Echocardiographic assessment of cardiac function in patients with atrial fibrillation

Echocardiography plays an essential role in the management of patients with 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. In this thesis, I have compared the reproducibility and validity of an index beat 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 and symptoms of heart failure. Transthoracic echocardiography was performed at baseline in 160 patients enrolled in the RAte control Therapy Evaluation in permanent AF randomised controlled trial (NCT02391337). Measurements of Simpson’s biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and the diastolic parameter E/e’ were obtained using three index beats and 3, 5 and 10 consecutive beats. All measurements were analysed offline with the analyser blinded to clinical details and with no pre-exclusions to image quality. The index beat method was shown to have a significantly lower within beat variability compared to consecutive beats and a single index beat measuring GLS and E/e’ was more reproducible or equally reproducible to averaging 10 consecutive beats when assessing intra and inter-operator reproducibility. Using a single index beat did not impact on the validity of LVEF, GLS or E/e’ when correlated with natriuretic peptides and substantially shortened the time taken for measurement of E/e’ (64% quicker than assessing 10 consecutive beats). This approach can enhance the reliability and efficiency of measurements for both systolic and diastolic left ventricular function in patients with AF

Thromboembolic events and vascular dementia in patients with atrial fibrillation and low apparent stroke risk

The prevention of thromboembolism in atrial fibrillation (AF) is typically restricted to patients with specific risk factors and ignores outcomes such as vascular dementia. This population-based cohort study used electronic healthcare records from 5,199,994 primary care patients (UK; 2005-2020). A total of 290,525 (5.6%) had a diagnosis of AF and were aged 40-75 years, of which 36,340 had no history of stroke, a low perceived risk of stroke based on clinical risk factors and no oral anticoagulant prescription. Matching was performed for age, sex and region to 117,298 controls without AF. During 5 years median follow-up (831,005 person-years), incident stroke occurred in 3.8% with AF versus 1.5% control (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.91-2.21; P &lt; 0.001), arterial thromboembolism 0.3% versus 0.1% (HR 2.39, 95% CI 1.83-3.11; P &lt; 0.001), and all-cause mortality 8.9% versus 5.0% (HR 1.44, 95% CI 1.38-1.50; P &lt; 0.001). AF was associated with all-cause dementia (HR 1.17, 95% CI 1.04-1.32; P = 0.010), driven by vascular dementia (HR 1.68, 95% CI 1.33-2.12; P &lt; 0.001) rather than Alzheimer's disease (HR 0.85, 95% CI 0.70-1.03; P = 0.09). Death and thromboembolic outcomes, including vascular dementia, are substantially increased in patients with AF despite a lack of conventional stroke risk factors.</p

Phenoage and longitudinal changes on transthoracic echocardiography in Alström syndrome: a disease of accelerated ageing?

Alström syndrome (AS) is an ultra-rare disorder characterised by early-onset multi-organ dysfunction, such as insulin resistance, obesity, dyslipidaemia, and renal and cardiovascular disease. The objective is to explore whether AS is a disease of accelerated ageing and whether changes over time on echocardiography could reflect accelerated cardiac ageing. Cross-sectional measurement of Phenoage and retrospective analysis of serial echocardiography were performed between March 2012 and November 2022. The setting is a single national tertiary service jointly run by health service and patient charity. Forty-five adult patients aged over 16 years were included, 64% were male and 67% of White ethnicity. The median Phenoage was 48 years (interquartile range [IQR]: 35-72) in the 34 patients for whom this was calculable, which was significantly higher than the median chronological age of 29 years (IQR: 22-39, p<0.001). Phenoage was higher than chronological age in 85% (N=29) of patients, with a median difference of +18 years (IQR: +4, +34). On echocardiography, significant decreases were observed over time in left ventricular (LV) size at end-diastole (average of 0.046 cm per year, p<0.001) and end-systole (1.1% per year, p=0.025), with significant increase in posterior wall thickness at end-diastole (0.009 cm per year, p=0.008). LV systolic function measured by global longitudinal strain reduced (0.34 percentage points per year, p=0.020) and E/e'lat increased (2.5% per year, p=0.019). Most AS patients display a higher Phenoage compared to chronological age. Cardiac changes in AS patients were also reflective of accelerated ageing, with a reduction in LV size and increased wall thickening. AS may be a paradigm disease for premature ageing

Phenoage and longitudinal changes on transthoracic echocardiography in Alström Syndrome:A disease of accelerated ageing?

