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Competing Interests: None.

Background: The sympathetic autonomic nervous system plays a major role in arrhythmia development and maintenance. Historical preclinical studies describe preferential increases in cardiac sympathetic tone upon selective stimulation of the subclavian ansae (SA), a nerve cord encircling the subclavian artery., Objectives: This study sought to define, for the first time, the functional anatomy and physiology of the SA in humans using a percutaneous approach., Methods: The authors prospectively recruited patients undergoing catheter ablation for paroxysmal atrial fibrillation (AF) under general anesthesia. SA stimulation (SAS) was performed on the left and/or the right (L/SAS and/or R/SAS, respectively) within the subclavian artery using an ablation catheter introduced via a femoral arterial sheath. Stimulation involved up to 70 V, 10 Hz, and a 2- to 4-millisecond pulse width for 15 to 30 seconds. Invasive blood pressure (BP), heart rate, and electrophysiological parameters were recorded. A positive response was a ≥10% increase in BP or heart rate from baseline., Results: Seventeen patients (median age 60 years [quartile 1-quartile 3: 58-67 years];11 male subjects; paroxysmal AF duration 24 months [quartile 1-quartile 3: 10-60 months) underwent the stimulation protocol before their clinical AF ablation procedure. A positive hemodynamic response was observed in 11 patients; of these, arrhythmia was inducible in 5 patients. The median sinus cycle length decreased after stimulation, and there was a larger decrease with R/SAS (L/SAS 1,008 milliseconds to 926 milliseconds [P = 0.037] vs R/SAS 1,029.5 milliseconds to 917 milliseconds [P = 0.005]). Both L/SAS and R/SAS led to a notable increase in median systolic BP (L/SAS 81 mm Hg to 128 mm Hg [P = 0.005] vs R/SAS 85 mm Hg to 104 mm Hg [P = 0.007]) and a similar trend in diastolic BP. In addition, there was a demonstrable decrease in interatrial conduction time and increase in P-wave dispersion., Conclusions: This study represents the first successful application of selective SAS in humans. The SA is a potentially important site for targeted autonomic neuromodulation therapy., Competing Interests: Funding Support and Author Disclosures This study was supported by an educational grant from Abbott. Dr Finlay has received research support from Abbott Cardiovascular; is Chief Medical Officer, founder, and shareholder of Echopoint Medical Ltd; and is founder of Rhythm AI. Dr Sridhar is a shareholder and director of ABVF. Dr Schilling has received speaker and travel grants from Biosense Webster; has received research grants from Biosense Webster; and is founder of Rhythm AI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older., Methods: In two randomised, active-controlled, double-blind, phase 3 trials, individuals aged 12 years and older with stable cystic fibrosis with F508del-minimal function (SKYLINE Trial VX20-121-102) or with F508del-F508del, F508del-residual function, F508del-gating, or elexacaftor-tezacaftor-ivacaftor-responsive-non-F508del genotypes (SKYLINE Trial VX20-121-103) were enrolled at 126 and 159 international sites, respectively. Eligible individuals were entered into a 4-week run-in period, during which they received elexacaftor (200 mg once daily), tezacaftor (100 mg once daily), and ivacaftor (150 mg once every 12 h) as two fixed-dose combination tablets in the morning and one ivacaftor tablet in the evening. They were then randomly assigned (1:1) to either elexacaftor (200 mg once daily), tezacaftor (100 mg once daily), and ivacaftor (150 mg once every 12 h) as two fixed-dose combination tablets in the morning and one ivacaftor tablet in the evening, or vanzacaftor (20 mg once daily), tezacaftor (100 mg once daily), and deutivacaftor (250 mg once daily) as two fixed-dose combination tablets in the morning, for the 52-week treatment period. All participants received matching placebo tablets to maintain the treatment blinding. Randomisation was done using an interactive web-response system and stratified by age, FEV 1 % predicted, sweat chloride concentration, and previous CFTR modulator use, and also by genotype for Trial VX20-121-103. The primary endpoint for both trials was absolute change in FEV 1 % predicted from baseline (most recent value before treatment on day 1) through week 24 (with non-inferiority of vanzacaftor-tezacaftor-deutivacaftor shown if the lower bound of the 95% CI for the primary endpoint was -3·0 or higher). Efficacy was assessed in all participants with the intended CFTR genotype who were randomly assigned to treatment and received at least one dose of study treatment during the treatment period. Safety was assessed in all participants who received at least one dose of study drug during the treatment period. These trials are registered with ClinicalTrials.gov, NCT05033080 (Trial VX20-121-102) and NCT05076149 (Trial VX20-121-103), and are now complete., Findings: In Trial VX20-121-102 between Sept 14, 2021, and Oct 18, 2022, 488 individuals were screened, of whom 435 entered the 4-week run-in period, and subsequently 398 were randomly assigned and received at least one dose of elexacaftor-tezacaftor-ivacaftor (n=202) or vanzacaftor-tezacaftor-deutivacaftor (n=196). Median age was 31·0 years (IQR 22·6-38·5), 163 (41%) of 398 participants were female, 235 (59%) were male, and 388 (97%) were White. In Trial VX20-121-103, between Oct 27, 2021, and Oct 26, 2022, 699 individuals were screened, of whom 597 entered the 4-week run-in period, and subsequently 573 participants were randomly assigned and received at least one dose of elexacaftor-tezacaftor-ivacaftor (n=289) or vanzacaftor-tezacaftor-deutivacaftor (n=284). Median age was 33·1 years (IQR 24·5-42·2), 280 (49%) of 573 participants were female, 293 (51%) were male, and 532 (93%) were White. The absolute change in least squares mean FEV 1 % predicted from baseline through week 24 for Trial VX20-121-102 was 0·5 (SE 0·3) percentage points in the vanzacaftor-tezacaftor-deutivacaftor group versus 0·3 (0·3) percentage points in the elexacaftor-tezacaftor-ivacaftor group (least squares mean treatment difference of 0·2 percentage points [95% CI -0·7 to 1·1]; p<0·0001), and for Trial VX20-121-103, was 0·2 (SE 0·3) percentage points in the vanzacaftor-tezacaftor-deutivacaftor group versus 0·0 (0·2) percentage points in the elexacaftor-tezacaftor-ivacaftor group (least squares mean treatment difference 0·2 percentage points [95% CI -0·5 to 0·9]; p<0·0001). Most adverse events were mild or moderate, with the most common being infective pulmonary exacerbation (133 [28%] of 480 participants in the pooled vanzacaftor-tezacaftor-deutivacaftor group vs 158 [32%] of 491 in the pooled elexacaftor-tezacaftor-ivacaftor group), cough (108 [23%] vs 101 [21%]), COVID-19 (107 [22%] vs 127 [26%]), and nasopharyngitis (102 [21%] vs 95 [19%])., Interpretation: Vanzacaftor-tezacaftor-deutivacaftor is non-inferior to elexacaftor-tezacaftor-ivacaftor in terms of FEV 1 % predicted, and is safe and well tolerated. Once daily dosing with vanzacaftor-tezacaftor-deutivacaftor reduces treatment burden, potentially improving adherence, compared with the twice daily regimen of the current standard of care. The restoration of CFTR function and the potential variants treated are also considerations that should be compared with currently available CFTR modulators., Funding: Vertex Pharmaceuticals., Competing Interests: Declaration of interests TF, PM, PRS, NN, RZ, HM, NA, and AL are employees of Vertex Pharmaceuticals and own stock or stock options in that company. FV reports grants from HIT-CF Project, Research Foundation Flanders Strategic Basic Research, University KU Leuven Internal Funds, Cystic Fibrosis Foundation, and King Baudouin Foundation; a service agreement with Ziphius vaccines; a consulting agreement with Vertex Pharmaceuticals; and financial support from Viatris and Mylan. DP reports grants, consulting fees, and speaker fees from Vertex Pharmaceuticals. RWL reports grants from Vertex Pharmaceuticals and Cystic Fibrosis Foundation, and consulting fees and travel support from Vertex Pharmaceuticals. AT reports support from Vertex Pharmaceuticals and Cystic Fibrosis Foundation, travel support from Cystic Fibrosis Foundation, and is a board member of the local Cystic Fibrosis Foundation chapter. TK reports speaker fees and travel support from Vertex Pharmaceuticals. JM reports grants from Cystic Fibrosis Foundation, 4D Molecular Therapeutics, Boehringer Ingelheim, Clarametyx