High Prevalence of New Clinically Significant Findings in Patients With Embolic Stroke of Unknown Source Evaluated by Cardiac Magnetic Resonance Imaging.

BACKGROUND: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS. METHODS AND RESULTS: In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow-up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2). CONCLUSIONS: CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04555538.

AF and in-hospital mortality in COVID-19 patients.

Background: There are conflicting data on whether new-onset atrial fibrillation (AF) is independently associated with poor outcomes in COVID-19 patients. This study represents the largest dataset curated by manual chart review comparing clinical outcomes between patients with sinus rhythm, pre-existing AF, and new-onset AF. Objective: The primary aim of this study was to assess patient outcomes in COVID-19 patients with sinus rhythm, pre-existing AF, and new-onset AF. The secondary aim was to evaluate predictors of new-onset AF in patients with COVID-19 infection. Methods: This was a single-center retrospective study of patients with a confirmed diagnosis of COVID-19 admitted between March and September 2020. Patient demographic data, medical history, and clinical outcome data were manually collected. Adjusted comparisons were performed following propensity score matching between those with pre-existing or new-onset AF and those without AF. Results: The study population comprised of 1241 patients. A total of 94 (7.6%) patients had pre-existing AF and 42 (3.4%) patients developed new-onset AF. New-onset AF was associated with increased in-hospital mortality before (odds ratio [OR] 3.58, 95% confidence interval [CI] 1.78-7.06, P < .005) and after (OR 2.80, 95% CI 1.01-7.77, P < .005) propensity score matching compared with the no-AF group. However, pre-existing AF was not independently associated with in-hospital mortality compared with patients with no AF (postmatching OR: 1.13, 95% CI 0.57-2.21, P = .732). Conclusion: New-onset AF, but not pre-existing AF, was independently associated with elevated mortality in patients hospitalised with COVID-19. This observation highlights the need for careful monitoring of COVID-19 patients with new-onset AF. Further research is needed to explain the mechanistic relationship between new-onset AF and clinical outcomes in COVID-19 patients.

Evaluation of an open-source pipeline to create patient-specific left atrial models: A reproducibility study.

This work presents an open-source software pipeline to create patient-specific left atrial models with fibre orientations and a fibrDEFAULTosis map, suitable for electrophysiology simulations, and quantifies the intra and inter observer reproducibility of the model creation. 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 and intra-operator variability. Each output model consisted of: (1) a labelled surface mesh open at the pulmonary veins and mitral valve, (2) fibre orientations mapped from a diffusion tensor MRI (DTMRI) human atlas, (3) fibrosis map extracted from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. Reproducibility in our pipeline was evaluated by comparing agreement in shape of the output meshes, fibrosis distribution in the left atrial body, and fibre orientations. Reproducibility in simulations outputs was evaluated in the LAT maps by comparing the total activation times, and the mean conduction velocity (CV). PS maps were compared with the structural similarity index measure (SSIM). The users processed in total 60 cases for inter and 40 cases for intra-operator variability. Our workflow allows a single model to be created in 16.72 ± 12.25 min. Similarity was measured with shape, percentage of fibres oriented in the same direction, and intra-class correlation coefficient (ICC) for the fibrosis calculation. Shape differed noticeably only with users' selection of the mitral valve and the length of the pulmonary veins from the ostia to the distal end; fibrosis agreement was high, with ICC of 0.909 (inter) and 0.999 (intra); fibre orientation agreement was high with 60.63% (inter) and 71.77% (intra). The LAT showed good agreement, where the median ± IQR of the absolute difference of the total activation times was 2.02 ± 2.45 ms for inter, and 1.37 ± 2.45 ms for intra. Also, the average ± sd of the mean CV difference was -0.00404 ± 0.0155 m/s for inter, and 0.0021 ± 0.0115 m/s for intra. Finally, the PS maps showed a moderately good agreement in SSIM for inter and intra, where the mean ± sd SSIM for inter and intra were 0.648 ± 0.21 and 0.608 ± 0.15, respectively. Although we found notable differences in the models, as a consequence of user input, our tests show that the uncertainty caused by both inter and intra-operator variability is comparable with uncertainty due to estimated fibres, and image resolution accuracy of segmentation tools.

The Impact of Atrial Fibrillation Treatment Strategies on Cognitive Function.

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.

State of the art paper: Cardiac computed tomography of the left atrium in atrial fibrillation.

The clinical spectrum of atrial fibrillation means that a patient-individualized approach is required to ensure optimal treatment. Cardiac computed tomography can accurately delineate atrial structure and function and could contribute to a personalized 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 personalized approach to atrial fibrillation management.

Synchronous atrioventricular sequential pacing utilizing conventional and leadless pacemakers in an elderly patient: a case report.

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.

Left Bundle Area Pacing for Tachycardia-Bradycardia Syndrome in a Patient With Dextrocardia.

We present the case of an 81-year-old woman with a background of situs inversus with dextrocardia who was successfully treated for tachycardia-bradycardia syndrome with left bundle area pacing. This report describes how this approach can circumvent the limitations of other pacing approaches to optimize patient outcomes. (Level of Difficulty: Intermediate.).

Impact of catheter ablation versus medical therapy on cognitive function in atrial fibrillation: a systematic review.

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 < 0.05)). 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.

Cardiac tamponade from anticoagulant-related spontaneous haemopericardium in a patient with ischaemic cardiomyopathy and heart failure.

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.

Hyponatraemia: the importance of obtaining a detailed history and corroborating point-of-care analysis with laboratory testing.

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.

ß3 -Adrenoceptor stimulation of perivascular adipocytes leads to increased fat cell-derived NO and vascular relaxation in small arteries.

BACKGROUND AND PURPOSE: In response to noradrenaline, healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT-derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the noradrenaline-induced PVAT anticontractile effect. EXPERIMENTAL APPROACH: In vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer. KEY RESULTS: PVAT elicited an anticontractile effect in response to noradrenaline but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the ß3 -adrenoceptor agonist, CL-316243, reduced the vasoconstrictor effect of phenylephrine but not noradrenaline. Kv 7 channel inhibition using XE 991 reversed the noradrenaline-induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with noradrenaline and CL-316243, but not phenylephrine, was associated with increased adipocyte-derived NO production, and the contractile response to noradrenaline was augmented following incubation of exogenous PVAT with L-NMMA. PVAT from eNOS-/- mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with noradrenaline stimulation implicating Gαs signalling in this process. CONCLUSIONS AND IMPLICATIONS: We have shown that adipocyte-located ß3 -adrenoceptor stimulation leads to activation of Gαs signalling pathways with increased cAMP and the release of adipocyte-derived NO. This process is dependent upon Kv 7 channel function. We conclude that adipocyte-derived NO plays a central role in anticontractile activity when rodent PVAT is stimulated by noradrenaline.

Feasibility of real-time capture of routine clinical data in the electronic health record: a hospital-based, observational service-evaluation study.

OBJECTIVES: The 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. DESIGN: A 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). RESULTS: During 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. CONCLUSION: Electronic 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.

Multidisciplinary surgical team approach for excision of squamous cell carcinoma overlying pacemaker site.

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.

Vasospastic myocardial infarction caused by a slimming agent-do not forget non-prescription drugs.

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.