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Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, yet its underlying pathophysiology remains poorly understood. This study assessed whether circulating biomarker concentrations differ in paroxysmal AF patients during an acute episode compared to sinus rhythm., Methods: The Time of Calamity study is a prospective biomarker study within the RACE V study. Patients underwent venous blood sampling in sinus rhythm at inclusion in RACE V, as well as during a subsequent acute episode of AF for which patients reported to the hospital. Ten biomarkers were analyzed., Results: Thirty-nine patients (mean age 60 ± 9 years, 10 (25 %) women) were enrolled. During an acute AF episode, dickkopf-related protein 3 and insulin-like growth factor binding protein 7 were significantly lower, while N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), growth differentiation factor 15, and interleukin 6 were significantly higher (all p < 0.05)., Conclusions: Biomarker concentrations in paroxysmal AF patients are dynamic and differ between sinus rhythm and acute AF episodes. Notably, NT-proBNP and hsTnT, commonly used in clinical practice, were significantly elevated during an acute AF episode., (Copyright © 2024. Published by Elsevier B.V.)

The selection of an appropriate implantable cardioverter-defibrillator (ICD) type and implantation strategy involves a myriad of considerations. While transvenous ICDs are standard, the rise of non-transvenous options like subcutaneous ICDs and extravascular ICDs is notable for their lower complication rates. Historical preferences for dual chamber ICDs have shifted to single-chamber ICDs. Single-coil ICDs are preferred for easier extraction, and the use of the DF-4 connector is generally recommended. Cephalic cutdown is the preferred venous access technique, while axillary vein puncture is a viable alternative. The right ventricular apex remains the preferred lead position until further evidence on conduction system pacing emerges. Left-sided, subcutaneous ICD implantation is considered reliable, contingent on specific cases. A meticulous perioperative plan, including antibiotic prophylaxis and an antithrombotic regimen, is crucial for successful implantation., Competing Interests: The authors declare no conflict of interest. Alexander H. Maass is serving as Guest Editor of this journal. We declare that Alexander H. Maass had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Matteo Bertini., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing summary statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people., Competing Interests: Declaration of interests The authors declare no competing interests. D.P.L. is now an employee of AstraZeneca. This is unrelated to the work of this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preventing high heart rates in patients with atrial fibrillation (AF) is a key objective of AF management. Data regarding heart rates in patients with paroxysmal AF (PAF) is lacking. This analysis aimed to provide insight into heart rates during PAF episodes measured with continuous implantable loop monitoring., Methods: In present analysis of the Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilization in the Progression of AF study, we included 349 patients with at least one year of continuous rhythm monitoring and an episode of AF. Mean heart rates and duration of AF episodes were used to calculate total AF duration and AF duration above different heart rate cut-offs., Results: The median age was 64.0 (58.4 to 70.5) years, 152 (44%) were women and CHA 2 DS 2 -VASc score ≥2 or higher in 255 (73%) patients. During 28.3 (21.3 to 35.0) months of follow-up, the median number of AF episodes was 62 (12 to 293) with a median total AF duration of 4.6 (0.8 to 26.8) days. At baseline, 172 (49%) patients used beta-blockers, 64 (18%) used diltiazem or verapamil and 5 (1%) used digoxin. A total of 133 patients (38%) experienced a heart rate >110 bpm for more than 50% of the time during AF. Fifty-six (16%) patients had a heart rate >130 bpm for more than 50% of the time while in AF. During follow-up, 39 patients (11%) received an increase of rate-controlling medication., Conclusion: Continuous rhythm monitoring revealed that more than a third of PAF patients had heart rates above 110 bpm for more than half of their time in AF., Trial Registration Number: Clinicaltrials.gov identifier NCT02726698., Competing Interests: Competing interests: RGT reports grants from Medtronic and Abbott, and personal fees from Boehringer Ingelheim, Bayer and Pfizer/Bristol Myers Squibb all outside submitted work. RGT is coinventor of the MyDiagnostick, not receiving royalties for the past 5 years. MDM is a Medtronic employee and WP Coordinator in the H2020 ITN My-Atria (No: 766082). The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Atrial fibrillation (AF) is often accompanied by comorbidities. Not only cardiovascular but also non-cardiovascular comorbidities have been associated with AF. Multimorbidity is therefore a common finding in patients with AF, especially in elderly patients. Multimorbidity is associated with adverse outcomes, adds complexity to AF management, and poses a significant burden on healthcare costs. It is expected that the prevalence of elderly patients with multimorbidity will increase significantly. It is therefore crucial to outline implications for clinical practice and guide comprehensive multimorbidity management., Areas Covered: This perspective article outlines multimorbidity in AF and the importance of comprehensive comorbidity management. It addresses current clinical practice guided by international guidelines and the need for integrated care including a patient-centered focus, comprehensive AF management, coordinated multidisciplinary care, and supporting technology. Moreover, it proposes a novel model of care delivery following a systematic approach to multimorbidity management., Expert Opinion: Providing comprehensive care by means of a multidisciplinary team and patient engagement is crucial to provide optimal personalized care for elderly patients with AF and multimorbidity. A systematic integrated care approach seems promising, but further studies are needed to investigate the feasibility of a systematic approach and prioritization of comorbidity management in patients with multimorbidity.

