Aims Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real-world practice across a healthcare system has not been previously reported. Methods and results Five thousand five hundred and three patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in the analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions, and relevant cardiovascular diagnoses, based on Kaplan-Meier analysis and Cox proportional hazard ratios (HRs). Median follow-up was 829 days (interquartile range 224-1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction [HR 2.71, 95% confidence interval (CI) 1.73-4.24, P < 0.001] and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41-2.93, P < 0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free 'warranty period' of at least 5 years in patients with no prior history of coronary artery disease and 4 years for those with disease. Conclusion In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorizes risk of future events over the next 5 years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period.

Abstract Background/Introduction Recent guidelines and randomised controlled trials have proposed less frequent use of invasive strategies for patients with stable chest pain, and demonstrated the non-inferiority of an initial medical management strategy. However, the impact of these updates on clinical practice in the United Kingdom has not been previously reported. Purpose We aimed to identify if recent guidelines and literature have changed the management of patients being referred for stress echocardiography to assess inducible ischaemia in a real-world, multi-centre national healthcare system, and determine if this has significantly impacted patient outcomes. Methods Patients were recruited to the EVAREST/BSE-NSTEP prospective cohort study between 2015 and 2023 across the UK as part of two phases (phase 1: Mar 2015-Sep 2020; phase 2: Oct 2020-Sep 2023). Patient demographics, and stress echocardiogram procedural details were collected by study team members at each participating hospital, and 1 year medical outcome data was collected via the Data Access Request Service from NHS England. Patient management decisions and outcomes including referral for invasive coronary angiography, mortality, and cardiovascular events were compared between recruitment phases using Kaplan-Meier analysis and Cox proportional hazard ratios. Results 5,082 participants were included in this analysis of patient management and outcomes (2,613 in phase 1, and 2,469 in phase 2), with a consistent age, sex, and BMI between recruitment cohorts. There was a higher rate of smoking and hypercholesterolaemia in phase 2 participants, but a decrease in hypertension and peripheral vascular disease (Table 1). There was a decrease in referral rate for invasive angiography for participants with a positive stress echocardiogram in phase 2 (p<0.05; Fig. 1B). Overall, participants in phase 2 had a higher rate of mortality (p<0.01) than those in phase 1, but there was no difference in cardiac event rate between phases (Fig. 1C-F). These results remained consistent after adjusting for covariates, with a reduced hazard ratio for invasive angiography in phase 2 participants who had a positive stress echocardiogram (HR 0.78, 95% CI 0.66-0.92, p<0.01). Additionally, phase 2 participants had an increased hazard ratio for mortality (HR 1.93, 95% CI 1.05-3.55, p<0.05), but no significant increase in risk of cardiac event (HR 0.69, 95% CI 0.43-1.12, p=0.13). Conclusions Since 2020, participants are being less frequently referred for invasive coronary angiography after stress echocardiography possibly in favour of an initial medical management strategy. However, this reduction in referral to coronary angiography does not appear to have a negative impact on patient health as measured by cardiac event rate.

Abstract Background/Introduction EVAREST is a large-scale prospective, multicenter, observational study evaluating the use and accuracy of stress echocardiography (SE) in patients recruited from 31 NHS hospitals. Purpose Sub-study analysis to assess whether SE practice and outcome varies with age of patients. Methods Patients were recruited sequentially on attendance at the SE clinic between March 2015 and March 2020. Differences in SE characteristics and outcomes were compared between two age groups separated by the median age of the study population into Younger and Older patients. Results We studied 7846 pts with a median age for all pts of 66 yrs. The mean age in the Younger Group was 55 (range 20-65) years and in the Older Group was 74 (range 66-94) years. An abnormal SE response occurred more commonly in the Older Group (19% vs 13%, p<0.001). Key demographic and risk factors that differed between groups were a higher proportion of females in the Older Group (2185 male, 1769 female) compared to the Younger group (2255 male, 1626 female), p=0.011, higher mean BMI in the Younger Group (29.61±5.8 vs 28.1±5.2 kg/m², p<0.001) and lower resting pulse pressure in the Older Group at 56.3±15.9 (95%CI 55.8-56.8) compared to 65.9±16.6 (95%CI 65.3-66.4), p<0.001. Exercise test was performed more commonly in the Younger Group compared to the Older Group (39% vs 23%, p<0.001). For those undergoing dobutamine stress, atropine was used more commonly in the Younger Group (36% vs 34%, p<0.001). However, dobutamine dosing was similar between groups, with the highest dose (40 µg/kg/min) achieved in 13% of the Younger Group and 14% of the Older Group, p=0.05. Ultrasound contrast was used less frequently in the Older Group (73% vs 70%, p=0.03) compared to the Younger group, (p<0.001). Complication rates were similar between groups with the Older Group having a lower peak SBP (150.7±29.3 (95%CI 149.7-151.7) vs 154.9±30.3 mm Hg (95%CI 153.8-155.9), p<0.001) and similar rates of an exaggerated BP response (defined as a peak SBP ≥220 mm Hg) evident in both groups (20% of the Younger Group compared to 21% of the Older Group, p=0.55). A low BP response (defined as peak systolic blood pressure <120 mm Hg) occurred in 8% of the Younger Group and 11% of the Older Group (p=0.001), while a severe hypotensive response (peak SBP<82 mm Hg) was very rare and occurred 0.31% of the Younger Group and 0.56% of the Older Group (p=0.09). Conclusions Stress echocardiography is being performed in patients with a wide age range from 20 to 94 years of age within the UK. Older patients undergoing stress echocardiography are more likely to be female and have a relatively lower cardiovascular risk profile. Delivery of stress echocardiography differs significantly with age, with lower contrast use and more frequent use of dobutamine. However, there is no evidence of higher rates of complications in older patients that might limit use of stress echocardiography in older populations.

