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Atrial fibrillation (AF) is the most frequently occurring sustained cardiac rhythm disturbance (Wolf, Mitchell, Baker, Kannel, & D’Agostino, 1998). Although relatively easy to diagnose by analysis of the surface ECG, AF has modalities, mechanisms, and predisposing conditions that still remain poorly understood. AF is not a direct life-threatening arrhythmia. However, because of the associated strong symptomatology, it frequently results in hospitalisation, physician visits, and drug therapy, hereby limiting the physical and social activities of many patients. It not only affects the quality of life, but it also increases the likelihood of prothrombotic effects and the risk for mortality because of cerebrovascular events or progressive ventricular dysfunction (Wolf et al., 1998).

Background: The Italian external quality assessment scheme in classical cytogenetics was started in 2001 as an activity funded by the National Health System and coordinated by the Italian Public Institute of Health. Objectives: The aim of our work is to present data from the first 4 years of activity, 2001–2004. Methods: Italian cytogenetics public laboratories were enrolled on a voluntary basis, and this nationwide program covered prenatal, postnatal and oncological diagnosis. The scheme is annual and retrospective; a panel of experts reviewed the quality of images and reports in order to assess technical, analytical and interpretative performance. Results: Over the 4-year period, the number of participating laboratories increased: from 36 in 2001, 46 in 2002, 49 in 2003 to 51 in 2004. The overall technical performance was satisfactory. Inadequacy or lack of information in reporting was the most frequent analytical inaccuracy identified in all parts of the scheme. However, the percentage of complete reports increased significantly during the period: by 36% in postnatal diagnosis between 2001 and 2004 (p < 0.001) and by 42% in oncological diagnosis between 2002 and 2004 (p = 0.003). Conclusions: Our experience reveals that participation in external quality assessment programs has significant advantages, helping to standardize and to assure quality in cytogenetic testing.

In this study we analyzed the problem of electromagnetic interference (EMI) between mobile telephones and cardiac pacemakers (PM), by looking at the mechanisms by which the radiated radio frequency (RF) GSM signal may affect the pacemaker function. From a literature review on this topic, we noticed that older pacemakers had a higher rate of being affected by mobile phones when compared to newer ones. This is probably due to the fact that new generation of PM are more protected against electromagnetic field, being equipped with RF feedthrough filters incorporated to the internal PM circuitry. In some experiments conducted by our group, we found that modulated RF signals are somehow demodulated by the PM internal non-linear circuit elements, if no feedthrough assembly is incorporated inside the PM. Such demodulation phenomenon poses a critical problem because digital cellular phones use extremely low-frequency modulation (as low as 2 Hz), that can be mistaken for normal heartbeat. The feedthrough assembly seems instead to prevents the RF signals from accessing the PM enclosure, thus attenuating EMI signals over a broad range of frequencies.

In this study a methodological approach for measuring temperature and local absorption rate (SAR) on thin metallic structures, such as pacemaker (PM) leads, is provided. First preliminary experiments were performed to evaluate the error in temperature and SAR measurements made by fluoroptic temperature probes when the temperature probe is in different contact configuration with the PM lead tip. Our results show how the position of temperature probes affects the temperature and SAR value measured at the lead tip. The transversal contact between the thermal sensor and the lead tip is the configuration which leads to the highest values for temperature and SAR. In the second part of this paper we describe two physical models of a human trunk and an experimental set-up to investigate the influence of the implant geometry and of the lead path on the heating and the local SAR deposition. Experiments reveled that the implant location and configuration are crucial elements for the heat generation at the lead tip.

Electromagnetic interference with life-sustaining medical care devices has been reported by various groups. Previous studies have demonstrated that volumetric and syringe pumps are susceptible to false alarm buzzing and blocking, when exposed to various electromagnetic sources. The risk of electromagnetic interference depends on several factors such as the phone-emitted power, distance and carrier frequency, phone model and antenna type. The main recommendations and the relevant harmonized standard are also reported and discussed.From the data available in literature emerges that, for distances lower than 1 m there is a non negligible risk of electromagnetic interferences, although significant differences exists in the reported minimum distances. Interference effects clinically relevant for the patients are rare. No permanent damage to the pumps has been ever reported, although in several cases intervention of personnel is required to resume normal operation.

Rate-responsive pacemakers (PMs) aim at having pacing rates as similar to physiological cardiac rhythms as possible. The pacemaker INOS/sup 2+/-CLS (Biotronik, Germany) implements a closed loop strategy (CLS) based on indirect measures of right ventricle contractility using intracardiac impedance signal. The contractility is, in turn, related to the autonomic nervous system control to the heart. Aim of this study was to evaluate the 24h beat-to-beat heart rate and blood pressure profiles in patients implanted with CLS rate adaptive PM. 24h ECG and arterial pressure waveform acquisition were performed by a digital Holter system by the Portapres equipment, respectively. A proper-designed algorithm was developed to classify PM pacing modalities. For each beat we estimated the heart rate (HR), and the systolic and diastolic pressure values (SP, DP). So far, 6 patients have been studied: 4 patients have been analyzed both with and without rate responsive modalities (DDD-R and DDD, respectively); 2 patients have been studied only with rate-responsive modality. Results obtained in 6 patients show that this rate adaptive PM accurately preserve the heart rate and blood pressure variability throughout the 24h. In particular, the rate adaptation of PM based on impedance measurements succeeds in maintaining the spontaneous HR, SP and DP on a beat-to-beat basis.

