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Matthew R Reynolds,1 Jonas Nilsson,2 Örjan Åkerborg,2 Mehul Jhaveri,3 Peter Lindgren2,41Beth Israel Deaconess Medical Center, VA Boston Healthcare System, Boston, MA, USA; 2OptumInsight, Stockholm, Sweden; 3sanofi-aventis Inc, Bridgewater, NJ, USA; 4Institute of Environmental Medicine, Karolinska Institute, Stockholm, SwedenBackground: The first antiarrhythmic drug to demonstrate a reduced rate of cardiovascular hospitalization in atrial fibrillation/flutter (AF/AFL) patients was dronedarone in a placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter (ATHENA trial). The potential cost-effectiveness of dronedarone in this patient population has not been reported in a US context. This study assesses the cost-effectiveness of dronedarone from a US health care payers’ perspective.Methods and results: ATHENA patient data were applied to a patient-level health state transition model. Probabilities of health state transitions were derived from ATHENA and published data. Associated costs used in the model (2010 values) were obtained from published sources when trial data were not available. The base-case model assumed that patients were treated with dronedarone for the duration of ATHENA (mean 21 months) and were followed over a lifetime. Cost-effectiveness, from the payers' perspective, was determined using a Monte Carlo microsimulation (1 million fictitious patients). Dronedarone plus standard care provided 0.13 life years gained (LYG), and 0.11 quality-adjusted life years (QALYs), over standard care alone; cost/QALY was $19,520 and cost/LYG was $16,930. Compared to lower risk patients, patients at higher risk of stroke (Congestive heart failure, history of Hypertension, Age ≥ 75 years, Diabetes mellitus, and past history of Stroke or transient ischemic attack (CHADS2) scores 3–6 versus 0) had a lower cost/QALY ($9580–$16,000 versus $26,450). Cost/QALY was highest in scenarios assuming lifetime dronedarone therapy, no cardiovascular mortality benefit, no cost associated with AF/AFL recurrence on standard care, and when discounting of 5% was compared with 0%.Conclusions: By extrapolating the results of a large, multicenter, randomized clinical trial (ATHENA), this model suggests that dronedarone is a cost-effective treatment option for approved indications (paroxysmal/persistent AF/AFL) in the US.Keywords: cost-effectiveness, dronedarone, ATHENA

Background: In patients with severe aortic stenosis who cannot have surgery, transcatheter aortic valve replacement (TAVR) has been shown to improve survival and quality of life compared with standard therapy, but the costs and cost-effectiveness of this strategy are not yet known.Methods and Results: The PARTNER trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgery to TAVR (n=179) or standard therapy (n=179). Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective. For patients treated with TAVR, mean costs for the initial procedure and hospitalization were $42 806 and $78 542, respectively. Follow-up costs through 12 months were lower with TAVR ($29 289 versus $53 621) because of reduced hospitalization rates, but cumulative 1-year costs remained higher ($106 076 versus $53 621). We projected that over a patient's lifetime, TAVR would increase discounted life expectancy by 1.6 years (1.3 quality-adjusted life-years) at an incremental cost of $79 837. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50 200 per year of life gained or $61 889 per quality-adjusted life-year gained. These results were stable across a broad range of uncertainty and sensitivity analyses.Conclusions: For patients with severe aortic stenosis who are not candidates for surgery, TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. [ABSTRACT FROM AUTHOR]

Background- Transcatheter aortic valve replacement (TAVR) has been shown to improve survival compared with standard therapy in patients with severe aortic stenosis who cannot have surgery. The effects of TAVR on health-related quality of life have not been reported from a controlled study. Methods and Results- The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgical valve replacement to TAVR (n=179) or standard therapy (n=179). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 12-item Short Form-12 General Health Survey (SF-12). The primary end point was the KCCQ overall summary score (range, 0-100; higher=better). At baseline, mean KCCQ summary scores (35±20) and SF-12 physical summary scores (28±7) were markedly depressed. Although the KCCQ summary score improved from baseline in both groups, the extent of improvement was greater after TAVR compared with control at 1 month (mean between-group difference, 13 points; 95% confidence interval, 8-19; P<0.001) with larger benefits at 6 months (mean difference, 21 points; 95% confidence interval, 15-27; P<0.001) and 12 months (mean difference, 26 points; 95% confidence interval, 19-33; P<0.001). At 12 months, TAVR patients also reported higher SF-12 physical and mental health scores with mean differences compared with standard care of 5.7 and 6.4 points, respectively (P<0.001 for both comparisons). Conclusions- Among inoperable patients with severe aortic stenosis, compared with standard care, TAVR resulted in significant improvements in health-related quality of life that were maintained for at least 1 year. Clinical Trials Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. [ABSTRACT FROM AUTHOR]

