| 1. |
- Bachi, Lorenzo, et al.
(författare)
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ECG Modeling for Simulation of Arrhythmias in Time-Varying Conditions
- 2023
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Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294. ; 70:12, s. 3449-3460
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Tidskriftsartikel (refereegranskat)abstract
- The present paper proposes an ECG simulator that advances modeling of arrhythmias and noise by introducing time-varying signal characteristics. The simulator is built around a discrete-time Markov chain model for simulating atrial and ventricular arrhythmias of particular relevance when analyzing atrial fibrillation (AF). Each state is associated with statistical information on episode duration and heartbeat characteristics. Statistical, time-varying modeling of muscle noise, motion artifacts, and the influence of respiration is introduced to increase the complexity of simulated ECGs, making the simulator well suited for data augmentation in machine learning. Modeling of how the PQ and QT intervals depend on heart rate is also introduced. The realism of simulated ECGs is assessed by three experienced doctors, showing that simulated ECGs are difficult to distinguish from real ECGs. Simulator usefulness is illustrated in terms of AF detection performance when either simulated or real ECGs are used to train a neural network for signal quality control. The results show that both types of training lead to similar performance.
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| 2. |
- Grut, Viktor, et al.
(författare)
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Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study
- 2021
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
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| 3. |
- Grut, Viktor, et al.
(författare)
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Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis : A presymptomatic case-control study
- 2022
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 29:8, s. 2335-2342
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: High levels of 25-hydroxyvitamin D3 (25[OH]D3 ) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS.METHODS: A nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3 /DBP) × 103 . MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15-0.91, p for trend across quintiles = 0.04). At age 30-39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15-0.85, p for trend = 0.02).CONCLUSIONS: These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.
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| 4. |
- Grut, Viktor, et al.
(författare)
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Systemic inflammation and risk of multiple sclerosis – A presymptomatic case-control study
- 2022
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Ingår i: Multiple Sclerosis Journal - Experimental, Translational and Clinical. - : SAGE Publications. - 2055-2173. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS). Objectives: To assess CRP as a risk factor for MS. Methods: Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z-scored CRP values. Results: Levels of CRP were not associated with MS risk. Conclusions: We found no association between CRP levels and risk of MS development.
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| 5. |
- Andersson, Richard, et al.
(författare)
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One algorithm to rule them all? : An evaluation and discussion of ten eye movement event-detection algorithms
- 2017
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Ingår i: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-3528. ; 49:2, s. 616-637
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Tidskriftsartikel (refereegranskat)abstract
- Almost all eye-movement researchers use algorithms to parse raw data and detect distinct types of eye movement events, such as fixations, saccades, and pursuit, and then base their results on these. Surprisingly, these algorithms are rarely evaluated. We evaluated the classifications of ten eye-movement event detection algorithms, on data from an SMI HiSpeed 1250 system, and compared them to manual ratings of two human experts. The evaluation focused on fixations, saccades, and post-saccadic oscillations. The evaluation used both event duration parameters, and sample-by-sample comparisons to rank the algorithms. The resulting event durations varied substantially as a function of what algorithm was used. This evaluation differed from previous evaluations by considering a relatively large set of algorithms, multiple events, and data from both static and dynamic stimuli. The main conclusion is that current detectors of only fixations and saccades work reasonably well for static stimuli, but barely better than chance for dynamic stimuli. Differing results across evaluation methods make it difficult to select one winner for fixation detection. For saccade detection, however, the algorithm by Larsson, Nyström and Stridh (IEEE Transaction on Biomedical Engineering, 60(9):2484–2493,2013) outperforms all algorithms in data from both static and dynamic stimuli. The data also show how improperly selected algorithms applied to dynamic data misestimate fixation and saccade properties.
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| 6. |
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| 7. |
- Aunes-Jansson, Maria, et al.
