Modeling and Estimation of Temporal Episode Patterns in Paroxysmal Atrial Fibrillation.

OBJECTIVE: The present study proposes a model-based, statistical approach to characterizing episode patterns in paroxysmal atrial fibrillation (AF). Thanks to the rapid advancement of noninvasive monitoring technology, the proposed approach should become increasingly relevant in clinical practice. METHODS: History-dependent point process modeling is employed to characterize AF episode patterns, using a novel alternating, bivariate Hawkes self-exciting model. In addition, a modified version of a recently proposed statistical model to simulate AF progression throughout a lifetime is considered, involving non-Markovian rhythm switching and survival functions. For each model, the maximum likelihood estimator is derived and used to find the model parameters from observed data. RESULTS: Using three databases with a total of 59 long-term ECG recordings, the goodness-of-fit analysis demonstrates that the proposed alternating, bivariate Hawkes model fits SR-to-AF transitions in 40 recordings and AF-to-SR transitions in 51; the corresponding numbers for the AF model with non-Markovian rhythm switching are 40 and 11, respectively. Moreover, the results indicate that the model parameters related to AF episode clustering, i.e., aggregation of temporal AF episodes, provide information complementary to the well-known clinical parameter AF burden. CONCLUSION: Point process modeling provides a detailed characterization of the occurrence pattern of AF episodes that may improve the understanding of arrhythmia progression.

Short-term reproducibility of parameters characterizing atrial fibrillatory waves.

OBJECTIVE: To study reproducibility of f-wave parameters in terms of inter- and intrapatient variation. APPROACH: Five parameters are investigated: dominant atrial frequency (DAF), f-wave amplitude, phase dispersion, spectral organization, and spatiotemporal variability. For each parameter, the variance ratio R, defined as the ratio between inter- and intrapatient variance, is computed; a larger R corresponds to better stability and reproducibility. The study population consists of 20 high-quality ECGs recorded from patients with atrial fibrillation (11/9 paroxysmal/persistent). MAIN RESULTS: The well-established parameters DAF and f-wave amplitude were associated with considerably larger R-values (13.1 and 21.0, respectively) than phase dispersion (2.4), spectral organization (2.4), and spatiotemporal variability (2.7). The use of an adaptive harmonic frequency tracker to estimate the DAF resulted in a larger R (13.1) than did block-based maximum likelihood estimation (6.3). SIGNIFICANCE: This study demonstrates a noticeable difference in reproducibility among f-wave parameters, a result which should be taken into account when performing f-wave analysis.

Model-Based Assessment of f-Wave Signal Quality in Patients With Atrial Fibrillation.

OBJECTIVE: The detection and analysis of atrial fibrillation (AF) in the ECG is greatly influenced by signal quality. The present study proposes and evaluates a model-based f-wave signal quality index (SQI), denoted , for use in the QRST-cancelled ECG signal. METHODS: is computed using a harmonic f-wave model, allowing for variation in frequency and amplitude. The properties of  are evaluated on both f-waves and P-waves using 378 12-lead ECGs, 1875 single-lead ECGs, and simulated signals. RESULTS: decreases monotonically when noise is added to f-wave signals, even for noise which overlaps spectrally with f-waves. Moreover, is shown to be closely associated with the accuracy of AF frequency estimation, where implies accurate estimation. When  is used as a measure of f-wave presence, AF detection performance improves: the sensitivity increases from 97.0% to 98.1% and the specificity increases from 97.4% to 97.8% when compared to the reference detector. CONCLUSION: The proposed SQI represents a novel approach to assessing f-wave signal quality, as well as to determining whether f-waves are present. SIGNIFICANCE: The use of  improves the detection of AF and benefits the analysis of noisy ECGs.

Atrial fibrillation frequency tracking in ambulatory ECG signals: The significance of signal quality assessment.

An approach to atrial fibrillation (AF) frequency tracking in long-term ambulatory ECG recordings is presented, comprising f-wave extraction, dominant atrial frequency (DAF) tracking, and signal quality assessment. Since poor signal quality is commonly encountered in ambulatory monitoring, a recently proposed index is employed to assess f-wave signal quality in a database containing 38 patients with permanent AF. The index ensures that DAF outliers, typically associated with poor-quality segments, are excluded from further analysis. 40% of all 5-s signal segments were excluded from the database due to poor quality. The exclusion of DAF outliers significantly reduces the standard deviation of the frequency estimates (p≤0.01), allowing more reliable evaluation of the difference between day- and night-time DAF. The results show that signal quality assessment plays a central role in DAF tracking, and therefore should be employed in ambulatory monitoring.

