Longer rhythm monitoring in ischaemic stroke patients increases rate of Atrial Fibrillation (AF) detection (1,2). However, prolonged rhythm monitoring is expensive and inappropriate for patients that are already diagnosed with AF. Conversely, pathways reliant on human factors can delay or miss indicated investigations. The extent of inappropriate and missed investigations is unknown as is whether pathways for AF detection can reduce inappropriate requests and improve rate of AF diagnosis. To evaluate the impact of a dynamic sequential AF detection pathway on outcomes and workload in a large specialist stroke service. Investigations and outcomes were reviewed in patients with ischemic stroke/TIA admitted to a large tertiary stroke service between January-March 2023. AF prevalence and detection on admission ECG and Holter/Zio monitoring were recorded as outcomes to determine appropriateness of onward investigation. Figure 1 outlines the interval pathway introduced to the service on 5th September 2023 based on National Guidance (3,4). Practice was re-evaluated in April-May 2024. The study was prospectively registered and endorsed by the Local Clinical Effectiveness Unit (study number 12024). Between January-March 2023, 109 people were admitted with an ischaemic stroke (n=98) or TIA (n=11). 13 patients had new AF detected on admission 12-lead ECG and 14 patients had known AF. 6/27 (22%) with known or newly diagnosed AF on admission ECG were inappropriately referred for further Holter/Zio monitoring for AF detection. 64/82 (78%) patients without an AF diagnosis had Holter/Zio monitoring requested. Of the 35 completed requests, 33 (94%) showed no AF. 0/33 (0%) had documented consideration or referral for implantable continuous monitoring (ICM). Between April-May 2024, after implementation of the AF detection pathway, 85 patients were admitted with an ischaemic stroke (n=81) or TIA (n=4). 2/27 (7%) patients with new or known AF were referred for Holter monitoring (X2 (1, N=130)=1.53, p=0.22). 58/58 (100%) patients without an AF diagnosis underwent Holter/Zio monitoring (X2 (1, N=140)=12.08, p<0.05) but no patients were considered for ICM. AF was detected in 2/35 (6%) patients with Holter/Zio monitoring between January-March 2023 compared to 1/21 (5%) patients in April-May 2024 (X2 (1, N=56)=0.02, p=0.88). 66/122 (54%) Holter/Zio requests from January-March 2023 (n=29) and April-May 2024 (n=37) are still being processed. Inappropriate AF investigations are frequent, while indicated prolonged monitoring may be delayed or missed. A dynamic, sequential pathway can reduce unnecessary tests and ensure access to appropriate monitoring. Longer-term follow-up of clinical outcomes and AF detection is warranted.

BACKGROUND:Patients with reduced left ventricular ejection fraction (LVEF) and rate-controlled atrial fibrillation (AF) may improve after restoring sinus rhythm. This may be due to the elimination of the short R-R intervals during AF even when mean heart rate is acceptable. OBJECTIVES:This work aims to evaluate a novel parameter representing the burden of short R-R intervals during AF and its association with reduced LVEF and LVEF recovery after catheter ablation (CA). METHODS:Patients with persistent AF were prospectively enrolled pre-CA and grouped as having reduced (LVEF ≤50%) or preserved LVEF. Sequential R-R intervals on resting Holter monitoring were measured. We sought to define a threshold R-R interval at which the difference in the percentage of short R-R intervals is greatest when comparing patients with reduced and preserved ejection fraction. We termed this threshold the restitution threshold (RT) in the belief that this may be possible to apply as a threshold to identify patients with AF-mediated cardiomyopathy. This percentage burden of intervals shorter than the RT was defined as the restitution threshold index (RTI). The association with reduced LVEF in AF and predicting improvement in LVEF after CA was then evaluated. RESULTS:A total of 104 patients were enrolled; 53 (51%) had a reduced LVEF. There was no difference in mean heart rate; however, at an RT of 660 ms, the RTI was higher in the reduced LVEF arm (56.1% ± 23.1% vs 39.5% ± 26.0%; P < 0.001). It was an independent predictor of left ventricular systolic dysfunction. The RTI in the reduced LVEF arm had an area under the receiver operating characteristic of 0.74 (95% CI: 0.47-0.95) and positive predictive value of 0.97 for LVEF improvement after CA, which was observed in 39 of 47 (83.0%) participants in sinus rhythm. CONCLUSIONS:The RTI in persistent AF was associated with a reduced LVEF, whereas mean heart rate was not. The RTI could be used to predict LVEF improvement after CA.

