Modeling Framework for the Generation of Synthetic RR Series during Atrial Arrhythmias.

We introduced a modeling framework for the generation of realistic ventricular interval (RR) series to be used in the validation of atrial arrhythmia detection algorithms. The framework included three previously proposed models, which reproduced the specific variability properties of RR series in normal sinus rhythm, atrial flutter (AFL) and atrial fibrillation (AF). Transitions between the three rhythms were governed by a three-state continuous-time Markov chain model, which could be tuned to obtain arrhythmic episodes of the requested length. As a representative application, the modeling framework was used to generate a database of RR series for the validation of a previously proposed AF detection algorithm, which was based on RR pattern similarity. The validation showed the deterioration of detector performance in presence of simulated AFL episodes. Thanks to the detailed reproduction of the specific features of the two most common atrial arrhythmias, our modeling framework may constitute a novel tool for the assessment and comparison of detection algorithm performance.

Dynamics of AV coupling during human atrial fibrillation: role of atrial rate.

The causal relationship between atrial and ventricular activities during human atrial fibrillation (AF) is poorly understood. This study analyzed the effects of an increase in atrial rate on the link between atrial and ventricular activities during AF. Atrial and ventricular time series were determined in 14 patients during the spontaneous acceleration of the atrial rhythm at AF onset. The dynamic relationship between atrial and ventricular activities was quantified in terms of atrioventricular (AV) coupling by AV synchrogram analysis. The technique identified n:m coupling patterns (n atrial beats in m ventricular cycles), quantifying their percentage, maximal length, and conduction ratio (= m/n). Simulations with a difference-equation AV model were performed to correlate the observed dynamics to specific atrial/nodal properties. The atrial rate increase significantly affected AV coupling and ventricular response during AF. The shortening of atrial intervals from 185 ± 32 to 165 ± 24 ms (P < 0.001) determined transitions toward AV patterns with progressively decreasing m/n ratios (from conduction ratio = 0.34 ± 0.09 to 0.29 ± 0.08, P < 0.01), lower occurrence (from percentage of coupled beats = 27.1 ± 8.0 to 21.8 ± 6.9%, P < 0.05), and higher instability (from maximal length = 3.9 ± 1.5 to 2.8 ± 0.7 s, P < 0.01). Advanced levels of AV block and coupling instability at higher atrial rates were associated with increased ventricular interval variability (from 123 ± 52 to 133 ± 55 ms, P < 0.05). AV pattern transitions and coupling instability in patients were predicted, assuming the filtering of high-rate irregular atrial beats by the slow recovery of nodal excitability. These results support the role of atrial rate in determining AV coupling and ventricular response and may have implications for rate control in AF.

Automatic reconstruction of activation and velocity maps from electro-anatomic data by radial basis functions.

The integration of mapping techniques with suitable methods for the characterization and visualization of propagation patterns may enhance the targeting of critical arrhythmic areas, thus optimizing the ablative treatment of atrial arrhythmias. In this study, we tested the feasibility of an innovative approach for the automatic determination of activation and velocity maps from sparse data as provided by electro-anatomic mapping systems. The proposed algorithm reconstructed the activation process by a radial basis function (RBF) interpolation of mapping point latencies. Velocity vectors were analytically determined by differentiation of the interpolation function. The method was tested by a multistate cellular automaton simulation model, implemented on a CARTO-derived atrial endocardial surface, and reconstruction accuracy was evaluated as a function of the number of mapping points. The RBF algorithm accurately reconstructed wave propagation patterns in simulated tissues with homogeneous and heterogeneous conduction properties, consistently with the data access afforded by clinical practice. These preliminary results suggest the possible integration of the method with clinically-used mapping systems to favor the identification of specific propagation patterns and conduction disturbances.

Long-term biatrial recordings in post-operative atrial fibrillation.

