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Background: Large-scale data on incidental premature ventricular contraction (PVC) prevalence and morphologies have been lacking, leaving many providers without guidance on further cardiac testing for patients with incidental PVCs on ECG. Athletes offer an intriguing cohort to understand the clinical significance, prevalence, and common morphologies of incidental PVCs because they often undergo ECG screening during preparticipation exams., Methods: Digital ECGs were obtained from 10 728 screened athletes aged 14 to 35 years during mass screenings in schools and professional sports teams between 2014 and 2021. A retrospective analysis of ECGs with PVCs was performed using the simultaneous display of frontal (limb) and horizontal (precordial) plane leads. PVCs were coded for morphology and categorized as benign or nonbenign using recommended criteria., Results: Twenty-six athletes (0.24%) were found to have at least 1 PVC. Among these, 50% were female, 65% were White, 8% were Asian, 4% were Hispanic, and 23% were Black. Nineteen of the 26 (73%) ECGs had PVCs with a left bundle branch block pattern compared with 7 (27%) with a right bundle branch block pattern. Twenty-four ECGs (96%) had PVCs with benign patterns, including 18 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology., Conclusions: There is a low prevalence of PVCs on routine ECG screening of young athletes, and most PVCs are of benign morphology in this population. This study highlights the value of using digital ECG recorders with simultaneous lead display to guide decision-making about further cardiac testing and referrals in young athletes with PVCs. Using our results and review of the literature, we propose methods and algorithms of PVC evaluation on screening ECGs to help guide many providers with risk stratification and decision-making about further cardiac testing and electrophysiology referrals in young athletes with PVCs., Competing Interests: Dr Perez is a consultant for Apple, Inc, Boston Scientific, Janssen, Bristol Myers Squibb, and Thryv, Inc, and has an ownership interest in QALY, Inc. Dr Wheeler had prior consulting income from BioTelemetry. Dr Hadley is employed by Cardiac Insight. Dr Froelicher was contracted by Cardiac Insight to develop patch interpretation software. The other authors report no conflicts.

Background: Industry sponsorship is an important source of funding for atrial fibrillation (AF) clinical trials, the implications of which have not been analyzed., Objective: The purpose of this study was to determine the characteristics of contemporary AF clinical trials and to evaluate their association with funding source., Methods: We systematically assessed all completed AF trials registered in the ClinicalTrials.gov database between conception to October 31, 2023, and extracted publicly available information including funding source, trial size, demographic distribution, intervention, location, and publication status. Trial characteristics were compared using the Wilcoxon rank-sum test and Fisher exact test for continuous and categorical variables, respectively., Results: Of the 253 clinical trials assessed, 171 (68%) reported industry funding. Industry funding was associated with a greater median number of patients enrolled (172 vs 80; P <.001), publication rate (56.7% vs 42.7%; P = .04), probability of being product-focused (48.0% vs 24.4%; P <.001), and multicontinental recruitment location (25.2% vs 2.4%; P <.001) when compared to nonindustry-funded trials. However, industry funding was not associated with a significant difference in median impact factor (7.7 vs 7.7; P = .723). The overall proportion of industry-funded trials did not change over time (P = 1)., Conclusion: Industry-funded clinical trials in AF often are larger, more frequently published, multicontinental, and product-focused. Industry funding was found to be associated with significant differences in study enrollment and publication metrics., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world use of mavacamten in 50 patients with oHCM at a tertiary care referral center. In both our highlighted case and in our aggregate data, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and New York Heart Association symptom class. Moreover, in our center's experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: we note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Moreover, our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings., Competing Interests: VP has consulting and advisory relationships with BioMarin, Lexeo Therapeutics and Viz.ai and receives funding from BioMarin, the John Taylor Babbitt Foundation. MW reports research grant and in kind support from Bristol Myers Squibb, consulting for Leal Therapeutics, outside the submitted work. EA reports advisory board fees from Apple and Foresite Labs. EA has ownership interest in SVEXA, Nuevocor, DeepCell, and Personalis, outside the submitted work. EA is a board member of AstraZeneca. CW reports consultancy fees from AiRNA Bio and Avidity Biosciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kim, Chu, Keamy-Minor, Paranjpe, Tang, O'Sullivan, Desai, Liu, Munsey, Hecker, Cuenco, Kao, Bacolor, Bonnett, Linder, Lacar, Robles, Lamendola, Smith, Knowles, Perez, Kawana, Sallam, Weldy, Wheeler, Parikh, Salisbury, Ashley and the Stanford Center for Inherited Cardiovascular Disease.)

The severity and invasiveness of clinical outcomes from organic responses to trauma are influenced by individual, surgical, and anesthetic factors. A stress response elicits neuroendocrine and immune reactions that may lead to multi-organ dysfunction. The degree of neuroinflammatory reflex activation from trauma can increase pro-inflammatory cytokine production, leading to endothelial dysfunction, glycocalyx damage, neutrophil activation, and multisystem tissue destruction. A shift in patient treatment towards a neuroinflammatory perspective has prompted a new evaluation protocol for surgical patients, required to understand surgical pathogenesis and its link to chosen anesthetic-surgical methods. The goal of this study is to summarize and disseminate the present knowledge about the mechanisms involved in immune and neuroendocrine responses, focusing on video laparoscopic surgeries. This article outlines various measures cited in the literature aimed at reducing the burden of surgical trauma. It reviews anesthetic drugs, anesthetic techniques, and intensive care procedures that are known to have immunomodulatory effects. The results show a preference for more sensitive inflammatory mediators to tissue trauma serving as care tools, indicators for prognosis, and therapeutic outcomes.

