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Background:\ud Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation.\ud Methods:\ud Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β blockers. All-cause mortality during median 1·3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm. The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach. This study was prospectively registered with ClinicalTrials.gov (NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012).\ud Findings:\ud 15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56–72) and LVEF 27% (IQR 21–33). 3708 (24%) patients were women. In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from β blockers, with odds ratios (ORs) ranging from 0·54 to 0·74. One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0·86, 95% CI 0·67–1·10; p=0·22). In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of β blockers versus placebo (OR 0·92, 0·77–1·10; p=0·37). One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with β blockers (OR 0·57, 0·35–0·93; p=0·023). The robustness and consistency of clustering was confirmed for all models (p

Background Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF). Methods For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist. Results Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations). Conclusions Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.

Aims The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. Methods and results This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. Conclusion The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

The validity and reproducibility of systolic function assessment in patients with atrial fibrillation (AF) using cardiac magnetic resonance, echocardiography, nuclear imaging and computed tomography is unknown. A prospectively-registered systematic review was performed, including 24 published studies with patients in AF at the time of imaging and reporting validity or reproducibility data on left ventricular systolic parameters (PROSPERO: CRD42018091674). Data extraction and risk of bias were performed by 2 investigators independently and synthesized qualitatively. In 3 cardiac magnetic resonance studies (40 AF patients), left ventricular ejection fraction and stroke volume measurements correlated highly with catheter angiography (r ≥0.85), and intra- and/or interobserver variability were low. From 3 nuclear studies (171 AF patients), there were no external validation assessments but intra and/or interobserver and intersession variability were low. In 18 echocardiography studies (2,566 AF patients), 2 studies showed high external validity of global longitudinal strain and tissue Doppler s' with angiography-derived dP/dt (r ≥0.88). Global longitudinal strain and myocardial performance index were both associated with adverse cardiovascular events. Reproducibility of echocardiography was better when selecting an index-beat (where 2 preceding R-to-R intervals are similar) compared to averaging of consecutive beats. There were no studies relating to computed tomography. Most studies were small and biased by selection of patients with good quality images, limiting clinical extrapolation of results. The validity of systolic function measurements in patients with AF remains unclear due to the paucity of good-quality data.

Aims We assessed the performance of modelsf (risk scores) for predicting recurrence of atrial fibrillation (AF) in patients who have undergone catheter ablation. Methods and results Systematic searches of bibliographic databases were conducted (November 2018). Studies were eligible for inclusion if they reported the development, validation, or impact assessment of a model for predicting AF recurrence after ablation. Model performance (discrimination and calibration) measures were extracted. The Prediction Study Risk of Bias Assessment Tool (PROBAST) was used to assess risk of bias. Meta-analysis was not feasible due to clinical and methodological differences between studies, but c-statistics were presented in forest plots. Thirty-three studies developing or validating 13 models were included; eight studies compared two or more models. Common model variables were left atrial parameters, type of AF, and age. Model discriminatory ability was highly variable and no model had consistently poor or good performance. Most studies did not assess model calibration. The main risk of bias concern was the lack of internal validation which may have resulted in overly optimistic and/or biased model performance estimates. No model impact studies were identified. Conclusion Our systematic review suggests that clinical risk prediction of AF after ablation has potential, but there remains a need for robust evaluation of risk factors and development of risk scores.

Europace : the European journal of pacing, arrhythmias and cardiac electrophysiology euac062 (2022). doi:10.1093/europace/euac062, Published by Oxford Univ. Press, Oxford