Although atrial fibrillation (AF) is a common complication of cardiac surgery, its pathophysiology remains unclear. The study of post-operative AF demands for the recording of cardiac electrical activity in correspondence of AF onset and progression. Long-term recordings in post-surgery patients could provide this information, but, to date, have been limited to surface signals, which precludes a characterization of the arrhythmic triggers and substrate. In this study we demonstrate the feasibility of a continuous long-term recording of atrial electrical activities from the right and left atria in post-surgery patients. Local atrial epicardial electrograms are acquired by positioning temporary pacing wires in the right and left atria at the end of the intervention, while three day recordings are obtained by a digital holter recorder, adapted to epicardial signal features. The capability of the system to map local atrial activity and the possibility to obtain quantitative information on atrial rate and synchronization from the processed epicardial signals are proven in representative examples. The quantitative description of local atrial properties opens new perspective in the investigation of post-surgery AF.

Causal linear parametric model for baroreflex gain assessment in patients with recent myocardial infarction.

Spectral and cross-spectral analysis of R-R interval and systolic arterial pressure (SAP) spontaneous fluctuations have been proposed for noninvasive evaluation of baroreflex sensitivity (BRS). However, results are not in good agreement with clinical measurements. In this study, a bivariate parametric autoregressive model with exogenous input (ARXAR model), able to divide the R-R variability into SAP-related and -unrelated parts, was used to quantify the gain (alpha(ARXAR)) of the baroreflex regulatory mechanism. For performance assessing, two traditional noninvasive methods based on frequency domain analysis [spectral, baroreflex gain by autogressive model (alpha(AR)); cross-spectral, baroreflex gain by bivariate autoregressive model (alpha(2AR))] and one based on the time domain [baroreflex gain by sequence analysis (alpha(SEQ))] were considered and compared with the baroreflex gain by phenylephrine test (alpha(PHE)). The BRS evaluation was performed on 30 patients (61 +/- 10 yr) with recent (10 +/- 3 days) myocardial infarction. The ARXAR model allowed dividing the R-R variability (950 +/- 1,099 ms(2)) into SAP-related (256 +/- 418 ms(2)) and SAP-unrelated (694 +/- 728 ms(2)) parts. alpha(AR) (12.2 +/- 6.1 ms/mmHg) and alpha(2AR) (8.9 +/- 5.6 ms/mmHg) as well as alpha(SEQ) (12.6 +/- 7.1 ms/mmHg) overestimated BRS assessed by alpha(PHE) (6.4 +/- 4.7 ms/mmHg), whereas the ARXAR index gave a comparable value (alpha(ARXAR) = 5.4 +/- 3.3 ms/mmHg). All noninvasive methods were significantly correlated to alpha(PHE) (alpha(ARXAR) and alpha(SEQ) were more correlated than the other indexes). Thus the baroreflex gain obtained describing the causal dependence of R-R interval on SAP showed a good agreement with alpha(PHE) and may provide additional information regarding the gain estimation in the frequency domain.

Capture window in human atrial fibrillation: evidence of an excitable gap.

INTRODUCTION: Local capture of atrial fibrillation (AF) was shown in animal experiments for a wide range of pacing rates, thus demonstrating the existence of an excitable gap. The aim of this study was to assess the existence of an excitable gap in human AF by studying the mechanism of local control and acceleration of AF over a wide range of pacing rates and by evaluating the time window of capture. METHODS AND RESULTS: Recording and stimulation of electrical activity in the right atrium during AF was performed by a monophasic action potential (MAP) contact electrode catheter in 17 patients with lone AF during electrophysiologic study. Stimulation was started at pacing intervals close to the mean AF interval, and the time window of capture was estimated by lengthening or shortening the pacing interval until capture was lost. Pacing intervals shorter than the minimum cycle length for capture were also tested. Beat-to-beat measurements of AF intervals during pacing were performed. Atrial MAP signal showed rapid irregular activity with an average AF interval of 151.3 +/- 16.1 msec and SD of 21.3 +/- 5.2 msec. Rapid pacing with a cycle length slightly shorter or longer than the mean AF interval resulted in local capture of AF. The width of time window of capture ranged from 22 to 36 msec, with a mean value of 28.8 +/- 4.9 msec. The average minimum pacing interval of stable capture was 129.2 +/- 19.5 msec, while the maximum was 158.1 +/- 18.7 msec, corresponding to 85% and 104% of mean AF cycle length, respectively. Pacing too rapidly resulted in a transient acceleration of AF, with an average shortening of fibrillation interval from 149.8 +/- 16.6 to 123.2 +/- 15.1 msec (P < 0.01). CONCLUSION: Local capture is feasible during AF in humans over a wide range of pacing rates, indicating the possibility of regional control of the fibrillatory process. This result demonstrates the presence of an excitable gap during AF in human atria.

