Complete heart block is a significant predictor of mortality in immune checkpoint inhibitor myocarditis.

BACKGROUND: Immune checkpoint inhibitor (ICI) myocarditis is associated with significant mortality risk. Electrocardiogram (ECG) changes in ICI myocarditis have strong prognostic value. However the impact of complete heart block (CHB) is not well defined. This study sought to evaluate the impact of CHB on mortality in ICI myocarditis, and to identify clinical predictors of mortality and CHB incidence. METHODS: We conducted a retrospective cohort study of patients with ICI myocarditis at three Mayo Clinic sites from 1st January 2010 to 31st September 2022 to evaluate mortality rates at 180 days. Clinical, laboratory, ECG, echocardiographic, and cardiac magnetic resonance imaging (CMR) characteristics were assessed. Cox and logistic regression were performed for associations with mortality and CHB respectively. RESULTS: Of 34 identified cases of ICI myocarditis, 7 (20.6%) had CHB. CHB was associated with higher mortality (HR 7.41, p = 0.03, attributable fraction 86.5%). Among those with CHB, troponin T (TnT) < 1000 ng/dL, low white blood cell count and high ventricular rate at admission were protective. There was trend towards increased survival among patients who underwent permanent pacemaker insertion (p = 0.051), although most experienced device lead complications. Factors associated with development of CHB included prolonged PR and QRS intervals and low Sokolow Lyon Index. Where these were normal and TnT was < 1000 ng/dL, no deaths occurred. Impaired myocardial longitudinal strain was sensitive for ICI myocarditis but was not prognostically significant. CONCLUSION: There is a strong temporal association between CHB and early mortality in people with ICI myocarditis. Focusing on arrhythmogenic complications can be helpful in predicting outcomes for this group of critically ill individuals.

Confronting ethical and social issues related to the genetics of musicality.

New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together diverse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.

Heritability of Childhood Music Engagement and Associations with Language and Executive Function: Insights from the Adolescent Brain Cognitive Development (ABCD) Study.

Music engagement is a powerful, influential experience that often begins early in life. Music engagement is moderately heritable in adults (~ 41-69%), but fewer studies have examined genetic influences on childhood music engagement, including their association with language and executive functions. Here we explored genetic and environmental influences on music listening and instrument playing (including singing) in the baseline assessment of the Adolescent Brain Cognitive Development study. Parents reported on their 9-10-year-old children's music experiences (N = 11,876 children; N = 1543 from twin pairs). Both music measures were explained primarily by shared environmental influences. Instrument exposure (but not frequency of instrument engagement) was associated with language skills (r = .27) and executive functions (r = .15-0.17), and these associations with instrument engagement were stronger than those for music listening, visual art, or soccer engagement. These findings highlight the role of shared environmental influences between early music experiences, language, and executive function, during a formative time in development.

Infants' neural sensitivity to social interactions varies by income and infant-directed speech.

Social interactions are essential for infant brain development, yet we know little about how infant functional connectivity differs between social and nonsocial contexts, or how sensitivity to differences between contexts might be related to early distal and proximal environmental factors. We compared 12-month-old infants' intrahemispheric electroencephalographic (EEG) coherence between a social and a nonsocial condition, then examined whether differences between conditions varied as a function of family economic strain and two maternal behaviors at 6 months, positive affect and infant-directed speech. We found lower EEG coherence from the frontal region to the central, parietal, temporal, and occipital regions during the social condition, but only for infants from higher-income families and infants whose mothers used higher proportions of infant-directed speech. In contrast, there were no differences between social and nonsocial conditions for infants from economically strained families or infants whose mothers used lower proportions of infant-directed speech. This study demonstrates that neural organization differs between a nonsocial baseline and a social interaction, but said differentiation is not present for infants from less privileged backgrounds. Our results underscore the importance of examining brain activity during species-typical contexts to understand the role of environmental factors in brain development.

Test of Prosody via Syllable Emphasis ("TOPsy"): Psychometric Validation of a Brief Scalable Test of Lexical Stress Perception.