Procedural Predictors in SMASH-VT. Background: The Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia (SMASH-VT) trial is the largest randomized trial in substrate-based ablation. We performed a retrospective analysis of patients randomized to prophylactic ablation of ventricular tachycardia to determine the predictive value of clinical and procedural variables on outcomes. Methods: In patients treated with catheter ablation, we examined predictors of ICD-therapy free survival using Cox proportional hazards models. Procedural variables tested included the scar location, number of VT morphologies (VTs) induced, tachycardia cycle length, catheter irrigation, catheter approach, procedural duration, and VT inducibility after ablation. Clinical variables including age, index arrhythmia, NYHA class, ejection fraction, prior revascularization, and baseline medication use were also analyzed. Results: Among 64 patients randomized to ablation, 61 received the assigned therapy and complete procedural data were available for 54 patients. Thirteen percent (7 of 54) experienced ICD therapies during 2-year follow-up. Patients with subsequent ICD therapies had significantly more VTs induced during the ablation procedure than those without (3.9 ± 2.1 vs 1.9 ± 1.8, P = 0.05). The hazard ratio for each additional VT induced was 1.51 (95% CI 1.07-2.13, P = 0.02). Two-year Kaplan-Meier event-free survival rates were 96% for 0-1 VTs induced, and 78% for two or more. The use of irrigated catheters was not predictive of ablation success. Conclusion: In this small retrospective analysis, the number of VTs induced during the procedure was predictive of 2-year outcomes. This likely reflects a more complex arrhythmia substrate in patients who fail ablation. (J Cardiovasc Electrophysiol, Vol. pp. 799-803, July 2010) [ABSTRACT FROM AUTHOR]

Background: For patients who have a ventricular tachyarrhythmic event, implantable cardioverter-defibrillators (ICDs) are a mainstay of therapy to prevent sudden death. However, ICD shocks are painful, can result in clinical depression, and do not offer complete protection against death from arrhythmia. We designed this randomized trial to examine whether prophylactic radiofrequency catheter ablation of arrhythmogenic ventricular tissue would reduce the incidence of ICD therapy.Methods: Eligible patients with a history of a myocardial infarction underwent defibrillator implantation for spontaneous ventricular tachycardia or fibrillation. The patients did not receive antiarrhythmic drugs. Patients were randomly assigned to defibrillator implantation alone or defibrillator implantation with adjunctive catheter ablation (64 patients in each group). Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary end point was survival free from any appropriate ICD therapy.Results: The mortality rate 30 days after ablation was zero, and there were no significant changes in ventricular function or functional class during the mean (+/-SD) follow-up period of 22.5+/-5.5 months. Twenty-one patients assigned to defibrillator implantation alone (33%) and eight patients assigned to defibrillator implantation plus ablation (12%) received appropriate ICD therapy (antitachycardia pacing or shocks) (hazard ratio in the ablation group, 0.35; 95% confidence interval, 0.15 to 0.78, P=0.007). Among these patients, 20 in the control group (31%) and 6 in the ablation group (9%) received shocks (P=0.003). Mortality was not increased in the group assigned to ablation as compared with the control group (9% vs. 17%, P=0.29).Conclusions: In this randomized trial, prophylactic substrate-based catheter ablation reduced the incidence of ICD therapy in patients with a history of myocardial infarction who received ICDs for the secondary prevention of sudden death. (Current Controlled Trials number, ISRCTN62488166 [controlled-trials.com].). [ABSTRACT FROM AUTHOR]

Health care resource utilization is high for patients presenting with acute atrial fibrillation (AF). The potential for treatment algorithms to safely reduce resource consumption in this setting has not been prospectively evaluated. We designed and implemented a practice guideline for the management of patients presenting to the emergency department (ED) with the primary diagnosis of AF, with emphasis on appropriate cardioversion, use of oral rate-controlling medications, and expedited referral to an outpatient AF clinic. We prospectively collected clinical and resource utilization data on all such patients for 14 months before and after institution of the guideline. Institution of the guideline was associated with a decreased rate of hospital admission (from 74% to 38%), with no differences in ED return visits or hospital readmission within 30 days. No strokes or deaths were observed. This large decrease in resource utilization during the intervention phase of the study translated to an average decrease in 30-day total direct health care costs of approximately $1,400 US dollars per patient. Our clinical and cost outcomes were minimally affected after statistical adjustment for baseline differences between study groups. We conclude that the implementation of our practice guideline was feasible, safe, and effective. Widespread adoption of such practices may have large financial implications for the health care system. [ABSTRACT FROM AUTHOR]