Aims: Digoxin is the oldest drug in cardiovascular (CV) medicine, and one trial conducted >25 years ago showed a reduction in heart failure (HF) hospitalizations but no effect on mortality. However, later studies suggested that the dose of digoxin used in that trial (and other studies) may have been too high. The DECISION (Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands) trial will examine the efficacy and safety of low-dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with a background of contemporary HF treatment., Methods: The DECISION trial is a randomized, double-blind, parallel-group, placebo-controlled event-driven outcome trial which will investigate the efficacy and safety of low-dose digoxin in patients with chronic HF and LVEF <50%. Both patients with sinus rhythm and atrial fibrillation will be enrolled and will be randomized (1:1) to low-dose digoxin or matching placebo. To maintain a target serum digoxin concentration of 0.5-0.9 ng/ml, dose adjustments are made throughout follow-up based on serum digoxin measurements with dummy values for the placebo group. The primary endpoint is a composite of CV mortality and total HF hospitalizations or total urgent hospital visits for worsening HF, and all endpoints are adjudicated blindly by a Clinical Event Committee. The estimated sample size was 982 patients who will be followed for a median of 3 years, and in December 2023 enrolment was completed after 1002 patients., Conclusions: The DECISION trial will provide important evidence regarding the effect of (low-dose) digoxin on CV mortality and total HF hospitalizations and urgent hospital visits when added to contemporary HF treatment of patients with reduced or mildly reduced LVEF., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03783429., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Atrial fibrillation (AF) is common in heart failure (HF) and negatively impacts outcomes. The role of ablation-based rhythm control in patients with AF and HF with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) is not known. The CABA-HFPEF-DZHK27 (CAtheter-Based Ablation of atrial fibrillation compared to conventional treatment in patients with Heart Failure with Preserved Ejection Fraction) trial will determine whether early catheter ablation for AF can prevent adverse cardiovascular outcomes in patients with HFpEF or HFmrEF., Methods: CABA-HFPEF-DZHK27 (NCT05508256) is an investigator-initiated, prospective, randomized, open, interventional multicentre strategy trial with blinded outcome assessment. Approximately 1548 patients with paroxysmal or persistent AF diagnosed within 24 months prior to enrolment and HFpEF or HFmrEF will be randomized to early catheter ablation within 4 weeks after randomization or to usual care. All patients receive anticoagulation, rate control, and HF management according to current guideline recommendations. Usual care can include rhythm control in symptomatic patients. Patients will be followed until the end of the trial for the primary outcome, a composite of cardiovascular death, stroke, and total unplanned hospitalizations for HF or acute coronary syndrome. The safety outcome comprises complications of catheter ablation and death. The trial is powered for a rate ratio of 0.75 (two-sided alpha = 0.05, 1-beta = 0.8)., Conclusion: CABA-HFPEF-DZHK27 will define the role of systematic and early catheter ablation in patients with AF and HFpEF or HFmrEF., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Because of the increasing use of cardiac implantable electronic devices (CIEDs) with one or more intracardiac electrodes, the rate of lead failure is increasing. Moreover, upgrade of the CIED frequently is indicated for cardiac resynchronization therapy or other reasons. Both these situations require a new intervention, preferably using ipsilateral venous access. However, venous obstruction after CIED insertion occurs in 10%-20% of patients and poses a major obstacle for implantation of additional leads. Possible solutions include lead extraction, contralateral lead insertion, and venoplasty. Preprocedural venoplasty is associated with the lowest short- and long-term risks. Here we describe a step-by-step approach to this technique, which can be introduced and safely performed in most interventional catheterization laboratories., Competing Interests: Disclosures Dr Lipšic has received an institutional educational grant from Abbott Medical Nederland B.V. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial., Methods: The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities., Results: 78 852 patients were included with AF, aged 40-75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87-0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83-0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94-1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96-1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97-1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45)., Conclusions: Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Atrial fibrillation (AF) is a globally prevalent cardiac arrhythmia with significant genetic underpinnings, as highlighted by recent large-scale genetic studies. A prominent clinical and genetic overlap exists between AF, heritable ventricular cardiomyopathies, and arrhythmia syndromes, underlining the potential of AF as an early indicator of severe ventricular disease in younger individuals. Indeed, several recent studies have demonstrated meaningful yields of rare pathogenic variants among early-onset AF patients (∼4%-11%), most notably for cardiomyopathy genes in which rare variants are considered clinically actionable. Genetic testing thus presents a promising opportunity to identify monogenetic defects linked to AF and inherited cardiac conditions, such as cardiomyopathy, and may contribute to prognosis and management in early-onset AF patients. A first step towards recognizing this monogenic contribution was taken with the Class IIb recommendation for genetic testing in AF patients aged 45 years or younger by the 2023 American College of Cardiology/American Heart Association guidelines for AF. By identifying pathogenic genetic variants known to underlie inherited cardiomyopathies and arrhythmia syndromes, a personalized care pathway can be developed, encompassing more tailored screening, cascade testing, and potentially genotype-informed prognosis and preventive measures. However, this can only be ensured by frameworks that are developed and supported by all stakeholders. Ambiguity in test results such as variants of uncertain significance remain a major challenge and as many as ∼60% of people with early-onset AF might carry such variants. Patient education (including pretest counselling), training of genetic teams, selection of high-confidence genes, and careful reporting are strategies to mitigate this. Further challenges to implementation include financial barriers, insurability issues, workforce limitations, and the need for standardized definitions in a fast-moving field. Moreover, the prevailing genetic evidence largely rests on European descent populations, underscoring the need for diverse research cohorts and international collaboration. Embracing these challenges and the potential of genetic testing may improve AF care. However, further research-mechanistic, translational, and clinical-is urgently needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding., Methods: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events., Results: A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA 2 DS 2 -VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups., Conclusions: Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: Concerns exist of women underrepresentation in atrial fibrillation (AF) studies, potentially limiting the generalisability of study findings to women with AF. We assessed the participation of women in AF clinical studies performed at a tertiary care centre in the Northern Netherlands., Methods: Eight AF clinical studies with screening logs were available for analysis. To identify sex-specific differences, patient inclusion and exclusion and reasons for exclusion were assessed. Participation-to-prevalence ratios (PPRs) were calculated to evaluate the representation of women in the studies relative to the AF sex distribution of the general population in the Netherlands (2019 Global Burden of Disease study)., Results: We included 1739 screened patients with AF in the analysis, of whom 722 (41.5%) were women. Of the patients screened, 161 (9%) were enrolled. Median age of screened patients was 69 years (interquartile range (IQR): 61-77), and women were older than men (71 years; IQR: 63-79 vs 68 years; IQR: 60-75; p < 0.001). Women were not underscreened compared with men (PPR: 1.09; 95% confidence interval (CI): 1.08-1.10), disproportionally excluded (92% vs 90%; p = 0.10) or less willing to participate (17% vs 15%; p = 0.36). Women had an overall PPR of 1.05 (95% CI: 1.05-1.06) compared with the general AF population., Conclusion: At our tertiary hospital in the Northern Netherlands, women appeared to be well-represented in AF studies. The current study advocates for the adoption of a more comprehensive measure of equity, such as the PPR, and screening log evaluation to improve the generalisability of study findings to the entire clinical AF population., (© 2024. The Author(s).)