Biosciences, and Spirovant Pharmaceuticals. ATB reports grants from Vertex Pharmaceuticals and Cystic Fibrosis Foundation. MO reports speaker fees and travel support from Arrowhead Pharmaceuticals, and speaker fees from Vertex Pharmaceuticals. SS reports grants, consulting fees, and speaker fees from Vertex Pharmaceuticals, Boehringer Ingelheim, and Insmed; and grants and speaker fees from AstraZeneca. BR reports grants from the US National Institutes of Health (NIH) and the Cystic Fibrosis Foundation, consulting fees from Vertex Pharmaceuticals, Cystetic Medicines, and Sionna Therapeutics; and participation on a data safety monitoring or advisory board for the NIH. MAM reports grants from the German Research Foundation, German Ministry for Education and Research, German Innovation Fund, Vertex Pharmaceuticals, and Boehringer Ingelheim; consulting fees from AbbVie, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Prieris, Recode, Splisense, and Vertex Pharmaceuticals; speaker fees from Vertex Pharmaceuticals; travel support from Boehringer Ingelheim and Vertex Pharmaceuticals; participation on a data safety monitoring board or advisory board for AbbVie, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Pari, and Vertex Pharmaceuticals; and is a Fellow of the European Respiratory Society. JLT-C reports grants and consulting fees from Vertex Pharmaceuticals and 4D Molecular Therapeutics; a grant from Eloxx; participation on a data safety monitoring board or advisory board for AbbVie; and serving as the adult patient care representative for the Cystic Fibrosis Foundation Board of Trustees, on the Cystic Fibrosis Foundation Clinical Research Executive Committee, as immediate past Chair of the Cystic Fibrosis TDN's Sexual Health, Reproduction and Gender Research Working Group, as Co-chair of the Health Equity Team Science Awards study section and on the Racial Justice Working Group, on the scientific advisory board for Emily's Entourage, on the American Thoracic Society Respiratory Health Awards and Scientific Grant Review Committees, as Chair-elect of the International Conference Committee, as Associate Editor for the Journal of Cystic Fibrosis, as a member of the International Advisory Board for The Lancet Respiratory Medicine, and on the Clinical Trials Review study section for the NIH. EFM reports grants and speaker fees from Vertex Pharmaceuticals, travel support from Menarini, and participation on a data safety monitoring board or advisory board for Cystic Fibrosis Storm Clinical Trial, Vertex Pharmaceuticals, Janssen, AbbVie, Insmed, and Enterprise Therapeutics. ET reports grants from St Michael's Hospital and consulting fees, speaker fees, and travel support from Vertex Pharmaceuticals. AH reports grants from Cystic Fibrosis Trust, Cystic Fibrosis Foundation, and Vertex Pharmaceuticals; consulting and speaker fees from Vertex Pharmaceuticals; and serves as the Chair of the Cystic Fibrosis Trust Clinical Trials Accelerator Platform and Chair of the National Institute for Health and Care Research (NIHR) Respiratory Translational Research Collaboration. LMY and CK declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with reduced left ventricular ejection fraction (LVEF) and rate-controlled atrial fibrillation (AF) may improve after restoring sinus rhythm. This may be due to the elimination of the short R-R intervals during AF even when mean heart rate is acceptable., Objectives: This work aims to evaluate a novel parameter representing the burden of short R-R intervals during AF and its association with reduced LVEF and LVEF recovery after catheter ablation (CA)., Methods: Patients with persistent AF were prospectively enrolled pre-CA and grouped as having reduced (LVEF ≤50%) or preserved LVEF. Sequential R-R intervals on resting Holter monitoring were measured. We sought to define a threshold R-R interval at which the difference in the percentage of short R-R intervals is greatest when comparing patients with reduced and preserved ejection fraction. We termed this threshold the restitution threshold (RT) in the belief that this may be possible to apply as a threshold to identify patients with AF-mediated cardiomyopathy. This percentage burden of intervals shorter than the RT was defined as the restitution threshold index (RTI). The association with reduced LVEF in AF and predicting improvement in LVEF after CA was then evaluated., Results: One hundred four patients were enrolled; 53 (51%) had a reduced LVEF. There was no difference in mean heart rate; however, at an RT of 660 ms, the RTI was higher in the reduced LVEF arm (56.1% ± 23.1% vs 39.5% ± 26.0%; P < 0.001). It was an independent predictor of left ventricular systolic dysfunction. The RTI in the reduced LVEF arm had an area under the receiver operating characteristic of 0.74 (95% CI: 0.47-0.95) and positive predictive value of 0.97 for LVEF improvement after CA, which was observed in 39 of 47 (83.0%) participants in sinus rhythm., Conclusions: The RTI in persistent AF was associated with a reduced LVEF, whereas mean heart rate was not. The RTI could be used to predict LVEF improvement after CA., Competing Interests: Funding Support and Author Disclosures This study was funded by a Clinical Research Training Fellowship grant from Barts Charity and a Research Grant from Abbott Inc. Drs Honarbakkhsh, Hunter, and Schilling were inventors of the STAR mapping system and are shareholders in Rhythm AI Ltd. Dr Hunter has received research grants and educational grants from Medtronic and Biosense Webster; and has received speaker fees and travel grants from Abbott, Biosense Webster, and Medtronic. Dr Schilling has received research grants and educational grants from Abbott, Biosense Webster, and Medtronic; and has received speaker fees and travel grants from Abbott, Biosense Webster, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is more common in patients with hypertrophic cardiomyopathy (HCM) and is often highly symptomatic. The impact of catheter ablation (CA) may be under-reported when evaluated by long-term freedom from any atrial arrhythmia., Objectives: This study aims to evaluate whether CA of AF in patients with HCM would significantly reduce AF burden and improve symptoms., Methods: A multicenter registry was established to enroll HCM patients with pre-existing cardiac implantable electronic devices undergoing CA of AF between 2017 and 2021. The first AF recurrence and burden 12 months before and after CA were determined., Results: A total of 81 HCM patients with cardiac implantable electronic devices underwent CA of AF. Patients were followed-up for a minimum of 1-year (35 [Q1-Q3: 23-50] months). AF was paroxysmal in 38 of 81 (46.9%) patients and burden pre-CA was 27.0% (Q1-Q3: 3.0% to 99.0%). A total of 35 (43.2%) patients had AF/atrial tachycardia recurrence within 12 months. AF burden reduced after CA to 0.5% (Q1-Q3 range: 0.0% to 11.1%) (P = 0.001); a 95% CI (13.8% to 100%) relative reduction. European Hearth Rhythm Association class improved by 1.8 ± 1.3 classes (P < 0.001). Of those with AF/atrial tachycardia recurrence, the reduction in AF burden was -33.7% (Q1-Q3: -88.9% to -13.8%) (P < 0.001) and 20 (57.1%) patients reported symptomatic improvement by ≥1 European Hearth Rhythm Association class. AF burden reduction was associated with symptomatic improvement. (r = -0.67; P < 0.001) CONCLUSIONS: AF recurrence is common after CA in HCM patients, but this may under-represent the impact of CA in this cohort. CA significantly reduced AF burden and improved symptoms. A comprehensive evaluation of AF burden, symptoms, and hard endpoints is needed to determine the utility of CA in this context., Competing Interests: Funding Support and Author Disclosures Dr Boveda has received consulting fees from Medtronic, Boston Scientific, Microport, and Zoll. Dr Rinaldi has received research funding and consulting fees from Abbott, Medtronic, Boston Scientific, Microport, and Siemens/EBR systems. Dr Ginks has received speaker fees and travel grants from Biosense Webster, Atricure, and Abbott. Dr Lambiase has received research grants from Medtronic, Abbott, and Boston Scientific; and his work has been supported by UCLH Biomedicine NIHR and Barts BRC. Dr Hunter has received research grants and educational grants from Medtronic and Biosense Webster; and has received speaker fees and travel grants from Medtronic, Biosense Webster, and Abbott. Drs Honarbakhsh and Hunter invented the STAR mapping system and are shareholders in Rhythm AI Ltd. 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.)