Long QT Syndrome (LQTS) is a genetic heart disorder that can induce cardiac arrhythmias. The most prevalent subtype, LQT1, stems from rare variants in the KCNQ1 gene. Utilizing induced pluripotent stem cells (iPSCs) enables detailed cellular studies and personalized medicine approaches for this life-threatening condition. We generated two LQT1 iPSC lines with single nucleotide nonsense mutations, c.1031 C > T and c.1121 T > A in KCNQ1. Both lines exhibited typical iPSC morphology, expressed high levels of pluripotent markers, maintained normal karyotype, and possessed the capability to differentiate into three germ layers. These cell lines serve as important tools for investigating the biological mechanisms underlying LQT1 due to mutations in the KCNQ1 gene., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph C. Wu reports financial support was provided by National Institutes of Health. Lu Ren reports financial support was provided by American Heart Association. Joseph C. Wu reports a relationship with Greenstone Biosciences Inc that includes co-founder and scientific advisory roles. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring., Objective: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring., Methods: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models., Results: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring., Conclusion: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making., Competing Interests: Disclosures Dr Perez is a consultant for Apple Inc, Boston Scientific, Janssen, Bristol Myers Squibb, and Thryv Inc and has ownership interest in QALY, Inc. Dr Wheeler had prior consulting income from BioTelemetry. Dr Froelicher has stock interest in Cardiac Insight (electrocardiographic patch company employed in this study) and is contracted by Cardiac Insight to develop patch interpretation software. The remaining authors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts to disclose.

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Rhabdomyolysis is a rare but potentially life-threatening complication of acute HIV infection. We present a case report of a young adult male who presented with fever, myalgia, and elevated creatine phosphokinase levels, ultimately diagnosed with acute HIV infection-associated rhabdomyolysis. This case highlights the importance of considering HIV infection in the differential diagnosis of rhabdomyolysis, particularly in at-risk populations, even in the absence of typical HIV-related symptoms., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mekonen et al.)

