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Na Li,1 Liufu Cui,1 Gary Tse,2,3 Panagiotis Korantzopoulos,4 Konstantinos P Letsas,5 George Bazoukis,6,7 Shuohua Chen,8 Nan Zhang,2 Xuemei Yang,9 Peipei Liu,10 Lili Wu,11 Gan-Xin Yan,12,13 Gregory Yoke Hong Lip,14,15 Shouling Wu,8 Tong Liu2 1Department of Rheumatology and Immunology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 4First Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece; 5Arrhythmia Unit, Laboratory of Cardiac Pacing and Electrophysiology, Onassis Cardiac Surgery Center, Athens, Greece; 6Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus; 7European University Cyprus, Medical School, Nicosia, Cyprus; 8Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China; 9School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 10School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, People’s Republic of China; 11Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 12Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA, USA; 13Department of Cardiology, Fuwai Huazhong Hospital, Zhengzhou, Henan Province, People’s Republic of China; 14Liverpool Centre for Cardiovascular Sciences, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; 15Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China, Email liutong@tmu.edu.cn; liutongdoc@126.com Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, People’s Republic of China, Email drwusl@163.comObjective: This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP.Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB.Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP.Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. Keywords: hyperuricemia, inflammation, cardiac conduction block, combined exposure, risk factors, mediation

Soonil Kwon,1,* So-Ryoung Lee,2,3,* Eue-Keun Choi,2,3 Kyung-Yeon Lee,2 JungMin Choi,2 Hyo-Jeong Ahn,2 Seil Oh,2,3 Gregory Yoke Hong Lip2– 5 1Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Chest & Heart Hospital, Liverpool, UK; 5Department of Clinical Medicine, Aalborg University, Aalborg, Denmark*These authors contributed equally to this workCorrespondence: Eue-Keun Choi, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-0688, Fax +82-2-762-9662, Email choiek17@snu.ac.krBackground: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks.Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk.Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events.Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk.Trial Registration: Clinicaltrials.gov: NCT05801068.Keywords: atrial fibrillation, direct factor Xa inhibitor, bleeding, oral anticoagulant, perioperative care

Hui Zhang,1 Zhigeng Jin,1 Hao Wang,2 Yutao Guo,1,3 Gregory YH Lip3,4 1Medical School of Chinese PLA, Department of Pulmonary Vessel and Thrombotic Disease, Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Cardiology, Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 4Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Yutao Guo, Department of Pulmonary Vessel and Thrombotic Disease, Six Medical Center, Chinese PLA General Hospital, 5 Fucheng Road, Beijing, 100048, People’s Republic of China, Email dor_guoyt@hotmail.comBackground: Guideline-recommended integrated care based on the ABC (Atrial fibrillation Better Care) pathway for “general” patients with atrial fibrillation (AF) improves clinical outcomes, as demonstrated in our prior mobile Atrial Fibrillation Application (mAFA)-II cluster randomized trial. The present study aims to investigate whether mAFA III-supported structured follow-up rehabilitation packages adapted to patient risk profiles and different treatment patterns (eg, for patients receiving drug treatment only, AF ablation, or left atrial appendage occlusion [LAAO]) will improve guideline adherence and reduce the risk of adverse cardiovascular events.Methods and Analysis: In this prospective, observational mAFA III pilot cohort study, patients with AF aged ≥ 18 years will be enrolled using the mAFA III App for self-management. Assuming an annual rate of composite outcome of “ischaemic stroke or systemic embolism, all-cause death and cardiovascular hospitalization” of 29.3% for non-ABC pathway compliance compared with 20.8% for ABC pathway compliance, at least 1475 patients would be needed to detect the outcome of the A, B and C components of the ABC pathway, assuming a withdrawal rate of 20% in the first year. The primary endpoint is adherence to guidelines regarding the A, B and C components of the ABC pathway. Ancillary analyses will be performed to determine the impact of the ABC pathway using smart technologies on the outcomes among the “high-risk” population (eg, ≥ 75 years old, with multimorbidities, with polypharmacy) and the application of artificial intelligence machine-learning AF risk prediction management in assessing AF recurrence. The individualised anticoagulants with AF burden will be monitored by smart devices.Trial Registration Number: ISRCTN13724416.Keywords: atrial fibrillation, rehabilitation, mobile health

