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Background: Atrial fibrillation (AF) has been linked to left atrial (LA) enlargement. Whereas most studies focused on 2D-based estimation of static LA volume (LAV), we used a fully-automatic convolutional neural network (CNN) for time-resolved (CINE) volumetry of the whole LA on cardiac MRI (cMRI). Aim was to investigate associations between functional parameters from fully-automated, 3D-based analysis of the LA and current classification schemes in AF. Methods: We retrospectively analyzed consecutive AF patients who underwent cMRI on 1.5T systems including a stack of oblique-axial CINE series covering the whole LA. The LA was automatically segmented by a validated CNN. In the resulting volume-time curves, maximum, minimum and LAV before atrial contraction were automatically identified. Active, passive and total LA emptying fractions (LAEF) were calculated and compared to clinical classifications (AF Burden score (AFBS), increased stroke risk (CHA2DS2VASc≥2), AF type (paroxysmal/persistent), EHRA score, and AF risk factors). Moreover, multivariable linear regression models (mLRM) were used to identify associations with AF risk factors. Results: Overall, 102 patients (age 61±9 years, 17% female) were analyzed. Active LAEF (LAEF_active) decreased significantly with an increase of AFBS (minimal: 44.0%, mild: 36.2%, moderate: 31.7%, severe: 20.8%, p<0.003) which was primarily caused by an increase of minimum LAV. Likewise, LAEF_active was lower in patients with increased stroke risk (30.7% vs. 38.9%, p = 0.002). AF type and EHRA score did not show significant differences between groups. In mLRM, a decrease of LAEF_active was associated with higher age (per year: -0.3%, p = 0.02), higher AFBS (per category: -4.2%, p<0.03) and heart failure (-12.1%, p<0.04). Conclusions: Fully-automatic morphometry of the whole LA derived from cMRI showed significant relationships between LAEF_active with increased stroke risk and severity of AFBS. Furthermore, higher age, higher AFBS and presence of heart failure were independent predictors of reduced LAEF_active, indicating its potential usefulness as an imaging biomarker. [ABSTRACT FROM AUTHOR]

Background: Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. Objective: We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. Materials and methods: Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. Results: Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850–0.948]; AUC for CRP 0.922 [95%CI 0.879–0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694–0.894]; AUC for CRP 0.807 [95%CI 0.721–0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. Conclusion: In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions. [ABSTRACT FROM AUTHOR]

Background: Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking. Objectives: To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation. Methods: Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed. Results: Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase. Conclusions: In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have an increased risk for the development of heart failure (HF). In this study, we aimed to detect predictors of HF hospitalizations in an unselected AF population. Methods: The Basel Atrial Fibrillation Cohort Study is an ongoing observational multicenter cohort study in Switzerland. For this analysis, 1193 patients with documented AF underwent clinical examination, venous blood sampling and resting 12-lead ECG at baseline. Questionnaires about lifestyle and medical history were obtained in person at baseline and during yearly follow-up phone calls. HF hospitalizations were validated by two independent physicians. Cox regression analyses were performed using a forward selection strategy. Results: Overall, 29.8% of all patients were female and mean age was 69 ±12 years. Mean follow-up time was 3.7 ±1.5 years. Hospitalization for HF occurred in 110 patients, corresponding to an incidence of 2.5 events per 100 person years of follow-up. Independent predictors for HF were body mass index (HR 1.40 [95%CI 1.17; 1.66], p = 0.0002), chronic kidney disease (2.27 [1.49; 3.45], p = 0.0001), diabetes mellitus (2.13 [1.41; 3.24], p = 0.0004), QTc interval (1.25 [1.04; 1.49], p = 0.02), brain natriuretic peptide (2.19 [1.73; 2.77], p<0.0001), diastolic blood pressure (0.79 [0.65; 0.96], p = 0.02), history of pulmonary vein isolation or electrical cardioversion (0.54 [0.36; 0.80], p = 0.003) and serum chloride (0.82 [0.70; 0.96], p = 0.02). Conclusions: In this unselected AF population, several traditional cardiovascular risk factors and arrhythmia interventions predicted HF hospitalizations, providing potential opportunities for the implementation of strategies to reduce HF among AF patients. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial (LA) enlargement is an important risk factor for incident stroke and a key determinant for the success of rhythm control strategies in patients with atrial fibrillation (AF). However, factors associated with LA volume in AF patients remain poorly understood. Methods: Patients with paroxysmal or persistent AF were enrolled in this study. Real time 3-D echocardiography was performed in all participants and analyzed offline in a standardized manner. We performed stepwise backward linear regression analyses using a broad set of clinical parameters to determine independent correlates for 3-D LA volume. Results: We included 210 patients (70.9% male, mean age 61±11years). Paroxysmal and persistent AF were present in 95 (45%) and 115 (55%) patients, respectively. Overall, 115 (55%) had hypertension, 11 (5%) had diabetes, and 18 (9%) had ischemic heart disease. Mean indexed LA volume was 36±12ml/m2. In multivariable models, significant associations were found for female sex (β coefficient -10.51 (95% confidence interval (CI) -17.85;-3.16), p = 0.0053), undergoing cardioversion (β 11.95 (CI 5.15; 18.74), p = 0.0006), diabetes (β 14.23 (CI 2.36; 26.10), p = 0.019), body surface area (BSA) (β 34.21 (CI 19.30; 49.12), p<0.0001), glomerular filtration rate (β -0.21 (CI -0.36; -0.06), p = 0.0064) and plasma levels of NT-pro brain natriuretic peptide (NT-proBNP) (β 6.79 (CI 4.05; 9.52), p<0.0001), but not age (p = 0.59) or hypertension (p = 0.42). Our final model explained 52% of the LA volume variability. Conclusions: In patients with AF, the most important correlates with LA volume are sex, BSA, diabetes, renal function and NT-proBNP, but not age or hypertension. These results may help to refine rhythm control strategies in AF patients. [ABSTRACT FROM AUTHOR]

Introduction: The advent of electroanatomical mapping (EAM) systems for pulmonary vein isolation (PVI) has dramatically decreased radiation exposure. However, the need for some fluoroscopy remains for obtaining left atrial (LA) access. The aim was to test the feasibility of fluoroscopy-free PVI in patients with atrial fibrillation (AF) and a patent foramen ovale (PFO) guided solely by an EAM system. Methods: Consecutive patients with AF undergoing PVI and documented PFO were studied. An EAM-guided approach without fluoroscopy and ultrasound was used. After completing the map of the right atrium, the superior vena cava and the coronary sinus, a catheter pull-down to the PFO was performed allowing LA access. The map of the LA and subsequent PVI was also performed without fluoroscopy. Results: 30 patients [age 61±12 years, 73% male, ejection fraction 0.64 (0.53–0.65), LA size in parasternal long axis 38±7 mm] undergoing PVI were included. The time required for right atrial mapping including transseptal crossing was 9±4 minutes. Total procedure time was 127±37 minutes. Fluoroscopy-free PVI was feasible in 26/30 (87%) patients. In four patients, fluoroscopy was needed to access (n = 3) or to re-access (n = 1) the LA. In these four patients, total fluoroscopy time was 5±3 min and the DAP was 14.9±13.4 Gy*cm2. Single-procedure success rate was 80% (24/30) after a median follow-up of 12 months. Conclusion: In patients with a documented PFO, completely fluoroscopy-free PVI is feasible in the vast majority of cases. [ABSTRACT FROM AUTHOR]

Cardiac Na+ channels encoded by the SCN5A gene are essential for initiating heart beats and maintaining a regular heart rhythm. Mutations in these channels have recently been associated with atrial fibrillation, ventricular arrhythmias, conduction disorders, and dilated cardiomyopathy (DCM). We investigated a young male patient with a mixed phenotype composed of documented conduction disorder, atrial flutter, and ventricular tachycardia associated with DCM. Further family screening revealed DCM in the patient's mother and sister and in three of the mother's sisters. Because of the complex clinical phenotypes, we screened SCN5A and identified a novel mutation, R219H, which is located on a highly conserved region on the fourth helix of the voltage sensor domain of Nav1.5. Three family members with DCM carried the R219H mutation. The wild-type (WT) and mutant Na+ channels were expressed in a heterologous expression system, and intracellular pH (pHi) was measured using a pH-sensitive electrode. The biophysical characterization of the mutant channel revealed an unexpected selective proton leak with no effect on its biophysical properties. The H+ leak through the mutated Nav1.5 channel was not related to the Na+ permeation pathway but occurred through an alternative pore, most probably a proton wire on the voltage sensor domain. We propose that acidification of cardiac myocytes and/or downstream events may cause the DCM phenotype and other electrical problems in affected family members. The identification of this clinically significant H+ leak may lead to the development of more targeted treatments. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is considered as risk factor for the development of mild cognitive impairment (MCI) and dementia. However, dynamics of cognitive functions are subtle, and neurocognitive assessments largely differ in detecting these changes. We aimed to develop and evaluate a score which represents the common aspects of the cognitive functions measured by validated tests (i.e., "general cognitive construct"), while reducing overlap between tests and be more sensitive to identify changes in overall cognitive functioning., Methods: We developed the CoCo (cognitive construct) score to reflect the cognitive performance obtained by all items of four neurocognitive assessments (Montreal Cognitive Assessment (MoCA); Trail Making Test; Semantic Fluency, animals; Digital Symbol Substitution Test). The sample comprised 2,415 AF patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF), 87% aged at least 65 years. Psychometric statistics were calculated for two cognitive measures based on (i) the full set of items from the neurocognitive test battery administered in the Swiss-AF study (i.e., CoCo item set) and (ii) the items from the widely used MoCA test. For the CoCo item set, a factor score was derived based on a principal component