Stress echocardiography is a key imaging modality for assessing coronary artery disease in the UK. Traditionally, stress echo services were led by consultant cardiologists, but evolving workforce models have increased the involvement of cardiac physiologists and scientists. This study, as part of the National Review of Stress Echocardiography Practice (BSE N-STEP), aimed to evaluate current stress echo workforce structures and test outcomes across a group of UK hospitals to inform future workforce planning. Data were analysed from 8506 stress echocardiograms, conducted between September 2020 and June 2023 across 34 UK hospitals. Based on the supervising workforce, stress echocardiograms were allocated into either a doctor-led (DL) or cardiac physiologist/scientist and nurse-led (CNL) model. 56.9

AIMS:To assess the real-world impact of updated clinical guidelines and literature on the management of patients undergoing stress echocardiography for the assessment of inducible ischaemia across a national health service. METHODS AND RESULTS:A total of 13 819 patients from 32 UK hospitals, referred for stress echocardiography between 2015 and 2023, were analysed across two phases: phase 1 (2015-2020) and phase 2 (2020-2023). Follow-up data for 1 year was available for 4920 participants through NHS Digital. Patients in phase 2 were younger and presented with a higher cardiovascular risk profile, although sex distribution remained similar across phases. There was an observed reduction in invasive angiography referrals within 1 year following a positive stress echocardiogram (P < 0.01), which appeared to be attributed to changes in the management of patients with moderate ischaemia (3-4 segments; P < 0.01). For those who did receive invasive assessment, there were no changes in intervention rate (P = 0.27), regardless of ischaemic burden. This trend was most evident in centres performing a higher volume of stress echocardiograms. CONCLUSION:Coronary disease management pathways have changed within the UK and fewer patients with moderate ischaemia are undergoing invasive coronary angiography. However, coronary intervention rates are unchanged, suggesting that stress echocardiography is being used to improve patient selection for invasive procedures while minimizing unnecessary referrals. Future work will assess if this reduction in angiography referrals is maintained long term, and if there are any effects on patient outcomes.

BackgroundIschaemia is a critical complication, and can result in poor surgical outcomes. While intra-operative overt ischaemia can be perceived with the naked eye, timely recognition of borderline perfusion can prevent post-operative ischaemic complications, which is particularly relevant for colorectal anastomoses. Consequently, there is a clinical need for new technologies to intra-operatively assess tissue oxygenation (indicative of end organ perfusion), with minimal disruption to the surgical workflow. Here we present a hyperspectral imaging (HSI) system for laparoscopic surgery. This system provides live, easy to interpret, tissue oxygenation (StO2) maps with associated quantitative values.MethodsWhite light view and tissue oxygenation maps were reconstructed from a protoype laparoscopic Hyperspectral Surgical System (HSS). First, in a live porcine model (55 kg female), the mesentery of a small bowel loop was temporarily occluded with a laparoscopic grasper, then released whilst being imaged with HSI. The quantitative StO2 values obtained from the HSS were compared with those of a non-invasive tissue oximetry probe (Moor VMS-Oxy, Moor Instruments Ltd, United Kingdom). Secondly, mimicking a laparoscopic colon resection and anastomosis, the colorectal junction was mobilised laparoscopically, exteriorised, transected, anastomosed and repositioned in the abdominal cavity. In order to compare healthy and ischaemic colon, the distal part was intentionally devascularised. Tissue oxygenation maps were compared with indocyanine green fluorescence angiography (ICG-FA) of the anastomotic region.ResultsThe HSS was used as the primary scope to complete a laparoscopic colorectal anastomosis, providing a simultaneous white light view and hyperspectral information. Quantitative results from small bowel imaging were shown to correlate with measurements from the superficial tissue oximetry probe. Real-time tissue oxygenation maps were shown to visually correlate with ICG-FA.ConclusionThe HSS can guide laparoscopic surgical procedures whilst providing visual and quantitative tissue oxygenation information in a live animal model. This paves the way for further studies to assess clinical applications.

