Flavia Ravelli

Lund University, Lund, Skane, Sweden

Are you Flavia Ravelli?

Claim your profile

Publications (65)176.04 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The identification of suitable markers for critical patterns during atrial fibrillation (AF) may be crucial to guide an effective ablation treatment. Single parameter maps, based on dominant frequency and complex fractionated electrograms, have been proposed as a tool for electrogram-guided ablation, however the specificity of these markers is debated. Experimental studies suggest that AF critical patterns may be identified on the basis of specific rate and organization features, where rapid organized and rapid fragmented activities characterize respectively localized sources and critical substrates. In this paper we introduce the logical operator map, a novel mapping tool for a point-by-point identification and localization of AF critical sites. Based on advanced signal and image processing techniques, the approach combines in a single map electrogram-derived rate and organization features with tomographic anatomical detail. The construction of the anatomically-detailed logical operator map is based on the time-domain estimation of atrial rate and organization in terms of cycle length and wave-similarity, the logical combination of these indexes to obtain suitable markers of critical sites, and the multimodal integration of electrophysiological and anatomical information by segmentation and registration techniques. Logical operator maps were constructed in 14 patients with persistent AF, showing the capability of the combined rate and organization markers to identify with high selectivity the subset of electrograms associated with localized sources and critical substrates. The precise anatomical localization of these critical sites revealed the confinement of rapid organized sources in the left atrium with organization and rate gradients towards the surrounding tissue, and the presence of rapid fragmented electrograms in proximity of the sources. By merging in a single map the most relevant electrophysiological and anatomical features of the AF process, the logical operator map may have significant clinical impact as a direct, comprehensive tool to understand arrhythmia mechanisms in the single patient and guide more conservative, step-wise ablation.
    Progress in Biophysics and Molecular Biology 07/2014; · 2.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) is the most common complication of cardiac surgery interventions. Several mechanisms are involved in the occurrence of this complex arrhythmia, which include electrical and structural remodeling. In particular, it has been shown that atrial fibrosis, which consists in the massive accumulation of the extracellular matrix (ECM) components between cardiomyocytes, may interfere with the electrical impulse propagation creating a substrate for AF. As well, microRNAs (miRNAs), a broad class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, have been recently indicated as regulators of diverse cardiovascular functions, which may potentially affect arrhythmia occurrence. This study investigates the molecular and structural features of atrial tissue biopsies obtained from patients undergoing cardiac surgery, aiming to identify potential correlations with the occurrence of AF. Specifically, the total RNA was extracted from small biopsies of the right atrial appendage, and the expression of a set of miRNAs, known to regulate structural proteins / ion channels, was evaluated by qRT-PCR. Concurrently, the total collagen content was assessed by applying histological techniques and polarized microscopy to Picro Sirius Red stained tissue slices. The analysis revealed specific profiles of fibrosis-related microRNAs and intramural fibrosis distribution in AF patients, suggesting the potential role of post-transcriptional regulation mechanisms in the creation of a pro-arrhythmic substrate.
    SIBBM 2014 - Frontiers in Molecular Biology; "Emerging Arenas in Molecular Biology: from basic mechanisms to personalized medicine", Trento - Italy; 06/2014
  • Flavia Ravelli, Michela Masè
    [Show abstract] [Hide abstract]
    ABSTRACT: This article discusses the latest development in computational mapping for the identification and localization of critical sources in patients with atrial fibrillation (AF). It focuses on the contribution of electrogram-derived anatomical maps, obtained by applying innovative signal and image processing methodologies, to the investigation of the mechanisms underlying the arrhythmia and to the planning of new target ablation strategies. Reviewed are the experimental studies which allowed to infer the peculiar rate and regularity features of critical sources, the signal processing methods for the quantification of these parameters from atrial electrograms, and the clinical studies mapping rate and organization in AF patients. Finally, we present a novel methodological framework, based on the construction of the logic operation map, designed to merge in a single map the most relevant electrophysiological and anatomical features of the AF process, which may guide the selective identification of critical sources.