Background: Early postoperative atrial fibrillation (POAF) is common after cardiac surgery and is associated with late-POAF recurrences. However, little is known about the burden of POAF and its potential impact on long-term outcomes after cardiac surgery, particularly on the risk for late-POAF recurrences., Objective: The purpose of this study was to establish the distribution of POAF burden and to determine the association between early-POAF burden and late-POAF recurrences during 2.5 years of continuous rhythm monitoring after cardiac surgery in patients with and without preoperative history of atrial fibrillation (AF)., Methods: Patients undergoing cardiac surgery were prospectively enrolled and postoperatively continuously monitored with an implantable loop recorder for 2.5 years. All patients underwent extensive clinical assessment at baseline. During follow-up, all AF episodes were registered, and AF associated metrics, such as burden, were calculated for different time intervals. Early-POAF was defined as AF within first 90 postoperative days and late-POAF as AF after this interval., Results: A total of 98 consecutive patients were included. POAF burden during the early postoperative phase was significantly higher compared to the late postoperative phase (P <.001). The longest individual POAF episode was strongly associated with increased POAF burden after adjusting for age, sex, and AF history (standardized Beta: 0.91, P <.001). Also, early-POAF burden was associated with late-POAF (re)occurrence after adjusting for age, sex, AF history (adjusted hazard ratio 1.93, 95% confidence interval 1.42-2.62, P <.001)., Conclusion: POAF burden was significantly associated with the longest individual POAF episode duration. Additionally, greater early-POAF burden was associated with increased late-POAF incidence, highlighting its potential in estimating the risk for long-term POAF recurrences., Competing Interests: Disclosures Dr Schotten received consultancy fees or honoraria from Università della Svizzera Italiana (USI, Switzerland), Roche Diagnostics (Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited (United Kingdom), and Bayer Healthcare (Germany); and is co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht. Dr Maesen is a consultant for AtriCure and Medtronic. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Long-term endurance exercise is suspect to elevate the risk of atrial fibrillation (AF), but little is known about cardiovascular outcome and disease progression in this subgroup of AF patients. We investigated whether previous exercise level determines cardiovascular outcome., Methods: In this post hoc analysis of the RACE 4 randomized trial, we analyzed all patients with a completed questionnaire on sports participation. Three subgroups were made based on lifetime sports hours up to randomization and previous compliance to the international physical activity guidelines. High lifetime hours of high dynamic activity patients were defined as more than 150 min·wk -1 of high-intensity physical exercise. The primary endpoint was a composite of cardiovascular death and hospital admissions., Results: A total of 879 patients were analyzed, divided in 203 high lifetime hours of high dynamic activity, 192 high lifetime hours of activity, and 484 low lifetime hours of activity patients. Over a mean follow-up of 36 months (±14), the primary endpoint occurred in 61 out of 203 (30%) high lifetime hours of high dynamic activity, 53 out of 192 (27%) high lifetime hours of activity, and 135 out of 484 (28%) low lifetime hours of activity patients ( P = 0.74). During follow-up, 42 high lifetime hours of high dynamic activity (35%), 43 high lifetime hours of activity (32%), and 104 low lifetime hours of activity patients (34%) with paroxysmal AF received electrical or chemical cardioversion or atrial ablation ( P = 0.90)., Conclusions: In patients included in the RACE 4, there seems to be no relation between previous activity levels and cardiovascular outcome and the need for electrical or chemical cardioversion or atrial ablation. Cardiovascular outcome was driven by AF-related arrhythmic events., (Copyright © 2024 by the American College of Sports Medicine.)

Aims: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms., Methods: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death., Conclusion: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: We aimed to evaluate the association between atrial fibrillation (AF) burden, duration and number of episodes with healthcare utilisation and quality of life in patients with early paroxysmal AF without a history of AF., Methods: In this observational cohort study, we included 417 patients with paroxysmal AF from the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V) Study. Patients were monitored with an insertable cardiac monitor for 1 year. Outcomes collected were healthcare utilisation, and quality of life assessed using the Atrial Fibrillation Severity Scale and EuroQol EQ-5D-5L questionnaires., Results: During 1 year of follow-up, 63 973 AF episodes were detected in 353 (85%) patients. The median AF burden was 0.7% (IQR 0.1-4.0%). AF ablation was performed more frequently in patients with intermediate-to-high AF burdens (>0.2%) (16.2% vs 5.9%, p=0.01) and longer AF episode duration (>1 hour) (15.8% vs 2.0%, p=0.01), whereas cardioversions were more frequent in patients with longer episode duration (>1 hour) (9.5% vs 0%, p=0.04) and intermediate (0.2-1.9%) (but not high) AF burdens (13.6% vs 4.2%, p=0.01). Patients with many episodes (>147) reported higher symptom severity (p=0.001). No differences in symptom severity nor in EQ-5D-5L scores according to AF burden or duration were observed., Conclusion: In patients with early paroxysmal AF, higher AF burden and longer episode duration were associated with increased rates of healthcare utilisation but not with symptoms and quality of life. Patients with a higher number of episodes experienced more severe symptoms., Trial Registration Number: NCT02726698., Competing Interests: Competing interests: MHJPF received consulting fees from Medtronic outside this work. MBK received speaker’s honoraria from Abbott outside this work. JCN was supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658). MR received consultancy fees from Bayer and InCarda Therapeutics (to the institution). MDM is an employee of Medtronic Bakken Research Center. RGT reports grants and personal fees from Medtronic and grants from St Jude Medical outside this work. In addition, RGT has a patent as co-inventor of the MyDiagnostick issued. The remaining authors declare no conflicts of interest., (© 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.)