Infant formulas (IF) can contain harmful chemical substances, such as pesticides and mycotoxins, resulting from the contamination of raw materials and inputs used in the production chain, which can cause adverse effects to infants. Therefore, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) methodology prior ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ-MS/MS) analysis was applied for the determination of 23 contaminants, in 30 samples of Brazilian IF. The method was validated in terms of limit of detection (0.2 to 0.4 μg/kg), limits of quantification (1 and 10 μg/kg), and recovery (64 % to 122 %); precision values, in terms of relative standard deviation (RSD), were ≤ 20 %. Fenitrothion, chlorpyrifos, and bifenthrin were the pesticides detected in the samples, but the values did not exceed the limit set by the European Union (EU), and ANVISA, and they were detected under their limits of quantification. Additionally, suspect screening and unknown analysis were conducted to tentatively identify 32 substances, including some compounds not covered in this study, such as pesticides, hormones, and veterinary drugs. Carbofuran was identified, confirmed and quantified in 10 % of the samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Despite the importance of racial and ethnic representation in clinical trials, limited data exist about the enrollment trends of these groups in atrial fibrillation (AF) trials over time., Objective: The purpose of this study was to examine the characteristics of contemporary AF clinical trials and to evaluate their association with race and ethnicity over time., Methods: We performed a systematic search of all completed AF trials registered in ClinicalTrials.gov from conception to December 31, 2023, and manually extracted composition of race/ethnicity. We stratified trials by study characteristics, including impact factor, publication status, funding source, and location. We calculated the participation to prevalence ratio (PPR) by dividing the percentage of non-White participants by the percentage of non-White participants in the disease population (PPR of 0.8-1.2 suggests proportional representation) over time., Results: We identified 277 completed AF trials encompassing a total of 1,933,441 adults, with a median proportion of non-White at 12% (interquartile range, 6%-27%), 121 (43.7%) device focused, and 184 (66.4%) funded by industry. Only 36.1% of trials reported comprehensive race information. Overall, non-White participants were underrepresented (PPR = 0.511; P < .001), including Black (PPR = 0.263) and Hispanic (PPR = 0.337) participants. The proportion of non-White participants did not change significantly between 2000 and 2023 (11% vs 9%; P = .343)., Conclusion: Despite greater awareness, race/ethnicity reporting and representation of non-White groups in AF clinical trials are poor and have not improved significantly over time. These findings demand additional recruitment efforts and novel recruitment policies to ensure adequate representation of these demographic subgroups in future AF clinical trials., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Deep learning methods have recently gained success in detecting left ventricular systolic dysfunction (LVSD) from electrocardiogram (ECG) waveforms. Despite their high level of accuracy, they are difficult to interpret and deploy broadly in the clinical setting. In this study, we set out to determine whether simpler models based on standard ECG measurements could detect LVSD with similar accuracy to that of deep learning models., Methods and Results: Using an observational data set of 40 994 matched 12-lead ECGs and transthoracic echocardiograms, we trained a range of models with increasing complexity to detect LVSD based on ECG waveforms and derived measurements. The training data were acquired from the Stanford University Medical Center. External validation data were acquired from the Columbia Medical Center and the UK Biobank. The Stanford data set consisted of 40 994 matched ECGs and echocardiograms, of which 9.72% had LVSD. A random forest model using 555 discrete, automated measurements achieved an area under the receiver operator characteristic curve (AUC) of 0.92 (0.91-0.93), similar to a deep learning waveform model with an AUC of 0.94 (0.93-0.94). A logistic regression model based on five measurements achieved high performance [AUC of 0.86 (0.85-0.87)], close to a deep learning model and better than N-terminal prohormone brain natriuretic peptide (NT-proBNP). Finally, we found that simpler models were more portable across sites, with experiments at two independent, external sites., Conclusion: Our study demonstrates the value of simple electrocardiographic models that perform nearly as well as deep learning models, while being much easier to implement and interpret., Competing Interests: Conflict of interest: E.A. reports consulting fees from Apple Inc. M.V.P. reports research funding from NIH/NHLBI and Apple Inc., consulting fees from Apple Inc., Boston Scientific, Biotronik Inc., Bristol Myers Squibb, QALY, Johnson & Johnson, and has an equity interest in QALY., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives  This study evaluated pain intensity in elderly subjects with hip fractures admitted to the emergency sector and undergoing preoperative pericapsular nerve group (PENG) block. Additionally, the degree of tolerable hip flexion was assessed. Methods  A prospective, randomized, and controlled clinical trial with parallel groups. The control group consisted of elderly subjects with hip fractures undergoing standardized intravenous systemic analgesia. The intervention group consisted of elderly patients with hip fractures undergoing PENG block and standardized systemic analgesia. The groups were evaluated at rest and during movement using the Pain Assessment in Advanced Dementia (PAINAD) scale. We determined pain intensity and reduction, in addition to the degree of tolerable flexion of the fractured hip. All patient assessments occurred before the medication or block administration and at 45 minutes, 12, 24, and 36 hours postmedication or block. Results  Preoperatively and 24 hours after PENG block, elderly subjects with hip fracture showed a significant reduction in pain at rest or movement compared to control patients ( p  < 0.05), with 60% of patients assessed at rest demonstrating desirable pain reduction (≥50%) and only 13.3% of the control group achieving the desired pain reduction. During movement, after undergoing PENG block, 40% of subjects demonstrated the desired pain reduction and no patient from the control group. The intervention group also showed a significant improvement in the tolerable hip flexion group ( p  < 0.05). Conclusion  Preoperative PENG block in elderly subjects with hip fractures admitted to the emergency sector provided a significant reduction in pain compared with the control group., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Laparoscopy represented one of the most innovative surgical techniques approached in the surgery field. Dexmedetomidine association with general anesthesia promotes the response control to trauma by altering the neuroinflammatory reflex, provides better clinical outcomes in the postoperative period and reduces the excessive use of drugs with risk for addiction. This trial aims to evaluate the potential drug treatment of dexmedetomidine on organic function, with the targets in neuroinflammation, perioperative pain control and blood pressure measurements in a medium-sized surgical model., Methods: Fifty-two patients were randomized in two groups: Sevoflurane and Dexmedetomidine - A (dexmedetomidine infusion [1 μg/kg loading, .2-.5 μg/kg/h thereafter]) vs Sevoflurane and Saline .9% - B. Three blood samples were collected at three times: before surgery, 4 to 6 hours after surgery and 24 hours postoperatively. The primary outcome was inflammatory and endocrine mediators dosage analisys. Finally, we evaluated pain and opioid use as secondary outcomes, also the hemodynamic values., Results: In Dexmedetomidine group A, a reduction of Interleukin 6 was found during 4-6 hours after surgery. A reduction of IL-10 was noted in the measurement of its values 24 hours after the procedure, with statistical significance. Also, systolic and diastolic blood pressure, as well heart rate were attenuated, and there was a lower incidence of pain and opioid consumption in the first postoperative hour ( P < .0001) in the anesthetic recovery room., Conclusions: Dexmedetomidine provided anti-inflammatory activity, sympatholytic effect and analgesia with cardiovascular safety. It reinforces the therapeutic nature of highly selective α2-adrenergic agonists when combined within anesthetic interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted., Competing Interests: Disclosures Dr Lubitz is a full-time employee of Novartis Institutes of BioMedical Research as of July 18, 2022. Dr Lubitz previously received sponsored research support from Bristol Myers Squibb, Pfizer, Boehringer Ingelheim, Fitbit, Medtronic, Premier, and IBM and has consulted for Bristol Myers Squibb, Pfizer, Blackstone Life Sciences, and Invitae.

Background: Deep learning models may combat widening racial disparities in heart failure outcomes through early identification of individuals at high risk. However, demographic biases in the performance of these models have not been well-studied., Methods: This retrospective analysis used 12-lead ECGs taken between 2008 and 2018 from 326 518 patient encounters referred for standard clinical indications to Stanford Hospital. The primary model was a convolutional neural network model trained to predict incident heart failure within 5 years. Biases were evaluated on the testing set (160 312 ECGs) using the area under the receiver operating characteristic curve, stratified across the protected attributes of race, ethnicity, age, and sex., Results: There were 59 817 cases of incident heart failure observed within 5 years of ECG collection. The performance of the primary model declined with age. There were no significant differences observed between racial groups overall. However, the primary model performed significantly worse in Black patients aged 0 to 40 years compared with all other racial groups in this age group, with differences most pronounced among young Black women. Disparities in model performance did not improve with the integration of race, ethnicity, sex, and age into model architecture, by training separate models for each racial group, or by providing the model with a data set of equal racial representation. Using probability thresholds individualized for race, age, and sex offered substantial improvements in F1 scores., Conclusions: The biases found in this study warrant caution against perpetuating disparities through the development of machine learning tools for the prognosis and management of heart failure. Customizing the application of these models by using probability thresholds individualized by race, ethnicity, age, and sex may offer an avenue to mitigate existing algorithmic disparities., Competing Interests: Disclosures Dr Narayan reports research grants from the National Institutes of Health (R01 HL149134 Machine Learning in Atrial Fibrillation and R01 HL83359 Dynamics of Atrial Fibrillation); consulting compensation from Abbott Inc, Up to Date, and LifeSignals.ai; and intellectual property rights from the University of California Regents and Stanford University. E.A. Ashley reports consulting fees from Apple Inc. Dr Perez reports consulting fees from Apple Inc, Boston Scientific, Biotronik Inc, Bristol Myers Squibb, QALY Inc, and Johnson & Johnson and has an equity interest in QALY Inc.

