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Objective: To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval., Methods: Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides., Results: 160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels., Conclusions: Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF., Competing Interests: Competing interests: KVB reports she was the research fellow for the RATE-AF trial funded by a National Institute for Health Research (NIHR) Career Development Fellowship awarded to DK. SG: none directly relevant to this work; funding through the BigData@Heart Innovative Medicines Initiative (grant no 116074). GL: none directly relevant to this work; consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi Sankyo; and speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi Sankyo; no fees are directly received personally. PK reports grants from NIHR, European Union and British Heart Foundation, during the conduct of the study; grants and non-financial support from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK) and German Centre for Heart Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies, outside the submitted work; in addition, PK is listed as inventor on two patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). JC: none directly relevant to this work; reports grants and personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer/BMS; and personal fees from Medtronic, Boston Scientific and Abbott. KR reports grants from NIHR Oxford Biomedical Research Centre, University of Oxford; grants from UKRI’s Global Challenge Research Fund (ESRC), PEAK Urban Programme Grant Ref: ES/P011055/1; grants from the British Heart Foundation (grant numbers: FS/19/36/34346 and PG/18/65/33872); grants from Oxford Martin School, University of Oxford, during the conduct of the study; and personal fees from PLOS Medicine and from BMJ Heart, outside the submitted work. DK reports grants from the National Institute for Health Research (NIHR CDF-2015-08-074 and NIHR HTA-130280), the British Heart Foundation (PG/17/55/33087 and AA/18/2/34218), the European Society of Cardiology supported by educational grants from Boehringer Ingelheim/BMS-Pfizer Alliance/Bayer/Daiichi Sankyo/Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre and British Heart Foundation/University of Birmingham Accelerator Award (STEEER-AF NCT04396418), EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074) and IRCCS San Raffaele/Menarini (Beta-blockers in Heart Failure Collaborative Group NCT0083244), in addition to personal fees from Bayer (Advisory Board), AtriCure (Speaker fees), Amomed (Advisory Board), Protherics Medicines Development (Advisory Board) and Myokardia (Advisory Board), all outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)