Prosody perception is fundamental to spoken language communication as it supports comprehension, pragmatics, morphosyntactic parsing of speech streams, and phonological awareness. A particular aspect of prosody: perceptual sensitivity to speech rhythm patterns in words (i.e., lexical stress sensitivity), is also a robust predictor of reading skills, though it has received much less attention than phonological awareness in the literature. Given the importance of prosody and reading in educational outcomes, reliable and valid tools are needed to conduct large-scale health and genetic investigations of individual differences in prosody, as groundwork for investigating the biological underpinnings of the relationship between prosody and reading. Motivated by this need, we present the Test of Prosody via Syllable Emphasis ("TOPsy") and highlight its merits as a phenotyping tool to measure lexical stress sensitivity in as little as 10 min, in scalable internet-based cohorts. In this 28-item speech rhythm perception test [modeled after the stress identification test from Wade-Woolley (2016)], participants listen to multi-syllabic spoken words and are asked to identify lexical stress patterns. Psychometric analyses in a large internet-based sample shows excellent reliability, and predictive validity for self-reported difficulties with speech-language, reading, and musical beat synchronization. Further, items loaded onto two distinct factors corresponding to initially stressed vs. non-initially stressed words. These results are consistent with previous reports that speech rhythm perception abilities correlate with musical rhythm sensitivity and speech-language/reading skills, and are implicated in reading disorders (e.g., dyslexia). We conclude that TOPsy can serve as a useful tool for studying prosodic perception at large scales in a variety of different settings, and importantly can act as a validated brief phenotype for future investigations of the genetic architecture of prosodic perception, and its relationship to educational outcomes.

The Musical Abilities, Pleiotropy, Language, and Environment (MAPLE) Framework for Understanding Musicality-Language Links Across the Lifespan.

Using individual differences approaches, a growing body of literature finds positive associations between musicality and language-related abilities, complementing prior findings of links between musical training and language skills. Despite these associations, musicality has been often overlooked in mainstream models of individual differences in language acquisition and development. To better understand the biological basis of these individual differences, we propose the Musical Abilities, Pleiotropy, Language, and Environment (MAPLE) framework. This novel integrative framework posits that musical and language-related abilities likely share some common genetic architecture (i.e., genetic pleiotropy) in addition to some degree of overlapping neural endophenotypes, and genetic influences on musically and linguistically enriched environments. Drawing upon recent advances in genomic methodologies for unraveling pleiotropy, we outline testable predictions for future research on language development and how its underlying neurobiological substrates may be supported by genetic pleiotropy with musicality. In support of the MAPLE framework, we review and discuss findings from over seventy behavioral and neural studies, highlighting that musicality is robustly associated with individual differences in a range of speech-language skills required for communication and development. These include speech perception-in-noise, prosodic perception, morphosyntactic skills, phonological skills, reading skills, and aspects of second/foreign language learning. Overall, the current work provides a clear agenda and framework for studying musicality-language links using individual differences approaches, with an emphasis on leveraging advances in the genomics of complex musicality and language traits.

Utility of Framingham Score for Optimizing Preoperative Evaluation Among Patients Undergoing Liver Transplant Evaluation.

BACKGROUND: Cardiac testing of candidates for liver transplant (LT) requires balancing risks and benefits of cardiac procedures. The goal of this study was to evaluate the utility of the Framingham score (FS) for optimizing preoperative risk stratification for coronary artery disease (CAD). METHODS: In this single-center retrospective study of 615 adults undergoing LT evaluation from 2016 to 2019, data of preoperative evaluation, post-LT 1-year mortality, and post-LT cardiac events were reviewed. Patients >30 years of age with normal echocardiogram underwent FS calculation. Elevated FS (≥35%) patients were triaged to undergo angiogram for CAD evaluation; FS <35% patients underwent stress testing as initial CAD evaluation. RESULTS: Of 615 patients referred for LT, 481 underwent cardiac testing. Ninety-five were excluded from the FS pathway because of age, abnormal baseline echocardiogram, or known CAD. Of the remaining 386 patients in the FS pathway, 342 had a low FS and 44 had a high FS. In patients with low FS, 90% underwent stress testing as initial test; 16% underwent invasive testing at some time. In those with elevated FS, 59% underwent invasive testing as initial test. Listing rate and posttransplant outcomes were similar between patients with low and high FS. CONCLUSION: We demonstrated the feasibility of a simple algorithmic evaluation process using FS for optimizing pre-LT risk stratification for CAD. Although exceptions to the protocol occur, the proposed protocol allows for a streamlined approach by prioritizing testing based on cardiac risk. This approach may maximize diagnostic yield while limiting invasive procedures.

Echocardiographic evaluation of ventricular septal defects.

Ventricular septal defects (VSDs) are the most common forms of acyanotic congenital heart disease accounting for 37% of congenital heart disease in children. A VSD is defined by parts of the ventricular septum involved. There are four major types of VSDs: perimembranous, muscular, outlet, and inlet VSDs. Echocardiography is the most important clinical tool to help diagnose and characterize a VSD. Although most VSDs are clinically nonsignificant or close on their own, echocardiography with Doppler and color flow mapping can be used to provide accurate anatomic and hemodynamic evaluation of VSDs in order to determine if surgical or transcatheter-based intervention is needed. Hence, understanding how to use echocardiography to characterize VSDs is of crucial importance when caring for patients with adult congenital heart disease.