Aims: Kleefstra syndrome (KS), often diagnosed in early childhood, is a rare genetic disorder due to haploinsufficiency of EHMT1 and is characterized by neuromuscular and intellectual developmental abnormalities. Although congenital heart disease (CHD) is common, the prevalence of arrhythmias and CHD subtypes in KS is unknown., Methods and Results: Inspired by a novel case series of KS patients with atrial tachyarrhythmias in the USA, we evaluate the two largest known KS registries for arrhythmias and CHD: Radboudumc (50 patients) based on health record review at Radboud University Medical Center in the Netherlands and GenIDA (163 patients) based on worldwide surveys of patient families. Three KS patients (aged 17-25 years) presented with atrial tachyarrhythmias without manifest CHD. In the international KS registries, the median [interquartile range (IQR)] age was considerably younger: GenIDA/Radboudumc at 10/13.5 (12/13) years, respectively. Both registries had a 40% prevalence of cardiovascular abnormalities, the majority being CHD, including septal defects, vascular malformations, and valvular disease. Interestingly, 4 (8%) patients in the Radboudumc registry reported arrhythmias without CHD, including one atrial fibrillation (AF), two with supraventricular tachycardias, and one with non-sustained ventricular tachycardia. The GenIDA registry reported one patient with AF and another with chronic ectopic atrial tachycardia (AT). In total, atrial tachyarrhythmias were noted in six young KS patients (6/213 or 3%) with at least four (three AF and one AT) without structural heart disease., Conclusion: In addition to a high prevalence of CHD, evolving data reveal early-onset atrial tachyarrhythmias in young KS patients, including AF, even in the absence of structural heart disease., Competing Interests: Conflict of interest: S.M.N. reports consulting support from Abbott Inc., UpToDate Inc., LifeSignals Inc., and TDK Inc., intellectual property owned by University of California Regents and Stanford University. P.J.W. is a consultant for EpiEndoAF. N.B. reports speaker fees from Abbott and Zoll. M.V.P. has grant funding support from Apple Inc., consulting support from Biotronik and Boston Scientific, and consulting and equity interest in QALY, Inc. All remaining authors have declared no conflicts of interest or disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. β-Adrenergic receptor antagonists (β-blockers) are the first-line therapy for HCM. However, β-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown., Methods: We screened 21 β-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure-volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM ( Myh6 R403Q /+ and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM ( MYH7 R403Q/+ )., Results: We identified that carvedilol, a β-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a β 1 -blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α 1 -adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of β-blocking effect, retains the ability to inhibit both α 1 -receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In Myh6 R403Q/+ mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in MYH7 R403Q/+ iPSC-derived cardiomyocytes., Conclusions: R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α 1 -adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction., Competing Interests: Disclosures K.S., V.N.P., and E.A.A. filed a US patent related to this work (Application No. 63/479,523; filed January 11, 2023). K.S. and S.Y., previously affiliated with Stanford University at the time of the study and manuscript preparation, are now employees of Bristol Myers Squibb. V.N.P. receives research funding from BioMarin, as well as consulting fees from Lexeo Therapeutics, Nuevocor, and Viz.ai and is a shareholder in Constantiam Bio. M.T.W. has consulted for, received clinical trial support from, and received in kind support from MyoKardia (which was acquired by Bristol Myers Squibb), and received clinical trial support from Novartis and CytoKinetics. E.A.A. is a founder of Personalis, Inc, DeepCell, Inc, and Svexa Inc; a founding advisor of Nuevocor; a nonexecutive director at AstraZeneca; and an advisor to SequenceBio, Novartis, Medical Excellence Capital, Foresite Capital, and Third Rock Ventures. The remaining authors declare no competing interests.

Background: The epidermal growth factor receptor (EGFR) pathway is involved in kidney tissue repair and growth. Preclinical interventional data and scarce human data have suggested a role for this pathway in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD), while other data have suggested that its activation is causally linked to repair of damaged kidney tissue. We hypothesize that urinary EGFR ligands, as a reflection of EGFR activity, are associated with kidney function decline in ADPKD in the context of tissue repair following injury, and as the disease progresses as a sign of insufficient repair., Methods: In the present study, we measured the EGFR ligands, EGF and heparin binding-EGF (HB-EGF), in 24-h urine samples of 301 ADPKD patients and 72 age- and sex-matched living kidney donors to dissect the role of the EGFR pathway in ADPKD. During a median follow-up of 2.5 years, the association of urinary EGFR ligand excretion with annual change in estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume in ADPKD patients was analyzed using mixed-models methods, and the expression of three closely related EGFR family receptors in ADPKD kidney tissue was investigated by immunohistochemistry. Additionally, the effect of reducing renal mass (after kidney donation), was assessed to investigate whether urinary EGF matches this reduction and thus reflects the amount of remaining healthy kidney tissue., Results: At baseline, urinary HB-EGF did not differ between ADPKD patients and healthy controls (P = .6), whereas a lower urinary EGF excretion was observed in ADPKD patients [18.6 (11.8-27.8)] compared with healthy controls [51.0 (34.9-65.4) μg/24 h, P < .001]. Urinary EGF was positively associated with baseline eGFR (R = 0.54, P < .001) and a lower EGF was strongly associated with a more rapid GFR decline, even when adjusted for ADPKD severity markers (β = 1.96, P < .001), whereas HB-EGF was not. Expression of the EGFR, but not other EGFR-related receptors, was observed in renal cysts but was absent in non-ADPKD kidney tissue. Finally, unilateral nephrectomy resulted in a decrease of 46.4 (-63.3 to -17.6) % in urinary EGF excretion, alongside a decrease of 35.2 ± 7.2% in eGFR and 36.8 ± 6.9% in measured GFR (mGFR), whereas maximal mGFR (measured after dopamine induced hyperperfusion) decreased by 46.1 ± 7.8% (all P < .001)., Conclusions: Our data suggest that lower urinary EGF excretion may be a valuable novel predictor for kidney function decline in patients with ADPKD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