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in acute heart failure (AHF), with a prevalence of approximately 35%. However, little is known about the clinical characteristics and outcomes of in-hospital conversion from AF to sinus rhythm and vice versa., Methods: In a post hoc secondary analysis of the randomized, double-blind, placebo-controlled PROTECT trial in patients with AHF, we identified 4 groups of patients: AF at admission and in-hospital conversion to sinus rhythm (n = 44); in-hospital development of AF (n = 31); persistent AF (n = 278); and continuous sinus rhythm (n = 410)., Results: Conversion from AF to sinus rhythm (13.7%) and from sinus rhythm to AF (7.0%) occurred only in a minority of patients. Patients with AF who converted to sinus rhythm were more often classified as being in New York Heart Association class IV, had higher heart rates and higher respiratory rates at hospital admission, whereas patients who developed AF were older, more likely to be female and had the highest ejection fractions compared to continuous sinus rhythm (all P < 0.05). Conversion to sinus rhythm or development of AF occurred mainly within the first 24 hours after hospital admission. Patients with persistent AF and those who developed AF had longer median lengths of hospital stay (8 vs 7 days; P < 0.001 and 9 vs 7 days; P < 0.001, respectively), compared to those with continuous sinus rhythm. In both univariable and multivariable analyses, there was no significant association between the AF groups and the primary clinical outcomes of either 180-day all-cause mortality or 60-day death or readmission for heart failure., Conclusion: In patients hospitalized for AHF, only few converted from AF to sinus rhythm or sinus rhythm to AF. Although development of AF or persistent AF was associated with longer lengths of hospitalization, midterm mortality and readmission rates were similar in the groups., Competing Interests: Disclosures The employer of AAV received consultancy fees and research support from Anacardio, AstraZeneca, BMS, Boehringer Ingelheim, Bayer AG, Cytokinetics, Corteria, EliLilly, Merck, Moderna, Novartis, NovoNordisk, Sphingotec, and Roche Diagnostics, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Serum bone morphogenetic protein 10 (BMP10) blood levels are a marker for history of atrial fibrillation (AF) and for major adverse cardiovascular events in patients with AF, including stroke, AF recurrences after catheter ablations, and mortality. The predictive value of BMP10 in patients undergoing cardiac surgery and association with morphologic properties of atrial tissues are unknown., Objectives: This study sought to study the correlation between BMP10 levels and preoperative clinical traits, occurrence of early and late postoperative atrial fibrillation (POAF), and atrial fibrosis in patients undergoing cardiac surgery., Methods: Patients with and without preoperative AF history undergoing first cardiac surgery were included (RACE V, n = 147). Preoperative blood biomarkers were analyzed, left (n = 114) and right (n = 125) atrial appendage biopsy specimens were histologically investigated after WGA staining, and postoperative rhythm was monitored continuously with implantable loop recorders (n = 133, 2.5 years)., Results: Adjusted multinomial logistic regression indicated that BMP10 accurately reflected a history of persistent AF (OR: 1.24, 95% CI: 1.10-1.40, P = 0.001), similar to NT-pro-BNP. BMP10 levels were associated with increased late POAF 90 occurrence after adjustment for age, sex, AF history, and early POAF occurrence (HR: 1.07 [per 0.1 ng/mL increase], 95% CI: 1.00-1.14, P = 0.041). Left atrial endomysial fibrosis (standardized β = 0.22, P = 0.041) but not overall fibrosis (standardized Β = 0.12, P = 0.261) correlated with circulating BMP10 after adjustment for age, sex, AF history, reduced LVF, and valvular surgery indication., Conclusions: Increased BMP10 levels were associated with persistent AF history, increased late POAF incidence, and LAA endomysial fibrosis in a diverse sample of patients undergoing cardiac surgery., Competing Interests: Funding Support and Author Disclosures Supported by Netherlands Heart Foundation (CVON2014-09, RACE V Reappraisal of Atrial Fibrillation: Interaction between hyper Coagulability, Electrical remodeling, and Vascular Destabilization in the Progression of AF); European Union’s Horizon 2020 research and innovation programmed under grant agreement No 965286. Dr Schotten has received consultancy fees or honoraria from Universitas' della Svizzera Italiana, Roche Diagnostics, EP Solutions Inc, Johnson & Johnson Medical Limited, and Bayer Healthcare, and is a cofounder and shareholder of Your Rhythmics BV, a spinoff company of the Maastricht University. 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.)