Mingfang Li,1 Jiaojiao Shi,1 Ming Chu,1 Youmei Shen,1 Shimeng Zhang,1 Xingxing Sun,1 Hengli Zhang,1 Qing Yan,1 Jinlong Gong,2 Gregory YH Lip,3,4 Minglong Chen1,5 1Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Division of Cardiology, Jiangdu People’s Hospital, Yangzhou, People’s Republic of China; 3Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Division of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Minglong Chen, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-68303115, Fax +86-25-6813-6479, Email chenminglong@njmu.edu.cnAbstract: China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥ 65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1± 5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China.Keywords: atrial fibrillation, elderly, village doctors, rural China

Nicklas Vinter,1– 3 Pia Cordsen,3 Gregory YH Lip,4,5 Emelia J Benjamin,6 Søren Paaske Johnsen,3 Lars Frost,1,2 Ludovic Trinquart7– 9 1Diagnostic Centre, University Clinic for Development of Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Chest & Heart Hospital, Liverpool, UK; 5Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 6Department of Medicine, Boston University School of Medicine and Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 7Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA; 8Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA; 9Department of Biostatistics, Boston University School of Public Health, Boston, MA, USACorrespondence: Nicklas Vinter, Diagnostic Centre, University Clinic for Development of Innovative Patient Pathways, Silkeborg Regional Hospital, Falkevej 3, Silkeborg, 8600, Denmark, Tel +45 25321675, Email nicvin@rm.dkObjective: Prior work estimated excess death rates associated with atrial fibrillation (AF) in heart failure (HF) with hazard ratios (HR). The aim was to estimate the life-years lost after newly diagnosed AF in HF patients.Methods: Among patients diagnosed with HF in 2008– 2018 in the nationwide Danish Heart Failure Registry, we compared patients with incident AF to referents matched on age, sex, and time since HF. We estimated the marginal hazard ratio (HR) for death and marginal difference in restricted mean survival times (RMST) between AF cases and referents at 10 years after AF diagnosis. We adjusted for sex, age at AF diagnosis, clinical and lifestyle risk factors, and medications.Results: Among 4463 AF cases and 17,792 referents (mean age 73.7 years, 29% women), the HR was 1.41 (95% CI 1.38; 1.44) but there was evidence of non-proportional hazards. The difference in RMST was − 18.2 months (95% CI − 16.8; − 19.6) at 10 years after AF diagnosis. There were differences in life-years lost between patients diagnosed with AF > 1 year and ≤ 1 year after HF (− 25.7 months, 95% CI − 23.7; − 27.7 vs − 10.4 months, 95% CI − 8.2; − 12.5, p < 0.001), women and men (− 20.3 months, 95% CI − 17.7; − 21.9 vs − 17.2 months, 95% CI − 15.5; − 19.0, p = 0.05), patients with low, medium, and high CHA2DS2-VASc (10.3 months, 95% CI − 4.6; − 16.1 vs − 18.5 months, 95% CI − 16.7; − 20.4 vs 22.1, 95% CI − 18.8; − 22.3, p = 0.002).Conclusion: HF patients with incident AF lost on average 1.5 life-years over 10 years after AF. Life-years lost were larger among patients diagnosed with AF > 1 year after HF, women, and patients with higher CHA2DS2-VASc.Keywords: atrial fibrillation, heart failure, RMST, prognosis, mortality, sex

