Flavia Ravelli

Wave Similarity Mapping Shows the Spatiotemporal Distribution of Fibrillatory Wave Complexity in the Human Right Atrium During Paroxysmal and Chronic Atrial Fibrillation

Introduction: The complexity of waveforms during atrial fibrillation may reflect critical activation patterns for the arrhythmia perpetuation. In this study, we introduce a novel concept of map, based on the analysis of the wave morphology, which gives a direct evidence in the human right atrium on the spatiotemporal distribution of fibrillatory wave complexity in paroxysmal (PAF) and chronic (CAF) atrial fibrillation.

Performance assessment of standard algorithms for dynamic R-T interval measurement: comparison between R-Tapex and R-Tend approach

Three automatic approaches to ventricular repolarisation duration measurement (R-Tapex, R-Tend threshold and R-Tend 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-Tend threshold method performs better than the R-Tend fitting one, and, hence, the latter should be used with caution when R-Tend variability is addressed. Whereas the R-Tapex method is more robust with regard to broadband noise than the R-Tend threshold one, the reverse situation is observed in the presence of periodical amplitude modulations. A high level of broadband noise does 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-Tend threshold series (31.8 ±3.8, 39.2±4.1 and 35.1±4.2, respectively), thus suggesting minor sensitivity of the R-Tend threshold measure to respiratory-related artefacts.

Quantification of synchronization during atrial fibrillation by Shannon entropy: Validation in patients and computer model of atrial arrhythmias

Atrial fibrillation (AF), a cardiac arrhythmia classically described as completely desynchronized, is now known to show a certain amount of synchronized electrical activity. In the present work a new method for quantifying the level of synchronization of the electrical activity recorded in pairs of atrial sites during atrial fibrillation is presented. A synchronization index (Sy) was defined by quantifying the degree of complexity of the distribution of the time delays between sites by Shannon entropy estimation. The capability of Sy to discriminate different AF types in patients was assessed on a database of 60 pairs of endocardial recordings from a multipolar basket catheter. The analysis showed a progressive and significant decrease of Sy with increasing AF complexity classes as defined by Wells (AF type I Sy = 0.73 +/- 0.07, type II Sy = 0.56 +/- 0.07, type III Sy = 0.36 +/- 0.04, p < 0.001). The extension of Sy calculation to the whole right atrium showed the existence of spatial heterogeneities in the synchronization level. Moreover, experiments simulated by a computer model of atrial arrhythmias showed that propagation patterns with different complexity could be the basis of different synchronization levels found in patients. In conclusion the quantification of synchronization by Shannon entropy estimation of time delay dispersion may facilitate the identification of different propagation patterns associated with AF, thus enhancing our understanding of AF mechanisms and helping in its treatment.

Deterioration of Organization in the First Minutes of Atrial Fibrillation: A Beat-to-Beat Analysis of Cycle Length and Wave Similarity

Introduction: It has been recently suggested that many episodes of atrial fibrillation (AF) may be partially organized at the onset and thus more suitable for antitachycardia pacing therapy. Nevertheless, the time course of organization in the first minutes of AF has not been quantified yet.

Acute Atrial Dilatation Slows Conduction and Increases AF Vulnerability in the Human Atrium

Stretch Slows Conduction in the Human Atrium. Introduction: The mechanisms by which atrial stretch favors the development of a substrate for atrial fibrillation (AF) are not fully understood. In this study, the role of stretch‐induced conduction changes in the creation of a proarrhythmic substrate has been investigated by quantifying the spatial distribution of local conduction velocities (CVs) in the human atrium during acute atrial dilatation.

A novel approach to propagation pattern analysis in intracardiac atrial fibrillation signals

The purpose of this study is to investigate propagation patterns in intracardiac signals recorded during atrial fibrillation (AF) using an approach based on partial directed coherence (PDC), which evaluates directional coupling between multiple signals in the frequency domain. The PDC is evaluated at the dominant frequency of AF signals and tested for significance using a surrogate data procedure specifically designed to assess causality. For significantly coupled sites, the approach allows also to estimate the delay in propagation. The methods potential is illustrated with two simulation scenarios based on a detailed ionic model of the human atrial myocyte as well as with real data recordings, selected to present typical propagation mechanisms and recording situations in atrial tachyarrhythmias. In both simulation scenarios the significant PDCs correctly reflect the direction of coupling and thus the propagation between all recording sites. In the real data recordings, clear propagation patterns are identified which agree with previous clinical observations. Thus, the results illustrate the ability of the novel approach to identify propagation patterns from intracardiac signals during AF, which can provide important information about the underlying AF mechanisms, potentially improving the planning and outcome of arrhythmia ablation.