Background: Long-term outcomes following left atrial appendage occlusion outside clinical trials and small registries are largely unknown. Collecting these data was a condition of US market authorization of the WATCHMAN device. The aim of this analysis was to evaluate the rates of stroke, bleeding, and death among Medicare beneficiaries following left atrial appendage occlusion implantation during initial commercial availability of the WATCHMAN left atrial appendage occlusion device overall and in important subgroups., Methods: All Medicare fee-for-service beneficiaries ≥65 years of age who underwent left atrial appendage occlusion from April 1, 2016, to August 31, 2020, were included based on the International Classification of Diseases, Tenth Revision , and Current Procedural Terminology codes. Over a 5-year follow-up period, the cumulative incidence over time of mortality, ischemic stroke, and major bleeding were calculated using the International Classification of Diseases, Tenth Revision , diagnosis codes for the full study cohort and within important prespecified subgroups., Results: WATCHMAN recipients (n=48 763) were a median of 77 (interquartile range, 72-82) years of age, 42% female, and mostly White (93%). The median CHA 2 DS 2 VASc score was 4 (interquartile range, 3-5) with prior major bleeding in 42% and prior stroke in 12%. At 5 years, death occurred in 44%, bleeding in 15% (with higher risk early following implantation), and ischemic stroke in 7%. Each of these end points was more common with greater baseline age. Male patients had greater 5-year mortality than female patients (46.9% versus 40.6%), but there was no difference between sexes in the rates of ischemic stroke (6.6% versus 7.5%) or major bleeding (14.9% for both). WATCHMAN recipients with prior ischemic stroke or a major bleeding event were older and frailer; these groups had higher rates of ischemic stroke, major bleeding, and death., Conclusions: Compared with patients enrolled in the pivotal clinical trials, Medicare beneficiaries undergoing WATCHMAN implantation were older, more female, and had more comorbid conditions. Substantial long-term mortality and major bleeding following WATCHMAN reflect the high-risk nature of the patient population, while the ischemic stroke rate was relatively low (<1.5% per year)., Competing Interests: Dr Zeitler reports consulting and speaking fees for Abbott, Biosense Webster, Medtronic, and Sanofi; travel support from Abbott, Biosense Webster, and Medtronic; and research support from Biosense Webster, Sanofi, and the National Institutes of Health. B. Bian, B.G., Dr Allocco, Dr Christen, and Dr Roy were full-time employees of Boston Scientific Corporation at the time of this work. Dr Cohen reports research grant support (to institution) from Boston Scientific, Abbott, Edwards Lifesciences, Philips, CathWorks, I-Rhythm, and Zoll Medical and consulting income from Boston Scientific, Abbott, Edwards Lifesciences, Medtronic, Elixir Medical, and HeartBeam. The other authors report no conflicts.

Background: Percutaneous left atrial appendage closure (LAAC) is an effective alternative strategy for stroke prevention in patients with atrial fibrillation (AF) at high risk for bleeding with anticoagulation (AC). Efficacy of this strategy in hypertrophic cardiomyopathy (HCM) remains uncertain., Objective: The study aimed to compare risk of stroke in HCM-AF patients treated with LAAC with those treated with AC., Methods: By use of the TriNetX Global Research Network, HCM-AF patients from 2015 to 2024 were assigned to categories of treatment with LAAC and treatment solely with AC and observed for 3 years for ischemic stroke, systemic embolism, and all-cause mortality. Propensity score matching was used to limit confounders., Results: Of 14,867 HCM-AF patients identified, 364 (2.5%) were treated with LAAC vs 14,503 (97.5%) treated with AC. HCM LAAC patients were older (72 vs 67 years; P < .001) and had more comorbidities and more prior bleeding events, including higher rate of prior gastrointestinal bleeding (68% vs 18%; P < .001), compared with HCM patients treated solely with AC. After propensity score matching, there was no baseline difference between groups including prior bleeding events (P > .05). During follow-up, HCM patients treated with LAAC had higher rates of ischemic stroke (13% vs 8%; hazard ratio, 1.9; P = .006) and systemic embolism (14% vs 9%; hazard ratio, 1.8; P = .006) but no difference in mortality compared with matched HCM patients receiving AC., Conclusion: These real-world data do not support percutaneous LAAC in HCM-AF patients as the primary treatment strategy during long-term AC to reduce stroke risk. However, LAAC may remain a reasonable option for HCM-AF patients who are unable to tolerate AC because of prohibitive bleeding risk., Competing Interests: Disclosures Martin S. Maron: consultant for Cytokinetics, iRhythm (with grant), Imbria Pharmaceuticals, Takeda Pharmaceuticals (with grant). Ethan J. Rowin: research funding from Pfizer, iRhythm. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary vein isolation (PVI) is increasingly recommended as first-line therapy for atrial fibrillation. Recent data suggest growing PVI volumes but rising complication rates, although comprehensive real-world outcomes including both inpatient and outpatient encounters remain unclear., Objectives: The purpose of this study was to evaluate patient characteristics, population rates, and 30-day outcomes of PVI in a nationwide sample of U.S. adults aged >65 years., Methods: First-time PVIs were identified among U.S. Medicare fee-for-service beneficiaries using Current Procedural Terminology procedural codes. Comorbidities were ascertained using International Classification of Diseases-10th Revision diagnosis codes associated with each procedural claim. Outcomes included periprocedural complications, all-cause hospitalizations, and mortality at 30 days., Results: From January 2017 through December 2021, a total of 227,133 patients