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The clinical spectrum of atrial fibrillation means that a patient-individualised approach is required to ensure optimal treatment. Cardiac computed tomography can accurately delineate atrial structure and function and could contribute to a personalised care pathway for atrial fibrillation patients. The imaging modality offers excellent spatial resolution and has been utilised in pre-, peri- and post-procedural care for patients with atrial fibrillation. Advances in temporal resolution, acquisition times and analysis techniques suggest potential expanding roles for cardiac computed tomography in the future management of patients with atrial fibrillation. The aim of the current review is to discuss the use of cardiac computed tomography in atrial fibrillation in pre-, peri- and post-procedural settings. Potential future applications of cardiac computed tomography including atrial wall thickness assessment and epicardial fat volume quantification are discussed together with emerging analysis techniques including computational modelling and machine learning with attention paid to how these developments may contribute to a personalised approach to atrial fibrillation management.

We present an open-source software pipeline to create patient-specific left atrial (LA) models with fibre orientations and a fibrosis map, suitable for electrophysiology simulations. The semi-automatic pipeline takes as input a contrast enhanced magnetic resonance angiogram, and a late gadolinium enhanced (LGE) contrast magnetic resonance (CMR). Five operators were allocated 20 cases each from a set of 50 CMR datasets to create a total of 100 models to evaluate inter/intra-operator variability. Each output model consisted of (1) a labelled surface mesh open at the pulmonary veins (PV) and mitral valve (MV), (2) fibre orientations mapped from a diffusion tensor MRI human atlas, (3) fibrosis map from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. We evaluated reproducibility in our pipeline by comparing agreement in shape of the output meshes, fibrosis distribution in the LA body, and fibre orientations; simulations outputs were evaluated comparing total activation times of LAT maps, mean conduction velocity (CV), and structural similarity index measure (SSIM) of PS maps. Our workflow allows a single model to be created in 16.72 +/- 12.25 minutes. Results in this abstract are reported as inter/intra. Shape only differed noticeably with users' selection of the MV and the length of the PV from the ostia to the distal end; fibrosis agreement (0.91/0.99 ICC) and fibre orientation agreement (60.63/71.77 %) were high. LAT maps showed good agreement, the median of the absolute difference of the total activation times was 2.02ms/1.37ms. The average of the mean CV difference was -4.04mm/s / 2.1mm/s. PS maps showed a moderately good agreement with SSIM of 0.648/0.608. Although we found notable differences in the models due to user input, our tests show that operator variability was comparable to that of image resolution or fibre estimation., Comment: 17 pages, 7 figures, submitted for review at Journal of Computers in Biology and Medicine (in press)

Background Leadless pacemakers present a viable alternative to conventional transvenous devices to mitigate the risk of lead- and/or pocket-related complications. In elderly patients who have encountered ventricular lead failures with transvenous pacemakers, this option may enable the delivery of atrioventricular synchronous pacing therapy, while obviating the requirement for lead extraction and lead-based pacemaker re-implantation. Case summary This case report describes the successful implantation of a leadless pacemaker in a 90-year-old who had undergone two dual-chamber permanent pacemaker implantation procedures with a failure of three of four previously implanted leads. Atrioventricular synchronous pacing was achieved, as the leadless device was able to track the atrial-paced rhythm from the pre-existing right-sided device. Discussion In elderly patients who have encountered issues with transvenous pacemakers, alternative approaches should be considered to mitigate the risk of future complications. Leadless pacemakers may offer a low-risk solution, enabling the delivery of atrioventricular synchronous pacing therapy in such patient groups. Future studies should be designed to delineate whether these devices could be utilized as a first-line approach in certain situations.

There is increasing evidence to suggest that atrial fibrillation is associated with a heightened risk of dementia. The mechanism of interaction is unclear. Atrial fibrillation-induced cerebral infarcts, hypoperfusion, systemic inflammation, and anticoagulant therapy-induced cerebral microbleeds, have been proposed to explain the link between these conditions. An understanding of the pathogenesis of atrial fibrillation-associated cognitive decline may enable the development of treatment strategies targeted towards the prevention of dementia in atrial fibrillation patients. The aim of this review is to explore the impact that existing atrial fibrillation treatment strategies may have on cognition and the putative mechanisms linking the two conditions. This review examines how components of the ‘Atrial Fibrillation Better Care pathway’ (stroke risk reduction, rhythm control, rate control, and risk factor management) may influence the trajectory of atrial fibrillation-associated cognitive decline. The requirements for further prospective studies to understand the mechanistic link between atrial fibrillation and dementia and to develop treatment strategies targeted towards the prevention of atrial fibrillation-associated cognitive decline, are highlighted.