BACKGROUND People born preterm (<37 weeks'gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation. OBJECTIVES The authors investigated whether preterm-born and term-born adults exhibit similar cardiac structural and functional remodeling following a 16-week aerobic exercise intervention. METHODS We conducted a randomized controlled trial in 203 adults (aged 18-35 years) with elevated blood pressure or stage 1 hypertension. Participants were randomized 1:1 to a 16-week aerobic exercise intervention or to a control group. In a prespecified cardiovascular magnetic resonance imaging (CMR) substudy, CMR was performed at 3.0-Tesla to assess left and right ventricular (LV and RV) structure and function before and after intervention. RESULTS A total of 100 participants completed CMR scans at baseline and after the 16-week intervention, with n = 47 in the exercise intervention group (n = 26 term-born; n = 21 preterm-born) and n = 53 controls (n = 32 term-born; n = 21 preterm-born). In term-born participants, LV mass to end-diastolic volume ratio decreased (-3.43; 95% CI:-6.29 to-0.56; interaction P = 0.027) and RV stroke volume index increased (5.53 mL/m(2); 95% CI: 2.60, 8.47; interaction P = 0.076) for those in the exercise intervention group vs controls. No significant effects were observed for cardiac structural indices in preterm-born participants. In preterm-born participants, LV basal-and mid-ventricular circumferential strain increased (-1.33; 95% CI:-2.07 to-0.60; interaction P = 0.057 and-1.54; 95% CI:-2.46 to-0.63; interaction P = 0.046, respectively) and RV global longitudinal strain increased (1.99%; 95% CI:-3.12 to-0.87; interaction P = 0.053) in the exercise intervention group vs controls. No significant effects were observed for myocardial deformation parameters in term-born participants. CONCLUSIONS Aerobic exercise training induces improved myocardial function but not cardiac structure in preterm-born adults. (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: People born preterm (<37 weeks' gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation. We sought to determine whether preterm-born adults with elevated and stage 1 hypertension exhibit similar cardiac structural and functional remodeling following a 16-week aerobic exercise intervention as their term-born peers. Methods: We conducted an open, parallel, two-arm superiority randomized controlled (1:1) trial in n=203 adults aged 18-35 years old with elevated or stage 1 hypertension. Participants were randomized to a 16-week aerobic exercise intervention targeting three, 60-minute supervised sessions per week at 60-80% peak heart rate (exercise intervention group) or sign-posted to educational materials on hypertension and recommended lifestyle behaviors (control group). In a pre-specified cardiovascular magnetic resonance imaging (CMR) sub-study, CMR was performed on a 3.0-Tesla Siemens scanner to assess left ventricular (LV) and right ventricular (RV) structure and function before and after the 16-week intervention period. Group differences in outcome variables after the intervention were examined using analysis of covariance (ANCOVA) adjusting for baseline outcome variables, sex, and age. Interactions between birth category and intervention effect were investigated by including an interaction term in the intervention ANCOVA analyses. Results: One hundred participants completed CMR scans both at baseline and after the 16-week intervention, with n=47 in the exercise intervention group (n=26 term-born; n=21 preterm-born) and n=53 controls (n=32 term-born; n=21 preterm-born). There was a significantly different response to the exercise intervention between preterm- and term-born participants. In term-born participants, LV mass to end-diastolic volume ratio decreased (adjusted mean difference: -3.43, 95% CI: -6.29,-0.56, interaction term p=0.027) and RV stroke volume index increased (adjusted mean difference: 5.53mL/m2, 95% CI: 2.60,8.47, interaction term p=0.076) for those in the exercise intervention group versus controls. No significant effects were observed for cardiac structural indices in preterm-born participants. In preterm-born participants, LV basal- and mid-ventricular circumferential strain increased (adjusted mean difference: -1.33, 95% CI: -2.07,-0.60, interaction term p=0.057 and adjusted mean difference: -1.54, 95% CI: -2.46,-0.63, interaction term p=0.046, respectively) and RV global longitudinal strain increased (adjusted mean difference=-1.99%, 95% CI=-3.12,-0.87, interaction p=0.053) for those in the exercise intervention group versus controls. No significant effects were observed for myocardial deformation parameters in term-born participants. Conclusions: Aerobic exercise training induces improved myocardial function but not cardiac structure in preterm-born adults. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The trial was registered on Clinicaltrials.gov on March 30, 2016 ([NCT02723552][1]). ### Funding Statement This work was supported by funding from the Wellcome Trust, British Heart Foundation (BHF), the Oxford BHF Centre for Research Excellence, and the National Institute for Health Research Oxford Biomedical Research Centre; a Medical Research Council Programme grant (MR/W003686/1) and St. Hilda?s College Oxford Stipendiary Junior Research Fellowship (W.L.), a BHF Intermediate Research Fellowship (FS/18/3/33292 to A.J.L.); a Wellcome Trust Clinical Research Training Fellowship (105741/Z/14/Z to W. Williamson); and the U.S. Air Force Institute of Technology (O.J.H.). The contents of this paper solely reflect the views of the authors and do not reflect or represent the views of the U.S. Air Force, the Department of Defense, or the U.S. government. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial protocol and any subsequent amendments were approved by the University of Oxford as host institution and study sponsor and by the South Central Research Ethics Committee for the National Health Service Health Research Authority (Reference: 16/SC/0016). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available upon request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02723552&atom=%2Fmedrxiv%2Fearly%2F2024%2F10%2F29%2F2024.10.28.24316322.atom