Stephanie L Harrison,1,2 Deirdre A Lane,1– 3 Benjamin JR Buckley,1,2 Kausik Chatterjee,4 Muath Alobaida,1,2,5 Emily Shipley,1,2 Gregory YH Lip1– 3 1Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK; 2Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK; 3Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Care of the Elderly Department, Countess of Chester Hospital NHS Foundation Trust, Chester, UK; 5Department of Basic Science, Prince Sultan Bin Abdulaziz College for Emergency Medical Services, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Stephanie L Harrison, Liverpool Centre for Cardiovascular Science, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK, Email stephanie.harrison@liverpool.ac.ukAbstract: Further research is needed to refine risk prediction models for adverse cardiovascular outcomes following stroke in contemporary clinical practice, such as incident atrial fibrillation (AF), recurrent stroke, and cognitive impairment and dementia. The aims of this study are to prospectively investigate cardiovascular outcomes and risk factors for incident cardiovascular disease in a post-stroke cohort, and to externally validate, refine and expand current risk prediction models for cardiovascular and cardiovascular-related outcomes. The study sample size was based on the development of post-stroke risk prediction models for AF and was calculated as 1222 participants. The study design is a multicentre, prospective, observational cohort study. Participants will be adult patients admitted for ischaemic stroke confirmed by stroke physician or transient ischaemic attack (TIA) confirmed by MRI. Routinely collected data will be used in addition to the completion of simple validated questionnaires by the participants. Follow-up will be undertaken 12-months from the date of admission to hospital, in addition to linkage to routinely collected follow-up hospitalisation and mortality data. The primary outcomes are cardiovascular outcomes (including incident AF, stroke, TIA and myocardial infarction) at 12-month follow-up, all-cause mortality and mortality from cardiovascular causes, and incident cognitive impairment and dementia. Secondary outcomes include changes in function, depression, anxiety, fatigue and quality of life. The study has received approval from the Health Research Authority Research Ethics Committee (21/WA/0209), and is registered on https://www.clinicaltrials.gov/ (Identifier NCT05132465). Recruitment for the study began in October 2021 with completion of recruitment at all participating centres anticipated by October 2022.Keywords: stroke, risk prediction, epidemiology, cohort study

Rungroj Krittayaphong,1 Satchana Pumprueg,1 Kasem Ratanasumawong,2 Poom Sairat,1 Gregory YH Lip3,4 On behalf of the COOL-AF Investigators1Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2Police General Hospital, Bangkok, Thailand; 3Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 4Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Rungroj KrittayaphongDivision of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandTel +66 2-419-6104Email rungroj.kri@mahidol.ac.thPurpose: Hypertension is associated with incident atrial fibrillation (AF) and AF-related complications. We investigated the associations between average systolic blood pressure (SBP) and outcomes in a nationwide cohort of Asian patients with non-valvular atrial fibrillation (NVAF).Patients and Methods: A multicenter nationwide registry of patients with NVAF in Thailand was conducted during 2014– 2017. Clinical data, including blood pressure, were recorded at baseline and then every 6 months. Average SBP was calculated from the average of SBP from every visit. Cox regression models were used to calculate the rate of clinical outcomes of interest, ie ischemic stroke or transient ischemic attack (TIA), intracerebral hemorrhage (ICH), and all-cause death. Average SBP was categorized into three groups: < 120, 120– 140, and ≥ 140 mmHg.Results: A total of 3402 patients were included, and the mean age was 67.4± 11.3 years. The mean (±SD) baseline and average SBPs were 128.5± 18.5 and 128.0± 13.4 mmHg, respectively. The mean follow-up duration was 25.7± 10.6 months. The median rate of ischemic stroke/TIA, ICH, and all-cause death was 1.43 (1.17– 1.74), 0.70 (0.52– 0.92), and 3.77 (3.33– 4.24) per 100 person-years, respectively. The rate of ischemic stroke/TIA and ICH was lowest in patients with average SBP < 120 mmHg, and highest among those with average SBP ≥ 140 mmHg. The death rates were consistent with a J-curve effect, being lowest in patients with an average SBP 120– 140 mmHg. Sustained SBP control is more important than the SBP from a single visit.Conclusion: Sustained control of SBP was significantly associated with a reduction in adverse clinical outcomes in patients with NVAF.Keywords: atrial fibrillation, ischemic stroke, intracerebral hemorrhage, blood pressure, hypertension