Background Intravenous (IV) beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl). Important pharmacodynamic differences exist amongst beta-blockers, and the choice of beta-blocker or other therapy is often not evidence-based. Purpose Systematic review and meta-analysis of randomised controlled trials (RCTs) in the setting of acute AF/AFl to assess the efficacy and safety of IV beta-blockers against other pharmacological interventions (diltiazem, verapamil, digoxin, anti-arrhythmic drugs or placebo). Methods Prospectively registered (PROSPERO: CRD42020204772). MEDLINE, EMBASE and Cochrane Register were searched from inception to August 2020. The primary outcomes were reduction in heart rate and proportion of patients achieving study-defined target heart rate. Secondary outcomes included conversion to sinus rhythm and incidence of adverse events. Beta-blockers were divided according to beta-1 adrenoreceptor selectivity. Meta-analysis was performed to calculate risk ratios (RR) and standardised mean differences (SMD) using random-effects, and fixed-effects within beta-1 subgroups. Results From 5974 studies, 12 RCTs were included with variable risk of bias, encompassing 1152 participants with mean age 62 years, 38% women and baseline heart rate 137 beats/minute. With high heterogeneity (I2=87%; p Conclusion There is no difference between IV beta-blockers overall and other medications for the control of acute AF/AFl, although better efficacy was shown for beta-blockers with higher beta-1 selectivity. IV beta-blockers were as safe as comparator agents, with the exception of non-selective beta-blockers. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Independent systematic review commissioned by Amomed Pharma. Target heart rate and hypotension events

AimsTo evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.Methods and resultsA total of 76 019 individuals with AF were identified in England in 1998–2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02–1.24), 1.20 (1.05–1.36), and 1.27 (1.19–1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.ConclusionPrevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a β-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, −1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, −2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.

Background: Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF). Methods: We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010–2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage. Results: Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata. Conclusions: This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.

Background Although observational studies have suggested an association between elevated blood pressure (BP) and increased risk of atrial fibrillation (AF), randomised evidence on the effects of pharmacological blood pressure lowering on the risk of new-onset AF remains limited. Purpose To investigate the effects of pharmacological BP lowering on the risk of AF overall and stratified by baseline risk of AF and by drug class. Methods We extracted individual participant data from trials with over 1,000 person-years of follow-up that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs vs placebo, or to more vs less intensive BP-lowering regimens. We investigated the effects of BP lowering on the risk of new-onset AF using fixed-effect one-stage individual participant data meta-analyses based on Cox proportional hazards models stratified by trial. Results Twenty-one trials were included with a total of 194,041 patients, in whom 6,357 new-onset and 516 recurrent AF events were recorded. The hazard ratio for new-onset AF was 1.01, 95% CI [0.95–1.07] per each 5-mmHg reduction in systolic BP, and meta-regression suggested that treatment effects were similar irrespective of the intensity of systolic BP reduction. Patients were overall at low risk of AF at baseline (median 2.3%, IQR [1.2–3.4%] at 5 years), and there was no evidence of heterogeneity in treatment effects across thirds of risk and 10-mmHg strata of baseline systolic BP (Figure). There was also no clear evidence that treatment effects differed between drug classes when renin-angiotensin-aldosterone system inhibitors and calcium channel blockers were compared with placebo and/or standard treatment. Conclusion In a low-risk population, pharmacological BP lowering did not reduce the risk of new-onset AF. Further research is needed to understand whether the effects would be different in high-risk individuals, and to better clarify the existence of class-specific effects. Figure 1. Forest plot Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson's biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e'). Results 160 patients (median age 75 years (IQR 69–82); 46% female) were included, with median heart rate 100 beats/min (IQR 86–112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Comparison for measurement of E/e' Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research UK