analysis, and its measurement properties were analyzed., Results: Both the MoCA item set and the full neurocognitive test battery revealed good psychometric properties, especially the full battery. A one-factor model with good model fit and performance across time and groups was identified and used to generate the CoCo score, reflecting for each patient the common cognitive skill performance measured across the full neurocognitive test battery. The CoCo score showed larger effect sizes compared to the MoCA score in relation to relevant clinical variables., Conclusion: The derived factor score allows summarizing AF patients' cognitive performance as a single score. Using this score in the Swiss-AF project increases measurement sensitivity and decreases the number of statistical tests needed, which will be helpful in future studies addressing how AF affects the risk of developing cognitive impairment., Competing Interests: DC has received consultant/speaker fees from Servier Canada outside of the submitted work; GC reports a research grant from the Swiss National Science Foundation, and research grants from Boston Scientific Inc., outside of this work; JHB reports grants from the Swiss National Foundation of Science, The Swiss Heart Foundation, grants from Bayer, lecture fees from Sanofi Aventis and Amgen, to the institution outside of this work; LHB received grants from the Swiss National Science Foundation, The Swiss Heart Foundation, an unrestricted research grant from AstraZeneca, and consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical, and travel grants from AstraZeneca and Bayer, all outside of this work; MK reports personal fees from Bayer, personal fees from Böhringer Ingelheim, personal fees from Pfizer BMS, personal fees from Daiichi Sankyo, personal fees from Medtronic, personal fees from Biotronik, personal fees from Boston Scientific, personal fees from Johnson & Johnson, grants from Bayer, grants from Pfizer BMS, grants from Boston Scientific, all outside of this work. CSZ reports a research grant from Medtronic and speaker fees from Vifor Pharma and Novartis, outside of this work. RS of the study group Swiss-AF Study Investigators is employed by Schiller AG Baar. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: This study aimed to analyse health related quality of life (HRQoL) for patients with different atrial fibrillation (AF) types and to identify patient characteristics, symptoms and comorbidities that influence HRQoL., Methods: We used baseline data from the Swiss Atrial Fibrillation (Swiss-AF) study, a prospective multicentre observational cohort study conducted in 13 clinical centres in Switzerland. Between April 2014 and August 2017, 2415 AF patients were recruited. Patients were included in this analysis if they had baseline HRQoL data as assessed with EQ-5D-based utilities and visual analogue scale (VAS) scores. Patient characteristics and HRQoL were described stratified by AF type. The impact of symptoms, comorbidities and socio-economic factors on HRQoL was analysed using multivariable regression analysis., Results: Based on 2412 patients with available baseline HRQoL data, the lowest unadjusted mean HRQoL was found in patients with permanent AF regardless of whether measured with utilities (paroxysmal: 0.83, persistent: 0.84, permanent: 0.80, p<0.001) or VAS score (paroxysmal: 73.6, persistent: 72.8, permanent: 69.2, p<0.001). In multivariable analysis of utilities and VAS scores, higher European Heart Rhythm Association (EHRA) score, recurrent falls and several comorbidities showed a strong negative impact on HRQoL while AF type was no longer associated with HRQoL., Conclusions: Multiple factors turned out to influence HRQoL in AF patients. After controlling for several comorbidities, the EHRA score was one of the strongest predictors independent of AF type. The results may be valuable for better patient assessment and provide a reference point for further QoL and health economic analyses in AF populations., Competing Interests: JHB has received research grant support from the Swiss National Science Foundation and from the Swiss Heart Foundation, grant support, lecture and conference fees from Böhringer, Pfizer, Bayer and Daiichi Sankyo. LHB has received grants from the Swiss National Science Foundation, the University of Basel, and the Swiss Heart Foundation, Switzerland; a grant from The Stroke Association, UK; an unrestricted research grant from AstraZeneca; and consultancy and advisory board fees from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical. The Department of Radiology, University Hospital Basel, holds a general research agreement with Siemens and receives support from Guerbet, Bracco and Bayer, all unrelated to this work. DC has received consulting fees from Servier, Canada. RK holds grants from Biotronik, Biosense Webster, Boston, Medtronic, Abbott. MK has received consultant fees from Bayer, Boehringer-Ingelheim, Pfizer-BMS, Daiichi-Sankyo, Medtronic, Biotronik, Boston Scientific, Biosense Webster, Astra Zeneca, Novartis. NR has received a grant from the Swiss Heart Foundation. CS has received speaker honoraria from Biosense Webster and Medtronic and research grants from Biosense Webster, Daiichi-Sankyo, and Medtronic. MS has received grants unrelated to the submitted work from Amgen, MSD, Novartis, Pfizer, The Medicines Company; received fees unrelated to the submitted work, from Amgen; and received a grant from the Swiss National Science Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.