The Italian External Quality Control Programme for cystic fibrosis molecular diagnosis started in 2001; public laboratories distributed throughout Italy participated on a voluntary basis.: The Italian Public Health Institute (Istituto Superiore di Sanità) sent six validated DNA samples to participating laboratories: technical and clinical information was provided for each sample. Laboratories were required to analyse all six samples. For each sample the laboratories had to provide the results (including raw data) and a report of molecular analysis within 2 months using current methods and nomenclature. Raw data and reports were evaluated by a Steering Committee and their comments were sent to each laboratory.: Genotyping results indicated a general good level of quality for all laboratories, i.e., ∼1% of alleles were incorrectly assigned each year due to analytical (45%) and misinterpretation (45%) errors. During the first 2 years, more than 70% of laboratories did not test for some regional Italian mutations. Commercial kits for reverse dot-blot and oligonucleotide ligation assay PCR were used to detect mutations by 52.8% and 29.5%, respectively, of the participating laboratories. Reporting of results was still inadequate; in 2004 a model for the written report was introduced, but not all laboratories used it.: Our data show that few genotyping errors were made by laboratories and were principally due to misinterpretation and analytical reasons. However, reports are still inadequate and it will be interesting to evaluate the introduction of the reporting model in future years.Clin Chem Lab Med 2007;45:254–60.

� Abstract— Aim of this study was to present a P-wave model, based on a linear combination of Gaussian functions, to quantify morphological aspects of P- wave in patients prone to atrial fibrillation. Five minutes ECG recordings were performed in 25 patients with permanent dual chamber pacemakers set at 40/min in order to have spontaneous beats. ECG signals were acquired using a 32-lead mapping system for high-resolution biopotential measurement (ActiveTwo, Biosemi, The Netherlands, sample frequency 2 kHz, 24 bit resolution). Four healthy subjects were also recorded as a control group. Up to 8 Gaussian models have been computed for each averaged P-wave extracted from every lead. The P- wave morphology is then evaluated by the following parameters: best model orders @ Degrees of Freedom Adjusted R-Square (AdjRsq ) =97.5%; minimum (�1 min) and maximum (�1 max) standard deviation of the gaussians included in the model, number of relative maxima and minima (max+min), and zeroes of the fit. Significant differences in the best model order were obtained between the control group and patients group. Accordingly, the number of relative maxima and minima was higher in the patient group. These parameters might all be markers of the fractionated electrical activity that characterizes paroxysmal AF patients in sinus rhythm.

Electromagnetic interference with critical medical care devices has been reported by various groups. Previous studies have demonstrated that volumetric and syringe pumps are susceptible to false alarm buzzing and blocking when exposed to various electromagnetic sources. The risk of electromagnetic interference depends on several factors such as the phone-emitted power, distance, and carrier frequency. The aim of this study was to assess the risk of GSM phone-induced electromagnetic interference with volumetric and syringe pumps, at various distances and emitted powers. Malfunctions were observed in 6 out of 8 volumetric pumps and in 1 out of 4 syringe pumps exposed to mobile phones at their maximum output, at distances up to 30 cm. The maximum power that did not induce any malfunction at zero distance was 50 mW at 900 MHz and 2.5 mW at 1,800 MHz. In state-of-the-art pumps, the presence of moderate-good base station coverage would significantly reduce the risk of electromagnetic interference.

Aim of this study was to in-vitro evaluate the effectiveness of the filtered feedthrough assembly used to filter out the electromagnetic interference at the Input stage of Implantable pace-makers. We used three modified pace-makers of the same model, with an electrical connection to the output of the input sensing amplifier. The pace-makers differed for the level of protection against electromagnetic interference. We used a dual-band mobile phone. For each pace-maker the output of the sensing amplifier was monitored in 4 status: 1) no inhibition signal; 2) inhibition signal with amplitude 50% greater than the sensing threshold; 3) inhibition signal slightly lower than the sensing threshold; 4) inhibition signal slightly greater than the sensing threshold. For each pace-maker, evaluation has been performed in basal condition (no radiated power), during ringing and during talking. We found that the PMK with only the block capacitor shows asynchronous pacing and inhibition, while the other two PMKs do not interfere with the mobile phone, in any stage and for any mobile status.

Aim of this study is to evaluate the degree of coupling among the cardiovascular variability series and the respiration in subjects susceptible to neurally mediated syncope, in comparison to normal subjects. 21 patients susceptible to syncope and 10 sex and age matched control subjects have been enrolled in the study. ECG, respiration activity, and arterial blood pressure were simultaneously recorded at rest (controlled and free breathing) and during 70/spl deg/ head-up TILT test (free breathing). The degree of non-linear coupling among heart rate. variability (HRV), blood pressure variability (BPV) and respiration has been quantified by means of a multivariate embedding-based approach. 11 patients developed syncope during the TILT test. The non-linear coupling among the cardiovascular variables and respiration turned out to be stronger during controlled breathing than during free breathing, both for TILT-positive and TILT-negative group. During late TILT phase, in the TILT-positive group, the non-linear coupling showed a significant increase. If the proposed non-linear coupling indexes can be considered expression of the coupling mechanisms involved in the vagal regulation of the cardiovascular system, an increase of the vagal tone accompanied by a decrease of the sympathetic activity seem to occur before a vasovagal event.