The electrocardiogram (ECG) is the most frequently performed cardiovascular diagnostic test, but it is unclear how much information resting ECGs contain about long term cardiovascular risk. Here we report that a deep convolutional neural network can accurately predict the long-term risk of cardiovascular mortality and disease based on a resting ECG alone. Using a large dataset of resting 12-lead ECGs collected at Stanford University Medical Center, we developed SEER, the Stanford Estimator of Electrocardiogram Risk. SEER predicts 5-year cardiovascular mortality with an area under the receiver operator characteristic curve (AUC) of 0.83 in a held-out test set at Stanford, and with AUCs of 0.78 and 0.83 respectively when independently evaluated at Cedars-Sinai Medical Center and Columbia University Irving Medical Center. SEER predicts 5-year atherosclerotic disease (ASCVD) with an AUC of 0.67, similar to the Pooled Cohort Equations for ASCVD Risk, while being only modestly correlated. When used in conjunction with the Pooled Cohort Equations, SEER accurately reclassified 16% of patients from low to moderate risk, uncovering a group with an actual average 9.9% 10-year ASCVD risk who would not have otherwise been indicated for statin therapy. SEER can also predict several other cardiovascular conditions such as heart failure and atrial fibrillation. Using only lead I of the ECG it predicts 5-year cardiovascular mortality with an AUC of 0.80. SEER, used alongside the Pooled Cohort Equations and other risk tools, can substantially improve cardiovascular risk stratification and aid in medical decision making., (© 2023. Springer Nature Limited.)

Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks ( P for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. Conclusions Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.

Background: Chronic kidney disease (CKD), especially diabetic CKD, is the condition that most increases the risk of lethal coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the underlying molecular mechanisms are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) regulate coronavirus cell entry and/or replication. We hypothesized that CKD may alter the expression of SCARF genes., Methods: A literature search identified 34 SCARF genes of which we selected 21 involved in interactions between SARS-CoV/SARS-CoV-2 and host cells, and assessed their mRNA expression in target tissues of COVID-19 (kidneys, lungs, aorta and heart) in mice with adenine-induced CKD., Results: Twenty genes were differentially expressed in at least one organ in mice with CKD. For 15 genes, the differential expression would be expected to favor SARS-CoV-2 infection and/or severity. Of these 15 genes, 13 were differentially expressed in the kidney and 8 were validated in human CKD kidney transcriptomics datasets, including those for the most common cause of CKD, diabetic nephropathy. Two genes reported to protect from SARS-CoV-2 were downregulated in at least two non-kidney target organs: Ifitm3 encoding interferon-induced transmembrane protein 3 (IFITM3) in lung and Ly6e encoding lymphocyte antigen 6 family member 6 (LY6E) in aorta., Conclusion: CKD, including diabetic CKD, is associated with the differential expression of multiple SCARF genes in target organs of COVID-19, some of which may sensitize to SARS-CoV-2 infection. This information may facilitate developing therapeutic strategies aimed at decreasing COVID-19 severity in patients with CKD., Competing Interests: A.O. is former Editor-in-Chief of CKJ and has received grants from Sanofi and consultancy or speaker fees or travel support from Advicciene, Astellas, AstraZeneca, Amicus, Amgen, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma, and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes. S.C. has received honoraria for consultancy from Otsuka and travel support from Menarini., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Arrhythmogenic cardiomyopathy (ACM) is a disease characterized by a progressive replacement of myocardium by fibro-adipose material, predisposing to ventricular arrhythmias (VA) and sudden cardiac death (SCD). Its prevalence is estimated at 1:2000 to 1:5000, with a higher incidence in males, and clinical onset is usually between the 2nd and 4th decade of life. The prevalence of ACM in SCD victims is relatively high, making it one of the most common etiologies in young patients with SCD, especially if they are athletes. Cardiac events occur more frequently in individuals with ACM who participate in competitive sports and/or high-intensity training. In effect, exercise activity can worsen RV function in cases of hereditary ACM. Estimating the incidence of SCD caused by ACM in athletes remains challenging, being reported frequency ranging from 3% to 20%. Here, we review the potential implications of exercising on the clinical course of the classical genetic form of ACM, as well as the diagnostic tools, risk stratification, and the different therapeutic tools available for managing ACM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Left ventricular hypertrophy (LVH) detection techniques on by electrocardiogram (ECG) are cumbersome to remember with modest performance. This study validated a rapid technique for LVH detection and measured its performance against other techniques., Methods: This was a retrospective cohort study of patients at Stanford Health Care who received ECGs and resting transthoracic echocardiograms (TTE) from 2006 through 2018. The novel technique, Witteles-Somani (WS), assesses for S- and R-wave overlap on adjacent precordial leads. The WS, Sokolow-Lyon, Cornell, and Peguero-Lo Presti techniques were algorithmically implemented on ECGs. Classification metrics, receiver-operator curves, and Pearson correlations measured performance. Age- and sex-adjusted Cox proportional hazard models evaluated associations between incident cardiovascular outcomes and each technique., Results: A total of 53,333 ECG-TTE pairs from 18,873 patients were identified. Of all ECG-TTE pairs, 21,638 (40.6%) had TTE-diagnosed LVH. The WS technique had a sensitivity of 0.46, specificity of 0.66, and AUROC of 0.56, compared to Sokolow-Lyon (AUROC 0.55), Cornell (AUROC 0.63), and Peguero-Lo Presti (AUROC 0.63). Patients meeting LVH by WS technique had a higher risk of cardiovascular mortality [HR 1.18, 95% CI (1.12, 1.24), P  < 0.001] and a higher risk of developing any cardiovascular disease [HR 1.29, 95% CI (1.22, 1.36), P  < 0.001], myocardial infarction [HR 1.60, 95% CI (1.44, 1.78), P  < 0.005], and heart failure [HR 1.24, 95% CI (1.17, 1.32), P  < 0.001]., Conclusions: The WS criteria is a rapid visual technique for LVH detection with performance like other LVH detection techniques and is associated with incident cardiovascular outcomes., Competing Interests: EA and MP reports consulting fees from Apple Inc., Boston Scientific, Biotronik Inc., Bristol Myers Squibb, ReadMyECG, Johnson & Johnson, and has an equity interest in ReadMyECG. Stanford University has filed a provisional patent on the described work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Somani, Hughes, Ashley, Witteles and Perez.)