Purpose Atrial fibrillation is associated with an increased risk of cognitive impairment. It is unclear whether the restoration of sinus rhythm with catheter ablation may modify this risk. We conducted a systematic review of studies comparing cognitive outcomes following catheter ablation with medical therapy (rate and/or rhythm control) in atrial fibrillation. Methods Searches were performed on the following databases from their inception to 17 October 2021: PubMed, OVID Medline, Embase and Cochrane Library. The inclusion criteria comprised studies comparing catheter ablation against medical therapy (rate and/or rhythm control in conjunction with anticoagulation where appropriate) which included cognitive assessment and/or a diagnosis of dementia as an outcome. Results A total of 599 records were screened. Ten studies including 15,886 patients treated with catheter ablation and 42,684 patients treated with medical therapy were included. Studies which compared the impact of catheter ablation versus medical therapy on quantitative assessments of cognitive function yielded conflicting results. In studies, examining new onset dementia during follow-up, catheter ablation was associated with a lower risk of subsequent dementia diagnosis compared to medical therapy (hazard ratio: 0.60 (95% confidence interval 0.42–0.88, p Conclusion The accumulating evidence linking atrial fibrillation with cognitive impairment warrants the design of atrial fibrillation treatment strategies aimed at minimising cognitive decline. However, the impact of catheter ablation and atrial fibrillation medical therapy on cognitive decline is currently uncertain. Future studies investigating atrial fibrillation treatment strategies should include cognitive outcomes as important clinical endpoints.

We describe the case of an 86-year-old man with a background of severe left ventricular dysfunction and ischaemic cardiomyopathy who, having been optimised for heart failure therapy in hospital, unexpectedly deteriorated again with hypotension and progressive renal failure over the course of 2 days. Common causes of decompensation were ruled out and a bedside echocardiogram unexpectedly diagnosed new pericardial effusion with tamponade physiology. The patient underwent urgent pericardiocentesis and 890 mL of haemorrhagic fluid was drained. Common causes for haemopericardium were ruled out, and the spontaneous haemopericardium was thought to be related to introduction of rivaroxaban anticoagulation. The patient made a full recovery and was well 2 months following discharge. This case highlights the challenges of diagnosing cardiac tamponade in the presence of more common disorders that share similar non-specific clinical features. In addition, this case adds to growing evidence that therapy with direct oral anticoagulants can be complicated by spontaneous haemopericardium, especially when coadministered with other agents that affect clotting, renal dysfunction and cytochrome P3A5 inhibitors.

We describe a 67-year-old man admitted from a mental health unit with an incidental finding of hyponatraemia on routine blood tests. Laboratory investigations were in keeping with syndrome of inappropriate antidiuretic hormone secretion (SIADH). He had been recently commenced on mirtazapine. During his inpatient stay, he became increasingly confused. Review of a previous admission with hyponatraemia raised the possibility of voltage-gated potassium channel antibody-associated limbic encephalitis, although subsequent investigations deemed this unlikely as a cause of hyponatraemia. Although his sodium levels improved with fluid restriction, serial point-of-care testing proved misleading in monitoring the efficacy of treatment as inconsistencies were seen in comparison with laboratory testing. The cause of hyponatraemia may have been medication-induced SIADH and/or polydipsia. This case highlights the importance of collating detailed histories and laboratory blood testing to guide management in cases of hyponatraemia of unknown aetiology.

A 41-year-old woman presented with central chest discomfort. She had been previously well, was an ex-smoker and reported no regular medication. The ECG developed T-wave changes inferiorly and anterolaterally and troponin I concentrations were elevated confirming non-ST elevation myocardial infarction. Cardiac catheterization showed severe spasm of the right and left anterior descending coronary arteries which resolved with intracoronary nitrates. She later volunteered that prior to presentation she had been taking non-prescription Acti-Phen a slimming agent containing phentermine. Acti-Phen had its licence withdrawn in 2001 because of cardiovascular side effects including coronary spasm. Accordingly, she was advised to avoid Acti-Phen in future. The case emphasizes the importance of obtaining a complete drug history, including non-prescription drugs, in patients presenting with acute coronary syndromes.

ObjectivesThe electronic health record (EHR) is underused in the hospital setting. The aim of this service evaluation study was to respond to National Health Service (NHS) Digital’s ambition for a paperless NHS by capturing routinely collected cardiac outpatient data in the EHR to populate summary patient reports and provide a resource for audit and research.DesignA PowerForm template was developed within the Cerner EHR, for real-time entry of routine clinical data by clinicians attending a cardiac outpatient clinic. Data captured within the PowerForm automatically populated a SmartTemplate to generate a view-only report that was immediately available for the patient and for electronic transmission to the referring general practitioner (GP).ResultsDuring the first 8 months, the PowerForm template was used in 61% (360/594) of consecutive outpatient referrals increasing from 42% to 77% during the course of the study. Structured patient reports were available for immediate sharing with the referring GP using Cerner Health Information Exchange technology while electronic transmission was successfully developed in a substudy of 64 cases, with direct delivery by the NHS Data Transfer Service in 29 cases and NHS mail in the remainder. In feedback, the report’s immediate availability was considered very or extremely important by >80% of the patients and GPs who were surveyed. Both groups reported preference of the patient report to the conventional typed letter. Deidentified template data for all 360 patients were successfully captured within the Trust system, confirming availability of these routinely collected outpatient data for audit and research.ConclusionElectronic template development tailored to the requirements of a specialist outpatient clinic facilitates capture of routinely collected data within the Cerner EHR. These data can be made available for audit and research. They can also be used to enhance communication by populating structured reports for immediate delivery to patients and GPs.