Agnieszka Kotalczyk,1,2 Zbigniew Kalarus,2 David Justin Wright,1 Giuseppe Boriani,3 Gregory Y H Lip1,2 1Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK; 2Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Medical University of Silesia, Silesian Centre for Heart Diseases, Zabrze, Poland; 3Cardiology Division, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, ItalyCorrespondence: Gregory Y H Lip Email gregory.lip@liverpool.ac.ukAbstract: Cardiovascular implantable electronic devices (CIEDs) are essential management options for patients with brady- and tachyarrhythmias or heart failure with concomitant optimal pharmacotherapy. Despite increasing technological advances, there are still gaps in the management of CIED patients, eg, the growing number of lead- and pocket-related long-term complications, including cardiac device–related infective endocarditis, requires the greatest care. Likewise, patients with CIEDs should be monitored remotely as a part of a comprehensive, holistic management approach. In addition, novel technologies used in smartwatches may be a convenient tool for long-term atrial fibrillation (AF) screening, especially in high-risk populations. Early detection of AF may reduce the risk of stroke and other AF-related complications. The objective of this review article was to provide an overview of novel technologies in cardiac rhythm–management devices and future challenges related to CIEDs.Keywords: cardiovascular implantable electronic devices, CIEDs, pacemaker, implantable cardioverter–defibrillator, cardiac resynchronization therapy, remote monitoring, wearable technology

Hani Essa, 1 Rajiv Sankaranarayanan, 1, 2 Gregory YH Lip 1, 3 1Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, Liverpool, UK; 2Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; 3Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Gregory YH Lip Email gregory.lip@liverpool.ac.ukHippocrates, the father of medicine, first recognised stroke 2400 years ago after noting that occlusion of the carotid arteries caused loss of consciousness.1 In the twenty-first century, stroke is ranked as the second leading cause of death with an estimated mortality of around 5.5 million in 2016.2 Additionally, over 50% of stroke survivors suffer chronic disability.3 Heart failure (HF) is a global cause of morbidity and mortality with an estimated 40 million cases in 2015.4 Long-term multi-system complications of HF (Figure 1) and multimorbid disease interactions are of increasing importance and demand a multidisciplinary approach. The prevalence of both stroke and HF is expected to increase due to an ageing population.5,6 It has thus far proven difficult to elucidate the strength of the association between HF and stroke.

Background: Although atrial fibrillation (AF) is accepted as the most common sustained cardiac arrhythmia, most published epidemiologic studies focus on predominantly white populations in North America or Europe, and information on AF in nonwhite populations is scarce. The objective of this study was to undertake a systematic review of the published literature on the epidemiology of AF in other regions.Methods: Systematic literature searches (MEDLINE; 1990-2010) identified epidemiologic studies reporting on the prevalence or incidence of AF, stroke in AF, risk factors for AF, or the use of antithrombotic therapy in countries outside North America and Europe. This report presents a descriptive analysis of the data; no meta-analysis was planned.Results: Many of the 38 articles identified were from the Far East, although Australia, New Zealand, the Middle East, and South America were also represented. The reported prevalence of AF varied among countries, with different ranges in community- and hospital-based studies (0.1%-4% and 2.8%-14%, respectively). The use of anticoagulant therapy varied widely among countries and studies, as did the reported prevalence of stroke in patients with AF (2.8%-24.2%).Conclusions: High-quality epidemiologic studies are clearly required to improve understanding of the worldwide burden of AF and stroke in AF. Major improvements in the provision of thromboprophylaxis are also needed in many countries, given the high proportion of untreated patients who are, hence, at risk of stroke. [ABSTRACT FROM AUTHOR]