    Europace 05/2014; 16(5):714-23. · 2.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionAlthough atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In the present study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy.Methods and ResultsRepeated electroanatomic mapping and tomographic evaluations were used to investigate the evolving arrhythmic substrate in 5 patients with isolated arrhythmogenic atrial cardiomyopathy, caused by Natriuretic Peptide Precursor A (NPPA) gene mutation. Atrial fibrosis was assessed using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The substrate of atrial tachycardia (AT) and atrial fibrillation (AF) was bi-atrial dilatation with patchy areas of low voltage and atrial wall scarring (in the right atrium: 68.5±6.0% and 22.2±10.2%, respectively). The evolution of the arrhythmic patterns to sinus node disease with atrial standstill (AS) was associated with giant atria with extensive low voltage and atrial scarring areas (in the right atrium: 99.5±0.7% and 57.5±33.2%, respectively). LGE-MRI-proven bi-atrial fibrosis (Utah stage IV) was associated with AS. Atrial conduction was slow and heterogeneous, with lines of conduction blocks. The progressive extension and spatial distribution of the scarring/fibrosis were strictly associated with the different types of arrhythmias.Conclusion The evolution of the amount and distribution of atrial scarring/fibrosis constitutes the structural substrate for the different types of atrial arrhythmias in a pure genetic model of arrhythmogenic atrial cardiomyopathy.This article is protected by copyright. All rights reserved.
    Journal of Cardiovascular Electrophysiology 04/2014; · 3.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the growing interest in cardiac miRNA expression profiling, having high quality and yield in RNA extraction from cardiac tissue is still challenging. We compared different methods of tissue homogenization and total RNA extraction from pig cardiac tissue aimed at miRNAs expression profiling. Small biopsies of right atrial appendages were obtained from pig hearts and treated according to four different protocols: no homogenization (P1) and homogenization by manual (P2) or automatic (P3 and P4) methods, followed by Proteinase K digestion (PKD) except in P4. Total RNA was extracted using miRNeasy mini kit, assessing RNA yield and quality by Nanodrop. cDNA synthesis and qRT-PCR were performed using TaqMan MicroRNA Assay. Homogenization was crucial to obtain high yield of pure total RNA. Automatic methods displayed higher yield (0.27 μg RNA/mg tissue in P3) than manual (0.06 μg RNA/mg tissue in P2), with better performance without PKD step (0.38μg RNA/mg tissue in P4). RNA from P4 was suitable for miRNA expression profiling, as demonstrated by qRT-PCR on miRNA 21 and 29. These results suggest the efficacy of an automatic homogenization to extract RNA suitable for miRNA expression profiling.
    9th European Biophysics Congress, Lisbon, Portugal 13-17 July 2013; 07/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biophysically-detailed and anatomically-realistic atrial models are emerging as a valuable tool in the study of atrial arrhythmias, nevertheless clinical use of these models would be favored by a reduction of computational times. This paper introduces a novel adaptive mesh algorithm, based on multiresolution representation (MR), for the efficient integration of cardiac ODE-PDE systems on unstructured triangle meshes. The algorithm applies a dynamically-adapted node-centered FVM scheme for integration of diffusion. The method accuracy and efficiency were evaluated by simulating propagation scenarios of increasing complexity levels (pacing, stable spirals, atrial fibrillation) on tomography-derived 3D monolayer atrial models, based on a monodomain reaction-diffusion formulation coupled with the Courtemanche atrial ionic model. All simulated propagation patterns were accurately reproduced with substantially reduced computational times (10 - 30% of the fullresolution simulation time). The proposed algorithm, combining the MR computational efficiency with the geometrical flexibility of unstructured meshes, may favor the development of patientspecific multiscale models of atrial arrhythmias and their application in the clinical setting.