We report an unusual case of an elderly man presenting with a fast-growing large malignant tumour involving the skin overlying his permanent pacemaker site. The fast-growing cutaneous squamous cell carcinoma appeared 2 years after pacemaker implantation. Joint specialist input was required to tackle this complex problem as a wide surgical excision would expose the pacemaker generator risking device infection particularly if the skin graft reconstruction failed. Having established that the patient had minimal pacing needs, it was determined through expedited multidisciplinary discussion that the best option was excision of the lesion with skin grafting of the defect by maxillofacial surgical team and pacemaker generator removal by a cardiologist in a joint surgical procedure. The procedure was successful and uneventful. This case highlights how effective multidisciplinary planning can help achieve a favourable clinical outcome in a patient with a rare case of a squamous cell carcinoma overlying a pacemaker site.

Background The electronic health record (EHR) is the major repository of clinical data in the NHS. It is a huge potential resource but remains severely under-utilised to the point that almost none of the UK’s audit and research output is based on routinely collected clinical data. The reasons are complex but ultimately reflect the fact that these data are rarely entered into the EHR in a form that allows for their organised storage and digital download. Methods We have developed a SNOMED-based electronic powerform comprising a user-friendly interface for real-time entry of clinical data into the hospital EHR during cardiac outpatient consultation. Our aim was to capture outpatient clinical data in a form that allows for automatic development of summary patient reports and for batch download of de-identified data for audit and research. Results During the first 4 months after installation of the powerform, consultant utilisation averaged 60% for the 327 new patients seen during that period. Presenting symptoms, examination findings, investigations, diagnosis, initial treatment and disposal (>120 fields) were entered in real time during consultation and a structured summary report was developed. This was made available for electronic transfer directly into the patients EMIS file in the primary care record, permitting same-day delivery of the report and obviating the need for a dictated clinic letter. Batched download of the digital data was successful, with sample analytic findings as follows: Patient ethnicity South Asian 44%, white 34%, black 15% Presenting symptom Chest pain 41%, dyspnoea 11%, palpitations 10%, dizzy attacks/syncope 8%, hypertension 7% Diagnosis Non-cardiac chest pain 24%, angina 11%, coronary disease 7% Disposal discharged to GP 74%, follow-up appointment 11%, cath lab waiting list 6%, referral to specialist clinic 9%. Ongoing are surveys of satisfaction with the power forms (cardiologists) and with the summary reports (GPs). Conclusion This is the first report of powerform development for entry of routinely collected cardiac outpatient data into the hospital EHR. The data are stored in a form that permits: (1) automatic generation of a summary report for same-day delivery into the primary care record and (2) batch download of de-identified digital data for audit. Integration of the system with programmes of generic patient consent will open up the EHR to real-world clinical research.