It is generally known that the pupil is under the control of the autonomic nervous system. Recently, those rhythms characterizing the autonomic fluctuations of heart period and arterial blood pressure have been detected in spontaneous pupil diameter (PD) fluctuations. The physiological mechanisms underlying such variability have not been widely investigated. The aim of this study was to investigate the origin of the pupil fluctuations in humans, using a non-invasive modulation of carotid baroreceptors by neck suction (NS). To this purpose, we simultaneously recorded ECG, respiration activity, NS pressure and PD fluctuations from 10 normal subjects. The equipment for the PD measurement and the NS stimulation was developed in our laboratory. The response of the pupil to the NS was studied at stimulation frequencies of 0.10 and 0.20 Hz, by using parametric spectral and cross-spectral estimation. In all subjects, the NS rhythms were clearly detectable in heart rate variability series in both stimulation frequencies and also in the PD spectra with significant coherences (>0.5). These findings suggest that blood pressure fluctuations propagate to the pupil via carotid baroreceptor afferent pathways. However a central contribution can not be excluded.

DRAGO, F., ET AL.: Beat to Beat Heart Rate Adaptation in Pediatric and Late Adolescent Patients with Closed Loop Rate-Responsive Pacemakers. The aim of this study was to evaluate the efficacy of physiological rate-responsive pacemakers (Closed Loop Stimulation - CLS) to pace pediatric and late adolescent patients undergoing rest, mental, standing, and exercise testing. Dual-chamber pacemaker is increasingly indicated for young patients. A new physiological pacing mode based on the indirect measure of ventricular contractility (CLS), has shown interesting results in adults, while no data on pediatric patients are available. RR intervals and beat-to-beat systolic and diastolic pressures were monitored in 12 pediatric patients (6 males, mean age 17 years [12-22 years]) who had a transvenous implant of Inos 2 + -CLS dual-chamber pacemaker (Biotronik GmbH, Berlin, Germany) and endocardial leads. All the patients showed correct electrical parameters at the implant and during the follow-ups. Paced RR intervals decreased significantly (F = 7.28, P = 0.01) from 0.85 ′ 0.08 seconds (rest) to 0.73 ′ 0.10 seconds (mental) and to 0.75 ′ 0.010 seconds (standing); systolic/diastolic pressure was significantly higher (F = 12.2, P = 0.002/F = 13.6, P = 0.001) in mental (134.4 ′ 19.9/74.4 ′ 8.1 mmHg) with respect to rest (115.1 ′ 18.3/61.0 ′ 6.1 mmHg), and standing (118.7 ′ 23.9/67.3 ′ 0.1 mmHg). During exercise the paced RR interval showed significant decrease of about 35% from baseline to maximum load (F = 24.90, P = 0.001) and systolic pressure increased significantly (F = 4.91, P = 0.019) by about 34% from baseline to maximum load. The comparison between paced and spontaneous rates showed very similar values and trend. In addition, CLS mode does not seem to overrun the spontaneous heart activity, when present. This is a study to evaluate CLS pacing in pediatric and late adolescent patients. The study shows that CLS pacing responds to both physical and non-physical stressors, providing physiological pacing rates, as previously observed in adults.

It has been recently demonstrated that the pulse transit time (PTT) variation between inspiration and expiration is a sensitive descriptor of inspiratory effort in healthy awake children and in standardize condition. Aim of this study was to automatically extract the amplitude variations of PTT at the respiration frequency by implementing a complex demodulation algorithm. Inspiratory effort was simulated by a custom designed nasal and mouth two-way non rebreathing face mask (Series 7910-Hans Rudolph Inc, Kansas City, Missouri-USA), with reduced inhalation valve port diameter (3, 5 and 8 mm). After the calculus of PTT, a complex demodulation algorithm has been used to extract its amplitude fluctuations. Results obtained from 5 children, who attended the pediatric service for routine assessment and without active nocturnal and diurnal respiratory symptoms and chronic cardiorespiratory diseases, show that the higher the inhalation valve port diameter, the smaller the PTT amplitude fluctuations.

The aim of this paper is to introduce and statistically characterize an estimator of the P-wave duration. The estimator is based on the computation of the P-wave area of an average P-wave. No fiducial points are needed for the estimation of P-wave duration. The computation of the total area is performed by summing up the absolute value of the average P-wave. The absolute value is used since P-wave can be polyphasic. The estimator is not biased even when the signal is corrupted by 0-mean noise, as a corrective term is introduced. The corrective term represents the mean error due to have taken the absolute value of the signal. The error depends on the value of the original signal, thus the corrective term has to be calculated for each sample. The computation of the corrective term, under the hypothesis of Gaussian noise, is based on the computation of the residual noise after the averaging procedure. The proposed estimator is characterised in terms of confidence interval in order to be used in a prediction model of atrial fibrillation. The accuracy obtained for the estimation of P-wave duration was -3.8% +7.5%. This accuracy is lower than that obtained with previously proposed methods.