    IEEE transactions on bio-medical engineering 05/2013; · 2.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: -Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983 we described 8-years follow-up of idiopathic 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 a same geographic area in the North-East 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) bi-atrial dilatation up to giant size; 3) early supraventricular arrhythmias with progressive loss of atrial electrical activity to atrial standstill; 4) thromboembolic complications; 5) stable, normal left ventricular function and NYHA functional class during the long-term course of the disease. By linkage analysis we mapped a locus at 1p36.22 containing the natriuretic precursor A (NPPA) gene. By sequencing NPPA 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 (ANP). Heterozygous mutation carriers were healthy and demonstrated normal levels of ANP. CONCLUSIONS: -Autosomal recessive Atrial Dilated Cardiomyopathy is a rare disease associated with homozygous mutation of the NPPA gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function and severely decreased levels of ANP.
    Circulation Cardiovascular Genetics 12/2012; · 6.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. 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). 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.
    JACC. Cardiovascular imaging 12/2012; 5(12):1211-20. · 14.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, sparse modeling is introduced for the estimation of propagation patterns in intracardiac atrial fibrillation (AF) signals. The estimation is based on the partial directed coherence function, derived from fitting a multivariate autoregressive model to the observed signal using least-squares (LS) estimation. The propagation pattern analysis incorporates prior information on sparse coupling as well as the distance between the recording sites. Two optimization methods are employed for estimation of the model parameters, namely, the adaptive group least absolute selection and shrinkage operator (aLASSO), and a novel method named the distance-adaptive group LASSO (dLASSO). Using simulated data, both optimization methods were superior to LS estimation with respect to detection and estimation performance. The normalized error between the true and estimated model parameters dropped from 0.20 ± 0.04 for LS estimation to 0.03 ± 0.01 for both aLASSO and dLASSO when the number of available data samples exceeded the number of model parameters by a factor of 5. For shorter data segments, the error reduction was more pronounced and information on the distance gained in importance. Propagation pattern analysis was also studied on intracardiac AF data, the results showing that the identification of propagation patterns is substantially simplified by the sparsity assumption.
    IEEE transactions on bio-medical engineering 02/2012; 59(5):1319-28. · 2.15 Impact Factor
  • Flavia Ravelli, Michela Masè
    [Show abstract] [Hide abstract]
    ABSTRACT: The localization of atrial fibrillation (AF) driver sources, characterized by rapid and regular electrical activity, is crucial for an effective ablation treatment. This work proposes a double-criteria approach for the identification of AF drivers based on a time-domain evaluation of atrial rate and AF organization. These two features are quantified by the measurement of atrial cycle length (ACL) and wave-similarity (WS). Based on ACL/WS formalism, AF drivers can be operatively defined as sites displaying electrical activity with high-rate and high-similarity (HR AND HS). The capability of ACL/WS analysis to identify AF driver sites and distinguish them from non-critical areas is shown in representative examples. The double-criteria evaluation for the identification of AF drivers, provided by our time-domain approach, might open new perspectives for the development of electrogram-guided ablation strategies in the single patient.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:5527-30.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study introduces sparse modeling for the estimation of propagation patterns in intracardiac atrial fibrillation (AF) signals. The estimation is based on the partial directed coherence (PDC) function, derived from fitting a multivariate autoregressive model to the observed signals. A sparse optimization method is proposed for estimation of the model parameters, namely, the adaptive group least absolute selection and shrinkage operator (aLASSO). In simulations aLASSO was found superior to the commonly used least-squares (LS) estimation with respect to estimation performance. The normalized error between the true and estimated model parameters dropped from 0.20 ± 0.04 for LS estimation to 0.03 ± 0.01 for aLASSO when the number of available data samples exceeded the number of model parameters by a factor of 5. The error reduction was more pronounced for short data segments. Propagation patterns were also studied on intracardiac AF data, the results showing that the identification of propagation patterns is substantially simplified by the sparsity assumption.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:5535-8.
  • Journal of Electrocardiology - J ELECTROCARDIOL. 01/2011; 44(2).
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Annals of Biomedical Engineering 01/2011; 39(1):310-23. · 3.23 Impact Factor
  • Journal of Electrocardiology - J ELECTROCARDIOL. 01/2011; 44(2).