Introduction: The introduction of novel agentshas revolutionised the treatment of multiple myeloma, with improvements in survival of newly diagnosed and relapsed/refractory patients. However, despite these advances, the role for allogeneic haematopoietic stem cell transplantation (HSCT) in the treatment of these patients remains in question. Reduced-intensity conditioning (RIC) HSCT with Seattle regimen (30 mg/m2 fludarabine and 2 Gray total-body irradiation, TBI) for multiple myeloma has been reported to be an effective treatment with low upfront toxicity, and the potential for graft-versus-myeloma effect (Niederwieser D et al, Blood, 2003). Its use as part of tandem HSCT (autologous HSCT followed by RIC-HSCT) is associated with a treatment-related mortality (TRM) rate as low as 15% (Björkstrand B et al, J Clin Onc, 2011). However, data on survival following auto-HSCT/RIC-HSCT is inconsistent and no unifying consensus has been reached regarding the optimal timing of RIC-HSCT in the treatment algorithm. In this retrospective multi-centre study, we investigated the safety, tolerability and efficacy of RIC-HSCT in multiple myeloma patients in remission following previous auto-HSCT. Methods: A retrospective series was conducted for early-phase, high-risk myeloma patients who underwent RIC-HSCT following prior auto-HSCT in two tertiary transplant centres in Manchester in North West England, between November 2006 and July 2014. Results: Over the eight-year period, 42 myeloma patients (male n=29, female n=13) underwent Seattle-conditioned RIC-HSCT following prior auto-HSCT. 66.6% (n=28) were performed in tandem. Median age at RIC-HSCT was 52 years (range 41-65), and median β2-microglobulin at diagnosis was 3.1 mg/L (range 1.6-18.0). 16 patients had cytogenetics assessed at the time of diagnosis, of which loss of TP53 and translocation of chromosome 14 were most common. 37 patients (88.1%) had previously been exposed to immunomodulatory agents (IMiDs). 53.3% patients (n=24) were in first remission at RIC-HSCT, whilst 37.8% (n=17) were in second remission. 31.1% (n=14) of RIC-HSCTs were performed after second auto-HSCT following previous relapse and re-induction chemotherapy. 34 patients (55.9%) had achieved at least a very good partial response (VGPR) prior to RIC-HSCT. RIC-HSCT was performed a median of 20 months (range 10-89) from diagnosis. Two patients (4.8%) required re-transplantation for failed engraftment, but subsequently engrafted following in vivo T cell-depleting regimens. Mortality at early and interim time-points was low relative to registry and trial series, with TRM of 2.4% (n =1) and 9.5% (n=4) at day 100 and 365, respectively. 37 patients (82.2%) experienced chronic graft-versus-host disease (GVHD). Chronic skin GVHD was observed in 21 patients (grade 1-2: n=20; grade 3-4: n=1); chronic gastrointestinal GVHD in four patients (grade 1-2: n=1; grade 3-4: n=3); chronic hepatic GVHD in six patients (grade 1-2: n=4; grade 3-4: n=2); chronic oral GVHD in 17 patients (grade 1-2: n=17); and chronic ophthalmic GVHD in five patients (grade 1-2: n=5). There was an association between GVHD and enhanced disease control, as complete response rates increased from 26.5% to 51.5% by day 100 post-RIC-HSCT. However, 22 patients (48.9%) eventually relapsed with a median time to relapse of 6.5 months. 13 patients remain in CR one year post-RIC-HSCT. Relapse was treated with escalating donor lymphocyte infusions (DLI, n=13) or IMiDs (n=16). Response to lenalidomide at relapse was potentiated, despite the majority of patients having prior exposure to IMiDs. The median length of follow-up from diagnosis was 27 months (range 1-90). Median overall survival (OS) has not been reached; OS at two years was 69.2% (Figure 1). Conclusions: In this retrospective series we demonstrate the feasibility of Seattle-conditioned RIC-HSCT in multiple myeloma. We observed a very low early TRM of 9.5% and presence of allo-immune disease control (graft-versus-myeloma effect), thereby augmenting IMiD efficacy. Chronic GVHD was prevalent and relapse occurred in a significant proportion of patients, but salvage with DLI and IMiDs highlighted the efficacy of the graft-versus-myeloma effect elicited by RIC-HSCT. Figure 1. Survival outcomes after RIC-HSCT in myeloma. Median OS has not been reached, two-year OS was 69.2%. Figure 1. Survival outcomes after RIC-HSCT in myeloma. Median OS has not been reached, two-year OS was 69.2%. Disclosures Cavet: Celgene: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Speaker. Tholouli:Pfizer: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Gibbs:Celgene: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Objective Healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect in response to various vasoconstrictor agonists which is lost in diabetes and hypertension. Solution transfer experiments have demonstrated the existence of an adipocyte-derived relaxing factor (s) that mediates anticontractile function; however controversy exists surrounding the release mechanisms and its identity. This study aimed to elucidate the pathways involved in the anticontractile response to adrenergic and non-adrenergic agonists. Methods The effects of PVAT on the contractility of isolated rat mesenteric arteries were investigated using wire myography. Concentration-response curves were generated to noradrenaline, phenylephrine or serotonin (1 × 10 –5 –3 × 10 –9 mol.l –1 ) following 30 min incubation with the s3-agonist, CL-316,243 (10 µmol.l –1 ); s3-antagonist, SR59230A (30 µmol.l –1 ); NOS inhibitor, L-NMMA (100 µmol.l –1 ); BKCa channel inhibitor, iberiotoxin (100nmol.l -1 ) or the KCNQ inhibitor, XE 991 (10 µmol.l –1 ). Results and conclusions PVAT elicited an anticontractile effect in response to both noradrenaline and serotonin, but not phenylephrine (noradrenaline: P s3-adrenoceptor manipulation did not alter the serotonin-induced PVAT anticontractile effect (SR 59230A: Incubation with iberiotoxin abrogated PVAT function in response to noradrenaline (P Overall, this study indicates that PVAT exerts an agonist-dependent anticontractile effect via distinct mechanisms potentially leading release of a number of adipocyte-derived relaxing factors.