Cardiology training in the UK is facing significant challenges due to a range of factors. Recent curriculum changes have further compounded this issue and significantly risk the ability to produce adequately trained consultants capable of managing patients with increasingly complex cardiovascular disease. The introduction of mandatory dual accreditation in general internal medicine (GIM) alongside cardiology, by design, results in significantly reduced training opportunities, including procedural and subspecialty exposure. Despite prolongation in training duration to mitigate these effects, most trainees now report needing post-certificate of completion of training fellowships to gain the standard competencies required for consultant roles, undermining the curriculum's aim of fostering independent practice. Furthermore, the current training model is misaligned with patient needs, lacking provisions for training in key and expanding services, such as complex structural interventions and inherited cardiac conditions. The increasing complexity of expectations placed on trainees also has the potential to significantly hinder academic training, discouraging research and innovation, thereby risking the future of UK clinical academia. Urgent curriculum reform is not only desirable but also essential and should include limiting GIM training time, improving subspecialty accreditation pathways and revising academic training provisions. If current bodies overseeing cardiology training fail to implement these essential changes, additional options, including an independent regulatory framework for cardiology training, should be considered. Without immediate action, UK cardiology training risks facing a generational crisis of inadequately skilled consultants, which could compromise future patient care.

IntroductionAtrial fibrillation (AF)-induced cardiomyopathy (AIC) is retrospectively defined after normalisation of left ventricular ejection fraction (LVEF) in sinus rhythm. It is unclear why some patients develop AIC.HypothesisPatients with AIC have a subtle cardiomyopathic process that precedes their AF-mediated LVEF reduction. Detailed assessment of cardiac function after successful catheter ablation will reveal this.ObjectiveTo evaluate the utility of measures to identify cardiomyopathic features that persist after LVEF normalisation in AIC.MethodsPatients with rate-controlled persistent AF and LVEF<50% undergoing catheter ablation (CA) were prospectively evaluated using echocardiography, cardio-pulmonary exercise testing and serum N-terminal pro b-type natriuretic peptide (NT-proBNP) at baseline and 6 months after CA. Participants with AIC, (LVEF recovery (≥50%) and no other cause for cardiac dysfunction) were evaluated using left ventricular (LV) longitudinal strain and left atrial (LA) reservoir strain (LARS). Changes in peak oxygen consumption and the minute ventilation/carbon dioxide production slope were measured as markers of functional capacity and ventilatory inefficiency. A control group of patients with persistent AF with preserved LVEF were also enrolled.Results34/41 (82.9%) participants recovered LVEF in sinus rhythm; defined as AIC. NT-proBNP levels were elevated in 18 (52.9%), and 16 reported ongoing heart failure (HF) symptoms. 10 (29.4%) had no improvement in functional capacity, and seven (20.6%) showed persistent ventilatory inefficiency. 20 (58.8%) had impaired global LV longitudinal strain with a relative apical sparing pattern. Nine (26.5%) had impaired LARS. There was an overlap of these abnormalities. 32 (94.1%) demonstrated at least one, 17 (50.0%) having no cardiovascular risk factors. Patients with preserved LVEF during persistent AF had similar demographics but a lower burden of short R-R intervals (<660 ms) on Holter monitoring.DiscussionAbnormal structural, metabolic and HF biomarkers are seen in patients with AIC in sinus rhythm. These features may represent a precedent subtle cardiomyopathic process predisposing them to left ventricular systolic dysfunction in AF.Trial registration numberNCT04987723.