Introduction: Not all patients experience debilitating symptoms during Atrial Fibrillation (AF), some are asymptomatic. The reasons for this inter- and intrasubject variability is unknown., Purpose: The study objective was NOAH characterize episode-level and clinical characteristics associated with symptomatic versus asymptomatic episodes of AF in patients with an implantable cardiac monitor (ICM)., Methods: Patients with an AF episode detected on an ICM between 2007 and 2021 with overlapping clinical data from aggregated Electronic Health Records in the Optum® deidentified data set were included. Symptomatic episodes were labeled in real-time by the patient. Heart rate (HR) at onset, mean HR, AF Evidence Score (a measure of beat-to-beat irregularity), episode duration and Activity Index were evaluated for association with symptom status using multivariable regression modeling., Results: 11 267 patients had AF episodes with clinical data available. The 1776 (15.8%) patients who reported symptomatic AF episodes were younger (67 ± 12 years vs. 71 ± 11 years old, p < .001) and had fewer cardiovascular co-morbidities than patients with asymptomatic AF exclusively. Symptomatic episodes were longer (5.5 [2.4, 14.4] h vs. 3.7 [1.7, 11] h, p < .001), had higher mean HR (103 ± 22 bpm vs. 88 ± 22 bpm, p < .001) and higher AF evidence scores (98 ± 27 vs. 82 ± 24, p < .001). These features were independently associated with symptomatic episodes on multivariable regression analysis and per-subject analysis in patients who had both symptomatic and asymptomatic episodes., Discussion: Episode-level characteristics differed between symptomatic AF episodes versus asymptomatic episodes in patients with ICMs. Symptomatic patients also had less comorbidities. These parameters may be useful in understanding variable symptomatic manifestation and remote stratification of AF episodes., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Introduction: Atrial fibrillation (AF)-induced cardiomyopathy (AIC) is retrospectively defined after normalisation of left ventricular ejection fraction (LVEF) in sinus rhythm. It is unclear why some patients develop AIC., Hypothesis: Patients with AIC have a subtle cardiomyopathic process that precedes their AF-mediated LVEF reduction. Detailed assessment of cardiac function after successful catheter ablation will reveal this., Objective: To evaluate the utility of measures to identify cardiomyopathic features that persist after LVEF normalisation in AIC., Methods: Patients with rate-controlled persistent AF and LVEF<50% undergoing catheter ablation (CA) were prospectively evaluated using echocardiography, cardio-pulmonary exercise testing and serum N-terminal pro b-type natriuretic peptide (NT-proBNP) at baseline and 6 months after CA. Participants with AIC, (LVEF recovery (≥50%) and no other cause for cardiac dysfunction) were evaluated using left ventricular (LV) longitudinal strain and left atrial (LA) reservoir strain (LARS). Changes in peak oxygen consumption and the minute ventilation/carbon dioxide production slope were measured as markers of functional capacity and ventilatory inefficiency. A control group of patients with persistent AF with preserved LVEF were also enrolled., Results: 34/41 (82.9%) participants recovered LVEF in sinus rhythm; defined as AIC. NT-proBNP levels were elevated in 18 (52.9%), and 16 reported ongoing heart failure (HF) symptoms. 10 (29.4%) had no improvement in functional capacity, and seven (20.6%) showed persistent ventilatory inefficiency. 20 (58.8%) had impaired global LV longitudinal strain with a relative apical sparing pattern. Nine (26.5%) had impaired LARS. There was an overlap of these abnormalities. 32 (94.1%) demonstrated at least one, 17 (50.0%) having no cardiovascular risk factors. Patients with preserved LVEF during persistent AF had similar demographics but a lower burden of short R-R intervals (<660 ms) on Holter monitoring., Discussion: Abnormal structural, metabolic and HF biomarkers are seen in patients with AIC in sinus rhythm. These features may represent a precedent subtle cardiomyopathic process predisposing them to left ventricular systolic dysfunction in AF., Trial Registration Number: NCT04987723., Competing Interests: Competing interests: RJH has received research grants and educational grants from Medtronic and Biosense Webster, and speaker fees and travel grants from Abbott and Biosense Webster and Medtronic. RS has received research grants and educational grants from Abbott and Biosense Webster and Medtronic, and speaker fees and travel grants from Abbott and Biosense Webster and Medtronic. RJH, SH and RS were inventors of the STAR mapping system and are shareholders in Rhythm AI. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Family members of critically ill patients spend significant periods of time in the intensive care unit (ICU) and hospital environment. We aimed to identify what services, resources, and conveniences are important to adult ICU visitors., Methods: We conducted a cross-sectional study including visitors in four adult ICUs in the province of Ontario, Canada. In the survey, we asked visitors to rate the importance of 58 items relating to the environment of patient rooms, the waiting room, and hospital facilities. For each item, we gave respondents five categorical response options, from "not at all important" to "extremely important." We used descriptive statistics to analyze the survey results., Results: We analyzed 224 surveys completed by ICU visitors (60% female, ages 14-87 yr). Respondents were predominantly children (41%) or the spouse/partner (23%) of adult ICU patients. Nearly half (51%) lived more than 30 km from the hospital, and 30% spent at least one night in the ICU waiting room, with a median of 2 nights (range, 1-20) spent in hospital. Within the hospital environment, the top four items rated as "extremely important" or "very important" were directional signage (82%), convenient parking (80%), discounted parking (80%), and healthy and affordable food (78%). Regarding ICU waiting rooms, 24/7 visitation (92%), convenient restrooms (87%), a water dispenser (83%), and Wi-Fi (80%) were priorities. Features of ICU patient rooms identified as most important included seating for visitors (92%), access to natural light (78%), and access to fresh air (74%)., Conclusions: Intensive care unit visitors prioritized pragmatic environmental elements. Many of these modifications are simple and inexpensive but may significantly improve visitors' comfort and experience., (© 2024. Canadian Anesthesiologists' Society.)

