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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

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: To provide robust data on mortality in patients with atrial fibrillation (AF) and heart failure (HF), accounting for differences in mode of death using post-mortem information. Methods and Results: Retrospective cohort of 1009 patients admitted to a Romanian hospital between 2014-2017, with mean age 73±11 years, 47% women, NYHA class 3.0±0.9, left ventricular ejection fraction (LVEF) 40.1±11.0% and 100% anticoagulated. The primary outcome was mortality during 1.5±0.9 years follow-up, of which 291 (29%) died. Post-mortems were performed in 186 (64%) of patients. Baseline factors associated with mortality were dependent on the cause of death. HF-related death in 136 (47%) was associated with higher NYHA class (hazard ratio [HR] 2.45 per one class increase, 95% CI 1.73-3.46; p Conclusions: Supported by post-mortem data, the cause of death in AF and HF patients is heterogeneous, and the relationships with typical markers of mortality are critically dependent on mode of death. The poor prognosis in this group demands further attention to improve management beyond anticoagulation.

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

Echocardiography plays an essential role in the diagnosis and assessment of cardiovascular disease. Measurements derived from echocardiography are also used to determine the severity of disease, its progression over time, and to aid in the choice of optimal therapy. It is therefore clinically important that echocardiographic measurements be reproducible, repeatable, and reliable. There are a variety of statistical tests available to assess these parameters, and in this article the authors summarize those available for use by echocardiographers to improve their clinical practice. Correlation coefficients, linear regression, Bland-Altman plots, and the coefficient of variation are explored, along with their limitations. The authors also provide an online tool for the easy calculation of these statistics in the clinical environment (www.birmingham.ac.uk/echo). Quantifying and enhancing the reproducibility of echocardiography has important potential to improve the value of echocardiography as the basis for good clinical decision-making.

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.

Deterministic approaches using iterative optimisation have been historically successful in diffeomorphic image registration (DiffIR). Although these approaches are highly accurate, they typically carry a significant computational burden. Recent developments in stochastic approaches based on deep learning have achieved sub-second runtimes for DiffIR with competitive registration accuracy, offering a fast alternative to conventional iterative methods. In this paper, we attempt to reduce this difference in speed whilst retaining the performance advantage of iterative approaches in DiffIR. We first propose a simple iterative scheme that functionally composes intermediate non-stationary velocity fields to handle large deformations in images whilst guaranteeing diffeomorphisms in the resultant deformation. We then propose a convex optimisation model that uses a regularisation term of arbitrary order to impose smoothness on these velocity fields and solve this model with a fast algorithm that combines Nesterov gradient descent and the alternating direction method of multipliers (ADMM). Finally, we leverage the computational power of GPU to implement this accelerated ADMM solver on a 3D cardiac MRI dataset, further reducing runtime to less than 2 seconds. In addition to producing strictly diffeomorphic deformations, our methods outperform both state-of-the-art deep learning-based and iterative DiffIR approaches in terms of dice and Hausdorff scores, with speed approaching the inference time of deep learning-based methods., Accepted to MICCAI 2021

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

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. Our aim was 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 multi-centre. 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% (95-99%); Figure A. 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 B. 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. Conflict of Interest EU grant -BigData@Heart EU/EFPIA IMI 11607

Background: Quality assurance (QA) of echocardiographic studies is vital to ensure that clinicians can act on findings of high quality to deliver excellent patient care. To date, there is a paucity of published guidance on how to perform this QA. The British Society of Echocardiography (BSE) has previously produced an Echocardiography Quality Framework (EQF) to assist departments with their QA processes. This article expands on the EQF with a structured yet versatile approach on how to analyse echocardiographic departments to ensure high-quality standards are met. In addition, a process is detailed for departments that are seeking to demonstrate to external bodies adherence to a robust QA process. Methods: The EQF consists of four domains. These include assessment of Echo Quality (including study acquisition and report generation); Reproducibility & Consistency (including analysis of individual variability when compared to the group and focused clinical audit), Education & Training (for all providers and service users) and Customer & Staff Satisfaction (of both service users and patients/their carers). Examples of what could be done in each of these areas are presented. Furthermore, evidence of participation in each domain is categorised against a red, amber or green rating: with an amber or green rating signifying that a quantifiable level of engagement in that aspect of QA has been achieved. Conclusion: The proposed EQF is a powerful tool that focuses the limited time available for departmental QA on areas of practice where a change in patient experience or outcome is most likely to occur.

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

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

ObjectivesTimely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.MethodsThis is a systematic review of MEDLINE, EMBASE and Cochrane (1980–December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.Results28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%–98%), with substantial heterogeneity (pConclusionPPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.

Background The prevalence of combined heart failure (HF) and atrial fibrillation (AF) is rising, and these patients suffer from high rates of mortality. This study aims to provide robust data on factors associated with death, uniquely supported by post-mortem examination. Methods A retrospective cohort study of hospitalized adults with a clinical diagnosis of HF and AF at a tertiary centre in Romania between 2014 and 2017. A standardized post-mortem examination was performed where death occurred within 24 h of admission, when the cause of death was not clear or by physician request. National records were used to collect mortality data, subsequently categorized and analysed as HF-related death, vascular death and non-cardiovascular death using Cox proportional hazards regression. Results A total of 1009 consecutive patients with a mean age of 73 ± 11 years, 47% women, NYHA class 3.0 ± 0.9, left ventricular ejection fraction (LVEF) 40.1 ± 11.0% and 100% anticoagulated were followed up for 1.5 ± 0.9 years. A total of 291 (29%) died, with post-mortems performed on 186 (64%). Baseline factors associated with mortality were dependent on the cause of death. HF-related death in 136 (47%) was associated with higher NYHA class (hazard ratio [HR] 2.45 per one class increase, 95% CI 1.73–3.46; p p p = 0.005) and higher LVEF (1.08 per 1% increase, 1.05–1.11; p p = 0.010) and higher LVEF (1.10 per 1% increase, 1.06–1.13; p p = 0.77), HF type (p = 0.85) or LVEF (p = 0.58). Conclusions Supported by post-mortem data, the cause of death in HF and AF patients is heterogeneous, and the relationships with typical markers of mortality are critically dependent on the mode of death. The poor prognosis in this group demands further attention to improve management beyond anticoagulation. Graphical Abstract