Inappropriate behaviour is an umbrella term including discrimination, harassment and bullying. This includes both actions and language and can affect any member of the cardiovascular workforce/team. Evidence has suggested that such behaviour is regularly experienced within UK cardiology departments, where inappropriate behaviour may represent longstanding cultural and practice issues within the unit. Inappropriate behaviour has negative effects on the workforce community as a whole, including impacts on recruitment and retention of staff and patient care. While only some members of the cardiology team may be directly impacted by inappropriate behaviour in individual departments, a wider group are significantly impacted as bystanders. As such, improving the culture and professional behaviours within UK cardiology departments is of paramount importance. As a negative workplace culture is felt to be a major driver of inappropriate behaviour, all members of the cardiovascular team have a role to play in ensuring a positive workplace culture is developed. Episodes of inappropriate behaviour should be challenged by cardiovascular team members. Informal feedback may be appropriate where 'one-off' episodes of inappropriate behaviour occur, but serious events or repeated behaviour should be escalated following formal human resources protocols.

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation (BHF), VASCage (Centre for Promoting Vascular Health in the Ageing Community) of the Austrian Research Promotion Agency FFG (COMET program - Competence Centers for Excellent Technologies) Introduction Antiplatelet therapy (APT) leads to reduced morbidity and mortality in patients with cardiovascular disease but some still have thrombotic events. Tailoring APT to platelet function is currently limited by a lack of suitable platelet function tests. It has been previously shown that different circulating microRNAs (miRNAs) are derived from platelets and their measurement could provide new markers of platelet reactivity. Purpose To compare the release of different platelet miRNAs in response to different platelet agonists. Methods Measurements of platelet function were performed by light transmission aggregometry (LTA) in participants of the 2015 follow-up of the Bruneck study (n=338), using the following agonists: arachidonic acid (1mM), adenosine diphosphate (5µM, 20µM), collagen (0.4 µg/ml, 4 µg/ml, 10µg/ml), TRAP-6 amide (25µM) and U46619 (10µM). LTA platelet releasates were then used for RT-qPCR measurements of five platelet-enriched miRNAs (miR-21, miR-126, miR-150, miR-197, miR-223). Platelet-poor plasma (PPP) served as negative control. Results Platelet activation led to aggregation and extracellular release of miRNAs, with aspirin users (n=155) showing significantly lower miRNA release than non-aspirin users (n=183). Agonist responsiveness differed among miRNAs, with miR-21 being hyperresponsive to arachidonic acid and miR-150 being hyperresponsive to adenosine diphosphate, whilst release of miR-126, miR-197 and miR-223 was strongest to collagen (10µg/ml). In non-aspirin users, inflammation markers such as granulocyte counts or C-reactive protein correlated positively with platelet-derived miRNAs measured in PPP, whilst they correlated negatively with platelet-derived miRNAs measured in releasates. These effects were absent in aspirin users. Conclusions MiRNAs released from activated platelets can be reliably detected in PPP and platelet releasates. Preferential release of miRNAs in response to specific agonists suggests a selective release mechanism. Elevated PPP levels and decreased releasate levels of platelet-derived miRNAs in inflammatory environments suggest platelet exhaustion ex vivo due to platelet pre-activation.

Abstract Background Antiplatelet therapy (APT) has improved cardiovascular outcomes, but some patients develop thrombosis despite APT. Adjusting APT to platelet reactivity with conventional platelet reactivity tests has proven unsuccessful. Many circulating noncoding RNAs (ncRNAs) are derived from platelets and could serve as novel platelet function markers. Material and methods Platelet reactivity was assessed using light transmission aggregometry (LTA) in the Bruneck 2015 study (N = 338), using the agonists arachidonic acid, adenosine diphosphate, collagen, TRAP-6 amide and U46619. LTA platelet releasates were then used for RT-qPCR of five platelet-enriched microRNAs, three circular RNAs and two long non-coding RNAs. Platelet-poor plasma (PPP) was used as negative control. Results and conclusions Platelet agonists induced aggregation and ncRNA release, with aspirin takers (N = 155) showing lower ncRNA release than individuals not on aspirin (N = 183). Agonist responsiveness differed among ncRNAs, with miR-150 being hyperresponsive to adenosine diphosphate and miR-21 being hyperresponsive to arachidonic acid, whereas other ncRNAs were most strongly released to collagen, suggesting a selective release mechanism. In individuals not on aspirin, the inflammation markers C-reactive protein and granulocyte counts correlated positively with platelet-derived ncRNAs in PPP, while they correlated inversely with platelet-derived ncRNAs in releasates. These correlations were not present in aspirin takers. Higher PPP levels and lower releasate levels of platelet-derived ncRNAs in inflammation suggest platelet exhaustion ex vivo due to platelet pre-activation in vivo. Funding sources British Heart Foundation, VASCage (Centre for Promoting Vascular Health in the Ageing Community) of the Austrian Research Promotion Agency FFG (COMET program - Competence Centers for Excellent Technologies).