Aims: Obesity and epicardial adiposity play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), and both are associated with increased filling pressures and reduced exercise capacity. The haemodynamic basis for these observations remains inaccurately defined. We hypothesize that an abundance of epicardial adipose tissue (EAT) within the pericardial sac is associated with haemodynamic signs of pericardial constraint., Methods and Results: HFpEF patients who underwent invasive heart catheterization with simultaneous echocardiography were included. Right atrial pressure (RAP), right ventricular end-diastolic pressure, and pulmonary capillary wedge pressure (PCWP) were invasively measured. The presence of a square root sign on the right ventricular pressure waveform and the RAP/PCWP ratio (surrogate parameters for pericardial constraint) were investigated. EAT thickness alongside the right ventricle was measured on echocardiography. Sixty-four patients were studied, with a mean age of 73 ± 10 years, 64% women, and a mean body mass index (BMI) of 28.6 ± 5.4 kg/m 2 . In total, 47 patients (73%) had a square root sign. The presence of a square root sign was associated with higher BMI (29.3 vs. 26.7 kg/m 2 , P = 0.02), higher EAT (4.0 vs. 3.4 mm, P = 0.03), and higher RAP (9 vs. 6 mmHg, P = 0.04). Women had more EAT than men (4.1 vs. 3.5 mm, P = 0.04), despite a comparable BMI. Women with a square root sign had significantly higher EAT (4.3 vs. 3.3 mm, P = 0.02), a higher mean RAP (9 vs. 5 mmHg, P = 0.02), and a higher RAP/PCWP ratio (0.52 vs. 0.26, P = 0.002). In men, such associations were not seen, although there was no significant interaction between men and women (P > 0.05 for all analyses)., Conclusions: Obesity and epicardial adiposity are associated with haemodynamic signs of pericardial constraint in patients with HFpEF. The pathophysiological and therapeutic implications of this finding need further study., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery that is associated with late atrial fibrillation (AF) recurrences (late-POAF) and increased morbidity and long-term mortality., Objectives: This study sought to determine device-detected POAF incidence and to identify clinical variables associated with POAF, both in patients with and without preoperative AF history., Methods: A total of 133 consecutive patients undergoing cardiac surgery were prospectively enrolled and continuously monitored with an implantable loop recorder for 2.5 years after surgery. Preoperative transthoracic echocardiography, 12-lead electrocardiogram, blood biomarkers, and clinical data were analyzed to develop prediction models for early- and late-POAF., Results: In patients without preoperative AF history, early-POAF within the first 90 postoperative days occurred in 41 (47.1%) of 87 patients. Late-POAF after the first 90 postoperative days occurred in 22 (25%) of 87 patients, and 20 of these patients also had early-POAF during the first 90 days (20 of 22 [91%]). Increased right atrial minimum volume indexed for body surface area (RAVI min ) and early-POAF were independently associated with late-POAF. A prediction model for late-POAF, which included RAVI min >11 mL/m 2 , age >65 years, and early-POAF, achieved an area under the curve of 0.82 (95% CI: 0.72-0.92). For patients with preoperative AF-history, late-POAF recurrences were frequent (22 of 33 [67%]). Increased RAVI min was independently associated with a higher incidence of late-POAF., Conclusions: In patients with and without AF history, late-POAF recurrences are frequent, including in patients undergoing surgical AF ablation. In patients with no history of AF, late-POAF might be predicted with excellent accuracy by using a combination of preoperative variables. In patients with a history of AF, signs of advanced AF substrate (eg, increased right atrial volumes) were associated with long-term AF recurrences. [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF; NCT03124576]., Competing Interests: Funding Support and Author Disclosures This work was supported by the Netherlands Heart Foundation (CVON2014-09, RACE V [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF]; and grant number 01-002-2022-0118, EmbRACE [Electro-Molecular Basis and the Therapeutic management of Atrial Cardiomyopathy, Fibrillation and Associated Outcomes]), the European Union (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network, grant number 860974; CATCH ME [Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly], grant number 633196; and MAESTRIA [Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation], grant number 965286). Dr Schotten has received consultancy fees or honoraria from Università della Svizzera Italiana, Roche Diagnostics, EP Solutions Inc, Johnson & Johnson Medical Limited, and Bayer Healthcare; and is co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht. 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: In patients with an implantable cardioverter-defibrillator (ICD) for secondary prevention, sex differences may exist in clinical outcomes. We sought to investigate sex differences in appropriate ICD therapy, appropriate and inappropriate shock, and all-cause mortality in this patient population. Methods: A total of 257 patients who received an ICD for a secondary prevention indication in the University Medical Centre Groningen (UMCG) between 1 January 2012 and 31 December 2018 were retrospectively included in a consecutive manner. Appropriate ICD therapy, comprising shock and antitachycardia pacing (ATP) for ventricular fibrillation (VF) or ventricular tachycardia (VT), was the primary outcome. Results: The patient population included 257 patients, of whom 45 (18%) were women and 212 (82%) were men. The median of the age was 64 (interquartile range (IQR) 53-72) years. During follow-up (median duration 6.2 (IQR 4.8-7.8) years), first appropriate device therapy took place in 10 (22%) patients for women and 85 (40%) patients for men. Female sex was negatively associated with the rate of appropriate ICD therapy, univariably (hazard ratio (HR) 0.48 [95% confidence interval (CI) 0.25-0.93]; p = 0.030) and multivariably (HR 0.44 [95% CI 0.20-0.95]; p = 0.036). Conclusions: Women with secondary prevention ICDs were less likely than men to receive appropriate ICD therapy.