(författare)
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Decrease of the atrial fibrillatory rate, increased organization of the atrial rhythm and termination of atrial fibrillation by AZD7009
- 2013
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The atrial fibrillatory rate (APR), on AZD7009 as compared to placebo, was investigated as a potential biomarker for electrophysiological effect in early antiarrhythmic drug development. Methods: Patients with permanent AF received infusions of AZD7009 and placebo in an exploratory two-way, single-blind, randomized cross-over study. The ECG was continuously recorded, and following QRST cancellation the APR, its standard deviation (SD), the exponential decay and the atrial electrogram amplitude were determined as 3-min averages. Results: The mean APR rapidly decreased by 43% from baseline (394 +/- 38 to 225 +/- 61 fibrillations/min, p = 0.0003) on AZD7009, but not on placebo. The SD of the AFR and the exponential decay decreased in parallel. In 2 of 8 patients, termination of AF occurred after the APR had decreased by 58% and 53%, respectively. Conclusions: The APR may potentially serve as a biomarker of electrophysiological effects in early evaluation of rhythm control agents. (C) 2013 Elsevier Inc. All rights reserved.
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| 8. |
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| 9. |
- Bollmann, Andreas, et al.
(författare)
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Analysis of surface electrocardiograms in atrial fibrillation: techniques, research, and clinical applications
- 2006
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Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 8:11, s. 911-926
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Forskningsöversikt (refereegranskat)abstract
- Atrial. fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy is sufficiently predictable by clinical and echocardiographic parameters. The purpose of this article is to describe technical aspects of novel electrocardiogram (ECG) analysis techniques and to present research and clinical applications of these methods for characterization of both the fibrillatory process and the ventricular response during AF Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface ECG using digital signal processing (extraction of atrial, signals and spectral analysis). This measurement shows large inter-individual variability and correlates well with intra-atriat cycle length, a parameter which appears to have primary importance in AF maintenance and response to therapy. AF with a tow fibrillatory rate is more likely to terminate spontaneously and responds better to antiarrhythmic drugs or cardioversion, whereas high-rate AF is more often persistent and refractory to therapy. Ventricular responses during AF can be characterized by a variety of methods, which include analysis of heart rate variability, RR-interval histograms, Lorenz plots, and non-linear dynamics. These methods have all shown a certain degree of usefulness, either in scientific explorations of atrioventricular (AV) nodal function or in selected clinical questions such as predicting response to drugs, cardioversion, or AV nodal modification. The role of the autonomic nervous system for AF sustenance and termination, as well as for ventricular rate responses, can be explored by different ECG analysis methods. In conclusion, non-invasive characterization of atrial fibrillatory activity and ventricular response can be performed from the surface ECG in AF patients. Different signal processing techniques have been suggested for identification of underlying AF pathomechanisms and prediction of therapy efficacy.
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| 10. |
- Bollmann, Andreas, et al.
(författare)
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Atrial fibrillatory rate and risk of left atrial thrombus in atrial fibrillation.
- 2007
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Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 9:8, s. 6-621
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Tidskriftsartikel (refereegranskat)abstract
- ims In atrial fibrillation (AF), a relation between electrocardiogram (ECG) fibrillatory wave amplitude and thrombus formation has been sought for long with conflicting results. In contrast, the possible relation between atrial fibrillatory rate obtained from the surface ECG and left atrial thrombus formation in patients with AF is unknown and was consequently evaluated in this study. Methods and results One-hundred and twenty-five patients (mean age 64 ± 12 years, 72% male) with persistent non-valvular AF (mean duration 28 ± 80 days) undergoing transesophageal echocardiography were studied. In all patients, standard 12-lead ECG recordings were acquired before the examination. Atrial fibrillatory rate was determined using spatiotemporal QRST cancellation and time–frequency analysis of lead V1. Atrial fibrillatory rate measured 401 ± 63 fibrillations per minute (fpm, range 235–566 fpm) and was related with age (R = −0.326, P < 0.001), ventricular rate (R = −0.202, P = 0.024), gender (407 ± 62 in males vs. 387 ± 64 fpm in females, P = 0.038) but not AF duration (R = 0.088, P = 0.374), presence of lone AF (408 ± 66 vs. 394 ± 58 fpm, P = 0.228), or beta-blocker or calcium channel blocker treatment (398 ± 63 vs. 405 ± 62 fpm, P = 0.556). Age was the only independent predictor of fibrillatory rate (B = −1.714, P < 0.001). In patients with left atrial thrombus (n = 10), spontaneous echo contrast (SEC) was more frequently present (70 vs. 29 %, p = 0.007) and left atrial appendage (LAA) outflow velocity was lower (26 ± 20 vs. 37 ± 15 cm/s, P = 0.012) than in patients without thrombus (n = 115). In contrast, mean fibrillatory rate, which showed a weak inverse correlation with LAA velocity (R = −0.118, P = 0.048) was not different between both groups (380 ± 56 vs. 403 ± 63 fpm, P = 0.226). Similarly, presence of thrombus and SEC combined was not related with fibrillatory rate. Conclusion Atrial fibrillatory rate obtained from surface ECG lead V1 is not a risk marker for left atrial thrombus formation in AF.