Purpose: This study aimed to evaluate and compare surgical outcomes among neovascular glaucoma patients undergoing trabeculectomy (Trab), glaucoma drainage device (GDD) implantation, or trans-scleral cyclophotocoagulation (TSCPC)., Methods: This study analyzed the records of 176 neovascular glaucoma cases treated surgically between January 2017 and December 2021 at four Indian centers. Procedures included trabeculectomy with MMC in 80 eyes, GDD implantation in 25 eyes, and TSCPC in 71 eyes. Outcome measures comprised intraocular pressure (IOP) reduction, antiglaucoma medication (AGM) usage, complications, and best-corrected visual acuity (BCVA)., Results: Following surgery, all groups exhibited a significant reduction in IOP. One year postoperatively, complete success rates were 42.9% for the implant group, 54.3% for the Trab group, and 33.3% for the TSCPC group, with corresponding qualified success rates of 57.1%, 36.7%, and 58.9%, respectively. Improvement in postoperative vision was noted, with an increase of 0.24 LogMAR in the Trab group, 0.11 in the GDD group, and a decrease of 0.35 in the TSCPC group. Complications occurred in 27% of Trab and 14% of TSCPC cases, while the GDD group experienced a hypertensive phase in 40% of eyes., Conclusion: In managing neovascular glaucoma, trabeculectomy, GDD, and TSCPC provide comparable IOP control, with GDD showing a higher medication dependency. Trabeculectomy yields superior vision outcomes but carries a higher risk of postoperative complications, emphasizing the importance of individualized treatment selection and vigilant postoperative care., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Familial hypercholesterolemia (FH) is a prevalent and underrecognized disorder. A young girl with previously undiagnosed homozygous FH presented with acute coronary syndrome. Severe coronary ostial stenosis and severe supravalvular aortic stenosis from atheromatous plaque was discovered. This case highlights the importance of screening and timely diagnosis of FH., Competing Interests: Dr Balakrishnan has received an honorarium from MedPanel, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Atrial fibrillation (AF) events in cardiac implantable electronic devices (CIEDs) are temporally associated with stroke risk. This study explores temporal differences in AF burden associated with HF hospitalization risk in patients with CIEDs., Methods: Patients with HF events from the Optum de-identified Electronic Health Records from 2007 to 2021 and 120 days of preceding CIED-derived rhythm data from a linked manufacturer's data warehouse were included. AF burden ≥5.5 h/d was defined as an AF event. The AF event burden in the case period (days 1-30 immediately before the HF event) was considered temporally associated with the HF event and compared with the AF event burden in a temporally dissociated control period (days 91-120 before the HF event). The odds ratio for temporally associated HF events and the odds ratio associated with poorly rate-controlled AF (>110 bpm) were calculated., Results: In total, 7257 HF events with prerequisite CIED data were included; 957 (13.2%) patients had AF events recorded only in either their case (763 [10.5%]) or control (194 [2.7%]) periods, but not both. The odds ratio for a temporally associated HF event was 3.93 (95% CI, 3.36-4.60). This was greater for an HF event with a longer stay of >3 days (odds ratio, 4.51 [95% CI, 3.57-5.68]). In patients with AF during both the control and case periods, poor AF rate control during the case period also increased HF event risk (1.78 [95% CI, 1.22-2.61]). In all, 222 of 4759 (5%) patients without AF events before their HF event had an AF event in the 10 days following., Conclusions: In a large real-world population of patients with CIED devices, AF burden was associated with HF hospitalization risk in the subsequent 30 days. The risk is increased with AF and an uncontrolled ventricular rate. Our findings support AF monitoring in CIED algorithms to prevent HF admissions., Competing Interests: J. Koehler, Dr Sarkar, N. Vasudevan, S. Majumder, and Dr Landman are employees of Medtronic. The other authors report no conflicts.

Pulmonary artery stent implantation has become integral in the treatment of pulmonary artery stenosis and is probably the most efficacious therapy for these lesions. Advancements in technology involving stent design and the equipment used for stent delivery have made this procedure much safer and more effective. Strategies to mitigate and successfully treat adverse events related to pulmonary artery stent implantation are reasonably well-established. Pulmonary artery stent implantation remains one of the most complex and technically challenging of congenital cardiac interventions., Competing Interests: Disclosure The authors have no financial or grant support conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In ambulatory patients with complete heart block (CHB), dual-chamber (DDD) pacing confers physiological benefits versus single-chamber (VVI) pacing, however, the impact on mortality is disputed. Nonagenarians constitute an expanding proportion of pacemaker recipients, yet data on device selection and outcomes are limited, especially in emergency situations. In nonagenarians with emergent CHB, we compared the clinical characteristics and outcomes of patients receiving VVI versus DDD pacemakers. Cox proportional-hazards analysis examined all-cause mortality and death from congestive cardiac failure (CCF). There were 168 consecutive patients followed-up for 30.6 ± 15.5 months. Of these, 22 patients (13.1%) received VVI pacemakers; when compared with DDD recipients, these patients had similar median age (93 vs. 91 years, p=0.15) and left ventricular (LV) systolic function (LV ejection fraction [EF] 49.2% ± 9.7 vs. 50.7% ± 10.1, p=0.71), but were more frail (Rockwood scale 5.2 ± 1.8 vs. 4.3 ± 1.1, p=0.004) and more likely to have dementia (27.3% vs. 8.9%, p=0.011). Post-implant, device interrogation demonstrated that VVI recipients had higher respiratory rates (21.3 ± 2.4 vs. 17.5 ± 2.6 breaths per minute, p=0.002), lower mean heart rates (65.5 ± 10.1 vs. 71.9 ± 8.6 bpm, p=0.002), and lower daily activity levels (0.57 ± 0.3 vs. 1.5 ± 1.1 hours of activity, p=0.016) than DDD recipients. Adjusting for age, frailty and dementia, VVI pacing was associated with an increased risk of all-cause mortality (adjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.08 to 4.1, p=0.03) and death from CCF (adjusted HR 7.1, 95%CI 2.5 to 20.6, p<0.001). In conclusion, in nonagenarians with emergent CHB, dual-chamber pacing was associated with improved symptomatic and prognostic outcomes versus singlechamber pacing., Competing Interests: Conflicts of interest None declared., (Copyright © 2024 Medinews (Cardiology) Limited.)

Background: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology., Methods: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation., Results: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9-6.1]; P <0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4-6.4]; P =0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6-17.9]; P <0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6-4.1]; P =0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P =0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P =0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P =0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P =0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446)., Conclusions: The BLISTER score (https://qxmd.com/calculate/calculator&#95;876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients., Competing Interests: Disclosures None.