Performance assessment of standard algorithms for dynamic R-T interval measurement: comparison between R-Tapex and R-T(end) approach.

Three automatic approaches to ventricular repolarisation duration measurement (R-Tapex, R-T(end threshold) and R-T(end fitting) methods) are compared on computer-generated and real ECG signals, in relation to their reliability in the presence of the most common electrocardiographic artefacts (i.e. additive broadband noise and additive and multiplicative periodical disturbances). Simulations permit the evaluation of the amount of R-T beat-to-beat variability induced by the artefacts. The R-T(end threshold) method performs better than the R-T(end fitting) one, and, hence, the latter should be used with caution when R-T(end) variability is addressed. Whereas the R-Tapex method is more robust with regard to broadband noise than the R-T(end threshold) one, the reverse situation is observed in the presence of periodical amplitude modulations. A high level of broadband noise dose not prevent the detection of the central frequency of underlying R-T periodical changes. Comparison between the power spectra of the beat-to-beat R-T variability series obtained from three orthogonal ECG leads (X,Y,Z) is used to assess the amount of real and artefactual variability in 13 normal subjects at rest. The R-Tapex series displays rhythms at high frequency (HF) with a percentage power on the Z lead (57.1 +/- 4.9) greater than that on the X and Y leads (41.9 +/- 4.6 and 46.1 +/- 4.9, respectively), probably because of respiratory-related artefacts affecting the Z lead more remarkably. More uniform HF power distributions over X,Y,Z leads are observed in the R-T(end threshold) series (31.8 +/- 3.8, 39.2 +/- 4.1 and 35.1 +/- 4.2, respectively), thus suggesting minor sensitivity of the R-T(end threshold) measure to respiratory-related artefacts.

Effects of atrial dilatation on refractory period and vulnerability to atrial fibrillation in the isolated Langendorff-perfused rabbit heart.

BACKGROUND: Atrial fibrillation (AF) is frequently observed under conditions that are associated with atrial dilatation. The aim of this study was to investigate the effects of atrial dilatation on the substrate of AF. METHODS AND RESULTS: In 15 Langendorff-perfused rabbit hearts, the interatrial septum was perforated, and after occlusion of the caval and pulmonary veins, biatrial pressure was increased by raising the level of an outflow cannula in the pulmonary artery. Right and left atrial effective refractory periods (AERPs), monophasic action potentials (MAPs), and inducibility of AF by single premature stimuli were measured as a function of atrial pressure. Increasing the atrial pressure from 0.5+/-0.7 to 16.2+/-2.2 cm H2O resulted in a progressive shortening of the right AERP from 82.2+/-9.8 to 48.0+/-5.1 ms. In the left atrium, an increase in pressure up to 7.4+/-0.3 cm H2O had no effect on the AERP. At higher pressures, however, the left AERP also shortened, from 67.5+/-7.5 to 49.3+/-2.0 ms. The duration of MAPs also decreased by an increase in atrial pressure, showing a high correlation with the shortening in AERP (r=.94, P<.01). All these changes were completely reversible within 3 minutes after release of the atrial stretch. Dilatation of the atria was a major determinant for the vulnerability to AF. The inducibility of AF increased from 0% at low pressures to 100% when the atrial pressure was >10 cm H2O. Release of the atrial wall stress resulted in prompt cardioversion of AF. The increased vulnerability for AF was highly correlated with the shortening in AERP (logistic regression r=.97). No correlation was found with the spatial dispersion between right and left AERPs. CONCLUSIONS: Increased atrial pressure in the isolated rabbit heart resulted in a significant increase in vulnerability to AF that was closely correlated to shortening of the AERP. These changes were completely reversible within 3 minutes after release of the atrial stretch, resulting in prompt termination of AF.