Aims: To compare the quality of life (QoL) of those in atrial fibrillation (AF) aged 75 years and over with that of the general population, to explore what factors affect the QoL of those with AF, and to assess the sensitivity of the EuroQol (EQ-5D) and Short-Form 12 (SF-12) generic health questionnaires in detecting differences in health status in those with AF in this age group. Methods and Results: The study population was 1762 men and women aged 75 years and over with confirmed AF who attended a randomization clinic for the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a primary care based trial of stroke prevention. Patients self-completed the EQ-5D and SF-12 questionnaires, and a simple measure of disability (Rankin). Cardiovascular co-morbidities were collected and number of drugs used as an additional proxy for co-morbidity. Quality-of-life outcomes were compared with general population samples of the same age. On multiple regression, female gender, greater medication use, and disability were independently associated with lower QoL scores in AF. Those in AF with a Rankin score ≥2 had lower QoL scores, while those with a Rankin score <2 had higher scores than the general population. Increasing co-morbidity was associated with reduced QoL scores, with the EQ-5D and SF-12 Physical Component Score showing similar sensitivity to these associations, and the SF-12 Mental Component Score showing less sensitivity. Conclusion: In the absence of co-morbidity, chronic AF has little impact on generic QoL in an elderly non-acutely ill population. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this EP wire is to examine clinical practice in the field of out-of-hospital cardiac arrest (OHCA) management, with special focus on in-hospital diagnostic and therapeutic strategies. Methods and Results: Fifty-three European centres, all members of the EHRA-EP Research network, completed the questions of the survey. A dedicated strategy for OHCA management is active in 85% of the centres. Shockable tachyarrhythmias such as initial OHCA rhythm are reported in >70% of the patients in 64% of the centres. In-hospital therapeutic hypothermia was applied in >50% of the patients in 53% of the centres and in <50% in 47% of the centres. In the year 2011 90% of the centres performed >10 primary percutaneous coronary angioplasties (PCI) in OHCA patients. The survival rate, when the initial documented rhythm was shockable, was >30% in 42% of the centres, and conversely, was significantly lower when asystole or pulseless electrical activity was the initial rhythm. A favourable neurological recovery was reported in >50% of the patients in 13 (26%) centres and in 21-50% of the patients in 21 (44%). Conclusions: This EP wire survey demonstrates a favourable implementation in OHCA of an invasive management strategy, including coronary angiography/PCI and implantable cardioverter defibrillator therapy, while therapeutic hypothermia appears to be underused. [ABSTRACT FROM AUTHOR]

Background: Lone atrial fibrillation (AF) has been suggested to have a favorable long-term prognosis. Significant interest has been directed at factors predicting arrhythmia progression, and the HATCH score (hypertension, age ≥ 75 years, transient ischemic attack or stroke [2 points], COPD, and heart failure [2 points]) recently has been proposed as a predictive score for AF progression. We investigated long-term outcomes in a large cohort of newly diagnosed lone AF and whether progression from paroxysmal to permanent AF confers an adverse impact on outcomes, including stroke and thromboembolism.Methods: The study was an observational cohort of 346 patients with newly diagnosed lone AF with a mean follow-up of 12.1 ± 7.3 years.Results: Baseline paroxysmal AF was confirmed in 242 patients, and of these, 65 (26.9%) subsequently experienced progression to permanent AF. Older age and development of congestive heart failure during follow-up were the multivariate predictors of AF progression (both P < .01), which was documented in 19.8% of patients with a HATCH score of 0 vs 63.2% with a score of 2 (P < .001), although the predictive validity of the HATCH score per se was modest (C statistic, 0.6). The annual rate of thromboembolism and heart failure during follow-up were low (0.4% each), and five patients (1.4%) died. AF progression, development of cardiac diseases, and older age were multivariate predictors of adverse outcomes, including thromboembolism (all P < .05). Baseline CHADS(2) (congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack) score was not predictive for thromboembolism (C statistic, 0.50; 95% CI, 0.31-0.69).Conclusions: This 12-year follow-up study provides confirmatory evidence of a generally favorable prognosis of lone AF, but adverse outcomes (including stroke and thromboembolism) are significantly influenced by age and the (new) development of underlying heart disease. Arrhythmia progression in lone AF is a marker of increased risk for adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. [ABSTRACT FROM AUTHOR]