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (pwCF) aged 2 years and older with at least one F508del-CFTR allele or more. After U.S. approval in 2019, reports emerged of depression-related adverse events in pwCF treated with ELX/TEZ/IVA. Objectives: To review available evidence on depression-related events in pwCF treated with ELX/TEZ/IVA in the context of background epidemiology in pwCF. Methods: Safety data from 14 ELX/TEZ/IVA clinical trials and 10 trials of CF transmembrane conductance regulator (CFTR) modulators in which placebo was administered, along with data from CF registries in the United States and Germany and cumulative postmarketing adverse event data from 61,499 pwCF who initiated ELX/TEZ/IVA after initial approval in the United States (October 2019) through October 2022, were reviewed and used to calculate exposure-adjusted rates of depression-related adverse events and prevalence of depression. In addition, a scientific literature review was conducted to identify ELX/TEZ/IVA publications reporting depression-related events or changes in depressive symptoms after treatment initiation. Measurements and Main Results: In clinical trials, the exposure-adjusted rate of any depression-related adverse event was 3.32/100 person years (PY) in the pooled ELX/TEZ/IVA group ( n  = 1,711) and 3.24/100 PY in the pooled placebo group ( n  = 1,369). The exposure-adjusted rates of suicidal ideation and suicide attempt were also similar between the pooled ELX/TEZ/IVA group and pooled placebo group (ideation: 0.23/100 PY vs. 0.28/100 PY; attempt: 0.08/100 PY vs. 0.14/100 PY). In the postmarketing setting, the exposure-adjusted reporting rates of depression-related events were low in context of the background prevalence in pwCF (all depression-related events: 1.29/PY; suicidal ideation: 0.12/100 PY; and suicide attempt: 0.05/100 PY). Assessments of individual case reports were confounded by preexisting mental health conditions, intercurrent psychosocial stressors (including coronavirus disease [COVID-19] lockdowns), and the heterogeneous and fluctuating nature of depression. Data from CF registries in the United States and Germany showed that patterns of depression prevalence in pwCF exposed to ELX/TEZ/IVA did not change after treatment initiation. Published studies utilizing the nine-item Patient Health Questionnaire did not show evidence of worsening depression symptoms in pwCF treated with ELX/TEZ/IVA. Conclusions: Our review of data from clinical trials, postmarketing reports, an ongoing registry-based ELX/TEZ/IVA postauthorization safety study, and peer-reviewed literature suggests that depression symptoms and depression-related events reported in pwCF treated with ELX/TEZ/IVA are generally consistent with background epidemiology of these events in the CF population and do not suggest a causal relationship with ELX/TEZ/IVA treatment.

As countries transition from external assistance while pursuing ambitious plans to achieve universal health coverage (UHC), there is increasing need to facilitate knowledge sharing and learning among them. Country-led and country-owned knowledge management is foundational to sustainable, more equitable external assistance for health and is a useful complement to more conventional capacity-building modalities provided under external assistance. In the context of external assistance, few initiatives use country-to-country sharing of practitioner experiences, and link learning to receiving guidance on how to adapt, apply and sustain policy changes. Dominant knowledge exchange processes are didactic, implicitly assuming static technical needs, and that practitioners in low- and middle-income countries require problem-specific, time-bound solutions. In reality, the technical challenges of achieving UHC and the group of policymakers involved continuously evolve. This paper aims to explore factors which are supportive of experience-based knowledge exchange between practitioners from diverse settings, drawing from the experience of the Joint Learning Network (JLN) for UHC-a global network of practitioners and policymakers sharing experiences about common challenges to develop and implement knowledge products supporting reforms for UHC-as an illustration of a peer-to-peer learning approach. This paper considers: (1) an analysis of JLN monitoring and evaluation data between 2020 and 2023 and (2) a qualitative inquiry to explore policymakers' engagement with the JLN using semi-structured interviews (n = 14) with stakeholders from 10 countries. The JLN's experience provides insights to factors that contribute to successful peer-to-peer learning approaches. JLN relies on engaging a network of practitioners with diverse experiences who organically identify and pursue a common learning agenda. Meaningful peer-to-peer learning requires dynamic, structured interactions, and alignment with windows of opportunity for implementation that enable rapid response to emerging and timely issues. Peer-to-peer learning can facilitate in-country knowledge sharing, learning and catalyse action at the institutional and health system levels., (© The Author(s) 2024. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Background: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients., Methods: In this phase 3, open-label, single-arm extension study, participants with F508del -minimal function (from a 24-week parent study; n=399) or F508del - F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary end-point is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit., Results: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (AEs) (586.6 events per 100 participant-years) and serious AEs (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 and 36.9 events per 100 participant-years, respectively); most participants had AEs classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. 14 participants (2.8%) had AEs that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in forced expiratory volume in 1 s (FEV 1 ) percentage predicted, Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbation rates that were maintained over the interim analysis period. The mean annualised rate of change in FEV 1 % pred was +0.07 (95% CI -0.12-0.26) percentage points among the participants., Conclusions: ELX/TEZ/IVA was generally safe and well tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA., Competing Interests: Conflicts of interest: All authors received nonfinancial support (assistance with manuscript preparation) from Nucleus Global, which received funding from Vertex Pharmaceuticals Incorporated. C.L. Daines has nothing further to disclose. E. Tullis has received consulting, speaker and travel fees from Vertex Pharmaceuticals. S. Costa serves on an advisory board for Vertex Pharmaceuticals. R.W. Linnemann serves on an advisory board and reports grants paid to her institution and consulting fees from Vertex Pharmaceuticals. M.A. Mall reports patient recruitment fees paid to his institution and advisory fees from Vertex Pharmaceuticals, consulting fees from Antabio, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Enterprise Therapeutics, Santhera, Sterna Biologicals and Vertex Pharmaceuticals, speaker fees from Arrowhead Pharmaceuticals, Boehringer Ingelheim and Vertex Pharmaceuticals, travel fees from Boehringer Ingelheim and Vertex Pharmaceuticals, advisory fees from Antabio, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Santhera and Vertex Pharmaceuticals, and serves on the European Cystic Fibrosis Society (ECFS) board. E.F. McKone reports grants, lecture fees and serving on an advisory board for Vertex Pharmaceuticals, lecture fees from Roche, travel fees from A. Menarini, and serving on advisory boards for Janssen, Insmed and CF Storm. D. Polineni reports grants from Laurent Pharmaceuticals, Parion Sciences, Proteostasis Therapeutics and Vertex Pharmaceuticals, consulting fees from Vertex Pharmaceuticals, nonfinancial support for travel to investigator meeting from Vertex Pharmaceuticals, and serves on an advisory board for Sanofi. B.S. Quon reports payments paid to his institution and speaker fees from Vertex Pharmaceuticals. F.C. Ringshausen reports grants paid to his institution from Basilea Pharmaceutica, German Center