL, compared with limited NFL exposure obtained primarily as an NFL replacement player during a league-wide strike, was not associated with a statistically significant difference in long-term all-cause mortality. Given the small number of events, analysis of longer periods of follow-up may be informative.

Hairy and enhancer of split-1 (HES1) is a basic helix-loop-helix transcription factor that is a key regulator of development and organogenesis. However, little is known about the role of HES1 after birth. Glucocorticoids, primary stress hormones that are essential for life, regulate numerous homeostatic processes that permit vertebrates to cope with physiological challenges. The molecular actions of glucocorticoids are mediated by glucocorticoid receptor-dependent regulation of nearly 25% of the genome. We now establish a genome wide molecular link between HES1 and glucocorticoid receptors that controls the ability of cells and animals to respond to stress. Glucocorticoid signaling rapidly and robustly silenced HES1 expression. This glucocorticoid-dependent repression of HES1 was necessary for the glucocorticoid receptor to regulate many of its target genes. Mice with conditional knockout of HES1 in the liver exhibited an expanded glucocorticoid receptor signaling profile and aberrant metabolic phenotype. Our results indicate that HES1 acts as a master repressor, the silencing of which is required for proper glucocorticoid signaling.

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A trial fibrillation (AF) is a major cause of stroke with this elevated stroke risk similar among patients with permanent, persistent, and paroxysmal AF.1 Traditionally, the mechanism for thromboembolism in patients with a history of AF yet in sinus rhythm (SR) has been ascribed to episodes of clinically silent AF that would be detected by long-term monitoring. 2In AF, the majority of left atrial (LA) thrombi involve the LA appendage (LAA). Anecdotal reports have noted that the surface ECG may not always reflect underlying LAA mechanical function. 3 Transesophageal echocardiography (TEE) in such patients has demonstrated an irregular, AF phenotype on LAA pulse wave Doppler (PWD), whereas the simultaneous surface ECG demonstrated SR. 4 This discordance may account for thromboembolism in patients with AF despite ECG SR. In this study, we sought to assess the prevalence of LAA mechanical discordance in consecutive patients undergoing TEE at our institution. MethodsConsecutive patients undergoing TEE by a single operator were retrospectively identified from our electronic medical records. The study was approved by the institution's investigational review board and written informed consent was waived.TEE ECG rhythm review was performed by an investigator (W.J.M.) blinded to TEE Doppler data. Patients were classified to be in SR or AF based on the ECG rhythm strip at the time of the TEE and anatomic M-mode of mitral valve motion (MVM). TEE images of the LAA were reviewed by a blinded independent investigator (H.J.W.). PWD flow pattern recorded from 1 cm into the mouth of the LAA at 0° and 90° was reviewed to determine LAA phenotype.5 These data were compared with the ECG/MVM data to identify cases of concordance/discordance.Statistical analyses were performed with Stata/MP 10.0 (Stata, College Station, TX). Continuous variables were expressed as mean±SD and categorical variables as frequency or percentage. Continuous variables within 2 patient groups were compared by using independent t sample test, whereas categorical variables were compared using Fisher exact test with a statistical significance level of P≤0.05. ResultsA total of 208 consecutive TEE studies were identified during the observation period, for which TEE LAA data were available on 201 (96%) patients (63.4±15 years, 61% men). The most common indications for TEE include AF or atrial flutter (n=75), endocarditis (n=64), and source of embolism (n=24). Most strokes (n=17/38) were embolic and most (n=16/17) patients undergoing TEE to identify embolic source were without a history of AF and were in SR. No subject was <7 days postelectrophysiological procedure.Discordance between the ECG/MVM rhythm and the LAA PWD phenotype was noted in 15 (7.5%) patient with 7 (3.5%) demonstrating AF discordance (SR on ECG/MVM and AF phenotype on LAA PWD; Figure 1), whereas 8 (4.0%)Background and Purpose-Thromboembolism in paroxysmal atrial fibrillation (AF) has often been attributed to occult AF.We hypothesized that the surface ECG may not always reflect left atrial appendage...

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Background and Aim Mitral valve (MV) surgeries create electrophysiological substrates that give rise to postoperative arrhythmias. MV surgical procedures have been associated with macro‐ and microreentrant arrhythmogenic circuits, as well as circuits involving the atrial roof. It is not well understood why such arrhythmias develop; therefore, the aim of this study was to describe clinical and procedure characteristics associated with atrial arrhythmias in patients with prior MV surgery. Methods This retrospective chart review evaluated patients who had prior MV surgery and ablation procedures for atrial tachycardia between 2014 and 2018 (n = 20). Patients were classified into those exhibiting typical atrial flutter or another atrial tachyarrhythmia. Results Within the 20 patient cases reviewed, 30 arrhythmias were documented. Two‐thirds of arrhythmias were typical atrial flutter; the percent incidence of arrhythmias originating in the right atrial (RA) roof, around the right atriotomy scar, in the left atrium, and at the crista terminalis was 20%, 3%, 7%, and 7%, respectively. Nearly every case of RA roof flutter (n = 5/6) and most arrhythmias (n = 20/30) occurred in patients who had a transseptal approach during MV surgery. Voltage maps did not show clear differences in scarring between groups. Conclusion Results from this study suggest that an arrhythmogenic substrate for RA roof tachycardias is generated by transseptal approaches for MV surgery. This substrate is not clearly related to a surgical scar. These data suggest that other approaches should be considered for MV surgeries. Additionally, more research is needed to determine the mechanism for this nonscar‐related arrhythmia substrate.