  • Journal of Electrocardiology. 01/2011; 44(2):e22.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.Methods and Results: Electroanatomic mapping of right atrial activation was performed in 10 patients during coronary sinus pacing under control condition and during acute atrial dilatation. Atrial stretch was obtained by simultaneous atrioventricular (AV) pacing at a cycle length of 450–500 ms. Local CVs were accurately estimated by applying the principle of triangulation and spatially mapped over the whole right atrial endocardial surface. Simultaneous AV pacing significantly increased right atrial volume from 72.0 ± 29.0 to 86.3 ± 31.3 mL (P < 0.001). The 23% increase in atrial volume resulted in an overall decrease in atrial CV from 65.8 ± 5.9 to 55.2 ± 7.2 cm/s (P < 0.001) and an increased incidence of slow conduction sites or local conduction blocks from 10.3 ± 4.2% to 15.9 ± 7.7% (P < 0.01). Acute atrial dilatation concurrently increased AF vulnerability, with 6 of 10 patients developing AF episodes under stretch condition.Conclusion: Quantification of stretch-induced conduction changes in the human atrium is feasible by combining simultaneous AV pacing and CV map construction. Acute atrial dilatation results in conduction slowing and significant increase in AF vulnerability, suggesting the role of stretch-induced conduction disturbances in the creation of a substrate for AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 394-401)
    Journal of Cardiovascular Electrophysiology 11/2010; 22(4):394 - 401. · 3.48 Impact Factor
  • M Masé, F Ravelli
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:2608-11.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:2654-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: New multispline mapping systems are now available for the study of atrial fibrillation, which aim at the identification of localized arrhythmic sources. Nevertheless quantitative methods for the analysis of these data are still lacking. In this paper a new method to identify arrhythmic sources, based on the quantitative characterization of the velocity vector field in the mapping area, is proposed and validated in a simulation model. The algorithm reconstructed the activation process by radial basis function (RBF) interpolation of the discrete activation times obtained from the PentaRay mapping system. Following interpolation the velocity vector field and its divergence were analytically determined. RBF interpolation proved to be flexible to reconstruct different simulated activation patterns, including ectopic foci and wavefront collision, and reliable even when part of the mapping sites was not available. Divergence analysis was effective to locate and characterize the peculiar features of arrhythmic activation patterns, identifying ectopic foci as sources of the vector field and collision lines as sinks. Although preliminary, the presented results suggest the potentialities of vector field analysis as a quantitative tool to identify localized arrhythmic sources and clarify arrhythmia mechanisms, thus optimizing the ablative treatment of atrial fibrillation.
    12/2009: pages 1014-1017;
  • Flavia Ravelli, Michela Masè
    [Show abstract] [Hide abstract]
    ABSTRACT: Atrial flutter (AFL) is a supraventricular arrhythmia, based on a reentrant mechanism, which presents small fluctuations in cycle length. We report on studies in humans and animals which disclosed the nature of these variations and supported their mechanical origin. The sources of the spontaneous variability of atrial flutter cycle length have been identified in ventricular contraction and respiration, which cause phasic variations in atrial interval. The phase-response curves have been shown to be closely related to atrial volume changes during ventricular and respiratory activities and oscillations in cycle length have been reported to be independent of autonomic tone. All this evidence has led to the formulation of the mechano-electrical feedback (MEF) paradigm, which suggests that changes in atrial volume directly affect atrial flutter cycle length variability via direct alteration of the reentrant circuit size and mechano-electrical modulation of conduction velocity. Theoretical predictions of experimental variability patterns by a closed-loop mathematical model of AFL variability, including a MEF branch, provided additional evidence in favour of a mechanically-mediated mechanism at the basis of atrial flutter cycle length variability. KeywordsAtrial flutter-Cycle length variability-Mechano-electrical feedback-Reentry-Mathematical modelling
    12/2009: pages 301-325;

Publication Stats

538 Citations
176.04 Total Impact Points

Institutions

  • 2011–2012
    • Lund University
      • Department of Electrical and Information Technology
      Lund, Skane, Sweden
  • 1994–2012
    • Università degli Studi di Trento
      • Department of Physics
      Trento, Trentino-Alto Adige, Italy
  • 2008
    • Santa Chiara Hospital
      Trient, Trentino-Alto Adige, Italy
  • 1996–1998
    • Politecnico di Milano
      • Department of Bioengineering
      Milano, Lombardy, Italy