Background: Laparoscopy revolutionizing digital and robotic technology for surgical practice. The ability of anesthetic agents and neuronal blockade to modify the response to surgical trauma has been widely studied in the last few years., Objectives: evaluate if Anterior Quadratus Lumborum Block contributes to attenuate surgical repercussions, having as primary parameters analgesia and secondary the pulmonary function and neuroendocrine response to trauma., Methods: prospective, controlled, Double-blind study, in which 51 patients scheduled for eletive laparoscopic cholecystectomy were randomly selected and distributed into 2 groups. Control group received general anesthesia, and the intervention group was submitted to general anesthesia plus Anterior Quadratus Lumborum Block. The parameters evaluated were: postoperative pain, respiratory muscle pressure, and inflammatory response to surgical stress with the plasma dosage of Interleukin 6, C-Reactive protein and cortisol. The following situations were excluded: refusal to participate in the study; body mass index greater than or equal to 40, peripheral neuropathies, coagulopathies or hypersensitivity to drugs used; infection at the puncture site; fever, purities; dementia or other states that would prevent the adequate understanding of the use of the numeric-verbal scale of pain; immunological diseases, diabetes, malignant neoplasia, use of opioids or anti-inflammatory drugs in the preoperative period; antidepressants and anticonvulsants, conversion open surgery, re-exploration and hospital stay., Results: Slowed Interleukin 6 cytokine production and decrease in cortisol release, accompanied by significant attenuation of surgical repercussion on lung function and significant reduction in postoperative pain scores and consumption of pain medication., Conclusion: An important strategy for analgesia in abdominal laparoscopic surgery.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a congenital arrhythmic syndrome caused by the RYR2 gene encoded ryanodine receptor. Mutations on RYR2 are commonly associated with ventricular tachycardia after adrenergic stimulation, leading to lethal arrhythmias and sudden cardiac death. We generated two human induced pluripotent stem cell (iPSC) lines from CPVT affected patients carrying single missense heterozygote RYR2 mutations, c.1082 G > A and c.100 A > C. Pluripotency and differentiation capability into derivatives of three germ layers were evaluated along with karyotype stability in the report. The generated patient-specific iPSC lines provide a reliable tool to investigate the CPVT phenotype and understand underlaying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Digital and robotic technology applications in laparoscopic surgery have revolutionized routine cholecystectomy. Insufflation of the peritoneal space is vital for its safety but comes at the cost of ischemia-reperfusion-induced intraabdominal organ compromise before the return of physiologic functions. Dexmedetomidine in general anesthesia promotes controlling the response to trauma by altering the neuroinflammatory reflex. This strategy may improve clinical outcomes in the postoperative period by reducing postoperative narcotic use and lowering the risk of subsequent addiction. In this study, the authors aimed to evaluate dexmedetomidine's therapeutic and immunomodulatory potential on perioperative organ function., Methods: Fifty-two patients were randomized 1:1: group A-sevoflurane and dexmedetomidine (dexmedetomidine infusion [1 µg/kg loading, 0.2-0.5 µg/kg/h maintenance dose]), and group B-sevoflurane with saline 0.9% infusion as a placebo control. Three blood samples were collected: preoperatively (T0 h), 4-6 h after surgery (T4-6 h), and 24 h postoperatively (T24 h). The primary outcome was the level analysis of inflammatory and endocrine mediators. Secondary outcome measures were the time to return to normal preoperative hemodynamic parameters, spontaneous ventilation, and postoperative narcotic requirements to control surgical pain., Results: A reduction of Interleukin 6 was found at 4-6 h after surgery in group A with a mean of 54.76 (27.15-82.37; CI 95%) vs. 97.43 (53.63-141.22); p = 0.0425) in group B patients. Systolic and diastolic blood pressure and heart rate were lower in group A patients, who also had a statistically significantly lower opioid consumption in the first postoperative hour when compared to group B patients ( p < 0.0001). We noticed a similar return to spontaneous ventilation pattern in both groups., Conclusions: Dexmedetomidine decreased interleukin-6 4-6 h after surgery, likely by providing a sympatholytic effect. It provides good perioperative analgesia without respiratory depression. Implementing dexmedetomidine during laparoscopic cholecystectomy has a good safety profile and may lower healthcare expenditure due to faster postoperative recovery.

