Objective To provide guidance on the use of cardiac MRI (CMR) in the UK in paediatric and adult patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) as well as recommendations for screening and monitoring females with dystrophin-gene variations. Specifically, to examine the ‘added value’ of CMR over echocardiography at selected time points in the assessment of individuals with or at risk of developing cardiac dystrophinopathy.Methods Initiated by an expert working group of UK-based and US-based imaging cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK cardiologists, consensus was reached on the optimal use of CMR in clinical decision-making about therapy.Results and conclusions Echocardiography should remain the predominant modality for cardiac surveillance and to guide therapy for patients with DMD in the UK. However, when tolerated, wider use of CMR at key stages in patients with DMD, older than age 10 years, and for males with BMD and females with DMD-gene variations would allow earlier detection of those with cardiac involvement and inform the earlier initiation of regimes of cardiac medications. In this way, greater use of CMR could contribute to improving cardiac health in each of these patient groups.

BACKGROUND:Right ventricular systolic pressure (RVSP) is an echocardiographic metric to monitor pulmonary hypertension (PH). However, there is no recommendation on what constitutes a meaningful change. In this study, we aimed to gain insight into how physicians at our institution report significant changes in RVSP. We then aimed to quantify the analytic variability of reported RVSP using duplicate analysis. METHODS:We utilized the Stanford CardioShare Registry to identify 5,934 patients with 32,656 echocardiogram pairs with reported RVSP. Natural Language Processing was employed to categorize pairs into decrease, increase, no change, and no direct mention. Classification and Regression Tree (CART) analysis was applied to these groups to identify reporting thresholds among physicians. To assess the performance of the CART model, accuracy, precision, recall, and F1-score were reported using a stratified cross-validation method. In a separate cohort comprising 210 healthy volunteers and 208 patients with PH, two blinded core laboratory cardiologists measured the peak tricuspid regurgitation velocity. We employed a duplicate analysis method to model bias and a robust precision method for reporting RVSP and assessing analytical variability. RESULTS:Of the total pairs of echocardiographic studies, RVSP was reported as stable in 48.9%, increased in 12.5%, decreased in 9.9% while 28.7% did not have a direct reference to RVSP change. CART analysis revealed that physicians most commonly determine change based on an absolute threshold of 8 mmHg and whether the change occurred within or outside the reference range. On cross-validation, the accuracy and F1-score were 83% and 79% for the increase and 81% and 74% for the decrease algorithms. In the duplicate analysis cohort, the analytic precision was 8-10% with worst relative precision at lower values of RVSP. This translates into a 15% reference change value, assuming a 4-5% biological variation. CONCLUSION:The study provides insights on real world practice of physician reporting in RVSP and provides directions for future recommendations regarding report changes.

Sudden cardiac death in a young physically active individual or athlete is a rare but tragic event. Pre-participation screening and follow-up investigations are utilised to reduce the risk and occurrence of these events. Echocardiography plays a key role in the cardiac diagnostic pathway and aims to identify underlying inherited or congenital structural cardiac conditions. In 2013 the British Society of Echocardiography and Cardiac Risk in the Young produced a joint guidance document to support echocardiographers in this setting. The document was subsequently updated in 2018, and it is now timely to provide a further update to the guideline drawing on the advances in our knowledge alongside the developments in ultrasound technology within this nuanced area of sports cardiology.

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.