Abstract Background People born preterm (<37 weeks’ gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation and may explain their increased risk of early heart failure and cardiovascular-related mortality. It remains unknown whether lifestyle or pharmacological interventions lead to beneficial left ventricle (LV) and right ventricle (RV) structural and/or functional changes in preterm-born adults. Purpose To determine whether preterm-born adults with elevated and stage 1 hypertension exhibit similar cardiac remodelling following a 16-week aerobic exercise intervention as their term-born peers with comparable blood pressures. Methods We conducted an open, parallel, two-arm superiority randomised controlled (1:1) trial in n=203 adults aged 18-35 years old with elevated or stage 1 hypertension. Participants were randomised to a 16-week aerobic exercise intervention targeting three, 60-minute supervised sessions per week at 60-80% peak heart rate (exercise intervention) or sign-posted to educational materials (controls). In a pre-specified cardiovascular magnetic resonance imaging (CMR) sub-study in n=100 individuals, CMR was performed before and after the 16-week intervention. Group differences in outcome variables after the intervention were examined using ANCOVA adjusting for baseline outcome variables, sex, and age. Interactions between birth category and intervention effect were investigated by including an interaction term in the intervention ANCOVA analyses. Results One hundred participants completed CMR scans at baseline and after the 16-week intervention, with n=47 in the exercise intervention group (n=26 term-born; n=21 preterm-born) and n=53 controls (n=32 term-born; n=21 preterm-born). Cardiac structural measures in preterm-born adults did not change following the intervention. However, term-born adults in the exercise intervention group decreased LV mass to end-diastolic volume ratio (adjusted mean difference: -0.03, 95% CI: -0.06,-0.01, interaction term p=0.027) and increased RV stroke volume (adjusted mean difference: 5.53mL/m2, 95% CI: 2.60,8.47, interaction term p=0.076) versus controls. Preterm-born adults in the exercise intervention group increased LV basal- and mid-ventricular circumferential strain versus controls (adjusted mean difference: -1.33%, 95% CI: -2.07,-0.60, interaction term p=0.057 and adjusted mean difference: -1.54%, 95% CI: -2.46,-0.63, interaction term p=0.046, respectively), which was not observed in term-born adults. Similarly, preterm-born adults improved RV longitudinal strain versus controls (adjusted mean difference: -0.51%, 95% CI: -1.49,0.46, interaction term p=0.053), which was also not observed in term-born adults. Conclusions Aerobic exercise training improves myocardial function but not cardiac structure in preterm-born adults. Modified exercise protocols or combination with pharmacological intervention may lead to additional cardiac remodelling benefits.