The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. Our understanding of this is incomplete, however, because of limitations in the technical approaches available to study platelets of different ages. In this study we have developed and validated an in vivo ‘temporal labelling’ approach using injectable fluorescent anti-platelet antibodies to sub-divide platelets by age and assess differences in functional and molecular characteristics. With this approach we found that young platelets (<24h old) in comparison to older platelets respond to stimuli with greater calcium flux and degranulation, and contribute more to the formation of thrombi in vitro and in vivo . Sequential sampling confirmed this altered functionality to be independent of platelet size with no size differences or changes relative to the global population seen at any age. The age associated decrease in thrombotic function was accompanied by significant decreases in the surface expression of GPVI and CD31 (PECAM-1) and an increase in CD9. Platelet mRNA content also decreased with age but at different rates for individual mRNAs indicating apparent conservation of those encoding granule proteins. Our pulse-chase type approach to define circulating platelet age has allowed timely re-examination of commonly held beliefs regarding size and reactivity of young platelets whilst providing novel insights into the temporal regulation of receptor and protein expression. Overall, future application of this validated tool will inform on age-based platelet heterogeneity in physiology and disease.

Background The first wave of the COVID-19 pandemic required rapid reconfiguration and reallocation of resources. We triaged all cardiac imaging requests from our referral network serving 2.5 million people, to our tertiary centre, performing only clinically urgent studies and cancelling non-urgent studies. Requesters received notification of cancellation in the same format as test reports and were encouraged to repeat their request when pandemic conditions had improved. The impact of this cancellation on patient outcomes is assessed. Methods Retrospective analysis of routinely collected clinical and administrative data from the institutional data warehouse determined patient outcomes for those with cancelled and performed stress echocardiography, nuclear stress perfusion studies, cardiac CT angiography and cardiac MRI. Mortality data was drawn from the NHS spine. Data analysis was performed using R. Results 1600 cardiac studies for 1592 patients were cancelled in April 2020, and 2234 cardiac studies were performed for 2184 patients between April and July 2020, representing high-risk outpatient requests. 41 patients who had cancelled scans died, and 105 patients with performed scans died (table 1). Of cancelled scans, 787 patients had a subsequent scan in some modality, of which 701 were the same modality as the original test. 761 patients had no repeat outpatient testing until October 2021. Mortality was higher in patients for whom scans were performed (log-rank p = 0.03, figure 1A). Non-elective admissions were higher in patients who had scans performed (4% in cancelled vs. 8% performed after 574 days of follow-up, log-rank p <0.001 figure 1B). Over the course of the pandemic, our wait-times for cardiac testing did not exceed the national standard of 16 weeks.Limitations: Data was not collected prospectively, due to the level of emergency; cancellation data may not be complete. All cause mortality under pandemic conditions cannot be extrapolated to non-pandemic situations. Conclusion Our approach to diagnostic testing in cardiology during the first wave of the COVID-19 pandemic accurately identified and tested high-risk patients without causing harm to those at lower risk, demonstrated by higher admission rates in patients in whom tests were performed, and the absence of an adverse impact on mortality. 49% of patients underwent subsequent cardiac testing after a cancelled test. We maintained low waiting times throughout the pandemic. Conflict of Interest None

Introduction: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. Methods: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. Results: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: −70.86 to −40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: −37.19 to −13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure ( p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) ( n = 5), phrenic nerve stimulation ( n = 3) and ventricular ectopy ( n = 1). Conclusion: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration.