The study aims to review the mathematical methods developed for the prediction of atrial fibrillation by analysis of surface electrocardiographic records in paroxysmal or post-cardiosurgery patients. A risk stratification based on ECG analysis would be very useful either to optimise the prophylactic antiarrhythmic treatment in high risk patients, or to limit drugs administration in low risk subjects. The works published so far managed to achieve good results in terms of sensitivity and specificity. However, since these methods are not completely reliable yet, their clinical application is still limited. The present study is divided in sections about time domain, frequency domain, premature complexes detection, heart rate variability, and non linear ECG analysis based methods.

The aim of this study was to validate the use of pulse transit time (PTT) as a method to monitor sleep apnea in children. PTT was estimated as the interval between the ECGR-wave and the point at which the pulse wave at the finger reached 50% amplitude. First, we assessed changes in the PTT during breathing against known resistances in 15 awake children; resistance was applied with a modified nose and mouth two-way nonrebreathing face mask, having the inhalation valve port fitted with drilled plastic cylinders of various diameters. Second, we analyzed 20 events of obstructive apnea and 90 events of central apnea during sleep in 10 children. Our data showed good correlation between the inspiratory effort and PTT oscillation amplitude. In addition, PTT oscillation amplitude tuned out to successfully discriminate central from obstructive apnea.

Cardiovascular autonomic rhythms (Low Frequency, LF and High Frequency, HF) can be detected in spontaneous Pupil Diameter (PD) fluctuations. Aim of this study is to investigate the origin of these pupil fluctuations in humans, using a non-invasive modulation of carotid baroreceptors by Neck Suction (NS). ECG, Respiration and NS pressure from 10 normal subjects were recorded simultaneously to PD fluctuations. The equipment for the PD measurement and the NS stimulation was developed in the authors' laboratory. To distinguish between the sympathetic and parasympathetic efferent activity the authors' studied the response of the pupil to the NS at two different frequencies of stimulation (0.10 and 0.20 Hz). Their findings showed that baroreceptor stimulation induces pupil fluctuations locked to both stimulation frequencies, suggesting blood pressure fluctuations propagate to the pupil via carotin baroreceptors afferent pathways. However a central contribution cannot be excluded.

Activation patterns underlying the electrical activity of the heart during Atrial Fibrillation (AF) are not entirely random. The aim of this study was to estimate the degree of coupling between two atrial sites by means of two indexes (Independence of Complexity and Independence of Predictability, IC and IF) based on a multivariate embedding procedure. We analyzed activation sequence of two atrial sites in 30 informed subjects during chronic AF of type I, II and III (Wells' classification), 10 episodes each type, lasting 6 seconds. Surrogates were used to reject the hypothesis that the time series were generated by linear stochastic dynamics. In type I and II AF, IC and IP were significantly lower than their surrogates. In type III no coupling was detected IC and IP succeeded in detecting a nonlinear interaction between different atrial sites in type I and to a minor extent, type II AF.

From recent studies of atrial fibrillation (AF) in animals and humans it appears that improvement in the success rate of ablation may be achieved by evaluating the local electrophysiological properties of the atrial tissue. The aim of this study was to develop an automated method for the assessment of the organization of the whole right atrium. Bipolar electrograms were obtained from multielectrode basket catheters (MBC) in the right atrium in 5 informed patients with AF. The local atrial period (AP) and number of occurrence (NO) were calculated from each electrogram. Organization of the whole atrium was estimated by bidimensional interpolation of the AP and NO measurements. AP and NO maps allowed to identify areas with different degree of organization. A larger database is needed to assess the clinical value of our approach.

The aim of this study is to evaluate the degree of coupling between the cardiovascular variability series and the respiration in subjects susceptible to neurally mediated syncope. Twenty-one informed patients susceptible to syncope and ten sex- and age-matched control subjects were enrolled in the study. ECG, respiration activity, and arterial blood pressure were simultaneously recorded at rest (controlled and free breathing) and during the 70° head-up TILT test (free breathing). The degree of nonlinear coupling among heart rate variability (HRV), blood pressure variability (BPV), and respiration was quantified by means of two indices according to a multivariate embedding-based approach. Eleven patients developed syncope during the TILT test. We found that during the late TILT phase, the TILT-positive group experienced a significant increase in nonlinear coupling respect to the mid TILT phase (p < 0.01, Wilcoxon nonparametric test for pair data) while the TILT-negative group did not (p < 0.01, Mann-Whitney U-test). If the proposed nonlinear coupling indexes can be considered expression of the coupling mechanisms involved in the vagal regulation of the cardiovascular system, an increase in vagal tone accompanied by a decrease in sympathetic activity seem to occur before a vasovagal event. © 2003 Biomedical Engineering Society.