for Lung Research (DZL), German Center for Infection Research (DZIF), Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis (iABC)/Innovative Medicines Initiative (IMI), European Federation of Pharmaceutical Industries and Associations (EFPIA), Insmed, Novartis and Polyphor, consulting fees from Grifols, Insmed, Parion, Shionogi and Zambon, speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Grifols, Insmed and Novartis, participation on advisory boards for Grifols, Insmed, Parion, Shionogi and Zambon, unpaid honoraria as co-chair of the German Bronchiectasis Registry (PROGNOSIS), and payments to his institution from AbbVie, AstraZeneca, Boehringer Ingelheim, Corbus, Celtaxsys, Insmed, Novartis, Parion, Polyphor, Vertex and Zambon; and is a steering committee member of the European Bronchiectasis Registry (EMBARC), a steering committee member of the European NTM registry (EMBARC-NTM), a core network lead in ERN-LUNG, a principal investigator for DZL, a chair of the cystic fibrosis working group of the German Respiratory Society (DGP), a steering committee member of the Group of German CF Physicians (AGAM), and co-chair of medical consultants of PCD Patient Advocacy Group (Kartagener Syndrom und Primäre Ciliäre Dyskinesie eV). S.M. Rowe reports grants paid to his institution from AbbVie, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Celtaxsys, Eloxx, Ionis Pharmaceuticals, Novartis, Proteostasis Therapeutics, Synedgen, Synspira Therapeutics, Translate Bio and Vertex Pharmaceuticals, nonfinancial support from AbbVie, Ionis Pharmaceuticals, Proteostasis Therapeutics, Renovion, Synedgen and Synspira Therapeutics, consulting fees from AbbVie, Arrowhead Pharmaceuticals, Bayer, Cystetic Medicines, Ionis Pharmaceuticals, Novartis, Renovion, Synedgen, Synspira Therapeutics and Vertex Pharmaceuticals, and serves as co-chair for the Next Generation Steering Committee on Vertex Pharmaceuticals. H. Selvadurai has nothing further to disclose. J.L. Taylor-Cousar serves on the board of trustees, clinical research executive committee, clinical research advisory board and Women's Health Research-Working Group for the US Cystic Fibrosis Foundation, serves on the scientific advisory board for Emily's Entourage, serves on the respiratory health awards working group, scientific grants review committee and clinical problems assembly programming committee for the American Thoracic Society; reports consulting fees from 4D Molecular Therapeutics, Celtaxsys, Prolarean Imaging, Protalix Biotherapeutics, Proteostasis Therapeutics and Santhera Pharmaceuticals, grants to her institution from Bayer, Celtaxsys, Eloxx Pharmaceuticals, Gilead, N30 and Proteostasis Therapeutics, speaking fees from Celtaxsys and Gilead, serves on advisory board for AbbVie, Genentech, Insmed and Novartis, and is an associate editor for the Journal of Cystic Fibrosis. N.J. Withers reports lecture fees from Vertex Pharmaceuticals and serves on an advisory board for Vertex Pharmaceuticals and Proteostasis Therapeutics. B. Ramsey reports travel fees and grants from, and serves on advisory board for Vertex Pharmaceuticals, and personal fees from Cystetic Medicines. M. Griese reports grants to his institution from Vertex Pharmaceuticals. N. Ahluwalia, S.M. Moskowitz, V. Prieto-Centurion, Y.V. Tan, S. Tian, T. Weinstock, F. Xuan and Y. Zhang are employees of Vertex and may own stock or stock options in Vertex., (Copyright ©The authors 2023.)

Background: Findings of the association between iron status and depressive symptoms in nonpregnant women of reproductive age (WRA) are equivocal, limited by a small sample size, or did not consistently control for confounders., Objective: We tested the association between iron status and depressive symptoms in WRA with the NHANES data (2005-2010)., Methods: Nonpregnant WRA (20-44 y) with complete data on iron (ferritin and transferrin receptor (TfR)) and anemia (hemoglobin) biomarkers, depressive symptoms (Patient Health Questionnaire-9), and sociodemographic variables were included. Logistic and negative binomial regressions were used to estimate presence (odds ratios) and magnitude (prevalence ratios), respectively, for depressive symptoms by iron deficiency (ID)/anemia/ID anemia in the total sample and stratified by poverty:income ratio (≤ 1.85 or >1.85)., Results: Among 2516 females, the prevalence of ID was 8 to 16% (depending on the iron biomarker used), of anemia 8%, of which 52 to 65% were also ID. The prevalence of depressive symptoms was 10%. Crude logistic models showed that females with ID (TfR ≥ 8.3 mg/L or body iron <0 mg/kg) from the total sample had 1.82 (95% confidence interval [CI]: 1.24, 2.68) and 1.62 (95% CI: 1.05, 2.48), respectively, higher odds of depressive symptoms than females with iron sufficiency; these associations were attenuated after adjustments for confounders. Adjusted negative binomial models showed that females with ID (TfR ≥ 8.3 mg/L) from the total and low-income samples showed 1.19 (95% CI: 1:00, 1.40) and 1.27 (95% CI: 1.03, 1.58), respectively, higher prevalence ratios of depressive symptoms scores than females with iron sufficiency., Conclusions: These nationally representative data indicate that nonpregnant WRA with ID (based on high TfR) in the United States have higher prevalence of somatic depressive symptoms scores than those with iron sufficiency, especially if they are of low income., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy., Methods: We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling., Results: Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity., Conclusions: Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Mechanisms sustaining persistent atrial fibrillation (AF) remain unclear., Objectives: The study sought to evaluate both the clinical outcomes and response to ablation of potential drivers in patients with recurrent persistent AF recurrence following pulmonary vein isolation (PVI)., Methods: A total of 100 patients with persistent AF of <2 years' duration underwent cryoballoon PVI (ECGI phenotyping of persistent AF based on driver burden and distribution to predict response to pulmonary vein isolation). Patients with documented recurrence of atrial arrhythmia within 12 months were recruited and underwent repeat PVI (if needed) followed by ablation of potential drivers (PDs) identified by electrocardiographic imaging (ECGI). PDs were defined as rotational activity >1.5 revolutions or focal activations. Cycle lengths were measured pre- and postablation. The primary outcome was freedom from atrial arrhythmia off antiarrhythmic drugs at 1 year as per guidelines., Results: Of 37 patients recruited, 26 had recurrent AF and underwent ECGI-guided ablation of PDs. An average of 6.4 ± 2.7 PDs were targeted per patient. The mean ablation time targeting PDs was 15.5 ± 6.9 minutes. An ablation response occurred in 20 patients (AF termination in 6, cycle length prolongation ≥10% in 14). At 1 year, 14 (54%) of 26 patients were free from arrhythmia, and 12 (46%) of 26 were off antiarrhythmic drugs. Considering the 96 patients who completed follow-up out of the original cohort of 100 patients undergoing cryoablation in this staged strategy, freedom from arrhythmia at 1 year following the last procedure was 72 (75%) of 96, or 70 (73%) of 96 off antiarrhythmic drugs., Conclusions: In patients with recurrent AF despite PVI, ECGI-guided ablation caused an acute response in a majority with reasonable long-term outcomes., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Optimal method for voltage assessment in AF remains unclear., Objectives: This study evaluated different methods for assessing atrial voltage and their accuracy in identifying pulmonary vein reconnection sites (PVRSs) in atrial fibrillation (AF)., Methods: Patients with persistent AF undergoing ablation were included. De novo procedures: voltage assessment in AF with omnipolar voltage (OV) and bipolar voltage (BV) methodology and BV assessment in sinus rhythm (SR). Activation vector and fractionation maps were reviewed at voltage discrepancy sites on OV and BV maps in AF. AF voltage maps were compared with SR BV maps. Repeat ablation procedures: OV and BV maps in AF were compared to detect gaps in wide area circumferential