Dynamic electrophysiological behavior of human atria during paroxysmal atrial fibrillation.

BACKGROUND: The aims of our study were to investigate the meaning of local atrial activation and its behavior during paroxysmal atrial fibrillation and to study the effect of overdrive pacing on local atrial activity. METHODS AND RESULTS: Twenty-five patients with lone paroxysmal atrial fibrillation underwent electrophysiological study. Functional and effective atrial refractoriness was determined. Mean and fifth percentile values of 100 consecutive atrial fibrillation intervals (FF) were evaluated at three atrial sites either at arrhythmia onset or at self-termination (or at minute 5). A high-voltage burst pacing was performed after 6 minutes of stable atrial fibrillation in 10 patients. Mean FF intervals were evaluated 5 seconds before and after atrial pacing. Forty-nine atrial fibrillation episodes were induced: 39 self-terminating within 5 minutes and 10 long-lasting. A significant correlation was found between mean FF and atrial functional refractory period (r = .73, P < .001) and between fifth percentile FF and atrial effective refractory period (r = .57, P < .005). Atrial fibrillation self-termination was associated with significant mean FF prolongation, whereas long-lasting fibrillation behaved the opposite. In 10 patients, burst pacing resulted in significant shortening of the mean FF at the stimulation site; no changes were observed in the two distant recording sites. CONCLUSIONS: The analysis of the FF intervals demonstrates a strict correlation with atrial functional refractoriness. The self-termination of atrial fibrillation is related to a prolongation of the functional refractoriness (mean FF), whereas a shortening of both functional and effective refractoriness (fifth percentile) is associated with atrial fibrillation persistence. The provoked shortening of the mean FF at the stimulation site is consistent with the presence of a gap of excitability during atrial fibrillation in the human atria.

Evidence of low- and high-frequency oscillations in human AV interval variability: evaluation with spectral analysis.

The spontaneous beat-to-beat variation of atrioventricular (AV) interval was analyzed in time and frequency domains and compared with atrial cycle length (A-A) variability. The analysis was applied in humans at rest and tilt position during sinus rhythm and atrial pacing. The AV intervals showed spontaneous oscillations of small amplitude with a relative standard deviation of 1.8%. Spectral analysis of AV interval series showed the existence of two main oscillatory components at low frequency (LF; 0.04-0.13 Hz) and at high frequency (HF; 0.17-0.4 Hz), synchronous with those of A-A interval series. The same LF and HF fluctuations were found in AV interval variability during atrial pacing. Tilt maneuver inducing a sympathetic stimulation and vagal withdrawal increased LF power and decreased HF power of A-A interval spectra (P < 0.05). On the contrary, tilt decreased the LF (46%, P < 0.05) and HF power (29%, P = NS) of AV conduction spectra. In parallel, tilt decreased (P < 0.0001) the mean A-A interval, leaving the mean AV interval unchanged. When heart rate was held constant by atrial pacing, tilt reduced the mean AV interval, the LF power (65%, P < 0.05), and HF power (10%, P = NS). These results indicate a direct influence of the autonomic nervous system on the LF and HF oscillations of AV conduction. The decrease of AV interval oscillations during tilt demonstrates a marked reduction of autonomic modulation of AV conduction mainly attributable to parasympathetic withdrawal.

Ventricular beats induce variations in cycle length of rapid (type II) atrial flutter in humans. Evidence of leading circle reentry.