Introduction Early diagnosis of atrial fibrillation (AF) is essential to reduce complications such as stroke, and improve patient quality of life. Novel screening techniques using smartphone camera photoplethysmography (PPG) can be used for AF detection, but their clinical applicability remains unclear. Purpose To assess the diagnostic accuracy of smartphone PPG compared to conventional ECG for AF detection. Methods We performed a systematic review of MEDLINE, EMBASE, Cochrane library, and other databases (1980-October 2019), including any study or abstract where smartphone finger-tip PPG was compared with a reference ECG (1, 3 or 12-lead). Outcomes were sensitivity (SE), specificity (SP), positive and negative predictive value (PPV; NPV) and overall accuracy. Bivariate hierarchical random effects meta-analysis was performed for studies with confidence intervals for SE and SP, and funnel plots were used to identify publication bias. Study quality was assessed using the established QUADAS-2 tool by two independent graders. Results 1350 publications were screened, of which 17 studies were included in the systematic review (7 full text publications and 10 abstracts), providing 21 comparisons of accuracy for AF detection. Most studies were based in secondary care and small (range n=33 to 1095), with a total of 5469 participants including 1384 with AF. Only 4 studies were multicentre. Smartphone applications used were Cardiio Rhythm, Fibricheck, Preventicus and Heartbeats, with 7 studies not specifying the tool used. Overall SE and SP for AF detection were high, ranging from 76 to 100%, and 85 to 100% respectively. PPV ranged from 54 to 100% and NPV from 77 to 100%, with overall accuracy between 61 and 99%. The meta-analysis included 12 comparisons from 10 studies (n=2714; 936 with AF). The pooled SE was 93% (95% CI 90–96%) and SP 97% (95% CI 95–99%); Figure 1A. QUADAS-2 assessment demonstrated poor quality of studies overall, with a high or unclear risk of bias in at least one domain for all studies. There was clear evidence of publication bias; Figure 1B. Conclusions PPG offers the potential for large scale, non-invasive, patient-led screening of AF. However, current evidence is limited to biased, low quality studies often with unrealistic results for AF detection. These are insufficient to advise clinicians on the true value of current smartphone PPG technology. Figure 1. Meta-analysis & publication bias Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): BigData@Heart EU/EFPIA IMI 116074.

AimsTo establish the extent and impact of symptoms in patients with atrial fibrillation (AF), the importance of different aspects of quality of life (QoL), and how we should assess wellbeing.MethodsFocus groups of patients with symptomatic permanent AF in a trial of heart rate control; the RATE-AF trial randomised 160 patients aged ≥60 years with permanent AF and at least NYHA class II dyspnoea to either digoxin or beta-blockers. Patient and public representatives led the focus groups and performed all data acquisition and analysis, using thematic approaches to interpret patient views about QoL and its measurement.ResultsSubstantial impairment of health-related QoL was noted in 160 trial patients, with impact on all domains apart from mental health. Eight women and 11 men aged 61–87 years participated in the focus groups. Common themes were a lack of information from healthcare professionals about AF, a lack of focus on QoL in consultations, and a sense of frustration, isolation and reduced confidence. There was marked variability in symptoms in individual patients, with some describing severe impact on activities of daily living, and profound interaction with comorbidities such as arthritis. Day-to-day variation in QoL and difficulty in attributing symptom burden to AF or other comorbidities led to challenges in questionnaire completion. Consensus was reached that collecting both general and AF-specific QoL would be useful in routine practice, along with participation in peer support, which was empowering for the patients.ConclusionsThe impact of comorbidities is poorly appreciated in the context of AF, with considerable variability in QoL that requires both generic and AF-specific assessment. Improvement in QoL should direct the appraisal, and reappraisal, of treatment decisions for patients with permanent AF.

Aims: To establish the extent and impact of symptoms in patients with atrial fibrillation (AF), the importance of different aspects of quality of life (QoL), and how we should assess wellbeing. Methods: Focus groups of patients with symptomatic permanent AF in a trial of heart rate control; the RATE-AF trial randomised 160 patients aged ≥60 years with permanent AF and at least NYHA class II dyspnoea to either digoxin or beta-blockers. Patient and public representatives led the focus groups and performed all data acquisition and analysis, using thematic approaches to interpret patient views about QoL and its measurement. Results: Substantial impairment of health-related QoL was noted in 160 trial patients, with impact on all domains apart from mental health. Eight women and 11 men aged 61–87 years participated in the focus groups. Common themes were a lack of information from healthcare professionals about AF, a lack of focus on QoL in consultations, and a sense of frustration, isolation, and reduced confidence. There was marked variability in symptoms in individual patients, with some describing severe impact on activities of daily living, and profound interaction with comorbidities such as arthritis. Day-to-day variation in QoL and difficulty in attributing symptom burden to AF or other comorbidities led to challenges in questionnaire completion. Consensus was reached that collecting both general and AF-specific QoL would be useful in routine practice, along with participation in peer support, which was empowering for the patients. Conclusions: The impact of comorbidities is poorly appreciated in the context of AF, with considerable variability in QoL that requires both generic and AF-specific assessment. Improvement in QoL should direct the appraisal, and reappraisal, of treatment decisions for patients with permanent AF.

Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson’s biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e’). Results 160 patients (median age 75 years (IQR 69-82); 46% female) were included, with median heart rate 100 beats/min (IQR 86-112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Conflict of Interest Nothing to declare

Background Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain. Methods We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence. Results We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke. Conclusions Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.

Objectives This study sought to document the closure rate, safety, and stroke rate after thoracoscopic left atrial appendage (LAA) clipping. Background The LAA is the main source of stroke in patients with atrial fibrillation, and thoracoscopic clipping may provide a durable and safe closure technique. Methods The investigators studied consecutive patients undergoing clipping as part of a thoracoscopic maze procedure in 4 referral centers (the Netherlands and the United States) from 2012 to 2016. Completeness of LAA closure was assessed by either computed tomography (n = 100) or transesophageal echocardiography (n = 122). The primary outcome was complete LAA closure (absence of residual LAA flow and pouch Results A total of 222 patients were included, with a mean age of 66 ± 9 years, and 68.5% were male. The mean CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65 to 74 years, sex category [female]) score was 2.3 ± 1.0. Complete LAA closure was achieved in 95.0% of patients. There were no intraoperative or clip-related complications, and the overall 30-day freedom from any complication rate was 96.4%. The freedom from cerebrovascular events after surgery was 99.1% after median follow-up of 20 months (interquartile range: 14 to 25 months; 369 patient-years of follow-up), and overall survival was 98.6%. The observed rate of cerebrovascular events after LAA clipping was low (0.5 per 100 patient-years). Conclusions LAA clipping during thoracoscopic ablation is a feasible and safe technique for closure of the LAA in patients with atrial fibrillation. The lower than expected rate of cerebrovascular events after deployment was likely multifactorial, including not only LAA closure, but also the effect of oral anticoagulation and rhythm control.

Aims Thoracoscopic surgical ablation has evolved into a successful strategy for symptomatic atrial fibrillation (AF) refractory to other therapy. More widespread referral is limited by the lack of information on potential complications. Our aim was to systematically evaluate 30-day complications of totally thoracoscopic surgical ablation. Methods and results We retrospectively studied consecutive patients undergoing totally thoracoscopic surgical ablation at a referral centre in the Netherlands (2007–2016). Patients received pulmonary vein isolation, with additional lesion lines as needed, and left atrial appendage exclusion. The primary outcomes were freedom from any complications and freedom from irreversible complications at 30-days. Secondary outcomes included intra- and post-operative complications according to severity. Included were 558 patients with median age 62 years (interquartile range 56–68 years), 70% male and 53% with a previous failed catheter ablation. The cohort consisted of 43% paroxysmal AF, 47% persistent AF, and 10% long-standing persistent AF. Freedom from any 30-day complication was 88.2%, and from complications with life-long affecting consequences 97.5%. The intra-operative complication rate was 2.3% with no strokes or death observed. The median hospital length of stay was 4 days. The percentage of patients with major and minor complications at 30-days was 3.2% and 8.1%, respectively, with one patient dying of an ischaemic stroke. The only patient groups with excess complications were women aged ≥70 years and patients with a history of congestive heart failure. Conclusions Totally thoracoscopic ablation is associated with a low complication rate in a referral centre and may be a useful alternative to other rhythm control strategies.

Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40–49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21–33%), including 575 patients with LVEF 40–49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40–49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34–1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24–0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when Conclusion Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF

The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO)

Aims Echocardiography is vital in the routine assessment and management of atrial fibrillation (AF). We performed a systematic review of the validity and reproducibility of echocardiographic left ventricular systolic and diastolic function in AF, and optimal acquisition methods. Methods and results Online databases were searched for studies in patients with AF at the time of echocardiography (1960 to August 2015), prospectively registered with PROSPERO (CRD42015025297). The systematic review included 32 studies from 3 066 search results (1 968 patients with AF). Average age was 67 years, 33% were women, mean LVEF 53% (±10%), and average E/e’ 11.7 (±2.7). Data on the validity and reproducibility of systolic indices were extremely limited. In contrast, diastolic parameters demonstrated correlation with invasive filling pressure and adequate reproducibility: E/e’ (n = 444) r = 0.47 to 0.79; IVRT (n = 177) r = –0.70 to –0.95; E/Vp` (n = 55) r = 0.63 and 0.65; pulmonary vein diastolic flow (n = 67) r = –0.80 and –0.91. Elevated E/e’ (>15) was associated with functional capacity, quality of life, and impaired prognosis. For optimal acquisition in AF patients, cardiac cycles with controlled heart rate (

Background:\ud Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy.\ud \ud Objectives:\ud This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR).\ud \ud Methods:\ud Analysis of 16,740 individual patients with left ventricular ejection fraction

Introduction Echocardiography plays an essential role in the management of atrial fibrillation (AF) and the diagnosis of heart failure in these patients. Assessment of systolic and diastolic function is challenging in AF due to the irregular RR interval, resulting in variability from beat to beat. We compared the reproducibility of an index beat (figure 1) approach (similar RR intervals for the two prior beats before measurement) versus conventional averaging of three, five and ten consecutive beats in patients with permanent AF. Methods Consecutive patients were evaluated with a Philips EPIC 7 and X5-1 transducer, and all measurements were analysed offline by an operator blinded to clinical details. A minimum of 30-beat loops were obtained of the apical 2, 3 and 4-chamber, lateral and septal e’ and mitral E Vmax. Global longitudinal strain (GLS), Simpson’s biplane ejection fraction (EF) and E/e’ were calculated and the coefficient of variation determined between 3x index beats, averaged 3 beats, averaged 5 beats and averaged 10 beats. Intra- and inter-observer variability of GLS and E/e’ were assessed in 30 and 10 patients respectively, using Bland and Altman analysis. Results 50 patients with permanent AF and symptoms of heart failure were included, with 46% women and mean age 78±9 years, heart rate 97±19 bpm, NTpro-BNP 1173±647 ng/L, NYHA class 2.5±0.6 and BMI 30±6 kg/m2. The index beat method had the lowest coefficient of variation (figure 1) for biplane ejection fraction, GLS and E/e’ (4.5%, 8.5% and 7.3%), when compared with the average of 3 beats (11.6%, 17.9% and 14.9%), average of 5 beats (11.9%,17.9% and 14.95) and average of 10 beats (12.3%, 18.5% and 16.2%). GLS intra and inter-observer variability were lowest for the index beat, with small bias and narrow limits of agreement [in brackets]: intra -1.1 [-4.9 to 2.7] and inter -0.7 [-5.4 to 3.9]; verses 3 averaged beats -1.1 [-5.4 to 3.1] and -2 [-6.5 to 4.7]; 5 averaged beats -1.1 [-5.6 to 3.4] and -1.2 [-6.6 to 4.2]; and 10 averaged beats -1.0 [-5.0 to 3.0] and -0.9 [-6.2 to 4.3]. Inter-observer limits of agreement for E/e’ were also the narrowest for the index beat method: -1.6 [-0.4 to 3.7]; verses 3 averaged beats -0.6 [-3.5 to 2.2]; 5 averaged beats -0.4 [-3.1 to 2.2]; and 10 averaged beats -0.1 [-2.5 to 2.2]. Conclusion In patients with AF, an index beat method is more reproducible than the conventional method of averaging multiple consecutive beats. This approach can enhance the reliability of measurements for both systolic and diastolic left ventricular function in patients with AF. Conflict of Interest Nothing to declare