ablation (WACA) lines that correlated with PVRS., Results: Forty patients were included: 20 de novo and 20 repeat procedures. De novo procedure: OV vs BV maps in AF; average voltage 0.55 ± 0.18 mV vs 0.38 ± 0.12 mV; P = 0.002, voltage difference of 0.20 ± 0.07 mV; P = 0.003 at coregistered points and proportion of left atrium (LA) area occupied by low-voltage zones (LVZs) was smaller on OV maps (42.4% ± 12.8% OV vs 66.7% ± 12.7% BV; P < 0.001). LVZs identified on BV maps and not on OV maps correlated frequently to wavefront collision and fractionation sites (94.7%). OV AF maps agreed better with BV SR maps (voltage difference at coregistered points 0.09 ± 0.03 mV; P = 0.24) unlike BV AF maps (0.17 ± 0.07 mV, P = 0.002). Repeat ablation procedure: OV was superior in identifying WACA line gaps that correlated with PVRS than BV maps (area under the curve = 0.89, P < 0.001)., Conclusions: OV AF maps improve voltage assessment by overcoming the impact of wavefront collision and fractionation. OV AF maps correlate better with BV maps in SR and more accurately delineate gaps on WACA lines at PVRS., Competing Interests: Funding Support and Author Disclosures Funding has been provided by the British Heart Foundation Clinical Intermediate Fellowship grant (FS/ICRF/22/26034). Prof Hunter has received research grants, educational grants, and speaker fees from Biosense Webster, Medtronic, and Abbott. Prof Lambiase has received speaker fees and research grants from Medtronic, Abbott, and Boston Scientific. Dr Honarbakhsh has received speaker fees from Abbott. Drs Honarbakhsh and Hunter are shareholders in Rhythm AI Ltd. Dr Honarbakhsh is a British Heart Foundation Clinical Intermediate Fellow; and has received a grant from the British Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele. To assess long-term effects of ELX/TEZ/IVA under real-world conditions of use, a 5-year observational registry-based study is being conducted. We report interim results from the first 2 years of follow-up., Methods: The study included people with CF in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) who initiated ELX/TEZ/IVA between October 2019 and December 2020. Pulmonary exacerbations (PEx), percent predicted forced expiratory volume in 1 second (ppFEV 1 ), hospitalizations, bacterial pathogens, body mass index (BMI), CF complications and comorbidities, and liver function tests (LFTs) after treatment initiation were compared with the 5-year pre-treatment period. Death and lung transplantation were assessed relative to 2019 CFFPR data., Results: 16,116 people with CF were included (mean treatment duration 20.4 months). Among those with 5 years of pre-treatment data, mean PEx/patient/year declined to 0.18 (95% CI: 0.17, 0.19) in Years 1 and 2 post-treatment from 0.86 (95% CI: 0.83, 0.88) in the baseline year (79% reduction), after a continued increase observed pre-treatment. Similarly, a decline in mean hospitalizations/patient/year was observed in Year 1 that was sustained in Year 2 (74% reduction from baseline year). The mean absolute change in ppFEV 1 from baseline was +8.2 percentage points (95% CI: 8.0, 8.4) in Year 1 and +8.9 percentage points (95% CI: 8.7, 9.1) in Year 2, after a continued decline observed pre-treatment. Positive bacterial cultures decreased for all evaluated pathogens, and mean BMI increased by 1.6 kg/m 2 (95% CI: 1.5, 1.6) by Year 2. No new safety concerns were identified based on evaluation of CF complications, comorbidities, and LFTs. The annualized rates of death (0.47% [95% CI: 0.39, 0.55]) and lung transplantation (0.16% [95% CI: 0.12, 0.22]) were considerably lower than reported in 2019 (1.65% and 1.08%, respectively)., Conclusions: ELX/TEZ/IVA treatment was associated with sustained improvements in lung function, reduced frequency of PEx and all-cause hospitalization, increased BMI, and lower prevalence of positive bacterial cultures. Additionally, there was a 72% lower rate of death and 85% lower rate of lung transplantation relative to the year before ELX/TEZ/IVA availability. These results, from the largest cohort of ELX/TEZ/IVA-treated people to date, extend our understanding of the broad clinical benefits of ELX/TEZ/IVA., Competing Interests: Declaration of Competing Interest Julie K. Bower, Nataliya Volkova, Neil Ahluwalia, Gurvaneet Sahota, Fengjuan Xuan, Anna Chin, and Tanya G. Weinstock are employees of Vertex Pharmaceuticals and may own stock or stock options in that company. Josh Ostrenga and Alexander Elbert are employees of the Cystic Fibrosis Foundation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one F508del-CFTR allele but has not been studied in younger children. Objectives: To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. Methods: In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.5 mg each evening; children weighing ⩾14 kg received ELX 100 mg qd, TEZ 50 mg qd, and IVA 75 mg every 12 hours. Measurements and Main Results: The primary endpoints for part A (15-d treatment period) were pharmacokinetics and safety and tolerability. For part B (24-wk treatment period), the primary endpoint was safety and tolerability; secondary endpoints included pharmacokinetics and absolute changes from baseline in sweat chloride concentration and lung clearance index 2.5 (LCI 2.5 , defined as the number of lung turnovers required to reduce the end tidal N 2 concentration to 2.5% of its starting value) through Week 24. Analysis of pharmacokinetic data from 18 children enrolled in part A confirmed the appropriateness of the part B dosing regimen. In part B, 75 children ( F508del /minimal function genotypes, n  = 52; F508del / F508del genotype, n  = 23) were enrolled and dosed. Seventy-four children (98.7%) had adverse events, which were all mild (62.7%) or moderate (36.0%) in severity. The most common adverse events were cough, fever, and rhinorrhea. Decreases in sweat chloride concentration (-57.9 mmol/L; 95% confidence interval [CI], -61.3 to -54.6; n  = 69) and LCI 2.5 (-0.83 U; 95% CI, -1.01 to -0.66; n  = 50) were observed from baseline through Week 24. Mean body mass index was within the normal range at baseline and remained stable at Week 24. Conclusions: In this open-label study in children 2-5 years of age, ELX/TEZ/IVA treatment was generally safe and well tolerated, with a safety profile consistent with that observed in older age groups, and led to clinically meaningful reductions in sweat chloride concentration and LCI 2.5 . Clinical trial registered with www.clinicaltrials.gov (NCT04537793).

Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for F508del and a minimal function CFTR mutation ( F /MF genotypes) or homozygous for F508del ( F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. Children weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, whereas children weighing ⩾30 kg received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours (adult dose). The 96-week analysis of part A of this extension study is reported here. Measurements and Main Results: Sixty-four children ( F /MF genotypes, n  = 36; F/F genotype, n  = 28) were enrolled and received one or more doses of ELX/TEZ/IVA. Mean (SD) period of exposure to ELX/TEZ/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV 1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride concentration decreased (-62.3 [95% CI, -65.9 to -58.8] mmol/L), Cystic Fibrosis Questionnaire-Revised respiratory domain score increased (13.3 [95% CI, 11.4 to 15.1] points), and lung clearance index 2.5 decreased (-2.00 [95% CI, -2.45 to -1.55] units). Increases in growth parameters were also observed. The estimated pulmonary exacerbation rate per 48 weeks was 0.04. The annualized rate of change in percent predicted FEV 1 was 0.51 (95% CI, -0.73 to 1.75) percentage points per year. Conclusions: ELX/TEZ/IVA continued to be generally safe and well tolerated in children aged ⩾6 years through an additional 96 weeks of treatment. Improvements in lung function, respiratory symptoms, and CFTR function observed in the parent study were maintained. These results demonstrate the favorable long-term safety profile and durable clinical benefits of ELX/TEZ/IVA in this pediatric population. Clinical trial registered with www.clinicaltrials.gov (NCT04183790).