Echocardiographic assessment of atrioventricular canal defects.

AV canal defects (AVCD) are caused by maldevelopment of the endocardial cushions and typically include a primum atrial septal defect (ASD), an inlet ventricular septal defect (VSD), and a common atrioventricular valve. The variations in deformities provide the basis for the many terms used in the anatomical classifications: partial, transitional, intermediate, and complete common AVCD (balanced or unbalanced). The balanced complete common AVCDs are classified as Rastelli A, B, C depending on the anomaly of the anterior bridging leaflet division and attachments. Unbalanced complete AVCDs occur when the common AV valve leads primarily into the RV or LV. Echocardiographic apical, subcostal, and parasternal views are the best views to image AV canal defects. These views can help determine the type of repair required for the various AV canal defects.

Etiology, Pathology, and Classification of Atrial Fibrillation.

Atrial fibrillation (AF) is a disorganized tachyarrhythmia with significant public health importance due to high morbidity, mortality, and health-care costs. Incidence rate of AF is on the rise and there are several modifiable and nonmodifiable risk factors that are responsible. Exact mechanisms and pathogenesis of AF are still poorly understood, yet they still have great implications in management. The aim of this article is to summarize the epidemiology, major risk factors, and their role in the pathogenesis of AF. Finally, we have reviewed the classification of AF as per professional society guidelines.

Is Catheter Ablation Better Than Antiarrhythmic Drugs for the Treatment of Atrial Fibrillation?

Long-standing atrial fibrillation is associated with significant morbidity including stroke and development of heart failure. Patients also report poor quality of life as a result of debilitating symptoms or treatment side effects from antiarrhythmic medications. Radio frequency or cryothermal mediated catheter ablation has a central role in the management of symptomatic patients with paroxysmal or persistent atrial fibrillation. Circumferential pulmonary vein isolation is vital to the success of this therapy and other ancillary techniques have been described, especially for persistent atrial fibrillation. Several randomized controlled studies have been reported over the last two decades studying important clinical outcomes in patients with atrial fibrillation. In this article, we aim to provide a review of the major studies that have helped define the role of catheter ablation in the management of symptomatic atrial fibrillation in patients with both diseased and structurally normal hearts.

Neural mechanisms of response-preparation and inhibition in bilingual and monolingual children: Lateralized Readiness Potentials (LRPs) during a nonverbal Stroop task.

Inhibitory control is a core executive function (EF) skill, thought to involve cognitive 'interference suppression' and motor 'response inhibition' sub-processes. A few studies have shown that early bilingualism shapes interference suppression but not response inhibition skills, however current behavioral measures do not fully allow us to disentangle these subcomponents. Lateralized Readiness Potentials (LRPs) are centroparietal event-related potentials (ERPs) that track motor response-preparations between stimulus-presentation and behavioral responses. We examine LRPs elicited during successful inhibitory control on a nonverbal Stroop task, in 6-8 year-old bilingual (n = 44) and monolingual (n = 48) children from comparable socio-economic backgrounds. Relative to monolinguals, bilinguals showed longer and stronger incorrect-response preparations, and a more mature pattern of correct-response preparation (shorter peak-latencies), underlying correct responses on Stroop-interference trials. Neural markers of response-inhibition were comparable between groups and no behavioral differences were found between-groups on the Stroop task. Results suggest group differences in underlying mechanisms of centroparietal motor-response preparation mechanisms in this age group, contrary to what has been shown using behavioral tasks previously. We discuss neural results in the context of speed-accuracy trade-offs. This is the first study to examine neural markers of motor-responses in bilingual children.

Performance Effects of Reward-Related Feedback on the Dimensional Change Card Sort Task.

The Dimensional Change Card Sort (DCCS) is one of the most widely used measures of preschool executive function, yet relatively little is known about how altering emotional demands of the task affects DCCS performance. This study examined the effects of emotionally evocative reward-related feedback on preschool children's performance on the DCCS in a sample of 105 children aged 3.5-4.5 years. In a within-subjects design, children completed the standard DCCS and a modified version of the DCCS in which sticker rewards were gained or lost after each trial. With a reward at stake, children were more accurate but had slower reaction time on the post-switch DCCS. Another sample (N = 20) of 3.5- to 4.5-year-olds who completed the standard DCCS twice without reward showed no change in performance, indicating results are not due to practice effects. Findings demonstrate preschool children's ability to adjust their approach to the DCCS in the presence of emotionally evocative reward-related feedback by prioritizing accuracy over speed. Trial-by-trial reward-related feedback may facilitate cognitive control in early childhood.