Background: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1β, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF., Methods: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease., Results: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1β log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log [pg/mL] increase, P= .24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-α. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF., Conclusions: In this large cohort of postmenopausal women, there was no significant association between IL-1β and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF., Competing Interests: Conflict of interest None reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are many surgical and anesthetic factors that affect pain and the endocrine-metabolic response to trauma. The ability of anesthetic agents and neuronal blockade to modify the response to surgical trauma has been widely studied in the last few years., Objective: To evaluate if the anterior quadratus lumborum block contributes to improved surgical recovery, using as parameters analgesia, pulmonary function and neuroendocrine response to trauma., Methods: We carried out a prospective, randomized, controlled, and blinded study, in which 51 patients scheduled for laparoscopic cholecystectomy. Patients were randomly selected and assigned to 2 groups. The control group received balanced general anesthesia and venous analgesia, and the intervention group was treated under general, venous analgesia and anterior quadratus lumborum block. The parameters evaluated were: demographic data, postoperative pain, respiratory muscle pressure and inflammatory response to surgical stress with the plasma dosage of IL-6 (Interleukin 6), CRP (C-Reactive protein) and cortisol., Results: Anterior quadratus lumborum block induced the slowing of IL-6 cytokine production and a decrease in cortisol release. This effect was accompanied by the significant reduction of postoperative pain scores., Conclusion: Anterior quadratus lumborum block is an important strategy for analgesia in abdominal laparoscopic surgery and contributes to reducing the inflammatory response to surgical trauma with an early return of preoperative baseline physiological functions.

Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH 4 + ) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H + . This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate., Competing Interests: Conflict of interest statement AO has received grants from Sanofi and consultancy or speaker fees or travel support from Advicciene, Astellas, Astrazeneca, Amicus, Amgen, Boehringer-Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Lilly, Menarini, Mundipharma, Kyowa Kirin, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: The repercussions of ischemia-reperfusion and inflammatory response to surgical injury may compromise the return of physiologic processes in video-laparoscopic surgeries. Dexmedetomidine, as an adjuvant drug in general anesthesia, alters the neuroinflammatory reaction, provides better clinical outcomes in the perioperative period, and may reduce the excessive use of chronic medication in patients with a history of addiction. This study evaluated the immunomodulatory potential of dexmedetomidine on perioperative organ function in video-laparoscopic cholecystectomy patients., Methods: There were two groups: Sevoflurane and Dexmedetomidine A (26 patients) vs. Sevoflurane and Saline 0.9% B (26 patients). Three blood samples were collected three times: 1) before surgery, 2) 4-6h after surgery, and 3) 24h postoperatively. Inflammatory and endocrine mediators were protocolized for analysis. Finally, hemodynamic outcomes, quality upon awakening, pain, postoperative nausea and vomiting, and opioid use were compared between groups., Results: We have demonstrated a reduction of Interleukin 6 six hours after surgery in group A: 34.10 (IQR 13.88-56.15) vs. 65.79 (IQR 23.13-104.97; p = 0.0425) in group B. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure was attenuated in group A in their measurement intervals ( p < 0.0001). There was a lower incidence of pain and opioid consumption in the first postoperative hour favoring this group ( p < 0.0001). We noticed better quality upon awakening after the intervention when comparing the values of peripheral oxygen saturation and respiratory rate., Conclusions: Dexmedetomidine provided anti-inflammatory benefits and contributed to postoperative analgesia without the depressive side effects on the respiratory and cardiovascular systems commonly observed with opioids., Trial Registration: Immunomodulatory Effect of Dexmedetomidine as an Adjuvant Drug in Laparoscopic Cholecystectomies, NCT05489900, Registered 5 August 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05489900?term=NCT05489900&draw=2&rank=1.

Background: Asymptomatic atrial fibrillation (AF) is associated with an increased risk of stroke. The yield of serial electrocardiographic (ECG) screening for AF is unknown., Objectives: The aim of this study was to determine the frequency of AF detected by serial, 7-day ECG patch screenings in older women identified as having an elevated risk of AF according to the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology)-AF clinical prediction score., Methods: Postmenopausal women with a 5-year predicted risk of new-onset AF ≥5% according to CHARGE-AF were recruited from the ongoing WHISH (Women's Health Initiative Strong and Healthy) randomized trial of a physical activity intervention. Participants with AF at baseline by self-report or medical records review were excluded. Screening with 7-day ECG patch monitors was performed at baseline, 6 months, and 12 months from study enrollment., Results: On baseline monitoring, 2.5% of the cohort had AF detected, increasing to 3.7% by 6 months and 4.9% cumulatively by 12 months. Yield of patch screening was higher among participants with a higher (≥10%) CHARGE-AF score: 4.2% had AF detected at baseline, 5.9% at 6 months, and 7.2% at 12 months. Most participants with patch-identified AF never had a clinical diagnosis of AF (36 of 46 [78%])., Conclusions: Older women with an elevated CHARGE-AF score had a high prevalence of AF on 7-day ECG patch screening. Serial screening over 12 months substantially increased the detection of AF. These data can be useful in helping identify high-risk participants for enrollment in future studies of the management of asymptomatic AF.(Women's Health Initiative Silent Atrial Fibrillation Recording Study [WHISH STAR]; NCT05366803.)., Competing Interests: Funding Support and Author Disclosures The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services, through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. This ancillary study was funded through 1R01HL136390. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