Autosomal Recessive Atrial Dilated Cardiomyopathy With Standstill Evolution Associated With Mutation of Natriuretic Peptide Precursor A

Background—Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. Methods and Results—We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Conclusions—Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

Anatomic Localization of Rapid Repetitive Sources in Persistent Atrial Fibrillation: Fusion of Biatrial CT Images With Wave Similarity/Cycle Length Maps

OBJECTIVES The aim of this study was to investigate the anatomic distribution of critical sources in patients with atrial fibrillation (AF) by fusion of biatrial computed tomography (CT) images with cycle length (CL) and wave similarity (WS) maps. BACKGROUND Experimental and clinical studies show that atrial fibrillation (AF) may originate from rapid and repetitive (RR) sources of activation. Localization of RR sources may be crucial for an effective ablation treatment. Atrial electrograms showing rapid and repetitive activations can be identified by combining WS and CL analysis. METHODS Patients with persistent AF underwent biatrial electroanatomic mapping and pre-procedural CT cardiac imaging. WS and CL maps were constructed in 17 patients by calculating the degree of repetitiveness of activation waveforms (similarity index [S]) and the cycle length at each atrial site. WS/CL maps were then integrated with biatrial 3-dimensional CT reconstructions by a stochastic approach. RESULTS Repetitive sources of activation (S ≥ 0.5) were present in most patients with persistent AF (94%) and were mainly located at the pulmonary veins (82% of patients), at the superior caval vein (41%), on the anterior wall of the right atrium (23%), and at the left atrial appendage (23%). Potential driver sources showing both rapid and repetitive activations (CL = 140.7 ± 25.1 ms, S = 0.65 ± 0.15) were present only in a subset of patients (65%) and were confined to the pulmonary vein region (47% of patients) and left atrial appendage (12%). Differently, the repetitive activity of the superior caval vein was characterized by a slow activation rate (CL = 184.7 ± 14.6 ms). CONCLUSIONS The identification and localization of RR sources is feasible by fusion of biatrial anatomic images with WS/CL maps. Potential driver sources are present only in a subset of patients with persistent AF and are mainly located in the pulmonary vein region.

Small-Sample Characterization of Stochastic Approximation Staircases in Forced-Choice Adaptive Threshold Estimation

Despite the widespread use of up—down staircases in adaptive threshold estimation, their efficiency and usability in forced-choice experiments has been recently debated. In this study, simulation techniques were used to determine the small-sample convergence properties of stochastic approximation (SA) staircases as a function of several experimental parameters. We found that satisfying some general requirements (use of the accelerated SA algorithm, clear suprathreshold initial stimulus intensity, large initial step size) the convergence was accurate independently of the spread of the underlying psychometric function. SA staircases were also reliable for targeting percent-correct levels far from the midpoint of the psychometric function and performed better than classical up—down staircases with fixed step size. These results prompt the utilization of SA staircases in practical forced-choice estimation of sensory thresholds.

Mechanical modulation of atrial flutter cycle length.

Although atrial flutter (AFL) is considered a highly regular rhythm, small fluctuations in cycle length have been described. The mechanisms responsible for these interval oscillations have been investigated by recent studies in humans which have shown that cyclic variations in atrial volume and pressure following ventricular contraction may account for the spontaneous variability of AFL. Other studies have shown that variations in the dimensions of the atria, caused by hemodynamical alterations due to imposed manoeuvres, directly modify the rate of AFL. All this evidence has led to the development of the mechano-electrical feedback (MEF) hypothesis, which assumes that changes in atrial volume directly affect AFL cycle length variability by modifying the conduction properties of the circulating impulse in the atrium. In the present study, we re-examined the variability pattern of typical AFL by spectral analysis aiming to support the MEF hypothesis for AFL cycle length variability. In a study population of 30 patients with typical AFL, we observed that AFL cycle length presented a spontaneous beat-to-beat variability, composed of two oscillations: a main oscillation at the frequency of ventricular contraction (1.70+/-0.48 Hz, spectral power: 15.4+/-17.6 ms2) and a second oscillation at the frequency of respiration (0.32+/-0.07 Hz, spectral power: 2.9+/-2.6 ms2). Both ventricular and respiratory oscillations persisted after pharmacologic autonomic blockade (ventricular spectral power: 17.7+/-14.7 ms2 (before block) vs 20.2+/-18.3 ms2 (after block), p=NS; respiratory spectral power: 6.0+/-3.8 ms2 (before block) vs 5.0+/-3.4 ms2 (after block), p=NS), suggesting a non-neurally mediated underlying mechanism. Contrary to respiratory modulation of heart rate during sinus rhythm, respiratory AFL cycle length oscillations displayed a reverse pattern, with longer cycle lengths during inspiration and shorter during expiration (AA insp=223.2+/-28.6 ms vs AA exp=221.1+/-28.2 ms, p<0.0005), which was consistent with a mechanical modulation of AFL reentry. The use of spectral analysis techniques applied to ventricular interval series and combined with computer simulations of atrioventricular conduction showed that the respiratory oscillation of atrial cycle length determined an oscillation in ventricular intervals with longer intervals during inspiration and shorter during expiration (VV insp=639.9+/-186.0 ms vs VV exp=634.8+/-182.9 ms, p<0.05). Ventricular interval oscillations resulted amplified by a factor 1.8 with respect to corresponding atrial cycle length oscillations. Thus, the mechanical fluctuations in AFL cycle length, although of small amplitude, might become clinically relevant through a magnified effect on ventricular variability.