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): MRC. Background Cardiac catheterisation is the gold standard for assessing cardiac pressures. However, this is an invasive and costly procedure. A minimally invasive alternative may be to use the subharmonic signal of microbubble ultrasound contrast agents to estimate pressure using echocardiography (Sub-Harmonic Assisted Pressure Estimation: SHAPE). Purpose The aim of this work was to investigate the ability of SHAPE to track dynamic diastolic pressures in a flow phantom at body temperature and at reduced microbubble concentrations. Methods A priming dose of 0.4 mL/L of sulphur hexafluoride microbubbles was circulated through a silicone tube using a peristaltic pump at a flow rate of 375 mL/min (generating 376 pressure cycles/min and maximum pressure gradient of 1.9 mmHg/ms; Fig. 1). The ULtrasound Advanced Open Platform (ULA-OP) was used with a cardiac phased array transducer to transmit a pulse-inversion sequence at 2.1 MHz. Radiofrequency data were recorded at five acoustic pressures (71–228 kPa peak-negative). To investigate the effects of temperature, the subharmonic-pressure relationship was measured over 60 min at both room and body temperature (37°C). Microbubble concentration was maintained by regular top-up (0.15 mL/L every 3–5 min). To investigate the effect of lower concentrations on the subharmonic-pressure relationship, a priming dose of 0.4, 0.3 or 0.2 mL/L was administered before a single acquisition was made. The system was immediately purged before testing the next concentration. The subharmonic (1.05 MHz) amplitude of the microbubbles was calculated over a 40% bandwidth. A solid-state catheter recorded ground-truth pressures. Correlation coefficient (r) and sensitivity (dB/mmHg) of the subharmonic signal to the pressure values were calculated. Results The mean correlation coefficient (r = 0.91 ± 0.04; Fig. 2) and sensitivity (0.20 ± 0.04 dB/mmHg) at body temperature (n = 20) were significantly greater than those for the same batch of microbubbles at room temperature (r = 0.81 ± 0.07 and 0.14 ± 0.02; n = 18; p < 0.05) at the optimal acoustic pressure (Fig. 2). No significant differences in the subharmonic-pressure relationship were observed between the three different microbubble concentrations (Correlation: r = 0.96 ± 0.00, 0.96 ± 0.01, 0.97 ± 0.01. Sensitivity: 0.26 ± 0.02, 0.26 ± 0.03, 0.28 ± 0.02 mmHg/dB for 0.4, 0.3 and 0.2 mL/L, respectively; n = 3) at the optimal acoustic pressure. Conclusions SHAPE can accurately track diastolic pressures five times faster than the average resting heart rate at body temperature and with reduced microbubble concentrations. SHAPE is a potential method for assessing cardiac diastolic pressures using ultrasound in a minimally invasive fashion, being suitable for use in patients with faster microbubble clearance or in the event of delayed acquisition. The use of SHAPE fits into routine clinical procedures and has the potential to improve the diagnosis and monitoring of cardiovascular diseases.

Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identified key factors that affect costs to help inform future clinical planning and guidelines. Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level. Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities and higher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95

Rationale: Premature birth is an independent predictor of long-term cardiovascular risk. Individuals affected are reported to have a lower rate of (V) over dot(O2) at peak exercise intensity ((V) over dot(O2PEAK)) and at the ventilatory anaerobic threshold ((V) over dot(O2VAT)), but little is known about their response to exercise training. Objectives: The primary objective was to determine whether the (V) over dot(O2PEAK) response to exercise training differed between preterm-born and term-born individuals; the secondary objective was to quantify group differences in (V) over dot(O2VAT) response. Methods: Fifty-two preterm-born and 151 term-born participants were randomly assigned (1:1) to 16 weeks of aerobic exercise training (n = 102) or a control group (n = 101). Cardiopulmonary exercise tests were conducted before and after the intervention to measure (V) over dot(O2PEAK) and the (V) over dot(O2VAT). A prespecified subgroup analysis was conducted by fitting an interaction term for preterm and term birth histories and exercise group allocation. Measurements and Main Results: For term-born participants, (V) over dot(O2PEAK) increased by 3.1 ml/kg/min (95% confidence interval [CI], 1.7 to 4.4), and the (V) over dot(O2VAT) increased by 2.3 ml/kg/ min (95% CI, 0.7 to 3.8) in the intervention group versus controls. For preterm-born participants, (V) over dot(O2PEA)K increased by 1.8 ml/kg/min (95% CI, 20.4 to 3.9), and the (V) over dot(O2VAT) increased by 4.6 ml/kg/min (95% CI, 2.1 to 7.0) in the intervention group versus controls. No significant interaction was observed with birth history for (V) over dot(O2PEAK) (P=0.32) or the (V) over dot(O2VAT) (P= 0.12). Conclusions: The training intervention led to significant improvements in (V) over dot(O2PEAK) and (V) over dot(O2VAT), with no evidence of a statistically different response based on birth history.