underwent PVI (mean age 72.5 years, 42% women, 92.7% White) with an increasing comorbidity burden over time. PVI volume increased from 83.8 (2017) to 111.6 per 100,000 patient-years (2021), which was driven by outpatient procedures (87.8% of all PVIs). Concurrently, there was a significant decrease in complication rates (3.9% in 2017 vs 3.1% in 2021; P < 0.001) and hospitalizations (8.8% vs 7.0%; P < 0.001), with no significant change in mortality (0.4%; P = 0.08). The most common periprocedural complications were bleeding (1.8%), pericardial effusion (1.4%), and vascular access damage (0.8%)., Conclusions: The use of PVI has steadily increased among older patients in contemporary U.S. clinical practice; yet, cumulative complication and hospitalization rates at 30 days have decreased over time, with stably low rates of short-term mortality despite rising comorbidity burden among treated patients. These data may reassure patients and providers on the safety of PVI as an increasingly common first-line procedure for atrial fibrillation., Competing Interests: Funding Support and Author Disclosures Dr Cohen has received institutional research grant support from Abbott, Boston Scientific, and I-Rhythm; and has received consulting income from Abbott and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Developmental Neuropsychological Assessment - II (NEPSY-II) is a widely used assessment battery in pediatric settings, but its internal structure has not been adequately examined. This study employed a rational, empirical approach to examine the construct validity of 23 NEPSY-II subtest scores from children ages 7-12 ( M  = 9.99, SD  = 2.76) in the NEPSY-II norming sample ( N  = 600; 50% girls). Competing higher-order models based on prior research, hypothesized NEPSY-II domains, and conceptual subtest classifications were evaluated via confirmatory factor analysis and a sequential approach to model comparisons. The results supported the multidimensionality of NEPSY-II subtests and the organization of subtests by hypothesized neuropsychological domains. The best fitting model included a general factor and four first-order factors. Factor loadings from the general factor to first-order factors were very strong. However, general factor loadings for most subtests were less than .50 (range = .21-.69, M  = .44), and domain-specific effects for all subtests, independent of the general factor, were even lower (range = .00-.45, M  = .44). Interestingly, all subtests demonstrated strong subtest-specific effects, but it is not clear what construct(s) the subtest-specific effects represent. Findings support NEPSY-II authors' emphasis on subtest-level interpretations rather than composite-level interpretations and highlight that NEPSY-II subtest scores should be interpreted carefully and with caution.

Introduction: There are limited and conflicting data regarding the impact of hepatitis C in pregnancy on adverse birth outcomes., Methods: Using the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET), a large surveillance cohort, we describe birth outcomes among a cohort of people with HCV in pregnancy in total and by reported substance use., Results: Among 1418 infants, 89% were born to people with reported substance use during pregnancy. The proportion born preterm was 20%, 13% were small-for-gestational age and 34% of term infants required intensive care., Conclusions: Assessments of recent changes to recommendations for HCV screening in pregnancy should evaluate the impact on maternal access to care for both HCV treatment as well as comorbidities such as substance use disorder which may contribute to adverse birth outcomes., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) has historically been regarded to have a deleterious impact on clinical course, strongly associated with progressive heart failure (HF) symptoms. However, there is a paucity of information regarding the impact of AF on HCM employing validated quality of life (QoL) surveys. Therefore, we evaluated the impact of AF on QoL utilizing patient reported outcome measures (PROMs)., Methods: 218 consecutive HCM patients with or without AF at the Lahey HCM center in 2022 completed PROMs at their most recent visit evaluating HF (Kansas City Cardiomyopathy Questionnaire [KCCQ]) and AF symptoms (AF Effect on QoL [AFEQT])., Results: Among the 218 patients, 50 (23%) had a history of AF and comprise the primary study cohort. AF was diagnosed at 55 ± 10 years of age, median of 5.5 years before PROM, with 66% of patients treated with a rhythm control strategy with antiarrhythmic drug and/or AF ablation. AFEQT indicated that 52% of patients experienced no or minimal AF-related disability, mild to moderate in 22%, and severe in 26%. There was no substantial difference in HCM phenotype in patients with no or minimal AF disability compared to those with severe disability. HF symptoms for most HCM patients with prior AF history was consistent with no or minimal (59%) or only mild (27%) disability as measured by KCCQ overall summary scores. In addition, with multivariate analysis, AF history was associated with less HF symptoms and improved QoL (OR 0.4, p = 0.02)., Conclusion: In contrast to prior perceptions, HCM patients with prior AF history were less likely to incur HF symptoms impairing QoL compared to HCM patients without AF. After treatment, prior history of AF did not substantially impact current QoL. These data provide a realistic appraisal for the impact that AF has on HCM patients and also offers a measure of reassurance for this patient subgroup., (© 2024 Wiley Periodicals LLC.)