Introduction: The Heliostar™ ablation system is a novel RF balloon ablation technology with an integrated three-dimensional mapping system. Here, we describe our early experience and procedural outcomes using this technology for atrial fibrillation catheter ablation., Methods: We sought to comprehensively assess the first 60 consecutive patients undergoing pulmonary vein isolation using the novel HELISOTAR™ RF balloon technology including procedural outcomes. A comparison of the workflow between two different anaesthetic modalities (conscious sedation [CS] vs. general anaesthesia [GA]) was made. Procedural data were collected prospectively from two high-volume centers (Barts Heart Centre, UK and University Hospital of Zurich, Zurich). A standardized approach for catheter ablation was employed., Results: A total of 35 patients had the procedure under CS and the remaining under GA. Mean procedural and fluoroscopy times were 84 ± 33 min and 1.1 min. The median duration of RF energy application was 7 (5-9.8) mins per patient. All veins were successfully isolated, and the median isolation time was 10 (7-15) seconds. Our cohort's rate of procedural complications was low, with no mortality within 30 days postprocedure., Conclusion: Our early experience shows that catheter ablation using the Heliostar™ technology can be performed efficiently and safely; however, long-term data is yet to be established. Low fluoroscopy requirements, short learning curves and use of this technology with CS is possible, including the use of an oesophageal temperature probe., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Study 661-110 (EXTEND) is a phase 3, open-label, three-part rollover study designed to assess the long-term safety and efficacy of tezacaftor/ivacaftor (TEZ/IVA) in participants aged ≥12 years homozygous for F508del (F/F) or heterozygous for F508del and a residual function mutation (F/RF). TEZ/IVA was shown to be safe and efficacious for up to 120 weeks in Part A. Here we report results from Part B, which evaluated safety and efficacy for an additional 96 weeks., Methods: Part B enrolled participants aged ≥12 years with CF and F/F or F/RF genotypes who completed TEZ/IVA treatment in either Study 661-110 Part A, Study 661-112 (F/F), or Study 661-114 (F/F). Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination once daily (morning) and IVA 150 mg once daily (evening) for 96 weeks. Safety endpoints included adverse events (AEs) and serum liver function tests. Efficacy endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV 1 ) and pulmonary exacerbation (PEx) rate., Results: 464 participants were enrolled from Part A (n=377) and other eligible studies (n=87); 463 received ≥1 dose of TEZ/IVA. Overall, 92.2% had ≥1 AE, 0.9% had AEs leading to treatment discontinuation, and 29.4% reported serious AEs. The most common AEs, which were generally consistent with common manifestations of CF, included infective PEx of CF, cough, nasopharyngitis, hemoptysis, and headache. Lung function was maintained over 96 weeks in both genotype groups. PEx rates per year were comparable with Part A., Conclusions: TEZ/IVA was generally safe and well tolerated over a further 96 weeks; safety data were consistent with Part A. Improvements in ppFEV 1 and PEx rates were maintained for an additional 96 weeks in Part B., Competing Interests: Declaration of Competing Interests PAF reports grants and personal fees from Vertex Pharmaceuticals outside the submitted work. RSH, HP-D, NA, MH, IB, and JLS are employees of Vertex Pharmaceuticals and may own stock or stock options in Vertex Pharmaceuticals. DC is a former employee of Vertex Pharmaceuticals and owns stock or stock options in Vertex Pharmaceuticals. GS reports personal fees from and advisory boards for Vertex Pharmaceuticals during the conduct of the study, and grants from Vertex Pharmaceuticals and personal fees from Gilead Sciences outside the submitted work., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Patients with hematological malignancies (HM) are at risk of acute respiratory failure (ARF). Malnutrition, a common association with HM, has the potential to influence ICU outcomes. Geriatric nutritional risk index (G-NRI) is a score derived from albumin and weight, which reflects risk of protein-energy malnutrition. We evaluated the association between G-NRI at ICU admission and ICU mortality in HM patients with ARF. We conducted a single center retrospective study of ventilated HM patients between 2014 and 2018. We calculated G-NRI for all patients using their ICU admission albumin and weight. Our primary outcome was ICU mortality. Secondary outcomes included duration of mechanical ventilation and ICU length of stay. Two hundred eighty patients were admitted to the ICU requiring ventilation. Median age was 62 years (IQR 51-68), 42% (n = 118) were females, and median SOFA score was 11 (IQR 9-14). The most common type of HM was acute leukemia (54%) and 40% underwent hematopoietic cell transplant. Median G-NRI was 87 (IQR 79-99). ICU mortality was 51% (n = 143) with a median duration of ventilation of 4 days (IQR 2-7). Mortality across those at severe malnutrition (NRI < 83.5) was 59% (65/111) compared to 46% (76/164) across those with moderate-no risk (p = 0.047). On multivariable analysis, severe NRI (OR 2.34, 95% CI 1.04-5.27, p = 0.04) was significantly associated with ICU mortality. In this single center, exploratory study, severe G-NRI was prognostic of ICU mortality in HM patients admitted with respiratory failure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: The ARC-HF and CAMTAF trials randomized patients with persistent atrial fibrillation (AF) and heart failure (HF) to early routine catheter ablation (ER-CA) versus pharmacological rate control (RC). After trial completion, delayed selective catheter ablation (DS-CA) was performed where clinically indicated in the RC group. We hypothesized that ER-CA would result in a lower risk of cardiovascular hospitalization and death versus DS-CA in this population., Methods and Results: Overall, 102 patients were randomized (age 60 ± 11 years, left ventricular ejection fraction [LVEF] 31 ± 11%): 52 to ER-CA and 50 to RC. After 12 months, patients undergoing ER-CA had improved self-reported symptom scores, lower New York Heart Association class (i.e. better functional capacity), and higher LVEF compared to patients receiving RC alone. During a median follow-up of 7.8 (interquartile range 3.9-9.9) years, 27 (54%) patients in the RC group underwent DS-CA and 34 (33.3%) patients died, including 17 (32.7%) randomized to ER-CA and 17 (34.0%) randomized to RC. Compared with DS-CA, a strategy of ER-CA exhibited similar risk of all-cause mortality (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.44-1.77, p = 0.731) and combined all-cause mortality or cardiovascular hospitalization (aHR 0.80, 95% CI 0.43-1.47, p = 0.467). However, analyses according to treatment received suggested an association between CA and improved outcomes versus RC (all-cause mortality: aHR 0.43, 95% CI 0.20-0.91, p = 0.028; all-cause mortality/cardiovascular hospitalization: aHR 0.48, 95% CI 0.24-0.94, p = 0.031)., Conclusions: In patients with persistent AF and HF, ER-CA produces similar long-term outcomes to a DS-CA strategy. The association between CA as a treatment received and improved outcomes means there is still a lack of clarity regarding the role of early CA in selected patients. Randomized trials are needed to clarify this question., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Amidst competing priorities for allocating finite health resources, using evidence-informed priority setting is a valuable tool for achieving population-level health goals. The paper by Baltussen et al comprehensively reports on the development of practical guidance for evidence-informed deliberative processes (EDPs) which will help with sustainability of programs aimed at universal health coverage (UHC). The authors' experience with the Joint Learning Network for UHC's (JLN) peer-to-peer learning platform on evidence-informed priority setting offers insights on the practical challenges faced by countries in health benefits package (HBP) design, especially to draw in actors to advocate for the priorities and values across the health system. Lessons harvested from JLN countries that have established such advisory committees can provide practical insights for countries in earlier stages of establishing a systematic process for HBP design. Peer-to-peer learning modalities among countries offer viable and effective approaches to institutionalizing EDPs and systematic priority setting., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)