Aortic stenosis is a condition which is fatal if left untreated. Novel quantitative imaging techniques which better characterise transvalvular pressure drops are being developed but require refinement and validation. A customisable and cost-effective workbench valve phantom circuit capable of replicating valve mechanics and pathology was created. The reproducibility and relationship of differing haemodynamic metrics were assessed from ground truth pressure data alongside imaging compatibility. The phantom met the requirements to capture ground truth pressure data alongside ultrasound and magnetic resonance image compatibility. The reproducibility was successfully tested. The robustness of three different pressure drop metrics was assessed: whilst the peak and net pressure drops provide a robust assessment of the stenotic burden in our phantom, the peak-to-peak pressure drop is a metric that is confounded by non-valvular factors such as wave reflection. The peak-to-peak pressure drop is a metric that should be reconsidered in clinical practice. The left panel shows manufacture of low cost, functional valves. The central section demonstrates circuit layout, representative MRI and US images alongside gross valve morphologies. The right panel shows the different pressure drop metrics that were assessed for reproducibility

Abstract Aims Stress echocardiography is widely used to identify obstructive coronary artery disease (CAD). High accuracy is reported in expert hands but is dependent on operator training and image quality. The EVAREST study provides UK-wide data to evaluate real-world performance and accuracy of stress echocardiography. Methods and results Participants undergoing stress echocardiography for CAD were recruited from 31 hospitals. Participants were followed up through health records which underwent expert adjudication. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, medical management of ischaemia, acute coronary syndrome, or cardiac-related death within 6 months. A total of 5131 patients (55% male) participated with a median age of 65 years (interquartile range 57–74). 72.9% of studies used dobutamine and 68.5% were contrast studies. Inducible ischaemia was present in 19.3% of scans. Sensitivity and specificity for prediction of a cardiac outcome were 95.4% and 96.0%, respectively, with an accuracy of 95.9%. Sub-group analysis revealed high levels of predictive accuracy across a wide range of patient and protocol sub-groups, with the presence of a resting regional wall motion abnormalitiy significantly reducing the performance of both dobutamine (P < 0.01) and exercise (P < 0.05) stress echocardiography. Overall accuracy remained consistently high across all participating hospitals. Conclusion Stress echocardiography has high accuracy across UK-based hospitals and thus indicates stress echocardiography is being delivered effectively in real-world practice, reinforcing its role as a first-line investigation in the assessment of patients with stable chest pain.

OBJECTIVES:The purpose of this study was to establish whether an artificially intelligent (AI) system can be developed to automate stress echocardiography analysis and support clinician interpretation.BACKGROUND:Coronary artery disease is the leading global cause of mortality and morbidity and stress echocardiography remains one of the most commonly used diagnostic imaging tests.METHODS:An automated image processing pipeline was developed to extract novel geometric and kinematic features from stress echocardiograms collected as part of a large, United Kingdom-based prospective, multicenter, multivendor study. An ensemble machine learning classifier was trained, using the extracted features, to identify patients with severe coronary artery disease on invasive coronary angiography. The model was tested in an independent U.S.STUDY:How availability of an AI classification might impact clinical interpretation of stress echocardiograms was evaluated in a randomized crossover reader study.RESULTS:Acceptable classification accuracy for identification of patients with severe coronary artery disease in the training data set was achieved on cross-fold validation based on 31 unique geometric and kinematic features, with a specificity of 92.7% and a sensitivity of 84.4%. This accuracy was maintained in the independent validation data set. The use of the AI classification tool by clinicians increased inter-reader agreement and confidence as well as sensitivity for detection of disease by 10% to achieve an area under the receiver-operating characteristic curve of 0.93.CONCLUSIONS:Automated analysis of stress echocardiograms is possible using AI and provision of automated classifications to clinicians when reading stress echocardiograms could improve accuracy, inter-reader agreement, and reader confidence.