Background: Objective data comparing the diagnostic performance of different ambulatory cardiac monitors (ACMs) are lacking., Objectives: To assess variation in monitoring strategy, clinical outcomes and healthcare utilization in patients undergoing ambulatory monitoring without a pre-existing arrhythmia diagnosis., Methods: Using the full sample (100%) of Medicare claims data, we performed a retrospective cohort study of diagnostic-naïve patients who received first-time ACM in 2017 to 2018 and evaluated arrhythmia encounter diagnosis at 3-months, repeat ACM testing at 6 months, all-cause 90-day emergency department (ED) and inpatient utilization, and cost of different strategies: Holter; long-term continuous monitor (LTCM); non-continuous, event-based external ambulatory event monitor (AEM); and mobile cardiac telemetry (MCT). We secondarily performed a device-specific analysis by manufacturer, identified from unique claim modifier codes., Results: ACMs were used in 287,789 patients (AEM = 10.3%; Holter = 53.8%; LTCM = 13.3%; MCT = 22.5%). Device-specific analysis showed that compared to Holter, AEM, MCT, or other LTCM manufacturers, a specific LTCM (Zio Ⓡ XT 14-day patch, iRhythm Technologies, San Francisco, CA) had the highest adjusted odds of diagnosis and lowest adjusted odds of ACM retesting. Findings were consistent for specific arrhythmia diagnoses of ventricular tachycardia, atrioventricular block, and paroxysmal atrial fibrillation. As a category, LTCM was associated with the lowest 1-year incremental health care expenditures (mean Δ$10,159), followed by Holter ($10,755), AEM ($11,462), and MCT ($12,532)., Conclusions: There was large variation in diagnostic monitoring strategy. A specific LTCM was associated with the highest adjusted odds of a new arrhythmia diagnosis and lowest adjusted odds of repeat ACM testing. LTCM as a category had the lowest incremental acute care utilization. Different monitoring strategies may produce different results with respect to diagnosis and care., Competing Interests: Disclosures Dr. Reynolds is a consultant for Medtronic, Philips, Edwards Lifesciences, and iRhythm and serves on a data safety and monitoring board for Affera. Dr Passman receives research support from the American Heart Association (#18SFRN34250013), research support and speaker fees from Medtronic, research support from Abbott, royalties from UpToDate, and is a consultant for iRhythm. Dr. Swindle and Dr. Mohammadi have no conflict of interest to disclose. Brent Wright is an employee of iRhythm Technologies. Dr. Boyle is an employee of iRhythm Technologies. Dr. Turakhia is an employee of iRhythm Technologies. Outside of the submitted work, Dr. Turakhia reports research grants from Bristol Myers Squibb, American Heart Association, Bayer, Gilead Sciences, and the Food and Drug Administration, consulting fees from Medtronic, Pfizer, Johnson & Johnson, Alivecor, and equity from iRhythm, Connect America, Forward, and Evidently. Dr. Mittal is a consultant for Boston Scientific and iRhythm Technologies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Characterizing antigen-specific B cells is a critical component of vaccine and infectious disease studies in rhesus macaques (RMs). However, it is challenging to capture immunoglobulin variable (IgV) genes from individual RM B cells using 5' multiplex (MTPX) primers in nested PCR reactions. In particular, the diversity within RM IgV gene leader sequences necessitates large 5' MTPX primer sets to amplify IgV genes, decreasing PCR efficiency. To address this problem, we developed a switching mechanism at the 5' ends of the RNA transcript (SMART)-based method for amplifying IgV genes from single RM B cells to capture Ig heavy and light chain pairs. We demonstrate this technique by isolating simian immunodeficiency virus (SIV) envelope-specific antibodies from single-sorted RM memory B cells. This approach has several advantages over existing methods for cloning antibodies from RMs. First, optimized PCR conditions and SMART 5' and 3' rapid amplification of cDNA ends (RACE) reactions generate full-length cDNAs from individual B cells. Second, it appends synthetic primer binding sites to the 5' and 3' ends of cDNA during synthesis, allowing for PCR amplification of low-abundance antibody templates. Third, the nested PCR primer mixes are simplified by employing universal 5' primers, eliminating the need for complex 5' MTPX primer sets. We anticipate this method will enhance the isolation of antibodies from individual RM B cells, supporting the genetic and functional characterization of antigen-specific B cells., (Copyright © 2023. Published by Elsevier B.V.)