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| 11. |
- Bollmann, Andreas, et al.
(författare)
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Atrial fibrillatory rate and risk of stroke in atrial fibrillation.
- 2009
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Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 11, s. 582-586
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Tidskriftsartikel (refereegranskat)abstract
- Aims In atrial fibrillation (AF), a relation between electrocardiogram (ECG) parameters such as fibrillatory wave amplitude and stroke has been sought with conflicting results. In this study, we tested the hypothesis that the atrial fibrillatory rate of surface ECG lead V1 is related to stroke risk and may consequently be helpful for identifying high-risk patients. Methods and results Atrial fibrillatory rate of 79 consecutive patients with AF and embolic stroke (age 83 +/- 7 years, 41% male) was compared with those of a matched AF population without stroke (n = 79). Atrial fibrillatory rate was determined from the surface ECG using spatiotemporal QRST cancellation and time-frequency analysis of lead V1. There was no significant difference in any clinical or echocardiographic variable in patients with stroke compared with AF controls without stroke. Atrial fibrillatory rate measured 373 +/- 55 fibrillations per minute (fpm; range 235-505 fpm) in the entire population. There was no fibrillatory rate difference between stroke patients (369 +/- 54 fpm, range 256-505 fpm) and AF controls without stroke (378 +/- 56 fpm, range 235-488 fpm). There was an inverse correlation between fibrillatory rate and age (R = -0.219, P = 0.006). Individuals aged >/=85 years had a significantly lower fibrillatory rate (356 +/- 44 fpm) than individuals aged 65-74 years (384 +/- 56 fpm, P = 0.033) and individuals aged 75-84 years (384 +/- 60 fpm, P = 0.016). In those subgroups, fibrillatory rates were, however, also similar in stroke patients and AF controls. Conclusion Atrial fibrillatory rate obtained from surface ECG lead V1 is not a risk marker for stroke in AF.
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| 12. |
- Bollmann, Andreas, et al.
(författare)
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Echocardiographic and electrocardiographic predictors for atrial fibrillation recurrence following cardioversion
- 2003
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 14:s10, s. 162-165
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Identification of suitable candidates for cardioversion currently is not based on individual electrical and mechanical atrial remodeling. Therefore, this study analyzed the meaning of atrial fibrillatory rate obtained from the surface ECG (as a measure of electrical remodeling) and left atrial size (as measure of mechanical remodeling) for prediction of early atrial fibrillation (AF) recurrence following cardioversion. Methods and Results: Forty-four consecutive patients (26 men and 18 women, mean age 62 ± 11 years, no antiarrhythmic medication at baseline) with persistent AF were studied. Fibrillatory rate was obtained from high-gain, high-resolution surface ECG using digital signal processing (filtering, QRST subtraction, Fourier analysis) before electrical cardioversion. Univariate and multivariate regression analysis revealed larger systolic left atrial area (Beta = 0.176, P = 0.031) obtained by precardioversion echocardiogram from the apical four-chamber view and higher atrial fibrillatory rate (Beta = 0.029, P = 0.021) to be independent predictors for AF recurrence (n = 13). Stratification based on the regression equation (electromechanical index [EMI]= 0.176 systolic left atrial area + 0.029 fibrillatory rate − 17.674) allowed identification of groups at low, intermediate, or high risk. No patient with an EMI < −1.85 had early AF recurrence, as opposed to 78% with an EMI > −0.25. Intermediate results (40% recurrence rate) were obtained when the calculated EMI ranged between −1.85 and −0.25 (P < 0.001). Conclusion: Fibrillatory rate obtained from the surface ECG and systolic left atrial area obtained by echocardiography may predict early AF recurrence in patients with persistent AF. These parameters might be useful in identifying candidates with a high likelihood of remaining in sinus rhythm after cardioversion.