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA)., Methods and Results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF., Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF., Competing Interests: Conflict of interest The 9th AFNET/EHRA consensus conference was partially supported by the European Union MAESTRIA project (grant agreement 965286) to AFNET. The following participants and authors are employees of companies active in cardiovascular health as indicated in their affiliations: M.D.M., E.D., C.E., G.H., L.H.H., T.H., R.H.v.L., M.W., and H.W. P.K. was partially supported by the European Union AFFECT-AF (grant agreement 847770) and MAESTRIA (grant agreement 965286), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers DZHK FKZ 81X2800182, 81Z0710116, and 81Z0710110), German Research Foundation (Ki 509167694), and Leducq Foundation. He receives research support for basic, translational, and clinical research projects from several drug and device companies active in AF and has received honoraria from several such companies in the past, but not in the last 3 years. He is listed as an inventor on two issued patents held by the University of Hamburg (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). J.G.A. was partially supported by the Canadian Arrhythmia Network and the Michael Smith Foundation for Health Research, Baylis Medical. He receives consulting fees/honoraria from Bayer, BMS/Pfizer Alliance, Servier, and Medtronic Inc. E.A. receives consulting fees/honoraria from Biosense Webster and Bayer. G.B. receives consulting fees/honoraria from Bayer, BMS, Boston Scientific, Daiichi Sankyo, Sanofi, and Janssen. A.J.C. receives consulting fees/honoraria from Bayer, Pfizer/BMS, Daiichi Sankyo, Menarini, Sanofi, Boston Scientific, Biosense Webster, Abbott, Acesion Pharma, Huya Bio, and Milestone. V.C. receives consulting fees/honoraria from Bayer, Boehringer Ingelheim, and Ever Pharma (paid to the institution of employment). W.D. receives consulting fees/honoraria from Reata and research grants from MicroPort, Boston Scientific, and Abbott. S.Z.D. receives consulting fees from BMS/Pfizer, Cortrium, and Acesion Pharma and speaker fees from MS/Pfizer and Bayer. He is listed as a medical advisor for Vital Beats. Dobromir D. receives consulting fees/honoraria from Elsevier, Springer Healthcare Ltd, and Daiichi Sankyo and research grants as follows: four NIH grants (partially) from Baylor College of Medicine, Houston; one NIH grant from UC Davis, one NIH grant from the University of Minnesota, and one EU-Project H2020. David D. receives consulting fees/honoraria from Abbott, Astra Zeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS/Pfizer, CVRx, Medtronic, MicroPort, and Zoll and research grants from Roche, CVRx, and Zoll. L.E. has received lecture fees from various companies in AF in the past but none related to the present work. L.F. receives consulting fees/honoraria from Roche (paid to the institution of employment). She is currently employed at the UKE and previously at the University of Birmingham. She was partially supported by the European Union AFFECT-EU (grant agreement 847770), MAESTRIA (grant agreement 965286), CATCH ME (grant agreement 633196), and the British Heart Foundation (AA/18/2/3218). D.F.-R. receives research grants from Abbott. He is listed as an inventor on two issued patents: EP3636147A1 (method for the identification of cardiac fibrillation drivers and/or the footprint of rotational activations) and PCT/EP2022/071364 (system and method of assessment of electromechanical remodelling). A.G. receives consulting fees/honoraria from Daiichi Sankyo, Bayer, BMS/Pfizer, Medtronic, Abbott, and Boston Scientific and was partially supported by the European Union MAESTRIA (grant agreement 965286). K.G.H. receives consulting fees/honoraria from Abbott, Alexion, Amarin, Astra Zeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS/Pfizer, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novaris, Portola, Premier Research, Sanofi, SUN Pharma, and W. L. Gore and Associates. J.S.H. receives speaking fees from BMS/Pfizer, Bayer, Servier, and Boston Scientific and consulting fees from Bayer and Boston Scientific. He receives research grants from BMS/Pfizer, Servier, Novartis, Boston Scientific, and Medtronic. H.H. receives lecture and consulting fees from Bayer, Biotronik, BMS/Pfizer, Daiichi Sankyo, Milestone Pharmaceuticals, Centrix India, C.T.I. Germany, ESC, Medscape, and Springer Healthcare Ltd. He receives research grants (paid to the institution of employment, University of Antwerp and/or University of Hasselt) from Abbott, Bayer, Biosense Webster, Boston Scientific, Daiichi Sankyo, Fibricheck/Qompium, Medtronic, and BMS/Pfizer. Z.H. receives consulting fees/honoraria from Boehringer Ingelheim, BMS/Pfizer, and Roche Diagnostics. He was partially supported by The Swedish Society for Medical Research (S17-0133), Hjärt-Lungfonden (The Swedish Heart-Lung Foundation, 20200722), and the institution he is currently employed at (Uppsala University Hospital). L.H.-M. receives research grants from the Spanish Ministry of Science and Innovation (PID2020-116927RB-C21) and Fondo Europeo de Desarrollo Regional (FEDER). D.K. receives consulting fees/honoraria from Bayer, Amomed, and Protherics Medicines Development. He receives research grants from the National Institute for Health Research (NIHR CDF-2015-08-074 RAE-AF; NIHR130280 DaRe2THINK; NIHR13274 D2T-NeuroVascular; and NIHR203326 Biomedical Research Centre), the British Heart Foundation (PG/17/55/33087, AA/182/3218, and FS/CDRF/21/21032), the EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074), EU Horizon and UKRI (HYPERMARKER 101095480) UK National Health Service—Data for R&D-Subnational Secure Data Environment programme, UK Department for Business, Energy Industrial Strategy Regulators Pioneer Fund, the Cook & Wolstenholme Charitable Trust, and the European Society of Cardiology supported by educational grants from Boehringer Ingelheim, BMS/Pfizer, Alliance, Bayer, Daiichi Sankyo, Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre, and the British Hear Foundation, the University of Birmingham Accelerator Award (STEEER-AF). J.L.M. receives consulting fees/honoraria from Biotronik, Medtronic, MicroPort, and Milestone Pharmaceuticals. A.M. receives consulting fees/honoraria from Medtronic, Biosense Webster, and Boston Scientific and lecture fees from Medtronic, Boston Scientific, Biosense Webster, BMS, and Bayer. L.M. receives consulting fees/honoraria from Abbott, Medtronic, Boston Scientific, and Johnson & Johnson. G.A.N. receives lecture fees from AliveCor, consultant fees from Biosense Webster, and research grants from Abbott and Biosense Webster. H.P. receives consulting fees/honoraria from Abbott, Boston Scientific, Biosense Webster, Medtronic, Daiichi Sankyo, Bayer, and Pfizer. P.S. receives consulting fees/honoraria from