Background: According to the latest European guidelines on the management of nonvalvular atrial fibrillation (NVAF), all patients aged ≥ 65 years should be treated with oral anticoagulation (if not contraindicated). Therefore, stroke risk factors should be investigated exclusively in patients with NVAF aged < 65 years.Methods: Patients diagnosed with NVAF in a four-hospital institution between 2000 and 2010 were identified. Event rates of stroke/thromboembolism were calculated according to age category (ie, age < 65, 65-74, and ≥ 75 years). Independent risk factors of stroke and thromboembolism were investigated in univariate and multivariate Cox regression models including patients with NVAF aged < 65 years only. The effect of adding vascular disease to the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke) score was examined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models.Results: Among 6,438 patients with NVAF, 2,002 (31.1%) were aged < 65 years. In patients with no CHADS(2) risk factors who were not treated with anticoagulation (n = 1,035), the stroke/thromboembolic event rate per 100 person-years was 0.23 (95% CI, 0.08-0.72), 2.05 (95% CI, 1.07-3.93), and 3.99 (95% CI, 2.63-6.06) in those aged < 65, 65-74, and ≥ 75 years, respectively. Heart failure, previous stroke, and vascular disease were significantly associated with increased risk of stroke/thromboembolism in both univariate and multivariate analyses, and vascular disease significantly improved the predictive ability of the CHADS(2) score (NRI, 0.40; IDI, 0.031).Conclusions: Patients with NVAF aged ≥ 65 years have event rates that merit oral anticoagulation. In patients with NVAF aged < 65 years, the risk of stroke/thromboembolism is independently increased by the presence of heart failure, previous stroke, or vascular disease. As proposed in the new CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke, vascular disease, age 65-74 years, sex category [female]) score, stroke risk stratification by the CHADS(2) score can be improved by the addition of age 65 to 74 years and vascular disease. [ABSTRACT FROM AUTHOR]

Background: In patients with atrial fibrillation (AF), adherence to guidelines for antithrombotic treatment is poorly followed, and undertreatment (or nonadherence with guidelines) is associated with a worse prognosis. The study objective was to evaluate whether this was also the case in a large contemporary series of unselected patients with AF in real-world clinical practice.Methods: All patients with AF or atrial flutter seen in our institution between 2000 and 2007 were identified in a database and followed up for mortality and stroke. Antithrombotic guideline adherence was assessed according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines.Results: We reviewed outcomes in 3,646 consecutive patients with AF or atrial flutter (aged 71 ± 14 years; mean CHADS(2) [congestive heart failure, hypertension, aged ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score, 1.5 ± 1.1). Antithrombotic treatment was in agreement with the guidelines in 53% of patients, whereas 31% were classified as undertreated and 16% as overtreated. Among other parameters, nonpermanent AF and atrial flutter were independently associated with an increased risk of undertreatment. After a follow-up of 953 ± 767 days (median, 771 days; interquartile range, 1,286 days), guideline adherence was associated with a lower risk of adverse events (death from all causes or stroke) compared with undertreatment (relative risk, 0.47; 95% CI, 0.40-0.55; P < .0001). Overtreatment was associated with a lower risk of adverse events compared with the guideline-adherent population (relative risk, 0.40; 95% CI, 0.28-0.58; P < .0001). Factors independently associated with increased risk of mortality or stroke were antithrombotic undertreatment, older age, heart failure, renal failure, diabetes, male sex, and previous history of stroke.Conclusions: Guideline nonadherence and undertreatment with antithrombotic agents in unselected real-world patients with AF or atrial flutter are independently associated with a high risk of stroke and mortality. [ABSTRACT FROM AUTHOR]

