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.

Atrial CARdiac Magnetic resonance imaging in patients with embolic stroke of unknown source without documented Atrial Fibrillation (CARM-AF): Study design and clinical protocol.

Background: Initiation of anticoagulation therapy in ischemic stroke patients is contingent on a clinical diagnosis of atrial fibrillation (AF). Results from previous studies suggest thromboembolic risk may predate clinical manifestations of AF. Early identification of this cohort of patients may allow early initiation of anticoagulation and reduce the risk of secondary stroke. Objective: This study aims to produce a substrate-based predictive model using cardiac magnetic resonance imaging (CMR) and baseline noninvasive electrocardiographic investigations to improve the identification of patients at risk of future thromboembolism. Methods: CARM-AF is a prospective, multicenter, observational cohort study. Ninety-two patients will be recruited following an embolic stroke of unknown source (ESUS) and undergo atrial CMR followed by insertion of an implantable loop recorder (ILR) as per routine clinical care within 3 months of index stroke. Remote ILR follow-up will be used to allocate patients to a study or control group determined by the presence or absence of AF as defined by ILR monitoring. Results: Baseline data collection, noninvasive electrocardiographic data analysis, and imaging postprocessing will be performed at the time of enrollment. Primary analysis will be performed following 12 months of continuous ILR monitoring, with interim and delayed analyses performed at 6 months and 2 and 3 years, respectively. Conclusion: The CARM-AF Study will use atrial structural and electrocardiographic metrics to identify patients with AF, or at high risk of developing AF, who may benefit from early initiation of anticoagulation.

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.

Predicting Atrial Fibrillation Recurrence by Combining Population Data and Virtual Cohorts of Patient-Specific Left Atrial Models.

BACKGROUND: Current ablation therapy for atrial fibrillation is suboptimal, and long-term response is challenging to predict. Clinical trials identify bedside properties that provide only modest prediction of long-term response in populations, while patient-specific models in small cohorts primarily explain acute response to ablation. We aimed to predict long-term atrial fibrillation recurrence after ablation in large cohorts, by using machine learning to complement biophysical simulations by encoding more interindividual variability. METHODS: Patient-specific models were constructed for 100 atrial fibrillation patients (43 paroxysmal, 41 persistent, and 16 long-standing persistent), undergoing first ablation. Patients were followed for 1 year using ambulatory ECG monitoring. Each patient-specific biophysical model combined differing fibrosis patterns, fiber orientation maps, electrical properties, and ablation patterns to capture uncertainty in atrial properties and to test the ability of the tissue to sustain fibrillation. These simulation stress tests of different model variants were postprocessed to calculate atrial fibrillation simulation metrics. Machine learning classifiers were trained to predict atrial fibrillation recurrence using features from the patient history, imaging, and atrial fibrillation simulation metrics. RESULTS: We performed 1100 atrial fibrillation ablation simulations across 100 patient-specific models. Models based on simulation stress tests alone showed a maximum accuracy of 0.63 for predicting long-term fibrillation recurrence. Classifiers trained to history, imaging, and simulation stress tests (average 10-fold cross-validation area under the curve, 0.85±0.09; recall, 0.80±0.13; precision, 0.74±0.13) outperformed those trained to history and imaging (area under the curve, 0.66±0.17) or history alone (area under the curve, 0.61±0.14). CONCLUSION: A novel computational pipeline accurately predicted long-term atrial fibrillation recurrence in individual patients by combining outcome data with patient-specific acute simulation response. This technique could help to personalize selection for atrial fibrillation ablation.

Applications of multimodality imaging for left atrial catheter ablation.

Atrial arrhythmias, including atrial fibrillation and atrial flutter, may be treated through catheter ablation. The process of atrial arrhythmia catheter ablation, which includes patient selection, pre-procedural planning, intra-procedural guidance, and post-procedural assessment, is typically characterized by the use of several imaging modalities to sequentially inform key clinical decisions. Increasingly, advanced imaging modalities are processed via specialized image analysis techniques and combined with intra-procedural electrical measurements to inform treatment approaches. Here, we review the use of multimodality imaging for left atrial ablation procedures. The article first outlines how imaging modalities are routinely used in the peri-ablation period. We then describe how advanced imaging techniques may inform patient selection for ablation and ablation targets themselves. Ongoing research directions for improving catheter ablation outcomes by using imaging combined with advanced analyses for personalization of ablation targets are discussed, together with approaches for their integration in the standard clinical environment. Finally, we describe future research areas with the potential to improve catheter ablation outcomes.

Secondary Stroke Prevention Following Embolic Stroke of Unknown Source in the Absence of Documented Atrial Fibrillation: A Clinical Review.

Approximately one-third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one-third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.

OpenEP: A Cross-Platform Electroanatomic Mapping Data Format and Analysis Platform for Electrophysiology Research.