Changes in f-wave characteristics during cryoballoon catheter ablation.

OBJECTIVE: Changes in ECG-derived parameters are studied in atrial fibrillation (AF) patients undergoing cryoballoon catheter ablation. APPROACH: Parameters characterizing f-wave frequency, morphology by phase dispersion, and amplitude are estimated using a model-based statistical approach. These parameters are studied before, during, and after ablation, as well as for AF type (paroxysmal/persistent). Seventy-seven (49/28 paroxysmal/persistent) AF patients undergoing de novo catheter ablation are included in the study, out of which 31 (16/15 paroxysmal/persistent) were in AF during the whole procedure. A signal quality index (SQI) is used to identify analyzable segments. MAIN RESULTS: f-wave frequency decreased significantly during ablation (p = 0.001), in particular after ablation of the inferior right pulmonary vein (p < 0.05). Frequency and phase dispersion differed significantly between paroxysmal and persistent AF (p = 0.001 and p < 0.05, respectively). SIGNIFICANCE: This study demonstrates that a decrease in f-wave frequency can be distinguished during catheter ablation. The use of an SQI ensures reliable analysis and produces results significantly different from those obtained without an SQI.

A Statistical Atrioventricular Node Model Accounting for Pathway Switching During Atrial Fibrillation.

OBJECTIVE: The atrioventricular (AV) node plays a central role in atrial fibrillation (AF), as it influences the conduction of impulses from the atria into the ventricles. In this paper, the statistical dual pathway AV node model, previously introduced by us, is modified so that it accounts for atrial impulse pathway switching even if the preceding impulse did not cause a ventricular activation. METHODS: The proposed change in model structure implies that the number of model parameters subjected to maximum likelihood estimation is reduced from five to four. The model is evaluated using the data acquired in the RATe control in atrial fibrillation (RATAF) study, involving 24-h ECG recordings from 60 patients with permanent AF. RESULTS: When fitting the models to the RATAF database, similar results were obtained for both the present and the previous model, with a median fit of 86%. The results show that the parameter estimates characterizing refractory period prolongation exhibit considerably lower variation when using the present model, a finding that may be ascribed to fewer model parameters. CONCLUSION: The new model maintains the capability to model RR intervals, while providing more reliable parameters estimates. SIGNIFICANCE: The model parameters are expected to convey novel clinical information, and may be useful for predicting the effect of rate control drugs.

Molecular effects of proinsulin C-peptide.

The proinsulin C-peptide has been held to be merely a by-product in insulin biosynthesis, but recent reports show that it elicits both molecular and physiological effects, suggesting that it is a hormonally active peptide. Specific binding of C-peptide to the plasma membranes of intact cells and to detergent-solubilised cells has been shown, indicating the existence of a cell surface receptor for C-peptide. C-peptide elicits a number of cellular responses, including Ca(2+) influx, activation of mitogen-activated protein (MAP) kinases, of Na(+),K(+)-ATPase, and of endothelial NO synthase. The pentapeptide EGSLQ, corresponding to the C-terminal five residues of human C-peptide, mimics several of the effects of the full-length peptide. The pentapeptide displaces cell membrane-bound C-peptide, elicits transient increase in intracellular Ca(2+) concentration and stimulates MAP kinase signalling pathways and Na(+),K(+)-ATPase. The Glu residue of the pentapeptide is essential for displacement of the full-length C-peptide, and free Glu can partly displace bound C-peptide, suggesting that charge interactions are important for receptor binding. Many C-peptide effects, such as phosphorylation of MAP-kinases ERK 1 and 2, stimulation of Na(+),K(+)-ATPase and increases in intracellular calcium concentrations are inhibited by pertussis toxin, supporting interaction of C-peptide with a G-protein-coupled receptor. However, all C-peptide effects cannot be explained in this manner, and it is possible that additional interactions are involved. Combined, the available observations show that C-peptide is biologically active and suggest a molecular model for its physiological effects.