This study evaluated the effect of feeding ergot contaminated grain continuously or intermittently through backgrounding (BG) and finishing (FN) in a mash or pelleted supplement on the growth performance, health and welfare parameters, and carcass characteristics of feedlot beef steers. Sixty black Angus steers (300 ± 29.4 kg BW) were used in a complete randomized 238-d study. Steers were stratified by weight and randomly assigned to four different diets (15 steers/treatment) and individually housed. Treatments included: (1) control [CON; no added ergot alkaloids (EA)], (2) continuous ergot mash (CEM; fed continuously at 2 mg total EA/kg of DM), (3) intermittent ergot mash (IEM; fed at 2 mg total EA/kg of DM, during the first week of each 21-d period and CON for the remaining 2 wk, this feeding pattern was repeated in each period), and (4) intermittent ergot pellet (IEP; fed at 2 mg of total EA/kg of DM as a pellet during the first week of each 21-d period and CON for the remaining 2 wk as described for IEM). Steers were fed barley based BG diets containing 40% concentrate:60% silage (DM basis) for 84 d (four 21-d periods), transitioned over 28 d (no ergot fed) to an FN diet (90% concentrate:10% silage DM basis) and fed for 126 d (six 21-d periods) before slaughter. In the BG phase, steer DMI (P < 0.01, 7.45 vs. 8.05 kg/d) and ADG (P < 0.01) were reduced for all EA diets compared to CON. The CEM fed steers had lower ADG (P < 0.01, 0.735 vs. 0.980 kg) and shrunk final BW (P < 0.01, 350 vs. 366 kg) than CON. CEM had lower gain:feed (P < 0.07, 0.130 vs. 0.142) than CON. In the FN phase, steer DMI (P < 0.01, 9.95 vs. 11.05 kg/d) and ADG (P = 0.04) were also decreased for all EA fed steers compared to CON. Total shrunk BW gain (P = 0.03, 202.5 vs. 225.2 kg), final BW (P = 0.03, 617.9 vs. 662.2 kg), and carcass weight (P = 0.06) decreased for all EA fed steers compared to CON. The percentage of AAA carcasses decreased for all EA fed steers (P < 0.01, 46.7 vs. 93.3%) compared to CON. EA fed steers had increased rectal temperatures (P < 0.01, 39.8 vs. 39.4 °C) compared to CON. Pelleting ergot contaminated grain did not reduce the impact of ergot alkaloids on any of the measured parameters during BG or FN. Continuously or intermittently feeding ergot contaminated diets (2 mg total EA/kg of DM) significantly reduced intake, growth performance, and carcass weight, with minimal impact on blood parameters in feedlot steers. Pelleting was not an effective method of reducing ergot toxicity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Background: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure., Methods: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively., Results: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay., Conclusion: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families., Impact: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The mSToPS study (mHealth Screening to Prevent Strokes) reported screening older Americans at risk for atrial fibrillation (AF) and stroke using 2-week patch monitors was associated with increased rates of AF diagnosis and anticoagulant prescription within 1 year and improved clinical outcomes at 3 years relative to matched controls. Cost-effectiveness of this AF screening approach has not been explored., Methods: We conducted a US-based health economic analysis of AF screening using patient-level data from mSToPS. Clinical outcomes, resource use, and costs were obtained through 3 years using claims data. Individual costs, survival, and quality-adjusted life years (QALYs) were projected over a lifetime horizon using regression modeling, US life tables, and external data where needed. Adjustment between groups was performed using propensity score bin bootstrapping., Results: Screening participants (mean age, 74 years, 41% female, median CHA 2 DS 2 -VASC score 3) wore on average 1.7 two-week monitors at a mean cost of $614/person. Over 3 years, outpatient visits were more frequent for monitored than unmonitored individuals (difference 190 per 100 patient-years [95% CI, 82-298]), but emergency department visits (-8.3 [95% CI, -12.6 to -4.1]) and hospitalizations (-15.2 [CI, -22 to -8.6]) were less frequent. Total adjusted 3-year costs were slightly higher (mean difference, $1551 [95% CI, -$1047 to $4038]) in the monitoring group. In patient-level projections, the monitoring group had slightly greater quality-adjusted survival (8.81 versus 8.71 QALYs, difference, 0.09 [95% CI, -0.05 to 0.24]) and slightly higher lifetime costs, resulting in an incremental cost-effectiveness ratio of $36 100/QALY gained. With bootstrap resampling, the incremental cost-effectiveness ratio for monitoring was <$50 000/QALY in 64% of study replicates, and <$150 000/QALY in 91%., Conclusions: Using lifetime projections derived from the mSToPS study, we found that AF screening using 2-week patch monitors in older Americans was associated with high economic value. Confirmation of these uncertain findings in a randomized trial is warranted., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02506244., Competing Interests: Disclosures Dr Reynolds is a consultant to iRhythm, Medtronic, Edwards Lifesciences, and Sanofi; Data and Safety Monitoring Board (DSMB) member (Affera). Drs Stein and Sun are employees of CVS Health. Dr Hytopoulos is an employee of iRhythm. Dr Cohen reports research grant support from iRhythm, Medtronic, and Boston Scientific; consulting income from Medtronic and Boston Scientific. Dr Steinhubl is an employee of physIQ and reports research funding from Janssen.