Abstract Introduction The British Society of Echocardiography National Review of Stress Echo Practice (BSE N-STEP) is a large, prospective, multicentre study investigating stress echocardiography (SE) practice within the UK National Health Service. We used this dataset to identify, categorise and compare the characteristics of the workforce groups delivering SE within this real-world study cohort. Method Recruitment occurred between September 2020 and June 2023 across 34 NHS trusts. All patients provided informed consent and underwent SE following the local policy of each trust. Baseline characteristics of participants and details of SE procedure were recorded including stress modality and test outcome data. In addition, workforce involved in delivery of each test was self-reported including a description of staff responsible for test delivery, reporting and overall test supervision. Based on this, studies were categorised as either doctor-led (DL) which included both consultants and doctors in training, or cardiac physiologist/nurse-led (CNL). Frequency data was reported for each workforce group with Chi-square analysis used to identify differences between categorical variables. Results Data from 8506 patients were included in this analysis. SE supervision was identified as DL in 4839 (56.9%) and CNL in 3636 (42.7%) of which 79% was supervised by a cardiac physiologist. 28 hospitals reported both DL and CNL services. CNL services tended to be within higher volume centres, so that 4 trusts (two regional hospitals and two tertiary) contributed 71% of the total SE activity. Patients in CNL services were of similar age compared to DL service but were more likely to be male (p=0.008) and had a higher risk factor profile including hypertension (54.9% vs 50.1%), hypercholesterolaemia (50.3% vs 39.6%), and diabetes (24.9% vs 18.8%) (p=<0.001). The proportion of patients seen for ischaemic heart disease tests was similar between DL and CNL clinics (89.1% vs 89.7%, p=ns) but CNL services performed more viability (0.8% vs 1.2%, p= 0.04) and pre-op studies (2.6% vs 3.4%, p= 0.03). DL services more commonly performed dobutamine stress studies (63.0% vs 56.3%, p=<0.001) whilst the CNL group performed more exercise SE (42.8% vs 36.4%, p=<0.001). Positivity rates for SE were similar across DL and CNL groups (17.1% vs 17.7%) as were inconclusive/ abandoned tests (3.8% vs 3.6%, p=ns). However, there was a lower rate of reported complications in the CNL services (2.2% vs 5.3% (p= <0.001). Discussion: Supervision of SE testing has traditionally been led by cardiologists with nursing and physiologist staff acting in supporting roles. This study demonstrates that the UK SE workforce is evolving, with non-medical-led services contributing significantly to the volume of SE activity although clear differences in the test modality remain between DL and CNL services at present.

Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for similar to 30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p < 0.001), owing to an increased frequency of CD3(-)CD56(+)CD16(+) NK-cells (+348%), HLA-DR(+)CD14(dim)CD16(+) monocytes (+125%), and HLA-DR(+)CD14(+)CD32(+) monocytes (+41%) in blood (p < 0.01). However, overall, total plasma cells (CD38(+)CD138(+)) nor clonal plasma cells (CD38(bright)CD138(+)CD45(-/dim)CD19(-) with light-chain restriction) increased in blood (p > 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide - whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 - the daratumumab target antigen - increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.

Impairment of left ventricular (LV) diastolic function is common amongst those with left heart disease and is associated with significant morbidity. Given that, in simple terms, the ventricle can only eject the volume with which it fills and that approximately one half of hospitalisations for heart failure (HF) are in those with normal/’preserved’ left ventricular ejection fraction (HFpEF) (Bianco et al. in JACC Cardiovasc Imaging. 13:258–271, 2020. 10.1016/j.jcmg.2018.12.035), where abnormalities of ventricular filling are the cause of symptoms, it is clear that the assessment of left ventricular diastolic function (LVDF) is crucial for understanding global cardiac function and for identifying the wider effects of disease processes. Invasive methods of measuring LV relaxation and filling pressures are considered the gold-standard for investigating diastolic function. However, the high temporal resolution of trans-thoracic echocardiography (TTE) with widely validated and reproducible measures available at the patient’s bedside and without the need for invasive procedures involving ionising radiation have established echocardiography as the primary imaging modality. The comprehensive assessment of LVDF is therefore a fundamental element of the standard TTE (Robinson et al. in Echo Res Pract7:G59–G93, 2020. 10.1530/ERP-20-0026). However, the echocardiographic assessment of diastolic function is complex. In the broadest and most basic terms, ventricular diastole comprises an early filling phase when blood is drawn, by suction, into the ventricle as it rapidly recoils and lengthens following the preceding systolic contraction and shortening. This is followed in late diastole by distension of the compliant LV when atrial contraction actively contributes to ventricular filling. When LVDF is normal, ventricular filling is achieved at low pressure both at rest and during exertion. However, this basic description merely summarises the complex physiology that enables the diastolic process and defines it according to the mechanical method by which the ventricles fill, overlooking the myocardial function, properties of chamber compliance and pressure differentials that determine the capacity for LV filling. Unlike ventricular systolic function where single parameters are utilised to define myocardial performance (LV ejection fraction (LVEF) and Global Longitudinal Strain (GLS)), the assessment of diastolic function relies on the interpretation of multiple myocardial and blood-flow velocity parameters, along with left atrial (LA) size and function, in order to diagnose the presence and degree of impairment. The echocardiographic assessment of diastolic function is therefore multifaceted and complex, requiring an algorithmic approach that incorporates parameters of myocardial relaxation/recoil, chamber compliance and function under variable loading conditions and the intra-cavity pressures under which these processes occur. This guideline outlines a structured approach to the assessment of diastolic function and includes recommendations for the assessment of LV relaxation and filling pressures. Non-routine echocardiographic measures are described alongside guidance for application in specific circumstances. Provocative methods for revealing increased filling pressure on exertion are described and novel and emerging modalities considered. For rapid access to the core recommendations of the diastolic guideline, a quick-reference guide (additional file 1) accompanies the main guideline document. This describes in very brief detail the diastolic investigation in each patient group and includes all algorithms and core reference tables.