Alström syndrome (AS) is an ultra-rare disorder characterised by early-onset multi-organ dysfunction, such as insulin resistance, obesity, dyslipidaemia, and renal and cardiovascular disease. The objective is to explore whether AS is a disease of accelerated ageing and whether changes over time on echocardiography could reflect accelerated cardiac ageing. Cross-sectional measurement of Phenoage and retrospective analysis of serial echocardiography were performed between March 2012 and November 2022. The setting is a single national tertiary service jointly run by health service and patient charity. Forty-five adult patients aged over 16 years were included, 64% were male and 67% of White ethnicity. The median Phenoage was 48 years (interquartile range [IQR]: 35-72) in the 34 patients for whom this was calculable, which was significantly higher than the median chronological age of 29 years (IQR: 22-39, p<0.001). Phenoage was higher than chronological age in 85% (N=29) of patients, with a median difference of +18 years (IQR: +4, +34). On echocardiography, significant decreases were observed over time in left ventricular (LV) size at end-diastole (average of 0.046 cm per year, p<0.001) and end-systole (1.1% per year, p=0.025), with significant increase in posterior wall thickness at end-diastole (0.009 cm per year, p=0.008). LV systolic function measured by global longitudinal strain reduced (0.34 percentage points per year, p=0.020) and E/e'lat increased (2.5% per year, p=0.019). Most AS patients display a higher Phenoage compared to chronological age. Cardiac changes in AS patients were also reflective of accelerated ageing, with a reduction in LV size and increased wall thickening. AS may be a paradigm disease for premature ageing

Development of automated neural network prediction for echocardiographic left ventricular ejection fraction

Introduction: The echocardiographic measurement of left ventricular ejection fraction (LVEF) is fundamental to the diagnosis and classification of patients with heart failure (HF).Methods: This paper aimed to quantify LVEF automatically and accurately with the proposed pipeline method based on deep neural networks and ensemble learning. Within the pipeline, an Atrous Convolutional Neural Network (ACNN) was first trained to segment the left ventricle (LV), before employing the area-length formulation based on the ellipsoid single-plane model to calculate LVEF values. This formulation required inputs of LV area, derived from segmentation using an improved Jeffrey’s method, as well as LV length, derived from a novel ensemble learning model. To further improve the pipeline’s accuracy, an automated peak detection algorithm was used to identify end-diastolic and end-systolic frames, avoiding issues with human error. Subsequently, single-beat LVEF values were averaged across all cardiac cycles to obtain the final LVEF.Results: This method was developed and internally validated in an open-source dataset containing 10,030 echocardiograms. The Pearson’s correlation coefficient was 0.83 for LVEF prediction compared to expert human analysis (p &lt; 0.001), with a subsequent area under the receiver operator curve (AUROC) of 0.98 (95% confidence interval 0.97 to 0.99) for categorisation of HF with reduced ejection (HFrEF; LVEF&lt;40%). In an external dataset with 200 echocardiograms, this method achieved an AUC of 0.90 (95% confidence interval 0.88 to 0.91) for HFrEF assessment.Conclusion: The automated neural network-based calculation of LVEF is comparable to expert clinicians performing time-consuming, frame-by-frame manual evaluations of cardiac systolic function

Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis

OBJECTIVES: Timely 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. METHODS: This 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. RESULTS: 28 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 (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias. CONCLUSION: PPG 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

Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial

Consumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate (n = 143,379,796) and physical activity (n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) −2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI −3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity (P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337

Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: a cluster-randomized trial by the European Society of Cardiology and European Heart Rhythm Association

Aims: The aim is to describe the rationale, design, delivery, and baseline characteristics of the Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European society of cardiology in a cluster-Randomized trial in patients with Atrial Fibrillation (STEEER-AF) trial. Methods and results: STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomized in six countries (France, Germany, Italy, Poland, Spain, and UK; 2022–23). The STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with a mean age of 68.9 years (SD 11.7), CHA2DS2-VASc score of 3.2 (SD 1.8), and 647 (37%) women. Eight hundred and forty-three patients (49%) were in AF at enrolment and 760 (44%) in sinus rhythm. Oral anticoagulant therapy was prescribed in 1543 patients (89%), with the majority receiving direct oral anticoagulants (1378; 89%). Previous cardioversion, antiarrhythmic drug therapy, or ablation was recorded in 836 patients (48.3%). Five hundred fifty-one patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomized to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers. Conclusion: The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice and evaluate if a structured educational programme for healthcare professionals can improve patient-level care. Clinical Trial Registration: Clinicaltrials.gov, NCT04396418

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction:An individual patient-level analysis of double-blind randomized trials

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 < 50% at baseline, but did not improve prognosis.  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 < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%