Objective: Platelets are central to acute myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome during MI and identify corresponding functional consequences. Approach and Results: Platelets from patients experiencing ST-segment-elevation MI (STEMI) before and 3 days after treatment (n=30) and matched patients with severe stable coronary artery disease before and 3 days after coronary artery bypass grafting (n=25) underwent quantitative proteomic analysis. Elevations in the proteins S100A8 and S100A9 were detected at the time of STEMI compared with stable coronary artery disease (S100A8: FC, 2.00; false discovery rate, 0.05; S100A9: FC, 2.28; false discovery rate, 0.005). During STEMI, only S100A8 mRNA and protein levels were correlated in platelets (R=0.46, P=0.012). To determine whether de novo protein synthesis occurs, activated platelets were incubated with 13C-labeled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was confidently detected. Platelet S100A8 and S100A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were coincubated under quiescent and activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Neutrophils released S100A8/A9 as free heterodimer, rather than in vesicles or extracellular traps. In the community-based Bruneck study (n=338), plasma S100A8/A9 was inversely associated with platelet reactivity-an effect abrogated by aspirin. Conclusions: Leukocyte-to-platelet protein transfer may occur in a thromboinflammatory environment such as STEMI. Plasma S100A8/A9 was negatively associated with platelet reactivity. These findings highlight neutrophils as potential modifiers for thrombotic therapies in coronary artery disease.

Background Delayed diagnosis of valvular heart disease carries a poor prognosis, and early identification is desirable. We undertook a retrospective analysis of echocardiographic and electronic health care record data from the largest single cardiovascular service in the UK, to identify the burden of acute presentations with previously undiagnosed valvular heart disease and to determine the geographical and demographic distribution. Methods and Results Automated text mining analysis was retrospectively applied to all echocardiographic examinations performed between 2015 and 2019 at Bart’s Health NHS trust, identifying 2043 reports containing text or numerical data indicating severe valvular lesions. Demographic and clinical data was integrated with the echocardiographic dataset, identifying the postcode and GP practices for with the highest proportion of patients with severe valvular disease that were diagnosed during acute inpatient admissions. 376 individuals had severe valvular lesions identified during acute admission, of which 269 (72%) had no previously documented echocardiogram. A cluster of 11 GP practices (9%, 11 of 117 practices) were identified as having a higher proportion of diagnoses of severe valvular disease on acute admissions [figure 1]. These 11 were plotted geographically, alongside correlating postcodes, to identify geographical hotspots [figure 2]. Analyses were undertaken using Matlab, R and ggplot2. Conclusions A geographical cluster of GP practices, centred around a single hospital, had a higher proportion of patients diagnosed with severe valvular disease during acute admissions without a previous echocardiogram. Outreach echocardiography provision in these regions could potentially identify patients with valvular disease before acute decompensation. Further work should focus on improving methodology to identify cases and investigating risk factors that predispose to diagnosis of severe valvular disease in extremis. Conflict of Interest none

Significance: Levels of platelet noncoding RNAs (ncRNAs) are altered by disease, and ncRNAs may exert functions inside and outside of platelets. Their role in physiologic hemostasis and pathologic thrombosis remains to be explored. Recent Advances: The number of RNA classes identified in platelets has been growing since the past decade. Apart from coding messenger RNAs, the RNA landscape in platelets comprises ncRNAs such as microRNAs, circular RNAs, long ncRNAs, YRNAs, and potentially environmentally derived exogenous ncRNAs. Recent research has focused on the function of platelet RNAs beyond platelets, mediated through protective RNA shuttles or even cellular uptake of entire platelets. Multiple studies have also explored the potential of platelet RNAs as novel biomarkers. Critical Issues: Platelet preparations can contain contaminating leukocytes. Even few leukocytes may contribute a substantial amount of RNA. As biomarkers, platelet RNAs have shown associations with platelet activation, but it remains to be seen whether their measurements could improve diagnostics. It also needs to be clarified whether platelet RNAs influence processes beyond platelets. Future Directions: Technological advances such as single-cell RNA-sequencing might help to identify hyperreactive platelet subpopulations on a single-platelet level, avoid the common problem of leukocyte contamination in platelet preparations, and allow simultaneous profiling of native megakaryocytes and their platelet progeny to clarify to what extent the platelet RNA content reflects their megakaryocyte precursors or changes in the circulation. Antioxid. Redox Signal. 34, 1200-1216.

Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS Trust, London EC1A 7BE, UK; Hatter Cardiovascular Institute, University College of London, London WC1E 6HX, UK; Department of Cardiology, University College Hospital, University College of London Hospitals NHS Foundation Trust, NW1 2BU, UK; NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; and Department of Cardiology, Newham University Hospital, Barts Health NHS Trust, London E13 8SL, UK