An app-based clinical trial enrolment process can contribute to duplicated records, carrying data management implications. Our objective was to identify duplicated records in real time in the Apple Heart Study (AHS). We leveraged personal identifiable information (PII) to develop a dissimilarity score (DS) using the Damerau-Levenshtein distance. For computational efficiency, we focused on four types of records at the highest risk of duplication. We used the receiver operating curve (ROC) and resampling methods to derive and validate a decision rule to classify duplicated records. We identified 16,398 (4%) duplicated participants, resulting in 419,297 unique participants out of a total of 438,435 possible. Our decision rule yielded a high positive predictive value (96%) with negligible impact on the trial's original findings. Our findings provide principled solutions for future digital trials. When establishing deduplication procedures for digital trials, we recommend collecting device identifiers in addition to participant identifiers; collecting and ensuring secure access to PII; conducting a pilot study to identify reasons for duplicated records; establishing an initial deduplication algorithm that can be refined; creating a data quality plan that informs refinement; and embedding the initial deduplication algorithm in the enrolment platform to ensure unique enrolment and linkage to previous records., (© 2022 The Authors. Stat published by John Wiley & Sons Ltd.)

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

There is a growing body of literature focusing on the morphology, management, and outcomes of PVCs in athletes. This review summarizes this literature and establishes recommendations on management, treatment, and indications for specialist referral in this patient population. The sports medicine physician's responses and recommendation should be made in conjunction with the athletes wishes. Medications or ablations are not always necessary in all athletes if they are followed with regular evaluations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Valvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR)., Objectives: This study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination., Methods: A total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model., Results: The deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively., Conclusions: Deep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program., Competing Interests: Funding Support and Author Disclosures This study was supported by a National Institutes of Health Institutional Training Grant (2T32HL007854-21) and National Institutes of Health/National Heart, Lung, and Blood Institute Award (R01HL148248) (to Dr Elias and Dr Perotte’s institution). Dr Elias has received research grant support provided to his institution from Pfizer, Eidos Therapeutics, Google, and Edwards LifeSciences; and is an inventor on a pending patent related to the ValveNet algorithm described in this paper. Dr Poterucha owns stock in Abbott Laboratories and Baxter International with research support provided to his institution from the Amyloidosis Foundation, Eidos Therapeutics, Pfizer, Edwards Lifesciences, and the Glorney-Raisbeck Fellowship Award from the New York Academy of Medicine; and is an inventor on a pending patent related to the ValveNet algorithm described in this paper. Dr Hahn has received speaker fees from Abbott Structural, Edwards Lifesciences, and Philips Healthcare; has institutional consulting contracts with Abbott Structural, Boston Scientific, Edwards Lifesciences, and Gore and Associates; has equity with Navigate; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr Tison has received research grants from General Electric, Janssen Pharmaceuticals, and Myokardia; has received personal fees from Myokardia Digital Health as an advisory group member; and has served as an unpaid advisor for Cardiogram. Dr Kodali has served as a consultant for or received honoraria from Admedus, Meril Lifesciences, JenaValve, and Abbott Vascular; has served on the scientific advisory board for and owns equity in Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and has received institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. Dr Khalique has served as a consultant for Boston Scientific, Edwards Lifesciences, and Abbott Structural. Dr Cohen has received research grant support and consulting income from Edwards Lifesciences, Abbott, Boston Scientific, and Medtronic. Dr Einstein has received speaker fees from Ionetix; has received consulting fees from W. L. Gore and Associates; has received authorship fees from Wolters Kluwer Healthcare–UpToDate; and his institution has grants/grants pending from Attralus, Canon Medical Systems, Eidos Therapeutics, GE Healthcare, Pfizer, Roche Medical Systems, W. L. Gore and Associates, and XyloCor Therapeutics. Dr Nazif has served as a consultant for or received honoraria from Edwards Lifesciences, Medtronic, Venus Medtech, and Boston Scientific. Dr Leon has received institutional grants for clinical research from Abbott, Boston Scientific, Edwards, JenaValve, and Medtronic; has received stock options (equity) for advisory board participation in Valve Medical, Picardia, and Venus MedTech; and is an inventor on a pending patent related to the ValveNet algorithm described in this paper. Dr Perotte is Chief Scientific and Innovation Officer at Spiden AG; and is an inventor on a pending patent related to the ValveNet algorithm described in this paper. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, and all-cause mortality. Although exact details regarding the ideal doses of ET, including resistance and, especially, aerobic ET, as well as the potential adverse effects of extreme levels of ET, continue to be investigated, there is no question that most of the world's population have insufficient levels of PA/ET, and many also have lower than ideal levels of CRF. Therefore, assessment and promotion of PA, ET, and efforts to improve levels of CRF should be integrated into all health professionals' practices worldwide. In this state-of-the-art review, we discuss the exercise effects on many areas related to CVD, from basic aspects to clinical practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The WHI (Women's Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women., Competing Interests: Funding Support and Author Disclosures The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D0004, and 75N92021D00005; with additional funding by HL151885 (WHISH Trial), HL130591 (WHISH-2-Prevent Heart Failure), HL136398 (WHISH-STAR), HL150170 (Cross-Cohort Consortium Heart Failure), HL148565 (CHIP), HL133684 (WHISPER), HL105065 and HL153462 (OPACH), and AG050657 (COSMOS-Mind). The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)