Study objectives The current criterion standard for measuring inspiratory effort, esophageal manometry, is an invasive procedure that young patients find intolerable. Inspiratory effort can also be assessed noninvasively by measuring the pulse transit time (PTT). PTT is the time the pulse wave (PW) takes to travel between two arterial sites (normally heart to finger). The speed at which the PW travels is directly proportional to arterial BP. When BP rises, PTT shortens. Conversely, when BP falls, PTT lengthens. In this study, we investigated PTT as a measure for evaluating inspiratory effort in children. Participants We studied 15 healthy children (age range, 5 to 12 years; mean age [± SD], 8.3 ± 2.74; 9 male children) selected from patients referred to our pediatric center for routine assessment. Measurements and results We assessed changes in the PTT during breathing against known resistances in awake children. Resistance was applied to the nose and mouth with a modified, two-way, nonrebreathing facemask. Our data show a good correlation between the induced inspiratory effort and the amplitude of PTT variations. Conclusions PTT should be a useful method for quantifying changes in inspiratory effort due to augmented upper airway resistance in awake children.

Analysis of interference and phase locking phenomena between respiration and short-term Heart Rate and Blood Pressure variability signals have been performed by using nonlinear signal processing techniques, such as Poincare Maps, Recurrence Maps, Time-Space Separation Plots and Bispectrum Estimation. Data obtained from normal subjects confirm the hypothesis of non-linear interaction of Low and High frequency rhythms with respiration.

The aim of this study was to use Recurrence Plot Analysis to test the hypothesis of deterministic non-linear dynamics of Atrial Period (AP) during type I Atrial Fibrillation (AF) (Wells' classification). The authors used three variables to quantify Recurrence Plots: Percent Recurrence (PR), Percent Determinism (PD) and Entropy of Recurrences (ER). They analyzed bipolar intra-atrial electrograms of electrically induced AF recorded in 3 different atrial sites in 15 informed subjects. The AP of each each site was obtained by using a peak detection algorithm based on threshold crossing. The authors compared the real data results with those obtained from their stochastic surrogate series (phase randomization). PR, PD and ER values obtained for the surrogate data were significantly lower than those values from original data, confirming the hypothesis of a nonlinear deterministic dynamics of the atrial depolarization period during AF.

Aim of this study is to investigate the effects of low energy internal cardioversion (LEIC) on the electrophysiological properties of the right atrial tissue. Thirteen patients were studied, selected a priori for LEIC (increasing energy levels: 1, 2, 3, 5, 7, 10, 15 and 20 J) and monitored by a multipolar basket catheter (32 intra-atrial recordings each patient). The atrial period, the levels of organization and the synchronization have been estimated for each electrogram, over 10-second windows, 10 seconds before and 10 seconds after each shock. Our results suggest that ineffective shocks do not affect the electrophysiological properties of the atria. This is consistent with the hypothesis that even though electrical activation ceases after the shock it spontaneously regenerates within few milliseconds and that the propagation pattern is expression of the organic substrate, which is not affected by an electric shock.

We have designed a procedure to evaluate rate-responsive pacemakers featuring rate adaptation through autonomic inputs. The proposed procedure is based on a set of neurovegetative stressors and on the analysis of the heart rate variability (HRV). The selected stressors include: controlled respiration in the supine position and during active standing, mental stress, hand grip, and non-invasive sinusoidal stimulation of carotid baroreceptors. Each test lasted five minutes. Completely or partially incompetent patients implanted with INOS/sup 2+/-CLS pacemakers (from Biotronik) were studied one month after the start of the rate-modulating program. ECG, respiration activity and non-invasive blood pressure (Finapres) were monitored. We found that the most effective stressors were active standing and hand grip. Spectral analysis was of limited value due to the distortion introduced by spontaneous beats. In conclusion, a procedure based on HRV analysis in response to selected neurovegetative stressors is able to quantify the rate adaptation of pacemakers.

Introduces a new measure of synchronization between electrical activity of relatively close atrial sites during Atrial Fibrillation (AF). It assesses the probability of finding synchronous activations in intra-atrial bipolar electrograms. Data were obtained using multipolar basket catheter in the right atrium, in informed patients during AF. The Index of Synchronization (IS) is based on the assumption that two activations closely spaced in time are likely to belong to the same depolarization wavefront (i.e. synchronized). Relevant features of the proposed index are the high temporal resolution and the robustness to activation time estimation error, to missing or false detections and to the ever changing pattern of propagation, typical of the AF.

The aim of this study was to investigate the origin of the pupil fluctuations in humans. The authors assess whether and to which extent LF and HF cardiovascular rhythms contribute to spontaneous pupil diameter fluctuations at rest, during sympathetic activation by Head-Up Tilt Test 70/spl deg/ and during a non-invasive modulation of carotid baroreceptors by Neck Suction (NS). The responses of the pupil to the NS was studied at stimulation frequencies of 0.10 and 0.20 Hz. The effect of tilting on PD fluctuations spectra and the physiological background of the pupil control are consistent with the hypothesis that pupil fluctuations reflect a generalized increase of the sympathetic tone. The findings obtained with the NS stimulation suggest that blood pressure fluctuations propagate to the pupil via carotid baroreceptor afferent pathways. However a central contribution can not be excluded.