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| 13. |
- Bollmann, Andreas, et al.
(författare)
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Fibrillatory rate response to candesartan in persistent atrial fibrillation.
- 2008
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Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 10, s. 1138-1144
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Angiotensin-receptor blockers may exert favourable anti-arrhythmic effects in atrial fibrillation (AF), but their mechanisms are not fully understood. In this study, we tested the hypotheses that (i) candesartan reduces atrial fibrillatory rate and (ii) fibrillatory rate and its response to candesartan are related with the outcome of cardioversion. For this purpose, a post hoc subanalysis of the randomized, placebo-controlled CAPRAF (Candesartan in the Prevention of Relapsing Atrial Fibrillation) trial was performed. Methods and results Patients with AF undergoing electrical cardioversion were randomized to receive candesartan 8 mg once daily (n = 58) or matching placebo (n = 66) and no additional class I or III anti-arrhythmic drugs. Fibrillatory rate was determined from ECG lead V1 at baseline and at the day of cardioversion using spatiotemporal QRST cancellation and time-frequency analysis. The median time on treatment was 29 days. Candesartan reduced fibrillatory rate [399 +/- 48 vs. 388 +/- 49 fibrillations/min (fpm), P = 0.04], but not placebo (402 +/- 58 vs. 402 +/- 61 fpm, P = 0.986). Candesartan effects were only observed if the baseline fibrillatory rate was high [>420 fpm: 445 +/- 21 vs. 415 +/- 49 fpm, P = 0.006 vs. intermediate (360-420 fpm): 397 +/- 19 vs. 391 +/- 37 fpm, P = 0.351 vs. low (<360 fpm): 326 +/- 26 vs. 338 +/- 29 fpm, P = 0.179]. Cardioversion success was 100% in patients with an on-treatment rate <360 fpm vs. 83% in patients with higher rates (P = 0.02). Risk for AF recurrence was similar in patients with low (64%), intermediate (75%), or high on-treatment rates (63%, P = 0.446) and was also independent of candesartan effects on the fibrillatory rate. Conclusion In patients with persistent AF, candesartan decreases the fibrillatory rate, but this effect is restricted to patients with high baseline fibrillatory rates and is not associated with improved cardioversion outcome. Fibrillatory rates <360 fpm are associated with successful cardioversion, but not with AF recurrence.
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| 14. |
- Bollmann, A, et al.
(författare)
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Frequency measures obtained from the surface electrocardiogram in atrial fibrillation research and clinical decision-making
- 2003
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 14:s10, s. 154-161
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Tidskriftsartikel (refereegranskat)abstract
- Frequency Measures in AF. Introduction: Frequency analysis of fibrillation (FAF) and time-frequency analysis (TFA) were developed recently in order to quantify atrial electrical remodeling in atrial fibrillation (AF) from the surface ECG. This article describes the experience with these two different frequency analysis techniques in consecutive AF patients and discusses possible applications in AF research and clinical decision-making. Methods and Results: Baseline 2-minute, high-gain, high-resolution ECG recordings using three bipolar leads were obtained from 80 consecutive patients with AF lasting >24 hours. A power spectrum was obtained using Fourier analysis following spatiotemporal QRST cancellation. The dominant fibrillatory rate (in fibrillations per minute [fpm]) was derived (FAF). Stability of the instantaneous fibrillatory rate measured in overlapping 1-second segments was expressed as the segment proportion with consecutive rate differences <6 fpm (TFA). An adequate power spectrum that could be submitted for determination of fibrillatory rate was obtained in all patients. Dominant atrial rates ranged between 288 and 534 fpm and showed a high correlation (R = 0.878-0.911, P < 0.001) when assessed from the three different leads. The average instantaneous fibrillatory rate was inversely related with its stability (R = -0.417, P < 0.001). It was closely related with the dominant fibrillatory rate obtained from FAF (R = 0.948, P < 0.001). A literature review revealed that pharmacologic or electrical cardioversion and AF pace termination success rates were highly dependent on fibrillatory rate. Conclusion: Atrial fibrillatory rate and its variability can be reliable obtained from the surface ECG in AF patients. These parameters exhibit a significant interindividual variability allowing individual quantification of the atrial electrical remodeling process and might prove useful for predicting therapy efficacy.