Medtronic, Boston Scientific, Abbott, CathRx, and PaceMate (paid to the institution of employment). He is currently employed at the University of Adelaide, which receives research grants from Medtronic, Boston Scientific, and Becton-Dickenson. R.B.S. receives consulting fees/honoraria from BMS/Pfizer. She was partially supported by the European Union Horizon 2020 research and innovation programme (grant agreement 648131 and 847770), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers 81Z1710103 and 81Z0710114), German Ministry of Research and Education (BMBF 01ZX1408A), ERACoSysMed3 (031L0239), Wolfgang Seefried project funding German Heart Foundation. U.S. receives consulting fees/honoraria from University Svizzerra Italiana, Stanford, and Johnson & Johnson and research grants from the European Union, Dutch Heart Foundation, Roche, and EP Solution. He is a shareholder of YourRhythmics B.V. T.T. receives consulting fees/honoraria from Boston Scientific and Medtronic. I.C.v.G. receives consulting fees/honoraria from Bayer (paid to the institution of employment). She is currently employed at the University of Groningen. K.V. receives consulting fees/honoraria from Abbott, Philips, Medtronic, Biosense Webster, and Boston Scientific and research grants from Medtronic and Biosense Webster. R.W. receives consulting fees/honoraria from Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Boston Scientific, Biotronik, Abiomed, and Zoll and a research grant from Boston Scientific, BMS/Pfizer, and Abiomed. S.W. receives consulting fees/honoraria from Boehringer Ingelheim, Boston Scientific, Abbott, and Bayer Vital and a research grant from Boston Scientific. All remaining authors (G.B., J.C.N., T.D.P., N.D., M.F., E.G., S.H., S.K., D.L., K.M.-R., M.O., A.S.P., U.R., M.R., D.S., C.S., G.S., D.S., S.T., R.H.v.L., and S.Z.) have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

There is an escalating trend in both the incidence and prevalence of atrial fibrillation (AF). AF is linked to numerous other comorbidities, contributing to the emergence of multimorbidity. The sustained rise in multimorbidity and AF prevalences exerts a significant strain on healthcare systems globally. The understanding of the relation between multimorbidity and AF is essential to determine effective healthcare strategies, improve patient outcomes to adequately address the burden of AF. It not only begins with the accurate identification of comorbidities in the setting of AF. There is also the need to understand the pathophysiology of the different comorbidities and their common interactions, and how multimorbidity influences AF perpetuation. To manage the challenges that rise from the increasing incidence and prevalence of both multimorbidity and AF, such as adverse events and hospitalisations, the treatment of comorbidities in AF has already gained importance and will need to be a primary focus in the forthcoming years. There are numerous challenges to overcome in the treatment of multimorbidity in AF, whereby the identification of comorbidities is essential. Integrated care strategies focused on a comprehensive multimorbidity management with an individual-centred approach need to be determined to improve healthcare strategies and reduce the AF-related risk of frailty, cardiovascular diseases and improve patient outcomes., Competing Interests: Competing interests: The authors disclosed the following financial support: MR reports unrestricted grants from ZonMW, the Dutch Heart Foundation; DECISION project 848090001, the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation; RACE V (CVON 2014–9), RED-CVD (CVON2017-11) and the Top Sector Life Sciences & Health to the Dutch Heart Foundation (PPP Allowance; CVON-AI (2018B017). ICVG reports grants from the Dutch Heart Foundation (CVON RACE V, grant 2014-09). The UMCG, which employs MR, has received consultancy fees from Bayer and InCarda Therapeutics. All the other 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.)

Objective: The study objective was to examine associations of relative fat mass (RFM) and BMI with all-cause mortality in the Dutch general population and to investigate whether additional adjustment for muscle mass strengthened these associations., Methods: A total of 8433 community-dwelling adults from the PREVEND general population cohort (1997-1998) were included. Linear regression models were used to examine associations of RFM and BMI with 24-h urinary creatinine excretion, a marker of total muscle mass. Cox regression models were used to examine associations of RFM and BMI with all-cause mortality., Results: The mean age of the cohort was 49.8 years (range: 28.8-75.7 years), and 49.9% (n = 4209) were women. In age- and sex-adjusted models, both RFM and BMI were associated with total muscle mass (24-h urinary creatinine excretion), and these associations were stronger with BMI (standardized beta [Sβ] RFM : 0.29; 95% CI: 0.27-0.31 vs. Sβ BMI : 0.38; 95% CI: 0.36-0.40; p difference  < 0.001). During a median follow-up period of 18.4 years, 1640 deaths (19.4%) occurred. In age- and sex-adjusted models, RFM was significantly associated with all-cause mortality (hazard ratio per 1-SD [HR RFM ]: 1.16; 95% CI: 1.09-1.24), whereas BMI was not (HR BMI : 1.04; 95% CI: 0.99-1.10). After additional adjustment for muscle mass, associations of both RFM and BMI with all-cause mortality increased in magnitude (HR RFM : 1.24; 95% CI: 1.16-1.32 and HR BMI : 1.12; 95% CI: 1.06-1.19). Results were broadly similar in multivariable adjusted models., Conclusions: In the general population, a higher RFM was significantly associated with mortality risk, whereas a higher BMI was not. Adjusting for total muscle mass increased the strength of associations of both RFM and BMI with all-cause mortality., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Atrial fibrillation (AF) is often associated with limiting symptoms, and with significant impairment in quality of life. As such, treatment strategies aimed at symptom control form an important pillar of AF management. Such treatments include a wide variety of drugs and interventions, including, increasingly, catheter ablation. These strategies can be utilised either singly or in combination, to improve and restore quality of life for patients, and this review covers the current evidence base underpinning their use. In this Review, we discuss the pros and cons of rate vs. rhythm control, while offering practical tips to non-specialists on how to utilise various treatments and counsel patients about all relevant treatment options. These include antiarrhythmic and rate control medications, as well as interventions such as cardioversion, catheter ablation, and pace-and-ablate., Competing Interests: DG reports: institutional research grants from Biosense Webster, Boston Scientific and Medtronic, and speaker fees from Boston Scientific., (© 2023 The Author(s).)