A new index of synchronisation (IS) between the electrical activity of pairs of close atrial sites during atrial fibrillation (AF) is introduced. The index assesses the probability of finding synchronous activations in intra-atrial bipolar electrograms and is based on the assumption that two activations closely spaced in time are likely to belong to the same depolarisation wavefront. A dedicated statistical treatment to test this hypothesis is also illustrated. Experimental data were obtained using a multipolar basket catheter in the right atrium in 20 patients during normal sinus rhythm (NSR), atrial flutter (AFL, one patient), high-frequency pacing (HFP, two patients) and chronic AF (17 patients), and 30 segments were obtained from each. From the 24 pairs of bipoles, a single averaged IS and its standard deviation were extracted. The IS was 1 in NSR and HFP and 0.95 +/- 0.02 during AFL. During AF, the IS provided a quantitative measure of the degree of coupling of various atrial sites. The IS varied significantly among the recording sites (range 0.38-0.96), showing a patient-dependent pattern, and decreased as the arrhythmia complexity increases. No temporal trends were observed for the IS values in any chronic AF patient. On average, in each site, the dispersion of the IS over time was lower than 32% of the mean, for all patients. Additional relevant features of the proposed index are its high temporal resolution (2s) and robustness to activation time estimation error, to missing or false detections and to the ever-changing pattern of propagation. The index of synchronisation is a descriptor of the electrophysiological properties of atrial tissues.

We performed a quantitative study of coupling patterns between respiration and spontaneous rhythms of heart rate and blood pressure variability signals by using the Recurrence Quantification Analysis (RQA). We applied RQA to both simulated and experimental data obtained in control breathing at three different frequencies (0.25, 0.20, and 0.13 Hz) from ten normal subjects. RQA succeeded in quantifying different degrees of non-linear coupling associated to several interference patterns. We found higher degrees of non-linear coupling when the respiratory frequency was close to the spontaneous Low Frequency (LF) rhythm (0.13 Hz), or almost twice the LF frequency (0.2 Hz), whereas weaker coupling was observed when the respiratory frequency was 0.25 Hz. Clinical applications of our approach should focus on new experimental protocols, featuring the stimulation of one of the two branches of the autonomic nervous system (ANS) or aimed at the analysis of pathologies linked to the ANS.

The aim of this study was to determine the presence of organization of atrial activation processes during atrial fibrillation (AF) by assessing whether the activation sequences are wholly random or are governed by deterministic mechanisms. We performed both linear and nonlinear analyses based on the cross correlation function (CCF) and recurrence plot quantification (RPQ), respectively. Recurrence plots were quantified by three variables: percent recurrence (PR), percent determinism (PD), and entropy of recurrences (ER). We recorded bipolar intra-atrial electrograms in two atrial sites during chronic AF in 19 informed subjects, following two protocols. In one, both recording sites were in the right atrium; in the other protocol, one site was in the right atrium, the other one in the left atrium. We extracted 19 episodes of type I AF (Wells' classification). RPQ detected transient recurrent patterns in all the episodes, while CCF was significant only in ten episodes. Surrogate data analysis, based on a cross-phase randomization procedure, decreased PR, PD, and ER values. The detection of spatiotemporal recurrent patterns together with the surrogate data results indicate that during AF a certain degree of local organization exists, likely caused by deterministic mechanisms of activation.

The aim of this study is to investigate the changes, in the frequency domain, of microvasculature blood flow (BF) occurring in neurally mediated syncope. We studied 20 patients with history of recurrent syncope and 10 control subjects. Peripheral BF was measured (laser Doppler technique) in the palmar region (PBF) and the manubrium sterni (SBF), together with ECG, respiration activity (RA) and blood pressure (BP), at rest (5 minute) and during 70/spl deg/ head-up tilt test. SBF and PBF appear to be characterized by oscillations around 0.16 Hz (0.15-0.19 Hz), that do not have correspondence in the other cardiovascular variability signals. Mean BF was not significantly altered in tilt negative, control and tilt positive groups (11 patients) during tilt. In the tilt-positive group a decrease of mean PBF and SBF and an increase of the oscillation frequency of PBF and SBF was observed in close proximity to the development of symptoms.

The aim of this paper was to investigate the relationship between spontaneous pupil diameter fluctuations and autonomic rhythms of cardiovascular variability signals. ECG, Finapres and respiration data from 10 normal subjects were recorded simultaneously to spontaneous pupil diameter fluctuations obtained from a portable infrared TV pupillometer. Power spectra of pupillary fluctuations showed in all the subjects a respiratory component with significant spectral coherence with the high frequency components of the tachogram and systogram. Moreover a discrete power distribution in the low frequency band have been identified; coherence with LF power in tachograms and systograms was significant in 6/10 subjects. It is concluded that cardiovascular autonomic rhythms can be detected in spontaneous pupil diameter fluctuations.