Background High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study ( N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. Methods In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity– monoclonal (M)-protein and free light chains (FLC)– plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. Results Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O 2PEAK . There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (− 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. Conclusions A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). Registration https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Background The National Echocardiography Database of the United Kingdom (NED-UK) pilot study demonstrates the feasibility of extracting echocardiographic (echo) 'big data' from NHS databases in a standardised way. Our aim was to demonstrate utility of NED-UK pilot data by showing associations of echo reported variables with patient outcomes, specifically the time from echo to cardiac surgery (bypass grafting and/or valve replacement or repair). Methods Data were collected under the 'EchoVision' project (UK HRA approval 251473). Data from consecutive echos, undertaken at an NHS Trust from 2017–2023 were extracted using Philips Advanced Analytics software. The data were pre-processed in RStudio (v2023.09.1) using R (v4.2.1) to remove scans with age <18 years or missing age, sex, height or weight. Echo report data (measurements, standardised interpretive phrases and free-text comments) were crossmatched with an existing internal cardiac surgery dataset (including date of surgery) to identify the earliest echo prior to patients receiving their first cardiac surgery. Patients with prior cardiac intervention, congenital heart disease or an implantable cardiac electronic device were excluded. The time from echo to cardiac surgery was calculated (time-to-surgery (TTS)). Variables or patients with >30% data incompleteness were removed. Residual missing values were imputed using the modal class (categorical variables) or trimmed scores regression in Matlab (numerical variables). Echo variables had normality determined using the Shapiro-Wilk test. Categorical variables were binary coded as 0/1. A multiple linear regression model was built using R in RStudio to predict TTS. The echo variables that significantly correlated with TTS were entered with forward-stepwise selection. Alpha was set at p<0.01 to account for multiple hypothesis testing. Visualisations were made using the 'ggplot2' R library. Results 367 patients (mean age 64±11 years, 295 (80.4%) male) receiving their first cardiac surgery with a suitable echo were obtained. TTS ranged from 1–2248 days (median 57, interquartile range 459). 7.3% of echo values were imputed. Of 39 possible predictor variables, 14 had significant correlations with the TTS (table 1). The final regression model contained 7 of these with the following equation; Predicted TTS = (21.58×EF) + (125.24×LVIDd) - (7.98×LAVi) + (294.72 if comment of LA dilation) + (147.22 if ≥moderate MR) + (460.08 if comment of hyperdynamic LV) + (178.78 if ≥moderate AS) - 1373. The predicted-TTS correlated with the actual-TTS (Spearman r=0.395, p<0.0001) with a near-linear locally weighted scatterplot smoothed trendline (figure 1). Conclusions This study demonstrates proof of concept that echo report data can be linked to patient outcomes. Routine echo variables are associated with, and could be used to predict, the time from echo to cardiac surgery. Multi-site application of NED-UK methods could be valuable in predicting cardiovascular outcomes in a diverse UK patient population. Conflict of Interest None