BACKGROUND: Electroanatomic mapping systems are used to support electrophysiology research. Data exported from these systems is stored in proprietary formats which are challenging to access and storage-space inefficient. No previous work has made available an open-source platform for parsing and interrogating this data in a standardized format. We therefore sought to develop a standardized, open-source data structure and associated computer code to store electroanatomic mapping data in a space-efficient and easily accessible manner. METHODS: A data structure was defined capturing the available anatomic and electrical data. OpenEP, implemented in MATLAB, was developed to parse and interrogate this data. Functions are provided for analysis of chamber geometry, activation mapping, conduction velocity mapping, voltage mapping, ablation sites, and electrograms as well as visualization and input/output functions. Performance benchmarking for data import and storage was performed. Data import and analysis validation was performed for chamber geometry, activation mapping, voltage mapping and ablation representation. Finally, systematic analysis of electrophysiology literature was performed to determine the suitability of OpenEP for contemporary electrophysiology research. RESULTS: The average time to parse clinical datasets was 400 ± 162 s per patient. OpenEP data was two orders of magnitude smaller than compressed clinical data (OpenEP: 20.5 ± 8.7 Mb, vs clinical: 1.46 ± 0.77 Gb). OpenEP-derived geometry metrics were correlated with the same clinical metrics (Area: R 2 = 0.7726, P < 0.0001; Volume: R 2 = 0.5179, P < 0.0001). Investigating the cause of systematic bias in these correlations revealed OpenEP to outperform the clinical platform in recovering accurate values. Both activation and voltage mapping data created with OpenEP were correlated with clinical values (mean voltage R 2 = 0.8708, P < 0.001; local activation time R 2 = 0.8892, P < 0.0001). OpenEP provides the processing necessary for 87 of 92 qualitatively assessed analysis techniques (95%) and 119 of 136 quantitatively assessed analysis techniques (88%) in a contemporary cohort of mapping studies. CONCLUSIONS: We present the OpenEP framework for evaluating electroanatomic mapping data. OpenEP provides the core functionality necessary to conduct electroanatomic mapping research. We demonstrate that OpenEP is both space-efficient and accurately representative of the original data. We show that OpenEP captures the majority of data required for contemporary electroanatomic mapping-based electrophysiology research and propose a roadmap for future development.

Standardised computed tomographic assessment of left atrial morphology and tissue thickness in humans.

AIMS: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. METHODS: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. RESULTS: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p < 0.001). Conditions known to predispose to the development of AF were not associated with differences in tissue thickness. CONCLUSIONS: The reported LACVi, LASAi, LATVi and tissue thickness derived from CCTA may serve as reference values for this age group and clinical characteristics for future studies. Increased LASAi in females in the absence of differences in LACVi or LATVi may indicate differential LA shape changes between the sexes. AF predisposing conditions, other than sex, were not associated with detectable changes in LAWT.Clinical trial registration:http://www.ClinicalTrials.gov/NCT01738828.

High-power, Short-duration Radiofrequency Ablation for the Treatment of AF.

High-power, short-duration (HPSD) ablation for the treatment of AF is emerging as an alternative to ablation using conventional ablation generator settings characterised by lower power and longer duration. Although the reported potential advantages of HPSD ablation include less tissue oedema and collateral tissue damage, a reduction in procedural time and superior ablation lesion formation, clinical studies of HPSD ablation validating these observations are limited. One of the main challenges for HPSD ablation has been the inability to adequately assess temperature and lesion formation in real time. Novel catheter designs may improve the accuracy of intra-ablation temperature recording and correspondingly may improve the safety profile of HPSD ablation. Clinical studies of HPSD ablation are on-going and interpretation of the data from these and other studies will be required to ascertain the clinical value of HPSD ablation.

Supraventricular tachycardia: An overview of diagnosis and management.

Supraventricular tachycardia (SVT) is a common cause of hospital admissions and can cause significant patient discomfort and distress. The most common SVTs include atrioventricular nodal re-entrant tachycardia, atrioventricular re-entrant tachycardia and atrial tachycardia. In many cases, the underlying mechanism can be deduced from electrocardiography during tachycardia, comparing it with sinus rhythm, and assessing the onset and offset of tachycardia. Recent European Society of Cardiology guidelines continue to advocate the use of vagal manoeuvres and adenosine as first-line therapies in the acute diagnosis and management of SVT. Alternative therapies include the use of beta-blockers and calcium channel blockers. All patients treated for SVT should be referred for a heart rhythm specialist opinion. Long-term treatment is dependent on several factors including frequency of symptoms, risk stratification, and patient preference. Management can range from conservative, if symptoms are rare and the patient is low risk, to catheter ablation which is curative in the majority of patients.

Anisotropic Cardiac Conduction.

Anisotropy is the property of directional dependence. In cardiac tissue, conduction velocity is anisotropic and its orientation is determined by myocyte direction. Cell shape and size, excitability, myocardial fibrosis, gap junction distribution and function are all considered to contribute to anisotropic conduction. In disease states, anisotropic conduction may be enhanced, and is implicated, in the genesis of pathological arrhythmias. The principal mechanism responsible for enhanced anisotropy in disease remains uncertain. Possible contributors include changes in cellular excitability, changes in gap junction distribution or function and cellular uncoupling through interstitial fibrosis. It has recently been demonstrated that myocyte orientation may be identified using diffusion tensor magnetic resonance imaging in explanted hearts, and multisite pacing protocols have been proposed to estimate myocyte orientation and anisotropic conduction in vivo. These tools have the potential to contribute to the understanding of the role of myocyte disarray and anisotropic conduction in arrhythmic states.