Abstract 3238 Poster Board III-175 We have used single nucleotide polymorphism (SNP) and comparative genomic hybridization array (aCGH) to study DNA copy number (CN) changes and loss of heterozygosity (LOH) in a series of 28 patients affected by Sézary syndrome (SS), a rare form of cutaneous-T-cell lymphoma (CTCL). Our data identified, further confirming previous studies, recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71 and 68% of cases respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in more than 30% of tumours: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. Individual chromosomal aberrations did not show a significant correlation with prognosis, however when more than three recurrent chromosomal alterations (gain or loss) were considered, a statistical association was observed using Kaplan-Meier survival analysis. Crossing genomic data mapping with those obtained from gene expression profiles of matching samples we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer related genes such as members of the NF-kB pathway (NKIRAS2, PSMD3, BAG4, BTRC, TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times we identify several common candidates that might exert critical roles in SS, like PIP5K1B and BUB3. Taken together this study confirms and maps more precisely the regions of gain and loss and, combined to transcriptional profiles, suggest a novel set of genes of potential interest in SS. Disclosures No relevant conflicts of interest to declare.

Background MRI induced heating on PM leads is a very complex issue. The widely varying results described in literature suggest that there are many factors that influence the degree of heating and that not always are adequately addressed by existing testing methods. Methods We present a wide database of experimental measurements of the heating of metallic wires and PM leads in a 1.5 T RF coil. The aim of these measurements is to systematically quantify the contribution of some potential factors involved in the MRI induced heating: the length and the geometric structure of the lead; the implant location within the body and the lead path; the shape of the phantom used to simulate the human trunk and its relative position inside the RF coil. Results We found that the several factors are the primary influence on heating at the tip. Closer locations of the leads to the edge of the phantom and to the edge of the coil produce maximum heating. The lead length is the other crucial factor, whereas the implant area does not seem to have a major role in the induced temperature increase. Also the lead structure and the geometry of the phantom revealed to be elements that can significantly modify the amount of heating. Conclusion Our findings highlight the factors that have significant effects on MRI induced heating of implanted wires and leads. These factors must be taken into account by those who plan to study or model MRI heating of implants. Also our data should help those who wish to develop guidelines for defining safe medical implants for MRI patients. In addition, our database of the entire set of measurements can help those who wish to validate their numerical models of implants that may be exposed to MRI systems.

The fluctuations of the human pupil in presence of light stimulation have been long investigated in several clinical applications, both in natural and artificial conditions. The pupil dynamics offer useful information in order to make non-invasive diagnoses of neurological diseases. Typically the pupil is shot by a CCD camera, which is the core of the measurement apparatus, called pupillometer, and the resulting image is analysed. In this paper we present the application of a multiscale approach to edge detection to identify the morphological parameters of the pupil edge. First, we determine the degradation parameters of the measured image, which is assumed to be blurred by a Gaussian kernel and corrupted by an additive white noise; then we apply the edge detection procedure and the optimal fitting, showing the main results; a first dynamical analysis is also presented.

The authors tested an Index of Synchronization (IS) between the electrical activations of relatively close atrial sites during various atrial tachiarrhythmias. Data were obtained using multipolar basket catheter in the right atrium, in 17 informed patients during normal sinus rhythm (NSR, 3 pts.), atrial flutter (AFlu, 2 pts.), high frequency pacing (HFP, 3 pts.) and Atrial Fibrillation (AF, 12 pts.), 10 segments each. From the 24 couples of bipoles of the same splines the authors extract a single averaged IS and its standard deviation. IS was 1 in NSR and HFP, 0.95/spl plusmn/0.02 during AFlu. During AF, IS varied significantly among the recording sites, showing a patient-dependent pattern and an increase of the arrhythmia complexity. In AF it provides a quantitative measure of the degree of coupling of various atrial sites. It can be considered as a descriptor of the electrophysiological properties of atrial tissues, whose clinical usefulness is worth to be further investigated.

In this study linear and non-linear indexes for the characterization of the dynamics in both intra-atrial (IA) signals and atrial period (AP) series are presented and used to discriminate among different atrial fibrillation (AF) episodes. The level of predictability (LP) of AP series and its regularity (R) were computed through the identification of an autoregressive model of the AP series and through the estimation of corrected conditional entropy (CCE), respectively. In addition non-linear synchronization (NLS) patterns were analyzed through indexes based on the mutual corrected conditional entropy (MCCE). Results evidence the capability of the proposed parameters to detect and quantify the different dynamics of IA signals during different type of AF episodes.

A numerical study to investigate the effects of the exposure to electromagnetic fields (EMF) at 900 and 1800 MHz on biological tissues implanted with thin metallic structures has been carried out, using the finite difference time domain (FDTD) solution technique. The results of the model show that the presence of a metallic wire yields to a significant increase in the local specific energy absorption rate (SAR). The present standards and/or guidelines on safe exposures of humans to EMF does not cover persons with implanted devices and thus the threshold levels to define safe exposure conditions might not apply in presence of high SAR gradients, such as the ones generated by thin metallic implanted objects. However, exposure to EMF fields below the actual safe levels even in presence of thin conductive structures cause rather low temperature rises (1 degrees C).