Background & Aim Large curated datasets of clinical echocardiographic measurements with associated interpretation are scarce. Due to standardised echocardiographic protocols and diverse patient populations, the UK offers a unique opportunity to link echocardiographic data to study patient outcomes through nationwide records of primary care visits, hospitalisations, and mortality. Our aims were to 1) Develop a toolkit for the extraction and anonymisation of clinical echocardiographic data and 2) Implement the toolkit in the first NHS Trust to demonstrate feasibility. Methods The data were collected under the 'EchoVision' project – an expanding resource of echocardiographic data (UK HRA approval 251473). Customisation of database queries were undertaken by Philips (Koninklijke Philips N.V, Netherlands) staff with input from the first author. Data (measurements, standardised interpretive phrases and free-text comments) from consecutive clinical echocardiograms, undertaken at an NHS Trust and reported upon within Philips Intellispace Cardiovascular system, were extracted using the built-in 'Advanced Analytics' functionality in date-ranged portions using the customised queries. Individual extract files (.csv) were formatted in Microsoft Excel using a 'Visual Basic for Applications' script to get a rectangular dataset, before being merged and processed in RStudio (v2023.09.1) using R (v4.2.1). Scans from patients with an age <18 years or missing age were excluded. After creating the unique study identifier for each scan via a one-way hash function (https://www.quickhash-gui.org/), protected health information was removed. Subsequently, the data were transferred to the research team, and stored on secure severs with password protected access by the study research staff. Results Standard operating procedures and training materials were written for the use of Philips software and for data anonymisation (the 'toolkit'). Data from n=19100 echocardiograms performed in 2022 were extracted, with n=291 exclusions leaving n=18809 scans. The median age was 68 [interquartile range 26] years – the age distribution is shown in figure 1. Female patients comprised n=8324 scans (44.3%), males n=10108 (53.7%) and n=377 (2.0%) had their sex unrecorded. 'Transthoracic' scan type represented n=18475 (98.2%), with the remainder being transoesophageal (n=190), stress (n=82), bubble (n=58), and intracardiac (n=4). The number of echocardiograms performed per month varied from n=1314 in April to n=1841 in November (figure 2). Conclusions The NED-UK pilot study demonstrates the ability to develop a functional toolkit for the extraction and anonymisation of clinical echocardiographic report data and the feasibility of large-scale extraction of echocardiographic data. Future aims should be focused on expanding NED-UK to become a multi-site multi-vendor resource for clinical research with the potential for predicting cardiovascular risk across diverse patient populations. Conflict of Interest None

BackgroundChronic lymphocytic leukaemia (CLL) typically presents with asymptomatic, early-stage disease that is monitored until disease progression (‘treatment-naïve’ CLL). The objective of this pilot study was to assess the feasibility and preliminary safety of an exercise program in treatment-naïve CLL. We also sought to preliminarily assess the impact of the exercise program on disease activity, as it has been proposed that exercise training may reduce disease outgrowth in treatment-naïve CLL.MethodsA total of 40 treatment-naïve CLL patients were recruited into this randomised-controlled pilot study, and after screening, n = 28 were randomised into a 16-week, home-based, partially supervised, personalised, progressive exercise intervention (n = 14: mean ± SD: age = 62 ± 12 years) or 16 weeks of usual care, control group (n = 14: mean ± SD: age = 61 ± 10 years). The primary outcome measures were safety (number and severity of adverse events) and feasibility (uptake, retention, and adherence to the trial). Disease activity (CD5+/CD19+ CLL cells clonally restricted to kappa or lambda) and other immune cell phenotypes, with a principal focus on T cells, were measured by flow cytometry. Other secondary outcomes included DEXA-derived body composition, cardiorespiratory and functional fitness, resting cardiovascular measures.ResultsTrial uptake was 40%, and the overall retention rate was 86%, with 79% of the exercise group and 93% of the control group completing the trial. Adherence to the exercise intervention was 92 ± 8%. One serious adverse event was reported unrelated to the trial, and one adverse event related to the trial was reported. The exercise intervention elicited a 2% increase in DEXA-derived lean mass in the exercise group compared with a 0.4% decrease in the control group (p = 0.01). No between-group differences were observed over time for whole-body mass, BMI, bone mineral density, body fat, blood pressure resting heart rate, or measures of cardiorespiratory or functional fitness (all p > 0.05). No between-group differences were observed over time for clonal CLL cells and CD4+ or CD8+ T-cell subsets (all p > 0.05).ConclusionThe exercise training program used in this study was feasible in people with treatment-naïve CLL who passed pre-trial screening, and we preliminarily conclude that the exercise training program was safe and also resulted in an increase in lean mass.Clinical trial registrationhttps://doi.org/10.1186/ISRCTN55166064, identifier ISRCTN 55166064.

Background Hospital admission due to breathlessness carries a significant burden to patients and healthcare systems, particularly impacting people in low-income countries. Prompt appropriate treatment is vital to improve outcomes, but this relies on accurate diagnostic tests which are of limited availability in resource-constrained settings. We will provide an accurate description of acute breathlessness presentations in a multicentre prospective cohort study in Malawi, a low resource setting in Southern Africa, and explore approaches to strengthen diagnostic capacity. Objectives Primary objective: Delineate between causes of breathlessness among adults admitted to hospital in Malawi and report disease prevalence. Secondary objectives: Determine patient outcomes, including mortality and hospital readmission 90 days after admission; determine the diagnostic accuracy of biomarkers to differentiate between heart failure and respiratory infections (such as pneumonia) including brain natriuretic peptides, procalcitonin and C-reactive protein. Methods This is a prospective longitudinal cohort study of adults (≥18 years) admitted to hospital with breathlessness across two hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Chiradzulu, Malawi. Patients will be consecutively recruited within 24 hours of emergency presentation and followed-up until 90 days from hospital admission. We will conduct enhanced diagnostic tests with robust quality assurance and quality control to determine estimates of disease pathology. Diagnostic case definitions were selected following a systematic literature search. Discussion This study will provide detailed epidemiological description of adult hospital admissions due to breathlessness in low-income settings, which is currently poorly understood. We will delineate between causes using established case definitions and conduct nested diagnostic evaluation. The results have the potential to facilitate development of interventions targeted to strengthen diagnostic capacity, enable prompt and appropriate treatment, and ultimately improve both patient care and outcomes.