Background: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) on recurrent atrial fibrillation (AF) among patients undergoing catheter ablation is not well described., Objectives: This study sought to assess the impact of SGLT2-Is on the recurrence of AF among patients with type 2 diabetes mellitus (DM) after catheter ablation., Methods: Using the TriNetX research network, we identified, by means of Current Procedural Terminology codes, patients ≥18 years of age with type 2 diabetes mellitus (DM) who had undergone AF ablation from April 1, 2014, to November 30, 2021. Patients were stratified based on the baseline SGLT2-I use. Propensity-score matching resulted in 2,225 patients in each cohort. The primary outcome was a composite of cardioversion, new antiarrhythmic drug (AAD) therapy, or re-do AF ablation after a blanking period after the index ablation. Additional outcomes included heart failure exacerbations, ischemic stroke, all-cause hospitalization, and death during 12 months of follow-up., Results: SGLT2-I use in patients with type 2 DM undergoing AF ablation was associated with a significantly lower risk of cardioversion, new AAD therapy, and re-do AF ablation (adjusted OR: 0.68; 95% CI: 0.602-0.776; P < 0.0001). At 12 months, patients on SGLT2-Is had a higher probability of event-free survival (HR: 0.85, 95% CI: 0.77-0.95; log-rank test chi-square = 8.7; P = 0.003). All secondary outcomes were lower in the SGLT2I group; however, the ischemic stroke did not differ between groups., Conclusions: Use of SGLT2-Is in patients with type 2 DM is associated with a lower risk of arrhythmia recurrence after AF ablation and thence a reduced need for cardioversion, AAD therapy, or re-do AF ablation., Competing Interests: Funding Support and Author Disclosures Dr Januzzi is a trustee of the American College of Cardiology and a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer-Ingelheim, Jana Care, Janssen, Novartis, Prevencio, Roche Diagnostics; and participates in clinical endpoint committees an data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Sustainable HIV remission after antiretroviral therapy (ART) withdrawal, or post-treatment control (PTC), remains a top priority for HIV treatment. We observed surprising PTC in an MHC-haplomatched cohort of MHC-M3+ SIVmac239+ Mauritian cynomolgus macaques (MCMs) initiated on ART at two weeks post-infection (wpi). None of the MCMs possessed MHC haplotypes previously associated with SIV control. For six months after ART withdrawal, we observed undetectable or transient viremia in seven of the eight MCMs, despite detecting replication competent SIV using quantitative viral outgrowth assays. In vivo depletion of CD8α+ cells induced rebound in all animals, indicating the observed PTC was mediated, at least in part, by CD8α+ cells. With intact proviral DNA assays, we found that MCMs had significantly smaller viral reservoirs two wpi than a cohort of identically infected rhesus macaques, a population that rarely develops PTC. We found a similarly small viral reservoir among six additional SIV+ MCMs in which ART was initiated at eight wpi, some of whom exhibited viral rebound. These results suggest that an unusually small viral reservoir is a hallmark among SIV+ MCMs. By evaluating immunological differences between MCMs that did and did not rebound, we identified that PTC was associated with a reduced frequency of CD4+ and CD8+ lymphocyte subsets expressing exhaustion markers. Together, these results suggest a combination of small reservoirs and immune-mediated virus suppression contribute to PTC in MCMs. Further, defining the immunologic mechanisms that engender PTC in this model may identify therapeutic targets for inducing durable HIV remission in humans., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Harwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Three recent randomized controlled trials have demonstrated that, as an initial rhythm control strategy, first-line cryoballoon ablation (cryoablation) reduces atrial arrhythmia recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF)., Objective: The study sought to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF from a U.S. Medicare payer perspective., Methods: Individual patient-level data from 703 participants with PAF enrolled into the Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518), and EARLY-AF (NCT02825979) trials were used to derive parameters for the cost-effectiveness model. The cost-effectiveness model used a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model. The Markov model used a 40-year time horizon (3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year., Results: Cryoablation was estimated to yield higher QALYs (+0.17) and higher costs (+$4274) per patient over a 40-year time horizon than AADs. Ultimately, this produced an average incremental cost-effectiveness ratio of $24,637 per QALY gained. Independent of initial treatment, individuals