Summary Background Exercise is advised for young adults with elevated blood pressure, but no trials have investigated efficacy at this age. We aimed to determine whether aerobic exercise, self-monitoring and motivational coaching lowers blood pressure in this group. Methods The study was a single-centre, open, two-arm, parallel superiority randomized clinical trial with open community-based recruitment of physically-inactive 18–35 year old adults with awake 24 h blood pressure 115/75mmHg-159/99 mmHg and BMI<35 kg/m2. The study took place in the Cardiovascular Clinical Research Facility, John Radcliffe Hospital, Oxford, UK. Participants were randomized (1:1) with minimisation factors sex, age (<24, 24–29, 30–35 years) and gestational age at birth (<32, 32–37, >37 weeks) to the intervention group, who received 16-weeks aerobic exercise training (three aerobic training sessions per week of 60 min per session at 60–80% peak heart rate, physical activity self-monitoring with encouragement to do 10,000 steps per day and motivational coaching to maintain physical activity upon completion of the intervention. The control group were sign-posted to educational materials on hypertension and recommended lifestyle behaviours. Investigators performing statistical analyses were blinded to group allocation. The primary outcome was 24 h awake ambulatory blood pressure (systolic and diastolic) change from baseline to 16-weeks on an intention-to-treat basis. Clinicaltrials.gov registered on March 30, 2016 (NCT02723552). Findings Enrolment occurred between 30/06/2016-26/10/2018. Amongst the 203 randomized young adults (n = 102 in the intervention group; n = 101 in the control group), 178 (88%; n = 76 intervention group, n = 84 control group) completed 16-week follow-up and 160 (79%; n = 68 intervention group, n = 69 control group) completed 52-weeks follow-up. There were no group differences in awake systolic (0·0 mmHg [95%CI, -2·9 to 2·8]; P = 0·98) or awake diastolic ambulatory blood pressure (0·6 mmHg [95%CI, -1·4. to 2·6]; P = 0·58). Aerobic training increased peak oxygen uptake (2·8 ml/kg/min [95%CI, 1·6 to 4·0]) and peak wattage (14·2watts [95%CI, 7·6 to 20·9]) at 16-weeks. There were no intervention effects at 52-weeks follow-up. Intepretation These results do not support the exclusive use of moderate to high intensity aerobic exercise training for blood pressure control in young adults. Funding Wellcome Trust, British Heart Foundation, National Institute for Health Research, Oxford Biomedical Research Centre.

Abstract Background Transvalvular pressure drops are assessed using Doppler echocardiography for the diagnosis of heart valve disease. However, this method is highly user-dependent and may overestimate transvalvular pressure drops by up to 54%. This work aimed to assess transvalvular pressure drops using velocity fields derived from blood speckle imaging (BSI), as a potential alternative to Doppler. Methods A silicone 3D-printed aortic valve model, segmented from a healthy CT scan, was placed within a silicone tube. A CardioFlow 5000MR flow pump was used to circulate blood mimicking fluid to create eight different stenotic conditions. Eight PendoTech pressure sensors were embedded along the tube wall to record ground-truth pressures (10 kHz). The simplified Bernoulli equation with measured probe angle correction was used to estimate pressure drop from maximum velocity values acquired across the valve using Doppler and BSI with a GE Vivid E95 ultrasound machine and 6S-D cardiac phased array transducer. Results There were no significant differences between pressure drops estimated by Doppler, BSI and ground-truth at the lowest stenotic condition (10.4 ± 1.76, 10.3 ± 1.63 vs. 10.5 ± 1.00 mmHg, respectively; p > 0.05). Significant differences were observed between the pressure drops estimated by the three methods at the greatest stenotic condition (26.4 ± 1.52, 14.5 ± 2.14 vs. 20.9 ± 1.92 mmHg for Doppler, BSI and ground-truth, respectively; p < 0.05). Across all conditions, Doppler overestimated pressure drop (Bias = 3.92 mmHg), while BSI underestimated pressure drop (Bias = -3.31 mmHg). Conclusions BSI accurately estimated pressure drops only up to 10.5 mmHg in controlled phantom conditions of low stenotic burden. Doppler overestimated pressure drops of 20.9 mmHg. Although BSI offers a number of theoretical advantages to conventional Doppler echocardiography, further refinements and clinical studies are required with BSI before it can be used to improve transvalvular pressure drop estimation in the clinical evaluation of aortic stenosis.