Purpose Physical activity is a key component of cardiac rehabilitation (CR). Despite the widely reported benefits of CR, uptake in the United Kingdom is still low. Alternative home-based and technology-facilitated delivery models are needed to improve CR uptake and physical activity. This study set out to explore patient and clinician views of personalised, multidimensional physical activity feedback and its potential use within CR.Methods We developed graphics for the presentation of personalised multidimensional physical activity feedback from data collected through wrist-worn monitors. Thirteen cardiac patients and nine healthcare professionals recruited from South West England wore research grade physical activity monitors for seven days. Participants then attended semi-structured interviews during which personalised physical activity feedback was provided. Interviews were audio-recorded, transcribed, and analysed thematically.Results Two main themes were derived from the data which covered: 1) the perceived value of multidimensional physical activity feedback, and 2) support needed to facilitate understanding. Within the first theme, participants acknowledged that multidimensional physical activity feedback was useful for monitoring progress, goal setting, and increasing self-awareness of physical activity behaviour among both patients and clinicians. Within theme two, the need for more guidance and support from clinicians to aid patient understanding and reassurance was highlighted, particularly for those with very low physical activity levels.Conclusions Multidimensional physical activity feedback delivered using a technology-enabled approach was perceived as acceptable among patients and clinicians. This study provides insights into the potential novel use of technology-enabled physical activity feedback to support and expand the delivery of CR.

Introduction Athletic training can result in electrical and structural changes of the right ventricle that may mimic phenotypical features of arrhythmogenic right ventricular cardiomyopathy (ARVC), such as T-wave inversion and right heart dilatation. An erroneous interpretation may have consequences ranging from false reassurance in an athlete vulnerable to cardiac arrhythmias, to unnecessary sports restriction in a healthy individual. The primary aim of this study was to define normal RV dimension reference ranges for academy adolescent footballers of different ethnicities. Secondary aims include analysis of potential overlap between this adolescent group with ARVC criteria and comparison with normal adult ranges. Results Electrocardiographic (ECG) and echocardiographic data of 1087 academy male footballers aged between 13 and 18 years old (mean age 16.0 ± 0.5 years), attending mandatory cardiac screening were analysed. Ethnicity was categorised as white (n = 826), black (African/Caribbean; n = 166) and mixed-race (one parent white and one parent black; n = 95). Arrhythmogenic right ventricular cardiomyopathy major criteria for T-wave inversion was seen in 3.3% of the cohort. This was more prevalent in black footballers (12%) when compared to mixed race footballers (6.3%) or white footballers (1%), P < 0.05. Up to 59% of the cohort exceeded adult reference ranges for some of the right ventricular parameters, although values were similar to those seen in adult footballers. There were no differences in right ventricular dimensions between ethnicities. In particular, the right ventricular outflow tract diameter would fulfil major criteria for ARVC dimension in 12% of footballers. Overall, 0.2% of the cohort would fulfil diagnosis for ‘definite’ arrhythmogenic right ventricular cardiomyopathy and 2.2% would fulfil diagnosis for ‘borderline’ arrhythmogenic right ventricular cardiomyopathy for RV dimensions and ECG changes. This was seen more frequently in black footballers (9.9%) than mixed race footballers (3.9%) or white footballer (0.6%), P < 0.05. Among athletes meeting definite or borderline arrhythmogenic right ventricular cardiomyopathy criteria, no cardiomyopathy was identified after comprehensive clinical assessment, including with cardiac magnetic resonance imaging, exercise testing, ambulatory electrocardiograms and familial evaluation. Conclusion Right heart sizes in excess of accepted adult ranges occurred in as many as one in two adolescent footballers. Structural adaptations in conjunction with anterior T-wave inversion may raise concern for ARVC, highlighting the need for evaluation in expert settings.