Background: All stroke risk stratification schemes categorize a history of stroke as a "truly high" risk factor. Therefore, stratifying stroke risk in atrial fibrillation (AF) should perhaps concentrate on primary prevention. However, the risk factors for stroke also lead to an increase in the risk of bleeding. Our objective was to evaluate the agreement among the currently used stroke risk stratification schemes in "real-world" patients with AF in the primary prevention setting, their correlation with adverse events recorded during warfarin treatment, and the relationship between stroke and bleeding risk.Methods: We prospectively followed up 3,302 patients with AF taking warfarin for primary prevention. Stroke risk was assessed using the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke or transient ischemic attack), Atrial Fibrillation Investigators, American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy, American College of Cardiology/American Heart Association/European Society of Cardiology, and National Institute for Health and Clinical Excellence schemas, and for bleeding risk, the outpatient bleeding risk index was calculated. Bleeding and thrombotic events occurring during follow-up were recorded.Results: Patients classified into various stroke risk categories differed widely for different schemes, especially for the moderate- and high-risk categories. The rates of bleeding and thrombotic events during follow-up were 1.24 and 0.76 per 100 patient-years, respectively. All stroke stratification schemes correlated closely to bleeding risk. Stroke rate increased progressively from low- to moderate- to high-risk patients.Conclusions: Stroke risk stratification models differed widely when categorizing subjects into the moderate- and high-stroke-risk categories. Bleeding and stroke risk were closely correlated and both were low among low-risk patients and were similarly high among moderate/high-risk groups. [ABSTRACT FROM AUTHOR]