BACKGROUND: Slight variation in cycle lengths of common and rapid atrial flutter in humans is an established phenomenon, but its mechanisms have not been completely clarified. In a previous study, we demonstrated that in common atrial flutter the variations in atrial cycle length were due to atrial stretch affecting the revolution time of a reentrant circuit. In the present study, we investigate the nature of atrial cycle length variations in the rapid type of human atrial flutter. METHODS AND RESULTS: Atrial interval variations of 17 episodes of rapid atrial flutter in 14 patients were investigated by measuring the sequence of atrial intervals from intraesophageal or intra-atrial leads and the onset of QRS complexes from a surface lead (V1). To study whether interval variation in flutter cycle was related to ventricular activity, a phase plot was constructed in which the flutter cycle length was plotted against the time after the previous QRS complex. This showed that the interval fluctuations were strictly coupled to the moment of ventricular activation. After the onset of the QRS complex, the rapid atrial flutter interval gradually decreased by an average of 4.1% (P < .001) and reached a minimum value after 300 to 600 milliseconds. Thereafter, the intervals increased again until the next ventricular beat occurred. In 10 patients developing both common and rapid atrial flutter, two different phase relations were found. Whereas during common atrial flutter the atrial interval increased after the QRS complex, it decreased during rapid atrial flutter. In three patients, intra-atrial pressure was recorded together with the electrical activity during both common and rapid atrial flutter episodes. This showed that variations in atrial flutter cycle length were associated with the rise of atrial pressure during ventricular contraction. CONCLUSIONS: These findings indicate a role of contraction-excitation feedback caused by atrial stretch after a ventricular activation. The shortening of the atrial interval after the onset of the QRS complex as found in patients during rapid atrial flutter can be explained by stretch-induced shortening of atrial refractoriness and consequent shortening of the revolution time of a functionally determined intra-atrial circuit.

Beat-to-beat measurement and analysis of the R-T interval in 24 h ECG Holter recordings.

This study assesses the feasibility of beat-to-beat measurement of the R-T interval in Holter ECG recordings. The low sampling rate of the Holter system was increased by a specific interpolating filter, and the precision and accuracy of two T-wave fiducial point (T-wave maximum: Tm, T-wave end: Te) detection algorithms were compared. The results of the validation tests show better performance of the Tm measurement procedure in the presence of high noise levels. The overall process for the beat-to-beat R-T interval measurement was then tested on ECG Holter recordings collected during free and controlled respiration. Finally, the R-Tm and the corresponding R-R intervals were measured on 24 h ECG recordings of healthy subjects and the spectral analysis was applied to the constructed series. Both R-R and R-Tm spectra show two main frequency components (low-frequency approximately 0.1 Hz, high-frequency approximately 0.25 Hz) changing in their power ratios continuously throughout the 24 h period. The method described seems to provide a dynamic index of the sympatho-vagal balance at the ventricle that can be useful for a deeper understanding of ventricular repolarisation duration variability.

Complex dynamics underlying the human electrocardiogram.

Sequences of different human cardiac rhythms terminating in ventricular fibrillation have been studied, both qualitatively and quantitatively, with methods of nonlinear dynamics. The analysis has been applied to ECG epochs belonging to rhythms of increasing electrocardiographic irregularity: from sinus rhythm to prefibrillatory rhythms and then to ventricular fibrillation. The phase portraits of these rhythms have been reconstructed from the ECG recording with the time-delay technique, and their correlation dimensions have been estimated with the algorithm of Grassberger and Procaccia (1983a, b). Different cardiac rhythms exhibit different correlation dimensions that describe the corresponding degrees of complexity. The correlation dimension increases as one proceeds from sinus rhythm to fully developed ventricular fibrillation via intermediate rhythms. The fully developed ventricular fibrillation shows the highest degree of complexity. The dimensional analysis supports the existence of complex dynamics underlying different cardiac rhythms and reveals an increase in dimensional complexity corresponding to an increase in electrocardiographic irregularity. Our results indicate that nonlinear dynamics may be used to assess various dynamic states of the heart and may offer a non-invasive tool to investigate the complex dynamic phenomena occurring during arrhythmia.