Background: Progressive cardiovascular diseases (eg, heart failure, atrial fibrillation, and coronary artery disease) are often diagnosed late in high-risk individuals with common comorbidities that might mimic or mask symptoms, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes. We aimed to assess whether a proactive diagnostic strategy consisting of a symptom and risk factor questionnaire and low-cost and accessible tests could increase diagnosis of progressive cardiovascular diseases in patients with COPD or type 2 diabetes in primary care., Methods: In this multicentre, pragmatic, cluster-randomised, controlled trial (RED-CVD), 25 primary care practices in the Netherlands were randomly assigned to usual care or a proactive diagnostic strategy conducted during routine consultations and consisting of a validated symptom questionnaire, followed by physical examination, N-terminal-pro-B-type natriuretic peptide measurement, and electrocardiography. We included adults (≥18 years) with type 2 diabetes, COPD, or both, who participated in a disease management programme. Patients with an established triple diagnosis of heart failure, atrial fibrillation, and coronary artery disease were excluded. In the case of abnormal findings, further work-up or treatment was done at the discretion of the general practitioner. The primary endpoint was the number of newly diagnosed cases of heart failure, atrial fibrillation, and coronary artery disease, adjudicated by an expert clinical outcome committee using international guidelines, at 1-year follow-up, in the intention-to-treat population., Findings: Between Jan 31, 2019, and Oct 7, 2021, we randomly assigned 25 primary care centres: 11 to usual care and 14 to the intervention. We included patients between June 21, 2019, and Jan 31, 2022. Following exclusion of ineligible patients and those who did not give informed consent, 1216 participants were included: 624 (51%) in the intervention group and 592 (49%) in the usual care group. The mean age of participants was 68·4 years (SD 9·4), 482 (40%) participants were female, and 734 (60%) were male. During 1 year of follow-up, 50 (8%) of 624 participants in the intervention group and 18 (3%) of 592 in the control group were newly diagnosed with heart failure, atrial fibrillation, or coronary artery disease (adjusted odds ratio 2·97 [95% CI 1·66-5·33]). This trial is registered with the Netherlands Trial Registry, NTR7360, and was completed on Jan 31, 2023., Interpretation: An easy-to-use, proactive, diagnostic strategy more than doubled the number of new diagnoses of heart failure, atrial fibrillation, and coronary artery disease in patients with type 2 diabetes or COPD in primary care compared with usual care. Although the effect on patient outcomes remains to be studied, our diagnostic strategy might contribute to improved early detection and timely initiation of treatment in individuals with cardiovascular disease., Funding: Dutch Heart Foundation., Competing Interests: Declaration of interests RAdB has received research grants from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals, Novo Nordisk, and Roche; has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche; has received honoraria from Abbott, AstraZeneca, Bristol Myers Squibb, Cardior Pharmaceuticals, NovoNordisk, and Roche; and has received travel support from Abbott, Cardior Pharmaceuticals, and NovoNordisk. FHR received a single fee from Novartis for speaker engagements in 2022. MR received consultancy fees from Bayer, Microport, and InCarda Therapeutics to the Department of Cardiology, UMC Groningen. All other authors 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: In the Rate Control versus Electrical Cardioversion Trial 7-Acute Cardioversion versus Wait and See, patients with recent-onset atrial fibrillation (AF) were randomized to either early or delayed cardioversion., Aim: This prespecified sub-analysis aimed to evaluate heart rate during AF recurrences after an emergency department (ED) visit identified by an electrocardiogram (ECG)-based handheld device., Methods: After the ED visit, included patients (n = 437) were asked to use an ECG-based handheld device to monitor for recurrences during the 4-week follow-up period. 335 patients used the handheld device and were included in this analysis. Recordings from the device were collected and assessed for heart rhythm and rate. Optimal rate control was defined as a target resting heart rate of <110 beats per minute (bpm)., Results: In 99 patients (29.6%, mean age 67 ± 10 years, 39.4% female, median 6 [3-12] AF recordings) a total of 314 AF recurrences (median 2 [1-3] per patient) were identified during follow-up. The average median resting heart rate at recurrence was 100 ± 21 bpm in the delayed vs 112 ± 25 bpm in the early cardioversion group (p = .011). Optimal rate control was seen in 68.4% [21.3%-100%] and 33.3% [0%-77.5%] of recordings (p = .01), respectively. Randomization group [coefficient -12.09 (-20.55 to -3.63, p = .006) for delayed vs. early cardioversion] and heart rate on index ECG [coefficient 0.46 (0.29-0.63, p < .001) per bpm increase] were identified on multivariable analysis as factors associated with lower median heart rate during AF recurrences., Conclusion: A delayed cardioversion strategy translated into a favorable heart rate profile during AF recurrences., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)