Background Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. Methods and findings The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. Conclusions In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF. Author summary Why was this study done? Atrial fibrillation (AF) is the most common cardiac arrhythmia across the world and is strongly associated with future vascular disease, particularly stroke. Blood pressure (BP) lowering is an established strategy for prevention of vascular disease, but whether patients with AF benefit similarly from pharmacological BP reduction is not well understood. What did the researchers do and find? We compared the preventive effect of BP-lowering treatment on cardiovascular outcomes in patients with and without AF at baseline. We conducted an individual participant data meta-analysis using published and unpublished data from large randomised clinical trials (22 trials involving 188,570 patients). We showed that BP-lowering treatment reduced the risk of a major cardiovascular events with no evidence that effects differed according to the presence or absence of AF at baseline. The relative risk reductions were proportional to the intensity of BP reduction in individuals with and without AF. In individuals with AF, the relative risk reduction was comparable irrespective of whether baseline systolic BP was under or over the conventional treatment threshold of 140 mm Hg. What do these findings mean? BP-lowering treatment reduces the risk of major cardiovascular events in patients with AF to a similar extent to that of patients without AF. Pharmacological BP-lowering treatment for prevention of cardiovascular events should be recommended as part of care for patients with AF.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are age-related conditions that are increasing in prevalence, commonly coexist, and share clinical features. This review provides a practical update on the epidemiology, pathophysiology, diagnosis, and management of patients with concomitant HFpEF and AF. Epidemiological studies highlight the close and complex links between HFpEF and AF, the shared risk factors, the high AF occurrence in the natural history of HFpEF, and the independent contribution of each condition to poor outcomes. Diagnosis of HFpEF in the setting of AF is challenging because the symptoms overlap. AF is associated with changes in echocardiographic parameters and circulating natriuretic peptides that confound HFpEF diagnosis. Symptomatic improvement with diuretic therapy supports the presence of HFpEF in patients with concomitant AF. Important knowledge gaps need to be addressed by a multidisciplinary and translational research approach to develop novel therapies that can improve prognosis.

Aims: Our objectives were to compare effectiveness and long-term prognosis after epicardial thoracoscopic atrial fibrillation (AF) ablation vs. endocardial catheter ablation, in patients with prior failed catheter ablation or high risk of failure. Methods and results: Patients were randomized to thoracoscopic or catheter ablation, consisting of pulmonary vein isolation with optional additional lines (2007–2010). Patients were reassessed in 2016/2017, and those without documented AF recurrence underwent 7-day ambulatory electrocardiography. The primary rhythm outcome was recurrence of any atrial arrhythmia lasting >30 s. The primary clinical endpoint was a composite of death, myocardial infarction, or cerebrovascular event, analysed with adjusted Cox proportional hazard ratios (HRs). One hundred and 24 patients were randomized with 34% persistent AF and mean age 56 years. Arrhythmia recurrence was common at mean follow-up of 7.0 years, but substantially lower with thoracoscopic ablation: 34/61 (56%) compared with 55/63 (87%) with catheter ablation [adjusted HR 0.40, 95% confidence interval (CI) 0.25–0.64; P

Heart failure and atrial fibrillation are conditions that pose considerable burdens on current and future healthcare, with high morbidity and mortality, frequent hospital admissions, and poor patient quality of life. The two conditions share many underlying pathophysiological mechanisms and common risk factors, which include each other. Hence these conditions often coexist, leading to even worse prognosis and challenges in management. The evidence base for heart failure treatments is limited in patients with concomitant atrial fibrillation, and atrial fibrillation management is often more difficult in the context of heart failure. Nearly all patients will benefit from oral anticoagulation, and yet many patients do not receive this important prognostic therapy in clinical practice. Prevention of incident atrial fibrillation is clearly an important target in heart failure patients, and can be achieved with appropriate guideline-recommended heart failure therapy. There is a huge opportunity for further research in patients with combined heart failure and atrial fibrillation, to improve patient well-being and long-term outcomes.