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| 15. |
- Corino, V. D. A., et al.
(författare)
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A Gaussian mixture model for time-frequency analysis during atrial fibrillation electrocardiograms
- 2007
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Ingår i: 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2007.. - 1557-170X. - 9781424407880 ; , s. 271-274
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Konferensbidrag (refereegranskat)abstract
- During atrial fibrillation (AF), time-frequency analysis of atrial signal has been applied to describe fibrillatory frequency trends. Recently, temporal changes in spectral shape have been investigated using the spectral profile technique. This profile is computed recursively by fitting each short-time log-spectrum to a spectral template, using amplitude scaling and frequency shifting. The purpose of the present study was to develop a Gaussian mixture model of the spectral profile in order to characterize the shape of AF waveforms. A novel index is introduced, the so-called harmonic index (HI), which reflects properties of the fundamental frequency peak and related harmonics peaks as estimated from the model. The index was tested on recordings from 9 patients with persistent AF, obtained before and after exercise testing. The HI succeeded in monitoring the response to exercise, i.e. change in the spectral profile to a less harmonic pattern, which is consistent with a reduction in AF organization (HI: 0.61±0.11 vs. 0.50±0.19, rest vs. exercise; p≪0.05).
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| 16. |
- Corino, Valentina D. A., et al.
(författare)
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Association between Atrial Fibrillatory Rate and Heart Rate Variability in Patients with Atrial Fibrillation and Congestive Heart Failure
- 2013
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Ingår i: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X. ; 18:1, s. 41-50
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Tidskriftsartikel (refereegranskat)abstract
- Background Even if atrial fibrillatory rate (AFR) has been related to clinical outcome in patients with atrial fibrillation (AF), its relation with ventricular response has not been deeply studied. The aim of this study was to investigate the relation between AFR and RR series variability in patients with AF. Methods Twenty-minute electrocardiograms in orthogonal leads were processed to extract AFR, using spatiotemporal QRST cancellation and time frequency analysis, and RR series in 127 patients (age 69 +/- 11 years) with congestive heart failure (NYHA IIIII) enrolled in the MUSIC study (MUerte Subita en Insufficiencia Cardiaca). Heart rate variability and irregularity were assessed by time domain parameters and entropy-based indices, respectively and their correlation with AFR investigated. Results Variability measures seem not to be related to AFR, while irregularity measures do. A significant correlation between AFR and variability parameters of heart rate variability during AF was found only in patients not treated with antiarrhythmics drugs (correlation = 0.56 P < 0.05 for pNN50), while this correlation was lost in patients taking rate- or rhythm-control drugs. A significant positive correlation between AFR and indices of RR irregularity was found, showing that a higher AFR is related to a less organized RR series (correlation = 0.33 P < 0.05 for regularity index for all patients, correlation increased in subgroups of patients treated with the same drug). Conclusions These results suggest that a higher AFR is associated with a higher degree of irregularity of ventricular response that is observed regardless of the use of rate-controlling drugs. Ann Noninvasive Electrocardiol 2013;18(1):41-50
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| 17. |
- Corino, Valentina D. A., et al.
(författare)
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Improved Time-Frequency Analysis of Atrial Fibrillation Signals Using Spectral Modeling
- 2008
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Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 55:12, s. 2723-2730
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Tidskriftsartikel (refereegranskat)abstract
- In patients with atrial fibrillation (AF), the fibrillatory frequency trend and the time-dependent spectral characteristics can be investigated using a spectral profile technique. The spectral profile is updated by fitting each short-time spectrum. The aim of this study is to develop model-based means for stricter control on the update of the spectral profile. A spectral model defined by a superposition of Gaussian functions is suggested for describing the fundamental and harmonics of the atrial waves during AF, thereby accounting for basic characteristics of the typical AF spectrum. The model parameters are obtained from weighted least squares fitting of the model to the observed spectrum. The method was tested on simulated signals as well as on 48 ECG recordings from 15 patients with persistent AF. Using simulated signals, we assessed the accuracy in terms of magnitude and width or the spectral peaks. For SNR = 0 dB, the maximum normalized error was less than 0.2 when estimating magnitude of both the fundamental and the harmonics, whereas it was less than 0.15 for the fundamental and 0.7 for the harmonics with respect to the estimation of the width. We observed a marked Improvement while tracking the main fibrillatory frequency as the error was reduced by more than 50% In comparison with the original method. Analyzing ECGs, reliable spectral profiles were obtained In all recordings, even In those cases (5/48) that were not well characterized by the original method.