Background: Mitral annular calcification (MAC) has been suggested as a reliable, time-averaged marker of atherosclerosis and is associated with coronary artery disease, heart failure, ischemic stroke, and increased mortality. Data on the relationship between MAC and cardiovascular morbidity and mortality in atrial fibrillation (AF) are sparse, with the exception of the relationship between MAC and stroke. We investigated the association of MAC with cardiovascular morbidity, stroke, cardiovascular mortality, and all-cause death in a cohort of middle-aged patients with AF with a mean 10-year follow-up.Methods: This was an observational study of patients with nonvalvular AF between 1992 and 2007.Results: Of 1,056 patients, 33 (3.1%) had MAC; they were more likely to be older and female and to have a dilated left atrium, reduced left ventricular ejection fraction, permanent AF, hypertension, and/or diabetes mellitus (all P < .05). Total follow-up was 10,418.5 years (mean, 9.9 ± 5.9 years), and the mean age was 52.7 ± 12.2 years. In univariate analysis, MAC was associated with all-cause death, cardiovascular death, stroke, new cardiac morbidity (all P < .05), and the composite end point of ischemic stroke, myocardial infarction (MI), and all-cause death (P < .001). In multivariate analyses, MAC was related to all-cause death (hazard ratio [HR], 4.3; 95% CI, 1.8-10.0; P < .001), cardiovascular death (HR, 3.5; 95% CI, 1.2-10.4; P = .025), the composite end point (HR, 2.1; 95% CI, 1.0-4.3; P = .048), and new cardiac morbidity (HR, 2.4; 95% CI, 1.3-4.5; P = .005). There was no significant relationship between MAC and stroke or MI in the multivariate analyses.Conclusions: MAC is associated with increased cardiovascular morbidity, cardiovascular mortality, and all-cause mortality of patients with AF. MAC should be acknowledged as a marker of increased cardiovascular risk in middle-aged patients with AF. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the impact of combination antithrombotic therapy on stroke and bleeding risk compared with anticoagulation therapy only in patients with atrial fibrillation (AF).Methods: Post hoc analysis of 4,576 patients with AF (mean ± SD age, 70.1 ± 9.1 years; men, 66.5%) enrolled in the Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation (AMADEUS) trial were randomized to receive either subcutaneous idraparinux (2.5 mg weekly) (n = 2,283) or dose-adjusted vitamin K antagonists (VKAs) (international normalized ratio, 2.0-3.0) (n = 2,293). Of these patients, 848 (18.5%) received antiplatelet therapy (aspirin, clopidogrel, ticlopidine, etc) in addition to anticoagulation treatment (combination antithrombotic therapy).Results: A total of 572 (15.3% per year) clinically relevant bleeding and 103 (2.6% per year) major bleeding events occurred. Patients receiving combination antithrombotic therapy had a 2.3- to 2.5-fold increased risk of clinically relevant bleeding events and major bleeding events, respectively, compared with those receiving anticoagulation therapy only. Multivariate analyses (hazard ratio, 95% CI) revealed that the risk of clinically relevant bleeding was significantly increased by age 65 to 74 years (1.44, 1.14-1.82) and ≥ 75 years (1.59, 1.24-2.04, P = .001) and by combination antithrombotic therapy (2.47, 2.07-2.96, P < .0001). The same held true for major bleeding events, with analogous figures for age 65 to 74 years (2.26, 1.08-4.71) and ≥ 75 years (4.19, 1.98-8.87, P = .0004) and for combination antithrombotic therapy (2.23, 1.49-3.34, P < .0001). Combination antithrombotic therapy was not associated with a decrease in ischemic stroke risk compared with anticoagulation therapy only (11 [1.4% per year] vs 22 [0.7% per year]; adjusted hazard ratio, 2.01; 95% CI, 0.94-4.30; P = .07).Conclusions: Combination antithrombotic therapy increases the risk of clinically relevant bleeding and major bleeding in patients with AF and does not appear to reduce the risk of stroke. [ABSTRACT FROM AUTHOR]

Background: There are various schemas designed to stratify the risk of thromboembolism (TE) in patients with atrial fibrillation (AF), of which the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 y, diabetes, stroke [doubled]) score is the most widely studied. We evaluated whether the CHADS(2) score was adequate for TE risk stratification while assessing cardiac risk in patients with AF revascularized with coronary artery stents.Methods: We reviewed 604 consecutive patients with AF treated with at least one stent between 2001 and 2008 in relation to TE risk using CHADS(2) score. We stratified our patients with a CHADS(2) score ≤ 1 as low-moderate thromboembolic risk (group 1: n = 193, 32%) and > 1 as high risk (and, hence, requiring anticoagulation; group 2: n = 411, 68%). We determined the benefits and/or risks of oral anticoagulation (OAC) therapy in both cohorts.Results: Completed follow-up was achieved in 90.4% (mean 642.2 days). Group 1 event-free survival was better than group 2 (major adverse cardiovascular events [MACEs], log-rank test P = .03; and death, log-rank test P = .03). In group 1, event-free survival was better on OAC vs non-OAC use (death 5% vs 15%, P = .04; MACE 10% vs 26%, P < .01) with a trend for more major hemorrhages (12% vs 4%, P = .08). Stroke rate was 4.1% per 100 patient-years in patients without OAC therapy and 1.38% in patients on OAC therapy. Group 2 had a lower incidence of death (20% vs 34%, P < .01) and MACE (26% vs 43%, P < .01) among those on OAC therapy on discharge, with a higher incidence of major hemorrhages (18% vs 8%, P < .01).Conclusion: In a population of patients with AF revascularized with stents, even those with CHADS(2) ≤ 1 should be regarded as being at high risk. OAC should be considered as thromboprophylaxis in patients with AF revascularized with coronary stents. [ABSTRACT FROM AUTHOR]