Aims To evaluate whether left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), automatically calculated by artificial intelligence (AI), increases the diagnostic performance of stress echocardiography (SE) for coronary artery disease (CAD) detection. Methods and results SEs from 512 participants who underwent a clinically indicated SE (with or without contrast) for the evaluation of CAD from seven hospitals in the UK and US were studied. Visual wall motion scoring (WMS) was performed to identify inducible ischaemia. In addition, SE images at rest and stress underwent AI contouring for automated calculation of AI-LVEF and AI-GLS (apical two and four chamber images only) with Ultromics EchoGo Core 1.0. Receiver operator characteristic curves and multivariable risk models were used to assess accuracy for identification of participants subsequently found to have CAD on angiography. Participants with significant CAD were more likely to have abnormal WMS, AI-LVEF, and AI-GLS values at rest and stress (all P < 0.001). The areas under the receiver operating characteristics for WMS index, AI-LVEF, and AI-GLS at peak stress were 0.92, 0.86, and 0.82, respectively, with cut-offs of 1.12, 64%, and -17.2%, respectively. Multivariable analysis demonstrated that addition of peak AI-LVEF or peak AI-GLS to WMS significantly improved model discrimination of CAD [C-statistic (bootstrapping 2.5th, 97.5th percentile)] from 0.78 (0.69-0.87) to 0.83 (0.74-0.91) or 0.84 (0.75-0.92), respectively. Conclusion AI calculation of LVEF and GLS by contouring of contrast-enhanced and unenhanced SEs at rest and stress is feasible and independently improves the identification of obstructive CAD beyond conventional WMSI.

Cardiac catheterization is the gold standard for assessing cardiac pressures. However, this is an invasive and costly procedure. An alternative may be to use the subharmonic signal of microbubble ultrasound contrast agents to estimate pressure using echocardiography. The aim of this work was to investigate the subharmonic response of the ultrasound contrast agent SonoVue (Bracco Spa, Milan, Italy) to dynamic pressures in a flow phantom. SonoVue was circulated through a silicone tube using a peristaltic pump. The ULtrasound Advanced Open Platform (ULA-OP) was used with a cardiac phased array transducer to transmit a pulse-inversion sequence at 2.1 MHz. Radiofrequency data were recorded at five acoustic pressures (71–228 kPa peak-negative) to investigate the effects of pulse length (7-, 12- and 16-cycle pulses) and flow rate (150, 200 and 375 mL/min). The subharmonic (1.05 MHz) amplitude of SonoVue was calculated over a 40% bandwidth. A solid-state catheter recorded ground-truth pressures. Increasing pulse length improved the correlation coefficient between the subharmonic signal of SonoVue and pressure (r = 0.74 ± 0.14, 0.79 ± 0.06 vs. 0.86 ± 0.04 for 7-, 12- and 16-cycle pulses, respectively; $n$ = 3 at optimal acoustic pressure). The strong correlations with 16-cycle pulses persisted at different flow rates ($r > 0.8$). This is the first report showing the ability of SonoVue to track pressure cycles five times faster than the average resting heart rate (376 cycles/min at 375 mL/min flow rate). SonoVue may potentially be used to assess diastolic and pulse pressures using ultrasound instead of cardiac catheterization.

Introduction Healthcare delivery is being transformed by COVID-19 to reduce transmission risk but continued delivery of routine clinical tests is essential. Stress echocardiography is one of the most widely used cardiac tests in the NHS. We assessed the impact of the first (W1) and second (W2) waves of the pandemic on the ability to deliver stress echocardiography. Methods Clinical echocardiography teams in 31 NHS hospitals participating in the EVAREST study were asked to complete a survey on the structure and delivery of stress echocardiography as well as its impact on patients and staff in July and November 2020. Results were compared to stress echocardiography activity in the same centre during January 2020. Results 24 completed the survey in July, and 19 NHS hospitals completed the survey in November. A 55% reduction in the number of studies performed was reported in W1, recovering to exceed pre-COVID rates in W2. The major change was in the mode of stress delivery. 70% of sites stopped their exercise stress service in W1, compared to 19% in W2. In those still using exercise during W1, 50% were wearing FFP3/N95 masks, falling to 38% in W2. There was also significant variability in patient screening practices with 7 different pre-screening questionnaires used in W1 and 6 in W2. Conclusion Stress echocardiography delivery restarted effectively after COVID-19 with adaptations to reduce transmission that means activity has been able to continue, and exceed, pre-COVID-19 levels during the second wave. Further standardization of protocols for patient screening and PPE may help further improve consistency of practice within the United Kingdom.