were expected to receive ∼1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in atrial fibrillation health states for those initially treated with cryoablation compared with AADs., Conclusion: Initial rhythm control with first-line cryoballoon ablation is highly cost-effective compared with first-line AADs from a U.S. Medicare payer perspective., (© 2023 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Implantable cardioverter-defibrillators (ICDs) represent transformational technology, arguably the most significant advance in cardiovascular medicine in 50 years. The vision and determination of pioneers Mirowski and Mower was fundamental to this monumental achievement, working with limited resources and confronted by skepticism/criticism from medical establishment. The inventors were followed >35 years in which a multitude of innovative clinical scientists and engineers introduced technological advances leading to the sophisticated devices in practice today. A pivotal patient experiment with automated termination of ventricular fibrillation (1980) led to U.S. Food and Drug Administration approval. Transvenous lead systems converted ICDs from thoracotomy-based secondary prevention to primary prevention of sudden death devices in countless patients worldwide. ICD acceptance was solidified by prospective randomized controlled trials showing reduced mortality superior to antiarrhythmic drugs. ICDs eventually expanded from coronary disease to inherited arrhythmia conditions (eg, hypertrophic cardiomyopathy). The ICD breakthrough story demonstrates how significant progress is possible in medicine against all odds, given fearless imagination to pursue novel ideas that conflict with accepted wisdom., Competing Interests: Funding Support and Author Disclosures Dr Estes has served as a consultant for Medtronic and Boston Scientific. Dr Rowin has received research funding from Pfizer and iRhythm. Dr M.S. Maron has served as a consultant for Cytokinetics, Imbria Pharmaceuticals, and TAKEDA Pharmaceuticals (with grant). Dr Reynolds has served as a consultant for Medtronic, iRhythm, and Edwards Lifesciences. Dr B.J. Maron has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Importance: The underuse of oral anticoagulation in patients with nonvalvular atrial fibrillation (AF) is a major issue that is not well understood., Objective: To understand the lack of anticoagulation by assessing the perceptions of patients with AF who are not receiving anticoagulation and their physician's about the risk of stroke and the benefits and risks of anticoagulation., Design, Setting, and Participants: This cohort study included patients with nonvalvular AF and a CHA2DS2-VASc score of 2 or more (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) who were not receiving anticoagulation and were enrolled from 19 sites within the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence Registry (PINNACLE Registry) between January 18, 2017, and May 7, 2018. Data were collected from January 18, 2017, to September 30, 2019, and analyzed from April 2022 to March 2023., Exposure: Each patient enrolled in the study completed a survey, and their treating physician then conducted a clinical review of their care., Main Outcomes and Measures: Assessment of willingness for anticoagulation treatment and its appropriateness after central review by a panel of 4 cardiologists. Use of anticoagulation at 1 year follow-up was compared vs similar patients at other centers in the PINNACLE Registry., Results: Of the 817 patients enrolled, the median (IQR) age was 76.0 (69.0-83.0) years, 369 (45.2%) were women, and the median (IQR) CHA2DS2-VASc score was 4.0 (3.0-6.0). The top 5 reasons physicians cited for no anticoagulation were low AF burden or successful rhythm control (278 [34.0%]), patient refusal (272 [33.3%]), perceived low risk of stroke (206 [25.2%]), fall risk (175 [21.4%]), and high bleeding risk (167 [20.4%]). After rereview, 221 physicians (27.1%) would reconsider prescribing oral anticoagulation as compared with 311 patients (38.1%), including 67 (24.6%) whose physician cited patient refusal. Of 647 patients (79.2%) adjudicated as appropriate or may be appropriate for anticoagulation, physicians would reconsider anticoagulation for only 177 patients (21.2%), while 527 patients (64.5%) would either agree to starting anticoagulation (311 [38.1%]) or were neutral (216 [27.3%]) to starting anticoagulation. Upon follow-up, 119 patients (14.6%) in the BOAT-AF study were prescribed anticoagulation, as compared with 55 879 of 387 975 similar patients (14.4%) at other centers in the PINNACLE Registry., Conclusions and Relevance: The findings of this cohort study suggest that patients with AF who are not receiving anticoagulation are more willing to consider anticoagulation than their physicians. These data emphasize the need to revisit any prior decision against anticoagulation in a shared decision-making manner.