Undetected atrial fibrillation (AF) is a major health concern. Blood biomarkers associated with AF could simplify patient selection for screening and further inform ongoing research towards stratified prevention and treatment of AF.Forty common cardiovascular biomarkers were quantified in 638 consecutive patients referred to hospital [mean ± standard deviation age 70 ± 12 years, 398 (62%) male, 294 (46%) with AF] with known AF or ≥2 CHA2DS2-VASc risk factors. Paroxysmal or silent AF was ruled out by 7-day ECG monitoring. Logistic regression with forward selection and machine learning algorithms were used to determine clinical risk factors, imaging parameters, and biomarkers associated with AF. Atrial fibrillation was significantly associated with age [bootstrapped odds ratio (OR) per year = 1.060, 95% confidence interval (1.04-1.10); P = 0.001], male sex [OR = 2.022 (1.28-3.56); P = 0.008], body mass index [BMI, OR per unit = 1.060 (1.02-1.12); P = 0.003], elevated brain natriuretic peptide [BNP, OR per fold change = 1.293 (1.11-1.63); P = 0.002], elevated fibroblast growth factor-23 [FGF-23, OR = 1.667 (1.36-2.34); P = 0.001], and reduced TNF-related apoptosis-induced ligand-receptor 2 [TRAIL-R2, OR = 0.242 (0.14-0.32); P = 0.001], but not other biomarkers. Biomarkers improved the prediction of AF compared with clinical risk factors alone (net reclassification improvement = 0.178; P 0.001). Both logistic regression and machine learning predicted AF well during validation [area under the receiver-operator curve = 0.684 (0.62-0.75) and 0.697 (0.63-0.76), respectively].Three simple clinical risk factors (age, sex, and BMI) and two biomarkers (elevated BNP and elevated FGF-23) identify patients with AF. Further research is warranted to elucidate FGF-23 dependent mechanisms of AF.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF.

Atrial fibrillation (AF) and heart failure frequently coexist, commonly resulting in serious adverse events. With both conditions increasing in prevalence and justified concerns about treatment efficacy, it is vital to understand how the type of heart failure impacts on prognosis.We performed a systematic review of studies examining cardiovascular outcomes in AF patients with heart failure and reduced ejection fraction (AF-HFrEF) compared to those with preserved ejection fraction (AF-HFpEF). The primary outcome was all-cause mortality, meta-analyzed using a random-effects model. Prospective registration: PROSPERO-CRD42014007305.Thirteen studies were included in the systematic review (n=54,587) with 10 suitable for meta-analysis, including retrospective/prospective cohorts and sub-group analyses of randomized trials. AF-HFrEF was present in 49% and these patients were younger, more often male and with higher NYHA class than AF-HFpEF. Oral anticoagulation use was 55% versus 50% respectively (p0.001). All-cause mortality was significantly higher in AF-HFrEF; risk ratio (RR) 1.24, 95% CI 1.12-1.36, p0.001 (n=45,100), with absolute death rates of 24% compared to 18% in AF-HFpEF over 2 years. There were no significant differences in incident stroke (RR 0.85, 95% CI 0.70-1.03, p=0.094; n=33,773) or heart failure hospitalization (RR 1.21, 95% CI 0.96-1.53, p=0.115; n=31,583). The risk of bias was generally low, but heterogeneity was substantial.All-cause mortality is significantly higher in AF patients with HFrEF compared to HFpEF, although stroke risk and heart failure hospitalization are similar. Further studies are needed to address the prevention of adverse outcomes in all AF patients with heart failure, regardless of ejection fraction.