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| 18. |
- Engdahl, Elin, et al.
(författare)
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Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
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| 19. |
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| 20. |
- Grut, Viktor, 1980-
(författare)
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Exposures associated with multiple sclerosis development : presymptomatic case-control studies
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Multiple sclerosis (MS) is a chronic immune-mediated disease affecting the central nervous system. The current view is that MS is caused by a complex interplay of several environmental factors, eliciting an immune reaction in genetically susceptible individuals. Most previous studies of MS aetiology were retrospective, conferring the risk of reverse causation or recall bias. Few studies have been performed on data collected before the onset of the disease. The objective of this project was to identify risk factors for MS by analysing markers of exposure in samples collected before the clinical onset of MS.Method: A series of nested case-control studies were performed by cross-linking Swedish MS registries with Swedish biobanks, thereby identifying serum or plasma samples from up to 837 cases who later developed MS. For each case, up to two matched controls were selected. The following environmental risk factors were assessed: Antibodies against herpesviruses Epstein-Barr virus (EBV), Human herpesvirus 6A (HHV-6A) and Cytomegalovirus (CMV); Free Vitamin D3 Index and Vitamin D Binding Protein (DBP); and C-reactive Protein (CRP). Early signs of neural injury were assessed by measuring the concentration of neurofilament light chain in serum (sNfL). The associations between the environmental factors and future development of MS were analysed with conditional logistic regression, calculating odds ratios (OR) with 95% confidence intervals (CI). Interactions were analysed on the multiplicative and additive scales. The temporal relation of HHV-6A serostatus and axonal injury was analysed with locally estimated scatterplot smoothing regression.Results: Serological evidence of CMV infection was associated with a lower risk of MS development (OR = 0.70, 95% CI 0.56–0.88). Antagonistic interactions were observed between serological signs of CMV, HHV-6A, and EBV infection. Antibodies against HHV-6A were associated with a higher level of sNfL. In MS cases, increasing levels of HHV-6A antibodies were detected several years before increasing sNfL. Among young individuals, high levels of Free Vitamin D3 Index were associated with a lower MS risk (OR = 0.37, 95% CI 0.15–0.91). In older individuals, high levels of DBP were associated with a lower risk of developing MS (OR = 0.36, 95% CI 0.15–0.85). Elevated levels of CRP were not associated with MS risk.Conclusions: These results strengthen the evidence for HHV-6A and EBV in MS aetiology. They also support the hypothesis that CMV infection and a high level of free Vitamin D3 during childhood and adolescence are associated with a lower risk of MS later in life.
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| 21. |
- Grut, Viktor, et al.
(författare)
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Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis
- 2024
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 147:1, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.
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| 22. |
- Grut, Viktor, et al.
(författare)
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Interactions between high seroreactivity to human herpes virus 6A and Epstein–Barr virus in MS development : a presymptomatic case–control study
- 2024
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 96:2, s. 302-305
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Tidskriftsartikel (refereegranskat)abstract
- Synergistic interactions between human herpesvirus 6A (HHV-6A) and Epstein–Barr virus (EBV) are hypothesized in the etiopathogenesis of multiple sclerosis (MS). This study investigated if HHV-6A and EBV seroreactivities interact regarding the risk of developing MS. Antibodies against viral antigens were analyzed in biobank samples from 670 individuals who later developed MS and matched controls. Additive interactions were analyzed. A significant interaction between HHV-6A and EBNA-1 seroreactivities was observed in study participants above the median age of 24.9 years (attributable proportion due to interaction = 0.45). This finding supports the hypothesis that HHV-6A and EBV infections interact in MS development. ANN NEUROL 2024.