The aim of this study was to assess the effect of filtering techniques on the time-domain analysis of the ECG. Multi-lead ECG recordings obtained from chronic atrial fibrillation (AF) patients after successful external cardioversion have been acquired. Several high-pass filtering techniques and three cut-off frequency values were used: Bessel and Butterworth four-pole and two-pole bidirectional and unidirectional filters, at 0.01, 0.05 and 0.5 Hz low cut-off frequency. As a reference, a beat-by-beat linear piecewise interpolation was used to remove baseline wander, on each P-wave. Results show that ECG filtering affects the estimation of P-wave duration in a manner that depends upon the type of filter used: particularly, the bidirectional filters caused negligible variation of P-wave duration, while unidirectional ones provoked an increase higher than 8%.

P wave morphology has been shown to be modified in patients with paroxysmal atrial fibrillation (AF) and in healthy subjects of different age. These changes are commonly evaluated in the signal averaged ECG, thus in average P waves. Aim of this study is to assess beat-to-beat variations in P wave characteristics. Five-minute 12-lead ECG were recorded from 10 healthy subjects (C group), 10/10 patients with/without an AF recurrence (R/NR groups), after electrical cardioversion. Principal component analysis was performed on a beat-to-beat basis. The dynamic of the first three eigenvalues series and the beat-to-beat variability of the first three principal components (PCs) morphology were analyzed by calculating the distance between the average morphology over all the beats acquired and the morphology identified on each beat for the first three PCs. Most of the indexes were statistically different between C group and the patients with history of AF, highlighting higher regularity of the eigenvalues series as well as more similar PCs in healthy subjects. In addition, the series of the first eigenvalues was significantly less regular in R group compared NR group (Reg: 0.029 ± 0.020, 0.062 ± 0.033, p

The authors performed a quantitative study of sub-harmonic synchronization and entrainment phenomena between respiration and short-term Heart Rate and Blood Pressure variability signals by the Recurrence Plot Analysis (RPA). Quantification of the recurrence plots has been obtained using descriptors such as Percent Recurrence, Percent Determinism and Entropy of Recurrences. The authors applied RPA to data obtained in control breathing at different frequencies from 10 normal subjects. The breathing frequencies were chosen to elicit interference phenomena between LF and HF frequency components. Unlike the power spectral estimation, RPA seems to be succeeds in detecting entrainment and transient phase locking phenomena; moreover, the recurrence descriptors turn out to be particularly suited for a quantitative evaluation of the different phenomena observed.

Electromagnetic interference (EMI) to critical care medical devices has been reported by various groups. Previuos study demonstrated that infusion pumps are susceptible of false alarm buzzing and block of infusion, when exposed to various EMI sources. Aim of this paper is to investigate the changes in the risk of EMI from the estimates of our previous 2005 survey and to extend the EMI risk assessment to newer telecommunication products: DECT phones and WiFi terminals. With regards to GSM phones, compare to the results obtained in 2005, we observed a decrease in the rate of failure (from 58% to 30%). From our findings, the use of WiFi and DECT does not pose a real risk to infusion systems.

The aim of this study is to investigate whether and to which extent the non-linearity of the sino-atrial node contributes to the complex interactions between autonomic control and heart rate variability (HRV). The authors analyzed a non-linear model of the autonomic control on the sino-atrial node under particular experimental conditions: they forced the autonomic nervous system to act at established frequencies, by a controlled breathing procedure and a non-invasive periodic modulation of carotid baroreceptors. The authors quantify the non-linear coupling between the stimuli and both the experimental and the simulated HRV series by using the recurrence plot quantification analysis. These results show that the nonlinear interaction between external stimuli and HRV is due to a certain extent to the non-linear features of the sino-atrial node.

The radio frequency field used in magnetic resonance imaging (MRI) procedures leads to temperature and local absorption rate (SAR) increase for patients with implanted pacemakers (PM). In this work a methodological approach for temperature and SAR measurements using fluoroptic probes is presented. Experimental measures show how the position of temperature probes affects the temperature and SAR value measured at the lead tip. The transversal contact between the active portion of the probe and the lead tip is the configuration associated with the highest values for temperature and SAR, whereas other configurations may lead to an underestimation close to 11% and 70% for temperature and SAR, respectively. In addition measurements were performed on a human-shaped phantom inside a real MRI system, in order to investigate the effect of the PM placement and of the lead geometry on heating and local SAR.

Aim of this study was to evaluate whether GSM cellular phones can affect the pacemaker (PM) functioning or the home monitoring (HM) function. We performed in vitro and in vivo tests on the BA03 PM (Biotronik, Germany). In vitro we evaluated whether the PM functioning was affected by a mobile phone or whether an improper HM procedure or an altered patient-activated HM function occurred. Two cellular phone models were used, with fixed external or internal antenna, positioned both close to the pacemaker and to the mobile cell-phone-like device, during handover, ringing and talking. All the tests have been done with the PM in air, at 900 and 1800 MHz GSM. We found that the neither the PM functioning nor the HM procedure are altered by a GSM communication. On the basis of these findings, we performed a subset of tests in 11 patients: the two phone models used for the in vitro protocol were moved both around the pacemaker implant site and the mobile cell-phone-like device at 900 MHz and 1800 MHz GSM during talking. All the patient-activated transmissions were correctly received by the service center, with a maximum transmission delay of 110 s.