We are in the midst of a digital revolution in health care, although the application of new and useful technology in routine clinical practice is variable. The Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME) Consortium, in collaboration with the European Society of Cardiology (ESC), has funded the creation of two applications (apps) in atrial fibrillation (AF) for use in smartphones and tablets. The patient app aims to enhance patient education, improve communication between patients and health care professionals, and encourage active patient involvement in the management of their condition. The health care professional app is designed as an interactive management tool incorporating the new ESC Practice Guidelines on AF and supported by the European Heart Rhythm Association (EHRA), with the aim of improving best practice approaches for the care of patients with AF. Both stand-alone apps are now freely available for Android and iOS devices though the Google Play, Amazon, and Apple stores. In this article, we outline the rationale for the design and implementation of these apps. Our objective is to demonstrate the value of integrating novel digital technology into clinical practice, with the potential for patient engagement, optimization of pharmacological and interventional therapy in AF, and ultimately to improve patient outcomes. Funding Agencies|CATCH ME Consortium (EU Horizon 2020 Grant) [633196]; European Society of Cardiology; National Institute of Health Research (NIHR) Career Development Fellowship [CDF-2015-08-074]; Heart Foundation of Australia; Netherlands Heart Foundation [CVON2014-09]; British Heart Foundation; European Union

Cardioversion of symptomatic atrial fibrillation (AF) is commonly used to restore sinus rhythm, both acutely and as part of a long-term rhythm control strategy [(1)][1]. This approach is associated with a risk of stroke; however, the efficacy of direct oral anticoagulants (DOACs) compared with

Background and Purpose— Atrial fibrillation (AF) and heart failure frequently coexist and are associated with increased morbidity and mortality. We investigated the prognosis of anticoagulated patients with permanent AF and nonpermanent AF according to preexisting heart failure in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. Methods— The primary outcome was a composite of cardiovascular death and stroke or systemic embolism, analyzed using a Cox proportional hazards model, adjusted for baseline age, sex, diabetes mellitus, hypertension, creatinine, and previous cardiovascular diseases. The median follow-up was 11.6 months (interquartile range, 6.2–15.2). Results— Nonpermanent AF was present in 2072 patients (46% of cohort), of which 339 (16%) had preexisting heart failure. A total of 2484 patients had permanent AF (54% of cohort), with a higher burden of heart failure including 730 patients (29%; P P =0.02). The presence of heart failure increased the risk of adverse outcomes in a similar way in both permanent and nonpermanent AF (interaction P value=0.76). Conclusions— The risk of cardiovascular death, stroke, or systemic embolism is higher in anticoagulated patients with permanent AF than in those with nonpermanent AF, regardless of preexisting heart failure.

Objectives: This study sought to document the closure rate, safety, and stroke rate after thoracoscopic left atrial appendage (LAA) clipping. Background: The LAA is the main source of stroke in patients with atrial fibrillation, and thoracoscopic clipping may provide a durable and safe closure technique. Methods: The investigators studied consecutive patients undergoing clipping as part of a thoracoscopic maze procedure in 4 referral centers (the Netherlands and the United States) from 2012 to 2016. Completeness of LAA closure was assessed by either computed tomography (n = 100) or transesophageal echocardiography (n = 122). The primary outcome was complete LAA closure (absence of residual LAA flow and pouch

BACKGROUND The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF).OBJECTIVES This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo.METHODS The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization.RESULTS A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p CONCLUSIONS Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm. (C) 2017 by the American College of Cardiology Foundation.

The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO)

Low magnesium levels have been implicated as a risk factor for the development of atrial fibrillation (AF).1 However, like many interventions before it, supplementing magnesium levels does not necessarily lead to a successful cardioversion or better prevention of AF in high-risk groups. This issue is clinically important in view of the high burden that AF poses, the increasing incidence of AF, and the association of AF with adverse long-term clinical outcomes.2 AF is not only prevalent in the general population (≈3%, with much higher rates in older patients) but also a frequent comorbidity and risk factor in patients with a range of cardiovascular conditions, including heart failure and after cardiac surgery.3,4 Identifying practical and effective methods for managing AF is a clinical imperative. See Article by Rajagopalan et al The attention on magnesium as a potential antiarrhythmic agent is founded on a small number of physiological assessments in human and animal models.5 Intravenous magnesium directly affects myocardial potassium channels, has voltage-dependent and indirect effects on calcium and sodium channels, prolongs the PR interval, and increases the refractory period of antegrade atrioventricular node conduction.6,7 However, although low serum magnesium levels were associated with incident AF in the ARIC study (Atherosclerosis Risk in …