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| 23. |
- Halvaei, Hesam, et al.
(författare)
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Detection of Non-Sustained Supraventricular Tachycardia in Atrial Fibrillation Screening
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Ingår i: IEEE Journal of Translational Engineering in Health and Medicine. - 2168-2372.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Non-sustained supraventricular tachycardia (nsSVT) is associated with a higher risk of developing atrial fibrillation (AF), and, therefore, detection of nsSVT can improve AF screening efficiency. However, the detection is challenged by the lower signal quality of ECGs recorded using handheld devices and the presence of ectopic beats which may mimic the rhythm characteristics of nsSVT. Methods: The present study introduces a new nsSVT detector for use in single-lead, 30-s ECGs, based on the assumption that beats in an nsSVT episode exhibits similar morphology, implying that episodes with beats of deviating morphology, either due to ectopic beats or noise/artifacts, are excluded. A support vector machine is used to classify successive 5-beat sequences in a sliding window with respect to similar morphology. Due to the lack of adequate training data, the classifier is trained using simulated ECGs with varying signal-to-noise ratio. In a subsequent step, a set of rhythm criteria is applied to similar beat sequences to ensure that episode duration and heart rate is acceptable. Results: The performance of the proposed detector is evaluated using the StrokeStop II database, resulting in sensitivity, specificity, and positive predictive value of 84.6%, 99.4%, and 18.5%, respectively. Conclusion: The results show that a significant reduction in expert review burden (factor of 6) can be achieved using the proposed detector. Clinical and Translational Impact: The reduction in the expert review burden shows that nsSVT detection in AF screening can be made considerably more efficiently.
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| 24. |
- Halvaei, Hesam, et al.
(författare)
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Detection of Short Supraventricular Tachycardias in Single-lead ECGs Recorded Using a Handheld Device
- 2022
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Ingår i: Computing in Cardiology, CinC 2022. - 9798350300970
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Konferensbidrag (refereegranskat)abstract
- Short supraventricular tachycardias (S-SVTs) have been associated with a higher risk of developing atrial fibrillation (AF). Hence, identification of participants with such arrhythmias may increase the yield of AF screening. However, the lower signal quality of ECGs recorded using handheld screening devices challenges the detection of S-SVT. In the present work, a new method for detection of S-SVT is presented, which is based on the requirement on morphologic similarity between the detected beats. Specifically, any episode with a sequence of beats of similar morphology is considered as an S-SVT candidate while any episode with detections of different morphology, either due to signal disturbances or aberrant ectopic beats, is excluded. For this purpose, a support vector machine (SVM) was trained and validated, using a simulated ECG database, to classify an episode as either consisting of beats of similar or non-similar morphologies. Episodes identified as S-SVT candidates are subject to two further rhythm criteria in order to confirm the presence of an S-SVT. The performance of the S-SVT detector is evaluated using a subset of the StrokeStop I database (305 S-SVT out of 8258), resulting in a sensitivity, specificity, and positive predictive value of 88.8%, 92.0%, and 29.9%, respectively. In conclusion, the results suggest that the detection of S-SVT in AF screening can be done at an acceptable balance between sensitivity and positive predictive value.
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| 25. |
- Halvaei, Hesam, et al.
(författare)
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False Alarm Reduction in Atrial Fibrillation Screening
- 2021
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Ingår i: 2020 Computing in Cardiology. - 9781728111056 - 9781728173825
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Early detection of AF is essential and emphasizes the significance of AF screening. However, AF detection in screening ECGs, usually recorded by handheld and portable devices, is limited because of their high susceptibility to noise. In this study, the feasibility of applying a machine learning-based quality control stage, inserted between the QRS detector and AF detector blocks, is investigated with the aim to improve AF detection. A convolutional neural network was trained to classify the detections into either true or false. False detections were excluded and an updated series of QRS complexes was fed to the AF detector. The results show that the convolutional neural network-based quality control reduces the number of false alarms by 24.8% at the cost of 1.9% decrease in sensitivity compared to AF detection without any quality control.
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